Transcript Chapter 17 Antipsychotic Agents

Chapter 18
Psychopharmacologic Drugs
•Classification of drugs
• Antipsychotic Agents
• Antimanic drugs
• Antidepressant drugs
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.
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
stereoselectively, for the most part,and their binding
affinity is very strongly correlated with clinical
antipsychotic potency.
Antipsychotic Agents
Classification of Antipsychotic Agents
Typical Antipsychotic drugs :
Phenothiazines
Chlorpromazine(氯丙嗪）
Atypical Antipsychotic drugs :
Clozapine and risperidone
Sulpiride
Antipsychotic Agents
Chlorpromazine(氯丙嗪）
[Pharmacological effects]
• Chlorpromazine can block a number of receptors.
These receptors include dopamine(DA) and alphaadrenoceptor, 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.
Chlorpromazine
[Pharmacological Effects]
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.
Chlorpromazine
[Pharmacological Effects]
3.General psychophysiological effects
After given drugs,psychotic patients initially may
become 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
4.Effects on chemoreceptor trigger zone (CTZ)
• Chlorpromazine can block apomorphine-induced vomiting.
This 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
mechanisms. It may produce hypothermia or hyperthermia,
depending on the environmental temperature.
Chlorpromazine
[Pharmacological Effects]
6.Effects autonomic nervous system
Chlorpromazine can block alpha-receptor, converting a
pressor of epinephrine.
Otherwise, chlorpromazine can depresses vasomotorstabiling center and dilates directly blood vessels.
In addition,chlorpromazine also block the muscarinic
actions of acetylcholine.
[Pharmacological Effects]
Chlorpromazine
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.
Chlorpromazine
Therapeutic Uses
• 1.Treatment of Schizophrenia（精神分裂症）
• 2.Prevention of nausea and vomiting caused by
drugs and radiation sickness.
• 3.Hibernation therapy冬眠疗法
chlorpromazine + promethazine（异丙嗪） +
pethidine （哌替啶）
Chlorpromazine
[Adverse Reactions]
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1.Extrapyramidal Reactions锥体外系反应:
(1) Parkinson’s syndrome;
(2) Akathisia(静坐不能);
(3) Dystonic reactions (肌张力障碍)；
These acute extrapyramidal reaction can be treated
with antimuscarinic drugs, artane.
• (4) Tardive dyskinesia （迟发性运动障碍）
• It has been proposed that it is caused by a relative
cholinergic deficiency secondary to supersensitivity
of dopamine receptors.
Chlorpromazine
[Adverse Reactions]
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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
Drugs used disorders Antidepressant
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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.
Imipramine （米帕明）
[Pharmacological Effects]
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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)
[Clinical Uses]
• 1. The major indication for these drug is to treat
depression.
• 2. Enuresis遗尿
• 3. Anxiety and phobia恐怖
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.
Antimanic Drugs
Lithium salts 锂盐
• This drug may decrease norepinephrine and
dopamine 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.