Acetazolamide is used acutely in metabolic alkalosis. It corrects alkalosis by which mechanism?

• A Inhibition of proximal tubular carbonic anhydrase (CA II and CA IV), reducing bicarbonate reabsorption and increasing bicarbonate excretion in urine ✓
• B Stimulation of aldosterone antagonism in the collecting duct, reducing sodium-bicarbonate cotransporter activity
• C Inhibition of distal tubular H+-ATPase, reducing active proton secretion and bicarbonate retention
• D Direct alkalinisation of urine increasing bicarbonate filtration by promoting glomerular albumin shedding

Explanation

Acetazolamide inhibits carbonic anhydrase isoforms II (cytoplasmic) and IV (luminal membrane-bound) in proximal tubular cells. CA normally catalyses the reaction CO2 + H2O → H2CO3 → H+ + HCO3-. By inhibiting CA, H+ generation for Na+/H+ exchange and HCO3- reabsorption are both impaired. The result is massive bicarbonate diuresis (bicarbonate-rich urine, pH ~8), correcting metabolic alkalosis. This is particularly useful in chloride-resistant metabolic alkalosis associated with diuretic use. The drug does not antagonise aldosterone (spironolactone does that) nor does it target H+-ATPase (which is in the collecting duct alpha-intercalated cells). Acetazolamide-induced bicarbonaturia also causes mild hyperchloraemic acidosis as a side effect.

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

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