1、第一章 药理学总论,蚌埠医学院 药学系药理教研室 2005.9,Chapter 1.,Introduction,General principles of pharmacology,Bengbu Medical CollegeFaculty of pharmacy Department of Pharmacology Zhu xiaoguang,薬,?,drug,葯,drug,alter,Physiology and pathology,prevent,diagnose,Cure,Chamical substance,1,sources of drugs (来源),天然: plants (植物
2、)animals (动物)minerals(矿物),2,合成： 1） full-synthetic drug (全合成)2）semi-synthetic drug (半合成),3）Genetic engineering drugs（基因工程药物）,Drug & poison,罂粟,药物,pharmacology,？,3,is the study of interaction between drug and body and the laws of drug actions.,Pharmacology,pharmacology,drugs,body,microbes,药效学,药动学,致病作用,
3、抵抗力,抑制或杀灭,抗药性,药动学,Pharmacokinetics,disposes,body,drug,4,1）absorption A. 吸收、 2）distribution D. 分布、 3）metabolism M. 代谢、 4）excretion E. 排泄,body,drugs,Pharmacodynamics,5、药效学,acts on,responds to,responds to,1）action （作用）、2）mechanism （作用机制）、 3）use （应用、用途）、 4）Adverse reaction（不良反应）,？,Why do you studypharma
4、cology?,characters of subject,？,特点,1、桥梁学科,2、基础学科,3、实验学科,基础课,临床课,解剖,生理,生化,病理,内科,外科,妇科,儿科,药理学,实验学科,？,1、direct rational usage of drug,2、Research and develop new drug,3、Provide scientific basis and research tool for other vital science.,tasks ：,二、Historical development of pharmacology,古代：药物学神农本草经本草纲目,现代
5、：药理学化学：提供纯品、单体生理学：提供实验方法生物化学：器官细胞分子水平,实验方法,1、实验药理学方法 2、实验治疗学方法 3、临床药理学方法,research of new drugs,三、Development and,1）preclinical research,2）clinical research 3）post-marketing surveilance,1、临床前研究2、临床研究3、上市后药物检测售后调研,药物化学,药理学,期临床,期临床,期临床,期临床,新药开发与研究,Chapter 2,Pharmacokinetics,qualitative research（定性研究）,A
6、、D、M、E及过程,quantitative research（定量研究）,用数学的方法研究体内药浓变化的规律，（药动学参parameter）,药动学,transportation （转运）药物 位置变化。（A、D、E、） transformation （转化） 药物 化学结构变化。（M）,体内,体内,Researching content,Transmembrane,drug,transport,？,1 transmembrane transportation of drugs,脂质双分子层,Manners of transport, non carrier mediated transpo
7、rt （非载体转运 Carrier mediated transport（载体转运,Mode of transmembrane transportation,1、filtration （滤过） 2、simple diffusion （简单扩散） （lipid diffusion ，脂溶扩散 ）,（被动扩散）,一、 passive diffusion,药物通过细胞膜的方式,1）filtrtion 滤过,2）Simple diffusion（简单扩散）Ion trapping,non carrier transport,（被动扩散）,passive diffusion,simple diffusi
8、on,1、大多数药物的转运方式(most common and important mode) 2、顺浓差(along the concentration gradient) 3、不耗能(does not expend energy) 4、不需载体(does not need carrier) 5、 没有饱和现象和竞争抑制(has not saturation competitive inhibition),？,transmembrane transportation,1）膜两侧药浓差,2）药物脂溶性,易跨膜,脂溶性,解离度小,极性低,pHpKa= log A- / HA,weak acid
9、(弱酸),Handerson-Hasselbalch equation,10 pH-pKa = A- / HA,HA = H+ + A-,Ka = H+ A- / HA,（解离常数）,pKa： Ka 的负对数,pH：H+浓度负对数,BH =H+ + B Ka =H+B/BH,weak base (弱碱),-,pKa-pH=logBH/B,10 pKa-pH=BH+/B,0,-1,-2,-3,1,2,3,50,20,80,100,50,80,100,20,Free%,口诀,酸酸碱碱促吸收，,酸碱碱酸促排泄,？,酸性药,盐,（碱）,Penicillin G,青霉素 + 钾（钠）,（酸）,？,碱性药
10、,Morphine,盐酸+吗啡,盐酸吗啡,（酸）（碱） （盐）,苯巴比妥钠,PH 7.0,PH 7.4,cell,？,Carrier mediated transport,（载体转运）,1）Active transport,（主动转运）,2）Facilitated diffusion,（易化扩散),Characteristics,Carrier mediated transport,/,？,1）Selectivity （选择性）2）Saturation （ 饱和性） 3）Competition（竞争性）Competitive inhibition（竞争性抑制）,transmembrane tr
11、ansportation,Factors affecting,？,drug,Permeable amount,Blood flow,（通透量）,（C1 C2）,膜面积通透系数,膜厚度,2 、,1、,2 Course of drug in the body,一、Absorption,？,drug,cellular membrane barrier,circulation,Administration of drug (给药途径),1、 Per os（口服）Molecular weight, velocity of disintegration、 dissolution,1）first pass
12、elimination （首关消除）,Orally administered drugs,the portal vein,the liver ，small intestine,the drugs may be metabolized,less drugs reach the systemic circulation,first-pass elimination or first-pass metabolism.,hapatic,per rectum,Sublingual,Per os,4、Sublingual （舌下给药）,2、Inhalation （吸入给药）,3、topical appli
13、cation（局部用药）,per rectum （直肠给药）,intravenous injection，iv or infusion（静脉注射或输液) intramucular injection，im（肌内注射） subcutaneous injection ，sc（皮下注射） intra-arterial ，ia（动脉注射） Transdermal （鞘内注射）,5、injection,factors affecting drug absorption,physicochemical properties preparations药物的理化性质和制剂特点 、 administration
14、 routes absorption environment 给药途径和吸收环境 、 pH of the environment 环境pH,二、 Distribution,all organs,？,drug,circulation,1）binding to Plasma protein 2 ）Blood flow of organs 3 ）Tissue binding 4 ） pKa and pH 5 ） Barrier,Factor affecting distribution:,binding to plasma protein,暂失活性,暂时贮存,难以跨膜转运,不易排泄,有竟争置换作用,
15、distribution redistribution-,Blood flow,A .,drug,blood,brain,B.,fat,blood,all organs,Plasma protein binding Saturable,Protein + drug A 90%,Free - drug A 10%,drug B binding 90%,drug A 10%,Free - drug A 90%,Competitive inhibition,1）,2）,4）thisodium fat (redistribution)（硫喷妥钠）,T issue binding:,1）Iodin（碘）
16、 thyroid gland,2）chloroquine liver, red cell infected（氯喹） by plasmodium,3）gentamicin hair, skin, nail（庆大霉素）,Blood-brain barrier（血脑屏障） 2) Placenta barrier（胎盘屏障） Blood eye barrier（血眼屏障）,Barrier (屏障),三、Transformation 1、(metabolism),？,The structure of drug is altered,by enzymatic system,Oxidation (氧化)Re
17、duction （还原）Hydrolysis （水解）,2、Phases of biotransformation:,Phase 2: Conjugation（结合）,Phase 1,3、results of metabolism,1) effect，polar，excretion 2) effec，toxin 3) metabolism activity 4) no metabolism in body,4、Factor affecting metabolism,3) metabolic enzymes,1) structure of drug,2) transformation,Hepat
18、ic microsomal drug-metabolizing enzyme system（肝微粒体药物代谢酶,肝药酶）1）Cytochromes P-450 2）hepatic mixed-function oxydase system，（混合功能氧化酶系统),Enzymes,hepatic mixed- function oxidase,1) low specificity,2) represent a mixed-function oxidase system,3) have individual variation,inducible and inhibition,4),Charact
19、eristics,enzyme inducer (肝药酶诱导剂)：使肝药酶活性的药物，如苯巴比妥,1） increase the activity of cytochrome P450 2）increase their own metabolism as well as that of other drugs.,enzyme inhibitor (肝药酶抑制剂)： the activity of cytochrome P450,Results ：,1) Most drugs become polarized molecule and secreted easily,2）Some drug be
20、come active metabolites,Conjugation,5、,Excretion,out of the body,?,are discharged,drugs,drug,administration,body,Pharmcodynamic effect,Pharmcokinetic process,excretion,out of,elimination,(A. D. M),（E）,Excretory routes:,Biliary excretion,Renal excretion（肾脏）,（胆囊）,Gaistriintestinal(胃肠道）,Rispiratory （呼吸
21、道）,milk（乳汁）,Sweat（汗）,Saliva（唾液） Tears （泪）,Sikin (皮肤）,Renal excretion, Filtration Nonspecific secretionmechanisms:acidic (anion，阴离子)basic (cation，阳离子)competitive inhibitionPassive reabsorption, Biliary excretion,hepato-enteral circulation,Cardiac glycoside,强心苷,Questions:,1. How many factors affect th
22、e absorption,distribution? 2. Whats hepatoenteral circulation? Whats its importance?,3. Do you can describe characteristics and importance of the hepatic biotransformation of drug.,Questions:,三、Model of compartment,1、 Model of one opening compartment (po.),Drug,body,A.,E.,D.,M.,2、 Model of two openi
23、ng compartment (po.),PO drug,中央室,周边室,E.,A.,D.,M.,血供丰富组织,血供贫乏组织,4. Eliminationkinetics of drug,zero-order kinetics （零级动力学) first-order kinetics （一级动力学),Constant fraction (恒定比例) of drug is eliminated per unit time.,1、first-order elimination kinetics,1、,properties：,1、the major pattern of elimination；,2
24、、Amount of drug eliminated per unit time is in direct ratio with the plasma concentration,3. t1/2 is constant.（t1/2 0.693 / ke),2、zero-order,Elimination kinetics,Constant amount of drug is eliminated per unit time.,单位时间内药物消除的量恒定。,3、t is not constant.,propertie（特点）,2、Amount of drug eliminated per uni
25、t time is no relationship,1、the few pattrn of elimination；,3、,Mixed elimination kinetics,混合动力学消除,properties ： 1、the few pattrn of elimination:aspirin、phenytoin 2、high concentration-constant amount low concentration constant fraction 。,3、t is constant.,quantitative lows of pharmacokinetics,一 、quantitytime relationship,药动学的 定量规律,（一） time - concentration curve（时浓曲线）,
