1,Drug adverse reaction and drug-induced disease,2,Drug adverse reaction,common/normal application dosageharmful and unexpected reaction,3,Drug adverse reaction,Side effect (副作用) toxic effect(毒性反应) Residual effect(后遗效应) dependence(依赖性) Idiosyncratic reaction/ Idiosyncrasy (特异质反应) allergic reaction/hypersensitive reaction (过敏反应/变态反应) Carcinogenesis, teratogenesis, mutagenesis(致癌、致畸和致突变反应) (not including Overdose; drug abuse; error treatment),4,Drug-induced disease,drug-induced functional or structural damage of the body; clinical course Essence: result/sequel of the Drug adverse reaction,5,Classify,adverse reactiondrug dosage adverse reactionpeculiarity WHO;World Health Organization,6,adverse reactiondrug dosage,concerned with dosage (A-type reaction)：有些药物不良反应与剂量大小有直接关系，这类反应也称为A型反应。 dosage indifference (B-type reaction)：某些药物不良反应与药物剂量无关，称为B型不良反应。,7,A型与B型药物不良反应的特点,8,adverse reactionpeculiarity,side effect(副作用) toxic effect(毒性作用) residual effect(后遗效应) dependence(依赖性) idiosyncratic reaction(特异质反应) allergic reaction(变态反应) carcinogenesis(致癌作用) teratogenesis(致畸作用) mutagenesis(致突变作用),9,adverse reaction classified by WHO,side effect (副反应) adverse event (不良事件) adverse reaction (不良反应) unexpected adverse reaction (意外不良反应) signal(信号),10,Aetiology of drug adverse reaction and drug-induced disease,congenital abnormality of patient reaction病人反应先天性异常 Acquired abnormity获得性异常 drug factor药物因素 drug interactions 药物相互作用 Indirect reaction间接反应,11,Congenital abnormality of patient reaction,allergic/hypersensitive reaction 、 、 、 、 autoimmune response genetic factor pharmacokinetics abnormality、pharmacodynamics abnormality、idiosyncrasy、 Inborn sensitivity age; cyesis/pregnancy,12,Acquired abnormality,Hepar affection kidney affection drug receptor abnormity,13,Drug factor,Overdosage、alter of bioavailability、incorrect administration route withdrawal symptom spatial isomerism,14,Indirect reaction,fetal anomaly thalidomide 3rd Generation effective diaethylstilbestrol carcinoma of vagina else Antihistamine drug traffic accident,15,Mainstay of drug adverse reaction,1.Reported or not 2.adverse event time series 3.adverse reaction amelioration 4.Rechallenge irritation,dischallenge,16,5.Questionable factor 6.Happen or not with the dummy 7.Detect or not from the blood or other body fluid 8. dosage irritation 9. identical reaction or not before 10. confirm or not,Mainstay of drug adverse reaction,17,Degree of probability,definite (肯定) probable(很可能) possible(可能) conditional(条件的) doubtful(可疑的),18,Standard of definite,1. reasonable chronologicaol order 2. confirmed from body fluid or tela 3. consistent with characteristic of reaction 4. amelioration by discontinue medication or irritation 5.no explanation,19,Therapeutic principle,to deal with drug-induced disease adopt treatment perscription,discontinue medication,doubt,drug allergy,inform patient,symptomatic treatment,serious,Specific antagon,withdrawal,relieve,20,Monitoring of drug adverse reaction,Effectiveness of drug monitoring Representative （clozapine；temafloxacin）,drug monitoring,latest / exceptional adverse reaction drug-induced disease,21,Means of drug monitoring,cohort study case control study submit a voluntary report,22,Cohort study,common/effective pharmacoepidemiology: retrospective study prospective study retrospective study: definite factor prospective study: follow-up visit Cohort study cannot discover exceptional adverse reaction,23,Case control study,Suspect adverse effect discover Diethylstilbestrol adenocarcinoma vagina thalidomide “phocomelia” infant,event,No application,application,compare,rare event,daughter,24,Submit a voluntary report,Earlier signal Delayed adverse reaction,Discover,Drug interactions,25,环丙沙星致皮下出血,26,蝮蛇抗栓酶致出血,27,蝮蛇抗栓酶致出血,28,蝮蛇抗栓酶致出血,29,环丙沙星致光敏性皮炎,30,环丙沙星致光敏性皮炎,31,尼达尔加心律平致皮肤反应,32,尼达尔加心律平致皮肤反应,33,急性肾功能衰竭 致过敏性紫癜和 环丙沙星和诺氟沙星,34,环丙沙星和诺氟沙星致过敏性紫癜,35,环丙沙星和诺氟沙星致过敏性紫癜,36,环丙沙星和诺氟沙星致过敏性紫癜,37,环丙沙星致双手剥脱性皮炎,38,环丙沙星致双手剥脱性皮炎,39,谢谢大家！,