药理学绪论山东大学药理学英文课件.ppt

1、,WELCOME TO PHARMACOLOGY,PHARMACOLOGY 药 理 学,张岫美 Zhang Xiu-mei 山东大学医学院 药理学研究所 教学八楼8325 Tel: 83146 Email: ,CHAPTER 1 INTRODUCTION,1. The Nature and Duties of PharmacologyPharmacology（药理学） To study the principles of interactions between drug and living system which includes human body, tumor cells and

2、microorganisms and its mechanisms.,Drug (药物，medicine, pharmakon, remedy, materia medica）,Chemical substances (exogenous or endogenous substances e.g., synthetic drugs, hormones, antibiotics, peptides, and DNA fragments etc.) used to treat, prevent and diagnosis diseases. Even including family planni

3、ng chemicals and rat poisons.,Poison （毒物） Chemical substances to harm or injure human health in small dose. Some times poison can be used as a drug in suitable dose, such as toxins from plant or animals(snake venom). Drug may be a poison when use overdose or long term use. Barbiturates usually as sl

4、eeping drug, when use over dose it may cause intoxication.,Poison,Sometimes, the differences between drug and poison is dose. The dose makes the poison. If something is not a poison， it is not a drug.,Sources of drugs,Plant - alkaloids, glycoside Animal insulin Microorganisms antibiotics Synthetic c

5、hemicals Genetic engineering drugs Preparations（制剂）,The Main Parts of Pharmacology,a. Pharmacodynamics (药物效应动力学，药效学) Drug Body b. Pharmacokinetics (药物代谢动力学，药动学),Pharmacodynamics 药效动力学,To explain the biochemical or physical actions of drugs on the body. Include action, mechanisms, indications, advers

6、e reactions, contraindications of the drug.,Pharmacokinetics 药代动力学,To reveal the principles of dynamic changes of drug in the body. What drugs do on the body.,The Processes of Drug in the Body,Pharmacokinetics 药代动力学,Mainly dealing with the change of drug concentration in the human or animal body fol

7、lowing administration, i.e., the changes of concentration in the dynamic system of liberation, absorption, distribution, metabolism and excretion (ADME).,The Duties of Pharmacology,a. To explain the action and its mechanisms of the drug, to provide the theoretical basis for clinic, enhancing the dru

8、g efficacy and reducing adverse drug reaction. b. To develop new drug and new indications of drug. c. To explore the pathway of physio-, biochemi- and pathology of the cells.,The Roles of Pharmacology,Key subject of basic medical sciences. Part of pharmacy. Bridges桥梁学科: Basic and clinic, medical and

9、 pharmacy. The Aims for Pharmacology Learning Exactly important for a physician to treat patients by drugs.,The Roles of Pharmacology,If you have learned Pharmacology, you can become a half of physician.,2. History and Development of Pharmacology,Materia Medica in China: long history Pen Tsao（本草） by

10、 Shennong, 100 B.C. Pen Tsao Gang Mu （本草纲目）by Li Shi-zhen (1596), 52 vols, 1 900 000 characters, 1 892 drugs, 1 160 figures, 11 000 prescriptions.,Pharmacology in the World,Chemistry, biochemistry, physiology development Germany chemist F.W. Serturner(1783-1841) - morphine（吗啡,1803） strychnine(1819),

11、 caffeine(1819) quinine(1820), atropine(1831),Pharmacology in the World,P. Ehrlich(German,1906): 新胂凡纳明, 606 R. Buchhneim(1820-1879): First pharmacol. lab, first pharmacol. textbook, first pharmacol. professor in the World.,Pharmacology in the World,O.Schmiedeberg(1838-1921): Experimental pharmacolog

12、y Organic pharmacology P. Ehrlich et J. N. Langley: Receptor theory.,Penicillin的发现(Fleming),1928年的一天，英国细菌学家弗莱明在他的实验室里研究葡萄球菌。他发现培养细菌用的琼脂上附了一层青霉菌。这是从楼上研究青霉菌的窗口飘落进来的。使弗莱明感到惊讶的是，在青霉菌的近旁，葡萄球菌却不见了。这个偶然的现象吸引了他，他设法培养这种霉菌进行多次试验，证明青霉菌产生的物质可以在几小时内将葡萄球菌全部杀死。这种物质就是弗莱明发明的葡萄球菌的克星青霉素。,弗莱明在实验室中,弗洛里（Florey),造福人类的抗生素,

13、美国制药企业1942年开始批量生产青霉素。青霉素在世界反法西斯战争中挽救了大量伤病员。为了表彰他们对人类健康的巨大贡献，弗莱明、钱恩、弗洛里于1945年共同获得诺贝尔医学和生理学奖。,Wonderful阿司匹林,Aspirin,阿司匹林具有悠久的历史。1853年夏尔.弗雷德里克.热拉尔（Gerhardt）用水杨酸与醋酐合成了乙酰水杨酸，但没能引起人们的重视；1898年德国化学家菲.霍夫曼（Felit Hoffmann）重新进行合成，并为他父亲治疗风湿性关节炎，取得巨大成功；1899年由德莱塞（Dreser）介绍到临床，并取名为阿司匹林（Aspirin）。,阿司匹林,1999年3月6日德国拜尔（

14、Bayer）公司在全世界范围内庆祝阿司匹林的百岁生日。100年全世界的人们大约服用了数十亿片阿司匹林，主要用于解热、镇痛、抗炎抗风湿，近年又在防治心脑血管疾病方面大显身手。阿司匹林的百年历史是二十世纪发明史中的辉煌篇章。,Pharmacology in Recent Years,Calcium channel blockers Angiotensin I converting enzyme inhibitors Satins AT receptor antagonist,Pharmacology in China,陈克恢(K K Chen): ephedrine(1923) “The Fath

15、er of American Pharmacology” (TIMES, 1988) “The Father of Chinese Pharmacology” (金荫昌, 1999) 张昌绍，邹冈：Analgesic site of morphine(1963). Qinghaosu(artemisinin，1970) 金国章：rotundine 秦伯益：dihydroetorphine,The Main Branches of Pharmacology,临床药理学：Clinical pharmacology 生化药理学：Biochemical pharmacology 分子药理学：Molec

16、ular pharmacology 免疫药理学：Immunopharmacology 心血管药理学：Cardiovascular pharmacology 神经药理学：Neuropharmacology 遗传药理学：Pharmacogenetics 化学治疗学：Chemotherapy,3. Pharmacology in New Drug Research and Development,New drugs(新药)：Drugs without marketing in China defined as new drug by Sino Food and Drug Administration

17、(SFDA,在中国未上市销售的药物) Western medicines Traditional Chinese medicines Biochemicals,Clinical,Marketing,Preclinical,_X13,Stages of Drug Development,The Steps for Drug Research and Development(R the second exam in the end of endocrine drugs. The type of exam is mainly choice questions and somewhat the pha

18、rmacological terms or answer question.,The Faculty Members for Pharmacology Teaching,张岫美教授 总论、中枢药理 刘慧青讲师（博士）心血管系统药（组长） 娄海燕讲师（博士）化学治疗药 王姿颖讲师 （博士生）自主神经药 张 斌讲师（博士生）中枢神经药 安 杰讲师（博士生）内脏、内分泌药 陈 琳 薛慧艳 硕士研究生,附：Appendices,一、处方药与非处方药 处方药（prescription-only medicines, ethical drugs, legend drugs） （1）疾病必须由医生或试验室确

19、诊，使用药物 需医师处方，并在医生指导下使用，如治疗心血 管疾病的药物。 （2）可产生依赖性的药物：吗啡类、中枢药物等。 （3）药物本身毒性较大：如抗肿瘤药。 （4） 刚上市的新药：对其活性、副作用还要进一步观察。,非处方药,（nonprescription drugs, over the counter drugs, home remedies, proprietary nonprescription drugs, OTC ） 中国2000年1月1日开始施行 遴选原则： 应用安全 疗效确切 质量稳定 使用方便 至今SFDA公布非处方药4109个药品制剂，其中甲类3017种，乙类1143种。,

20、处方药与非处方药的区别,处方药 非处方药 疾病类型 较重、需医师确诊 较轻 诊断者 医师 患者自我认识和辨别、自我选择 取药凭据 医师处方 无需处方 取药地点 医院药房、药店 药店（甲类）超市（乙类） 剂量 较大 较小，有限定 疗程 长，医嘱指导 短，有限定 保护 新药保护、专利保护 品牌 宣传对象 医师 消费者 广告 不可上广告 批准后，可上大众媒体或广告,二、国家基本药物（essential drugs, basic drugs）,遴选原则： 临床必需、安全有效、价格合理、使用方便 综合评价突出、中西药并重、稳定提高。 1994年完成中药遴选，1998进行调整， 176个病种，4441个症

21、，1333个品种。 19921995年分四批完成西药遴选， 1997年进行调整，共27类740个品种。,三、药品名称,1 中文名 采用中国药品通用名称（药典名称） 2 英文名 采用国际非专利药名（International nonproprietary names for pharmaceutical substances, INM） 3 商品名（trade mark name） 普萘洛尔 Propranolol 心得安，恩得来，萘心安 inderal, angilol, cardinol,CHAPTER 3,PHARMCODYNAMICS 药物效应动力学 SECTION 1 Basic Ac

22、tions of Drug,1. Drug Actions and Effects of Pharmacological on the body作用与效应,Action（作用） referred to the initial or primary interaction between drug molecule with receptors on the cells. Adrenaline（肾上腺素） stimulate receptors on the myocardial cell to stimulate the heart.,Effects（效应）,Pharmacological e

23、ffect: physical effects secondary to initial drug action. Adrenaline act on receptors called action of adrenaline, stimulating heart called effects of adrenaline.,Effects,Excitation(stimulation，兴奋): the body function increase or potentiated by the drug. Adrenaline accelerate the heart rate and outpu

24、t. Acetylcholine contracts the gastro-intestinal smooth muscle. These effects are called stimulation. With the dose increase of the drug it may induce augmentation（亢进）. For example, overdose of adrenaline may cause heart failure.,Effects,Inhibition（抑制）: the body function decrease or suppressed by th

25、e drug. If dose increase largely it may produce paralysis（麻痹） or failure（衰竭）. For instances, diazepam安定 induce sedation and hypnosis. Aspirin lowers the elevated body temperature.,Selectivity or specificity of drug action,Selectivity or specificity（选择性，特异性） Ideally, specificity means that a drug onl

26、y binds to one single type of receptor and cause one single effect. Selectivity means that a drug binds to one or a few types of receptors with higher affinity than to other receptors.,2. Therapeutic Effects of Drugs治疗效果,Therapeutic Effects治疗作用 The effects produced by the drug are the purposes for t

27、he drug use, i.e., the beneficial effects of the drug. Therapeutic effects are useful to prevent or treat diseases.,Therapeutic Effects of Drugs,Etiological treatment 对因治疗(治本) Symptomatical treatments 对症治疗(治标),(1)Etiological treatment对因治疗,Elimination of the etiological factors by using drug to cure

28、diseases a. Therapy by killing pathogens If an inflammation is caused by the invasion of pathogens, the application of suitable antibiotics is preferred. Antibiotics selectively kill bacteria without harming the body. Gene therapy, immunotherapy.,b. Supplementary (replacement) therapy,Lack of endoge

29、nous substance may cause many kinds of diseases. For example, lack of vitamin A may cause night blindness; lack of thyroid hormones congenitally may cause cretinism. In these cases, supplement of the corresponding substances is an effective way to restore the body to normal function. The supplement

30、of vitamins, hormones and other necessary substances of the body is called replacement therapy.,(2) Symptomatic treatment对症治疗,The disease symptom improvement without eliminating the cause of the disease. For instance, pain relieved by aspirin; hypertension lowered by anti-hypertensive drugs.,3.Adver

31、se Drug Reactions(ADR),药物不良反应 The World Health Organization(WHO) defined the drug adverse reaction: “Any response to drug that is noxious and unintended and that occurs at dose used in man for prophylaxis, diagnosis or therapy of a disease, or for the modification of physiological function”.,(1) Sid

32、e effects副反应,In the range of therapeutic doses, the drug effects, which are not related to the current therapeutic purpose, are called side effects. The pharmacological basis of the presence of side effects is low selectivity of the drug.,Side effects副反应,For instance, if a muscarine receptor antagon

33、ist, atropine is used to prevent airway secretion caused by anesthetics, all other effects of atropine, such as mydriasis, dry mouth, belong to the side effects; however, if it is used in ophthalmology (eye), all other effects such as, dry mouth, accelerate cardiac rate etc., belong to the side effe

34、cts.,(2) Toxic reaction毒性反应,All drugs are capable of producing toxic reactions if the dose is high enough or drugs long term used. A. According to on-speed of drug toxicity: if toxicity caused by short term use of a drug, it is called acute toxicity, and if caused by long term use, called chronic to

35、xicity.,Toxic reaction毒性反应,B. According to the distribution of drug toxicity: drug toxicity may be classified local or systemic toxicity. C. According to the extent of drug toxicity: Pharmacological toxicity(most cases are reversible) and pathological toxicity(part of cases irreversible),Toxic react

36、ion毒性反应,Special toxications特殊毒性: Carcinogenesis致癌: some drug may cause cancer. Teratogenesis致畸: in few cases some drug may induce teratogenesis, such as thalidomide. Mutagenesis致突变: some special drug can induce DNA change, resulting in carcinogenesis or teratogenesis.,(3) After effect (residual effe

37、ct) 后遗效应,After withdrawal of the drug, the drug concentration is below the threshold, the effect still exists, such as after taking barbiturates, the second morning, the patient feels hangover, drowsiness, and fatigue.,After effect后遗效应,For instance, stop administration of hydrocortisone after its lo

38、ng-term use will cause hypoadrenocorticism which need several months to recover.,(4)Withdrawal reaction (rebound) 停药反应,Rapid withdrawal when long-term use some drug may lead to accelerate the symptoms of ordinary disease, such as when stop use propranolol for its long-term use in angina patients, wh

39、ich can provoke angina attacks, arrhythmias, or myocardial infarction, even more severe than before.,(5) Allergic reaction变态反应,Hypersensitive reaction: drug allergy is an altered response to a drug resulting from a previous sensitizing exposure and an immunological mechanism. It is also a pathologic

40、al allergic reaction of a drug.,Allergic reaction变态反应,Drug induced allergy have been reported for almost every drug in extensively clinical use. Some agents, such as streptokinase, penicillin, iodides, phenytoin, and sulfonamides are truly allergic in nature. （过敏反应, hypersensitivity）,Allergic reacti

41、on变态反应,The drug allergies are manifested as skin eruption, edema, anaphylactoid reactions, eosinophilia, immune complex disorders and contact dermatitis, and may be most severe allergic shock in some cases, such as penicillin caused allergic shock.,(6)Idiosyncrasy特异质反应,Drug idiosyncrasy refers to an

42、 abnormal response to a drug by an individual. It is quite likely that idiosyncrasy are genetically abnormalities of enzymes and receptors. Therefore, these abnormal response are often referred to as phamacogenetic disorders.,Idiosyncrasy特异质反应,For example, hemolytic anemia elicited by primaquine in

43、patients whose red blood cells are deficient in glucose-6-phosphate dehydrogenase; apnea caused by succinylcholine in patients with abnormal serum ACh esterase which is incapable of destroying succinylcholine as usual.,SECTION 2Drug Dose and Dose-Effect Relationship,Drug dose(dosage): Amount of drug

44、 used in the prevention or treatment of diseases.,Dose-Effect Relationship,Concentration-effect relationship(CER) In a certain range of doses, the pharmacological response is increased with the increase in doses without evident toxic effects(usually log concentration is used), the relationship betwe

45、en dose(or concentration) called CER. The curve of this relationship called dose-effect curve.,Drug Dose and Dose-Effect Relationship,Concentration-effect relationship(CER) Dose-effectc urve Sshape Dose-effect relationship(DER),1. Graded Dose Response量反应,Graded dose response means the pharmacologica

46、l effects of the drugs expressed in quantity or number, such as the heart rate by beat, blood pressure by mmHg, also the contract of ileum in height effected by the drugs.,Graded Dose Response量反应,(1)Minimum effective dose最小有效量 (最小有效浓度，minimum effective concentration, threshold concentration, 阈浓度, Cm

47、in) Cmin means in that minimum dose can cause the pharmacological effect, indicate the least amount of drug needed to exert therapeutic effects.,Graded Dose Response,(2)Maximum efficacy(最大效应，效能, efficacy, Emax) Emax means the drug is capable of exerting maximal effect. The term describes the maximal

48、 biological response produced by a drug. Efficacy of a drug depends on the receptor density or the number of active receptors.,Graded Dose Response,(3)Concentration for 50% of maximum effect(半最大效应浓度， EC50) The concentration of a drug that gives rise to to one-half of the maximum response (continuous

49、 effect)is called median effective concentration.,Graded Dose Response,(4)Potency效价强度 The term describes the comparative expression of a drug activity measured in term of dose required to produce a particular effect of given intensity related to a given standard reference. 引起等效反应的相对浓度或剂量。,Potency效价,

50、ED50 is often used to compare potency of drugs. A drug with low ED50, is more potent than that with large ED50. (5)Slope(斜率),2. Quantal Response质反应 (all-or-non-response),Quantal Response(all-or-non-response) That is the pharmacological effects are expressed in positive or negative, indicating that a

51、 given dose of a drug has or has not evoked a certain effect in the various subject under investigation. For example, to test either presence or absence of hypnosis for a sedative.,Quantal Response质反应 (all-or-non-response),Quantal Response,(1) Median effective dose(半数有效量，ED50): For all-or-none respo

52、nse, the dose of a drug that gives rise to a positive response in 50% of the subject. The more potent the drug, the lower its ED50.,Quantal Response,(2) Lethal dose致死量 The dose of a drug can cause the experimental animal to death. (3) Median lethal dose(半数致死量，LD50) A dose of a drug that gives rise t

53、o the death of 50% of experimental animals is called LD50.,Quantal Response,(4) Minimum toxic dose(最小中毒量) (5)Median toxic dose(TD50) A dose of a drug that cause a toxic effect in 50% of experimental animal is called TD50.,3. The Safety of Drug药物的安全性,(1)Maximum dose（极量） The largest dose of drug is pe

54、rmeated in clinical use by Pharmacopoeias, if a doctor uses a dose beyond the maximum dose, it is over the law. If some thing happened inducing some harm or injure on the patient, the doctor prescribed drug is responsible for this.,The Safety of Drug,(2) Therapeutic index (TI) LD50/ED50 TI describes

55、 the safety of a drug. The larger value of the TI is, the wider margin between effective dose and toxic dose is safe.,安全范围,(3) Margin of safety Margin of safety of the drug is also described as. ED99 LD1 or ED95 LD5,SECTION 3 DRUG AND RECEPTORS,Drugs can do two things to recepters: (1) bind to them

56、(affinity) and (2) possibly change their behavior toward the host cell system (efficacy).,1. Mechanisms of Drug Action,The Types of Mechanism of Drug Action: (1) Physical and chemical reaction Some drugs are used to treat diseases by physical and chemical reaction in the body. Such as antacids neutr

57、alizing gastric acid are used to treat ulcer and osmotic diuretic dextran increasing osmolarity of plasma, is used to treat edema; and metal chelating agents combine to toxic metals.,(2)Joining or interfering with cell metabolism,Vitamins, iron preparations and some anticancer drugs whose chemical s

58、tructure resemble purine or pyrimidine are called counterfeit incorporation or antimetabolite. The effects of these substances are through joining or interfering with cell metabolism.,(3) Affecting transportation of physical substances,The actions of ephedrine and aramine induce partly the release o

59、f norepinephrine from noradrenergic nerve endings. And reserpine, a hypotensive agent, affect the uptake of norepinephrine.,(4) Affecting enzyme activity,Many drugs produce their effects by selectively interacting with corresponding enzymes, for example, neostigmine exerts its cholinergic effect by inhibiting activity of AChE; digitalis enhance the cardiac contraction by inhibiting Na