Ethosuximide valproate sodium

It is a benzodiazepine useful in the treatment of petitmal epilepsy, myoclonic seizures and infantile spasms. It is used in the treatment of petitmal epilepsy not responding to ethosuximide and sodium valproate. Clonazepam and diazepam act by increasing the effectiveness of the inhibitory neurotransmitter GABA, within the central nervous system. 

Antiepilepsy. General note of caution observe the infant for sedation and poor suckling. Primidone, ethosuximide and phenobarbital are present in milk in high amounts phenytoin and sodium valproate less so. 

Antiepilepsy drugs pass into breast milk (see p. 116), phenobarbital, primidone and ethosuximide in significant quantities, phenytoin and sodium valproate less so. There is a risk that the baby will become sedated or suckle poorly but, provided a watch is maintained for these effects, the balance of advantage favours breast feeding whilst taking antiepilepsy drugs. 

Sodium Valproate Enteric-coated Tablets BP Ethosuximide Oral Solution BP... 

McLean MJ, Macdonald RL. Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture. J Pharmacol Exp Ther 1986 237(3) 1001-1011. 

What are the hazards of therapy with ethosuximide With sodium valproate ... 

Moderate social drinking does not appear to affect the serum levels of carbamazepine, ethosuximide or phenytoin. Some small changes are seen in the serum levels of phenobarbital and sodium valproate, but no changes in the control of epilepsy seem to occur. No pharmacokinetic interaction was detected between tiagabine and alcohol, and tiagabine did not alter the cognitive effect of alcohol. The adverse effects of both alcohol and antiepileptics, such as enhanced sedation, may be additive. 

Minor to modest falls in serum ethosuximide levels may occur if carbamazepine, primidone or phenytoin are also given, whereas methylphenobarbital or sodium valproate may cause a rise in ethosuximide levels. The effect of all these changes on seizure control is uncertain. Lamotrigine appears not to affect ethosuximide levels. 

Four out of 5 patients taking ethosuximide (average dose 27 mg/kg) had an increase in their serum levels of about 50% (from 73 to 112 micrograms/mL), within 3 weeks of starting to take sodium valproate (adjusted to the maximum tolerated dose). Sedation occurred and ethosuximide dose reductions were necessary. In a single-dose study in 6 healthy subjects, treatment with sodium valproate for 9 days was reported to have increased the ethosuximide half-life and reduced the clearance by 15%." However, other studies have described no changes or even lower serum ethosuximide levels (level to dose ratio reduced by 36%). ... 

Mode of action. The specific site of action of felbamate is unknown. There is experimental evidence that felbamate blocks NMDA receptors, but less potently than carbamazepine, ethosuximide, phenytoin or valproate. It also modulates sodium channel conductance but does not enhance GABAergic function. In addition to its protective action against chemically induced seizures felbamate has also been shown to have a neuroprotective action in models of hypoxic ischaemia as induced by bilateral carotid ligation. 

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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