A 65-year-old man with heart failure is started on spironolactone. After 2 weeks he develops peaked T waves on ECG. His serum potassium is 6.4 mEq/L. What is the mechanism of this drug's adverse effect?
- A Inhibition of Na-K-ATPase pump in renal tubules
- B Blockade of Na-K-2Cl cotransporter in thick ascending limb
- C Competitive antagonism of aldosterone at mineralocorticoid receptors in collecting duct ✓
- D Inhibition of carbonic anhydrase in proximal tubule
Correct answer: C. Competitive antagonism of aldosterone at mineralocorticoid receptors in collecting duct
Explanation
Spironolactone competitively blocks aldosterone at mineralocorticoid receptors in the principal cells of the collecting duct, preventing sodium reabsorption and potassium secretion. This potassium-sparing mechanism leads to hyperkalaemia, which is the drug's most dangerous adverse effect, manifesting on ECG as peaked (tall, narrow, tent-shaped) T waves in early stages. Caution is warranted when combined with ACE inhibitors or ARBs.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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