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1、影响药物作用的因素(Factors of Influencing Drug Effect)彭 青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 ViewoPharmaceutical factors:zPhysical and chemical property of drugzDrug preparation(药物制剂)zMethods of drug administrationzDrug i
2、nteraction oBiological factors:Physiological factorsPsychological factorsGenetic factorsPathological factorsBody response changes induced by long-term medicationBiorhythm(生物节律)living habit and environmentPharmaceutical FactorsSection 11.Physical and Chemical Property of DrugoSolubleoExposure decompo
3、se(见光分解)2.Drug PreparationoOral administration:tablet,capsule,oral liquoroInjection:aqua(水剂),oils(油剂),emulsion(乳剂)oNew praparation:nSlow release formulation(SLF):extended release formulatuion(延迟释放剂),sustained release formulatuion(持续释放剂)nControlled release formulation(CLF):transdermal patch(透皮贴剂)bioe
4、quivalence3.Methods of Drug AdministrationoDose:gtt,ml,oRoute:p.o.,i.m.,i.v.,p.r.(直肠给药)oTime:a.c.(饭前),p.c.(饭后)oInterval:q.d.,b.i.d.,npost antibiotic effect(PAE,抗菌后效应)oPeriod of treatment:4.Drug InteractionoPharmacokinetics:nabsorption,distribution,metabolism,excretionoPharmacodynamics:nSynergism(协同作
5、用):oaddition(相加作用):=1+1opotentiation(增强作用):1+1nAntagonism(拮抗作用):osubtraction(相减作用):1ocounteraction(抵消作用):0oIncompatibility(配伍禁忌配伍禁忌)Biological FactorsSection 21.Physiological FactorsoAge:nChildren:nThe aged:oGender:oBody weight(BW):oInterindividual variation:nhypersensitivity&hyposensitivitynanaphyl
6、axis(allergy)nidiosyncrasy(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（terfenadine，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
7、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 Factorsoplacebooplacebo effects3.Genetic FactorsoGenetic polymorphismoRacial differences in drug responseoIdiocyncrasy种族(ETHNICITY)GenesSocialCulturalEnvironmentINTRINSICEXTRINSICIn the age of the Genome，Why do people respond d
8、ifferently to drugs?oVariability in:-nDrug metabolism genotypenDrug transporter genotypenDrug receptor genotypenDrug/drug/environment/genotype interactionsGeneChip Analysis S M A R T C A R DFen-Fei GaoGENOME(Confidential)Personalized Medication in the FutureIn the future(?years),your doctor will be
9、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 FactorsoLiver disease:oKidney disease:oDystrophia(营养不良):oacid-base disturbance(酸碱平衡失调)o5.Body Response Changes Induced by Lo
10、ng-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:nPhysiological dependence(physical dependence)nPsychological dependence4.W
11、ithdrawal symptoms(withdrawal syndrome)nRebound phenomenon(反跳现象)6.BiorhythmoChronopharmacology(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 EnvironmentoDiet:component,quantity,time;oSmoking:hepatic drug enzyme activityoDrinking wine or liquor:Alcohol enhances hepatic drug enzyme activity;when acute a
12、nd large amount administration,it makes the hepatic drug enzyme saturation.oDrinking tea:Tannic acid(鞣酸)influences drug absorption.Elixophylline(茶碱)excites the central nervous system and heart,promotes diuresis(利尿).oEnvironment: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。