《藥物效應(yīng)動(dòng)力學(xué)》ppt課件(文件)
【正文】 受體的調(diào)節(jié) 受體處于不斷代謝的 動(dòng)態(tài)平衡狀態(tài)，其數(shù)量、親和力和反應(yīng)性經(jīng)常受各種生理及藥理因素的影響而向上、下調(diào)節(jié) 調(diào)節(jié)方式 ? 受體脫敏 (receptor desensitization) 長期使用一種 激動(dòng)劑 后，組織或細(xì)胞對(duì)其敏感性和反應(yīng)性下降的現(xiàn)象 ? 受體增敏 (receptor hypersensitization) 與受體脫敏相反的一種現(xiàn)象，可因受體激動(dòng)劑水平降低或長期使用 拮抗劑而造成 Pharmacodynamics (how drugs work on the body) The action of a drug on the body, including receptor interactions, doseresponse phenomena, and mechanisms of therapeutic and toxic action. dose response relationship ? Graded – response measured on a continuous scale ? Quantal – response is an either/or event ? often derived from frequency distribution of doses required to produce a specified effect ? relates dose and frequency of response in a population of individuals graded dose response curves ? Efficacy is the maximal response a drug can produce ? Potency is the different dose of tow drugs that are needed to produce the same effect (such as EC50) quantal dose response curves (used in populations, response is yes/no) Therapeutic index =LD50orTD50/ED50) Quantification of drug safety The higher the TI the safer the drug Agonists and antagonists ?agonist has affinity plus full intrinsic activity ?antagonist has affinity but no intrinsic activity ?partial agonist has affinity and less intrinsic activity Competitive Antagonist ? petes with agonist for receptor ? Competitive antagonists cause a parallel shift of the apparent EC50 of an agonist to the right without changing the Emax ? Competitive antagonists make the agonist look less potent Nonpetitive Antagonist ? drug binds to receptor and stays bound irreversible – does not let go of receptor ? Nonpetitive antagonists limit an agonist’s efficacy 。 作用于同一受體的藥物分類 親和力 效應(yīng)力 完全激動(dòng)藥 強(qiáng) 強(qiáng)（ α= 1 ） 部分激動(dòng)藥 強(qiáng) 弱（ 0α1 ） 拮抗藥 強(qiáng) 無（ α= 0 ） 二類藥合用時(shí)互相競爭 完全激動(dòng)藥 full agonist ，既有親和力又有內(nèi)在活性（ α=1 ） 2. 不同藥物比較 : 效能看曲線高度 （效應(yīng)力） 強(qiáng)度看位置 ，靠左為強(qiáng)（親和力） ： KD， 負(fù)相關(guān) pD2， 正相關(guān)，常用 拮抗藥 antagonist ? 有較強(qiáng)的親和力，而無內(nèi)在活性(α=0) 的藥物 ? 可依據(jù)拮抗藥與受體之間的結(jié)合是否可逆及可否被競爭結(jié)合分為： 競爭性拮抗藥 petitive antagonists 非競爭性拮抗藥 nonpetitive antagonists petitive antagonists ? 與激動(dòng)劑互相競爭與受體可逆性
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