Sedatives and Hypnotics—镇静剂和安眠药.pptVIP

Chapter 16 Sedatives and Hypnotics Graded dose-dependent depression of central nervous system function is a charicteristic of sedative-hypnotics. Classification of drugs Benzodiazepines are the most important sedative-hypnotics. Barbiturates Other agents Sub-classify of Benzodiazepines Short-acting(t1/26 hours) Triazolam（三唑仑） intermediate -acting(t1/2 6~24 hours) Oxazepam(奥沙西泮），nitrazepam（硝基安定） long-acting(t1/224 hours) Diazepam(地西泮,安定）,flurazepam（氟西泮，氟安定）,and chlordiazepoxide（氯氮卓） [Pharmacological effects and clinical uses] 1. Antianxiety Diazepam reduces anxiety at doses that do not produce sedation. This action is related to selective inhibition of neuronal circuits in the limbic边缘 system of the brain. 2. Sedative and hypnosis It shortens the latency潜伏期 of sleep onset,decreases intermittent awakening and prolongs the duration of sleep. 3. Anticonvulsant effects and antiepileptic effects Benzodiazepines are capable of inhibting the development and spread of epileptic form activity in the central nervous system. 4.Muscle relaxation The mechanism is that it exerts inhibitory effects on polysynaptic reflexes and internuncial transmission,and at high doses may depress transmission at the skeletal myoneural junction. Therapeutic applications Anxiety disorders Insomnia失眠 Anticonvulsion and antiepilepsy Muscle disorders GABAA receptor has a structure comprised of multiple subunits( alpha, beta,gamma, etc). Combinations of the three major subunits appear to be essential for normal physiologic and pharmacologic function of the macromolecule. GABA binds to receptor sites on the beta subunits and that this interaction initiates gating of the chloride channel current. The benzodiazepine receptor sites are probably located on alpha subunits. Benzodiazepine drugs can binds to these sites,but they don’t substitute for GABA. They appear to enhance GABA’effects without directly activating GABA receptors or opening the associated chloride channels. The enhancement in c