Chapter 18

Psychopharmacologic Drugs
Antipsychotic Agents Antimanic drugs Antidepressant drugs

Classification of 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() The mechanism of the main adverse effects is blackade of the dopamine receptors in the tuberoinfundibular nigrostriatal 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 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
Typical Antipsychotic drugs : Phenothiazines Chlorpromazine(

Classification of Antipsychotic Agents

Atypical Antipsychotic drugs :

Clozapine and risperidone

Sulpiride

Antipsychotic Agents

Chlorpromazine(
[Pharmacological effects] Chlorpromazine can block a number of receptors. These receptors include dopamine(DA) and alphaadrenoceptor, muscarinic, H1 histaminic receptors(DA , , 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,delusions,and incoherent thinking 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 2.Prevention of nausea and vomiting caused by drugs and radiation sickness. 3.Hibernation therapy chlorpromazine + promethazine + pethidine

Chlorpromazine

[Adverse Reactions] 1.Extrapyramidal Reactions: (1) Parkinsons syndrome; (2) Akathisia(); (3) Dystonic reactions () These acute extrapyramidal reaction can be treated with antimuscarinic drugs, artane. (4) Tardive dyskinesia It has been proposed that it is caused by a relative cholinergic deficiency secondary to supersensitivity of dopamine receptors.

Chlorpromazine

[Adverse Reactions]
2.Behavioral effects include toxic psychosis 3. Adverse effects on autonomic nerve system Orthostatic hypotention Dry mouth Tachycardia Blurred vision

Drugs used disorders Antidepressant

Nonspecific reuptake inhibitors(NE,5-HT,DA) imipramine Tricyclic Antidepressants Selective serotonin-reuptake inhibitors (5-HT) fluoxetine () 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 [Pharmacological Effects]

Tricyclics antidepressants block the amine (norepinephrine or serotonin) reuptake pumps. Such an action presumably permits a longer sojourn 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 3. Anxiety and phobia

Adverse effects of Tricyclics antidepressants

Sedation Sleepiness,additive effects with other sedative drugs Sympathomimetic Antimuscarinic Tremor, insomnia Blurred vision, constipation, urinary hesitancy.

Cardiovascular

Orthostatic hypotension,conduction defects,

arrhythmias

Neurological Endocrine

Seizures Weight gain.

Antimanic Drugs
Lithium salts
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.