Chapter 25 Antipsychotic Drugs

1. Chapter 25 Antipsychotic Drugs

2. 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

3. 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

4. Nature of psychosis /schizophrenia • The dopamine hypothesis excessive dopaminergic activity plays a role in the disorder. • The enhancement of function of 5-HT2 Dopaminergic Systems • The nigrostriatal pathway (coordination of voluntary movement )

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

6. Antipsychotic drugs Classification： • 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

7. Antipsychotic/Neuroleptics Phenothiazin 吩噻嗪类 chlorpromazine 氯丙嗪 (wintermine 冬眠灵) Pharmacologic effects blocking DA2、α 、M 、5HT2、H1 receptors

8. BlockingMesolimbicsystem and mesocorticalD2-R • More effective for treating positive symptom • Substantia nigra- corpus striatum • ---- extrapyramidal effects 锥体外系反应 • Node-funnel --- endocrine system action • neuroleptic effect (神经安定作用)

9. powerful antiemetic action 镇吐作用 blocking CTZ 催吐化学感受区 D2-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

10. autonomic NS effects • 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

11. 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）

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

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

14. 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

15. Clozapine (氯氮平) Benzodiazepines Pharmacological effect • Blocking 5-HT, D2 receptor • Strong efficacy, rapidly • No extrapyramidal reaction • Blocking H1, M andαreceptor • hypogranulocytosis

16. 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）

17. 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

18. 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

19. Antidepressants • Tricyclic antidepressants • 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 • Serotonin reuptake inhibitor • 5-羟色胺再摄取抑制剂 • Others

20. Tricyclic antidepressants • imipramine 丙咪嗪（米帕明） • Action • CNS: inhibit NA and 5-HT reuptake 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

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

22. 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 Prostatic hypertrophy and glaucoma青光眼

23. 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 • overdose can cause low blood pressure, arrhythmia, dry mouth, constipation

24. 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

25. 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

26. MAOI & Dietary Tyramine