Acetazolamide (carbonic anhydrase inhibitor) is used to prevent high-altitude sickness. The mechanism by which it prevents acute mountain sickness is:

• A It inhibits cerebral carbonic anhydrase reducing CSF production, preventing cerebral oedema
• B It inhibits renal carbonic anhydrase causing bicarbonate diuresis, producing a metabolic acidosis that stimulates ventilation and improves arterial oxygenation at altitude ✓
• C It acts as a respiratory stimulant via adenosine antagonism in the brainstem
• D It promotes EPO release from the kidney by acidifying the renal medulla

Explanation

Acetazolamide inhibits renal carbonic anhydrase (CA II and CA IV in proximal tubule), reducing bicarbonate reabsorption and causing bicarbonaturia. The resulting metabolic acidosis stimulates peripheral chemoreceptors (carotid bodies), increasing ventilation and improving arterial pO2 at altitude. Increased ventilation also reduces the degree of respiratory alkalosis that normally blunts the hypoxic ventilatory response. The renal acid-base adjustment mimics acclimatisation that would otherwise take days. Acetazolamide also inhibits choroid plexus CA, mildly reducing CSF production (relevant to idiopathic intracranial hypertension treatment) but this is not the primary mechanism for altitude sickness prevention.

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

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Written and medically reviewed by the StethoPrep medical team.