A 24-year-old woman on topiramate for migraine prophylaxis reports weight loss, paresthesias around the mouth, and passing a small urinary stone. Laboratory studies show a normal anion gap metabolic acidosis. These findings collectively reflect which property of topiramate?

• A Induction of CYP3A4 increasing conversion of vitamin D to inactive metabolites
• B Inhibition of carbonic anhydrase in proximal tubule and glia ✓
• C Inhibition of AMPA receptors causing renal bicarbonate wasting
• D Antagonism of NMDA receptors producing type 2 renal tubular acidosis

Explanation

Topiramate weakly inhibits carbonic anhydrase, reducing bicarbonate reabsorption and producing hyperchloremic non-anion gap metabolic acidosis, perioral paresthesias, and calcium phosphate or calcium oxalate nephrolithiasis from alkaline urine. Weight loss reflects AMPA antagonism and appetite suppression, a separate action. The acidosis is corrected by dose reduction, potassium citrate, or stopping the drug.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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