Acetazolamide, a carbonic anhydrase inhibitor, is used for altitude sickness. Its prophylactic benefit comes from:

• A Reducing cerebrospinal fluid production, preventing high-altitude cerebral oedema
• B Causing a mild hyperchloraemic metabolic acidosis (by inhibiting HCO3– reabsorption in the proximal tubule), which augments ventilatory drive and blunts hypoxia-induced alkalosis at altitude ✓
• C Inhibiting red blood cell carbonic anhydrase, enhancing CO2 transport and O2 offloading at altitude
• D Acting as a central respiratory stimulant via adenosine receptor antagonism

Explanation

At high altitude, hypoxic hyperventilation causes a respiratory alkalosis that blunts the hypoxic ventilatory drive (peripheral chemoreceptors are less stimulated when pH is alkaline). Acetazolamide inhibits proximal tubular carbonic anhydrase, reducing HCO3– reabsorption and producing a mild hyperchloraemic metabolic acidosis. This metabolic acidosis counteracts the respiratory alkalosis, sustaining the hypoxic ventilatory drive and improving arterial oxygenation. Reduction of CSF production (option A) is also a mechanism contributing to HACE prevention but is not the primary prophylactic benefit.

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

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Written and medically reviewed by the StethoPrep medical team.