chapter 25 antipsychotic drugs antipsychotic drugs schizophrenia 精神分裂症 literal translation...
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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