Antiepileptic Drugs

Abstract

Approximately 20 to 30% of patients with active intractable epilepsy are commonly treated with polytherapy antiepileptic drug regimens, and these patients may experience complicated drug interactions. Furthermore, because of the long term nature of treatment, the possibility of drug interactions with drugs used for the treatment of concomitant disease is high. Classically, clinically significant drug interactions, both pharmacokinetic and pharmacodynamic, have been considered to be detrimental to the patient, necessitating dosage adjustment. However, this need not always be the case. With the introduction of new drugs (e.g. vigabatrin and lamotrigine) with known mechanisms of action, the possibility exists that these can be used synergistically. The most commonly observed clinically significant pharmacokinetic interactions can be attributed to interactions at the metabolic and serum protein binding levels. The best known examples relate to induction (e.g. phenobarbital, phenytoin, carbamazepine and primidone) or inhibition [e.g. valproic acid (sodium valproate)] of hepatic monoxygenase enzymes. The extent and direction of interactions between the different antiepileptic drugs are varied and unpredictable. Interactions in which the metabolism of phenobarbital, phenytoin or carbamazepine is inhibited are particularly important since these are commonly associated with toxicity. Some inhibitory drugs include macrolide antibiotics, chloramphenicol, cimetidine, isoniazid and numerous sulphonamides. A reduction in efficacy of antibiotic, cardiovascular, corticosteroid, oral anticoagulant and oral contraceptive drugs occurs during combination therapy with enzyme-inducing antiepileptic drugs. Discontinuation of the enzyme inducer or inhibitor will influence the concentrations of the remaining drug(s) and may necessitate dosage readjustment.

The Modified Atkins Diet in Refractory Epilepsy

“…Several severe catastrophic epilepsies present in childhood, including severe infantile myoclonic epilepsy, West syndrome, Lennox-Gastaut syndrome, and myoclonic-astatic epilepsy (Doose syndrome) [2]. Seizures in these epilepsy syndromes are difficult to control, with the added problems of multiple and toxic levels of antiepileptic medications [3]. Epilepsy surgery may not work in these patients and also the costs are prohibitively high.…”

Mechanism-Based Inactivation of Cytochrome P450 Enzymes: Chemical Mechanisms, Structure-Activity Relationships and Relationship to Clinical Drug-Drug Interactions and Idiosyncratic Adverse Drug Reactions

“…The reactive acyl chloride is then thought to react with the -amino group in lysine residues. The competitive inhibition of human P450 appears to be consistent with the pharmacokinetic interactions of chloramphenicol and substrates for these enzymes including cyclosporine, tacrolimus, and phenytoin [136,137]. (19)) metabolites of chloramphenicol analogs upon alkaline Fig.…”

Determination of vigabatrin in human plasma and urine by high-performance liquid chromatography with UV-Vis detection

“…It shows no significant protein-binding. Its pharmacokinetics is not affected by foods and other drugs [3,4].…”