课件：抗癫痫药遗传药理学研究进展.ppt

Immunogenetic background Carbamazepine-induced Stevens Johnson Syndrome (SJS) and HLA-B*1502 Pharmacogenetics and Genomics 2006, 16:297–306 Pharmacogenetics and Genomics 2006, 16:297–306 Carbamazepine-induced Stevens Johnson Syndrome (SJS) and HLA-B*1502 后面内容直接删除就行 资料可以编辑修改使用 资料可以编辑修改使用 资料仅供参考，实际情况实际分析 * * 抗癫痫药遗传药理学研究进展 Differential drug efficacy Same symptoms Same findings Same disease (?) Same Drug…. Different Effects ? Genetic Differences Possible Reasons: Non-Compliance… Drug-drug interactions… Chance… Or…. Polymorphisms Affect Drug Handling and Drug Targets Genetic Polymorphism Pharmacokinetics Pharmacodynamics Receptors Ion Channels Enzymes Metabolism Transporters Protein Binding Normal Population Distribution . 10 5 0 0 10 15 20 Enzyme activities, Units/ml Percent of subjects per 0.5 Units/ml of activity Genetic polymorphism of drug metabolizing enzymes . 10 5 0 0 5 10 15 20 Enzyme activities, Units/ml Percent of subjects per 0.5 Units/ml of activity Slight adverse effects Severe adverse effects Product Function MDR1/ABCB1 P-glycoprotein Transmembrane transport SCN1A α1 subunit sodium channel Movement of sodium ions cross membrane GABBR1 Gamma-aminobutyric acid receptor B Membrane receptor GABA-B TNFα Subunit of tumour necrosis factor Associated with the inflammatory pathway HLA HLA Associated with immune response. CYP3A Cytochrome p450 enzyme Associated with hydroxylation CYP2C19 Cytochrome p450 enzyme Associated with hydroxylation CYP2C9 Cytochrome p450 enzyme Omega oxidati