A 55-year-old man with hypertension and type 2 diabetes is on an ACE inhibitor. Eplerenone is added for cardiovascular protection. Compared to spironolactone, eplerenone is preferred primarily because:

• A Eplerenone has greater mineralocorticoid receptor affinity, giving stronger potassium-sparing effect
• B Eplerenone is a selective mineralocorticoid receptor antagonist with minimal off-target progestogenic and androgenic receptor affinity, reducing gynecomastia risk ✓
• C Eplerenone is more effectively renally cleared, preventing drug accumulation in renal failure
• D Eplerenone does not cause hyperkalemia unlike spironolactone

Explanation

Spironolactone, while effective as a mineralocorticoid receptor antagonist, also binds to androgen and progesterone receptors, causing gynecomastia, erectile dysfunction, and menstrual irregularities. Eplerenone is a selective mineralocorticoid receptor antagonist with ~100-fold lower affinity for androgen and progesterone receptors, virtually eliminating these sex hormone-related side effects. Both drugs carry the risk of hyperkalemia, especially when combined with ACE inhibitors or ARBs. Eplerenone does not have greater mineralocorticoid potency — it is actually somewhat less potent per mg than spironolactone.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.