8Antipsychoticdisordersdrugs

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1、Chapter 8Chapter 8 objective objective 掌握掌握 氯丙嗪的药理作用、作用机制、氯丙嗪的药理作用、作用机制、临床应用与主要不良反应等。临床应用与主要不良反应等。熟悉熟悉 抗精神失常药的概念和分类抗精神失常药的概念和分类;其他抗精神病药的作用特点其他抗精神病药的作用特点;碳酸锂、米帕明的药理作用特点。碳酸锂、米帕明的药理作用特点。了解了解 精神失常的概念、分型精神失常的概念、分型.神经神经兮兮兮兮 神经稀稀神经稀稀 神经搭错神经搭错NeuroNeuropathypathypathypathynotenote（神经病）（神经病）（精神病）（精神病）Introdu

2、ctionIntroduction1 1、ConceptConceptPsychotic disordersPsychotic disorders various reason severe mental disorders.2 2、classificationclassification1、schizophrenia 精神分裂症精神分裂症2、mania-depressive disorder 躁狂抑郁症躁狂抑郁症 3、anxiety 焦虑症焦虑症4、others1）the most familiar,2）inpatient 6070%;3）thought and behavior -clov

3、en(分裂分裂)4）limbic system(边缘系统边缘系统)DA function.Schizophrenia Schizophrenia (I type,II type )(I type,II type )Mania-depressive disorder mania5-HT NA NA 1）Mania-depressive 2）depression5-HT 3 3、anxietyanxiety 焦虑症焦虑症4 4、othersothers青春期、青春期、周期性、周期性、更年期更年期1010月月1010日是世界精神卫生日日是世界精神卫生日健康体魄健康体魄+健康心理健康心理美好人生美好人

4、生Classification of drugs Antipsychotic drugs chlorpromazine Antimanic drugs lithium carbonate Antidepressants imipramine Anxiolytics diazepam氯丙嗪氯丙嗪碳酸锂碳酸锂米帕明米帕明地西泮地西泮1 Antipsychotic Drugs吩噻嗪类吩噻嗪类：chlorpromazine硫杂蒽类硫杂蒽类：chlorprothixene丁酰苯类丁酰苯类：haloperidol其他类其他类：sulpiride，clozapine chlorpromazine,CPZ 氯

5、丙嗪氯丙嗪 （wintermin 冬眠灵冬眠灵）pharmacokinetics 1、po.slow and irregular,F variable,im.absorb quickly ；2、pass BBB easily,distribution is wide(in brain higher);3、metabolize mainly in liver;4、elimination：kidney.chlorpromazine actions uses I.CNS 1、Antipsychotic effects(抗抗精神病作用精神病作用)characteristics 1)long use,c

6、ant produce tolerance;2)symptomatic treatment(对症治疗对症治疗););3)the onset of effect is slow(6W-6M).four important dopaminergic pathways:1)mesolimbic pathway 中脑边缘系统中脑边缘系统 2)mesocortical pathway 中脑皮质通路中脑皮质通路 3)nigrostriatal pathway 黑质纹状体通路黑质纹状体通路 4)tubero-infundibular pathway 结节漏斗通路结节漏斗通路CPZ()D2-R antipsy

7、chotic effects Clinical uses psychotic disorder：1）schizophrenia-first choice;2）other psychotic states:manic states;delirium(谵妄谵妄)states.no effect on depression.(I typeII type )2、Antiemetic effects(镇吐作用镇吐作用)Antiemetic effect is strong;But no effect on motion sickness.(晕动性呕吐晕动性呕吐)CPZlow dosageCTZ（催吐化学

8、感受区）（催吐化学感受区）(+)vomiting centerlarge dosagevomitchemoreceptor trigger zone nausea and vomit induced by uremia(尿毒症尿毒症),cancer,pregnant toxemia(妊娠毒血症妊娠毒血症),radiation(辐辐射射)and some drugs.stubborn hiccup 顽固性呃逆顽固性呃逆 Clinical uses 3、influence of temperature regulation1)temperaturenormal person and patient

9、s with fever;2)action correlative with environmental temperature(环境温度环境温度);3）produce fever,dispel fever(散热散热).Clinical uses 1）hypothermal anesthesia 低温麻醉低温麻醉 2）artificial hibernation 人工冬眠人工冬眠 CPZ+pethidine(哌替啶哌替啶)+promethazine(异丙嗪异丙嗪)hibernation mixture 配合物理降温配合物理降温使体温降至使体温降至34以下以下 机体进入机体进入“冬眠冬眠”状态。

10、状态。BMR，对，对各种病理刺激的反应性各种病理刺激的反应性，组织对缺氧的，组织对缺氧的耐受力耐受力 。mostly used for 严重感染、中毒性休克、严重感染、中毒性休克、高热惊厥、甲状腺危象等高热惊厥、甲状腺危象等辅助治疗辅助治疗。人工冬眠人工冬眠4、the effects of CNS depressants e.g.general anaesthetics,sedative-hypnotics,analgesics(镇痛药镇痛药),alcohol,II.autonomic nerve system 1、cardiovascular(-)-R(-)血管运动中枢血管运动中枢dilat

11、e the blood vessel directlyBPorthostatic hypotension 体位性低血压体位性低血压adrenaline reversalcannot use in the hypertension:tolerance2、(-)M R dry mouth,constipation(便秘便秘),blurred vision(视力模糊视力模糊)III.endocrine system CPZ(-)D2-R (tubero-infundibular pathway)prolactin inhibitory factor(催乳素释放抑制因子催乳素释放抑制因子);the s

12、ecretion of growth hormone;the secretion of GnRH(促性腺激素促性腺激素);the secretion of ACTH;（内分泌系统）（内分泌系统）adverse reactions 1、common adverse reaction 1)CNS,2)M-R,3)-R:BP ,orthostatic hypotension 4)local irritative(刺激性刺激性).2.extrapyramidal system reactions 锥体外系反应锥体外系反应 1)parkinsonism 帕金森综合征帕金森综合征 2)acute dyst

13、onia 急性肌张力障碍急性肌张力障碍 3)akathisia 静坐不能静坐不能 4)tardive dyskinesia 迟发性运动障碍迟发性运动障碍中枢抗中枢抗胆碱药胆碱药 CPZ()nigrostriatal pathway D2-R 3.allergic reactions 4.acute toxication po.large dose:12 g/time，clinical symptoms：narcoma，Bp shock，（麻醉性昏睡）（麻醉性昏睡）cardiac damage,arrhythmia contraindications p.160brief summaryCPZ

14、blocking中脑中脑-皮质通路皮质通路D2-R中脑中脑-边缘叶通路边缘叶通路D2-R抗精神病作用抗精神病作用黑质黑质-纹状体通路纹状体通路DA-R锥体外锥体外系反应系反应结节结节-漏斗通路漏斗通路DA-R影响内分泌影响内分泌 other antipsychotic drugs p.161-163 硫杂蒽类硫杂蒽类 tardan 泰尔登泰尔登 丁酰苯类丁酰苯类 haloperidol 氟哌啶醇氟哌啶醇 其他口服长效类其他口服长效类 penfluridol 五氟利多五氟利多 sulpiride 舒必利舒必利 clozapine 氯氮平氯氮平 risperidone 利培酮利培酮2 2 Anti

15、manic drugs lithium carbonate 碳酸锂碳酸锂 1.absorbed well；wide distribution；2.Na+enhance the excretion of Li+;incept Na+renal discharge Li+3.onset of effect is slow,individual variation（个体差异）（个体差异）;4.mechanism is complex;p.1645.mania and the manic state of schizophrenia clinical first choice;6.adverse re

16、action safe margin is narrow;common adverse reaction acute toxication:CNS()coma,death.withdrawal,treatment:iv.0.9%NaCl important!3 3 Antidepressant drugs Imipramine 米帕明米帕明（丙咪嗪）（丙咪嗪）characteristics 1.po.absorbed well；wide distribution；2.Antidepressant selectivity high;action slow;normal-CNS()depresse

17、d-uplift(情绪高涨情绪高涨).mechanism：inhibit the reuptake of NA、5-HT in the brain.4.Clinical uses:different types of depression,enuresis(遗尿症遗尿症),anxiety and phobia(恐怖症恐怖症).5.Adverse reactions:M-R(),CNS symptom drug interaction p.165Other drugs p.166-170 amitriptyline 阿米替林阿米替林 maprotiline 马普替林马普替林 mianserin 米安色林米安色林 1.Describe the actions and uses of CPZ.2.Please explain the effects and adverse reactions of CPZ by receptor theory.3.List the name used for mania or depressive.