抗精神失常药

第18章 抗精神失常药药学系药理教研室

Chapter 18 Antipsychotic disorders drugs Zhu xiaoguang

objecter • 掌握氯丙嗪的药理作用、作用机制、临床应用与主要不良反应等。 • 熟悉抗精神失常药的概念和分类; 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。 • 了解精神失常的概念、分型.

Why ?

神经兮兮 神经稀稀神经搭错

note Neuropathy ≠ （神经病） psychopathy （精神病）

Introduction 1、Concept Psychotic disorders various reason severe mental disorders .

2、classification 1、schizophrenia 精神分裂症 2、mania-depressive disorder 躁狂抑郁症 3、anxiety 焦虑症 4、 others

Schizophrenia ( I type, II type ) 1）the most familiar, 2）inpatient 60~70%; 3）thought and behavior ----cloven(分裂) 4） limbic system (边缘系统) DA function.

Mania-depressive disorder 1） Mania-depressive 2） mania 5-HT ↓ NA  depression NA ↓ 5-HT ↓

3、anxiety 焦虑症 4、 others 青春期、周期性、更年期

10月10日是世界精神卫生日 健康体魄美好人生 + 健康心理

Classification of drugs • Antipsychotic drugs chlorpromazine • Antimanic drugs lithium carbonate • Antidepressantsimipramine • Anxiolyticsdiazepam 氯丙嗪碳酸锂米帕明地西泮

§1Antipsychotic Drugs 吩噻嗪类：chlorpromazine 硫杂蒽类： chlorprothixene 丁酰苯类： haloperidol 其他类： sulpiride，clozapine…

chlorpromazine, CPZ氯丙嗪（wintermin 冬眠灵） [ pharmacokinetics ] 1、po. slow and irregular, F variable , im. absorbquickly ； 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 (抗精神病作用) characteristics 1) long use, can’t produce tolerance ; 2) symptomatic treatment (对症治疗); 3) the onset of effect is slow ( 6W-6M).

mechanism four important dopaminergic pathways: 1) mesolimbic pathway 中脑－边缘系统 2) mesocortical pathway 中脑－皮质通路 3) nigrostriatal pathway 黑质－纹状体通路 4) tubero-infundibular pathway 结节－漏斗通路 CPZ (－) D2-R →antipsychotic effects

Clinical uses psychotic disorder ： 1）schizophrenia-----first choice; 2）other psychotic states: manic states; delirium (谵妄)states. no effect on depression. ( I type＞II type )

2、Antiemetic effects(镇吐作用) chemoreceptor trigger zone • Antiemetic effect is strong; • But no effect on motion sickness. (晕动性呕吐) CTZ（催吐化学感受区） low dosage㈠ CPZ (+) large dosage㈠ vomiting center vomit

Clinical uses  nausea and vomitinduced by uremia(尿毒症), cancer, pregnant toxemia(妊娠毒血症), radiation(辐射)and some drugs. stubborn hiccup顽固性呃逆

3、influence of temperature regulation characteristics: 1) temperature normal person and patients with fever; 2) action correlative with environmental temperature (环境温度); 3）produce fever ,  dispelfever(散热).

Clinical uses hibernation mixture 1）hypothermal anesthesia 低温麻醉 2）artificial hibernation 人工冬眠 CPZ + pethidine(哌替啶) + promethazine (异丙嗪)

人工冬眠 配合物理降温使体温降至34℃以下 机体进入“冬眠”状态。BMR，对各种病理刺激的反应性，组织对缺氧的耐受力  。 mostly used for严重感染、中毒性休克、高热惊厥、甲状腺危象等辅助治疗。

4、 the effects of CNS depressants e.g. general anaesthetics, sedative-hypnotics, analgesics(镇痛药), alcohol, ……

II. autonomic nerve system 1、cardiovascular (-)  - R (-)血管运动中枢 dilate the blood vessel directly orthostatic hypotension 体位性低血压 BP↓ adrenaline reversal cannot use in the hypertension:tolerance 2、(-) M – R dry mouth, constipation(便秘), blurred vision (视力模糊)…

III. endocrine system （内分泌系统） • CPZ(-) D2-R(tubero-infundibular pathway) prolactin inhibitory factor (催乳素释放抑制因子) ;  the secretion of growth hormone;  the secretion of GnRH (促性腺激素); the secretion of ACTH ; ……

[adverse reactions] • 1、common adverse reaction 1) ㈠CNS, 2) M-R ㈠, 3) -R ㈠: BP , orthostatic hypotension… 4) local irritative(刺激性).

2. extrapyramidal system reactions 锥体外系反应 CPZ()nigrostriatal pathway D2-R 1) parkinsonism 帕金森综合征 2) acute dystonia 急性肌张力障碍 3) akathisia 静坐不能 4) tardive dyskinesia 迟发性运动障碍中枢抗胆碱药

3.allergic reactions 4.acute toxication po. large dose: 1~2 g / time， clinical symptoms： narcoma ，Bpshock，（麻醉性昏睡） cardiac damage, arrhythmia…… [contraindications] p.160

brief summary 中脑-皮质通路D2-R 中脑-边缘叶通路D2-R 抗精神病作用 CPZ blocking 黑质-纹状体通路DA-R 锥体外系反应结节-漏斗通路DA-R 影响内分泌

other antipsychotic drugs p.161-163 硫杂蒽类tardan 泰尔登丁酰苯类haloperidol 氟哌啶醇其他口服长效类 penfluridol五氟利多 sulpiride舒必利 clozapine氯氮平 risperidone利培酮

§2 Antimanic drugs • lithium carbonate碳酸锂 [characteristics] 1.absorbed well；wide distribution ； 2. Na+ enhance the excretion of Li+ ; inceptNa+ renal dischargeLi+  3. onset of effect is slow, individual variation（个体差异）;

4. mechanism is complex; p.164 5. mania and the manic state of schizophrenia clinical first choice; 6. adverse reaction safe margin is narrow; common adverse reaction  acute toxication: CNS(–) coma…, death . withdrawal, treatment:iv. 0.9% NaCl TDMimportant !

§3 Antidepressant drugs • Imipramine 米帕明（丙咪嗪）［characteristics］ 1. po.absorbed well；wide distribution ； 2.Antidepressant selectivityhigh; action slow; normal----CNS(–) depressed----uplift (情绪高涨)

３. mechanism： inhibit the reuptake of NA、5-HT in the brain. 4. Clinical uses: different types of depression, enuresis(遗尿症),anxiety and phobia(恐怖症). 5. Adverse reactions: M-R (–), CNS symptom… [ drug interaction ]p.165

Other drugsp.166-170 amitriptyline 阿米替林 maprotiline 马普替林 mianserin 米安色林 ……

questions 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.

good bye

抗精神失常药

抗精神失常药

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