2. Chapter 25 Antipsychotic Drugs

3. Antipsychotic drugs Schizophrenia 精神分裂症 literal translation “split mind” separate emotional side from intellectual side emotional & cognitive processes don't function together a group of severe disorders characterized by: disorganized and delusional thinking （妄想） disturbed perceptions inappropriate emotions & action

4. Psychotropic Drugs 抗精神失常药 Classification ： antipsychotic drugs 抗精神病药物 neurotropic drugs 神经安定剂 antimanic drugs 抗躁狂药物 antidepressants 抗抑郁药物 anxiolytics 抗焦虑药物

5. Nature of psychosis /schizophrenia The dopamine hypothesis excessive dopaminergic activity plays a role in the disorder. The enhancement of function of 5-HT 2 Dopaminergic Systems The nigrostriatal pathway (coordination of voluntary movement )

6. Mesolimbic- mesocortical ( behavior ) Tuberoinfundibular- pituitary system (endocrine) The medulla oblongata (vomit) Medullary - periventricular pathway ( eating behavior)

7. Antipsychotic drugs Classification ： 氯丙嗪 chloropromazine  Phenothiazin 吩噻嗪类 ( 氯丙嗪 chloropromazine )  Thioxanthenes 硫杂蒽类 ( chlorprothixene 氯普噻吨 （泰尔登） )  Butyrophenones 丁酰苯类 ( haloperidol 氟哌啶醇 )  Others

8. Antipsychotic/Neuroleptics Phenothiazin 吩噻嗪类 chlorpromazine 氯丙嗪 (wintermine 冬眠灵 ) Pharmacologic effects blocking DA 2 、 α 、 M 、 5HT 2 、 H 1 receptors

9. neuroleptic effect ( 神经安定作用 )  Blocking Mesolimbic system and mesocortical D 2 -R  More effective for treating positive symptom   Substantia nigra- corpus striatum ---- extrapyramidal effects 锥体外系反应  Node-funnel --- endocrine system action

10. powerful antiemetic action 镇吐作用 blocking CTZ 催吐化学感受区 D 2 -R (small dosage) directly inhibiting vomiting center 呕吐中枢 (large dosage) altering temperature-regulating mechanisms decrease temperature no matter normal or high temperature body temperature varies with the environment

11. autonomic NS effects α blocking α-R vasodilatation “epinephrine reversal” blocking M-R atropine-like action endocrine system action increasing prolactin 催乳素 secretion inhibiting gonadotropic hormone 促性腺激素 ， growth hormone 生长激素 secretion

12. Therapeutic uses schizophrenia 精神分裂症 more effective in treating positive symptoms severe nausea and vomiting useful in the treatment of drug-induced nausea hypothermic anesthesia 低温麻醉 and artificial hibernation 人工冬眠 chlorpromazine – promethazine – pethidine （氯丙嗪 – 异丙嗪 – 哌替啶）

13. Adverse effects common adverse effects common adverse effects CNS depression (drowsiness, indifference) CNS depression (drowsiness, indifference) M-R block (blurred vision, dry mouth) M-R block (blurred vision, dry mouth) α -R block (orthostatic hypotension 体位性低血压 ) α -R block (orthostatic hypotension 体位性低血压 ) extrapyramidal reaction 锥体外系反应 extrapyramidal reaction 锥体外系反应 Parkinson's syndrom Parkinson's syndrom akathisia 静坐不能 akathisia 静坐不能 acute dystonia 急性肌张力障碍 acute dystonia 急性肌张力障碍 treated by antimuscarinic drugs (artane, 安坦 ) treated by antimuscarinic drugs (artane, 安坦 )

14. tardive dyskinesia 迟发性运动障碍 treated by antidopamine drugs (clozapine, 氯氮平 ) treated by antidopamine drugs (clozapine, 氯氮平 ) Neural antagonist severe symdrome Neural antagonist severe symdrome drug-induced mind abnormality drug-induced mind abnormality convulsion 惊厥 and epilepsy 癫痫 convulsion 惊厥 and epilepsy 癫痫 allergic reaction allergic reaction acute hypogranulocytosis ( 粒细胞减少症 ) acute hypogranulocytosis ( 粒细胞减少症 ) cardiovascular and endocrine system reaction cardiovascular and endocrine system reaction acute poisoning 急性中毒 acute poisoning 急性中毒

15.  Thioxanthenes 硫杂蒽类 chlorprothixene 氯普噻吨（泰尔登）  Butyrophenones 丁酰苯类 haloperidol 氟哌啶醇  Others penfluridol 五氟利多 clozapine 氯氮平

16. Clozapine ( 氯氮平 ) Benzodiazepines Benzodiazepines Pharmacological effect  Blocking 5-HT, D 2 receptor  Strong efficacy, rapidly  No extrapyramidal reaction  Blocking H 1, M andαreceptor  hypogranulocytosis

17. Antimanic drugs Bipolar affective disorder （双极性情感障碍） Cyclic manic attacks （往复性躁狂发作） In high spirit （情绪高涨） Overactivity （过度活动） Paranoid thoughts （妄想）

18. Lithium Carbonate （碳酸锂） Clinical use Based on the Li + treatment for bipolar disorder manic phase particularly prophylactic Li may block both manic and depressive

19. Adverse effects GI tract nausea, vomiting, diarrhea mental confusion, tremor, aphasia 失语症, choreoathetosis 舞蹈症, coma Management of Li overdosage: peritoneal dialysis 腹膜透析 or hemodialysis iv NaCl

20. Antidepressants Antidepressants  Tricyclic antidepressants 三环类抗抑郁药（抑制 NA 再摄取） 三环类抗抑郁药（抑制 NA 、 5- 羟色胺再摄取）  NA reuptake inhibitor NA 再摄取抑制剂 NA 再摄取抑制剂  Serotonin reuptake inhibitor 再摄取抑制剂 5- 羟色胺再摄取抑制剂  Others

21. Tricyclic antidepressants imipramine 丙咪嗪（米帕明） imipramine 丙咪嗪（米帕明） Action Action  CNS : inhibit NA and 5-HT reuptake normal individals: normal individals: depressant effect depression: mood elevation, spirit excitation The onset of the mood-elevation is slow, 2~3 weeks  autonomic nerve system Blocking M-R effects: blurred vision, dry mouth, constipation, urinary retention Blocking M-R effects: blurred vision, dry mouth, constipation, urinary retention

22.  cardiovascular system low blood pressure arrhythmia Clinical uses  depression  depression various kinds especially ， especially endogenous ， involutional depression  enuresis in children older than six  enuresis 遗尿症 in children older than six  phobic anxiety  phobic anxiety 恐惧性焦虑 ( 症 )

23. Adverse effects Adverse effects dry mouth, mydrasis, blurred vision, orthostatic hypotension 体位性低血压 agranulocytosis 粒细胞缺乏症 urinary retention ocular pressure increase Contraindication Contraindication and glaucoma 青光眼 Prostatic hypertrophy and glaucoma 青光眼

24. NA reuptake inhibitor desipramine 地昔帕明, 去甲丙咪嗪  inhibit NA reuptake selectively  treat mild, moderate depression sedation and hypotension   side effect is slight compared with imipramine dry mouth, constipation overdose can cause low blood pressure, arrhythmia, dry mouth, constipation

25. 5-HT reuptake inhibitor fluoxetine 氟西汀, 百忧解  inhibit 5-HT reuptake selectively  treat depression: improve attention emotion  adverse effects: GI tract reaction, tremor  risk of life-threatening “serotonin-syndrome” co-administered with MAO inhibitors

26. MAO inhibitor Phenelzine 苯乙肼  inhibit MAO nonselectively  treat mild, moderate depression, also phobic states 恐怖状态  side effects: orthostatic hypotension, nausea, headache, insomnia, tremor, hallucination  not co-administered with tricyclic antidepressants and food rich of tyramine 酪胺

27. MAOI & Dietary Tyramine