Nephrology · USMLE Step 1 and Step 2

Potassium-Sparing Diuretics song

Spironolactone & Amiloride - Mechanism & Effects, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Potassium-Sparing Diuretics

Full song on YouTube ↗Spotify ↗

Key points in this song10

Spironolactone and eplerenone block aldosterone receptors in the cortical collecting duct, preventing sodium reabsorption and potassium excretion; eplerenone is more selective with fewer antiandrogenic side effects.
Amiloride and triamterene directly block ENaC (epithelial sodium channels) in the collecting duct independent of aldosterone, making them effective even in adrenal insufficiency.
The primary risk of all potassium-sparing diuretics is hyperkalemia, which is potentiated by concurrent ACE inhibitors, ARBs, or NSAIDs.
Spironolactone is a first-line agent for primary hyperaldosteronism (Conn syndrome) and reduces mortality in systolic heart failure (NYHA class III–IV) per the RALES trial.
Gynecomastia, decreased libido, and menstrual irregularities are classic antiandrogenic side effects of spironolactone due to its non-selective steroid receptor binding.
Triamterene can precipitate in urine and cause triamterene kidney stones, a high-yield cause of drug-induced nephrolithiasis.
Potassium-sparing diuretics are used in combination with thiazides or loop diuretics to counteract hypokalemia, as seen in the classic combination of hydrochlorothiazide plus triamterene.
Spironolactone is the preferred diuretic for managing ascites in cirrhosis, often combined with furosemide in a 100 mg:40 mg ratio to maintain normokalemia.
Eplerenone is used post-myocardial infarction in patients with reduced ejection fraction and either diabetes or heart failure to reduce cardiovascular mortality.
Amiloride is the treatment of choice for Liddle syndrome, a gain-of-function ENaC mutation causing hypertension, hypokalemia, and low aldosterone levels unresponsive to spironolactone.