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Accommodating Disabilities in Experiential Education: Easier Than it Seems, Full of Reward

Learning Objectives

 

After completing this application-based continuing education activity, pharmacist preceptors will be able to

  • DEFINE types of learning disabilities that preceptors are likely to encounter
  • LIST the information the school of pharmacy should provide to preceptors
  • IDENTIFY accommodation that are appropriate for specific students
  • DESCRIBE reasonable accommodation in experiential education

    Education for disabled children. Handicapped kid on wheelchair in kindergarten. Equal opportunities, preschool program, special needs. Vector isolated concept metaphor illustration

     

    Release Date: December 10, 2023

    Expiration Date: December 10, 2026

    Course Fee

    Pharmacists: $5

    UConn Faculty & Adjuncts:  FREE

    There is no grant funding for this CE activity

    ACPE UANs

    Pharmacist: 0009-0000-23-059-H04-P

    Session Code

    Pharmacist:  23PC59-ACA37

    Accreditation Hours

    1.0 hours of CE

    Accreditation Statements

    The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-059-H04-P  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

     

    Disclosure of Discussions of Off-label and Investigational Drug Use

    The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

    Faculty

    Jennifer Luciano, PharmD
    Director, Office of Experiential Education; Associate Clinical Professor
    UConn School of Pharmacy
    Storrs, CT

    Neha Patel
    2025 PharmD Candidate
    UConn School of Pharmacy
    Storrs, CT

    Jeannette Y. Wick, RPh, MBA, FASCP
    Director, Office of Pharmacy Professional Development
    UConn School of Pharmacy
    Storrs, CT

     

     

     

     

     

     

    Faculty Disclosure

    In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

    Jeannette Wick, Neha Patel, and Jennifer Luciano do not have any relationships with ineligible companies

     

    ABSTRACT

    From time to time, preceptors need to address the needs of students who have disabilities, be they visible or invisible. Students’ disabilities may include chronic diseases, physical limitations, or difficulty with processing information. This continuing education activity introduces various types of disabilities that preceptors may encounter and suggests a stepwise process to develop accommodation plans. It discusses information that preceptors will need or want to have on hand, and potential sources to obtain the information. It also describes the various stakeholders and the accommodation process and the potential benefits for the entire workplace.

    CONTENT

    Content

    INTRODUCTION

    Some pharmacy students have visible or invisible disabilities that require accommodation (a change or adaptation to adjust a situation to meet the student’s unique needs). Anecdotally, faculty at the University of Connecticut School of Pharmacy report that between 5% and 12% of students in a typical class in the last 10 years need accommodation. In terms of physical disabilities, institutions of higher learning have almost always built or altered existing buildings to accommodate students with disabilities with ramps, elevators, wide doors, and similar structural changes. Preceptors who work in larger organizations may have support teams that address or have already addressed physical disabilities. Those who work in smaller organizations or older buildings may be intimidated by the need to accommodate but will find that the law requires “reasonable” accommodation.

     

    Pharmacy preceptors are more likely to encounter students who have chronic disease (e.g., asthma, autoimmune syndromes, diabetes, etc.) or learning disabilities, including those who are neurodivergent (the SIDEBAR explains the concept of neurodiversity). While taking classes, pharmacy schools often (and are legally required to) provide accommodation for students with learning disabilities (see Table 1). They may provide double time or access to a quiet room during exams, permission to take breaks during class, or notetakers to help them depending on the disability type. Students with learning disabilities acquire, organize, retain, comprehend, or use verbal or nonverbal information differently than others. They have impaired perception, thinking, remembering, or learning processes.1

    Table 1. Types of Learning Disabilities1-7

     

    Learning disability Description
    Anxiety disorder Anxiety that does not go away and can worsen over time. Symptoms can interfere with daily activities such as job performance, schoolwork, and relationships. Subtypes of anxiety disorders include generalized anxiety disorder, panic disorder, social anxiety disorder, and various phobia-related disorders.
    Attention deficit hyperactivity disorder Causes an ongoing pattern of inattention and/or hyperactivity that interferes with functioning and/or development.
    • Inattention may manifest as difficulty staying on task, sustaining focus, and staying organized; these problems are not due to insubordination or lack of comprehension.
    • Hyperactivity manifests as involuntary constant movement, even when it is inappropriate, or excessive fidgeting, tapping, or talking. Adults with ADHD are often extremely restless or talkative.
    • Impulsivity is acting without thinking or difficulty with self-control. It may include a desire for immediate reward or inability to delay gratification. It may manifest as interrupting others or making key decisions while ignoring long-term consequences.
    Autism spectrum disorder (ASD) A neurologic and developmental disorder that affects how people interact with others, communicate, learn, and behave. Autism is known as a “spectrum” disorder because its wide variation in presentation and symptom severity.

    People with ASD often have:

    ·       Difficulty with communication and interaction with other people

    ·       Restricted interests and repetitive behaviors

    ·       Symptoms that affect their ability to function in school, work, and other areas of life

    Dysgraphia A neurological disorder characterized by writing disabilities that appear as distorted or incorrect writing (inappropriately sized and spaced letters, or wrong or misspelled words despite focused instruction).
    Dyscalculia Causes consistent failure to achieve in mathematics marked by difficulties with counting, working memory, visualization; visuospatial, directional, and sequential perception and processing; retrieval of learned facts and procedures; quantitative reasoning speed; motor sequencing; perception of time; and the accurate interpretation and representation of numbers when reading, copying, writing, reasoning, speaking, and recalling.
    Dyslexia Impairs a person’s ability to read. Although varies by individual, common characteristics include difficulty with
    • Phonological processing (the manipulation of sounds)
    • Rapid visual-verbal responding
    • Spelling

     

    SIDEBAR: Emerging Terminology and Necessary Understanding: Neurodiversity8-11

     

    Neurodiversity refers to the diversity of all people, but is often used in the context of autism spectrum disorder (ASD), neurological or developmental conditions, and learning disabilities. It is neither a medical term nor a diagnosis; it’s a descriptor used to replace the tendency to think of behaviors as normal or abnormal or to marginalize certain people based on their behaviors. When thinking about neurodiversity, it’s critical to remember that there is no one right way of thinking, learning, and behaving, and all differences are not necessarily deficits. Neurodiversity is not preventable, treatable, or curable. It’s the result of normal variation in the human genome. The term is used to promote equity and social justice for people who are members of a neurologic minority.

     

    Students who are neurodivergent experience and interact with the world around them in many different ways. Common characteristics among students who are neurodivergent include eye contact, facial expressions, and body language that are different than many other people’s.

     

    Students may or may not disclose (or even know) they are neurodivergent. When students do, it is important for preceptors to acknowledge neurodiversity and ask directly about a person’s preferred communication style and accommodations, many of which are described in the text of this continuing education activity. Many of the accommodations for people who are neurodiverse also help other students and employees who do not fall into neurologic minority categories, including

    • Offering or allowing individuals to make small adjustments to the workspace
    • Avoiding sarcasm, idioms, euphemisms, and implications
    • Providing concise instructions
    • Posting information about due dates and meetings as far in advance as possible
    • Treating all people with respect

     

    Preceptors should foster environments that are conductive to neurodiversity, and to recognize and emphasize each person’s individual strengths and talents while also providing support for their differences and needs. It’s also helpful to know that many large companies are now adjusting their hiring processes to attract people who are neurodivergent. They’ve found that although some people have trouble navigating the hiring process, their unique abilities are valuable, increase the company’s productivity, and often lead to remarkable product and process improvements.

     

     

    This continuing education activity is designed to help preceptors who encounter pharmacy students with disabilities develop workable plans. Preceptors should start by acknowledging a critical fact: accommodation isn’t special treatment. Accommodation levels the playing field so student pharmacists (and employees) can learn and do their best work.

     

     

    PAUSE AND PONDER: You’re a preceptor for your state university. In April, the experiential education office notifies that you have one student per month from June through April. Shortly after, a staff member from the experiential education office calls and tells you that the student scheduled for August needs accommodation. What should you expect going forward, and what is the best time to plan?

     

    Providing Reasonable Accommodation

    Institutions of higher learning usually have entire departments that develop policies, document the student’s type and degree of disability, and develop student-specific accommodation plans. When students who have disabilities go on clinical rotations, rotation sites may have no processes or policies to provide the same accommodation. Preceptors may not know how to cater to their needs. Often, practice sites need only to make minor adjustments to their environments, policies, and procedures. Once the organization makes the changes, the policies will be ready for future students! A PRO TIP is that an astute student who has disabilities may be willing to help edit and adjust policies; this insight can be valuable. However, the student may not want to help as this can be an added burden that other students don’t have.

     

    Five basic principles help schools ensure that clinical rotation sites provide reasonable accommodation for students on clinical rotations1,11,12:

     

    • Before going on rotation, it is critical for the school to document the student’s disability with a reliable diagnosis. The school’s department for students with disabilities usually does this.
    • All parties will need to work together to identify elements of the student’s disability that would cloud the preceptor’s ability to assess the student’s competence. Any accommodation should mitigate those elements.
    • Preceptors should work with the school to develop accommodation tailored to the specific rotation site and tasks to be accomplished at that site.
    • Three hundred sixty-degree communication is essential. Preceptors, students, school and rotation site administration, and disability service staff must collaborate and communicate.
    • Throughout the whole process, all parties must protect the student’s privacy.

     

    Students with disabilities are subject to a great deal of stigma not only from the outside world but also from preceptors. Ideally, schools should match these students with rotation sites and preceptors with prior experience accommodating students with disabilities.13 However, this may not always be possible. In ideal situations, preceptors are sympathetic and the relationship between the student and preceptor is open, non-judgmental, friendly, and relaxed. These characteristics set the stage for students to disclose their learning needs without fear of discrimination.14

     

    The school, however, must identify sites and preceptors based on the student’s accommodation needs without disclosing student-specific accommodation descriptions. Open and honest communication between students, the experiential education team, and representative(s) of the school’s disabilities office before they develop the rotation schedule can prevent problems later.13 Once the school confirms the student’s sites, it can share very basic student-specific details with the preceptor but only the student can share specific health information.1 In other words, the school can communicate the accommodation the student needs, but not the underlying diagnosis; that is private and only the student may disclose it.

     

    A challenge for students with physical disabilities is needing accommodation through multiple sites, which requires significant coordination and planning. A solution is providing multiple rotations at a single site where accommodation is available. When this solution is available, students can acclimate once.13 This can provide the best possible experience for the student, providing a level of comfort in the environment; conversely, this solution may force disabled students to stay at one site while their peers rotate from site to site and experience different healthcare teams. In institutions without pre-existing policies, schools would benefit by working with preceptors and the sites to develop guidelines for accommodating students. For students with physical disabilities, guidelines should address different types of mobility devices, physical dimensions of hospital facilities, safety requirements of the pharmacies, and access to particular areas.13 The preceptor should do this before the student begins working at the site. It would be unfortunate if a student arrived at a site only to find it was inaccessible.

     

    Step-by-Step to Accommodation

    Using a stepwise approach on site helps preceptors ensure that they provide reasonable accommodation to students.

     

    1. Raising awareness among the clinical team regarding disabilities, accommodation, and inclusive learning environments is a prudent first step. The team is able to do this by reviewing the literature, laws, and regulations. The Americans with Disabilities Act (ADA) Titles I, II, and III and the Rehabilitation Act (see Table 2) are the constellation of laws that prohibit discrimination and govern accommodation in pharmacy experiential education.15 Individual states may also have additional laws that protect disabled students.

     

    Table 2. Federal Laws and Regulations that Protect Students with Disabilties15

    Law/regulation Description
    Americans with Disabilities Act (ADA)
    Title 1: Employment ·       Prohibits discrimination in recruitment, hiring, promotions, training, pay, social activities, and other privileges of employment.

    ·       Restricts questions that can be asked about an applicant’s disability before a job offer is made

    ·       Requires that employers make reasonable accommodation for known physical or mental limitations of otherwise qualified individuals with disabilities, unless it results in undue hardship.

     

    Title II: Public sector ·       Requires state and local governments to give people with disabilities an equal opportunity to benefit from their programs, services, and activities

    ·       Requires reasonable modifications to policies, practices, and procedures where necessary to avoid discrimination, unless doing so would fundamentally alter the nature of their service

    ·       Does not require actions that would result in undue financial and administrative burdens

    ·       Indicates governmental agencies must communicate effectively

    Title III: Private sector ·       Explains public accommodation in businesses and nonprofits must not discriminate, exclude, segregate, or provide unequal treatment

    ·       Requires businesses and nonprofits to make  reasonable modifications to polices, practices and procedures and communicate effectively with people with hearing, vision, or speech disabilities

    ·       Requires employers to remove barriers and meet other access requirements.

    Rehabilitation Act of 1973
    Section 504 Prohibits programs or activities that receive federal funding from discriminating against disabled people.

     

    One area that all employers and employees need to understand is that accommodation can include variations on the workspace or equipment needed to complete various tasks, how work is assigned and communicated, the specific tasks, and the time and place that the work is done.16

     

    1. Establishing essential learning activities and outcomes for students helps all students, not just those with learning or physical disabilities. This means specifying essential functions, minimum competencies, expectations, and procedures that all students must be able to perform by the end of the rotation.15 Preceptors should note that accommodating a student’s needs does not mean lowering expectations.1 A PRO TIP here is that sometimes a student can meet the expectation with only small changes in the preceptor’s style. For students who have information processing issues, asking questions and then pausing for five seconds to allow the student to answer is better than rapid fire questions.1 (This is actually an approach that all preceptors and teachers need to use more in all situations. Pausing benefits everyone, including people who are not native English speakers.)

     

    1. The rotation site should make reasonable accommodation based on a reliable diagnosis that the student has documented via the school’s office of student disabilities. The pharmacy school’s office will also provide documentation of the requested accommodation to preceptors; students who have disabilities should not make the requests to preceptors on their own; they may, however, provide the accommodation letter and any information they want to share with the preceptor and copy the school’s director of experiential education if that is the school’s policy. One area that can be difficult for preceptors is the student’s healthcare appointments.1 A PRO TIP is to ask the student at the beginning of the rotation if you need to be aware of any scheduled appointments. Preceptors should also be very clear that the student must notify them of unanticipated appointments as soon as possible (or even before they call to schedule the appointment). If students miss time at rotations, they are responsible for making up the time.

     

    Documenting and discussing reasonable accommodation with the individual student who has a disability may be an uncomfortable or unfamiliar task for preceptors but will avoid problems later. Preceptors should meet with students to discuss exactly what they need in relation to their experiential outcomes (using the aforementioned list of specifying essential functions, minimum competencies, expectations, and procedures), asking questions such as1,15

    • What limitations do you anticipate experiencing on the rotation?
    • What tasks will you find problematic?
    • What have you done in the past to reduce or eliminate these limitations?
    • Do you anticipate needing us to make any modifications while you are here?
    • What will you do if you encounter an unanticipated obstacle?

     

    Here’s another PRO TIP: Knowing a few ways to accommodate disabilities will help preceptors help the student. For example, a student who has severe anxiety will find many rotations difficult and threatening. A preceptor can suggest that the student observe or “preview” activities before requiring interaction, especially if the site is fast-paced or chaotic. Allowing the student to arrive early may also help. Students who are challenged organizationally may benefit from one (not multiple) outline of what to expect every day.1

     

    1. The student should self-assess and document how the disability affects each general competency and how accommodation could mitigate each concern.1 Figure 1 describes the process of preceptors choosing accommodation.

     

     

     

    The preceptor and student should develop an accommodation plan together and document it in writing. An ideal plan would list the intervention or accommodation and how it supports the student, those involved in creating the accommodation, and the parties responsible for any financial costs (discussed below). 11 For example, in a pharmacy setting where a great deal of business is conducted over the phone using headphones, a student who has difficulty hearing may need a phone amplifier. If the student wears hearing aids, headphones may interfere with her ability to hear. The plan should also include specific days/times for periodic check-ins so the student and preceptor can assess whether the intervention/accommodation meets the students’ needs and is still reasonable for the site.11

     

    A PRO TIP for preceptors is to stay abreast of technology changes.16 If students have difficulty reading or writing—these are students with dyslexia or dysgraphia—many programs now have read-aloud or voice-to-text programs that are remarkably accurate. Some calculators will talk. Encourage students to use them. Asking students to listen to their work using a read-aloud program will also help them catch errors.

     

    PAUSE AND PONDER: You meet with your new APPE student and learn that he has serious visual impairment. He indicates he needs to use assistive devices (supplemental lighting, a magnifier). How would you initiate a discussion about who will secure these devices?

     

    The last step, which overlaps with the previous steps to some extent, is providing reasonable accommodation. Readers may read the term “reasonable accommodation” and wonder what is considered reasonable. Accommodation should not pose an undue financial or administrative hardship to the practice site.15 The law would not consider an accommodation reasonable if it decreased quality or posed safety issues to patients or imposed undue financial or administrative burden on the institution. It would also be unreasonable to change curricular elements or alter course objectives substantially. Preceptors might reach out to the school’s experiential education office who can contact the university’s legal department to determine whether a specific accommodation is reasonable. Or, preceptors can contact their own legal representatives. Preceptors and students need to communicate openly and honestly to determine reasonable accommodation together. Table 3 describes some examples of reasonable accommodation.

     

    Table 3. Examples of Reasonable Accommodation in Clinical Experiential Learning8,15-17

     

    Student Limitation Accommodation
    Anxiety ·       Embrace the learning experience and don’t be too hard on students when they make an error. Provide feedback and guidance for them to improve.

    ·       Plan the days and weeks, setting achievable goals, and prioritizing tasks.

    ·       Offer counseling services and other resources to support the student.

    Concentration difficulties ·       Use organization techniques that help students manage time and stay on track.

    ·       Ask students if using a highlighter to emphasize assignments that are priorities will help.

    ·       Step away from busy workplaces to provide directions in a quieter location.

    ·       Develop or have the student develop checklists for common tasks.

    Distractibility ·       Provide or allow students to use their own noise-canceling headphones or give them a private room to work.

    ·       Provide a quiet space away from noise and busy office traffic and a “Do Not Disturb” sign so students can work without interruption.

    ·       Avoid allowing or encouraging multitasking. Have students complete one thing at a time.

    Dyslexia ·       Encourage use of appropriate read-aloud and voice-to-text software.

    ·       Explain and provide a list of common or site-specific acronyms and other jargon.

    Neurodiversity ·       Sound sensitivity: offer a quiet break space, communicate expected loud noises (like fire drills), offer noise-canceling headphones.

    ·       Tactile: allow modifications to the usual work uniform

    ·       Movement: allow the use of fidget toys, allow extra movement breaks, offer flexible seating

    ·       Use a clear communication style:

    o   Avoid sarcasm, euphemisms, and implied messages.

    o   Provide concise verbal and written instructions for tasks, and break tasks down into small steps.

    ·       Inform people about workplace etiquette, and don’t assume someone is deliberately breaking the rules or being rude.

    ·       Try to give advance notice if plans are changing and provide a reason for the change

    ·       Don’t make assumptions – ask a person’s individual preferences, needs, and goals.

    ·       Be kind, be patient

    Poor organization ·       Set aside 15 minutes at the end of the day to plan the next day’s work.

    ·       Have students and all employees return important shared items to the same place each time they use them.

    ·       Consider a color-coding system for assignments or shelving.

    ·       Keep things visible on shelves, bulletin boards, or other places; avoid storage in drawers or closets.

    ·       Attach important objects physically to the place they belong.

    Processing disorders ·       Provide both written and oral instructions.

    ·       Follow-up important conversations with a brief e-mail

    ·       Ask the student to make notes and provide them to you for review.

    ·       Use the teach-back method; ask the student to repeat the information back so you can be sure you covered everything (and they heard the key messages)

     

    Emphasis on Planning Ahead

     

    Before rotations start, students with disabilities and preceptors should complete a practice walk-through at the rotation site to identify, modify, and make necessary adjustments.13 The experiential team must also understand the student’s career aspirations. Frank discussion will help all involved with rotation planning. The experiential team and the preceptor can address the students’ and preceptors’ concerns, needs, and goals in advance. Also, the person coordinating this process should identify and discuss costs and financial resources for the accommodation plan with all parties involved and determine who is responsible for the costs. This creates clear expectations. 13

     

    If during the check-in or at any time a situation changes, the plan needs revision to find a more acceptable or effective reasonable accommodation or an urgent concern arises, the student or the preceptor should contact the school immediately.13

     

    CONCLUSION

    Preparing and executing accommodation can be challenging. Preceptors who develop skills in this area help student pharmacists develop communication, collaboration, and planning skills they will use and improve all during their careers. Preceptors also assess the actual barriers associated with the student’s disability in a controlled environment and help students learn how to mitigate the challenges associated with their disabilities in future employment. A PRO TIP is to keep in mind that many employees have disabilities or have slightly different learning styles. Learning how to accommodate them from students and schools of pharmacy will benefit your entire work force. It may even help you!

     

     

     

     

    Pharmacist Post Test (for viewing only)

    1. A student has been diagnosed with attention deficit hyperactivity disorder (ADHD), a type of learning disorder. Which of the following BEST describes ADHD?
    A. A disorder characterized by writing disabilities that appear as distorted or incorrect writing
    B. A disorder that affects how people interact with others, communicate, learn, and behave
    C. A disorder that causes ongoing patterns of inattention and/or hyperactivity that interferes with functioning and/or development

    2. You observe that a student has difficulties counting, putting documents in numerical order, and calculating doses when the order specifies a mg/kg dosing. What type of disability is this MOST LIKELY to be?
    A. Dyslexia
    B. Dyscalculia
    C. Dysgraphia

    3. Once the school confirms a student’s site, what information can the school share with the preceptor?
    A. The required accommodation
    B. The student’s diagnosis
    C. The student’s health information

    4. How can the school of pharmacy help students with disabilities to be comfortable and meet their needs at various clinical sites?
    A. Informing the site that the student will be doing all their clinical rotations at that site
    B. Providing policies and student-specific accommodation plans that can be adjusted
    C. Only using preceptors who have experience accommodating students with disabilities

    5. Mary, a preceptor, is preparing for Elwin to start a rotation at her site. Elwin told the preceptor that he struggles with organization. They are identifying accommodation and exploring if they need to make any changes to the site. Which of the following is the most appropriate accommodation to keep the site organized for the student?
    A. Color-code the shelving system in the pharmacy
    B. Provide both written and oral instructions
    C. Provide directions away from the workplace

    6. A pharmacy student, Sarah, has attention deficit hyperactivity disorder (ADHD) and will be going on her clinical rotation. She has been in communication with the school and the preceptor about accommodation, indicating her key limitation is distractibility. Which of the following is the is the BEST accommodation the preceptor can provide?
    A. Encourage use of appropriate read aloud and voice to text software
    B. Plan the days and weeks, setting achievable goals, and prioritizing tasks.
    C. Provide a quiet space away and a “Do Not Disturb” sign

    7. Which of the following factors would a preceptor consider when providing a reasonable accommodation?
    A. The accommodation’s feasibility and financial cost
    B. The student’s academic grade point average
    C. The student’s specific diagnosis

    8. Which answer correctly lists the steps when choosing an accommodation for a student?
    A. Lower your expectations, assess whether the accommodation is meeting the student’s needs, analyze the required tasks
    B. Maintain your expectations, analyze the required tasks, periodically assess whether the accommodation is meeting the student’s needs
    C. Meet with the student, ask about the specific diagnosis of neurodiversity, develop a plan you think is suitable for the student

    References

    Full List of References

    REFERENCES
    1. Vos S, Kooyman C, Feudo D, et al. When Experiential Education Intersects with Learning Disabilities. Am J Pharm Educ. 2019;83(8):7468.
    2. Anxiety Disorders. National Institutes of Mental Health. Accessed August 9, 2023. https://www.nimh.nih.gov/health/topics/anxiety-disorders
    3. Autism Spectrum Disorder. National Institutes of Mental Health. Accessed August 14, 2023. https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd
    4. Attention-Deficit/Hyperactivity Disorder. National Institute of Mental Health. Accessed August 5, 2023. https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd
    5. Dysgraphia. National Institutes of Neurological Disorders and Stroke. Accessed August 5, 2023. https://www.ninds.nih.gov/health-information/disorders/dysgraphia
    6. Dyscalculia. Dycalculia.org. Accessed August 5, 2023. https://www.dyscalculia.org/
    7. Dyslexia. National Institutes of Neurological Disorders and Stroke. Accessed August 5, 2023. https://www.ninds.nih.gov/health-information/disorders/dyslexia
    8. Baumer N. What is Neurodiversity? Accessed August 14, 2023. https://www.health.harvard.edu/blog/what-is-neurodiversity-202111232645
    9. Neurodivergent. The Cleveland Clinic. Accessed August 15, 2023. https://my.clevelandclinic.org/health/symptoms/23154-neurodivergent
    10. Austin RD, Pisano GP. Neurodiversity as a Competitive Advantage. Harvard Business Review. May-June 2017. Accessed August 15, 2023. https://hbr.org/2017/05/neurodiversity-as-a-competitive-advantage
    11. Elliott HW, Arnold EM, Brenes GA, et al. Attention deficit hyperactivity disorder accommodations for psychiatry residents. Acad Psychiatry. 2007;31(4):290-296.
    12. Shrewsbury D. Dyslexia in general practice education considerations for recognition and support. Educ Prim Care. 2016;27(4):267-270.
    13. Kieser M, Feudo D, Legg J, et al. Accommodating Pharmacy Students with Physical Disabilities During the Experiential Learning Curricula. Amer J Pharm Ed. Published online April 2, 2021:8426.
    14. L’Ecuyer KM. Clinical education of nursing students with learning difficulties: An integrative review (part 1). Nurse Educ Pract. 2019;34:173-184.
    15. Vos SS, Sandler LA, Chavez R. Help! Accommodating learners with disabilities during practice‐based activities. 2021;4(6):730-737.
    16. Job Accommodation Ideas for People with Learning Disabilities. Learning Disabilities Association of American. Accessed August 5, 2023. https://ldaamerica.org/info/job-accommodation-ideas-for-people-with-learning-disabilities/
    17. Horesh A. Conquer Anxiety in Clinical Rotations: A Guide for Medical Students. Accessed August 9, 2023. https://futuredoctor.ai/anxiety-in-clinical-rotations/

    Patient Safety: Workplace Bullying

    Learning Objectives

     

    After completing this application-based continuing education activity, pharmacists and pharmacy technicians will be able

    1. Define workplace bullying in the healthcare setting
    1. Explain the impact of workplace bullying on individuals, organizations, and patient care
    1. Differentiate workplace bullying from harassment and workplace dysfunction
    1. Describe the necessary steps to address and counteract workplace bullying

      Individuals talking to each other behind another individual's back

       

      Release Date: November 20, 2023

      Expiration Date: November 20, 2026

      Course Fee

      Pharmacists: $7

      FREE FOR UConn Preceptors

      Pharmacy Technicians: $4

      There is no funding for this CE.

      ACPE UANs

      Pharmacist: 0009-0000-23-058-H05-P

      Pharmacy Technician:  0009-0000-23-058-H05-T

      Session Codes

      Pharmacist:  23YC58-ABC28

      Pharmacy Technician: 23YC58-BCA49

      Accreditation Hours

      2.0 hours of CE

      Accreditation Statements

      The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-058-H05-P/T will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

       

      Disclosure of Discussions of Off-label and Investigational Drug Use

      The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

      Faculty

      Giovanni Fretes, PharmD Candidate 2025
      UConn School of Pharmacy
      Storrs, CT

                                         

      Jeannette Y. Wick, RPh, MBA, FASCP
      Director OPPD, UConn School of Pharmacy
      Storrs, CT

      Faculty Disclosure

      In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

      Giovanni Fretes and Jeannette Wick have no relationships with ineligible companies.

       

      ABSTRACT

      Several healthcare professional organizations have identified workplace bullying as a problem. Workplace bullying can decrease morale, but additionally, it can also compromise patient safety. Some studies have found that physicians tend to be identified most often as workplace bullies, but additional studies indicate that bullying in pharmacy is present and under reported. The most likely type of workplace bullying in pharmacy is verbal bullying, which includes mocking, name-calling, teasing, or intimidating a target. In some instances, physical or nonverbal bullying may occur. Unaddressed bullying can lead to diminished morale, strained employee relations, loss of respect for management, and increased absenteeism or tarnished reputation of the workplace. Establishing a reasonable definition of bullying, differentiating it from harassment, and training employees in bystander intervention can help improve the workplace and decrease the likelihood of damage from bullying.

      CONTENT

      Content

      INTRODUCTION

      Bullying is a popular topic these days. Hardly a day goes by without a story in the media about school bullies, social media bullies, celebrity bullies, political bullies, and even chef bullies. In addition, lawsuits have found people and organizations liable for suicides when they bullied the victim (called the target) or failed to address bullying.1 And many times, serial killers or individuals who conduct mass shootings are later identified as having been bullied. Clearly, the United States (U.S.) has a bullying problem. Does healthcare and, on a smaller scale, pharmacy, have a bullying problem?

      This continuing education activity discusses bullying in the workplace because healthcare and on a smaller scale, pharmacy, do have bullying problems and students sometimes experience bullying as they are introduced to the profession on rotations or in residencies. Unlike harassment, bullying isn’t illegal in the U.S., but it has serious repercussions to individuals and organizations. Recognizing and addressing workplace bullying is essential to foster healthy and supportive work environments in healthcare settings, ultimately benefiting both staff and patients. Although the authors drafted this activity to address the bullying that students sometimes experience in experiential rotations, during extensive peer review, reviewers indicated this topic is of interest to all pharmacy personnel, not just preceptors.

      Mock, Taunt, Intimidate

      Workplace bullying is a widespread issue that affects various industries, including pharmacies and other healthcare settings. Most of the data in healthcare comes from studies of physicians’ interactions with other disciplines, and the American Medical Association (AMA) recognizes the problem. AMA defines workplace bullying as “repeated, emotionally or physically abusive, disrespectful, disruptive, inappropriate, insulting, intimidating or threatening behavior targeted at a specific individual.”2 Bullying’s purpose is to control, embarrass, undermine, threaten, or cause harm toward an individual. Various factors at the individual, organizational, and health system level can contribute to creation of an unprofessional workplace climate or culture.2

      Workplace bullying is important to address because it can impact patient care, resulting in preventable mistakes. In a 2021 survey, roughly 35% of healthcare providers had concerns about medication orders but chose to assume correctness to avoid engaging with specific providers. One pharmacist was shamed by a colleague after seeking an independent double check for a vancomycin order with incorrect timing. Multiple errors like this occur annually because of the culture of shaming.3 Some data about how bullying affects the medication prescribing and administration process demonstrates this subject’s importance.

      Every few years, the Institute for Safe Medication Practices (ISMP) surveys healthcare professionals about disrespectful behaviors and intimidation in the workplace.4,5 ISMP conducted its most recent survey in September 2021.3 Among the 1,047 respondents, 26% worked in the pharmacy, suggesting that bullying is a problem in pharmacies since a disproportionate number of pharmacy employees responded compared to more populous health care providers like physicians and nurses. A full 37% of respondents were pharmacists and 6% were pharmacy technicians.3

      Disrespectful behaviors were clearly linked to medication concerns3:

      • 40% of respondents said past disrespectful behaviors had altered the way they handled order clarifications or questions about medication orders.
      • Roughly half of respondents said that they had relied on colleagues to interpret or validate an order rather than contact the prescriber in the past year; the reason was to avoid contact with the disrespectful prescriber.
      • 11% of respondents indicated they avoided talking to a prescriber to interpret or validate an order’s safety more than ten times in the previous year.
      • 7% said that they had been pressured to accept an order, dispense a product, or administer a drug despite safety
      • Slightly more than one-third reported having concerns about a medication order but assumed it was correct rather than interact with a specific prescriber; roughly the same number of respondents said that a prescriber’s stellar clinical reputation often made them reluctant to question or clarify orders even if they had concerns.

      TYPES OF WORKPLACE BULLYING IN HEALTHCARE

      In the limited research that addresses workplace bullying in pharmacies and other health care settings, researchers frequently bemoan the fact that, the AMA’s definition aside, we have no consensus definition of bullying. It would be ideal if we could provide a concise definition of bullying or a checklist that would help managers, supervisors, coworkers, and preceptors ascertain when bullying is occurring. In fact, bullying occurs in many different forms.

       

      Verbal Bullying

      Verbal bullying encompasses various forms of harmful language and communication. Examples of verbal bullying include mocking, name-calling, teasing, or intimidating someone to belittle or demean them. Insults and derogatory comments can degrade a person's self-esteem, creating a hostile working environment. Fans of the television show NCIS may recall that the section supervisor, Leroy Jethro Gibbs, always dubbed the newest hire “Probie,” which appears to have been short for probationary employee. People watching this show who are familiar with human resources regulations often shuddered when Gibbs did this, as it could be perceived as a form of bullying. Especially in government organization where the rules are very clear, such behavior would be dangerous. In pharmacies, calling people by unwelcome nicknames could be perceived as bullying.

      Public humiliation is another form of verbal bullying that aims to embarrass the person who is being bullied in front of others. Trainees commonly report persistent attempts from their preceptors or trainers to humiliate them in front of colleagues. According to a study, “The abuse of students is ingrained in medical education and has shown little amelioration despite numerous publications and righteous declarations by the academic community over the past decade.”6

      PAUSE AND PONDER: A preceptor asked a student a question in front of the rounding team. The student, who was unable to answer, blushed and stuttered. The preceptor said, “What school of pharmacy did you go to again? I need to call them and ask them what they're teaching because you clearly should have known the answer to this question.” The student reddened even more, and the preceptor said, “Oh! So, you're a blusher are you?” Was this teasing, was this misplaced humor, or was it bullying?

      The term bullying does not appear in the Accreditation Council for Pharmacy Education (ACPE) standards. Researchers reviewed the professional literature and American Association of Colleges of Pharmacy (AACP) survey data collected from student evaluations of preceptors (N = 2087); students provided low evaluations for preceptors in at least one area in 119 evaluations.6 When the researchers scanned the comments for words or phrases closely associated with bullying, they found respondents reported 34 instances indicating bullying. Figure 1 shows the distribution of comments and includes examples of troublesome comments.6

      Comments related to workplace bullying involve offensive behavior, humiliation, intimidation, exclusion or denial to opportunities, and excessive criticisms.

      Figure 1. Comments Related to Bullying from Pharmacy Survey Data6

      This data came from one college of pharmacy, but the researchers compared their data to that of a national study.6 It was similar. Although the rates of bullying seemed low, the researchers believed that bullying is seriously underreported in pharmacy. Some reasons may include the small number of pharmacists compared to physicians and nurses, the use of assessment tools that are not intended to identify bullying (asking the wrong questions), and students’ reluctance to complain because it may be perceived as unprofessional. Students may also be afraid that reporting bullying may affect their grades. The researchers recommend ACPE place more emphasis on bullying and develop of a consensus definition.6

      Intimidation and threats instill fear and anxiety, leaving the target feeling vulnerable and powerless. Intimidating behaviors in the healthcare workplace are far from isolated incidents. A survey conducted with more than 2,000 healthcare providers revealed that subtle, yet effective forms of intimidation were more common than explicit forms.4 Respondents reported encountering behaviors such as condescending language, impatience with questions, and reluctance to answer or return calls. Physicians and prescribers were identified as the primary perpetrators of intimidation, exhibiting behaviors such as condescension, reluctance to answer questions, and verbal abuse more frequently than other healthcare providers.4

      Additionally, destructive criticism is another unjustified way in which someone can wear down the target emotionally and psychologically. Constructive criticism and destructive criticism differ based on their delivery and the ways in which they impact individuals and their work.7 Constructive criticism uplifts people by providing suggestions and potential solutions while highlighting both positive aspects of someone's work and identifying areas for improvement. Destructive criticism undermines confidence, belittles efforts, and focuses on ridicule, leading to decreased morale and performance. It creates a hostile atmosphere and restrains productivity.7

      Constructive feedback begins and ends with positive comments and present information in a supportive way, as this “compliment sandwich” exemplifies:

      “Jacob, I appreciate your dedication and commitment to our pharmacy team. However, I've observed a higher number of medication errors when you’re dispensing prescriptions, which is unusual based on your work history. I know how dedicated you are to the team, so if you're facing any challenges that may be impacting your performance, please don't hesitate to reach out to me or any team member. We are here to support you and provide the best patient care possible."

      Destructive feedback is replete with negativity:

      "Jacob, your work recently in the pharmacy has been extremely disappointing. Why are you making so many mistakes? It's causing a lot of problems for the team, and frankly, I don't have the time or patience to fix everything for you. You really need to step up and improve your performance because it's negatively impacting our overall productivity."

      It’s not always possible to use a compliment sandwich when addressing issues in the pharmacy. It is always possible to be kind.

      Verbal bullying is usually easy to spot if the bully conducts the browbeating in public. In one pharmacy, a seasoned technician seemed to have a bias against students who were accruing IPPE or APPE hours. She would frequently tell students loudly, “If you can’t work any faster, it would be lovely if you would just get out of the way.” Her colleagues would turn a blind eye, but the section supervisor eventually took action and referred her to employee assistance. However, many bullies are adept at mounting their campaigns of terror when no one is looking. (Remember that the most likely place for bullying is schools is in the most difficult place to supervise: the playground.8)

       

      Non-Verbal Bullying

      Non-verbal bullying in healthcare manifests through actions that undermine and harm the target without using explicit words.9 Bullies use exclusion and social isolation to insulate targets from their colleagues, fostering a sense of loneliness and alienation. Undermining and sabotage minimize the target's work and efforts, eliminating a culture of safety.9

       

      PAUSE AND PONDER: A preceptor assigned one pharmacy student to sort and file a large backload of paperwork. She also assigned a technician to explain what needed to be done and how. The technician was frustrated by the student’s questions, but two hours later, the student finished sorting. He asked the technician to check his work before he filed it. The technician riffled through the pile, said, “This is correct,” and then said, “Oops!” and intentionally dropped the entire pile on the floor. Was that bullying?

       

      Ignoring and dismissing ideas invalidates targets’ contributions and suggestions which diminishes their confidence and ability to perform well.10 Additionally, intentionally withholding information deprives targets of essential knowledge needed to perform their assigned tasks effectively.9 Individuals who use “the silent treatment” (refusing to engage in discussion and making no eye contact) are also bullies. Researchers have found that people in positions of power who use the silent treatment also frequently assign unreasonable or unnecessary tasks.11

       

      Finally, bullies may also use noise in subtle ways to intimidate or disturb targets. In one situation, students were assigned to work in an office across from a pharmacist who did not like to precept but did so because he was assigned the task. He kept his door closed most of the time but would slam it hard when coming and going. He’d watch to see if the students reacted.

       

      Physical Bullying

      While less common in healthcare, physical bullying involves direct aggression towards the target.12 This can include pushing or shoving, which poses a threat to the target’s safety and well-being. Damaging personal belongings is another form of physical bullying, violating the target's personal space and property. Also forcing physical exertion on the target, such as excessive workloads or tasks beyond their capacity, can cause physical harm and exhaustion.12

      Healthcare workers are already at risk for physical violence, and four times more likely to experience violence requiring an absence from work than people employed in other industries.12 According to 2013 Bureau of Labor Statistics (BLS) data, 80% of serious violent incidents were a result of interactions with patients. The remaining incidents were attributed to visitors, coworkers, or individuals outside of the healthcare facility with 3% of the incidents from coworkers.12

      BLS found one fact of particular note: Employees were significantly less likely to report bullying and other forms of verbal abuse. They cited three contributing reasons: (1) lack of a reporting policy, (2) lack of faith in the reporting system, and (3) fear of retaliation, which is discussed below.12 Although healthcare workers appear to be more likely to be bullied by patients than coworkers, concerns about reporting flaws and retaliation may skew the data.12

      SIGNS AND EFFECTS OF BULLYING

      Absent a clear definition, healthcare managers and workers may struggle to identify bullying or differentiate it from harassment. Signs may be obvious—as in the example of the technician who tells students to get out of the way—or subtle.

      Signs of Workplace Bullying

      Recognizing the signs of workplace bullying is crucial for early intervention. Behavioral changes in targets, such as increased irritability, anxiety, or withdrawal, may indicate they are experiencing bullying.13

      Effect on Workers and Patients

      Workplace bullying has detrimental effects on both healthcare professionals and the quality of patient care.9 The emotional and psychological impact on targets can lead to heightened levels of stress, anxiety, and depression. This affects their well-being and their ability to provide optimal care to patients. Bullying can contribute to higher rates of medication errors, increased infections, and other negative patient outcomes. This is partly due to staff members' fear of speaking up against physicians or prescribers who are bullies.14 Physician Alan Rosenstein, an expert in disruptive behavior, highlights the existence of a "hidden code of silence" that keeps coworkers or colleagues from reporting or appropriately addressing many incidents.14

      Rosenstein has collected anecdotes from his work. He doesn’t report any from situations involving pharmacists or technicians, some examples of disparaging remarks/actions may feel somewhat familiar to pharmacy workers who have had unfortunate interactions with prescribers14:

      • During a tense operation, a surgeon insulted a male nurse, who had a special needs son, by saying, "You're a [r-word] just like your boy." The nurse filed a written complaint because of the insulting, disrespectful remark.
      • At Vanderbilt University Medical Center in Nashville, a surgeon proceeded with an operation without washing his hands. Instead of openly addressing the issue, a nurse discreetly offered the surgeon gloves, but he simply discarded them into the trash.
      • An OB/GYN patient was experiencing excruciating pain while the doctor sutured without providing sufficient anesthetic. When questioned by a medical student, the doctor made a joke saying that the patient could be given memory-erasing ketamine to forget about the experience.

      It is essential for pharmacy owners to recognize the consequences of workplace bullying on their businesses. Table 1 lists negative consequences of unaddressed bullying and provides examples. Preceptors, supervisors, mentors, and organizations must address factors that promote bullying (like power imbalances, addressed below) and provide employees with support to maintain healthy, successful pharmacy settings.

      Table 1. Negative Consequent of Unaddressed Bullying15

      Consequences Examples
      Diminished morale A seasoned pharmacy technician (whose pronouns = they/them), who has been working diligently for years, consistently faces belittling comments and criticism from the pharmacist. As a result, their overall enthusiasm for their work decreases, affecting their productivity and leading to a sense of resignation or disengagement. The rest of the staff will also feel disengaged and resigned.
      Strained employee relations One pharmacist consistently questions another pharmacist’s decisions and recommendations in front of colleagues and patients leading to tension and hostility between them. This strained relationship might extend beyond work-related matters, making collaboration difficult and creating an uncomfortable atmosphere for other team members.
      Loss of respect for management Employees witness a manager ignoring complaints, failing to provide a safe and supportive environment. The affected employees lose respect for the management team as they perceive the lack of intervention as a sign of management’s incompetence, leading to a diminished view of their leadership abilities.
      Increased absenteeism/

      tarnished reputation

      Over time, employees are subjected to behaviors of bullying and begin to experience high levels of stress and anxiety due to the hostile environment. So, the employees start taking more sick days or even extended leaves of absence to cope with bullying’s emotional toll. The toxic work environment spreads through word of mouth among colleagues, potential hires, and even patients. The pharmacy’s reputation suffers as news of the toxic work environment and unaddressed bullying gets around.

      Ultimately, workplace bullying may reduce everyone’s job satisfaction and productivity resulting from the negative work environment created by workplace bullying.16 Extensive studies have confirmed the association between workplace bullying and perceptions of organizational settings, including job satisfaction and commitment. Job dissatisfaction, which leads to emotional distress, can be regarded as a factor that influences employees’ commitment to their work.16

       

      CAUSES AND RISK FACTORS

      To effectively address workplace bullying, preceptors—and all staff—need to understand the underlying causes and risk factors contributing to its occurrence in healthcare settings.

       

      Power Imbalances

      Power imbalances can contribute to disruptive behavior in healthcare settings, leading to a range of negative consequences. (Yes, this means the bully might be the boss!8) While some may associate disruptive behavior with overt bullying and intimidation, the broader definition preferred by experts includes any actions that undermines safety culture.14

      The issue of power imbalances in pharmacy is a growing concern, as evidenced by a 2015 report from the United Kingdom’s Advisory, Conciliation, and Arbitration Service (ACAS).15 Workplace bullying has been on the rise in the U.K., with a staggering 20,000 calls annually reporting bullying incidents to ACAS. Disturbingly, this problem extends to community pharmacies, where staff members face bullying from pharmacy owners, managers, supervisors, and colleagues.15 The level of labor stability also has a significant impact on vulnerability to bullying because lower-status employees often hold the most unstable and temporary jobs. An empirical study (a study that uses observation, measured phenomena, and participant’s experience rather than theory or belief) conducted among university employees in an academic center aimed to demonstrate that flexible working arrangements contribute to the prevalence of bullying.16 One reason for the increase in bullying within organizations is the restructuring processes and higher levels of outsourcing, which have widened the power gap between managers and employees.16

      High Stress Levels and Demanding Work Environment

      The demanding nature of healthcare work, coupled with high stress levels, can create an environment prone to workplace bullying.16 Healthcare professionals often face intense pressure, long working hours, and challenging situations that may increase tension and exacerbate conflicts. Stress can amplify negative behaviors and create a breeding ground for bullying. Bullying within a stressful environment can lead to burnout and cause talented, compassionate individuals to leave the healthcare profession.17,16

       

      Do pharmacy employees experience stress? In a recent survey, 61.2% of pharmacists reported experiencing significant burnout in their practices.17 This trend is prevalent among hospital pharmacists, with consistent rates across various practice settings and areas. The study reveals that those most affected by burnout were often unmarried, had no children, and worked extended hours, surpassing 40 hours per week. Pharmacists can be impacted by stress and burnout in all practice settings. Thus establishing support systems with family, friends, and coworkers is vital to enhancing morale and alleviating feelings of burnout.17

       

      High Expectations from Society

      Healthcare professionals are entrusted with caring for the health and well-being of individuals, and society places high expectations on them. The pressure to meet these expectations, combined with limited resources and time constraints, can contribute to stressful work environments that may foster workplace bullying.18 Most healthcare workers feel like they are held to higher standards than the general public. This feeling is rooted in centuries of traditions and most medical organizations emphasize respect in personal interactions.18

       

      Healthcare workers also believe that the general public’s expectations of them outside the healthcare setting are set too high.12 The demanding and high-stress nature of healthcare work can make it challenging for professionals to enjoy their personal lives. The constant feeling of being at work and the fear that their actions could be scrutinized even during off-hours creates additional stress and anxiety. This work-life imbalance can have a significant impact on well-being and overall quality of life.18

       

      Lack of Policies and Procedures to Address Bullying

      The absence of comprehensive policies and procedures specifically targeting workplace bullying in healthcare settings can perpetuate its occurrence.19 Without clear guidelines and protocols in place, both targets and bystanders may feel powerless and unsure of how to address and report bullying. Instances of bullying and verbal abuse are often under-reported for various reasons. As revealed by the 2022 National Pharmacy Workplace Survey by industry experts, the lack of robust policies and procedures to address bullying in the pharmacy profession is a pressing concern.19 The study highlights the absence of a formal mechanism for pharmacists and pharmacy personnel to discuss workplace issues with supervisors and management. This leads to an unwelcoming atmosphere, resulting in heightened stress and eventual burnout. Over 60% of respondents indicated that their employers did not actively seek their opinions, nor did employers respect or value employee input.19 Employers, insurers, lawmakers, and the public must come together to ensure ample resources, address patient safety concerns, and promote the well-being of pharmacy personnel.

       

      One topic also needs more attention: the bullying individual. The SIDEBAR provides information about people who tend to bully others.

       

      SIDEBAR: Some People are Simply Bullies20,8,21,22

       

      Bullies Unveiled: Bullies are individuals who employ intimidation and control tactics to further their own objectives. While they might appear cooperative when their goals align with the team’s or the employer’s, their methods are unfair and dishonest. In the workplace, bullies often target coworkers in lateral or lower responsibility positions, resorting to manipulation and terrorizing behaviors. They may even intimidate superiors, using tactics like threats of resignation during crises.

       

      The Hidden Shame: Some psychologists attribute bullying to ingrained shame, although others cite insecurities, disparate socioeconomic backgrounds, personality traits that make them outliers, and basic insecurities. Some theories indicate that targets of bullying are more likely to become bullies. Contrary to common belief, bullies don't necessarily suffer from low self-esteem. Instead, their behavior can stem from internalized shame. While some individuals who harbor shame may have low self-esteem, those who engage in bullying tend to have high self-esteem, and hubristic (overbearing or presumptuous) pride. Bullies may also be quite clever. Their attacks on others are defense mechanisms to alleviate their own feelings and ignore their real emotions.

       

      Shame's Impact on Coping: Early in life, people develop various responses to shame, which solidify into personality traits by adulthood. These coping mechanisms can be categorized by attacking others, self-attacking, avoidance, and withdrawal. For those who bully, the fear of shame, such as being perceived as inadequate at work, drives them to target others. Bullies exploit others' vulnerabilities—and especially others’ insecurities—and redirect their own shame onto their targets. The bully’s ultimate feeling is power.

       

      Narcissism and Withdrawal: Some bullies ultimately develop narcissistic traits, continually attacking others as a means to cope with deeply rooted shame. Conversely, targets are often sensitive individuals who respond to shame by self-blame. This response might maintain a connection with the bully and perpetuates a victim or target mentality. Withdrawal, another reaction to shame, involves concealing one's emotions and can lead to depression. Prolonged exposure to workplace bullying often triggers this response, proving just as harmful as self-attacking.

       

      Seeking Solutions: Bullying deflects a bully's shame and also provides a sense of power. However, many bullies remain unaware of their own inadequacies. The key to dealing with workplace bullies is solidarity among coworkers. Banding together against a bully offers support, as targets of bullying often face isolation and by confronting the bully's behavior collectively, coworkers can neutralize their power. Banding together does not mean ganging up on the bully. It means using the principles of bystander intervention (discussed below) and firmly calling out bullying when one sees it in a respectful but direct manner. Documenting repeated episodes of bullying is also critical.

       

      Readers should note, however, that when the bully’s target is someone that others tend to dislike or find little sympathy for, the team may not coalesce to support the target. Supervisors, managers, or observers who are leaders need to jump in and remind staff that bullying is unacceptable, and if the target leaves, who knows who will be next. Further, some research indicates that bullies may eventually become targets; backlash is not an ideal solution.

       

      A Path Forward: Ultimately, bullies can change their behavior by developing better coping mechanisms and learning to process their feelings constructively. Recognizing that bullies are driven by a response to shame or other factors, rather than consciously acknowledging it, is essential for devising effective strategies to address this issue. Supervisors and managers should refer employees with bullying tendencies to their employee assistance programs or similar programs.

       

      DIFFERENTIATING WORKPLACE BULLYING, HARASSMENT, AND DYSFUNCTION

      To address workplace bullying effectively, healthcare workers and managers must differentiate it from harassment and dysfunction within the healthcare setting.

       

      Key Differences in Behaviors and Intent

      While workplace bullying and harassment share similarities, such as the creation of a hostile work environment, they differ in terms of intent and behaviors. Again, bullying is often described as offensive, intimidating, malicious, or insulting behavior intended to undermine, humiliate, denigrate, or injure the recipient, and it may involve individuals or groups.23 It can take various forms, including spreading rumors, excluding someone, giving unachievable tasks, and more.

       

      Harassment, as defined by U.S. employment discrimination laws, involves unwelcome conduct based on various protected characteristics including race, color, religion, sex, national origin, age, disability, or genetic information. Title VII of the Civil Rights Act of 1964, the Age Discrimination in Employment Act of 1967 (ADEA), and the Americans with Disabilities Act of 1990 (ADA) all prohibit harassment as a form of employment discrimination.24 The difference between bullying and harassment is subtle. For example, calling a coworker or a student a skinny witch is bullying. Calling a coworker or a student a skinny Catholic witch introduces the element of religion. While neither is acceptable, the introduction of religion crosses the line to harassment. While bullying is not necessarily illegal, harassment based on protected characteristics is unlawful.

       

      PAUSE AND PONDER: Consider a technician who announces to all who are on duty that the new student smells terrible. Is that bullying or harassment? If he follows it up with, “It’s because people from his culture cook all that stinky food!” Is that bullying or harassment?

       

      Laws and Regulations against Workplace Harassment

      Various laws and regulations protect employees against workplace harassment. Title VII, ADEA, and ADA prohibit harassment on a federal level, while individual states also have laws that require employers to enact anti-harassment policies.24,25  Harassment is illegal and someone—meaning anyone who is harassed or observes harassment—should report it when it creates a work environment that a reasonable person would find intimidating, hostile, or abusive. It is crucial to prevent harassment, and employers should establish clear anti-harassment policies, provide training, and address complaints appropriately.

       

      Supervisors, co-workers, or non-employees may harass others, and the employer may be liable for harassment by supervisors resulting in disciplinary actions.24,25 For non-supervisory harassment, employers can be liable if they knew or should have known about the harassment and failed to take corrective action. The Equal Employment Opportunity Commission (EEOC) assesses each case of harassment individually by considering the nature and context of the conduct. Overall, addressing harassment requires proactive measures and a commitment to maintaining a respectful work environment. 24,25

       

      Protection of Whistleblowers

      Whistleblowers are protected under OSHA’s Whistleblower Protection Program, which enforces provisions from more than 20 whistleblower statutes safeguarding employees from retaliation for reporting violations.26 Retaliation is strictly prohibited under these laws and encompasses actions such as firing, demoting, denying benefits, intimidation, harassment, and other adverse actions. Retaliative actions may dissuade an employee from raising concerns about potential violations. Subtle actions like exclusion from important meetings or false accusations of poor performance can be considered retaliation. Temporary workers supplied by staffing agencies are also protected from retaliation. OSHA's program not only safeguards whistleblowers reporting violations, but also shows some similarities between retaliation and workplace bullying. Exclusion and intimidation are shared tactics in both retaliation and bullying, mainly differing in the employer's intent.26 Many experts in bullying indicate that given these parallels, employees who are targets of bullying should be protected in the same manner that whistleblowers are safeguarded. This approach would foster a work environment where all individuals can voice concerns and engage in their roles without fear of adverse consequences.

       

      PREVENTION AND INTERVENTION STRATEGIES

      Although the U.S. hadn’t yet addressed workplace bullying formally, Australia has.27 Its Fair Work Act 2009 (Cth), allows its Fair Work Commission to hear bullying claims and order any corrective action other than monetary compensation) to stop bullying from continuing. In 2019, the Fair Work Commission heard a claim from a pharmacist. The SIDEBAR summarized the case, which ended in a ruling in favor of the employer but raised many questions. It highlights the complexities of these kinds of cases and the fact that some people have little insight into their behaviors.

       

      SIDEBAR: Who’s Bullying Who?27

      A pharmacist alleged the pharmacy’s management was bullying him by scheduling him to work on Saturdays without adequate assistance. The employer had replaced a dispensing technician with an intern pharmacist who he considered incompetent. The pharmacist claimed it created unnecessary stress, doubling his work. He alleged that the pharmacy’s Saturday workload was similar to weekday workloads and required more staff.

       

      The employer demonstrated successfully that its Saturday workflow was significantly lower than weekdays. CCTV footage revealed that the pharmacist spent considerable time on Saturdays looking at his phone rather than working. The employer also indicated the pharmacist engaged in aggressive and intimidating conduct, even reducing the intern to tears on one occasion. His hostile behavior extended to other employees, leading two of them to seek counseling. The employer stated that the pharmacist's inability to work cooperatively with colleagues was the root of the problem, not the intern's competence.

      The deciding official ruled no one acted unreasonably towards the pharmacist. He acknowledged the pharmacist's unacceptable behavior that involved mistreating several other employees. Some readers are no doubt reading this and nodding their heads, having seen, been subject to, or accused of bullying rightly or wrongly. Others are thinking, “Why is this guy still employed?”

      To combat workplace bullying effectively in healthcare, a multi-faceted approach involving various strategies is necessary.

       

      Policy Development and Enforcement

      It is essential to develop policies to combat workplace bullying in all pharmacy settings. Drawing from the AMA's report, pharmacy management can adopt key steps to create an effective anti-bullying policy and cultivate a positive work environment.2 Everyone involved needs to realize that developing a policy takes time, and implementing it requires an endless, consistent effort on the part of managers, supervisors, and staff. People from every level of the organization should have input into the draft and the review process. Putting the issue on the department’s staff meeting agenda will ensure that it doesn’t fall through the cracks.8

       

      First, management must ensure that the administration is fully aware of the impact of unprofessional behavior. The team can create strategies proactively to address and prevent bullying by recognizing the problem. One strategy might be to identify when and where the bullying occurs. Changes to the workflow, the schedule, or the supervision can improve the situations.8

       

      Second, management can arrange to educate the entire pharmacy staff about the harmful consequences of unprofessional or hostile conduct. When employees perceive that their leaders are committed to addressing bullying, they are more likely to report incidents or even intervene when witnessing inappropriate behavior among colleagues. Two types of education can help28:

      • Federal law requires certain organizations to provide compliance training on harassment and discrimination. The U.S. Equal Employment Opportunity Commission also recommends (but does not require) workplace civility training. Workplace civility training promotes workplace respect and civility. Good training would include workplace norms, appropriate and inappropriate behaviors in the workplace, and possibly interpersonal skills, conflict resolution, and effective supervisory techniques.
      • Bystander intervention training, usually associated with sexual harassment in schools, is increasingly recognized as a critical element of efforts to decrease harassment and inappropriate behaviors. Its goal is to refine employees’ sensitivity to harassment or bullying and empower them act. This training would need to identify offensive behaviors, describe employment non-discrimination laws, and explain how bystanders should respond upon witnessing a harassment incident.

       

      These crucial management steps and well-structured anti-bullying policies can foster a respectful and supportive workplace, promoting the well-being of all employees and enhancing overall patient care.

       

      Promoting a Supportive and Respectful Workplace Culture

      Healthy working relationships are crucial to promoting a supportive and respectful workplace culture in the pharmacy. The most important characteristics that build good working relationships include29

      • mutual respect
      • open communication
      • empathy
      • building rapport with every member of the team.

      Table 2 defines these terms. Practicing mindfulness (awareness of one’s feelings and the impact they have on themselves and others) can further improve relationships by reducing stress and anxiety, increasing emotional intelligence, and improving communication. It is essential to address inappropriate behavior promptly to prevent escalation, with support and guidance available to deal with bullying or harassment.

       

      Table 2. Key Characteristics of Healthy Working Relationships29

      Characteristic Definition
      Mutual respect The foundation of a healthy workplace where all members of the pharmacy team are valued and their views are acknowledged.
      Open communication Free expression of ideas without fear of criticism, fostering trust and understanding
      Empathy Compassionate comprehension of others’ states when connecting with colleagues and patients so effective communication, negotiation, problem-solving, and assertiveness to enhance collaboration and conflict resolution is possible.
      Building rapport Fostering a positive dynamic with every team member to enhance workplace happiness

       

      PAUSE AND PONDER: Janine supervises three employees, Mary, Alice, and Siobhan. Mary and Alice are very close and tend to gossip. They dislike Siobhan, speak badly of her to others, and often fail to provide the information Siobhan needs to complete her work. They criticize her work cruelly in the weekly staff meeting. Siobhan’s name is pronounced shi-VON, but Mary and Alice consistently mispronounce it and misspell it. What should Janine do, and how can she support Siobhan?

       

      Encouraging Reporting and Providing Confidential Channels

      Managers, supervisors, and preceptors should encourage healthcare workers to report incidents of bullying without fear of retaliation.14 They should establish confidential reporting channels to protect the identities of those who come forward.14

       

      When addressing bullying within the pharmacy setting, it is essential to establish a comprehensive reporting system that includes confidential channels for employees to voice their concerns.14 Vanderbilt University uses a slowly escalating corrective approach, where trained professionals engage in open discussions with alleged offenders, fostering an environment of respect and mutual understanding. Second offenses are met with warnings, followed by formal letters outlining the issues and potential interventions such as mental and physical screening (in case a health condition is causing symptoms of anger, frustration, and lack of patience). Repeat offenders may face the consequence of losing staff privileges.14

       

      Apart from corrective measures, effective strategies can also focus on providing help and support to offenders, such as anger management classes, counseling, or assistance with medical or addiction issues.14 Creating a reporting system that ensures confidentiality empowers pharmacy staff to come forward with their concerns, enabling prompt intervention.

       

      CONCLUSION

      Workplace bullying in healthcare is a pressing issue that requires attention and action. It negatively impacts healthcare professionals’ well-being and compromises patient care. It is crucial to define and emphasize workplace bullying so we can shed light on the significance of addressing this problem. To reiterate

      • Understanding the types, signs, and effects of workplace bullying allows us to recognize its presence and take appropriate measures.
      • Identifying the causes and risk factors helps us understand the underlying factors contributing to its persistence in healthcare settings.
      • Differentiating workplace bullying from harassment and dysfunction clarifies the specific behaviors and intent involved, leading to more effective interventions.
      • Upholding laws and ethical obligations, along with whistleblower protection, ensures legal and ethical accountability.
      • Creating prevention and intervention strategies, such as developing policy and promoting a supportive culture, provide a framework for addressing workplace bullying.
      • Reporting incidences through mechanisms and confidential channels empower individuals to seek help and create a safer environment.

      In conclusion, by recognizing, preventing, and intervening in cases of workplace bullying, healthcare organizations can create a better work environment that supports their employees and promotes optimal patient outcomes.

      Pharmacist Post Test (for viewing only)

      Patient Safety: Workplace Bullying
      Post-test
      Learning objectives
      After completing this continuing education activity, pharmacists and pharmacy technicians will be able to
      1. Define workplace bullying in the healthcare setting
      2. Explain the impact of workplace bullying on individuals, organizations, and patient care
      3. Differentiate workplace bullying from harassment and workplace dysfunction
      4. Describe the necessary steps to address and counteract workplace bullying
      1. Which of the following statements correctly describes findings about bullying in pharmacies?
      A. Researchers have a consistent definition to identify bullying in pharmacy and it includes behaviors that are mocking, taunting, or intimidating.
      B. Leading pharmacy organizations have embraced the AMA's definition of workplace bullying and apply it consistently.
      C. One study found several comments related to bullying, but the study wasn't designed to identify bullying and rates are probably higher.

      2. What is the focus of the Institute for Safe Medication Practices periodic survey of health care professionals?
      A. Disrespectful behaviors and intimidation
      B. Causes of medication errors
      C. Harassment as defined by the US government

      3. Which of the following did approximately half of ISMP survey respondents report?
      A. Respondents said that they had been pressured to accept an order or administer a drug despite safety concerns.
      B. Respondents said they had avoided talking to a prescriber to validate an order about a safety concern more than ten times in the previous year.
      C. Respondents said they relied on colleagues to interpret or validate an order rather than contact the prescriber.

      4. A competent floating pharmacist is occasionally assigned to a store where a technician consistently calls out, “How many times do I have to tell you this? You've worked here before! You should know where these things are!” every time he asks her a question. Which of the following might the staff experience when observing this behavior?
      A. Decreased absenteeism
      B. Diminished morale
      C. Relief that they are not targets

      5. A prescriber who works in a hospital is notorious for his disrespectful treatment of nurses and pharmacists. He frequently scolds nurses if they call to clarify orders, and he often hangs up by slamming the phone in pharmacists’ ears. Which of the following potential negative patient outcomes have studies associated with this type of behavior?
      A. Higher medication error rates and increased infections
      B. Increased rates of falls and hip fracture
      C. Strained employee relations reducing collaboration

      6. Aadhil is a practicing Muslim who steps away from the work site to pray a couple of times a day. He's also a new father and has been up all night. He mentions this fact to his coworkers during the morning huddle, and asks for their support during the day. The pharmacist on duty finds that Aadhil has made two mistakes in filling a physician's order within the first three hours of work. He calls out, “Hey Aadhil, maybe next time you go to pray you could pray for better accuracy!” Aahil laughs uncomfortably. How would you classify this behavior?
      A. The pharmacist is bullying Aadhil but it's OK because Aadhil laughed.
      B. The pharmacist is bullying Aadhil and this behavior is never OK.
      C. The pharmacist is harassing Aadhil and the pharmacist’s behavior is illegal.

      7. Two technicians, Maria and Dolores don't get along. Maria develops a sinus infection and presents a prescription to be filled late in the day when Dolores is the only technician on duty. Maria is unable to come to work for a week because of her illness, and Delores whispers to anyone who will listen that Maria had a prescription filled to treat a sexually transmitted disease. In addition to the fact that Dolores has violated HIPAA rules, what kind of behavior is this?
      A. Harassment; Maria is a member of a protected class
      B. Bullying; Spreading false rumors is unacceptable behavior
      C. Neither harassment nor bullying; it's just gossip

      8. What is the best way to combat workplace bullying effectively in healthcare?
      A. Use a multifaceted approach that employs different strategies concurrently
      B. Have management and supervisors develop and enforce a policy against bullying
      C. Advise everyone in the workplace including the target to ignore the bully

      9. It's a busy day in the pharmacy and the pharmacy’s resident bully is in great form this morning. She has called several technicians names including Dumbo, Idiot, and Sweet Cheeks. She has also made fun of one of the pharmacist’s pants, remarking on how poorly they fit him. How can the seven people who were on duty and have witnessed these attacks best address this issue?
      A. Ignore it, because giving her any attention will increase her attacks
      B. Use bystander intervention and ask the bully to stop the name calling
      C. Make a note to ask the manager to refer the targets to the employee assistance program (EAP)

      10. Janine supervises Mary, Alice, and Siobhan. Janine witnesses Mary and Alice treating Siobhan very badly at a staff meeting. They consistently mispronounce Siobhan’s name. How should Janine approach this situation after she has corrected them several times in previous meetings and also corrected the spelling of Siobhan’s name on several documents that Mary and Alice have prepared? HINT: What process has Vanderbilt university used?

      A. Janine should meet with Mary and Alice privately and warn them that their behavior constitutes bullying and it needs to stop. She should say that she will pursue corrective and disciplinary action if the bullying behavior continues.
      B. Janine should continue to correct Mary and Alice each and every time that they mispronounce Siobhan’s name and send any documents with misspellings back to Mary and Alice for correction. Reinforcement is the key to success!
      C. Janine should meet with Mary, Alice, and Siobhan and try to get to the bottom of the problem. It's clear that Siobhan has done something to irritate Mary and Alice and correcting Siobhan’s behavior will fix the entire problem.

      Pharmacy Technician Post Test (for viewing only)

      Patient Safety: Workplace Bullying
      Post-test
      Learning objectives
      After completing this continuing education activity, pharmacists and pharmacy technicians will be able to
      1. Define workplace bullying in the healthcare setting
      2. Explain the impact of workplace bullying on individuals, organizations, and patient care
      3. Differentiate workplace bullying from harassment and workplace dysfunction
      4. Describe the necessary steps to address and counteract workplace bullying
      1. Which of the following statements correctly describes findings about bullying in pharmacies?
      A. Researchers have a consistent definition to identify bullying in pharmacy and it includes behaviors that are mocking, taunting, or intimidating.
      B. Leading pharmacy organizations have embraced the AMA's definition of workplace bullying and apply it consistently.
      C. One study found several comments related to bullying, but the study wasn't designed to identify bullying and rates are probably higher.

      2. What is the focus of the Institute for Safe Medication Practices periodic survey of health care professionals?
      A. Disrespectful behaviors and intimidation
      B. Causes of medication errors
      C. Harassment as defined by the US government

      3. Which of the following did approximately half of ISMP survey respondents report?
      A. Respondents said that they had been pressured to accept an order or administer a drug despite safety concerns.
      B. Respondents said they had avoided talking to a prescriber to validate an order about a safety concern more than ten times in the previous year.
      C. Respondents said they relied on colleagues to interpret or validate an order rather than contact the prescriber.

      4. A competent floating pharmacist is occasionally assigned to a store where a technician consistently calls out, “How many times do I have to tell you this? You've worked here before! You should know where these things are!” every time he asks her a question. Which of the following might the staff experience when observing this behavior?
      A. Decreased absenteeism
      B. Diminished morale
      C. Relief that they are not targets

      5. A prescriber who works in a hospital is notorious for his disrespectful treatment of nurses and pharmacists. He frequently scolds nurses if they call to clarify orders, and he often hangs up by slamming the phone in pharmacists’ ears. Which of the following potential negative patient outcomes have studies associated with this type of behavior?
      A. Higher medication error rates and increased infections
      B. Increased rates of falls and hip fracture
      C. Strained employee relations reducing collaboration

      6. Aadhil is a practicing Muslim who steps away from the work site to pray a couple of times a day. He's also a new father and has been up all night. He mentions this fact to his coworkers during the morning huddle, and asks for their support during the day. The pharmacist on duty finds that Aadhil has made two mistakes in filling a physician's order within the first three hours of work. He calls out, “Hey Aadhil, maybe next time you go to pray you could pray for better accuracy!” Aahil laughs uncomfortably. How would you classify this behavior?
      A. The pharmacist is bullying Aadhil but it's OK because Aadhil laughed.
      B. The pharmacist is bullying Aadhil and this behavior is never OK.
      C. The pharmacist is harassing Aadhil and the pharmacist’s behavior is illegal.

      7. Two technicians, Maria and Dolores don't get along. Maria develops a sinus infection and presents a prescription to be filled late in the day when Dolores is the only technician on duty. Maria is unable to come to work for a week because of her illness, and Delores whispers to anyone who will listen that Maria had a prescription filled to treat a sexually transmitted disease. In addition to the fact that Dolores has violated HIPAA rules, what kind of behavior is this?
      A. Harassment; Maria is a member of a protected class
      B. Bullying; Spreading false rumors is unacceptable behavior
      C. Neither harassment nor bullying; it's just gossip

      8. What is the best way to combat workplace bullying effectively in healthcare?
      A. Use a multifaceted approach that employs different strategies concurrently
      B. Have management and supervisors develop and enforce a policy against bullying
      C. Advise everyone in the workplace including the target to ignore the bully

      9. It's a busy day in the pharmacy and the pharmacy’s resident bully is in great form this morning. She has called several technicians names including Dumbo, Idiot, and Sweet Cheeks. She has also made fun of one of the pharmacist’s pants, remarking on how poorly they fit him. How can the seven people who were on duty and have witnessed these attacks best address this issue?
      A. Ignore it, because giving her any attention will increase her attacks
      B. Use bystander intervention and ask the bully to stop the name calling
      C. Make a note to ask the manager to refer the targets to the employee assistance program (EAP)

      10. Janine supervises Mary, Alice, and Siobhan. Janine witnesses Mary and Alice treating Siobhan very badly at a staff meeting. They consistently mispronounce Siobhan’s name. How should Janine approach this situation after she has corrected them several times in previous meetings and also corrected the spelling of Siobhan’s name on several documents that Mary and Alice have prepared? HINT: What process has Vanderbilt university used?

      A. Janine should meet with Mary and Alice privately and warn them that their behavior constitutes bullying and it needs to stop. She should say that she will pursue corrective and disciplinary action if the bullying behavior continues.
      B. Janine should continue to correct Mary and Alice each and every time that they mispronounce Siobhan’s name and send any documents with misspellings back to Mary and Alice for correction. Reinforcement is the key to success!
      C. Janine should meet with Mary, Alice, and Siobhan and try to get to the bottom of the problem. It's clear that Siobhan has done something to irritate Mary and Alice and correcting Siobhan’s behavior will fix the entire problem.

      References

      Full List of References

      References

         
        1. Meko H. School Will Pay $9.1 Million to Settle Lawsuit Over a Student’s Suicide. The New York Times. July 29, 2023. Accessed August 20, 2023. https://www.nytimes.com/2023/07/29/nyregion/new-jersey-student-suicide-settlement.html?searchResultPosition=1
        2. Murphy B. Why bullying happens in health care and how to stop it. American Medical Association. Published April 2, 2021. Accessed August 4, 2023. https://www.ama-assn.org/practice-management/physician-health/why-bullying-happens-health-care-and-how-stop-it
        3. Survey Suggests Disrespectful Behaviors Persist in Healthcare: Practitioners Speak Up (Yet Again) – Part I. Institute for Safe Medication Practices. February 24, 2022. https://www.ismp.org/resources/survey-suggests-disrespectful-behaviors-persist-healthcare-practitioners-speak-yet-again
        4. Intimidation: Practitioners Speak Up About This Unresolved Problem (Part I). Institute For Safe Medication Practices. Published March 11, 2004. https://www.ismp.org/resources/intimidation-practitioners-speak-about-unresolved-problem-part-i
        5. Disrespectful Behaviors: Their Impact, Why They Arise and Persist, and How to Address Them (Part II). Institute for Safe Medication Practices. April 14, 2024. Accessed August 4, 2022. https://www.ismp.org/resources/disrespectful-behaviors-their-impact-why-they-arise-and-persist-and-how-address-them-part
        6. Knapp K, Shane P, Sasaki-Hill D, Yoshizuka K, Chan P, Vo T. Bullying in the clinical training of pharmacy students. Am J Pharm Educ. 2014;78(6):117. doi:10.5688/ajpe786117
        7. Calvello M. Constructive vs. Destructive Feedback: Examples + Template | Fellow. Fellow.app. Published April 25, 2023. https://fellow.app/blog/feedback/constructive-vs-destructive-feedback-examples-template/
        8. Ryan M. Besting the Workplace Bully. Reference & User Services Quarterly. 2016;55(4):267-269.
        9. The Joint Commission. Bullying has no place in health care. www.jointcommission.org. Published June 2021. https://www.jointcommission.org/resources/news-and-multimedia/newsletters/newsletters/quick-safety/quick-safety-issue-24-bullying-has-no-place-in-health-care/bullying-has-no-place-in-health-care/
        10. Manzoni JF, Barsoux JL. The Set-Up-To-Fail Syndrome. Harvard Business Review. Published March 1998. https://hbr.org/1998/03/the-set-up-to-fail-syndrome
        11. Stein M, Vincent-Höper S, Schümann M, Gregersen S. Beyond Mistreatment at the Relationship Level: Abusive Supervision and Illegitimate Tasks. Int J Environ Res Public Health. 2020;17(8):2722. doi:10.3390/ijerph17082722
        12. Caring for Our Caregivers Caring for Our Caregivers Workplace Violence in Healthcare. https://www.osha.gov/sites/default/files/OSHA3826.pdf
        13. Infrontadmin. The 6 Stages of Bullying. https://truesport.org/bullying-prevention/stages-of-bullying/
        14. “Disruptive” doctors rattle nurses, increase safety risks. USA TODAY. Accessed August 3, 2023. https://www.usatoday.com/story/news/2015/09/20/disruptive-doctors-rattle-nurses-increase-safety-risks/71706858/
        15. Bullying in the workplace. www.independentpharmacist.co.uk. Accessed August 3, 2023. https://www.independentpharmacist.co.uk/services/bullying-in-the-workplace
        16. Ariza-Montes A, Muniz N, Montero-Simó M, Araque-Padilla R. Workplace Bullying among Healthcare Workers. International Journal of Environmental Research and Public Health. 2013;10(8):3121-3139. doi:https://doi.org/10.3390/ijerph10083121
        17. Glenn R. Grantner, PharmD, BCPS Clinical Pharmacist Sacred Heart Hospital Pensacola. Pharmacist Burnout and Stress. www.uspharmacist.com. Published May 15, 2020. https://www.uspharmacist.com/article/pharmacist-burnout-and-stress
        18. Medscape: Medscape Access. Medscape.com. Published 2023. Accessed August 9, 2023. https://www.medscape.com/slideshow/2022-physicians-misbehaving-6015583?icd=login_success_email_match_norm#13
        19. Staff B. Customer Harassment, Bullying Affecting Pharmacists’ Ability to Do Their Jobs. www.uspharmacist.com. https://www.uspharmacist.com/article/customer-harassment-bullying-affecting-pharmacists-ability-to-do-their-jobs
        20. Lamia M. The psychology of a workplace bully. the Guardian. Published March 28, 2017. https://www.theguardian.com/careers/2017/mar/28/the-psychology-of-a-workplace-bully
        21. Smith PK. Commentary III: Bullying in Life‐Span Perspective: What Can Studies of School Bullying and Workplace Bullying Learn from Each Other? J Community Appl Soc Psychol. 1997;7:249-255.
        22. Vramjes I, Elst TV. Griep Y, De Witte H, Baillen E. What Goes Around Comes Around: How Perpetrators of Workplace Bullying Become Targets Themselves. Group Organ Manag. 2023;48(4):1135-1172.
        23. Bullying and harassment. Pharmacist Support. Accessed August 3, 2023. https://pharmacistsupport.org/i-need-help-managing-my/work-life/bullyin-fact-sheet/
        24. Harassment | U.S. Equal Employment Opportunity Commission. www.eeoc.gov. https://www.eeoc.gov/harassment#:~:text=Harassment%20becomes%20unlawful%20where%201
        25. Anti-Harassment Policy Requirements By State. getimpactly.com. Accessed August 9, 2023. https://www.getimpactly.com/resources/anti-harassment-policy-requirements-by-state
        26. United States Department of Labor. The Whistleblower Protection Programs | Whistleblower Protection Program. Whistleblowers.gov. Published 2019. https://www.whistleblowers.gov/
        27. Koelmeyer S. An elbow in the waist: What is and isn’t bullying in the workplace. SmartCompany. Published May 20, 2019. Accessed August 3, 2023. https://www.smartcompany.com.au/business-advice/legal/bullying-workplace/
        28. Harassment Training Requirements by State. Project WHEN (Workplace Harassment Ends Now). Accessed August 4, 2023.
        29. Building positive workplace relationships. Pharmacist Support. https://pharmacistsupport.org/i-need-help-managing-my/work-life/building-positive-workplace-relationships/

        Beyond Medication Management: A Multi-Disciplinary Approach to Pain Management and Fall Risk Reduction

        Learning Objectives

         

        After completing this application-based continuing education activity, pharmacists will be able to:

        1.     Recognize opportunities to reduce pain medication and mitigate risk of falls
        2.     Identify appropriate patients for referral to physical therapy for non-pharmacologic pain management
        3.     Discuss deprescribing of "fall risk increasing pain medication" (FRIDs) with prescribers
        4.     Review the types of OTC assistive and adaptive devices available at the pharmacy to support pain relief, safety, or mobility

        After completing this application-based continuing education activity, pharmacy technicians will be able to:

        1. Identify classes of FRIDs that contribute to fall risk
        2. Complete fall risk screening to identify at-risk patients
        3. Recognize patients to refer to the pharmacist or other healthcare providers (HCPs) for further consultation
        4. List OTC assistive and adaptive devices to support pain relief and safer mobility

          Older adult fallen on the floor

           

          Release Date: November 15, 2023

          Expiration Date: November 15, 2026

          Course Fee

          Pharmacists: $7

          Pharmacy Technicians: $4

          There is no funding for this CE.

          ACPE UANs

          Pharmacist: 0009-0000-23-056-H08-P

          Pharmacy Technician: 0009-0000-23-056-H08-T

          Session Codes

          Pharmacist:  23YC56-TKF43

          Pharmacy Technician:  23YC56-FTX83

          Accreditation Hours

          2.0 hours of CE

          Accreditation Statements

          The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-056-H08-P/T  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

           

          Disclosure of Discussions of Off-label and Investigational Drug Use

          The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

          Faculty

          Carolyn J. Graziano, DPT, MSPT, MBA
          Senior Manager
          Global Strategic Marketing
          Health Economics & Reimbursement
          Avanos Medical
          Alpharetta, GA

          Faculty Disclosure

          In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

          Carolyn Graziano works for Avanos Medical and any potential conflicts of interest have been mitigated.

           

          ABSTRACT

          Pharmacists and pharmacy technicians often come in contact with older adults who have had or are at risk for falls. Often they are treated with opioid analgesics or non-steroidal anti-inflammatory drugs. Unfortunately, using medication alone to treat pain and discomfort can often increase risk for falls. If members of the multidisciplinary team work together, they can use a combination of non-pharmacologic approaches and medication management to improve the patient’s functioning and reduce risks of falls. Knowing which drugs are associated with falls is a first step to identifying patients who need additional attention. Pharmacies can provide screening for fall risk and help ensure that patients get the help they need to find appropriate assistive devices. Including a physical therapist on the team is one way to ensure that patients take advantage of the many services they provide.

          CONTENT

          Content

          INTRODUCTION

          Dotty is an 84-year-old widow suffering from osteoarthritis of the knees. Most days, she manages her pain with acetaminophen and has remained active in her community. Some days however, her painful knees make her unsteady on her feet and she has come close to falling, especially during the long walk from the parking lot through the senior center to get to BINGO.

          Managing chronic pain—pain lasting three months or more—in older community dwellers is a challenge due to the link between pain and increased risk of falls. Over-the-counter (OTC) and prescribed pain medication further compound fall risk through adverse effects. More than 100 million adults in the United States (U.S.) suffer from chronic pain.1 Common types of chronic pain include neuropathic, musculoskeletal, inflammatory, and mechanical pain. Between 30% and 40% of community-dwelling people older than 65 and 50% older than 80 fall each year.2

          Despite the use of fall prevention programs, the rate of falls resulting in injury has not declined. Researchers conducted a pragmatic, cluster-randomized trial (N = 5451) at 86 primary care practices across 10 U.S. health care systems. The trial evaluated the effectiveness of a multifactorial intervention including fall risk assessment and individual fall reduction plans compared to a control group receiving usual care. The results of the study found intervention did not significantly lower fall rates.3

          Many factors contribute to falls, but compelling evidence suggests that chronic musculoskeletal pain increases fall risk and people living with chronic pain show poorer executive function (mental skills that include working memory, flexible thinking, and self-control). Signs of poor executive function such as impaired impulse control, reduced ability to pay attention or focus, and problems starting, organizing or planning tasks can all contribute to fall risk. Treatment options for chronic pain include physical and behavioral medicine, neuromodulation, and surgical intervention. Despite a variety of treatment options, providers most frequently use pharmacologic approaches.

          Integrated, patient-centric, multi-disciplinary management of chronic pain offers a practical solution to reducing pain, over-medication, and risk of falls. Practitioners from several disciplines can help:

          • Pharmacists understand how medications work individually and in combination and provide medication management that is more informed than other professionals’ medication management.
          • Pharmacists and pharmacy technicians interact routinely with the community and can provide risk screening, patient education, and referrals to other HCPs.
          • Primary care physicians provide medication management including medication review and reconciliation and oversight for changes from multiple providers. Providers correctly prescribe but may not evaluate medications regularly for appropriateness.
          • Physical therapists can reduce pain and improve functional mobility through exercise, modalities (i.e., ultrasound, electric stimulation, iontophoresis), manual techniques, and prescription and training on assistive and adaptive devices.
          • Physical or occupational therapists may provide in-home safety evaluation and recommend modifications and equipment to reduce the risk of falls.
          • Collaborative relationships between community rehabilitation therapists and local pharmacies can support patient decisions and pathways for obtaining needed devices and aids to reduce pain and fall risk.

          THE CLINICAL PROBLEM

          Scope of Chronic Pain and Fall Risk

          Falls are the leading cause of death and injury in people 65 years of age and older. Pain often contributes to fall-risk. According to a recent Helsinki Aging Study, 61% of community-dwelling people 74 years and older reported they suffer from musculoskeletal pain that interferes with activities of daily living.4

          Because pain contributes to falls that result in further painful injuries, a cyclical pattern occurs. More than 50% of older Americans report pain at multiple sites.5 The most prevalent painful conditions affecting older adults include arthritis, chronic disease complications (i.e., diabetes, cancer) and post-stroke pain).6

          In Dotty’s case, her painfully arthritic knees prompted her to purchase a three-wheeled folding walker with a seat from an infomercial she saw on daytime television. Unfortunately, it folded while in use, collapsing to the ground along with Dotty. She ended up with a severely bruised and painful hip as a result of the fall.

          While environmental accidents and age-related changes can contribute to falls, chronic pain with medication use is a significant fall risk factor. In addition to polypharmacy, studies have shown both opioid use and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) contribute to fall risk. A retrospective, observational, multicenter cohort study of registry data in Canada (N = 67,929) concluded that recent opioid use is associated with an increased risk of falls in older adults and an increased likelihood of death from fall-related injuries.7 A systematic review also found an increased risk of falls is probable when elderly individuals are exposed to NSAIDs.8

          A pharmacologic approach to pain may be necessary when pain is significant, unremitting, and affects physical function or quality of life. However, health care professionals should not overlook the importance of nonpharmacologic pain management. Non-pharmacologic pain management and the reduction of falls is an important health topic for consideration by pharmacists and pharmacy technicians.9

          Economic and Socioeconomic Burden of Pain Related Falls

          Serious injuries from falls can lead to permanent injury, functional and cognitive decline, reduced quality of life and the need for institutional care resulting in significant cost.10 The American College of Rheumatology, a leading authority and partner of rheumatology professionals, considers pain chronic when it lasts more than three months, the normal time for tissue healing. Chronic pain is a major cause of disability and linked to mental health deterioration including depression and anxiety.11

          Professionals use many evidence-based fall prevention programs, such as those listed on the National Council on Aging website (Evidence-Based Falls Prevention for Older Adults (ncoa.org) to reduce falls in the community. These interventions vary in length such as 2-hour workshops, in-home interviews, or 8 week to 5-month programs that focus on aging in place, exercise, balance, removal of home hazards, adaptive equipment, task modification, education, and self-management.

          Even with fall prevention programs, the number of falls among older community dwellers is increasing. The reason for the rising number of elderly falls is multifaceted12,13:

          • The population of older adults is growing with more people living longer and remaining in their homes.
          • Access to and participation in fall prevention programs varies among community elderly.
          • In an aging population, musculoskeletal disability and resulting pain increases.
          • As musculoskeletal disability increases, the number of invasive joint surgeries such as hip and knee replacements rises. The projected volume of primary total knee replacements alone will increase by more than 400% over the next 20 years.
          • 7% to 23% of patients after hip and 10% to 34% after knee replacement have long-term post-operative pain.

          When surgeries such as joint replacement result in chronic pain, providers primarily use medication to address pain due to limited treatment options. The combination of aging, more joint replacement surgeries, and concomitant medication use requires more attention to pharmaceutical services in the role of fall prevention. Furthermore, age-related changes in pharmacokinetics and pharmacodynamics may increase the risk and incidence of adverse drug events related to falls.6

          IMPACT OF PAIN MEDICATION ON FALLS

          Risk of Opioid Use in the Elderly

          After her fall, an ambulance whisked Dotty to the hospital. Luckily, she did not sustain any fractures and the emergency department physician sent her home with a prescription for opioids, advised follow up with her primary care doctor, and gave her a flyer for a local fall prevention program.

          The use of opioids for pain management is a significant public health concern particularly among older community dwellers at risk for falls. Prescribed opioid use among middle-aged and older adults is more prevalent than among younger adults.14 Moreover, one-fourth (25.4%) of adults aged 65 years and older who take opioids report being long-time opioid users for a period of 90 days or longer (see Figure 1).15

          Age 40-59 have the highest opioid use, followed by age 60+

          An average of 8.6 million non-institutionalized older adults filled at least one opioid prescription between 2018 and 2019, while 2.7 million older people filled five or more opioid prescriptions or refills. Older women were more likely than men to fill one or more opioid prescriptions.16 In addition to age, socioeconomic factors and patient demographics impact opioid use. According to the statistical brief published by the Agency for Healthcare Research and Quality (AHRQ), elderly adults who were poor filled five or more opioid prescriptions compared to low- and middle-income adults (see Figure 2).16

          Poor and low income elderly adults have the highest amounts of individuals filling 5 or more opioid prescriptions

          A large retrospective, observational, multicenter cohort study of registry data of 67,929 Canadian patients with a mean age of 80.9 (±8.0) evaluated the link between recent opioid use and fall-related injuries. The study identified patients who had filled an opioid prescription in the two weeks preceding an injury were 2.4 times more likely to have a fall than any other type of injury. Patients who had a fall-related injury who used opioids were also at increased risk of in-hospital death.7

          A systematic review and meta-analysis of 30 studies evaluated the impact of opioid use on falls, fall injuries, and factures among adults at least 65 years old. The study found that opioid use was associated with falls, fall injuries, and fractures.17

          Sedation is a common adverse effect of opioids. Medication with sedative effects can lead to daytime drowsiness, reduced alertness, and impaired motor function. Older adults experience these adverse effects more frequently, particularly during the first few days of taking a new pain medication.18 Anticholinergic burden is one of the opioids’, such as oxycodone, lesser-known effects. Anticholinergic drugs impact central nervous system functions and can result in cognitive impairment, confusion, and blurred vision compounding the risks of sedation.19

          Because opioids cause drowsiness, orthostatic hypotension (dizziness or lightheadedness when standing up or otherwise changing position), and hyponatremia (low sodium levels leading to nausea, vomiting, loss of energy and confusion), they can increase fall risk. Risk is more prominent in older adults already prone to falls. Active drug half-life and metabolites are prolonged in older adults with renal impairment because most drugs, particularly water-soluble drugs, are eliminated by the kidneys.20 Understanding renal function is therefore important when assessing dosing risks in the older population. Reviewing for combination opioid use is also important in all patients, and particularly older patients. For example, physicians and pharmacists must take caution with patients using codeine and oxycodone together.21

          Risk of OTC Pain Medication

          Physicians often prescribe acetaminophen as a first-line or preferred OTC pain medication for older adults with nociceptive pain, which is pain caused by physical trauma, burns or surgery, because of potential adverse effects of NSAID (diclofenac, etodolac, fenoprofen, ibuprofen, ketorolac, meloxicam , naproxen) use. Long-term NSAID use is associated with adverse gastrointestinal, renal, and cardiovascular effects. An observed decrease in prescription NSAID and acetaminophen use may be due in part to the increased availability and variety of OTC NSAIDs over time, a phenomenon reported for other medications after becoming available OTC.22

          NSAIDs are among the 5% to 10% most commonly prescribed medications for pain and inflammation. The prevalence of NSAID use in the over-65 population is as high as 96%.23 Physicians and other healthcare providers often prescribe NSAIDs for acute or chronic arthritic pain because of their anti-inflammatory results over just the analgesic effect of acetaminophen.22

          Problems may arise related to NSAID-related toxicity in the elderly. Similar to opioids, age-related changes in pharmacokinetics may affect how the elderly metabolize NSAIDs. Dose reduction is appropriate for naproxen, ketoprofen, and salicylates in healthy older patients. Additionally, prescribers may need to reduce the dosage of diflunisal, indomethacin, sulindac, and mefenamic acid for the elderly in the presence of renal disease.24

          Table 1 lists the adverse effects of long-term use of NSAIDs that can impact fall risk.

          Table 1. NSAIDs Adverse Effects23

          System Adverse Effects
          Kidney Increased risk of nephrotoxicity

          Promotes renal vasoconstriction and reduced renal perfusion

          Electrolyte imbalance such as hyperkalemia

          Reduced glomerular filtration rate

          Nephrotic syndrome

          Chronic kidney disease

          Acute interstitial nephritis

          Sodium retention

          Edema

          Renal papillary necrosis

          Gastrointestinal Increased risk of GI bleeding
          Cardiovascular Edema

          Myocardial infarction

          Thrombotic events

          Stroke

          Hypertension

           

          Study data has been inconsistent but overall trends support an association of falls with NSAIDs use in the elderly. A systematic review of 13 studies published between 1966 and 2008 specifically reviewed fall risk associated with NSAIDs in the elderly population. The overall mean age of study participants was high, preventing generalizability to a larger population. However, all studies showed an increased risk of falling associated with NSAIDs.8 A similar systematic review identified 22 studies that enrolled patients older than 60 years to assess the association between medication use and falling. These analysts reviewed nine different drug classes (antidepressants, antihypertensives, benzodiazepines, beta-blockers, diuretics, narcotics, neuroleptics and antipsychotics, NSAIDs, and sedatives and hypnotics) encompassing 79,081 participants. The use of sedatives and hypnotics, neuroleptics and antipsychotics, antidepressants, benzodiazepines and NSAIDS resulted in an increased likelihood of falling. The unadjusted odds ratio estimate for likelihood of falls related to NSAIDs was 1.21 (95% CI, 1.01-1.44) compared to 0.96 (95%CI, 0.78-1.18) for narcotics.25

          The Case for Non-Pharmacologic Pain Management

          The evidence supporting the need for nonpharmacologic pain management treatment is compelling. The population is aging, the prevalence and incidence of musculoskeletal disability is on the rise, and use of pain medication is associated with known risks. While all adverse effects of taking pain medication are important, falls can be among the most debilitating and costly for the elderly.

           

          Pharmacists and pharmacy technicians are front line community healthcare providers in pivotal positions to positively impact fall reduction. By moving beyond medication management, pharmacists and pharmacy technicians can proactively participate in a multi-disciplinary approach to reduce reliance on pain medication and facilitate non-pharmacologic treatment including physical therapy.

          DEVELOPING AN INTEGRATED PATIENT-CENTRIC TEAM-BASED APPROACH TO FALL PREVENTION

          Pharmacists’ Role in Medication Management

          Pharmacists play a key role in fall prevention by recognizing “fall risk-increasing drugs” (FRIDs), identifying at-risk patients, and collaborating with other healthcare professionals including physicians, home care nurses, and physical therapists by making appropriate referrals.

           

          A traditional first step for pharmacists and pharmacy technicians is medication management. Knowing FRIDs is important (see Table 2).

          Table 2. FRIDs at-a-glance

          Classes of Fall Risk-Increasing Drug
          Antidepressants Antihypertensives Opioids NSAIDs
          Anticonvulsants Antipsychotics Sedative hypnotics Antispasmodics
          Anticholinergics Benzodiazepines Antihistamines Antispastics

           

          Polypharmacy, exposure to FRIDs, or the combination of polypharmacy including FRIDs can be associated with fall risk. Pharmacists should also consider exposure to potentially inappropriate medications (PIMs) as described in prescribing guidance tools such as the American Geriatric Society (AGS) Beers Criteria.26

          The Beers Criteria considers five broad categories of potentially inappropriate medications used in the elderly27:

          1. Medications considered potentially inappropriate
          2. Medications potentially inappropriate in patients with certain diseases or syndromes
          3. Medications to be used with caution
          4. Potentially inappropriate drug-drug interactions
          5. Medications whose dosages should be adjusted based on renal function.

          Additionally, the National Council on Aging (NCOA) advocates for a thorough medication review for older adults at risk of falling, noting that OTC medications can cause harmful interactions and increase falls.

          The five important problem areas identified by pharmacists in conjunction with the program’s algorithms include28

          1. Unnecessary therapeutic duplication
          2. Use of medications that can cause falls and confusion
          3. Use of medications that can cause cardiovascular problems
          4. Inappropriate use of non-steroidal anti-inflammatory drugs
          5. Review for effectiveness of opioid prescriptions and alternate options

          An example of unnecessary therapeutic duplication occurs when patients take a muscle relaxer such as meloxicam with an OTC for inflammation like naproxen. Many patients are also unaware of medications that can cause falls and confusion such as OTC antihistamines. Patient education directly from pharmacists or pharmacy technicians can be beneficial in preventing falls related to these types of OTC drugs.

          After her fall, Dotty filled her opioid prescription and continued taking acetaminophen due to the pain in her knees and hip from the fall. Since her providers or pharmacist had not “prescribed” acetaminophen, they were unaware of the unnecessary analgesic duplication.

          While medication management and identification of FRIDs is important to reducing risk of falls, it is not a substitute for a comprehensive multi-disciplinary approach. A recently published systematic review of the use of fall risk-increasing drugs looked at 14 observational or intervention studies that assessed FRID use in participants 60 years or older. Participants had experienced a fall resulting in a hospitalization or emergency department (ED) visit. The studies reported the prevalence of FRID use was 65% to 93% at the time of hospitalization or ED admission among older adults with a fall-related injury. Further, studies within the review found FRID use did not decrease at one and six months following a fall. Intervention trials included in the review demonstrated that interventions to reduce FRIDs did not result in a significant reduction in falls. The authors conclude that medication review with suggestions to the primary care provider as a stand-alone intervention was ineffective in preventing falls. Interventions to reduce FRID use are only one part of a more comprehensive strategy.29

          Dosing and Deprescribing to Reduce Falls

          When making decisions to deprescribe opioids, prescribers and pharmacists should consider whether the opioid use matches an appropriate indication. Since opioids are strong analgesics, their indications should be for moderate to severe acute pain, post-operative pain, or palliative care. Prescribers and pharmacists should always consider deprescribing when there are no indications for prescribing an opioid and safer alternatives are available.6

          Opioid dosing should always be specific to the individual with lower doses for older adults. Reducing the dose or switching to a less potent analgesic to maintain effective pain management is a viable strategy while implementing other nonpharmacologic techniques such as physical therapy.6

          Pharmacists are skilled in identifying medications for discontinuation based on known risks. A careful plan for tapering and discontinuing drugs at an appropriate pace is critical to avoid increasing patients’ pain, stress, and discouragement. Various tools are available to pharmacists to collaborate with patients to create a deprescribing plan.30 Examples of resources to assist healthcare providers optimize medications while minimizing adverse events include the Medication Appropriateness Index Calculator ( https://globalrph.com/medcalcs/medication-appropriateness-index-calculator/) and the AGS Beers Criteria available from the American Geriatrics Society (https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.18372). No one tool is the gold standard and inconsistencies exist among the various resources.31

          For example, the STOPPFall tool provides deprescribing in a stepwise manner.18 STOPPFall recommends reducing the opioid dose by 5% to 25% of the daily dose every one to four weeks. If adverse effects occur during deprescribing, prescribers can reduce the dose more slowly. If the patient dose is high or he or she has been using the opioid for a longer period, deprescribing should proceed very slowly.

          Conversely another tool, MedStopper, indicates when a patient has been taking an opioid daily for more than four weeks, prescribers should reduce the dose by 25% every three to four days. Upon any symptoms of withdrawal, they should increase the dose back to 75% of the previous tolerated dose. Once at 25% of the original dose with no withdrawal symptoms, they can discontinue the drug.32 Prescribers and pharmacists should monitor patients during and after deprescribing for symptoms of withdrawal such as musculoskeletal or gastrointestinal symptoms, restlessness, anxiety, insomnia, diaphoresis (excessive sweating), anger, and chills.

          Pharmacy Fall Risk Prevention Service

          To be an integral part of a more comprehensive fall prevention intervention, pharmacies should consider offering a fall prevention service. Establishing a community fall prevention service consists of fall risk screening, consultation to assess modifiable fall risk factors with referral to appropriate non-pharmacological intervention, medication check, and comprehensive medication review and adjustment by the pharmacy and primary prescriber.

          Use of an appropriate screening tool by pharmacists or pharmacy technicians is a major step to reducing risk of falls. To assist healthcare professionals in reducing fall risk, the Centers for Disease Control and Prevention (CDC) developed the STEADI (Stopping Elderly Accidents, Deaths, and Injuries) initiative. This initiative includes three steps for providers to address their patient’s fall risk.31,33

          • Screening for fall risk by asking patients if they have experienced past falls, feel unsteady, or are afraid of falling
          • Reviewing and managing their medications to determine if they impact fall risk and stopping, switching, or reducing them
          • Studies shows recommending vitamin D supplements to improve bone, muscle, and nerve can reduce risk of falls in the elderly

          The CDC and the University of North Carolina Eshelman School of Pharmacy and School of Medicine developed an algorithm called STEADI-RX to improve collaboration between healthcare providers and pharmacists based on the CDC’s STEADI initiative. STEADI-RX incorporates the Joint Commission of Pharmacy Practitioners (JCPP) Pharmacists’ Patient Care Process and an algorithm for integrating fall screening and prevention into pharmaceutical care. It also includes a tool kit for use by healthcare providers to help reduce risk of falls.34 Figure 3 shows the STEADI-Rx’s key steps.

          Steadi-Rx steps: 1 (screen), 2 (assess), 3 (coordinate care), 4 (response)                                                                     

          The STEADI-RX Community Fall Risk Checklist35 (https://www.cdc.gov/steadi/pdf/provider/steadi-rx/STEADIRx_pharmacy_fallrisk_checklist-508.pdf) is available to help the pharmacy staff quickly identify risk factors including fall history, postural hypotension episodes, and review medication classes associated with fall risk.

          Getting Started with A Fall Risk Service

          The STEADI-Rx Older Adult Fall Prevention Guide for Community Pharmacists, available from the CDC at https://www.cdc.gov/steadi/steadi-rx.html,36 provides a framework for how to start a fall prevention service, identifies best practices, and provides tools and references for implementing a successful program.

          To start an in-pharmacy fall reduction program, a key recommendation is to first identify a program champion. This is either a pharmacist or trained pharmacy technician who will serve as the lead role and ensure proper design and implementation of the program. Next, an environmental scan may help identify the patient population that will benefit from the service and how it fits into existing workflow. A fundamental aspect of conducting an environmental scan may include an analysis of strengths, weaknesses, opportunities, and threats (SWOT) to identify any internal or external obstacles to implementation, described in Sample Fall Prevention SWOT Analysis.

           

          SIDEBAR: SAMPLE FALL PREVENTION SERVICE SWOT ANALYSIS

          STRENGTHS - Internal factors include available resources and staff

          WEAKNESSES - Internal obstacles may be poor workflow or documentation procedures

          OPPORTUNITIES - External factors to support a successful service include an age-appropriate population, supportive providers, and state physical therapy direct access provisions to facilitate referrals

          THREATS - External factors that may hinder a successful service such as nearby pharmacies with strong prevention services, reimbursement or other financial factors inhibiting patient participation

           

          The guide also recommends conducting a readiness assessment to determine the steps needed to implement the service and to develop an action plan. The readiness assessment addresses staffing, resources, and training needed and assure there is appropriate support from leadership before moving forward. Depending upon existing pharmacy workflow, a pharmacy technician can lead a fall prevention service with pharmacist support when they need clinical judgement and expertise.

           

          Coordinating Care: Physical Therapy and Physician Support

          Dotty eventually came into the pharmacy looking for a “better” assistive device. She seemed confused about what device to choose and reported she recently had a fall. With her permission, a fall risk screening revealed she was taking both NSAIDs and opioids and had not been referred to physical therapy. She stated the ED gave her a flyer for a fall prevention program, but she didn’t go because it conflicted with BINGO at the senior center.

           

          Pharmacists and prescribers should consider practice guideline recommendations to determine when to make referrals to physical therapy for the nonpharmacologic treatment of pain. It is important to consider reducing reliance on opioids and inappropriate use of NSAIDs.

           

          Data from the National Ambulatory Medical Care Survey identified 11,994 visits representing a cross-section of all age patients between 2007-2015 where ICD-9 (diagnosis) codes indicated new chronic musculoskeletal pain. The survey found that healthcare providers prescribed patients opioids 21.5% of the time when they presented with new symptoms of chronic musculoskeletal pain but prescribed physical therapy just 10% of the time.37

          Numerous studies have examined the relationship between early physical therapy and opioid use for chronic musculoskeletal pain including back neck, shoulder, and knee. Due to its incidence, prevalence and associated costs, a preponderance of studies focused on low back pain (LBP). A retrospective analysis using commercial health insurance claims data from 2009-2013 observed 148,866 patients aged 18 to 64 years with a new primary diagnosis of LBP over a 1-year period. Compared to patients who received late or no physical therapy, patients who saw a PT first had an 89.4% lower probability of obtaining an opioid prescription.38

          Another cross-sectional observational study using the National Ambulatory and National Hospital Ambulatory Medical Care Surveys between 1997 and 2010 also identified lower PT referral rates among LBP patients aged 16 to 90 years old insured by Medicare and Medicaid. The study estimated 170 million visits for LBP led to 17.1 million PT visits. Further, visits not associated with PT referrals were more likely to be associated with opioid prescriptions.39

          Healthcare providers do not always prescribe nor do patients use physical therapy as a frontline treatment for chronic pain. Patients may use physical therapy along with other nonpharmacologic treatments, such as behavior health interventions or medication. Physical therapy is an integral part of multidisciplinary care, particularly to support success with opioid taper or cessation. Physical therapy treatments to reduce pain include exercise, manual therapy, electrical nerve stimulation, and other physical agents.

          When conducting a pharmacy fall risk service, pharmacy staff may encounter patients with chronic pain who have not received physical therapy prior to treatment with pain medication. The screening process will be the first step in assessing true risk.

          Pharmacy staff can use the STEADI-RX Provider Consult Form(s) for Medication or Fall Screening to share medication therapy problems with the patient’s provider or to refer the patient to a physical therapist for a full fall risk assessment.40,41 A physical therapist’s formal fall risk assessment is more in-depth than the screening tool used at the pharmacy and includes an evaluation of gait, balance, and strength. When using these forms or any other type of communication, states have different physical therapy direct access provisions and limitations. Pharmacies can verify the levels of patient access to physical therapist services in the U.S. through the American Physical Therapy Association (https://www.apta.org/contentassets/4daf765978464a948505c2f115c90f55/direct-access-by-state-map.pdf). After referral, physical therapists should respond within seven days. If they don’t, the patients or pharmacy should contact the PT again.

          Pharmacists and pharmacy technicians identifying at-risk patients during an initial fall risk screening performed at the pharmacy should refer patients to physical therapy for a full fall risk assessment. Physical therapists use a variety of objective assessment tools to address gait and balance such as the Tinetti Balance and Gait Assessment, Berg Balance Scale, or Timed Up and Go test to determine fall risk and areas for intervention. Therefore, when implementing a pharmacy fall reduction service, it is important for pharmacists to develop relationships with local outpatient physical therapy clinics able to accept referrals for fall risk evaluations.

          Because musculoskeletal pain is highly prevalent and a leading cause of disability, physical therapists are crucial members of the interdisciplinary pain management team. Physical therapists work effectively by providing nonpharmacologic treatment of pain incorporating various pain-relieving modalities such as transcutaneous electrical stimulation, heat or cold therapy, joint or soft tissue mobilizations or the use of braces or splints. In addition to physical therapy treatment to address pain, physical therapists also recommend various assistive and adaptive devices. Patients may use these devices to reduce pain through off-loading a painful limb or making mobility including ambulation and transfers (i.e., moving from one position to another such as from sitting to standing, or getting in or out of bed) easier and safer.

          Improperly selected or poorly fitted devices can result in further injury, pain or falls. Receiving instructions and training on proper use of assistive devices and compliance with instructions has not been strongly correlated. A small (N=17) observational cross-sectional study and focus group investigated older adults’ use of walkers in the home setting compared to current guidance in an attempt to identify circumstances leading to deviation from instructions for use. This study observed incorrect use of walkers 16% to 29% of the time associated with reduced stability.42 Another study found comparable results from a questionnaire of 94 patients using a cane for hip pathology.;47% of these patients were using the aid in the incorrect hand and of this group, 64% used their dominant hand. Furthermore, 66% of respondents reported they never received instruction on the correct hand to use. The study concluded that a significant percentage of patients are using canes incorrectly which may be due to lack of education.43

          A patient-appropriate assistive device, when fitted and used correctly, can reduce pain and increase physical activity in patients with chronic pain, painful or impaired gait and other mobility issues. Selection and fitting of an assistive device should always be conducted through a PT evaluation. PTs use a multi-factorial assessment of the patient’s physical and cognitive abilities of and consider the environment in which the patient will use the device (see 5 Factors of Device Prescription). PTs will also ensure devices match a patient’s height, weight, and size when selecting the best assistive device.

           

          SIDEBAR: 5 FACTORS OF DEVICE PRESCRIPTION

          1. Cognitive Function
          2. Coordination
          3. Upper-body, hand and grip strength
          4. Physical endurance
          5. Walking environment

           

          Upon competition of their evaluation, it is important for the therapists to know what types of OTC assistive and adaptive devices are available for purchase at local pharmacies to support patient needs. Although assistive devices are often available at physical therapy clinics, a patient’s health insurance plan may not include reimbursement for devices. Often OTC devices and aids are priced lower at retail locations and purchased directly by patients or family members.

          Rather than have Dotty guess and purchase a “better” assistive device, the pharmacy referred her to a physical therapist who determined that at least initially, a 4-point walker with front wheels would provide her the most stability and allow her to walk safely in both her home and the community.

          Table 3 describes items often recommended by therapists to reduce pain, fall risk, and improve home safety. See Fun Facts to learn about the history of walkers.

          Table 3. Assistive & Adaptive Devices

          Item Description Purpose
          Bed Rails Railing inserted between mattress and box spring or physically attached to bedframe Assist with transfer out of bed by allowing people to pull their body to change position using arms/upper body
          Cane, Walker Ambulation assist devices. Canes can be single point, multi point (quad) and walkers with or without wheels Provides additional point of contact to improve balance, alleviate weakness, or offload a painful joint
          Commode, Raised Toilet Seat, Toilet Seat Rails Portable toilet, elevated seat or arm rails Assist with safe transfer on and off toilet
          Grab Bars Bars and railings permanently affixed to walls near showers, toilets, entry ways, steps, stairs Promotes safe transfers from sit to stand, up and down stairs, in and out of shower
          Grabbers or Reachers Reaching aid with grab assist Allows items to be safely grabbed if out of reach or if mobility, pain, or strength impairs reaching and grabbing
          Neoprene braces and wraps Supportive and compressive wraps and braces for ankles, knees, wrists Provide joint protection, stability, and pain relief
          Shoe wedges or inserts Partial or full inserts used inside of shoes Cushion or improve postural alignment to offload painful foot
          Shower Chairs Waterproof, quick dry, slip resistant stool or chair Allows safe seating in shower to reduce slipping or falling and fatigue with standing

           

           

          SIDEBAR: FUN FACTS43,44,45,46

          A walker, walking frame, or rollator is a mobility device used by people suffering from leg or back pain, weakness, impaired balance, amputation, or poor stamina.

          • Walkers first appeared in the 1950s.
          • The first US Patent was awarded in 1953 to William Cribbes Robb of the United Kingdom for device called a “walking aid” filed with the British patent office in 1949.
          • Two US patents in 1957 are for variants with wheels.
          • The first non-wheeled designed walker was patented in 1965 by Elmer F. Ries of Ohio. In 1970, Alfred Smith of California patented the first walker resembling modern day walkers.

           

          Establishing Effective Team Communications

          Communication between pharmacists, prescribers, and therapists is important to monitor progress and avoid symptoms of medication withdrawal. As patients progress with their therapy plan of care, medication dosing may be easier to adjust. Ongoing patient education from pharmacists and pharmacy technicians can help avoid unnecessary patient self-medication with OTC pain relievers during the transition period.

           

          The physician or primary care provider receives regular updates from the physical therapy team and can provide the pharmacy with necessary progress to help coordinate dose reduction or deprescribing. When designing the workflow for a pharmacy fall prevention service, the program champion should be sure to include a schedule for giving and receiving team updates.

           

          With ongoing treatment, the physical therapist reported Dotty was making progress toward her therapy plan of care goals. Upon completion of therapy Dotty would be stronger, have less pain, and reduce or eliminate pain medication, and graduate to using a single point cane as needed. Since Dotty’s Medicare insurance plan only covered the cost of the 4-point wheeled walker, she would have to purchase the cane out-of-pocket and would be returning to the pharmacy with the PT’s recommendation so that the PT could fit and train Dotty on its proper use during her therapy sessions.

          Closing the Treatment Gap

          The benefits of a pharmacy fall reduction service are multi-fold. Moving beyond medication management closes the current treatment gap in the delivery of consistent and effective fall prevention. By working collaboratively with other HCPs, pharmacists help achieve better fall prevention outcomes by reducing or eliminating pain medications while facilitating non-pharmacologic pain management and improved functional mobility improvement.

          Contact Joanne Nault to describe this figure

          Pharmacist Post Test (for viewing only)

          Beyond Medication Management: A Multi-Disciplinary Approach to Pain Management & Fall Risk Reduction

          Pharmacists Post-test
          After completing this continuing education activity, pharmacists will be able to
          1. Recognize opportunities to reduce pain medication and mitigate risk of falls
          2. Identify appropriate patients for referral to physical therapy for non-pharmacological pain management
          3. Discuss deprescribing of fall risk increasing pain medication with physician prescribers
          4. Review the types of OTC assistive and adaptive devices available at the pharmacy to support pain relief, safety, or mobility

          1. Which of the following patients presents with an opportunity to reduce pain medication and fall risk?
          a. 53-year-old male tennis coach taking methocarbamol and hydrocodone/acetaminophen for recent back surgery
          b. 84-year-old frail widow taking ibuprofen, diazepam, lisinopril and gabapentin
          c. 62-year-old male with a transtibial amputation taking metformin and acetaminophen
          d. 74-year-old female with early onset Alzheimer’s taking meloxicam, alendronic acid, and vitamin D

          2. Which of the following patients should be referred to physical therapy for fall risk assessment?
          A. 92-year-old male who plays tennis daily but fell trying to jump over the net after a victory and is now taking ibuprofen for pain
          B. 85-year-old female active in her community who takes gabapentin for nerve pain
          C. 82-year-old female who lives alone, has a history of advanced cancer and has “tripped” several times at home without injury and takes lisinopril, bupropion, and pilocarpine

          3. Betty is 84 years old, suffers from osteoarthritis of the spine and has fallen twice in the past year. Which of the following is an example of unnecessary therapeutic duplication?
          A. Metformin and Valium
          B. Meloxicam and Aleve
          C. Lisinopril and Lipitor
          4. What class of medication is among the top 5-10% of drugs prescribed for pain and inflammation?
          A. Muscle relaxers
          B. Opioids
          C. NSAIDs

          5. Which of the 5 broad categories of the Beers Criteria is particularly important when performing pain medication management for fall risk prevention?
          A. Use of cardiovascular medications
          B. Medications whose dosages should be adjusted based on renal function
          C. Medications considered as potentially inappropriate

          6. Which of the following items are adaptive devices used for safety commonly sold in pharmacies?
          A. Reachers
          B. Cordless telephones
          C. Canes
          D. Crutches

          7. A template for starting a pharmacy fall service can be found through which CDC initiative?
          A. STEADI-Rx
          B. MedStopper
          C. STOPPFall

          8. Which of the following are ambulation assistive devices a patient may request to purchase at a pharmacy?
          A. Canes and walkers
          B. Shower chairs
          C. Raised toilet seats
          9. In addition to antidepressants, anticonvulsants and antihypertensives, which category of drugs is often overlooked as a contributor to falls?
          A. NSAIDs
          B. Antivirals
          C. Antibiotics

          10. 84-year-old Dotty is nearing the completion of physical therapy and her PT reports a significant reduction in her bilateral arthritis knee pain but is still currently being prescribed opioids since a recent fall what should you do?
          A. Nothing. Opioids were correctly prescribed by the ED physician and continued by her primary care doctor
          B. Have a discussion with the primary care about deprescribing the opioids
          C. Just tell her to wean off the opioids herself in a step-wise fashion

          Pharmacy Technician Post Test (for viewing only)

          Beyond Medication Management: A Multi-Disciplinary Approach to Pain Management and Fall Risk Reduction

          Pharmacy Technician Post-test

          After completing this continuing education activity, pharmacy technicians will be able to
          1. Identify classes of fall-risk increasing drugs (FRIDs) that contribute to fall risk
          2. Complete fall risk screening to identify at-risk patients
          3. Recognize patients to refer to the pharmacist or other healthcare providers (HCPs) for further consultation
          4. List OTC assistive and adaptive devices to support pain relief and safer mobility
          1. What percentage of people over the age of 65 fall each year?
          A. Between 5 and 10%
          B. Between 30 and 40%
          C. Over 50%

          2. Which of the following patients should be referred to the pharmacist for consultation?
          A. An 88-year-old female reporting new onset of dizziness after beginning a new pain medication
          B. A 68-year-old male purchasing acetaminophen while picking up a prescription for oxycodone
          C. A 90-year-old male asking where he can find canes to replace the one he is using
          3. Which of the following is a common adverse effect of taking opioids?
          A. Increased energy
          B. Improved vision
          C. Drowsiness

          4. Which one of the 5 important problem areas that the National Council on Aging (NCOA) identified can be corrected through medication review to reduce fall risk?
          A. Low vitamin D levels
          B. Unnecessary therapeutic duplication
          C. Past history of falling

          5. Which of the following are Fall-Risk Increasing Drugs?
          A. Opioids, NSAIDs, Antidepressants
          B. Antihistamines, Antibiotics, Statins
          C. Antihypertensives, Antivirals, Proton Pump Inhibitors

          6. What is the first step of the STEADI-RX program?
          A. Eliminate all fall-risk increasing medications
          B. Screen patients for fall risk in the pharmacy
          C. Assess modifiable risk factors

          7. Which of the following assistive devices may make mobility safer and reduce pain?
          A. Reacher
          B. Cane or walker
          C. Shower chair

          8. Which initiative recommends reducing an opioid dose by 25% if patients have been taking opioids daily for four or more weeks?
          A. STEADI-Rx
          B. MedStopper
          C. STOPPFall

          9. In addition to antidepressants, anticonvulsants and antihypertensives, which category of drug is often overlooked as a contributor to falls?
          A. NSAIDs
          B. Antivirals
          C. Antibiotics

          10. What class of medication is among the top 5-10% of drugs prescribed for pain and inflammation?
          A. Muscle relaxers
          B. Opioids
          C. NSAIDs

          References

          Full List of References

          References

             
            1. Nahin RL. Estimates of pain prevalence and severity in adults: United States, 2012. J Pain. 2015;16(8):769. Epub 2015 May 29.
            2. Moreland B, Kakara R, Henry A. Trends in Nonfatal Falls and Fall-Related Injuries Among Adults Aged ≥65 Years - United States, 2012-2018. MMWR Morb Mortal Wkly Rep. 2020;69(27):875-881. doi:10.15585/mmwr.mm6927a5
            3. Bhasin S, Gill TM, Reuben DB, et al. A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries. N Engl J Med. 2020;383(2):129-140. doi:10.1056/NEJMoa2002183
            4. Lehti TE, Rinkinen MO, Aalto U, et al. Prevalence of musculoskeletal pain and analgesic treatment among community dwelling older adults: changes from 1999 to 2019. Drugs Aging. 2021;38(10):931-937. doi:10.1007/s40266-021-00888-w
            5. Patel KV, Guralnik JM, Dansie EJ, et al. Prevalence and impact of pain among older adults in the United States: findings from the 2011 national health and aging trends study. Pain. 2013;154:2649-2657.
            6. Virnes RE, Tiihonen M, Karttunen N, van Poelgeest EP, van der Velde N, Hartikainen S. Opioids and Falls Risk in Older Adults: A Narrative Review. Drugs Aging. 2022;39(3):199-207. doi: 10.1007/s40266-022-00929-y.
            7. Daoust R, Paquet JM, Moore L, Emond M, Gosselin S, Lavigne G, et al. Recent opioid use and fall related-injury among older patients with trauma. CMAJ 2018; 190:E500-6. Doi:10.1503/cmaj.171286
            8. Hegeman, J., van den Bemt, B.J.F., Duysens, J. et al. NSAIDs and the Risk of Accidental Falls in the Elderly. Drug-Safety 2009;32;489-498.. https://doi.org/10.2165/00002018-200932060-00005
            9. Gemmeke M, Koster ES, van der Velde N, Taxis K, Bouvy ML. Establishing a community pharmacy-based fall prevention service - An implementation study. Res Social Adm Pharm. 2023;19(1):155-166. doi:10.1016/j.sapharm.2022.07.044
            10. Woo AK. Depression and anxiety in pain. Rev Pain. 2010; 4(1):8-12.
            11. Burns E, Kakara R. Deaths from falls among persons aged ≥ 65 years—United States, 2007–2016. Morb Mortal Wkly Rep. 2018;67:509–514.
            12. Singh JA, Yu S, Chen L, Cleveland JD. Rates of Total Joint Replacement in the United States: Future Projections to 2020-2040 Using the National Inpatient Sample. J Rheumatol. 2019;46(9):1134-1140. doi:10.3899/jrheum.170990
            13. Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What portion of patients report long-term pain after total hip or knee replacement for osteoarthritis. A systematic review of prospective studies in unselected patients. BMJ Open. 2012;2(1):e000435.
            14. Frenk SM, Porter KS, Paulozzi LJ. Prescription opioid analgesic use among adults: United States, 1999–2012. NCHS Data Brief. Hyattsville, MD: National Center for Health Statistics;2015:89.
            15. Mojtabai R. National trends in long-term use of prescription opioids. Pharmacoepidemiol Drug Saf. 2018;27:526–534. doi: 10.1002/pds.4278
            16. Moriya AS, Fang Z. Any Use and “Frequent Use” of Opioids among Elderly Adults in 2018–2019, by Socioeconomic Characteristics. 2022 Mar. In: Statistical Brief (Medical Expenditure Panel Survey (US)) [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2001-. STATISTICAL BRIEF #541. Accessed July 13, 2023. https://www.ncbi.nlm.nih.gov/books/NBK581184/
            17. Yoshikawa A, Ramirez G, Smith ML, et al. Opioid Use and the Risk of Falls, Fall Injuries and Fractures among Older Adults: A Systematic Review and Meta-Analysis. J Gerontol A Biol Sci Med Sci. 2020;75(10):1989-1995. doi:10.1093/gerona/glaa038
            18. Seppala LJ, Petrovic M, Ryg J, et al. STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs. Age Ageing. 2021;50(4):1189-1199. doi:10.1093/ageing/afaa249
            19. Staskin DR, Zoltan E. Anticholinergics and central nervous system effects: are we confused?. Rev Urol. 2007;9(4):191-196
            20. Merck Manual, Le J. Drug Elimination. Sep 2022. Accessed July 6, 2023. https://merckmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-excretion
            21. Niscola P, Scaramucci L, Vischini G, Giovannini M, Ferrannini M, Massa P, Palumbo R. The use of major analgesics in patients with renal dysfunction. Curr Drug Targets. 2010;11:752-758.
            22. Davis JS, Lee HY, Kim J, et al. Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic. Open Heart 2017;4:e000550. doi: 10.1136/openhrt-2016-000550
            23. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging Dis. 2018;9(1):143-150. Published 2018 Feb 1. doi:10.14336/AD.2017.0306
            24. Johnson AG, Day RO. The problems and pitfalls of NSAID therapy in the elderly (Part I). Drugs Aging. 1991;1(2):130-143. doi:10.2165/00002512-199101020-00005
            25. Woolcott JC, Richardson KJ, Wiens MO, Patel B, Marin J, Khan KM, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169:1952-1960.
            26. Fick DM, Semla TP, Steinman M, et al. American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674–694. doi: 10.1111/jgs.15767
            27. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;1- 30. doi:10.1111/jgs.18372
            28. National Council on Aging. How Can Medication-Related Falls Be Prevented in Older Adults? Accessed June 20, 2023. https://ncoa.org. How Can Medication-Related Falls Be Prevented in Older Adults? (ncoa.org)
            29. Hart LA, Phelan EA, Yi JY, Marcum ZA, Gray SL. Use of Fall Risk-Increasing Drugs Around a Fall-Related Injury in Older Adults: A Systematic Review. J Am Geriatr Soc. 2020;68(6):1334-1343. doi:10.1111/jgs.16369
            30. Murphy L, Ng K, Isaac P, Swidrovich J, Zhang M, Sproule BA. The Role of the Pharmacist in the Care of Patients with Chronic Pain. Integr Pharm Res Pract. 2021;10:33-41. doi:10.2147/IPRP.S248699
            31. Karani MV, Haddad Y, Lee R. The Role of Pharmacists in Preventing Falls among America's Older Adults. Front Public Health. 2016;4:250. doi:10.3389/fpubh.2016.00250
            32. MedStopper: MedStopper. Accessed 21 Jun 2023. https://medstopper.com/
            33. Murad MH, Elamin KB, Abu Elnour NO, et al. Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis [published correction appears in J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1495]. J Clin Endocrinol Metab. 2011;96(10):2997-3006. doi:10.1210/jc.2011-1193
            34. Pharmacy Care (STEADI-Rx) | STEADI - Older Adult Fall Prevention | CDC Injury Center https://www.cdc.gov/steadi/steadi-rx.html. Accessed Jun 22, 2023.
            35. Steadi-Rx Community Pharmacy Fall Risk Checklist (cdc.gov) https://www.cdc.gov/steadi/pdf/provider/steadi-rx/STEADIRx_pharmacy_fallrisk_checklist-508.pdf. Accessed Jun 27, 2023.
            36. Steadi-rx Older Adult Fall Prevention Guide for Community Pharmacists (cdc.gov) https://www.cdc.gov/steadi/pdf/Steadi-Implementation-Plan-508.pdf. Accessed Jun 22, 2023.
            37. George SZ, Goode AP. Physical therapy and opioid use for musculoskeletal pain management: competitors or companions? Pain Rep. 2020;5(5):e827. Published 2020 Sep 24. doi:10.1097/PR9.0000000000000827
            38. Frogner BK, Harwood K, Andrilla CHA, Schwartz M, Pines JM. Physical therapy as the first point of care to treat low back pain: an instrumental variables approach to estimate impact on opioid prescription, health care utilization, and costs. Health Serv Res. 2018;53:4629-4646
            39. Zheng P, Kao MC, Karayannis NV, Smuck M. Stagnant Physical Therapy Referral Rates Alongside Rising Opioid Prescription Rates in Patients with Low Back Pain in the United States 1997-2010. Spine (Phila Pa 1976). 2017;42(9):670-674. doi:10.1097/BRS.0000000000001875
            40. Provider Consult - Medication (cdc.gov) https://www.cdc.gov/steadi/pdf/provider/steadi-rx/STEADIRx_provider_consult_medication_form-508.pdf. Accessed Jun 27, 2023.
            41. Provider Consult - Fall Screening (cdc.gov). https://www.cdc.gov/steadi/pdf/provider/steadi-rx/STEADIRx_provider_consult_fallscreening_form-508.pdf. Accessed Jun 27, 2023.
            42. Thies SB, Bates A, Costamagna E, et al. Are older people putting themselves at risk when using their walking frames?. BMC Geriatr. 2020;20(1):90. Published 2020 Mar 4. doi:10.1186/s12877-020-1450-253. Shepherd AJ. Incorrect use of walking aids in patients with hip pathology. Hip Int. 2005;15(1):52–4.
            43. Walking Aid. U.S. Patent US2656874. Accessed August 31, 2023. https://patents.google.com/patent/US2656874
            44. Invalid walker and transfer device. U.S. Patent US2792052. Accessed August 31, 2023. https://patents.google.com/patent/US2792052
            45. Orthopedic walker. U.S. Patent US2792874. Accessed August 31, 2023. https://patents.google.com/patent/US2792874
            46. Invalid walker. U.S. Patent US3517677. Accessed August 31, 2023. https://patents.google.com/patent/US3517677

            Who are you? Who are We? Professional Identity in Experiential Learning

            Learning Objectives

             

            After completing this application-based continuing education activity, pharmacist preceptors will be able to

              1. Describe professional identify formation
              2. Apply the steps in development of a professional identity
              3. Identify activities that develop professional identity appropriately

              Healthcare professionals with arms crossed.

               

              Release Date: November 1, 2023

              Expiration Date: November 1, 2026

              Course Fee

              Pharmacists: $7

              UConn Faculty & Adjuncts:  FREE

              There is no grant funding for this CE activity

              ACPE UANs

              Pharmacist: 0009-0000-23-049-H04-P

              Session Code

              Pharmacist:  23PC49-ABC37

              Accreditation Hours

              2.0 hours of CE

              Accreditation Statements

              The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-049-H04-P  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

               

              Disclosure of Discussions of Off-label and Investigational Drug Use

              The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

              Faculty

              Jennifer Luciano, PharmD
              Director, Office of Experiential Education; Associate Clinical Professor
              UConn School of Pharmacy
              Storrs, CT

              Jeannette Y. Wick, RPh, MBA, FASCP
              Director, Office of Pharmacy Professional Development
              UConn School of Pharmacy
              Storrs, CT

              Ethan Yazdanpanah
              PharmD Candidate 2025
              UConn School of Pharmacy
              Storrs, CT

               

               

              Faculty Disclosure

              In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

              Jeannette Wick, Ethan Yazdanpanah, and Jennifer Luciano do not have any relationships with ineligible companies

               

              ABSTRACT

              Discovering what it means to be a good healthcare provider goes beyond knowledge acquisition and education for pharmacy students; it demands a transformative journey of professional identity formation (PIF). The pharmacy profession, through its professional organizations, has identified a number of core values, but as the profession changes, new core values are emerging. PIF occurs over a trajectory, starting in pharmacy school (or even before) and continuing throughout life. Preceptors can use a number of techniques to help pharmacy students with PIF, assuring that our future pharmacists hold the same values ats the profession at large. Exposing students to a variety of situations, asking open-ended questions, using teach-back methods, and introducing students to professional organizations are a few.

              CONTENT

              Content

              INTRODUCTION

              Let’s begin this continuing education activity with some questions. What makes a nurse a nurse? What makes a nurse a good or exceptional nurse? What makes an electrician an electrician? What makes an electrician a good or exceptional electrician? What makes a pharmacist a pharmacist? What makes a pharmacist a good or exceptional pharmacist? Those questions are no doubt difficult to answer. Preceptors may be making a list mentally of the qualities that the ideal nurse, electrician, or pharmacist should possess. Certainly, for each of these professions, education will be the foundation. Here’s a harder question: Is it possible to be a good or exceptional nurse, electrician, or pharmacist but a terrible person? And is it possible to be a good and loyal pharmacy employee, but not such a good pharmacist? All these questions speak to the concept discussed here: professional identity.

               

              Discovering what it truly means to be a healthcare provider goes beyond knowledge acquisition and education for pharmacy students; it demands a transformative journey of professional identity formation (PIF) starting even before introductory pharmacy practice experiences (IPPE) (perhaps with acceptance into a pharmacy program or during professionalism ceremonies) and continuing past graduation and over an entire career. As the introduction hints, preceptors must distinguish between education, professionalism, and professional identity. A quick way to differentiate between the latter two is that a student’s professionalism is outwardly observable. Professional identity, however, is defined by a student’s internal thinking, feeling, and acting like a member of the pharmacy profession and its community.1

               

              Pharmacists can use their extensive, science-based education to assume many professional identities; they may work in community, hospital, health-system, research, information technology, marketing, or a vast number of other positions. Viewing the history of the profession in just the last century, various identities have accumulated (rather than shifted) over time.2 The typical pharmacist’s main responsibility was once compounding. As the industrial revolution made it possible to produce dosage forms en masse, compounding fell out of favor and dispensing manufactured products became the primary focus of a typical pharmacist. Within just the last 20 years, pharmacists have made major inroads into establishing their role as necessary health care professionals rather than just retailers.3 Pharmacists have been shown to be key in improving therapeutic outcomes with a new focus on patient focused intervention.4 Pharmacists’ employment opportunities are growing and adapting to a changing field but the profession’s fundamental or core values are somewhat fixed. Table 1 lists the pharmacy profession’s current core values as promulgate by the American Pharmacists Association.

               

              Table 1. The Pharmacist’s Core Values5,6

              Commitment to the patient’s well-being ·       Engage in shared decision making and respect patients’ right to self determination

              ·       Protect patient life and aim for best outcomes

              Pharmaceutical expertise ·       Maintain competence in knowledge and abilities to ensure the safe and effective use of medication
              Reliability and care ·       Find balance between risk and benefit in treatments

              ·       Maintain trust and confidentiality with patients

              ·       Collaborate reliably with other healthcare professionals to ensure best health outcomes

              Social responsibility ·       Act with honesty and integrity in professional relationships

              ·       Avoid discrimination and seek healthcare equity in society

               

              PAUSE AND PONDER: Look at Table 1. What other values would you add to the table?

               

              As the profession’s identity evolves, pharmacists’ identities and their core values must follow suit. While pharmacists must be lifelong learners and adapt over time to new conditions, change is most readily achieved in the initial learning process as pharmacy students. In other words, you can teach old dogs new tricks, but it’s easier to teach puppies. In class, faculty teach students information a pharmacist should know and address how to outwardly act like a professional, but the profession demands something more: the development of a professional identity. We rely on our community of pharmacist preceptors to augment the various didactic courses to cultivate new pharmacist graduates who identify strongly with our core values.

               

              PIF is a crucial aspect of pharmacy experiential education. Students require experiential learning and immersion into the profession to assimilate the qualities that make pharmacists unique and different from other healthcare providers. The Accreditation Council for Pharmacy Education (ACPE)-required IPPE rotations provide students with important opportunities to influence PIF, and the PIF process continues during a student’s advanced pharmacy practice experiences (APPE).7

               

              The Pharmacy Student’s IPPE Rotation

              IPPE rotations serve a much broader purpose than students fulfilling educational requirements and completing dreaded 50-page workbooks that some schools use that aim to help them reflect on or consolidate learning. IPPE rotations should introduce students to the way front line pharmacists navigate real-world pharmacy practice situations. Students primarily relegated to counting pills and organizing stock in the back of a pharmacy are unlikely to develop professional identities. If students perceive that preceptors think of them as free labor or burdensome obligations, they will not engage in the deeper discussions about the preceptor as a person fulfilling professional obligations. Students should observe and actively take part in various aspects of the profession, applying theoretical knowledge acquired in classrooms to real-world situations. Practical knowledge gained through these experiences helps students to develop essential professional skills and test their learning.

               

              Experiential learning rotations should also expose students to different types of pharmacist positions and responsibilities. By observing different practice settings and interacting with pharmacists, patients, and other healthcare professionals, students can explore their interests, while realizing their strengths and developing professional values.

               

              Step-by-Step to Professional Identity

              Throughout pharmacy education, faculty members encourage students to exhibit professionalism; they may

              • suggest more productive ways to present ideas
              • prompt students to elevate or refine language or speak in ways patients will understand, or
              • suggest that certain clothing choices can diminish peoples’ view of them and their credibility

               

              While classroom faculty can teach and model the concept of professionalism, preceptors have the responsibility of supporting students in their PIF journey. Teaching starts the learning process; ultimately, students will need to “create their own adventures.” In other words, they must learn to apply aspects of specific material and explore different experiences to develop a professional identity. Relating to the definition of PIF, a pharmacy student’s PIF process must involve thinking, feeling, and acting like a pharmacist.

               

              To discuss professional identity, preceptors and all pharmacists who influence the student’s learning process must acknowledge the steps inherent in PIF. Personal identity is based on an individual’s concept of who they are and how others perceive them.7 Individuals develop personal identity in stages starting at birth but personal identity begins at birth and continues throughout life. Professional identity develops in a similar but slightly different way.

               

              Robert Kegan, a Harvard psychologist, developed a framework for longitudinal development of the self into a moral meaning-making entity that has had lasting impact on PIF in education of professionals.3,8-10 His framework includes six stages with stage 0 beginning at birth. Stages 0 and 1 concern young children’s development of basic motor function and sensing the physical world around them (and are not discussed here).8

               

              In relation to PIF, the health professional must pass through at least stages 2 through 4 of the framework: imperial, interpersonal, and institutional.10 This framework, with steps 2 through 5 shown in Table 2, defines the personal characteristics and related professional context of an individual in continuous stages of development. Individuals who reach the final stage, stage 5, or the inter-individual self-transforming stage, open themselves to multiple identities and other value systems, achieving full personal autonomy.8 Research shows that not all individuals reach stage 5.10,11 However, with effective socialization partnered with experience in the pharmacist’s potential identities, students may reach this level during their careers.

               

              Table 2. Kegan’s Stages of Personal and Professional Identity Development­8,10

              Stage Personal characteristics Professional context
              2. Imperial Individuals put their own needs and interests first but consider other people’s views. Individuals fill their professional roles but do so with a primary motivation of following rules. Individuals exhibit low self-reflection and may struggle to balance emotions with reason.
              3. Interpersonal Individuals are concerned with others’ perceptions of them and able to reduce focus on self-interest. Individuals balance multiple perspectives simultaneously. Individuals are idealistic and self-reflective, seeking others to guide them. Individuals manage emotions acceptably and generally understand right and wrong.
              4. Institutional Individuals assess relationships with a focus on self-defined principles and standards. Individuals define themself independently of others. Individuals can understand relationships by appreciating different values and expectations. They internalize professional values and do not allow emotion relating to needs, desires, and passion to gain control over reason.
              5. Self-transforming Individuals reconcile contradictory or paradoxical ways of constructing meaning. They can recognize the interdependencies of different systems or ways of thinking. The self-transforming professional has a strong sense of self but also relies upon others knowledge and opinion in professional development. The professional integrates other identities into the total professional identity.

               

               

              The constantly evolving pharmacy profession and the lack of a specific list of steps for PIF makes it challenging for students to define an identity (and preceptors to help them). As the profession continues to develop to offer a wide range of opportunities for pharmacists, preceptors will observe students finding varying paths of PIF. Different pharmacists will define the profession differently depending on their experiences. Pharmacy students might generally navigate this list of steps, common among many young people developing professionally12-15:

               

              1. Exploration: In any career path, exploration is the first step in PIF. In pharmacy, the American Pharmacists Association offers the Career Pathway Evaluation (https://www.pharmacist.com/Career/Career-Pathways) to help aspiring pharmacists find a path forward. IPPE and APPE rotations should ideally provide students with opportunities to explore various pharmacy practice settings and work with pharmacists with a range of responsibilities. Students need to augment their existing identities—formed by their upbringing and personal beliefs—as they begin their pharmacy education and careers. Students come from diverse backgrounds with varying past experiences, cultural values, learning styles, and personal characteristics.
              2. Reflection and integration: Educators should encourage students to reflect on their experiences, strengths, values, and areas for improvement. Reflection helps students align personal and professional values, shaping their professional identities. Self-reflection and reflection from preceptors during IPPE rotations is necessary for growth. For example, a technician told Jayne, a pharmacist for a chain pharmacy, that a patient was in the counseling room and ready for an immunization. Jayne took her student with her to observe. Jayne asked the student to review the necessary paperwork and make sure the patient, a 17-year-old adolescent, met all the criteria for the human papilloma virus vaccine. The student said he did. When Jayne reviewed the paperwork, she found one problem. She asked the patient, “Which of your parents is here with you today?” In Jayne’s state, the legal age of consent was 18. When contacted by phone, the parent agreed to come in immediately and Jayne administered the vaccination. After all was done, she spent just a few minutes talking to the student about the duty to protect and comply with the law, describing a couple of other instances when she encountered similar situations.
              3. Commitment and advocacy: Commitment to the pharmacy profession and dedication to lifelong learning are essential elements in the development of a professional identity. Pharmacy students will become spokespeople for the profession and advocate for the inevitable change from retail-based to clinically- or service-based work. Pharmacists with solid professional identities will be lifelong learners and educators.

               

              Students who have never worked in a pharmacy or observed a pharmacist at work (and some who have) may have inaccurate ideas about the profession. Preceptor Eddie encountered a curious situation when Adam, a P2 student, reported for an IPPE rotation. Adam was more than self-assured; Adam had an exaggerated sense of self-worth. He was bumptious (self-important or smug), so Eddie needed to work around Adam’s personal identity. Adam told Eddie that his older brother was a pharmacist who had told him that pharmacy schooling is pretty worthless. Adam said, “All you need to do is pass and you’re on your way to a darned good salary.” Eddie was astounded. Adam needed help reaching Step 2 of the PIF model—he was putting his own needs and beliefs first and disregarding others’ views. Eddie created a plan to help Adam develop more insight.

               

              Each day when Adam came to work, Eddie presented two or three situations from his work experience that required more than just a body behind a computer. He would ask Adam to work through the problems and present the answers by the end of the day. In this way, he educated Adam about professional responsibility and clarified the difference between a person with a pharmacy degree and an exceptional pharmacist. PIF’s goal is for students to move from playing or imagining the pharmacist’s role to internalizing the pharmacist’s identity and acting as pharmacists at the unconscious level. The process shifts emphasis from ‘doing’ to ‘being.’ While professionalism can be put on and taken off like a white coat, professional identity stays with the healthcare professional at all times. Eddie was able to improve Adam’s professionalism, which was poor at the rotations start, and contribute to Adam’s professional identity.

               

              PAUSE AND PONDER: When you were a student, which preceptors influenced your core values and how did you internalize them?

               

              Activities that Develop Professional Identity

              Preceptors who work in different types of positions need to acknowledge their personal and professional strengths and limitations to determine what they can realistically offer to students. Before taking on the preceptor’s or mentor’s responsibilities, professionals must be familiar with their own skillsets.7,14

              • The first step preceptors should take is to embrace self-reflection. Just as preceptors should encourage students to engage in reflective practice, pharmacy is a profession in which preceptors must be lifelong learners. Established pharmacists will continue to accumulate PIF-related experiences over time to aid their effectiveness in guiding others.
              • Preceptors will then need to plan intentionally and commit to helping students develop professional identity. A reluctant or unprepared preceptor usually cannot teach students effectively. Sometimes pharmacists with extensive work experience on the frontlines might feel that students come with a more contemporary knowledge base and therefore, they have nothing to teach them. However, that pharmacist could be well-positioned to support the student’s PIF by embracing how their professional experiences led to a deeper understanding of their profession and the pharmacist’s role in supporting patient outcomes.

               

              PAUSE AND PONDER: What are the most efficient ways to help your students develop professional identity in your practice location? What are the most important ideas you can teach? Are they the same?

               

              PIF is a gradual process that revolves around socialization, not classroom lecture. IPPE rotations provide an ideal platform for students to engage in activities that promote professional development. Preceptors can work with students to facilitate PIF during an IPPE rotation in several ways. 7,16,17

               

              Patient interactions: Direct patient interaction during IPPE can help students apply theoretical learning and develop communication skills, empathy, and a patient-centered approach to care. These experiences help students internalize a sense of responsibility toward patient well-being and strengthen trust in the caregiver-patient relationship.

               

              Preceptors should expose students to patient counseling sessions as observers as often as possible. Consider Leonard, a preceptor who frequently tells students, “I am not going to bring you into this counseling session because it is too complicated. You won’t understand what’s going on.” This is a mistake. IPPE is an opportunity for students to be exposed to difficult real-life examples before they have to handle them alone. These experiences help develop professional identity and may even stimulate an “ah-HA!” moment about pharmacist responsibility for the student. Preceptors who ask students a few open-ended questions (e.g., What did you see that surprised you? What three points did I emphasize? What counseling techniques will you remember from this?) prompt students to engage. Inviting students to see a situation that requires pharmacists to work at the top of their license introduces step 4 (institutional)  and epitomizes PIF. Leonard has the opportunity to show his version of an independent and talented pharmacist who contributes to healthcare positively.

               

              PIF opportunities need not be complicated. Sometimes PIF occurs concurrent with simple everyday tasks. Preceptors who walk students through their thought process when processing an order (i.e., Why does this document go here in the electronic medical record? Why am I looking at that lab before processing the order?) introduce students to the necessity of questioning routinely as a professional function. They can also ask students to find or calculate doses, explore drug interactions, and then provide the information to another interdisciplinary team member.

               

              Not all patient interactions are pleasant or welcome, but they may be professionally necessary. Alex, the pharmacist, was dismayed when a technician came to him and said, “Mrs. Royce is here and wants to talk to you,” while rolling her eyes. Mrs. Royce was notorious for being loud, disrespectful, and a know-it-all. Alex didn’t answer immediately. The technician said, “Shall I tell her you are busy?” Alex said he would talk to her and briefed the IPPE student on Mrs. Royce’s personality. He said he was concerned because Mrs. Royce had recently had surgery, had a reaction to the opioid that was prescribed, and was switched to tramadol. He explained that regardless of his personal feelings, he needed to deal with the situation. When he asked Mrs. Royce how he could help her, she said, “The oxycodone made me sick as a dog. My friend up the street who is a nurse says the tramadol I am taking now is not worth anything. I am taking it and it is super mild but at least it’s something. I have an anti-inflammatory, too. I know this is a first-world problem since this was an elective surgery, so I should not complain. I am just a whiner with pain.” Alex reassured her that no one deserves pain, even if the surgery was elective. Alex counseled the patient with these points18-20:

              • Tramadol is a funny drug. People with certain genetic variations called CYP2D6 deficiencies get less relief from it. It gets a bad reputation because many clinicians don't know that. Take it if it helps. And it sounds like it helps a bit.
              • Schedule your anti-inflammatory around the clock. Don't wait until the pain is horrible. Take it every four to six hours for a few days. Eat a little something when you take it.
              • Use warm or cold compresses if they help but use them only for 10 minutes at a time once every hour. (You don't want to fry or freeze your skin.) If warm helps, use warm. If cold helps, use cold.
              • Move around as much as you can. It increases blood flow to the area.
              • Have you tried some acetaminophen? Some people find that taking a couple of acetaminophen once or twice a day for a couple of days helps--it won't address the inflammation but it may help with pain.
              • Consider finding an acupuncturist and/or a massage therapist who specializes in pain.

              After the session, Alex explained that dealing with patients like Mrs. Royce is an obligation, as is not showing whether he likes her. This attitude aligns with the “interpersonal” step of PIF (step 3)—balancing multiple perspectives and putting others’ needs first. He said that all pharmacists encounter difficult patients. He also said that he planned to check in on her by phone the next day. He asked the student if anything surprised her, and she said, “Yes. You didn’t say anything about the nurse’s bad advice!” Alex explained that professionals don’t speak badly of each other, especially when the information from Mrs. Royce was hearsay. He said he trusts that Mrs. Royce, the consummate know-it-all, will talk to the nurse and the nurse will call if she wants more information. The student was able to teach-back the key points of professional identity:

              • Treat all patients with respect, even when they don’t return the favor
              • Counsel carefully
              • Do not disparage other healthcare providers (talk to them directly if you have a concern about their advice)
              • Follow-up.

              When the student asked this preceptor for a letter of reference several months later, the preceptor said, “Remember Mrs. Royce? Her attitude is entirely different now. She’s kind and respectful when she comes in.”

               

              Collaborative Practice: Preceptors can highlight interdisciplinary healthcare experiences, demonstrating teamwork, collaboration, and the ability to contribute effectively within a healthcare setting. In a health system setting, for example, many different pharmacists work in the same organization with varying responsibilities. A health system may include an inpatient and outpatient, specialized clinical, emergency department, investigational drug service, and oncology pharmacy. Each position requires modified professional identities and collaboration with different healthcare professionals. A preceptor can join forces with other pharmacists—a model that is increasingly popular and often called team precepting—to ensure students receive a well-rounded education in the short period of time provided.

               

              Exposure to eustress (healthy, stimulating kind and level of stress): A preceptor should take the time to facilitate a learning environment that optimizes the likelihood that PIF will occur. Preceptors can discuss situations that present ethical dilemmas during IPPE rotations, prompting critical thinking, ethical decision-making, and the development of moral reasoning. As students are exposed to common ethical dilemmas, they will begin to develop problem solving skills; build confidence; and think, act, and feel like pharmacists. Students who have not yet assimilated the second step of PIF—the imperial—may be more concerned with packing up to leave at their assigned quitting time than finishing a task. Helping students learn that sometimes the clock should not dictate decisions also develops professional identity.

               

              Exposure to unanticipated, stressful misadventure. Marguerite was precepting a student when a technician came behind the bench with arms raised and a robber holding a gun behind her. The four other employees and the student froze, and Marguerite handled the situation, emptying the vault into the robber’s duffel bag. After the robbery, everyone was shaken but no one was hurt. Although the store manager’s opinion was to send the student home, Marguerite insisted on a post-incident stress debriefing. It gave everyone the opportunity to vent and identify what they did well and what they could do better, and reduced the likelihood of post-incident stress.21 As they met, the police returned and said they had apprehended the robber because Marguerite had placed a tracking device in the duffel bag. Marguerite has traversed all the steps of PIF. She considered others in her decisions, balanced multiple perspectives, and maintained her standards.

               

              Although this is an extreme example that underscores the meaning of “unanticipated,” the student reported feeling better and understanding more about the pharmacist’s responsibilities. Other unanticipated events that can convey PIF include dealing with irrationally irate customers, diffusing the situation with a vaccine refuser who wants to espouse her opinion loudly to other patients, or dealing with a patient or employee medical emergency in the workplace. Appropriate and deliberate use of emotion can also focus learners and enhance learning, especially when the material is moving or highlights the patient’s perspective. Preceptors should employ emotion as a teaching tool carefully, since negative emotion (e.g., anger, embarrassment) erodes trust and can disenfranchise students.

               

              Professional involvement: If time allows, preceptors can encourage students to engage with professional organizations. Attending conferences, workshops, state pharmacy board meetings, or seminars that promote professional growth, networking, and exposure to current trends in the pharmacy field builds professional identity. Preceptor Eddie, discussed previously, took Adam to a Board of Pharmacy meeting. Adam seemed uninterested until the Board discussed disciplinary action against a pharmacist who had failed to perform due diligence, leading to a patient’s death and a pharmacist with a drug abuse problem. Adam was less bumptious in the car on the way back to work, and Eddie took time to ask open-ended questions to mold Adam’s professional identity. He asked, “What questions do you have for me?” Adam said, “What is the chance they will get their licenses back?” It created a chance to talk about professional responsibilities and how state boards monitor and ensure public safety. Eddie asked a question of his own “What do you think the patients who experienced poor care or unprofessional behavior from those pharmacists think about the profession of pharmacy? In the world of social media, how far do you think those negative sentiments about pharmacists can spread?" This discussion moved Adam further through Step 2, and away from a preoccupation with self-interest.

               

              Formative feedback (feedback that helps students recognize knowledge gaps and molds the student’s beliefs and values; see the SIDEBAR) and encourage reflection. Preceptors should7

              • Provide students with regular feedback, but also schedule time for check-ins and reviews mid-rotation. As students’ professional identities develop, they will become their own sources of feedback.
              • Employ teaching methods such as using teach-back and open-ended questions.
              • Schedule time for students to work on workbooks or other tools for reflection and encourage discussion and questions.
              • Assign meaningful work to help students integrate ethical principles, evidence-based practice, effective communication, and patient-centered care.

               

               

              SIDEBAR: Formative Feedback22,23

              Formative feedback

              • refers to informal constructive feedback provided throughout a learning process
              • is ongoing and proactive
              • is specific and actionable
              • helps to develop self-awareness and independence
              • gives students the opportunity to reflect and adjust without being graded
              • and is not summative feedback (a method of assessment where students are evaluated and/or graded on their overall performance usually at the end of a learning period)

               

              Open ended questions are important in formative feedback. Just as healthcare professionals are encouraged to ask patients open-ended questions, preceptors should do the same with their students. Open-ended questions

              • give students the opportunity to participate in discussion actively and gain a deeper understanding of a topic or situation
              • can help the preceptor identify gaps in a student’s understanding
              • develop students’ critical thinking skills and autonomy to further their PIF
              • are especially useful after patient counseling or other interaction.

               

              Teach-back, or the "show-me" method, confirms whether a person—a patient or in this case, a student—understands the topic being explained. Pharmacists and other healthcare providers use the teach-back in patient counseling to facilitate better communication between patient and provider. This tool allows a healthcare provider to assess patient understanding by having a patient explain, or teach-back, what they took away from the counseling session. The healthcare provider can gently correct misunderstandings. Using teach-back with students is especially effective when

              • Students observe a complicated counseling session or process
              • Students are learning about a new medical device or a medication with an unusual administration route or schedule
              • Students need to research a topic that is new to them and may have missed some critical information
              • Students witness a situation that is emotionally charged or creates a safety concern

               

               

              Demonstrating vulnerability. Preceptors often want to hide their deficiencies, limitations, or weaknesses from students so students will have greater confidence in the preceptor’s expertise. Students need to see how mistakes happen and lead to improvement. They also need to see the ethical challenges that are inherent in pharmacy practice. Preceptor Terry received a phone call from a pharmacist who worked at another of her chain’s locations. She knew the pharmacist quite well, and the pharmacist said she had received a prescription for a patient well known to them for hydromorphone 8 milligrams. They were out of hydromorphone and the pharmacist asked if Terry had any 8 milligram tablets. Terry said she did, and the pharmacist said she would send the patient over and to expect him within 30 minutes. When the patient arrived, Terry filled the prescription and being alone with just the IPPE student, prepared to dispense it at the cash register. As required by law, she asked the patient for identification. Much to her surprise, the person presented his driver’s license and he was not the patient. In fact, the identification card was for the prescriber who had written the prescription, a medical resident at a local hospital. She asked the prescriber why he was picking up the prescription and he said that he was helping out the patient who was in terrible pain. It was late in the day, and Terry had received this referral from a colleague who she trusted. She dispensed the prescription despite her misgivings.

               

              The next day when the IPPE student arrived, Terry explained the immediacy of the situation and conflicting professional interests led to dispensing the prescription yesterday, but she still had some nagging doubts. With the prescription volume a bit slower now, she decided to do some follow up. She found that the “patient” had a number of prescriptions filled over months, most of which were filled at her colleague’s pharmacy. However, the initial prescriptions were filled in a town 40 miles away. She eventually called the hospital, found the name of the residents’ supervising physician, and contacted him. After brief discussion, he indicated that he would handle it going forward and that he appreciated the information. Although the supervising physician did not say outright that he suspected this resident of wrongdoing, the implication was that was the case. The supervising physician did follow through and eventually, the state requested documentation. Terry was able to talk through the situation with the student and explain the pharmacist's responsibility in cases like this. Terry exemplifies Step 4 of PIF. She was secure in her identity and despite the way others had handled this situation, she was concerned and confident enough to do the right thing.

               

              Teach-back is useful in many situations, but especially when processes are involved. In one busy pharmacy, a man approached the pharmacy student at counter. He said, “Can I get a shingles vaccine today?” The student, having no prior experience in a community pharmacy, politely asked the patient to wait while she asked the pharmacist. Her preceptor said quickly, “Get the patient’s insurance information and enter him into the system.” With the patient’s insurance card in hand, she began to enter his information. Unsure how to proceed, she asked the pharmacist for assistance again. A line began to form behind the man, so the pharmacist said, “Don’t worry, I’ll do it and you can watch.” The intern watched and thought the process looked easy enough. The pharmacist asked if she understands (a close-ended question), and she said yes. Later in the day, a new patient came in and the student began to enter the patient’s insurance information. She hit a point where she was unsure how to continue. But earlier she told her preceptor that she understood how to do it! She really thought she did know how! The student, becoming flustered, was embarrassed to ask for help again on something she had just learned. How could this situation have been avoided? If the preceptor had asked the student to describe the process, correcting any inaccuracies in recollection, and explained why pharmacies need to provide accurate information, the student would have been in a better position to help.

               

              Overall, preceptors need to provide students with the best experience possible with available time and resources. For example, a student may be in a health systems rotation in a department that has little patient interaction and plenty of down time. The preceptor may worry he cannot give the student the experience she deserves. This preceptor could assign the student to review a journal article on a relevant subject and present it to an interprofessional team of nurses, pharmacists, and doctors. Subsequently, the student may realize the pharmacist’s potential impact and help the student internalize what it means to be a pharmacist.

               

              PAUSE AND PONDER: Can you recall a time when you were taught how to do something, told your teacher you understood it, then could not perform the action on your own? As a preceptor, how would you avoid this situation with your own student?

               

              Finally, let's return to the questions asked at the beginning of this continuing education activity. In particular, the question of whether a pharmacist can be a good employee, but a bad pharmacist, is of tremendous interest right now. The situation it brings to mind is that of the good employee pharmacist whose supervisors urge him to dispense opioid prescriptions as written and avoid asking too many questions. Doing so makes customers happy, increases prescription volume, and reflects positively in the store’s metrics. Many pharmacists conducted themselves this way for many years, despite the fact that they probably had an inkling that they should be checking more closely or perhaps turning some prescriptions away. These pharmacists were not necessarily bad pharmacists, but their employers considered them good employees because they followed directions and turned a blind eye to a developing opioid epidemic.

               

              In November 2021, a federal jury in Ohio found three of the nation's largest pharmacy chains liable for contributing to the U.S. opioid crisis.24,25 The jury found that the prosecution provided ample evidence that some medications dispensed at chain pharmacies legally were sold on the black market. That finding has resonated nationally as state after state filed similar lawsuits. In December of 2022, two chain pharmacies agreed to share a $10.7 billion fine to settle allegations that they failed to oversee opioid analgesic prescriptions adequately. These funds are being distributed to states, local governments, and federally recognized tribes to improve opioid crisis abatement and remediation programs. Both chains agreed to improve their controlled substance compliance programs and provide mandatory training to pharmacists. Expediency in the short term and compliance with procedures that are unethical seldom avoid long term consequences.

               

              Other states have also secured settlements from pharmacies, and independent pharmacies have also been prosecuted. Discussing situations related to pharmacy that appear in the media is another way that preceptors can introduce discussion of our professional values. The nation is hopeful that pharmacists everywhere have learned that part of our professional identity is the necessity to speak up and to challenge our employers when they ask us to do things that walk the line of professionally ethical behaviors. Starting discussions with students about newsworthy events like this in which preceptors talk about self-interest, other people’s perception of pharmacy and pharmacists, and maintaining standards can advance our profession. Pharmacists are part of a complex system of drug distribution. We need to establish our core values and uphold them to keep society’s respect.

               

              CONCLUSION

              Pharmacy educators, preceptors, and mentors must realize the significance of IPPE and APPE rotations and their influence in shaping future pharmacists’ professional identities. Professional identity formation is essential for students’ transformation into successful and compassionate pharmacists. IPPE rotations with effective preceptors enable students to observe, participate, and reflect on various aspects of pharmacy practice. Often these exercises take very little time, and small actions can have tremendous impact. Through exploration, reflection, and commitment to the profession, students can develop professional identities that align with the core values and beliefs of the pharmacy profession and their own personal values.

               

              As students grow throughout their educational and professional careers, they will internalize what it means to be a pharmacist. Changes may not be apparent in the short amount of time a preceptor is with a student. If students are comfortable with the idea, preceptors can connect with them on LinkedIn, stay in contact through email, and be open to being a mentor to the student after the rotation ends. Pharmacy is a profession of many interconnected individuals with unique and valuable professional identities.

               

               

              Pharmacist Post Test (for viewing only)

              Who are you? Who are We? Professional Identity in Experiential Learning

              Post-test

              After competing this continuing education activity, preceptors will be able to
              ● Describe professional identify formation
              ● Apply the steps in development of a professional identity
              ● Identify activities that develop professional identity appropriately

              1. Lyle is a preceptor whose student arrives to work wearing a tee shirt with a silly slogan on it, a ball cap, and brightly colored foam clogs. The student puts on a wrinkled and somewhat dirty white coat and steps out behind the register to start helping patients in the line. What is Lyle’s main concern with regard to this student?
              A. Professionalism
              B. Cleanliness
              C. Professional identity

              2. As the end of the day approaches, a prescriber calls in a set of prescriptions for a child who has a serious infection. Lyle assigns his student to check the dosing. The student asks if he can do the task tomorrow morning, as it's late and he'd like to head home for dinner. He also says that the prescriber probably double checked her own work. What is the BEST way for Lyle to explain the importance of completing the task today?
              A. Explaining that one never knows when a patient will arrive to pick up prescriptions and how that reflects on the pharmacy staff. He is trying to help develop the student’s professionalism.
              B. Explaining that most prescribers rarely double check their own work so the pharmacy needs to do it before the prescriber leaves for the day. This encourages professional identity formation.
              C. Explaining that pharmacists have a duty to be diligent about medication doses, especially in pediatric patients. This should contribute to the student’s professional identity formation.

              3. Mr. Walker, a patient who has successfully overcome an addiction to heroin, presents a prescription for oxycodone after having dental work. He wants to talk to the pharmacist, and you invite your student to join you. Mr. Walker asks if the prescription is for an addictive substance and says that the dentist never asked if he had a current or previous addiction problem. He would like you to call the dentist and have the prescription changed. You agree, and when you return to the pharmacy, your student asks, “Why don't you have him call the dentist himself? We're really busy.” What part of the pharmacist core values should you discuss with this student?
              A. Pharmaceutical expertise
              B. Commitment to the patient’s well-being
              C. Social responsibility

              4. Which of the following describes Step 2 in Kegan’s Stages of Personal and Professional Identity Development?
              A. A student's primary concern is understanding others’ values and expectations.
              B. A student's primary concern is ensuring the team approves of her work.
              C. A student’s primary concern is in learning and following the rules of dispensing.

              5. Which of the following accurately represents the sequence in which students can be expected to develop professional identity?
              A. Learning the rules of pharmacy; learning to differentiate between right and wrong and working with other team members; removing emotion and using reason to make decisions
              B. Learning to differentiate between right and wrong and work with other team members; removing emotion and using reason to make decisions; learning the rules of pharmacy
              C. Removing emotion and using reason to make decisions; learning the rules of pharmacy; learning to differentiate between right and wrong and work with other team members

              6. Which of the following accurately describes PIF opportunities in the pharmacy?
              A. Preceptors who take IPPE students should use the simplest of examples to help students with PIF because students have little experience.
              B. Preceptors should concentrate on situations that are complex so that students see pharmacists practicing at the top of their licenses.
              C. Preceptors can use simple everyday tasks to help students understand the pharmacist's role and develop their professional identities.

              7. Which of the following activities would be MOST appropriate for an IPPE student who has never worked in a pharmacy with regard to professional identity formation?
              A. Having the student observe a controlled substance inventory and asking questions like, “Why do you think we conduct an inventory every day? What would we do if we found a discrepancy?”
              B. Having the student observe a technician who is running the cash register and coaching the technician to ask questions like, “Do you have any experience running a cash register or dealing with customers?”
              C. Having the student restock the OTC section of the pharmacy and make a list of OTCs that need to be ordered, and asking the student to justify her reasons for ordering the various drugs and the quantity she designates.

              8. Which of the following activities is MORE appropriate for an APPE student than an IPPE student to develop professional identity?
              A. Reviewing the case of a patient with drug resistant tuberculosis and several drug allergies and presenting the case on medical rounds with physicians and nurses
              B. Checking that the dose of amoxicillin for a 5-year-old child who weighs 36 pounds is correct and that the child has no allergy to penicillin antibiotics
              C. Asking the student to shadow you while you provide counseling to a patient who has a question about OTC cough and cold formulations

              9. A new IPPE student has a casual attitude about pharmacy and expresses opinions that indicate that she knows very little about professional responsibilities. Several times and despite gentle correction, she has counted controlled substances incorrectly and returned control substance bottles to the regular shelves, not the vault. Which of the following activities might increase her awareness of the pharmacist’s responsibilities and legal obligations?
              A. Having the student accompany you to your state’s Board of Pharmacy meeting
              B. Abandoning formative feedback and pointing out the student’s errors forcefully
              C. Restricting this student’s activity to handling the front end of the store only

              10. Your state announces that it will now impose significant restrictions on all prescriptions for a certain drug because of a growing number of patient deaths related to its abuse. During the morning huddle, your staff discusses the increased paperwork burden and the potential that patients will be upset. After the huddle, the student asks, “Why is this our problem? Shouldn't this be handled by the drug’s manufacturer?” What is the best answer?
              A. Technically pharmacists are nothing more than the medication police. Our job is to enforce the rules other create strictly and unemotionally.
              B. In an ideal world, pharmaceutical companies would take complete responsibility for the damage their drugs do. This is not an ideal world.
              C. Pharmacists are part of a complex system of drug distribution. We need to establish our core values and uphold them to keep society’s respect.

              References

              Full List of References

              REFERENCES
              1. Larose-Pierre M, Cleven AJ, Renaud A, et al. Reevaluating core elements of emotional intelligence in professional identity formation for inclusion in Pharmacy Education. American Journal of Pharmaceutical Education. 2023;87(6):100082. doi:10.1016/j.ajpe.2023.100082
              2. Kellar J, Paradis E, van der Vleuten CPM, oude Egbrink MGA, Austin Z. A historical discourse analysis of Pharmacist Identity in Pharmacy Education. American Journal of Pharmaceutical Education. 2020;84(9). doi:10.5688/ajpe7864
              3. Jarvis‐Selinger, S., Pratt, D.D., and Regehr, G. (2012). Competency is not enough: integrating identity formation into the medical education discourse. Academic Medicine 87: 1185
              4. Toklu HZ, Hussain A. The changing face of pharmacy practice and the need for a new model of pharmacy education. J Young Pharm. 2013;5(2):38-40. doi:10.1016/j.jyp.2012.09.001
              5. Kruijtbosch M, Göttgens-Jansen W, Floor-Schreudering A, van Leeuwen E, Bouvy ML. Moral dilemmas reflect professional core values of pharmacists in community pharmacy. Int J Pharm Pract. 2019;27(2):140-148. doi:10.1111/ijpp.12490
              6. https://www.ashp.org/-/media/assets/policy-guidelines/docs/endorsed-documents/code-of-ethics-for-pharmacists.ashx
              7. Johnson JL, Arif S, Bloom TJ, Isaacs AN, Moseley LE, Janke KK. Preparing pharmacy educators as expedition guides to support professional identity formation in Pharmacy Education. American Journal of Pharmaceutical Education. 2023;87(1). doi:10.5688/ajpe8944
              8. Kegan, R. (1982). The Evolving Self: Problem and Process in Human Development. Cambridge, MA: Harvard University Press
              9. Irby, D.M. and Hamstra, S.J. (2016). Parting the clouds: three professionalism frameworks in medical education. Academic Medicine 91: 1606–1611
              10. Swanwick T, Forrest K, O’Brien BC, Cruess RL, Cruess SR. The Development of Professional Identity. In: Understanding Medical Education: Evidence, Theory and Practice. Wiley-Blackwell; 2019:239-254.
              11. Hafferty, F.W. (2016). Professionalism and the socialization of medical students. In: Teaching Medical Professionalism (ed. R.L. Cruess, S.R. Cruess and Y. Steinert), 54–68. Cambridge: Cambridge University Press.
              12. Briceland LL, Martinez T. Exploring the impact of reflecting upon pharmacy experts’ written career guidance on Student Professional Identity Formation. INNOVATIONS in pharmacy. 2022;13(3):5. doi:10.24926/iip.v13i3.4778
              13. Arnoldi J, Kempland M, Newman K. Assessing student reflections of significant professional identity experiences. Currents in Pharmacy Teaching and Learning. 2022;14(12):1478-1486. doi:10.1016/j.cptl.2022.10.003
              14. Janke KK, Bloom TJ, Boyce EG, et al. A pathway to professional identity formation: Report of the 2020-2021 AACP student affairs standing committee. American Journal of Pharmaceutical Education. 2021;85(10). doi:10.5688/ajpe8714
              15. Luyckx K, Goossens L, Soenens B, Beyers W. Unpacking commitment and exploration: Preliminary validation of an integrative model of late adolescent identity formation. Journal of Adolescence. 2005;29(3):361-378. doi:10.1016/j.adolescence.2005.03.008

              16. AFPC Educational Outcomes for First Professional Degree Programs in Pharmacy in Canada 2017. Association of Faculties of Pharmacy of Canada. Accessed August 26, 2023. http://www.afpc.info/system/files/public/AFPC-educational%20Outcomes%202017_final%20Jun2017.pdf
              17. Elnicki DM. Learning with emotion: which emotions and learning what? Acad Med 2010;85:1111.
              18. Poulsen L, Brosen K, Arendt-Nielsen L, et al. Codeine and morphine in extensive and poor metabolizers of sparteine:pharmacokinetics, analgesic effect and side effects. Eur J Clin Pharmacol. 1996. 51(3-4): 289-295.
              19. Caraco Y, Sheller J, and Wood AJ. Pharmacogenetic determination of the effects of codeine and prediction of drug interactions. J Pharmacol Exp Ther. 1996. 278: 1165-1174.
              20. Lalovic B, Phillips B, Resler LL, et al. Quantitative contribution of CYP2D6 & CYP3A4 to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004. 32: 447-454.
              21. Campfield KM, Hills AM. Effect of timing of critical incident stress debriefing (CISD) on posttraumatic symptoms. J Trauma Stress. 2001;14(2):327-340. doi:10.1023/A:1011117018705
              22. Formative Assessment and Feedback. Stanford | Teaching Commons. Accessed August 16, 2023. https://teachingcommons.stanford.edu/teaching-guides/foundations-course-design/feedback-and-assessment/formative-assessment-and-feedback#:~:text=Formative%20feedback%20helps%20students%20recognize,to%20meet%20the%20course%20outcomes.
              23. Formative and Summative Feedback. Teaching@Tufts. Accessed August 6, 2023. https://sites.tufts.edu/teaching/assessment/assessment-approaches/formative-and-summative-feedback/.
              24. Mann B. 3 of America's biggest pharmacy chains have been found liable for the opioid crisis. November 23, 2023. Accessed August 16, 2023. Ohio jury holds CVS, Walgreens and Walmart liable for opioid crisis : NPR
              25. Wile R. CVS and Walgreens to pay a combined $10.7 billion settlement for alleged opioid prescription lapses. December 12, 2022. Accessed August 16, 2023. CVS, Walgreens to pay $10.7 billion for alleged opioid prescription lapses (nbcnews.com)

              Considerations in Veterinary Compounding

              Learning Objectives

               

              After completing this application-based continuing education activity, pharmacists and pharmacy technicians will be able to

              1.     List food items which may be harmful to certain pets
              2.     Identify additives which should not be used in veterinary compounding
              3.     Discover when veterinary compounding is acceptable
              4.     Recognize federal laws pertaining to veterinary compounding
              5.     Investigate labeling requirements for veterinary compounds

               

                Watercolor cat veterinarian treating smaller cat.

                 

                Release Date: October 15, 2023

                Expiration Date: October 15, 2026

                Course Fee

                Pharmacists: $7

                Pharmacy Technicians: $4

                There is no funding for this CE.

                ACPE UANs

                Pharmacist: 0009-0000-23-046-H07-P

                Pharmacy Technician: 0009-0000-23-046-H07-T

                Session Codes

                Pharmacist:  23YC46-BMX34

                Pharmacy Technician:  23YC46-XBM78

                Accreditation Hours

                2.0 hours of CE

                Accreditation Statements

                The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-047-H07-P/T  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

                 

                Disclosure of Discussions of Off-label and Investigational Drug Use

                The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

                Faculty

                Laura Nolan, CPhT, CSPT
                Academic Assistant
                UConn School of Pharmacy
                Storrs, CT

                Faculty Disclosure

                In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

                Laura Nolan does not have any relationships with ineligible companies.

                 

                ABSTRACT

                With an estimated 65.1 million households with dogs and another 46.5 million households with cats in the U.S., veterinary practices are booming with business. Knowing what to feed them and how to keep them well is becoming increasingly important in compounding pharmacies.

                CONTENT

                Content

                Introduction:

                For many people, pets are a major part of everyday life. They become part of their households and are like family, but like children, none of them come with true owner’s manuals. Sure, there are many books on the subject, but who do you trust? And who has the time to read all that stuff? What happens if or when they become sick or injured and need medication?

                As a somewhat reticent parent of a very large Weimaraner (OK, my husband and daughter bought him without my knowledge), I was forced to learn rather quickly about the ins and outs of pet ownership. Still, he arrived, and we needed to determine what’s best for this 99-pound dufus, who amazingly survived eating an entire box of oatmeal raisin cookies. It wasn’t pretty, but that story is reserved for an antidote CE.

                At the University of Connecticut School of Pharmacy, advanced compounding students are trained in some veterinary compounding, but most pharmacy schools do not teach it. This is a bit upsetting since people spend millions of dollars on pets every year. An estimated 65.1 million households are home to dogs and another 46.5 million households have cats in the U.S. With pet ownership comes the responsibility of caring for them. The average cost of veterinary care for a dog is $730 per year, with cats averaging $253 per year. In 2022, Americans spent $136.8 billion dollars on their pets.1

                Increasingly, pharmacy staff need to know some basics about companion animals and their health issues. Pet owners can request a paper prescription from the veterinarian and fill it at community pharmacies. The American Veterinary Medical Association (AVMA) incorporated prescription guidelines into their 1991 bylaws. It states that “a veterinarian shall honor a client's request for a prescription or veterinary feed directive in lieu of dispensing but may charge a fee for this service.”2 What do you do when a pet owner brings a prescription to your pharmacy?

                People’s perceptions about feeding human food to dogs and cats are surprising. An old wives’ tale, passed from generation to generation, tells us that dogs can eat just about anything, including bones. Most of us now know that sharp bone shards can penetrate the soft tissues at the back of the throat, they can lodge in the esophagus, or they can pierce the intestines. It is also possible for a piece of bone to lodge in the trachea (windpipe), interfering with a dog’s ability to breathe.3 The controversy still continues today, but no pet owner wants their pet to have broken teeth, mouth injuries, or intestinal blockages if they can avoid it. If cooked bones are out, what else is bad for them? Certain foods create a risk for most pets, so compounders must not use these items as ingredients in their compounds. Table 1 contains a list of some human foods that should be avoided in pets.

                Table 1. Human Foods That Should Not Be Given to Pets4

                 

                Food Item Type of Pet Toxicity/Reasoning
                Alcohol Dogs, cats, chickens, rabbits Alcohol poisoning
                Tobacco Dogs, cats Nicotine
                Onions, chives, garlic (Allium family) Dogs, cats, chickens,  rabbits Sulfates, disulfides
                Avocado Dogs, cats, chickens, horses, cows, pet birds Persin
                Salt Dogs, cats, chickens Fluid imbalance
                Spicy foods Dogs G.I. upset
                Grapes, raisins Dogs, cats, rabbits Kidney failure
                Caffeine Dogs, cats, rabbits Methylxanthines
                Chocolate Dogs, cats, horses, rabbits Theobromine and caffeine
                Citrus fruits Cats, chickens Citric Acid, essential oils
                Cinnamon Dogs, cats Mouth and throat irritant
                Nutmeg Dogs, cats Myristicin
                Macadamia nuts Dogs, cats Toxicity unknown
                Mushrooms Dogs, cats Mycotoxins
                Green tomatoes, raw potatoes Dogs, cats, chickens, horses, rabbits Solanine
                Raw bread dough, raw yeast, bread Dogs, cats, horses, rabbits G.I. upset, bloating, empty calories
                Rhubarb Chickens, rabbits
                Dairy items, ice cream Dogs, cats, chickens, horses, rabbits High sugar, high fat, lactose intolerance. Adult cats become lactose intolerant
                Sugar free gum and sugar free candy Dogs, cats Xylitol
                Seeds and Pits Dogs, cats, chickens, horses, rabbits Cyanide
                Turkey skin, chicken skin, ham Dogs, cats, rabbits High fat content, can cause acute pancreatitis
                Marijuana Dogs, cats, horses, rabbits Tetrahydrocannabinol (THC)

                 

                Items like alcohol, tobacco, caffeine, and chocolate make sense. Alcohol and tobacco affect dogs and cats as they do humans, but our pets are much smaller, so it takes significantly less alcohol or tobacco to cause catastrophic events such as breathing problems, vomiting, diarrhea, coma, or even death. Dogs are curious, and a tobacco or marijuana “cigarette” on the ground might be pretty tasty. The average tobacco cigarette contains 10 to 12 milligrams of nicotine. A toxic dose of nicotine for a pet is 0.5 to 1 milligram per pound, and a 4-milligram dose per pound can be lethal.5 Doing some quick math, consuming as little as three or four cigarettes could be fatal to a 10-pound dog.

                Vaping has become extremely popular, which has caused an increase in nicotine poisonings. An average 6 mL, 5% nicotine e-cigarette can contain up to 300 mg of nicotine. Pets can be subjected to nicotine poisoning by secondhand smoke, through spillage on skin, and by drinking the vaping liquid. Consider this: a 40-pound dog would only need to be exposed to a 1 mL dose for it to become poisoned.5 Nicotine is not the only toxin in e-cigarettes. They also contain volatile organic compounds, heavy metals (e.g., cadmium, copper, lead, nickel, tin) and they contain propylene glycol. All of these components are harmful to pets.

                Those other “cigarettes” can be pretty tasty too. Marijuana use is on the rise in the U.S. since it is now legal in more than 21 states, and for the first time, it has now made its way onto the list of the top 10 items that cause pet poisonings. The two major components of marijuana are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). CBD is nontoxic to animals, whereas THC is the psychoactive ingredient that is extremely toxic. CBD is widely advertised for human and pet use, but consumers must read labels carefully. Most CBD products are not entirely pure. They contain small amounts of THC.6

                Although secondhand smoke and consuming raw marijuana leaves can be toxic, the most reported intoxications come from pets eating infused edibles. Edibles like brownies, cookies or gummies are made with concentrated THC infused oils or THC-infused butter. They tend to be a more significant threat since most edibles also contain chocolate or xylitol.7  If pets exhibit any symptoms, they should be taken to a veterinarian. THC poisoning closely mimics the signs of antifreeze poisoning which is fatal and an antidote needs to be given as quickly as possible.6,7

                Symptoms of marijuana intoxication can become visible within 30 to 60 minutes after ingestion. Pets may stumble and cross their feet, walking as if they were drunk, they may have enlarged pupils, become lethargic and flinch in reaction to sudden movements. Pets with severe cases of intoxication may vomit, have tremors, shake uncontrollably and in extreme cases become comatose. Roughly 50% of dogs develop urinary incontinence and dribble urine uncontrollably (which might make the drug less popular if this happened in humans).7

                Some medications contain significant amounts of alcohol. If unsecured, a dog or cat could consume them. Certain formulations of diphenhydramine (Benadryl, Sominex), guaifenesin with codeine (Cheracol Plus), dextromethorphan, guaifenesin, pseudoephedrine combinations (Dimetane, Robitussin, Triaminic, Vicks), hydrocodone and pseudoephedrine combinations (Novahistine), and certain multivitamin liquids (Geritol) contain alcohol. Some remedies can contain up to 25% alcohol, which can harm pets (and children).8  Alcohol is sweet tasting to dogs, so they will not stop drinking it until it is all gone.

                Caffeine and chocolate ingestion should also be taken seriously. Caffeine contains methylxanthines, which can cause bronchodilatory and stimulatory effects in humans. In animals, they can also cause vomiting, diarrhea, hyperactivity, seizures, and cardiac arrhythmias. Chocolate, derived from the roasted seeds of Theobroma cacao, contains methylxanthine, theobromine, and caffeine. The theobromine content in chocolate is three to ten times that of caffeine. Cats do not have taste buds that can detect sweetness, but dogs do have a sweet tooth and love the taste of chocolate. One ounce (28 grams) of chocolate could be a lethal dose in a small dog. Theobromine has a half-life of two to three hours in humans, but it is longer in dogs. The half-life of theobromine in dogs is 17.5 hours.9,10 The SIDEBAR provides more information about chocolate toxicity in dogs.

                 

                How Much Chocolate is Too Much?10,11

                Different cocoa beans and chocolate products contain various amounts of methylxanthines. Compounders and veterinary care providers must consider the dog or cat’s weight and the amount of chocolate consumed.

                Methylxanthine doses of 15 mg/kg (7.5 mg per pound) or less should not harm a dog. This is equivalent to one square of dark chocolate for a 3 kg (6 lb.) dog or seven squares of chocolate for a 15 kg (33lb.) dog. One square of chocolate is approximately 6 grams (0.21 oz). This formula calculates the dose consumed:

                Theobromine dose = concentration in type of chocolate x amount eaten/weight

                Caffeine dose = concentration in type of chocolate x amount eaten/weight

                Theobromine + caffeine = Total methylxanthines

                The caffeine and theobromine amounts in the specific type of chocolate may be on the label, and the Table10 below provides some information about common products. However, in emergencies, healthcare providers can use calculators on the Internet that performs this calculation quickly and efficiently. This is not to say that cats never get into chocolate and get sick. There are also cat chocolate toxicity calculators online in case of emergency.

                Methylxanthines in Chocolate 10

                Product Methylxanthines per 1 gram chocolate mg methylxanthines /ounce of chocolate
                Dry cocoa powder 28.5 mg 800 mg
                Unsweetened bakers chocolate 16 mg 450 mg
                Milk Chocolate bar 2.3 mg 64 mg
                Dark Chocolate bar 5.7 mg 150- 160 mg
                Cocoa bean hulls (mulch) 9.1 mg 225 mg
                White chocolate Negligible

                 

                Excess salt (sodium chloride) can cause fluid imbalances which could lead to seizures and spicy foods can cause painful vomiting, diarrhea, or stomach ulcers. Dogs, cats, and even birds are very sensitive to salt, so pet owners and compounders should be aware of common items that contain large amounts of salt. For example, sea water, baking soda, homemade play dough, and driveway deicer all contain high concentrations of salt. Sodium chloride poisonings in dogs are most often caused by pet owners who use salt to induce vomiting after the dog has ingested a different toxin. It is important to consult with a veterinarian or pet helpline before administering any type of antidote.12

                Even seemingly harmless spices can be harmful. Cinnamon can cause mouth irritations and nutmeg, which contains myristicin, can cause hallucinations in smaller animals. Mushrooms contain mycotoxins which can also cause hallucinations, diarrhea, vomiting, or kidney failure and in extreme cases, liver failure.4

                Although more toxic to cats than dogs, onions, chives, garlic,  and all members of the allium family of herbs contain sulfoxides and disulfides, and an oxidant called n-propyl disulfide. These can cause a fatal anemia, called oxidative hemolysis, which affects dogs, cats, rabbits and chicken. Signs of anemia may take several days to appear.4,17,18  If a dog is fed a little garlic once in a while it should not be a problem but avoid giving pets garlic supplements. It was once believed that garlic supplements given to dogs could help to repel fleas and ticks, but this has now been proven to be ineffective.13

                Other problematic vegetables include green tomatoes, raw potatoes, and avocado. The tomato plant’s green parts, its stems and leaves, and raw potatoes contain solanine. Solanine is poisonous, even to humans. It has pesticide-like properties and is part of the plant’s natural defenses. Solanine can be found in green potatoes and potato tubers (eyes).14 It is also found in other members of the nightshade family (e.g., eggplant skin).

                Avocado is only slightly dangerous to dogs and cats, but extremely dangerous to birds and large animals such as cows, goats, sheep and horses. The bark, leaves, skin, pits and fruit of the avocado contain persin, which is a fungicidal toxin. Persin is an oil soluble compound that seeps into the fruit from the large seed inside. It is similar in structure to a fatty acid, and is harmless to humans, but toxic to most animals. Symptoms of persin toxicity range from edema and mastitis to respiratory distress and heart failure.15,16

                Chickens, which are increasingly popular in back yards, are sensitive to many food items. They should not be fed most human foods, but especially avoid feeding them citrus fruits, uncooked rice and uncooked dried beans, fruit seeds and pits, tomato leaves, green potatoes, and rhubarb.17 Rhubarb’s high oxalic acid content binds to minerals and can form kidney stones. Although high in calcium and phosphorus, certain dried beans are acidic and contain hemagglutinin. Hemagglutinins bind to receptors on red blood cells to initiate viral attachment and infection.

                Rabbits, guinea pigs, and most herbivores have similar dietary restrictions. Fruit seeds and pits contain small amounts of cyanide, which can be a concern to smaller animals. Cabbage, cauliflower, other gassy vegetables and iceberg lettuce must be avoided. Iceberg lettuce contains lactucarium. Lactucarium (also called lettuce opium), a milky fluid excreted near the base of the lettuce plant, has sedative properties. Rabbits and other herbivores should stick to darker greens.18

                Factors That Influence Toxicity

                Each species of animal reacts to toxins differently due to variations in absorption, metabolism, or elimination. The dose of toxin per body weight is a major concern. Other factors include the animal’s age, size, nutritional status, stress level, and overall health. For example, most young animals do not have a fully developed system of metabolism, which may cause a toxin to remain in their system longer, causing more harm. Horses, rabbits, and small rodents do not have the ability to vomit, which means that they may be poisoned at a lower dose.19

                One must also consider the chemical nature of a food, drug or poison that is consumed. If the drug or toxin dissolves in water easily, it will spread throughout the body easier. If there are substances added to an active ingredient, such as a binding agent or outer coating, or if it is a sustained release product, it will affect absorption.19 Overall, pharmacists should become familiar with species specific toxins and the factors that affect the risk of toxicity. Animals absorb, distribute, metabolize, and eliminate medications and toxins differently from humans, and the interspecies differences are also notable. See the SIDEBAR for a list of the top ten toxic items.

                 

                ASPCA: The Official Top 10 Toxins of 202220

                Each year, the Animal Poison Control Center of America (ASPCA) compiles a yearly list of toxic items. They received 335,136 pet poisoning calls in 2022 and have tabulated the results as follows:

                1. Over the Counter Medications. Ibuprofen and acetaminophen are the most common.
                2. Food items. Protein bars, xylitol, grapes and raisins top the list.
                3. Human prescription medications
                4. ASPCA received approximately five calls per hour regarding chocolate.
                5. Plants
                6. Household chemicals. Disinfecting wipes top the list.
                7. Veterinary products
                8. Rodenticides
                9. Insecticides. Ant baits are an example.
                10. Recreational drugs. Edible THC products are the most common.

                 

                Evolution has influenced species-specific diets. Dogs have evolved to become opportunistic gorgers, while cats are very picky. A dog will eat every bit of chocolate once he starts, which is the reason why dog poisonings are more common. Cat poisonings are less common and are usually the result of intentional harm by human beings.

                Pause and Ponder: Have you tried to give a dog a tablet or capsule? Did you wrap it in some meat or cheese? How did you get a cat to take his dose?

                When to Compound

                Pharmacists should consider compounding veterinary products under three conditions:

                1. When a commercial product is unavailable. This could be due to drug recalls, drug shortages, or because a commercial product has yet to be developed. In some cases, rapid changes in disease state management create an urgent need for medication.
                2. When an approved drug needs to be modified. This would include an increase or decrease in dosage due to a lack of appropriate dosage size, or a lack of formulation for a desired route, for example, making a dilution, adding flavoring, or changing the form of the drug. A popular compounding task is changing a tablet into a suspension.
                3. When the likelihood of nonadherence is high. Owners’ adherence is greater when they can administer one combination product instead of two or three. For example, combining two injectable vaccines or allergy medications into one syringe for ease of use would be helpful to the pet owner. Of course, it is also more beneficial to the animal, since it will minimize harm and stress, which will lead to a better prognosis. Our students have recently formulated a compound of ketoconazole, gentamicin sulfate, and mometasone furoate all in one for a dog with an external ear bacterial yeast infection.

                Dogs and cats can be very particular, and their sense of smell will give that medication away every time. This means that compounding must be creative. The most popular forms of medications for veterinary consideration include capsules, transdermal medications, flavored liquids, tablets, chews, or treats. Oral formulations can be difficult to give, but devices such as droppers, mechanical pill injectors, oral syringes, and oral pastes and gels can mask medications. Pill pockets—soft, flexible treats—can be molded around a tablet or capsule. Medicated oral pastes and gels, when placed on a cat’s paw, are an ingenious way for the cat to lick his medicine up. Compounders make a variety of products from hairball pastes and pectin gels, used for diarrhea, to dental licks and probiotic powders which are placed on a cat’s fur.

                Human compounding caters to the customer, and the same is true for pets. Tuna or salmon flavoring attracts cats; beef or chicken flavoring may fool dogs; and birds love seeds. Other ingredients can be rather generic. Compounders can choose from a myriad of thickeners, sweeteners, and preservatives. Choosing the correct excipient could be crucial.

                Pause and Ponder: Take another look at the list of forbidden foods. Which items on your pharmacy compounding shelf could be harmful to pets?

                Ingredients for veterinary compounding

                In human compounding we tend to lean toward avocado or grapeseed oil to soothe and treat the skin, which are lighter than other oils. We use alcohol, propylene glycol, polysorbate 80 (Tween 80), and essential oils in compounds and peanut butter quite often for dog treats. These may not be the best choices in some veterinary situations. Let’s look at what is safe and what should not be used for pets.

                Sweeteners

                Sugar substitutes are game changers for people who have diabetes or are on low calorie diets. Xylitol is a current human favorite, occuring naturally in small amounts in berries, cauliflower, corn, mushrooms, oats, plums, and pumpkins. In industrial production, the purest form is extracted from raw biomass materials such as hard and soft wood, and especially from the birch tree. More economical processing uses hydrolyzed, purified agricultural corn, wheat, and rice waste. Economists expect xylitol production to become a $1.4 billion industry by 2025.21 Why the increase in popularity? Xylitol contains two-thirds of the calories of sucrose and has a mild increased saliva effect. Unfortunately, xylitol is extremely toxic to dogs.

                When dogs consume xylitol, it is quickly released into the bloodstream, causing an immediate and potent release of insulin from the pancreas. This leads to severe hypoglycemia, with onset that can occur anywhere from 10 to 60 minutes after ingestion. Without treatment, the dog may develop liver failure, have seizures, or become comatose.22

                Products that contain xylitol are ubiquitous. It’s found in foods such as barbeque sauce, candy, gum, jam, ketchup, low calorie maple syrup, and peanut butter (meaning that compounders who use peanut butter need to check labels carefully; xylitol may be listed as 1,4-anhydro-d-xylitol, anhydroxylitol, birch bark extract, birch sugar, D-xylitol, Xylite, xylitylglucoside, or zylatol). In fact, sugar-free gum is the most common source of xylitol poisoning in dogs. For example, one piece of gum or one breath mint can be fatal to a 10-pound dog. The Pet Poison Helpline responded to 5,846 xylitol poisoning cases in 2020.22

                Xylitol can also be found in many pharmaceuticals and personal care products: cough syrup, deodorant, digestive aids, gummy vitamins, laxatives, mouthwash, nasal sprays, shampoo, skin care products, sleep supplements, toothpaste, and especially orally dissolving tablets. Small traces of xylitol can even be found in prescription medications.22 Gabapentin tablets and capsules do not contain xylitol, but gabapentin oral solution contains xylitol. The side bar discusses one xylitol poisoning case.

                 

                SIDE BAR: POOR MIMI23

                In 2020, Mimi, a pet poodle passed away after receiving gabapentin. The veterinarian prescribed gabapentin oral solution, for ease of use and medication adherence for Mimi’s seizures. The owner administered the dose and Mimi’s seizures increased, so the owner called the veterinarian, who increased the dose of medication to be given. Within 24 hours Mimi was gone.

                How could this happen?

                Many veterinarians are unfamiliar with the added ingredients in human formulations. Also, drug manufacturers may change sweeteners without notice. A retail pharmacist filled her prescription for gabapentin oral solution with the commercially available product, which contained xylitol.  When the dogs owners went to the pharmacy to investigate, they found several factors which caused the problem.

                • They were told that the pharmacist did not know that the solution contained xylitol and he was also unaware that xylitol was harmful to dogs.
                • The pharmacy had no drug utilization reviews processes in place for veterinary drugs.
                • The existing built-in computer software was not programmed to issue alerts for xylitol or other veterinary toxins.
                • The pharmacy did not have a veterinary drug reference book, for example, Plumbs Veterinary Medicine, or a veterinary drug formulary. Unfortunately, the majority of state boards of pharmacy do not require pharmacies to carry a veterinary drug reference book.

                Pharmacists and pharmacy technicians need to be aware of additives in human drug formulations that can be harmful to pets. Mimi’s death could have been avoided.23

                 

                Many other sugar substitutes are considered safe to use in veterinary compounding. Erythritol, a sugar used mainly in keto desserts and baked goods, is safe in small amounts. Stevia and aspartame are also considered safe to use, although pets may experience stomach aches or slight diarrhea. Saccharin (Sweet-n-Low), sucralose (Splenda), or monk fruit, a newer sweetener, are all considered safe in pets.24 Dogs have more of a sweet tooth than cats, but in general, sweeteners should be kept to a minimum.

                Flavors

                Using an optimal flavor profile helps mask the active ingredient’s taste and will promote animal adherence. Compounders should use only flavorings that are intended for compounding use. They shouldn’t use meat-flavored bouillon cubes or bouillon powders for compounding since they contain high amounts of salt, onion powder, and other harmful spices. Table 2 lists common flavorings and the species that find them enjoyable.

                 

                Table 2. Common Flavorings for Pets25

                Animal Flavor Reasoning
                Birds Banana, grape, orange, raspberry, tangerine, tutti-fruiti, piña colada Birds prefer sweet and fruity flavors
                Dogs Bacon, beef, liver, chicken, turkey, cheese, peanut butter, molasses, caramel, anise, marshmallow, raspberry, strawberry, honey Dogs prefer meats and sweets
                Cats Fish, liver, tuna, cod liver oil, sardines, mackerel, salmon, beef, chicken, cheese, bacon, molasses, peanut butter, butterscotch, marshmallow Cats do not like very much sweetness but hate bitterness
                Gerbil Banana cream, orange, peach, tangerine, tutti-fruiti Gerbils like sweet and fruity flavors
                Iguana Banana, cantaloupe, kiwi, orange, tangerine, watermelon, other melons Iguanas and most reptiles rely on their sense of smell more than taste, so it must smell good
                Rabbits Banana cream, carrot, celery, lettuce, parsley, pineapple, vanilla, butternut Find their favorite vegetable or fruit and use it
                Poultry Cantaloupe, corn, meal, milk, vanilla, butternut, watermelon Research is ongoing to determine the sense of taste in chickens.

                 

                Preservatives and Additives

                The Food and Drug Administration (FDA) maintains a list of additives generally recognized as safe (GRAS) for use in pet foods. Manufacturers must submit food additives used in their pet foods for FDA review, which if approved, are added to the GRAS list.26

                Still, many excipients should not be used for veterinary compounding 27,28,31

                • Butylated hydroxyanisole (BHA)
                • Butylated hydroxytoluene (BHT)
                • Ethoxyquin
                • Propylene glycol
                • Polysorbate 80 (Tween 80)

                BHA and BHT are preservatives that are added to oils and rendered fats in certain pet foods and treats. They have been found to be carcinogens and can cause liver and kidney damage in rats, but the FDA has cleared them for use in small amounts in pet foods and treats. Ethoxyquin, a preservative, is used as a hardening agent. It is also used in pesticides and rubber and is illegal for human use, yet the FDA has ruled the additive “may be safely used in animal feeds” when used according to regulations.27 Which is the best preservative to use? The answer is to stick to more natural preservatives. Vitamin C and E are great choices, as are lemon, except for use in cats and chickens, and honey. Honey is packed with vitamins A, B, C, D, E, and K and also contains potassium, calcium, magnesium, copper, and antioxidants. Giving a pet a small amount of honey can even help to build immunity from some allergens, such as pollen.29

                Propylene glycol is a controversial excipient used as a humectant, or moisturizing agent, in many pharmaceutical formulations. Propylene glycol is derived from ethylene glycol, which is antifreeze’s main component. Small amounts may be used in dog formulations, but it is extremely toxic to cats. Extended exposure to propylene glycol over several years has been shown to cause seizures and possible blood disorders in both dogs and cats.28 Cats may develop Heinz body hemolytic anemia, which can lead to death.

                Cats and dogs are also extremely reactive to essential oils. Popular essential oils (e.g., eucalyptus oil, peppermint oil, tea tree oil) can be found in some natural flea repellents, perfumes, and aromatherapy products. These are safe to use in humans and can be found in many topical preparations; using these oils in topical preparations for dogs or especially cats (since they are continual groomers), can be harmful. Signs of toxicity are lethargy, depression, ataxia, tremors, seizures, or death.30

                Polysorbate 80 (Tween 80) is a surfactant used in soaps and as a lubricant in eye drops. It is also used as an excipient quite often to stabilize aqueous formulations of lipophilic drugs for vaccines and for parenteral administration. Many Chinese herbal injectable medications contain high amounts of polysorbate 80. When dogs are given intravenous (IV) medications that contain high levels of polysorbate 80, for example vitamin K, it causes systemic histamine release, which causes allergic reactions and tachycardia and may lead to an anaphylactic reaction.31

                Corn syrup is a cheap humectant, sweetener, and flavoring agent all-in-one, but it can be addictive to dogs and can increase blood sugar significantly. A vegetable-based glycerin, such as coconut glycerin is a better choice.32

                Food dyes and colorants should be used sparingly when compounding. Blue dye #2, red #40, yellow #5 and #6 can cause hypersensitivity or allergic reactions in some pets. Also, caramel color 4-methylimidazole (4-MIE) is under investigation as a possible carcinogen in pets.32 In actuality, pets do not care about the color of the compound. Artificial coloring only appeals to the pet owner.

                 

                When to Call a Professional

                When should pet owners or concerned pharmacy staff call a professional for a suspected pet poisoning? The sooner the better. The first call should be to the pet’s veterinarian, but national hotlines are also available for emergencies 24/7 for a fee.

                • ASPCA Animal Poison Control

                https://www.aspca.org/pet-care/animal-poison-control

                888-426-4435

                Free access to website

                $95.00 fee for hotline service

                *90% of the fee is covered with ASPCA insurance

                 

                • Pet Poison Helpline

                http://www.petpoisonhelpline.com

                855-746-7661

                Free access to website. $85.00 fee for hotline service

                 

                General Recommendations for Compounding

                Under the Federal Food, Drug, and Cosmetic Act (FD&C Act), the FDA permits compounding of animal drugs when the source of the active ingredient is a finished FDA-approved drug, and not a bulk drug substance (BDS), unless certain exceptions, described below, are followed. A “bulk drug substance” is a substance used to make a drug that becomes an active ingredient in the drug’s finished dosage form.33 Most pharmacists would recognize that as an active pharmaceutical ingredient (API).

                A commercially available drug may not always be available or appropriate for veterinary use. For example, an FDA-approved drug may have excipients or preservatives that are unsuitable for pets, the dose may be too large, or the flavoring may be unacceptable. In this case, the FDA has acknowledged the need for certain bulk drug substances. On April 14, 2022, the FDA released the Guidance for Industry (GFI #256), entitled “Compounding Animal Drugs from Bulk Drug Substances” which became effective in April 2023.The FDA has also created approved BDS lists for use in veterinary preparations.35  Separate BDS lists exist for non-food producing animals, for food producing animals, for veterinary office stock drugs, and certain wildlife species.36 GFI #256 allows pharmacies to purchase and use bulk drug substances from FDA-registered suppliers if a certificate of analysis (COA) is included with the compounding record. The FDA also requires compounders to report any adverse reactions to the FDA within 15 days. Veterinarians must also provide more patient specific detailed clinical information explaining why a pet cannot use an FDA approved manufactured product.

                The FDA has composed a check list for pharmacists regarding veterinary compounding.34

                1. Confirm whether patient(s) is a nonfood-producing animal or a food-producing animal. Make sure that chicken is just a pet! Food-production animals (cattle, chickens, etc.) have an additional set of rules (not discussed here). Check the FDA guidelines for more information.33
                2. Follow all state laws and regulations that apply to compounding animal drugs. Compounders need to check their state regulations. It appears that most states tend to merely restate FDA animal compounding guidance.
                3. Meet USP standards and FD&C Act requirements. Use FDA-approved drugs or FDA-approved BDS, follow USP guidelines and monographs, if they exist, and follow FD&C act requirements.
                4. Include all labeling information. See below.
                5. Dispense the compounded drug(s) to the patient’s owner or caretaker or the veterinarian who prescribed or ordered it. A valid veterinarian-client relationship must exist, and a veterinarian must provide a valid prescription.
                6. Report adverse events and product defects associated with the compounded drug to the FDA on Form FDA 1932a.
                7. Consider other FDA-approved options first. Check to see if alternative options are available. Compounding is permitted if the active ingredient is a different salt, ester, or other derivative.
                8. Determine if you are compounding a copy of an FDA-approved product. If the exact form of medication is commercially available, it cannot be compounded.
                9. Obtain a medical rationale and retain it in your records if a copy is needed. The rationale for the compound must be documented on the prescription.

                Other considerations include determining the physical and chemical compatibility of the drugs, the drugs’ solubility and stability, and the active ingredients’ pharmacodynamics.

                Labeling

                In addition to including the client's name on the label, the American Veterinary Medical Association (AVMA) recommends veterinarians and compounders in veterinary offices convey the following information to animal owners when prescribing all compounded preparations37:

                • Name, address, and telephone number of veterinarian
                • Identification of animal(s) treated, species, and number of animals treated, when possible
                • Date of treatment, prescribing, or dispensing of drug
                • Name, active ingredient, and quantity of the drug (or drug preparation) to be prescribed or dispensed
                • Drug strength (if more than one strength available)
                • Dosage and duration
                • Route of administration
                • Number of refills
                • Cautionary statements, as needed
                • Beyond-use date (BUD)
                • Slaughter withdrawal and/or milk withholding times, if applicable

                Per FDA regulations, pharmacies must include the following on the compounded drug’s labeling: name and strength or concentration of drug; species and name or identifier of patient(s); name, address, and contact information for the compounding pharmacy and name of the prescribing veterinarian; a beyond use date; the withdrawal time as determined by the prescribing veterinarian; and the following statements must be included33:

                • “Report suspected adverse reactions to the pharmacist who compounded the drug and to FDA using online Form FDA 1932a.”
                • “This is a compounded drug. Not an FDA approved or indexed drug.”
                • “Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.”

                CONCLUSION

                On June 10, 2021, the FDA finalized Guidance for Industry (GFI) # 263, (not to be confused with GFI #256 which was mentioned previously) requesting that participating animal drug companies voluntarily transition certain antimicrobials from over-the-counter availability to veterinary prescription within two years. The aim of this guidance is to decrease antibiotic resistance in animals, and the target date to introduce new prescription labels onto the market was June 11, 2023.38 These include well known antibiotics such as erythromycin, gentamicin, penicillin, sulfamethoxazole, and tetracycline. This FDA requirement is now in effect for food-production animals and pets, and it may be one reason why many pharmacies have seen an increase in pet prescriptions. Another reason may be that more pet owners trust their local pharmacy to prepare the correct formula for their furry family members.

                The field of veterinary medicine is expanding seemingly daily, and it is a field where compounding pharmacies can be instrumental. Veterinary compounding has its challenges, but when collaborating with a veterinarian, the compounder can impart professional judgment to ensure that the compound is safe, effective, and therapeutic. That’s a rewarding practice in the end.

                 

                 

                 

                Pharmacist Post Test (for viewing only)

                Considerations in Veterinary Compounding
                Post-test
                Learning Objectives: After completing this continuing education activity, pharmacists and pharmacy technicians will be able to
                1. List food items which may be harmful to certain pets
                2. Identify additives which should not be used in veterinary compounding
                3. Discover when veterinary compounding is acceptable
                4. Recognize federal laws pertaining to veterinary compounding
                5. Investigate labeling requirements for veterinary compounds

                1. Which of the following is a major source of poisoning in dogs?
                a. Turkey skin
                b. Chocolate
                c. Bones

                2. A client asks if she can feed her chickens dried corn, table scraps, or dried beans. Which of those foods would be inappropriate?
                a. Dried corn
                b. Table scraps
                c. Dried beans

                3. Which is not considered a factor when evaluating the toxicity of a drug or food item?
                a. The age or maturity of an animal
                b. The weight and size of an animal
                c. Whether it is a food-producing animal

                4. A compounder receives a prescription for a feline. This cat is picky, and the final product needs a humectant and flavoring. Which ingredient is contraindicated?
                a. Propylene glycol
                b. Glycerin
                c. Salmon flavoring

                5. When a sweetener is required, what is a good choice for veterinary compounding?
                a. Xylitol
                b. Sucralose
                c. Corn syrup

                6. Select the safe preservative to use when compounding for dogs.
                a. Vitamin C and E
                b. Ethoxyquin
                c. Propylene glycol

                7. Which of the following is an appropriate flavoring agent for dogs?
                a. Chicken bouillon cubes
                b. Bacon flavoring
                c. Grape flavoring

                8. Mrs. MacDonald, wife of Old MacDonald, brings you a prescription for her favorite chicken. She confirms that all of the following facts (answers a, b, and c) are true. Which fact forces you to tell her you cannot compound the medication?
                a. The chicken needs a small dose of medication
                b. The owner has a valid prescription from a veterinarian
                c. The chicken is food producing

                9. Under what condition can a pharmacist compound a veterinary prescription?
                a. The drug is on the FDA list of approved drugs
                b. The drug is cheaper to make than the available product
                c. There is no USP monograph for this drug

                10. According to GFI 256, a compounder must not
                a. Use a product on the FDA bulk drug substance list
                b. Attach the COA to the compounding record
                c. Purchase BDS from a non-FDA approved supplier

                11. What should a compounder do before mixing a prescription?
                a. Confirm that the patient is a pet
                b. Inform the FDA
                c. Call the veterinarian

                12. How soon should compounders report adverse events in veterinary compounding to the FDA?
                a. Within 7 days
                b. Within 15 days
                c. Within 30 days

                13. As you prepare a prescription label for a compounded product for a pet hamster, what must you include on the label?
                a. Not for use in food producing animals
                b. For office use only, not for resale
                c. This is a compounded drug. Not an FDA approved or indexed drug

                14. The compounding technician has prepared a label for a compounded veterinary product. The label is terribly crowded and hard to read. Which of the following can you tell the technician to remove?
                a. Species of pet
                b. Name of active ingredient
                c. Veterinary phone number

                15. Which FDA Guidance for Industry mandates the transition of certain antibiotics from OTC to prescription?
                a. 256
                b. 263
                c. 265

                Pharmacy Technician Post Test (for viewing only)

                Considerations in Veterinary Compounding
                Post-test
                Learning Objectives: After completing this continuing education activity, pharmacists and pharmacy technicians will be able to
                1. List food items which may be harmful to certain pets
                2. Identify additives which should not be used in veterinary compounding
                3. Discover when veterinary compounding is acceptable
                4. Recognize federal laws pertaining to veterinary compounding
                5. Investigate labeling requirements for veterinary compounds

                1. Which of the following is a major source of poisoning in dogs?
                a. Turkey skin
                b. Chocolate
                c. Bones

                2. A client asks if she can feed her chickens dried corn, table scraps, or dried beans. Which of those foods would be inappropriate?
                a. Dried corn
                b. Table scraps
                c. Dried beans

                3. Which is not considered a factor when evaluating the toxicity of a drug or food item?
                a. The age or maturity of an animal
                b. The weight and size of an animal
                c. Whether it is a food-producing animal

                4. A compounder receives a prescription for a feline. This cat is picky, and the final product needs a humectant and flavoring. Which ingredient is contraindicated?
                a. Propylene glycol
                b. Glycerin
                c. Salmon flavoring

                5. When a sweetener is required, what is a good choice for veterinary compounding?
                a. Xylitol
                b. Sucralose
                c. Corn syrup

                6. Select the safe preservative to use when compounding for dogs.
                a. Vitamin C and E
                b. Ethoxyquin
                c. Propylene glycol

                7. Which of the following is an appropriate flavoring agent for dogs?
                a. Chicken bouillon cubes
                b. Bacon flavoring
                c. Grape flavoring

                8. Mrs. MacDonald, wife of Old MacDonald, brings you a prescription for her favorite chicken. She confirms that all of the following facts (answers a, b, and c) are true. Which fact forces you to tell her you cannot compound the medication?
                a. The chicken needs a small dose of medication
                b. The owner has a valid prescription from a veterinarian
                c. The chicken is food producing

                9. Under what condition can a pharmacist compound a veterinary prescription?
                a. The drug is on the FDA list of approved drugs
                b. The drug is cheaper to make than the available product
                c. There is no USP monograph for this drug

                10. According to GFI 256, a compounder must not
                a. Use a product on the FDA bulk drug substance list
                b. Attach the COA to the compounding record
                c. Purchase BDS from a non-FDA approved supplier

                11. What should a compounder do before mixing a prescription?
                a. Confirm that the patient is a pet
                b. Inform the FDA
                c. Call the veterinarian

                12. How soon should compounders report adverse events in veterinary compounding to the FDA?
                a. Within 7 days
                b. Within 15 days
                c. Within 30 days

                13. As you prepare a prescription label for a compounded product for a pet hamster, what must you include on the label?
                a. Not for use in food producing animals
                b. For office use only, not for resale
                c. This is a compounded drug. Not an FDA approved or indexed drug

                14. The compounding technician has prepared a label for a compounded veterinary product. The label is terribly crowded and hard to read. Which of the following can you tell the technician to remove?
                a. Species of pet
                b. Name of active ingredient
                c. Veterinary phone number

                15. Which FDA Guidance for Industry mandates the transition of certain antibiotics from OTC to prescription?
                a. 256
                b. 263
                c. 265

                References

                Full List of References

                References

                   
                  REFERENCES
                  1. Megna M. Pet Ownership Statistics, June 21.2023. Forbes Magazine. Accessed August 5, 2023. https://www.forbes.com/advisor/pet-insurance/pet-ownership-statistics/#
                  2.Principles of Veterinary Medical Ethics of the AVMA. American Veterinary Association. August 2019. Accessed July 6, 2023 https://www.avma.org/resources-tools/avma-policies/principles-veterinary-medical-ethics-avma
                  3.Veterinary Centers of America (VCA) Animal Hospitals: Why Bones are not Safe for dogs. By Ryan Llera, BSc, DVM; Robin Downing, DVM, CVPP, CCRP, DAAPM. Accessed 07/04/2023. https://vcahospitals.com/know-your-pet/why-bones-are-not-safe-for-dogs#:~:text=Dogs%20can%20choke.,your%20dog's%20ability%2
                  4. 20 Foods Dogs Can’t Eat, and 13 Foods Safe for your Pup! Dr. Chris Roth DVM, July 21, 2022. Accessed August 5, 2023. https://www.petsbest.com/blog/20-foods-dogs-shouldnt-eat/?utm_source=nmpi&utm_medium=pmax&utm_campaign=max&utm_term=p
                  5. Brooks, Wendy, DVM,DABVP. Nicotine Poisoning in Pets. Revised January 23, 2023. Accessed August 5, 2023. https://veterinarypartner.vin.com/default.aspx?pid=19239&id=4952080#
                  6. Chapin. Pets On Pot, Just High or Highly Dangerous? Michigan State College of Veterinary Medicine, Decenber 4, 2018. Accessed August 5, 2023. https://cvm.msu.edu/vetschool-tails/pets-on-pot-just-high-or-highly-dangerous#
                  7. Johnstone, Gemma, American Kennel Club. Marijuana Poisoning in Dogs. April 10, 2023. Accessed August 5, 2023. https://www.akc.org/expert-advice/health/marijuana-poisoning-in-dogs/.
                  8. Liquid medicine may contain a high level of alcohol. Use with caution when administering to a child. Consumer Med Safety.org. Accessed August 5, 2023. https://www.consumermedsafety.org/safety-articles/liquid-medicine-may-contain-a-high-level-of-alcohol-use-with-caution-when#:~
                  9. Myers J. Chocolate toxicosis (Methylxanthine Toxicosis) in Dogs. September 9, 2022. Accessed August 5, 2023. https://vetster.com/en/conditions/dog/chocolate-toxicosis-methylxanthine-toxicosis-in-dogs
                  10. Gwaltney-Brant SM. Chocolate Toxicosis in Animals. Accessed August 5, 2023. https://www.merckvetmanual.com/toxicology/food-hazards/chocolate-toxicosis-in-animals#:~:text=DVM%2C%20PhD%2C%20DABVT,Modified%20Nov%202022
                  11. Zaborowska, Ł. Dog Chocolate Toxicity Calculator. Accessed August 5, 2023. https://www.omnicalculator.com/biology/dog-chocolate-toxicity.
                  12. American College of Veterinary Pharmacists. Salt. Accessed August 5, 2023. https://vetmeds.org/pet-poison-control-list/salt/#!form/PPCDonations.
                  13. Burle A. Can Dogs Eat Garlic? August 4,2022. Accessed August 5, 2023.. https://www.akc.org/expert-advice/nutrition/can-dogs-eat-garlic/
                  14. Medline plus, National Library of Medicine. Potato plant poisoning. Accessed August 5, 2023. https://medlineplus.gov/ency/article/002875.htm
                  15. Oelrichs PB, Ng JC, Seawright AA, Ward A, Schäffeler L, MacLeod JK. Isolation and identification of a compound from avocado (Persea americana) leaves which causes necrosis of the acinar epithelium of the lactating mammary gland and the myocardium. Nat Toxins. 1995;3(5):344-349. doi:10.1002/nt.2620030504
                  16. Avocado. Pet Poison Helpline. Accessed August 5, 2023. https://www.petpoisonhelpline.com/poison/avocado/#
                  Reviewed/Revised Jun 2021 | Modified Nov 20
                  17. What not to feed chickens, 33 Foods to Avoid. Backyard chicken project.com. Accessed August 5, 2023. https://backyardchickenproject.com/what-not-to-feed-chickens/
                  18. Foods Rabbits should never eat. February 15, 2021. Oxbow Animal Health. Accessed August 5, 2023. https://oxbowanimalhealth.com/blog/foods-rabbits-should-never-eat/
                  19. Factors Affecting the Activity of Poisons. Merck Veterinary Manual. Accessed August 5, 2023.https://www.merckvetmanual.com/special-pet-topics/poisoning/factors-affecting-the-activity-of-poisons#
                  20. The Official Top 10 Toxins of 2022. March 23,2023. ASPCA. Accessed August 5, 2023. https://www.aspca.org/news/official-top-10-pet-toxins-2022
                  21. Xylitol, Drugs.com. Accessed August 5, 2023. https://www.drugs.com/npp/xylitol.html
                  22. Xylitol Poisoning in Dogs. VCA. Accessed August 5, 2023. https://vcahospitals.com/know-your-pet/xylitol-toxicity-in dogs#:~:text=What%20is%20xylitol%3F,corn%20fiber%20or%20birch%20trees.
                  23. Dog Dies After Being Treated with Gabapentin Exposing Flaws in the Divide Between Human and Animal Drugs. Pet Food Safety News and Information. Accessed August 5, 2023. https://www.poisonedpets.com/dog-dies-after-being-treated-with-gabapentin-exposing-flaws-in-the-divide-between-human-and-animal-drugs/.
                  24. Brahlek A. Not-So Sweet Toxic Sweeteners for Dogs: Xylitol and Others. November 21, 2022, Accessed August 5, 2023. https://grubblyfarms.com/blogs/the-flyer/toxic-for-dogs-xylitol
                  25. Allen, LV Chapter 29, Veterinary Pharmaceuticals. The Art, Science, and Technology of Pharmacy Compounding. 6th edition, American Pharmacists Association, 2020.
                  26. Current Animal Food GRAS Notices Inventory. U.S. Food and Drug Administration. Accessed August 5, 2023. https://www.fda.gov/animal-veterinary/generally-recognized-safe-gras-notification-program/current-animal-food-gras-notices-inventory
                  27. Mahaney P. Pet Food: The Good, the Bad, and the Healthy. Accessed August 5, 2023. https://www.petsafe.net/learn/pet-food-the-good-the-bad-and-the-healthy
                  28. Dog Food Advisor. These 6 Dog Food Preservatives Could Be Toxic to Your Pet. Accessed August 5, 2023. https://www.dogfoodadvisor.com/red-flag-ingredients/dog-food-preservatives/
                  29. People Foods Dogs Can and Can’t Eat. AKC staff. April 3, 2022. Accessed August 5, 2023. https://www.akc.org/expert-advice/nutrition/human-foods-dogs-can-and-cant-eat/
                  30. Schmid R, Brutlag A. Flint C. DVM Essential Oil and Liquid Potpourri Poisoning in Cats. Accessed August 5, 2023. https://vcahospitals.com/know-your-pet/essential-oil-and-liquid-potpourri-poisoning-in-cats#
                  31. Qiu S, Liu Z, Hou L, et al. Complement activation associated with polysorbate 80 in beagle dogs. Int Immunopharmacol. 2013;15(1):144-149. doi:10.1016/j.intimp.2012.10.021
                  32. 10 Ingredients to avoid in dog food. TPLO info. November 12, 2021. Accessed August 5, 2023. https://tploinfo.com/blog/10-ingredients-to-avoid-in-dog-food/
                  33. Animal Drug Compounding. U.S. Food and Drug Administration. Accessed August 5, 2023. https://www.fda.gov/animal-veterinary/unapproved-animal-drugs/animal-drug-compounding
                  34. Check List for Pharmacists: Compounding Animal Drugs. U.S. Food and Drug Administration. Accessed August 5, 2023. https://www.fda.gov/media/157331/download
                  35. GFI # 256- Compounding Animal Drugs from Bulk Drug Substances. August 2022. U.S. Food and Drug Administration Center for Veterinary Medicine. Accessed August 5, 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-256-compounding-animal-drugs-bulk-drug-substances
                  36. FDA list of Bulk Drug Substances for compounding office stock drugs for Non-food producing animals. Accessed August 5, 2023. https://www.fda.gov/animal-veterinary/animal-drug-compounding/list-bulk-drug-substances-compounding-office-stock-drugs-use-nonfood-producing-animals
                  37. Compounding: Facts for Veterinarians. American Veterinary Medicine Association. Accessed August 5, 2023. https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/compounding/compounding-faq-veterinarians
                  38. Over-the-counter antimicrobials changing to prescription-only . American Veterinary Medicine Association. Accessed August 5, 2023. https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance/over-counter-antimicrobials-changin

                  The Path to Time Management: Time to Hit the Road!

                  Learning Objectives

                  After completing this knowledge-based continuing education activity, pharmacy technicians will be able to

                    • Describe how an individual technician’s time management impacts the whole pharmacy’s efficiency
                    • List three time management techniques that could improve a technician's function
                    • Recognize time management techniques to apply in specific settings and situations

                     

                    Re-Release Date: September 24, 2023

                    Expiration Date: September 24, 2026

                    Course Fee

                    Pharmacy Technicians: $4

                    There is no funding for this CE.

                    ACPE UAN

                    Pharmacy Technician: 0009-0000-23-027-H04-T

                    Session Codes

                    Pharmacy Technician:  20YC65-TJX49

                    Accreditation Hours

                    1.0 hours of CE

                    Accreditation Statements

                    The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-027-H04-T  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

                     

                    Disclosure of Discussions of Off-label and Investigational Drug Use

                    The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

                    Faculty

                     

                    Isabella Bean
                    PharmD Candidate 2022
                    UConn School of Pharmacy
                    Storrs, CT

                    Sara Miller, PharmD, RPh
                    CVS
                    Foxboro, MA

                    May Zhang
                    PharmD Candidate 2022
                    UConn School of Pharmacy
                    Storrs, CT

                    Faculty Disclosure

                    In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

                    Isabella Bean, Sarah Miller and May Zang do not have any relationships with ineligible companies.

                     

                    VIDEO

                    html

                    Pharmacy Technician Post Test (for viewing only)

                    The Path to Time Management: Time to Hit the Road!

                    LEARNING OBJECTIVES
                    After completing this continuing education activity, the pharmacy technician should be able to
                    1. Describe how an individual technicians' time management impacts the whole pharmacy’s efficiency
                    2. List three time management techniques that could improve a technician's function
                    3. Recognize time management techniques to apply in specific settings and situations

                    1. Barbara and Linda are great multitaskers. They are able to work and talk while getting everything done effectively. While ringing out a customer, Barbara continues her conversation with Linda. What should Barbara have done instead?
                    a. Paused the conversation, because it makes the customer feel unimportant
                    b. Done nothing different—in situations like this, she never makes errors
                    c. Asked someone else to ring the customer so she can go on her 15 minute break

                    2. Lilly makes it to work within the 7 minute grace period every day. Technically she is on time, but she’s not ready and at her station at her 7:30 shift time. How does this disturb workflow when she takes advantage of the grace period every day?
                    a. It doesn’t disturb workflow because she is not late. The grace period is in effect so that she doesn’t have to be in right when her shift starts.
                    b. Exploiting the grace period means the other technicians who arrive before the official start time have to cover her station until she comes in.
                    c. Employers know how often employees are late and why, and communicate problems like traffic congestion to local governments, so the effect on the workplace is positive.

                    3. You’re heading to work and you know it takes exactly 11 minutes to travel there. Your shift starts at 9 am. What time do you leave?
                    a. I leave by 8:40 am at the latest so that I have time to park and walk in.
                    b. I leave at 8:49 am because I know it takes 11 minutes to get there.
                    c. I leave at 9:00 am because I know they can handle me being a little late.

                    4. You are entering in an insurance card that you haven’t seen before. You’ve been struggling with it for five minutes and can’t figure it out. You are unsure of how to proceed, but the pharmacist is busy. What do you do?
                    a. Politely interrupt the pharmacist to ask your question
                    b. Ask a more senior technician if they have seen it before
                    c. Go to a different station to avoid this insurance card

                    5. Laura is a new pharmacy technician. The customers will ask her where to find an OTC or grocery item frequently, but she doesn’t know yet. She asks you how she can become more familiar with where everything is. What do you say?
                    a. Suggest that she ask the manager for front store training so that she can become more familiar with the store
                    b. Tell Laura that it takes time to learn the store, and to keep asking the other techs and pharmacists
                    c. Tell Laura she that she should identify this problem’s quadrant and decide whether to ask or act

                    6. You are working in the pharmacy and a huge order arrives. You know you have to finish putting away the order before your shift ends, but prescriptions and patients keep popping up. What do you do?
                    a. Prioritize the customers and prescriptions that are here now and do as much of the order as possible
                    b. The other technicians are busy too, but leave it for them because you’ve had to put the order away on three recent days
                    c. Multitask by putting the order away as you ring customers and retrieve and count controlled substances

                    7. The phone is ringing! When you answer it, a provider is on the line. She’s very frustrated because she’s been on hold for 10 minutes, and she “doesn’t have the time for this kind of thing” and “needs an answer ASAP.” She has a clinical question about a medication you fill very frequently. What is the most appropriate response?
                    a. ACT—you’ve been a tech for four years; you’ve seen this medication dozens of times. You know enough to answer the provider’s question.
                    b. ASK—you’re in the middle of something else right now. Ask another tech to handle this provider.
                    c. ASK—the pharmacist should take the call, since it involves a clinical question and you may not know all the details.

                    8. The phone is ringing! When you answer it, a provider is on the line. She’s very frustrated because she’s been on hold for 10 minutes, and she “doesn’t have the time for this kind of thing” and “needs an answer ASAP.” She has a clinical question about a medication you fill very frequently. What quadrant of workplace activity best describes this situation?
                    a. Quadrant 1: important and urgent
                    b. Quadrant 2: important but not urgent
                    c. Quadrant 4: not important and not urgent

                    9. Flu season is coming. Martha, an experienced pharmacy technician, knows that the store serves a very elderly population. She decides to ask the pharmacist to order more high potency flu vaccines, in anticipation of a higher customer demand. This best describes which time management technique?
                    a. Good organization
                    b. Planning ahead
                    c. Multitasking effectively

                    10. You’ve just transferred pharmacies, and you’re trying to figure out the lay of the land. It’s really hard to find things in your new pharmacy. Some meds are ordered by brand name, some by generic. Topicals, inhalers, and DME are all combined on the same shelf. When you bring this up to other techs, they sympathize but say you’ll figure it out eventually, like they had to. Which time management technique would best solve this issue?
                    a. Acting instead of asking
                    b. Multitasking effectively
                    c. Good organization

                    References

                    Full List of References

                    References

                       

                      Motivation to be the Best Drug Information Station

                      Learning Objectives

                       

                      After completing this application-based continuing education activity, pharmacists will be able to

                      • Recognize key elements of a drug information request
                      • Describe a typical process for researching drug information requests
                      • Prioritize information in the final written response
                      • Identify the best language to use based on the inquiring party’s needs

                      After completing this application-based continuing education activity, pharmacy technicians will be able to

                      • Identify questions that are within the pharmacy technician’s scope of practice
                      • Recognize tools and resources to use when attempting to answer a drug information question
                      • Complete the steps to completing a drug information request that is within the pharmacy technician’s scope of practice

                        Cartoon person standing in front of gigantic question mark

                         

                        Release Date: September 15, 2023

                        Expiration Date: September 15, 2026

                        Course Fee

                        Pharmacists: $7

                        Pharmacy Technicians: $4

                        There is no funding for this CE.

                        ACPE UANs

                        Pharmacist: 0009-0000-23-035-H01-P

                        Pharmacy Technician: 0009-0000-23-035-H01-T

                        Session Codes

                        Pharmacist:  23YC35-PXK63

                        Pharmacy Technician:  23YC35-KPX44

                        Accreditation Hours

                        2.0 hours of CE

                        Accreditation Statements

                        The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-035-H01-P/T  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

                         

                        Disclosure of Discussions of Off-label and Investigational Drug Use

                        The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

                        Faculty

                        Sumoda Achar
                        PharmD and MBA Candidate 2024
                        UConn School of Pharmacy
                        Storrs, CT

                        Shelly Evia
                        PharmD Candidate 2024
                        UConn School of Pharmacy
                        Storrs, CT

                        Stefanie Nigro, PharmD, BCACP, CDCES
                        Associate Clinical Professor
                        UConn School of Pharmacy
                        Storrs, CT

                        Jeannette Y. Wick, RPh, MBA
                        Director Office of Pharmacy Professional Development
                        UConn School of Pharmacy
                        Storrs, CT

                        Faculty Disclosure

                        In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

                        Samoda Achar, Shelly Evia, Jeannette Wick, and Stefanie Nigro do not have any relationships with ineligible companies.

                         

                        ABSTRACT

                        Pharmacists and pharmacy technicians often field questions from patients or other healthcare providers. Pharmacists may be more accustomed to answering questions than pharmacy technicians are, but that doesn't mean that pharmacy technicians can't answer appropriate questions. Pharmacy staff members should know their scope of practice and be willing and able to answer questions that fall within the scope of practice. Using an organized approach can help pharmacy staff members answer questions efficiently and effectively. Documentation is also an important aspect of drug information questions, as is saving the information in case it is needed later.

                        CONTENT

                        Content

                        INTRODUCTION

                        A drug information (DI) request is a medication-related question posed by any interested party, but usually a healthcare professional or a patient. As the healthcare team’s drug expert, one of a pharmacist’s main duties is answering these queries effectively and providing an answer that is appropriate for the inquirer’s level of expertise. Pharmacy technicians and pharmacy interns also answer some drug information questions (see TECH TALK SIDEBAR). This continuing education activity outlines various drug information questions that pharmacy staff field most often and describes a methodical approach to ensure pharmacy staff answer requests effectively and accurately.1

                         

                         

                        TECH TALK SIDEBAR: Questions within the Pharmacy Technician’s Scope of Practice?2,3

                        Pharmacy technicians and interns can answer general questions that are within the bounds of their education and training. That vague statement requires some interpretation. If the answer is common knowledge (not specialized pharmaceutical knowledge), technicians can answer. In addition to working with supervising pharmacists to interpret the statement, pharmacy technicians and interns need to know state law governing their scope of practice.

                         

                        Pharmacy technicians and interns are often the first point of contact for customers who want over-the-counter (OTC) medications. Technicians can answer general questions about ingredients if the information is on the label. Some examples include

                        • Does this product contain acetaminophen? What brands of acetaminophen do you stock?
                        • Where are the medicines for pain?
                        • Is there a less expensive generic or store brand for this product?
                        • Do you have any [insert name of prescription medication] in stock?
                        • Do I need to refrigerate this liquid antibiotic?
                        • What does “analgesic” mean?
                        • What does “sustained release” mean?
                        • Is this prescription for a controlled substance?
                        • Why can’t I refill this prescription today?

                         

                        Pharmacy technicians and interns can also convey information from the pharmacist but should be careful. A PRO TIP is that if technicians or interns don’t understand what the pharmacist says, they should ask the pharmacist to make the information clearer. And if the answer is long or complicated, they should write it down and recite it back to the pharmacist before transmitting it to the person with the question.

                         

                        Helping customers find specific medications or classes of medications is within the technician’s scope of practice. When patients have questions about their medications, doses, and how best to administer them, technicians may hesitate to answer. If the information is clearly printed on the prescription label, on the auxiliary labels, or contained in an FDA-approved Medication Guide, the technician or intern can answer.

                         

                        Technicians and interns need to work with the supervising pharmacist to determine if they can answer other questions. When in doubt, technicians should consult with or refer the question to the pharmacist. Technicians and interns must refer questions about potential adverse effects, administration problems, possible alternative medications, and clinical issues to the pharmacist. Before referring the patient, they can collect some baseline information. They cannot counsel or give advice, even if the medication is OTC.

                         

                         

                        Depending on the practice setting, the nature and complexity of DI requests can vary. Being able to answer DI requests is every pharmacy employee’s responsibility (although the type of information varies and at a certain level, the response is the pharmacist’s primary responsibility). Having an organized approach to answering DI questions is highly relevant when working within the community and hospital settings.4

                         

                        Pharmacy employees who work primarily within a community setting can expect to receive DI requests from patients and from practitioners. These requests can range from asking about drug storage requirements (which a technician can usually answer) to consequences of taking an OTC medication in combination with prescription drugs, to requests regarding the safety of a medication for an uncommon or off-label indication. Pharmacists who work in hospital settings can expect to receive most DI requests from colleagues within the care team. For instance, a DI request could come from a prescriber asking about medication absorption and distribution in a patient with comorbid conditions, or from a nurse asking if a medication can be crushed. Pharmacists who work in industry settings, however, may receive medication information requests that vary greatly from those received in clinical settings.4

                         

                        All DI requests require referencing reliable materials and sometimes, various internal policy or research documents. While DI requests are diverse, they all require similar analysis of sources and communication to provide a quality answer. Because pharmacy employees at different levels of responsibility can answer DI questions, this continuing education activity will call the person asking the question the requestor and the person finding the answer the respondent.

                         

                        SCREENING THE REQUEST

                        One of the most confounding situations in the pharmacy occurs when someone asks a question, the respondent spends times finding an answer, and then the requestor says, “Oh, that’s not what I needed to know!” Sometimes, requestors don’t really know how to ask questions effectively. This is a problem that all customer service fields encounter, and answering DI requests is both a clinical function and a customer service. It’s why when you call many customer service lines, the customer service representative will say, “OK, what I hear you asking is….” and then rephrase the question.5

                         

                        To answer DI requests effectively, the respondent must thoroughly understand the question.5 Very specific questions tend to be easily answerable, while others are more general or vague. In both instances, respondents need to ensure they understand the question. They can rephrase the question in their own words and say, “Let me make sure I understand. Do you mean….”, or they can use open ended questions (questions that cannot be answered with a yes or a no) to ask the requestor to provide more information. This avoids answering a question that wasn’t asked or intended or was poorly formulated.

                         

                        Often, requestors don’t know how to ask a question that will provide the information they need. The hallmark of this type of question is that the requestor may use jargon inappropriately or words that don’t seem to make sense. Respondents can say, “Excuse me, I’m not sure I understood entirely. Can you rephrase the question?” or “Pardon me, but I didn’t quite understand the question. Can you tell me a little more about what you want to know and why?” That final word—WHY—provides the impetus for the requestor to provide necessary information.

                         

                        Once the question has coalesced and both parties agree on its intent, the respondent can solicit important details from the requester and, if applicable, the patient, before delving into a search. At this point, the respondent needs to spend time actively listening to the requestor’s explanations.

                         

                        This can be difficult if the requestor is long-winded, difficult to understand, or cognitively impaired, so it requires patience. Here’s a PRO TIP for listening: it’s called the traffic-light-rule.6 During the first 30 seconds (which seems like a short period of time, but is actually relatively long), the requestor’s “talking light” is green. Pharmacy staff should let them talk. In the next 30 seconds, the requestor’s light is yellow: pharmacy staff probably have enough information and should make note of comments or questions. After one minute, the requestor’s talking light is red: pharmacy staff should be comfortable stopping the requestor politely or asking questions.6

                         

                        Before continuing, review the following DI requests. How would you proceed? Later  in this activity, we’ll provide a description of the ideal process.

                         

                        Pharmacist DI request #1: TN, 35-year-old obese female (BMI = 32.4 kg/m2) with uncontrolled type 2 diabetes will start on an atypical antipsychotic today to manage schizophrenia. TN’s psychiatric nurse practitioner (NP) calls with questions about drug selection. The NP mentions that TN’s drug formulary lists aripiprazole, haloperidol, olanzapine, and quetiapine as tier 1 preferred options. The NP wants your opinion as to which atypical antipsychotic may be most appropriate to prescribe for TN. What do you suggest?

                         

                        Pharmacist DI Request #2: You work at a tertiary care internal medicine center. MS, an 80-year-old female, was recently admitted to the medicine floor. She had fallen when she was trying to use the restroom at her nursing home and presented to the emergency department with a wrist fracture. She suffers from insomnia and other comorbidities. Her medication list includes lisinopril 20 mg daily, metformin 500 mg twice daily, rosuvastatin 20 mg daily, and lorazepam 0.5 mg PRN anxiety and sleep. The nursing home staff states that MS received more doses of lorazepam in recent weeks. The medical resident believes that the increased lorazepam use could have contributed to the fall and wants to know if trazodone would be a safer replacement for MS’s insomnia. How do you respond?

                         

                        Technician DI Request #1: I left this medication in my bathroom for four days, and then I noticed it says, “Keep in the refrigerator.” My house is cold, and the bottle didn’t feel warm. Is this still good, and if it isn’t, what should I do?

                         

                        Technician DI Request #2: My child is having trouble swallowing her medication and refuses to take it. Are there any easier ways I could give it to her?

                         

                        Identify Critical Information

                        Although it may seem counterintuitive, beginning with the end in mind is critical and the person gathering information must determine the requestor’s preferred response format. This means asking how the requester wants to receive the response. The respondent will need to adjust the answer according to the requestor’s preferences. Some requestors will want to wait for an answer. If the information is to be communicated through email or an electronic medical record, respondents may use their organization’s required format (a SOAP note or similar formats; see Table 1), but formats used in medical records may not be the most efficient approach in person or over phone. In person or on the phone, respondents need to use a more conversational tone. Furthermore, the respondent will need to determine the requestor’s level of medical competency and tailor the response accordingly. If the requestor is a patient, it is more appropriate to use simple language than if a provider asked the same or  similar question. Respondents will have to evaluate these factors critically to provide a sound and comprehensive answer.7

                        Table 1. Formats for Communicating Critical Information8,9

                        Communication Format Parts of the format Uses
                        SOAP S: Subjective information

                        This section includes descriptive information about a patient’s symptoms, feelings and experiences.

                         

                        O: Objective information

                        This section includes pertinent lab values, imaging, or diagnostic tests.

                         

                        A: Assessment

                        In this section the subjective and objective information are taken into consideration to make an assessment regarding the patient's disease states.

                         

                        P: Plan/ Follow Up

                        This section outlines a detailed plan regarding the patient's treatment and the follow-up and monitoring required.

                        This format is a widely-used written format in healthcare. It helps organize pertinent patient information and efficiently present an answer. This format is especially useful when the respondent must consider multiple pieces of information.
                        ISBAR I: Introduction

                        Introduction of the pharmacist and the respondent, and the pharmacist’s role and location.

                         

                        S: Situation

                        What are the current events regarding the patient?

                         

                        B: Background

                        What has happened in the past with the patient?

                         

                        A: Assessment

                        Identify the problem at hand and make assessments regarding the patient's disease state.

                         

                        R: Recommendation

                        Outline the next steps and your plan.

                        This format is beneficial for verbal communication. It helps the presenter explain the problem at hand and the solution in a time efficient way.
                        TITRS T: Title

                        Introduction of who you are and your purpose in helping the patient.

                         

                        I: Introduction

                        Present the patient and the problems that the patient needs help with.

                         

                        T: Text

                        State subjective and objective information that is necessary to support any recommendations.

                         

                        R: Recommendation

                        Outline the treatment plan in a clear, complete, and concise manner.

                         

                        S: Signature

                        Include name, title, and phone number.

                        This format is beneficial when a brief and concise formal consult is needed to communicate a progress note towards a medical team.

                         

                        Assess the Urgency of the Response

                        While it is critical to provide an appropriate response for the question, doing so in a timely manner is just as critical. Asking the requestor is the simplest way to determine the expected response time. However, many times the requestor isn’t present or cannot be reached, and it is up to the respondent to determine which questions require immediate responses and which may not. Clinically critical topics include

                        • Medication safety: does the DI request ask if a certain therapy could cause or have caused harm to the patient?
                        • Time sensitivity of the treatment: how important is timeliness to the treatment and disease progression?
                        • How much of a concern is the problem to the requestor: does it seem that the requestor needs an immediate response?

                         

                        Sometimes, respondents don’t know the answer to the question immediately.10,11 Pharmacy staff will never be able to answer every question, but they can handle every question gracefully and provide a complete, accurate answer within a reasonable time. When they don’t know the whole answer, they should answer what they can immediately and tell the respondent that they need to do a little more research to answer the remainder. A PRO TIP is to tell the requestor when to expect an answer (and to be sure to follow through).10-12

                         

                        Obtain Sufficient Background Information

                        In simple words, this step is about getting to know the patient or problem or establishing a strong understanding of the patient’s relevant characteristics by obtaining background information. Since some patients have low health literacy, obtaining this information can be a challenge. However, narrowing the search to only include relevant information and filtering unnecessary information can make the process more efficient. This could be achieved by7

                        • Asking targeted questions to patients. For example, instead of asking patients if they take their medication regularly (a closed-ended question that can be answered with yes or no), asking when they last took their medications provides a more precise answer.
                        • Identifying avenues that can provide accurate information. For example, instead of asking patients what other medications they take, checking the local profile and/or contacting their community or specialty pharmacist to receive a medication list can be more accurate.
                        • Reviewing any available records like medical charts or dispensing records.

                         

                        Identify Extraneous Information

                        Obtaining complete information is important but ensuring that the information is pertinent to the question being asked is just as important.

                         

                        Many times, DI requests are in-depth and require researching two or more sources before arriving at an answer. While conducting this search, ensure that the sources are relevant to the problem at hand. For example, if a study suggests that a medication is contraindicated in a patient, determine if the patient’s characteristics are similar to the study’s population. Furthermore, extraneous information could come from data gathering as well. For example, a patient may have multiple diseases, but they may not all impact the problem at hand. Making this distinction is important to provide a thorough and accurate answer.7

                         

                        Answers to Pause and Ponder

                        Pharmacist DI request #1: Haloperidol is not an atypical antipsychotic; therefore, it would be eliminated immediately and the remaining atypical antipsychotics would be reviewed as outlined below:

                        Screen Request Pertinent patient information: past medical conditions (uncontrolled diabetes, schizophrenia). Medications on tier 1 of patient's formulary: quetiapine, olanzapine, haloperidol, aripiprazole.
                        Reformulate Request This is a therapeutics drug information request because the provider is looking for the best medication to treat the patient's schizophrenia without adding any contraindications to the patient's current medication list or concomitant medical conditions.
                        Formulate Response The provider made the request in writing, so a written response is most appropriate. The SBAR format would succinctly and effectively convey the message. First, we conducted a Google search and a tertiary source search (PubMed) including the pertinent patient information and request. Our search read "effects of antipsychotics on obesity and diabetes." Through this, we determined that some antipsychotics lead to changes in metabolic activity. Because the patient has diabetes that is exacerbated by weight gain, the best choice is an antipsychotic that does not have a significant effect on the metabolism. After conducting a more thorough primary source search on the metabolic effects of antipsychotics, we found that the best drug would be aripiprazole. Additionally, monitoring the BMI and efficacy would be appropriate.
                        Assess Understanding Provide the response in a professional and timely manner. Document the request to display accountability and in case there is a similar question in the future. Follow up with the requestor to access the outcomes and ensure that there are no lingering questions or concerns.

                         

                        Pharmacist DI request #2:  Off-label use of low-dose (25 to 100 mg) trazodone, a decades-old antidepressant with drowsiness as a side effect, is common.13 In fact, off-label usage for insomnia has surpassed its use for depression.14 The American Academy of Sleep Medicine does not recommend trazodone because of limited supporting data. A 2018 Cochrane review found equivocal evidence supporting its short-term use for insomnia, but little data on long‐term safety and efficacy exists.15 The Beers Criteria doesn’t highlight trazodone as a potentially inappropriate medication in older adults, not because of evidence demonstrating safety, but because of lack of studies demonstrating harm. However, a retrospective cohort study found low-dose trazodone was no safer with respect to fall-related injury risk than benzodiazepines among 15,582 nursing home residents aged 66 years and older. Future studies need to confirm trazodone’s safety with respect to other risks such as dependence, withdrawal, and cognitive impairment.16

                         

                        Technician DI request #1:

                        It would depend on the medication. Some medications, like amoxicillin, are refrigerated to preserve the taste while most others, such as insulin, are refrigerated to preserve the compound. The technician should ask what medication the patient is referring to and then look up the specific storage requirements for that medication. Some places where this information is available include Drugs.com (https://www.drugs.com/medical-answers/drugs-that-require-cold-storage-166784/) and (https://www.iehp.org/en/members/helpful-information-and-resources?target=emergency-safety). If the medication is not listed in these resources or the medication’s stability has possibly been compromised (such as exposure to extreme heat), the technician should consult the pharmacist.

                         

                        Technician DI request #2:

                        It would vary depending on the medication. Some medications have specific coating that needs to stay intact to ensure proper drug delivery, and such medications should not be crushed. Other medications do not have such restrictions and can be crushed, split in half, sprinkled in foods like applesauce, or have a liquid formulation that can be considered as an alternative with a doctor’s approval. The technicians should ask, “What medication is your child taking so that I can look it up?” Information regarding which medications can be crushed can be found in the following website https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2014/Aug/Meds-That-Should-Not-Be-Crushed-7309. If the medication or the specific dosage form is not available on the list, the technician should ask the pharmacist to review the medication.

                         

                        Recognize when to ask for additional support or information. While drug information requests can be challenging, involving other healthcare professionals to hear about their experiences with similar clinical situations can offer a new perspective. Some benefits of consulting with experts include formulating a patient-specific answer to the question whereas a study may be irrelevant. When the request requires analysis beyond the scope of a drug information search, it is appropriate to reach out to a professional. While this may take additional time, arriving at the correct answer is more important than to harm the patient unknowingly. And a PRO TIP is that if reaching out will mean you cannot answer the question in the time frame promised, contact the requestor and say you need more time and why.

                         

                        REFORMULATING THE REQUEST 

                        To ensure the core request is clear, the respondent will need to ask many questions, especially if requesters don’t know what question they need to ask. Before starting to research the answer, respondents need to gather information needed from the requestor. In addition, it’s prudent to identify resources the requestor has already consulted (and their reliability in case information needs to be corrected).

                         

                        Categorize the Request

                        Requests can be based on complex patient specific cases, for educational purposes, or geared towards a decision-making process in medication therapy for a specific patient demographic. To fully optimize patient care and provide evidence-based recommendations, it is helpful to ask specific questions and consider all factors pertinent to the specific DI request. Categorizing the request can help stay on track, address all concerns, and point the respondent to the appropriate resources. Table 2 lists common categories and the questions that can clarify the request.

                         

                        Table 2. Common DI Categories and Related Questions1

                        DI Category Related Questions
                        Allergy/Cross-reactivity

                         

                        Does the patient have any documented allergies?

                        What caused or is suspected to have caused the allergic reaction?

                        When did the patient take the medication, and when did the reaction occur?

                        What type of allergic reaction occurred?

                        Is this a class or drug specific effect?

                        Alternative, or Complementary Medicine

                         

                        Where did the patient obtain the medication?

                        Why is the requestor taking or interested in taking the medication?

                        What other medications or treatments are available?

                        ADR/Safety

                         

                        What are the possible side effects?

                        What monitoring parameters need to be considered?

                        Compatibility (Y-site, syringe, IV)

                         

                        What solution will medication be used in?

                        If applicable, how will the medications be administered?

                        Dosage/Route/Administration

                         

                        What is the route of administration?

                        What is the recommended therapeutic dose for pediatrics, adults, and geriatrics?

                        How should the medication be taken (with/without food, with water, etc)

                        Drug Identification

                         

                        What was the source of the medication (e.g., domestic or foreign)?

                        What is the generic and brand name?

                        Where did the medication come from?

                        Ingredients/Stability

                         

                        What physical conditions exist? (Temperature, light protectant, storage duration, diluents)

                        Are there IV admixture compatibility/non-admixture stability data available?

                        Interactions

                         

                        What are the possible interactions between:

                        ●      Drug-drug

                        ●      Drug-food

                        ●      Drug-lab

                        ●      Drug allergy

                        Kinetics

                         

                        What is the onset/half-life/duration?

                        What are the serum levels?

                        Is dialysis a consideration?

                        What is the medication’s bioavailability?

                        Pharmacoeconomics

                         

                        Are there other competitors on the market?

                        Are there cheaper alternatives with the same therapeutic effects?

                        What is the AWP pricing?

                        Pharmaceutics

                         

                        What is the drug route of administration and drug dosage?

                        What patient factors will affect the drug?

                        Age, weight, gender, organ function, current medications

                        Pharmacology What factors will affect drug metabolism and bioavailability?
                        Pregnancy/Lactation What health conditions does the mother have?

                        What medications is the mother currently taking?

                        What is the current trimester?

                        How long has the mother been taking the medication or expected to take this medication?

                        Will the drug be present in breast milk?

                        How will the drug affect the infant?

                        What is the infant's age?

                        What health conditions do the mother and infant have?

                        Was the infant a full term or premature delivery?

                        Vaccinations

                         

                        Is the vaccination appropriate for the patient?

                        What are some side effects to monitor?

                        When should the patient get the vaccination?

                        Therapeutics

                         

                        What is the desired effect?

                        Is the goal cure or prophylaxis?

                        What previous medications and doses has the patient used?

                        Is this medication being used for an FDA approved or off-label use?

                        Toxicity

                         

                        What are possible sequelae?

                        What management strategies are available?

                        Abbreviations: ADR = adverse drug reaction; AWP = Average Wholesale Price; FDA = Food Drug Administration; IV = Intravenous

                         

                        Finding Reliable Sources

                        Being able to locate sources efficiently and correctly for a DI request is very important. Three main types of sources are available: primary, secondary, and tertiary.

                        • A primary source is any original research found in journals. Examples of primary sources are trial results found in the New England Journal of Medicine (NEJM) or similar journals in which researchers use a trial design to answer a specific question. (Note that NEJM and similar journals also publish secondary source materials, too.) This is the strongest Limitations of using this evidence include lack of access to journals that require paid subscriptions and lack of good search skills to find relevant papers.
                        • Secondary sources analyze, interpret, present, or restate information from primary sources. Textbooks, books and review articles, commentaries, guidelines, and Medline are examples of secondary sources.
                        • Tertiary sources compile information from other sources and organize it. Lexicomp , Micromedex, and DynaMed are common tertiary sources for DI requests as they use information from Food and Drug Administration-approved complete prescribing information (package inserts) and clinical studies. One limitation to be aware of is these sources are not updated rapidly therefore the information could be old and outdated.

                         

                        Determine the Best Source

                        When evaluating DI requests, in most cases the best course of action is to start with tertiary sources, such as textbooks or DI databases, when possible.1 These platforms provide a starting point and often suggest a basic idea for the answer. For many DI requests such as dosage, half-life, or adverse effects, the tertiary resource may provide a sound answer. Requests asking to compare two medications’ efficacy or assess the appropriateness of an uncommon or off-label medication use may require further research. Databases that identify off-label use include Micromedex.  In such cases, a primary source is the best resource. References sections of databases like DynaMed and Micromedex can be a great start for finding appropriate primary sources. Using search engines such as MEDLINE, PubMed or Google Scholar (scholargoogle.com) can provide access to relevant primary literature as well.1 Reviewing two to three sources is good practice for most drug information requests. Respondents must determine the relevance of the studies by evaluating if the trial size was large enough to be statistically reliable, if its findings were clinically significant, and if the patient population is similar to the patient.

                         

                        Use General Search Engines Appropriately

                        Using general search engines like Google, and Microsoft Edge can be an acceptable starting point for a search. A metasearch engine is usually better. A metasearch engine is a platform that aggregates the results from multiple search engines and organizes them based on their relevance. Examples of metasearch engines include Dogpile, ixquick, and Metacrawler which aggregate information from sources like Google and Yahoo as well as videos posted on various platforms.

                        Researchers must consider the following factors when determining a source’s credibility17:

                        • Is the information’s original source listed and reliable?
                        • Does the funding for the site come from a sound source such as a university (.edu), an established patient advocacy organization or a professional society (.org), or a government-funded organization (.gov)?
                        • How is the information presented and how is it supported?
                        • Who wrote the article on the webpage? Is the author a credible healthcare provider or a journalist writing about a medical topic?
                        • Is the information updated and verifiable with other sources?

                         

                        Table 3 matches types of information and reliable sources to find information.

                         

                        Table 3. Finding Reliable Sources for Drug Information Requests

                        Type of Request Source
                        Alternative or Complementary medicine Natural Medicine Comprehensive Database
                        ADR/Safety Lexicomp*, UpToDate*, Micromedex*, Package Inserts
                        Compatibility FDA-approved prescribing information, Trissel’s Stability of Compounded Formulations*
                        Dosage/Route/Administration Complete prescribing information, Lexicomp*, Micromedex*, etc.
                        Drug Identification Lexicomp* (Drug I.D) Drugs.com, WebMD Pill identifier, RxResouce.org (pill identification tool)
                        Ingredients/Stability Complete prescribing information, Lexicomp*
                        Interactions

                         

                        CYP Complete prescribing information, Lexicomp*
                        HIV HIV Drug Interactions

                        Clinicalinfo Drug Database

                        Kinetics Complete prescribing information, Lexicomp*
                        Pharmacoeconomics Studies published in pharmacoeconomics journals
                        Pharmaceutics PubMed* and primary sources
                        Pharmacology Lexicomp*, Micromedex* and could require further research with primary sources
                        Pregnancy/Lactation LactMed
                        Regulatory The Pharmacy Practice Act, Pharmacist's Manual
                        Therapeutics Dynamed*, UpToDate*, DiPiro’s textbook
                        Toxicity MSDS, PubChem, Micromedex*
                        Vaccinations CDC vaccine and immunization schedule, Lexicomp
                        Veterinary Information Plumb’s Veterinary Drug Handbook

                        *=sources requiring a subscription or payment

                        Abbreviations: ADR = Adverse Drug Reactions; CDC = Center for Disease Control and Prevention; CYP = Cytochrome P450; FDA = Food and Drug Administration; MSDS = Material Safety Data Sheet;  HIV = Human immunodeficiency virus

                         

                        Another relevant option that many healthcare professionals are considering for answering drug information requests is artificial intelligence (AI) platforms such as ChatGPT. While these seem to be able to provide responses that are based on data and research, the issue that users run into is the AI is not able to approach/appraise situations critically. While AI can provide information that may be or seem accurate, it is cannot assess the data that it uses to ensure that it is relevant to the situation or specific patient. Additionally, AI doesn’t cite its sources, meaning that it can be difficult to assess the appropriateness of the source. Last, it is important to realize that AI has sometimes provided wrong answers that could lead to patient harm and therefore need to be checked against reliable sources.

                         

                        Figure 2 summarizes a typical drug information process.

                        Figure 2. The Drug Information Process


                        FORMULATE THE RESPONSE 

                        Verbal responses tend to be easier for most people than written responses, but respondents should document every request. One simple rule should guide the response: Use principles of clear communication. Clear communication reduces risks of misinterpretation and increases the requestor’s understanding. It optimizes patient care. Clear, concise sentences that are short (fewer than 25 to 32 words) and straightforward create an ideal response.18 It is best to be comprehensive with adequate information and complete sentences that leave no confusion. Each statement should have a clear purpose with no extraneous information or unnecessary words. Respondents must paraphrase important information from accumulated data taken from reliable sources, while avoiding copying and pasting from other outside sources. The response must focus on the audience (the requestor) and the requestor’s background, remembering that different types of professionals have different education and focus.18

                         

                        Organize and Evaluate Information 

                        Organizing information makes research and presentation straightforward and simple for the audience to understand quickly. Templates are available to help keep information organized and formulated, but they have advantages and disadvantages.

                         

                        • Pros: Templates provide consistency that makes it easier for requesters to follow. (Saving your responses to DI requests is a PRO TIP, discussed in the SIDEBAR) Templates also provide an idea about how the completed presentation will look and reduce the time associated with creating the response. Some organizations provide templates for their employees. Lacking an approved template, respondents can find customizable templates from their workplace or university. Example templates found in the appendices show how useful templates can be. Templates can act as checklists to remember what should be included in a drug information response.
                        • Cons: Many templates limit the amount of allowable customization or text, and respondents must be knowledgeable about editing templates. Templates may also limit the approach to the topic and limit the information to standard or predictable fields; this is a problem when the question is unique or unusual. It is important to understand that templates are guides in answering requests and are not restrictions.

                         

                        Templates that can be used while answering drug information questions have different strengths and limitations. The choice of template can be dependent on the pharmacist’s preference as well as the type of drug information request. We reviewed the templates in the addendum and assessed their utility. Take a minute to look at them. How do your assessments compare to ours?

                         

                        Template 1 located in Appendix 1:

                        Pros: Extensive prompts for what should be included in a drug information response. This format is very detailed which could be useful for less experienced users.

                        Cons: Could be too detailed to be used for a wide range of requests. It lacks space, so users will have to use it against a document that they have already created.

                         

                        Template 2 located in Appendix 2:

                        Pros: This format displays the drug information request topic quickly, organizes patient information and the response, and includes references to use for evidence-based literature support. It is broad enough to be used for multiple types of requests. It could be especially helpful for pharmacists who receive a wide variety of requests as it allows them to focus and tailor responses appropriately.

                        Cons: Insufficient prompts or guidance responders, making it more suitable for experienced pharmacy staff. This would too broad for beginners or pharmacy students because it does not outline various aspects of drug information responses.

                         

                        SIDEBAR: Saving FAQs for Future Use: The FAQ File19,20

                        Pharmacy staff often notice that they receive the same or similar questions repeatedly. Each time a requestor asks the question, the respondent must answer again. When employees in the pharmacy discuss questions they receive, they may find that although each of them has only answered a specific question once or twice, collectively they are answering the same question often. A frequently asked question (FAQ) file has numerous advantages. It can

                        • Save time for everyone including the requestor
                        • Standardize the answer so that it is consistent each time staff answer the specific question
                        • Provide the answer in clear language
                        • Create an answer that technicians and students can give to requestors without asking the pharmacist to intervene
                        • Refer requestors to web sites or documents for additional information

                         

                        To develop a reliable FAQ file, pharmacy staff should take several steps:

                        • Identify the questions that are asked frequently.
                        • Develop a simple format for all FAQs. Usually, the actual question appears at the top of the documents, with the answer below.
                        • Start small and ask one employee to draft the FAQ.
                        • Have two or three people review the FAQ, including a pharmacist and at least one or two support personnel. Encourage reviewers to provide constructive criticism. If the FAQ usually comes from a colleague or patient, involve colleagues and patients in the review.
                        • A good process for reviewing FAQs is to ask a reviewer to read to a certain point and then stop. The project coordinator should ask, “Can you tell me in your own words what you just read?” If the reviewer explains and the information is incorrect, the project coordinator should not correct the reviewer; rather, the project coordinator should make a note that the section needs work and why.
                        • The project reviewer should ask additional, open-ended questions including
                          • What’s your general reaction to this draft FAQ?
                          • What did you like about this draft FAQ?
                          • What did you dislike about this draft FAQ?
                          • Is anything in this draft FAQ confusing?
                          • What would you do if you got this document?
                          • What do you think the writer was trying to do with this document?
                          • And here’s a PRO TIP: Often, people will not answer directly because they do not want to appear uneducated or picky. A way to circumvent this issue is to ask, “Thinking of other people you know who might get this document…”
                            • What about the document might work well for them?
                            • What about the document might cause them problems?
                          • Once the FAQ completes the process and is ready for “prime time,” save it in a format that cannot be edited (i.e. a PDF that is locked for editing) and upload it to a shared file or drive where all employees can access the document and print or clip it to an email when needed.

                         

                        Finally, drugs and drug information change over time. Organizations that use FAQ files must schedule routine review (at least annually and more often if necessary) to ensure that the content in FAQ files remains current and correct.

                         

                        Proofing and Editing Drafts 

                        Proofing and editing written drafts entails first fact-checking the narrative and the sources used, and then reviewing the text to ensure it is clear and professional. The respondent must re-assess and re-evaluate each source and the information gathered. Asking other healthcare professionals who have expertise to contribute to or proofread the draft is smart. Collaborating with colleagues can be beneficial, especially in healthcare. The recent emphasis on interdisciplinary approaches reminds us that healthcare professionals from multiple backgrounds need to collaborate and exchange information more often than not. Colleagues can also help confirm or modify any information, while also giving feedback to learn how to better future drug information requests.

                        Once the data is confirmed as accurate, the last step is to double check for spelling and grammar errors and ensure the response is clear and concise. A skilled pharmacy technician is often an exceptional collaborator in this step.

                         

                        Document, Document, Document

                        Documentation is helpful when pharmacy employees have to refer back to that specific topic on a similar drug information question or when colleagues have a similar request in the future. Documenting the response will aid as a reference point and could help clinicians in the future make decisions regarding patient care.21 Documentation will also display accountability and the respondent’s value to the organization and the interdisciplinary team. Many healthcare organizations have policies and procedures for documenting DI requests, and all staff should follow them if they exist.

                         

                        ASSESS REQUESTOR’S UNDERSTANDING AND SATISFACTION 

                        Following up after responding to a DI request is a professional action. The respondent should follow up with the requestor in a timely manner and assess the outcomes. If the requestor is not completely satisfied, the respondent can adjust the answer and recommendations appropriately.7 Follow-up will also reveal if the requestor has implemented the recommendation (and if it worked), provide feedback for potential modifications in future DI requests, and show professionalism and dedication to patient care. A PRO TIP is to document the follow-up and outcomes.

                         

                        CONCLUSION

                        Pharmacy teams have serious responsibilities related to DI requests, which can cover a broad spectrum of topics and specialties. Pharmacists, pharmacy technicians, and pharmacy students should use a methodical approach, followed by documentation. As the ever-changing landscape of healthcare, medicine, and technology continues to advance, the providing drug information will remain an integral part of the pharmacist’s responsibilities.

                         

                        Table 4 provides additional resources.

                         

                        Table 4. Additional Resources

                        Systematic Approach to Answering Drug Information Requests

                         

                        This resource helps characterize the various types of drug information requests

                        https://www.ashp.org/-/media/assets/pharmacy-practice/resource-centers/preceptor-toolkit/sicp-busy-day-systematic-approach-answering-drug-info-requests.ashx?la=en&hash=7C8B36648FAB999DE761D3AE37BFE48A847B8551
                        7 Tips on Improving Communication in Your Pharmacy

                         

                        This resource provides guidance on how best to speak with patients

                        https://www.pbahealth.com/elements/7-tips-on-improving-communication-in-your-pharmacy/
                        Formulating an Effective Response: A Structured Approach

                         

                        This resource provides strategies to answer formulated drug information requests.

                        https://accesspharmacy.mhmedical.com/content.aspx?bookid=2275&sectionid=177197497 :
                        ASHP Guidelines on the Pharmacist’s Role in Providing Drug Information

                         

                        This resource provides suggestions on how to answer a formulated drug information request.

                        https://www.ashp.org/-/media/assets/policy-guidelines/docs/guidelines/pharmacists-role-providing-drug-information.pdf
                        How To Evaluate Health Information on the Internet: Questions and Answers

                         

                        This resource provides approaches on how to find credible sources to answer drug information requests.

                        https://ods.od.nih.gov/HealthInformation/How_To_Evaluate_Health_Information_on_the_Internet_Questions_and_Answers.aspx

                         

                         

                        Templates:

                        Requirements checklist for drug information Response1 - UBC Blogs. Accessed July 3, 2023. https://blogs.ubc.ca/oeetoolbox/files/2019/01/Requirements-Checklist-for-Drug-Information-Response.pdf.

                        Drug Information Request and Response Form.; 2017. Accessed July 3, 2023.

                        https://blogs.ubc.ca/oeetoolbox/files/2019/01/DIR-Example.pdf

                        PHRM Handbook. Accessed July 3, 2023.

                        https://blogs.ubc.ca/oeetoolbox/files/2019/01/Drug-Information-Request-and-Response-Fillable-Form-.pdf

                        Pharmacist Post Test (for viewing only)

                        Pharmacy: Motivation to be the Best Drug Information Station

                        Pharmacists Post-test

                        After completing this education activity, pharmacists will be able to
                        1) Recognize key elements of a drug information request
                        2) Describe a typical process for researching drug information requests
                        3) Prioritize information in the final written response
                        4) Identify the best language to use based on the inquiring party’s needs

                        1. Which of the following describes a good practice in answering complicated drug information requests?
                        A. Reviewing at least two sources when looking for answers
                        B. Using a couple of metasearch engines (e.g., Dogplie)
                        C. Using tertiary sources (e.g., Micromedex, Lexicomp)

                        2. A patient approaches the community pharmacy counter asking about experiencing GI upset when taking his daily medications. His medications include metformin, prednisone and lisinopril. Which of the following is an appropriate targeted question to obtain key information?
                        A. Are you taking your medications at the correct times?
                        B. How are you taking your medications?
                        C. Are you taking your medications with food?

                        3. Which of the following are elements of screening a response to correctly identify the key elements in a drug information request?
                        A. Setting aside extraneous information to focus on pertinent information
                        B. Relying solely on the patient’s recollection of medical information
                        C. Asking closed-ended questions to extract targeted information

                        4. Which of the following correctly identifies the process of answering a drug information request?
                        A. Screen request for pertinent information, reformulate request, formulate response, assess understanding
                        B. Assess understanding, reformulate request, screen request for pertinent information, formulate response
                        C. Formulate response, reformulate request, access understanding, screen request for pertinent information

                        5. A doctor asks how many hours prior to dialysis medication X should be administered to ensure an optimal response. Which category would the question fall under?
                        A. ADR inquiry
                        B. Therapeutics
                        C. Kinetics

                        6. If asked a question about the dosing for atorvastatin for a 40-year-old patient recently diagnosed with dyslipidemia, which of the following sources would be the most appropriate place to look for the answer?
                        A. Natural medicine comprehensive database
                        B. LactMed
                        C. Lexicomp

                        7. Which of the following correctly pairs the appropriate language and the type of requestor who is asking for information?
                        A. Patient: “Possible adverse events include gastrointestinal upset and an increase frequency of bowel movements.”
                        B. Provider: “The patient may have a tummy ache and have to go to the bathroom to poop a lot.”
                        C. Nurse: “Patients who take this medication may develop some side effects including nausea and diarrhea”

                        8. Which of the following statements identifies the purpose of the “assess understanding” step
                        A. To gauge requestors’ satisfaction and determine if they implemented the recommendation or need further assistance
                        B. To test the requesters health literacy and attempt to match the language you use to the language they understand
                        C. To provide new information to requestors so that they have multiple options in case the first answer didn’t resolve their problem

                        9. You have been tasked with creating a general drug information template. Which of the following are important aspects to include in your template
                        A. Prior medical history; lab values; current medications
                        B. Patient’s education; reference authors; siblings’ ages
                        C. Patient’s age, financial status, current medications

                        10. A patient approaches the pharmacy stating that she left a refrigerated medication on her front porch for more than 24 hours. She asks if it is still safe to use the medication. Which of the following is the most efficient way to answer?
                        A. Google the name of the drug and look for a patient or nurse blog site
                        B. Look at the package insert for the medication in the pharmacy database
                        C. Find two the primary sources for the stability in various temperatures

                        Pharmacy Technician Post Test (for viewing only)

                        Pharmacy: Motivation to be the Best Drug Information Station

                        Pharmacy Technician Post-test

                        After completing this education activity, pharmacy technician’s will be able to
                        1) Identify questions that are within the pharmacy technician’s scope of practice
                        2) Recognize tools and resources to use when attempting to answer a drug information question
                        3) Complete the steps to completing a drug information request that is within the pharmacy technician’s scope of practice

                        1. Which of the following questions would require counseling from a licensed pharmacist?
                        A. Do I store this liquid antibiotic at room temperature or refrigerate it?
                        B. Is there a less expensive generic or store brand for this product?
                        C. What other medications should I avoid taking with this prescription?

                        2. A patient approaches the community pharmacy counter asking about experiencing GI upset when taking his daily medications. His medications include metformin, prednisone, and lisinopril. Which of the following is an appropriate targeted question to obtain key information?
                        A. Are you taking your medications at the correct times?
                        B. How are you taking your medications?
                        C. Are you taking your medications with food?

                        3. When can pharmacy technicians answer questions and help customers find specific medications or classes of medications while staying within their scope of practice?
                        A. If information is clearly printed on the prescription label, on auxiliary labels, or in an FDA-approved Medication Guide.
                        B. If the supervising pharmacist is busy and will not have time to help a customer for at least 15 minutes to an hour.
                        C. When the technician does not like the specific customer and would like to see the customer leave as soon as possible

                        4. Which of the following correctly identifies the process of answering a drug information request?
                        A. Screen request for pertinent information, reformulate request, formulate response, assess understanding
                        B. Assess understanding, reformulate request, screen request for pertinent information response, formulate response
                        C. Formulate response, reformulate request, access understanding, screen request for pertinent information

                        5. A 58-year-old woman comes to the pharmacy counter and tells you she received her Shingrix vaccine two weeks ago and does not remember when she needs to come back for her next Shingrix dose. Where would a pharmacy technician be able to find information about vaccine scheduling to answer the patient’s question?
                        A. Trissel’s Stability Compendium
                        B. LactMed and lexicomp
                        C. CDC Vaccine and Immunization Schedule

                        6. According to the traffic-light-rule, what should the pharmacy staff member do after one minute of listening?
                        A. Pharmacy staff should let patients continue to talk because it’s unlikely they have disclosed enough information.
                        B. Pharmacy staff probably has enough information and should make note of comments or questions.
                        C. Pharmacy staff should be comfortable stopping the requestor politely or asking additional questions.

                        7. A mother is picking up her son’s antibiotic prescription and asks if there is a specific way that her son should take the medication. Where would you find this information about the route of administration for antibiotics?
                        a) PubMed
                        b) Pharmacists Manual
                        c) Lexicomp

                        8. Which of the following statements identifies the purpose of the “assess understanding” step
                        A. To gauge requestors’ satisfaction and determine if they implemented the recommendation or need further assistance
                        B. To test the requesters health literacy and attempt to match the language you use to the language they understand
                        C. To provide new information to requestors so that they have multiple options in case the first answer didn’t resolve their problem

                        9. You have been tasked with creating a general drug information template. Which of the following are important aspects to include in your template
                        A. Prior medical history; lab values; current medications
                        B. Patient’s education; reference authors; siblings’ ages
                        C. Patient’s age, financial status, current medications

                        10. A patient approaches the pharmacy stating that she left a refrigerated medication on her front porch for more than 24 hours. She asks if it is still safe to use the medication. Which of the following is most efficient way to answer?
                        A. Google the name of the drug and look for a patient or nurse blog site
                        B. Look at the package insert for the medication in the pharmacy database
                        C. Find two the primary sources for the stability in various temperatures

                        References

                        Full List of References

                        References

                           
                          1. Systematic Approach to Answering Drug Information Requests Systematic Approach to Answering Drug Information Requests Step 1: Obtain Background Information. Accessed August 8, 2023. https://www.ashp.org/-/media/assets/pharmacy-practice/resource-centers/preceptor-toolkit/sicp-busy-day-systematic-approach-answering-drug-info-requests.ashx?la=en&hash=7C8B36648FAB999DE761D3AE37BFE48A847B8551
                          2. Understanding Your Scope of Practice as a Pharmacy Technician. Career Advice. Accessed March 25, 2023. https://www.careerstep.com/blog/news/understanding-your-scope-of-practice-as-a-pharmacy-technician/
                          3. Foster P. What You Can and Can’t Say to Customers as a Pharmacy Technician. October 28, 2016. Accessed March 25, 2023. https://www.pennfoster.edu/blog/2016/october/what-you-can-and-can-not-you-say-to-customers-as-a-pharmacy-technician
                          4. ASHP Guidelines on the Pharmacist’s Role in Providing Drug Information Background and Rationale. Accessed August 8, 2023. https://www.ashp.org/-/media/assets/policy-guidelines/docs/guidelines/pharmacists-role-providing-drug-information.pdf
                          5. Martin SW. Strategies for Answering Your Customers’ Toughest Questions. Harvard Business Review. June 28, 2012. Accessed March 25, 2023. https://hbr.org/2012/06/handling-customers-toughest-qu
                          6. Nemko M. How to handle difficult clients. Psychology Today. February 25, 2021. Accessed March 25, 2023. https://www.psychologytoday.com/us/blog/how-do-life/202102/how-handle-difficult-clients
                          7. Malone PM, Witt BA, Malone MJ, Peterson DM. Formulating an Effective Response: A Structured Approach | Drug Information: A Guide for Pharmacists, 6e | AccessPharmacy | McGraw Hill Medical. Accessed August 8, 2023. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2275§ionid=177197497
                          8. Podder V, Lew V, Ghassemzadeh S. SOAP Notes. Published 2022. Accessed August 8, 2023. https://www.ncbi.nlm.nih.gov/books/NBK482263
                          9. Burgess A, van Diggele C, Roberts C, Mellis C. Teaching clinical handover with ISBAR. BMC Medical Education. 2020;20(2):1-8. doi:https://doi.org/10.1186/s12909-020-02285-0
                          https://bmcmededuc.biomedcentral.com/articles/10.1186/s12909-020-02285-0
                          10. Compassionate Geek. IT Customer Service Skills: What To Do When You Don’t Know The Answer To A Customer Question. Accessed March 25, 2023. https://compassionategeek.com/customer-service-skills-when-you-dont-know-the-answer/
                          11. Expert Panel Forbes Councils Member. Leaders: Nine Good Ways To Handle A Business Question You Don't Know The Answer To. June 7, 2021. Accessed March 25, 2023. https://www.forbes.com/sites/theyec/2021/06/07/leaders-nine-good-ways-to-handle-a-business-question-you-dont-know-the-answer-to/?sh=39d2b40823ba
                          12. Csizmadia A. Oops, I don’t know: How to respond to a customer’s question when you don’t know the answer. September 25, 2018. Accessed March 25, 2023. https://www.liveagent.com/blog/oops-i-don’t-know-how-to-respond-to-a-customers-question-when-you-don’t-know-the-answer/
                          13. Gill LL. Consumer Reports. Should You Take Trazodone for Insomnia? Accessed January 26, 2022. https://www.consumerreports.org/insomnia/trazodone-for-insomnia-should-you-take-a9455377183/
                          14. Jaffer KY, Chang T, Vanle B et al. Trazodone for insomnia: a systematic review. Innov Clin Neurosci 2017;14:24-34.
                          15. Everitt H, Baldwin DS, Stuart B et al. Antidepressants for insomnia in adults. Cochrane Database of Systematic Reviews 2018;5:CD010753.
                          16. Bronskill SE, Campitelli MA, Iaboni A et al. Low-dose trazodone, benzodiazepines, and fall-related injuries in nursing homes: a matched-cohort study. J Am Geriatr Soc 2018;66:1963-71.
                          17. How To Evaluate Health Information on the Internet: Questions and Answers. ods.od.nih.gov. National Institutes of Health. Published June 24, 2011. Accessed August 8, 2023. https://ods.od.nih.gov/HealthInformation/How_To_Evaluate_Health_Information_on_the_Internet_Questions_and_Answers.aspx
                          19. U.S. Department of Health & Human Services. National Institutes of Health Naional Cancer Institute. Making Health Communications Programs Work. Accessed March 25, 2023. https://www.cancer.gov/publications/health-communication/pink-book.pdf
                          18. Clear Writing Assessment. Centers for Disease Control and Prevention. Accessed match 25, 2023. https://www.cdc.gov/nceh/clearwriting/docs/Clear_Writing_Assessment-508.pdf
                          20. JIMDO. How to Write an FAQ Page–with Example. October 21, 2021. Accessed March 25, 2023. https://www.jimdo.com/blog/how-to-write-an-faq-page-with-examples/
                          21. 7 Steps to Respond to Drug Information Requests. Pharmacy Times. Accessed August 8, 2023. https://www.pharmacytimes.com/view/7-steps-to-respond-to-drug-information-requests

                          The upcoming USP changes and its impact on immediate use medications

                          Learning Objectives

                           

                          After completing this application-based continuing education activity, pharmacists and pharmacy technicians will be able to

                            1. Point out an immediate use medication
                            2. Recognize locations where immediate use medications may be compounded
                            3. Investigate the designated person’s responsibilities
                            4. Identify core competencies required for immediate use compounding

                            Image of person with syringe between their teeth.

                             

                            Release Date: September 1, 2023

                            Expiration Date: September 1, 2026

                            Course Fee

                            Pharmacists: $5

                            Pharmacy Technicians: $2

                            There is no grant funding for this CE activity

                            ACPE UANs

                            Pharmacist: 0009-0000-23-031-H07-P

                            Pharmacy Technician: 0009-0000-23-031-H07-T

                            Session Codes

                            Pharmacist:  23YC31-ABC28

                            Pharmacy Technician:  23YC31-BCA82

                            Accreditation Hours

                            1.5 hours of CE

                            Accreditation Statements

                            The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-031-H07-P/T  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

                             

                            Disclosure of Discussions of Off-label and Investigational Drug Use

                            The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

                            Faculty

                            Laura Nolan, CPhT, CSPT
                            Pharmacy Lab Coordinator
                            UConn School of Pharmacy
                            Storrs, CT

                             

                                       

                            Faculty Disclosure

                            In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

                            Laura Nolan does not have any financial relationships with ineligibile companies.

                             

                            ABSTRACT

                            The United States Pharmacopeia (USP) recently published updated guidelines on sterile compounding that become effective on November 1, 2023. These guidelines affect not only sterile medications compounded in pharmacy clean rooms, but also injectable medications that may be compounded in healthcare institutions, medical and surgical treatment sites, infusion facilities, pharmacies, and physician and veterinarian practice sites. This affects personnel such as chiropractors, dentists, naturopaths, nurses, pharmacists, pharmacy technicians, physicians, veterinarians, and any other medical professional who compounds sterile products. The USP made these changes to minimize harm, including death, to human and animal patients. By reviewing these updates, and by making changes, medical professionals will be able to comply with state and federal regulations and prevent harm to their patients.

                            CONTENT

                            Content

                            INTRODUCTION

                            In 1905, a person in excruciating pain in a dentist’s office would have been thrilled to receive an injection of procaine (Novocain) delivered in a reusable glass hypodermic syringe. Besides the dentist’s white coat, it’s likely nothing else used in the procedure was clean or remotely sterile. Today, given what we know about sterile products, an educated patient would have turned and run in the opposite direction.

                            Yet, according to the U.S. Food and Drug Administration (FDA), the number of trendy med spas and intravenous (IV) hydration clinics, some mobile, that treat patients with medications such as injectable vitamin infusions, have exploded. Many operate under the FDA’s radar. The FDA may not be aware of which compounders are making such drugs, and some states may have insufficient resources to adequately oversee them. The FDA has recently documented varying offenses from personnel  wearing street clothing and not wearing gloves while preparing injections to using toaster ovens for sterilization.2

                             

                            Human drug compounding is a practice in which ingredients are combined, mixed, or altered to create a medication tailored to an individual patient’s medical needs. The Federal Food, Drug and Cosmetic Act (FD&C Act) governs human compounding. Section 503A describes the conditions under which compounded human drug products are exempt from its regulations2:

                            • Section 505 concerning approval prior to marketing
                            • Section 501(a)(2)(B) concerning current good manufacturing practice (CGMP) requirements
                            • Section 502(f)(1) concerning labeling with adequate directions for use

                            The FDA act exempts one condition—compounds are exempt when a licensed pharmacist or physician prepares the medication in a licensed facility based on a valid patient specific prescription. An explosion of naturopathic clinics, which often use unapproved nutritional, herbal, and homeopathic products and administer them by injection, have become a growing concern for the FDA. A brief Internet search revealed that nurses run many clinics with a physician consulting offsite. The FDA has become increasingly aware of drug products compounded at medical offices and clinics that may be prepared under unsanitary conditions. The FDA has also become aware of business models, such as IV hydration clinics, medical spas, and mobile IV infusion services, that are compounding drugs that may not meet the conditions of the FD&C Act’s section 503A or comply with state regulations.2

                            Unsanitary conditions are more common than one would think. The FDA cites a recent example (February 2021) wherein a 50-year-old patient was hospitalized and treated for suspected septic shock with multi-organ failure after receiving an IV vitamin infusion in her home.2 The patient’s blood cultures grew Pseudomonas fluorescens, which is a gram-negative bacterium of emerging concern.3 A California medical clinic that specialized in services including IV therapies and vitamin injectables, sexual health products, hormone replacement therapy, weight loss/management products, and diagnostic laboratory assays prepared and dispensed the contaminated bag.2 When state and federal agents inspected the facility, they observed several deficiencies2:

                            • Lack of an International Organization for Standardization (ISO) air quality classification of ISO-5; in other words, a clean room which is certified to contain a particle count of less than 3,520 particles per cubic meter in the air, required for sterile compounding
                            • Contamination in compounding areas including peeling paint, stained work surfaces, visibly dirty equipment, and air vents with dust and grime
                            • Difficult-to-clean equipment and surfaces (e.g., carpeting in the IV storage and mixing room)
                            • Standing water in a refrigerated storage area used to store sterile vials
                            • Use of expired active pharmaceutical ingredients to prepare drug products intended to be sterile

                            The full extent of this nationwide problem is unknown since many practitioners operating in medical offices or clinics do not register with the FDA. The FDA encourages all patients who experience adverse effects to report them to the FDA MedWatch Adverse Event Reporting program (www.fda.gov/medwatch/report.htm).2 

                            Defining Immediate Use Medication

                            According to the proposed USP<797> Pharmaceutical Compounding-Sterile Preparations, sterile compounding is defined as combining, admixing, diluting, pooling, reconstituting, repackaging, or otherwise altering a drug product or bulk drug substance to create a sterile preparation. Compounding personnel must follow aseptic techniques, processes, and procedures for preparing any sterile medication.1

                            Within a hospital setting, urgent situations may arise where compounding cannot occur in a USP<797> compliant area. Often, acute care situations require STAT (meaning with no delay; at once) doses for critical patients, or medication for an unanticipated procedure.4 Compounders do not necessarily need to comply with all requirements detailed in USP<797> to make these immediate use medications. These frequently asked questions can help clarify when an immediate use medication may be needed and who can compound it.1,4

                            • Can nurses mix compounded sterile preparations (CSPs) for immediate use? Any qualified health professional can prepare an immediate use preparation as long as (1) it is within their scope of practice, (2) the facility’s policies allow it, and (3) the designated person (defined and discussed below) has documented the health care professional’s competency.
                            • Is docking a vial onto a proprietary bag system considered an immediate use medication? Yes and no. Docking a vial onto a proprietary bag for future activation and use is considered compounding and must be performed in an ISO class 5 environment. However, docking a vial onto a proprietary bag according to manufacturer's instructions for immediate administration to a single patient is considered an immediate use medication and is not considered compounding.
                            • Can a nurse prepare an immunoglobulin (IGG) solution in a home care setting, by reconstituting the powder vial with the sterile water supplied by the manufacturer in a kit? This is an example of preparation that is compliant with FDA-approved labeling. Preparing a sterile product in accordance with the manufacturer's approved labeling is not considered compounding as long as
                              • the product is prepared as a single dose for a single patient
                              • the approved labeling includes the following information: the diluent, the final strength, the container closure system, and storage time
                            • If a nurse reconstitutes an antibiotic vial and adds it to a piggyback bag, is this considered immediate use? If the pharmacy is open, this should be done in a sterile clean room. If it is a STAT dose or the pharmacy is closed, then this could be considered immediate use. The nurse mixing the medication needs to have documented competency and the compound should not involve more than three products. One vial of drug, one vial of diluent, and one piggyback bag are three products, which is allowed.

                            In 2020, the American Society of Health Systems Pharmacists conducted a study among professionals who compounded outside of the pharmacy setting. Of the 444 respondents, 77% were nurses, and the rest were primarily anesthesia providers and decentralized pharmacists. Eighty-one percent performed compounding in a acute care settings; other locations included ambulatory surgery centers, infusion centers, physicians’ practices, and long-term care.5

                            The most frequently prepared items were5

                            • IV pushes drawn directly from vials into syringes. (i.e., antibiotics, antiemetics, opioids, proton pump inhibitors)
                            • Intermittent infusions, all of which were proprietary vial and bag systems.
                            • Intramuscular injections including vaccines, antipsychotics, and antibiotics

                             

                            Personnel and Settings Affected by USP<797>

                            All personnel who prepare CSPs are required to comply with USP<797> guidelines. This includes but is not limited to chiropractors, dentists, naturopaths, nurses, pharmacists, technicians, physicians, and veterinarians.1

                            All sites including but not limited to hospitals, infusion facilities, medical and surgical patient treatment sites, pharmacies, physician or veterinarian sites, and other healthcare institutions must meet at least the minimum requirements in USP<797>.1

                            The compounding facility must designate one or more individuals to be responsible and accountable for the facility’s performance, operation, and personnel in the preparation of CSPs and for performing other functions described in USP<797>.1 The facility’s standard operating procedures (SOPs) must identify the person deemed “the designated person.” All designated persons now have immense jobs; failure to meet the USP’s expectations  comes with considerable consequences.

                            The Designated Person

                            The USP mentions the designated person more than 50 times in section <797> alone and several other chapters also refer to the designated person. Below is a list of some, but not all tasks required of a designated person, which will become effective on November 1, 2023. Many states, such as Connecticut and Texas, have already embraced the designated person. The designated person or persons must be identified in the facilities SOPs and registered with the state. In Texas and Connecticut, pharmacists must also complete 30 hours of sterile compounding training to become a designated person. Duties include1

                            • Overseeing a training program to ensure competency of personnel involved in compounding, handling, and preparing CNSPs
                            • Selecting components
                            • Monitoring and observing compounding activities and taking immediate corrective action if deficient practices are observed
                            • Ensuring that SOPs are fully implemented. The designated person(s) must ensure that follow-up is carried out if problems, deviations, or errors are identified
                            • Establishing, monitoring, and documenting procedures for the handling and storage of CNSPs and/or components of CNSPs.

                            The SIDEBAR discusses an issue of emerging importance.

                            SIDEBAR: Who Inspects Physicians’ Offices? 6

                            In 2016, the Pew Charitable Trust conducted a study and asked boards of pharmacy in all 50 states and the District of Columbia to respond to several compounding questions. Of the 51 states, 43 responded to the questionnaire. Although the survey consisted of pages of questions, three of them were forward thinking.

                            1. Does your state have a mechanism to track which in-state physicians’ offices or clinics perform sterile compounding? The answer: 2 % yes, 74% no, 24% don’t know.
                            2. Does the state require physicians’ offices or clinics to be held to the same quality standards as pharmacies? The answer: 17% yes, 38% no, 45% don’t know.
                            3. How do states provide oversight of physician’s offices or clinics that perform sterile compounding to ensure compliance with applicable standards? The answer: 7 by the state board of medicine, 1 by the board of pharmacy (way to go, IDAHO!), 24 reported no oversight system to ensure compliance and 11 states chose not to respond to this question.

                            Who knew Idaho would be so revolutionary? Keep in mind that this study took place in 2016, four years after the New England Compounding mishap of 2012. The Pew study reported, “The Drug Quality and Security Act of 2013, among other reforms, added a new category of compounders called outsourcing facilities that can compound supplies of drugs without obtaining prescriptions.”

                            The new category—outsourcing facilities—was intended to reduce the number of medications made in offices. However, it is obvious that state policies are not uniform. Some states are still working to advance change, and others have yet to act. The Pew report concluded that we are still in a state of transition and that “The variations in sterile compounding policy across states suggest that an opportunity exists to review state oversight systems for potential weaknesses, and consequently to advance regulatory practices to better protect patients.”

                             

                            Gap Analysis

                            In some states, as in the state of Connecticut, the designated person must be a pharmacist. That means that the designated person or persons are responsible for the oversight of all compounding within an institution including the operating room, emergency room, clinics, and nursing station medication rooms.

                            PAUSE AND PONDER: In what areas of your facility could people possibly be compounding without your designated person’s knowledge?

                            A gap analysis compares the current situation with a future state. Creating a gap analysis could help identify areas where compounding is done without the designated person’s knowledge. A gap analysis is performed in three steps7:

                            1. Identify objectives and goals. Most designated persons will create a sheet with three columns: current state, future state, and actions. They will need to identify who, what, where and when immediate use compounding occurs. Using a team approach and including nurses and physicians is a good place to start.
                            2. Analyze the current state. Gather data. One critical area to examine is medications in short supply or backordered. (Aren’t there always a few of these lately!?!) Checking purchasing records and delivery slips to see where medications are being used can be eye-opening. Facilities that substitute vials because the premixed bag is backordered will find that this is a target area.
                            3. Determine how to bridge the gap. Collaborating with the team to create policies and procedures for compounding and writing them into standard operating procedures is critical. Facilities should create a designated compounding area in each unit and establish a cleaning routine. They should also create a training document for nurses and other professionals who compound and set date that each person should complete training as a goal.

                            Immediate Use Gap Analysis

                            All facilities that compound need to compare the current (2008) USP<797> Pharmaceutical Compounding-Sterile Preparations guidelines with the proposed (2022) USP<797> guidelines. In short, the proposed changes are few in number but may cause significant impact throughout the facility.8 Table 1 compares a few minor changes.

                            Table 1.  Less Strict Changes to USP<797> 1,8,9

                            Subject Current Proposed
                            Compounding Process

                            and number of components

                            Only low risk level

                            NMT 3 sterile packages

                            NMT 3 sterile products
                            Situation Emergency use or immediate

                            administration

                            No emergency stipulation
                            Number of manipulations NMT 2 entries into any container/bag Not defined
                            Maximum BUD 1 Hour 4 hours
                            Aseptic technique Aseptic technique is followed Aseptic technique, processes, and procedures followed per written SOPs
                            Risk Level Medium and high risk not prepared as immediate use Category 1, 2, and 3 requirements do not apply
                            Hazardous Drugs Only non-hazardous drugs may be used Must follow USP<800>

                            BUD = beyond use date; NMT = Not More Than

                            A quick glance at the table shows that compounders can now assign a beyond use date (BUD) of four hours for immediate use products. Hurray! This prompts the question, “Is that all I need to implement, and can I do it right now?” Not so fast! These are changes to existing subjects within <797> guidelines, but the proposed guidelines also include many new stipulations, so let’s dig deeper. The following requirements have now been added which pertain to immediate use medications1,8:

                            • Written SOPs must be in place and compounding personnel must follow aseptic technique, processes, and procedures.
                            • Personnel must be trained and demonstrate competency according to the facility SOPs.
                            • SOPs must include methods to minimize contamination and decrease mix-up errors.
                            • The product must be compounded in accordance with evidence-based information for physical and chemical compatibility, per labeling or stability studies.
                            • Any unused starting component from a single use container must be discarded.
                            • Single dose containers must not be used for more than one patient.
                            • A compounding record is required when preparing immediate use medications for more than one patient.

                             

                            Training and Evaluation

                            Training is the elephant in the room. Many nurses and other health professionals have mixed or prepared single use medications for ages, so it might be difficult to teach an old dog new tricks. Demonstration of competency can be difficult and perhaps this is where the nursing team can shine. Luckily, immediate use compounders need not perform fingertip and thumb sampling, or media fill tests as is required for sterile clean room staff.

                            All personnel who compound must now be initially trained and qualified by demonstrating their knowledge and competency of sterile compounding before they can perform their job independently. The designated person(s) is responsible for creating and implementing a training program but may assign training to other qualified personnel. The training procedure for immediate use CSPs must be written into the facilities SOPs.1 One interesting note, the proposed USP<797> states that personnel who are compounding in a clean room, or who have direct oversight of those personnel, must complete training initially, and at least every 12 months. However, immediate use compounders only need to complete training as required by the facilities SOPs.1 A best practice would be to evaluate yearly.

                            Skills may vary from one location to another, but at a minimum, healthcare professionals who will perform immediate use compounding must demonstrate the following core skills8:

                            • Hand hygiene and proper gloving
                            • Calculations, measuring and mixing
                            • Aseptic technique and compounding procedures

                            Required skills will depend on the clinic’s location; for example, an oncology clinic will need to follow USP<800> Standards for Hazardous Drugs, along with USP<797>. Other skills may include cleaning, garbing, documentation, and labeling and should align with the immediate use procedures in the facilities SOPs.

                            Competency assessment must be based on the aseptic processes that are related to the tasks being performed, which can be difficult to recreate. Demonstration of a simulated manipulation may be acceptable in most cases. A simulated aseptic manipulation using empty vials, syringes, sterile water, or saline could consist of the three maximum products allowed, with no need to incubate the sample.7 Using a convenient checklist, like the one in Table 2, helps trainers evaluate staff and document consistently.

                            The SIDEBAR highlights one practice that needs to end immediately.

                            Normal Saline Flush Prefilled Syringes7,10

                            The Institute for Safe Medical Practices (ISMP) released the results of a 2018 immediate use compounding survey. Of the 977 practitioners who responded to the survey, almost all were nurses. ISMP discovered that 81% of the respondents used premixed 5 mL and 10 mL normal saline flushes to dilute medications. The FDA considers a premixed normal saline flush as a medical device and they are “not approved for dilution and administration of IV push medications.”

                            Some clever (but forbidden) uses of prefilled syringes include

                            • Using prefilled syringes as vials: withdrawing and or adding part of a prefilled syringe into another prefilled syringe for administration (Example: adding 5 mL from one syringe to another 5 mL syringe to make a 10 mL syringe).
                            • Using a prefilled syringe to reconstitute a powder vial, then drawing the dose back into the same syringe. (Example, using a 10 mL flush, adding 5 mL from the flush, reconstituting, and withdrawing the 5 mL back into the syringe to create a 10 mL dose.)

                            Using prefilled syringes in these ways is dangerous, since most of the time the health care professional conducting these “procedures” fail to relabel these syringes, so the syringes still have a bright yellow or white label and can be easily picked up by another person and administered in error.

                            Why would prefilled flushes be used for compounding? First, among the many recent drug shortages, normal saline topped the list for a very long time. Second, they are quick and easy to use, and third, healthcare professionals cling to many misconceptions. Some professionals believe that a syringe does not need to be labeled. There is also a myth that a 10 mL syringe must be used to administer IV push medications. Perhaps it is due to “telephone tag” teaching, where one procedure is passed from one to another.

                            So, how do we fix this? Clear procedures need to be established for compounding each medication. Staff training is a must, and a simple roll of blank labels in the compounding area can go a long way to avoiding errors.

                             

                            Table 2. Sample Immediate Use Compounding Evaluation

                            Name of person assessed: Jonathan the Husky Dog  Location:

                             

                            Husky Clinic

                             Evaluation of Handwashing, Garbing, Gloving and Aseptic technique:

                            In left-hand boxes, indicate for each activity

                             P = acceptable completion of the described activity in the correct order,

                            X = the order is incorrect or the activity is performed incorrectly or

                            N/O = the activity was not observed.

                            Notes/

                            Comments on any of the activities.

                            Removes all jewelry and outer garments
                            Uses nail pick under running water
                            Washes hands with soap and water for 30 seconds
                            Dries hands with approved wipe
                            Dons required garb
                            Applies alcohol-based hand sanitizer, allows to air dry
                            Selects the correct pair of gloves
                            Correctly dons sterile gloves
                            Applies sterile alcohol to gloves, allows to air dry
                            Disinfects compounding area with facility approved agent
                            Selects proper components
                            Disinfects critical sites with 70% alcohol wipe

                             

                            Punctures vial at a 45-degree angle to avoid coring
                            Withdraws the correct amount of fluid from vial
                            Disposes waste in proper container
                            Visually inspects final product
                            Demonstrates proper labeling
                            Applies correct 4-hour BUD
                            Name of evaluator________________________Date:_____ Pass   /   Fail

                             

                            CONCLUSION

                            Whether you are the designated pharmacist or just a team member, it is important for you to recognize immediate use medications and locations where they may be compounded. With the implementation of USP<797> commencing on November 1, 2023, now is the time to look at the pharmacy clean room and all areas in your facility where compounding may be occurring. Huge changes in workflow as well and policies and procedures may need to be adopted. Create a well-balanced team of professionals and get to work!

                             

                            Pharmacist Post Test (for viewing only)

                            The Upcoming USP<797> Changes: Impact on Immediate Use Medications
                            Post-test Pharmacists and Technicians
                            After completing this continuing education activity, pharmacists and pharmacy technicians will be able to:
                            1. Point out an immediate use medication
                            2. Recognize locations where immediate use medications may be compounded
                            3. Investigate the designated person’s responsibilities
                            4. Identify core competencies required for immediate use compounding

                            1. Jerry is the designated person for a large health system. He is preparing to implement the new USP<797> changes. Today, he is making a list of potential immediate use situations. Which of the following situations should he add to his list?
                            a. A technician docking ten vials onto proprietary bags
                            b. A pharmacist reconstituting TPA in the emergency department
                            c. An anesthesiologist using a premade fentanyl syringe

                            2. Abdul and Allyssa are having coffee at break. Abdul says that he receives e-mail notifications from the FDA’s automated system. Alyssa asks, “have they reported anything interesting lately about compounding?” What does Abdul report?
                            a. The FDA has seen an uptick in community-based clinics compounding under unsanitary conditions
                            b. The MedWatch Adverse Event Reporting reports more errors caused by choosing the wrong syringe
                            c. The FDA indicates that they are having trouble tracking problems when patients pay cash for infusions

                            3. A veterinarian works in a veterinary practice that employs a certified veterinary technician and has taken all necessary steps to be USP<797> compliant. She needs to prepare and administer an injection of an analgesic immediately for a dog that was hit by a car. Can she do this?
                            a. Yes, because veterinary medications do not need to comply with USP <797>
                            b. Yes, if the certified veterinary technician prepares the dose in the medication room
                            c. Yes, because the practice has taken steps to comply completely with USP<797>

                            4. Clara applies for a job as a “designated person” at a naturopathic clinic. The person interviewing indicates that the facility’s staff seems to prepare immediate use medications in many different (and USP<797> noncompliant) ways. She asks Clara how she would solve this problem. What is the BEST answer?
                            a. Training all staff personally and documenting the training in the facility’s SOPs
                            b. Purchasing medications from a wholesaler that is licensed by the federal government
                            c. Establishing, monitoring, and documenting procedures for CSP handling and storage

                            5. It’s October 31, 2023, at 10:22 PM and Andy needs to prepare an immediate use medication that will probably be given in the emergency department shortly after midnight. The facility’s SOPs are compliant with the revised USP<797> chapter that becomes effective on November 1, 2023. He determines that he can prepare the medication now for its administration after midnight. What do you think?
                            a. Since the USP <797> is not effective until tomorrow, the facility needs to use the maximum BUD allowed in the previous version (2 hours)
                            b. Since the facility is already USP <797> compliant and its SOPs have been updated, 4 hours is the maximum BUD
                            c. Andy needs to wait until midnight and prepare the immediate use medication closer to the time it will be administered.

                            6. Sally’s supervisor is checking her competencies as required by the USP<797>. She asks, “Which of the following represents an appropriate situation that would be considered an immediate use medication?”
                            a. Using a premixed normal saline syringe for reconstituting vial contents
                            b. Completing a compounding record for more than one patient
                            c. Using a single dose vial for two patients within four hours

                            7. Maria considers herself a responsible healthcare professional. She hasn’t needed to prepare an immediate use medication in several months, but today, she needs to compound an antibiotic on site. What should she do before compounding this medication?
                            a. Ensure the designated pharmacist has evaluated the facility’s training procedures
                            b. Complete a standard USP form that is a declaration that she knows how to compound.
                            c. Schedule a media fill test and thumb and fingertip test using an agar plate

                            8. What information is the designated person responsible for updating in the SOPs?
                            a. Training and competency procedures
                            b. Names of personnel who have been trained
                            c. The cost of training to the hospital

                            9. When must immediate use compounders have their training completed?
                            a. Initially and then annually
                            b. Initially and every 6 months
                            c. As required by the facilities SOPs

                            10. Which core competencies apply to immediate use compounding?
                            a. Hand hygiene and sterile filtration
                            b. Hand hygiene, measuring and mixing
                            c. Measuring, mixing and principles of high-efficiency filters

                            Pharmacy Technician Post Test (for viewing only)

                            The Upcoming USP<797> Changes: Impact on Immediate Use Medications
                            Post-test Pharmacists and Technicians
                            After completing this continuing education activity, pharmacists and pharmacy technicians will be able to:
                            1. Point out an immediate use medication
                            2. Recognize locations where immediate use medications may be compounded
                            3. Investigate the designated person’s responsibilities
                            4. Identify core competencies required for immediate use compounding

                            1. Jerry is the designated person for a large health system. He is preparing to implement the new USP<797> changes. Today, he is making a list of potential immediate use situations. Which of the following situations should he add to his list?
                            a. A technician docking ten vials onto proprietary bags
                            b. A pharmacist reconstituting TPA in the emergency department
                            c. An anesthesiologist using a premade fentanyl syringe

                            2. Abdul and Allyssa are having coffee at break. Abdul says that he receives e-mail notifications from the FDA’s automated system. Alyssa asks, “have they reported anything interesting lately about compounding?” What does Abdul report?
                            a. The FDA has seen an uptick in community-based clinics compounding under unsanitary conditions
                            b. The MedWatch Adverse Event Reporting reports more errors caused by choosing the wrong syringe
                            c. The FDA indicates that they are having trouble tracking problems when patients pay cash for infusions

                            3. A veterinarian works in a veterinary practice that employs a certified veterinary technician and has taken all necessary steps to be USP<797> compliant. She needs to prepare and administer an injection of an analgesic immediately for a dog that was hit by a car. Can she do this?
                            a. Yes, because veterinary medications do not need to comply with USP <797>
                            b. Yes, if the certified veterinary technician prepares the dose in the medication room
                            c. Yes, because the practice has taken steps to comply completely with USP<797>

                            4. Clara applies for a job as a “designated person” at a naturopathic clinic. The person interviewing indicates that the facility’s staff seems to prepare immediate use medications in many different (and USP<797> noncompliant) ways. She asks Clara how she would solve this problem. What is the BEST answer?
                            a. Training all staff personally and documenting the training in the facility’s SOPs
                            b. Purchasing medications from a wholesaler that is licensed by the federal government
                            c. Establishing, monitoring, and documenting procedures for CSP handling and storage

                            5. It’s October 31, 2023, at 10:22 PM and Andy needs to prepare an immediate use medication that will probably be given in the emergency department shortly after midnight. The facility’s SOPs are compliant with the revised USP<797> chapter that becomes effective on November 1, 2023. He determines that he can prepare the medication now for its administration after midnight. What do you think?
                            a. Since the USP <797> is not effective until tomorrow, the facility needs to use the maximum BUD allowed in the previous version (2 hours)
                            b. Since the facility is already USP <797> compliant and its SOPs have been updated, 4 hours is the maximum BUD
                            c. Andy needs to wait until midnight and prepare the immediate use medication closer to the time it will be administered.

                            6. Sally’s supervisor is checking her competencies as required by the USP<797>. She asks, “Which of the following represents an appropriate situation that would be considered an immediate use medication?”
                            a. Using a premixed normal saline syringe for reconstituting vial contents
                            b. Completing a compounding record for more than one patient
                            c. Using a single dose vial for two patients within four hours

                            7. Maria considers herself a responsible healthcare professional. She hasn’t needed to prepare an immediate use medication in several months, but today, she needs to compound an antibiotic on site. What should she do before compounding this medication?
                            a. Ensure the designated pharmacist has evaluated the facility’s training procedures
                            b. Complete a standard USP form that is a declaration that she knows how to compound.
                            c. Schedule a media fill test and thumb and fingertip test using an agar plate

                            8. What information is the designated person responsible for updating in the SOPs?
                            a. Training and competency procedures
                            b. Names of personnel who have been trained
                            c. The cost of training to the hospital

                            9. When must immediate use compounders have their training completed?
                            a. Initially and then annually
                            b. Initially and every 6 months
                            c. As required by the facilities SOPs

                            10. Which core competencies apply to immediate use compounding?
                            a. Hand hygiene and sterile filtration
                            b. Hand hygiene, measuring and mixing
                            c. Measuring, mixing and principles of high-efficiency filters

                            References

                            Full List of References

                            References

                               
                              REFERENCES:
                              1. United States Pharmacopeia (USP). General Chapter, <797> Pharmaceutical Compounding—Sterile Preparations. (2023) USP-NF. Rockville, MD: United States Pharmacopeia. Accessed June 19, 2023.
                              2. FDA highlights concerns with compounding of drug products by medical offices and clinics under insanitary conditions. Oct. 25,2021. https://www.fda.gov/drugs/human-drug-compounding/fda-highlights-concerns-compounding-drug-products-medical-offices-and-clinics-under-insanitary
                              3. Scales BS, Dickson RP, LiPuma JJ, Huffnagle GB. Microbiology, genomics, and clinical significance of the Pseudomonas fluorescens species complex, an unappreciated colonizer of humans. Clin Microbiol Rev. 2014 Oct;27(4):927-48. doi: 10.1128/CMR.00044-14. PMID: 25278578; PMCID: PMC4187640.
                              4. ASHP, The sterile compounding answer book. Chapter 8, Immediate use and preparation for administration. page 33-34
                              5. Pedersen CA, Schneider PJ, Ganio MC, Scheckelhoff DJ. ASHP National survey of pharmacy practice in hospital settings: Dispensing and administration- 2020. Am J Health Syst Pharm. 2021;78(12):1074–93.
                              6. National Assessment of State Oversight of Sterile Drug Compounding. The Pew Charitable Trust. February 2016. Accessed August 7, 2023. https://www.pewtrusts.org/~/media/assets/2016/02/national_assessment_of_state_oversight_of_sterile_drug_compounding.pdf
                              7. Mind Tools, Gap Analysis. Accessed Jun18,2023. https://www.mindtools.com/afv9hac/gap-analysis

                              8. Pharmacy Purchasing & Products Magazine, USP <797> Immediate-Use CSPs: Small Changes, Big Impact. Feb.2023 Vol.20 No.2, page 10. Kevin N. Hansen, PharmD, MS, BCPS, BCSCP Amanda M. Choi, PharmD, MBA Annie Lambert, PharmD, BCSCP February 2023 - Vol.20 No. 2

                              9. United States Pharmacopeia (USP). General Chapter, <797> Pharmaceutical Compounding—Sterile Preparations. (2008) USP-NF. Rockville, MD: United States Pharmacopeia. Accessed June 20, 2023.

                              10. Institute of Safe Medical Practices. Part II Survey results suggest action is needed to improve safety with adult IV push medications. Dec. 2018, Vol.16, Issue 12. Accessed June 22, 2023.https://www.ismp.org/sites/default/files/attachments/201812/NurseAdviseERR201812.pdf

                              The Nitty Gritty: Dry Eye Guidance for the Pharmacy Team

                              Learning Objectives

                               

                              After completing this application-based continuing education activity, pharmacists and technicians will be able to

                              1. Describe the etiology and pathophysiology of dry eye disease (DED) and its impact on quality of life
                              2. Identify available and emerging over-the-counter and prescription therapies to treat DED
                              3. Optimize artificial tear selection based on patient-specific characteristics
                              4. Infer when to refer patients to the pharmacist or an eye care provider for DED

                                 

                                Release Date: August 15, 2023

                                Expiration Date: August 15, 2025

                                Course Fee

                                Pharmacists: FREE

                                Pharmacy Technicians: FREE

                                This CE was funded by:  Alcon Vision, LLC

                                ACPE UANs

                                Pharmacist: 0009-0000-23-030-H01-P

                                Pharmacy Technician: 0009-0000-23-030-H01-T

                                Session Codes

                                Pharmacist:  23YC30-TVX83

                                Pharmacy Technician:  23YC30-XVT99

                                Accreditation Hours

                                2.0 hours of CE

                                Accreditation Statements

                                The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-030-H01-P/T  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

                                 

                                Disclosure of Discussions of Off-label and Investigational Drug Use

                                The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

                                Faculty

                                Jennifer Salvon, RPh
                                Clinical Pharmacist
                                Mercy Medical Center
                                Springfield, MA

                                Faculty Disclosure

                                In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

                                Ms. Salvon does not have any relationships with ineligible companies.

                                 

                                ABSTRACT

                                Dry eye disease (DED) is a multifactorial condition affecting the ocular surface and tear function. Symptoms include burning, itching, and watery eyes. DED affects millions of people in the United States. Many underlying factors contribute to DED making therapeutic management difficult. Left untreated, DED can result in visual changes affecting everyday activities such as reading and driving. Simple environmental changes often help alleviate symptoms. Before seeking healthcare professional assistance, many people self-treat with over-the-counter artificial tear products, leading to high costs and frustration. Treatment involves patient education, environmental and lifestyle modifications, topically applied products, and, in severe cases, surgical procedures. Several recently approved products offer alternative treatment approaches. A knowledgeable, informed pharmacy team is prepared to counsel patients on product choice and to make appropriate referrals contributing to better patient outcomes.

                                CONTENT

                                Content

                                INTRODUCTION

                                The feeling of grit under the eyelids is uncomfortable, annoying, and frustrating and can pose a serious health issue. This feeling, often accompanied by burning, itching, redness, and visual disturbances, is a symptom of keratoconjunctivitis sicca, otherwise known as dry eye disease (DED). At its simplest, DED is inflammation of the cornea and conjunctiva from tear hyperosmolarity (higher concentration of solutes like salts, sugars, or other dissolved particles) and tissue dryness. Left untreated, DED may result in severe eye inflammation, corneal ulcers, and vision loss.1

                                 

                                DED affects approximately 16.4 million people, or 6.8% of the United States (U.S.) adult population.2,3 DED is likely underreported and underdiagnosed, with estimates as high as 22.9 million adults experiencing symptoms.2 Researchers estimate DED’s global prevalence is as high as 50%.4

                                 

                                Despite this prevalence, experts began to recognize DED as a disease state only about 30 years ago.5,6 Initially described as a component of Sjogren’s syndrome (an autoimmune disease involving tear and saliva glands), DED emerged as a separate condition as ocular surface study progressed. The National Eye Institute first defined DED in 1995.1

                                 

                                The Tear Film and Ocular Surface Society (TFOS) is a non-profit organization focused on eye health research and education.5 In 2015, the Dry Eye Workshop II (DEWS II), organized by TFOS, examined multiple aspects of DED. The workshop updated the definition, diagnosis, and classification of DED, the disease’s impact, therapeutic management options, and clinical trial design.5

                                 

                                TFOS DEWS II defines DED as "… a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles."5 In simpler terms, DED occurs when the tear film, which keeps the eyes moist, becomes imbalanced, leading to problems like tear film instability, high concentration of substances in the tears, inflammation and damage on eye surface, and abnormal nerve sensations.

                                 

                                Many risk factors contribute to DED development (Table 1). Women are two to three times more likely to develop DED than men.3,4 Risk of developing DED increases with age. Adults aged 50 or older are three times more likely to develop symptoms than those 18 to 49 years old.2,3 However, DED’s incidence is rising steadily in the younger population, possibly due to increased disease awareness.3 Digital device use may also contribute. Studies show that using digital devices decreases blink rate and increases incomplete blinks, leading to ocular surface dryness and, ultimately, DED.4.7

                                 

                                Table 1. Dry Eye Disease Risk Factors1,4,5

                                Modifiable Non-modifiable
                                Androgen deficiency

                                Computer use

                                Contact lens wear

                                Environment

                                Medications

                                Age ≥ 50 years

                                Asian race

                                Connective tissue diseases (e.g., rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus)

                                Diabetes

                                Female sex

                                Meibomian gland dysfunction

                                 

                                 

                                DED impacts the American economy significantly. Several factors contribute to DED burden: direct costs of medical care, the impact of lost productivity, and the associated quality of life burden. In the U.S., estimates of direct medical costs exceed $3.84 billion, fueled by healthcare professional visits, pharmacologic therapies, and surgical procedures.4,8 The cost of lost productivity (i.e., time spent seeking and receiving treatment, avoidance of aggravating work environments, and inability to perform work due to visual changes) is even more substantial. One study estimates that these indirect costs total $11,302 per patient annually.8 If more than 16 million people have DED, that totals more than $150 billion annually.4,8

                                 

                                Beyond monetary costs associated with DED, the disease also affects vision-related quality of life (VR-QoL). As DED progresses, visual quality decreases. Individuals with DED are three times more likely to report visual difficulties than those without.4 This impacts many daily activities such as reading, driving, watching television, and smartphone use.4 DED-associated pain and discomfort, along with difficulty in activities of daily living, impact mental health negatively.8 A 2021 study examined self-reported health status and psychological burden in patients with DED. The study associated DED with having a negative self-perception of health status and experiencing increased psychological stress.9

                                 

                                A Deeper Look at DED

                                A better understanding of DED requires review of the surface anatomy of a healthy eye (see Figure 1). The eye's surface consists of the ocular surface and ocular adnexa (accessory anatomical parts).10 The ocular surface includes the cornea, conjunctiva (including goblet cells), and tear film. The ocular adnexa includes the eyelids, lacrimal and meibomian glands, tear ducts, and the connecting muscles and nerves.10

                                 

                                Figure 1. Eye Surface Anatomy and Tear Film Formation

                                Anatomical image of the eye and tear film.

                                 

                                Tears lubricate the eye, and the tear film—which provides nutrients and moisture, removes microbes, and smooths the ocular surface—has three layers10,11:

                                • Outermost lipid layer, produced by meibomian glands
                                • Aqueous layer, produced by the lacrimal gland
                                • Innermost mucin layer, produced by goblet cells

                                 

                                Tear film instability, primarily increased tear osmolarity, leads to ocular surface damage in DED.7 DED's categorization is based on the mechanism leading to tear hyperosmolarity. In aqueous deficient dry eye disease (ADDE), decreased tear secretion increases tear film osmolarity. Increased evaporation of tears leads to hyperosmolarity in (you guessed it) evaporative dry eye disease (EDE).5

                                 

                                ADDE is further categorized based on the underlying cause: Sjogren’s Syndrome or non-Sjogren’s syndrome. As mentioned, Sjogren’s syndrome is an autoimmune disease attacking the salivary and lacrimal glands resulting in dry mouth and eyes. Non-Sjogren’s syndrome ADDE has various causes, including lacrimal deficiency, lacrimal gland duct obstruction, and systemic drugs. These mechanisms decrease tear secretion, resulting in tear hyperosmolarity.5,10

                                 

                                Meibomian gland dysfunction (MGD) is the primary cause of EDE.12,13 Meibomian glands line the inside of the upper and lower eyelid. Lipid secretion by meibomian glands forms a coating on the aqueous layer, impeding tear evaporation and providing protection against environmental irritants. Risk factors for MGD include aging, hormonal changes, contact lens wear, diet, and systemic and topical medications.13

                                 

                                Separation of DED into ADDE and EDE implies mutual exclusivity, but many patients presenting with DED exhibit characteristics of both. Recent evidence indicates the two classifications co-exist, with more patients presenting with EDE due to MGD. 6,14,15 Regardless of the subtype or mechanism, the result is a vicious, self-perpetuating cycle of inflammation.6,16 Tear film hyperosmolarity triggers an innate inflammatory immune response, activating CD4+ T-cells. This leads to conjunctival and corneal cell death and impaired lacrimal gland function, further decreasing tear production.16,17 This further increases tear hyperosmolarity, which continues the cycle.

                                 

                                Diagnosing DED is problematic due to its multi-factorial nature and inconsistent symptom presentation. Exploring differential diagnoses using triaging questions is crucial to exclude diseases that mimic DED, including allergic, bacterial, or viral conjunctivitis; blepharitis; and rheumatic disorders.5,18 A thorough patient history screens for risk factors such as smoking, contact lens wear, and certain systemic and topical medications. Several questionnaires also exist to help clinicians screen for DED. The Dry Eye Disease Questionnaire (DEQ-5) contains five items asking patients to rate the frequency of eye discomfort, eye dryness, and watery eyes during a typical day.18 The Ocular Surface Disease Index (OSDI) is another popular questionnaire. The OSDI questionnaire asks a series of 12 questions assessing eye symptoms, vision issues (e.g., reading, driving), and environmental conditions.18

                                 

                                Patients with positive questionnaire results should progress to a more detailed tear film and ocular surface examination. A positive result in any of the following tests is diagnostic of DED18:

                                • Tear breakup time (TBUT): There are two methods for measuring TBUT, using fluorescein dye or illumination of the cornea. Both measure how long it takes for tears to break up after a blink. Lower TBUT scores indicate tear instability.
                                • Osmolarity: Clinicians use a device with a test strip to gain a sample of the tear film from both eyes to check tear osmolarity. An osmolarity of 308 mOsm/L or greater in either eye or a difference of more than 8 mOsm/L between the eyes is diagnostic of DED.
                                • Ocular surface staining: After applying dye to the lower eyelid’s inner lining, clinicians examine the ocular surface for missing or damaged epithelial cells. Positive scores range from five to nine spots depending on the dye used.

                                 

                                Clinicians also commonly deploy the Schirmer test to evaluate the eye’s ability to produce tears. A notched paper strip placed over the lower eyelid stimulates tear production during the test. After five minutes, a length of wetting greater than 10 mm indicates normal tear function. Values less than 5 mm signify tear insufficiency.18

                                Pause and ponder: How would vision loss affect your everyday life?

                                 

                                Treatment Goals

                                Treatment goals for DED are to decrease ocular inflammation and restore ocular surface homeostasis (balance). DED's complexity and heterogeneous presentation necessitate an individualized approach. TFOS DEWS II recommendations emphasize identifying the disease’s root cause to determine an appropriate management approach.14 From there, the report outlines a stepwise, flexible approach to guide treatment based on patient-specific disease etiology and severity.14 Table 2 briefly summarizes recommended management steps.

                                 

                                Table 2. Treatment Steps in DED Management14

                                Step 1:

                                ·       Education

                                ·       Environmental modifications

                                ·       Lifestyle modifications

                                ·       Dietary supplementation

                                ·       Eyelid hygiene

                                ·       Medication review

                                ·       Artificial Tears

                                Step 2:

                                ·       Preservative-free artificial tears

                                ·       Prescription therapy

                                ·       Tear Conservation

                                ·       Overnight treatments

                                ·       In-office treatments

                                Step 3:

                                ·       Tear stimulation

                                ·       Biological tear substitutes

                                ·       Therapeutic contact lenses

                                Step 4:

                                ·       Prescription therapy

                                ·       Surgical intervention

                                 

                                 

                                NON-PHARMACOLOGIC TREATMENT

                                One of the first steps, patient education, is essential for successful disease management.14 Patient education starts with thoroughly explaining DED’s chronic nature, including the ongoing, often long-term nature of therapeutic management. Discussing the patient’s home and work environment during the session may identify contributing factors.14 The environment affects overall health and well-being. Air pollution, low humidity, high altitude, and wind contribute to DED development.14 Adding an air humidifier inside or using protective eyeglasses outside can help mitigate DED symptoms. Other strategies include minimizing exposure to digital screens, cigarette smoke, and air conditioning.19

                                 

                                Proper lid hygiene is important in managing many eye conditions, including DED.14 Patients can use a cotton swab to scrub the eyelid with a dilute solution of baby shampoo to keep the area free of crusty build-up and environmental contaminants. Warm eye compresses also promote good lid hygiene and help alleviate DED symptoms. Unfortunately, lid hygiene adherence is poor, with estimates of just over 50% adherence at six weeks.14 Reinforcing the importance of lid hygiene with patients is an important component of DED patient counseling.

                                 

                                Identifying medications that may contribute to DED is an important task for pharmacy staff. Many medication classes produce drying effects on the body, intentionally or as an adverse effect.14,19 Table 3 lists examples of medications that may worsen DED. Pharmacists and pharmacy technicians should review patient profiles to identify drying medications, including ophthalmic formulations, as medications for glaucoma (an eye condition causing progressive vision loss) may contribute to DED.14 Mitigating options to consider include changing the route of administration from oral to topical, substituting with a therapeutic alternative, and adjusting doses.14

                                Table 3. Examples of Medications that Worsen Dry Eye Disease14,19

                                Drug Class Examples
                                Antihistamines and decongestants

                                 

                                Chlorpheniramine

                                Diphenhydramine

                                Fexofenadine

                                Loratadine

                                Pseudoephedrine

                                Antidepressants

                                ·       TCA

                                ·       SSRI

                                ·       SNRI

                                 

                                Amitriptyline

                                Citalopram

                                Duloxetine

                                Fluoxetine

                                Sertraline

                                Venlafaxine

                                Anti-Parkinson’s Levodopa
                                Antipsychotics

                                 

                                Aripiprazole

                                Perphenazine

                                Quetiapine

                                Beta-blockers

                                 

                                Atenolol

                                Carvedilol

                                Metoprolol

                                Propranolol

                                Diuretics

                                 

                                Furosemide

                                Hydrochlorothiazide

                                Proton pump inhibitors

                                 

                                Omeprazole

                                Pantoprazole

                                Hormone therapy Estrogen

                                DED = dry eye disease; TCA = tricyclic antidepressants; SSRI = serotonin-selective reuptake inhibitor; SNRI = serotonin-norepinephrine reuptake inhibitor

                                 

                                Diet and Nutrition

                                An emerging body of evidence suggests that certain diet changes and nutritional supplementation may play a role in DED treatment. Dehydration increases tear osmolarity, so maintaining adequate hydration is important to disease control.14 Lactoferrin is an anti-inflammatory glycoprotein found in natural tears. Studies have found decreased lactoferrin levels in patients with DED leading researchers to the explore lactoferrin topical application and oral supplementation as treatment for the condition. One study found improved dry eye symptoms and tear film stability in patients taking an oral lactoferrin supplement.20 Oral lactoferrin is available as a supplement in many retail locations.

                                 

                                Supplementation with omega-3 fatty acids also shows potential in DED. Omega-3 fatty acids block proinflammatory substances and are essential for ocular surface homeostasis.14 Some studies have found that omega-3 fatty acid supplementation improves TBUT and Schirmer scores.21,22 Conversely, The Dry Eye Assessment and Management (DREAM) trial reported no difference between groups receiving omega-3 fatty acids and placebo.23 While oral omega-3 fatty acids show benefit for some patients, further study is necessary. These conflicting results prompted studies for alternative administration routes. Topical application of omega-3 fatty acids shows promise. A systematic review of 10 studies (five in animals and five in humans) showed overall improvement in ocular surface staining and TBUT.24 Further study is necessary to evaluate long-term efficacy and optimize dosage and delivery formulations.

                                 

                                Artificial Tears

                                Patients often attempt self-treatment before seeking healthcare professional assistance. Tear replacement with artificial tear (AT) formulations is essential for patient comfort and a mainstay of initial and ongoing therapy. Global sales of AT reached $2.64 billion in 2019, and experts predict this to reach $4.30 billion by 2027.25 Many AT products line the pharmacy shelves, all touting their ability to lubricate the eye. Faced with the confusing array of products, patients often employ a trial-and-error approach for AT selection, leading to high costs and frustration. Knowing the differences between ATs enhances the pharmacy team’s ability to counsel patients effectively.

                                 

                                AT supplementation is generally safe and well tolerated and associated adverse effects are mild, including blurred vision and ocular discomfort.14 Most ATs are water-based with viscosity-enhancing agents added for lubrication. Osmolarity, viscosity, and pH vary between products. Table 4 describes the components of AT products and their functions.

                                 

                                Table 4. Components of Artificial Tear Products11,14,26

                                Component Purpose Examples
                                Viscosity-enhancing agents (lubricants) Aid lubrication

                                Increase tear film thickness

                                Protect ocular surface

                                Promote tear retention

                                Improve goblet cell density

                                Carbomer 940 (polyacrylic acid)

                                Carboxymethyl cellulose (CMC)

                                Dextran

                                Glycerin

                                Hyaluronic acid (HA)

                                Hydroxypropyl-guar (HP-guar)

                                Hydroxypropyl methylcellulose (HPMC)

                                Polyvinyl alcohol

                                Polyvinylpyrrolidone

                                Polyethylene glycol (PEG)

                                Lipids

                                 

                                Restore the lipid layer

                                Increase lipid layer thickness

                                Prevent evaporation

                                Mineral oil

                                Castor oil

                                Flaxseed oil

                                Osmoprotectants

                                 

                                Balance osmotic pressure

                                 

                                Trehalose

                                Levocarnitine

                                Erythritol

                                Betaine

                                Preservatives

                                 

                                Prevent microbial growth in multi-dose formulations Benzalkonium chloride (BAK)

                                Sodium chlorite

                                Sodium perborate

                                Buffers

                                 

                                Control pH Sodium borate

                                Sodium citrate

                                Sodium phosphate

                                Electrolytes

                                 

                                Promote ocular surface homeostasis Potassium

                                Calcium

                                Magnesium

                                Phosphate

                                 

                                 

                                Viscosity-enhancing agents, or demulcents, are the most common ingredient in AT and typically listed as the active ingredient on product packaging. The higher the viscosity (i.e., the thicker the product), the longer the ocular surface retention time, but differences in viscosity can influence product choice. High viscosity can create visual disturbances and buildup on the eyelid leading to decreased adherence.26 These products are best for nighttime use, and patients should use lower-viscosity products during the day.26 Many products contain multiple viscosity-enhancing agents. Commonly paired agents include carboxymethyl cellulose (CMC) with hyaluronic acid (HA) and hydroxypropyl-guar (HP-guar) with HA.14,26 Studies suggest that combining viscosity-enhancing components improves symptom control.14

                                 

                                There is significant interest in developing novel formulations to increase the spreading and retention time of applied drops.14 Lipid-containing eye drops are gaining in popularity as understanding of DED’s pathophysiology progresses.14 Lipids restore and thicken the lipid layer of the tear film and prevent tear evaporation. Formulated as oil-in-water emulsions, lipid-containing products contain macro-, micro-, or nano-particles. Particle size is important. Macro particles are associated with cloudy, blurred vision. As particle size decreases, blurring decreases.14

                                 

                                Osmoprotectants balance osmotic pressure, as the name implies, to protect and prevent corneal and conjunctival cell death.26 Levocarnitine and erythritol protect cells from hyperosmolar stress and improve DED’s symptoms.26 Clinical trials have shown that trehalose is more effective at improving ocular surface staining than saline.14,26

                                 

                                Multi-dose products contain preservatives to prevent microbial growth, but these can also worsen symptoms in DED. Benzalkonium chloride (BAK), the most common preservative, may cause corneal damage and interfere with tear film stability.14 Newer “disappearing preservatives” (e.g., sodium chlorite, sodium perborate) have a lower impact on the ocular surface. Exposure to light or the ocular surface breaks down these compounds, minimizing toxicity.14,27 Even newer preservatives carry risk, making preservative-free drops the best choice, especially in patients with severe DED. Preservative-free AT products are available in disposable single-use units but are generally more expensive.14

                                 

                                The pH of ATs affects product activity, stability, patient comfort, and safety.14 Adding electrolytes to reproduce the electrolyte profile of the tear film aids osmotic balance. Studies show that hypotonic solutions (i.e., having a lower osmotic pressure) decrease DED signs.26

                                 

                                No large-scale, randomized clinical trials have evaluated all currently available AT formulations. Some clinical trials evaluate individual AT products, and a few head-to-head studies exist.16,28 Several published systematic reviews have concluded that ATs treat DED safely and effectively. One systematic review of more than 60 studies published in 2022 drew the following conclusions27:

                                • Combination formulations, including the following, may be more effective than single-ingredient products: CMC and HA, HA and trehalose, CMC and glycerin, and HA and coenzyme Q10.
                                • Formulations containing polyethylene glycol (PEG) may be more effective than those with CMC.
                                • Preservative-free formulations are preferable.
                                • Patients with EDE and/or MGD should use drops containing phospholipids.
                                • Patients should administer AT four times daily for one month to assess efficacy.
                                • Patience is key; sometimes, it may take up to four months of consistent use to see improvement.

                                 

                                Another literature review of 18 studies compared commercially available AT products and concluded that products containing CMC, hydroxypropyl methylcellulose (HPMC), or HA were the most beneficial in improving patient comfort level.29 This study also determined that clinicians should recommend administration three to four times daily for two months to assess patient response before escalating therapy. The use of a preservative-free formulation is preferable.29 If patients choose or clinicians recommend preservative-containing eye drops, administration should be limited to four to six times daily.29 Researchers created a stepwise approach to selecting AT products29:

                                • Step 1: Start with CMC, HPMC, or HA-based formulations
                                • Step 2: Move to formulations with PEG or PEG and glycerin
                                • Step 3: Consider gel or lipid formulations
                                • Step 4: Progress to ointments, liposomal sprays, or prescription inserts

                                 

                                Both studies reached similar conclusions. Adherence and persistence are key to successfully evaluating an individual product, a fact that pharmacy staff should reiterate to patients. While some trial and error may be necessary, following the above recommendations allows patients and providers an organized approach to AT selection. While AT are a mainstay of early symptomatic treatment of dry eye disease, they do not address DED’s underlying causes. Prescription therapies target the underlying inflammatory processes.

                                 

                                Hydroxypropyl cellulose ophthalmic insert (HCOI) is a prescription-only lubricant insert containing 5 mg of hydroxypropyl cellulose. The insert is preservative-free and designed to provide continuous lubrication throughout the day. Patients insert HCOI once daily using an applicator.30 They rinse the applicator in hot water then use the grooved end to pick up the insert. Patients then place the insert in a pocket created by pulling out the outer corner of the eyelid. The HCOI softens and slowly dissolves, stabilizing and thickening the tear film, prolonging TBUT. One study comparing HCOI to using AT four or more times a day found increased TBUT and decreased foreign body sensation with HCOI compared to AT.30,31 Reported adverse effects include blurred vision, eye irritation, eyelid matting, and light sensitivity.30

                                 

                                Pause and Ponder: A patient approaches the pharmacy counter with a plastic bag full of bottles of different brands of artificial tears. Dumping them on the counter, she states, “None of these work! I don’t know what to do next.” What advice would you give her?

                                 

                                PRESCRIPTION THERAPIES

                                Available prescription therapies (outlined in Table 5) target the inflammatory cycle of DED through different mechanisms with varying degrees of success.

                                 

                                Table 5. Prescription Therapies to Treat Dry Eye Disease28,32-36

                                Drug Brand Name (Manufacturer) Formulation(s) Dosing Supplied
                                Cyclosporine A Restasis

                                (Allergan)

                                0.05% emulsion 1 drop in each eye BID Single-use vials
                                Cequa

                                (Sun Pharma)

                                0.09% solution 1 drop in each eye BID Single-use vials
                                Generic

                                (Mylan)

                                0.05% solution 1 drop in each eye BID Single-use vials
                                Lifitegrast Xiidra

                                (Novartis)

                                5% solution 1 drop in each eye BID Single-use containers
                                Loteprednol Eysuvis

                                (Kala Pharma)

                                0.25% suspension 1-2 drops in each eye QID for up to 2 weeks Multi-dose 10 mL bottle
                                Perfluorohexyloctane Meibo

                                (Bausch & Lomb)

                                100% solution 1 drop in each eye QID Multi-dose 5 mL bottle
                                Varenicline Tyrvaya

                                (Oyster Point Pharma)

                                0.03 mg/0.05ml solution 1 spray in each nostril BID Multi-dose nasal spray

                                ABBREVIATIONS: BID, twice daily; QID, four times daily

                                 

                                Cyclosporine A

                                Cyclosporine A (CsA) is an anti-inflammatory immune modulator approved for use in DED more than two decades ago.16 Calcineurin activates T-cells, increasing inflammatory cytokine production. CsA inhibits calcineurin to prevent T-cell activation, disrupting the inflammatory cycle in DED.16

                                 

                                Many clinical trials have evaluated CsA’s safety and efficacy in DED treatment.1,5,14,37 Results consistently show that CsA improves Schirmer test scores, corneal staining results, and goblet cell density. Improvement often takes several months, making patient education key to adherence.1,5,14,37 Topical CsA alleviates symptoms in approximately 50% of patients.1 Patients using CsA experience decreases in blurred vision, ocular dryness, foreign body sensation, and watery eyes.1,14 Treatment often causes stinging and irritation. Other adverse effects include blurred vision, ocular itching, eye redness, and foreign body sensation.37 Pretreatment with an ophthalmic steroid such as loteprednol may decrease CsA’s adverse effects.1,38

                                 

                                As a hydrophobic (water-fearing) substance, CsA is challenging to formulate into an ophthalmic topical formulation. Initially, products used castor oil and corn oil as vehicles, but poor bioavailability and adverse effects preclude their use.16 The first commercially available CsA product, a 0.05% emulsion, uses a castor oil-in-water emulsion, which reduces but does not eliminate adverse reactions.37

                                 

                                Approval of CsA 0.09% nanomicellar solution introduced a novel formulation.16,37 Clinical efficacy trials found a response as early as day 28.16At the end of 12 weeks, 17% of study participants receiving CsA 0.09% experienced increased tear production with a Schirmer score greater than 10 mm. Reported adverse effects included mild instillation site pain, eye irritation, blepharitis, and headache.32 Preliminary studies suggest CsA 0.09% is more effective and better tolerated than CsA 0.05%.16

                                 

                                Lifitegrast

                                Approved in 2016, the novel drug lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist.33 LFA-1 binds to intracellular adhesion molecule-1 during inflammation, activating T-cell migration and resulting in ocular inflammation. Lifitegrast binds to LFA-1, preventing this interaction and decreasing T-cell-mediated inflammation.33 The U.S. Food and Drug Administration (FDA) approved this drug based on four randomized, double-masked, 12-week efficacy and safety trials. 33,39-41 All studies showed a reduction in patient-rated eye dryness scores at the end of 12 weeks. Patients in three of the four studies experienced reduced corneal staining scores.33

                                 

                                The one-year multicenter, randomized, placebo-controlled SONATA study evaluated lifitegrast safety.42 Reported adverse effects included burning, reduced visual acuity, dry eye, and taste changes. Researchers observed no serious adverse events and discontinuation rates were 12.3% and 9% for lifitegrast and placebo, respectively.42 A 2021 retrospective review of 600 patient charts examined real-world experience with lifitegrast in DED.43 Most patients continued treatment for six months and showed improvement in DED symptoms. Patients also experienced improved quality of life at three and 12 months of treatment.43

                                 

                                Perfluorohexyloctane

                                Perfluorohexyloctane, formerly known as NOV3, reduces tear evaporation from the ocular surface.44 The drug’s exact mechanism in DED is unclear. In May 2023, the FDA approved an ophthalmic formulation containing perfluorohexyloctane for treating DED in adults 18 and older based on data from two phase 3 clinical trials: GOBI and MOJAVE.44,45

                                 

                                These trials evaluated efficacy and safety in more than 1,200 patients with DED meeting similar inclusion and exclusion criteria based on tear film break-up time, ocular surface disease scores, and MGD evaluations. Both trials were multi-center, randomized, double-masked, and saline-controlled.44,45 GOBE and MOJAVE results also consistently showed statistically significant reductions in reported symptoms of DED. Reported adverse events occurred in less than 4% of study participants and included blurred vision, blepharitis, instillation site pain, and conjunctival redness.44,46 Patients must remove contact lenses before and for at least 30 minutes after administration of perfluorohexyloctane drops.34

                                 

                                Perfluorohexyloctane should be available in the second half of 2023.44

                                 

                                Short-Term Corticosteroids

                                Corticosteroids are potent inhibitors of inflammatory mediators.14 Many clinical trials have demonstrated their efficacy in breaking the inflammatory cycle of DED. Unfortunately, long-term therapy is associated with increased intraocular pressure, cataracts, and risk of infection.14

                                 

                                Loteprednol is a synthetic corticosteroid derived from prednisolone. Its rapid breakdown into inactive metabolites reduces risk of adverse reactions.47 A retrospective safety study concluded that loteprednol therapy carries a low risk of treatment-related elevated intraocular pressure compared to other steroids.48 Several loteprednol ophthalmic formulations are available, but only the 0.25% suspension is FDA approved for the short-term treatment of DED. This formulation uses mucus-penetrating particle (MPP) technology to allow nanoparticle penetration through the mucin layer.47,49

                                 

                                The FDA approved loteprednol 0.25% suspension based on the STRIDE series of trials.36 These trials randomized patients with DED to the drug or a vehicle control four times daily in both eyes for two weeks. All trials reported significant improvements in eye redness and discomfort at the end of two weeks.36

                                 

                                One role for topical steroids in DED is pre-treatment prior to topical CsA therapy. A 2014 study compared loteprednol versus AT during a two-week lead-in period to CsA.38 Patients self-administered either loteprednol or AT four times daily for two weeks, followed by CsA twice daily plus either loteprednol or AT twice daily for an additional six weeks. Both groups showed improved ocular staining and OSDI and Schirmer scores. Loteprednol provided more rapid relief of DED symptoms and resulted in a lower CsA discontinuation rate than AT.38

                                 

                                Patients with moderate-to-severe DED with adequate long-term control may still experience periodic symptom exacerbation. Short-term pulse steroid therapy (using steroids of a week or two, then tapering and resuming if necessary) can be useful for patients with symptom exacerbations.14

                                 

                                Varenicline Nasal Spray

                                Pharmacy staff may recognize varenicline as a treatment for smoking cessation, but a newer nasal spray formulation shows utility for treating DED. Tear film production results from stimulating afferent nerves in the cornea and conjunctiva and parasympathetic nerves in the lacrimal gland, meibomian glands, and goblet cells.50,51 This neural pathway is accessible through central nervous system or peripherally through the nasal cavity. While the drug’s mechanism in DED is not fully understood, experts theorize that varenicline, a cholinergic agonist, activates this pathway to stimulate tear production.50,51

                                 

                                The randomized, double-masked, vehicle-controlled, 28-day ONSET-1 and ONSET-2 trials evaluated varenicline nasal spray’s safety and efficacy.50,51 Participants self-administered one spray of varenicline solution or vehicle in each nostril twice daily. Both studies found a significant improvement in tear production measured by Schirmer scores. The most common patient-reported adverse effects included sneezing, cough, throat irritation, and nasal irritation.50,51 The 2021 MYSTIC study examined varenicline nasal spray's long-term safety and efficacy compared to placebo over a 12-week period.52 Patients reported no severe or serious adverse events during the study; sneezing was the most common adverse reaction, occurring in 82% of patients.52

                                 

                                Varenicline packaging includes two glass bottles, each containing a 15-day drug supply. Patients must initially prime the bottle by pumping seven sprays into the air away from the face. Re-priming by pumping one spray into the air is necessary after five days of nonuse.35

                                 

                                Steps for administration of varenicline nasal spray35:

                                • Blow nose if needed to clear nostrils
                                • Remove the cap and clip from the bottle
                                • Hold the bottle upright, placing one finger on each side of the applicator and thumb on the bottom of the bottle
                                • Tilt head back slightly
                                • Insert the applicator tip into one nostril, pointing it toward the ear on the same side of the nostril, leaving space between the tip and the wall of the nostril
                                • Place tongue on roof of mouth and breath gently while pumping one spray into the nostril
                                • Repeat in other nostril
                                • Wipe the applicator with a clean tissue and replace the cap and clip

                                 

                                Antibiotics

                                Clinicians sometimes use oral or topical antibiotics with anti-inflammatory effects off-label to treat DED due to MGD.14 Many patients experience MGD due to overgrowth of eyelid flora, so reduction of eyelid flora and inflammation improves patient-reported symptoms.53 Oral administration of doxycycline and minocycline in small doses (40 to 400 mg of doxycycline and 50 to 100 mg of minocycline) to treat MGD improves patient-reported symptoms.1,53 Unfortunately, gastrointestinal adverse effects limit the use of these medications. One study found that azithromycin 1% eyedrops improved eyelid inflammation and tear film lipid layer stability.54

                                 

                                EMERGING THERAPIES

                                New and novel therapies are also in the pipeline for DED treatment. Pharmacy staff should be aware of their potential place in therapy and prepared to incorporate them upon approval.

                                 

                                Reproxalap

                                Exploring another causative mechanism in DED, reproxalap is a reactive aldehyde species (RASP) inhibitor. RASP molecules are found at the top of the inflammatory cascade and are elevated in many inflammatory diseases. They bind to and disrupt the function of enzymes and ion channels, which activates pro-inflammatory mediators. RASP inhibition, therefore, decreases pro-inflammatory substances associated with DED.55,56

                                 

                                A randomized, double-masked, phase 2a trial evaluated the efficacy of three formulations of reproxalap: 0.1% and 0.5% solutions and a 0.5% lipid solution.55 Participants used the products four times daily for 28 days. The study found a significant improvement in four questionnaire scores, Schirmer test values, tear osmolarity, and tear staining scores. Within one week, patients reported symptom improvement. Researchers concluded that reproxalap could potentially alleviate DED symptoms.55

                                 

                                A separate randomized, double-masked, phase 2b trial compared reproxalap 0.01% and 0.25% to a control vehicle solution.56 Patients self-administered drops four times daily for a total of 12 weeks. The study found statistically significant improvements in ocular dryness and staining over 12 weeks.56

                                 

                                A 2021 tolerability study compared ocular adverse effects between two formulations of reproxalap 0.25% (one solution, one lipid-based) and lifitegrast 5% solution.57 Over seven days, study participants received one dose of each solution with a 3-day washout period between administrations. Researchers assessed adverse effects after 1 hour. Reproxalap formulations were similar to one another and superior to lifitegrast in ocular discomfort, blurry vision, and dysgeusia.57

                                 

                                Reproxalap offers a novel approach to treating the underlying inflammatory process involved in DED. Preliminary study results show improvements in DED symptoms and better patient tolerability, potentially leading to lower discontinuation rates and improved patient outcomes.

                                 

                                Cationic Cyclosporine

                                A cationic (positively charged) 0.1% CsA nanoemulsion is available in Europe to treat DED.58 Experts theorize that a cationic emulsion increases the surface time of CsA on ocular tissues. All FDA-approved products are anionic (negatively charged). Clinical trials are evaluating CsA 0.1% nanoemulsion for FDA approval.58

                                 

                                PHARMACY TEAMS: FRONT-LINE SUPPORT

                                Pharmacists and pharmacy technicians are among the most accessible healthcare providers. People routinely turn to neighborhood pharmacies for advice on many health topics. Most people self-treat dry eye symptoms long before seeking professional help. These facts make the pharmacy team essential in supporting people suffering from DED. The SIDEBAR provides basic counseling information about eye products.

                                 

                                SIDEBAR: Counseling Tips for Eyedrop and Eye Ointment Administration59,60

                                Proper administration of ophthalmic formulations is key to their success. Administration is awkward, and many patients struggle with it. Advising patients on proper technique is a key role for the pharmacy team. General tips for all ophthalmic products include

                                • Confirm you have the correct product
                                • Check expiration date
                                • Read the directions
                                • Wash your hands
                                • If using both eyedrops and eye ointment, wait five to ten minutes between drops, and administer the eyedrops at least 10 minutes before the ointment
                                • Using a mirror may make it easier to see what you are doing

                                 

                                Eyedrops:

                                1. Gently shake the bottle
                                1. Be sure the eye dropper is clean, and do not let it touch any surface
                                2. Tilt your head back and look up
                                1. Pressing your finger gently on the skin just beneath the lower eyelid, pull your lower eyelid down and away from your eyeball to make a “pocket” for the drops
                                2. With the other hand, hold the eye drop bottle upside down with the tip just above the pocket
                                3. Squeeze the prescribed number of eye drops into the pocket
                                4. If you think you did not get the drop of medicine into your eye properly, use another drop
                                5. Blink a few times so that the medicine spreads across your eye
                                6. For at least 1 minute, close your eye and press your finger lightly on your tear duct (small hole in the inner corner of your eye) to keep the eye drop from draining into your nose
                                1. Wash your hands
                                1. Wait at least 10 minutes before you use other eye products, especially ointments, gels, or other thick eye drops

                                 

                                Eye ointment:

                                1. Be sure the top of the ointment tube is clean, and don’t let it touch any surface, including the eye, eyelid, or lashes. (If it does, call your pharmacy and arrange to get another tube of eye ointment.)
                                2. Tilt your head back and look up
                                3. With one hand, pull the lower eyelid down with one or two fingers to create a small pouch
                                4. With the other hand, position the medicine above your eye
                                5. Put a thin line of ointment in the pouch. Close the eye for 30 to 60 seconds to let the ointment absorb
                                6. Wash your hands
                                7. Eye ointments can cause some temporary blurring of vision

                                 

                                Knowledge of risk factors, including precipitating medications (revisit Table 3 for a refresher), aids in identifying patients at risk for developing DED. Technicians are often the first point of contact at the pharmacy counter, routinely fielding questions. Actively listening and asking open-ended questions help gather necessary information. Patients reporting dry eye symptoms or buying AT products may need counseling or a referral to a pharmacist or an eye care professional.

                                 

                                Educating patients about avoiding certain environmental factors is important. Remind patients that minimizing exposure to wind or smoke, taking a break from digital screens, and using a humidifier may help alleviate symptoms. Adherence to therapeutic interventions is key in DED treatment. Some interventions, such as lid hygiene, are time-consuming, and many patients stop after only a few days.  Reinforcing the importance of lid hygiene with patients is an important component of DED patient counseling.

                                 

                                 

                                Advising patients on selecting an appropriate AT product decreases frustration and increases overall patient satisfaction. Proper administration of ophthalmic preparations can be difficult for some patients, particularly older individuals. Taking the time to counsel on proper technique sets patients up for successful administration and improved outcomes.

                                 

                                Patients with severe refractory DED may not benefit enough from lifestyle modifications and pharmacologic therapy. Many other interventions exist including14

                                • Punctal plugs blocking the tear ducts to promote tear conservation
                                • Pulsed light therapy delivered in office with a handheld flash gun
                                • Tear stimulation utilizing topical and systemic secretagogues
                                • Biological tear substitutes utilizing patient-derived serum
                                • Use of therapeutic contact lenses made of silicone hydrogel
                                • Surgery to correct any causative physiological abnormalities

                                Pharmacy staff should recognize when patients with worsening DED symptoms may require escalation of therapy and refer them to an eye care provider when appropriate.

                                 

                                Pause and Ponder: Consider your home and work environment. Could you take steps to minimize conditions contributing to developing dry eye?

                                 

                                CONCLUSION

                                You may have noticed a recurring theme throughout this activity: education. Helping patients understand the chronic nature of DED and navigate treatment options improves patient care and outcomes. Education must include the entire pharmacy team. Understanding the roles of each treatment allows for effective management and counseling. Educated pharmacy teams can assist patients with product selection, counsel on the timing and administration of treatments, improve safety, and provide referrals when appropriate.

                                 

                                Pharmacist Post Test (for viewing only)

                                The Nitty Gritty: Dry Eye Guidance for the Pharmacy Team

                                Posttest

                                Learning Objectives:
                                1. Describe the etiology and pathophysiology of dry eye disease (DED) and its impact on quality of life
                                2. Identify available and emerging over-the-counter and prescription therapies to treat DED
                                3. Optimize artificial tear selection based on patient-specific characteristics
                                4. Infer when to refer patients to the pharmacist or an eye care provider for DED

                                Pharmacists:
                                1. Which of the following is a risk factor for developing DED?
                                A. Caucasian race
                                B. Digital device use
                                C. Obesity

                                2. How does meibomian gland disease (MGD) contribute to DED?
                                A. Decreased lipid secretion affecting the outer layer of the tear film
                                B. Increased lipid secretion affecting the outer layer of the tear film
                                C. Decreased tear secretion leading to tear film instability

                                3. Prince Charming shares with you his recent DED diagnosis. Which of the following medications in his profile is most likely contributing to his symptoms?
                                A. Duloxetine
                                B. Donepezil
                                C. Erythromycin

                                4. Which of the following is a function of viscosity-enhancing agents in artificial tears?
                                A. Balance osmotic pressure
                                B. Control pH
                                C. Increase lubrication

                                5. Olaf stops by the pharmacy asking for assistance selecting an artificial tear product. He describes mild dry eye symptoms he is experiencing with the change in seasons. As a first choice, you suggest a product containing which of the following?
                                A. Carboxymethylcellulose (CMC)
                                B. CMC and hyaluronic acid (HA)
                                C. Polyvinyl alcohol

                                6. Which of the following is the most appropriate way to advise Olaf to use the recommended AT product to effectively manage symptoms and assess efficacy?
                                A. Apply 1-2 drops in each eye 1-2 times a day for 4-6 months
                                B. Apply 1-2 drops in each eye 4-6 times a day for 1-2 weeks
                                C. Apply 1-2 drops in each eye 3-4 times a day for 1-2 months

                                7. Buzz Lightyear recently received a diagnosis of DED due to MGD. Which of the following would be an appropriate first-line treatment choice?
                                A. Artificial tears formulated with mineral oil
                                B. Loteprednol 0.25% ophthalmic suspension
                                C. Oral omega-3 fatty acid supplements

                                8. Elsa started using cyclosporine A 0.05% eye drops for DED last month. While picking up her first refill, she mentions the drops are controlling her symptoms well but causing a burning sensation when she administers them. Which of the following is the most appropriate response?
                                A. Let her know this is a known adverse effect and to continue therapy as prescribed
                                B. Recommend she stop using the drops immediately, as she may be harming her eyes
                                C. Offer to contact her eye care provider to switch to cyclosporine A 0.09%

                                9. Which of the following is a novel eye drop approved for long-term use in DED?
                                A. Perfluorohexyloctane
                                B. Varenicline
                                C. Loteprednol

                                10. Snow White frequently stops by the pharmacy to ask for guidance about treating her DED. Today she shared that her AT is no longer working, and it’s the fifth one she has tried. You confirm she is properly and consistently administering ATs. Which of the following is the BEST recommendation for Snow White?
                                A. Assist her in selecting a more appropriate AT product to try based on trial-and-error
                                B. Advise her to reach out to her ophthalmologist to explore prescription therapies
                                C. Tell her that she must move out of the dusty cabin she shares with the seven dwarves

                                Pharmacy Technician Post Test (for viewing only)

                                Pharmacy Technicians:
                                1. Dry eye disease (DED) affects approximately how many U.S. adults?
                                A. 7 million
                                B. 16 million
                                C. 23 million

                                2. Which of the following is a risk factor for developing DED?
                                A. Caucasian race
                                B. Digital device use
                                C. Obesity

                                3. Prince Charming shares his recent diagnosis of DED. Which of the following medications in his profile may be a contributing factor?
                                A. Duloxetine
                                B. Donepezil
                                C. Erythromycin

                                4. Why is it important to engage with patients at the counter and ask open-ended questions?
                                A. So you can stay updated with their vacation plans and get some destination ideas
                                B. To help gather important health-related patient information and optimize therapy
                                C. It’s not important; the patient wants to pick up their prescription as quickly as possible

                                5. Which of the following is a function of viscosity-enhancing agents in artificial tears?
                                A. Balance osmotic pressure
                                B. Control pH
                                C. Increase lubrication

                                6. Cinderella approaches the register with two open bottles of AT and a receipt from one week ago. She asks if she can return the products, as they did not work. Which of the following is the BEST response?
                                A. Refer Cinderella to the front end of the store to process the refund
                                B. Issue Cinderella a refund and suggest she speak to an ophthalmologist
                                C. Refer Cinderella to the pharmacist for counseling

                                7. Buzz Lightyear stops at the counter to purchase artificial tear eye drops. When he asks you how to use them, what should you do?
                                A. Tell him to follow the directions on the box; they clearly outline how to use them
                                B. Offer Buzz a patient handout explaining eye drop use, and refer him to the pharmacist
                                C. Explain that his doctor is the best person to educate him about eye drop administration

                                8. Olaf stops by the pharmacy, complaining that his eyes always feel dry, especially when he is outside sledding. Which of the following is the BEST suggestion?
                                A. Wear eye protection when sledding to reduce wind exposure
                                B. Watch YouTube videos of other people sledding instead
                                C. Build a snowman friend on top of the mountain and play there

                                9. Elsa seems quieter than usual when picking up her prescriptions. When you ask her if everything is OK, she shares that it feels like something is in her eye all the time and she is having a hard time reading her book for book club. Which of the following is the BEST response?
                                A. Suggest that she get the audiobook instead so she can still enjoy her book club
                                B. Let her know that this is common and over-the-counter therapies may help
                                C. Recommend that she see an eye care provider to prescribe loteprednol eye drops

                                10. While picking up a prescription, Snow White also purchases 4 bottles of artificial tears, stating that she goes through them like water. When you ask her if they help, she replies “Eh, not really…” How should you respond?
                                A. Tell her to keep it up; sometimes, artificial tears take a while to work
                                B. Explain that this isn’t typical and refer her to the pharmacist for counseling
                                C. Let her know it’s okay to stop using them if they aren’t working

                                References

                                Full List of References

                                References

                                   
                                  References
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                                  2. Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017;182:90-98. doi:10.1016/j.ajo.2017.06.033
                                  3. Dana R, Bradley JL, Guerin A, et al. Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System. Am J Ophthalmol. 2019;202:47-54. doi:10.1016/j.ajo.2019.01.026
                                  4. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II Epidemiology Report. Ocul Surf. 2017;15(3):334-365. doi:10.1016/j.jtos.2017.05.003
                                  5. Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II Report Executive Summary. Ocul Surf. 2017;15(4):802-812. doi:10.1016/j.jtos.2017.08.003
                                  6. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15(3):276-283. doi:10.1016/j.jtos.2017.05.008
                                  7. Al-Mohtaseb Z, Schachter S, Shen Lee B, Garlich J, Trattler W. The Relationship Between Dry Eye Disease and Digital Screen Use. Clin Ophthalmol. 2021;15:3811-3820. Published 2021 Sep 10. doi:10.2147/OPTH.S321591
                                  8. McDonald M, Patel DA, Keith MS, Snedecor SJ. Economic and Humanistic Burden of Dry Eye Disease in Europe, North America, and Asia: A Systematic Literature Review. Ocul Surf. 2016;14(2):144-167. doi:10.1016/j.jtos.2015.11.002
                                  9. Wang MT, Muntz A, Wolffsohn JS, Craig JP. Association between dry eye disease, self-perceived health status, and self-reported psychological stress burden. Clin Exp Optom. 2021 Nov;104(8):835-840. doi: 10.1080/08164622.2021.1887580. Epub 2021 Mar 3. PMID: 33689664.
                                  10. Clayton JA. Dry Eye. N Engl J Med. 2018;378(23):2212-2223. doi:10.1056/NEJMra1407936
                                  11. Kathuria A, Shamloo K, Jhanji V, Sharma A. Categorization of Marketed Artificial Tear Formulations Based on Their Ingredients: A Rational Approach for Their Use. J Clin Med. 2021;10(6):1289. Published 2021 Mar 21. doi:10.3390/jcm10061289
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                                  13. Chhadva P, Goldhardt R, Galor A. Meibomian Gland Disease: The Role of Gland Dysfunction in Dry Eye Disease. Ophthalmology. 2017;124(11S):S20-S26. doi:10.1016/j.ophtha.2017.05.031
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                                  15. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012;31(5):472-478. doi:10.1097/ICO.0b013e318225415a
                                  16. de Oliveira RC, Wilson SE. Practical guidance for the use of cyclosporine ophthalmic solutions in the management of dry eye disease. Clin Ophthalmol. 2019;13:1115-1122. Published 2019 Jul 1. doi:10.2147/OPTH.S184412
                                  17. Pflugfelder SC, de Paiva CS. The Pathophysiology of Dry Eye Disease: What We Know and Future Directions for Research. Ophthalmology. 2017;124(11S):S4-S13. doi:10.1016/j.ophtha.2017.07.010
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                                  19. Messmer EM. The pathophysiology, diagnosis, and treatment of dry eye disease. Dtsch Arztebl Int. 2015;112(5):71-82.
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                                  21. Bhargava R, Kumar P, Kumar M, Mehra N, Mishra A. A randomized controlled trial of omega-3 fatty acids in dry eye syndrome. Int J Ophthalmol. 2013;6(6):811-816. Published 2013 Dec 18. doi:10.3980/j.issn.2222-3959.2013.06.13
                                  22. Liu A, Ji J. Omega-3 essential fatty acids therapy for dry eye syndrome: a meta-analysis of randomized controlled studies. Med Sci Monit. 2014;20:1583-1589. Published 2014 Sep 6. doi:10.12659/MSM.891364
                                  23. Zhao M, Yu Y, Ying GS, Asbell PA, Bunya VY; Dry Eye Assessment and Management Study Research Group. Age Associations with Dry Eye Clinical Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study. Ophthalmol Sci. 2023;3(2):100270. Published 2023 Jan 12. doi:10.1016/j.xops.2023.100270
                                  24. Paik B, Tong L. Topical Omega-3 Fatty Acids Eyedrops in the Treatment of Dry Eye and Ocular Surface Disease: A Systematic Review. Int J Mol Sci. 2022;23(21):13156. Published 2022 Oct 29. doi:10.3390/ijms232113156Intro
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                                  26. Labetoulle M, Benitez-Del-Castillo JM, Barabino S, et al. Artificial Tears: Biological Role of Their Ingredients in the Management of Dry Eye Disease. Int J Mol Sci. 2022;23(5):2434. Published 2022 Feb 23. doi:10.3390/ijms23052434
                                  27. Semp DA, Beeson D, Sheppard AL, Dutta D, Wolffsohn JS. Artificial Tears: A Systematic Review. Clin Optom (Auckl). 2023;15:9-27. Published 2023 Jan 10. doi:10.2147/OPTO.S350185
                                  28. Restasis [package insert]. Irvine, CA: Allergan. Accessed June 5, 2023. https://media.allergan.com/actavis/actavis/media/allergan-pdf-documents/product-prescribing/Combined-Restasis-and-MultiDose-PI_8-3-17.pdf
                                  29. Moshirfar M, Pierson K, Hanamaikai K, Santiago-Caban L, Muthappan V, Passi SF. Artificial tears potpourri: a literature review. Clin Ophthalmol. 2014;8:1419-1433. Published 2014 Jul 31. doi:10.2147/OPTH.S65263
                                  30. Lacrisert (hydroxypropyl cellulose ophthalmic insert). Accessed June 23, 2023. https://www.lacrisert.com
                                  31. Lacrisert [package insert]. Bridgewater, NJ: Bausch & Lomb; 2019. Accessed June 23, 2023. https://www.lacrisert.com/siteassets/pdf/Lacrisert-package-insert.pdf
                                  32. Cequa [package insert]. Cranberry, NJ: Sun Pharmaceuticals. Accessed June 5, 2023. https://www.cequapro.com/CequaPI.pdf
                                  33. Xiidra [package insert]. East Hannover, NJ: Novartis. 2020. Accessed June 1, 2023. https://www.novartis.com/us-en/sites/novartis_us/files/xiidra.pdf
                                  34. Meibo [package insert]. Bridgewater, NJ: Bausch & Lomb. 2023. Accessed June 5, 2023. https://www.bausch.com/globalassets/pdf/packageinserts/pharma/miebo-package-insert.pdf
                                  35. Tyrvaya [package insert]. Princeton, NJ: Oyster Point Pharma. 2021. Accessed June 5, 2023. https://www.tyrvaya-pro.com/files/prescribing-information.pdf
                                  36. Eysuvis [package insert]. Watertown, MA: Kala Pharmaceuticals. Accessed June 14, 2023. https://www.eysuvis-ecp.com/pdf/prescribing-information.pdf
                                  37. Periman LM, Perez VL, Saban DR, Lin MC, Neri P. The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options. J Ocul Pharmacol Ther. 2020;36(3):137-146. doi:10.1089/jop.2019.0060
                                  38. Sheppard JD, Donnenfeld ED, Holland EJ, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens. 2014;40(5):289-296. doi:10.1097/ICL.0000000000000049
                                  39. Sheppard JD, Torkildsen GL, Lonsdale JD, et al. Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study. Ophthalmology. 2014;121(2):475-483. doi:10.1016/j.ophtha.2013.09.015
                                  40. Tauber J, Karpecki P, Latkany R, et al. Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study. Ophthalmology. 2015;122(12):2423-2431. doi:10.1016/j.ophtha.2015.08.001
                                  41. Holland EJ, Luchs J, Karpecki PM, et al. Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3). Ophthalmology. 2017;124(1):53-60. doi:10.1016/j.ophtha.2016.09.025
                                  42. Donnenfeld ED, Karpecki PM, Majmudar PA, et al. Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study. Cornea. 2016;35(6):741-748. doi:10.1097/ICO.0000000000000803
                                  43. Hovanesian JA, Nichols KK, Jackson M, et al. Real-World Experience with Lifitegrast Ophthalmic Solution (Xiidra®) in the US and Canada: Retrospective Study of Patient Characteristics, Treatment Patterns, and Clinical Effectiveness in 600 Patients with Dry Eye Disease. Clin Ophthalmol. 2021;15:1041-1054. Published 2021 Mar 8.
                                  44. Tauber J, Berdy GJ, Wirta DL, Krösser S, Vittitow JL; GOBI Study Group. NOV03 for Dry Eye Disease Associated with Meibomian Gland Dysfunction: Results of the Randomized Phase 3 GOBI Study. Ophthalmology. 2023;130(5):516-524. doi:10.1016/j.ophtha.2022.12.021
                                  45. Bausch + Lomb News Releases. www.bausch.com. Accessed June 9, 2023. https://www.bausch.com/news/releases/?id=156
                                  46. Sheppard JD, Kurata F, Epitropoulos AT, Krösser S, Vittitow JL; MOJAVE Study Group. NOV03 for Signs and Symptoms of Dry Eye Disease Associated With Meibomian Gland Dysfunction: The Randomized Phase 3 MOJAVE Study [published online ahead of print, 2023 Mar 21]. Am J Ophthalmol. 2023;252:265-274. doi:10.1016/j.ajo.2023.03.008
                                  47. Venkateswaran N, Bian Y, Gupta PK. Practical Guidance for the Use of Loteprednol Etabonate Ophthalmic Suspension 0.25% in the Management of Dry Eye Disease. Clin Ophthalmol. 2022;16:349-355. Published 2022 Feb 9. doi:10.2147/OPTH.S323301
                                  48. Sheppard JD, Comstock TL, Cavet ME. Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure. Adv Ther. 2016;33(4):532-552. doi:10.1007/s12325-016-0315-8
                                  49. Gupta PK, Venkateswaran N. The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares. Ther Adv Ophthalmol. 2021;13:25158414211012797. Published 2021 May 5. doi:10.1177/25158414211012797
                                  50. Wirta D, Torkildsen GL, Boehmer B, et al. ONSET-1 Phase 2b Randomized Trial to Evaluate the Safety and Efficacy of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease. Cornea. 2022;41(10):1207-1216. doi:10.1097/ICO.0000000000002941
                                  51. Wirta D, Vollmer P, Paauw J, et al. Efficacy and Safety of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease: The ONSET-2 Phase 3 Randomized Trial. Ophthalmology. 2022;129(4):379-387. doi:10.1016/j.ophtha.2021.11.004
                                  52. Quiroz-Mercado H, Hernandez-Quintela E, Chiu KH, Henry E, Nau JA. A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study. Ocul Surf. 2022;24:15-21. doi:10.1016/j.jtos.2021.12.007
                                  53. Thulasi P, Djalilian AR. Update in Current Diagnostics and Therapeutics of Dry Eye Disease. Ophthalmology. 2017;124(11S):S27-S33. doi:10.1016/j.ophtha.2017.07.022
                                  54: Arita R, Fukuoka S. Efficacy of Azithromycin Eyedrops for Individuals With Meibomian Gland Dysfunction-Associated Posterior Blepharitis. Eye Contact Lens. 2021;47(1):54-59. doi:10.1097/ICL.0000000000000729
                                  55. Clark D, Sheppard J, Brady TC. A Randomized Double-Masked Phase 2a Trial to Evaluate Activity and Safety of Topical Ocular Reproxalap, a Novel RASP Inhibitor, in Dry Eye Disease. J Ocul Pharmacol Ther. 2021;37(4):193-199. doi:10.1089/jop.2020.0087
                                  56. Clark D, Tauber J, Sheppard J, Brady TC. Early Onset and Broad Activity of Reproxalap in a Randomized, Double-Masked, Vehicle-Controlled Phase 2b Trial in Dry Eye Disease. Am J Ophthalmol. 2021;226:22-31. doi:10.1016/j.ajo.2021.01.011
                                  57. McMullin D, Clark D, Cavanagh B, Karpecki P, Brady TC. A Post-Acute Ocular Tolerability Comparison of Topical Reproxalap 0.25% and Lifitegrast 5% in Patients with Dry Eye Disease. Clin Ophthalmol. 2021;15:3889-3900. Published 2021 Sep 22. doi:10.2147/OPTH.S327691
                                  58. Gupta PK, Asbell P, Sheppard J. Current and Future Pharmacological Therapies for the Management of Dry Eye. Eye Contact Lens. 2020;46 Suppl 2:S64-S69. doi:10.1097/ICL.0000000000000666
                                  59. How to Put in Eye Drops. National Eye Institute. Accessed May 30, 2023. https://www.nei.nih.gov/Glaucoma/glaucoma-medicines/how-put-eye-drops
                                  60. Eye Problems: Using Eyedrops and Eye Ointment. Kaiser Permanente. Accessed May 30, 2023. https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.eye-problems-using-eyedrops-and-eye-ointment.za1098

                                  Set Your Ascites on Improving Patient Care: The Pharmacy Team’s Role in Hepatorenal Syndrome Management

                                  Learning Objectives

                                   

                                  After completing this application-based continuing education activity, pharmacists and technicians will be able to

                                  1. Describe the prevalence, pathophysiology, and prognosis of hepatorenal syndrome (HRS)
                                  2. Explain updated guidelines for diagnosis and treatment of HRS
                                  3. Discuss current and emerging therapies for HRS
                                  4. Identify the role of pharmacists and pharmacy technicians in HRS treatment

                                    Cartoon image depicting a person with ascites.

                                     

                                    Release Date: August 15, 2023

                                    Expiration Date: August 15, 2025

                                    Course Fee

                                    Pharmacists: FREE

                                    Pharmacy Technicians: FREE

                                    This CE was funded by:  Mallinckrodt

                                    ACPE UANs

                                    Pharmacist: 0009-0000-23-029-H01-P

                                    Pharmacy Technician: 0009-0000-23-029-H01-T

                                    Session Codes

                                    Pharmacist:  23YC29-HPX34

                                    Pharmacy Technician:  23YC29-XPX38

                                    Accreditation Hours

                                    2.0 hours of CE

                                    Accreditation Statements

                                    The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.  Statements of credit for the online activity ACPE UAN 0009-0000-23-029-H01-P/T  will be awarded when the post test and evaluation have been completed and passed with a 70% or better. Your CE credits will be uploaded to your CPE monitor profile within 2 weeks of completion of the program.

                                     

                                    Disclosure of Discussions of Off-label and Investigational Drug Use

                                    The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

                                    Faculty

                                    Rachel Eyeler, PharmD, BCPS
                                    Adjunct Clinical Professor
                                    UConn School of Pharmacy
                                    Storrs, CT

                                                               

                                    Nicole A. Pilch, PharmD, BCPS
                                    Associate Professor Department of Pharmacy and Clinical Sciences
                                    Medical University of South Carolina
                                    Charleston, SC

                                    Faculty Disclosure

                                    In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

                                    Drs. Eyeler and Pilch do not have any relationships with ineligible companies.

                                     

                                    ABSTRACT

                                    Hepatorenal syndrome (HRS) is a specific type of kidney injury unique to patients with end stage liver disease, also known as cirrhosis. Patients with cirrhosis have scarred, stiff livers in which blood cannot flow through easily. Portal hypertension changes blood flow resulting in several consequences: ascites, esophageal varices, and HRS. The American Association for the Study of Liver Diseases guidelines describe two distinct forms of HRS. Therapies such as volume resuscitation (e.g., with crystalloids or albumin) and vasoconstrictors (e.g., norepinephrine or terlipressin) focus on restoring blood flow to the kidneys before they are irreparably injured. Sometimes, clinicians must select therapies based on availability of intensive care unit beds and monitoring equipment. Clinicians also need to consider factors when patients leave the hospital and are discharged to home. Pharmacists and pharmacy technicians who are familiar with the basics of HRS can help clinicians make appropriate choices, counsel patients thoroughly, and contribute to better patient outcomes.

                                    CONTENT

                                    Content

                                    INTRODUCTION

                                    Hepatorenal syndrome (HRS), a type of kidney injury unique to patients with advanced liver disease, carries a grim prognosis. Therapies such as volume resuscitation (e.g., crystalloids or albumin) and vasoconstrictors (e.g., norepinephrine or terlipressin) focus on restoring blood flow to the kidneys before they are irreparably injured. Pharmacists and pharmacy technicians can play a crucial role in helping select and monitor therapies for treatment of this syndrome, and perhaps more importantly, by helping patients avoid developing HRS in the first place. By educating patients to avoid certain over the counter (OTC) medications that can worsen the condition (e.g., non-steroidal anti-inflammatory drugs [NSAIDs]), and teaching patients to monitor their diuretic use by weighing themselves daily and monitoring their blood pressure, engaged pharmacists and pharmacy technicians can make a large difference in their patients’ clinical outcomes.

                                     

                                    HRS: A Complication of Cirrhosis

                                    Cirrhosis, an advanced state of liver disease, is increasingly common and an important cause of mortality.1 Globally, in 2017 the estimated incidence of people living with compensated cirrhosis was 112 million. In 2019, cirrhosis was associated with 2.4% of deaths worldwide.2 Classically, cirrhosis in developed countries is most commonly due to hepatitis C infection and alcohol misuse.1 However, over the past decade, the incidence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically with improvement in diagnostic criteria and screening. At the same time, treatment improvements for hepatitis B and C infections have decreased viral hepatitis-related deaths in some areas of the world. The COVID-19 pandemic has also had significant impact, with data collected from multiple countries showing a substantial increase in alcohol consumption, and an increase in alcohol-associated cirrhosis deaths.2,3 Testing and treatment rates for hepatitis B and C declined internationally between January 2019 and December 2020,4 and treatment delays are predicted to lead to excess liver-related deaths.2,5

                                    PAUSE AND PONDER: How will the new hepatitis C direct-acting antivirals (e.g., elbasvir, glecaprevir, ledipasvir, pibrentasvir, sofosbuvir, velpatasvir, and voxilaprevir) change the landscape of HRS?

                                    Although the causes of cirrhosis may be shifting, the transition from chronic liver disease to cirrhosis is generally the same. Chronic inflammation of the liver leads to fibrosis and scarring, causing structural and hemodynamic changes within the liver (Figure 1). One of the main consequences is development of portal hypertension. Portal hypertension results because the scarring of the liver makes it more difficult for blood to flow through it, leading to increased blood pressure in the portal vein as blood is delivered from the splanchnic organs (stomach, small intestine, colon, pancreas, and spleen) (Figure 2). The obstruction of blood flow through the portal vein additionally results in dilation of the splanchnic circulation as a compensatory mechanism aimed at restoring blood flow. In turn, increased blood flow to the splanchnic circulation worsens portal hypertension.1  

                                    Figure 1. Stages of Liver Disease.

                                    Graphic showing the stages of liver disease, from healthy liver to cirrhosis.

                                     

                                    Figure 2. The splanchnic circulation. The splanchnic circulation describes blood flow to the abdominal organs. Blood from these “splanchnic” organs is delivered to the portal vein, and accounts for the majority of the blood flow to be processed by the liver.

                                    Graphic showing the blood flow from the aorta, through organs and liver, and then finally to the inferior vena cava.

                                     

                                    Pathophysiology of HRS

                                    Portal hypertension and the changes in blood flow that result are the main drivers of several consequences of cirrhosis. These complications include the development of ascites, espophageal varices, and HRS.

                                     

                                    Ascites is fluid accumulation in the peritoneal cavity that commonly appears as abdominal swelling or bloat. A patient with significant ascites will often test positive for a “fluid wave.” That is, when a patient is lying flat and someone applies pressure to the abdominal midline, a clinician can tap one flank sharply, and an impulse or “shock wave” will travel through the fluid in the abdomen. The clinician will be able to be feel the tap on the other side.

                                     

                                    Esophageal varices are enlarged veins in the esophagus that can lead to bleeding that commonly presents as “coffee ground” looking emesis (or vomitus) that is a result of the blood being digested in the stomach then regurgitated through the esophagus. In the case of HRS, the portal hypertension and splanchnic vessel dilation mean that blood tends to pool in the splanchnic circulation, decreasing effective arterial volume (i.e., a decreased amount of blood effectively perfusing organ tissue, including the kidneys). Additionally, the body activates various compensatory mechanisms aimed at increasing blood volume (e.g., the renin-angiotensin system and the sympathetic nervous system). This action is an attempt to restore effective blood volume, which leads to vasoconstriction of the kidney arterioles and further hypoperfusion of the kidney (Figure 3).6

                                    Figure 3. Changes in blood flow with cirrhosis. The image on the left represents normal splanchnic and portal blood flow. The image on the right shows blood flow to a cirrhotic liver. Blood from the splanchnic organs meets increased resistance in the portal vein, leading to portal hypertension. The splanchnic arteries vasodilate which worsens portal hypertension and leads to decreased blood flow to the kidneys.

                                    Cartoon showing the difference in blood flow between a normal liver and cirrhotic liver. The main difference is backup of blood flow, causing portal hypertension.

                                    ABBREVIATIONS: ADH: antidiuretic hormone, IMA: inferior mesenteric artery, RAAS: renal angiotensin aldosterone system, RBF: renal blood flow, GFR: glomerular filtration rate, SMA: superior mesenteric artery

                                    Prevalence and Prognosis

                                    HRS is a type of acute kidney injury (AKI) that is unique to patients with decompensated cirrhosis. HRS occurs in the absence of hypovolemia or any structural changes to the kidney—in fact, the kidneys often function normally following liver transplantation.7 HRS is common in patients with cirrhosis, and risk of development increases as the severity of cirrhosis and the duration with which the patient has had it increase. In one study of patients with cirrhosis and ascites, the incidence of HRS increased from 18% at one year to 39% after five years.8 The development of HRS is unfortunately associated with a very poor prognosis, and often the only way to reverse the kidney failure is to receive a liver transplant.7

                                     

                                    Classification and Diagnosis

                                    Two distinct forms of HRS have been described. According to the American Association for the Study of Liver Diseases (AASLD) guidelines9

                                    • Type 1 HRS is a rapid increase in creatinine (0.3 mg/dL or greater) within 48 hours or an increase in serum creatinine to levels that are at least 50% higher than the most recent baseline value measured within three months. It often has a precipitating factor, such as a bacterial infection, gastrointestinal bleeding, or over-diuresis. This type of HRS is more common and more severe, making up 75% of cases and having a median survival of one month.
                                    • Type 2 HRS takes a longer time to develop and is defined as an estimated glomerular filtration rate of less than 60 mL/minute/1.73m2 for three months or more in the absence of other (structural) causes. This is the same definition used for all patients with chronic kidney disease (CKD). Type 2 HRS often co-occurs with other complications of cirrhosis (i.e., refractory ascites) and has a median survival of about seven months.8

                                     

                                    In recent years the nomenclature has been updated so that type 1 HRS is referred to as HRS-AKI and type 2 is called HRS-CKD.6,9

                                     

                                    Sometimes it is hard to know that a patient with end-stage liver disease is in kidney failure. These patients may have decreased muscle mass, are prone to malnutrition, and may take diuretics to control volume status. All three of those factors make serum creatinine an unreliable surrogate measure of kidney function.10

                                    In patients with cirrhosis and ascites who meet the criteria for AKI, the diagnosis of HRS-AKI becomes one of exclusion. Clinicians must attempt to rule out hypovolemia, shock, medication-induced AKI, and structural kidney injury. In the absence of these alternative causes for AKI, a diagnosis of HRS-AKI can be made, and treatment commenced as soon as possible, as early intervention is key to decreasing mortality.9

                                     

                                    Sidebar: Why is serum creatinine unreliable in advanced liver disease?

                                    In clinical practice, clinicians often estimate kidney function by measuring a patient’s serum creatinine and inputting the value into a kidney function estimating equation. Creatinine is a byproduct of creatine, an amino acid produced by the liver and released into the circulation to reach target tissues, such as muscle. Creatinine is released during normal muscle metabolism. It is used in kidney function estimates because the glomerulus filters it freely, and so theoretically the rate at which the kidneys clear creatinine should be similar to the glomerular filtration rate itself.

                                     

                                    However, a patient’s serum creatinine value is not affected by glomerular filtration rate alone. A malfunctioning liver may produce lower amounts of creatinine’s precursor, creatine. Additionally, patients with cirrhosis may have decreased oral intake due to nausea, ascites, and/or ongoing alcohol use. This means they consume less creatine is consumed from the diet as well. Finally, since creatinine is a product of muscle tissue breakdown and patients with cirrhosis tend to have significantly reduced muscle mass, they may generate less creatinine from the creatine. The end result is a serum creatinine that is normal or even lower than that seen in healthy individuals.

                                     

                                    Hence, kidney function estimates that rely on creatinine tend to overestimate kidney function in these patients and even small absolute increases in creatinine could represent an acute kidney injury.

                                    PAUSE AND PONDER: Is there a better way to measure true kidney function in patients with end-stage liver disease?

                                     

                                    Current and Emerging Therapies for HRS

                                    Therapies used to treat HRS aim at removing the precipitating factor and increasing blood flow to the kidneys. First, clinicians must identify and treat the potential etiology leading to the decline in kidney function (e.g., antibiotic therapy in the treatment of an infection of ascites fluid called spontaneous bacterial peritonitis [SBP], proton pump inhibitors, and endoscopic intervention to stop a gastrointestinal bleed). Removing the cause is one of the most important factors in ensuring that the change in kidney function is not permanent.

                                     

                                    Fundamentally the kidney receives insufficient blood flow secondary to a decrease in effective arterial blood flow, so initial therapy’s main goal is to improve the patient’s mean arterial pressure as soon as possible. The most common goal cited is to increase the patient’s mean arterial pressure (MAP) to greater than 65 mmHg to improve perfusion to target end organs, specifically the kidney.11,12 The goal is to improve kidney function and give the patient additional time to secure a liver transplant or stabilize the end stage disease and decrease mortality. This continuing education activity will review the agents used to improve kidney function in the setting of HRS. Table 1 summarizes guideline recommendations for initial management of patients with HRS-AKI.

                                     

                                    Table 1. Summary of Society Guidelines for Initial Management of HRS-AKI in the ICU9,22,23,32,33
                                    Society HRS-AKI Definition Volume expander Vasopressor of choice Target
                                    American Association for the Surgery of Trauma 2022 Increase in SCr > 0.3 mg/dL within 48 hours or > 50% increase in SCr in preceding 7 days in patients with cirrhosis/ascites without another cause Lactate ringers or Plasmalyte over Normal Saline; albumin 20-25% 1 gm/kg/day x 48 hours Norepinephrine, Terlipressin MAP > 65 mmHg, increased urine output
                                    American Association for the Study of Liver Disease 2021 Increase in SCr > 0.3 mg/dL within 48 hours or > 50% increase in SCr in preceding 7 days in patients with cirrhosis/ascites without another cause; use SCr values for the last 3 months prior to event to evaluate baseline Albumin 1 gm/kg on day 1, then 40 to 50 gm daily while receiving vasopressor therapy Terlipressin,* Norepinephrine 0.5 mg/h ; max 3 mg/h Increase MAP by at least 10 mmHg above pre-treatment baseline or urine output >200 mL over 4 hours; albumin to maintain CVP between 4-10 mmHg;

                                    Continue treatment until SCr back to baseline up to 14 days; if SCr remains at or above pre-treatment values after 96 hours stop vasopressor therapy

                                    European Association for the Study of the Liver 2010 Kidney failure in the setting of liver disease unexplained by another cause Albumin 1 gm/kg/day (max 100 gm/day) Terlipressin 1 mg every 4 to 6 hours in combination with albumin, if SCr does not improve by at least 30% in 72 hours increase dose to 2 mg every 4 hours Increase in MAP by at least 5 mmHg by day 3
                                    American Gastroenterological Association 2022 Increase in SCr > 0.3 mg/dL within 48 hours or > 50% from baseline or urine output is <0.5 mL/kg/hr for > 6 hours Albumin 1 gm/kg/day x 48 hours, if no improvement continue 1 gm/kg x 1 day then 20 to 40 gm daily while receiving vasopressor therapy Terlipressin 1 mg every 4 to 6 hours; increase to 2 mg every 4 to 6 hours if reduction in SCr < 25% by day 3 if available up to 14 days, alternative norepinephrine or midodrine/octreotide Increase MAP by at least 10 mmHg or urine output by at least 50 mL/h for at least 2 hours, maintain priority for liver transplant if survive
                                    *not approved in US at the time of guideline construction

                                     

                                    ABBREVIATIONS: CVP = central venous pressure; MAP = mean arterial pressure; SCr = serum creatinine

                                     

                                     

                                     

                                    PAUSE AND PONDER: When might these interventions be considered “too late?” What would you do then?

                                     

                                    Crystalloids

                                    Initial evaluation of patients includes an assessment of their effective arterial blood volume status. Early cessation of home medications that impact blood pressure or volume status, such as diuretics (e.g., spironolactone, furosemide) will allow a more accurate determination. If the patient’s effective arterial blood volume is not optimized, inadequate blood flow to the kidney can precipitate acute kidney injury in the setting of cirrhosis.

                                     

                                    Crystalloids, such as normal saline and Lactated Ringer’s, stay within the intravascular space and provide appropriate initial fluid replacement. However, clinicians must provide fluid replacement (also referred to in this case as fluid resuscitation) carefully and with appropriate monitoring as patients can become volume overloaded. Patients with end stage liver disease have low albumin levels and tend to lack the oncotic pressure (a type of osmotic pressure induced by plasma proteins, especially albumin) required to keep crystalloids within the intravascular space. Even minimal resuscitation can produce significant peripheral edema and pulmonary edema, and worsen ascites.13

                                    Pharmacists should provide support in appropriate monitoring of volume status and ensuring serum electrolytes are frequently obtained. Fluids may need to be stopped abruptly in response to volume overload to prevent hypervolemic hyponatremia (low sodium levels).14 Appropriate understanding of the patient’s intravascular volume status will determine if using albumin during resuscitation is appropriate.

                                     

                                    Albumin

                                    Patients with end-stage liver disease typically have reduced or low albumin levels because the liver is no longer able to manufacture these proteins. Reduced albumin decreases the circulating oncotic pressure which yields fluid leakage from blood vessels into other areas of the body (e.g., peritoneal space), reducing the arterial blood volume going to the kidney. This becomes especially apparent when a precipitating event such as a hemorrhage or infection occurs, which further decreases circulating blood volume. Clinicians often administer concentrated albumin (e.g., 25% or 25 grams/100 mL) every six to eight hours to increase the intravascular circulating blood volume. Albumin allows fluid to move from the interstitial spaces back into the blood stream and keeps exogenously administered crystalloids in the vessels, thereby increasing blood flow to the kidneys.12 Clinicians should reserve concentrated albumin for patients with baseline low serum albumin (e.g., less than 3 mg/dL) who are also volume overloaded and limit them to just the amount that restores hemodynamic stability.15

                                     

                                    Patients who have inadequate total body volume or those who have capillary leak (e.g., septic shock) may benefit from less concentrated (e.g., 5%) albumin infusions. A recent single center open-label, randomized study evaluated hypotensive patients with end-stage liver disease and compared volume replacement with albumin to normal saline.16 The primary outcome was to determine which approach could reverse a mean arterial pressure less than 65 mmHg more effectively within the first hours of resuscitation. Of note this trial excluded patients who needed immediate interventions, such as variceal bleed or vasopressor agents.17 The researchers randomized patients to receive 250 mL of 5% albumin over 30 minutes followed by 50 mL/hr for three hours or normal saline 30 mL/kg over 15 to 30 minutes followed by 100 mL/h over three hours. Albumin was more effective than normal saline in improving mean arterial pressure above 65 mmHg in the first hour (25.3% albumin vs 14.9% normal saline, p = 0.03) of resuscitation. The benefit continued over the next three hours (p < 0.001) and survival was also better in patients resuscitated with albumin than those treated with saline (43.5% vs 38.3%).16,18 The researchers note that results are predicated on appropriate management of the underlying causes of hypotension (i.e., sepsis).

                                     

                                    Albumin is expensive, can be and has been subject to shortages. It should be used with stewardship in end stage liver disease and HRS; however, the evidence for benefit is robust especially when combined with other modalities.16 It is important to understand the patient’s volume status and hemodynamic goals to select the appropriate concentration and frequency.19,20 The AASLD Guidelines for the Diagnosis, Evaluation and Management of Ascites, Spontaneous Bacterial Peritonitis and HRS suggest that patients who present with HRS should receive 1 gram/kg albumin on day 1 and then 40 to 50 grams per day until kidney function improves and other therapies are no longer needed.9,15 The daily dose may be reduced (e.g., 20 to 40 grams/day) if given in combination with vasopressor agents with a goal to maintain adequate volume. Clinicians sometimes use a surrogate measure of volume using a central venous catheter to measure central venous pressure (CVP), which reflects the amount of blood in the patient’s anterior vena cava and venous tone. In this case, a CVP goal between 10 and 15 mmHg is targeted.10,21 Unfortunately CVP can be unreliable when ascites is present and clinicians may need to employ other invasive methods along with close monitoring for the development of pulmonary edema.9,22,23

                                     

                                    Ensuring albumin is available for patients with HRS is necessary. Some ways to aid centers in managing their supplies when shortages occur include limiting scheduled orders to 24 hours (e.g., 1 gram of 25% every 8 hours for 24 hours). Limiting “evergreen” orders to 24 hours will ensure clinicians assess patients appropriately before administering additional albumin and may prevent unappreciated volume overload. Also, standardized order sets will prevent use of partial vials, larger than needed vials (e.g., 250 mL or 500 mL) and inappropriate ordering of the incorrect concentration (e.g., 5% versus 25%). Teaching hospitals may also benefit from limiting albumin orders to certain clinical situations or diagnoses to avoid ubiquitous use for volume resuscitation in patients (e.g., trauma) who can be resuscitated with crystalloid.

                                     

                                    Vasopressors

                                    Vasopressors are given in combination with resuscitation, specifically albumin. The exogenous albumin facilitates adequate oncotic pressure to keep fluid in the vasculature, allowing vasopressors to constrict the vessels, increase mean arterial pressure, and supply fluid to the kidney. Vasopressors will be ineffective and can make kidney function worse if fluid in the vasculature is insufficient. Therefore, prescribers should only institute vasopressors along with or after volume resuscitation. The main adverse effects associated with any vasopressor therapy are related to ischemia (poor blood flow) in the peripheral limbs/tissues (e.g., fingertips, skin), gastrointestinal tract, or heart.9 Limited head-to-head trials exist to identify which agent or combination is the most effective in reversing HRS beyond early implementation of therapy in combination with albumin volume expansion. Table 2 summarizes the pros, cons, and considerations related to vasopressor agents used in the treatment of HRS.

                                     

                                    Table 2. Vasopressor Agents Pros, Cons and Considerations
                                    Medication Pros Cons Considerations
                                    Norepinephrine Frequently used in the ICU setting, team comfort with monitoring for adverse effects and ease/experience with titration May be less effective in hypothermia, pH dysregulation, continuous infusion May require ICU setting, especially for acute titration; may require a central line
                                    Terlipressin Does not require a central line, or continuous infusion Requires additional monitoring for ischemia which may require ICU level care to ensure safety Requires monitoring for ischemic events
                                    Octreotide Can be given outside the ICU Slow response, IV or subcutaneous administration May be continued as an outpatient
                                    Midodrine Available as an oral agent, can be given outside the ICU Slow response, only available as an oral agent; frequency of dosing May be provided on discharge to help maintain blood pressure in the setting of hypotension

                                    ABBREVIATIONS: ICU = intensive care unit; IV = intravenous

                                     

                                    Norepinephrine

                                    Norepinephrine is an exogenous catecholamine that targets alpha-1-adrenergic receptors which helps improve peripheral vascular resistance.24 Norepinephrine has been used consistently in the United States (U.S.) for many years and has been the agent of choice until the recent approval of terlipressin. Norepinephrine’s limitation is that it can be less effective, as are other catecholamines, if patients have temperature or pH dysregulation. Appropriate resuscitation and correction of these variables can improve norepinephrine’s efficacy. A meta-analysis comparing the effectiveness of norepinephrine and terlipressin suggests that norepinephrine is as effective in increasing mean arterial pressure and reversal of kidney dysfunction.24 The most frequent doses of norepinephrine cited in terlipressin head-to-head trials were between 0.5 to 3 mg/hour and/or 0.05 to 0.7 mcg/kg/minute titrated to increase mean arterial pressure 10 mmHg above baseline or increasing urine output to more than 200 mL/hour.24 Clinicians must monitor norepinephrine administration carefully to prevent complications of vasoconstriction, such as cardiac or digital ischemia and therefore it is often restricted to the intensive care unit (ICU).24

                                     

                                    Terlipressin

                                    Terlipressin is a prohormone of lysine-vasopressin, causing extended release of lysine-vasopressin and activation of V1 and V2 receptors allowing intermittent administration.24 V1 receptors are predominantly located in the smooth muscles of the arterial vasculature in the splanchnic region. Activating V1 receptors constricts the splanchnic vessels (reducing delivery of blood flow to the portal vein, lowering portal pressure) which subsequently may improve blood flow to kidneys. Additionally, activation of the V2 receptors causes reabsorption of water in the kidney.24,25 Terlipressin has been evaluated in several prospective, placebo-controlled clinical trials evaluating its efficacy in improving kidney function in HRS.18 Specifically, a recent prospective, randomized, double-blind controlled trial evaluated the effectiveness of terlipressin against placebo in combination with albumin in reversing HRS-AKI.25 Terlipressin was more effective than placebo in reversing HRS (32% vs 17%, p < 0.006), but did yield more respiratory failure.25 This trial was an impetus for U.S. Food and Drug Administration (FDA) approval of terlipressin in 2023.

                                     

                                    The FDA approved terlipressin for rapid reduction in kidney function in the setting of cirrhosis with no other etiology, or reversal of HRS at a dose of 1 mg administered by intravenous bolus every six hours.10 If the patient’s serum creatinine fails to improve or increases within the first 96 hours then prescribers should discontinue terlipressin. If improvement is marginal (e.g., less than 30% from baseline) the dose can be increased to 2 mg every six hours.10 Therapy should be continued until the patient’s serum creatinine is 1.5 mg/dL or less for two days or a maximum of 14 days. Prescribers should use terlipressin with caution in patients with a history of ischemic conditions (e.g., cardiac, mesenteric).10 Terlipressin should not be used in patients who have a serum creatinine exceeding 5 mg/dL, in patients who are hypoxic (SpO2 less than 90%), or in patients who develop ischemia.10,23

                                     

                                    Terlipressin is often given outside the ICU and does not need continuous cardiac monitoring, which may make it desirable for longer term administration.10 Initial clinical trials compared norepinephrine continuous infusion (1 mcg/kg/minute increased every four hours to increase MAP by 10 mmHg) to terlipressin (1 mg every four hours; increased to 2 mg every four hours after three days) combined with albumin to maintain a CVP between 10 and 15 mmHg. These trials defined a complete response as an improvement in serum creatinine by at least 30% from baseline within 14 days of therapy. There was no difference in responders between norepinephrine and terlipressin (70% and 83%).21,26,27 Therefore terlipressin’s benefit may lie in its intermittent dosing and ability to be administered outside the ICU.

                                     

                                    Terlipressin’s most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea. Terlipressin does have some additional considerations. It also has a boxed warning for possible serious or fatal respiratory failure, and clinicians need to monitor patients’ oxygen saturation carefully.28

                                     

                                    Terlipressin is supplied as a single dose 0.85 mg vial that must be stored under refrigeration and protected from light. Vials are reconstituted with 5 mL of sodium chloride and if not used, must be refrigerated and expire after 48 hours. The initial dose based on the approved labeling is one vial (0.85 mg) every six hours; which can be increased to two vials (1.7 mg) every six hours.28

                                     

                                    Midodrine and Octreotide

                                    Midodrine and octreotide in combination have been a staple in the treatment of acute HRS for the last two decades in the U.S. Midodrine, an oral tablet, is like norepinephrine and produces vasoconstriction through alpha-1-adrenergic receptors.24 Octreotide injection is a somatostatin analogue that decreases the release of vasodilatory substances and glucagon leading to vasoconstriction of the splanchnic circulation.24 Because norepinephrine must be administered in the ICU, some healthcare facilities favor the combination of midodrine and octreotide. They also use midodrine/octreotide if they have not added terlipressin to their formularies.23 Unfortunately, patients tend to respond slowly to the combination and the combination requires an extended duration for full benefit.23 Octreotide cannot be given without midodrine but midodrine may be continued long-term (e.g., post-discharge) to maintain blood pressure in patients who are persistently hypotensive.23,29

                                     

                                    Researchers recently published a single center experience with standardizing administration of midodrine and octreotide for treatment of HRS at their center.29 They wanted to standardize the use and dosing of albumin in combination with midodrine dosed at 2.5 to 10 mg three times daily and octreotide 50 to 100 mcg subcutaneously three times daily for 14 days and compare it to previous unstandardized prescribing. The goal was to obtain a full response: a serum creatinine within 0.3 mg/dL of baseline within seven to 14 days. Use of the standardized protocol was more effective in producing a full response than the historical unstandardized practice (25% vs 10%, p = 0.07).29 Additionally, the researchers also found that fewer patients in the protocol group required kidney replacement therapy. Guidelines suggest initiating midodrine at a dose of 7.5 mg three times daily and titrating it to 12.5 mg three times daily in combination with octreotide.23 The combination may still be in favor because it is a cost-effective alternative to terlipressin outside the ICU.

                                     

                                    Midodrine is supplied in three tablet strengths which include 2.5 mg, 5 mg and 10 mg.30 This allows outpatient tapering or adjustment if the patient experiences tachycardia. Unfortunately, it is short acting and requires three times daily dosing initially. In practice, dropping the middle of the day dose without reducing the strength allows improved adherence once the patient’s blood pressure is stable. Midodrine’s labeling includes a boxed warning for possible marked elevation of supine blood pressure, and clinicians should monitor supine and standing blood pressure regularly.30

                                     

                                    Octreotide is supplied in single dose ampules or multidose vials that must be stored in the refrigerator and protected from light; multidose vials must be discarded within 14 days. Octreotide is stable for 14 days at room temperature.31 Doses of 50 mcg to 100 mcg are administered every eight hours around the clock during the inpatient stay. If patients continue on octreotide as outpatients, the hospital pharmacy often needs to supply the doses. Patients and caregivers need appropriate education on subcutaneous injections and disposal of injection materials. In practice, the dose used in the hospital with success is often continued and not reduced to allow for the shortest duration possible. Octreotide subcutaneous injections on the outpatient side typically require additional insurance approval and preparation so discharge planning early is important.31

                                     

                                    The Role of Pharmacists and Pharmacy Technicians in the Treatment of HRS

                                    Pharmacists and pharmacy technicians can play an integral role in improving outcomes for patients presenting with or who have a history of HRS. Prevention is the key! Patients with end-stage liver disease should avoid medications that can precipitate HRS such as non-steroidal anti-inflammatory drugs and will require appropriate adjustment or discontinuation (if possible) of potential nephrotoxic agents (e.g., certain antimicrobials).

                                     

                                    Ensuring patients with a history of spontaneous bacterial peritonitis (SBP) are on appropriate antibiotic prophylaxis can prevent subsequent SBP events that decrease blood flow to the kidneys. In the ambulatory setting, careful blood pressure monitoring and adjustment of blood pressure medications commonly used to treat portal hypertension (e.g., carvedilol), can ward off hypotensive events that can precipitate HRS.

                                     

                                    Table 3 summarizes some lifestyle counseling tips that can help empower patients to play an active role in optimizing their care and preventing HRS episodes. Additionally, general management of concurrent disease states, such as heart failure and diabetes, can aid in maintaining optimal hemodynamics.

                                    Table 3. Lifestyle Counseling Points for Patients with Cirrhosis at risk for HRS35-37
                                    Avoid alcohol Even if the cause of liver damage isn’t drinking, alcohol use can increase the amount of damage. Patients who cease alcohol can experience dramatic improvements in some of the complications of cirrhosis.
                                    Low sodium diet (especially in patients with ascites) Limit sodium intake. This can be quite difficult, but if it can be done will help quite a bit with volume management. Patients with ascites are often asked to target ≤2 g/day. (For reference, 1 teaspoon of salt contains 2.3 g!)
                                    Weight loss in patients who are overweight Even a small amount of weight loss (e.g., a few pounds) can have a beneficial effect in patients with NAFLD or chronic HCV.
                                    Protect yourself from infections Patients need to stay up to date on vaccinations, wash their hands frequently, and avoid people who are sick.
                                    Organize medication schedule Patients with liver impairment can take seven to 10 medications a day—some administered multiple times a day. Investing in a strong adherence-enhancing system with alarm reminders or reminders from caregivers can be key.
                                    Use OTC medications carefully NSAIDs, such as ibuprofen and naproxen, can precipitate acute kidney injury.
                                    Monitor weight daily (if on diuretic treatment) Patients need to weigh themselves first thing in the morning after urinating. They should report significant weight changes to their providers (e.g., losing 1 pound or more a day or gaining more than 5 pounds in a week).

                                     

                                     

                                    SIDEBAR: Did you know…acetaminophen can be a great choice for patient with HRS?34

                                    Imagine a situation where a medical intern is cross-covering in the medical intensive care unit and receives a call from a nurse about a patient with HRS. The patient is experiencing some mild pain and the nurse would like an as-needed medication to help.

                                     

                                    Or…

                                     

                                    You are working in the pharmacy and receive an order for oxycodone 5 mg every six hours as needed for mild pain. You are very concerned that this patient has both kidney and liver insufficiency and oxycodone is not a good choice but what else can you recommend?

                                     

                                    What about acetaminophen?!?

                                     

                                    Acetaminophen tends to have a bad rap mainly because it is in so many prescription and OTC products. It’s often in the news for causing liver toxicity. Oftentimes patients and providers do not think about the total acetaminophen exposure (the total daily dose of acetaminophen) and that is where the danger can come in. When the amount of acetaminophen’s toxic intermediary N-acetyl-p-benzoquinone imine (NAPQI) exceeds the liver’s glutathione stores, NAPQI starts to stick to hepatocytes (the liver’s main structural component). NAPQI acts like an antigen and stimulates the immune system to attack the liver.

                                     

                                    Fortunately, it takes a significant amount administered at one time or consistently over several days to expend the glutathione stores. Doses up to 2,000 mg per day are safe and effective in most patients with severe liver insufficiency. (The maximum daily dose in healthy adults is 3900 mg.) Pharmacists and pharmacy technicians can ensure providers and patients with liver disease know they have alternative options. They can also help patients avoid reaching for a NSAID, especially if the patient has had a recent bout of HRS or if the patient is taking other medications that would suggest the presence of liver insufficiency (e.g., lactulose, rifaximin, norfloxacin). Remember prevention of HRS is the key!

                                     

                                    When a hospital admits a patient, healthcare providers need to understand what the patient was taking at home and stop or continue the appropriate medications at the right doses. For example, prescribers should discontinue medications that could be reducing blood pressure (e.g., beta blockers and alpha beta blockers) on admission.11,16 They need to consider adjusting home medications for kidney dysfunction and restarting medications needed to manage other complications of end-stage liver disease (e.g., lactulose for encephalopathy).

                                     

                                    When prompt administration of resuscitation with albumin is needed, the team may need help selecting the appropriate concentration. Patients who are significantly volume overloaded but have fluid in the extravascular space (e.g., in the abdominal cavity) would likely benefit from concentrated (25%) albumin. With the multidisciplinary team, the pharmacy team needs to understand the patient’s volume status and goals of therapy. Helping teams develop protocols to treat HRS can aid in goal-directed therapy and allow quick implementation of pharmacologic interventions to improve blood flow to the kidneys.

                                     

                                    At discharge pharmacists and pharmacy technicians must ensure that medications are appropriately adjusted for the patient’s current kidney and liver function after the acute event has resolved or stabilized. The pharmacy team should be involved in educating patients on how to organize their new medication regimens, how to monitor their responses to therapy and recognize common adverse effects, and how appropriate lifestyle changes can increase the effectiveness of therapy and help avoid the advanced complications of liver disease.

                                     

                                    CONCLUSION

                                    HRS is a common complication for patients with advanced liver disease and ascites. Patients are in a state of decreased effective arterial blood flow to the kidneys and other end organs, and kidney injury is easily precipitated by nephrotoxic agents, over-diuresis, or bacterial infection. Acute treatment is aimed at restoring blood flow to the kidneys with the use of volume resuscitation and splanchnic vasoconstrictors. Pharmacists and pharmacy technicians can identify medications that may worsen kidney function, and assist in the appropriate prescribing, monitoring, and stewardship of these agents. Additionally, appropriate patient education—empowering patients to monitor their fluid/blood pressure status and avoiding OTC medications that can worsen their condition or precipitate HRS—is key in optimizing patient outcomes.

                                    Pharmacist Post Test (for viewing only)

                                    Set Your Ascites on Improving Patient Care: The Pharmacy Team’s Role in HRS Management
                                    Pharmacist post-test
                                    JC is a 56-year-old patient with end-stage liver disease secondary to non-alcoholic steatohepatitis (NASH) who presents to the emergency department with her caregiver after she was found disoriented in the backyard overnight. An arterial line is placed and the initial mean arterial pressure is 40 mmHg with a central venous pressure of 3 mmHg.

                                    Past Medical History:
                                    • Type 2 diabetes
                                    • NAFLD, biopsy proven six years ago
                                    • variceal bleed last year
                                    • ascites and recent worsening encephalopathy.
                                    Vital signs:
                                    • blood pressure 72/30 mmHg
                                    • temperature 102.3 F (39 C)
                                    • weight 56 kg, last weight 58 kg one week ago
                                    • no urine output
                                    Labs:
                                    • Scr 3.8 mg/dL (Scr 0.7 mg/dL last week).
                                    No signs of edema or ascites.
                                    Current medications: pantoprazole 40 mg daily, furosemide 40 mg every other day, carvedilol 6.25 mg twice daily, lactulose 30 mL TID, glipizide 10 mg daily, citalopram 10 mg daily.

                                    Please use the case above to answer the next 5 questions.

                                    1. JC’s blood pressure is 80/50 mmHg in triage, an arterial line is placed and CVP is initially 3 mmHg. What is the most appropriate immediate intervention given this information?
                                    A. Normal saline 500 mL bolus
                                    B. Vasopressin 0.04 units/min continuous infusion
                                    C. Midodrine 10 mg three times daily

                                    2. During JC’s admission the team requests your evaluation of the patient’s home medications. Which home medication would you discontinue on admission?
                                    A. Carvedilol
                                    B. Lactulose
                                    C. Citalopram

                                    3. What should the patient’s goal mean arterial pressure (MAP) be?
                                    A. Increase MAP by 30%
                                    B. Decrease MAP to 30 mmHg
                                    C. MAP of at least 65 mmHg

                                    4. The team is trying to determine what dose and concentration of albumin to administer. Based on only the information in the case, which initial dose and concentration is the most appropriate?
                                    A. 100 grams of 5% albumin
                                    B. 60 grams of 25% albumin
                                    C. 60 grams of 5% albumin

                                    5. The hospital is currently on ICU diversion and no critical care beds are available, so she must be cared for on the internal medicine unit. That unit cannot manage central lines. What is the most appropriate regimen to improve the patient’s MAP in addition to the currently infusing albumin?
                                    A. Terlipressin
                                    B. Norepineprhine
                                    C. Octreotide

                                    6. A patient has received terlipressin 1 mg every 6 hours for the past four days and the patient’s serum creatinine has increased from 3.5 mg/dL to 5 mg/dL. How should terlipressin be adjusted?
                                    A. Stop terlipressin
                                    B. Increase terlipressin dose to 1 mg every four hours
                                    C. Increase terlipression dose to 2 mg every six hours

                                    7. Which of the following medications should be avoided in patient with hepatorenal syndrome and/or liver cirrhosis?
                                    A. Acetaminophen
                                    B. Naproxen
                                    C. Guaifenesin

                                    8. HR is a 53-year-old Hispanic male who presents from hepatology clinic with an acute rise in serum creatinine. Admission medication reconciliation notes that his primary care doctor recently started him on losartan, and his blood pressure was 74/52 mmHg on admission. Following hydration with normal saline and stopping all other offending medications, the doctor prescribes midodrine and octreotide. What hemodynamic change can you expect following initiation of midodrine?

                                    A. Decrease in blood pressure
                                    B. Increase in portal pressure
                                    C. Increased blood pressure

                                    9. Which of the following is the most accurate rationale for combining albumin with other agents that cause vasoconstriction to manage hepatorenal syndrome?

                                    A. Exogenous albumin administration decreases intravascular oncotic pressure and allows for a decrease in mean arterial pressure when combined with vasoconstricting agents
                                    B. When specifically used in the setting of infection, exogenous albumin administration allows for enhanced delivery of protein bound antimicrobials to their required site of action
                                    C. Use of intravenous concentrated albumin allows fluid from the extravascular space to be pulled into the blood stream and increases blood volume and delivery to the kidney

                                    10. Which of the following best describes the pathophysiology of HRS?
                                    A. Increased blood flow to the kidney in the setting of splenic vasodilation
                                    B. Decreased blood flow to the kidney in the setting of portal hypertension
                                    C. Decreased blood flow to the kidney in the setting of splenic vasoconstriction

                                    11. Which of the following is a definitive treatment required to resolve HRS?
                                    A. Liver transplant
                                    B. Kidney transplant
                                    C. Portal vein transplant

                                    12. Which of the following best describes the main difference between Type I HRS and Type II HRS?
                                    A. Type 1 HRS is associated with a higher rise in serum creatinine (at least 0.3 mg/dL from baseline).
                                    B. Type 1 HRS happens more quickly (increase in serum creatinine over the most recent baseline taken within the past three months).
                                    C. Type 1 HRS shows the presence of structural kidney disease (e.g., polycystic kidney disease or glomerular, interstitial, or vascular diseases).

                                    Pharmacy Technician Post Test (for viewing only)

                                    Set Your Ascites on Improving Patient Care: The Pharmacy Team’s Role in HRS Management
                                    Pharmacy technician post-test
                                    1. Which of the following is a reason that liver disease affects the kidneys?
                                    A. Toxins that are cleared by the liver are toxic to the kidneys
                                    B. The treatments for liver disease release nephrotoxins
                                    C. Liver disease affects blood flow to the kidneys

                                    2. Which of the following best describes main difference between Type I HRS and Type II HRS?
                                    A. Type 1 HRS is associated with a higher rise in serum creatinine (at least 0.3 mg/dL from baseline) over any time period.
                                    B. Type 1 HRS happens more quickly (increase in serum creatinine over most recent baseline taken within the past three months).
                                    C. Type 1 HRS shows the presence of structural kidney disease (e.g., polycystic kidney disease or glomerular, interstitial, or vascular diseases).

                                    3. A patient with a past medical history of cirrhosis and ascites comes into the pharmacy complaining of mild to moderate knee pain and asks for help picking an over-the-counter analgesic. Which of the following will the pharmacist most likely recommend because of safety concerns?
                                    a. Naproxen
                                    b. Low dose acetaminophen
                                    c. Ibuprofen

                                    4. A patient is picking up prescriptions for furosemide and spironolactone. Which of the following should the patient remember to do to prevent an over-diuresis that can precipitate HRS?
                                    a. Weigh himself daily in the morning after he urinates; record his weights
                                    b. Eat a high sodium diet; read labels carefully and aim for more than 2 grams/day
                                    c. Practice good sleep hygiene; aim for an average 7 hours/night

                                    5. JC is a 55-year-old patient admitted to the intensive care unit with worsening ascites and hepatorenal syndrome. His mean arterial pressure is 50 mmHg, and the ICU doctor orders IV crystalloids. Which home medication might the team want to discontinue?
                                    A. Carvedilol
                                    B. Lactulose
                                    C. Citalopram

                                    6. Which of the following is a definitive treatment required to resolve HRS?
                                    A. Liver transplant
                                    B. Kidney transplant
                                    C. Portal vein transplant

                                    7. Which of the following is a vasopressor of the splanchnic circulation?
                                    A. Lactated ringers
                                    B. Terlipressin
                                    C. Albumin

                                    8. Which of the following is the most accurate rationale for combining albumin with other agents that cause vasoconstriction in the management of hepatorenal syndrome?
                                    A. Exogenous albumin administration decreases intravascular oncotic pressure and allows for a decrease in mean arterial pressure when combined with vasoconstricting medications
                                    B. When specifically used in the setting of infection, albumin allows for enhanced delivery of protein bound antimicrobials to their required site of action
                                    C. Use of intravenous concentrated albumin pulls fluid from the extravascular space into the blood stream and increases blood volume and delivery to the kidney

                                    9. What is a drawback to the use of midodrine and octreotide in the treatment of HRS?
                                    A. It constricts the splanchnic circulation.
                                    B. It was not available in the United States until 2023.
                                    C. It takes an extended number of days for full benefit.

                                    10. Which of the following medications needs to be administered in the intensive care unit?
                                    A. Albumin
                                    B. Norepinephrine
                                    C. Octreotide

                                    References

                                    Full List of References

                                    References

                                       
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