Mechanisms Of Drug Resistance In Epilepsy

Background:Epilepsy can be classified as a multifactor neurological disease which affects 1% of the world s population. Approximately 30% of epileptic patients do not favourably respond to antiepileptic drug treatment, but--on the other hand--the mechanism of drug-resistance has not been satisfactorily elucidated so far. Understanding the mechanisms of RSE is important to prevent or reverse its development and it will ultimately provide new treatment options for RSE. Findings:Mechanisms are categorized into diffrent types, Which include the following;1) Upregulation of P-glycoprotein 1 and 2: reduce the local concentration of antiepileptic drugs.These data suggest resistance to phenobarbital, phenytoin, lamotrigine,levetiracetam,topirramate and an oxcarbazepine metabolites. 2) Overexpression of protein drug transporters MRP: leads to the enhanced removal of antiepileptic drugs from the brain and subsequently, their reduced concentrations in the target tissue. 3) Overexpression of ABC transporters: perform the funcions of a drug efflux pump, which can reduce the effective drug concentration at epilepsy lesions by reducing the permeability of the blood brain barrier to antiepileptic drugs. 4) Overactivity expressed nonspecific MD transporter proteins at the blood–brain barrier and within epileptogenic cerebral parenchyma prevents adequate AED concentrations being established where they are needed .These data suggest resistance to topiramate 5) Insensitivity of the epileptogenic tissue to some sodium channel blockers and GABA-mimetic agents. 6) Genetic polymorphism: single nucleotide polymorphisms (SNPs) of the voltage-gated sodium channel genes (SCN1A, SCN1B, and SCN2A).These data suggest resistance to carbamazepine and phenytoine 7) Cortical dysplasia. 8) hippocampal sclerosis 9) Mutations:9.1) Ion channel mutations 9.2) Receptor mutations: GABAA receptors. These data suggest resistance to10) Autoimmune. 11) Other drugs unrelated to epilepsy (i.e. theophylline) or ingestion of stimulatory substances (f.e. caffeine) are likely to reduce the protective potential of antiepileptic drugs. Conclusion:Considering the specific challenges outlined in this article, molecular and genome-wide association and whole-genome sequencing studies might present a basis for future progress in the understanding of drug-resistant epilepsy.

Keywords:

Drug-resistant Epilepsy , mechanism , Epilepsy