Potassium-sparing diuretics are a class of diuretic medications that increase diuresis (urine production) while conserving potassium, contrasting with thiazide and loop diuretics that promote potassium loss. They are used primarily to counteract hypokalemia and as adjuncts in conditions involving excessive fluid retention or aldosterone excess.
Classification and Key Agents
Class
Main Drugs
Site of Action
Mechanism
Aldosterone antagonists
Spironolactone, eplerenone
Collecting duct
Competitive inhibition at mineralocorticoid (aldosterone) receptor
CYP3A4 inhibitors (for eplerenone): May increase concentration/toxicity.
Contraindications: Hyperkalemia, severe renal insufficiency, Addison disease.
Comparative Summary Table
Feature
Spironolactone
Eplerenone
Amiloride
Triamterene
Receptor target
Aldosterone
Aldosterone
ENaC
ENaC
Relative potency
+++
++
+
+
CV effect
Proven mortality benefit (HF)
Proven (HF)
None
None
Endocrine effects
Gynecomastia, menstrual changes
Minimal
None
None
Use in hyperaldosteronism
Yes
Yes
No
No
Renal dosing
Reduce/avoid in dysfunction
Reduce in dysfunction
Avoid in dysfunction
Avoid in dysfunction
References
Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill; 2022.
Potassium-sparing diuretic. Wikipedia. 2023.
Amiloride—StatPearls [Internet]. 2024 Feb 27.
Potassium sparing diuretics—Osmosis. Jan 2025.
Key Pearls:
Not potent diuretics alone; best used in combination to reduce K⁺ loss.
Regularly monitor renal function and serum potassium.
Spironolactone, eplerenone: mainstay in heart failure and hyperaldosteronism; be mindful of hormonal side effects with spironolactone, less with eplerenone.
Amiloride/triamterene: primarily adjuncts; do not affect hormonal pathways.
Reference
Mentor, Pharmacology. Pharmacology of Potassium-Sparing Diuretics. Pharmacology Mentor. Available from: https://pharmacologymentor.com/potassium-sparing-diuretics-pharmacology-mechanism-of-action-and-clinical-use/. Accessed on October 8, 2025 at 23:19.
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