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Estudio de genes candidatos sobre la efectividad y seguridad de la medicación anticonvulsiva en un grupo de pacientes colombianos afectados de epilepsia

dc.rights.licenseAtribución-SinDerivadas 4.0 Internacional
dc.contributor.advisorAristizábal Gutiérrez, Fabio Ancízar
dc.contributor.authorCalderón Ospina, Carlos Alberto
dc.date.accessioned2020-03-05T21:03:26Z
dc.date.available2020-03-05T21:03:26Z
dc.date.issued2019-03-13
dc.identifier.citationCalderón-Ospina CA. Estudio de genes candidatos sobre la efectividad y seguridad de la medicación anticonvulsiva en un grupo de pacientes colombianos afectados de epilepsia [tesis de doctorado]. Bogotá: Universidad Nacional de Colombia; 2019. 161 p.
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/75902
dc.description.abstractObjectives: to explore possible genetic determinants of response to anticonvulsant treatment in a group of Colombian epileptic patients. Design: prospective cohort analytical observational study. We included 77 adult Colombian epileptic patients, from the Liga Central Contra la Epilepsia and Méderi, to evaluate the following genetic polymorphisms: CYP2C9 * 2 (rs1799853), CYP2C9 * 3 (rs1057910), C3435T (rs1045642) and IVS5-91 G > A (rs3812718), and the association with treatment response. Patients were followed long enough to confirm the existence of drug-resistant epilepsy (EFR) or treatment response, and the occurrence of adverse drug reactions (ADR). These were evaluated according to the causality, preventability, intensity and clinical presentation by predetermined criteria. Results: 53.2% of the patients had EFR and 87% of them used phenytoin. There was no association between the genetic variants evaluated and EFR, or the maintenance dose of phenytoin. An association was found between the presence of mutant alleles of CYP2C9 and adverse neuro-ophthalmological reactions (p = 0.001). 78% of the patients presented at least one ADR, the most frequent being those that affected the central nervous system (57%). 30% of the ADRs were associated with the patient's genetic factors and 69% of them were classified as preventable. 36.6% of the cases of therapeutic failure could be explained by drug interactions, so in fact, they could correspond to cases of "pseudo resistance". Conclusions: the alleles * 2 and * 3 of CYP2C9 were significantly associated with neuro- ophthalmologic ADRs in a sample of Colombian epileptic patients. It is possible that the ABCB1 and SCN1A genes not only play a role as pharmacogenes but as biomarkers of disease. It is necessary to implement pharmacovigilance programs in epileptic patients in order to optimize the benefit-risk ratio of antiepileptic drugs.
dc.description.abstractObjetivos: explorar posibles determinantes genéticos de respuesta al tratamiento anticonvulsivante, en un grupo de pacientes epilépticos colombianos. Diseño: estudio observacional analítico prospectivo de cohorte. Se incluyeron 77 pacientes epilépticos colombianos adultos, procedentes de la Liga Central Contra la Epilepsia y de Méderi, para evaluar los siguientes polimorfismos genéticos: CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), C3435T (rs1045642) y IVS5-91 G>A (rs3812718), y la asociación con la respuesta al tratamiento. Los pacientes fueron seguidos durante el tiempo suficiente para confirmar la existencia de epilepsia farmacorresistente (EFR) o de respuesta al tratamiento, y la ocurrencia de reacciones adversas al medicamento (RAM). Estas fueron evaluadas de acuerdo con la causalidad, prevenibilidad, intensidad y presentación clínica mediante criterios predeterminados. Resultados: 53,2% de los pacientes padecía EFR y el 87% de ellos empleaba fenitoína. No hubo asociación entre las variantes genéticas evaluadas y EFR, o la dosis de mantenimiento de fenitoína. Se encontró asociación entre la presencia de alelos mutantes de CYP2C9 y el desarrollo de reacciones adversas vestíbulo-cerebelosas (p = 0,001). El 78% de los pacientes presentó por lo menos una RAM, siendo las más frecuentes las que afectaron el sistema nervioso central (57%). El 30% de las RAM se asociaron con factores genéticos del paciente y el 69% de ellas se catalogaron como prevenibles. 36,6% de los casos de fallo terapéutico pudieron explicarse por interacciones medicamentosas, por lo que en realidad pudieron corresponder a casos de “pseudorresistencia”. Conclusiones: los alelos *2 y *3 de CYP2C9 se asociaron significativamente con RAM vestíbulo-cerebelosas en una muestra de pacientes epilépticos colombianos. Es posible que los genes ABCB1 y SCN1A no solo cumplan un rol como farmacogenes sino como biomarcadores de enfermedad. Es necesario implementar programas de farmacovigilancia en pacientes epilépticos con el fin de optimizar la relación beneficio – riesgo de la medicación antiepiléptica.
dc.format.extent161
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.rightsDerechos reservados - Universidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by-nd/4.0/
dc.subject.ddcMedicina y salud
dc.titleEstudio de genes candidatos sobre la efectividad y seguridad de la medicación anticonvulsiva en un grupo de pacientes colombianos afectados de epilepsia
dc.title.alternativeStudy of candidate genes on the effectiveness and safety of anticonvulsant medication in a group of Colombian patients affected by epilepsy
dc.typeOtro
dc.rights.spaAcceso abierto
dc.description.additionalDoctor en Ciencias Farmacéuticas.
dc.type.driverinfo:eu-repo/semantics/other
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.contributor.researchgroupFarmacogenética del Cáncer
dc.description.degreelevelDoctorado
dc.publisher.departmentDepartamento de Farmacia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.proposalPolimorfismo genético
dc.subject.proposalGenetic polymorphism
dc.subject.proposalAdverse drug reaction
dc.subject.proposalReacción adversa a medicamento
dc.subject.proposalEpilepsy
dc.subject.proposalEpilepsia
dc.subject.proposalPhenytoin
dc.subject.proposalFenitoína
dc.subject.proposalPharmacogenetics
dc.subject.proposalFarmacogenética
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dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
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