A 26-year-old man on topiramate for migraine prophylaxis presents with renal colic. CT scan confirms a radiolucent calculus. Which properties of topiramate explain this complication and are also responsible for his reported weight loss?

• A Inhibition of carbonic anhydrase producing alkaline urine, with reduced appetite through AMPA antagonism
• B Induction of CYP enzymes increasing oxalate production, with appetite stimulation
• C Increased renal calcium reabsorption causing calcium oxalate stones, with appetite stimulation
• D Inhibition of carbonic anhydrase producing acidic urine and bicarbonate loss, plus CNS effects that reduce appetite ✓

Explanation

Topiramate weakly inhibits carbonic anhydrase, causing renal bicarbonate loss, metabolic acidosis, and acidic, low-citrate urine, which promotes calcium phosphate stone formation. The same class effect underlies paraesthesias. Weight loss occurs through poorly defined CNS mechanisms and contrasts with valproate-associated weight gain, making it useful clinically. Carbonic anhydrase inhibition produces acidosis rather than alkaline urine, so option A is incorrect despite naming the enzyme.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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