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Zonisamide – Multiple Mechanisms — SCE Neurology MCQ

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ModerateEpilepsy & Seizure DisordersZonisamide – Multiple MechanismsSCE Neurology

A 60-year-old man with drug-resistant focal epilepsy is started on safinamide as adjunctive therapy. His neurologist explains the dual mechanism. Wait — safinamide is not an antiseizure medication. It is used in Parkinson's disease. His actual medication is zonisamide. What are the mechanisms of zonisamide?

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Correct answer: C — Zonisamide has multiple mechanisms: sodium channel blockade, T-type calcium channel blockade, carbonic anhydrase inhibition, enhanced GABA transmission, and free radical scavenging

Zonisamide is a broad-spectrum AED with multiple mechanisms: (1) sodium channel blockade, (2) T-type calcium channel blockade, (3) weak carbonic anhydrase inhibition (which contributes to side effects — metabolic acidosis, renal stones, weight loss), (4) enhanced GABAergic transmission, and (5) free radical scavenging. Side effects include weight loss (which can be beneficial), cognitive slowing, kidney stones (2–4%), metabolic acidosis, and oligohidrosis (particularly in children). It requires a Pregnancy Prevention Programme in women of childbearing potential per MHRA 2024 guidance. A: Multiple mechanisms. C: Not pure GABA. D: Not pure glutamate antagonism. E: Not a potassium channel opener.

Reference: BNF – Zonisamide; NICE NG217 (2025)