A 26-year-old man started on an antiepileptic for refractory focal seizures develops renal colic. Imaging shows a radiolucent calculus. He also complains of word-finding difficulty and tingling around the mouth. Serum bicarbonate is low. The offending drug acts by which mechanism?

• A Blockade of AMPA receptors
• B Enhanced slow inactivation of voltage-gated sodium channels
• C Inhibition of carbonic anhydrase with modulation of AMPA receptors ✓
• D Binding to the synaptic vesicle protein SV2A

Explanation

Topiramate has multiple actions including inhibition of carbonic anhydrase, which produces metabolic acidosis, urinary alkalinisation and calcium phosphate stones. Its other effects are sodium channel blockade, potentiation of GABA-A activity and AMPA/kainate antagonism. Cognitive slowing and word-finding difficulty are characteristic of topiramate. Lacosamide (slow inactivation) and levetiracetam (SV2A) do not cause stones or acidosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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