Spironolactone reduces mortality in heart failure with reduced ejection fraction primarily by which mechanism?

• A Blocking the epithelial sodium channel in the collecting duct
• B Competitively antagonizing the mineralocorticoid receptor in the distal nephron ✓
• C Inhibiting carbonic anhydrase in the proximal tubule
• D Inhibiting the Na-Cl cotransporter in the distal convoluted tubule

Explanation

Spironolactone is a competitive antagonist of the mineralocorticoid receptor, blocking aldosterone-mediated sodium reabsorption and potassium secretion in the collecting duct. The RALES trial demonstrated mortality benefit in severe heart failure. ENaC blockade is the mechanism of amiloride, not spironolactone.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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