Chapter 14 Antipsychotic [,æntisai'kɔtik] drugs 抗精神病药

1 Introduction of psychotic disorders Definition The patients with psychotic [sai'kɔtik]精神病的 disorders exhibit major disturbances in reasoning, often with delusions [di'lu:ʒən] 妄想 and hallucinations [hə,lu:si'neiʃən]幻觉. Hallucination: is a perception in the absence of external stimulus that has qualities of real perception. Delusion: are false beliefs that a person holds on to, without adequate evidence.

Psychotic disorders include: Schizophrenia /,skidzəu'freniə; ,skitsəu-/精神分裂症 Mania /'meiniə/狂躁 Depression 抑郁

Pathogenesis 1 Schizophrenia: associated with excessive dopaminergic /,dəupəmi'nə:dʒik/多巴胺的 activity; also associated with the abnormal 5-HT activity and α receptors; 2 Depression: decreased NA activity in certain encephalic /,ensə'fælik/脑的 region; 3 Mania: increased NA activity coupled with decreased 5-HT activity in certain encephalic region.

The dopamine hypothesis for schizophrenia Evidence: (1) Many antipsychotic drugs strongly block postsynaptic D2 receptors in CNS; (2) Drugs that increase dopaminergic activity either aggravate schizophrenia psychosis or produce psychosis de novo 重新 in some patients; (3) Increased dopamine levels and D2-receptor density in the brains of schizophrenic subjects ; (4) Imaging studies have shown increased striatal dopamine synthesis and release.

Symptoms of schizophrenia Positive symptoms: Include delusions, disordered thoughts and speech, and tactile, auditory, visual, olfactory and gustatory hallucinations; Negative symptoms: Include flat expressions or little emotion, poverty of speech, inability to experience pleasure, lack of desire to form relationships, and lack of motivation. Self-portrait of a person with schizophrenia, representing that individual's perception of the distorted experience of reality in the disorder

Chlorpromazine /klɔ:'prəuməzi:n/氯丙嗪 Effects: 1 CNS effects: (1) Sedative 镇静的 and neuroleptic /,njuərəu'leptik/安定的effects Mechanism: block α1 and H1 receptor;

(2) Antipsychotic effect: Mechanism: block D2 receptor in mesolimbic [miːsə'lɪbɪk] 中脑-边缘的and mesocortical 中脑皮质的 pathway;

(3) Antiemetic /,æntii'metik/ effect 止吐: Mechanism: Low dose: block D2 receptor in the chemoreceptor trigger zone (CTZ) 化学催吐感受区of the medulla [me‘dʌlə]髓质 oblongata [ɔblɔŋ‘geitə] 延髓 High dose: directly inhibit the vomiting center 呕吐中枢 in the medulla oblongata

(4) Disable the thermoregulation center 体温调节中枢 in hypothalamus /,haipəu'θæləməs/下丘脑: 5）Enhance the inhibitory effects of central nervous depressant 抑制剂

2 Autonomic nervous system Presents as side effects: Block α receptors—postural hypotension； Block M receptors—dry mouth, constipation /,kɔnsti'peiʃən/便秘, blurred vision 3 Endocrine system内分泌系统 Mechanism: block the D2 receptors in tuberoinfundibular pathway 结节漏斗通路（下丘脑垂体通路）

Clinical application 1 Positive symptoms of schizophrenia: p.o. in mild cases; i.m. in severe cases i.v. in acute cases 2 Symptoms of agitation in manic or other psychotic disorders

3 Omitting and intractable /in'træktəbl/难治的hiccup /'hikʌp; -əp/呃逆 4 Hypothermic anesthesia 低温麻醉 and artificial hibernation 人工冬眠 1) Hibernation mixture (chlorpromazine, promethazine 异丙嗪, pethidine 哌替啶） 2) Physical cooling is needed

Adverse reactions Mechanism: 1 Extrapyramidal /,ekstrəpi'ræmidəl/symptoms椎体外系反应： ① Parkinson‘s disease帕金森综合症； ② Akathisia [ˌækəˈθiːzɪə] 静坐不能； ③ Acute dystonia急性肌张力障碍； ④Tardive dyskinesia 迟发性运动障碍 Mechanism: block D2 receptor in nigrostriatal pathway 黑质纹状体通路 Reduce dosage or add central anticholinergic agent (benzhexol 苯海索） Increase dosage or add central antidopaminergic agents

2 Central inhibitory effects; 3 Side effects caused by blocking M receptors—dry mouth, constipation, blurred vision; 4 Side effects caused by blocking α receptors—postural hypotension; 5 Endocrine disorder; 6 Anaphylaxis [,ænəfɪ‘læksɪs] 过敏

Antimanic drug 抗燥狂症药 Representative drugs： Chlorpromazine氯丙嗪; Haloperidol氟哌啶醇; Lithium ['lɪθɪəm] carbonate碳酸锂

Antidepressant 抗抑郁药 Representative drugs： Tricyclic antidepressant: imipramine [ɪ‘mɪprəmiːn] 丙咪嗪

Supplementary reading Depression is a state of low mood and aversion [ə‘vɜːʃ(ə)n] 讨厌 to activity that can affect a person’s thoughts, behavior, feelings and sense of well-being. People with depressed mood can feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable [‘ɪrɪtəb(ə)l]易怒的 or restless焦躁不安的. They may lose interest in activities that were once pleasurable, experience loss of appetite or overeating, have problems concentrating, remembering details or making decisions, and may contemplate思考, attempt or commit suicide. Insomnia [in’sɔmniə] 失眠, excessive sleeping, fatigue, pains, digestive problems or reduced energy may also be present. The causes of depression include: (1) Life events. Adversity [əd‘vɜːsɪtɪ] 不幸 in childhood, such as bereavement [bɪ‘riːvm(ə)nt]丧亲, neglect, unequal parental [pə’rentl]父母亲的 treatment of siblings [’sibliŋz]兄弟姐妹, physical abuse or sexual abuse, significantly increases the likelihood of experiencing depression over the life course. Life events and changes that may precipitate [prɪ‘sɪpɪteɪt]使陷入 depressed mood include childbirth 分娩, menopause更年期, financial difficulties, job problems, a medical diagnosis (cancer, HIV, etc.), bullying [‘buliiŋ]欺负, loss of a loved one, natural disasters, social isolation, relationship troubles, jealousy, separation, and catastrophic [ˌkætəˈstrɒfɪk]毁灭性的injury. (2) Medical treatments. Certain medications are known to cause depressed mood in a significant number of patients. These include interferon therapy for hepatitis C. (3) Non-psychiatric illnesses. Depressed mood can be the result of a number of infectious diseases, nutritional deficiencies, neurological conditions and physiological problems, chronic pain, stroke, diabetes, cancer, et al. (4) Psychiatric syndromes. A number of psychiatric syndromes feature depressed mood as a main symptom. The mood disorders are a group of disorders considered to be primary disturbances of mood. These include major depressive disorder (MDD; commonly called major depression or clinical depression) , dysthymia [dɪs‘θaɪmiə]心境恶劣, bipolar disorder, seasonal affective disorder, borderline personality disorder , adjustment disorder, posttraumatic [,posttraʊ’mætɪk]外伤后的 stress disorder, and anxiety disorder et al. (5) Drug use. Depression is associated with abusive [ə'bjuːsɪv]滥用的drug use. Both legal and illegal drugs can be abused.

大纲要求 Objective and requirements Teaching contents Be familiar with the classification of antipsychotic drugs; Master the effects, mechanism, indications, and adverse reactions of chlorpromazine; Be familiar with the characters of anti-manic drugs and tricyclic anti-depressive drugs. Teaching contents (1) Definition and classification of antipsychotic drugs; (2) Pharmacokinetics and effects (on center, autonomic nervous system, and endocrine systems), mechanisms, indications (schizophrenia, mania, psychotic functional disorder, vomiting, hypothermic anesthesia and artificial hibernation), and adverse reactions (postural hypotension, extrapyramidal motor disorder, anaphylaxis, endocrine secretion disorder) of chlorpromazine. (3). Pharmacological effects of anti-manic drugs and tricyclic anti-depressive drugs.

Essential vocabulary Antipsychotic drugs Psychotic Delusions Hallucinations Schizophrenia Mania Depression Positive symptoms/Negative symptoms Antiemetic Hypothermic anesthesia/artificial hibernation