Antiepileptics Basics

Antiepileptic drugs (AEDs) suppress seizure activity by modulating the balance between neuronal excitation and inhibition through several key mechanisms. Sodium channel blockers (phenytoin, carbamazepine, lamotrigine, lacosamide) stabilize inactivated voltage-gated sodium channels, preventing repetitive neuronal firing without affecting normal single action potentials—this use-dependent blockade selectively targets hyperexcitable neurons. GABAergic agents enhance inhibitory neurotransmission: benzodiazepines increase the frequency of GABA-A chloride channel opening, barbiturates increase the duration of channel opening, and vigabatrin irreversibly inhibits GABA transaminase (the enzyme that degrades GABA). Calcium channel modulators (ethosuximide) block T-type calcium channels in thalamic relay neurons, specifically targeting the 3-Hz spike-and-wave discharges of absence seizures. Glutamate antagonists (perampanel) block AMPA receptors to reduce excitatory transmission. Newer agents have unique mechanisms: levetiracetam binds synaptic vesicle protein SV2A (modulating neurotransmitter release), and valproate has multiple mechanisms including sodium channel blockade, enhanced GABA levels, and T-type calcium channel inhibition—making it broad-spectrum. Drug selection is guided by seizure type (focal vs generalized), epilepsy syndrome, patient-specific factors (age, sex, childbearing potential, comorbidities), and pharmacokinetic profile.