Acetazolamide (carbonic anhydrase inhibitor) used as a diuretic causes metabolic acidosis rather than alkalosis. Why?

• A It causes hyperchloraemia by increasing renal chloride reabsorption
• B Acetazolamide activates aldosterone receptors, retaining H+ in the collecting duct
• C Acetazolamide inhibits renal ammoniagenesis, causing proton accumulation
• D By inhibiting proximal tubular carbonic anhydrase, it prevents H+ secretion and HCO3- reabsorption, causing urinary bicarbonate loss and hyperchloraemic metabolic acidosis ✓

Explanation

Carbonic anhydrase in the brush border and cytoplasm of proximal tubular cells catalyses: CO2 + H2O → H2CO3 → H+ + HCO3-. H+ is secreted into the tubular lumen (driving Na+ absorption via NHE3) and HCO3- is reabsorbed. Acetazolamide inhibition prevents this, causing bicarbonate to be excreted in urine (HCO3- wasting) along with Na+, K+, and water. The loss of base (HCO3-) from the body results in hyperchloraemic metabolic acidosis. This contrasts with loop and thiazide diuretics, which cause metabolic alkalosis (from volume contraction and H+ loss with K+).

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

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