Which of the following antiepileptic drugs acts primarily by blocking voltage-gated sodium channels and is contraindicated in absence seizures?

Explanation

## Mechanism of Action **Key Point:** Phenytoin blocks voltage-gated sodium channels by stabilizing the inactive state, preventing repetitive neuronal firing. This mechanism is effective for generalized tonic-clonic and partial seizures but is contraindicated in absence seizures. ## Why Phenytoin Worsens Absence Seizures Absence seizures involve a 3 Hz spike-and-wave pattern on EEG driven by thalamic T-type calcium channels. Sodium channel blockers like phenytoin do not suppress this mechanism and may paradoxically worsen absence seizures by increasing seizure frequency and duration. ## Drug Comparison Table | Drug | Primary Mechanism | Seizure Type | Contraindication | | --- | --- | --- | --- | | **Phenytoin** | Voltage-gated Na^+^ channel block | GTCS, partial | Absence (worsens) | | **Ethosuximide** | T-type Ca^2+^ channel block | Absence only | GTCS, partial | | **Valproic acid** | GABA enhancement + Na^+^ channel block | Broad spectrum | Hepatotoxicity risk | | **Lamotrigine** | Na^+^ channel + Ca^2+^ channel block | Broad spectrum | Rash (SJS/TEN) | ## Clinical Pearl **High-Yield:** Phenytoin is a first-line agent for generalized tonic-clonic seizures and focal seizures but should NEVER be used in absence or atypical absence epilepsy. Ethosuximide is the drug of choice for absence seizures because it selectively blocks thalamic T-type calcium channels responsible for the 3 Hz spike-and-wave discharge. ## Mnemonic **PHEN = Phenytoin blocks Na^+^ channels** — effective for grand mal and focal seizures, but **Phenytoin Harms Absence Epilepsy Neurologically** (worsens absence).