Acetazolamide causes metabolic acidosis as a side effect of its primary mechanism. This occurs because:

• A Acetazolamide stimulates chloride-bicarbonate exchange in the collecting duct, promoting bicarbonate secretion
• B Inhibition of carbonic anhydrase in proximal tubule prevents bicarbonate reabsorption, causing bicarbonate wasting and a hyperchloraemic metabolic acidosis ✓
• C Acetazolamide inhibits ammoniagenesis in the proximal tubule, impairing acid excretion
• D Acetazolamide increases potassium secretion in the distal tubule, causing acidosis by K+/H+ exchange

Explanation

Carbonic anhydrase in the proximal tubule catalyses the conversion of CO2 + H2O to H2CO3 (then H+ + HCO3−), providing H+ for secretion and enabling bicarbonate reabsorption via the luminal apical membrane. Acetazolamide inhibits this enzyme, preventing bicarbonate reclamation and causing urinary bicarbonate wasting. The resulting loss of buffer base leads to a normal anion gap (hyperchloraemic) metabolic acidosis, limiting its long-term use as a diuretic.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.