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,Sedative-Hypnotic Drugs,Several terms,1.Anxiety2.Sedation3.Hypnosis,Sleep phases,Non-rapid eye movement sleep(NREM) 1)Drowsy stage 2)Light sleep stage 3) moderately sleep stage 4)Deep sleep stage(slow wave sleep, SWS)Rapid eye movement sleep(REM)Importance of sleep phasesNREM and REM necessary for persons. NREM is responsible to recover physical capacity and promote growth as well as development of body. REM may be related to keeping and development of intelligence.REM must be compensated if one of them is deprived.,Benzodiazepines (BZs),【Chemical classification 】 1,4-benzodiazepines in the 7-membered heterocyclic ring structure, usually with a substituent of halogen or nitron group in the 7 position. First compound is chlordiazepoxide (1961).Long-acting BZs:diazepam, flurazepamIntermediate-acting BZs: chlordiazepoxide, alprazolam, lorazepam, oxazepam. Short-acting BZs:triazolam, midazolam.,【Actions and uses】,BZs have neither analgesia nor affect on the autonomic nervous system.Anti-anxiety: At low doses, release punishment-supressed behavior. Use for anxiety disorders, such as depression and schizophrenia with anxiety, phobia, etc,Sedative and hypnotic actions: At higher doses, Having replaced barbiturates to use for sleep disorders and controlling ethanol withdrawal states.Muscle relaxation action: BZs relax the spasticity of skeletal muscles caused by central disorders.Anticonvulsant action: epilepsy: diazepam iv for grand mal epilepsy; Clonazepam and nitrozepam for tonic seizures; other convulsions.Anesthetic action: At large doses, cause amnesia; some of BZs are used for inducing anesthesia or electric defibrillation of patients,【Mechanism of action】,Activate BZ-R, enhance GABA function, and increase the frequency of chloride ion channel opening.,【Properties of pharmacokinetics】,Except trizolam, high lipophilic, rapidly and completely absorbed by alimentary canal,metabolized in the liver.,【Adverse reacitons】,Low toxicity, high therapeutic index, less side reactions at usual doses except drowsiness and confusion. At high doses: ataxia, motor coordination trouble and cognitive impairment. FlumazenilPsychological and physical dependence develops when used over a prolonged period.,Barbiturates,【Chemical and history】 Barbituric acid (malonyl urea) derivatives, 100 years【Actions and uses】1. Sedative-hypnotic effects without distinct anxiolytic action and muscle relaxation. Shorten REM time. Uses:,Anticonvulsant and anti-epileptic effect: Phenobarbital is often used. Anesthetic effect: Thiopental is often used as intravenous anesthetics, but with respiratory supression and unsatisfactory analgesia.Inductive effect of cytochrome P450 enzyme system: Drug interactions;treat hyperbilirubinemia and kernicterus of neonates.,【Mechanism of action】,Enhance GABA function and prolong the duration of chloride ion channel opening at usual doses without marked effects on frequency. At high doses stimulate directly GABAA-R. 【Adverse reactions】Markedly respiratory inhibition, tolerance, dependence, allergic reaction, drug interactions. over dose?,Other drugs,Chloral hydrateZolpidem(唑吡坦)zopiclone (佐匹克隆)BuspironeSpecial mechanism of action: A partial agonist of 5-HT1A receptor and modulate release of 5-HT.Relieve anxiety without markedly sedative, hypnot
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