Trimethoprim-sulfamethoxazole, or TMP-SMX, and spironolactone can impair renal potassium excretion through different mechanisms. This lecture explains how trimethoprim’s amiloride-like inhibition of ENaC converges with mineralocorticoid-receptor antagonism—and why that can increase the risk of clinically important hyperkalemia.

Dr. Busti will explain how normal distal-nephron potassium handling works, which patients are most vulnerable, how to interpret the observational safety signal, and how clinicians can approach indication review, renal dosing, laboratory monitoring, medication reconciliation, and patient counseling.

Evidence discussed:
- Antoniou T, et al. BMJ. 2011;343:d5228. https://pubmed.ncbi.nlm.nih.gov/21911446/
- Antoniou T, et al. CMAJ. 2015;187(4):E138-E143. https://pubmed.ncbi.nlm.nih.gov/25646289/
- Spironolactone prescribing information: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=4239da9e-dd0c-9af0-e063-6394a90a3cbb
- Sulfamethoxazole/trimethoprim prescribing information: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b89b5502-ce87-45a6-a43c-9891da3cfca4

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Chapter Table of Contents
00:00 - Introduction
01:31 - Why This Drug Interaction Causes Hyperkalemia
03:27 - How the Distal Nephron Handles Potassium
05:16 -  Spironolactone + Trimethoprim: The Two-Hit Mechanism
07:50 - Who Is Most Vulnerable?
09:18 - Evidence: Hyperkalemia Hospitalization & Sudden Death
11:06 - Clinical Prevention, Monitoring & Management
14:47 - Four Key Takeaways

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Speaker:
Anthony Busti, MD, PharmD, MSc, FAHA, FNLA, is a licensed healthcare professional and medical educator with over 30 years of experience in clinical practice and academic teaching. He has trained and practiced as a nurse, pharmacist, and physician, bringing a uniquely comprehensive perspective to patient care and medical education.
Dr. Busti is dedicated to advancing evidence-based medicine and helping clinicians understand the underlying “why” behind clinical decisions to improve patient outcomes.

About This Channel:
This content is created by Anthony Busti, MD, PharmD, MSc, FAHA, FNLA, a board-certified physician with training at Johns Hopkins School of Medicine and University of Oxford and a medical educator for healthcare professionals and students. All material is based on current medical literature and evidence-based guidelines aligned with the principles of evidence-based medicine (EBM) and Evidence-Based Healthcare (EBHC).

Disclaimer:
This content is for educational purposes only and is not medical advice. It does not replace individualized evaluation, diagnosis, or treatment. Always seek the advice of a qualified health provider with questions about a medical condition and never delay care because of educational content.