Drug treatment of seizures Epilepsy, a chronic disease, occurs in approximately 1% of the population. Antiepileptic drugs (AEDs) are effective, at least to some degree, for about 80% of these patients. Lifelong treatment may be necessary. It may take weeks to establish adequate drug plasma levels and to determine the adequacy of therapeutic improvement. Lack of compliance is responsible for many treatment failures. AEDs are most effective and have the least adverse effects when they are used as monotherapy. Addition of a second drug to the therapeutic regimen should be gradual, as should discontinuance of the initial drug before the substitution of an alternative drug, because seizures may occur on withdrawal. Some AEDs have teratogenic potential. This may call for the reduction or termination of therapy during pregnancy or before planned pregnancy. However, maternal seizures also present a significant risk to the fetus. AEDs may also be used to treat seizures that result from various neurologic disorders, as well as from metabolic disturbances, trauma, and exposure to certain toxins. AEDs may increase the risk of suicidal ideation. Classification of epilepsies and drug selection Epilepsies are characterized by either focal or generalized abnormal neuronal discharges. Drug selection, based on seizure classificationPartial seizures oSimple: Localized discharge; consciousness unaltered oComplex: Localized discharge that becomes widespread; accompanied by loss of consciousness Phenytoin Carbamazepine lamotrigine Valproic acid phenobarbital Generalized seizures oTonic–clonic (grand mal): Dramatic bilateral movements with either clonic jerking of the extremities or tonic rigidity of the entire body; accompanied by loss of consciousness. Phenytoin Carbamazepine Topiramate other newer AEDs. oAbsence(petit mal): Sudden onset of altered consciousness that lasts 10–45 seconds, with up to hundreds of seizures per day; begins in childhood or adolescence Ethosuximide. Valproic acid (when absence seizures coexist with tonic–clonic seizures). Clonazepam Lamotrigine Topiramate oMyoclonic syndromes: Lightning-like jerks of one or more extremities occurring singly or in bursts of up to a hundred; accompanied by alteration of consciousness. Valproic acid Lamotrigine Other newer AEDs oStatus epilepticus: Prolonged seizure (>20 min) of any of the types. the most common is life-threatening generalized tonic–clonic status epilepticus. IV diazepam or lorazepam IV fosphenytoin (or phenytoin) or phenobarbital. Mechanism of action Phenytoin Carbamazepine Valproic acid lamotrigine oblock channels and inhibit the sodium generation of action potentials.