Psychotropic drugs Liming Zhou ( 周黎明 ) Department of pharmacology

Psychotropic drugs

Liming Zhou ( 周黎明 )

Department of pharmacology

Classification Antipsychotic Drugs

Antimanic drugs

Antidepressants

anxiolytics

Antipsychotic Drugs

Contents Overview

Inreuduction of Schizophrenia

Classification of antipsychotic drugs

Chlorpromazine

Overview Antischizophrenic,neuroleptic drugs

These agents are prescribed for treating schizophrenia or management of psychotic symptoms

Overview What is schizophrenia ?

There appears to be a genetic component to schizophrenia.

There is also evidence for changes in brain structure.

Schizophrenia schizophrenia

Clinical Manifestations Characteristics-- perturbations affecting: language perception thinking volition Behavior social activity

size of ventricles

Schizophrenia Syndrome overview:

Typically begins in late adolescence Insidious onset.  Poor outcome. Social withdrawal /perceptual distorti

ons lead to chronic delusions （错觉） /hallucinations （幻觉） .

Schizophrenia Positive Symptoms:

Conceptual disorganization Delusions Hallucinations

Schizophrenia

Negative Symptoms:

Anhedonia ( 快感缺乏 ) Decreased emotional expression Impaired concentration Diminished socialization

Classification of antipsychotic drugs Phenenothiazines （吩噻嗪类 ) (Chlorpromazine) Thioxanthenes( 硫杂蒽类） (Tardan,flupenthixol) Butyrophenones （丁酰苯类） (Haloperidol) Atypicals )( 非典型药物） (Cloz

apine)

Chlorpromazine (wintermine)

Pharmaciolgical effects CNS effects

1.neuroleptic effect: hallucination and delusions （ 错

觉） improvement

Mechanism of action

Blockade dopaminergic neurotransmission

-the limbic

- nigrostriatal

- hypothalamic system.

Dopamine Hypothesis:This idea was suggested by observation that

drugs which reduced dopaminergic activity reduced acute symptoms/signs of psychoses.

Symptoms notably Decreased -- agitation anxiety hallucinations

Four pathway of dopaminergic neurotransmission

1)Mesolimbic-mesocortical pathway (one most closely related to behavior )

2)nigrostriatal pathway(it is involved in the coordination of voluntary movement)

3)tuberoinfundibular pathway (inhibits prolactin secreation)

4 ） medullary-periventricular pathway (the function is not clear ,may be involved eating behavior)

Dopamin receptor: two type, five subtype

- DA1 (D1-like receptor): D1,D5

- DA2 (D2-like receptor): D2,D3, D4

D2 like receptors (D2, D3, D4) Activate Gi cAMP Block Ca++ channels Open K+ channels

D2: putamen( 壳核） , olfactory tubercle （嗅结节）

D3: frontal cortex, medulla, midbrain D4: ???

D2 receptor activation motor activity aggravates schizophrenia

D2 receptor blockade alleviation of schizophrenia

Neuroleptic effect: blocking DA2

Side effect

(extra-pyramidal symptoms.): blocking DA2

Pharmalogical effects Antiemetic effect. -This is a results of blocking DA2 rece

ptor. -In low doses, blocking DA2 receptor i

n chemoreceptor trigger zone(CTZ). -In high doses, chlorpromazine may d

irectly depress the medulla vomiting center.

Pharmalogical effects Altering temperature-regulating mec

hanisms. in a cold climate it decrease tempera

ture in body in a hot climate they can cause hype

rthermia

Pharmalogical effects Sympathetic and parasympathetic nervo

us system effect: -Blocking α-adrenergic receptor Orthostatic h

ypotension. -Blocking M-receptor. Blurred vision Constipation Dry mouth Decreased sweating

Pharmalogical effects

Endocrine system effect Increasing the lactogenic hormone( 催乳素 ).In

creased levels of prolactin may lead to galactorrhea （溢乳 ).

phenothiazines decrease FSH and ACTH. Decreasing release and secretion of pituitary

growth hormone.

Prolactin FSH ACTH growth hormone.

Therapeutic uses 1. Psychotic disorders, all kind of schizo

phrenia. 2. Nausea and vomiting.(except carsickn

ess). 3. Decrease the temperature. 4. Control of intractable hiccup （呃逆打

嗝 ). 5.Therapy gigantism( 巨人症 ).

untoward effects (1) Special side effect:

Extrapyramidal symptoms A. Parkinsonian syndrome: the patients di

splay rigidity( 僵化 )and tremor B. Acut dystonia: patients display facial gr

imacing ( 面部的歪扭 ,) torticollis( 斜颈 ) C.Akathisia ( 静坐不能 ) D. tardive dyskinesia ( 迟发性运动障碍）

patient display sucking of the lips and other involuntary facial movement. (The dyskinesia may persist for after discontinuation of the therapy).

Untoward effects

(2)General side effect:

A. CNS depression B. M-receptor blocking: The sympto

m of M- receptor blocking C. Orthostatic hypotension

Untoward effects (3)Inducing psychosis by drug

(4)seizure and epilepsy

(5)allergic reaction

(6)cardiovascular effect

Untoward effects (7)Endocrine disorder: Hyperprolactinemia--causes:

For women:   Amenorrhea(abnormal suppression or absence of menstrual flow), galactorrhea , infertility

For men: impotence  infertility,diminished libido

For children: decreasing growth.

Drug interaction: 1)Increasing CNS inhibition with ethanol, se

dative-hypnotics, morphine.

2)Inhibiting the of L-Dopa (agonist of the doparmin-receptor).

3)Increase the dose with phentoin and carbamazepine.

Atypical antipsychotic drugs Clozapine and Risperidone selectively inhib

it D4 and 5-HT2-receptors. Risperidone selectively inhibit D2 and 5-HT

2-receptors. Sulpiride selectively inhibit D2-receptors in

the mesolimbic and mesocortical areas of the brain.

Sulpiride ,Clozapine and risperidone have low risk of extra-pyramidal adverse reaction.

Atypical antipsychotic drugsSulpiride Selectively inhibit D2-receptors in the

mesolimbic and mesocortical areas of the brain.

Producing low extra-pyramidal adverse reaction.

Antimanic drug Lithium carbonate

Pharmacodynamics

Possible mechanisms of action:

-effects on electrolyte/ion transport neurotransmitter

-neurotransmitter release modulation influence on second messengers.

Lithium salts how to affect second messengers?(learning by yourself)

Antidepressants

Overview

Classification

TCA Antidepressants

Overview Depression is an alteration of mood

characterized by sadness, worry, and anxiety.

The patient may suffer from losses of weight, libido, and enthusiasm.

DepressionClinical depression is a syndrome that may i

nclude: Sustained mood disturbances Impaired memory and concentration Disturbed sleep Reduced energy level Reduced libido Impaired sleep.

Depression Patient complaints suggestive of dep

ression may include:   Pain (headaches, body aches)  A mood of apathy, anxiety, or irritabi

lity   Sexual complaints low energy, excessive tiredness  reduced capacity for enjoyment.

Classification of Antidepressant Drugs Five of antidepressant Tricyclic antidepressants (TCA) Monoamine oxidase inhibitors (MAO) NA reuptake inhibitors Serotonin-specific reuptake inhibitors (SS

RIs) Serotonin and NA-specific reuptake inhibit

ors

Most antidepressants are believed to improve by increasing NT

Catecholamine 5-HT stores

Tricyclic antidepressant TCAs

Imipramine

Pharmalogic effects CNS -In the depressed patients , an elevat

ion of mood occur 2-3 weeks after administration begins, the latency period can be as long as 4 weeks.

-The imipramine blocks the re-uptake of serotonin and NA

Pharmalogic effects

Autonomic nervous system

Blocking m-receptor

Pharmalogic effects

Cardovascular effect: Hypotensin (blocking α receptor) Tachycardia

Mechanism of TCA:

Blocking re-uptake of neurotransmitter

Norepinephrine(NA) Serotonin(5-HT)

Clinic use

1)Therapy depression 2)Therapy enuresis 3)Therapy anxiety and phobic-anxiet

y syndromes 4)Obsessive-compulsive neurosis co

mpanied by depression

Untoward effects 1)anticholinergic effect

2)cardiac arrhythmas

3)manic excitement can occur in patient with bipolar manic-deprssive illness

Untoward effects 4)The combination of a MAO inhibtor

with tricyclic antipressants should not be avoided ,since hyperpyrexia, convulsions and coma can result

Selective serotonin reuptake inhibitors

A.Fluoxrtine B.Paroxrtine

Home work

Suggested further readingsRojas-Corrales,MO.and Mico JA. Antip

ressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, inhelpless rats.life science.2002,72(2):143-152

1.How are agents in this chapter classified?

2.Describe the pharmacological effects of Chlorpromazine.

What are the major differences between the TCA and SSRIs?