Acetazolamide, a carbonic anhydrase inhibitor, is used for altitude sickness prophylaxis. The mechanism by which it prevents acute mountain sickness (AMS) is:

• A Causes metabolic acidosis by blocking HCO3- reabsorption in the proximal tubule, stimulating peripheral chemoreceptors and increasing respiratory rate (ventilatory acclimatisation) ✓
• B Reduces cerebrospinal fluid (CSF) production by inhibiting carbonic anhydrase in the choroid plexus, reducing intracranial pressure at altitude
• C Inhibits carbonic anhydrase in erythrocytes, reducing CO2 transport to the lungs and promoting hyperventilation
• D Increases pulmonary blood flow by inhibiting hypoxic pulmonary vasoconstriction via carbonic anhydrase inhibition in pulmonary endothelium

Explanation

At high altitude, hypobaric hypoxia drives hyperventilation; however, the resultant hypocapnia produces respiratory alkalosis that acts as a negative feedback inhibiting further ventilatory increase, slowing acclimatisation. Acetazolamide inhibits carbonic anhydrase in the proximal tubule, blocking HCO3- reabsorption and causing obligatory bicarbonate diuresis — producing a metabolic acidosis that offsets the respiratory alkalosis. This acidosis stimulates peripheral chemoreceptors (carotid bodies) to maintain and augment ventilatory drive, facilitating faster ventilatory acclimatisation and reducing AMS symptoms. The CSF production effect is secondary and relevant for chronic use (pseudotumour cerebri, not AMS).

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

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Written and medically reviewed by the StethoPrep medical team.