Zonisamide Sodium valproate

The effects of concomitant carbamazepine, phenytoin, sodium valproate, and zonisamide on the steady-state serum concentrations of clonazepam have been investigated in 51 epileptic in-patients under 20 years of age (14). Serum concentrations of clonazepam correlated positively with the dose of clonazepam and negatively with the doses of carbamazepine and valproic acid, but not with phenytoin or zonisamide. These results confirm that as the oral doses of carbamazepine and sodium valproate increase, the serum concentration of clonazepam falls, but there is no interaction with either phenytoin or zonisamide. In the case of carbamazepine the mechanism of action is thought to be enzyme induction, increasing the metabolism of clonazepam. It is not known what the mechanism is with sodium valproate. In patients with epilepsy, the co-administration of either sodium valproate or carbamazepine will reduce the serum concentration of clonazepam and increase the risk of a seizure. When... 

Another study found that zonisamide did not affect the serum levels of sodium valproate in 12 children. A further study similarly found no marked changes in the plasma level of valproic acid in 7 patients also given zonisamide. ... 

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). 

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). 

There are three proposed major mechanisms of action of AEDs (1) sodium channel inactivation, (2) calcium channel blockade, and (3) interaction with GABA-A receptors/ channels. With sodium channel inactivation antiepileptic dmgs have the ability to extend the inactivation of sodium channels which reduces the frequency of the firing of the neurons, which is a feature of the seizures. Dmgs that are associated with this inactivation include phenytoin, carbamazepine and valproate. Calcium channel blockade (T-type) is related to the modulation of neuronal firing associated with absence of seizures and is associated with ethosuximide and zonisamide activity. L-type calcium channel blockade is reportedly associated... 

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