Acetazolamide is a carbonic anhydrase inhibitor used as a diuretic and for altitude sickness. Which acid-base disturbance does chronic acetazolamide use predictably cause?

• A Metabolic alkalosis due to bicarbonate retention
• B Respiratory acidosis due to central respiratory depression
• C Metabolic acidosis due to increased urinary bicarbonate loss reducing serum HCO3– ✓
• D Respiratory alkalosis due to CNS stimulation

Explanation

Acetazolamide inhibits carbonic anhydrase in proximal tubular cells, reducing H+ secretion and HCO3– reabsorption, causing significant bicarbonate wasting in the urine. This is a form of Type 2 (proximal) renal tubular acidosis. The resulting hyperchloremic (normal anion gap) metabolic acidosis is the reason acetazolamide helps altitude sickness: the metabolic acidosis stimulates compensatory hyperventilation, increasing PaO2. With prolonged use, the drug becomes less effective as a diuretic due to bicarbonate depletion.

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

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