Carbonic anhydrase inhibitors (acetazolamide) cause metabolic acidosis and are used in glaucoma and altitude sickness. In altitude sickness, the pharmacological rationale is:

• A Acetazolamide-induced mild metabolic acidosis stimulates peripheral and central chemoreceptors, increasing the ventilatory drive and raising arterial PaO2; accelerated bicarbonate excretion corrects respiratory alkalosis, improving sleep and reducing periodic breathing (Cheyne-Stokes respiration) ✓
• B Acetazolamide reduces CSF production by inhibiting choroid plexus CA, lowering intracranial pressure and reducing altitude headache
• C Acetazolamide stimulates erythropoietin production, increasing oxygen-carrying capacity at altitude
• D Acetazolamide acts as a direct pulmonary vasodilator, reducing hypoxic pulmonary vasoconstriction at altitude

Explanation

At altitude, the primary adaptation is hyperventilation in response to hypoxia, which blows off CO2 and creates respiratory alkalosis. Respiratory alkalosis paradoxically suppresses the ventilatory drive, causing periodic (Cheyne-Stokes) breathing and contributing to altitude sickness. Acetazolamide inhibits renal carbonic anhydrase, increasing urinary bicarbonate (NaHCO3) excretion and causing a mild metabolic acidosis. This counteracts the respiratory alkalosis, removes inhibition of chemoreceptors, stimulates a more sustained ventilatory response, and reduces periodic breathing. This is distinct from its CSF-reducing effect in glaucoma.

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

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Written and medically reviewed by the StethoPrep medical team.