Zonisamide Lamotrigine

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

U.K. guidelines Tiagabine Topiramate Zonisamide Children Gabapentin Lamotrigine Oxcarbazepine Topiramate Gabapentin ... 

Lamotrigine Levetiracetam Topiramate Valproic acid Zonisamide... 

Vigabatrin (irreversible GABA aminotransferase inhibitor), zonisamide, lamotrigine (217) (glutamate inhibitor), oxcarbazepine (218), levetiracetam (219), piracetam, tiagabine (220),... 

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. 

Partial seizures Carbamazepine Phenytoin Lamotrigine Valproic acid Oxcarbazepine Gabapentin Topiramate Levetiracetam Zonisamide Tiagabine Primidone, phenobarbital Felbamate... 

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). 

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... 

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... 

Preliminary evidence suggests that serum zonisamide concentrations can be increased by lamotrigine (17). 

McJilton J, DeToledo J, DeCerce J, Huda S, Abubakr A, Ramsay R. Cotherapy of lamotrigine/lamictal results in significant elevation of zonisamide levels. Epilepsia 1996 37(Suppl. 5) 173. 

Figure 6.11. Suggested pharmacophore model for anticonvulsants acting at the voltage-dependent sodium channel on the basis of molecular dynamics simulations on phenytoin (1), carbamazepine (2), lamotrigine (11), zonisamide (13), and rufinamide (60). Rema-oemide (58)is discussed in the text. (AfterRef 281.)...

Several authors have provided insight into the putative MBS receptor based on their structure-activity data. As noted by Unverferth et al. (281), there have been several attempts to postulate a general pharmacophore for the different anticonvulsant classes, all of which are anti-MES in animal studies and are, or have the potential to be, effective in generalized tonic-clonic seizures. These include benzodiazepines (282) barbiturates (283) triazolines (284) semicarbazones (248-261) and enami-nones (286-288), respectively and for different compounds with similar anticonvulsant profiles (289-292). The Unverferth model (Fig. 6.11) provides an excellent representation of the current anticonvulsants phenytoin (1), carbamazepine (2), lamotrigine (11), zonisamide (13), and rufinamide (60). Remace-mide (58) is also included as a possible candidate (Fig. 6.12). 

Figure 6.12. Selected anticonvulsants for the development of a pharmacophore model. The essential structural elements are indicated by dotted rectangles. 1 = phenytoin 2 = carbamazepine 11 = lamotrigine 13 = zonisamide 60 = rufinamide inset, 58 = remacemide. R, hydrophobic unit D, electron-donor group HAD, hydrogen donor/acceptor unit. (AfterRef 281.)...

Myoclonic Valproic acid, clonazepam Lamotrigine, topiramate, felbamate, zonisamide, levetiracetam... 

The traditional treatment of tonic-clonic seizures is phenytoin or phenobarbital however, the use of carbamazepine and valproic acid is increasing because these AEDs have a lower incidence of side effects and equal efficacy. Valproic acid generally is considered the drug of first choice for atonic seizures and for juvenile myoclonic epilepsy. Lamotrigine and perhaps topiramate and zonisamide may be alternative agents for these seizure types. 

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... 

PHARMACOKINETICS Zonisamide is almost completely absorbed after oral administration, has a long tj, ( 63 hours), and is -40% bound to plasma protein. Approximately 85% of an oral dose is excreted in the urine, principally as unmetaboUzed zonisamide and a glucuronide of the CYP3A4 metabolite, sulfamoylacetyl phenol. Phenobarbital, phenytoin, and carbamazepine decrease the plasma concentration/dose ratio of zonisamide, whereas lamotrigine increases this ratio. Zonisamide has Uftle effect on the plasma concentrations of other antiseizure drugs. 

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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