Zonisamide Valproate

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. 

Carbamazepine, phenytoin, valproate, gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate, zonisamide... 

Specific myoclonic syndromes are usually treated with valproate an intravenous formulation can be used acutely if needed. It is nonsedating and can be dramatically effective. Other patients respond to clonazepam, nitrazepam, or other benzodiazepines, although high doses may be necessary, with accompanying drowsiness. Zonisamide and levetiracetam may be useful. Another specific myoclonic syndrome, juvenile myoclonic epilepsy, can be aggravated by phenytoin or carbamazepine valproate is the drug of choice followed by lamotrigine and topiramate. 

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). 

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... 

BARBITURATES 1. CARBAMAZEPINE 2. LAMOTRIGINE 3. TIAGABINE 4. VALPROATE 5. ZONISAMIDE L levels of these antiepileptics Induction of metabolism Watch for poor response to these antiepileptics... 

Chronic treatment with phenobarbital, phenytoin, and carbamazepine is associated with reduced serum folate concentrations. Although megaloblastic anemia is rare, macrocytic changes in red cells are common in these patients. The fact that serum folate is not reduced by valproate and zonisamide, which do not induce liver enzymes, is consistent with the hypothesis that enzyme induction plays a role in the pathogenesis of folate deficiency (99). 

Drugs that inhibit carbonic anhydrase (acetazolamide, topiramate, and zonisamide) are associated with a small risk (up to 1.5%) of nephrolithiasis. Increased excretion of V-acetyl-beta-glucosaminidase, a marker of renal tubular integrity, has been reported with valproate and carbamazepine, but it is probably not clinically significant (SEDA-18, 60). 

Phenobarbital Phenytoin Primidone Felbamate Lamotrigine Tiagabide Topiramate Valproate Zonisamide Clobazam Clonazepam Diazepam usually compensated by the effect of the added drug risk of toxicity when interfering drug is discontinued drug... 

Complex partial Partial with secondarily Impaired consciousness lasting 30 seconds to 2 minutes, often associated with purposeless movements such as lip smacking or hand wringing. Simple or complex partial seizure evolves into a Carbamazepine, phenytoin, valproate Gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate, zonisamide... 

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). 

Therefore, plasma concentrations for drugs metabolized by these isoforms will be affected (see Chapter 10). Thus, the addition of phenytoin to an AED regimen can reduce their plasma levels by inducing their CYP3A4 metabolism for carbamazepine, felbamate, lamotrigine, oxcarbazepine, tiagabine, valproate, and zonisamide. Other drugs for which metabolism is induced by phenytoin include methadone, theophylline, warfarin, and oral contraceptives. On the other hand, plasma phenytoin levels are increased by carbamazepine, felbamate, cimetidine, warfarin, chloramphenicol, isoniazid, and disulfiram. Plasma phenytoin levels are decreased by rifampin, antacids, and valproate (free phenytoin levels remain the same). 

Because of its inducing effect on hepatic enzymes, phenobarbitai has many drug interactions, decreasing plasma levels of CBZ, valproate, lamotrigine, tiagabine, zonisamide, warfarin, theophylline, cimetidine, and those of other CYP3A4 substrates. Serum concentrations of phenobarbitai are increased by valproate. 

Primidone use Is associated with decreases In CBZ, lamotrigine, valproate, tiagabine, and zonisamide serum levels. Primidone levels are increased by nicotinamide and Isonlazid. Hydantoins increase the plasma concentrations of primidone, phenobarbital, and PEMA. CBZ Increases levels of phenobarbital derived from primidone. Primidone levels are decreased by succinimides, CBZ, and acetazolamide. 

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