药理学课件：药物效应动力学.pptVIP

Classification of drugs that acting on receptors Affinity Intrinsic activity Effects Agonist Yes Yes（100％） Yes Antagonist Yes None（ 0％） None， blocking agonist Partial Yes Weak（0～100％） Weak , agonist blocking agonist 4- Drug receptors Different patterns of receptor-acting drugs Box 4 Recently，there are new classes of drugs that act on the receptors： inverse agonist (反向激动剂) or negative antagonist （负拮抗剂） 具有拮抗剂特点，本身又产生与激动剂相反的效应。 co-agonist (协同激动剂) 与其它激动剂共同发挥效应。 4.5 Competitive and non-competitive antagonism Competitive antagonists: that compete with agonist for the same binding site on the receptor. Response curve for the agonist are shift to the right without depression of maximal response. 竞争性拮抗药与激动药并用时，能与激动药相互竞争与受体的结合，降低激动药与受体的亲和力，而不降低内在活性（量效曲线平行右移，最大效能不变） 4- Drug receptors Non-competitive antagonists: that cause (or not cause) a shift of the response curve to the right with depression of maximal response. 非竞争性拮抗药与激动药并用时，可使亲和力及内在活性均降低，一般可影响受体功能或与受体不可逆性结合。 Because of Irreversible or pseudo-irreversible binding Allosteric effects 4- Drug receptors A：Effect of a competitive antagonist on agonist concentration- response curve B： Effect of a non-competitive antagonist on agonist concentration-response curve agonist agonist Antagonist none lower higher none lower higher Antagonist Possible mechanisms of antagonisms 竞争 不可逆/假不可逆 变构 Possible mechanisms of antagonisms Competitive antagonists: Affinity is determined by agonist-antagonist interaction: [A] / [A]－1＝[I] / KI log {[A] / [A]－1}＝log [I]－logKI if [A ] / [A]＝2, then log [I]＝log KI＝pA2 4- Drug receptors Log ( [A’ ]/[A]-1) -log molar concentration of antagonist or -log [I] 0 If [A’ ] = 2[A] Then Log ( [A’]/[A]-1) = 0 pA2 Schild plot for calculat