1、右美托咪啶的基础与临床右美托咪啶的基础与临床天津医科大学总医院天津医科大学总医院王国林王国林2013-62013-6内容一般介绍作用机制、药代学、用药方法文献借鉴我们的研究一、一般介绍、作用机制背景临床工作中镇静非常重要，但近年新药很少一些常用药物特点Opiate/benzodiazepine tolerance, efficacyPentobarbital agitation, durationPropofol limited access in some jurisdictionsKetamine emergencereactions, tolerance 2-adrenoreceptor
2、 agonism 背景（2 受体激动剂）Prototype agent is clonidineMore recent applications in clinical practiceSedationBehavior disorders Drugwithdrawal HypertensionProblem hypotensionSolution 2 nd generation - 2specificity右美托嘧啶Pharmacologically activeD- isomer of medetomidine1 st synthesizedinlate 1980s,Phase1 studi
3、es in early 1990s, clinical trials late1990s 8-fold greater 2:1 selectivity than clonidine1620:1 vs200:1清除半衰期较可乐定短：2-3vs8-12hrFDA approved for ICU sedation in adults中枢作用机制Locus ceruleus（蓝斑）: Brainstem center -modulateswakefulnessMajorsite forhypnotic actions (sedation, anxiolysis)Mediatedvia various
4、 efferent pathways:Thalamus andsubthalamus cortexNociceptive transmissionvia descendingspinal tractsVasomotorcenter andreticular formationSpinal cord: Binding to 2 receptors analgesia via releaseofsubstanceP中枢作用机制Dexmedetomidine Sedation central, G-proteins (inhibition) Analgesia spinal cord, Substa
5、nce P机制 CENTRAL 2Presynapticreceptors:Location:Sympathetic nerve endingsNoradrenergic CNS neuronsMechanism/action:TransmembranereceptorsCoupledtoGo-and Gi- type G-proteins adenylate cyclase andcAMPformationHyperpolarization (K+-channels) Ca+conductanceNE releaseCELLULARMECHANISMCa+Ca+Ca+ +Decrease in influx of Ca+Decrease in actionpotential due tohyperpolarization2A2ARGo Gk K+K+K+
