A 19-year-old student on topiramate for migraine prophylaxis reports tingling in her fingers, passage of small kidney stones, and difficulty finding words during conversation. The single unifying mechanism explaining the paresthesias and the stones is:

• A Blockade of voltage-gated calcium channels in peripheral nerve and renal tubule
• B Induction of CYP3A4 increasing conversion of citrate to oxalate
• C Antagonism of AMPA receptors expressed in sensory neurons and renal epithelium
• D Carbonic anhydrase inhibition producing metabolic acidosis with alkaline urine ✓

Explanation

Topiramate weakly inhibits carbonic anhydrase, causing proximal renal tubular bicarbonate loss with hyperchloremic metabolic acidosis. Systemic acidosis shifts calcium handling and produces paresthesias resembling those of acetazolamide, while alkaline urine with reduced urinary citrate promotes calcium phosphate stone formation. Word-finding difficulty and weight loss are independent CNS effects related to AMPA antagonism and other actions, but they do not share the mechanism asked for here. Citrate metabolism is unrelated to CYP enzymes.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.