十五章镇静催眠药

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,十五章镇静催眠药,Teaching outline(教学大纲),掌握：,苯二氮卓类药理作用、作用机制、临床应用、体内过程、不良反应。,了解：镇静药、催眠药的概念，效应与剂量的关系；巴比妥类中枢抑制作用，主要适应症，不良反应及其注意事项。,Concepts,To inhibit selectively CNS，small dose produces quiet or somnolence（嗜睡）, which is called,sedation（镇静）,; larger dose produces,hypnosis（催眠）,.,Features,With the increase of dose, drugs can cause sedation,（镇静）, hypnosis,（催眠）, anti-convulsion (anesthesia),（抗惊厥,-,麻醉）,and paralysis (death),（麻痹死亡）,.,Benzodiazepines(BZs,，苯二氮卓类,),:No anesthetic action, safe.,Being administered for long time dependence,（依赖性）,withdrawal syndrome,（,戒断综合症,）,Categories,1. BZs（苯二氮卓类）,Diazepam（地西泮）, flurazepam（氟西泮）, chlordiazepoxide (氯氮卓) and triazolam (三唑仑),2. Barbiturates,Phenobarbital（苯巴比妥）, amobarbital (异戊巴比妥) and thiopental sodium（硫喷妥钠）,3. Other,Buspirone(丁螺环酮) and chloral hydrate（水合氯醛） etc,Section 1 BZs,【分子结构】,1，4-苯并二氮卓的衍生物。常用药物20多种：,diazepam, oxazepam, flurazepam and triazolam etc.,Their basic actions are similar.,Diazepamrepresentative；widespread application.,【Categories】,According to their,half life,:,1.Long-acting (t,1/2,20h): diazepam and flurazepam etc,（中效） (t,1/2,6-20h): nitrazepam and chlordiazepoxide etc,3.Short-acting(t,1/2, 95%,Hepatic metabolism,（肝代谢）,Renal excretion,（肾排泄）,Adverse Reaction（不良反应）,Somnolence,（嗜睡）, dizziness,（头昏）, debility,（乏力）,and decreasing memory. Large dose,ataxy,(,共济失调,) and interfering skill action and drive safety.,.local pain or,thrombophlebitis,（血栓性静脉炎）, even the inhibition of respiration and circulationrespiratory and cardiac arrest,（呼吸心跳停止）,.,Long usetolerance and dependence; withdrawal symptom,（戒断症状）,.,肌力正常情况下运动的协调障碍,Cautious use:,老年患者、肝、肾和呼吸功能不全者、驾驶员、高空作业和机器操作者以及青光眼和重症肌无力者慎用,Contraindications,禁忌症,:,antepartum,（产前）,and suckling women,（哺乳妇女）,通过胎盘和乳汁,Overdose,toxication,:,洗胃、对症、,特效拮抗药,flumazenil,Section 2 Barbiturates(巴比妥类),Traditional sedative-hypnotics, non-specific central supressants（抑制药）.,With the application of BZs (优点:,速效、高效、安全,), they are replaced in sedation and hypnosis（镇静和催眠）.,Categories,Long acting,Barbital（巴比妥） anti-convulsion,Phenobarbital（苯巴比妥） anti-convulsion and epilepsy,Intermediate acting,Pentobarbital（戊巴比妥） anti-convulsion,Amobarbital（异戊巴比妥） sedation and hypnosis,Short acting,Secobarbital（司可巴比妥） anti-convulsion, sedative and hypnosis,Ultra-short acting,Penthiobarbital（硫喷妥钠） intravenous anesthesia,【Action and application】,1. Sedation and hypnosis,Low dosequiet, alleviating anxiety（焦虑） and dysphoria（烦躁不安）.,Intermediate doseshortening sleep latency, reducing awareness number and prolonging sleep time, but,shortening REMS（缩短异相睡眠）;,long usetolerance and dependence, obvious withdrawal symptoms多梦、睡眠障碍,Disadvantages,of barbiturates taken as hypnotics:,Easily causing tolerance,（耐受性）, dependence,（依赖性）,and severe withdrawal symptoms,（戒断症状）,Many adverse reactions; overdosesevere toxicity,Inducing the activities of hepatic enzymes,（肝药酶）,to impact hepatic metabolism of other drugs,Therefore, they have,not taken as common sedative-hypnotics.,2. Anti-convulsion and epilepsy 抗惊厥、抗癫痫,Phenobarbital（苯巴比妥）: intensive anti-convulsion and epilepsy. Treating many convulsionstetanus（破伤风）, eclampsia（子痫） and children ardent fever（小儿高热） etc.,Phenobarbital and pentobarbital（戊巴比妥） may be used to treat grand mal（癫痫大发作） and status epilepticus（持续状态）.,（麻醉）,Long and intermediate actingpreanesthetic medication（麻醉前给药）, but their effects are inferior to diazepam.,Some short and ultra-short acing (e.g. pentothal) can cause short anesthetic action and be used in the inductive and intravenous anesthesia（诱导麻醉和静脉麻醉）,.,【Action mechanism】,There are the binding sites of barbiturates on GABA,A,receptor-,Cl,-,channel complex. The binding promotes the binding of GABA and its receptor. The different from BZ-increasing,Cl,-,influx by,prolonging the open time of,Cl,-,channel,（,通过延长,Cl,-,通道的开放时间来增加,Cl,-,内流）,.,Blocking glutamate-induced EPSP.,Barbital,Cl,-,BZ,re,ceptor,GABA,r,ecept,or,Cl,-,channel,Cl,-,GABA,+,+,-,-,+,+,-,GABA,A,receptor：ligand-gated Cl,-,channel,【Adverse reactions】,Hypnotic dose: after effect(,后遗效应,) and allergic response,（过敏反应）,Intermediate dose: inhibiting respiratory center mildly,Long use: habituation and dependence; suddenly withdrawalrebound phenomenon; additionobvious withdrawal symptoms,Overdose: acute poisoning,Coma,（昏迷）, respiratory inhibition, BP, and reflex abolition,（反射消失）, finally respiratory,failure,death,Early treatment: clear poison, maintaining respiration and circulation; performing the alkalization,（碱化）,of urine with bicarbonate,（碳酸氢钠）,to promote drug excretion,服药次晨可头晕、无力、困倦、恶心、呕吐等症状,hangover,Insomnia（失眠）, excitation, anxiety, tremor, tears and snot（流涕）, even convulsion,Barbiturates,BZs,Sedation Hypnosis Anti-convulsion Anesthesia ,Antianxiety,Safety low high,Comparison of BZs and Barbiturates,Other Sedative-hypnotics,Chloral hydrate,：,no after effect, intensive hypnosis, and quick and long action,Meprobamate,（甲丙氨酯）,and,glutethimide,（格鲁米特）,:,sedation and hypnosis; long use-addiction,【Review Subjects】,苯二氮卓类药物与巴比妥类药物比较有何优点？,苯二氮卓类药物临床主要用途有哪些？,苯二氮卓的镇静催眠机制与巴比妥相比较有何不同？,谢谢大家！,