Pharmacogenetics of adverse reactions to antiepileptic drugs


Abstract:

Introduction: Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients’ quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. Development: To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. Conclusions: Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow pbkp_redicting ADRs to AEDs could improve pharmacotherapy for epilepsy.

Año de publicación:

2018

Keywords:

  • ABCC2
  • human leukocyte antigen (HLA)
  • pharmacogenetics
  • Antiepileptic drugs
  • CYP2C9
  • adverse drug reactions

Fuente:

scopusscopus

Tipo de documento:

Other

Estado:

Acceso abierto

Áreas de conocimiento:

  • Farmacología
  • Farmacología

Áreas temáticas:

  • Farmacología y terapéutica