Clinical Pharmacology of Current Antiepileptic Drugs
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abstract
This article describes current antiepileptic drugs (AEDs) that are available for treatment of epilepsy. Epilepsy is characterized by repeated occurrence of seizures, which are clinical manifestations of abnormal electrical discharges in the brain. Epileptic seizures arise from a multiplicity of factors that regulate neuronal excitability and synchrony. Epilepsy is caused because of certain genetic defects or acquired due to brain injury. Epileptic seizures are classified into partial (simple partial and complex partial) and generalized (absence, tonic-clonic, myoclonic, and atonic seizures) types. Around two-dozen AEDs, classified as standard and newer agents, are available for treating epilepsy. AEDs act on diverse molecular targets to selectively modify the abnormal excitability of neurons by reducing the focal seizure discharges or preventing spread of excitation. AEDs suppress seizures by blocking the voltage-gated sodium channels (phenytoin, carbamazepine, valproate, lamotrigine, oxcarbazepine, topiramate), voltage-activated calcium channels (ethosuximide, gabapentin), potentiation of GABA inhibition (barbiturates, benzodiazepines, tiagabine), and reduction of glutamate excitation (felbamate). Carbamazepine, phenytoin, and valproate are the first-line agents for partial seizures and generalized tonic-clonic seizures. Ethosuximide is the drug of choice for absence seizures. Intravenous benzodiazepines diazepam or lorazepam are effective in terminating status epilepticus. AEDs are orally-active and show unique pharmacokinetic features. Some AEDs cause enzyme induction and hence produce drug interactions. Newer AEDs such as gabapentin, levetiracetam, tiagabine, zonisamide and pregabalin do not cause enzyme induction. Treatment in pregnancy must consider optimizing therapy while preventing teratotoxicity of AEDs. There are alternative options (ketogenic diet) for children. Despite many advances in epilepsy research, nearly 30% of people with epilepsy have intractable seizures that do not respond to drug therapy. Presently, there is no cure for epilepsy. Therefore, newer and better AEDs that can better prevent seizures and modify the disease are needed for curing epilepsy.
