Spironolactone is a potassium-sparing diuretic used in primary hyperaldosteronism and heart failure. Its mechanism of action is:
- A Inhibits the epithelial sodium channel (ENaC) directly in the collecting duct principal cells
- B Blocks aldosterone synthesis by inhibiting CYP11B2 in the adrenal cortex
- C Competitively antagonises aldosterone at its mineralocorticoid receptor in the collecting duct nucleus ✓
- D Inhibits the Na-Cl cotransporter (NCC) in the distal convoluted tubule
Correct answer: C. Competitively antagonises aldosterone at its mineralocorticoid receptor in the collecting duct nucleus
Explanation
Spironolactone is a competitive antagonist at the intracellular mineralocorticoid receptor (MR) in principal cells of the collecting duct. By blocking aldosterone from binding to its receptor, spironolactone prevents the transcriptional upregulation of ENaC and Na/K-ATPase, reducing sodium reabsorption and potassium secretion (potassium-sparing diuresis). Triamterene and amiloride directly inhibit ENaC (not spironolactone). NCC blockade is the mechanism of thiazides. Adrenal CYP11B2 inhibition is the mechanism of metyrapone.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.