药理学教学课件：药物效应动力学 pharmacodynamics.pptVIP

(1) Agonist Affinity with efficacy. Full agonist: α= 1 Partial agonist： Affinity with weak intrinsic activity: α 1 Drugs act on receptors 激动剂达最大效应一半时所需浓度的负对数值。 值越大，亲和力越大。 pD2 (亲和力参数) 图 药物与受体的亲和力及其内在活性对量效曲线的影响 A图 a,b,c 三药与受体的亲和力（pD2）相等，但内在活性（Emax）不等 B图 a,b,c 三药与受体的亲和力（pD2）不等，但内在活性（Emax）相等 Partial agonists produce a lower response compared with full agonists. Partial agonists produce concentration-effect curves that resemble those observed with full agonists in the presence of an antagonist that irreversibly blocks receptor sites. partial agonist: dualism (2) Antagonist Affinity without intrinsic activity. α= 0 Drugs act on receptors A. Competitive antagonist B. Non-competitive antagonist In the presence of a fixed concentration of agonist, increasing concentrations of a competitive antagonist progressively inhibit the agonist response. Competitive antagonist pA2 is the antagonism parameter. 激动剂与竞争性拮抗剂合用时，激动剂浓度加倍，其效应曲线方能达到单用激动剂最大效应，此时所需拮抗剂浓度负对数值称为pA2。 此值越大，拮抗力越大。 pA2 （拮抗参数)： 竞争性拮抗药（A图）、非竞争性拮抗药（B图） Competitive Antagonist 特点： 拮抗剂 (B) 与激动剂 (A) 竞争相同的受体； 竞争性拮抗剂其拮抗作用是可逆的； 随拮抗剂浓度增加,激动剂A+B的累积浓度效应曲线平行右移； 斜率和最大效应不变。 Some receptor antagonists bind to the receptor in an irreversible, i.e., not competitive. The antagonists affinity for the receptor may be so high that for practical purposes, the receptor is unavailable for binding of agonist. non-competitive antagonist (irreversible antagonists) 特点： ●拮抗剂B与激动剂A争夺非同一受体，它与受体结合后妨碍A与特异性受体结合。或竞争同一受体，但共价键结合。 ●不断提高A药浓度也不能达到单独使用A药时的最大效应。 ●非竞争性拮抗剂B也可使激动剂A+B的量效曲线右移，斜率降低，最大效应降低。 II. Drug Dose and Dose-Effect Relationship Concentration-effect Relationship (CER) Dose-effect curve S–shape Dose-effect Relationship (DER) minimal effective dose (minimal effective concentration): threshold dose or concentration. (2) maximal dose: maximum effect (Emax). Emax is the maximal response that can be produced by the drug, and EC50 is the concentration of drug that produces 50% o