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

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.

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.

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

Pharmacistscan 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 Values^5,6

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.⁷Individuals 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.^3,8-10His 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 Development^8,10

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 professionally^12-15:

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.
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.
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 points^18-20:

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 Feedback^22,23

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.

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
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)

Itching for Relief: Understanding Contact Dermatitis

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

Recognize contact dermatitis types, signs and symptoms, and common treatments
Identify common topical allergens associated with contact dermatitis
Characterize over-the-counter products that are allergen-containing and allergen-free

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

Recognize contact dermatitis types, signs and symptoms, and common treatments
Identify common topical allergens associated with contact dermatitis
Differentiate over-the-counter products that are allergen-containing and allergen-free

Contact dermatitis is a common inflammatory skin condition affecting approximately 15% to 20% of the population and accounting for the majority of occupational skin disease cases. Pharmacist teams can help patients recognize symptoms, identify potential triggers, and select appropriate treatment options. This continuing education (CE) activity provides an in-depth review of contact dermatitis, with a focus on the two main subtypes: irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Participants will examine clinical presentation, common causative agents, and diagnostic approaches used to identify allergens, such as patch testing. This course outlines evidence-based management strategies, including topical corticosteroids, emollients, antihistamines, nonpharmacologic interventions, and prevention methods to reduce recurrence. Additionally, participants will learn to identify common allergens in personal care and household products in order to guide patients toward allergen-free alternatives. This CE will equip readers with the knowledge to provide effective care to patients with contact dermatitis and to support improved dermatologic health outcomes through patient education and preventive counseling.

INTRODUCTION

Imagine you’re working a late shift at your local pharmacy when a mother rushes in with her child, whose hands are red and covered in small, weeping lesions. The child says they itch constantly, and the mother explains the pediatrician mentioned “contact dermatitis,” but mom’s unsure how to help. She didn’t know who else to turn to but hopes you could provide some suggestions on what products can help her child.

While skin conditions aren’t necessarily the pharmacy staff’s bread and butter, your expertise can still make a difference. You can scrutinize the affected area and ask some guided questions to decide what products may help the child.

PAUSE AND PONDER: What questions may help determine the best remedy for this child?

Before recommending products, it’s important to first understand what contact dermatitis is, how it develops, and the most effective treatment options.

WHAT IS CONTACT DERMATITIS?

Contact dermatitis is a form of eczema (a group of inflammatory skin conditions that cause dry skin, itchiness, rashes, scaly patches, blisters, and skin infections) that occurs when a substance comes into contact with the skin and causes irritation or an allergic reaction.^1,2 Contact dermatitis occurs in 15% to 20% of people. Contact dermatitis is the most common form of reported occupational skin disease accounting for approximately 90% to 95% of cases.^1,3 Although contact dermatitis has no cure, patients can manage symptoms effectively with topical treatments and by identifying and avoiding the triggering substance.

It's important to note many different clinical patterns of contact dermatitis exist. Some common patterns include^4-10

Erythema multiforme—lesions present as macules (flat, distinct spot on the skin that's a different color than the surrounding area but doesn't impact the skin's texture or thickness), papules (red bumps), bullae (blisters filled with clear fluid), or urticarial eruptions (itchy welts), often demonstrating a characteristic 'target lesion' pattern predominantly affecting the extremities
Urticarial papular plaques—skin lesions that appear as itchy papules and raised patches, often appearing in lines or clusters
Lichen-planus—presents as shiny red, purple, gray, or brown bumps that may merge into plaques, commonly on wrists, arms, legs, or lower back; may cause mild to intense itching
Purpuric petechial reactions—skin or mucous membrane discoloration as a result of hemorrhage from small blood vessels. Lesions are often 1 mm to 2 mm across
Pustular reactions—a rash consisting of small pustules (bumps) less than 5 mm to 10 mm that are filled with pus
Pigmentation disturbances
Pemphigoid—present as large fluid-filled blisters that rupture and form crusted erosions

Types of Contact Dermatitis

Contact dermatitis has two main presentations: irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Table 1 provides more information on these two presentations.

PAUSE AND PONDER: How does ICD differ from ACD?

Table 1. The Main Types of Contact Dermatitis and their Characteristics.^1,2-4,11-14

Irritant contact dermatitis

Allergic contact dermatitis

● Makes up approximately 80% of contact dermatitis cases.

● Mechanism: Involves a chemical or substance causing damage and inflammation to the skin. Damage occurs over time and with repeated exposure to the irritant.

● Reaction type: Non-immune mediated reaction. Damage is limited to the place where the chemical or substance is absorbed.

● Onset: Reactions occur within minutes to hours.

● Defining characteristics: Occurs as a dose-dependent inflammatory reaction. Harsher agents or more vigorous abrasions produce more severe injury.

● Clinical manifestations: Clinical features of acute ICD include erythema (redness), vesicles (small fluid filled bumps), edema, bullae, and oozing. Patients often experience burning, stinging, and pain. Clinical features of chronic ICD include erythema, lichenification (hyperpigmentation, skin thickening), scaling, hyperkeratosis (skin thickening), and fissuring (small cracks in dry, thickened skin). Patients often experience burning and pain more than itchiness.

● Causative factors:

○ Highly irritating chemicals (e.g., acids, bases, oxidizing or reducing agents)

○ Mild irritants (e.g., water, detergents, weak cleaning agents, soaps)

● Makes up approximately 20% of contact dermatitis cases.

● Mechanism: Involves the body producing an allergic reaction to a chemical or allergen the skin has absorbed.

● Reaction type: Immune mediated reaction.

● Onset: Can be a delayed reaction that occurs more than 24 hours past exposure.

● Defining characteristics: Improves more slowly than ICD and recurs faster when exposure is re-established.

● Clinical manifestations: Acute ACD has clinical features including thin, erythematous, scaly, and eczematous plaques. Lesions may also be vesicular (small bubble-like sacs formed when fluid is trapped under the epidermis) or bullous (hive-like welts or large, fluid-filled blisters). Chronic ACD has clinical features including indurated and scaly lesions. Over time, the skin may become lichenified. Other features of the rash are sensations of burning, redness, stinging, swelling, oozing, crusting, and flaking.

● Causative factors:

○ Poison ivy and other plants

○ Commercial chemicals (e.g., toluene-2,5-diamine sulfate, panthenol, cetrimonium chloride and bromide, chlorphenesin)

○ Industrial compounds (e.g., metals, epoxy, acrylic resins, rubber additives)

○ Agrochemicals (e.g., pesticides, fertilizers)

ABBREVIATIONS: ICD, irritant contact dermatitis; ACD, allergic contact dermatitis

Apart from these two main types of contact dermatitis, other less common presentations can develop. Photoallergic and photoirritant contact dermatitis are reactions primarily affecting sun-exposed areas including the face, back of the hands, arms, upper chest, and lower legs.¹¹

Photoallergic contact dermatitis requires ultraviolet radiation to activate the allergic agent to trigger an allergic reaction. The most common causative agents are chemicals found in sunscreens. Benzophenones (most commonly oxybenzone) are common sunscreen components and chemical triggers. Other agents include ethylhexyl methoxycinnamate (octinoxate), butyl methoxydibenzoylmethane (avobenzone), ethylhexyl dimethyl (padimate O), and octocrylene. A less common cause implicated in photoallergic contact dermatitis reactions is ketoprofen, a topical nonsteroidal anti-inflammatory drug.¹¹

Photoirritant (phototoxic) contact dermatitis requires ultraviolet radiation to activate the irritant and cause cellular damage. It occurs after contact with plants that contain furocoumarins or psoralens (e.g., lime, lemon, parsnips, parsley, celery, hogweed, rue [Ruta graveolens], meadow-grass, fig tree). Due to its association with limes and sunlight, photoirritant contact dermatitis is commonly referred to as “Margarita dermatitis.”¹¹

Protein contact dermatitis is caused by exposure to high-molecular-weight proteins often found in foods, latex, and other biologic material. Common foods involved include vegetables, animal proteins, spices, wheat, and milk. Most cases are occupation-related with food handlers frequently developing this form of dermatitis.¹¹

Systemic allergic contact dermatitis, also known as hematogenous contact dermatitis, occurs when an individual who has been previously sensitized to an allergen through skin contact later encounters the same substance through a systemic route (e.g., ingestion, injection, inhalation, implantation, or suppository use). Common triggers include metals (most commonly nickel); medications (e.g., aminoglycoside antibacterials, corticosteroids, and aminophylline); chemicals (e.g., parabens, formaldehyde, and propylene glycol); certain foods (e.g., soy, chocolate, nuts, and spices); and plants. Common plant sources include those in the Compositae family (known as the “daisy” family such as dandelions, sunflowers, and ragweed) andAnacardiaceae family (known as the “cashew” family and such as cashews, mango, and sumac), garlic, and balsam of Peru.^11,13,15-17

Pathogenesis of Allergic Contact Dermatitis

The difference in mechanism between ACD and ICD results in their distinct pathogenic pathways. See the SIDEBAR for definitions on the immune cells involved in contact dermatitis’ pathogenesis.

SIDEBAR: Overview of Immunomodulatory Cells Involved in the Pathogenesis of Contact Dermatitis^18-22

T-effector cells: Activated T-cells that migrate to infection sites to eliminate pathogens. These cells develop through antigen recognition (following presentation by antigen-presenting cells), leading to T-cell proliferation and differentiation to effector cells.
T-memory cells: Form of activated T-cells that become long-lived memory cells. These cells rapidly expand and mount a stronger immune response upon re-exposure to the same antigen.
Interleukin-1 alpha (IL-1α): A pro-inflammatory cytokine found in most cell types, especially barrier tissues. It’s released during cell injury or stress to trigger local inflammation, recruit immune cells, and promote tissue repair.
Interleukin-1 beta (IL-1β): A pro-inflammatory cytokine produced by activated immune cells that requires inflammasome processing (enzymatic activation of an inactive precursor by intracellular immune complexes) to become active. It mediates systemic inflammation, fever, and leukocyte recruitment.
Interleukin-1 receptor antagonist (IL-1RA): A natural inhibitor that blocks IL-1α and IL-1β from receptor binding, preventing excessive inflammation and maintaining immune balance.
Interleukin-10 (IL-10): An anti-inflammatory cytokine that suppresses pro-inflammatory cytokine production and limits tissue damage by controlling immune cell activation.
Interleukin-6 (IL-6): A multifunctional cytokine produced during infection or stress that activates immune cells, induces acute-phase responses, and contributes to systemic inflammation and metabolic changes.
Tumor necrosis factor-alpha (TNF-α): A key inflammatory cytokine—secreted mainly by macrophages—that regulates immune responses, promotes inflammation, and influences metabolism and tissue repair.
Chemokine ligand 20 (CCL20): A chemokine that binds CCR6 (C-C chemokine receptor type 6) to attract lymphocytes and dendritic cells to inflamed or infected tissues. It plays a central role in Th17-driven inflammation and autoimmune disease.
Chemokine ligand 21 (CCL21): A chemokine that binds CCR7 (C-C chemokine receptor type 7) to direct T-cells and dendritic cells to lymphoid organs, supporting immune cell organization and adaptive immune responses.
Chemokine ligand 8 (CXCL8)/Interleukin-8 (IL-8): A chemokine that binds CXCR1 (C-X-C motif chemokine receptor 1) and CXCR2 (C-X-C motif chemokine receptor 2) to recruit neutrophils to infection sites, contributing to inflammation, angiogenesis, and tissue remodeling.
Intercellular adhesion molecule 1 (ICAM-1): An adhesion molecule on endothelial cells and leukocytes that mediates immune cell attachment and migration during inflammation and supports T-cell activation.

Pathogenesis of ACD can be broken down into three stages: sensitization, elicitation, and resolution.¹³

Sensitization occurs during initial allergen exposure. The skin absorbs the allergen (antigen) which then binds to dendritic cells (immune cells that present antigens to T-cells and help drive adaptive immunity) and migrate to lymph nodes.²³ In the lymph nodes, these allergens trigger the development of allergen-specific T-cells. The T-cells then differentiate into T-effector cells and T-memory cells and recirculate into the blood and skin. This process may take up to 15 days. Patients may not develop active dermatitis during this phase.¹³

Elicitation occurs upon allergen re-exposure. The allergen binds to the dendritic cells and is presented to the antigen-specific T-cells. This triggers a rapid inflammatory response cascade that releases pro-inflammatory cytokines and recruits inflammatory cells. This process occurs hours to days after the exposure and manifests as an itchy rash at the contact site. The dermatitis response can last days to weeks following exposure.¹³

Resolution occurs post-exposure. A large population of T-memory cells replace T-effector cells. This ensures that if individuals experience subsequent exposures, the immune reaction to the allergen is of increasing intensity. As a result, patients may experience a worsening severity of symptoms with repeated exposures due to the increasing population of T-memory cells in the skin.¹³

Pathogenesis of Irritant Contact Dermatitis

ICD’s pathogenesis is less clearly understood than ACD’s pathogenesis; however, experts have determined a few key mechanisms involved. These mechanisms include disruption of the epidermal barrier (the stratum corneum) and the loss of lipids, damage to keratinocyte cell membranes, cytotoxic effect on keratinocytes, inflammatory cytokine release from keratinocytes, and activation of innate immunity.¹²

Previous experimental studies show that disruption of the epidermal barrier by occlusion or by physical/chemical irritation results in increased skin permeability, transepidermal water loss, and reduced natural moisturizing factor. These steps are considered the initiation event of ICD. ICD’s pathogenesis also varies depending on whether the condition is acute or chronic.¹²

In acute ICD, studies using both human and animal models show that acute damage to the epidermal barrier (such as that caused by sodium lauryl sulfate, a surfactant used in many cleaning and hygiene products) triggers the release of preformed cytokines from keratinocytes, including interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor (TNF)-α. IL-1α and TNF-α serve as key mediators, initiating the release of additional pro-inflammatory cytokines (e.g., CCL20, CCL21, CXCL8) that recruit mononuclear and polymorphonuclear cells to the irritation site. TNF-α stimulates the expression of ICAM-1 on keratinocytes, facilitating leukocyte migration to the epidermis. Concurrently, the body produces anti-inflammatory mediators such as IL-10 and IL-1RA in response to irritant exposure, helping to regulate and resolve the inflammatory process.¹²

Researchers don’t fully understand the underlying mechanisms of chronic ICD yet. One proposed theory suggests repeated exposure to mild irritants or persistent wet work (occupations that involve frequent or prolonged contact with water or other liquids; e.g., healthcare, hairdressing, or construction). Continuous exposure leads to downregulation of the inflammatory response while promoting keratinocyte proliferation and differentiation. Studies comparing normal skin with areas repeatedly exposed to irritants, such as sodium lauryl sulfate, have shown decreased levels of pro-inflammatory cytokines (IL-1 and TNF-α) and increased levels of IL-1RA in chronically affected skin.¹²

Additionally, ICD appears to involve unique gene expression changes within the skin that distinguish it from ACD. Some individuals develop a tolerance to chronic irritant exposure, a process referred to as the “hardening phenomenon.” Although the exact mechanisms remain unclear, structural and biochemical adaptations—such as epidermal thickening (acanthosis [patches of thickened, velvety, darkened skin that appear within body folds and creases] and hyperkeratosis), alterations in stratum corneum lipid composition, changes in barrier permeability, and modulation of inflammatory mediator expression may contribute to this adaptive response.^12,24

Risk Factors

Risk factors for contact dermatitis are a mix of circumstantial and inherent traits. For example, a circumstantial trait is cosmetic preference. A woman partial to perfumes or jewelry has a greater risk of contact dermatitis than a woman who is not. An example of inherent risk is skin type; individuals with thin skin, for instance, are at an increased risk of contact dermatitis. Table 2 describes additional risk factors.

Table 2. Common Risk Factors of Contact Dermatitis.^4,11,25

Characteristic	Those at Increased Risk
Age	● Young children and infants. Contact dermatitis affects close to 20% of children.
Occupation	● Occupations with more exposure to irritants ○ Cleaners ○ Construction/metal work ○ Cosmetology/hairdressing ○ Electronic industry ○ Farming ○ Food production/handling ○ Forestry/landscaping/florists ○ Healthcare ○ Mechanics
Skin type	● People with red hair or thin skin (e.g., reduced thickness of epidermis/dermis, reduced keratinocytes, increased risk of skin tearing).
Comorbidities	● Other skin conditions, such as atopic dermatitis or psoriasis. ● Genetic factors, such as the TNF-α (-308 G/A) single nucleotide polymorphism or loss-of-function mutations in the FLG gene.
ABBREVIATIONS: TNF-α, tumor necrosis factor-alpha; FLG, filaggrin

In addition to these risk factors, higher dermal absorption may increase an individual’s risk for contact dermatitis.²⁶ Factors that impact dermal absorption include skin integrity, absorption location, the chemical’s physical and chemical properties, chemical concentration, absorption time of the chemical, and the surface area of skin that absorbs the chemical.¹

Signs and Symptoms

Signs and symptoms of contact dermatitis depend on whether the reaction is acute or chronic. An acute reaction, such as contact with poison ivy, can cause the skin to appear red and swollen and may have small vesicles. However, a chronic reaction caused by repeated reactions is more akin to a presentation of eczema with a rash that appears to thicken, scale, or crack.^3,13

The symptom location will also vary depending on the substance’s contact location. For example³

A reaction to a skin care product’s ingredient may be localized to the face or eyes
A reaction to poison ivy may be localized to the legs or hands
A reaction to jewelry may be centralized around the neck or wrists

Common symptoms of contact dermatitis include^1,2

Dry, flaking, scaly skin (may crack, ooze clear fluid, or crust)
Inflamed skin (may look pink, red, brown, purple, or gray depending on skin tone)
Itching (may lead to intense scratching and even bleeding)
Pain
Redness
Small blisters or wheals (itchy, red circles that have a white center)
Swelling

PAUSE AND PONDER: What over-the-counter products are appropriate to suggest to a patient with a poison ivy rash?

Diagnosis

Contact dermatitis often resolves once patients identify the trigger and avoid the substance going forward. With acute examples such as poison ivy, symptoms may resolve prior to a doctor’s visit.

However, for persistent symptoms that warrant an office visit, clinicians diagnose contact dermatitis by evaluating symptoms based on appearance and duration. They consider factors such as occupation and hobbies and use patch testing to confirm allergens.²⁶ Clinicians can perform skin biopsies to rule out additional skin conditions such as psoriasis and seborrheic dermatitis among others.²

During testing, clinicians apply small amounts of diluted allergens to the patient’s back under paper tape patches. After 48 hours, they remove the patches and evaluate the skin for signs of a reaction; the evaluation is repeated 72 to 96 hours later. A patch test helps identify chemicals or substances a patient is allergic to so they can be avoided in the future. The baseline patch test (baseline patch testing panels vary by geographic location, depending on the allergens available in each region ) finds approximately 70% of allergens.^2,3,28

The American Contact Dermatitis Society (ACDS) updated their “Core Allergen

Series” in 2020 to increase the chances of finding the responsible agent in contact dermatitis cases. This series is a patch-test panel designed to provide clinicians a tool to identify clinically relevant allergens beyond the standard baseline series.²⁹

Since job-specific allergies are common, patch testing is available for certain industries. For example, dermatologists and allergy specialists can use patches specific for florists or dental technicians. This expanded patch testing finds approximately 80% of allergens. Additional series may be applied based on the site of dermatitis, the suspected allergen exposure, and if patients bring their own products to be tested (may require dilution).^27,28

Reactions to patch testing are graded for each allergen on a spectrum as seen in Table 3.

Table 3. Grading and Interpreting Results to a Patch Test^28,30,31

Symbol	Reaction	Presentation
-	Negative	No reaction
?	Doubtful	Faint erythema only
+	Weak positive reaction	Mild reaction: erythema, infiltration, and possible papules
++	Strong positive reaction	Strong reaction: erythema, infiltration, papules, and vesicles
+++	Extreme positive reaction	Very strong reaction: intense erythema, infiltration, blisters, and coalescing vesicles
IR	Irritant reaction	Irritant reaction of different types

Positive reactions can be further classified based on their relevance or potential risk. A current relevance reaction indicates the identified allergen explains the patient’s present dermatitis. A past relevance reaction reflects an allergen responsible for a previous episode but not the current one. A future relevance reaction suggests sensitization to an allergen the patient is likely to encounter again. An uncertain relevance reaction identifies an allergen whose significance remains unclear until further investigation or inspection of the patient’s personal care or occupational exposures. Finally, a potential cross-reaction indicates that sensitivity to one allergen may cause a reaction to related substances.²⁸

TREATMENT OF CONTACT DERMATITIS

Pharmacologic Treatment

Currently, no cure for contact dermatitis exists. However, a variety of over-the-counter (OTC) and prescription products can provide patients with symptom relief.

Clinicians tailor treatment based on contact dermatitis type, location, severity, and classification (acute versus chronic). Clinicians classify cases as extensive, severe, or disabling if they involve over 20% of the total body surface area or involve the face, hands, feet, or genitalia.³²

While pharmacologic treatment provides rapid symptom control, prevention is the mainstay of management for both ACD and ICD. ACD treatment usually involves topical corticosteroids or tacrolimus with added emollients, while ICD treatment focuses on consistent emollient use and topical corticosteroids (when necessary to control irritation).^12,32

Providers must recognize that while topical corticosteroids may be used in ICD, evidence supporting their ability to restore the epithelial barrier remains limited. However, they may be prescribed for their anti-inflammatory properties. In ICD, ointments are generally preferred over creams as they are more occlusive. Formulations of products ordered from most to least occlusive are ointment, creams, lotions, and oils.^12,33 See the SIDEBAR for information on the uses and products that fall under each corticosteroid group.

SIDEBAR: Groups of Corticosteroids³⁴

Topical corticosteroids are grouped into seven classes based on their potency, ranging from superpotent (Group I) to least potent (Group VII). Potency affects both therapeutic efficacy and risk of adverse effects, making appropriate selection essential for safe and effective treatment.

Group I (superpotent): used for thick, resistant plaques (e.g., clobetasol propionate 0.05%, halobetasol propionate 0.05%).
Group II to III (high to medium-high potency): commonly used for less severe lesions or shorter treatment courses (e.g., betamethasone dipropionate 0.05%, fluocinonide 0.05%, triamcinolone acetonide 0.5%).
Group IV to V (medium potency): appropriate for most body areas and moderate conditions (e.g., triamcinolone acetonide 0.1%, mometasone furoate 0.1%).
Group VI to VII (low to least potent): preferred for sensitive areas such as the face, groin, or intertriginous areas (e.g., hydrocortisone 1%, desonide 0.05%).

For acute, localized ACD affecting the hands, feet, and nonflexural areas (areas of the body that do not naturally bend; e.g., the torso), treatment is a group I to III corticosteroid used once or twice daily for two to four weeks (treatment may be shorter if symptoms resolve).³²

For acute, localized ACD affecting the face or flexural areas (areas of the body that naturally form folds; e.g., the elbow or knee joints), treatment is a group IV to VI corticosteroid used once or twice daily for one to two weeks and then tapered off over two weeks. If treatment duration must be longer than two weeks, topical tacrolimus is used twice daily until improvement and is then tapered off. If the contact dermatitis is resistant to other treatments, topical ruxolitinib is used once daily until symptom resolution.³²

For extensive, severe, or disabling ACD, treatment is systemic corticosteroids. Prednisone is dosed at 0.5 mg/kg per day (or an equivalent dose, with a max daily dose of 60 mg/kg) for seven days. This dose is then reduced by 50% for five to seven days and then tapered off over two weeks.³²

For chronic ACD localized to the hands, feet, and nonflexural areas, treatment is a group I to III corticosteroid once daily for seven to 10 days, then once every other day.

For chronic ACD localized to the face and intertriginous (area where two skin areas may touch or rub together e.g., between digits or the armpit) areas and resistant to topical corticosteroids, treatment is topical tacrolimus used once or twice daily until symptom resolution. If it is resistant to other therapies, topical ruxolitinib is used once daily until symptom resolution.³²

Last, for chronic ACD that is resistant to topical treatments, phototherapy (bath psoralen plus ultraviolet A photochemotherapy or narrowband ultraviolet B has demonstrated clinical improvement in chronic hand eczema cases), or systemic immunosuppressive medication (such as oral methotrexate, cyclosporine, mofetil, azathioprine, mycophenolate) are used.³²

For mild, non-facial ICD, treatment is a group II or III corticosteroid that is used once or twice daily for two to four weeks. For severe, non-facial ICD, treatment is a group I corticosteroid used once or twice daily for two to four weeks. For facial or flexural ICD, treatment is a group IV to VI corticosteroid used once or twice daily for one to two weeks.Last, for chronic ICD with lichenification, treatment is petroleum jelly with or without a medium potency (group IV to V) corticosteroid overnight (under occlusion) for a few days.¹²

Over-the-Counter Treatment

In addition to prescription products, patients can use several OTC options to manage ACD or ICD. OTC products are chosen based on the symptoms the patient wants to treat.

Cold compresses or antihistamines (such as cetirizine, diphenhydramine, or loratadine) may reduce itching. Pharmacists and pharmacy technicians can recommend calamine lotion or aluminum acetate to dry oozing lesions. Alternatively, patients can take oatmeal baths; this is helpful in cases where the lesions are widespread over the body. Emollients and moisturizers effectively reduce irritation and improve the skin barrier. Additionally, hydrocortisone cream or ointment can decrease inflammation.^3,4,12

While people use the terms emollients and moisturizers interchangeably, knowing the distinction can prove useful when recommending products. Moisturizers help hydrate and maintain the skin’s moisture balance. Emollients help soften and smooth the skin by forming a protective layer that reduces water loss. Often, emollients can be used as an ingredient in the formulation of a moisturizer.³³

The two main types of emollients are occlusives and humectants. Occlusives create a lipophilic (“water-repelling”) film on the skin’s surface that acts as a barrier, helping to prevent moisture from evaporating from the outermost layer of the epidermis. Occlusives help skin retain moisture, but don’t provide additional moisture. Examples of occlusives include petroleum jelly, lanolin, oil (mineral or vegetable), beeswax, ceramides, and liquid paraffin.^12,33,35 However, some patients may experience “lanolin allergy,” which is a separate condition from contact dermatitis. Lanolin was the ACDS’s 2023 “Allergen of the Year” and some patients should avoid this ingredient.³⁶

Humectants are hydrophilic (“water-attracting”) and draw in and hold moisture within the stratum corneum, functioning in a way similar to the skin’s natural moisturizing factors found in corneocytes. Examples of humectants include glycerin, hyaluronic acid, urea, sorbitol, and propylene glycol.^12,33,35

Consistent application throughout the day improves the efficacy of emollients. Reapplication after handwashing and before bedtime especially help maintain the skin barrier and prevent flare-ups.¹²

Moisturizers reduce skin dryness, scaling, and transepithelial water loss which helps maintain skin integrity, flexibility, and barrier function.³³ Moisturizers are primarily comprised of emollients, occlusives, and humectants but may contain additional ingredients such as fragrances, surfactants (cleansers), and preservatives. Some special formulations may include ingredients with antimicrobial, anti-itch, and anti-inflammatory functions.

Choosing the ideal product for a patient depends on the target allergies, the skin’s condition and characteristics (inherent risk factors), and personal preference. Patients using a combination of prescription and OTC products may see symptom resolution within as early as one to two weeks.

Prevention

Prevention is the mainstay treatment for both ACD and ICD. Patients can take several actions to help prevent contact dermatitis.

First, patients should identify and avoid known allergens and irritants to prevent possible reactions. Making lifestyle choices such as selecting hypoallergenic jewelry, changing hair or skin care products, and putting cloth covers on metal fasteners (e.g., a jean button) can minimize reactions.^13,37

Patients can also improve and protect their skin barrier by continuously moisturizing and hydrating their skin. Various OTC products with different formulations allow patients to find a regimen that works best for their skin.^12,37

Patients should wash skin exposed to the allergen or irritant immediately after exposure to remove the irritant (e.g., poison ivy, poison oak) that cause the reaction. Products like Tecnu cleanser, Zanfel cleanser, and Cutter scrub effectively remove urushiol oil (the component of poison ivy and poison oak that causes the red, itchy rash patients experience). Urushiol oil binds to skin proteins within 10 to 15 minutes so immediate use of these products is vital.^13,37,38

Patients should also be mindful of pets. Sometimes, allergens can be carried from outside into the house by clinging to a pet’s fur. If patients suspect their pet encountered an allergen (such as poison ivy), they should bathe the animal to reduce the risk of spreading it to people.^13,37

Wearing gloves or protective clothing provides an excellent alternative for patients to avoid contact with irritants. This is especially vital for many occupational contact dermatitis cases. Barrier creams are another alternative that function to protect skin from irritants. Barrier creams prevent penetration of hazardous materials into the skin. These products contain compounds such as glycerin, silicones, ceramides, squalene, petrolatum, and other water repelling compounds. Barrier creams should be applied to exposed skin two to three times per day.^12,37

ALLERGENS IN CONTACT DERMATITIS

Common Causes of Allergic Contact Dermatitis

ACD is caused by a variety of common chemicals and substances. Common causes include^{11,13,32,37,39-43}

Excipients (propylene glycol, lanolin)
Fragrances (limonene, linalool, fragrance mix 1, fragrance mix 2)
Glues (acrylates)
Hair dyes and hair care products (toluene-2,5-diamine sulfate, para-phenylenediamine, cetrimonium chloride, cetrimonium bromide)
Latex (balloons)
Medications (antibiotics, glucocorticoids, topical antihistamines)
Metals (nickel, cobalt, and gold); commonly used in jewelry, buckles, claps, buttons, etc.
Personal care products such as body washes, cosmetics, and skin care products (panthenol, chlorphenesin, parabens, balsam of Peru, colophony [rosin])
Plants (Toxicodendron genus is the most common; includes poison ivy, poison oak, and poison sumac)
Preservatives (benzisothiazolinone, formaldehyde, methylisothiazolinone, quaternium-15)
Surfactants (cocamidopropyl betadine, decyl glucosides)

This list is not exhaustive but serves as a strong starting point for identifying products or substances that may trigger ACD. As new cases are reported, experts continue to identify potential allergens, reflecting evolving exposure patterns and improving diagnostic awareness. Notably, toluene-2,5-diamine sulfate, a chemical commonly used in hair dye, was named the 2025 Allergen of the Year, highlighting its emerging significance in contact dermatitis.³⁹

Common Causes of Irritant Contact Dermatitis

ICD can be caused by a range of common chemicals and substances. Common causes include^11,12,37,40

Acids and alkalizing agents (sulfuric acid, sodium hydroxide, ammonia)
Adhesives
Bleach, detergents, and solvents (benzene, toluene)
Cosmetics
Dust
Fertilizers and pesticides
Hair products
Oxidizing agents (sodium hypochloride)
Paints and varnishes
Perfumes
Personal care products
Plant parts (thorns)
Plastics
Rubber gloves
Soap
Water

Pharmacy staff should recognize that certain products, such as hair and personal care items, can cause both ACD and ICD reactions. However, the underlying mechanisms and nature of the reactions differ between the two conditions.

ALLERGEN ALTERNATIVES

Once an allergen has been identified, the most effective management strategy is avoidance. Because many ingredients appear under multiple names, careful review of product labels is essential. For example, balsam of Peru has several names including, but not limited to, Balsamum peruvianim, Black balsam, China oil, Indian balsam, Myroxylon pereirae Klotzsch resin, Myroxylon pereirae Klotzsch oil, and Toluifera Pereira balsam.⁴⁴

Patients may need guidance selecting products that provide the desired symptom relief while avoiding their allergens. Many items contain suitable substitute ingredients and pharmacy staff can support patients by reviewing product labels for potential allergens.

For example, toluene-2,5-diamine sulfate is frequently used in hair dyes as a primary intermediate (main reactive dye precursor).⁴⁵ An alternative to this chemical is paraphenylenediamine.³⁹ Other strategies include replacing nickel-containing jewelry with sterling silver or titanium; selecting products preserved with phenoxyethanol or benzyl alcohol instead of chlorphenesin or parabens; choosing formulations that minimize preservatives through plant-derived alternatives or hydrosols; and opting for fragrance-free products to avoid balsam of Peru.^46,47

It is also important that pharmacy staff understand various terminology used to describe products that would be better suited for patients with allergies. Currently, no Food and Drug Administration regulated definition for the term “hypoallergenic” exists.⁴⁸ Therefore, terms such as “fragrance-free,” “noncomedogenic,” and “dermatologist-tested” are indicators of products that may be better suited for patients with allergies. Pharmacists and pharmacy technicians should notify patients that products with these terms may be more expensive. These products are often placed on lower shelves as they tend to sell slower compared to other popular, branded items.

Additionally, pharmacy staff can recommend swatch testing new products before use to minimize risk of a reaction. Patients can apply a quarter-sized amount of the new product on a spot of their skin where the product won’t be washed away or rubbed off, such as the underside of the arm or the bend of the elbow. Patients should follow the instructions of the product to determine how long the product would normally stay on the skin (if the product [e.g., a cleanser] has no specific instructions, leave on the skin for five minutes). The product should be applied to this test spot twice daily for seven to ten days. If there is no reaction after this period, the patient can safely use the new product.⁴⁹

Common Allergen-Free Over-the-Counter Products

Finding allergen-free products or brands can be tricky, however online resources can alleviate this burden.

One helpful resource is the Contact Allergen Management Program (CAMP) created by the ACDS. CAMP is a web-based tool designed to help patients manage ACD and find personal care products that are safe for them to use. However, CAMP is an exclusive tool for ACDS members and their patients, so access may be limited for some healthcare providers.

In addition to using this resource, pharmacists and pharmacy technicians should counsel patients to always read and scrutinize product labels. One tool to navigate product labels and ingredients is skinsafeproducts.com. This website allows patients, providers, and pharmacy teams to scan barcodes or search products to determine if they contain ingredients a patient would react to. It’s important to note this website does not have a filter for every possible allergen.

For example, consider Alvin, a 35-year-old man allergic to parabens and various fragrance mixes. He asks for help finding an aftershave and body lotion. Using the SkinSAFE website (skinsafeproducts.com) you identify that “Clubman Pinaud Reserve Aftershave, Whiskey Woods” is paraben-free and “Minimalist Body Lotion, Niacinamide 0.5%” is fragrance-free.

Pharmacy staff should always consider recommending a switch in product. For instance, if a patient has a small cut, pharmacists and pharmacy technicians can recommend petrolatum over bacitracin. Bacitracin was named the Contact Allergen of the Year for 2003 by the ACDS and patients have an increased risk of reaction with this product.⁵⁰ Pharmacy staff have the unique opportunity to help patients make safe and informed product changes.

One thing to keep in mind is that formulations change! A product may be safe the first time a person uses it, but it may not be safe the next time. It’s essential to ensure healthcare providers and pharmacy staff always verify the accuracy of all information they provide to each unique patient!

CONCLUSION

Now that you’ve reviewed the key concepts of contact dermatitis, let’s revisit our opening case.

To start, ask the patient clarifying questions such as, “When did the rash appear?”, “Have you done anything out of the ordinary recently?”, and “Has the child started any new products?” You then discover the family went camping over the weekend. When this information is combined with the child’s current symptoms, poison ivy is the likely culprit. Suggesting OTC products such as calamine lotion (for lesions) and a cold compress or antihistamine (for itching) can help the manage the patient’s symptoms. However, it’s important to advise the mother to bring her child to the pediatrician if symptoms persist or worsen.

By identifying likely triggers, recommending appropriate symptomatic relief, and knowing when to refer the patient to seek additional medical attention, pharmacy staff can improve outcomes for patients with contact dermatitis.

Learning Objectives
After completing this continuing education activity, pharmacists will be able to:
1) Recognize contact dermatitis types, signs and symptoms, and common treatments
2) Identify common topical allergens associated with contact dermatitis
3) Characterize over-the-counter products that are allergen-containing and allergen-free topicals

1. Which of the following best describes irritant contact dermatitis (ICD)?
a. Delayed immune reaction
b. Direct skin barrier damage
c. Immediate histamine response

2. Which statement most accurately describes chronic ICD?
a. Vesicles and weeping lesions on the skin
b. Skin thickening with repeated exposure
c. Symptoms fully resolve after one exposure

3. Which characteristic best differentiates allergic from irritant contact dermatitis?
a. ACD reactions are dose-dependent
b. ACD involves immune sensitization
c. ACD reactions occur within minutes to hours

4. Which topical corticosteroid formulation provides the best occlusion?
a. Lotion
b. Cream
c. Ointment

5. Which ingredient in a moisturizer provides a protective oily barrier?
a. Lanolin
b. Glycerin
c. Methylisothiazolinone

6. Which ingredient is a common allergen in hair dyes that can trigger allergic contact dermatitis?
a. Panthenol
b. Benzisothiazolinone
c. Toluene-2,5-diamine sulfate

7. A patient develops a rash after using sunscreen. Which chemical is a likely trigger?
a. Oxybenzone
b. Octinoxate
c. Octocrylene

8. A 32-year-old patient comes to the pharmacy complaining of itchy, red patches on her hands. When you ask if she has started any new products recently, she mentions that she recently got a new lotion set that has three products in it. Which of the following actions is the best first step in determining the cause of the reaction?
a. Recommend the patient immediately discontinue use of all three products
b. Recommend the patient go to her dermatologist and undergo a patch test
c. Recommend the patient swatch test each product on the underside of her arm

9. The same patient returns to the pharmacy a week later and informs the pharmacy that she had a reaction to every product in the set. She wants to switch to a product that is hypoallergenic and won’t cause a reaction. What is the best response to this patient’s request?
a. Recommend the patient avoid all lotions due to the possibility of a reaction
b. Recommend the patient go to her dermatologist to undergo a patch test
c. Recommend the patient try the most popular brand of lotion as it’s on sale

10. The patient returns to the pharmacy after a visit to her dermatologist and has found out she’s reactive to lanolin, fragrance mix 1, and parabens. What is a suitable product that can be recommended to this patient? Use safeskinproduct.com to determine if these products are free from the patient’s allergens.
a. Vermont's original bag balm skin moisturizer
b. Bath and Body Works Japanese cherry blossom lotion
c. Vaseline original healing jelly

Learning Objectives
After completing this continuing education activity, pharmacists will be able to
1) Recognize contact dermatitis types, signs and symptoms, and common treatments
2) Identify common topical allergens associated with contact dermatitis
3) Differentiate over-the-counter products that are allergen-containing and allergen-free topicals

1. Which product can soothe mild ICD?
a. Fragranced lotion
b. Petrolatum
c. Alcohol sanitizer

2. When should a patient with a rash be referred to a healthcare provider?
a. If it covers more than 20% of body
b. If it lasts less than 24 hours
c. If it improves with moisturizer

3. When is the best time to apply an emollient for a contact dermatitis?
a. After handwashing and before bed
b. Once daily in the morning upon waking
c. 30 minutes to one hour before bathing

4. What is the purpose of barrier creams?
a. Replace corticosteroid use
b. Provide hydration to skin
c. Protect skin from irritants

5. Which of the following occupations is associated with an increased risk of contact dermatitis?
a. Hairdresser
b. Lawyer
c. Police officer

6. What allergen was dubbed 2025’s Allergen of the Year by the American Contact Dermatitis Society?
a. Cetrimonium bromide
b. Toluene-2,5-diamine sulfate
c. Limonene

7. A patient comes into the pharmacy with complaints of contact dermatitis around her finger. You notice she wears several rings on each hand. What metal could be the cause of this reaction?
a. Sterling silver
b. Titanium
c. Nickel

8. Which of the following names is synonymous for balsam of Peru?
a. Peru oil
b. Japan oil
c. China oil

9. A patient comes to the counter on Monday and explains that she had spent the weekend weeding her garden. She suspects she came into contact with poison ivy and is asking what she should do. What is not an appropriate suggestion?
a. Recommend the patient to use calamine lotion
b. Recommend the patient to use Tecnu cleanser
c. Recommend the patient to bathe pets exposed to the poison ivy

10. A mom comes into the pharmacy with her 9-year-old daughter. She has an almost empty bottle of a moisturizing lotion. She selects the same product from the lotion shelves and brings it to the register. She explains that her daughter is allergic to fragrance and asks you to ascertain if the product's ingredients have changed. What is the best response?
a. Compare the ingredients from the new bottle to the old bottle to be sure the formulation hasn’t changed
b. There's no need to check. If the patient has used this before it will most certainly be okay because companies rarely change formulas
c. Ask the pharmacist to help you because tasks like this are outside of your scope of practice

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38. Grand L. How to remove poison oak plants and treat a rash. OSU Extension Service. February 10, 2025. Accessed November 18, 2025. https://extension.oregonstate.edu/gardening/flowers-shrubs-trees/how-remove-poison-oak-plants-treat-rash.
39. Atwater AR, Botto N. Toluene-2,5-Diamine Sulfate: Allergen of the Year 2025. Dermatitis. 2025;36(1):3-11. doi:10.1089/derm.2024.0384.
40. Johnson J. Common causes of contact dermatitis. National Eczema Association. December 4, 2024. Accessed October 21, 2025. https://nationaleczema.org/blog/common-causes-contact-dermatitis/?gad_source=1&gad_campaignid=21711219806&gbraid=0AAAAAB0npNYM67FQOHjAv-hUjsQY3Sbsp&gclid=CjwKCAjwr8LHBhBKEiwAy47uUvI6-eQJ_GmU_4FwHZoVXavg3hH3SDWckrJrIsYZfjfSUNhaL7JTzhoCu8QQAvD_BwE.
41. Weber B, Hylwa S. Panthenol Allergic Contact Dermatitis: Sources of Exposure, Reported Cases, and a Call for More Frequent Testing. Dermatitis. 2025;36(4):343-351. doi:10.1089/derm.2024.0489.
42. Arnold WA, Blum A, Branyan J, et al. Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern. Environ Sci Technol. 2023;57(20):7645-7665. doi:10.1021/acs.est.2c08244.
43. Moreira de Nogueira CM, Dias Cerqueira C, Santos Ribeiro MÂ, Marques Pereira Cabral Ribeiro TM. Chlorphenesin-Induced Allergic Contact Dermatitis: An Overlooked Phenomenon?. Dermatitis. 2025;36(5):555-556. doi:10.1089/derm.2024.0433.
44. Ngan V. Balsam of Peru Contact Allergy. DermNet. April 2023. Accessed October 23, 2025. https://dermnetnz.org/topics/balsam-of-peru-allergy.
45. National Center for Biotechnology Information. PubChem Compound Summary for CID 22856, 2,5-Diaminotoluene sulfate. https://pubchem.ncbi.nlm.nih.gov/compound/2_5-Diaminotoluene-sulfate. Accessed Oct. 23, 2025.
46. Markel K, Silverberg N, Pelletier JL, Watsky KL, Jacob SE. Art of prevention: A piercing article about nickel. Int J Womens Dermatol. 2019;6(3):203-205. Published 2019 Mar 16. doi:10.1016/j.ijwd.2019.03.001.
47. Poddębniak P, Kalinowska-Lis U. A Survey of Preservatives Used in Cosmetic Products. Applied Sciences. 2024; 14(4):1581. https://doi.org/10.3390/app14041581.
48. “Hypoallergenic” cosmetics. U.S. Food and Drug Administration. February 25, 2022. Accessed November 19, 2025. https://www.fda.gov/cosmetics/cosmetics-labeling-claims/hypoallergenic-cosmetics#:~:text=For%20many%20years%2C%20companies%20have,to%20produce%20an%20allergic%20reaction.
49. How to test skin care products. American Academy of Dermatology. August 10, 2021. Accessed November 19, 2025. https://www.aad.org/public/everyday-care/skin-care-secrets/prevent-skin-problems/test-skin-care-products.
50. Wick JY. Bacitracin and Boo-boos: Becoming a no-no. Pharmacy Times. April 14, 2024. Accessed November 19, 2025. https://www.pharmacytimes.com/view/bacitracin-and-boo-boos-becoming-a-no-no.

Patient Safety: Toxic Human Drugs and Their Impact on Household Pets

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

DESCRIBE common pathways through which pets are exposed to toxic human medications
IDENTIFY the clinical signs and symptoms of toxicity from antidepressants, ADHD medications, NSAIDs, opioids, and recreational drugs in companion animals
DISCUSS veterinary management strategies and outcomes for pets exposed to toxic medications, including decontamination, symptom management, and diagnostic testing
RECOGNIZE best practices to counsel pet-owning patients on safe medication storage, disposal, and early signs of pet poisoning

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

RECOGNIZE common human medications that are toxic to pets
IDENTIFY signs and symptoms of drug toxicity in companion animals that may be mentioned by pet owners at the pharmacy counter
LIST proper techniques for medication storage and disposal that can reduce the risk of pet exposure
RECOGNIZE when to refer pet-owning patients to the pharmacist for counseling or poison control center guidance

Medications are the leading cause of toxic exposure in household pets (cats and dogs), surpassing traditional hazards like chocolate or household cleaners. As prescriptions for antidepressants, attention-deficit/hyperactivity disorder (ADHD) medications, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and recreational drugs increase nationwide, so does the risk to companion animals. Pharmacists and pharmacy technicians—often on the front lines of medication safety—can educate pet-owning patients on how to prevent accidental poisonings and recognize early signs of toxicity. This continuing education activity provides an overview of the most dangerous drug classes for cats and dogs, including clinical symptoms, treatment strategies, and emerging trends in veterinary toxicology. It also explores ethical and legal concerns, such as reporting obligations and the growing need for pet-safe medication packaging. Participants will gain evidence-based tools to support safe medication use in homes with animals and strengthen their role in harm prevention and patient education.

INTRODUCTION

Pharmacists and pharmacy technicians often think of medication safety in terms of human patients, families, and caregivers. But what about their pets? Companion animals are increasingly victims of preventable medication poisoning. Many of these cases start with a dropped pill, an open purse, or a topical patch worn on the skin.

According to the American Society for the Prevention of Cruelty to Animals (ASPCA) Animal Poison Control Center (APCC), prescription and over-the-counter (OTC) drugs are in the top three causes of pet toxicities reported each year. OTC medications were reported as #1, accounting for 16.5% of all exposures, and human prescription medications as #3. Human food and drinks are at #2, with 16.1% of exposures.¹This trend shouldn’t be surprising. Many homes contain a wide array of medications, increasing the risk of accidental pet exposure.² Our environments are filled with substances that can be fatal to a curious cat or an aimless labrador.

Since 2020, pet ownership in the United States (U.S.) has surged. According to the American Pet Products Association, nearly 70% of U.S. households now own at least one pet.³ As medication safety educators, pharmacists are increasingly expected to support patients as pet owners, not just as individuals. Technicians, too, often serve as the first line of communication at the pharmacy counter. Pharmacy employees might wonder, "But how am I supposed to help? I don’t treat animals." Pharmacy teams don’t have to treat animals. Pharmacy employees’ jobs include protecting the whole household—including pets. That means

Educating pet-owning patients about safe storage and disposal
Recognizing red flags during patient conversations
Referring to the correct veterinary resources when exposure is suspected

Veterinarians can’t be the only line of defense. Poisonings can happen at home, where nearly every room poses a risk.⁴ By the time a pet reaches the animal hospital, irreversible damage may have already occurred. Pharmacy professionals are positioned to intervene upstream, at the point of medication access.

HIDDEN RISKS AT HOME

Pets are curious by nature. Their attraction to novel smells, crinkling containers, or flavored suspensions often leads to unintentional ingestion. If a patient says, "My dog ate my pills, but it was only a few," how would a responsible, educated pharmacy employee respond? Many pharmacy professionals would hesitate. It's easy to assume that exposure is rare or that a small amount won't matter. But the reality is that pets are exposed to human drugs every day, often in ways humans don’t think about. Understanding the routes of exposure helps pharmacy professionals anticipate risk and educate patients more effectively. Below are the three most common ways pets come into contact with toxic medications.

Direct Ingestion

This is the most well-known route—and often the most severe due to immediate high exposure.⁴Examples include

A pill falls on the floor and the pet swallows it before the owner notices
A dog chews through a medication bottle, blister pack, or weekly organizer
A cat licks liquid formulations left on a countertop

It’s reasonable to wonder, "Wouldn’t a dog spit out a bitter-tasting pill?" (like most do when given their own pills). Not necessarily. Dogs may chew through plastic out of boredom, and some drugs (like venlafaxine [Effexor] or amphetamine/dextroamphetamine [Adderall] tablets) have sweeteners or coatings that make them more palatable.

Secondary Exposure

Pets may lick topical medications—like estrogen creams or lidocaine patches—directly from human skin. This route is especially dangerous because it often happens without anyone noticing. For example, if a patient applies a lidocaine patch and then holds her pet for an hour, the pet could absorb significant amounts of the drug. This could happen transdermally or orally if the pet grooms after exposure.⁵

Toxic exposure is not only a problem for pets—it’s a problem for children. According to a review of adverse event reports collected by the Swedish Medical Products Agency, children experienced serious health effects after contact with transdermal hormone-containing products. Documented symptoms include precocious (early) puberty, accelerated growth, unresolved virilization, and female infertility.⁵ These cases highlight the need for better public awareness and clearer instructions for storage and use to protect pets and children.

PRO TIP: When patients pick up topical or transdermal medications, ask, "Do you have pets or children at home that come into contact with your skin or laundry?" If the answer is yes, explain the risk and recommend covering the treated area or changing clothes before interacting with pets and children. A 20-second conversation might prevent a life-threatening exposure.

Environmental Contamination

Improperly discarded medications or drug-laced household waste can lead to inhalation or ingestion of drug residues by pets. Trash scavenging is common—pets often ingest discarded medications, wrappers, or even tissues soaked in drug residue.⁴ Some medications are excreted in urine or feces; pets that drink from the toilet may be exposed.Pharmacy technicians can help here. During OTC purchases or casual conversations, technicians may hear, "My dog gets into everything!" That’s a red flag that indicates it’s time to include a pharmacist and educate the pet owner on trash safety, sealed storage, and disposal. Never assume a drug is pet-safe unless it has a veterinary-approved label.

PAUSE AND PONDER: How would you explain the difference between a pet’s metabolism and a human’s?

LOW DOSE, HIGH RISK

Small doses that are safe for humans can be dangerous for pets due to differences in size, metabolism, and enzyme activity. Doses of ibuprofen exceeding 250 mg/kg of body weight can cause gastric ulcers or kidney failure in a small dog or cat.⁶

Let’s break it down^7-9

Researchers develop flat dosing for medications for humans. But most cats and dogs weigh a fraction of the average human weight. A 10 lb dog or 8 lb cat might receive a lethal dose from licking a coated tablet. Sustained-release medications can remain in an animal’s system far longer than in a human’s, causing extended toxicity.
Pets sometimes lack the enzymes humans rely on. Specifically, cats lack glucuronyl transferase—an enzyme essential to eliminate NSAIDs, acetaminophen, and opioids—making them highly susceptible to toxicity. Studies show that dogs often excrete a portion of certain drugs—such as NSAIDs and extended-release formulations—in the feces unchanged. This highlights pets’ limited ability to metabolize and eliminate these substances compared to humans. Both species have different gastric pH levels and gut flora that can affect absorption and breakdown.

Counseling should address two things. First, the pharmacist should explain that pets process medications differently than humans. Second, when accidental poisonings occur, pet owners should call a veterinary poison control hotline. They have veterinarians on staff around the clock and can determine if the dose the pet consumed is dangerous. The ASPCA APCC and Pet Poison Helpline are excellent, reliable resources. These calls often prevent unnecessary vet visits and guide lifesaving intervention when minutes matter.¹⁰ The SIDEBAR provides contact information for these resources.

SIDEBAR: Animal-specific Poison Control Centers

Human poison control centers do not manage veterinary cases. Instead, pharmacy teams and pet owners should be aware of the following specialized services.¹⁰

ASPCA Animal Poison Control Center (APCC)
	Phone: 1-888-426-4435
	Website: www.aspca.org/apcc
	Available 24/7; staffed by veterinary toxicologists
	Fee: $95 per case (covers phone consultation and follow-up)

Pet Poison Helpline
	Phone: 1-855-764-7661
	Website: www.petpoisonhelpline.com
	Available 24/7; includes licensed veterinarians
	Fee: $89 per case (includes updates to the attending veterinarian)

These hotlines charge a fee because they don’t receive government funding like human poison centers do. The cost supports rapid access to board-certified veterinary toxicologists and real-time risk assessments. After the client/pet owner pays for the consultation and the poison control specialist creates a case number, there are no further costs for following up on the case. The poison control center will work with the customer and a veterinarian until the case is resolved.¹⁰ In many cases, a single call can mean the difference between a $90 consultation and a $3,000 emergency vet bill.

TOP OFFENDERS

In veterinary toxicology, several drug classes account for most pet poisoning cases reported to animal poison control centers every year. Table 1 describes the five categories that are critical to know and how to recognize when a pet may be at risk.^2,11,12

Table 1. Impact of Common Drug Poisonings on Pets^6,11,13-15

Medication Type	Common Symptoms
ADHD medications (amphetamine/dextroamphetamine [Adderall], methylphenidate [Ritalin, Concerta], lisdexamfetamine [Vyvanse])	Agitation, hyperactivity, hypertension, mydriasis (dilation of the pupil), overheating, pacing, seizures, tachycardia, tremors
Antidepressants (fluoxetine [Prozac], sertraline [Zoloft], venlafaxine [Effexor])	Agitation, diarrhea, hyperactivity, hypertension, rapid heartbeat, seizures, tremors, vomiting
NSAIDs (ibuprofen [Advil], naproxen [Aleve, Naprosyn], diclofenac [Voltaren])	Abdominal pain, black or tarry stools, diarrhea, frequent urination, increased thirst, lethargy, loss of appetite, seizures, vomiting
Opioids (hydrocodone/acetaminophen [Norco], oxycodone [Oxycontin], fentanyl transdermal patch [Duragesic], buprenorphine [Suboxone])	Collapse, coma, lethargy, low body temperature, pinpoint pupils, sedation, slowed breathing, unresponsiveness
Recreational drugs (Cannabis, cocaine, methamphetamine [Desoxyn])	Dilated pupils, disorientation, high body temperature, hyperactivity, lethargy, seizures, stumbling, tremors, vomiting
ABBREVIATIONS: CNS = central nervous system

SIDEBAR: Universal Early Symptoms Across Agents

Behavioral changes – restlessness, vocalization, agitation
Cardiovascular distress – irregular heartbeat, high blood pressure, collapse
Gastrointestinal symptoms – vomiting, excessive drooling, diarrhea
Hyperthermia – elevated body temperature, excessive panting, drooling
Neurological signs – tremors, disorientation, seizures, agitation
Respiratory changes – labored breathing, excessive panting, wheezing

ADHD Medications

ADHD medications are potent central nervous system (CNS) stimulants. They have a narrow margin of safety in animals and can result in life-threatening cardiovascular or neurologic complications. Fast referral is critical. The symptoms described in Table 1 may appear within two hours.¹¹

Antidepressants

Many antidepressants increase serotonin in humans and animals, which can cause serotonin syndrome in both species. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are common in homes and highly dangerous to pets.

NSAIDs

As noted above, pets metabolize NSAIDs designed for humans poorly, if at all. Cats and dogs tolerate diclofenac, ibuprofen, and naproxen poorly. These medications can cause ulcers, renal injury, or liver failure at human therapeutic doses. One important sign of toxicity is blood in vomit.⁶ Some pet owners may assume human and pet NSAIDs are interchangeable. It's important to note cats and dogs have their own species-approved NSAIDs and analgesics formulated for safer metabolism. Use of human medications without veterinary guidance can lead to serious harm.

Carprofen (Rimadyl) is a Food and Drug Administration (FDA) approved in dogs for osteoarthritis and soft tissue pain. It is highly protein‑bound and eliminated via hepatic metabolism, with metabolites excreted in feces and urine. Meloxicam (Metacam) is approved for use in dogs in the U.S., and in some regions for cats in single‑dose or limited regimens. In cats, it undergoes oxidative metabolism (rather than glucuronidation) with approximately 80% of the drug eliminated in feces. Robenacoxib (Onsior) is another NSAID used in cats and dogs (for short durations), with cautious use in cats due to their limited ability to detoxify NSAIDs. These formulations are engineered to match each species’ pharmacokinetics, metabolism, and safety thresholds, making them safer than human NSAIDs.¹⁶

Opioids

Topical patches pose a particular risk if chewed or licked. Naloxone access in veterinary settings has become increasingly important. A 2020 study looked at 189,594 calls to the ASPCA’s APCC involving opioids from 2006 to 2014.¹⁴ It found small, young, intact (compared to neutered) dogs living in areas with high opioid prescribing were more likely to be involved in opioid-related emergency calls. Smaller and younger dogs were at higher risk than larger and older dogs. These researchers also found veterinarians were more likely to call the poison control hotline than owners. Owners may be reluctant to report exposures to illicit opioids. The research showed a strong positive non-linear link between dog poisonings and local opioid prescription rates.¹⁴

Recreational Drugs (Marijuana, Cocaine, Methamphetamine, Psilocybin)

Tetrahydrocannabinol (THC) and stimulants affect pets differently than humans, often with prolonged or unpredictable effects. Marijuana, cocaine, and methamphetamine can cause severe toxicity.¹⁵ Pets may appear frightened or "zoned out."

As marijuana becomes legal in more states, accidental pet exposures are rising—and costly. Pet health insurance provider Trupanion reported 1,852 marijuana-related toxicity claims over five years, mostly from pets ingesting edibles, plants, or baked goods. Figure 1 shows poisoning rates are higher in states with legalized recreational marijuana. Since 2020, California led with 428 claims, followed by Massachusetts, New York, and Florida.¹⁷

Figure 1. Marijuana Toxicity-Related Claims in Dogs & Cats in 2024¹⁷

Pharmacists and technicians should treat any known ingestion of these medications by a pet as an urgent referral to ASPCA APCC or Pet Poison Helpline. Ideal documentation would include the brand, strength, dosage form, and time of ingestion. Pharmacy staff should encourage owners to have the information handy when calling and to take the packaging with them to the veterinarian. Even if the owner reports their pet “seems fine” hours after exposure, toxicity can be delayed or progressive and serious harm may still occur without visible symptoms. Erring on the side of caution and referring patients and their pets to a veterinarian immediately is crucial.

Other Common Toxins

Human formulations may contain excipients or flavoring agents that are hazardous to pets. Certain gabapentin oral solutions contain xylitol (also labeled as birch sugar), which is rapidly toxic to dogs in small amounts. Xylitol triggers a potent insulin release in dogs, leading to hypoglycemia within 15 to 30 minutes. Symptoms often begin with vomiting and progress to lethargy, ataxia, tremors, seizures, or collapse. In severe cases or with higher doses, liver failure can occur.¹⁸ Pharmacists must check for inactive ingredients in liquid formulations and educate pet owners about this. It is important to note that xylitol is found in many common household items, including peanut butter and sugar-free candy.

Dogs are commonly prescribed levothyroxine to treat hypothyroidism and typically require significantly higher doses per kilogram of body weight than humans. Dosing must be carefully titrated, with regular monitoring of serum T₄ levels to avoid under- or over-dosing. Cats experience hyperthyroidism more often, and are treated with methimazole or radioactive iodine. They rarely need levothyroxine unless iatrogenic hypothyroidism occurs. Differences in thyroid disorders, metabolism, and treatment protocols make it dangerous to assume human thyroid medication doses apply to pets.¹⁹

Prednisone dosages vary based on whether the animal is being treated for inflammation or for immune suppression, as higher doses are typically required for immunosuppressive effects. Cats metabolize corticosteroids differently than dogs and humans, requiring different dosing protocols and careful consideration of duration and tapering. In dogs, veterinarians commonly use prednisone to manage allergic, musculoskeletal, or autoimmune conditions. Prolonged use requires monitoring for adverse effects such as polyuria (frequent urination), polydipsia (unusual thirst), or gastrointestinal ulceration.²⁰ In cats, prescribers often prefer prednisolone (rather than prednisone) because of their reduced hepatic conversion capacity, making direct administration of the active form more effective and safer.²¹

Even a single tablet of acetaminophen may be enough to kill a cat. In one published case, a cat experienced acetaminophen toxicity after exposure to a single dose. The patient exhibited hallmark signs such as cyanosis and facial swelling. The case highlighted the need for rapid intervention, and the diagnostic challenge this toxicosis can present. This report highlights the narrow safety margin of acetaminophen in cats and the importance of pharmacist awareness when reviewing shared medications between humans and pets.²²

PAUSE AND PONDER: If a pet owner says, “My dog is acting weird today after I dropped my pill,” what specific behaviors or symptoms should prompt you to refer them to a veterinarian or poison control center?

CLINICAL SIGNS OF TOXICITY IN PETS

A common question a pharmacy professional might hear from a pet owner is, "How do I know if my pet is poisoned?" Often, symptoms go unnoticed until they’re severe, and by then, the window for successful treatment may have narrowed. Pharmacists and technicians can recognize red flags early.

This section outlines key clinical signs of toxicity in pets across various drug classes, with an emphasis on phrases owners might use when describing the issue. This helps pharmacy teams know when to probe further and when to refer to a veterinarian or animal poison control center.

Tails of Toxicity

Pets may exhibit nonspecific signs that warrant urgent attention. Since pets cannot verbalize how they are feeling, owners must rely on observation of behavioral changes or physical symptoms. Table 2 lists ways to determine if a pet is ill.

Table 2. Analyzing Pet Behaviors for Signs of Poisoning^{4, 23-25}

Clinical Manifestation	Points to Remember
Lethargy or weakness	The owner may say “She’s not acting like herself,” or “He’s been sleeping all day.”
Vomiting and/or diarrhea	Immediate referral is warranted, especially if it is persistent, contains blood, or is paired with other symptoms.
Loss of appetite	The owner may report the pet eating only part of the regular meal size, skipping meals, or refusing favorite treats.
Tremors or seizures	● Often, owners see twitching, drooling, or frothing at the mouth and don’t realize the pet is experiencing a seizure. This often appears with exposure to stimulants (e.g., ADHD medications, pseudoephedrine, caffeine). ● Pet owners should stay calm, move nearby objects so the pets cannot knock them over or harm themselves. They should not touch or restrain the animal. They should also time how long the seizure lasts.
Hyperthermia	● Cats and dogs have a narrow normal temperature range (approximately 100-102.5°F). ● A body temperature of above 102.5-103°F in cats and dogs is considered hyperthermic and can lead to tissue damage or organ stress. ● Having a rectal or digital thermometer at home is important because pets don’t display fever the way humans do. The only reliable way to detect a fever in cats and dogs is by taking their rectal temperature.
Ataxia (uncoordinated movement)	The owner might say “He’s stumbling all over the place.”
Collapse or unconsciousness	● This is an emergency situation—immediate referral is critical. ● Advise owners to call ahead and tell the veterinary service they are on the way. If the pet is large, advise them to get help, and place the animal on a hard flat surface (i.e., an ironing board or a piece of plywood).
Changes in urination	This includes increased frequency (polyuria) or total suppression (anuria, especially with NSAID or antidepressant toxicity).

VETERINARY RESPONSE: MANAGEMENT & TREATMENT

Veterinary intervention is critical in pet poisoning cases. Most toxic exposures require decontamination, symptomatic management, and monitoring.⁷

Assessment and Diagnosis

Veterinarians rely heavily on the owner’s report. The most helpful information a pharmacy professional can encourage owners to bring to the vet includes²⁶

The exact name of the medication ingested
Strength and dosage form (e.g., extended-release, chewable, liquid)
Approximate time of ingestion
Estimated number of pills or quantity consumed
The observed symptoms
The pet’s weight and species

Veterinarians perform a thorough clinical examination, medical history, and toxicology screening. They will assess the pet’s vital signs (heart rate, respiratory rate, temperature) and observe neurologic status (agitation, tremors, seizures). They will also determine if the pet is suffering with dehydration or shock, and start supportive care based on the suspected toxin and symptoms.

Common diagnostic tests used in suspected poisoning cases include bloodwork and biochemical panels to assess organ function, glucose levels, and electrolyte imbalances. Urinalysis is often performed to detect drug metabolites and evaluate kidney function. Imaging techniques, such as X-rays and ultrasound, help identify ingested pills. Electrocardiography is used to monitor for cardiac abnormalities.⁷

Decontamination Strategies

Removing toxins from the body prevents further absorption. Veterinarians use multiple decontamination methods based on the substance and time since ingestion. Induced emesis (causing the animal to vomit) is often used within two hours of exposure. Apomorphine (in dogs) or xylazine/medetomidine (in cats) are commonly used to induce vomiting when appropriate. Hydrogen peroxide may be used in dogs, but its use is declining due to the risk of esophagitis and gastroenteritis even at therapeutic doses.²⁵ Highly acidic or alkaline chemicals can burn the mouth and digestive tract wall if regurgitated. The veterinarian may administer activated charcoal to absorb toxins and limit further drug absorption in the gastrointestinal tract. In more severe cases, gastric lavage (stomach pumping) is performed under anesthesia, particularly for life-threatening poisonings involving opioids or stimulants.²⁵

PRO TIP: Pharmacy teams can emphasize that inducing vomiting at home using hydrogen peroxide or other DIY methods can be dangerous. Owners shouldn’t attempt it without veterinary instruction.

Symptom Management

Veterinary treatment focuses on stabilization and organ protection. Table 3 describes specific therapies depending on the drug involved and clinical symptoms.Outcomes depend on the timing of intervention, known or suspected dosage, and pet health status. Delayed treatment increases risks of organ damage, seizures, or fatal outcomes. Follow-up veterinary care ensures no lingering effects on liver, kidneys, or heart function.

Table 3. Pet Toxicity Treatments^15,27

Toxicity Type	Treatment	Purpose
Cardiovascular	Beta-blockers (propranolol, atenolol)	Stabilizes heart rate and blood pressure
	IV lipid emulsion therapy	Reduces systemic circulation of lipophilic drugs like THC and certain antidepressants
	Oxygen therapy and mechanical ventilation	Used in opioid-induced respiratory depression
Gastrointestinal	Gastroprotectants (sucralfate, omeprazole, misoprostol)	Prevent stomach ulcers caused by NSAIDs.
Gastrointestinal	Liver protectants (SAMe, silymarin)	Supports liver function in cases of acetaminophen or NSAID toxicity
Neurological	Cooling measures	Used in hyperthermic pets with stimulant toxicity
	Sedation (benzodiazepines, barbiturates)	Controls seizures and agitation
	IV fluid therapy	Prevents dehydration and supports kidney function
ABBREVIATIONS: IV = intravenous; NSAID = nonsteroidal anti-inflammatory drug; THC = tetrahydrocannabinol

Antidotes and Specialized Therapies

In some poisonings, antidotes are available. Table 4 lists specific reversal agents.

Table 4. Toxins and Their Antidotes⁷

Toxin	Antidote
Acetaminophen	N-acetylcysteine
Alpha-2 agonists	Atipamezole (in some cases)
Benzodiazepines	Flumazenil
Benzodiazepines	Flumazenil
Opioids	Naloxone

Use of naloxone deserves extra attention. If a pet consumes an opioid and has collapsed, lost consciousness and/or has shallow breathing, owners can administer naloxone intranasally. Ideally, owners should administer naloxone under the direction of a veterinarian, who would determine the dose. Canine police officers have naloxone on hand because they have a prescription and are given detailed instructions on how to administer it. Regardless of who administers the naloxone, pets need to be taken to emergency care immediately after receiving the dose. Owners who have opioids in the home for prescribed or recreational use should be trained to use naloxone before an emergency happens.²⁸

Exposures to many medications, like antidepressants or ADHD medications, have no direct antidote. Management focuses on controlling symptoms and preventing complications. While many pets make full recoveries, outcomes depend on the type and amount of drug ingested, the time between ingestion and treatment, the pet’s size and species, and access to antidotes or critical care. Some cases (e.g., extended-release ADHD medications in small dogs) can be fatal even with treatment.

Costs and Outcomes

Veterinary care for toxicity can be expensive. Some ER visit costs include²⁹

ER exam: ~ $100 – $200
IV catheter: ~ $60 – $75
IV fluids (per bag): ~ $60 – $95
Blood tests (basic): ~$80 – $200
Urine tests (basic): ~$40 – $70
X-ray (basic): ~$150 – $250
Ultrasound: ~ $300 – $600
Blood pressure measurement: ~ $25 – $75
Pain medication: ~ $40 – $80
Oxygen therapy: ~ $500 – $3,000
Wound treatment and repair: ~ $800 – $2,500
Emergency surgery (bloat, foreign body, hit by care, caesarian): ~ $1,500 – $5,000
Hospitalization and monitoring:
- 1 – 2 days (vomiting, diarrhea, seizures cases): ~ $600 – 1,700
- 3 – 5 days (parvo, blocked cat, kidney failure): ~ $1,500 – $3,500

The Pharmacy Team’s Duty

When a poisoning occurs or is suspected, pharmacy employees can help in three ways. They can provide medication bottle labels or manufacturer information for veterinarians, reinforce that owners shouldn’t wait for symptoms to appear, and help set expectations about potential costs. A better way to deal with this issue is to implement preventive measures.

PREVENTION: PAWS OFF THE PILLS

Veterinary professionals stress education, secure medication storage, and responsible disposal practices to reduce the chances of pet poisonings.Pet owners are responsible for ensuring a safe environment free from toxic drug exposure.

Keeping drugs out of reach helps prevent accidental ingestion. Veterinary toxicologists recommend using childproof containers, since pets can easily chew through standard plastic pill bottles. Pet owners should store medications in cabinets with secure latches, as pets—especially cats—can access countertops and nightstands.³⁰ It is important to keep bags closed, because pets can get into backpacks or handbags containing loose medications.

Improper disposal of medications increases the risk of pet exposure. Veterinary professionals advise using take-back programs, as many pharmacies and veterinary clinics offer safe disposal services for unused medications. Discarded medications should be sealed in containers, such as plastic bags filled with coffee grounds or cat litter, to discourage pets from scavenging through trash bins. In some cases, the FDA recommends flushing high-risk drugs, such as opioids, to prevent exposure to humans and pets. These drugs are on the FDA's "Flush List" due to their danger if used by anyone other than the prescribed individual. Flushing these medications is only advised when a take-back option is not readily available.³⁰

COUNSELING POINTS FOR PET-OWNING PATIENTS

Pharmacists and pharmacy technicians are well-positioned to help prevent pet poisonings by proactively counseling pet-owning patients. These conversations don’t need to be long—but they need to be specific, timely, and relevant to the patient’s situation. The goal is to raise awareness, encourage safe practices, and direct patients to resources before an emergency occurs.³¹

Proactive counseling doesn’t just protect pets. It builds trust with patients, strengthens the pharmacist’s contribution in the community, and positions the pharmacy as a reliable source for pet-related safety guidance.³¹

Sniffing Out Red Flags

Counseling opportunities often arise when patients pick up medications known to be toxic to pets (e.g., antidepressants, ADHD medications, liquid gabapentin, NSAIDs, opioids). Patients may mention they have a new pet or ask about pet-related topics. Pharmacy staff may also notice a customer has pet-related OTC products in their basket (e.g., flea treatments, joint supplements, pet toothpaste). Sometimes, pets appear in the background of a telepharmacy call or accompany the owner into the store. All of these situations may prompt a discussion about medication toxicity.

Tips for Technicians

Technicians are often the first team member a patient interacts with. They can³¹

Ask, "Do you have pets at home?" when checking out medications
Flag high-risk medications that are toxic to pets
Share printed materials or magnets with animal poison control info
Update standard operating procedures to include referral language for veterinary poison concerns
Give a reminder at the register when a patient picks up a flavored ADHD medication
Refer to the pharmacist any time a pet is mentioned in relation to medications

Fetch the Right Tools

Keep a laminated cheat sheet behind the counter with common pet-toxic medications
Use stickers on vials to warn of danger to pets (e.g., "TOXIC TO PETS – KEEP OUT OF REACH")
Partner with local veterinary clinics to distribute safety flyers

PAUSE AND PONDER: What would you say to a pet owner who asks you to help them “put their dog down” because they can’t afford treatment after a drug exposure incident?

PETS AND PENALTIES

Accidental drug exposure in pets presents legal and ethical concerns. Pet owners must ensure their pet’s safety, while veterinarians navigate ethical obligations when treating drug-related poisonings.³²

Laws regarding pet poisoning vary by state, but owners can face legal consequences if their negligence results in harm. Unintentionally or intentionally exposing pets to drugs may lead to negligence claims, with owners remaining civilly liable for preventable injuries. In some states, reckless or intentional poisoning is classified as animal cruelty and can result in misdemeanor or felony charges.³² Recreational drug-related poisonings, especially those involving THC, have also brought increased legal scrutiny to pet owners in states where cannabis is legal.¹²

In several states, veterinary professionals are classified as mandatory reporters of suspected neglect or abuse. In cases of drug toxicity, ethical dilemmas often arise. Veterinarians must weigh client confidentiality against their duty to report suspected drug-related neglect. Some pet owners request euthanasia instead of pursuing costly treatment, raising additional ethical concerns. Legal protections for veterinarians who report drug-related neglect, such as immunity laws, are continuing to evolve.³²

Understanding the Pharmacy Boundaries

Pet poisoning incidents that stem from human medication exposure often raise legal and ethical questions for pharmacy professionals. Pharmacists and pharmacy technicians must understand their scope of practice and operate within it, while still providing meaningful support to pet-owning patients.³³

Pharmacists are legally bound to avoid giving direct medical advice about animal-specific treatment unless they are licensed veterinarians or have specialized training in veterinary pharmacy. Examples that are out of the pharmacist’s scope of practice include suggesting a dosage of activated charcoal or recommending OTC human medications for a pet without a veterinarian’s guidance. Doing so may open the door to legal liability, even if intentions are good.³³ Pharmacists should document counseling as they do with any human consultation when possible. The pet owner is ultimately responsible for storing their medications safely. However, pharmacy staff may bear ethical responsibility if they miss clear opportunities to prevent harm. For example, pharmacy staff must check that the medication strength and instructions align with veterinary guidance. It's a pharmacist’s duty to promote medication safety.³¹

With the rise in pet prescriptions being filled at human pharmacies, another legal concern has emerged. Medications like amoxicillin, gabapentin, prednisone, and levothyroxine are commonly prescribed to both humans and animals. However, the dosages, formulations, and routes of administration can differ. It is unsafe to give dogs human‑formulated gabapentin liquid—these often contain xylitol. Gabapentin for pets should only be used under veterinary supervision with a weight‑based dose.³⁴ Pharmacists must exercise due diligence in checking drug references that include veterinary considerations, such as VetMedux and Plumb’s Veterinary Pharmacy, especially when unfamiliar with a prescription’s purpose.

While legal boundaries are clear, ethical considerations require pharmacy staff to act with compassion, respect, and clarity. Pet owners in crisis may arrive at the counter distraught, panicked, or angry. Some may be grieving a pet’s death. If that happens, pharmacy staff must acknowledge the emotional distress and not minimize or dismiss the concerns. They can say, “We’re not veterinarians, but here’s what I can do to help.” The staff should refer owners clearly and quickly, providing poison control numbers, emergency vet locations, or printouts.

In cases where a pet owner requests euthanasia due to financial constraints after a drug exposure, veterinary and pharmacy professionals must respond with empathy but remain ethically grounded. A compassionate response might be: “I’m sorry you’re going through this. While I can’t give treatment advice, I urge you to contact an emergency veterinarian—there may be lower-cost options or payment plans available.” This approach balances empathy, defers clinical decisions to appropriate professionals, and reinforces that a pet’s life may still be saved with timely care.

A PET-SAFE FUTURE

In the evolving landscape of pharmacy practice and public health, one area rapidly gaining attention is the intersection of human medications and companion animal safety. The COVID-19 pandemic increased pet adoption rates and work-from-home opportunities. The overall shift in household routines has created new opportunities—and new risks—for pet exposures to toxic substances.

Ongoing research continues to improve diagnostic tools and treatment options for pets exposed to human medications. Future innovations include the development of rapid toxicology screening kits that allow faster, in-clinic detection of opioids, amphetamines, and antidepressants. Additionally, genetic studies on drug metabolism aim to identify species-specific sensitivities, helping to advance more personalized approaches in veterinary care.⁸

Many states now require cannabis products to be sold in child-resistant, often opaque, packaging to reduce the risk of accidental ingestion, particularly in children.³⁵ These measures may also help limit accidental exposures in pets. As telehealth and online pharmacy services expand, fewer patients are interacting face-to-face with pharmacists.³⁶ This limits opportunities to reinforce safe medication storage. As a result, it becomes essential for pharmacists and technicians to include safety messaging on prescription labels, auxiliary stickers, or digital communications.

Digital Defenses

Advances in technology are improving awareness, prevention, and emergency response for pet poisoning cases. Future tools include AI-powered toxicology apps that provide instant poisoning risk assessments and smart storage systems like electronic pill dispensers to prevent accidental exposures.^37,38 Wearable pet monitors may also detect toxicity through changes in heart rate or body temperature.³⁹ These innovations aim to support pet owners and veterinarians in managing drug-related emergencies more effectively.

Other tools are being developed to assist in identifying potential poison risks. These include the ASPCA APCC app, offering a searchable database of common toxins, and ASPCA AnTox database—a veterinary database system to help identify and characterize toxic exposure data. In the future, pharmacy software may integrate pet-safety alerts when filling medications known to be high risk. Until then, it falls on pharmacy professionals to stay educated and vigilant.

CONCLUSION

The rising incidence of pet poisonings due to human medications is more than an unfortunate trend—it’s a public health concern extending beyond species lines. Pharmacy professionals are often the first point of contact for patients navigating their own medications and their households’ safety practices. Future research will continue improving diagnosis, treatment, and toxicology education. Collaboration between veterinarians, policymakers, and pet owners remains essential to reducing risks. Let’s increase awareness and protect all members of the household—on two legs and four.

PATIENT SAFETY: Toxic Human Drugs and Their Impact on Household Pets
26-001 Pharmacist Post-test

After completing this continuing education activity, pharmacists will be able to:
● DESCRIBE common pathways through which pets are exposed to toxic human medications
● IDENTIFY the clinical signs and symptoms of toxicity from antidepressants, ADHD medications, NSAIDs, opioids, and recreational drugs in companion animals
● DISCUSS veterinary management strategies and outcomes for pets exposed to toxic medications, including decontamination, symptom management, and diagnostic testing
● RECOGNIZE best practices to counsel pet-owning patients on safe medication storage, disposal, and early signs of pet poisoning

1. Which of the following statements is TRUE regarding pet exposure to human medications?
A. Cats and dogs have the same liver enzymes as humans and can metabolize medications similarly
B. Human medications now account for fewer poisonings in pets than chocolate or household cleaners
C. Even small doses of human medications can be toxic to pets due to species-specific metabolism

2. A 35 lb Labrador retriever is brought to the veterinary clinic one hour after chewing through and ingesting an unknown quantity of its owner’s fluoxetine (Prozac). Which of the following symptoms is most likely to be observed?
A. Bradycardia, lethargy, and coma
B. Vomiting, tremors, and hyperactivity
C. Constipation, slow breathing, and pinpoint pupils

3. Which of the following best describes secondary exposure in the context of pet poisoning?
A. A pet inhaling prescription aerosol medications left on a counter
B. A pet licking topical medication off a human’s skin
C. A pet chewing through an unopened blister pack of pills

4. A dog is brought to the veterinary clinic after ingesting an unknown medication from the street. A few hours later, the dog begins vomiting and shows signs of lethargy. Bloodwork reveals early signs of kidney impairment. Which class of medication is most likely responsible for these symptoms?
A. SSRIs
B. Amphetamines
C. NSAIDs

5. Which of the following is part of standard veterinary decontamination for a recent ingestion of a toxic medication?
A. Naloxone and activated charcoal only
B. Induced vomiting, activated charcoal, and supportive care
C. Benzodiazepines and antipsychotics

6. A man brings a dog into the emergency veterinary clinic late at night. The owner admits that an edible marijuana product may have gone missing from the kitchen counter. The dog is showing abnormal behavior. The veterinary team suspects a toxic ingestion. Which of the following combinations of symptoms would best support the suspected diagnosis?
A. Agitation, seizures, and vomiting
B. Excessive drooling, tremors, and elevated body temperature
C. Stumbling, lethargy, and dilated pupils

7. Which of the following is a correct counseling point for a patient asking how to dispose of unused opioids in a pet-safe manner, assuming a take-back program is unavailable?
A. Flush the medication only if it’s on the FDA flush list
B. Mix the medication with cat litter and throw it in an open trash bin
C. Store it on the kitchen counter until you need it again

8. What is a legal or ethical concern pharmacists should be aware of when advising pet owners about medication safety?
A. Veterinarians are never required to report suspected neglect involving pet poisonings
B. Euthanasia is always recommended in cases of drug ingestion due to cost
C. Pet owners can face civil or criminal liability for preventable poisonings

9. A patient mentions her dog chewed up her partner’s Adderall, but “seems fine now.” What is the BEST pharmacist response?
A. “Monitor the dog at home and call a veterinarian only if symptoms start.”
B. “Give the dog a dose of diphenhydramine to counteract the stimulant.”
C. “Take the dog to a veterinarian or emergency clinic immediately.”

10. A pet owner asks whether topical lidocaine cream could harm his cat, who licked some off her hand. What is the most appropriate next step?
A. Reassure them that lidocaine is safe for cats in small doses
B. Tell them to wash the cat’s mouth with water and monitor at home
C. Advise them to call a veterinary-specific poison control center

PATIENT SAFETY: Toxic Human Drugs and Their Impact on Household Pets
26-001 Technician Post-test

After completing this continuing education activity, pharmacy technicians will be able to:
● RECOGNIZE common human medications that are toxic to pets
● IDENTIFY signs and symptoms of drug toxicity in companion animals that may be mentioned by pet owners at the pharmacy counter
● LIST proper techniques for medication storage and disposal that can reduce the risk of pet exposure
● RECOGNIZE when to refer pet-owning patients to the pharmacist for counseling or poison control center guidance

1. What is the BEST way to store prescription medications to prevent pet exposure?
A. On a high shelf in the kitchen next to food storage
B. In a closed cabinet or drawer out of reach of pets
C. On a bedside table for easy access

2. A pharmacist receives a phone call from a pet owner who is panicked because her dog is stumbling and uncoordinated. Which of the following substances is the most likely cause of the dog’s symptoms?
A. Adderall
B. Aspirin
C. Cannabis

3. What is the most important action a technician should take when a pet owner mentions their animal ingested human medication?
A. Suggest giving the pet activated charcoal from the pharmacy
B. Tell them to watch for symptoms before doing anything
C. Refer them to the pharmacist or a poison control center

4. A pharmacy technician receives a call from a pet owner who says his dog chewed through a pill bottle that had fallen on the floor. The label reads “Adderall XR 20 mg.” Which of the following symptom combinations best aligns with amphetamine toxicity in pets?
A. Lethargy, cold paws, and vomiting
B. Hyperactivity, tremors, and increased heart rate
C. Head tilt, circling, and loss of balance

5. Which medication class is known to cause ulcers and kidney damage in pets?
A. SSRIs
B. NSAIDs
C. Benzodiazepines

6. A cat owner calls their local pharmacy and asks whether their pet can take the same OTC pain medication they use. What should the pharmacist do?
A. Recommend a small dose based on the cat’s weight
B. Advise the owner to contact their veterinarian before giving any medication
C. Suggest a liquid version of the same drug for easier swallowing

7. An owner rushes her pet to the clinic after it chewed through a prescription bottle labeled "fluoxetine." Which symptoms will likely occur?
A. Seizures, vomiting, and slowed breathing
B. Vomiting, tremors, and hyperactivity
C. Dehydration and joint pain

8. A patient picks up a prescription for a topical hormone patch. What should a technician do if the patient mentions having a cat?
A. Say nothing; the pharmacist will handle it later
B. Tell them the patch is safe as long as the cat doesn’t lick it
C. Refer the patient to the pharmacist to explain the risk of secondary exposure

9. Which of the following is a proper disposal method for unused opioids that prevents pet access?
A. Throw the bottle in the trash
B. Use a take-back program or follow FDA flush list
C. Leave them on a shelf for future use

10. A customer picks up his prednisone prescription and mentions that he’s been giving a “small amount” of his prednisone to his dog because the dog seems itchy. He asks if it’s okay to continue. As the pharmacy technician, what is the best action?
A. Tell the customer that prednisone is commonly used in dogs and they can continue for a few days
B. Suggest the customer purchase an over-the-counter antihistamine formulated for pets instead C. Say you cannot provide advice for animals and refer the question to the pharmacist, who may contact animal poison control if needed
C. Say you cannot provide advice for animals and refer the question to the pharmacist, who may contact animal poison control if needed

1. The Official Top 10 Toxins of 2024. ASPCA. March 13, 2025. Accessed October 2, 2025. https://www.aspca.org/news/official-top-10-toxins-2024
2. Cortinovis C, Pizzo F, Caloni F. Poisoning of dogs and cats by drugs intended for human use. Vet J. 2015;203(1):52-58. doi:10.1016/j.tvjl.2014.11.004
3. 70% of U.S. households have pets, APPA finds in new survey. Veterinary Advantage. June 2021. Accessed September 20, 2025. https://vet-advantage.com/companion-news/70-of-u-s-households-have-pets-appa-finds-in-new-survey/
4. Fitzgerald KT, Bronstein AC, Flood AA. "Over-the-counter" drug toxicities in companion animals. Clin Tech Small Anim Pract. 2006;21(4):215-226. doi:10.1053/j.ctsap.2006.10.006
5. Sjöström K, Mount J, Klocker AK, Arthurson V. A review of adverse events in animals and children after secondary exposure to transdermal hormone-containing medicinal products. Vet Rec Open. 2022;9(1):e48. Published 2022 Oct 28. doi:10.1002/vro2.48
6. Khan SA, McLean MK. Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs and cats. Vet Clin North Am Small Anim Pract. 2012;42(2):289-vii. doi:10.1016/j.cvsm.2012.01.003
7. Houchen E. Recognizing & treating toxicities. Oregon Veterinary Medical Association. Accessed September 10, 2025. https://www.oregonvma.org/sites/default/files/Houchen%20Recognizing%20%26%20Treating%20Toxicities.pdf
8. Court MH. Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms. Vet Clin North Am Small Anim Pract. 2013;43(5):1039-1054. doi:10.1016/j.cvsm.2013.05.002
9. Lees P, Pelligand L, Elliott J, Toutain PL, Michels G, Stegemann M. Pharmacokinetics, pharmacodynamics, toxicology and therapeutics of mavacoxib in the dog: a review. J Vet Pharmacol Ther. 2015;38(1):1‑14. doi:10.1111/jvp.12185.
10. Pet Poison Helpline: 24/7 animal poison control center. Pet Poison Helpline. Accessed September 19, 2025. https://www.petpoisonhelpline.com/
11. Stern L, Schell M. Management of Attention-Deficit Disorder and Attention-Deficit/Hyperactivity Disorder Drug Intoxication in Dogs and Cats: An Update. Vet Clin North Am Small Anim Pract. 2018;48(6):959-968. doi:10.1016/j.cvsm.2018.07.007
12. Fitzgerald KT, Bronstein AC, Newquist KL. Marijuana poisoning. Top Companion Anim Med. 2013;28(1):8-12. doi:10.1053/j.tcam.2013.03.004
13. Pugh CM, Sweeney JT, Bloch CP, Lee JA, Johnson JA, Hovda LR. Selective serotonin reuptake inhibitor (SSRI) toxicosis in cats: 33 cases (2004-2010). J Vet Emerg Crit Care (San Antonio). 2013;23(5):565-570. doi:10.1111/vec.12091
14. Howard-Azzeh M, Pearl DL, O'Sullivan TL, Berke O. The identification of risk factors contributing to accidental opioid poisonings in companion dogs using data from a North American poison control center (2006-2014). PLoS One. 2020;15(1):e0227701. doi:10.1371/journal.pone.0227701
15. Oster E, Čudina N, Pavasović H, et al. Intoxication of dogs and cats with common stimulating, hallucinogenic and dissociative recreational drugs. Vet Anim Sci. 2023;19:100288. Published 2023 Jan 31. doi:10.1016/j.vas.2023.100288
16. Edwards SG. Nonsteroidal Anti-Inflammatory Drugs in Animals. Merck Veterinary Manual. Updated September 2024. Accessed October 17, 2025. https://www.merckvetmanual.com/pharmacology/inflammation/nonsteroidal-anti-inflammatory-drugs-in-animals
17. California tops list of marijuana toxicity cases in pets, new data shows. Veterinary Practice News. April 21, 2025. Accessed April 22, 2025. https://www.veterinarypracticenews.com/marijuana-toxicity-pets/
18. Hayes C. Xylitol Toxicosis in Dogs. Merck Veterinary Manual. Revised September 2024, modified June 2025. Accessed October 21, 2025. https://www.merckvetmanual.com/toxicology/food-hazards/xylitol-toxicosis-in-dogs
19. Heseltine J, Kritchevsky J. Hypothyroidism in Animals. Merck Veterinary Manual. Revised May 2024, modified May 2025. Accessed October 21, 2025. https://www.merckvetmanual.com/endocrine-system/the-thyroid-gland/hypothyroidism-in-animals
20. Edwards SH. Corticosteroids in Animals. Merck Veterinary Manual. Revised November 2021, modified May 2025. Accessed October 21, 2025. https://www.merckvetmanual.com/pharmacology/inflammation/corticosteroids-in-animals
21. Forsythe LR, Gollakner R. Prednisone in Dogs & Cats: Uses & Side effects. VCA Animal Hospitals. 2024. Accessed December 2, 2025. https://vcahospitals.com/know-your-pet/prednisoloneprednisone
22. Allen AL. The diagnosis of acetaminophen toxicosis in a cat. Can Vet J. 2003;44(6):509-510. https://pmc.ncbi.nlm.nih.gov/articles/PMC340185/
23. Fever in Dogs and Cats. Schwarzman American Medical Center. Updated June 17, 2024. Accessed October 4, 2025. https://www.amcny.org/pet_health_library/does-my-pet-have-a-fever/
24. Morrison B. What Things Are Poisonous to Cats? PetMD. Updated November 11, 2025. Accessed December 2, 2025. https://www.petmd.com/cat/poisoning/poisons-in-cats
25. Lee JA. Therapeutic Updates in Veterinary Toxicology. Today’s Veterinary Practice. July/August 2014. Accessed December 2, 2025. https://todaysveterinarypractice.com/toxicology/therapeutic-updates-in-veterinary-toxicology/
26. What to expect when calling ASPCA Animal Poison Control Center. ASPCA. April 1, 2020. Accessed September 19, 2025. https://www.aspca.org/news/what-expect-when-calling-aspca-animal-poison-control-center
27. Gwaltney-Brant S, Meadows I. Use of intravenous lipid emulsions for treating certain poisoning cases in small animals. Vet Clin North Am Small Anim Pract. 2012;42(2):251-vi. doi:10.1016/j.cvsm.2011.12.001
28. Dodman DrN. Naloxone (Narcan®) for Dogs and Cats. PetPlace. July 16, 2015. Accessed October 10, 2025. https://www.petplace.com/article/drug-library/drug-library/library/naloxone-narcan-for-dogs-and-cats
29. Pet emergency statistics and veterinary costs. Preventive Vet. Accessed December 5, 2025. https://www.preventivevet.com/pet-emergency-statistics
30. Properly store medications to keep your pet safe. U.S. Food and Drug Administration. Updated June 14, 2024. Accessed April 27, 2025. https://www.fda.gov/animal-veterinary/animal-health-literacy/properly-store-medications-keep-your-pet-safe
31. Immonen H, Raekallio MR, Holmström AR. Promoting veterinary medication safety - Exploring the competencies of community pharmacy professionals in veterinary pharmacotherapy. Vet Anim Sci. 2023;21:100310. Published 2023 Aug 19. doi:10.1016/j.vas.2023.100310
32. Arkow P, Boyden P, Patterson-Kane E. Practical Guidance for the Effective Response by Veterinarians to Suspected Animal Cruelty, Abuse and Neglect. American Veterinary Medical Association; 2013. Accessed April 27, 2025. https://www.avma.org/sites/default/files/2023-12/AVMA-Suspected-Animal-Cruelty.pdf
33. Pharmacy and prescription issues. American Veterinary Medical Association. Accessed September 19, 2025. https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/pharmacy.
34. Gabapentin. VCA Animal Hospitals. Accessed October 17, 2025. https://vcahospitals.com/know-your-pet/gabapentin
35. Swinburne M. Cannabis regulation: packaging restrictions to reduce appeal to children [fact sheet]. Network for Public Health Law; October 25, 2022. Accessed April 27, 2025. https://www.networkforphl.org/wp-content/uploads/2022/11/Packaging-Regulation.pdf
36. Chong RLK, Chan ASE, Chua CMS, Lai YF. Telehealth Interventions in Pharmacy Practice: Systematic Review of Reviews and Recommendations. J Med Internet Res. 2025;27:e57129. Published 2025 May 7. doi:10.2196/57129
37. Hartung T. Artificial intelligence as the new frontier in chemical risk assessment. Front Artif Intell. 2023;6:1269932. doi:10.3389/frai.2023.1269932
38. Faisal S, Ivo J, Patel T. A review of features and characteristics of smart medication adherence products. Can Pharm J (Ott). 2021;154(5):312-323. Published 2021 Jul 30. doi:10.1177/17151635211034198
39. Riddick K. Wearable Technology in Veterinary Medicine. Georgia Veterinary Medical Association. September 18, 2024. Accessed April 27, 2025. https://gvma.net/2024/09/18/wearable-technology-in-veterinary-medicine/

PATIENT SAFETY: ADRENAL DRAMA: HOW STRESS BECAME A MARKET

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

RECALL the physiology of cortisol, including its regulation and effects on the body’s major systems.
DESCRIBE the pathophysiology, presentation, and evidence-based treatments of Cushing’s syndrome and Addison’s disease.
ANALYZE patient case scenarios and determine whether a new intervention or adjustment of a current regimen related to cortisol levels is appropriate.
IDENTIFY common misinformation tactics and strategies to combat them through patient education

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

RECALL the physiology of cortisol, including its regulation and effects on the body’s major systems.
DESCRIBE the pathophysiology and presentation of Cushing’s syndrome and Addison’s disease.
OUTLINE evidence-based treatments of Cushing’s syndrome and Addison’s disease.
RECOGNIZE common misinformation tactics and strategies to combat them through patient education.

Cushing’s syndrome and Addison’s disease are manifestations of inappropriately high or low cortisol, respectively. Both wreak havoc on patients’ lives, affecting cardiac health, metabolism, and more. Social media trends have highlighted the negative effects of abnormal cortisol levels, especially high cortisol. They also talk up supplements and lifestyle practices to reduce cortisol levels. It is important for pharmacists to understand these disease states, both to treat patients who are diagnosed with them and counsel others regarding information they hear online. Treatment of Cushing’s syndrome may be surgical, pharmacologic, or both. Steroidogenesis inhibitors and the glucocorticoid antagonist mifepristone are the most common medications used for Cushing’s syndrome. The treatment of Addison’s disease focuses on cortisol replacement with glucocorticoids. Pharmacists’ expertise primes them to counsel patients on medications and recognize important signs and symptoms of cortisol-related disease states. Pharmacy technicians can play an important role in recognizing patients who need counseling and preventing medication errors.

INTRODUCTION

We often refer to cortisol as the “stress hormone” for good reason. The body releases it during acute, chronic, or traumatic stress as part of a fight-or-flight response. To keep the body on high alert during stressful situations, it decreases insulin and increases glucagon for quick energy, suppresses inflammation, increases blood pressure, and encourages wakefulness.¹ While this whole-body reaction can be quite useful in scenarios like running from an axe murderer or trying a new HIIT workout class, we don’t need our cortisol levels running high all the time.

Having excess or insufficient cortisol can cause significant damage to the body over time. Table 1 describes how high and low cortisol cause quite opposite effects.

Table 1. Opposing High vs. Low Cortisol Symptoms^1,2

High Cortisol	Low Cortisol
Weight gain	Unintentional weight loss & loss of appetite
Hyperglycemia	Hypoglycemia
Hypertension	Hypotension
Hirsutism	Body hair loss

Unraveling the HPA Axis

The adrenal glands produce cortisol and are a part of the hypothalamic-pituitary-adrenal (HPA) axis. Understanding the axis is key to knowing how the body makes and regulates cortisol.³

The HPA axis is a system made up of three parts named in its title: the hypothalamus, the pituitary gland, and the adrenal glands.

When a person is stressed, the sympathetic nervous system (SNS) acts as a gas pedal to rev up the HPA axis.
When the SNS signals the hypothalamus, it releases corticotropin-releasing hormone (CRH).
CRH signals the pituitary gland to release adrenocorticotropic hormone (ACTH).
ACTH signals the adrenal glands to release cortisol.
Cortisol signals the whole body to respond to the stressful trigger.
When the stressful event is over, the parasympathetic nervous system (PNS) acts as a brake, slowing the flow of hormones in the HPA axis.³

Stress upregulates a properly responsive HPA axis and rest downregulates it. Both improper upregulation and downregulation can cause health issues, manifesting as Cushing’s syndrome (CS) and Addison’s disease (AD), respectively.

THE “CORTISOL CRAZE”

Despite the relative rarity of diagnosed cortisol abnormalities, related hashtags on social media have racked up millions of views.⁴

NOTE: About 6 people in a million are diagnosed with AD and 49 people in a million are diagnosed with CS in the U.S. each year.⁵

The major concern for most people sharing online is chronic stress, leading to high cortisol. Low cortisol can be just as debilitating, but the Cushingoid appearance seems to be the highlight in advertising. A Cushingoid appearance is a catch-all term for the physical signs and symptoms of high cortisol, including excess weight in the face, abdomen, back of the neck, and chest, excess body hair, limb atrophy, acne, and easy bruising.^6-8Users selling supplements and diet plans often refer to the product reducing “cortisol face” and “cortisol belly.”^9-11 “Cortisol detoxing” is another trend focused on weight loss and improved mood by reducing stress, thus reducing cortisol.¹²

The question is whether symptoms are severe enough to require intervention. It seems that urgent concern about cortisol itself is unproductive, but focusing on lowering daily stress may be beneficial for those in this scenario. A wide gap exists between being stressed and being diagnosed with CS (discussed in more detail below).

Safety and Efficacy of Select Supplements and Natural Remedies

So, if a patient comes to the pharmacy counter saying she wants to lower her cortisol, are any common supplements safe and effective? Let’s dig further into a couple of supplements touted for their ability to lower cortisol.

Supplement companies advertise ashwagandha for improving sleep and reducing stress and anxiety. Influencers sometimes include it on posts listing supplements to lower cortisol. Per NatMed Pro, tolerability in adults is established for a maximum dose of 1,250 mg daily when used for up to six months, and adverse effects are generally mild, including gastrointestinal (GI) upset, nausea, and drowsiness. Notably, ashwagandha should not be taken during pregnancy due to potential abortifacient effects.^13,14 Weak evidence suggests that ashwagandha may lower cortisol by reducing stress response. Small studies suggest that it may be effective for stress, anxiety, and poor sleep quality.^13,14 One meta-analysis and a small randomized control trial (RCT) found a statistically significant reduction in perceived stress, Hamilton Anxiety score, and serum cortisol levels.^15,16 However, the authors of the meta-analysis admit that it is difficult to apply these results clinically due to major differences between included studies, and the RCT only including 60 patients.^15,16

L-theanine is another supplement advertised as a cortisol-lowering agent. L-theanine is an amino acid found in tea leaves. Advertisements mainly highlight increased relaxation, lower stress and anxiety, and improved sleep. It is considered fairly safe, but evidence of efficacy is weak. Adult patients have tolerated doses of up to 900 mg daily used for up to eight weeks.¹⁷ It is unlikely to cause harm but the potential benefits remain murky.¹⁸

Lifestyle interventions promoted on social media often focus on reducing chronic stress. Things like good sleep, frequent exercise, and healthy eating can benefit everyone.¹⁹ Chronic stress can heighten cortisol levels, but this type of cortisol elevation is significantly different than having CS. Most lifestyle changes will benefit patients to some extent. (Note that although stress-reducing lifestyle changes have benefits, a patient with CS will need further medical intervention for the best outcomes.)

If a patient truly has symptoms of high cortisol, it is worthwhile to see a healthcare provider for a full workup. Over-the-counter supplements are not a substitute for prescription medications and monitoring by a licensed provider.

HIGH CORTISOL DUE TO CUSHING’S SYNDROME

Patient case: Eva is 38-year-old female patient with a past medical history of hypertension and prediabetes. She presents to the clinic reporting recent health changes. In particular, Eva says that her blood sugar and blood pressure, which she self-monitors at home, have been higher than usual lately. She also describes bruising with no known source or after events that would not have elicited a bruise in the past. When asked if there’s been any recent changes to her lifestyle or medications, Eva notes that she’s been gaining weight despite maintaining frequent exercise and a healthy diet. She feels that the weight gain is most visible in her face and abdomen.

PAUSE AND PONDER: Which of Eva’s symptoms are red flags? What stands out to you?

Pathophysiology of Cushing’s Syndrome

Patients with CS, or chronic high cortisol, either have an exogenous or endogenous cause of disease. The most common cause is several months of continuous exogenous exposure to glucocorticoids. Patients taking steroids for asthma, autoimmune disease, and other conditions may be at risk. Endogenous CS affects 2-3 people per million.⁶ About 80% of those rare cases result from an ACTH-dependent tumor, while the other 20% are associated with an ACTH-independent cause.⁶

The most common CS patient is a female in her 20s or 30s, although men and people of other ages can have CS.⁶ Seventy percent of patients with CS are women, and most are under the age of 50.⁷

Presentation and Complications

Table 2 lists common signs and symptoms that may be present in patients with CS. Encourage patients experiencing several of these symptoms to speak with a provider, especially if they are on a corticosteroid.

Table 2. Signs and Symptoms of CS^6-8

Rapid weight accumulation in the face (moon face), abdomen, back of the neck (buffalo hump), and chest	Red, round face
Poor wound healing	Hypertension
Hirsutism	Diabetes
Purple striae	Easy bruising
Fatigue	Blurry vision and dizziness
Muscle weakness and atrophy of limbs	Libido changes and/or erectile dysfunction
Irritability	Acne

NOTE: Hirsutism is excessive dark hair growth, especially on the face and body. Patients may also experience balding on their head. Striae are stretch marks, which are large, purple, and often seen on the abdomen in CS patients.⁷

CS can significantly reduce patients’ quality of life. Physical changes, like weight gain and excess body hair, may be embarrassing to some.⁷ Some recent studies associate psychiatric symptoms, especially depression, with the onset of CS. Most patients who experience depression with CS improve with correction of high cortisol, but depression may not completely resolve.²⁰ Untreated CS has consequences beyond the list of signs and symptoms. Table 3 lists high-risk complications that patients with active CS are at risk of developing. While they are at highest risk with active CS, some risk factors may persist after remission and require further treatment.²¹

Table 3. Complications of Active CS^6,21

Cardiovascular Complications

Metabolic Complications

Other

Arterial hypertension

Atherosclerosis

Heart failure

Hyperlipidemia

Thrombosis

Insulin resistance

Glucose impairment

Visceral obesity

Higher infection risk

Myopathy

Neuropsychiatric disorders

Osteoporosis

NOTE: Due to the increased risk of infection, CS patients benefit from age-appropriate vaccines like influenza, Herpes zoster, and pneumonia.²⁰

Testing Cortisol Levels for CS

Clinicians have several ways to determine if a patient’s cortisol levels are above normal limits. Common test strategies include a 24-hour urinary free cortisol test, midnight plasma cortisol/late-night salivary cortisol, and dexamethasone suppression tests.²² Of note, two of the options include specific times of day for measurement. Cortisol is usually lower at night, so abnormally high measurements at night are notable. Table 4 highlights the differences between testing options.

Table 4. Cortisol Testing^8,22

Testing Method	Description
24-hour urinary free cortisol	Multiple urine collections over 24 hours tested
Midnight plasma/ late-night salivary	Blood or saliva level taken at night for ≥ 2 nights Saliva samples can be done at home
Overnight dexamethasone suppression test	The patient receives 1 mg of dexamethasone late at night Cortisol measured the next morning
Low-dose dexamethasone suppression test	The patient receives low-dose dexamethasone by mouth every six hours for two days Multiple urine collections starting before the first dose and continuing through the test

Treatment

Treatment of CS depends on the cause. For those with an exogenous source of cortisol causing the issue, tapering down or completely off the causative glucocorticoid will return cortisol to normal limits.⁷ For those with an ACTH-dependent tumor causing CS, the 2015 Endocrine Society Clinical Practice Guidelines recommend surgical removal of the tumor, if possible.²³ After surgery, a patient may have hypocortisolism, hypercortisolism, or eucortisolism. Eucortisolism does not need further treatment.²³

If patients experience hypocortisolism after surgery, they will require glucocorticoid replacement. Patients must be monitored every six hours for 24-72 hours after pituitary surgery for ACTH abnormalities. Use of glucocorticoids intraoperatively and postoperatively varies by institution. Providers may start glucocorticoids during surgery or wait to see if the patient starts displaying signs of adrenal insufficiency before starting glucocorticoids. All patients with a cortisol level less than 5 mcg/dL, and some with a level 10 to 15 mcg/dL, will require replacement. The recommend dosing of hydrocortisone to a physiologic level is 10 to 12 mg/m²/day in divided doses. Some institutions may use supraphysiologic replacement up to 20 mg of hydrocortisone two to three times daily with a 2- to 4-week taper.²⁴

Several options are available for those who don’t qualify for surgery or who continue to experience hypercortisolism after surgery. These include repeat surgery, radiation therapy, or pharmacological treatment. This continuing education (CE) will mainly focus on the pharmacologic options.

Three types of medications can treat CS²⁵:

Steroidogenesis inhibitors, which block the enzymes that make cortisol.
Glucocorticoid antagonists, which block cortisol’s action by preventing it from binding to its receptor.
ACTH neuromodulators, which inhibit pituitary action and block the signal to the adrenals to release cortisol.

Table 5 provides a complete list of medications in each class.

Table 5. Medications Used to Treat CS²⁵

Steroidogenesis inhibitors

Glucocorticoid antagonist

ACTH neuromodulators

Etomidate

Ketoconazole

Levoketoconazole

Mitotane

Metyrapone

Osilodrostat

Mifepristone

Cabergoline

Pasireotide

Steroidogenesis inhibitors are the most commonly used medications for CS. They can be used on their own or as an adjunct treatment. See pros and cons to consider for each medication in Table 6.^23,25

The glucocorticoid antagonist mifepristone is used as primary therapy or after a failed surgery in patients with diabetes and/or uncontrolled high blood sugar in CS.^23,26 However, mifepristone can also be used in medical abortions. Prescribing and dispensing mifepristone can be complicated in the U.S. as a result of the indication for terminating pregnancy. More than 10 states restrict mifepristone’s use. Some ban its use entirely, while others only allow mifepristone prescriptions from certified providers and dispensing from authorized pharmacies.^26,27 Despite the controversy, mifepristone remains a highly effective treatment option for CS.^25-27 See Table 6 for more information.

Providers may use ACTH neuromodulators as monotherapy or an adjunct option. Cabergoline is an off-label medication for CS, but both formulations of pasireotide are FDA-approved. Pasireotide offers convenient dosing as an intramuscular injection every four weeks but comes with a high risk of hyperglycemia. Three quarters of patients managed with pasireotide require other medication for glucose management.²⁸

Table 6. Clinical Pearls for Common CS Medications^25,27-32

Medication	Dosing	Clinical Pearls
Steroidogenesis Inhibitors
Etomidate	0.03 mg/kg IV bolus 0.1–0.3 mg/kg/h	Off-label for CS Administered parenterally Rapid maximum effect, around 11 hours Requires intensive inpatient monitoring (not for long-term use)
Ketoconazole	TDD of 200 to 1,200 mg, split 2-3 times daily	Off-label for CS Rapid onset but can take weeks for full effect Decreases testosterone Boxed warning: liver toxicity Adverse effects include GI symptoms, gynecomastia, skin rash, edema, transient LFT elevations and rarely hepatotoxicity Monitor EKG (QT prolongation) and LFTs Requires low gastric pH for absorption Major CYP3A4 substrate and strong inhibitor, potential for significant drug interactions
Levoketoconazole	TDD of 300 mg to 1.2 g, split BID	Monitor EKG (QT prolongation) and LFTs Most common adverse events include GI symptoms, headache, arthralgias, myalgias, and fatigue Major CYP3A4 substrate and strong inhibitor, potential for significant drug interactions
Mitotane	TDD of 500 mg to 8 g, split TID	Off-label for CS Teratogenic Maximum effect after 2-3 months of treatment Adverse effects include GI symptoms, impaired mentation and dizziness, gynecomastia, rash, elevated LFTs, and hypercholesterolemia Almost 30% of patients discontinue treatment due to adverse effects Give largest dose in the evening
Metyrapone	TDD 500 mg to 6 g, split up to 4 times daily	Off-label for CS Cortisol levels decrease within two hours of administration May be used with caution in pregnancy Take with food Adverse effects include GI symptoms, hirsutism, hypertension, and hypokalemia
Osilodrostat	TDD 2 to 14 mg, split BID Max maintenance TDD is 60 to 80 mg	Monitor EKG for QTc prolongation Initial dose adjustments for moderate-severe renal impairment Effective in hours-days Note drug interactions Adverse effects include GI symptoms, arthralgia, dizziness, hypertension
Glucocorticoid Antagonist
Mifepristone	300 to 1,200 mg once daily	FDA approved to control hyperglycemia due to hypercortisolism Also used to terminate pregnancy, providers must confirm negative pregnancy status in patients of childbearing potential prior to starting this medication Has a REMS program Monitor thyroid function Major CYP3A4 interactions Adverse effects include nausea, fatigue, headache, hypokalemia, hypertension, abnormal vaginal bleeding
ACTH Neuromodulators
Cabergoline	0.5 to 4 mg total per week, split twice weekly	Off-label for CS Requires cardiac valve monitoring Adverse events include GI symptoms and dizziness May cause psychiatric effects; not recommended with history of bipolar or impulse disorder
Pasireotide	0.3 to 0.9 mg twice daily OR 10 to 40 mg per month	BID formulation given via subcutaneous injection, monthly formulation is via intramuscular injection Maximum dose of 0.6 mg BID or 20 mg monthly in moderate hepatic impairment Monitor glucose, LFTs, EKG Not recommended in diabetes
ABBREVIATIONS: BID (two times daily), CS (Cushing's syndrome), CYP3A4 (cytochrome P450 3A4), EKG (electrocardiogram), FDA (Food and Drug Administration), GI (gastrointestinal), LFTs (liver function tests), REMS (Risk Evaluation and Mitigation Strategy), TDD (total daily dose), TID (three times daily)

Only patients with an established diagnosis of CS and active signs and symptoms require treatment. Patients without an established diagnosis or borderline abnormalities with no signs and symptoms are unlikely to benefit from treatment.²³

NOTE: Metyrapone and mifepristone appear on the ISMP List of Look-Alike drug names. Be careful not to confuse metyraPONE with metyroSINE and miFEPRIStone with miSOPROStol.³³

Recently Approved Agents

The adverse effects from current CS medications are less than ideal. As a result, researchers are looking for new ways to treat the disease.

The FDA approved osilodrostat (Istrusia), an oral medication for CS, in March 2020. Patients start on 2 mg twice daily and titrate by 1 to 2 mg every two weeks based on tolerability and clinical response. Most patients can be maintained on 2 to 7 mg twice daily and the maximum dosage is 30 mg twice daily.³⁴ It works by preventing cortisol synthesis by inhibiting the 11-beta-hydroxylase enzyme.³⁵ Clinical trials included patients who were not cured by surgery or who were not surgical candidates. In a phase 3 trial, significantly more patients in the osilodrostat group had cortisol levels within normal limits (n = 37, 77.1%) than in the placebo group (n = 2, 8%) by week 12. By week 36, over 80% (n = 40) of patients in the osilodrostat group achieved normal cortisol. As a result, the drug improved signs of CS, like weight, fasting plasma glucose, blood pressure, and cholesterol.³⁶ Common adverse effects included adrenal insufficiency, headache, nausea and vomiting, fatigue, and edema. Rare but serious adverse effects include QTc prolongation and androgen elevation.³⁵

Levoketoconazole (Recorlev) is another recently approved medication for CS as of December 2021. Patients start on 150 mg twice daily and titrate up by 150 mg/day every two to three weeks based on tolerability and cortisol levels. The maximum dose is 600 mg twice daily.³⁷ It is a stereoisomer of ketoconazole, which is thought to be more potent than a racemic mix. A single-armed study of 94 patients found that 31% (n = 29) of patients in the intention-to-treat population responded to treatment with levoketoconazole. Despite the increased potency allowing for a lower dose compared to ketoconazole, almost all patients (n = 92, 98%) experienced an adverse event. The most common were nausea, headache, and peripheral edema. Rare but serious events included prolonged QT interval, abnormal liver function tests, and adrenal insufficiency.³⁸

It is important to note that CS is considered an orphan disease due to its rarity.³⁵ RCTs are often small, with fewer than 100 patients in the population of some phase 3 trials. These new medications are not incorporated into the most recent guidelines. This is reflective of the age of the most recent Endocrine Society guidelines, which came out in 2015, not the effectiveness or appropriateness of newer medications. Use of newer medications is likely to be reflected when new guidelines come out.

LOW CORTISOL DUE TO AD

Patient case: Liam is a 56-year-old man who arrives at the emergency department (ED) after three days of severe nausea and vomiting. He says his wife made him come in because she’s worried that he’s dehydrated. He reveals that he has new joint pain with this illness and it’s getting worse, up to a 7/10 on the pain scale. Liam reports that he spent most of the morning sitting on the floor of his bathroom because he feels lightheaded when he stands up and is afraid that he’ll fall. The ED physician completes a physical exam and notes that Liam’s skin is darker in some areas, like his gums, palm creases, and knuckles.

PAUSE AND PONDER: What testing is necessary to determine the cause of Liam’s condition? Do his symptoms sound like a run-of-the-mill virus? Something else?

Pathophysiology of AD

AD, named after Thomas Addison who discovered the disease, is adrenal insufficiency. AD occurs when a patient’s body does not produce enough cortisol. There are three different etiologies³⁹:

Primary: destruction of the adrenal cortex
Secondary: insufficient production of ACTH
Tertiary: insufficient stimulation of the adrenal gland by CRH

Primary AD can be either congenital or acquired. Most cases of congenital AD are linked to a genetic mutation affecting cortisol and aldosterone synthesis. On the other hand, autoimmune adrenalitis is the main cause of acquired AD. Although they remain uncommon causes in the U.S., tuberculosis and human immunodeficiency virus infections can also trigger AD.³⁹

NOTE: Autoimmune adrenalitis is when the immune system attacks and destroys the adrenal glands with no known reason. It takes months to years of active autoimmune adrenalitis for symptoms of AD to show.⁴⁰

Secondary AD is due to a deficiency in ACTH secretion or a pituitary adenoma. Pituitary adenomas tend to cause deficiencies in all pituitary hormones.³⁹

Tertiary AD has an exogenous cause, usually sudden withdrawal from long-term corticosteroid use. This is why tapering corticosteroids matters; slowly reducing exogenous corticosteroids allows the body to adjust and helps prevent withdrawal. Providers should also warn patients not to self-discontinue corticosteroids. Sometimes chronic opioid use can cause tertiary AD by suppression of the entire HPA axis.³⁹

Presentation and Complications

Table 7 lists common signs and symptoms of AD. It is important to note that primary AD tends to present with more severe symptoms than secondary AD and has aldosterone abnormalities. Patients with secondary AD still have some cortisol and aldosterone may remain normal. These patients are unlikely to experience hyperpigmentation, dehydration, or hyperkalemia. Tertiary AD differs in that patients may experience a mix of Cushingoid appearance and AD symptoms.³⁹

Table 7. Signs and Symptoms of AD^2,39

Fatigue	Hyperpigmentation (scars, skin creases, gums)
Abdominal pain	Nausea and vomiting
Diarrhea	Loss of appetite, unintentional weight loss
Muscle and joint pain, muscle spasms	Dehydration
Hypotension	Irritability, depression, poor concentration
Craving salty food	Hypoglycemia
Hair loss	Abnormal menstruation
Hyperkalemia	Hyponatremia

Patients with AD may experience acute, life-threatening symptoms during severe injury, illness, or stress. This is known as an Addisonian crisis or acute adrenal failure. Hallmarks of the crisis include extreme pain and weakness, mental status changes, severe vomiting and diarrhea, hypotension, and possibly loss of consciousness.²

Testing Cortisol Levels for AD

Patients with signs and symptoms of AD should undergo a corticotropin stimulation test. In the test, patients receive 250 mcg of IV corticotropin. If the patient’s cortisol does not reach at least 500 nmol/L at 30 or 60 minutes, it indicates AD. Plasma ACTH is helpful to determine if a patient’s AD is primary in nature. High ACTH indicates primary AD.⁴¹

PAUSE AND PONDER: What medications are available to replace cortisol?

Treatment of AD

AD requires steroid replacement. Treatment for primary AD is lifelong. Patients with secondary and tertiary AD may require long-term treatment with a gradual taper or treatment for life. Appropriate choices for glucocorticoid replacement include 15 to 25 mg of oral hydrocortisone or 20 to 35 mg of cortisone acetate per day. If the hydrocortisone formulation is not modified-release, patients will need to take it two to three times per day. The first dose of the day should be the largest and no more than a maximum of 10 mg. Taking a steroid close to bedtime can disturb sleep and should be avoided.^39,41

When possible, providers should avoid prescribing prednisolone and dexamethasone. Prednisolone has a higher risk of dyslipidemia and bone weakening compared to other glucocorticoids. The advantage, however, is the lower dosing frequency of one to two times daily, which may increase adherence. Dexamethasone has an extremely long half-life, increasing the risk of Cushingoid adverse effects significantly.^39,41

Monitoring and adjusting glucocorticoid treatment should be based on patients’ signs and symptoms, not hormonal monitoring. In particular, providers must track body weight, postural blood pressure, energy levels, and Cushingoid symptoms at baseline and throughout treatment.⁴¹

Adjusting the dose of glucocorticoids is necessary in stressful situations, like surgery, severe illness, and pregnancy. More severe conditions, like major surgery and childbirth, require higher dosing than average illnesses. Patients may develop adrenal crisis if they take the same glucocorticoid dose during more stressful times.⁴¹

NOTE: Mineralocorticoid replacement in aldosterone deficiency is not the focus of this CE, but it is still important to mention. Patients with primary AD require mineralocorticoid replacement, while secondary and tertiary AD do not. Destruction of the adrenal gland in primary AD creates a deficiency in all hormones it produces. Secondary and tertiary AD are related to ACTH signaling, which does not affect aldosterone production. The treatment is 0.05 to 0.2 mg of fludrocortisone each morning. Monitoring blood pressure and electrolytes is necessary.³⁹

NOTE: Women with primary AD may also experience adrenal androgen deficiency. This manifests as low libido, depression, and low energy.⁴¹ Dehydroepiandrosterone (DHEA) treatment may be necessary if patients still have symptoms after appropriate glucocorticoid and mineralocorticoid management. The goal is to have a normal morning serum DHEAS (sulfate-bound, stored DHEA) level.^39,41

Emerging Treatments

New treatments for AD have focused more on modifying hydrocortisone release to improve patient satisfaction than on coming up with a brand new drug. The hydrocortisone modified-release hard capsule (Efmody) is a newer innovation to hydrocortisone that was approved by the European Commission in 2021. It is not yet available in the U.S..⁴²

Clinical trials are underway for a hydrocortisone subcutaneous pump, meant to closely mirror cortisol secretion. A small trial of 21 patients tested the pump. Over 6 weeks, the pump improved patients’ quality of life subjectively. Patients reported waking up more easily, better mood upon awakening, and an overall positive mood.⁴³ Larger studies are necessary to prove the objective benefits of a pulse pump, though improvement in mood may be significant considering AD’s link to irritability and depression.

One of the newest innovations under development in AD treatment is implantable cell therapy. Bioprinted tissue has the potential to replace the adrenal gland’s function in primary AD patients. At this time, research is in the preclinical stage. Researchers removed the adrenal glands of mice and replaced them with bioprinted tissue in one group. When researchers injected ACTH into the mice, those with bioprinted tissue replacement responded by producing cortisol, while those with no renal replacement showed no change.^44,45 In time, bioprinted tissue may offer a permanent treatment for primary AD.

NOTE: Bioprinted tissue is human tissue created in a lab. The new technology involves 3D printing bioink, a mixture of live cells and material to support cell growth, to create tissues and organs.⁴⁶

HANDLING MISINFORMATION AND DISINFORMATION

PAUSE AND PONDER: How would you speak to a patient that asks you about an article she saw online sharing incorrect information? What if she doesn’t believe you?

Misinformation is information that is false, but not shared to cause harm. Disinformation is information that is false and deliberately shared to cause harm.⁴⁷

People who spread misinformation and disinformation may use many strategies to distract from false claims. Tactics include⁴⁸

Emotional triggering, especially sparking fear or anger
Treating anecdotes like facts
Sharing old or outdated information

People have access to a plethora of information with the Internet. With such an overwhelming amount of information available to consume online, it can be difficult to find factual medical advice. Additionally, social media companies are lax about false posts. For example, social media sites do not take action against 95% of posts reported for COVID-19 and vaccine misinformation.⁴⁷ As healthcare providers, pharmacists can offer patients an analysis of information they find and strategies for them to evaluate information on their own in the future.

One popular way to break down how to address disinformation and misinformation with patients is the “Three C” approach. This involves

Compassion
Connection
Collaboration

It is important to recognize that being a trusted source of information requires mutual respect. Communicating in a nonjudgmental and compassionate way is important. If patients think pharmacy staff are judging them for believing something incorrect, they are more likely to get defensive and close off future opportunities for discussion. Pharmacy staff should make sure patients know their intent is to help them make the best health decisions and that the conversation is worthwhile. Staff should ask patients to share more of their point of view with open-ended questions and listen.^47,49 When patients explain their point of view, it will help to pick out what matters to the patient. Cultural, individual, and social values can play a part.⁴⁷

Connection directly links to compassion. Pharmacy staff should speak affirmatively to patients for seeking further information on a subject and acknowledge the parts of the patient’s narrative that are true. When it is necessary to correct false information, pharmacists and technicians should focus more on the evidence behind the correction than on the fact that the patient was wrong. Staff should continue to ask patients if they have further thoughts and questions. Pharmacists and technicians can also ask patients where they get their medical information and suggest reputable resources for them to use in the future.⁴⁷

At the end of the discussion, collaborate with the patient on the next steps. Trying to coerce or compel the patient to agree with everything you say often backfires. Remind patients that you’re on their side when you make recommendations. Allow them to share their thoughts and ask further questions about those recommendations.⁴⁷ To improve patient health literacy and confidence, consider sharing strategies to combat misinformation in the future. Online guides written in layman’s terms, like the ones posted by San Diego Circuit libraries (https://libguides.sdsu.edu/health/avoid-misinformation) and the Department of Health and Human Services (https://www.hhs.gov/surgeongeneral/reports-and-publications/health-misinformation/index.html), can help patients analyze other misinformation they come across.^50,51

Given the heavy discussion of cortisol on social media, pharmacists and technicians may run into situations where patients talk about false or overstated claims. Keep compassion, connection, and collaboration in mind when this happens.

CONCLUSION

The adrenal glands produce cortisol, which is necessary to respond to stress. However, when the adrenals release too much or too little cortisol, it can cause serious problems. Despite the rarity of adrenal diseases, people have been discussing cortisol, especially high cortisol, on online platforms. It has become a way to advertise supplements to reverse perceived symptoms of high stress. CS is treated first with surgery or cessation of exogenous steroids when possible. Medication therapy is still important and necessary for many CS patients. AD patients require long-term glucocorticoids, which may sometimes be for life. Pharmacists play an important role in educating patients on CS and AD medications. They can also break down expectations versus the low-evidence reality with “cortisol-lowering” supplements, while still validating patient concerns.

Patient Safety: Adrenal Drama: How Stress Became a Market
26-017 Pharmacist Post-test

After completing this continuing education activity, pharmacists will be able to
1. RECALL the physiology of cortisol, including its regulation and effects on the body’s major systems.
2. DESCRIBE the pathophysiology, presentation, and evidence-based treatments of Cushing’s syndrome and Addison’s disease.
3. ANALYZE patient case scenarios and determine whether a new intervention or adjustment of a current regimen related to cortisol levels is appropriate.
4. IDENTIFY common misinformation tactics and strategies to combat them through patient education.

1. Which of the following important cardiovascular measures is affected by cortisol levels?
A. Heart rate
B. Heart rhythm
C. Blood pressure

2. AT is a 35-year-old male at your clinic who has Cushing’s syndrome. His prior treatment includes tumor resection and post-surgical treatment of remaining symptoms with metyrapone. He does not complain of any new symptoms today. Based on his BMP in the following table, which option is the safest treatment option?

Lab (Reference range) AT’s Lab Results
Glucose (60-100 mg/dL) 90 mg/dL
Calcium (8-10 mg/dL) 8.4 mg/dL
Sodium (135-145 mEq/L) 136 mg/dL
Potassium (3.5-5 mEq/L) 3.0 mEq/L
Chloride (95-105 mEq/L) 97 mEq/L
Bicarbonate (22-28 mEq/L) 23 mEq/L
BUN (10-20 mg/dL) 12 mEq/L
Creatinine (0.6-1.2 mg/dL) 1.0 mEq/L

A. Continue treatment with metyrapone
B. Discontinue metyrapone, initiate ketoconazole
C. Discontinue metyrapone, initiate mifepristone

3. Patient NL comes up to the pharmacy counter and asks to speak with the pharmacist. He shows you an Instagram post he saw about ashwagandha and exclaims that its effects on cortisol will allow him to lose 20 pounds and stop taking his antihypertensive medication. He asks what you have heard about this supplement and if the pharmacy carries it. You recognize that the post is making falsely exaggerated claims. How would you proceed with the conversation?
A. Ask NL open-ended questions about his motivations and discuss reasonable expectations for ashwagandha supplementation given current evidence.
B. Immediately tell NL that the post is all wrong and supplement companies are trying to take advantage of him.
C. Show NL the aisle with ashwagandha and say you’ve heard it helps with stress management, too.

4. Tuberculosis and HIV can trigger which type of Addison’s disease?
A. Primary
B. Secondary
C. Tertiary

5. HS is a 44-year-old male patient recently diagnosed with Addison’s disease. He is coming in for a follow-up visit a month after starting a total daily dose of 15 mg oral hydrocortisone. Upon further questioning, HS reveals that he has had fewer GI symptoms in the past month and feels that it is easier for him to concentrate at work. He has gained 3 pounds in the last month and denies any Cushingoid symptoms. What is the best way to continue management?
A. Decrease the hydrocortisone dose by 5 mg per day.
B. Maintain the same regimen.
C. Increase the hydrocortisone dose by 5 mg per day.

6. Which part of the HPA axis is responsible for releasing adrenocorticotropic hormone (ACTH)?
A. Hypothalamus
B. Pituitary gland
C. Adrenal glands

7. Patient FY arrives at the pharmacy to receive a flu and pneumococcal vaccine. FY shares that her doctor recommended both vaccines because she has Cushing’s syndrome. She’s okay with the flu shot, as she gets one every year, but hesitant about the pneumococcal vaccine due to potential adverse effects. After deeper discussion, she decides to get the flu shot today and think about the pneumococcal vaccine over the next week. What is the best way to end this conversation?
A. Remind FY that you’re on her side and attempt to administer the pneumococcal vaccine without consent.
B. Deny the reported adverse effects of the pneumococcal vaccine because you’ve never had someone come back and complain.
C. Acknowledge FY’s concerns and recommend trusted resources for FY to review at home.

8. Which of the following is a metabolic complication of Cushing’s syndrome?
A. Insulin resistance
B. Hypoglycemia
C. Thrombosis

9. What is the mechanism of action of mitotane?
A. Prevent the release of enzymes needed to make cortisol.
B. Prevent cortisol from binding to its receptors.
C. Inhibit the pituitary gland from signaling the adrenals to release cortisol.

10. Patient FT comes up to the pharmacy counter looking for a recommendation. She is concerned that she may have Cushing’s syndrome after seeing an Instagram video about it. Upon further questioning, she reveals that her symptoms include recent poor sleep and acne. How would you proceed?
A. Tell FT to make an appointment with her provider right away.
B. Dismiss her concerns as an overreaction to a social media video.
C. Show FT over-the-counter options [MH2.1]to address her concerns and share red flag symptoms that indicate she should see her provider.

Patient Safety: Adrenal Drama: How Stress Became a Market
26-017 Pharmacy Technician Post-test

After completing this continuing education activity, pharmacy technicians will be able to
1. RECALL the physiology of cortisol, including its regulation and effects on the body’s major systems.
2. DESCRIBE the pathophysiology and presentation of Cushing’s syndrome and Addison’s disease.
3. OUTLINE evidence-based treatments of Cushing’s syndrome and Addison’s disease.
4. RECOGNIZE common misinformation tactics and strategies to combat them through patient education.

1. Which part of the HPA axis releases cortisol?
A. Hypothalamus
B. Pituitary gland
C. Adrenal glands

2. The title of an article linked on a Facebook post is “I Cut Out Coffee for 7 Days and It Balanced My Cortisol, Science Says Yours Will Too.” Which misinformation tactic does the article use to catch readers’ attention?
A. Emotional triggering
B. Treating anecdotes like facts
C. Sharing outdated information

3. Withdrawal from which medication is most likely to cause tertiary Addison’s disease?
A. Prednisone
B. Ibuprofen
C. Opioids

4. Which medication used to treat Cushing’s syndrome is only available parenterally?
A. Ketoconazole
B. Mifepristone
C. Etomidate

5. What effect, if any, does low cortisol have on body hair?
A. No difference
B. Body hair loss
C. More body hair

6. What part of the body regulates the HPA axis, and thus, cortisol?
A. Nervous system
B. Lymphatic system
C. Cardiovascular system

7. Taking a glucocorticoid should be avoided at which time of day?
A. Morning
B. Afternoon
C. Evening

8. Which “C” in the “Three C” approach best describes the following statement? Communicate nonjudgmentally and make sure patients know you are trying to help them make the best health decisions.
A. Compassion
B. Connection
C. Collaboration

9. Which of the following is a glucocorticoid antagonist used to treat Cushing’s syndrome?
A. Mitotane
B. Mifepristone
C. Cabergoline

10. Which of the following is a symptom of Cushing’s syndrome?
A. Hypotension
B. Craving salty food
C. Purple striae

1. Cortisol: What it is, function, symptoms & levels. Cleveland Clinic. Updated February 14, 2025. Accessed January 12, 2026. https://my.clevelandclinic.org/health/articles/22187-cortisol
2. Addison’s Disease - Symptoms and Causes. Mayo Clinic. Published December 21, 2024. Accessed January 13, 2026. https://www.mayoclinic.org/diseases-conditions/addisons-disease/symptoms-causes/syc-20350293
3. LeWine HE. Understanding the stress response. Harvard Health. Accessed January 15, 2026. Published April 3, 2024. https://www.health.harvard.edu/staying-healthy/understanding-the-stress-response
4. Mohamed Z. The Rise Of #HowToReduceCortisol On TikTok. ELLE. Published May 18, 2023. Accessed January 13, 2026. https://www.elle.com/uk/life-and-culture/culture/a43629233/how-to-reduce-cortisol-tiktok-trend/
5. Endocrine Facts and Figures First Edition. Endocrine Society. Published 2016. Accessed February 11, 2026. https://www.endocrine.org/-/media/endocrine/files/facts-and-figures/endocrine_facts_figures_adrenal.pdf
6. Barbot M, Zilio M, Scaroni C. Cushing's syndrome: Overview of clinical presentation, diagnostic tools and complications. Best Pract Res Clin Endocrinol Metab. 2020;34(2):101380. doi:10.1016/j.beem.2020.101380
7. Cushing Syndrome: Causes, Symptoms & Treatment. Cleveland Clinic. Published December 27, 2022. Accessed January 12, 2026. https://my.clevelandclinic.org/health/diseases/5497-cushing-syndrome
8. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540. doi:10.1210/jc.2008-0125
9. Sadie! [@slim_sadie] Tiktok Page. Lower your freakin cortisol bruh. Published June 6, 2025. Accessed January 15, 2026. https://www.tiktok.com/@slim_sladie/video/7513024679938952494?_r=1&_t=ZT-935xQpOyiPG
10. Harleen D, BDS [@harleenbds] Tiktok Page. Why your belly fat won’t go away (It’s not your fault). Published January 3, 2026. Accessed January 15, 2026. https://www.tiktok.com/@harleenbds/video/7591210341200153863?_r=1&_t=ZT-935xaLAKulL
11. Somatic Exercises with Liz Tenuto [@theworkoutwitch_] Instagram Page. HOW TO TEST IF YOU HAVE A CORTISOL BELLY. Published April 15, 2025. Accessed January 15, 2026. https://www.instagram.com/reel/DIeY1BhJYSW/?igsh=cjdwNGduaTRocG9l
12. First For Women Facebook Page. Struggling with stress and belly fat? A cortisol detox diet may be your solution! Published May 30, 2025. Accessed January 15, 2025. https://www.facebook.com/firstforwomenmag/photos/struggling-with-stress-and-belly-fat-a-cortisol-detox-diet-may-be-your-solution-/1108216754672848/?_rdr
13. Ashwagandha: Is It Helpful for stress, anxiety, or sleep? National Institutes of Health Office of Dietary Supplements. Published October 24, 2023. Accessed January 16, 2026. https://ods.od.nih.gov/factsheets/Ashwagandha-HealthProfessional/
14. Ashwagandha. NatMed Pro. Updated February 11, 2026. Accessed February 11, 2026. https://naturalmedicines.therapeuticresearch.com/Data/ProMonographs/Ashwagandha
15. Arumugam V, Vijayakumar V, Balakrishnan A, et al. Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: A systematic review and meta-analysis. Explore (NY). 2024;20(6):103062. doi:10.1016/j.explore.2024.103062
16. Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019;98(37):e17186. doi:10.1097/MD.0000000000017186\\
17. Theanine. NatMed Pro. Updated February 11, 2026. Accessed February 11, 2026. https://naturalmedicines.therapeuticresearch.com/Data/ProMonographs/Theanine
18. Dashwood R, Visioli F. l-theanine: From tea leaf to trending supplement - does the science match the hype for brain health and relaxation?. Nutr Res. 2025;134:39-48. doi:10.1016/j.nutres.2024.12.008
19. Davidson K, Hobbs H. 11 Natural Ways to Lower Your Cortisol Levels. Updated January 29, 2024. Accessed January 20, 2026. https://www.healthline.com/nutrition/ways-to-lower-cortisol
20. Lin TY, Hanna J, Ishak WW. Psychiatric Symptoms in Cushing's Syndrome: A Systematic Review. Innov Clin Neurosci. 2020;17(1-3):30-35.
21. Puglisi S, Perini AME, Botto C, Oliva F, Terzolo M. Long-Term Consequences of Cushing Syndrome: A Systematic Literature Review. J Clin Endocrinol Metab. 2024;109(3):e901-e919. doi:10.1210/clinem/dgad453
22. Cushing’s Syndrome. UCSF Department of Surgery. Accessed January 16, 2026. https://surgery.ucsf.edu/condition/cushings-syndrome
23. Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(8):2807-2831. doi:10.1210/jc.2015-1818
24. Varlamov EV, Vila G, Fleseriu M. Perioperative Management of a Patient With Cushing Disease. J Endocr Soc. 2022;6(3):bvac010. Published 2022 Jan 28. doi:10.1210/jendso/bvac010
25. Fleseriu M, Petersenn S. Medical therapy for Cushing's disease: adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers. Pituitary. 2015;18(2):245-252. doi:10.1007/s11102-014-0627-0
26. Endocrine Society alarmed by Texas court ruling banning mifepristone. Endocrine Society. Published April 10, 2023. Accessed January 12, 2026. https://www.endocrine.org/news-and-advocacy/news-room/2023/endocrine-society-alarmed-by-texas-court-ruling-banning-mifepristone
27. What Is Mifepristone, aka “The Abortion Pill”? Johns Hopkins Bloomberg School of Public Health. Published October 8, 2025. Accessed January 12, 2026. https://publichealth.jhu.edu/2025/what-is-mifepristone-aka-the-abortion-pill
28. Guignat L, Bertherat J. Medical Treatment of Cushing's Syndrome. Endocrinol Metab (Seoul). 2025;40(1):26-38. doi:10.3803/EnM.2024.501
29. Varlamov EV, Han AJ, Fleseriu M. Updates in adrenal steroidogenesis inhibitors for Cushing's syndrome - A practical guide. Best Pract Res Clin Endocrinol Metab. 2021;35(1):101490. doi:10.1016/j.beem.2021.101490
30. National Institute of Diabetes and Digestive and Kidney Diseases. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Ketoconazole. Updated May 17, 2017. Accessed February 15, 2026. https://www.ncbi.nlm.nih.gov/books/NBK547869/
31. 31. Mifepristone. UpToDate Lexidrug. UpToDate Inc. Updated February 13, 2026. Accessed February 15, 2026. https://online-lexi-com.ezproxy.lib.uconn.edu/lco/action/doc/retrieve/docid/patch_f/7301?cesid=9S5vRBs81OS&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3DmiFEPRIStone%26t%3Dname%26acs%3Dtrue%26acq%3Dmifeprist
32. Levoketoconazole. UpToDate Lexidrug. UpToDate Inc. Updated February 2, 2026. Accessed February 16, 2026. https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7188624?cesid=7pB4pVg1YLd&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dlevoketoconazole%26t%3Dname%26acs%3Dfalse%26acq%3Dlevoketoconazole#doa
33. FDA and ISMP Lists of Look-Alike Drug Names with Recommended Tall Man Letters. Institute for Safe Medical Practices. Published 2016. Accessed January 15, 2026. https://www.ismp.org/sites/default/files/attachments/2017-11/tallmanletters.pdf
34. Osilodrostat. UpToDate Lexidrug. UpToDate Inc. Updated January 9, 2026. Accessed February 15, 2026. https://online-lexi-com.ezproxy.lib.uconn.edu/lco/action/doc/retrieve/docid/patch_f/6928224?cesid=07iW9xxMCMH&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dosilodrostat%26t%3Dname%26acs%3Dtrue%26acq%3Dosilod
35. Newman M. FDA Approves New Drug to Treat Cushing’s Disease. Endocrine News. Published March 9, 2020. Accessed January 15, 2026. https://endocrinenews.endocrine.org/fda-approves-new-drug-to-treat-cushings-disease/
36. Gadelha M, Bex M, Feelders RA, et al. Randomized Trial of Osilodrostat for the Treatment of Cushing Disease. J Clin Endocrinol Metab. 2022;107(7):e2882-e2895. doi:10.1210/clinem/dgac178
37. Levoketoconazole. UpToDate Lexidrug. UpToDate Inc. Updated February 2, 2026. Accessed February 15, 2026. https://online-lexi-com.ezproxy.lib.uconn.edu/lco/action/doc/retrieve/docid/patch_f/7188624?cesid=5Yq2xwJTKja&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dlevoketoconazole%26t%3Dname%26acs%3Dtrue%26acq%3Dlevoketoco
38. Fleseriu M, Pivonello R, Elenkova A, et al. Efficacy and safety of levoketoconazole in the treatment of endogenous Cushing's syndrome (SONICS): a phase 3, multicentre, open-label, single-arm trial. Lancet Diabetes Endocrinol. 2019;7(11):855-865. doi:10.1016/S2213-8587(19)30313-4
39. Kumar R, Wassif WS. Adrenal insufficiency. Journal of Clinical Pathology. 2022;75(7):435-442. doi:10.1136/jclinpath-2021-20789539
40. Addison’s Disease. Cleveland Clinic. Updated July 6, 2022. Accessed January 21, 2026. https://my.clevelandclinic.org/health/diseases/15095-addisons-disease
41. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. doi:10.1210/jc.2015-1710
42. Efmody® (hydrocortisone modified-release hard capsules). Neurocrine.com. Published 2021. Accessed January 15, 2026. https://uk.neurocrine.com/UkResidents/HCP/efmody-r-hydrocortisone-modified-release-hard-capsules
43. Russell G, Kalafatakis K, Durant C, et al. Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial. J Intern Med. 2024;295(1):51-67. doi:10.1111/joim.13721
44. Aspect Biosystems Presents New Preclinical Data on Adrenal Bioprinted Tissue Therapeutics at ENDO 2025. Aspect Biosystems. Published July 14, 2025. Accessed January 15, 2026. https://aspectbiosystems.com/news-resources/aspect-biosystems-presents-new-preclinical-data-on-adrenal-bioprinted-tissue-therapeutics-at-endo-2025
45. Implantable cell therapy has potential to restore adrenal function and treat primary adrenal insufficiency. Endocrine Society. Published July 14, 2025. Accessed January 25, 2026. https://www.endocrine.org/news-and-advocacy/news-room/endo-annual-meeting/endo-2025-press-releases/dickman-press-release
46. Ricci G, Gibelli F, Sirignano A. Three-Dimensional Bioprinting of Human Organs and Tissues: Bioethical and Medico-Legal Implications Examined through a Scoping Review. Bioengineering (Basel). 2023;10(9):1052. Published 2023 Sep 7. doi:10.3390/bioengineering10091052
47. Pasquetto IV, Shajahan A, Winner D, et al. Misinfo Rx: A Toolkit for Healthcare Providers. Published 2022. Accessed January 16, 2025. https://misinforx.com/wp-content/uploads/2021/11/hghi_Misinfo_Rx_NEW_v22-003.pdf
48. How to Spot Health Misinformation. National Foundation for Infectious Diseases. Accessed January 19, 2026. https://www.nfid.org/resource/how-to-spot-health-misinformation/
49. Responding to Medical Misinformation and Disinformation and Protecting Scientific Discourse and Integrity. ACP Online. Accessed January 16, 2025. https://www.acponline.org/clinical-information/medical-ethics-and-professionalism/ethics-case-studies-education-resources/responding-to-medical-misinformation-and-disinformation-and-protecting-scientific-discourse-and
50. Avoid Health Misinformation. San Diego Circuit. Updated February 10, 2023. Accessed January 19, 2026. https://libguides.sdsu.edu/health/avoid-misinformation
51. Health Misinformation. US Department of Health and Human Services. Updated February 20, 2025. Accessed January 19, 2026. https://www.hhs.gov/surgeongeneral/reports-and-publications/health-misinformation/index.html

Only Skin Deep: The Pharmacist’s Guide to Intradermal Vaccine Administration 2025

Researchers have studied intradermal vaccination for various diseases for over a decade, so it was only a matter of time before pharmacists would be asked to learn this route of administration. This is arguably the most challenging method of vaccine administration, and inaccurate technique could render an immunization ineffective. Given the need for intradermal administration of the monkeypox vaccine, pharmacists should be prepared to offer intradermal vaccination to eligible individuals to increase immunization rates, slow viral spread, and improve outcomes for affected individuals.

INTRODUCTION

Major developments to vaccines and vaccine administration in recent years have demanded a great deal from pharmacists. The coronavirus disease-19 pandemic asked us to fight misinformation and vaccine hesitancy to educate the public about a new virus and new vaccine technology. We’ve been challenged to keep up with booster recommendations and the increased workflow that comes with vaccine administration. Many of us also taught our pharmacy technicians how to immunize.

Now, with the emergence of monkeypox comes yet another new vaccine with an unfamiliar method of administration (see our FREE monkeypox activity for a more in-depth discussion about this virus). In August 2022, the United States (U.S.) declared monkeypox a public health emergency and ramped up efforts to vaccinate at-risk individuals subcutaneously (a method with which pharmacists are generally familiar).¹ Shortly thereafter, the U.S. Food and Drug Administration (FDA) recognized that the country’s supply of monkeypox vaccine was unable to meet the current demand given the rapid spread of the virus.² Administering the vaccine intradermally only requires one-fifth of the subcutaneous dose, so the FDA issued an emergency use authorization (EUA) allowing healthcare providers to use this method of administration. This effectively increased the total number of available doses by up to five-fold.²

In September 2022, the U.S. Department of Health and Human Services authorized pharmacists, pharmacy interns, and pharmacy technicians, as appropriate, to administer monkeypox vaccines and therapeutics, under certain conditions.³ Pharmacists should be prepared to offer intradermal vaccination to eligible individuals to increase vaccination rates, slow viral spread, and improve outcomes both for this virus and any future viruses for which this applies.

THE ROLE OF INTRADERMAL ADMINISTRATION

Researchers have studied intradermal vaccination for a range of viral diseases, but only a few things are administered intradermally including^4,5

tuberculosis skin testing
BCG (tuberculosis) vaccine
rabies vaccine
allergy skin testing

Intradermal administration occurs in the dermis just below the epidermis (see Figure 1).⁴ The epidermis—the thinnest layer—is made up mostly of epithelial cells, but also contains melanocytes (pigment-producing cells), Merkel cells (for light-touch stimuli), and Langerhans cells (tissue-resident macrophages).⁵ The dermis is a thicker layer containing cells of the adaptive and innate immune systems including macrophages, mast cells, Langerhans cells, and dermal dendritic cells. Cells of the dermis are essential in processing incoming antigens to decide if they are harmful and activate the immune system accordingly.⁵

Figure 1. Methods of Vaccine Administration

High levels of antigen-presenting cells in the dermis induce a more potent immune response, making this an attractive (and potentially superior) vaccination site.^5,6 This significant reactivity in the dermis also prompts a strong immune response to a smaller quantity of vaccine antigen—as little as one-fifth to one-tenth the dose—compared to intramuscular or subcutaneous administration.^5,7 For this reason, intradermal administration is dose-sparing and potentially cost saving.⁵ Intradermal administration also avoids the rare risk of nerve, blood vessel, or joint space injury.⁷

Clinical studies are evaluating intradermal delivery of other vaccines, but none are currently available in the U.S. aside from monkeypox under the recent EUA.⁵ In years past, an intradermal influenza vaccine was available, but the manufacturer stopped production after the 2017-2018 flu season for unknown reasons.⁸ Of all parenteral routes, intradermal injections have the longest absorption time due to the lack of blood vessels and muscle tissue in this area. This is attractive for sensitivity testing, as reactions are easier to visualize and assess for severity.⁴

While intradermal administration is more efficient and cost-effective, it requires more skill and practice compared to subcutaneous or intramuscular administration.⁹ If incorrectly administered, the vaccine may enter the subcutaneous tissue instead and be ineffective because the dose is too small.

INTRADERMAL ADMINISTRATION TECHNIQUE

The most common intradermal injection sites are the volar aspect (inner surface) of the forearm and the upper back below the scapula (shoulder blade).⁴ Intradermal injection is not the best choice for every patient. Skin should be free of lesions, rashes, moles, or scars that could alter visual inspection of the injection site (or interpretation of test results, when applicable).⁴ In the case of the monkeypox vaccine, intradermal administration is only authorized for patients 18 years or older without a history of keloids (thick, raised scars).¹⁰

Researchers have developed various devices for intradermal drug delivery, but in the absence of specialized devices, individuals can employ the Mantoux technique using a hypodermic needle.⁵ The Mantoux technique is named for French physician Charles Mantoux who used this method for tuberculosis testing in the early 1900s.¹¹ The optimum needle size for this method is 26 to 27 gauge and ¼ to ½ inch long.⁴

The Mantoux technique is new to pharmacists (we know because we could only find information about administration technique in nursing resources), so listen up, take notes, and remember that practice makes perfect^4,10:

Inspect the injection site and select an area that is free from lesions, rashes, moles, or scars. Avoid vaccination in an area where there is a recent tattoo (less than one month old). If tattoos cover both arms, select an area without pigment (ink) if possible. If the tattoo is unavoidable, administer through it.
Clean the site with an alcohol or antiseptic swab using a firm, circular motion. Allow the site to dry completely to prevent alcohol from entering the tissue, which can cause stinging and irritation.
Using the nondominant hand, spread the skin taut at the injection site. Taut skin provides easy entrance for the needle. This is especially important in older individuals with less elastic skin.
Hold the syringe in the dominant hand between the thumb and forefinger at a 5- to 15-degree angle at the selected injection site with the bevel of the needle facing up.
Place the needle almost flat against the patient’s skin and insert the needle into the skin no more than 1/8-inch (about 3 mm) to cover the bevel. Keeping the bevel side up allows the needle to smoothly pierce the skin and deliver the medication to the dermis.
Once the needle is in place, use the thumb of the nondominant hand to slowly push the plunger to inject the medication.
Inspect the injection site for a bleb (small blister) which should appear under the skin. The presence of a bleb indicates that the medication is correctly placed in the dermis. The bleb is desired but not required, so if it doesn't appear, don't panic. Simply adjust your technique for next time.
Withdraw the needle at the same angle it was placed so as not to disturb the bleb and to minimize patient discomfort and tissue damage. Safely discard the syringe in a sharps container.

More visual learners can find a video demonstrating how to administer a vaccine intradermally at https://www.youtube.com/watch?v=dRsQf_UHsjs.

CONCLUSION

Vaccines work, that much we know. However, this is only true if they’re accessible, trusted, and used appropriately. Pharmacists can help promote access, education, and vaccine uptake if they have the knowledge and skills to do so. New vaccines and administration recommendations are challenging, but don’t let it get under your skin. We hope this quick-and-dirty overview of intradermal vaccines boosted your confidence and made it easier for you to give it a shot.

Only Skin Deep: The Pharmacist’s Guide to Intradermal Vaccine Administration
25-073 Posttest

Learning Objectives
• DISCUSS the potential benefits of intradermal vaccine delivery
• IDENTIFY how to administer intradermal injections

1. Which of the following is a benefit of intradermal vaccine delivery?
A. It can deliver a larger vaccine dose
B. It has the fastest rate of absorption
C. It avoids the risk of nerve injury

2. Which of the following makes the dermis a good site for vaccine administration?
A. High levels of Merkel cells
B. High levels of antigen-presenting cells
C. Low levels of Langerhans cells

3. About how far should you insert the needle to administer an intradermal injection via the Mantoux technique?
A. 1/8-inch
B. 1/4-inch
C. 1/2-inch

4. Travis Barker comes into your pharmacy asking for an intradermal vaccine. You inspect his forearms full of tattoos and find a small space without ink. You complete intradermal administration and notice a small bubble form under his skin. What does this mean?
A. You administered the vaccine subcutaneously
B. You administered the vaccine too close to a tattoo
C. You administered the vaccine correctly

5. Which of the following is appropriate technique for intradermal administration?
A. Insert the needle at a 5- to 15-degree angle with the bevel facing up
B. Pinch the skin between the thumb and forefinger of the nondominant hand
C. Remove the needle slowly at a 45-degree angle to reduce discomfort

Only Skin Deep: The Pharmacist’s Guide to Intradermal Vaccine Administration
25-073 Posttest

Learning Objectives
• DISCUSS the potential benefits of intradermal vaccine delivery
• IDENTIFY how to administer intradermal injections

1. Which of the following is a benefit of intradermal vaccine delivery?
A. It can deliver a larger vaccine dose
B. It has the fastest rate of absorption
C. It avoids the risk of nerve injury

2. Which of the following makes the dermis a good site for vaccine administration?
A. High levels of Merkel cells
B. High levels of antigen-presenting cells
C. Low levels of Langerhans cells

3. About how far should you insert the needle to administer an intradermal injection via the Mantoux technique?
A. 1/8-inch
B. 1/4-inch
C. 1/2-inch

References

REFERENCES
1. U.S. Department of Health and Human Services. Biden-Harris Administration Bolsters Monkeypox Response; HHS Secretary Becerra Declares Public Health Emergency. August 4, 2022. Accessed October 26, 2022. https://www.hhs.gov/about/news/2022/08/04/biden-harris-administration-bolsters-monkeypox-response-hhs-secretary-becerra-declares-public-health-emergency.html
2. U.S. Food and Drug Administration. Monkeypox Update: FDA Authorizes Emergency Use of JYNNEOS Vaccine to Increase Vaccine Supply. August 9, 2022. Accessed October 26, 2022. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply
3. U.S. Department of Health and Human Services. Notice of Amendment to the January 1, 2016 Republished Declaration under the Public Readiness and Emergency Preparedness Act. October 3, 2022. Accessed October 26, 2022. https://public-inspection.federalregister.gov/2022-21412.pdf
4. Administering intradermal medications. Open Resources for Nursing (Open RN). Accessed October 26, 2022. https://wtcs.pressbooks.pub/nursingskills/chapter/18-4-administering-intradermal-medication/
5. Kim YC, Jarrahian C, Zehrung D, Mitragotri S, Prausnitz MR. Delivery systems for intradermal vaccination. Curr Top Microbiol Immunol. 2012;351:77-112.
6. Hickling JK, Jones KR, Friede M, Zehrung D, Chen D, Kristensen D. Intradermal delivery of vaccines: potential benefits and current challenges. Bull World Health Organ. 2011;89(3):221-226.
7. Brooks JT, Marks P, Goldstein RH, Walensky RP. Intradermal Vaccination for Monkeypox - Benefits for Individual and Public Health. N Engl J Med. 2022;387(13):1151-1153.
8. Influenza vaccine. Aetna Clinical Policy Bulletins. Reviewed August 1, 2022. Accessed October 26, 2022. https://www.aetna.com/cpb/medical/data/1_99/0035.html
9. Miller K. What Is an Intradermal Injection, the New Way the Monkeypox Vaccine Is Being Given? Prevention. August 12, 2022. Accessed October 26, 2022. https://www.prevention.com/health/health-conditions/a40869782/what-is-intradermal-injection/
10. Centers for Disease Control and Prevention. JYNNEOS Smallpox and Monkeypox Vaccine:
ALTERNATE REGIMEN Preparation and Administration Summary (Intradermal Administration). Updated September 27, 2022. Accessed October 26, 2022. https://www.cdc.gov/poxvirus/monkeypox/files/interim-considerations/guidance-jynneos-prep-admin-alt-dosing.pdf
11. Kis EE, Winter G, Myschik J. Devices for intradermal vaccination. Vaccine. 2012;30(3):523-538.

Patient Safety: Ketogenic Diet: Fad Weight Loss or True Medical Benefits?

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

Describe the components and mechanisms of the ketogenic diet for medical purposes.

List disease states in which the ketogenic diet has been proven to help

Use this information to counsel patients who are interested in the ketogenic diet’s medical benefits

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

Describe the components of the ketogenic diet for medical purposes

List disease states in which the ketogenic diet has been proven to help

Identify situations in which patients need referral for additional information

The ketogenic diet, despite its current popularity, was initially developed to address seizure disorders. Its reliance on high fat, moderate protein, low carbohydrate intake can make it a challenge for patient adherence. By maintaining a constant state of ketogenesis from eating fatty foods, patients on the ketogenic diet change their natural fuel source from glucose to ketone bodies. Its medical uses include obesity, glaucoma, diabetes, seizures, and other neurode-generative disorders. A key concept is that patients must strive for ketosis (not ketoacidosis) and monitor medical conditions closely. It is contraindicated in patients with liver failure, pancreatitis, inborn disorders of fat metabolism, primarycarnitine deficiency, carnitine palmitoyl transferase deficiency, carnitine translocase deficiency, porphyria, and pyruvate kinase deficiency. People who have type1 diabetes or who are pregnant should not follow this diet. Some people develop the “keto-flu,” a slang term for symptoms indicative of carbohydrate withdrawal. Numerous reliable resources are available for patients and healthcare providers.

INTRODUCTION

Did you know that the ketogenic diet was NOT initially created for weight loss? Recently, the “keto” diet has become another fad diet for people trying to lose weight. Since 2000, more researchers have started to study the ketogenic diet, causing an increase in dieters who are employing this diet.¹

For decades, various entities have promoted fad diets as a way to lose weight and accrue other health benefits, with no data to back them up. The ketogenic diet began to reach the public’s consciousness in the 1970s, gained popularity in the early 2010s, and by 2017, it was a frequent topic in national news media. Google searches for the ketogenic diet (sometimes called the paleo diet, which is similar but not identical) quadrupled that year; questions about this diet were in the top 10 health questions.² Many people started using the ketogenic diet without understanding how it works or its associated benefits and risks. In 2014, celebrities like Lebron James, Kim Kardashian, and Megan Fox started using the ketogenic diet during its fad weight loss phase. In 2020, around 6% of Americans were consuming a ketogenic, high fat diet.³

In the 1920s, researchers noticed that some patients with epilepsy experienced benefits during fasting, so they discovered a way to mimic fasting to treat the disease.¹ Soon, physicians began to use the ketogenic diet for its antiepileptic properties.¹However, in the next decades, researchers introduced antiepileptic medications and the ketogenic diet’s popularity faded. Treatment for epilepsy still includes some of the first antiepileptic medications: phenobarbital and phenytoin.⁴ Although physicians began using phenobarbital in 1912 for epilepsy, the U.S. Food and Drug Administration did not approve phenytoin for use in epilepsy until 1938.⁵ In the 1940s, clinicians used troxidone, but its toxicity profile was unacceptable. Ethosuximide, approved in 1958, replaced it. Approval of carbamazepine and valproic acid in the 1960s made the ketogenic diet unnecessary and obsolete for the most part.⁵

Although pharmacists are the medication experts on the clinical team, they must understand all types of treatment, including nonpharmacologic interventions. During a ketogenic diet, patients eat a limited number of carbohydrates so the body will enter ketosis. Because of the diet’s intensity, pharmacists and technicians need to understand how the diet works to ensure patient safety. When patients start or are on the ketogenic diet, pharmacists need to counsel patients to ensure no drug interactions occur. Pharmacists also need to counsel patients who may have started the diet by themselves about its benefits and the risks. Also, remember interested dieters might embrace a New Year's resolution regarding ketogenic dieting, because National Keto Day is January 5th!

This continuing education activity summarizes knowledge of the ketogenic diet, the diet’s mechanism and its positive and negative effects, current medical uses for patients with epilepsy, diabetes, polycystic ovary syndrome (PCOS), and others, and recommendations for patient education and counseling.

KETOGENIC DIET

The ketogenic diet alters how the body burns energy, from carbohydrates to lipids. The traditional food pyramid places fats in the smallest section at the top, with carbohydrates in the largest bottom section. The ketogenic diet flips the pyramid, so most recommended foods are fats and very few are carbohydrates.

According to the Dietary Guidelines for Americans, 25% to 35% of an adult’s diet should come from fats, 45% to 65% from carbohydrates, and 10% to 30% from protein.⁶ In a 2000 calorie day for ketogenic diet patients, fat should account for 70% to 80% or 165 g of daily caloric intake.⁷

Although an exact timeframe is unknown, researchers believe that it can take the body up to four weeks to adapt to the ketogenic diet and ketosis.⁸ Patients initiating the diet could try daily exercise to force the body to break down fats, but its efficacy for reducing time to ketosis is unknown.⁸

Ketogenesis

The ketogenic diet uses ketosis and ketogenesis. When people eat carbohydrates, the body uses cellular respiration to produce energy from breaking down glucose molecules. However, if no carbohydrates are available, which would be the case during extended exercise or fasting periods, the body will naturally enter ketosis. Ketosis is a state of elevated ketone bodies, which include beta-hydroxybutyric acid, acetoacetic acid, and acetone in the blood.⁹ When the body needs energy, ketogenesis occurs to produce these ketone bodies, which can be used as an alternative energy source.

In normal cellular respiration, acetyl-CoA is condensed with oxaloacetate to begin the citric acid cycle. Beta-oxidation of fatty acids can produce acetyl-CoA, similar to the production of acetyl-CoA from glycolysis of glucose. In times of reduced glucose (i.e., fasting, extended exercise, ketogenic diet), the body diverts the acetyl-CoA produced from the fatty acids into ketogenesis.

Ketosis begins with fatty acid oxidation and the production of acetyl-CoA. Using the enzyme 3-ketothiolase, acetyl-CoA is converted into acetoacetyl-CoA. Then, the enzyme HMG-CoA synthase converts acetoacetyl-CoA to HMG-CoA.⁹ Low glucose levels during starvation or a high fat diet—a signal that the body needs to produce an alternative energy source for the brain—trigger this step of ketogenesis.¹⁰

The last step of energy production during ketosis is the conversion of HMG-CoA to the ketone bodies acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB). Using HMG-CoA lyase, AcAc and 3HB are cleaved from HMG-CoA.⁹By being in a constant state of ketogenesis from eating fatty foods, patients on the ketogenic diet change their natural fuel source from glucose to ketone bodies.

Ketone Bodies

The 3 main types of ketone bodies are AcAc, 3HB, and least commonly, acetone. The liver produces AcAc, 3HB, and acetone in a 78:20:2 ratio, respectively, during fatty acid oxidation.¹¹ Acetone is produced the least because it’s the byproduct of the uncommon and spontaneous decarboxylation of 3HB.¹¹ Ketone bodies are the only non-glucose derived energy source for the brain.¹⁰ The brain cannot process fatty acids, so they must be converted into ketone bodies first. They provide energy to the brain because both AcAc and 3HB can diffuse across blood brain barrier.⁹

During a normal day, ketone bodies account for only 2% to 6% of an individual's energy requirements. However, after a three- to four-day fast, ketone bodies account for 30% to 40% of the body's energy source.⁹ The liver can produce 185 grams of ketone bodies daily, which is enough to satisfy a person’s daily energy needs.⁹

By using ketone bodies, patients can avoid breaking down carbohydrates as an energy source, similar to how the body naturally functions during fasting. Ketone bodies are thought to have a direct beneficial mechanism, which will be discussed later, in disorders like epilepsy.

Effects of Insulin and Glucagon

Insulin and glucagon are important in ketosis and ketone bodies. Low insulin levels trigger steps in the ketosis process. Insulin, also called the antiketogenic hormone, decreases 3HB production, whereas glucagon, the ketogenic hormone, increases 3HB production.¹²

When humans consume carbohydrates and blood glucose levels rise, the pancreas releases insulin to absorb the blood sugar for energy storage.¹³ Insulin inhibits hormone-sensitive lipase and HMG-CoA synthase, enzymes that take part in fatty acid breakdown. It also stimulates acetyl-CoA carboxylase, causing the conversion of acetyl-CoA to malonyl-CoA, and blocking fatty acid transport into the mitochondria.¹⁰ As a result, insulin decreases the need for fatty acid oxidation and ketone bodies are decreased. The ketogenic diet requires patients to avoid carbohydrates to diminish insulin production and promote these mechanisms.

Glucagon does the opposite of insulin. The body uses epinephrine and glucagon to stimulate adipose (fat) tissue to produce more fatty acid.⁹ Glucagon triggers phosphorylation of hormone-sensitive lipase and HMG-CoA synthase, thus promoting ketogenesis.⁹ The body releases fatty acids from triglycerides, so they can be broken down by the newly activated enzymes.

A successful ketogenic diet requires a high glucagon/insulin ratio, similar to that experienced during fasting and by patients with diabetes. The high ratio increases fatty acid production and oxidation. Ketogenesis will follow.

Foods Consumed

Most foods for a ketogenic diet will have moderate amounts of proteins, no carbohydrates, with many fats. To prevent heart disease, physicians and pharmacists can counsel patients to eat healthy fats. Table 1 describes some examples of foods that are common in the ketogenic diet.

Table 1. Food Options Commonly Used in the Ketogenic Diet¹⁴

Fish and Seafood	- Full of protein - No carbs - Associated with positive cardiovascular and health benefits
Poultry and Meat (Chicken, beef)	- Rich in protein - No carbs - Limit processed meats
Nuts (Almonds, walnuts, pecans, cashews)	- High in fiber, protein, and unsaturated fats - Very low carbs - Antioxidants
Non-starchy Vegetables (Broccoli, green beans, bell peppers)	- Include other vitamins and nutrients - Antioxidants
Cheese	- No carbohydrates - High in fats, protein, calcium - Too many saturated fats
Avocados	- Potassium, unsaturated fats - Most carbohydrates in avocados are fiber

Patients on the ketogenic diet must understand how to track their nutrition to diet properly, calculating proteins, carbohydrates, and fats daily. Patients must calculate carbohydrates to account for dietary fiber because fiber is not digested with other carbohydrates.¹⁴ When tracking nutrition, patients on the ketogenic diet must track net carbohydrates, which can be found by subtracting the dietary fiber content from the total carbohydrates. The total carbohydrate level reported on nutrition labels does not accurately reflect the carbohydrate content the patient has consumed.

Most of the foods mentioned in Table 1 are high in fat. Fish, seafood, meat, poultry, and eggs are main staples. Processed meats, like bacon, should be eaten more sparingly compared to non-processed meats, like chicken and beef.¹⁴ Patients can eat chicken and fish more frequently because they promote cardiovascular health, unlike red meat. Many people believe that berries are not allowed on the ketogenic diet, but strawberries, raspberries, and blackberries have very low net carbohydrates. The total carbohydrates in berries may appear high, but their high fiber content allows berries to have a low net carbohydrate content.

A vegetarian ketogenic diet is a possibility, even though options are more limited. Vegetarian options with high protein and low carbohydrates include nuts, tofu, and seitan (a meat substitute made from the gluten in wheat).¹⁵ These dieters can also enjoy peanut butter-based desserts for more proteins. Seeds are high in fat and have high dietary fiber. For higher calorie meals, eggs and dairy (hard cheeses and plain yogurt) are an important fat option. Eggs have many fats, but essentially no carbohydrates.¹⁵

Any food that is high in net carbohydrates will disrupt the body's ketosis. These are foods like starchy vegetables, juices, syrup, chips, and crackers.¹⁴ Foods high in carbohydrates will give the body enough energy to not oxidize fatty acids and prevent the production of ketone bodies.¹⁴

PAUSE AND PONDER: Would a fasting patient reach ketosis quicker than a patient who is not fasting?

WHO BENEFITS FROM THE KETOGENIC DIET?

Obesity

Obesity, a leading risk factor for many chronic health conditions, continues to rise in the United States. According to the CDC, the prevalence of diabetes has increased to 41.9% from 2017 to 2020.¹⁶ Many have adopted low-carbohydrate, high fat lifestyles to lose weight. A 2016 meta-analysis of 11 randomized control trials assessed the efficacy of the ketogenic diet. Among the 1369 participants, those on the ketogenic diet experienced greater weight loss than those who participated in a low-fat diet.¹⁷ After six months to two years of intervention, patients experienced significant weight loss, HDL cholesterol increase, and triacylglycerol (TAG) reduction. The studies were limited by moderate to high heterogeneity and possible publication bias. A 2021 study evaluated the efficacy of the ketogenic diet using a mobile health application in comparison to a calorie restricted, low-fat application.¹⁸ Of the 155 participants, those using the ketogenic diet app experienced greater weight loss (12.3 pounds) at 12 weeks. Hemoglobin A1c (HbA1c) and liver enzymes also improved for the ketogenic diet group. This study was limited by operating fully remotely via the application. Patients could have benefited from in-person counseling or on-site visits to promote adherence.¹⁸

Another meta-analysis of 13 randomized controlled trials showed that participants on the ketogenic diet benefited from greater weight loss than those on a low-fat diet proving that the ketogenic diet can be used for obese patients. The low-fat diet group consisted of 787 patients while the ketogenic diet group consisted of 790. Patients that were part of the keto group lost approximately 3.6 pounds (1.6 kilograms) more than the low-fat group.¹⁹ Patients saw a greater increase in HDL and a more significant reduction in TAG in the keto group.

Type 2 Diabetes

Patients with type 2 diabetes (T2D) sometimes benefit from the ketogenic diet through improved glycemia and reduced insulin resistance. A study of 28 patients with T2D following a ketogenic diet showed that blood glucose and HbA1c improved. The ketogenic diet could potentially help patients with T2D reduce the number or dose of medications.²⁰ Another comparative study showed that obese patients with T2D had improvement in blood glucose profiles, insulin sensitivity, and HbA1c when adhering to the ketogenic diet for two consecutive weeks.²¹ However, the study was limited by short duration and small sample size.

Polycystic Ovary Syndrome

Similar benefits seem to apply to patients with polycystic ovarian syndrome (PCOS). Patients with PCOS experience hyperandrogenism, insulin resistance, and ovulatory dysfunction.²² Current treatment options include metformin, clomiphene, and letrozole; the ketogenic diet may provide good results for these women through insulin reduction.

In addition to the symptoms listed above, women with PCOS tend to gain weight, develop acne, and experience hirsutism.²³ Physicians recommend lifestyle modifications and hormonal contraceptives as first line interventions, but often, these interventions are insufficient, and symptoms persist.²³

Researchers have conducted many studies to evaluate the benefits of the ketogenic diet for women with PCOS, yet the studies are greatly limited by sample size. For example, a 2019 study consisting of 14 women with PCOS struggling with their weight assessed changes in body weight, BMI, fat body mass, lean body mass, HDL, and several other parameters. At 12 weeks, participants saw a 9.43-kilogram (20.7 pound) reduction in body weight, 3.35 reduction in BMI, and an 8.29-kilogram (18.2 pound) reduction in fat body mass.²³

A pilot study consisting of five women tested the ability of the ketogenic diet to reduce PCOS symptoms. Researchers provided the women with low-carbohydrate diet books and handouts alongside group meetings to test the ketogenic diet’s efficacy for PCOS. Participants consumed fewer than 20 grams of carbohydrates per day for six months. To test participants’ adherence, researchers measured ketones and body weight. Throughout the 24-week period, participants lost weight with a mean BMI decrease of four kilograms (approximately 8.8 pounds) which was a 14.3% total reduction in body weight.²⁴ The study resulted with clear reductions in testosterone, fasting serum insulin, and an overall improvement of PCOS symptoms.

Additionally, an eight-week crossover study involving 30 women with PCOS demonstrated various benefits. On average, weight loss ranged from 1.3 to 1.6 kg (2.8-3.5 pounds). When compared to baseline, the results of this study highlight the relationship between decreases in testosterone and fasting insulin.²⁵ Overall, improvements in insulin resistance, testosterone levels, and weight loss, the ketogenic diet may help patients with PCOS.

Epilepsy

The original use for the ketogenic diet was as an antiepileptic therapy in children.¹After the discovery of antiepileptic medications, the need for the ketogenic diet diminished. However, researchers are bringing the ketogenic diet back to help treat patients who are refractory to modern antiepileptic medications.

In combination with medications, researchers have seen up to a 50% reduction in the number of seizures patients are having, with 10% to 15% becoming seizure free.²⁶ Co-administration with antiepileptics is possible for some medications. However, most patients are children and maintaining this strict diet is difficult.

During a retrospective study, researchers compared the effects of the ketogenic diet to modern anticonvulsant medications in 150 children. At one year, 55% of patients remained on the diet, and 27% of the patients who remained in the trial had a greater than 90% decrease in seizure frequency.²⁷ The diet allowed children to reduce their medication burden (patients averaged having 6.2 anticonvulsant medications before the trial), and proved to be more effective than many medications. More studies in larger patient populations are needed over longer periods of time to make stronger conclusions.

Research attributes the ketogenic diet’s anticonvulsant properties to an increased seizure threshold. Mitochondria in the brain have healthier biogenesis and density, leading to increased resistance to metabolic stress.²⁸ Another way the diet increases seizure threshold is through decreased glucose consumption and production of glycolytic ATP.²⁸ Subsequently, potassium channels remain open and hyperpolarize the neuronal membrane.²⁸

Researchers have found that ketone bodies produced from fatty acid oxidation have their own anticonvulsant effects. Although different ketone bodies have different effects, researchers have found that they can alter various neuronal membrane transporters to decrease excitability. Ketone bodies can inhibit transporters like the vesicular glutamate transporter and neuronal potassium channels. Inhibition of these transporters prevents signal transmission and causes decreased excitability of neuronal cells.²⁹

Other Neurodegenerative Disorders

In addition to epilepsy, promising evidence shows that the ketogenic diet has favorable effects for other neurodegenerative disorders. As the incidence of Alzheimer’s disease (AD) increases, few treatment options are available. The ketogenic diet may reduce deposition of amyloid beta (Aβ) plaques in patients with AD. With the addition of D-β-hydroxybutyrate (an enantiomer of the ketone body 3HB) to the ketogenic diet, ketones were able to increase neuron survival by reversing Aβ (1-42) toxicity.³⁰ By increasing ketone production in the liver, the ketogenic diet can reduce the production of reactive oxygen species.³¹ Ketone bodies also work to block histone hyper-acetylation initiated by histone deacetylases (HDACs), increasing antioxidant levels. The ketogenic diet can improve metabolic efficiency which improves ATP concentrations resulting in further protective effects.³¹

Ketones’ neuroprotective effects can potentially help patients with Parkinson’s disease by reducing oxidative stress, maintaining energy supply, and modulating deacetylation and inflammatory responses.^31,32 Because they can reduce inflammation and inhibit the glutamate excitatory synapse, infusions of ketone bodies like 3HB may lead to small improvements in Parkinson’s symptoms.³²The use of the ketogenic diet for Parkinson’s is still controversial, thus further research is necessary.

Glaucoma

Glaucoma is the second leading cause of vision loss in the world.³³ Because ketone bodies are the major source of energy when participating in the ketogenic diet, mitochondrial dysfunction in the retina and optic nerves associated with glaucoma may be decreased.^32,34 A 2020 observational study assessed the benefit of the ketogenic diet in 185,638 adults with glaucoma from three studies between 1976 and 2017. Results showed that following a low carbohydrate diet was associated with 20% lower risk of developing primary open-angle glaucoma with initial paracentral visual field loss.³⁵ However, evidence is still lacking, and researchers need to investigate more to prove the ketogenic diet’s efficacy for glaucoma.

Colorectal Cancer

According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and women in the United States.³⁶ A 2022 study suggests that the ketone body, 3HB, can suppress colorectal cancer.³⁷ In one experiment, investigators evaluated the ability of the ketogenic diet to prevent tumor growth and development in mice.

They discovered that 3HB could suppress tumor growth by reducing proliferation of colonic crypt cells.³⁷ 3HB induced positive changes in tumor growth through the upregulation of the homeodomain-only protein X (HOPX). The HOPX protein inhibits cancer organoid growth when overexpressed.³⁷ Mice fed the ketogenic diet showed elevated levels of HOPX specific to the colonic tissue.

Overall, mice assigned to the ketogenic diet experienced improved long-term survival rates. To test the efficacy of the ketogenic diet for existing tumors, after two cycles of dextran sodium sulfate, researchers introduced the diet to the mice. After exposure to the diet, tumor growth decreased. When researchers discontinued the ketogenic diet from the mice, tumor development proceeded.³⁷

This discovery led to further testing, this time in human organoids. Organoids are tissue cultures derived from stem cells.³⁸ In the right environment, they are used to replicate organs. They are an essential tool to monitor disease development. Findings mimicked the results from the mice in 41 patients with colorectal cancer. This suggests that the ketogenic diet may be used for the prevention and treatment of colorectal cancer in the future.³⁷

PAUSE AND PONDER: How do you think patients would feel using the ketogenic diet as a primary treatment for neurodegenerative diseases in the future?

Contraindications to the Ketogenic Diet

Some patients should not follow the ketogenic diet. It is contraindicated in patients with liver failure, pancreatitis, inborn disorders of fat metabolism, primary carnitine deficiency, carnitine palmitoyl transferase deficiency, carnitine translocase deficiency, porphyria, and pyruvate kinase deficiency.^39,40

Because of the high risk of developing diabetic ketoacidosis (DKA), patients with type 1 diabetes on SGLT2 inhibitors should not participate in the ketogenic diet.⁴¹ DKA occurs when the body produces a dangerously high level of ketones at a rapid pace. Feeling extremely thirsty and frequent urination are early symptoms of DKA. Later symptoms of DKA include dry skin and mouth, flushing, fatigue, stomach upset, and pain. Another notable warning sign of DKA is a fruity odor on the patient’s breath. Acetone is responsible for the sweet scent and indicates high levels of ketones in the body.⁴² If left untreated, DKA can further develop, ultimately leading to death.

Pregnancy is also a contraindication. The CDC recommends 340 additional calories per day during the second trimester of pregnancy and 450 additional calories per day during the third trimester.⁴³ The CDC also recommends a well-balanced diet for women who are expecting. Losing weight during pregnancy is not safe and can be harmful to a patient’s baby.⁴³ Folic acid and iron supplementation is pivotal in a fetus’ development. The World Health Organization recommends daily iron and folic acid supplements to reduce the risk of low birth weight.⁴⁴ If a pregnant woman were to go on the ketogenic diet, she would need to ensure she consumes the suggested dose of 120 mg elemental iron and 2800 µg (2.8 mg) folic acid daily.⁴⁴ Overall, no evidence indicates that the ketogenic diet is safe for pregnant women.

KETOGENIC DIET SAFETY AND COUNSELING

Although several studies suggest the ketogenic diet can be effective for weight loss, limited literature is available concerning its long-term effects. Long-term effects include hepatic steatosis, hypoproteinemia, kidney stones, and vitamin and mineral deficiencies.⁴⁰

Currently, no guidelines address the ketogenic diet specifically, and other guidelines do not include the ketogenic diet for the treatment of the previously mentioned diseases. Researchers must complete longer term studies with larger patient populations to prove the ketogenic diet’s benefits and elucidate any long-term risks. Pharmacists and other healthcare providers should keep this in mind when recommending the diet to patients.

The Keto-Flu

A common adverse effect of the ketogenic diet is the “keto-flu.” The symptoms are indicative of carbohydrate withdrawal that can create symptoms like brain fog, fatigue, nausea, vomiting, constipation, and muscle soreness.^{40, 39} Symptoms usually begin within one to two days and resolve within a week or less. Pharmacists can counsel patients on proper hydration, light exercise, rest, and starting the diet slowly to try to prevent the keto-flu.

Cardiovascular Effects

As research has previously shown, the ketogenic diet shows short-term benefits for obesity and cholesterol. Due to the overconsumption of fats, researchers wondered about the longer-term effects. In rodent studies, the ketogenic diet led to the development of hepatic inflammation and nonalcoholic fatty liver disease.⁴⁵ Limited research has been done for nonalcoholic fatty liver disease in humans and more study is needed.

Other Adverse Effects

While on the ketogenic diet, patients may experience constipation. The healthcare team should implement a bowel regimen for the patient including an agent like polyethylene glycol 3350 (MiraLAX^®) that’s sugar-free, meaning it adds no additional carbs. Other notable side effects are kidney stones and a decrease in bone density. To prevent kidney stone occurrence, pharmacists can counsel patients on drinking large amounts of liquids.. Patients can reach out to their providers to ensure they check bone health routinely. Several advisory groups recommend bone mineral density screening for women aged 65 and older and men aged 70 and older, and for other patients who are at high risk. Patients participating in the ketogenic diet are no exception, and could be considered high-risk if they do not consume enough calcium and vitamin D. Pharmacists can counsel patients to monitor their calcium and vitamin D intake and supplement it if necessary. Upon screening, providers may also recommend calcium and vitamin D supplementation for patients who experience a decline in bone mineral density.⁴⁶

What Can Health Professionals Do?

Pharmacists can counsel patients on ketone testing to prevent occurrences of DKA. When a patient’s blood glucose exceeds 240 mg/dL, testing ketone levels every four to six hours is warranted.⁴⁷ Ketones can be monitored through the urine and blood. A urine stick test is the most common and changes color depending on the ketone level. Although urine tests are convenient, blood ketone tests from finger sticks are more accurate because they measure 3HB and/or AcAc in the blood.⁴⁸ If ketone tests indicate high levels, the patient is at moderate or high risk for ketoacidosis and patients should seek medical attention. Table 2 shows normal ketone levels, the optimal state of nutritional ketosis, and the level for ketoacidosis.

Table 2. Ketone Levels⁴⁸
Normal Ketone	≤ 0.5 mmol/L
Nutritional Ketosis	1 - 3 mmol/L
Ketoacidosis	≥ 20 mmol/L

Patient adherence to long-term regimens always becomes challenging. Counseling patients on the importance of sticking to their diet and other medications will increase the likelihood of desired results.

PAUSE AND PONDER: On average, how long do you think a patient can remain adherent to the ketogenic diet lifestyle?

Medication management is a vital component of patient safety. To ensure that starting the ketogenic diet is safe, a healthcare professional should perform a complete medication reconciliation. Pharmacists, with an interdisciplinary team, should then develop a plan for medication adjustments (including OTCs) and carbohydrate intake. The use of medication package inserts, institutional databases, and manufacturer helplines can assist the team in determining carbohydrate content of drugs to make the process more seamless.⁴⁶ The following oral suspensions contain high carbohydrate contents:⁴⁹

Amoxicillin
Nystatin
Levetiracetam
Midazolam
Phenobarbital
Phenytoin
Baclofen
Ibuprofen

Making patients aware that they must inform the healthcare team of any new medications is equally as important.

Some medications are of concern with the ketogenic diet.

Patients taking SGLT2 inhibitors should not participate in nutritional ketosis due to the increased risk of diabetic ketoacidosis.
Clinicians need to monitor patients taking the anticonvulsant valproate (a fatty acid) and might need to adjust their doses since the ketogenic diet increases metabolic efficiency and valproate can be burned by cells for energy.⁵⁰ Patients may feel as though valproate is not as effective after starting the ketogenic The dose, in this case, may need to be increased temporarily.
A case study showed that topiramate can increase blood pH, inducing metabolic acidosis and kidney stones.⁵¹ This may become hazardous if patients are already in nutritional ketosis.
Patients may experience hypotension while taking antihypertensive agents and following the ketogenic They should monitor blood pressure frequently.

Pharmacists and other health professionals should inform patients to stay hydrated to reduce the risk for kidney stones and eat low salt food items.

MYTHS AND FACTS

The ketogenic diet has become increasingly popular over the years. Halle Berry, Vanessa Hudgens, Kourtney and Kim Kardashian are a few of many celebrities that have tried the ketogenic diet and have seen incredible results. MTV’s Jersey Shore star, Vinny Guadagnino, also known as the Keto Guido, is no stranger to the diet and has even written a keto cookbook. Seeing such drastic transformations all over tabloids and social media, without a doubt leaves people wondering “Why not? If they can do it, so can I,” while others think, “This can’t be real.”

Many misconceptions create skepticism among patients from the abundance of information available on the internet. Pharmacists can alleviate patient worries by staying informed and referring patients to reliable resources. Table 3 below dispels common myths.

Table 3. Myths and Facts About the Ketogenic Diet⁵²
MYTH	FACT
The ketogenic diet is bad for your health.	The ketogenic diet has several health benefits including: ● Weight loss ● Improved brain function ● Reduction of seizures ● Blood sugar management ● Improvement of PCOS symptoms Side effects may include nausea, vomiting, constipation, or other common side effects.
All I have to do is consume any type of fat while going keto.	Patients should eat healthy fats like avocados, nuts, seeds, and fish. Healthy fats lower LDL levels and raise HDL levels. Unhealthy fats saturated and trans fatty acids (e.g., fried foods, pastries, butter, and cream) raise LDL levels.
If I go keto, I will get ketoacidosis.	Ketosis and ketoacidosis are different conditions. The ketogenic diet induces ketosis. ● In ketosis, the body burns fat since carbohydrates are unavailable. Nutritional ketosis is a normal response. ● Ketoacidosis is a complication seen primarily in patients with T2D where the blood becomes acidic. It can be life-threatening.
I will have no energy if I start a ketogenic diet.	Some people may experience an adjustment period while beginning the ketogenic diet. They may experience temporary fatigue, brain fog, or the “keto-flu.” Eventual ketone production fuels the brain with energy and resolves symptoms.
The ketogenic diet is only useful for weight management.	The ketogenic diet has proven effective in patients with diabetes, PCOS, metabolic syndromes, Alzheimer’s disease, and obesity.
I can’t drink any alcohol while on the ketogenic diet.	Various low-carb alcoholic beverages can be substituted. Light beer, vodka, gin, and rum are a few examples, but patients should keep intake low-moderate. Patients should avoid sweet drinks and cocktails to prevent high sugar intake.

Another common misinterpretation is that any low-carbohydrate food is considered keto. No food item has the same benefit as the other. The healthcare team must work with patients to create dietary plans that are more feasible for them. With a tailored diet plan, patients are more likely to feel structured and reach their goals. Overall, providers should conclude that patient education is necessary to certify patient trust and safety.

PATIENT RESOURCES

Reliable resources for patients are hard to find. Table 4 describes some resources that pharmacists can provide to patients for more information.

Table 4. Resources About the Ketogenic Diet for Patients

Cleveland Health Clinic	- Discusses what patients eat on the ketogenic diet - Small tidbits on benefits and risks - Includes information on populations that could benefit from the diet - https://health.clevelandclinic.org/what-is-the-keto-diet-and-should-you-try-it/
Harvard University Health	- Discusses key-takeaways from a ketogenic diet review - Gives food examples - Easy-to-understand - Discusses health implications for certain patient populations - https://www.health.harvard.edu/blog/ketogenic-diet-is-the-ultimate-low-carb-diet-good-for-you-2017072712089
Academy of Nutrition and Dietetics	- Popular nutrition website that presents findings on various health topics - Discusses populations that the ketogenic diet would not be safe in - Gives background on the diet - https://www.eatright.org/health/wellness/fad-diets/what-is-the-ketogenic-diet
Everyday Health	- Discusses risks and benefits of the diet - Provides food substitutions and daily meal plans - Discussion potential supplements and vitamins that may be beneficial to dieters - Discusses other nutrition techniques for other topics - Articles are peer-reviewed - https://www.everydayhealth.com/diet-nutrition/ketogenic-diet/comprehensive-ketogenic-diet-food-list-follow/
EatingWell	- Brief explanation about the ketogenic diet - Provides variety of food options for dieters - Easy-to-understand and discusses other nutrition techniques - Peer reviewed and gives background on all authors/editors - https://www.eatingwell.com/article/290697/ketogenic-diet-101-a-beginners-guide/

CONCLUSION

Following a low-carbohydrate, high fat diet that uses ketone production to fuel the body requires a large selection of foods if patients are to maintain this diet. This is the challenge of the ketogenic diet. Pharmacists and technicians need a good understanding of what this diet is—and what it is not—so they know when prescribers are likely to use it for diseases. Pharmacists, as they screen for contraindications, should identify the signs of ketosis and counsel patients on managing safe ketone levels.

Patient education is the key to reaching patient goals. Pharmacists must be ready to address patient questions and concerns regarding the ketogenic diet in conjunction with current medications. When pharmacists are a part of the care process, outcomes improve.

Ketogenic Diet: Fad Weight Loss or True Medical Benefits?
PHARMACIST POST TEST QUESTIONS
25-072 P

LEARNING OBJECTIVES
After completing this continuing education activity, pharmacists will be able to:
- Describe the components and mechanisms of the ketogenic diet for medical purposes.
- List disease states in which the ketogenic diet has been proven to help
- Use this information to counsel patients who are interested in the ketogenic diet’s medical benefits

1. Which of the following statements is a MYTH regarding the ketogenic diet?
a. The ketogenic diet benefits patients wanting to lose weight from PCOS.
b. A patient starting the ketogenic diet will have ketoacidosis.
c. The ketogenic diet does not prevent patients from alcohol consumption.

2. James is a 46-year-old male with type 1 diabetes with a BMI of 28. His current medications include insulin-glargine, empagliflozin, and hydrochlorothiazide. He would like to start the ketogenic diet to lose weight. Would you recommend James start the ketogenic diet?
a. Yes, James should start the ketogenic diet right away. It has proven to be efficacious in patients with type 1 diabetes.
b. No, James is currently on an SGLT2 inhibitor. He is at an increased risk of developing DKA.
c. James needs to contact his primary care physician for more information.

3. Which of the following chronic conditions needs more information for the ketogenic diet to be a proven treatment?
a. PCOS
b. Epilepsy
c. Glaucoma

4. Mary is an obese 34-year-old female who comes into the pharmacy with a concern. She recently started the ketogenic diet and is experiencing fatigue, nausea, and brain fog. What advice can you give Maria?
a. Inform Maria that she should stop the ketogenic diet immediately and contact her doctor.
b. Inform Maria that this is completely normal, and she may be experiencing the keto-flu.
c. Recommend Maria take over-the-counter acetaminophen for her nausea. Her symptoms will resolve in a few days.

5. Which neurodegenerative disorder has substantial evidence that the ketogenic diet may be beneficial?
a. Refractory epilepsy
b. Dementia
c. Parkinson’s Disease

6. Which of the following best describes ketogenesis?
a. The process of producing ketone bodies for energy, an alternative pathway to normal metabolism
b. The last step in the creation of ketone bodies, when AcAc and 3HB are cleaved from HMG-CoA
c. The process that breaks down fatty acids acetyl-CoA, so the body can enter the citric acid cycle

7. Which of the following disorders was seen in animal models after long term use of the ketogenic diet?
a. Hematoma
b. Non-alcoholic fatty liver disease
c. Major rashes

8. What was the ketogenic diet originally created for?
a. Weight loss
b. Type 2 Diabetes
c. Epilepsy

9. Becky comes into the pharmacy and is asking for help for recommendations on starting a ketogenic diet. If she is consuming 2000 calories per day, how many fats should you recommend for Becky to consume each day?
a. About 100g of fats daily, which is around 50% of her daily calories
b. About 165g of fats daily, which is around 70% of her daily calories
c. About 30g of fats daily, which is around 15% of her daily calories

10. What are the general effects of insulin and glucagon on ketosis?
a. Insulin and glucagon are both anti-ketogenic
b. Insulin is pro-ketogenic, and glucagon is anti-ketogenic
c. Insulin is anti-ketogenic, and glucagon is pro-ketogenic

Ketogenic Diet: Fad Weight Loss or True Medical Benefits?
TECHNICIAN POST TEST QUESTIONS
25-072 T

LEARNING OBJECTIVES
After completing this continuing education activity, pharmacy technicians will be able to:
- Describe the components of the ketogenic diet for medical purposes
- List disease states in which the ketogenic diet has been proven to help
- Identify situations in which patients need referral for additional information

2. James is a 46-year-old male with type 1 diabetes and is 156 lbs. He is currently taking empagliflozin (an SGLT2 inhibitor). He would like to start the ketogenic diet to lose weight. From what you learned, why should James avoid the ketogenic diet?
a. James is not overweight. He does not need the ketogenic diet to lose more weight.
b. James is currently on an SGLT2 inhibitor. He is at an increased risk of developing DKA.
c. James needs to contact his primary care physician to see if he is a candidate before starting the diet.

3. Which of the following chronic conditions needs more information for the ketogenic diet to be a proven treatment?
a. PCOS
b. Epilepsy
c. Glaucoma

4. Mary is an obese 34-year-old female who comes into the pharmacy with a concern. She recently started the ketogenic diet and is experiencing fatigue, nausea, and brain fog. What is Maria experiencing?
a. Maria is experiencing withdrawal from not being adherent to the diet. She should create a new care-plan with her provider.
b. Maria is experiencing the “keto-flu.” Refer her to the pharmacist so she can further explain the adverse effect.
c. Maria is ketoacidotic. Ask Maria if anyone has mentioned that her breath smells fruity.

5. Which neurodegenerative disorder has substantial evidence that the ketogenic diet is beneficial for their condition?
a. Epilepsy
b. Parkinson’s Disease
c. Dementia

6. A patient comes into the pharmacy after beginning a new ketogenic diet. The patient is worried because she read online that long term effects of the diet could cause a “fat liver.” What is the best response to the patient?
a. Refer the patient to the pharmacist for additional information.
b. Describe the many long-term effects of the ketogenic diet
c. Describe a study about non-alcoholic fatty liver with long term dieting

7. What was the ketogenic diet originally created for?
a. Weight loss
b. Type 2 Diabetes
c. Epilepsy

8. Becky comes into the pharmacy and is asking for help for recommendations on starting a ketogenic diet. If she is consuming 2000 calories per day, how many fats should Becky consume each day?
a. About 100g of fats daily, which is around 50% of her daily calories
b. About 165g of fats daily, which is around 70% of her daily calories
c. About 30g of fats daily, which is around 15% of her daily calories

9. Which of the following best describes ketogenesis?
a. The process of producing ketone bodies for energy, an alternative pathway to normal metabolism
b. The last step in the creation of ketone bodies, when AcAc and 3HB are cleaved from HMG-CoA
c. The process that breaks down fatty acids acetyl-CoA, so the body can enter the citric acid cycle

10. What is the best response to a patient who is wondering how to count carbohydrates for her ketogenic diet?
a. Use any carbohydrate counting app, all you must do is enter the amount of carbohydrates on the nutrition label.
b. Subtract the fiber carbohydrates from the total carbohydrates to get net carbohydrates and record that number.
c. Record only the carbohydrates from fiber. Other types of carbohydrates do not count because they are not digested the same.

References

RE FERENCES
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18. Falkenhain K, Locke SR, Lowe DA, et al. Keyto app and device versus WW app on weight loss and metabolic risk in adults with overweight or obesity: A randomized trial. Obesity (Silver Spring). 2021;29(10):1606-1614. doi:10.1002/oby.23242
19. Bueno NB, de Melo IS, de Oliveira SL, da Rocha Ataide T, et al. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110(7):1178-1187. doi:10.1017/S0007114513000548
20. Yancy WS Jr, Foy M, Chalecki AM, Vernon MC, Westman EC, et al. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr Metab (Lond). 2005;2:34. Published 2005 Dec 1. doi:10.1186/1743-7075-2-34
21. Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP, et al. Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med. 2005;142(6):403-411. doi:10.7326/0003-4819-142-6-200503150-00006
22. Batch JT, Lamsal SP, Adkins M, Sultan S, Ramirez MN, et al. Advantages and Disadvantages of the Ketogenic Diet: A Review Article. Cureus. 2020;12(8):e9639. Published 2020 Aug 10. doi:10.7759/cureus.9639
23. Paoli A, Mancin L, Giacona MC, Bianco A, Caprio M, et al. Effects of a ketogenic diet in overweight women with polycystic ovary syndrome. J Transl Med . 2020;18(1):104. Published 2020 Feb 27. doi:10.1186/s12967-020-02277-0
24. Mavropoulos JC, Yancy WS, Hepburn J, Westman EC, et al. The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study. Nutr Metab (Lond). 2005;2:35. Published 2005 Dec 16. doi:10.1186/1743-7075-2-35
25. Gower BA, Chandler-Laney PC, Ovalle F, et al. Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS. Clin Endocrinol (Oxf). 2013;79(4):550-557. doi:10.1111/cen.12175
26. Ketogenic diet. Epilepsy Foundation. Accessed July 20, 2022. https://www.epilepsy.com/treatment/dietary-therapies/ketogenic-diet
27. Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC, Kelly LM , et al.The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998;102(6):1358-1363. doi:10.1542/peds.102.6.1358
28. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, Pluta R , et al. Ketogenic Diet and Epilepsy. Nutrients. 2019;11(10):2510. Published 2019 Oct 18. doi:10.3390/nu11102510
29. Zhang Y, Xu J, Zhang K, Yang W, Li B, et al. The A nticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms. Curr Neuropharmacol. 2018;16(1):66-70. doi:10.2174/1570159X15666170517153509
30. Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL, et al. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc Natl Acad Sci U S A. 2000;97(10):5440-5444. doi:10.1073/pnas.97.10.5440
31. Yang H, Shan W, Zhu F, Wu J, Wang Q, et al. Ketone Bodies in Neurological Diseases: Focus on Neuroprotection and Underlying Mechanisms. Front Neurol. 2019;10:585. Published 2019 Jun 12. doi:10.3389/fneur.2019.00585
32. Gough SM, Casella A, Ortega KJ, Hackam AS, et al. Neuroprotection by the Ketogenic Diet: Evidence and Controversies. Front Nutr. 2021;8:782657. Published 2021 Nov 23. doi:10.3389/fnut.2021.782657
33. Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol. 1996;80(5):389-393. doi:10.1136/bjo.80.5.389
34. Zarnowski T, Tulidowicz-Bielak M, Kosior-Jarecka E, Zarnowska I, A Turski W, Gasior M, et al. A ketogenic diet may offer neuroprotection in glaucoma and mitochondrial diseases of the optic nerve. Med Hypothesis Discov Innov Ophthalmol. 2012;1(3):45-49.
35. Hanyuda, A., Rosner, B.A., Wiggs, J.L. et al. Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: Data from three US cohorts. Eye (2020). https:/doi.org/10.1038/s41433-020-0820-5
36. American Cancer Society. Key Statistics for Colorectal Cancer. Cancer.org. Published 2019. https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html
37. Dmitrieva-Posocco, O., Wong, A.C., Lundgren, P. et al. β-Hydroxybutyrate suppresses colorectal cancer. Nature 605, 160–165 (2022). https://doi.org/10.1038/s41586-022-04649-6
38. Organoids: A new window into disease, development and discovery. hsci.harvard.edu. https://hsci.harvard.edu/organoids#:~:text=Organoids%20are%20tiny%2C%20self%2Dorganized
39. Intermountain Healthcare. Beware the Keto Flu. intermountainhealthcare.org. Published November 2, 2017. Accessed July 20, 2022. https://intermountainhealthcare.org/blogs/topics/live-well/2018/03/beware-the-keto-flu/
40. Masood W, Annamaraju P, Uppaluri KR. Et al. Ketogenic Diet. [Updated 2021 Nov 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Accessed July 20, 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499830/
41. Bolla AM, Caretto A, Laurenzi A, Scavini M, Piemonti L. Et al. Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes. Nutrients. 2019;11(5):962. Published 2019 Apr 26. doi:10.3390/nu11050962
42. Ruzsányi V, Péter Kalapos M. Breath acetone as a potential marker in clinical practice. Journal of Breath Research. 2017;11(2):024002. doi:10.1088/1752-7163/aa66d3
43. Weight Gain During Pregnancy . Pregnancy .Maternal and Infant Health | CDC. www.cdc.gov. Published June 14, 2022. Accessed July 20, 2022. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregnancy-weight-gain.htm#:~:text=Eat%20a%20balanced%20diet%20high
44. Antenatal iron supplementation. www.who.int. Accessed July 25, 2022. https://www.who.int/data/nutrition/nlis/info/antenatal-iron-supplementation
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46. Medication Management on the Ketogenic Diet. Accessed July 20, 2022. https://www.choc.org/wp/wp-content/uploads/2017/03/RT-6-CurlessJ-RDsInPractice-Keto.pdf
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48. Volek JS, Phinney SD. The Art and Science of Low Carbohydrate Performance. Beyond Obesity Llc; 2012.
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51. Salek T, Andel I, Kurfurstova I. Topiramate induced metabolic acidosis and kidney stones - a case study. Biochem Med (Zagreb). 2017;27(2):404-410. doi:10.11613/BM.2017.042
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PATIENT SAFETY: The Art of Insulin Dose Adjustments in the Setting of GLP-1 RAs and GIP/GLP-1 RAs

Pharmacist Educational Objectives

After completing the continuing education activity, pharmacists will be able to

Describe different types of insulin along with their appropriate use
Recall newer non-insulin medications for diabetes, along with risks vs. benefits
Analyze clinical information pertaining to insulin + GLP-1 or GLP-1/GIP agonist medication adjustments
Demonstrate medication adjustment recommendations while incorporating patient-specific data

Pharmacy Technician Educational Objectives

After completing the continuing education activity, pharmacy technicians will be able to

Describe different types of insulin along with their appropriate use
Recognize over the counter treatment options for hypoglycemia
Recall newer non-insulin medications for diabetes, along with risks and benefits
Identify when to refer patients with questions about their diabetes medications to the pharmacist

Insulin remains a cornerstone of treatment for diabetes mellitus (DM). Access to newer DM medications, which have cardiorenal benefits and a lower risk of hypoglycemia, is increasing with improved insurance coverage and lower cost options. With these newer medications having greater accessibility, the need to adjust the patient’s current medication regimen to incorporate the new medicines safely is increased. The adjustments should account for the patient’s current glycemic control, glycemic targets, planned lifestyle changes, risk of hypoglycemia or hyperglycemia, and risk of adverse drug reactions.

INTRODUCTION

This continuing education (CE) activity aims to guide safe insulin dose adjustments when adding glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1-RAs), and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs (GIP/GLP-1 RAs) in those with type 2 diabetes (T2D). Clinical utilization of GLP-1 RAs and GIP/GLP-1 RAs in combination with insulin has been lagging despite their benefits.¹This is due to a lack of clinician comfort with insulin adjustment despite Food and Drug Administration (FDA) approval and improved insurance coverage. Pharmacists can optimize a patient’s regimen by reducing the risk of hyperglycemia or hypoglycemia, adverse drug reactions (ADRs), and medication/injection burden.

Diabetes Basics

Diabetes is an endocrinological disorder characterized by metabolic imbalance (glucose utilization and insulin effect).² In patients who have diabetes, hyperglycemia occurs and could lead to long-term complications such as myocardial infarction, cerebrovascular accident, peripheral artery disease, retinopathy, nephropathy, and neuropathy.²

A glycated hemoglobin level (A1c) greater than or equal to 6.5% indicates a person has diabetes.³ When discussing how an A1c correlates to a patient’s self-monitored blood glucose (SMBG; home blood glucose testing using a glucometer or a continuous glucose monitor [CGM]), it can be helpful to consider an estimated average glucose (eAG).³The complete equation and calculator can be found at https://professional.diabetes.org/glucose_calc. A simplification is remembering that an A1c of 7% equals an eAG of 154 mg/dL and that each A1c percentage represents about 30 mg/dL. Generally, for an A1c goal of less than 7%, fasting blood sugars (FBGs) should be between 80 and 130 mg/dL, and 2-hour post-prandial glucose (PPGs) values should be less than 180 mg/dL.³

Previously, mainstay treatment options for glycemic control included metformin, sulfonylureas (glimepiride, glipizide, and glyburide), thiazolidinediones (pioglitazone), and dipeptidyl peptidase-4 inhibitors (alogliptin (Nesina), linagliptin (Tradjenta), saxagliptin (Onglyza), and sitagliptin (Januvia). Newer treatment options that are focused on cardiorenal benefits, weight management, and glycemic control include⁴

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors: canagliflozin (Invokana), bexagliflozin (Brenzavvy), dapagliflozin (Farxiga), empagliflozin (Jardiance), and ertugliflozin (Steglatro)
GLP-1-RAs: dulaglutide (Trulicity), exenatide ER (Bydureon), exenatide IR (Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), and semaglutide (Ozempic)
GIP/GLP-1 RA (tirzepatide [Mounjaro])

The diabetes management landscape is changing. Even if patients have appropriate glycemic control, their medication regimen may not be optimal based on co-morbidities. Please see the following link to the American Diabetes Association’s recommendations on medication selection: https://diabetesjournals.org/view-large/figure/5311673/dc25S009f3.tif.

Insulin

Insulin has been a cornerstone of diabetes management for decades. With the advent of newer medication classes, it can appear as though insulin’s importance in current practice is diminishing. Many individuals still benefit from the use of insulin, including those with type 1 diabetes (T1D), patients with newly diagnosed T2D with an elevated A1c, and those with access/cost concerns regarding branded medications.

Although treatment options for diabetes have advanced and include SGLT-2 inhibitors, GLP-1-RAs, and GIP/GLP-1 RAs, these drugs can be cost prohibitive depending on the situation.⁴ Insulin itself can also be cost-prohibitive depending on insurance coverage (or lack thereof) and patient-specific dosing needs. In certain situations where patients pay out-of-pocket, reducing the daily insulin dose can help reduce the cost.

Insulin’s onset of action, duration of action, and concentration help to categorize it.

Patients use bolus insulins such as ultra rapid, short, or regular insulin prior to meals to manage blood glucose spikes. These insulin types generally help lower PPGs. Checking SMBGs two hours after a meal helps to understand the effect while checking prior to mealtimes ensures safety.
Patients use basal insulins, injected once or twice daily, to provide constant insulin action throughout the day and night. Options include intermediate, long-acting, and ultra-long-acting. These insulin types generally help lower FBGs and patients who use these insulins should check their SMBGs when in a fasting state as well.
Examples of concentrated insulins include insulin lispro U-200 (insulin lispro U-200), insulin degludec (Tresiba U-200), insulin glargine U-300 (Tuojeo U-300), and insulin regular U-500. Testing for insulin degludec U200 and insulin glargine U-300 would match basal insulin testing. Testing for insulin lispro U-200 and insulin regular U-500 would match bolus insulin testing.
Mixed insulins contain a mix of a bolus/regular insulin and an intermediate insulin in pre-fixed percentages to reduce the injection burden. Examples include insulin aspart protamine/insulin aspart (Novolog 70/30), insulin lispro protamine/insulin lispro (Humalog 75/25 or Humalog 50/50), and insulin isophone (NPH)/insulin regular (Humulin 70/30 or Novolin 70/30). For safety, these require fixed meal timings and portions and thus testing is recommended two hours before and after breakfast and dinner.

Insulin Dosing

In practice, clinicians usually start patients on a basal insulin rather than a bolus insulin as it involves fewer injections and provides steadier coverage throughout the day. Generally, a starting basal insulin dose is calculated using 0.1 to 0.2 units/kg/day or 10 units daily.⁵ When insulin needs increase beyond 0.5 units/kg/day of basal insulin, providers (such as clinical pharmacists) can consider the addition of bolus insulin.⁶Using greater than 0.5 units/kg/day of basal insulin is referred to as overbasalization (see SIDEBAR).

SIDEBAR: Overbasalization^6,7

Overbasalization describes the situation in which the patient’s bedtime glucose readings are significantly higher (greater than 50 points) than their fasting values. Ideally, bedtime and fasting readings should be in equilibrium. Overbasalization is common in patients whose basal insulins are titrated to a fasting goal without considering the patient’s end-of-day blood sugars. It also occurs if prescribers think adding a medication would increase the patient’s injection/medication burden. This generally occurs when the patient’s basal insulin dosing exceeds 0.5 units/kg/day. Ideally, the provider should consider a medication that helps lower PPGs.

Using GLP-1 RAs and GIP/GLP-1 RAs has increased the ability to minimize the need for bolus insulin, reduce the risk of hypoglycemia, and lower PPG. Using a collaborative practice agreement within an interprofessional collaborative team has significantly reduced overbasalization and A1c.

The total amount of insulin a patient takes in a day is their total daily dose (TDD). This TDD is a helpful starting point when making insulin adjustments. For example, if a patient is taking 100 units of insulin per day (this could be basal or basal + bolus) then generally 10% to 15% is a reasonable adjustment.⁵ This equates to an increase or decrease of 10 to 15 units. For a smaller TDD of 20 units the adjustment would be 2 to 3 units. Alternately, patients can self-adjust the dosing within specified parameters such as increasing a basal insulin by 2 units (up to a pre-specified maximum) every three days that the FBGs are above goal.⁵

Patient/situation specific parameters that additionally need to be considered are the patient specific glycemic goal, glycemic trends (variability vs. stability), planned lifestyle changes, hypo/hyperglycemia, and ADRs. The prior recommendations only account for medication changes while everything else remains constant. Realistically, dosing changes will likely need to be made at larger percentages to accommodate multiple changing factors.

If PPGs indicate a need for improvement of glycemic control, clinicians can consider either a GLP-1 RA (for T2D) or bolus insulin (T1D or T2D). Adding a GLP-1 RA can be more complex for those on a multiple daily injection (MDI) insulin regimen (basal + bolus). Guidance regarding basal + bolus insulin dose deprescribing varies.

Insulin Dose Adjustment with GLP-1 RAs and GIP/GLP-1 RAs

Three studies have reviewed the efficacy of adding liraglutide to an MDI insulin regimen in patients with T2D.^8-10 They documented a significant reduction in A1c from baseline in the GLP-1 RA group compared to the MDI control groups. Two studies—one conducted by researchers at the Mountain Diabetes and Endocrine Center, Asheville, North Carolina and a second conducted in Europe and Saudi Arabia called the MDI Liraglutide Trial—showed significantly reduced insulin dosing in the liraglutide groups.^8,9 In contrast, the third study (N = 71), conducted at the University of Texas Southwestern Medical Center (UTSMC), Dallas, did not show a significant reduction in insulin dosing.¹⁰

The Mountain Diabetes and Endocrine Center study made insulin dose adjustments based on A1c but included only 37 participants. The study protocol indicated that researchers should reduce the basal dose by 20% for those with an A1c less than or equal to 8%.⁸

In the MDI Liraglutide Trial (N = 124), the insulin adjustments were based on FBGs and PPGs . When fasting values were less than 90 mg/dL or participants had nocturnal hypoglycemia, the researchers reduced the basal dose by 20% to 40%. If the fasting values were 90 to 126 mg/dL, the researchers reduced the basal doses by 20% to 30%. The researchers did not adjust the basal insulin dose if fasting glucose levels were above 126 mg/dL. If they found the patient’s pre-meal glucose value to be less than 126 mg/dL, they reduced the bolus dose of the prior meal by 10% to 20%. If participants experienced daytime hypoglycemia, the researchers reduced the bolus dose of the preceding meal by more than 20%.⁹

The UTSMC study protocol reduced insulin doses by 20% if the A1c was less than or equal to 8%. The investigators did not adjust the insulin dose if the A1c was greater than 8%. They did not define the specific bolus and basal insulin dose adjustments.¹⁰

The TRANSITION2D study (N = 60) reviewed insulin deintensification with once weekly semaglutide.¹¹ These researchers transitioned patients who were reasonably well controlled (A1c 7.5% or less) from bolus insulin to a GLP-1 RA (semaglutide) in a one-step approach. They discontinued bolus insulin upon initiating semaglutide, then titrated the semaglutide dose.¹¹ A limitation to real-world applicability was that less than 25% of the participants were on 80 to 120 units of insulin per day.¹¹ Concerns in the real world would be a lack of tolerance to semaglutide or lack of follow-up on the patients’ behalf, as this would lead to hyperglycemia. Also, shared decision making between the patient/provider would first need to optimize glycemic control using insulin dose adjustments to reduce the risk of hyperglycemia/diabetic ketoacidosis (DKA)/hyperosmolar hyperglycemic state (HHS).

Traditional insulin dosing guidance and these studies show that insulin dose adjustments can vary widely from 10% to 40%. One path isn’t necessarily correct as adjusting insulin doses is an art of sorts.

HYPOGLYCEMIA TREATMENT

Accounting for and incorporating historical patient-specific parameters helps minimize the risk of hypoglycemia. Patient education regarding appropriate identification, treatment, and prevention of recurrence is paramount for safety. Common hypoglycemia symptoms are hunger, difficulty concentrating, headache, shakiness, sweating, and irritability. The 15-15 Rule advises patients with low blood sugar, defined as less than 70 mg/dL, to consume 15 g of carbohydrates and then wait 15 minutes to recheck the SMBG. Options to increase the blood sugar are 4 ounces of regular juice or non-diet soda, 1 tablespoon of sugar, honey, or syrup, 3 to 4 glucose tablets, or 1 dose glucose gel.¹²It is important to know that glucose tablets and gel are available without a prescription. Most patients know that if they experience hypoglycemia, they should eat something sweet. However, without following the treatment/prevention steps, patients may experience additional concerns. Table 1 describes appropriate action steps.

Table 1. Action Steps to Address Hypoglycemia¹³

Appropriate step	Assessment questions
Patients must check initial and subsequent glucose values to have objective data	What values did you see when you checked your blood sugar?
Initial treatment should consist of 15 grams of simple carbohydrates for the quickest improvement of hypoglycemia symptoms. Of note, treatment with complex carbohydrates or carbohydrates + protein/fat* will delay the improvement of hypoglycemia symptoms.	What food/drink/treatment option did you initially use to address the low blood sugar?
Overtreatment with more than 15 grams of carbohydrates leads to overcorrection (hyperglycemia)	How much of the food/drink/treatment option did you initially use to address the low blood sugar?
After consuming a simple carbohydrate, the patient should consume a complex carbohydrate + protein pairing, to prevent hypoglycemia from recurring within two hours	Once the blood sugar returned to a safe range, what did you eat to keep the blood sugar steady?

^*Examples of complex carbohydrates (wheat/corn/peas/potatoes/fruit) and carbohydrates + protein/fat (apple + peanut butter/pizza/candy bar)

NEWER THERAPIES

As this activity discusses newer therapies, new information is consistently being learned. To provide comprehensive and current or guideline-directed care, these must be a part of the patient assistance process. Some patients have strong feelings for or against newer therapies, so it is helpful to be able to provide the information in a non-biased manner.

SGLT-2 Inhibitors

SGLT-2 inhibitors increase urinary excretion of excess glucose and thus can increase the risk of genitourinary infections such as yeast infections and urinary tract infections. This class of medications also has significant long-term cardiorenal benefits.¹⁴ Optimization of these medications would also be ideal, especially when affordable, to reduce the need for insulin.

Although this CE activity’s focus is to review insulin dosing adjustments when introducing concurrent GLP-1 RA and GIP/GLP-1 RA dose adjustments, clinicians can apply some of the same practices when adjusting other medications, such as SGLT2-inhibitors.

GLP-1 RAs

The FDA approved the first GLP-1 RA, exenatide, in 2005, and patients needed to inject it twice daily.¹⁵Now, patients can inject GLP-1 RAs daily or weekly. In 2019, the FDA approved the first non-injectable GLP-1 RA, oral semaglutide (Rybelsus).¹⁵Additionally, this group of medications provides cardiorenal protective effects and weight loss.¹⁶Common ADRs are gastrointestinal intolerances such as nausea, upset stomach, constipation, and vomiting.¹⁶

Semaglutide is the most effective medication in this class from a glycemic management perspective.¹⁶ Dulaglutide, liraglutide, and exenatide are the most tolerated in this class; however, of these options dulaglutide is the most effective.¹⁶ Before these newer DM medications were available, the commonly utilized PPG-lowering options were metformin, sulfonylureas, bolus insulin, and mixed insulin. Of those, metformin is the only one that does not increase risk of hypoglycemia.

GIP/GLP-1 RAs

GIP/GLP-1 RAs have a dual hormonal activation that promotes satiety, slows digestion, and reduces hunger. Common ADRs are similar to that of GLP1-RAs but even though tirzepatide is more potent at improving glycemic control than semaglutide, it is also better tolerated.¹⁶ Currently, the FDA has approved tirzepatide as the only medication in this class. Additionally, despite the dual activation, patients tend to tolerate tirzepatide better than some GLP-1 RAs based on anecdotal experience. Tirzepatide also provides cardiorenal protective effects.¹⁷

Combination basal insulin + GLP-1 RA medications

Currently, the FDA has approved two fixed-ratio combinations (FRC) of basal insulin/GLP-1 RA: insulin degludec/liraglutide, also known as iDeglira (Xultophy), and insulin glargine/lixisenatide, also known as iGlarlixi (Suliqua).¹⁸ These medications have a fixed level of a basal insulin and a once daily GLP-1 RA combined into a single pre-filled pen. Insulin has no maximum daily limit but the GLP-1 RAs do. Thus (because these products are fixed ratios combinations) the maximum daily GLP-1 RA dose limits the daily insulin dose in FRCs.¹⁹ The dosing is based on units of the insulin component.

For example, each unit of iDeglira contains 1 unit of insulin and 0.036 units of liraglutide.²⁰ The maximum dose is 50 units, which contains 50 units of insulin degludec and 1.8 mg of liraglutide (liraglutide's maximum daily dose). The manufacturer advises patients who are insulin and GLP-1 RA naïve to start at 10 units daily, whereas those that are currently on basal insulin can start at 16 units daily.¹²

IGlarlixi is available in the United States as Soliqua 100/33, indicating that there is 0.33 mg of lixisenatide for every unit of insulin glargine. The maximum dosage of iGlarlixi is 60 units; however, this is based on the lixisenatide daily maximum of 20 mcg. Those transitioning from less than 30 units of basal insulin would be started on 15 units of iGlarlixi. For those between 30 to 60 units of basal insulin, the starting dose would be 30 units of iGlarlixi.²¹

A study completed at the Diabetes Center of the Békés County Central Hospital in Hungary (N = 62) sought to review the safety and efficacy of switching well-managed patients with T2DM (A1c less than 7.5%) from basal/bolus insulin (low TDD) to insulin degludec/liraglutide combination.²⁰ The study defined low TDD as less than or equal to 70 units of insulin per day. The transition method was to stop the prior basal/bolus insulin regimen and to start 16 units of iDeglira. Then the FBGs were titrated to 90 to 108 mg/dL by increasing the iDeglira dose by 2 units every 3 days. The study continued or initiated metformin and titrated it up to 3000 mg (the maximum daily dose of metformin is higher in Hungary than in the United States). The intervention reduced the TDD from 43.3 units to 22.55 units, which was significant.²⁰

Theoretically, this is a wonderful way to reduce injection burden and optimize adherence.⁶ These medications’ clinical utility depends on the patient’s lifestyle patterns, insurance coverage, medication availability, and out-of-pocket cost. Depending on the patient, the fixed ratio dosing and once-daily dosing could be a benefit or a drawback. Patients who would like to minimize injection burden and can safely delay insulin may prefer a once weekly GLP-1 RA or GIP/GLP-1 RA injection. Having the ability to titrate basal insulin and a GLP-1 RA separately allows more dosing individualization, which leads to more patients achieving goal FBGs.²²

INTRODUCTION TO THE CASES

The rest of this activity focuses on case-based learning. For these cases, learners should assume that any information not provided is within normal limits, there is no change from baseline, or any change has been addressed. These cases derive from patients in a primary care setting, but this information can help in various settings. Also, due to the focus on insulin dose adjustments, the healthcare provider does not discuss the use of GLP-1 RAs or GIP/GLP-1 RAs for an indication of obesity. As obesity can co-exist with T2D, healthcare providers should monitor weight during initiation and titration of GLP-1 RAs or GIP/GLP-1 RAs.

CGMs have been more accessible in recent years, and they provide excellent graphic review of glycemic control. This learning experience uses glycemic charts. The charts depicted here would be gathered from a patient’s glucometer or SMBG log and commonly depict the last 14 days of glycemic control. Clinicians should crosscheck values from a SMBG log with the patient’s glucometer if they have concerns about inaccuracy. Each column that lists a glucose value specifies the timing with regard to meals; acB is before breakfast, acL is before lunch, acD is before dinner, and HS is at bedtime. During the initial pharmacist visit, pharmacists need to manage patients expectations and urge frequent testing because it allows for the safest insulin dose adjustments. It also ideally decreases the testing needs moving forward by limiting the patient’s insulin doses and frequency.

PAUSE AND PONDER: Thought Questions

Safety:

Is the patient tolerating the current regimen?
Is the patient experiencing any hypoglycemia?

Efficacy:

Is the current regimen helping the patient achieve glycemic goals?
What medication adjustments would help move the current glycemic patterns towards the goal?

CASE 1: Arya Brown–pronouns: he/him/his

Arya is a patient who presents for his first pharmacist visit. First, the pharmacist reviews the electronic medical record for Arya’s recent history.

Visit 1

Arya reported that he was doing well with dulaglutide 0.75 mg weekly and his current insulin glargine dose of 18 units daily. He reported that his appetite was more controlled, and he felt more energetic since starting dulaglutide. The patient was excited to increase the dose of dulaglutide.

The patient’s current SMBG log shows he checks his FBGs only sporadically, and they fall between 128 and 154 (average = 143), no hypoglycemia, and consistent values above goal. Based on the anticipated improvement of glycemic control throughout the day by increasing the dulaglutide dose to 1.5 mg weekly, the pharmacist started shared decision making to continue the current insulin glargine for now. The pharmacist asked the patient to check his blood sugars in the evening, either before dinner or at bedtime, to allow for further assessment of glycemic trends throughout the day. Arya verbalized understanding of this request, but reports that he will likely only check blood sugars once a day and therefore asked to alternate testing times.

Visit 2

Arya presented for his second pharmacist visit after his third dose of dulaglutide 1.5 mg. He said that his blood sugars were at goal and that he had slight but tolerable nausea with the current dulaglutide dose. He reported that the nausea improved since the first injection at this dose. The pharmacist and Arya discussed the option of maintaining the dulaglutide dose for the next prescription to allow additional time for tolerance. However, Arya prefers to increase it to dulaglutide 3 mg weekly with the next prescription after four doses of 1.5 mg have been taken. He indicates the symptoms have improved over time and are barely noticeable.

His current SMBGs show FBGs ranging from 128 to 141 (average = 135). Since his glycemic control is now closer to goal than previously, he will need to adjust insulin glargine dosing to minimize the risk of hypoglycemia. The risk of causing temporary hypoglycemia is higher than that of causing temporary hyperglycemia. Thus, the pharmacist decides to reduce the insulin dose by 6 units. This is a 33% insulin reduction.

Visit 3

At Arya’s third visit, he reports feeling nauseous and vomiting after injecting the second dose of dulaglutide 3 mg weekly. He says he vomited after the first dose and thought it may have been related to a food choice at that time. The vomiting improved after a couple of days, but it recurred after the second dose of dulaglutide 3 mg. The patient shows his glucometer for SMBGs as noted in Table 3.

Table 3. Arya Visit 3

Date	AcB	HS	HS dose (insulin glargine)	comment
			12 units
	134		12 units
		147	12 units
	136		12 units
			12 units
	124	149	12 units
			12 units	Dulaglutide 3 mg (dose 1)
			12 units
	117	146	12 units
			12 units
		137	12 units
	120		12 units
		131	12 units
	116		12 units	Dulaglutide 3 mg (dose 2)
		127	12 units
Visit 3			12 units
Average	125	140

The SMBGs indicate improved glycemic control. The pharmacist suggested that Arya’s ADRs seem intolerable. Arya agrees. He was amenable to stopping the dulaglutide 3 mg weekly and resuming the lower 1.5 mg weekly dose when his symptoms abate (at least a week after the last dose). Now the discussion turned to what insulin dose the patient should take with the lower dose of dulaglutide.

The patient’s prior glycemic control is a blueprint for patient specific response to insulin dose adjustments. Since Arya is returning to the 1.5 mg of dulaglutide weekly, and he has taken that dose before, the glycemic control information presented during visit 2 is helpful. The general takeaway is that his glycemic control was close to goal while on dulaglutide 1.5 mg weekly and insulin glargine 18 units daily. The pharmacist and the patient make a shared decision to adjust the insulin glargine to 20 units daily to move the patient’s glycemic control closer to goal.

They agree to re-try dulaglutide 3 mg weekly in the future if he tolerates the 1.5 mg weekly dose better over time. They also discuss the possibility of using a different GLP-1 RA or a GIP/GLP-1 RA, as tolerance between medications can vary.

CASE 2: Alex Devi–pronouns: they/them/theirs

Visit 1

Alex presented to their first pharmacist visit and reports that their insurance now covers tirzepatide for diabetes at a reasonable cost, so they would like to minimize MDI insulin regimen. The patient denies any contraindications to GIP/GLP-1 RA. The pharmacist tells Alex that they can adjust their insulin doses based on tolerance to tirzepatide, but there is no guarantee that insulin can be stopped.

Based on the current optimized glycemic control (Table 4), starting and titrating tirzepatide will necessitate insulin dose adjustments. They are currently injecting insulin degludec 36 units daily and insulin lispro 8 units with breakfast, 10 units with lunch, and 14 units with dinner. To limit the risk of hypoglycemia, the pharmacist and Alex planned to decrease doses and assess this specific patient’s response. As tirzepatide will primarily impact post-prandial glycemic control, and the patient is on a medication (insulin lispro) that can cause post-prandial hypoglycemia, the goal was to focus on bolus insulin reduction. In this case, glycemic control appears steady throughout the day. The pharmacist planned to reduce all prandial doses equally to allow blood sugars to rise throughout the day and let the full effect of tirzepatide occur while limiting hypoglycemia due to insulin. Due to tirzepatide’s potency as a dual GIP/GLP-1 RA and Alex’s current glycemic control, they will reduce the insulin lispro dose by 4 units per meal. Thus, the patient’s total daily insulin dose was reduced by 12 units per day, an 18% reduction in TDD of insulin.

Table 4. Alex Visit 1

Date	acB	acB dose (insulin lispro)	acL	acL dose (insulin lispro)	acD	acD dose (insulin lispro)	HS	HS dose (insulin degludec U100)	Notes
	117	8	109	10	137	14	171	36 units
	93	8	129	10	128	14	161	36 units
	107	8	91	10	145	14	127	36 units
	126	8	79	10	141	14	152	36 units
	93	8	133	10	147	14	131	36 units
	82	8	121	10	124	14	170	36 units
	107	8	132	10	128	14	160	36 units
	112	8	125	10	111	14	165	36 units
	105	8	89	10	147	14	170	36 units
	77	8	96	10	133	14	130	36 units
	108	8	111	10	91	14	146	36 units
	92	8	103	10	113	14	164	36 units
	97	8	110	10	118	14	151	36 units
	101	8	89	10	97	14	132	36 units
	122	8	131	10	121	14	130	36 units
Visit 1	104	8	125	10				36 units	Start tirzepatide 2.5 mg
Average	103		111		125		151

Visit 2

Table 5 summarizes Alex’s glycemic control when they returned for their second appointment. The pharmacist looks for trends and sees that the blood sugar averages appear to be lowest pre-dinner and then highest at bedtime. A potential concern is that Alex may overeat at dinnertime as a response to rapidly decreasing blood sugars between lunch and dinner. Alex denies any hypoglycemia symptoms or adverse effects from tirzepatide. They just finished the fourth dose of tirzepatide 2.5 mg and are interested in increasing the dose. To increase tirzepatide, the pharmacist used the information gathered to minimize the patient’s insulin intake. Based on the response and current SMBGs, roughly 4 units is an appropriate dose reduction per meal. Logistically, this would eliminate the breakfast insulin, reduce the lunchtime dose to 2 units, and reduce the dinnertime insulin dose to 6 units. The pharmacist needs to evaluate the lunchtime dose of 2 units further. For someone with T2D, 2 units is a minimal dose of insulin. The actual effect is questionable, especially in this individual, where another medication is being titrated up.

Table 5. Alex Visit 2

Date	acB	acB dose (insulin lispro)	acL	acL dose (insulin lispro)	acD	acD dose (insulin lispro)	HS	HS dose (insulin degludec U-100)	Notes
	113	4	95	6	79	10	150	36 units
	79	4	122	6	91	10	139	36 units
	107	4	107	6	113	10	162	36 units
	102	4	125	6	91	10	172	36 units
	104	4	118	6	99	10	164	36 units	tirzepatide 2.5 mg (Dose 3)
	81	4	118	6	81	10	156	36 units
	120	4	102	6	101	10	158	36 units
	85	4	123	6	75	10	169	36 units
	77	4	127	6	79	10	168	36 units
	84	4	108	6	103	10	126	36 units
	111	4	89	6	79	10	139	36 units
	112	4	115	6	92	10	140	36 units	tirzepatide 2.5 mg (Dose 4)
	87	4	87	6	101	10	174	36 units
	73	4	102	6	76	10	139	36 units
	85	4	127	6	98	10	163	36 units
Visit 2	107	4						36 units
Average	95		111		91		155

Reviewing the pre-dinner glycemic values (the lowest throughout the day) and eliminating the lunchtime insulin dose would help reduce the risk of hypoglycemia. Thus, the consensus was to eliminate the breakfast and lunchtime insulin doses while reducing the dinner time dose to 6 units. Therefore, they decided to reduce the patient’s total daily insulin dose by 14 units, a 25% reduction in TDD of insulin. The pharmacist advised the patient that he can skip testing his SMBG before lunch as he is not injecting a bolus insulin at that time.

Visit 3

Alex presented for their third appointment and denies any adverse effects with tirzepatide 5 mg weekly. Alex was happy with reducing injection burden from four times a day to twice a day! They reported they have lost some weight. They have also increased activity slightly and are planning to make that a priority in the upcoming month. They would like to continue titrating tirzepatide when able. Looking at current glycemic values (Table 6), the adjustments made at the last visit stabilized control again.

Table 6. Alex Visit 3

Date	acB	acB dose (insulin lispro)	acD	acD dose (insulin lispro)	HS	HS dose (insulin degludec U100)	Notes
	110	0	111	6	115	36 units
	119	0	106	6	132	36 units
	133	0	129	6	96	36 units
	126	0	100	6	99	36 units
	126	0	99	6	151	36 units	tirzepatide 5 mg (Dose 2)
	118	0	111	6	97	36 units
	130	0	110	6	124	36 units
	112	0	131	6	149	36 units
	134	0	106	6	144	36 units
	99	0	105	6	103	36 units
	97	0	117	6	154	36 units
	98	0	111	6	153	36 units	tirzepatide 5 mg (Dose 3)
	115	0	121	6	141	36 units
	119	0	96	6	129	36 units
	122	0	98	6	154	36 units
Visit 3	102	0				36 units
Average	116		110		129

Based on this patient’s previous responses, it seems that the insulin dose should be reduced by about 12 to 14 units of insulin to accommodate the tirzepatide dose increase. Additionally, due to Alex’s anticipated activity change, they may need to reduce the total daily insulin dose further. The pharmacist can help reduce the injection burden by eliminating the dinnertime dose of insulin lispro. Next, the basal dose needs to be adjusted. There is room for discussion, based on the factors noted (current glycemic control, planned activity changes, and dose increase of tirzepatide). To limit the risk of hypoglycemia, they decide to reduce insulin degludec from 36 units to 26 units. This is a reduction of 16 units of insulin. They could have reduced the patient’s basal dose to accommodate everything except the activity change if it was unclear that they were planning to make a change soon.

All plans must be patient-specific, and with this discussion, the patient is reliable and was waiting to change their activity once this discussion occurred. For other patients who are not as clear that they are planning a change, the pharmacist could advise reducing the basal insulin dose to approximately 30 units daily for now and then communicate with the clinic when they make the change for review of SMBGs to allow for additional adjustments.

CASE 3: Zephyr Hernandez–pronouns: she/her/hers

Visit 1

Zephyr’s provider referred her to the pharmacist because her A1c was above goal and she was experiencing hypoglycemic episodes. From a complete assessment of the patient’s medication and lifestyle routine, it appeared that the patient’s mealtimes were inconsistent. Zephyr indicated her schedule dictates whether she can eat breakfast and/or lunch, but that she tries to eat dinner consistently. She injects insulin aspart protamine/insulin aspart 70/30 mix, 24 units in the morning and 30 units in the evening. Based on Zephyr’s readings (Table 7), she has hypoglycemia before dinner when she skips lunch. She treats the hypoglycemia with soda or candy. The patient says she skips her breakfast mixed insulin dose when she skips breakfast but then ends up with hyperglycemia pre-dinner.

Table 7. Zephyr Visit 1

Date	acB	acB dose (insulin aspart protamine/insulin aspart 70/30 mix)	acL	acD	acD dose (insulin aspart protamine/insulin aspart 70/30 mix)	HS	Notes
	123	24	122	113	30	137
	134	24	106	78	30	257	skipped lunch
	88	24	114	112	30	118
	159	24	109	76	30	188	skipped lunch
	76	24	121	111	30	123
	118	0	156	187	30	187	skipped breakfast
	123	0	164	190	30	128	skipped breakfast
	139	24	116	106	30	164
	95	24	96	68	30	196	skipped lunch
	113	24	107	102	30	141
	117	24	120	109	30	186
	159	0	145	189	30	145	skipped breakfast
	149	24	132	72	30	179	skipped lunch
	117	24	127	109	30	125
	107	24	114	79	30	212	skipped lunch
Visit 1	96	0	163				skipped breakfast
Average	120		126	113		166

During the visit, the pharmacist and Zephyr reviewed the 15-15 Rule for identifying and treating hypoglycemia. They also discussed the fact that mixed insulin, unfortunately, does not allow mealtime flexibility due to the fixed ratio. The patient says she will try to maintain steady mealtimes and portions. She also asked to try a medication like semaglutide and has no contraindications.

The pharmacist explained that the first dose of semaglutide is a tolerance dose and is not expected to have a significant clinical impact. Transitioning to an MDI insulin regimen would help stabilize blood sugars, minimize hypoglycemia, and provide insulin dosing flexibility. However, Zephyr preferred not to switch insulin to MDI insulin at this time. She stated she will focus on having consistent meals instead. Based on her preference, they adjusted the current insulin regimen to reduce the risk of hypoglycemia. The pharmacist advised her to reduce the insulin aspart protamine/insulin aspart 70/30 morning dose to 20 units, the evening dose to 26 units, and to start semaglutide 0.25 mg weekly.

Visit 2

At the second visit, Zephyr reported that she could not maintain steady meal times despite her efforts. She initially reduced her insulin doses as requested, but once she realized she couldn’t maintain steady mealtimes, she resumed her previous dosing. Therefore, her current SMBG values closely resemble her last visits' values (Table 7). The pharmacist advised Zephyr to communicate questions, concerns, and changes to the clinic in between appointments moving forward. As Zephyr was unable to maintain steady meal choices, she couldn’t safely remain on mixed insulin due to safety concerns.

Consequently, the pharmacist talked with Zephyr about two options based on her goal to increase the semaglutide dose to 0.5 mg weekly. One option would be to transition to basal/bolus insulin (administered TID or QID), but the patient previously rejected this option. An alternative option (dependent on the patient’s prandial insulin dose) would be to transition the patient to basal-only insulin and eliminate prandial insulin. This option creates a risk of hyperglycemia until the semaglutide doses can be titrated. Thus, periodic clinical assessment of hyperglycemia would be critical. DKA and HHS are a concern with significantly elevated blood sugars. Still, temporary elevations in the high 100s to low 200s may be acceptable if the patient is not safe or willing to take alternate recommended options.

After this review, Zephyr stated she cannot tolerate more than two insulin injections a day. They decided to transition Zephyr to once daily basal insulin and then a bolus insulin with dinner, as that is her largest and most consistent meal of the day. Based on her current regimen, she was injecting 37.8 units of basal insulin and 16.2 units of prandial insulin per day. She could transition to a bolus insulin dose of 4 to 8 units and a basal dose of 34 to 38 units with a goal of a total insulin dose of 42 units per day (~22% reduction from the prior TDD). Eliminating the prandial insulin would be risky. Dependent on Zephyr’s motivation, ability to tolerate semaglutide, and attention to portion sizes and SMBGs, she may do well without any prandial insulin.

Semaglutide does not require set mealtimes or portions for safety. The pharmacist believed that with time, the patient would do well on basal insulin + semaglutide at higher doses, if tolerated. Sometimes, this interim period is the toughest for clinical decision-making.

CASE 4: Sahar Kim–pronouns: they/them/theirs

Visit 1

Sahar presented for their first visit, reporting that despite their FBGs being at goal, their A1c has been above goal. The insurance company did not cover their CGM so the pharmacist asked Sahar to test SMBGs more frequently. They sporadically checked, when possible, at the day's beginning or end (Table 8).

They were currently prescribed insulin glargine-yfgn (Semglee), which is a biosimilar to insulin glargine (Lantus), and inject 52 units once daily. The SMBG chart indicates FBGs of 80 to 100 mg/dL, and bedtime values are in the high 100s to low 200s.

Table 8. Sahar Visit 1

Date	acB	HS	HS insulin (insulin glargine-yfgn)
	78	198	52
	89		52
		201	52
	123	188	52
	111		52
			52
	97	187	52
	79		52
		210	52
	83	218	52
	98		52
		189	52
	109		52
		186	52
	87	199	52
Visit 1	98		52
Average	96	197

PAUSE AND PONDER: What would be the appropriate term for this situation regarding glycemic control/treatment?

Sahar declined an oral medication, as they have trouble swallowing them. They were amenable to an alternate once daily injection, as they would prefer not to have more than one injection daily. Sahar and the pharmacist deemed that an FRC would be the preferred option due to overbasalization and the patient’s preference to minimize injections. After some investigation into insurance coverage and discussion, they determined that iGlarlixi would be reasonable.

The pharmacist started Sahar on 30 units of iGlarlixi daily, which equates to 30 units of insulin glargine and 10 mcg of lixisenatide. Additionally, they were previously injecting at bedtime, but the FDA-approved labeling recommends morning dosing of iGlarlixi.²¹ Sahar reported that they will not be able to attend the next appointment (intended to be in approximately 2 weeks) or speak on the phone for the next 6 weeks. As they have been reliable and this was a transitional period in their treatment, the pharmacist developed a self-adjustment dosing plan. The pharmacist advised Sahar to increase iGlarlixi by 2 units once a week (up to 42 units daily) for each week that all their FBGS are greater than 130 mg/dL.

Visit 2

Sahar returned 6 weeks later and indicates that they increased iGlarlixi to 42 units over time based on the guidance the pharmacist provided at the last visit. They denied any ADRs (including hypoglycemia) associated with the FRC. A review of SMBGs shows stabilization between morning and bedtime values, indicating that the bedtime values have come down and the FBGs have increased. Although the FBG average is above 136, the trend shows decreasing FBGs over the last week or so. Through shared decision-making, Sahar and the pharmacist decided to maintain the current dose. The pharmacist expects to see an improvement in the A1c based on this improved PPG control. This is because although FBG and HS readings are being tested for ease, the improvement in HS readings indicates an improvement in PPGs.

TAKEAWAYS

We’ve reviewed many situations where insulin still plays a significant role in diabetes care. The advent of newer medications and greater coverage and affordability require a balance between new and old therapies to maximize the benefits and minimize the risks of both. Many medications for diabetes or coexisting obesity and diabetes (diabesity) are in the pipeline. This balance of optimal medication management will continue to change as the FDA approves new medications for diabetes.

Patient safety, especially prevention of hypoglycemia, is paramount in insulin dose adjustments, but monitoring and education regarding side effects is a close second. The pharmacist will need to adjust the dose or medication if there is a safety risk. Especially with the positive benefits associated with GLP-1 RAs, some patients may want to tolerate the adverse effects or hope they improve.

While these cases are extrapolated from the ambulatory care perspective, this knowledge can be helpful in a variety of settings. For example, pharmacists can use the principles discussed here for people obtaining their medications in the retail setting or those in the process of being titrated who are then hospitalized.

The Art of Insulin Dose Adjustments in the Setting of GLP-1 RAs and GIP/GLP-1 RAs
Pharmacist Post-test
25-059 P

After completing this continuing education activity, pharmacists will be able to:
1. Describe different types of insulin along with their appropriate use
2. Recall newer non-insulin medications for diabetes, along with risks vs. benefits
3. Analyze patient reported data pertaining to insulin + GLP-1 RA and GIP/GLP-1 RA medication adjustments
4. Demonstrate medication adjustment recommendations while incorporating patient-specific data

1. Which of the following situations is most appropriate for using mixed insulin?
A. A patient who intermittently fasts and eats around lunch and dinnertime.
B. A patient who eats three meals a day and two snacks.
C. A patient who eats snack size portions throughout the day.

2. Austin is a 46-year-old patient who is newly diagnosed with type 2 diabetes. Their initial A1c is 11% and they are working through the diabetes self-management education and support (DSMES) classes. They are open to starting insulin to help improve glycemic control in the interim until their lifestyle changes can be implemented. Their current weight is 64 kg or 141 lbs. What would be the best medication option to initiate?
A. 10 units of insulin glargine daily
B. 20 units of insulin glargine daily
C. 10 units of insulin aspart three times daily

3. Which of the following medications is most likely to cause a yeast infection?
A. Bexagliflozin
B. Sitagliptin
C. Liraglutide

4. Which of the following is an oral GLP-1 RA?
A. Semaglutide (Ozempic)
B. Semaglutide (Rybelsus)
C. Dulaglutide (Trulicity)

5. Which combination of medication classes should not be used together?
A. GLP-1 RA + SGLT-2 inhibitor
B. GLP-1 RA + DPP-4 inhibitor
C. Basal insulin + SGLT-2 inhibitor

6. Which of the following SMBG trends could be described as overbasalization?
A. FBG: 120s, HS: 150s
B. FBG: 160s, HS: 180s
C. FBG: 80s, HS: 160s

7. Autumn has been taking metformin 1000 mg BID for years and recently her A1c has increased to 8.7%. Her FBGs average 162 and her bedtime values average 210s. She has never used a GLP-1 RA or insulin. Of the options listed which would be the simplest and safest next step for the patient?
A. IDeglira 10 units daily
B. Glipizide 10 mg BID
C. Insulin lispro 10 units TID with meals

8. August is a 36-year-old patient. He reports he is tolerating the side effects he is experiencing with dulaglutide 3 mg weekly but is not comfortable increasing the dose just yet. He is also taking insulin glargine 32 units daily and his FBGs average 170. Which of the following is the next best step?
A. Increase the insulin dose
B. Stop the insulin
C. Reduce the insulin dose

9. April is a 59-year-old, 66 kg patient who has had more energy for the day since starting injectable semaglutide. She is currently injecting semaglutide 1 mg weekly and is excited to increase to 2 mg weekly as she has not experienced side effects. She reports that she has enough energy to begin participating in dance class twice a week. She is currently injecting insulin degludec 8 units daily and her FBGs are between 80-100. Which of the following is the next best step?
A. Increase the insulin dose
B. Stop the insulin
C. Reduce the insulin dose

10. Andrew is a 42-year-old patient who is currently taking insulin glargine 50 units daily and is excited to begin tirzepatide 2.5 mg weekly. His FBGs are in the 140s. The patient will continue the current insulin dose while starting tirzepatide. A few weeks later the patient communicates that his blood sugars have decreased to the 70s and 80s, and he is feeling shaky consistently with these values. What would be the next step be?
A. Increase the insulin dose
B. Stop insulin
C. Reduce the insulin dose

The Art of Insulin Dose Adjustments in the Setting of GLP-1 RAs and GIP/GLP-1 RAs
Pharmacy Technician Post-test
25-059 T

After completing this continuing education activity, pharmacy technicians will be able to
1. Describe different types of insulin along with their appropriate use
2. Recognize over the counter treatment options for hypoglycemia
3. Recall newer non-insulin medications for diabetes, along with risks and benefits
4. Identify when to refer patients with questions about their diabetes medications to the pharmacist

1. Which of the following is a bolus insulin?
A. Insulin aspart
B. Insulin glargine
C. Insulin aspart protamine/insulin aspart

2. Which of the following is a mixed insulin?
A. Insulin lispro
B. Insulin lispro protamine/insulin lispro
C. Insulin degludec

3. Which of the following insulins works at steady levels throughout the day?
A. Insulin degludec U200
B. Insulin lispro
C. Insulin regular U500

4. Which of the following is an oral GLP-1 RA?
A. Semaglutide (Ozempic)
B. Semaglutide (Rybelsus)
C. Dulaglutide (Trulicity)

5. How are oral glucose tablets and oral glucose gel categorized as medications?
A. Prescription
B. Behind the counter
C. Over the counter

6. August comes to the pharmacy to pick up his medications regularly. As a retail pharmacy technician, you’ve noticed that he is purchasing glucose tablets more frequently than before, and he has also had medication changes recently . What would be the next best step?
A. Mind your own business, it’s their choice to purchase what they would like.
B. Make the pharmacist aware and ask the patient if they would be open to having a consultation with the pharmacist.
C. Advise the patient that their medication is causing low blood sugars, and they should stop taking it.

7. You’re a medication reconciliation technician in a primary care clinic. While reviewing the patient’s medications you see they are taking antibiotics again as they were a couple months prior. With further discussion you learn that they have had multiple urinary tract infections in the last year. Which of the following medications is most likely to cause urinary tract infections?
A. Bexagliflozin
B. Sitagliptin
C. Liraglutide

8. While working as a retail pharmacy technician and checking out a patient, you notice that they look nauseous. With discussion you learn that the last time they ate was yesterday morning. You see that their tirzepatide dose was increased. What would be the next best step?
A. Advise the patient to try this new ginger supplement you’ve found to help with the nausea and then check the patient out.
B. Assume they’ll talk about the medication with their provider, wish them well, provide them with their new prescription, and take the next patient
C. Ask the pharmacist to complete further assessment because you have concern that the higher dose of tirzepatide warrants review.

9. You’re a medicine reconciliation technician in the emergency room, and the patient is being evaluated for significant nausea and vomiting. Which of the following medications is associated with these adverse effects?
A. Ertugliflozin
B. Semaglutide
C. Insulin glargine

10. You’re a retail pharmacy technician, and a patient is picking up a new prescription for dulaglutide 3 mg weekly along with their insulin degludec 56 units daily. They were previously prescribed dulaglutide 1.5 mg weekly and insulin degludec 68 units daily. The patient tells you that they plan on continuing the insulin degludec 68 units daily despite increasing the dulaglutide dose.
A. Advise the patient that the choice is between them and their doctor.
B. Check the patient out.
C. Seek consultation from the pharmacist.

1. Van Dril E, Allison M, Schumacher C. Deprescribing in type 2 diabetes and cardiovascular disease: Recommendations for safe and effective initiation of glucagon-like peptide-1 receptor agonists in patients on insulin therapy. Am Heart J Plus. 2022;17:100163. doi:10.1016/j.ahjo.2022.100163
2. ElSayed NA, McCoy RG, Aleppo G, et al. 2. Diagnosis and Classification of diabetes: Standards of Care in Diabetes—2025. Diabetes Care. 2024;48(Supplement_1):S27-S49. doi:10.2337/dc25-s002
3. ElSayed NA, McCoy RG, Aleppo G, et al. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2025. Diabetes Care. 2024;48(Supplement_1):S128-S145. doi:10.2337/dc25-s006
4. ElSayed NA, McCoy RG, Aleppo G, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025. Diabetes Care. 2024;48(Supplement_1):S181-S206. doi:10.2337/dc25-s009
5. Chun J, Strong J, Urquhart S. Insulin Initiation and Titration in Patients With Type 2 Diabetes. Diabetes Spectr. 2019;32(2):104-111. doi:10.2337/ds18-0005
6. Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update [published correction appears in Endocr Pract. 2023 Jan;29(1):80-81. doi: 10.1016/j.eprac.2022.12.005.]. Endocr Pract. 2022;28(10):923-1049. doi:10.1016/j.eprac.2022.08.002
7. Champion M, Wills Avila G, Garcia AE, Álvarez Delgado FM, Valdez CA. Impact of Initiating a GLP1 Agonist and/or SGLT2 Inhibitor Therapy on De-Escalation and Discontinuation of Insulin and Diabetes Control When Managed by an Interprofessional Collaborative Team. J Prim Care Community Health. 2024;15:21501319241231398. doi:10.1177/21501319241231398
8. Lane W, Weinrib S, Rappaport J, Hale C. The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial. Diabetes Obes Metab. 2014;16(9):827-832. doi:10.1111/dom.12286
9. Lind M, Hirsch IB, Tuomilehto J, et al. Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections: randomised clinical trial (MDI Liraglutide trial). BMJ. 2015;351:h5364. doi:10.1136/bmj.h5364
10. Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose Insulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016;176(7):939-947. doi:10.1001/jamainternmed.2016.1540
11. Rodriguez P, Breslaw N, Xiao H, et al. De-intensification of basal-bolus therapy by replacing prandial insulin with once-weekly subcutaneous semaglutide in individuals with well-controlled type 2 diabetes: A single-centre, open-label randomised trial (TRANSITION-T2D). Diabetes Obes Metab. 2025;27(2):642-651. doi:10.1111/dom.16057
12.Online Xultophy. Novo Nordisk Inc. Accessed June 1, 2025. https://www.novo-pi.com/xultophy10036.pdf
13. Treatment of low blood sugar (Hypoglycemia). Diabetes. Published May 15, 2024. https://www.cdc.gov/diabetes/treatment/treatment-low-blood-sugar-hypoglycemia.html
14. Vallon V, Verma S. Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. Annu Rev Physiol. 2021;83:503-528. doi:10.1146/annurev-physiol-031620-095920
15. Latif W, Lambrinos KJ, Patel P, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs). In: StatPearls. Treasure Island (FL): StatPearls Publishing; February 25, 2024.
16. Yao H, Zhang A, Li D, et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ. 2024;384:e076410. doi:10.1136/bmj-2023-076410
17. Nauck MA, Müller TD. Incretin hormones and type 2 diabetes. Diabetologia. 2023;66(10):1780-1795. doi:10.1007/s00125-023-05956-x
18. McGill JB, Hirsch IB, Parkin CG, Aleppo G, Levy CJ, Gavin JR 3rd. The Current and Future Role of Insulin Therapy in the Management of Type 2 Diabetes: A Narrative Review. Diabetes Ther. 2024;15(5):1085-1098. doi:10.1007/s13300-024-01569-8
19. Tramunt B, Disse E, Chevalier N, et al. Initiation of the Fixed Combination IDegLira in Patients with Type 2 Diabetes on Prior Injectable Therapy: Insights from the EASY French Real-World Study. Diabetes Ther. 2022;13(11-12):1947-1963. doi:10.1007/s13300-022-01327-8
20. Taybani Z, Bótyik B, Katkó M, Gyimesi A, Várkonyi T. Simplifying Complex Insulin Regimens While Preserving Good Glycemic Control in Type 2 Diabetes. Diabetes Ther. 2019;10(5):1869-1878. doi:10.1007/s13300-019-0673-8
22. Candido R, Nicolucci A, Larosa M, Rossi MC, Napoli R; RESTORE-G (Retrospective analysis on the therapeutic approaches after GLP-1 RA treatment in type 2 diabetes patients) Study Group. Treatment intensification following glucagon-like peptide-1 receptor agonist in type 2 diabetes: Comparative effectiveness analyses between free vs. fixed combination of GLP-1 RA and basal insulin. RESTORE-G real-world study. Nutr Metab Cardiovasc Dis. 2024;34(8):1846-1853. doi:10.1016/j.numecd.2024.03.023
21. Online Soliqua. Prescribing Information. Sanofi-Aventis U.S. LLC. Accessed June 1, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208673s000lbl.pdf

Henry A. Palmer CE Finale, LIVE December 19, 2025

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 activities:

ACPE UAN 0009-0000-25-062-L03-P

ACPE UAN 0009-0000-25-063-L99-P

ACPE UAN 0009-0000-25-064-L01-P

ACPE UAN 0009-0000-25-065-L01-P

ACPE UAN 0009-0000-25-066-L05-P

ACPE UAN 0009-0000-25-067-L01-P

ACPE UAN 0009-0000-25-068-L01-P

ACPE UAN 0009-0000-25-069-L06-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.

Faculty

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

Jennifer Luciano, PharmD, Director of Office of Experiential Education, University of Connecticut School of Pharmacy, Storrs, CT

William L. Baker, PharmD, FCCP, FACC, FHFSA, Clinical Professor, University of Connecticut School of Pharmacy, Storrs, CT

Devra Dang, PharmD, CDCES, FNAP, Clinical Professor, University of Connecticut School of Pharmacy, Storrs, CT

Michael White, PharmD, FCP, FCCP, FASHP, Distinguished Professor and Chair, Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT

Kelsey Giara, PharmD, University of Connecticut School of Pharmacy, Storrs, CT

Kristin Waters, PharmD, BCPS, BCPP, Assistant Clinical Professor, University of Connecticut School of Pharmacy, Storrs, CT

Jeff Aeschlimann, PharmD, University of Connecticut School of Pharmacy, Storrs, CT

HANDOUTS for Presentations

8:10 - 9:10 a.m. – LAW: Identifying Imposters: Counterfeit Drugs in the Pharmacy Distribution Chain

2 Slides per page

6 Slides per page

9:15 - 10:15 a.m. – Step by Step: Tackling Imposter Syndrome in Every Transition

2 Slides per page

6 Slides per page

10:20-11:20 a.m. – NKOTB: 2025 Updates on Management of Hypertension in Adults

2 Slides per page

6 Slides per page

11:25-12:25 p.m. - NKOTB: New and Emerging Roles for GLP-1-Based Medications

2 Slides per page color graphs

2 Slides per page black and white

6 Slides per page color graphs

6 Slides per page black and white

12:45-1:45 p.m. – PATIENT SAFETY: Biosimilar Doppelgangers

2 Slides per page

6 Slides per page

1:50-2:50 p.m. – Hormone Therapy’s Twin Faces: Sorting Science from Misconception

2 Slides per page

6 Slides per page

2:55-3:55 p.m. – Breaking the Mold: Novel Mechanisms in Psychiatry’s New Kids on the Block

2 Slides per page

6 Slides per page

4:00-5:00 p.m. – IMMUNIZATION: Mountebanks, Grifters, and Frauds (Oh My!): An Update on the Management of Vaccine-Preventable Illnesses in 2025

2 Slides per page

6 Slides per page

7:30-8:00 a.m. - Registration and Check-In/Sign-In

8:00-8:05 a.m. - Opening Remarks- Philip M. Hritcko, Dean and Clinical Professor, University of Connecticut School of Pharmacy

8:05-8:10 a.m. – Operational Instructions- Jeannette Y. Wick, RPh, MBA, Director of the Office of Professional Pharmacy Development, University of Connecticut School of Pharmacy, Storrs, CT

8:10 - 9:10 a.m. – LAW: Identifying Imposters: Counterfeit Drugs in the Pharmacy Distribution Chain

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

0009-0000-25-062-L03-P (0.1 CEU or 1 contact hour) (Application-based)