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1、影响药物作用的因素 (Factors of Influencing Drug Effect),彭 青,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 View,Pharmaceutical factors: Physical and chemical property of drug Drug preparation(药物制剂) Methods of drug administration Drug interaction,Biological factors: Physiological factors Psychological factors Gene
2、tic factors Pathological factors Body response changes induced by long-term medication Biorhythm(生物节律) living habit and environment,Pharmaceutical Factors,Section 1,1. Physical and Chemical Property of Drug,Soluble Exposure decompose (见光分解),2. Drug Preparation,Oral administration: tablet, capsule, o
3、ral liquor Injection: 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,3. Methods of Drug Administration,Dose: gtt
4、, 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 Interaction,Pharmacokinetics: absorption, distribution, metabolism, excretion Pharmacodynamics: Synergism(协同作用): addition(相加作用): =1+1 potentiati
5、on(增强作用): 1+1 Antagonism(拮抗作用): subtraction(相减作用): 1 counteraction(抵消作用): 0 Incompatibility(配伍禁忌),Biological Factors,Section 2,1. Physiological Factors,Age: Children: The aged: Gender: Body weight (BW): Interindividual variation: hypersensitivity & hyposensitivity anaphylaxis (allergy) idiosyncrasy(
6、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）,100,80,60,40,20,30,50,70,90,Gender,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.
7、Psychological Factors,placebo placebo effects,3. Genetic Factors,Genetic polymorphism Racial differences in drug response Idiocyncrasy,种族(ETHNICITY),Genes,Social Cultural Environment,INTRINSIC,EXTRINSIC,In the age of the Genome， Why do people respond differently to drugs?,Variability in:- Drug metab
8、olism genotype Drug transporter genotype Drug receptor genotype Drug/drug/environment /genotype interactions,GeneChip Analysis,Personalized Medication in the Future,In the future (? years), your doctor will be able to select the best drug to treat your disease and the appropriate dose based on knowl
9、edge of your specific genetic makeup!,Xenobio GeneChip,End of 3rd session,4. Pathological Factors,Liver 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 Medication,Tolerance: body drug, pharmacodynamic tolerance and metabolic tol
10、erance (肝药酶活性被诱导增强所致) Acute tolerance (tachyphylaxis) Brady-phylaxis Cross tolerance Drug resistance: pathogen(病原体), tumor cells drug Dependence: Physiological dependence (physical dependence) Psychological dependence Withdrawal symptoms (withdrawal syndrome) Rebound phenomenon(反跳现象),6. Biorhythm,Ch
11、ronopharmacology(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 Environment,Diet: component, quantity, time; Smoking: hepatic drug enzyme activity Drinking 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) excites the central nervous system and heart, promotes diuresis(利尿). Environment:,医生就是药,医生每用一次药，就可能： 产生副作用； 维持药物作用相当时期； 引起毒性反应； 给以正确的病症； 给以应当禁忌的病人； 剂量过大； 剂量过小； 给药间隔时间正确； 给药间隔时间不当； 仅产生安慰剂效应。,