Which antiepileptic drug acts primarily by blocking voltage-gated sodium channels and is contraindicated in absence seizures due to paradoxical worsening?

Explanation

## Mechanism of Action **Key Point:** Phenytoin stabilizes the inactive state of voltage-gated sodium channels, preventing repetitive neuronal firing and propagation of seizure activity. ## Clinical Significance **High-Yield:** Phenytoin is a first-generation antiepileptic effective for generalized tonic-clonic and focal seizures, but it **worsens** absence seizures—a critical contraindication. ## Why Phenytoin Worsens Absence Seizures Absence seizures involve thalamic T-type calcium channels and require drugs that suppress these channels (e.g., ethosuximide). Phenytoin's sodium channel blockade does not address the underlying 3 Hz spike-and-wave mechanism and may paradoxically increase seizure frequency. ## Phenytoin: Key Properties | Property | Detail | | --- | --- | | **Primary mechanism** | Voltage-gated Na^+^ channel blockade | | **Seizure types** | Generalized tonic-clonic, focal, post-traumatic | | **Contraindicated in** | Absence, atypical absence, myoclonic seizures | | **Metabolism** | Hepatic (CYP2C9, CYP2C19); saturable kinetics | | **Adverse effects** | Gingival hyperplasia, hirsutism, ataxia, peripheral neuropathy | **Clinical Pearl:** Phenytoin exhibits **zero-order (saturable) kinetics** at therapeutic doses—small increases in dose can cause disproportionate plasma level rises and toxicity. [cite:KD Tripathi 8e Ch 12]