Patient Safety: Medication Refusal: Understanding the Why “They Just Say No”

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

Recognize and define types and leading causes of treatment/medication refusal

Describe the ethical and legal principles associated with medication refusal, covert medication, and surreptitious prescribing

Determine treatment alternatives for patients with dietary, religious, or other restrictions

Identify and implement key components of a medication refusal protocol

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

Recognize and define types and leading causes of treatment/medication refusal

Describe the ethical and legal principles associated with medication refusal, covert medication, and surreptitious prescribing

Determine treatment alternatives for patients with dietary, religious, or other restrictions

Identify and implement key components of a medication refusal protocol

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.

Based on the principle of informed consent, competent patients always
have the right to refuse medical treatment. Patients may refuse treatment
for a variety of reasons, including dietary restrictions, religious reasons, medical
misconceptions, a desire to avoid adverse effects, and mistrust of the medical
team. Patient refusals can create serious dilemmas in the healthcare setting. On
the one hand, clinicians have an ethical and legal obligation to honor patient autonomy.
On the other hand, a patient’s refusal of treatment often leads to adverse
medical outcomes, resulting in harm to the patient. Healthcare
professionals should search for acceptable treatment alternatives that honor patients’
wishes while meeting their medical needs. Every institution—whether in
the community, long-term care, or inpatient setting—should have a protocol to
guide and standardize the approach to managing treatment refusals. In complex
cases, it may be beneficial to use expert ethics consultations.

Medication Refusal: Understanding the Why "They Just Say No"
After participating in this activity, pharmacists and pharmacy technicians will be able to
1. Recognize and define types and leading causes of treatment/medication refusal
2. Describe the ethical and legal principles associated with medication refusal, covert medication, and surreptitious prescribing
3. Determine treatment alternatives for patients with dietary, religious, or other restrictions
4. Identify and implement key components of a medication refusal protocol

1. Which of the following is an example of ACTIVE medication refusal?
a. A patient ingests her medication when the caregiver administers it, but secretly spits it out half an hour later.
b. A patient states that she does not wish to take her oral medication, then refuses to open her mouth to ingest the medication.
c. A patient initially refuses to take her medication, but concedes when the caregiver repeatedly asks her to.

2. A patient states that he is vegetarian and wishes to avoid animal products. Which of the following excipients is INAPPROPRIATE for this patient?
a. Gelatin
b. Peanut oil
c. Mannitol

3. Which of the following best describes motivational interviewing?
a. An interviewing style that involves the use of ethics counselors, who help healthcare professionals navigate complicated cases
b. The process by which patients are educated about a treatment’s risks, benefits, and alternatives
c. A behavioral technique that motivates patients to change by empowering them and motivating them with their own values

4. Which of the following statements is FALSE about the practice of covert medication?
a. It refers to administering medications without a patient’s knowledge, such as by concealing medications in food or drink.
b. It is justifiable in mentally competent patients who refuse treatment against medical advice.
c. It may be better received than more aggressive methods, such as forced injections.

5. A practicing Sikh patient tells you that her religion prevents her from consuming Medication X, which contains animal by-products. She wants to know what alternatives are available, and what she should avoid. Which of the following best describes her reasons for refusing Medication X?
a. Dietary restriction
b. Medical misconception
c. Mistrust of the medical team

6. A practicing Sikh patient tells you that her religion prevents her from consuming Medication X, which contains animal by-products. She wants to know what alternatives are available, and what she should avoid. Which is the best resource to refer her to?
a. Pillbox, so she can research medications’ ingredients and avoid those containing animal products
b. The primary literature and PubMed or GoogleScholar, so she can find the most recent data
c. The patient should not be referred; Medication X is the most effective option for her illness, and she should take it regardless of her beliefs

7. Why might an ethics consultation be useful in certain instances of treatment refusal?
a. Ethics counselors are authorized to make healthcare decisions on behalf of incompetent patients.
b. Ethics counselors are compensated based on patient outcomes, so they persuade patients to choose the most medically effective option.
c. Ethics counselors are trained in core ethics and healthcare competencies and can help navigate difficult situations.

8. Patient BT is newly diagnosed with a disease. His doctor recommends Treatment X and describes the treatment’s risks and benefits. BT refuses his doctor’s suggestion. Instead, he decides to try natural OTC products. This is an example of:
a. Beneficence
b. Primum non nocere
c. Autonomy

9. Patient BT is newly diagnosed with a disease. His doctor recommends Treatment X and describes the treatment’s risks and benefits. BT refuses his doctor’s suggestion. Instead, he decides to try natural OTC products. Which of the following is the LEAST appropriate response to BT?
a. Inform BT of the risks and benefits of OTC products, and show him how to interpret the Drug Facts labels.
b. Identify BT’s reason for refusal—ask about his beliefs, perceptions, and concerns. Counsel him accordingly.
c. Inform BT that you will request an ethics consultation to advise in this situation, which in your opinion is untenable.

10. Patient WG is prescribed a new medication and told to take one capsule twice a day. WG misunderstands—he takes two capsules once a day, instead. Which of the following best describes WG’s behavior?
a. Intentional non-adherence
b. Unintentional non-adherence
c. Passive refusal

11. Patient AU tells you, “Dr. S prescribed five different pills for me, but I’m not taking any of them. I’m a regular churchgoer and I know I should love and respect all people, but I don’t have a good feeling about Dr. S. I think she has it out for me. I’m going to get the meds from Dr. G instead.” Based on this statement, AU’s primary reason for refusal is:
a. Religious refusal
b. Lack of belief in the medications’ effect
c. Mistrust of the medical provider

12. Patient LG is a 5-year-old female who requires a life-saving blood transfusion. Her caretaker refuses to consent to the procedure since it goes against her religious beliefs. Which of the following statements is TRUE of this situation?
a. The attending physician must request an ethics consultation, since this is legally required for all cases involving a minor.
b. LG’s caretaker has the ultimate say in her medical decisions but LG’s doctors are ethically obligated do what is beneficial for the patient.
c. Since LG does not suffer from any brain disorders, she can make her own medical decisions. The medical team only needs LG’s consent, not the caretaker’s.

2. A patient states that he is vegetarian and wishes to avoid animal products. Which of the following excipients is INAPPROPRIATE for this patient?
a. Gelatin
b. Peanut oil
c. Mannitol

Patient Safety: Seven Secrets for Patient Safety with Dietary Supplements

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

· Discuss the importance of knowing about a patient’s dietary supplement usage

· Identify commonly used dietary supplements, their regulation, and the value of certification

· Recognize potential medication-dietary supplement interactions

· Demonstrate the ability to locate different sources of information about dietary supplements

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

· Discuss the importance of knowing about a patient’s dietary supplement usage

· Identify commonly used dietary supplements, their regulation, and the value of certification

· Recognize potential medication-dietary supplement interactions

· Recognize the need for pharmacist counseling when a patient is taking a dietary supplement

Consumer consumption of dietary supplements is at an all-time high. Available products number in the tens of thousands, generating millions in annual spending. Increasing interest in overall health and wellness, preventive medicine, and immune function contribute to the rise in usage. It is a common misconception that dietary supplements are safe because they are “natural.”
Ingestion of dietary supplements poses serious health risks including adverse reactions, drug interactions, and toxicity. Adulterated, mislabeled, and contaminated products exist in the marketplace, further increasing consumer risk. Existing federal regulation and oversight for supplements differs from prescription and over-the-counter medications, occurring primarily on a post-marketing basis. Self-reporting by consumers, healthcare professionals, and industry personnel identifies these issues. Patients often omit dietary supplements from medication histories, leaving healthcare professionals unaware that patients are using them. While misinformation abounds on the Internet, many online clinically-backed sources exist.

Introduction

Consuming natural substances to produce a desired effect on the body dates back thousands of years to ancient Egypt, Rome, China, and many other cultures. Records from early Mesopotamia include written formulas using many oils still in use today, including cedar, cypress, and licorice. Around 300 B.C., the Greek philosopher Theophrastus described the medicinal benefits of natural substances in his History of Plants. Throughout the centuries, many philosophers, scientists, and physicians continued collecting, combining, and documenting the use of natural products to treat different illnesses.¹

As the science of medicine developed, so did the science of pharmacology. Isolation of the active ingredients found in herbal substances lead to the development of synthetic compounds with similar properties. The first synthetic medication, chloral hydrate, derived from chloroform and discovered in the 1800s by German chemist Justus von Lieberg, is still in use today.²

Fast forward to modern day, and the interest and use of prescription medications, over-the-counter (OTC) products, and dietary supplements are at an all-time high. In 2020, consumers filled 6.3 billion prescriptions in the United States³ (U.S.) and purchased more than 6 billion OTC products.⁴ The dietary supplement market reached an unprecedented level in 2020 with a global spend of $61.2 billion. Experts predict it will reach $128.64 billion by 2028.⁵

The COVID-19 pandemic, caused by the SARS-CoV-2 acute respiratory coronavirus, significantly impacted our perception and approach to healthcare.⁶ More and more people use complementary and alternative approaches to healthcare than ever before.⁷ For example, sales of elderberry supplements more than doubled and zinc products quadrupled shortly after the pandemic's start.⁸

Pharmacists, widely recognized as drug information experts, and pharmacy technicians routinely field consumers' questions about dietary supplements. Many pharmacists lack the necessary knowledge or don't know where to look to answer these questions. Pharmacy schools educate future pharmacists on prescription and OTC medications with courses about nutrition and dietary supplementation, if offered, available as electives. This continuing education activity presents information about dietary supplements through a series of seven common pharmacy situations and lets learners in on seven secrets they can apply to their practices.

Situation: Continuing education is a professional requirement many pharmacists find tedious. Looking through the UCONN online CE library and seeing a new continuing education activity entitled ‘Seven Secrets of Patient Safety with Dietary Supplements,’ a pharmacist remarks to the pharmacy team, "What a waste, no one even takes dietary supplements."

Secret #1: Almost 60% of people in the United States used a dietary supplement in the last 30 days.^11,12

Dietary supplements crowd the aisles in drug stores, supermarkets, warehouse clubs, and even corner convenience stores. The sheer number of products is staggering. The Dietary Supplement Database (DSLD) is an online, searchable database developed by the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH). The database contains product labeling information on dietary supplements sold in the United States, including both on and off-market products. DSLD currently lists more than 140,000 labels.⁹

In the early 1960s, the National Center for Health Statistics began a program named the National Health and Nutrition Examination Survey (NHANES). NHANES is a continuous program focusing on various health and nutritional measurements and assesses adults' and children's health and nutritional status in the U.S.¹⁰ Scientific and technical journals publish the study results.

One section of the program assesses dietary supplement use among adults. Results from the 2017-2018 NHANES show that^11,12

57.6% of adults 20 years or older used a dietary supplement in the past 30 days
Women (63.8%) had a higher utilization than men (50.8%)
Use of dietary supplements increased with age, with women 60 years or older reporting the highest usage at 80.2%
Use of multiple dietary supplements increased with age
Most common dietary supplements used by all age groups include multivitamin-mineral supplements, vitamin D, and omega-3 fatty acids

The Council for Responsible Nutrition (CRN) is a trade association for the dietary supplement and functional food industry. Annually, the CRN performs a survey gathering data on consumer use of dietary supplements. The 2019 survey conducted by the CRN underscored dietary supplement usage with the following results¹³:

77% of US adults take dietary supplements, including 79% of American women and 74% of males
Top reasons for taking supplements included:
- Energy
- Immune health
- Filling nutrient gaps
- Healthy aging
- Heart health

The COVID-19 pandemic significantly impacted our perception and approach to healthcare.⁶ As of August 5, 2022, SARS-CoV-2 has infected more than 580 million people worldwide.¹⁴ Interest in boosting our overall immunity and protecting ourselves from viral infections has dramatically increased as a result.⁷ Many vitamins and minerals play essential roles in proper immune function.^7,15 Sales of supplements associated with boosting immunity increased over the last two years, including vitamins C and D, zinc, omega-3, garlic, ginger, and turmeric.¹⁶

Table 1. Common Dietary Supplements and Potential Uses^7,17,18

Dietary Supplement	Potential Use
Black Cohosh	Menopausal symptoms
Calcium	Dyspepsia Osteoporosis Premenstrual syndrome
Echinacea	Prevention and treatment of the common cold Promotion of wound healing
Elderberry	Prevention of upper respiratory tract infections Reduction in duration and severity of symptoms of the common cold
Folic acid	Folate deficiency Kidney failure Neural tube defects
Ginkgo	Anxiety Dementia Memory improvement Premenstrual syndrome
Ginger	Dysmenorrhea Nausea and vomiting Osteoarthritis
Ginseng	Cognitive function Erectile dysfunction
Iron	Anemia Restless leg syndrome
Magnesium	Constipation Dyspepsia
Melatonin	Sleep disorders
Multivitamin with minerals	General supplementation
Omega-3 fatty acids	Alzheimer’s disease Cardiovascular disease Dementia Depression Reduction of triglycerides
Potassium	Hypokalemia Hypertension Kidney stones
Probiotics	Atopic dermatitis Antibiotic-associated diarrhea Irritable bowel syndrome
St. John’s Wort	Anti-depressant Menopausal symptoms
Turmeric	Allergic rhinitis Osteoarthritis Pruritis
Valerian	Insomnia
Vitamin A	Aging skin Healthy vision
Vitamin B-12	Vitamin B-12 deficiency
Vitamin C	Anemia Antioxidant effects Prevention of the common cold Vitamin C deficiency
Vitamin D	Osteomalacia Osteoporosis Vitamin D deficiency
Vitamin E	Alzheimer's disease Dysmenorrhea Premenstrual syndrome
Zinc	Acne Depression Diabetes Diarrhea Treatment of common cold

Eating a healthy diet is essential for good health and nutrition. The Dietary Guidelines for Americans advise professionals, including policymakers, health care providers, and nutrition educators, about what to eat to meet the body’s nutritional needs. It emphasizes eating a diet rich in nutrient-dense foods, such as fruits and vegetables, as the best way to meet the body’s nutritional needs. The guideline identifies specific populations in which dietary supplementation may be necessary, such as women who are pregnant or lactating and adults older than 50.¹⁹

In addition to these defined special populations, many pharmacy patients may find it necessary to take specific vitamins or minerals due to medication-induced nutrient deficiencies.

Table 2. Examples of Nutrient Depletion Induced by Medications^7,17

Nutrient	Medication(s)	Mechanism
Vitamin D	Anticonvulsants	Increase hepatic metabolism
	Bile acid sequestrants	Decrease absorption
	Orlistat	Decrease absorption
Magnesium	Estrogens	Decrease serum levels by increasing uptake into tissues
	Loop diuretics	Increase excretion
	Proton pump inhibitors	Decrease absorption
Vitamin B₁₂	Biguanides	Decrease absorption
	Proton pump inhibitors	Decrease absorption
	H-2 blockers	Decrease absorption
Potassium	Loop diuretics	Increase excretion
	Thiazide diuretics	Increase excretion
	Corticosteroids	Increase excretion

The pharmacist's dismissal of dietary supplement education is understandable. No one wants to waste precious time on irrelevant continuing education. However, the facts presented here illustrate the need for pharmacist education on dietary supplements.

Pause and ponder: A patient presents information about taking lemon and baking soda tea to prevent COVID-19 infection and asks you if it really works. How would you approach this conversation?

Situation: Sunday afternoons sometimes (but not often!) present the opportunity to catch up on administrative activities. While completing an inventory reconciliation of the vitamin section, a technician inquires, "Why does the FDA approve so many different products?" Looking up distractedly from the CII safe count, the pharmacist pauses, then replies in a weary voice, "You know, I’m not sure, probably just to make it more confusing for us."

Secret #2: Regulatory oversight of dietary supplements differs from prescription and OTC medications.

What is a Dietary Supplement?

On the most basic level, a dietary supplement is a substance consumed to add nutrients to a diet or to lower the risk of certain health problems. The use of natural substances has been around for millennia, but it is only within the last five decades that countries worldwide have formalized language and regulations around dietary supplements. Terminology, quality control, and safety assessment differ depending on the country and governing legislative body.²⁰

In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA), an amendment to the Food, Drug, and Cosmetic Act. DSHEA defines the term dietary supplement as a product intended for ingestion and containing an ingredient that supplements the diet. Dietary supplement labeling must include the term ‘dietary supplement’ or an equivalent term such as ‘herbal supplement’ or ‘magnesium supplement.’ DSHEA also stipulates that a dietary supplement must be free of contamination, adulteration, and properly labeled.²¹ We will discuss dietary supplement product integrity and labeling later in this activity.

According to DSHEA, dietary supplements include vitamins, minerals, herbs, other botanicals, amino acids, and live microbials (probiotics).Dietary supplements are available in many different formulations including tablets, capsules, soft gels, gel caps, powders, and liquids.²¹

DSHEA defined the term ‘new dietary ingredient’ as an ingredient that meets the above criteria and was unavailable in the U.S. before October 15, 1994. If manufacturers want to market a product containing a new dietary ingredient, they must notify the U.S. Food and Drug Administration (FDA) before marketing. The FDA then reviews the product for safety but not effectiveness.²¹

Regulation of Dietary Supplements

The FDA and the Federal Trade Commission (FTC) share regulation and oversight of dietary supplements. The FDA is responsible for the information provided on dietary supplement product labeling, including the package labeling, product inserts, and information available at the point of sale. The FTC monitors dietary supplement advertising, ensuring advertisements are truthful, substantiated, and not misleading. Both agencies have the authority to address violations and work together to ensure their efforts are consistent with one another.²²

The FDA does not have the authority to approve dietary supplement products before manufacturers market, distribute, and sell them to consumers. Manufacturers are responsible for ensuring the products they produce and distribute meet all quality standards defined by federal law. Quality standards include²²

Ensuring the safety of the dietary ingredients used in the product
Following current Good Manufacturing Practices (cGMP)
Meeting all product labeling requirements
Ensuring substantiation of all claims made about the product
Ensuring products are free of adulteration or misbranding

cGMP, defined and regularly updated by the FDA, establish the minimum requirements for manufacturing, packaging, and labeling products to ensure product quality. cGMP includes guidance on obtaining quality ingredients, operating procedures, and quality controls.²³ Failure to follow cGMP results in possible product contamination.

While the FDA may not have the authority to approve dietary supplements before the product marketing and distribution, it can monitor products via post-marketing surveillance and auditing. The FDA routinely performs manufacturer inspections, monitors the marketplace, and investigates adverse event reports. Follow-up includes working with the manufacturer to bring the product into compliance, issuing warning letters, and recalling products.²¹

Reporting Issues with Dietary Supplements

Post-marketing surveillance is essential for documenting and monitoring any issues with dietary supplements. Information about severe reactions and product quality are important issues to report. The FDA Safety Reporting Portal is an online tool used to report safety issues on several categories of products, including pet or livestock foods, tobacco products, animal drugs, and dietary supplements.²⁴

The website address for the portal is https://safetyreporting.hhs.gov. Anyone can use the portal to report issues, including consumers, healthcare professionals, manufacturers, and researchers. Generating a new report starts on the home screen. The reporter chooses to file the report as a guest or by creating an account. Creating an account streamlines data entry and allows the reporting individual to save a draft of the report, follow up on a report, and view previous submissions.²⁴

Generation of an Individual Case Safety Report ID (ICSR) occurs after report submission. The ICSR allows the reporter to identify the report for future reference including submission of a follow-up report with additional information. FDA reviewers assess the seriousness of the reported issue and assign follow-up. Submission of this information allows the FDA to identify potentially dangerous products and potentially remove them from the market.²⁴

Traditionally, insurance companies limit coverage to prescription medications. Recent trends show an expansion of coverage to include some dietary supplements. Insurance coverage of dietary supplements blurs the regulatory differences between prescription medications and dietary supplements. Understanding the differences in oversight is beneficial and allows the pharmacy staff to counsel patients effectively.

Situation: While running back to the pharmacy after a much-needed bathroom break, a pharmacist stops when approached by a customer asking for advice about an iron supplement. Overhearing the inquiry, another customer comments, "You should buy that online; it’s cheaper, and the quality is just as good." The pharmacist nods assent, turns, and hurries back to the pharmacy amid the erupting sounds of chaos behind the counter.

Secret #3: Product integrity fluctuates between manufacturers and sources of dietary supplements.

Integrity of Dietary Supplements

The lack of government oversight opens the door for substandard products to flood the market. Poor ingredient quality, heavy metal or microbial contamination, adulteration, and mislabeling occur regularly. In the current economy, with rising prices, consumers are turning to less expensive options, and cheaper is not necessarily better, especially with dietary supplements.

In the literature, many studies exist that analyze dietary supplement product integrity. A study published in 2021 tested multiple bottles of 29 herbal supplements for consistency of ingredient activity and the presence of metal and fungal contaminants. The analysis showed inconsistent ingredient activity not only between bottles of the same product manufactured by the same company, but also between bottles manufactured by different companies. Assaying for metal contamination found zinc in 88% of bottles and nickel in 40% of bottles. In 37 of 58 bottles tested, fungal contamination was present, with 21 bottles having multiple strains.²⁵

Another study analyzed 41 dietary supplements for the presence of cadmium, lead, and mercury. Results revealed that 68.3% of samples contained contamination with cadmium and lead, and 29.3% with mercury.²⁶ One research team evaluated 121 dietary supplements along with 49 prescription drugs for levels of toxic element contamination. A small percentage of the dietary supplement products exceeded safety levels for mercury, lead, cadmium, arsenic, or aluminum. None of the prescription products exceeded these safety levels.²⁷

Adulterated products contain substances not listed on the product labeling, substitution of inferior materials for active ingredients, or may contain a lesser amount of ingredients. Weight loss, sports enhancement, and sexual function supplements commonly contain banned substances.²⁸

The FDA created and currently maintains the Health Fraud Product Database to increase awareness. This database contains information about products cited in warning letters, advisory letters, recalls, public notifications, and press announcements for various issues. Issues cited include products claiming to cure, treat, or prevent a disease and products containing undeclared ingredients or a new dietary ingredient.²⁹ The database is available in the consumer section of the FDA website at https://www.fda.gov/consumers/health-fraud-scams/health-fraud-product-database.

On January 2, 2022, the FDA issued a warning letter to the manufacturers of Nasitrol, a nasal spray based on the ingredient iota carrageenan. A review of the product’s website found claims that the product is intended to mitigate, prevent, treat, diagnose, or cure COVID-19 in people. Federal regulations define products making these claims as drugs and subject to review by the FDA before approval and subsequent marketing. As discussed earlier, this is in direct violation of federal regulations.³⁰

In another example, on July 15, 2022, the FDA issued a public notice advising consumers to refrain from purchasing Adam’s Secret Extra Strength Amazing Black, a product promoted for sexual enhancement. Laboratory analysis found that the product contained tadalafil, a prescription medication used for erectile dysfunction.³¹ Due to the potential for severe side effects such as hypotension, tadalafil administration requires medical supervision by a physician.³²

A study published in 2018 analyzed FDA warning letters issued from 2007 through 2016, using data from the Health Fraud Product Database. During this time frame, the FDA found 776 adulterated dietary supplements from 146 different companies. A total of 157 products contained more than one unapproved ingredient. Products marketed for sexual enhancement accounted for 45.5% of letters, weight loss 40.9%, and muscle building 11.9%. Unapproved ingredients included sildenafil in sexual enhancement, sibutramine in weight loss, and synthetic steroids or steroid-like ingredients in muscle building supplements.³³

One way for consumers to know they are purchasing a valid product is by looking for a certified product. The certification process involves an independent, third-party company testing a company’s products, offering quality assurance for dietary supplements. Parameters tested include³⁴

Product contains the ingredients stated on the label
Presence of harmful ingredients
Presence of contamination
Proper dissolution
cGMP followed during manufacture

Three independent, private, third-party certifying organizations operate in the United States: the US Pharmacopeial Convention (USP), NSF International, and Consumerlabs.com. All three companies offer product certification programs for a fee. Each company allows products passing certification to display a seal on product labeling. Table 3 summarizes information about each organization.

Table 3. Dietary Supplement Certification Organizations

Certifying Organization	US Pharmacopeial Convention	NSF International	Consumerlab.com
Website	www.usp.org www.qualitysupplements.org	www.nsf.org	www.consumerlab.com
Services offered	Dietary supplement verification program including GMP facility audits, product QCM process evaluation, and product testing	Product and ingredient certification GMP Certification Certified for Sport	Product reviews Quality Certification Program
Information available on the website	Program information, list of verified products, and educational resources	Program information, product search engine, and educational resources	Product reviews, health condition information
GMP = Good Manufacturing Practice

Source: adapted from reference 33

Online product ordering is a convenient shopping option rapidly gaining popularity in recent years, especially during the pandemic. While tempting to order the least expensive product, investigating the source and quality of dietary supplements available online is essential. Proactive training of the entire pharmacy team aids in providing patients with accurate information.

Situation: A weary technician finally finishes ringing out the last customer after two hours straight at the register. A sigh of relief quickly turns into a disgruntled groan as another customer approaches. With a bottle labeled ‘Menopausal Support’ in hand, the customer points to the bottle label and asks, "What does ‘proprietary blend’ mean?" The technician glances over her shoulder, sees the pharmacist engaged in an intense phone conversation, and replies to the customer, "The bottle label clearly lists the ingredients."

Secret #4: Federal regulations define required dietary supplement label information. Unfortunately, ambiguity still exists, making it challenging to identify exactly what the product contains.

Federal regulations define the information required on dietary supplement product labeling in detailed, specific terms. Product labeling must include³⁵

Product name
The term ‘dietary supplement’ or similar term (i.e., herbal supplement)
Name and location of the manufacturer, along with a domestic address and phone number for reporting serious adverse events
Nutrition labeling in the form of a “Supplement Facts” panel with the following information (see Figure 1):
- Serving size
- Number of servings per container
- Listing of each dietary ingredient in the product
- Amount of dietary ingredient per serving (Exception: ingredients in a proprietary blend)
- Amount per serving listed as a quantitative amount by weight, as a percentage of the Daily Value, or as both
A list of other ingredients not declared on the Supplement Facts label (usually excipients such as preservatives or dyes)
Net quantity of contents

Figure 1. Supplemental Facts Label (sourced from reference 36)

One area of ambiguity in dietary supplement product labeling is the listing of a proprietary blend. The term proprietary blend refers to a blend of dietary ingredients unique to a manufacturer and product. Federal labeling regulations allow the listing of proprietary blends on dietary supplement products, however, only the total weight of the blend is required, not the weight of individual ingredients.³⁵ There is no way for the healthcare professional or consumer to know exactly how much of a particular ingredient the proprietary blend contains.

Consumerlabs.com cautions consumers about products containing proprietary blends or formulas. In many instances, the blend's name sounds like a desired, expensive ingredient that is only a small part of the formula. Marketing of products containing proprietary blends may mislead the consumer with claims meant to impress the consumer and drive sales of the product.³⁷

FDA regulations do allow structure/function claims on dietary supplement labeling. Structure/function claims describe how a nutrient or dietary ingredient may affect or act to maintain the structure or function of the body.³⁵Examples of structure/function claims include³⁵

Calcium builds strong bones
Antioxidants maintain cell integrity
Fiber maintains bowel integrity

If a dietary supplement label contains a structure/function claim it must also contain the following statement: "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease."³⁵

The example in this situation involved a product marketed for menopausal support. Menopausal symptoms affect more than 1 million women in the US annually and include symptoms such as hot flashes and sleep disturbances.³⁸ A search of the DSLD using the term ‘menopausal support’ and filtering for on-market products containing the ingredient ‘proprietary blend’ returned almost 3,000 products.⁹ This abundance of products illustrates the ambiguity that exists on dietary supplement labeling.

Pharmacy technicians are often the first line of contact at the pharmacy. Training and development of pharmacy technicians on the facts surrounding dietary supplements empower technicians, allowing them to answer factual questions and provide effective patient education.

Situation: The pharmacy phone constantly rings throughout the day, and today is no exception. The new COVID vaccine is out, and everyone wants to know if the pharmacy has it in stock. Answering yet another call, the technician is surprised when a patient asks to talk to the pharmacist, complaining about dizziness. The pharmacist checks the patient’s profile, finding no underlying causative medication. Further questioning the patient, the pharmacist uncovers the recent addition of melatonin at night for sleep.

Secret #5: Like prescription medications, dietary supplements have pharmacologic and physiologic effects on the body, potentially resulting in health risks and side effects.

Consumers perceive dietary supplements as safe due to their source from natural substances. While generally well tolerated, dietary supplements affect the body like prescription medications, capable of producing an undesired effect. Lack of regulatory oversight allows products to reach consumers without adequate safety evaluation.

Information describing adverse effects of dietary supplements is anecdotal, derived from case reports and reports submitted through the FDA Safety Reporting Portal. Most dietary supplements have not been studied in pregnant or lactating women or children.

A study published in 2015 evaluated ten years of emergency room data to assess the number of annual visits resulting from dietary supplement adverse events. The authors calculated an average of more than 23,000 emergency room visits stemmed from the consumption of dietary supplements, resulting in more than 2,000 hospitalizations annually.³⁹

Events in older adults accounted for the highest percentage of visits, with 40% of visits due to difficulty swallowing. Incidence in young adults aged 20 to 34 was significant at 28% and primarily involved weight loss and energy products. Side effects reported include heart palpitations, chest pain, and tachycardia.³⁹

Unsupervised child ingestions accounted for 21% of visits. Unlike prescription medications, regulations do not require child-resistant packaging for dietary supplements, except for iron-containing products.³⁹ The authors note the numbers evaluated in the study are likely underreported as patients do not always include dietary supplements with the current medication list.³⁹

Table 4. Adverse Effects of Common Dietary Supplements^7,17

Supplement	Adverse Effects
Black Cohosh	Breast tenderness, diarrhea, gastrointestinal upset, nausea/vomiting
Calcium	Burping, constipation, gastrointestinal upset
Echinacea	Diarrhea, constipation, gastrointestinal upset/pain, heartburn, nausea/vomiting, skin rashes
Ginseng	Gastrointestinal side effects, headache, sleep difficulty
Ginger	Burping, diarrhea, heartburn
Iron	Abdominal pain, constipation, diarrhea, nausea/vomiting
Magnesium	Diarrhea, gastrointestinal irritation, nausea/vomiting
Melatonin	Dizziness, drowsiness, headache
Omega-3 fatty acids	Bad breath, headache, heartburn, nausea, diarrhea, unpleasant taste
Potassium	Abdominal pain, burping, diarrhea, nausea/vomiting
St. John’s Wort	Diarrhea, dizziness, dry mouth, fatigue, headache, insomnia
Turmeric	Constipation, dyspepsia, gastrointestinal reflux, nausea/vomiting
Vitamin C	Abdominal cramping, heartburn, kidney stones (if history of kidney stones)
Zinc	Abdominal cramping, diarrhea, metallic taste, nausea/vomiting

Patients often fail to report usage of dietary supplements and most pharmacy software lacks the ability to note dietary supplement usage in the patient profile. In this situation, the pharmacist took the extra time to further question the patient about dietary supplement usage and successfully identified the causative agent.

Pause and Ponder: In what ways could you incorporate activities into the daily workflow to increase awareness of patients’ use of dietary supplements?

Situation: Today, the workload in the pharmacy is lighter than usual. With a grateful sigh, the pharmacist sinks onto a stool reaching for a quick snack. Then the phone rings… The caller is a triage nurse from the local hospital to verify a patient’s medication profile. Pulling up the profile, the pharmacist verifies the list of medications, including digoxin. The triage nurse confirms atrial fibrillation as the cause for admission, adding that the patient recently started taking St. John’s Wort for depression.

Secret #6: Some dietary supplements affect the CYP450 liver enzymes, potentially altering the pharmacokinetics of medications, leading to treatment failure and/or toxicity.

Dietary supplement-drug interactions

Drug-drug interactions result in altered absorption, metabolism, or excretion. Drug-dietary supplement interactions occur through the same pathways as those used by FDA-approved drugs. The cytochrome P450 (CYP P450) enzymes in the liver are responsible for the metabolism of most medications.^41,42 The ability of a drug to either induce or inhibit these enzymes is a significant factor in drug-drug interactions. The natural ingredients found in dietary supplements are capable of inhibition or induction, also having the potential to interact with medications.

St. John’s Wort, an herbal commonly taken for the relief of mild to moderate depression, induces the activity of CYP3A4.^43,44 This induction increases the clearance of medications metabolized by CYP3A4. Examples of medications cleared by CYP3A4 include alprazolam, atorvastatin, cyclosporine, oral contraceptives, oxycodone, and warfarin.^43,44 Patients need counseling about potential drug interactions with St. John’s Wort.

Limited clinical studies evaluating the impact of drug-dietary supplement interactions exist. Many interactions are theoretical, based on limited clinical evidence, animal research, and case reports.⁷

Table 5. Examples of Potential Drug-Dietary Supplement Interactions^7,17

Dietary Supplement	Medication	Interaction
Calcium	Quinolone and tetracycline antibiotics	Decreased antibiotic efficacy Take antibiotic 2 hours before or 4-6 hours after calcium
Calcium	Dolutegravir Elvitegravir	Reduced serum levels Take medication 2 hours before or 2 hours after calcium
Ginseng	Diabetes medications	Increase risk of hypoglycemia
Ginseng	Immunosuppressants	Decreased effectiveness of immunosuppressant
Ginkgo	Anticoagulants	Increased risk of bleeding
Iron	Quinolone and tetracycline antibiotics	Decreased levels of antibiotics due to decreased absorption Take antibiotics 2 hours before or 4-6 hours after iron
Magnesium	Bisphosphonates	Decreased absorption
Magnesium	Levodopa/carbidopa	Decreased bioavailability of levodopa/carbidopa
Niacin	Statins	Increased risk of myopathy or rhabdomyolysis
	Thyroid hormones	Antagonize the effects of thyroid hormone replacement
	Antihypertensive medications	Increased risk of hypotension due to niacin’s vasodilating effects
St. John’s Wort	Alprazolam	Decreased effects of alprazolam
	Oral Contraceptives	Decreased efficacy Counsel patients to use other forms of contraception
	Digoxin	Decreased levels of digoxin
	Omeprazole	Decreased effects of omeprazole
Valerian	CNS depressant drugs	Additive sedative effects
Vitamin B6	Phenytoin	Decrease levels and clinical effects of phenytoin
Vitamin D	Atorvastatin	Decreased absorption of atorvastatin
Vitamin E	Anticoagulants	Increased risk of bleeding
Zinc	Quinolone antibiotics	Decreased levels and effects of antibiotics Take antibiotic 2 hours prior or 4-6 hours after zinc

Pharmacy training emphasizes the importance of drug-drug interactions. It is important to remember that any substance introduced to the body, including food, beverages, and dietary supplements, has the potential to interact with medications.

Situation: It is another busy day in the pharmacy; prescriptions cover the bench, the phone rings constantly, and a pickup queue extends around the corner. A technician nervously approaches the pharmacist about a patient at the counter with a question regarding a supplement. The pharmacist throws down the spatula, muttering angrily about lacking the knowledge and training to answer the question properly. Sighing, he says, "I’ll just Google it."

Secret #7: Many websites provide clinically backed information on dietary supplements (and Google is not one of them!).

The vast amount of health information available via the Internet with just a few clicks of the keyboard is both a blessing and a curse. Google is now a verb, and a simple search returns millions of results in seconds. While this may seem like a blessing, the curse lies in the searcher's inability to recognize valid, accurate sources of information. In many searches, ads appear as search results adding to the confusion.

In addition to the Internet, consumers turn to social media for health information. Social media use increased from 27% in 2009 to 86% in 2019.⁴⁵ Information posted on social media provides communication about healthcare issues, potentially resulting in improved health care.⁴⁵ Unfortunately, inaccurate information abounds on the Internet and social media platforms, leading to consumer misinformation.^47-49

The FDA recently launched a new dietary supplement education initiative geared towards consumers, healthcare professionals, and teachers. The program, Supplement Your Knowledge, presents information about dietary supplements through a series of three videos. Educational materials, including fact sheets and infographics, are available in English and Spanish.⁵⁰

Many government agencies provide free access to information about dietary supplements and their side effects, toxicity, and drug interactions. There are also several paid subscription resources available. Table 6 lists many of the available information options.

Table 6. Sources of Information about Dietary Supplements

Resource	Website	Information
Dietary Supplement Education Program	https://www.fda.gov/food/healthcare-professionals/dietary-supplement-continuing-medical-education-program	Continuing medical education program Collaboration between FDA and AMA Series of 3 videos about dietary supplements Also contains links to educational materials and other websites with information about dietary supplements
Dietary Supplement Label Database	https://dsld.od.nih.gov	Current and historical label information on dietary supplement products marketed in the United States Useful to determine the contents of dietary supplement products
Food and Drug Administration	https://www.fda.gov/food/dietary-supplements/information-consumers-using-dietary-supplements	Information for consumers on using dietary supplements Links to educational resources and materials, consumer updates, alerts, recalls and other information
Google Scholar	https://scholar.google.com/	Source of information from many avenues including journals, books, and conference proceedings
Lexi-Comp Natural Products Database	Available via mobile app	Requires a paid subscription Alphabetical, searchable natural product database
Memorial Sloane Kettering Cancer Center	https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs	Information on herbs, botanicals, and other products for both consumers and healthcare professionals Dietary supplement monographs IOS app: About Herbs Part of an online integrative medicine resource center
National Cancer Institute Office of Cancer Complementary and Alternative Medicine	https://cam.cancer.gov	Information for consumers and healthcare professionals about CAM as it relates to cancer therapy Information on current NCI CAM research
National Center for Complementary and Integrative Health	https://www.nccih.nih.gov	Information for both consumers and healthcare professionals about complementary health products and practices
National Library of Medicine - Medline Plus	https://medlineplus.gov/druginfo/herb_All.html	Online health information about drugs, herbs, and supplements for consumers Information sourced from the National Center for Complementary and Integrative Health and Natural Medicines Comprehensive Database
Natural Medicines Comprehensive Database	https://naturalmedicines.therapeuticresearch.com	Requires a paid subscription Professional monographs including information about effectiveness, safety, adverse effects, and interactions Information on specific commercial products Interaction checker Patient handouts in English, Spanish and French
Office of Dietary Supplements	https://ods.od.nih.gov	Information for both consumers and healthcare professionals General supplement information Information on supplements for specific purposes Fact sheets on dietary supplements and their ingredients
PubMed	https://pubmed.ncbi.nlm.nih.gov	Search engine for the National Library of Medicine Source of information from journals
United States Department of Agriculture	https://www.nutrition.gov/topics/dietary-supplements	Links to general information and resources on dietary supplements

Performing an Internet search via Google may seem like the quickest and easiest way to find the answer to an inquiry. Engaging with the patient, gaining additional information, and knowing where to look ultimately saves time. It is not necessary for one to be an expert in all dietary supplements, just to self-educate one supplement at a time.

Pause and Ponder: A patient shares the unfortunate news about a recent cancer diagnosis. He asks you about the use of herbs in the treatment of cancer. What advice would you give?

Conclusion

You may have noticed a recurring theme throughout this activity. Education. Dietary supplement education is essential to patient safety given the current usage patterns and accessibility of the retail pharmacy team. Education needs to include the entire pharmacy team. Technicians are often the first point of contact at the pharmacy, commonly fielding patient questions. Knowing when to answer questions and when to involve the pharmacist is a necessary skill. Understanding the differences in oversight, the physiological effects of dietary supplement consumption, and the potential for drug interactions allows effective management and counseling of patients. It is important for healthcare providers to solicit information regarding patient consumption of dietary supplements.

Sidebar: Tips for Counseling Patients about Dietary Supplements

Carefully inspect the product to ensure intact product labeling

Ensure the safety seal is intact

Check for an expiration date or best used by date

Check for customer service or return information before ordering

Buy direct from a reputable company; many reputable companies sell through Amazon, avoid 3^rd party resellers

Check for the presence of a third-party certification seal

Before purchase, check the company’s website for information on quality standards

Pay attention to the appearance and smell of the product upon opening

Child-resistant packaging is not a requirement for dietary supplements; advise on proper storage of product

Reinforce the importance of including dietary supplements on a current medication list

Seven Secrets for Patient Safety with Dietary Supplements

Pharmacist post-test

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

1. Discuss the importance of knowing about a patient’s dietary supplement usage (K)
2. Identify commonly used dietary supplements, their regulation, and the value of certification (K, or A?)
3. Recognize potential medication-dietary supplement interactions (K)
4. Demonstrate the ability to locate different sources of information about dietary supplements (A)

1. According to The National Health and Nutrition Examination Survey more than what percentage of adults have used a dietary supplement in the last 30 days?

A. 45%
B. 50%
C. 55%

2. Which of the following is a commonly used dietary supplement?

A. Boswellia
B. Turmeric
C. Quercetin

3. Which government agencies regulate dietary supplements?

A. USDA, FDA
B. FTC, DEA
C. FTC, FDA

4. Patient MW fills a new prescription for bumetanide. Which potential nutrient depletion may occur?

A. Magnesium
B. Vitamin D
C. Vitamin B12

5. While completing an inventory reconciliation of the vitamin section, a technician inquires, ‘Why does the FDA approve so many different products?’ Which of the following is the most appropriate answer?

A. ‘The FDA does not have the authority to approve dietary supplements, the FTC approves dietary supplements, including vitamins.’
B. ‘The FDA does not have the authority to approve dietary supplements before they are marketed, allowing manufacturers to flood the market with products.’
C. ‘You know, I’m not sure, probably just to make it more confusing for us.’

6. Which of the following companies offer independent third-party dietary supplement certification services?

A. Consumer Reports
B. NSF International
C. Certified Naturally Grown

7. Patient ED is a 58-year-old male new to your pharmacy. He provides the pharmacy team with a list of his current medications including:
• Warfarin 3 mg PO QD
• Atorvastatin 10 mg PO QD
• Donepezil 10 mg PO QHS
• Metformin 1,000 mg PO BID
Use of which of the following supplements would be cause for concern in this patient?

A. Ginkgo
B. Omega-3 fatty acids
C. Niacin

8. A patient calls with questions about a supplement recommended by a friend. The name of the supplement is Mind and Memory Essentials, and the patient does not know the product ingredients. Where would you go to find this information?

A. Dietary Supplement Label Database
B. Office of Dietary Supplements
C. United States Department of Agriculture

9. A patient asks you about the potential side effects of taking turmeric. Where would you go to find this information?

A. Google
B. PubMed
C. Office of Dietary Supplements

10. You are verifying a new birth control prescription for a patient, recalling that the patient strongly believes in alternative medicine and dietary supplementation. Thankfully her profile contains a list of dietary supplements. You see St. John’s Wort listed and suspect a drug-supplement interaction. Where would you go to find more information?

A. Natural Medicines Database
B. Google Scholar
C. National Library of Medicine

11. One of your regular patients stops by the counter to ask your opinion on a dietary supplement product purchased on the Internet. What should you assess when looking over the product?

A. Product labeling, color of bottle, structure/function disclaimer, certification
B. Certification, expiration date, product labeling, intact seal
C. Expiration date, product price, certification, product labeling

12. Pharmacy patient ML approaches the pharmacy counter to purchase several bottles of oral glucose tablets. When questioned, the patient reveals the recent occurrence of several hypoglycemic episodes. The patient confirms compliance with taking their prescription for metformin 1 gm PO BID. ML reports no changes in other prescriptions or dietary habits but does state they started taking a dietary supplement a few days ago but cannot recall the name. Which product would you suspect based on the information provided?

A. Vitamin E
B. Valerian
C. Ginseng

Pharmacy Technician

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

1. Discuss the importance of knowing about a patient’s dietary supplement usage (K)
2. Identify commonly used dietary supplements (A)
3. Define dietary supplement oversight and different levels of quality (K)
4. Recognize the need for pharmacist counseling when a patient is taking a dietary supplement (K)

1. Why is it important to ask about a patient’s usage of dietary supplements?

A. It is not important to ask about dietary supplement usage.
B. To identify which dietary supplements the pharmacy should feature on the front counter.
C. Dietary supplements potentially interact with prescription medications.

2. Which of the following is a commonly used dietary supplement?

A. Boswellia
B. Turmeric
C. Quercetin

3. Which government agencies regulate dietary supplements?

A. USDA, FDA
B. FTC, DEA
C. FTC, FDA

4. A patient approaches the counter with 2 different magnesium products and asks your opinion on which to purchase. Which of the following is an appropriate answer?

A. Let’s look at these a little closer.
B. Neither, it’s better to buy supplements online.
C. The one that’s on sale.

5. Reasons for dietary supplementation include which of the following?

A. To supplement a poor diet.
B. Promotion of optimal immune health
C. No one needs to take dietary supplements.

6. Which of the following companies offer independent third-party dietary supplement certification services?

A. Consumer Reports
B. NSF International
C. Certified Naturally Grown

7. You are entering a new patient into the pharmacy system. In addition to asking about allergies, demographics, and current medications, what else should you ask?

A. How many hours of sleep do you average a night?
B. Do you take any over-the-counter medications or dietary supplements?
C. How many children do you have and how old are they?

8. You are finally heading out for a lunch break and walk past a pharmacy patient in the aisle looking at 2 different brands of St. John’s Wort. What should you do?

A. Keep going, you already punched out and only have 30 min to eat your lunch.
B. Stop and offer to accompany them to the pharmacy to talk to the pharmacist.
C. Stop and help them make a choice between the products.

9. A patient picks up a medication and purchases a bottle of magnesium at the same time. What should you do?

A. Advise the patient that there may be an interaction between the prescription and the magnesium.
B. Ring out the patient as usual.
C. Touch base with the pharmacist to make sure there are no potential interactions between the products.

10. Where should adverse reactions or issues with dietary supplements be reported?

A. FDA Safety Reporting Portal
B. Federal Trade Commission
C. Office of Dietary Supplements

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Ketamine and Its Kissing Cousins

Ketamine is Food and Drug Administration-approved as a general anesthetic. Researchers found higher dose ketamine therapy had a more desirable adverse effect profile than the previously used anesthetic phencyclidine (PCP). N-methyl-D-aspartate (NMDA) antagonism from subanesthetic ketamine doses produces dissociative and analgesic effects. As such, prescribers are exploring off-label uses for ketamine in patients with agitation, depression, and pain while considering potential risks to multiple organ systems. Ketamine has the potential to cause complications and providers need to monitor patients closely. Illicit and inappropriate use by abusers and untrained law enforcement officers highlight ketamine’s potentially harmful effects. Educating patients and healthcare providers is vital to allow potential benefits while minimizing harm.

Introduction

Consider this: It’s 10:30 PM on a Friday night, 30 minutes before you leave for the weekend. Suddenly, from across the emergency department you hear, “Get OFF me! No, I have not t-t-taken anything! If you come ANY CLOSER, things are going to get physical!” Not a moment later, an order pops up for ketamine hydrochloride 500 mg intramuscularly (IM) for severe agitation. Concerned, a colleague asks you, “Is this safe? Is this effective? I have never seen a dose this high before. Isn’t this just for horses?”

Ketamine made its debut in human clinical practice in the 1960s when several chemists at Parke Davis Company were searching for an anesthetic with similar effects to phencyclidine (PCP). PCP, ketamine’s notorious kissing cousin, was a promising new anesthetic in the 1950s because of its dissociative effects. However, the chemists quickly became unimpressed with its adverse effect profile (i.e., long-lasting psychoactive effects after anesthesia). Humans experienced intense prolonged emergence delirium following PCP anesthesia, relegating its use to veterinary practice.¹ Chemists searched for a better anesthetic and found ketamine, which has similar dissociative effects without PCP’s negative consequences. Ketamine is a more desirable anesthetic because it has a shorter half-life (2.5 hours) compared to PCP (21 hours) and it causes less delirium.^1,2

Prescribers have begun using ketamine for several off-label uses and patients have also started using the drug or structural analogs in a variety of formulations illicitly. Pharmacists and technicians can ensure ketamine’s safe use by keeping current with new formulations and indications, both approved and unapproved. This continuing education activity will dive into the clinical and social consequences of ketamine use.

What’s Ketamine?

Ketamine is a schedule III-controlled substance approved by the U.S. Food and Drug Administration (FDA) for use as a general anesthetic for diagnostic and surgical procedures.²Ketamine is commercially available in the United States as a solution/injection under its brand (Ketalar) and as generic ketamine.² Healthcare providers most often use intravenous (IV) ketamine, but it may be used IM or compounded into an oral solution.

Healthcare providers also use ketamine off-label for analgesia, agitation, and major depressive disorder. These indications emanate from ketamine’s mechanism of action: it acts specifically on the N-methyl-D-Aspartate (NMDA) receptor as a non-competitive antagonist to block glutamate binding.³Glutamate, a major excitatory neurotransmitter, binds to receptors throughout the nervous system. The NMDA receptor is an ionotropic receptor responsible for the brain’s neuroplasticity, memory, learning, and recovery.^4-6 Blocking this receptor with high ketamine doses (ranging from 0.5 to 2 mg/kg) results in dissociation, decreases in spinal reflexes, and produces a cataleptic state (loss of voluntary movements and reduced consciousness) that is applicable to its current clinical use in anesthesia.² However, at low doses, ketamine can produce analgesia and stimulate new pathways within the brain that reduce depressive symptoms and improve mood.

Although ketamine has useful applications in medicine, prescribers must be aware of the adverse effects and risk factors associated with use and should consider how these effects apply to their patients before initiating the medication. Ketamine adversely impacts multiple organ systems (see Table 1), including but not limited to the cardiovascular system. Increases in blood pressure and heart rate are important cardiovascular effects associated with ketamine therapy.² These cardiovascular effects make it a drug of choice for anesthesia induction in patients with cardiovascular shock, where it anesthetizes patients while improving blood pressure and improving organ perfusion. However, clinicians must avoid ketamine use in patients with preexisting hypertensive conditions or other patients who have limited baroreceptor buffering capacity (baroreceptor buffering is the body’s ability to sense blood pressure) because of those same effects mentioned above.⁶

Table 1. General Adverse Effects of Ketamine^2,6

System	Adverse effects
Cardiovascular	Cardiac arrhythmias, increased blood pressure,* increased heart rate
Central nervous system	Prolonged emergence from anesthesia,* psychosis,* dissociation,* drug dependence, increased intracranial pressure
Dermatologic	Injection site irritation
Gastrointestinal	Nausea,* vomiting, anorexia
Genitourinary	Lower urinary tract dysfunction, bladder dysfunction
Respiratory	Laryngospasm,* respiratory depression,* apnea
Immunologic	Anaphylaxis
Other	Hypersalivation, diplopia (double vision), nystagmus (uncontrollable rapid eye movement)

*Common or serious adverse effects of ketamine use

Further contraindications include hypersensitivity to ketamine or its components.⁷ The American College of Emergency Physicians (ACEP) does not recommend ketamine use in patients with schizophrenia or in children younger than three months of age. The ACEP also advises against solely using ketamine as an anesthetic in procedures involving the pharynx, larynx, and bronchial tree. This recommendation primarily applies to patients with airway instability because ketamine can cause laryngospasms.⁵ Table 2 lists additional considerations in special populations.

Table 2. Special Population Considerations with Ketamine^2,6-8

Special population	Concerns	Recommendation
Pregnancy	Crosses the placenta; may have potential risk to fetus	Avoid use; evaluate benefits vs risk
Breastfeeding	Compatibility and safety unknown	Avoid breastfeeding to children with respiratory risk factors
Pediatrics	Can be given with anticholinergics to minimize hypersalivation	Refer to pediatric dosing. Avoid in infants < 3 months of age
Elderly	May be sensitive to dissociative adverse effects	Refer to adult dosing
Kidney dysfunction	No additional concerns	Refer to dosing parameters
Liver dysfunction	Hepatobiliary dysfunction with recurrent use	Refer to dosing parameters; monitor LFTs with repeated ketamine use
LFTs = liver function tests

Healthcare providers should monitor patients' vital signs closely during treatment with ketamine. Anesthesiologists and pharmacists must continuously watch patients undergoing surgical or diagnostic procedures for proper induction and maintenance of dissociative effects.² In patients who must take repeated doses of ketamine (e.g., for chronic pain management or psychiatric disorders), healthcare providers should order liver function tests at baseline and every one to two days during treatment.^2,6,9,10

Ketamine’s Kissing Cousins

As shown in Figure 1, ketamine is structurally related to many compounds. The drugs in Figure 1 antagonize the NMDA receptor and exhibit a dissociative effect.¹ PCP is one of the most notoriously abused drugs. Compared with ketamine, PCP is 10 times more potent and has a longer duration of action due to its strong affinity for the NMDA receptor. Both ketamine and PCP can replicate schizophrenia’s positive, negative, and cognitive symptoms and exacerbate underlying schizophrenia. But because ketamine has lower potency and a shorter duration of action, it induces fewer severe psychiatric effects than PCP.¹

Figure 1. Molecular structure of ketamine and structurally related dissociative drugs¹¹

Although ketamine’s labeling includes many precautions, it is an emerging option because of its therapeutic benefits. Xi Biopharmaceuticals is developing a sublingual wafer to treat acute pain while Janssen Pharmaceuticals has developed a nasal spray formulation for treatment resistant depression.^12,13 Table 3 compares the current ketamine formulations that are FDA-approved or under investigation.

Table 3. Ketamine Counterparts^12-14

Cousins	Formulation	Use & Dose	Approval or Trial Phase
Ketalar (ketamine hydrochloride)	Injectable	Anesthesia 0.25 – 0.35 mg/kg followed by CIVI 1 mg/kg/hr	FDA-approved
Wafermine (ketamine)	Sublingual Wafer	Acute Pain 25 mg, 50 mg & 75 mg PRN for 12 hrs	End-of-Phase 2 Clinical Trials
Spravato (esketamine)	Nasal Spray	Treatment Resistant Depressive Disorder 28 mg, 56 mg, 84 mg twice a week	FDA-approved
ABBREVIATION: CIVI = continuous intravenous infusion

ABUSE, ADDICTION, DEPENDENCE

Why is Ketamine Dangerous?

Long-term ketamine abuse is associated with memory, attention, and judgment impairment. The actual risk of ketamine abuse in the general population is low compared to other substances of abuse, but patients with polysubstance abuse disorder tend to use it.¹⁵ A study examining polysubstance abuse conducted in New York City found that polydrug use occurred because of an unexpected opportunity to use ketamine after already consuming other drugs. Researchers also determined that polysubstance abusers purposefully used ketamine with another substance to achieve an individually desired effect. Oftentimes polydrug-using events occurred within a group and each member contributed something: ketamine, knowledge, other drugs, or space to use drugs.¹⁶

Currently, ketamine is only commercially available as an injectable liquid. Dealers illegally sell ketamine as a recreational injectable substance or a white powder that resembles cocaine. The Department of Justice and Drug Enforcement Administration report that illegally distributed ketamine is diverted or stolen from veterinary clinics or smuggled into the United States from Mexico.¹⁷ Dealers can then synthesize ketamine into a powder or sell it as an injectable liquid.¹⁸ Prices average from $20-$25 per dose (50 mg to 100 mg).¹⁹ Drug abusers find ketamine’s dissociative sensations and hallucinations appealing. Users can inject liquid ketamine, or snort or smoke powdered ketamine.¹⁷ Ketamine is a popular drug to facilitate physical or sexual assault because it is a colorless, tasteless, and odorless liquid making it difficult for victims to detect. Additionally, ketamine is known to cause impaired coordination, confusion, and memory loss.²⁰

Ketamine’s IV administration started in the early 1990s. Injection events occur most frequently in large cities with high rates of homelessness, like New York City and Los Angeles.¹⁸ Researchers conducted a study with 213 people who abused IV ketamine.¹⁸ Among these users, 84% admitted to abusing ‘harder’ drugs first, with heroin predominating. Users reported their first ketamine injection happening among a group of people. This group often included people well known to them who provided knowledge and the materials for injecting.¹⁸

What attracts people to a dissociative drug with unknown psychoactive effects? Exactly that: the unknown. With most abused drugs, the user understands the effects they will experience. When someone takes ketamine, the reaction to each dose is unknown. Some users seek variety. Ketamine users have described an out of body experience that expands internal and external realms and realities.¹⁸ On the other hand, abusers also describe a “K-Hole”—an experience that they describe as near-death that results when they ingest too much ketamine.¹⁷

Timothy Wyllie, a spiritualist, describes ketamine doses as a curve over time through realms. He describes the domains abusers experience as they dose ketamine²¹:

The realm “I,” for internal reality, occurs at doses 30 to 75 mg roughly 10 minutes after injection.
The extraterrestrial reality realm, “They,” occurs at doses 75 to 150 mg approximately 15 minutes after injection.
The realm “We,” for network creation realm, occurs at doses from 150 to 300 mg mg approximately 15 minutes after injection.
An unknown realm exists at doses of more than 300 mg.

The doses studied for depression fall in the realm of internal reality. At these doses, users can see areas needing self-improvement that they were unaware they had the ability to fix. Drug users prefer subanesthetic doses but those that are higher than doses studied for treating depression. As the dose increases, users become so far removed from reality that “extraterrestrial” experiences begin.²¹

KETAMINE USES

Anesthesia

Patients unable to maintain and protect their airways require endotracheal intubation. Healthcare providers use ketamine as a sedative to facilitate rapid sequence induction and intubation (RSII), by inducing an anesthetized state, prior to paralyzing the patient. The decision to intubate is based on the patient’s Glasgow Coma Score.^22,23A score of 8 or less qualifies a patient to receive endotracheal intubation.²³ Healthcare providers follow a RSII strict algorithm, shown in Table 4, detailing the order in which medications should be administered based upon the onset and duration of action.

Table 4. Algorithm of Rapid Sequence Induction & Intubation^22,23

Step of RSII	What and Why	Medications Used
Premedication^*	Airway manipulation causes a sympathetic activation due to a pressor response. This sympathetic response leads to an increase in intracranial pressure and mean arterial pressure.	alfentanil, fentanyl, lidocaine, sufentanil
Sedation	Used to induce an anesthetic state before a paralytic is used and the airway manipulated. Crucial that a patient is properly sedated before paralyzed.	Also known as induction agents: etomidate, ketamine, midazolam, propofol
Paralytics^±	Neuromuscular blocking agents are given to relax pharyngeal and diaphragmatic muscles allowing for an endotracheal tube to be placed.	rocuronium, succinylcholine, vecuronium

*: Based upon time constraints/needs this step may be omitted

±: It is imperative to confirm a patient is properly sedated before beginning paralysis because if the patient is awake, they may feel the tube insertion

The drugs used in RSII possess unique characteristics, including IV use, quick onset, and short duration of action.²³ Traditionally, etomidate has been the gold standard for RSII, but ketamine is quickly becoming a commonly used alternative.²³ Table 5 highlights the differences between etomidate and ketamine.

Table 5. Comparison of Etomidate and Ketamine^22,23

	Etomidate	Ketamine
Dose for Induction	0.3 mg/kg	1.5 mg/kg or 0.1-0.5 mg/kg/min with 10% given as induction bolus
Onset of Action	10-15 seconds	< 30 seconds
Duration of Action	4-10 minutes	10-15 minutes
Benefits	Stable hemodynamic profile, decreases metabolic rate, decreases cerebral blood flow, increases generalized seizure threshold	Sedative and analgesic properties,^* cardiovascular and respiratory stimulation, and smooth muscle relaxation (beneficial in reactive airway disease, hypotensive, volume depleted, and septic patients)
Risks	Adrenal suppression, do not use in septic shock, lowers focal seizure threshold, increased incidence of ARDS	Potentiates effect of epinephrine, increases cardiac oxygen demand, may increase ICP,** emergent reactions, infusion related respiratory depression, hypersalivation
ABBREVIATIONS: ARDS = acute respiratory distress syndrome, ICP = intracranial pressure * Ketamine can be used as a combined premedication and induction step ** Data is conflicting, however, may not be suitable for patients with head trauma

The differences between etomidate and ketamine create a significant role in RSII for both drugs, but for different presenting conditions. Ketamine is gaining popularity for its use in septic patients, hypotensive patients, and those with reactive airway diseases. Choosing etomidate is preferable for patients with a hemodynamically stable profile and patients with traumatic brain injury where it could be cerebroprotective.

Analgesia (pain)

Ketamine’s use in pain management is controversial due to limited data, but this dataset is growing.^15,24 Before considering subanesthetic ketamine doses, prescribers should collaborate with patients and other clinical team members to try other approved pain regimens.²⁵ Using ketamine for its analgesic properties should be based on patient-specific criteria. The prescriber must assess the patient’s treatment goals, current medical conditions, pain types, and available protocols.

Ketamine is not discussed in available pain guidelines. Some literature recommends its use after unsuccessful trials of at least two opioids. Data supporting ketamine’s use in both acute and chronic pain management is mixed in its findings.^26,27 Most trials conclude ketamine can reduce acute pain exacerbations but note that prescribers must be cautious of its adverse effects.¹⁵ Data from small trials indicate using ketamine to overcome opioid withdrawal and opioid-induced-hyperalgesia (neuropathic pain) may be possible. Ketamine has a unique ability to counteract the unfavorable responses patients might experience on chronic high-dose opioids by its mechanism of action.^24,28 Overstimulated opioid receptors from high dose opioid use causes more hyperalgesia. Several small case reports describe patients on high-dose chronic opioid therapy who reduced their opioid doses after low-dose ketamine administration.²⁹

An open labeled audit determined that IV ‘burst’ ketamine therapy improved analgesia in neuropathic pain and painful bone metastases. Researchers enrolled 39 cancer patients who were refractory to opioid therapy. Patients received bursts of low-dose ketamine (100 to 500 mg/day) over three to five days and reported somatic and neuropathic pain relief for up to eight weeks.¹⁵

Limited evidence supports oral ketamine’s effect in chronic pain and most studies that examine its use are case reports or non-comparative trials. Compared to IV administration, lower oral ketamine concentrations are associated with analgesic effects. Oral ketamine has been associated with higher serum levels of its metabolite, norketamine. This metabolite seems to contribute to oral ketamine’s analgesic effects due to its shorter half-life and ability to reach much higher peak plasma concentrations than after IV administration. However, researchers have not extensively explored this in current literature.²⁹

Healthcare providers and patients face many hurdles when using ketamine for pain relief. Prescribers should avoid high ketamine doses that may cause a range of serious adverse effects. Unlike opioids, ketamine has a ceiling effect and maximum dose. Oral ketamine administration has a low bioavailability and is directly linked with a high rate of adverse effects.^15,27

Agitation

Due to ketamine’s dissociative properties, clinicians are increasingly using ketamine for treating pre-hospital and in-hospital agitation. Lacking a uniform definition for agitation, healthcare providers, institutions, and organizations may use different criteria to choose medication intervention in an agitated patient. Although the picture of agitation may change depending on the situation, validated scales like the Altered Mental Status Scale (AMSS) can define agitation’s severity.³⁰ The AMSS translates agitation into a quantifiable, real concept. The line between agitation and delirium is often unclear but has major ramifications for a patient’s treatment and outcome.³⁰ For example, excited delirium, an agitation subtype, classifies a patient’s agitation past the emotional component and includes psychomotor, metabolic, and contributing disease states as possible reasons for agitation.³⁰

As with most psychiatric disorders, identifying and treating agitation has been suboptimal. Since the 1980s, a popular cocktail of medications, known among emergency department physicians as the “B-52” order, has been the mainstay of agitation treatment in psychiatric facilities and emergency departments.³¹ When examining the B-52 order’s components, it is easy to see the correlation between the regimen and the American jet-powered strategic bomber from which it derives its name: Benadryl 50 mg IM, haloperidol 5 mg IM, lorazepam 2 mg IM.³¹ The B-52 order serves as a reminder of the suboptimal approach traditionally taken when confronted with an agitated patient.

Ketamine’s different routes of administration have benefits and disadvantages. Although less invasive, oral ketamine takes a longer time to reach the therapeutic range, something that is undesirable in an overly aggressive patient. Intravenous administration has the quickest onset but is the most invasive. Securing IV access may not always be possible. The IM route is the most often used method for agitation control for its quick “on/off” onset and duration of action, and its applicable dosage form.

A review explains ketamine’s uses and benefits in comparison to other, more traditional agitation treatments.³⁰ In terms of agitation efficacy, ketamine provides the same, if not better, response when compared to its more traditional counterparts.³⁰ Ketamine has a significantly faster onset of action when compared to haloperidol (5 minutes versus 17 minutes) and requires less redosing (5% of patients re-dosed versus 20% of patients re-dosed, respectively).³⁰ However, ketamine continues to show a higher incidence of adverse effects when compared to its anti-psychotic counterpart (percent incidence calculated from six studies where adverse events were recorded as a secondary outcome):³⁰

emergence reaction 12.3% (8/65 patients)
- An “emergence reaction” is an often hostile, psychiatric episode brought about by ketamine use
hypersalivation 31.8% (22/69 patients)
nausea and vomiting 8.5% (7/82 patients)
respiratory complications 7.6% (9/118 patients)

Although studies report a higher incidence of adverse reactions when using ketamine for agitation, it is important to consider study limitations: small patient populations, co-administration of drugs, and lack of adverse event reporting (only half of 12 studies included adverse reactions).³⁰ If used properly, ketamine can be a safe, quick-acting drug to stop agitation when compared to traditional treatments.

Some law enforcement agencies use ketamine. However, when they use ketamine improperly, or when adverse effects arise, ketamine can have dangerous consequences. Over a four-day period during late August of 2019 in Colorado, police gave 23-year-old Elijah McClain and 25-year-old Elijah McKnight excessive ketamine doses for agitation.³² McClain died from cardiac arrest and McKnight survived but required life support in the hospital.³² It is inappropriate to allow untrained police officers to inject ketamine as a law enforcement tool. However, police defend using ketamine saying suspects with mental health issues or suspects taking drugs can be belligerent and dangerous. A Minnesota whistleblower lawsuit filed by a former emergency medical services worker claims police pressured them to allow ketamine use uneccessarily.³² In Minneapolis, ketamine used by police rose from four incidents per year in 2015 to 62 in 2017.³² This marked increase in ketamine use is upsetting many healthcare professionals. Dr. Mary Dale Peterson, president of the American Society of Anesthesiologists, says that ketamine can have “dangerous complications,” just like any other anesthetic. Dr. Peterson points out that justifiably using ketamine occurs very rarely.³²

Whistleblowers cite complications from unwarranted ketamine use are associated with emergence reactions, and improper dosages.³² McClain died when he was given a ketamine dose for a 200-pound man but only weighed 143 pounds.³² Pharmacists can play a role in educating other healthcare professionals about proper dosing and management of ketamine’s serious adverse effects.

Major Depressive Disorders

Generally, major depressive disorder’s (MDD) treatment focuses on pathophysiology and regulates serotonin, norepinephrine, and dopamine.³² Medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibits (SNRIs), tricyclics, tetracyclics, and serotonin modulators all target an increase in synaptic neurotransmitter levels.³² Unfortunately, these drugs are not consistently effective for all patients, require an 8-week trial period, and have unfavorable adverse effects. For many providers and their patients, MDD treatment can feel like an awful waiting game—one that they sometimes lose.

Ketamine is becoming increasingly popular for its use in treating refractory depression. However, it requires healthcare providers to understand how it works to avoid putting patients into a “K-hole.” It offers a different approach to the current FDA-approved drugs for MDD. Ketamine prevents glutamate reuptake; excess glutamate produces an antidepressant effect. Ketamine, at subanesthetic doses, produces euphoria, and improves symptoms within 24 hours after infusion.^4,14,32,33 Depressive symptoms improve rapidly, but the effects last only a few days to weeks. As a result, ketamine is most useful as an adjunctive treatment option. Patients feel better for a brief period, giving their antidepressants a chance to start working.

In addition, prescribers have few options for patients with MDD who have suicidal behaviors and ideation. Ketamine seems promising for patients at an elevated risk for self-harm. The Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression trial examined ketamine’s potential benefits for 80 suicidal patients with MDD. The results of this randomized controlled study showed that ketamine was superior to midazolam in improving the Scale for Suicidal Ideation (SCI). Patients’ SCI scores improved 4.96 points within 24 hours after a ketamine infusion of 0.5 mg/kg over 40 minutes.³² This suggests clinical use of ketamine as an adjuvant agent for acute episodes of suicide ideation in patients maintained on guideline recommended therapy for MDD may be appropriate. However, patient safety remains a concern (e.g., dissociative effects, abuse potential, respiratory, and cardiovascular effects).

As mentioned earlier, esketamine (Spravato) is ketamine’s S-enantiomer and FDA-approved for treatment-resistant depression.³³ In the TRANSFORM-1 randomized controlled trial, the antidepressant/esketamine groups did not have a statistically significant change in Montgomery-Asberg Depression Rating Scale (MADRS) total score (from baseline to study day 28) when compared to the antidepressant placebo group.^34,35 However, the changes based on the MADRS were clinically meaningful and showed that esketamine has a beneficial role in treatment-resistant depression when used as an adjuvant agent.^36,37 The combination of esketamine with an antidepressant produced desirable outcomes while minimizing adverse effects. Although adverse effects were low, several adverse effects are possible: vertigo, nausea, vomiting, anxiety, sedation, abuse potential, increased blood pressure, dissociation, and suicidal thoughts/behaviors.³³

CONCLUSION

To paraphrase the father of toxicology, Paracelsus, it’s all about the dose. Ketamine is the poster child drug for this statement. Ketamine has the potential to be an important adjuvant therapy for the treatment of a range of conditions. Those listed in this CE—anesthesia, analgesia, and major depressive disorder—are currently the most studied disorders where ketamine and its derivatives may be useful. Due to ketamine’s dissociative and analgesic effects through NMDA antagonism, there may be additional future potential uses for ketamine in pain control and psychiatric disorders. Simply, ketamine treats not only the physical manifestations of these conditions but the emotional component that providers can easily overlook. However, the current data sets are small, many use rating scales instead of final health outcomes, and a larger and longer term series of trials are required to fully determine the place of ketamine in the treatment armamentarium for patients.

Pharmacists and other healthcare providers will need to distinguish between therapeutic use and addiction. Often, these lines are muddled. Providing education is a first step to preventing abuse. Usually, addiction is a manifestation of an untreated, or undertreated, medical condition. Pharmacist intervention helps patients and healthcare providers to make the safest, most informed decisions possible to ensure the best possible outcomes.

Pharmacist Post-Test
Objectives:
1. Identify patient populations in which ketamine use is justified based on its FDA approved indications and for off-labeled use where it has been sufficiently studied
2. Compare the different formulations of ketamine and its “kissing cousins”
3. Describe potential risks associated with ketamine use

1. Patient AV has a GCS score of 8 and requires intubation. He presents with volume depletion, hypotension, and sepsis. What drug would the anesthesiologist probably use for sedation?
a. Fentanyl
b. Etomidate
c. Ketamine

2. In which patients would you avoid recommending ketamine?
a. Patients with reactive airway disease
b. Patients with sepsis or hypotension
c. Patients with traumatic brain injury

3. Which formulation of esketamine is FDA-approved for treatment resistant depressive disorder?
a. Injectable
b. Nasal spray
c. Infusion

4. What is the most commonly used route of administration when using ketamine for agitation?
a. IV
b. IM
c. PO

5. A clinician asks you about ketamine’s adverse effects. What would you say to start?
a. Ketamine can cause cardiac arrythmias.
b. Ketamine can decrease blood pressure.
c. Ketamine can worsen peptic ulcers.

6. What is the correct order of administration for RSII medications?
a. Premedication, sedative, paralytic
b. Premedication, paralytic, sedative
c. Sedative, premedication, paralytic

7. When should prescribers monitor liver function in patients who receive repeated ketamine doses?
a. At baseline and every 1 to 2 months
b. At baseline and every 1 to 2 weeks
c. At baseline and every 1 to 2 days

8. What is a “K-hole?”
a. A networking experience
b. A near-death experience
c. An extraterrestrial experience

9. What is a limitation of using ketamine in MDD?
a. Depressive symptoms improve slowly
b. Requires an 8-week trial period first
c. Effects last only a few days to weeks

10. A police officer asks you to discuss ketamine and asks why you refer to similar drugs as “kissing cousins.” How would you explain it?
a. They all have similar potency and antagonize NMDA receptor
b. They are used in similar doses and act as a NMDA receptor agonist
c. They are structurally similar and antagonize NMDA receptor

Technician Post-Test
Objectives:
1. Identify patient populations in which ketamine use is justified based on its FDA approved indications and for off-labeled use where it has been sufficiently studied
2. Compare the different formulations of ketamine and its “kissing cousins”
3. Describe potential risks associated with ketamine use

1. In which patient should prescribers avoid using ketamine?
a. patient with serious peptic ulcer
b. patient older than 3 months old
c. patient with uncontrolled hypertension

2. What ketamine dose results in dissociation?
a. 0.1 to 0.5 mg/kg
b. 0.5 to 2 mg/kg
c. 2 to 3.5 mg/kg

3. What is a risk associated with using ketamine in RSII?
a. adrenal suppression
b. increase ARDS incidence
c. emergent reactions

4. What ketamine formulation is currently available by prescription?
a. sublingual tablet
b. injectable solution
c. 24-hour patch

5. What risk is associated with ketamine use?
a. exacerbates underlying schizophrenia
b. lowers focal seizure threshold
c. increases incidence of ARDS

6. What is a key difference between PCP and ketamine?
a. PCP has a shorter duration of action than ketamine
b. PCP is 10 time more potent than ketamine
c. PCP has less severe psychiatric effects than ketamine

7. What is a benefit of using ketamine for agitation in comparison to haloperidol?
a. faster onset
b. more redosing
c. fewer side effects

8. What is ketamine’s FDA-approved indication?
a. agitation
b. analgesia
c. anesthesia

9. What can be expected when people use oral ketamine?
a. high bioavailability
b. high rate of adverse effects
c. low plasma peak concentrations

10. What is ketamine’s role in RSII?
a. premedication
b. sedative
c. paralytic

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11. Ho JH, Dargan PI. Arylcyclohexamines (Ketamine, Phencyclidine, and Analogues). In: Critical Care Toxicology. Brent J, Burkhart K, Dargan P, Hatten B, Megarbane B, Palmer R, eds. Springer; 2016. https://doi.org/10.1007/978-3-319-20790-2_124-1

12. Lodge D, Mercier MS. Ketamine and phencyclidine: the good, the bad and the unexpected. Br J Pharmacology. 2015;172(17):4254-4276. doi:10.1111/bph.13222

13. Study of Wafermine™ for post-bunionectomy or abdominoplasty pain. ClinicalTrials.gov identifier: NCT03246971. Updated July 23, 2018. Accessed Jul 25, 2022. https://clinicaltrials.gov/ct2/show/study/NCT03246971

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15. Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60(7):341-348. doi:10.1016/j.biopha.2006.06.021

16. Lankenau SE, Clatts MC. Patterns of polydrug use among ketamine injectors in New York City. Subst Use Misuse. 2005;40(9-10):1381-1397. doi:10.1081/JA-200066936

17. Drug Fact Sheet: Ketamine. Department of Justice and Drug Enforcement Administration. Published April 2020. Accessed July 25, 2022. https://www.dea.gov/sites/default/files/2020-06/Ketamine-2020.pdf

18. Lankenau SE, Sanders B, Bloom JJ, et al. First injection of ketamine among young injection drug users (IDUs) in three U.S. cities. Drug Alcohol Depend. 2007;87(2-3):183-193. doi:10.1016/j.drugalcdep.2006.08.015

19. Average Cost of Illicit Street Drugs. AddictionResource.net. Updated June 21, 2021. Accessed July 25, 2022. https://www.addictionresource.net/cost-of-drugs/illicit/

20. Świądro M, Stelmaszczyk P, Lenart I, Wietecha-Posłuszny R. The Double Face of Ketamine-The Possibility of Its Identification in Blood and Beverages. Molecules. 2021;26(4):813. Published 2021 Feb 4. doi:10.3390/molecules26040813

21. Morris, H. Hamilton’s Pharmacopeia Ketamine: Realms and Realities. [Video]. Vice TV. December 26, 2017. Accessed July 25, 2022. https://www.vicetv.com/en_us/video/hamiltons-pharmacopeia-ketamine-realms-and-realities/59cd5d0b7752d1ac3e90aacf

22. Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283-290. doi:10.4103/0259-1162.143110

23. Scarponcini TR, Edwards CJ, Rudis MI, Jasiak KD, Hays DP. The role of the emergency pharmacist in trauma resuscitation. J Pharm Pract. 2011;24(2):146-159. doi:10.1177/0897190011400550

24. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145-161.

25. Johnstone-Petty, M. Ketamine use for complex pain in the palliative care population. J Hosp Palliat Nurs. 2018;20(6):561-567. doi: 10.1097/NJH.0000000000000488.

26. Mercadante S, Caruselli A., Casuccio A. The use of ketamine in a palliative-supportive care unit: a retrospective analysis. Ann Palliat Med. 2018;7(2): 205-210. doi: 10.21037/apm.2018.01.01

27. Bell RF, Kalso EA. Ketamine for pain management. Pain Rep. 2018;3(5):e674. Published 2018 Aug 9. doi:10.1097/PR9.0000000000000674

28. Lalanne L, Nicot C, Lang JP, et al. Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report. BMC Psychiatry. 2016;16(1):395. doi:10.1186/s12888-016-1112-2

29. Blonk MI, Koder BG, Van Den Bemt PMLA, Huygen FJPM. Use of oral ketamine in chronic pain management: a review. Eur J Pain. 2012;14(5): 466-472. https://doi-org.ezproxy.lib.uconn.edu/10.1016/j.ejpain.2009.09.005

30. Linder LM, Ross CA, Weant KA. Ketamine for the acute management of excited delirium and agitation in the prehospital setting. Pharmacotherapy. 2018;38(1):139-151. doi:10.1002/phar.2060

31. Lulla AA, Singh M. The Art of the ED Takedown. emDOCs.net - Emergency Medicine Education. Published March 4, 2015. Accessed July 25, 2022. http://www.emdocs.net/the-art-of-the-ed-takedown/

32. Young R, McMahon S. Some States Allow Authorities to Use Ketamine to Subdue Suspects in The Field. But Is It Safe? Some States Allow Authorities to Use Ketamine to Subdue Suspects in The Field. But Is It Safe? | Here & Now. Published September 8, 2020. Accessed July 25, 2022. https://www.wbur.org/hereandnow/2020/09/08/ketamine-police-safety-elijah-mcclain

33. Ketamine. In: Lexi-Drugs. Lexi-Comp, Inc. Updated July 20, 2022. Accessed July 25, 2022. http://usj-ezproxy.usj.edu:2099/lco/action/doc/retrieve/docid/patch_f/7135?cesid=a8n33eDrj1M&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dketamine%26t%3Dname%26acs%3Dfalse%26acq%3Dketamine#rfs

34. Montgomery-Asperg Depression Rating Scale. Accessed July 27, 2022. https://www.mdcalc.com/calc/4058/montgomery-asberg-depression-rating-scale-madrs

35. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630. doi:10.1093/ijnp/pyz039

36. Spravato. Prescribing information. Janssen Pharmaceutical Companies; 2019. Accessed July 25, 2022. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf

37. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630. doi:10.1093/ijnp/pyz039

Arthur E. Schwarting Symposium LIVE Event 2027 TBD

Arthur E. Schwarting was an internationally recognized leader in the transformation of pharmacognosy from a plant-based discipline to a science based on the chemistry of natural products. He also was the preeminent pharmacognosist in the U.S. to engage in the study of medicinal agents from microorganisms, and he was a pioneer in the use of radio isotopes to elaborate the biochemical pathways by which plants and microorganisms make medicinally active products. The Arthur E. Schwarting Symposium is now an educational conference focused on pharmacy practice for pharmacists in many settings.

Measure Twice, Cut Once: A Carpentry Approach to Pharmacy

Five hours of live streaming CE including Law, Patient Safety, and Immunization

2026 AGENDA

11:00am-12:00 pm

Load-Bearing Walls: Getting Cardiovascular Therapy Right the First Time

Katelyn Galli, PharmD, BCCP, UConn School of Pharmacy, Storrs, CT

Type of Activity: Application

ACPE UAN 0009-0000-26-009-L01-P

Learning Objectives: At the end of this presentation the learner will:

Identify high-risk cardiovascular medications that are most commonly associated with preventable adverse drug events amid transitions of care
Describe evidence-based principles for precise cardiovascular medication dosing, including clinically relevant pharmacokinetic considerations that influence drug and dose selection
Explain the benefits and limitations of clinical decision support tools in cardiovascular pharmacotherapy
Recognize common system-level and cognitive factors contributing to cardiovascular medication near misses and adverse effects

12:05-1:05 pm

LAW: The Legal Blueprint: Designing Error-Proof Pharmacy Policies

Dylan DeCandia, PharmD, RPh, Franklyn’s Pharmacy in Ho-Ho-Kus, New Jersey

Type of Activity: Application

ACPE UAN 0009-0000-26-010-L03-P

Learning Objectives: At the end of this presentation the learner will:

Describe the roles and responsibilities of each pharmacy staff member
Articulate when a pharmacist should seek legal clarification
Identify common pharmacy mistakes that may leave pharmacists liable
Construct policies and procedures that prevent future pharmacy errors

1:10-2:10 pm

Patient Safety: Blueprints Before Builds: Patient Assessment in Clinical Decision-Making

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

Type of Activity: Application

ACPE UAN 0009-0000-26-013-L05-P

Learning Objectives:

Explain the Pharmacists’ Patient Care Process and strategies to optimize the “Collect” and “Assess” steps to improve assessment and clinical decision-making
Identify common pitfalls that affect optimal patient assessment across healthcare settings
List strategies to incorporate patient-centered approaches into patient assessment and clinical decision-making

2:15-3:15 pm

Immunization: The Right Tool for the Job: Precision and Preparation in Immunization Practice

Thomas E. Buckley, RPh, MPH, FNAP; Associate Clinical Professor Emeritus, UConn School of Pharmacy, Storrs, CT

Type of Activity: Application

ACPE UAN 0009-0000-26-011-L06-P

Learning Objectives: At the end of this presentation the learner will:

Analyze contraindications as the “measurement” step
Determine the correct vaccine, dose, route, and needle length
Document and report finishing work
Detect administration errors and adverse events
Illustrate reliable vaccine information

3:20-4:20 pm

Right Fit, Tight Seal: Building Better Cancer Care

Thomas M Levay, PharmD, CSP, Yale New Haven Health, New Haven, CT

Type of Activity: Application

ACPE UAN 0009-0000-26-012-L01-P

Learning Objectives: At the end of this presentation the learner will:

Recognize ways that general education and consultation contributes to better care
Identify crucial elements of a patient’s non-clinical care for patients with cancer
Demonstrate different ways to help patients at each phase of care

Handouts will be posted 72 hours prior to the event in 2 slides per page and 6 slides per page below:

11:00am-12:00 pm Load-Bearing Walls: Getting Cardiovascular Therapy Right the First Time

12:05-1:05 pm LAW: The Legal Blueprint: Designing Error-Proof Pharmacy Policies

1:10-2:10 pm Patient Safety: Blueprints Before Builds: Patient Assessment in Clinical Decision-Making

2:15-3:15 pm Immunization: The Right Tool for the Job: Precision and Preparation in Immunization Practice

3:20-4:20 pm Right Fit, Tight Seal: Building Better Cancer Care

“The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.”

Continuing Education Units

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 will be awarded at CE Finale based on full sessions attended and completed online evaluations. Pharmacists can earn up to 5 contact hours (0.50 CEU) one of which is a law credit, one is an Immunization Credit, and one is a Patient Safety Credit.

Please Note: Pharmacists who wish to receive credit for the presentations MUST ACCURATELY complete the registration and online evaluations within 45 days of the live program (before February 1, 2026). Participants are accountable for their own continuing education requirements for license renewal and are required to follow up with Heather.Kleven@uconn.edu to resolve a discrepancy in a timely manner. PLEASE CHECK YOUR CPE MONITOR PROFILE within 3 days of submission to ensure that your credits have been properly uploaded. Requests for exceptions will be handled on a case-by-case basis and may result in denial of credit.

Registration Fees: 50% discount for UConn faculty/preceptors

Guideline-Driven Treatment for Mental Illnesses and Substance Abuse Disorders

Pharmacists possess the training and skills necessary to administer certain long-acting injectable (LAI) medications used in the management of mental illnesses and substance use disorders. Through collaborative practice agreements, pharmacists can administer Long Acting Injectables in almost every state. In some states, including the state of Connecticut, this occurs via collaborative agreements, and necessary injection and disease state training. Administration of these medications by pharmacists can increase accessibility of care for patients.

UConn has developed web-based continuing pharmacy education activity to enhance pharmacists’ skills and help them make sound clinical decisions about long acting injectables administration. This course includes eight hours of CPE (or eight hours of credit), required by the State of Connecticut. Successful completion of these eight hours (with four activities consisting of three hours online pre-requisite work and five hours of LIVE CE) will earn the pharmacist a Certificate in Long-Acting Injectables of Psychotropic Medication.

The three activities below are available separately for $17/hour each, or as pre-requisites for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program at $299 which includes both the prerequisites and the full day of LIVE training.

At the end of this application-based continuing education activity, the learner will be able to:

Describe first- and second-line treatment options for the following disease states:

· Schizophrenia

· Bipolar disorder

· Alcohol use disorder

· Opioid use disorder

Identify where long-acting injectable medications fit into treatment guidelines for each disorder

Apply clinical treatment guidelines to select optimal pharmacologic treatment for a patient diagnosed with these disorders

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

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

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Long-Acting Injectable Medication Products

At the end of this application-based continuing education activity, the learner will be able to:

Compare and contrast among different long-acting injectable (LAI) medications currently available for the

treatment of schizophrenia, bipolar disorder and substance use disorders including:

· Dosing

· Generic and brand names

· Adverse effects

· Administration schedule

· Overlap with oral medications

· FDA-approved indications

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Mental Illness and Substance Use Disorders: Background

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Hour 1: Mental Illness and Substance Use Disorders: Background

1. A 38-year-old patient with an unknown psychiatric history is dropped off at the emergency department by police after being found wandering the streets and knocking on doors at random. The patient admits that they believe they are being monitored by the FBI and that “the mafia” wants to recruit them as a spy. The patient is observed having a conversation with themselves while alone in the examination room.

Which of the following positive symptoms is the patient likely experiencing?
A. Psychosis and auditory hallucinations
B. Auditory hallucinations and delusions
C. Delusions and anhedonia
D. Paranoia and agitation

2. Which of the following is the correct term for fixed, false beliefs that patients with schizophrenia may experience?
A. Delusions
B. Hallucinations
C. Disorganized speech
D. Catatonia

3. A patient with schizophrenia has experienced both positive and negative symptoms for several years. They are now presenting with signs of mania, including pressured speech and grandiosity. Which of the following is true?
A. The patient’s diagnosis will likely change to schizoaffective disorder, bipolar type
B. The patient’s diagnosis will likely change to schizoaffective disorder, depressive type
C. The patient will now be diagnosed with schizophrenia and bipolar disorder
D. The patient will now be diagnosed with schizophrenia and major depressive disorder

4. Which of the following is true about bipolar disorder?
A. The most common time that patients are diagnosed is during childhood
B. Most patients are initially diagnosed with schizophrenia
C. It has a higher mortality rate than major depressive disorder
D. Type II bipolar disorder is associated with more severe episodes of mania than type I

5. Most patients with bipolar disorder spend the majority of their time in which mood phase?
A. Mania
B. Depression
C. Hypomania
D. Euthymia

6. A patient with bipolar disorder presents to their outpatient provider and reports that they believe they are on the verge of a “breakthrough” and will soon become a world-famous author once their manuscript is published. They have recently stopped going to work and have been writing “all day and all night” for the past week. They also report spending thousands of dollars on a new computer so that they have “the best equipment” with which to write their manuscript.
Which of the following symptoms of mania is the patient displaying?
A. Grandiosity, decreased need for sleep, increased goal directed activity
B. Flight of ideas, distractibility, grandiosity
C. Disorganized thoughts, decreased need for sleep, flight of ideas
D. Confusion, excessive spending, distractibility

7. Patient NP was diagnosed with bipolar disorder, type II approximately 5 years ago. They have rarely missed work due to hypomanic symptoms, and are generally able to perform all day-to-day activities without impairment. Following a breakup, NP begins to display signs of grandiosity, flight of ideas, decreased sleep, and increased spending. They also begin to hear the voice of their ex-partner telling them that they are worthless.

Which of the following is most appropriate?
A. NP’s diagnosis should be changed to bipolar disorder type I
B. NP’s diagnosis should remain the same
C. NP’s diagnosis should be changed to schizoaffective disorder
D. NP’s diagnosis should be changed to bipolar disorder, mixed type

8. Which of the following is a risk factor for the development of a substance use disorder?
A. Female gender
B. Age > 65 years
C. Co-occurring psychiatric disorder
D. Parenthood

9. Which type of opioid receptor contributes to the stimulation of the dopamine-related reward system?
A. Mu-opioid receptor
B. Kappa-opioid receptor
C. Delta-opioid receptor
D. Beta-opioid receptors

Patient Safety: Pharmacy Metrics-Recorded Webinar

The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Pharmacists and Pharmacy Technicians are eligible to participate in this application-based activity and will receive up to 1.0 CE Hours (or 0.1 CEUs) for completing the activity ACPE UAN 0009-0000-23-026-H05-T, passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor online system and your participation will be recorded with CPE Monitor within 72 hours of submission.

1. Which of the following is NOT a use for metrics in pharmacies?
A. Quantify workflow
B. Exhaust staff
C. Establish comparators

2. Patient-centered metrics are based on which of the following?
A. Profits
B. Public health initiatives
C. Patient complaints

3. _____ is a metric used to assess productivity.
A. Time-to-fill
B. Rate of medication errors
C. Out-of-stock prescriptions

4. Which of the following is a good way to reach vaccination metrics?
A. Letting the patient contact the pharmacy about vaccinations
B. Reminding patients of vaccinations at the register
C. Relying on advertising to encourage patients

5. What does SMART goals, a great way to develop an approach to improve metrics, stand for?
A. Specific, Measurable, Achievable, Relevant, Time-Bound
B. Specific, Measurable, Achievable, Resourceful, Time-Bound
C. Specific, Measurable, Accurate, Reasonable, Time-Bound

6. What is the most important skill in the workplace when tackling metrics?
A. Speed
B. Communication
C. Knowledge

7. Many metrics focus on efficiency. What other consideration is crucial?
A. Type of pharmacy
B. Patient safety
C. Workload or volume

8. Select the statement that is TRUE:
A. Metrics usually refer to a general aspect of pharmacy tasks, so they are the same in community and clinical settings.
B. While metrics often refer to a general aspect of pharmacy tasks, they can vary greatly between community and clinical settings.
C. While metrics often refer to a general aspect of pharmacy tasks, pharmacies should stay away from standard metrics and develop new approaches.

9. Super Tech is worried about her pharmacy’s time-to-fill metric. Wonder Pharmacist is focused on inventory metrics. Three months go by and they haven’t made good progress on either. Why?
A. They are working alone on each metric, but need to be working together.
B. It’s not possible to work on two metrics at the same time.
C. Improving time-to-fill metrics will adversely influence inventory metrics.

10. Which of the following activity falls heavily on pharmacy technicians and contributes heavily to pharmacy metrics in the community setting?
A. Vaccinations
B. Insurance and billing
C. In-person patient interaction

CT MPJE Law Review Handouts

Are you new to Connecticut?

Do you need to take the Connecticut Law Exam for licensure?

Study Guide/Handouts from the 2026 program are now available for $50.

To Order the 2026 Handouts-$50

Replacement Immunization Certificates

Have you lost or misplaced your Immunization Certificate? If you attended the University of Connecticut School of Pharmacy’s “Immunization Training for Pharmacists” or you completed your Immunization Training as a UConn School of Pharmacy student, and need a replacement certificate, you can order your replacement copy online. The cost is $15 for the certificate. Just add to your cart!

CONTINUING EDUCATION CREDIT:
The University of Connecticut, School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Disclaimer:
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.

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Measure Twice, Cut Once: A Carpentry Approach to Pharmacy

2026 AGENDA

About this Course

Target Audience

Pharmacist Learning Objectives

Bundle Options

Accreditation Statement

Grant Funding

Requirements for Successful Completion

Faculty

Faculty Disclosure

Disclaimer

Program Content

Program Handouts

Post Test Evaluation

View Questions for Mental Illness and Substance Use Disorders: Background

Additional Courses Available for Long Acting Injectable Training

About this Course

Target Audience

Pharmacist Learning Objectives

Bundle Options

Accreditation Statement

Grant Funding

Requirements for Successful Completion

Faculty

Faculty Disclosure

Disclaimer

Program Content

Program Handouts

Post Test Evaluation

View Questions for Long-Acting Injectable Medication Products

Additional Courses Available for Long Acting Injectable Training

About this Course

Target Audience

Pharmacist Learning Objectives

Bundle Options

Accreditation Statement

Grant Funding

Requirements for Successful Completion

Faculty

Faculty Disclosure

Disclaimer

Program Content

Program Handouts