Acetazolamide inhibits carbonic anhydrase. In acute mountain sickness (AMS), acetazolamide is given prophylactically. The mechanism by which it facilitates acclimatization is:

• A Inhibiting proximal tubular HCO3- reabsorption causes metabolic acidosis, stimulating hypoxic ventilatory drive at altitude ✓
• B Reducing aqueous humor formation decreases CSF pressure, protecting against cerebral edema at altitude
• C Carbonic anhydrase inhibition in erythrocytes shifts the oxygen-hemoglobin dissociation curve leftward, improving O2 loading
• D Inhibiting renal bicarbonate reabsorption causes alkalinization of urine, correcting respiratory alkalosis indirectly

Explanation

At altitude, hypoxia stimulates increased ventilation, but the resulting respiratory alkalosis (elevated pH, reduced PCO2) blunts the respiratory drive—limiting further ventilatory increase. Acetazolamide inhibits renal proximal tubular carbonic anhydrase, preventing HCO3- reabsorption and causing bicarbonaturia. This produces a mild metabolic acidosis that counteracts respiratory alkalosis, lowering blood pH and restoring chemoreceptor sensitivity to hypoxia—thus sustaining the ventilatory stimulus. The resulting improved ventilation raises PaO2 during sleep (reducing periodic breathing) and during waking, facilitating acclimatization. Acetazolamide also prevents fluid shift into CNS by reducing CSF production, aiding in prevention of high-altitude cerebral edema.

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

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Written and medically reviewed by the StethoPrep medical team.