Acetazolamide is a carbonic anhydrase inhibitor used in altitude sickness prophylaxis. Its benefit in acute mountain sickness is primarily through:

• A Inducing metabolic alkalosis that stimulates peripheral chemoreceptors to increase ventilation
• B Causing bicarbonate diuresis and a compensatory metabolic acidosis that stimulates central chemoreceptors to increase ventilation, correcting altitude-related hypoxic hypoventilation ✓
• C Inhibiting pulmonary carbonic anhydrase, reducing CO2 retention at altitude
• D Reducing intracranial pressure by decreasing CSF production via choroid plexus carbonic anhydrase inhibition

Explanation

At altitude, hypoxia-driven hyperventilation causes respiratory alkalosis, which then acts as a brake on further ventilation (chemoreceptor feedback). Acetazolamide inhibits renal proximal tubule carbonic anhydrase, causing loss of bicarbonate in the urine, inducing a mild metabolic acidosis. This metabolic acidosis removes the alkalosis-driven inhibition of ventilation and stimulates further breathing, improving oxygenation. This is the primary mechanism for altitude sickness prophylaxis. The CSF production reduction (relevant for benign intracranial hypertension) and intracranial pressure effects are secondary benefits. Pulmonary carbonic anhydrase is not the primary target.

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

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Written and medically reviewed by the StethoPrep medical team.