In this episode, we discuss the very early stages of drug targets and drug development with Dr. Mohd Shahid, PhD. Dr. Shahid’s research involves the IER3 gene, which is an important modulator of the body’s inflammatory response via its action in major immune cells, including macrophages and T-cells, and plays a role in metabolic disorders such as obesity, diabetes, and atherosclerosis, revealing a previously unknown function of this protein.

Key Concepts

1. Drug development is a multi-decade journey – human clinical trials occur very late in the process. Drug development often starts before a drug molecule is even conceived by identifying potential drug targets.
2. Chronic inflammation is important for a variety of diseases, including obesity and atherosclerosis. Dr. Shahid’s work focuses on a specific gene, Immediate Early Response 3 Gene (IER3 or IEX-1), and its role in modulating the inflammatory response in these disease states.
3. The research process frequently leads to unexpected discoveries and new lines of inquiry. With Dr. Shahid, his work in obesity and inflammation actually led to a new understanding of the IER3’s role in the interplay between macrophages, inflammation, and energy expenditure.

References

• Shahid M, Javed AA, Chandra D, et al. IER3 deficiency induces browning of white adipose tissue and resists diet-induced obesity. Sci Rep. 2016;6:24135. Published 2016 Apr 11. doi:10.1038/srep24135
• Shahid M, Hermes EL, Chandra D, et al. J Am Heart Assoc. 2018;7:e009261. DOI: 10.1161/JAHA.118.009261.
• Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. doi:10.1056/NEJMoa0807646
• Tardif JC, Kouz S, Waters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381(26):2497-2505. doi:10.1056/NEJMoa1912388

In this episode, we review the new 2025 ACC/AHA Acute Coronary Syndrome (ACS) guidelines, with a particular focus on guideline recommendations for analgesics, P2Y12 inhibitors, parenteral anticoagulation, and lipid management.

Key Concepts

1. Nitrates and opioids are recommended for symptomatic relief of chest pain. Some patients may not be appropriate for nitrates (e.g. recent PDE-5 inhibitor use, hypotension, or right ventricular infarction). Opioids are used for nitrate-refractory angina but have a theoretical risk of delaying the effect of oral antiplatelet medications.
2. Prasugrel and ticagrelor are preferred P2Y12 inhibitors over clopidogrel in most patients. Patient-specific factors, including the use of PCI, play a role in P2Y12 inhibitor selection.
3. Anticoagulation with heparin is recommended in nearly all acute coronary syndrome (ACS) scenarios. Alternative anticoagulants may be used depending on whether PCI/CABG is planned and whether the anticoagulant is used prior to PCI/CABG (“upstream”) or during the PCI procedure itself.
4. LDL goals after ACS have changed again. All ACS patients should have an LDL goal < 70 with a consideration of an LDL goal of 55-69. A variety of non-statin therapies may be added to a high intensity statin regimen if LDL is not at goal.

References

• Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. Published online February 27, 2025. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001309

In this episode, we interview Morgan Anderson, PharmD, BCIDP, a graduate of the RFUMS College of Pharmacy, about her career path from a pharmacy resident, emergency medicine specialist, infectious diseases specialist, and now a medical sciences liaison.

The views, thoughts, and opinions expressed in this podcast are solely Dr. Anderson’s own and do not necessarily reflect the views, positions, or policies of her employer. This podcast is conducted in a personal capacity, and any reference to her professional background is for context only.

Key Concepts

1. Having a wide breadth of skills and making yourself marketable is important when transitioning between jobs or career paths. Skills like communication and teamwork can be improved and are applicable to a wide variety of careers within pharmacy.
2. Medical Science Liaisons (MSLs) are a common role for pharmacists in the pharmaceutical industry. MSLs are field-based roles within the medical affairs department of the company. MSLs are medical and scientific experts who build collaborative relationships with key thought leaders, facilitate exchange of scientific information and insights, and serve as a conduit between these thought leaders and other areas of the company.
3. Two common career paths to pharmacists becoming an MSL are via a fellowship program or after years in clinical practice. A fellowship program provides a more structured approach, including mentoring and networking, with access to a variety of areas of the company outside of medical affairs. A pathway after clinical practice is more self-directed with less structure, but provides pharmacists with a strong clinical background that can be helpful in an MSL role.
4. Being a scientific communicator, possessing strong emotional intelligence, and being adaptable are critical soft skills that are essential for success in an MSL role. These soft skills can be improved with practice!

References

• https://www.industrypharmacist.org/

In this episode, we discuss the efficacy and safety of semaglutide and tirzepatide for weight loss with a particular focus on the legal, regulatory, and safety aspects of these “compounded” GLP-1 receptor agonist medications.

Key Concepts

1. Semaglutide and tirzepatide have growing evidence that their clinical benefits extend beyond the treatment of diabetes. Evidence now shows benefit in a variety of obesity-related disease states regardless of a patient’s diabetes status.
2. Insurance coverage and drug cost is a major barrier to these medications, with cash prices exceeding $1000 per month in the US. There are many companies that are combining telemedicine visits with “compounded” GLP-1s to provide these medications at a reduced cost.
3. The Food, Drug, and Cosmetic (FD&C) Act regulates compounded drugs. These regulations provide the legal context for pharmacies to compound GLP-1 medications. These regulations describe who can compound, what drugs can be compounded, and other unique circumstances (e.g. compounding in the context of a drug shortage).
4. The FDA has released warnings regarding safety risks of compounded GLP-1s. The main safety concern is dosing errors; however, the warnings also include concerns of patients accessing drug products that are outside of the legal scope of the FD&C Act. The recent ADA statement recommends against the use of compounded GLP-1s due to these concerns.

References

• Karagiannis T, Malandris K, Avgerinos I, et al. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. Diabetologia. 2024;67(7):1206-1222. doi:10.1007/s00125-024-06144-1
• Müllertz ALO, Sandsdal RM, Jensen SBK, Torekov SS. Potent incretin-based therapy for obesity: A systematic review and meta-analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety. Obes Rev. 2024;25(5):e13717. doi:10.1111/obr.13717
• Jastreboff AM, Le Roux CW, Stefanski A, et al. Tirzepatide for Obesity Treatment and Diabetes Prevention. New England Journal of Medicine. 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2410819
• Contract Year 2026 Policy and Technical Changes to the Medicare Advantage Program, Medicare Prescription Drug Benefit Program, Medicare Cost Plan Program, and Programs of All-Inclusive Care for the Elderly (CMS-4208-P). https://www.cms.gov/newsroom/fact-sheets/contract-year-2026-policy-and-technical-changes-medicare-advantage-program-medicare-prescription
• Human Drug Compounding. https://www.fda.gov/drugs/guidance-compliance-regulatory-information/human-drug-compounding
• Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act. https://www.fda.gov/media/98973/download
• FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products. https://www.fda.gov/drugs/human-drug-compounding/fda-alerts-health-care-providers-compounders-and-patients-dosing-errors-associated-compounded
• FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
• Nomination of Semaglutide Products to the Demonstrable Difficulties for Compounding Lists. https://www.regulations.gov/document/FDA-2017-N-2562-0029
• Neumiller JJ, Bajaj M, Bannuru RR, et al. Compounded GLP 1 and dual GIP/GLP 1 receptor agonists: A statement from the American Diabetes Association. Diabetes Care. 2024 Dec 2:dci240091. doi: 10.2337/dci24-0091.

In this episode, we review the recommendations from the 2024 SCCM/ASHP stress ulcer prophylaxis guidelines and highlight three of the more recent landmark critical care trials investigating the role of stress ulcer prophylaxis.

Key Concepts

1. After 25 years, the stress ulcer prophylaxis guidelines have been updated by SCCM and ASHP. These guidelines make 13 recommendations in a PICO format.
2. Three large, landmark randomized controlled trials (SUP-ICU, PEPTIC, and REVISE) have significantly contributed to the body of literature regarding stress ulcer prophylaxis.
3. The SCCM/ASHP guidelines recommend stress ulcer prophylaxis in patients with coagulopathy, shock, chronic liver disease, and possibly in neurocritical care patients. They do not specifically recommend prophylaxis in mechanically ventilated patients; this is a controversial recommendation.
4. The SCCM/ASHP guidelines equally prefer proton pump inhibitor (PPI) and histamine-2 receptor antagonists (H2RA) drug therapies given either intravenously or orally. The prophylaxis regimen should be continued until the indication for prophylaxis has resolved or the patient leaves the ICU.

References

• MacLaren R, Dionne JC, Granholm A, et al. Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults. Crit Care Med. 2024;52(8):e421-e430. doi:10.1097/CCM.0000000000006330
• SUP-ICU study. Krag M, Marker S, Perner A, et al. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. N Engl J Med. 2018;379(23):2199-2208. doi:10.1056/NEJMoa1714919
• PEPTIC study. PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group, Young PJ, Bagshaw SM, et al. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial. JAMA. 2020;323(7):616-626. doi:10.1001/jama.2019.22190
• REVISE study. Cook D, Deane A, Lauzier F, et al. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med. 2024;391(1):9-20. doi:10.1056/NEJMoa2404245

In this episode, we discuss the approach to deprescribing for several drugs such as benzodiazepine receptor agonists, cholinesterase inhibitors, memantine, antipsychotics, and antihyperglycemics.

Key Concepts

1. Medication appropriateness including indication and risk vs. benefit should be evaluated for all stages of life; however, more importantly in older individuals to address polypharmacy.
2. There is an emerging trend of deprescribing networks that conduct research and provide evidence-based recommendations for how to deprescribe certain medications used for specific indications.
3. Evidence-based deprescribing guidelines for PPIs, benzodiazepines, benzodiazepine receptor agonists, opioids, antipsychotics, cholinesterase inhibitors, memantine, and antihyperglycemics are available for patient-provider shared decision making. 
4. A general deprescribing approach is gradual tapering of the drug leading to discontinuation over several weeks while monitoring patients for withdrawal symptoms or benefits of discontinuation. 

References

• http://deprescribing.org
• https://www.australiandeprescribingnetwork.com.au

In this episode, we review the pharmacology, pharmacokinetics, adverse effects, monitoring, medicinal chemistry, and more of loop diuretics.

Key Concepts

1. Loop diuretics (furosemide, torsemide, bumetanide, ethacrynic acid) are the most potent type of diuretic and are used to relieve edema.
2. Loop diuretics cause an increased loss of sodium, chloride, potassium, hydrogen, magnesium, and calcium ions into the urine. Excessive loss of these ions manifests as hypokalemia, hypomagnesemia, and metabolic alkalosis.
3. Loop diuretics have an S-shaped dose response curve – a minimum dose is required for diuresis and a “ceiling” effect occurs at higher doses (leading to more ADRs). Doses should be individualized based on the clinical response of the patient.
4. Ethacrynic acid is incorrectly used in patients with a “sulfa” allergy. The other loop diuretics contain a sulfa moiety but are safe for use in patients with “sulfa” allergy (e.g. allergy to sulfamethoxazole-trimethoprim).
5. The TRANSFORM-HF trial strongly suggests that there is no clinical difference between furosemide and torsemide.

References

• Rachoin JS, Cerceo EA. Four nephrology myths debunked. J Hosp Med. 2011;6(5):E1-E5. doi:10.1002/jhm.703
• Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med. 2003;349(17):1628-1635. doi:10.1056/NEJMoa022963
• Buggey J, Mentz RJ, Pitt B, et al. A reappraisal of loop diuretic choice in heart failure patients. Am Heart J. 2015;169(3):323-333. doi:10.1016/j.ahj.2014.12.009
• Mentz RJ, Anstrom KJ, Eisenstein EL, et al. Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. JAMA. 2023;329(3):214-223. doi:10.1001/jama.2022.23924

In this episode, we discuss principles for medication use in the geriatric patient population and summarize the updated 2023 American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.

Key Concepts

1. The Beer’s Criteria was originally developed by Dr. Mark Beers in 1991 to identify medications in which the risks may outweigh the benefits in nursing home patients. This list is now maintained by the American Geriatrics Society and includes a variety of drug safety information related to elderly patients including medications that are considered potentially inappropriate (Table 2 and 3), medications used with caution (Table 4), drug-drug interactions (Table 5), drugs with renal dose adjustments (Table 6), and drugs with anticholinergic properties (Table 7).
2. The newest update prefers apixaban over other DOACs for VTE and atrial fibrillation in elderly patients. This is a very controversial recommendation given that other guidelines (e.g. from the ACC/AHA) have not published a similar preference of one DOAC over another.
3. Many of the medications that are potentially inappropriate involve drugs that have anticholinergic properties and drugs that increase the risk of incoordination and falls.
4. Other resources exist to guide drug therapy decisions in elderly patients. As an example, the STOPP/START criteria (published in the European Geriatric Medicine journal) outlines drugs to avoid but also drugs to consider in elderly patients.

References

• By the 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J AM Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372.
• O'Mahony D, Cherubini A, Guiteras AR, Denkinger M, Beuscart JB, Onder G, Gudmundsson A, Cruz-Jentoft AJ, Knol W, Bahat G, van der Velde N, Petrovic M, Curtin D. STOPP/START criteria for potentially inappropriate prescribing in older people: version 3. Eur Geriatr Med. 2023 Aug;14(4):625-632. doi: 10.1007/s41999-023-00777-y.

In this episode, we discuss artificial intelligence large language models (LLMs) and how these will impact the future of the practice of pharmacy.

Key Concepts

1. Generative AI with large language models (LLMs) have already changed how healthcare is delivered to patients. In the future, these changes will be more substantial and require pharmacists and other healthcare professionals to understand the benefits and downsides of this technology.
2. Commercial LLMs, such as ChatGPT, are not HIPAA compliant and should not be used with protected health information. Companies currently offer software products that are HIPAA compliant and can integrate directly into electronic health records in a HIPAA-compliant manner.
3. Currently, most commercial use cases of LLMs for healthcare providers focus on expediting or simplifying the documentation process (e.g. generating a first draft of a progress note or summarizing a patient encounter from an audio recording).
4. In the future, LLMs will be used to perform a variety of clinical tasks, including drug interaction checking, renal dose adjustments, duplication of therapy, and even the appropriateness of a patient’s drug regimen for a given medical condition. These clinical tasks will almost certainly be done as a “first pass” to highlight or flag specific aspects of a patient’s chart and will then be reviewed by a licensed (human) healthcare provider as a final check prior to clinical decisions being made.

References

1. Large Language Models (LLMs) referenced in the episode: https://chat.openai.com, https://coral.cohere.com, https://claude.ai, https://gemini.google.com.
2. Prompt Engineering Guide (https://www.promptingguide.ai/techniques)
3. OpenAI - Prompt engineering (https://platform.openai.com/docs/guides/prompt-engineering/six-strategies-for-getting-better-results)

In this episode, we review the pharmacology, indications, adverse effects, monitoring, and unique drug characteristics of HMG CoA reductase inhibitors (“statins”).

Key Concepts

1. Statins reduce LDL cholesterol by 20-60% (depending on the dose and statin potency). They have modest favorable effects on HDL and triglycerides. Clinically, statins reduce the risk of major adverse cardiac events by about 30% depending on the statin potency.
2. There are four main groups of patients who are indicated for a statin: LDL >= 190 mg/dL, diabetes with age 40-75 years with LDL 70-189 mg/dL, those with an elevated 10-year ASCVD risk of > 7.5% (or possibly > 5%), and those who have had an ASCVD event (“secondary prevention”).
3. Atorvastatin, lovastatin, and simvastatin heavily rely on CYP 3A4 metabolism and tend to be most susceptible to drug interactions compared to the other statins.
4. When a statin is started, baseline lipid panel and liver function tests should be obtained. After 4-12 weeks, a lipid panel should be repeated. Liver function and creatine kinase testing should only be done if a patient has a symptom (e.g. jaundice, right upper quadrant pain, muscle pain or weakness, dark urine, etc.)

References

• Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625