Topiramate Sodium valproate

In addition to phenytoin, carbamazepine, and lamotrigine, metabolically optimized analogs of these drugs, such as fosphenytoin and oxcarbazepine, show clinical promise. Other anticonvulsants that block sodium channels, among several mechanisms of action, include zonisamide, felbamate, topiramate, and valproate (Fig. 5). 

Individual drugs carbamazepine, phenytoin, sodium valproate, lamotrigine, vigabatrin, gabapentin, clonazepam, topiramate, levetiracetam. 

Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete. Phenobarbital, introduced in 1912, controlled patients resistant to bromides. The next success was the discovery in 1938 of phenytoin (a hydantoin) which is structurally related to the barbiturates. Since then many other drugs have been discovered, but phenytoin still remains a drug of choice in the treatment of major epilepsy. Over the past ten years there has been a dramatic increase in the number of new anticonvulsant drugs (vigabatrin, gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam), but none has been shown to be superior to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). 

An isolated report describes a 22-month-old girl treated with phenytoin, sodium valproate and topiramate for epilepsy and then with quinine sulfate (initially intravenously, then orally) followed by a single dose of sul-fadoxine/pyrimethamine for malaria. Her malaria film became negative after 4 days of the 7-day quinine course. About 1 month later she was found to have recrudescent falciparum malaria, which was treated with quinine sulfate and then atovaquone/proguanil. Although it is possible that quinine resistance may have occurred, the authors also considered that enzyme induction by phenytoin may have led to suboptimal quinine levels. Although quinine does not appear to affect phenytoin levels, the isolated case report suggests that levels of quinine may be reduced in the presence of phenytoin and it would seem prudent to monitor carefully concurrent use. 

After each depolarization, voltage-dependent sodium channels adopt an inactive state and remain refractory to reopening for a period of time. While those channels are unable to open, rapid repetitive firing is diminished, and spread of electrical seizure activity to adjacent brain regions is suppressed (14). Stabilization and prolongation of this inactive state appears to be the primary mechanism of action of phenytoin, carbamazepine, and lamotrigine and may be instrumental in the antiseizure actions of phenobarbital, oxcarbazepine, valproate, topiramate, and zonisamide (Fig. 20.2). 

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