药理学总论课件：影响药物作用的因素

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吸收、分布代谢、排泄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在本次课结束时，每位同学能列举影响药物作用的各个因素。General ViewPharmaceutical factors:Physical and chemical property of drugDrug preparation(药物制剂)Methods of drug administrationDrug interaction Biolo

2、gical 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 DrugSolubleExposure decompose (见光分解)2. Drug P

3、reparationOral administration: tablet, capsule, oral liquorInjection: aqua(水剂), oils(油剂), emulsion(乳剂)New praparation:Slow release formulation (SLF): extended release formulatuion(延迟释放剂), sustained release formulatuion(持续释放剂)Controlled release formulation (CLF): transdermal patch(透皮贴剂)bioequivalence

4、3. Methods of Drug AdministrationDose: gtt, ml, Route: p.o., i.m., i.v., p.r.(直肠给药) Time: a.c.(饭前), p.c.(饭后)Interval: q.d., b.i.d., post antibiotic effect (PAE, 抗菌后效应)Period of treatment:4. Drug InteractionPharmacokinetics: absorption, distribution, metabolism, excretionPharmacodynamics:Synergism(协同

5、作用): addition(相加作用): =1+1potentiation(增强作用): 1+1Antagonism(拮抗作用): subtraction(相减作用): 1counteraction(抵消作用): 0Incompatibility(配伍禁忌)Biological FactorsSection 21. Physiological FactorsAge:Children:The aged:Gender:Body weight (BW):Interindividual variation:hypersensitivity & hyposensitivityanaphylaxis (a

6、llergy)idiosyncrasy(特异质反应)Age小儿的药物代谢清除率较高小儿对药物较敏感发育阶段，易受药物影响老年的器官功能降低对药物敏感性增高肾小球滤过率心脏指数生活能力肾血流量最大呼吸能力功 能 （%）年 龄（岁）1008060402030507090Gender药物反应和药物代谢酶活性有性别差异。酒精在女性代谢较男性慢（女性更易发生中毒反应女性对特非那定（terfenadine，抗组胺药）的心脏毒性更敏感激素作用： 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 / Obesity影响分布容积影响清除率2. Psychologic

7、al Factorsplaceboplacebo effects3. Genetic FactorsGenetic polymorphismRacial differences in drug responseIdiocyncrasy种族(ETHNICITY)GenesSocialCulturalEnvironmentINTRINSICEXTRINSICIn the age of the Genome，Why do people respond differently to drugs?Variability in:-Drug metabolism genotypeDrug transport

8、er genotypeDrug receptor genotypeDrug/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 able to select the best drug to treat your disease and the appropriate dose

9、 based on knowledge of your specific genetic makeup!XenobioGeneChipEnd of 3rd session 4. Pathological FactorsLiver disease:Kidney disease:Dystrophia(营养不良):acid-base disturbance(酸碱平衡失调)5. Body Response Changes Induced by Long-term MedicationTolerance: body drug, pharmacodynamic tolerance and metaboli

10、c tolerance (肝药酶活性被诱导增强所致)Acute tolerance (tachyphylaxis)Brady-phylaxisCross toleranceDrug resistance: pathogen(病原体), tumor cells drugDependence:Physiological dependence (physical dependence)Psychological dependenceWithdrawal symptoms (withdrawal syndrome)Rebound phenomenon(反跳现象)6. BiorhythmChronoph

11、armacology(时间药理学)时间药物效应时间毒理时间药物代谢7. Living Habit and EnvironmentDiet: component, quantity, time;Smoking: hepatic drug enzyme activityDrinking wine or liquor: Alcohol enhances hepatic drug enzyme activity; when acute and large amount administration, it makes the hepatic drug enzyme saturation.Drinking tea: Tannic acid(鞣酸) influences drug absorption. Elixophylline(茶碱)