Antiepileptic Drugs (AEDs)
Antiepileptic drugs (AEDs), also known as anticonvulsants, are medications used to prevent and control seizures in individuals with epilepsy and other seizure disorders.
Classification
- Sodium Channel Blockers: Phenytoin, Carbamazepine, Oxcarbazepine
- Calcium Channel Blockers: Ethosuximide, Gabapentin, Valproate
- GABA Enhancers: Phenobarbital, Benzodiazepines (Diazepam, Clonazepam), Tiagabine
Pharmacodynamics
- Sodium Channel Blockers:
- Stabilize neuronal membranes by inhibiting voltage-gated sodium channels, preventing repetitive firing.
- Reduce neuronal excitability, decreasing seizure activity.
- Calcium Channel Blockers:
- Reduce neuronal excitability by inhibiting voltage-gated calcium channels.
- Ethosuximide specifically blocks T-type calcium channels, making it effective for absence seizures.
- GABA Enhancers:
- Enhance inhibitory GABAergic activity by:
- Increasing GABA receptor activity.
- Inhibiting GABA reuptake (Tiagabine).
- Preventing GABA degradation (Vigabatrin).
- Increase neuronal inhibition, reducing seizure occurrence.
Pharmacokinetics
- Sodium Channel Blockers:
- Well absorbed orally, metabolized in the liver (CYP450 enzymes).
- Excreted in urine.
- Phenytoin can also be administered IV.
- Highly protein-bound (~90%), readily crosses the blood-brain barrier.
- Variable half-lives, requiring dose adjustments.
- Calcium Channel Blockers:
- Orally absorbed, with high bioavailability.
- Gabapentin & Pregabalin are renally excreted unchanged.
- Short half-lives, requiring multiple daily doses.
- Ethosuximide has moderate protein binding and wide CNS distribution.
- GABA Enhancers:
- Phenobarbital & Benzodiazepines:
- Administered orally, IV, or rectally (diazepam).
- Metabolized in the liver.
- Phenobarbital has a long half-life.
- Benzodiazepines have intermediate to long half-lives.
- Tiagabine:
- Orally administered, metabolized in the liver, excreted in urine.
- Vigabatrin:
- Orally absorbed, not extensively metabolized, excreted unchanged in urine.
- Long duration of action.