Ethosuximide Valproate

FIGURE 37-4 Antiseizure mediated reduction of IT. Certain antiseizure drugs reduce the flow of calcium through T-type Ca2+ channels (ethosuximide, valproate), thereby reducing the pacemaker current that underlies spike-wave discharges of generalized absence epilepsy. 

Phenobarbitone, benzodiazepines Valproate, benzodiazepines, adreno-corticotrophic hormone Ethosuximide, valproate, benzodiazepines, acetazolamide... 

Ethosuximide Valproate Fall in valproate concentrations inconsistent therapeutic synergism common Therapeutic synergism due to pharmacodynamic interaction... 

Absence seizure Abrupt onset of impaired consciousness associated with staring and cessation of ongoing activities typically lasting <30 seconds. Ethosuximide, valproate Lamotrigine... 

Absence Seizures (Petit mal) Generalized seizures in children or teens which present as brief episodes of blank staring but no convulsions. Effective drugs include ethosuximide, valproate, clonazepam and trimethadione. 

The oxa2ohdinedione trimethadione [127-48-0] C H NO (50), at one time the dmg of choice for the treatment of absence sei2ures, has been replaced by ethosuximide (41) and valproate (49). (50) has a distinct profile from that of phenytoin but causes photophobia and night blindness in approximately 30% of the patients taking it and has the CNS and sedative properties seen for other anticonvulsants together with moderate neutropenia, hepatitis, and skin rashes (13). Trimethadione does not appear to produce its effects via modulation of GABA-mediated responses. 

Outside of the evidence-based guidelines, other pharmacologic treatments are commonly used or avoided. For initial treatment of absence seizures, ethosuximide and valproate are commonly used, not only in the United Kingdom, but also in the United States. Zonisamide may be also used for initial treatment of absence and myoclonic seizures. In absence and myoclonic seizures, carbamazepine, oxcarbazepine, gabapentin, tiagabine, and pregabalin should be avoided, as they have been associated with an exacerbation of these types of seizures. 

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. 

At least three drugs are effective against absence seizures. Two are nonsedating and therefore preferred ethosuximide and valproate. Clonazepam is also highly effective but has disadvantages of dose-related adverse effects and development of tolerance. Lamotrigine and topiramate may also be useful. 

Ethosuximide Reduces low threshold Ca2+ currents (T-type) Well absorbed orally, with peak levels in 3-7 h not protein-bound completely metabolized to inactive compounds tjy2 typically 40 h Absence seizures Toxicity Nausea, headache, dizziness, hyperactivity Interactions Valproate, phenobarbital, phenytoin, carbamazepine, rifampicin... 

Valproate (SED-12, 134) (124,125), ethosuximide (126), and some benzodiazepines (127) have also been implicated in the precipitation of acute attacks of porphyria, although valproate is considered safe for patients with porphyria cutanea tarda (SED-13,150) (128). 

For simple and complex partial seizures and secondary generalized tonic-clonic seizures, the first line drugs are - carbamazepine, valproate and phenytoin. Second line drugs include - acetazolamide, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxacarbamazepine, primidone, tiagabine, topiramate and vigabactin. 

For generalized absence seizures, first line treatment is with valproate or ethosuximide and second line treatment with acetazolamide, clobazam, clonazepam, lamotrigine, phenobarbitone and primidone. 

Myoclonic seizures are best treated with valproate but, as a second choice, with clobazam, clonazepam, ethosuximide, lamotrigine, phenobarbitone, piracetam or primidone. 

Valproate, phenobarbitone, carbamazepine, diphenylhydantoin Valproate, ethosuximide, primidone... 

Carbamazepine is a hepatic microsomal enzyme inducer and therefore will lower the serum concentration of a wide variety of drugs given concurrently. These include the antiepileptic drugs phenytoin, primidone, valproate, ethosuximide and clonazepam. In addition, carbamazepine can compromise the therapeutic effects of oral contraceptives, oral anticoagulants, beta-blockers, haloperidol and theophylline. 

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. 

Plasma levels of valproate may be lowered by carbamazepine, phenytoln, ethosuximide, phenobarbital, rifampin... 

Valproate inhibits metabolism of ethosuximide, phenobarbital, and phenytoin, and can thus Increase their plasma levels... 

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... 

Isonlazid Carbamazepine Diazepam Ethosuximide Phenobarbital Phenytoin Primidone Valproate High risk of toxicity, especially with carbamazepine and phenytoin Inhibition of metabolism of the object drugs... 

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. 

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