Acetazolamide is used in high-altitude sickness. The mechanism by which it reduces symptoms of altitude illness is:

• A It stimulates erythropoietin production, accelerating acclimatisation-related polycythaemia
• B It inhibits carbonic anhydrase, reducing bicarbonate reabsorption in the proximal tubule, causing metabolic acidosis that stimulates peripheral chemoreceptors to increase ventilation and arterial pO2 ✓
• C It dilates pulmonary vasculature, preventing high-altitude pulmonary oedema by reducing pulmonary artery pressure
• D It reduces CSF production by inhibiting carbonic anhydrase in the choroid plexus, preventing high-altitude cerebral oedema

Explanation

Acetazolamide inhibits carbonic anhydrase in the proximal tubule, reducing HCO3- reabsorption and causing a metabolic acidosis. The resulting decrease in plasma pH stimulates carotid body peripheral chemoreceptors, increasing ventilatory drive and arterial PO2 at altitude — simulating the hyperventilation that occurs with acclimatisation. This is the primary mechanism for AMS prophylaxis; the reduction in CSF production (option D) is an additional benefit for cerebral oedema treatment.

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

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Written and medically reviewed by the StethoPrep medical team.