Acetazolamide, a carbonic anhydrase inhibitor, is used in altitude sickness prophylaxis. The mechanism by which it prevents acute mountain sickness relates to:

• A Acetazolamide stimulates peripheral chemoreceptors by increasing blood pCO2, driving hyperventilation and acclimatisation
• B Acetazolamide reduces cerebrospinal fluid (CSF) production by inhibiting choroid plexus carbonic anhydrase, preventing high-altitude cerebral oedema
• C Acetazolamide increases EPO production in the kidney via carbonic anhydrase inhibition, accelerating erythropoietic acclimatisation to altitude hypoxia
• D Acetazolamide inhibits carbonic anhydrase in renal tubular cells, reducing HCO3- reabsorption, producing a metabolic acidosis that directly stimulates peripheral and central chemoreceptors, increasing ventilatory drive at altitude ✓

Explanation

At altitude, hypoxic hyperventilation causes respiratory alkalosis (low pCO2, high pH), which inhibits the central and peripheral chemoreceptors and limits the ventilatory response — the 'hypocapnic brake'. Acetazolamide inhibits carbonic anhydrase in renal tubular cells, preventing HCO3- reabsorption and generating a mild metabolic acidosis. This acidosis independently stimulates chemoreceptors, eliminating the blunting effect of hypocapnic alkalosis and permitting sustained hyperventilation, which maintains higher alveolar pO2. Additionally, reduced CSF HCO3- speeds CSF pH normalisation after hyperventilation, improving central chemoreceptor responsiveness. The net effect is facilitated acclimatisation and reduced incidence of AMS.

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

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Written and medically reviewed by the StethoPrep medical team.