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1、影响药物作用的因素(Factors of Influencing Drug Effect)作用与效应量效关系靶点药效学药效学吸收、分布代谢、排泄药动学药动学生理精神遗传疾病生物节律习惯环境机体因素联合用药长期用药给药方法药物因素理化性质药物剂型配伍用药药学学习目标o 在本次课结束时，每位同学能n 列举影响药物作用的各个因素。General Viewo Pharmaceutical factors:z Physical and chemical property of drugz Drug preparation(药物制剂)z Methods of drug administrationz Dr
2、ug interaction o Biological factors:Physiological factors Psychological factors Genetic factors Pathological factors Body response changes induced by long-term medication Biorhythm(生物节律)living habit and environmentPharmaceutical FactorsSection 11.Physical and Chemical Property of Drugo Solubleo Expo
3、sure decompose(见光分解)2.Drug Preparationo Oral administration:tablet,capsule,oral liquoro Injection:aqua(水剂),oils(油剂),emulsion(乳剂)o New praparation:n Slow release formulation(SLF):extended release formulatuion(延迟释放剂),sustained release formulatuion(持续释放剂)n Controlled release formulation(CLF):transderma
4、l patch(透皮贴剂)bioequivalence3.Methods of Drug Administrationo Dose:gtt,ml,o Route:p.o.,i.m.,i.v.,p.r.(直肠给药)o Time:a.c.(饭前),p.c.(饭后)o Interval:q.d.,b.i.d.,n post antibiotic effect(PAE,抗菌后效应)o Period of treatment:4.Drug Interactiono Pharmacokinetics:n absorption,distribution,metabolism,excretiono Pharm
5、acodynamics:n Synergism(协同作用):o addition(相加作用):=1+1o potentiation(增强作用):1+1n Antagonism(拮抗作用):o subtraction(相减作用):1o counteraction(抵消作用):0o Incompatibility(配伍禁忌配伍禁忌)Biological FactorsSection 21.Physiological Factorso Age:n Children:n The aged:o Gender:o Body weight(BW):o Interindividual variation:n
6、hypersensitivity&hyposensitivityn anaphylaxis(allergy)n idiosyncrasy(特异质反应)Ageo 小儿的药物代谢清除率较高o 小儿对药物较敏感o 发育阶段，易受药物影响 老年的器官功能降低老年的器官功能降低 对药物敏感性增高对药物敏感性增高肾小球滤过率肾小球滤过率心脏指数心脏指数生活能力生活能力肾血流量肾血流量最大呼吸能力最大呼吸能力功功 能能（%）年年 龄（岁）龄（岁）1008060402030507090Gendero药物反应和药物代谢酶活性有性别差异。n 酒精在女性代谢较男性慢（女性更易发生中毒反应n 女性对特非那定（terf
7、enadine，抗组胺药）的心脏毒性更敏感o激素作用：雌、孕激素抑制药物代谢女性对药物的清除能力多比男性弱，如女性利眠宁T1/2为男性的2倍Size/Obesityo 影响分布容积影响分布容积o 影响清除率影响清除率2.Psychological Factorso placeboo placebo effects3.Genetic Factorso Genetic polymorphismo Racial differences in drug responseo Idiocyncrasy种族(ETHNICITY)GenesSocialCulturalEnvironmentINTRINSICE
8、XTRINSICIn the age of the Genome，Why do people respond differently to drugs?oVariability in:-n Drug metabolism genotypen Drug transporter genotypen Drug receptor genotypen Drug/drug/environment/genotype interactionsGeneChip Analysis S M A R T C A R DFen-Fei GaoGENOME(Confidential)Personalized Medica
9、tion in the FutureIn the future(?years),your doctor will be able to select the best drug to treat your disease and the appropriate dose based on knowledge of your specific genetic makeup!XenobioGeneChipEnd of 3rd session 4.Pathological Factorso Liver disease:o Kidney disease:o Dystrophia(营养不良):o aci
10、d-base disturbance(酸碱平衡失调)o 5.Body Response Changes Induced by Long-term Medication1.Tolerance:body drug,pharmacodynamic tolerance and metabolic tolerance(肝药酶活性被诱导增强所致)nAcute tolerance(tachyphylaxis)nBrady-phylaxisnCross tolerance2.Drug resistance:pathogen(病原体),tumor cells drug3.Dependence:nPhysiolo
11、gical dependence(physical dependence)nPsychological dependence4.Withdrawal symptoms(withdrawal syndrome)nRebound phenomenon(反跳现象)6.Biorhythmo Chronopharmacology(时间药理学)n 时间药物效应n 时间毒理n 时间药物代谢7.Living Habit and Environmento Diet:component,quantity,time;o Smoking:hepatic drug enzyme activityo Drinking w
12、ine or liquor:Alcohol enhances hepatic drug enzyme activity;when acute and large amount administration,it makes the hepatic drug enzyme saturation.o Drinking tea:Tannic acid(鞣酸)influences drug absorption.Elixophylline(茶碱)excites the central nervous system and heart,promotes diuresis(利尿).o Environment:医生就是药o 医生每用一次药，就可能：n 产生副作用；n 维持药物作用相当时期；n 引起毒性反应；n 给以正确的病症；n 给以应当禁忌的病人；n 剂量过大；n 剂量过小；n 给药间隔时间正确；n 给药间隔时间不当；n 仅产生安慰剂效应。
