Chapter 25Chapter 25

Antipsychotic DrugsAntipsychotic Drugs

Antipsychotic drugsSchizophrenia 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

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

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 vo

luntary movement )

Mesolimbic- mesocortical ( behavior )

Tuberoinfundibular- pituitary system (en

docrine)

The medulla oblongata (vomit)

Medullary - periventricular pathway ( eating

behavior)

Antipsychotic drugs

Classification ： Phenothiazin 吩噻嗪类 ( 氯丙嗪氯丙嗪

chloropromazinechloropromazine ) Thioxanthenes 硫杂蒽类 (chlorprothixene 氯普噻

吨（泰尔登） )

Butyrophenones 丁酰苯类 (haloperidol 氟哌啶醇 )

Others

Antipsychotic/NeurolepticsAntipsychotic/Neuroleptics

Phenothiazin 吩噻嗪类 chlorpromazine 氯丙嗪 (wintermine 冬眠灵 )

Pharmacologic effectsPharmacologic effects

blocking blocking DADA22 、、 α α 、、 M M 、、 5HT5HT22 、、 HH1 1 receptorreceptor

ss

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

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 te

mperature

body temperature varies with the environment

autonomic NS effects blocking αα-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

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）

Adverse effectsAdverse effects common adverse effectscommon adverse effects

CNS depression (drowsiness, indifference)CNS depression (drowsiness, indifference)

M-R block (blurred vision, dry mouth)M-R block (blurred vision, dry mouth)

αα-R block (orthostatic hypotension -R block (orthostatic hypotension 体位性低血压体位性低血压 ) )

extrapyramidal reaction extrapyramidal reaction 锥体外系反应锥体外系反应 ParkinsonParkinson's syndrom 's syndrom

akathisia akathisia 静坐不能静坐不能 acute dystonia acute dystonia 急性肌张力障碍 急性肌张力障碍 treated by antimuscarinic drugs (artane,treated by antimuscarinic drugs (artane, 安坦 安坦 ))

tardive dyskinesia tardive dyskinesia 迟发性运动障碍迟发性运动障碍 treated by antidopamine drugs (clozapine,treated by antidopamine drugs (clozapine, 氯氮平氯氮平 ))

Neural antagonist severe symdromeNeural antagonist severe symdrome

drug-induced mind abnormality drug-induced mind abnormality

convulsionconvulsion 惊厥 惊厥 and epilepsyand epilepsy 癫痫癫痫 allergic reactionallergic reaction

acute hypogranulocytosis (acute hypogranulocytosis ( 粒细胞减少症粒细胞减少症 ))

cardiovascular and endocrine system reactioncardiovascular and endocrine system reaction

acute poisoning acute poisoning 急性中毒急性中毒

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

ClozapineClozapine ( ( 氯氮平氯氮平 )) Benzodiazepines Benzodiazepines

Pharmacological effectPharmacological effect

Blocking 5-HT, DBlocking 5-HT, D22 receptor receptor

Strong efficacy, rapidlyStrong efficacy, rapidly

No extrapyramidal reactionNo extrapyramidal reaction

Blocking HBlocking H11, M and, M andααreceptorreceptor

hypogranulocytosis

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）

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

Adverse effects

GI tract nausea, vomiting, diarrhea

mental confusion, tremor, aphasia 失语症 , c

horeoathetosis 舞蹈症 , coma

Management of Li overdosage:

peritoneal dialysis 腹膜透析 or hemodialysis

iv NaCl

AntidepressantsAntidepressants

Tricyclic antidepressantsTricyclic antidepressants

三环类抗抑郁药（抑制三环类抗抑郁药（抑制 NANA 、 5- 羟色胺再摄取）再摄取）

NA reuptake inhibitorNA reuptake inhibitor

NANA 再摄取抑制剂再摄取抑制剂

Serotonin reuptake inhibitorSerotonin reuptake inhibitor

5- 羟色胺再摄取抑制剂再摄取抑制剂

OthersOthers

Tricyclic antidepressantsTricyclic antidepressants imipramine imipramine 丙咪嗪（米帕明）丙咪嗪（米帕明）

ActionAction CNSCNS: : inhibit NA and 5-HT reuptakeinhibit 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 systemautonomic nerve system

Blocking M-R effects: blurred vision, dry mouth, cBlocking M-R effects: blurred vision, dry mouth, c

onstipation, urinary retentiononstipation, urinary retention

cardiovascular systemcardiovascular system

low blood pressure

arrhythmia

Clinical usesClinical uses

depressiondepression various kinds

especially especially endogenous ，， involutional depression

enuresis enuresis 遗尿症 in children older than sixin children older than six

phobic anxietyphobic anxiety 恐惧性焦虑 ( 症 )

Adverse effectsAdverse effects

dry mouth, mydrasis, blurred vision, dry mouth, mydrasis, blurred vision,

orthostatic hypotension orthostatic hypotension 体位性低血压体位性低血压agranulocytosis agranulocytosis 粒细胞缺乏症粒细胞缺乏症urinary retentionurinary retention

ocular pressure increaseocular pressure increase

ContraindicationContraindication

Prostatic hypertrophy and glaucoma and glaucoma 青光眼青光眼

NA reuptake inhibitorNA reuptake inhibitordesipramine desipramine 地昔帕明地昔帕明 ,, 去甲丙咪嗪去甲丙咪嗪

inhibit NA reuptake selectivelyinhibit NA reuptake selectively

treat mild, moderate depression

sedation and hypotension

side effect is slight compared with imipramine

overdose can cause low blood pressure, arrhythm

ia, dry mouth, constipationdry mouth, constipation

5-HT reuptake inhibitorfluoxetine 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

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 antidepress

ants and food rich of tyramine 酪胺

MAOI & Dietary TyramineMAOI & Dietary TyramineMAOI & Dietary TyramineMAOI & Dietary Tyramine