Acetazolamide is used in the prevention of high-altitude cerebral oedema (HACE). The pharmacological rationale is:

• A Carbonic anhydrase inhibition causes metabolic acidosis which stimulates ventilation, improving oxygenation ✓
• B Acetazolamide reduces CSF production in the choroid plexus, directly reducing cerebral oedema
• C Acetazolamide is a loop diuretic reducing total body sodium and water
• D Acetazolamide blocks cortical HIF-1alpha upregulation preventing VEGF-mediated vasodilation

Explanation

At high altitude, hypoxia triggers compensatory hyperventilation. However, the resulting respiratory alkalosis inhibits the carotid body chemoreceptors, limiting further ventilatory response. Acetazolamide inhibits carbonic anhydrase in the proximal tubule, reducing bicarbonate reabsorption and causing metabolic acidosis (bicarbonate diuresis). This counteracts the respiratory alkalosis, removing the chemoreceptor inhibition and allowing sustained hyperventilation — improving alveolar PO2. Option B (CSF reduction) is secondary and not the main mechanism for altitude prophylaxis; option C is incorrect (acetazolamide is a CA inhibitor, not a loop diuretic).

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

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Written and medically reviewed by the StethoPrep medical team.