Pharmacodynamics 药效学,Ph. D, Prof.Department of Pharmacology, Dalian Medical University,学习要点： 基本要求：该部分的学习目的为掌握药理学的基本概念；熟悉与药理学基本概念相关的知识；了解药动学与药效学的相关公式与知识。 延伸要求：将总论中的概念与相关生理生化知识各论中药物的效应联系起来，该种联系贯穿药理学及其它基础与临床医学知识学习的始终。 学习方法：注意各种概念间的联系：如药物的治疗作用药物的不良反应以及机体状态间的关系；药物治疗指数与药物治疗窗间的关系等。,Q What does Pharmacodynamics mean? Pharmacodynamics describe biochemical and biophysical actions of drugs on the body, the mechanisms of their actions, the dose-effect relationship of drugs, and the basis for reasonable application of the drugs in clinics. 药效动力学是研究药物对机体作用的原理与规律的一门学问。,Pharmacodynamics: 对于药效学的形象理解(1) How to produce pharmacological effects?Drug (agonist, antagonist, partial agonist, inverse agonist) receptor (membrane, intracellular) , drug-enzyme, drug-DNA.药理作用是怎样产生的？ (2) Weak or strong (pharmacological effects)? dose-effect relationship药理作用的强弱/量效关系？ (3) What pharmacological effects produced?Therapeutic effects,side effects, toxic effects,drug dependence, tolerance.Or more simply How to produce, What are produced产生了什么药理作用？,受体的特征,Q What is a Receptor? A receptor can be defined as any biologic target macromolecule in cells that interacts specifically with extra-cellular signals, e.g., a neurotransmitter or a drug and converts it into intracellular effects. Receptor determines the maximal effects of a drug, i.e., the response extent is proportional to the number of drug-receptor interaction. Q What decide the effects, the structure of the receptor or the structure of the drug, why?,（受体可定义为细胞膜（细胞内）可与细胞外信号（如神经递质，药物等）特异性结合，并将这种结合转变为细胞内信号的大分子；药物的效应与受体的数量及与药物与受体的亲和力相关，受体决定药物的作用。Q How are receptors classified?,受体分类 Ligand gated ion channel receptors (response: m-seconds); (Nicotinic,GABAA, 5-HT3) G-protein-coupled receptors (response: seconds); (M, adrenergic alpha, beta, Dopamine, histamine) Transmembrane kinase receptors (tyrosine kinase-linked receptor) (response: minuts), (insulin) Intracellular receptors (response: hours); (corticoids, thyroid hormone),Ligand gated ion channel receptors (LGICR) 配体门控离子通道受体,LGICRs are located on plasma membrane mainly involved in fast synaptic neurotransmission. (ms),G protein coupled receptor (GPCR)G蛋白耦合受体,GPCRs are located on cell surface; the binding of extracellular ligand to the G-protein- coupled receptors induces the activation of G-protein (s),Transmembrane kinase receptors (membrane ) (e.g., Tyrosine kinase linked receptor), (m)酪氨酸激酶相联受体,Drugs acting on intracellular receptors, (h) 细胞内受体,Pharmacological Effects of a drug,I. What is “drug action作用” and “drug effects效应”Drug action: drug binding to target (receptor)Drug effects: biological effects induced II. What is “Stimulation”Enhancement of the body function III. What is “Inhibition”Inhibition of the body function IV. drugs do not provide body any new function 药物只增强或减弱机体原有的功能，不提供机体新的功能。,I. Drugs affecting receptors (1) Direct (2) Indirect, e.g., Ephedrine（麻黄素） acts directly on 1 and 2 receptors, and indirectly on 1 receptors by causing noradrenaline release. II. Drugs affecting specific targets Enzyme as a targetNeostigmine （新斯的明） and cholinesterase; Digitalis （洋地黄） and Na+/K+-ATPase Change of inner environment Antacids and gastric acid, osmotic diuretics （渗透性利尿药）and osmolarity of plasma,药物怎样作用于机体？,Immunosystem as a target (a) active immunity - vaccine; (b) passive immunity -immuoglobulin; (c) inhibition of immuno-system by glucocorticoids. DNA as a target Gene therapy; (b) Drugs influence gene replication. Endogenous substance synthesis as a target(prostaglandin(前列腺素), glucocorticoids（糖皮质激素） and aspirin 抑制前列腺素的合成),Q- 给出以下概念定义 Affinity （亲和力）(the measures of the propensity (ability) of a drug to bind with a given receptor. 1/Kd) Intrinsic activity （内在活性） (biological response induced by drug-receptor interaction. The efficacy of a drug is decided by its intrinsic activity, and numbers of receptor) Agonist （激动药） (can bind to receptor and exert biologic effects). Partial agonist （部分激动药）(can bind to receptors and produce low intrinsic activity). Antagonist （拮抗药）A pure antagonist can bind to receptors without intrinsic activity but can antagonize the biologic effects of corresponding agonist.问题：激动剂只产生兴奋作用吗？,Competitive antagonist （竞争行拮抗药）(reversibly binds to receptors; the maximal effects of an agonist are not depressed by the corresponding competitive antagonist) Non-competitive antagonist （非竞争行拮抗药）(irreversibly binds to receptors; the antagonism can not be overcome agonist) Inverse agonist （反向激动药）An inverse agonist can bind to receptor (R), and produce effects opposite to an endogenous agonist. Inverse agonists can be used to prevent agonist stimulation and to inhibit spontaneous receptor activity.,Q-What is the common characteristics of agonist, partial agonist, and inverse agonist, and indicate whether agonist only produce stimulation. Affinity, intrinsic activity, inverse binding. Q- What are the difference among agonist, partial agonist, and inverse agonist?,Drug Receptor Interactions,Agonist,Agonist-Receptor Interaction,