Clinical implications of mechanisms of resistance to antiepileptic drugs.
BACKGROUND
Despite the currently available armamentarium of antiepileptic drugs, seizures are not adequately controlled in about one-third of epileptic patients. The mechanisms of antiepileptic drug resistance are multiple and not fully clarified.


METHODS
We conducted a literature search in PubMed and the Cochrane Library databases with the terms: "Drug Resistance" [MeSH] and "Epilepsy" [MeSH],


CONCLUSIONS
added to PubMed in the last 5 years, only items with abstracts, English, Spanish, Humans.


RESULTS
It is currently known that membrane transporter proteins are increased in brain tissue of refractory epileptic patients and in animal models of epilepsy and that overexpression of these transporters and their inhibition are correlated with a reduction and an increase, respectively, of epileptic drugs in epileptic tissue (pharmacokinetic hypothesis). It has also been shown that alterations in voltage-gated sodium channels and GABAA receptors are responsible for resistance to some epileptic drugs. These changes may be constitutional (genetically determined) or acquired (as a consequence of the seizures themselves or disease progression) and may seem alone or combined with each other (pharmacodynamic hypothesis). Associations have been shown between certain genetic polymorphisms and resistance to epileptic drugs, and although they have not been replicated by all authors, they constitute a very attractive line of research. More detailed knowledge of these molecular mechanisms will probably lead to the development of new strategies for pharmacological treatment of epilepsy.
Sánchez Alvarez
Juan Carlos
JC
Department of Neurology, Virgen de las Nieves University Hospital, Granada, Spain.
Serrano Castro
Pedro J
PJ
Serratosa Fernández
José María
JM
D000927:Anticonvulsants / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology
D000927:Anticonvulsants; D026901:Membrane Transport Proteins