第二章药效学课件

Chapter 2 PharmacodynamicsDepartment of Pharmacology,Department of Pharmacology,Medical school of Nankai UniversityMedical school of Nankai UniversityJingling ZhangJingling ZhangTel:(office)Tel:(office)E-mail:E-mail:Pharmacodynamics教学目的教学目的 掌握药效学的基本概念和药掌握药效学的基本概念和药理作用的基本规律，为各论理作用的基本规律，为各论药物的学习提供理论基础。药物的学习提供理论基础。2Pharmacodynamics教学内容教学内容药物的基本作用和效应；药物的基本作用和效应；器官功能的升高或降低，器官功能的升高或降低，即兴奋和抑制。药物作用的选择性和可逆性。即兴奋和抑制。药物作用的选择性和可逆性。药物作用的临床效果药物作用的临床效果，即治疗作用和不良反应。，即治疗作用和不良反应。药物作用原理；药物作用原理；药物作用原理的多样性；药物作用原理的多样性；受体和配体的概念受体和配体的概念，受体在药物作用中的意义；，受体在药物作用中的意义；3Pharmacodynamics亲和力（亲和力（pD2），内在活性（），内在活性（），），受体激活至受体激活至效应器反应的中间过程；反馈的生理意义。效应器反应的中间过程；反馈的生理意义。激动药，部分激动药，对抗药的共性与个性，拮激动药，部分激动药，对抗药的共性与个性，拮抗参数抗参数pA2，药物的构效关系。药物的构效关系。药物作用的量效关系药物作用的量效关系：质反应与量反应。量效关：质反应与量反应。量效关系曲线，作用强度与最大效应，半数效应量，系曲线，作用强度与最大效应，半数效应量，阈剂量，治疗量，极量，中毒量及致死量。阈剂量，治疗量，极量，中毒量及致死量。4PharmacodynamicsConcept of pharmacodynamics It is the study of drug effects and their mechanisms of action.5PharmacodynamicsI.Drug action II.The therapeutic effect of drug and adverse drug reaction (ADR)III.Dose-effect relationshipIV.Structure-activity relationshipV.Targets for drug action VI.Theory about interaction of drug and receptor6Drug action1.Drug action2.Types of drug action3.Selectivity of drug action4.Pharmacological effectexcitationinhibition7The therapeutic effect of drug1.Etiological treatment2.Symptomatic treatment3.Supplementary therapy or replacement therapycomplementary the loss of nutrition&metabolism of the body8adverse drug reaction concept type The effect that is not the accord with the purpose of drug use,which is lead to the harm&pain of the patient.The therapeutic effect&side effect are the intrinsic properties of the drug.lSide effectlToxic effectlafter effectl Allergic reactionlSecondary reactionlWithdrawal reactionlIdiosyncrasy reactionlDependence1.Acute toxicity2.Chronic toxicity:(carcinogenesis,teratogenesis,mutagenesis)1.Physical dependence(withdrawal syndrome)2.Psychic dependence9Dose-effect relationship1.Concept2.Dose-effect curve 3.TypeGraded response;Quantal response(All-or-none response)4.Significance10Special points：1.Slope2.Minimum effective concentration，threshold concentration 3.Maximum effect or Efficacy4.Median effective dose,ED50 TD50 LD505.Potency6.Effective dose；Toxic dose；Lethal dose；Maximum dosethe effect cannot increase with the addition of the drug.the equivalent dose among the different drugs which produce the same therapeutic effect.1314Safety1.Therapeutic index：TI=LD50/ED50；2.Margin of safety：ED95TD5；lStructure-activity relationship15Targets for drug action1.Receptors 2.Enzymes 3.Ion channels4.Carrier molecules(transporters)5.Gene18Mechanism of drug actionlNonspecific mechanism of drug actionlSpecific Mechanisms of drug action19Interaction between drug and receptor1.Concept of the receptor The term receptor is used in different ways.In pharmacology,it describes protein molecules whose function is to recognise and respond to endogenous chemical signals.22Interaction between drug and receptor The concept of receptors is central to pharmacology,and the term is most often used to describe the target molecules through which soluble physiological mediators-hormones,neurotransmitters,inflammatory mediators,etc.-produce their effects.23Interaction between drug and receptor2.Property of receptorSensitivity SpecificitySaturabilityReversibilityMultiple-variationAffinityCompetition3.Type of receptorG proteins-coupled receptorLigand gated ion channel receptorTyrosine kinase receptorIntracellular receptors24Interaction between drug and receptor4.LigandConceptType5.Receptor theory:Occupation theory;Rate theory;Two model theory;Exterior ligand Drug,Toxin,Ag;Inner ligand Transmitters,Hormones,Autacoids;The term“ligand”denotes the chemical agents that recognize and bind to receptors.29Occupation theoryA+R AR EK1K2When receptors are occupied,the pharmacological effects will occur.The effects of drug are directly proportional to the numbers of receptors occupied.31Development of occupation theory令 KD=K2/K1；A+R AR EK1K2Clark（1926）32Development of occupation theory整理后得：AR(KD+A)=A RT因为:RT=R+AR，R=RT-AR；代入R得：33Development of occupation theory1.When AR/RT=0,E=0.2.When AKD,AR/RT=1,AR=RT,E=Emax.3.When AR/RT=1/2,E=50%Emax,KD=A.34Interaction between drug and receptorpD2 (affinity index)35Development of occupation theoryAriens(1954)：intrinsic activity(内在活性内在活性)pD2affinity index(亲和力指数亲和力指数)Stephenson(1956)：spare receptor(储备受体储备受体)silent receptor(沉默受体沉默受体)(01)When pD2 of drug A is the same as that of drug B,effect of drug is decided by .When of drug A is the same as that of drug B,effect of drug is decided by pD2.36Classification of the drug 7.Drug can be divided into different group according to the receptor theory:Agonista.Absolute agonist b.Partial agonist c.Inverse agonistsPartial agonist can evoke weak agonist effects but may also displace full agonists from the binding sites and reduce their biologic effect.38Classification of the drug Antagonist a.Competitive antagonistpA2=-log(I)2b.Noncompetitive antagonistpA2=-log(I)2 Antagonist binds to a receptor without producing any of the effects associated with agonist binding.39KD=A4041 测试题1.下列关于竞争性拮抗药拮抗参数（pA2）的描述中不对的是：A、pA2值是表示拮抗相应激动药的强度；B、pA2大表示拮抗药与相应受体的亲和力大；C、pA2值越大对相应激动药拮抗力越强；D、不同亚型受体 pA2值不尽相同；E、pA2是拮抗药摩尔浓度的对数值。422、pD2值可以反映药物与受体亲和力，pD2值大说明：A、药物与受体亲和力大，用药剂量小；B、药物与受体亲和力大，用药剂量大；C、药物与受体亲和力小，用药剂量小；D、药物与受体亲和力小，用药剂量大；E、以上均不对。4350100E%lg CANA+C药物A、N及A+C的对数-效应曲线3、已知药物均作用于同一种受体，指出下列正确的叙述：A、A药和N药有同等的效能；B、N药是一种完全激动药；C、N药是A药的一种竞争性拮抗药；D、C药是A药的一种竞争性拮抗药；E、N药作用效价高于A药。44提问与解答环节Questions And Answers谢谢聆听 学习就是为了达到一定目的而努力去干,是为一个目标去战胜各种困难的过程,这个过程会充满压力、痛苦和挫折Learning Is To Achieve A Certain Goal And Work Hard,Is A Process To Overcome Various Difficulties For A Goal