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Chapter 18 Psychopharmacologic Drugs Antipsychotic Agents Antimanic drugs Antidepressant drugs...
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Transcript of Chapter 18 Psychopharmacologic Drugs Antipsychotic Agents Antimanic drugs Antidepressant drugs...
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Chapter 18 Psychopharmacologic Drugs
• Antipsychotic Agents
• Antimanic drugs
• Antidepressant drugs
•Classification of drugs
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mechanism of action of antipsychotics
• Blockade of the dopamine receptors in the mesolimbic and mesocortical areas in the brain.
• Blocking of the serotonin receptors: clozapine( 氯氮平 )
• The mechanism of the main adverse effects is blackade of the dopamine receptors in the tuberoinfundibular 结节漏斗 nigrostriatal 黑质纹状体 areas.
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Several important dopaminergic pathway
• Several important dopaminergic pathway are now recognized in the brain.
• (1)The first pathway the one most closely related to behavior is the mesolimbic-mesocortical pathway.
• (2) Nigrostriatal pathway, involving in the coordination of voluntary 自主 movement.
• (3) tuberoinfundibular pathway.• The antipsychotic agents block D2 receptors stereoselec
tively, for the most part,and their binding affinity is very strongly correlated with clinical antipsychotic potency.
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Antipsychotic Agents
Typical Antipsychotic drugs : Phenothiazines Chlorpromazine(氯丙嗪)
Atypical Antipsychotic drugs :
Clozapine and risperidone
Sulpiride
Classification of Antipsychotic Agents
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Chlorpromazine(氯丙嗪)[Pharmacological effects]
• Chlorpromazine can block a number of receptors. These receptors include dopamine(DA) and alpha- adrenoceptor, muscarinic, H1 histaminic receptors(DA , α, M , H1 receptors)
• Of these receptors, the dopamine receptor effects quickly became the major focus of interest.
• Chlorpromazine proved to have a wide variety of central nervous system,autonomic,and endocrine effects.
Antipsychotic Agents
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1.Sedative and anti-antianxiety effects Antipsychotic drugs possess calming effect and
lower spontaneous physical movement.
2.Effects on Conditioned response Antipsychotic drugs selectively inhibit the ability of
animals to make a conditioned avoidance response.
[Pharmacological Effects]
Chlorpromazine
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3.General psychophysiological effects After given drugs,psychotic patients initially may b
ecome somewhat slow in response to external stimuli and drowsiness,and then the patients become less agitated,aggressive and impulsive behavior diminishes, and gradually,symptoms of hallucinations 幻觉 ,delusions 错觉 ,and incoherent thinking 妄想 tent to disappear.
[Pharmacological Effects]
Chlorpromazine
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4.Effects on chemoreceptor trigger zone (CTZ)• Chlorpromazine can block apomorphine-induced vomiting. T
his action is due to dopamine receptor blockade, both centrally(in the chemoreceptor trigger zone of the medulla) and peripherally(on receptors in the stomach). However, large doses of chlorpromazine may depress the vomiting center directly.
5.Effects on body-temperature regulation• The chlorpromazine depress temperature-regulating mechanis
ms. It may produce hypothermia or hyperthermia, depending on the environmental temperature.
[Pharmacological Effects] Chlorpromazine
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6.Effects autonomic nervous system
Chlorpromazine can block alpha-receptor, converting a
pressor of epinephrine.
Otherwise, chlorpromazine can depresses vasomotor-
stabiling center and dilates directly blood vessels.
In addition,chlorpromazine also block the muscarinic
actions of acetylcholine.
[Pharmacological Effects]
Chlorpromazine
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7.Effects on endocrine system
More prolactin releasing induces lactation;
Inhibiting corticotropin-releasing hormone(CRH)
release which results in decreased release of
glucocorticoids;also impairing glucose tolerance and
insulin release.
8.Potentiation of other central depressive agents
Antipsychotic drugs potentate the effects of sedatives,
analgesics, antipyretic-analgesics and general
anesthetics.
[Pharmacological Effects] Chlorpromazine
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Therapeutic Uses
• 1.Treatment of Schizophrenia (精神分裂症)• 2.Prevention of nausea and vomiting caused by dru
gs and radiation sickness.
• 3.Hibernation therapy 冬眠疗法 chlorpromazine + promethazine (异丙嗪) + pethi
dine (哌替啶)
Chlorpromazine
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[Adverse Reactions]
• 1.Extrapyramidal Reactions锥体外系反应 : • (1) Parkinson’s syndromeParkinson’s syndrome;; • (2) AkathisiaAkathisia( 静坐不能 ); • (3) Dystonicystonic reactions ( 肌张力障碍 ) ;• These acute extrapyramidal reaction can be treated w
ith antimuscarinic drugs, artane.• (4) TTarardive dyskindive dyskineesiasia (迟发性运动障碍)• It has been proposed that it is caused by a relative ch
olinergic deficiency secondary to supersensitivity of dopamine receptors.
Chlorpromazine
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• 2.Behavioral effects
• include toxic psychosis
• 3. Adverse effects on autonomic nerve system
• Orthostatic hypotention 体位性低血压• Dry mouth
• Tachycardia
• Blurred vision 视力模糊
[Adverse Reactions]
Chlorpromazine
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Drugs used disorders Antidepressant
• Nonspecific reuptake inhibitors(NE,5-HT,DA) • imipramine (米帕明) Tricyclic Antidepressants• Selective serotonin-reuptake inhibitors (5-HT)• fluoxetine ( 氟西汀 )
• Mono-amine oxidase(MAO) inhibitors• Atypical antidepressants• Mirtazapine increases the concentration of 5-HT and
NE in the nerve ending by blocking the presynaptic negative feedback receptors.
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[Pharmacological Effects]
• Tricyclics antidepressants block the amine (norepinephrine or serotonin) reuptake pumps. Such an action presumably permits a longer sojourn 逗留 of neurotransmitter at the receptor site.
(The pathogenesis of depression- the Amine-Hypothesis)
Imipramine (米帕明)
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• 1. The major indication for these drug is to treat depression.
• 2. Enuresis 遗尿• 3. Anxiety and phobia 恐怖
[Clinical Uses]
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Adverse effects of Tricyclics antidepressants
Sedation Sleepiness,additive effects with other
sedative drugs
Sympathomimetic Tremor, insomnia
Antimuscarinic Blurred vision, constipation, urinary hesitancy.
Cardiovascular Orthostatic hypotension,conduction defects,
arrhythmias
Neurological Seizures
Endocrine Weight gain.
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Antimanic Drugs
Lithium salts 锂盐• This drug may decrease norepinephrine and dopamin
e release. These effects might be relevant to its antimanic action.
• Lithium salt counteracts mood changes without producing sedation.
• Phenothiazines have calming and depressant effects which are useful in controlling all kinds of mania ,but do not normalizing behavior.