总论-效应动力学.pptVIP

* 激动剂剂量增加1倍而产生相同的效应时,加入竞争性拮抗药浓度的负对数 反映拮抗药的拮抗强度，pA2越大，所需拮抗药浓度越小，拮抗作用越强 拮抗参数(antagonist parameter, pA2, ) 激动药 药物的对数浓度 最大效应（%） ＋竞争性拮抗药 ＋非竞争性拮抗药 竞争性拮抗药和非竞争性拮抗药的比较 * 储备受体 Spare receptor 活性高的药物只需与一部分受体结合就能达到最大效应 未结合的受体，常有95%-99%，称为储备受体 * 五、受体类型 门控离子通道型受体 2. G 蛋白耦联受体 4. 细胞内受体 3. 具酪氨酸激酶活性受体 * 六、细胞内信号转导  (Intracellular Signal transduction) cAMP cGMP Calcium Phosphoinositides（磷酸肌醇) * bilayer lipid Receptor β肾上腺素受体的细胞内信号转导 * β1肾上腺受体 Adrenergic receptor Basal Agonist Carvedilol * 受体调节 受体脱敏 (receptor desensitization) 受体增敏 (receptor hypersensitization) * 受体的下调 * β肾上腺素受体的脱敏 受体脱敏的原因 ①受体磷酸化 ②受体下调 ① ② * * * * * This outline presents only that part of drug teaching which can be judged by the pharmacologist, and is, therefore, not a compendium of therapy. The pharmacologist does not deal with therapy, the practicing clinician does. The complexity of treatment in modern medicine on one side and the scope of pharmacology on the other no longer allow anybody to represent both disciplines if he is not to become a dilettante in one of them. Without pharmacologic knowledge the physician will stumble around in the dark whenever he employs drugs. Transmission of such knowledge is one of the tasks of the pharmacologist. Yet, he cannot tell physicians how to treat illnesses. Rather, he must content himself with describing the actions of important pharmacologic agents on man, with characterizing the consequences for the entire organism of the use of such agents under various conditions, and with deriving general rules for the use of drugs from pharmacologic facts. Whether the actions exerted by a drug on the organism can be therapeutically useful depends not only on the nature of the illness but most importantly on the features of each particular case. * 埃尔利希（Paul Ehrlich，1854-1915） 1910年保罗·埃尔利希与他的日本助手秦佐八郎从上万只兔子上实验，一共做了 606次实验，发明砷凡纳明（第六○六号化合物，即二氨基二氧偶砷苯）治疗梅毒，可穿入人体的特定部位，杀死梅毒，成为梅毒特效药，被称为“神弹”。 * GRK：G蛋白偶联受体蛋白激酶，使受体磷酸化而失活（G protein-coupled receptors (GPCRs) ；