title: [Drug resistant epilepsy. Clinical and neurobiological concepts].
abstract: Drug-resistant epilepsy, is a condition defined by the International League Against Epilepsy as persistent seizures despite having used at least two appropriate and adequate antiepileptic drug treatments. Approximately 20-30% of patients with epilepsy are going to be resistant to antiepileptic drugs, with different patterns of clinical presentation, which are related to the biological basis of this disease (de novo resistance, relapsing-remitting and progressive). Drug resistant epilepsy, impacts negatively the quality of life and significantly increases the risk of premature death. From the neurobiological point of view, this medical condition is the result of the interaction of multiple variables related to the underlying disease, drug interactions and proper genetic aspects of each patient. Thanks to advances in pharmacogenetics and molecular biology research, currently some hypotheses may explain the cause of this condition and promote the study of new therapeutic options. Currently, overexpression of membrane transporters such as P-glycoprotein, appears to be one of the most important mechanisms in the development of drug resistant epilepsy. The objective of this review is to deepen the general aspects of this clinical condition, addressing the definition, epidemiology, differential diagnosis and the pathophysiological bases.
authors.affiliation: Hospital Occidente de Kennedy, Bogota DC, Colombia.
authors.forename: Camilo A
authors.initials: CA
authors.lastname: Espinosa-Jovel
authors.forename: Fidel E
authors.initials: FE
authors.lastname: Sobrino-Mejía
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000502:physiology; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001692:Biological Transport; D001711:Biotransformation; D017281:Cost of Illness; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000502:physiology; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics / Q000502:physiology; D003937:Diagnosis, Differential; D004347:Drug Interactions; D004351:Drug Resistance / Q000502:physiology; D057915:Drug Substitution; D004827:Epilepsy / Q000188:drug therapy* / Q000191:economics / Q000401:mortality; D006801:Humans; D008017:Life Expectancy; D008959:Models, Neurological; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000187:drug effects / Q000235:genetics; D009422:Nervous System Diseases / Q000175:diagnosis; D020641:Polymorphism, Single Nucleotide; D011788:Quality of Life; D012008:Recurrence; D012306:Risk
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D062551:NAV1.2 Voltage-Gated Sodium Channel; C568251:SCN2A protein, human; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19