八版药理学2015-培训课件.pptVIP

pA2（拮抗参数）：指加入竞争性拮抗剂后激动剂浓度加倍才能达到激动剂原先的效应。此时该竞争性拮抗剂(I)的摩尔浓度的负对数值。 pA2 = –Log [I] ，pA2越大，拮抗越强 非竞争性拮抗剂 noncompetitive antagonist agonist Noncompetitive antagonist 可与R牢固结合，使能与A结合的R数量减少，相当于灭活部分受体。 Dose of agonist idealized dose-response curve of an agonist a b c response Geometric scale slope1 slope2 slope3 特点：亲和力下降； 激动剂的Emax下降：效能下降，量效曲线右移 。 Lg [D] 储备受体：活性较高的药物只需与一部分受体结合就能发挥最大效能，在产生最大效能时，常有95%受体未被占领，剩余未被结合的受体------。 受体二态模型 Ri Ra D·Ri D·Ra 反向激动药(苯二氮类） 五、受体的类型 G蛋白耦联受体 G protein-coupled receptor 配体门控离子通道受体 ligand-gated ion channel 酪氨酸激酶受体 Tyrosine kinase receptor ，胰岛素 细胞内受体 糖皮质激素、甲状腺素等 其他酶类受体 GC receptor G protein agonist Muscarinic cholinoceptors; adrenoceptors ; receptors for dopamine, histamine, glutamate, morphine. G蛋白耦联受体 配体门控离子通道受体 acetylcholine γ-aminobutyric acid GABA excitatory amino acids (eg, glycine, aspartate, and glutamate). Nicotinic acetylcholine receptor pentamer membrane depolarization, and triggering of an action potential ligand-operated enzyme hormone-binding domain cytoplasmic enzyme domain serine kinase, guanylyl cyclase hydrophobic segment 酪氨酸激酶受体 Tyrosine kinase insulin, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor- (TGF- ) and many other trophic hormones. Glucocorticoid thyroid hormone A lipid-soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor 细胞内受体 nuclear translocation response element Regulatory protein 受体脱敏 receptor desensitization激动药特异性及非特异性脱敏;-------耐受 受体增敏 receptor hypersensitization 停药反应 受体的向下调节 down regulation 受体的向上调节 up regulation 六、受体的调节 Total Body Water (40-42 liters) Vascular 3 L 4% BW Extravascular 9 L 13% BW Extracellular Intracellular 28 L 41% BW How can we measure the extent of distribution? 70kg adult Physical Volumes ethanol IV, 3L total Body Water Vascular Gentamicin(