Biological Causes for Resistance to Antiepileptic Drugs
Aya Ahmed Ashour;
Abstract
Epilepsy is a cluster of disorders rather than a single disease. It affects about one in 200 people and may last a person’s whole life. The individual, who suffers from epilepsy is vulnerable to economic, social and legal difficulties and might experience deep psychological problems. The goals of epilepsy management are to prevent discharges and to avoid their propagation. The understanding of the pathophysiology of the epilepsies is still incomplete.
The management of seizures in the patient with epilepsy relies heavily on antiepileptic drug (AED) therapy. Fortunately, for a large percentage of patients, AEDs provide excellent seizure control at doses that do not adversely affect normal function.
About 30% of epileptic patients do not respond to the usual antiepileptic drugs (AEDs), representing a major health problem associated with increased morbidity and mortality. An important characteristic of pharmacoresistant epilepsy is that these patients do not respond to most, and often all, AEDs, pointing to nonspecific and possibly adaptive mechanisms.
Intractability was defined as lack of seizure control despite use of maximized doses of two first-line anticonvulsants, and the presence of more than one seizure per month for an 18 month period.
Currently, two major hypotheses may explain medical refractoriness of epilepsy, the target hypothesis and the multidrug-transporter hypothesis. Based on the target hypothesis, intrinsic or acquired changes in AED targets in the brain underlie the development of drug-resistant epilepsy, whereas the multidrug-transporter hypothesis claims that the target is never reached because intrinsic or acquired overexpression of multidrug transporters at the blood–brain barrier (BBB) restricts brain uptake of AEDs. Of course, these hypotheses are not exclusive but may coexist in the same patient. Furthermore, intrinsic or acquired resistance to AEDs is certainly a multifactorial phenomenon, and it would be naive to expect that two hypotheses are sufficient to explain intractability.
The management of seizures in the patient with epilepsy relies heavily on antiepileptic drug (AED) therapy. Fortunately, for a large percentage of patients, AEDs provide excellent seizure control at doses that do not adversely affect normal function.
About 30% of epileptic patients do not respond to the usual antiepileptic drugs (AEDs), representing a major health problem associated with increased morbidity and mortality. An important characteristic of pharmacoresistant epilepsy is that these patients do not respond to most, and often all, AEDs, pointing to nonspecific and possibly adaptive mechanisms.
Intractability was defined as lack of seizure control despite use of maximized doses of two first-line anticonvulsants, and the presence of more than one seizure per month for an 18 month period.
Currently, two major hypotheses may explain medical refractoriness of epilepsy, the target hypothesis and the multidrug-transporter hypothesis. Based on the target hypothesis, intrinsic or acquired changes in AED targets in the brain underlie the development of drug-resistant epilepsy, whereas the multidrug-transporter hypothesis claims that the target is never reached because intrinsic or acquired overexpression of multidrug transporters at the blood–brain barrier (BBB) restricts brain uptake of AEDs. Of course, these hypotheses are not exclusive but may coexist in the same patient. Furthermore, intrinsic or acquired resistance to AEDs is certainly a multifactorial phenomenon, and it would be naive to expect that two hypotheses are sufficient to explain intractability.
Other data
| Title | Biological Causes for Resistance to Antiepileptic Drugs | Other Titles | الأسبــاب الحيويـة لمقاومـة العقاقيـر المضـادة للصـرع | Authors | Aya Ahmed Ashour | Issue Date | 2014 |
Recommend this item
Similar Items from Core Recommender Database
Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.