A 24-year-old woman on topiramate for migraine prophylaxis complains of tingling around the mouth, difficulty finding words, and has passed two kidney stones. Arterial blood gas shows pH 7.30 with normal anion gap and serum bicarbonate of 16 mEq/L. Which property of topiramate best explains these findings?
- A Carbonic anhydrase inhibition causing metabolic acidosis and alkaline urine ✓
- B Renal tubular acidosis type 1 from direct tubular toxicity
- C Induction of CYP3A4 increasing conversion of citrate to oxalate
- D Proximal tubular Fanconi syndrome from mitochondrial toxicity
Correct answer: A. Carbonic anhydrase inhibition causing metabolic acidosis and alkaline urine
Explanation
Topiramate weakly inhibits carbonic anhydrase, causing renal bicarbonate loss with hyperchloraemic non-anion-gap metabolic acidosis, paraesthesiae, and alkaline urine that favours calcium phosphate stone formation. Cognitive slowing and word-finding difficulty are also attributed to this property. Fanconi syndrome is described with valproate and tenofovir, not topiramate, and topiramate does not induce CYP3A4 or cause distal RTA by tubular necrosis.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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