HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

• 194 - 5-HT3 Receptor Antagonists for Nausea/Vomiting: An In-Depth Drug Class Review

  In this episode, we review the pharmacology, indications, adverse effects, and unique drug characteristics of 5-HT3 receptor antagonists such as ondansetron (Zofran) and palonosetron (Aloxi). Key Concepts There are four 5-HT3 (serotonin subtype 3) receptor antagonists on the market: ondansetron, granisetron, dolasetron, and palonosetron. These have primarily been studied for acute chemotherapy-induced nausea and vomiting (within 24 hours of chemotherapy administration) and for post-operative nausea and vomiting. When used for chemotherapy-induced nausea/vomiting, 5-HT3 receptor antagonists are given prior to chemotherapy (usually 30-60 minutes before) on day #1. They are not given on subsequent days because they are not as effective for delayed nausea and vomiting. Palonosetron has the longest half-life, longer binding affinity to the 5-HT3 receptor, and trends towards having the best efficacy among the 5-HT3 receptor antagonists. 5-HT3 receptor antagonists are associated with QTc prolongation and may cause headache, dizziness, constipation, or diarrhea. Their association with an increased risk of serotonin syndrome is controversial and not supported from a mechanistic perspective. References Simino GP, Marra LP, Andrade EI, et al. Efficacy, safety and effectiveness of ondansetron compared to other serotonin-3 receptor antagonists (5-HT3RAs) used to control chemotherapy-induced nausea and vomiting: systematic review and meta-analysis. Expert Rev Clin Pharmacol. 2016;9(9):1183-1194. doi:10.1080/17512433.2016.1190271 Tricco AC, Soobiah C, Blondal E, et al. Comparative efficacy of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis. BMC Med. 2015;13:136. Published 2015 Jun 18. doi:10.1186/s12916-015-0371-y Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 Herrstedt J, Clark-Snow R, Ruhlmann CH, et al. 2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting. ESMO Open. 2024;9(2):102195. doi:10.1016/j.esmoop.2023.102195 Rojas-Fernandez CH. Can 5-HT3 Antagonists Really Contribute to Serotonin Toxicity? A Call for Clarity and Pharmacological Law and Order. Drugs Real World Outcomes. 2014;1(1):3-5. doi:10.1007/s40801-014-0004-3 Li WS, van der Velden JM, Ganesh V, et al. Prophylaxis of radiation-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials. Ann Palliat Med. 2017;6(2):104-117. doi:10.21037/apm.2016.12.01

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• 193 - Elevate Your Guideline Knowledge, Not Your BP: The New 2025 Hypertension Guidelines

  In this episode, we review the newly published 2025 ACC/AHA hypertension guidelines. Key Concepts Instead of the Pooled Cohort Equations (PCE) from 2013, the 2025 hypertension guidelines recommend a new risk equation called PREVENT, which incorporates new risk factors and does not include race as part of the risk calculation. The guidelines recommend starting two antihypertensive medications for initial therapy in stage II hypertension and one antihypertensive medication for stage I hypertension. The guidelines no longer recommend specific first-line therapies for black patients. Instead, all patients without compelling indications should be initiated on a thiazide, ACE inhibitor, ARB, or dihydropyridine calcium channel blocker regardless of race/ethnicity. All patients should have a blood pressure goal of References Jones DW, Ferdinand KC, Taler SJ, Johnson HM, Shimbo D, Abdalla M, Altieri MM, Bansal N, Bello NA, Bress AP, Carter J, Cohen JB, Collins KJ, Commodore-Mensah Y, Davis LL, Egan B, Khan SS, Lloyd-Jones DM, Melnyk BM, Mistry EA, Ogunniyi MO, Schott SL, Smith SC Jr, Talbot AW, Vongpatanasin W, Watson KE, Whelton PK, Williamson JD. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025 Aug 14. doi: 10.1161/CIR.0000000000001356. Epub ahead of print. PMID: 40811497.

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• 192 - Opioids Optional: Journavx, the New Acute Pain Management Alternative

  In this episode, we discuss the evidence, safety, and place in therapy of Journavx® (suzetrigine), a newly approved analgesic with a unique non-opioid mechanism of action and additional considerations for its use. Key Concepts Suzetrigine is a first in its class NaV1.8 sodium channel blocker approved for short-term (14 days or less) pain relief in adults with moderate-to-severe pain. Unlike opioids, suzetrigine is non-sedating and non-dependence forming. Suzetrigine is taken as a whole pill without cutting, crushing, or chewing following a particular dosing schedule where the first dose is taken on an empty-stomach.  The most common side effects of suzetrigine include pruritus, muscle spasms, increased CPK, rash, and transient (reversible) eGFR decrease. Suzetrigine goes through CYP3A metabolism and therefore has significant interactions with CYP3A inducers and inhibitors. Use with strong inhibitors and moderate to strong inducers is not recommended. Dose reduction of suzetrigine is required if used with moderate inhibitors of CYP3A.  Although not formally adopted in a guideline recommendation, suzetrigine's current place in therapy can be moderate-to-severe acute pain relief in adult patients after NSAIDs/APAP options are exhausted, but before or in place of opioid therapy.  References Bertoch T, D'Aunno D, McCoun J, et al. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. 2025;142(6):1085-1099. doi:10.1097/ALN.0000000000005460

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• 191 - The Ultimate Guide to ARBs: An In-depth Drug Class Review

  In this episode, we review the pharmacology, indications, adverse effects, monitoring, and unique drug characteristics of angiotensin receptor blockers (ARBs).  Key Concepts ARBs are equally efficacious as ACE inhibitors when used for hypertension, heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD) with proteinuria, and post-MI care. Some limited evidence suggests that they might be better in reducing albuminuria in patients with diabetes. ARBs are generally better tolerated than ACEi due to a lower risk of angioedema and dry cough.  While most ARBs are comparable to each other, small differences exists regarding hepatic metabolism (CYP metabolism for losartan, telmisartan, and azilsartan), degree of blood pressure lowering (generally better with azilsartan, olmesartan, valsartan, and candesartan), and additional pharmacological effects (telmisartan with PPAR-Y agonism, losartan with uricosuric effect). ARBs are contraindicated in pregnancy, those with bilateral renal artery stenosis, and those with previous angioedema to ARBs. The most common adverse effects include hypotension and hyperkalemia, but in rare cases acute renal impairment can also occur. Baseline serum creatinine and potassium should be monitored in patients taking ARBs. After initiation or dose adjustment, blood pressure, serum creatinine, and potassium should be repeated in 1-2 weeks. Signs and symptoms of hypotension as well as angioedema should be monitored throughout the treatment period.

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• 190 - Can't Stop, Won't Drop … The BP That Just Won't Quit: Diagnosis and Treatment of Resistant Hypertension

  In this episode, we discuss the diagnosis and treatment of resistant hypertension, including a newer endothelin receptor antagonist (ERA) called aprocitentan (Tryvio®). Key Concepts The diagnosis of true resistant hypertension is based on requiring more than 3 antihypertensives (ACE inhibitor or ARB + calcium channel blocker + diuretic) to achieve goal BP, ruling out inaccurate BP readings, and ensuring patient adherence to their antihypertensive therapy. Non-pharmacologic therapy (especially dietary sodium restriction), medication adherence, and lifestyle changes are critical to the treatment of resistant hypertension. The preferred 4th line option for most patients with resistant hypertension is spironolactone. After adding spironolactone, additional therapies are based on expert opinion and patient-specific factors. These additional therapies may include beta blockers, alpha-2 agonists, alpha-1 blockers, hydralazine, minoxidil, and aprocitentan. References Carey RM, Calhoun DA, Bakris GL, et al. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018;72(5):e53-e90. doi:10.1161/HYP.0000000000000084 Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41(12):1874-2071. doi:10.1097/HJH.0000000000003480

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