Vigabatrin Phenytoin

Figure 16.7 The structure of some established antiepileptic drugs (AEDs) and some newer ones. Note that while the structures of phenytoin and ethosuximide are similar and also close to that of phenobarbitone, they are effective in different forms of epilepsy. Vigabatrin, progabide and gabapentin are clearly related to GABA. Muscimol is a GABAa agonist but is not an effective antiepileptic drug...

Antiepileptics Phenytoin Carbamazepine Valproic acid Gabapentin Vigabatrin Ethosuximide Benzodiazepines... 

Anticonvulsants (barbiturates, including phenobar-bital and primidone carbamazepine felbamate phenytoin topiramate vigabatrin)... 

II.e. 5.2. Interactions between first and second generation AEDs. Felbamate raises plasma concentrations of phenytoin, valproic acid and carbamazepine. Clearance of tiagabine, topiramate and zon-isamide is increased in the presence of an enzyme inducer. Vigabatrin reduces phenytoin concentrations after 4-5 weeks of comedication (via an unknown mechanism). For tiagabine, the elimination half-life may be reduced by 2-3 hours in the presence of an enzyme-induction AED. Lamotrigine elimination is slower if given with valproic acid. Topiramate reduces elimination of phenytoin. 

Drug therapy includes the use of anticonvulsant or anti-epileptic drugs, such as sodium valproate, sodium phenytoin, lamotrigine, vigabatrin. 

VIGABATRIN 1. BARBITURATES-phenobarbital, primidone 2. PHENYTOIN i levels of these antiepileptics Possibly induction of metabolism Watch for poor response to these antiepileptics... 

Individual drugs carbamazepine, phenytoin, sodium valproate, lamotrigine, vigabatrin, gabapentin, clonazepam, topiramate, levetiracetam. 

Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete. Phenobarbital, introduced in 1912, controlled patients resistant to bromides. The next success was the discovery in 1938 of phenytoin (a hydantoin) which is structurally related to the barbiturates. Since then many other drugs have been discovered, but phenytoin still remains a drug of choice in the treatment of major epilepsy. Over the past ten years there has been a dramatic increase in the number of new anticonvulsant drugs (vigabatrin, gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam), but none has been shown to be superior to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). 

Other antiepileptic drugs can also alter visual evoked potentials and brainstem evoked potentials. Visual field defects associated with various antiepileptic drugs (carba-mazepine, diazepam, gabapentin, phenytoin, tiagabine, and vigabatrin) have been reviewed (37). 

Vigabatrin can reduce serum phenytoin concentrations by about one-third, but this interaction is inconsistent. 

Importantly, Loscher et al. found that carbamazepine, felbamate, gabapentin, lamotrigine, phenobarbital, and topiramate are substrates of ABCBl (P-gp) [38]. Crowe et al. also studied the transport of a variety of antiepileptic drugs including vigabatrin, gabapentin, phenobarbitone, lamotrigine, phenytoin, carbamazepine, and acetazolamide in colorectal tumor-derived Caco-2 cell monolayers. They found that only one antiepileptic, acetazolamide, is a weak ABCBl substrate [39]. 

Adverse effects of vigabatrin include sedation, dizziness and behavioural changes similar to those seen with phenytoin. Vigabatrin may cause irreversible visual field defects, which limits its use. 

Barbiturates phenobarbital 1 Benzodiazepines alprazolam, diazepam, i lorazepam, oxazepam Carbamazepine, ethosuximide, valproic acid, phenytoin, diazepam, lorazepam, gabapentin, lamotrigine, felbamate, topiramate, tiagabin, vigabatrin... 

Carbamazepine s mechanism of action is similar to that of phenytoin, blocking sodium ion channels. Ethosuximide blocks calcium channels benzodiazepines and barbiturates facilitate the inhibitory actions of GABA topiramate may block glutamate receptors and vigabatrin inhibits GABA metabolism. The answer is (A). 

Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiseizure drugs in pediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine, and felbamate. Clin Pharmacokinet 1995 29 341-369. 

Battino, D., Estienne, M., and Avanzini, G., Chnical pharmacokinetics of antiepUeptic drugs in paediatric patients. Part II. Phenytoin, carhamazepine, sulthiame, lamotrig-ine, vigabatrin, oxcarbazepine and felbamate, Clin. Pharmacokinet., 29 341-369,... 

Vigabatrin causes a small to moderate fall in serum phenytoin levels. 

Gatti G, Bartoli A, Marchiselli R, Michelucci R, Tassinari CA, Pisani F, Zaccara G, Timmings P, Richens A, Perucca E. Vigabatrin-induced decrease in serum Jienytoin concentiation does not involve a change in phenytoin bioavailability. BrJ Clin Pharmacol (1993) 36,603-6. 

Rimmer EM, Richens A. Interaction between vigabatrin and phenytoin BrJ Clin Pharmacol (1989) 27,27S-33S. 

The interaction between phenytoin and vigabatrin would appear to be established. Vigabatrin causes a modest decrease in phenytoin levels in some patients, which takes a number of weeks to become apparent. A small increase in the dosage of phenytoin may possibly be needed in some patients. 

In an early clinical study, tiagabine was reported to have no significant effect on the plasma levels of carbamazepine, phenytoin, valproate, and vigabatrin. Similarly, tiagabine (titrated from 8 mg up to a maximum of 48 mg daily over 18 days) did not alter the steady-state pharmacokinetics of phenytoin or carbamazepine in 12 patients with epilepsy. However, in another similar study, it reduced the AUC of valproate by 10%, but this reduction is not expected to be elinieally significant. ... 

Antiepileptic drug-induced encephalopathies have been reviewed [50 ]. These complications have been reported with phenytoin, carbamazepine, and valproate and less often with vigabatrin, lamotrigine, and topiramate. 

Noninterfering carbamazepine, carbamazepine dihydrodiol, carbamazepine epoxide, N-desmethylsuximide, ethosuximide, lamotrigine, loreclezole, monohydroxycarba-mazepine, phenobarbital, phenytoin, primidone, valproic acid, vigabatrin... 

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