A 20-year-old woman on topiramate for migraine prophylaxis reports weight loss, tingling in her fingers, difficulty finding words, and passage of a small painful stone in urine. The combination of cognitive slowing, paraesthesiae, nephrolithiasis, and weight loss is best explained by which property of topiramate?
- A Blockade of T-type calcium channels in the distal tubule
- B Inhibition of carbonic anhydrase causing systemic acidosis and alkaline urine ✓
- C Induction of CYP3A4 increasing oxalate production
- D Antagonism of NMDA receptors in renal epithelium
Correct answer: B. Inhibition of carbonic anhydrase causing systemic acidosis and alkaline urine
Explanation
Topiramate inhibits carbonic anhydrase, producing mild metabolic acidosis, urinary alkalinisation, and hypercalciuria, which promotes calcium phosphate stone formation. The same property explains paraesthesiae, a classic examination clue. Cognitive effects include word-finding difficulty and psychomotor slowing, and appetite suppression causes weight loss, making it useful in obesity. Acetazolamide shares the carbonic anhydrase mechanism and also causes stones and paraesthesiae. Dose reduction or discontinuation usually reverses the cognitive complaints.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.