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Antipsychotic Drug
Prepared By
Md.Sayeed Ahmed
Nafisa yeamin

ID:1531293672
152225

Major Psychiatric Disorders


Psychoses
Affective

disorders

Psychoses
False

perceptions (Hallucinations)

False

beliefs (Delusions)

Affective Disorders
Emotional

disturbances:
Mood is very low (Depression)
Mood is very high (Mania)

Schizophrenia

Most common form of psychosis (1% of world population)

Most typical features are :


-Delusions
-Hallucinations
-Disorganised thinking
-Emotional abnormalities

Aetiology and pathogenesis

Children of two schizophrenic parents have about 40% risk of disease

So heredity appears to have a major role

Dopamine hypothesis or= phamacocentric hypothesis

Hypofrontality hypothesis

Linked hypothesis

Antipsychotic Drugs

Mechanisms of action
-competitive blockade of dopamine receptors and serotonin receptors
-adverse effect result from blockade of different receptors

Typical antipsychotic drugs

They have an equal or greater affinity for D2 receptors than for 5-HT2
receptors

Antagonism of D2 receptors in mesolimbic pathways suppress the positive


symptoms of SCh

Blockade of D2 receptors in the basal ganglia is responsible for parkinsonian


and other extrapyramidal side effects of anti psychotic drugs

Atypical antipsychotic drugs

eg clozapine have a greater affinity for 5-HT2 receptors than for D2 receptors

Some atypical drugs have increased affinity for D 3 or D4 receptors

Three time-dependent changes in


dopamine neuroteransmission

Compensatory response (increase in dopamine synthesis and release)


to acute blockade of postsynaptic dopamine receptors

Continued dopamine receptor blockade


dopaminergic neurons

Inactivation of

reduced dopamine release from mesolimbic and nigrostriatal neurons,


So, alleviate positive symptoms of schizophrenia and cause
extrapyramidal side effects.

Continued

Dopamine reduction causes dopamine up-regulation and super sensitivity to


dopamine agonists and then delayed extrapyramidal side effect called
tardive dyskinesia.

In mesocortical and nigrostriatal pathways, 5-HT2 receptors mediate


presynaptic inhibition of dopamine release.

Blockade of 5-HT2 receptors by atypical drugs increase dopamine release in


these pathways.

Continued

In mesocortical pathway, this action alleviate negative symptoms of Sch.


In nigrostriatal pathway, increased dopamine release counteracts the
extrapyramidal side effects caused by D2 receptor blockade.

Drug Classification

Typical antipsychotic drugs


-Phenothiazines
-Thioxanthenes
-Butyrophenones
- some Azepines (eg loxapine)

Atypical antipsychotic drugs


-other Azepines (clozapine, olanzapine)
-Benzisoxasole (risperidone)

Phenothiazines

Chlorpromazine, Fluphenazine, Thioridazine, Trifluoperazine

Similar therapeutic effects

Different potency and side effect

Chlo. And Thio. lower potency, more autonomic side effects and fewer
extrapyramidal side effects than high potency

Flu. Higher potency

Mechanisms of therapeutic effects

Blockade of D2 receptors

Positive symptoms of Sch. Decrease in 1-3 weeks

Less agitated, fewer auditory hallucinations, disappear of paranoid delusions

Behavioural improvement

Adverse effects
1- Extrapyramidal side effects
-Acute: 1- Akathisia
2- Pseudoparkinsonism
3- Dystonias
-Chronic: Tardive dyskinesia

continued
2- neuroleptic malignant syndrome
3-increase serum prolactin levels
4-impair thermoregulation cause poikilothermy

Treatment of adverse side effects

Acute extrapyramidal side effects

Decrease dose

Change to atypical drug

Counteract with benztropine, diphenhydramine, amantadine

Chronic extrapyramidal side effects

Decrease dose

Drug treatment

Continued
Neuroleptic malignant syndrome

Supportive care

Discontinuing of drug

Administration of bromocryptine

Change to atypical

Indication of Phenothiazines

Schizophrenia

Drug-induced psychosis

Psychosis associated with the manic phase of bipolar disorder.

Dementia

Severe mental retardation

Some of them for management of nausea and vomiting

Chlorpromazine and thioridazine

Thioridazine causes greater antichloinergic activity

And so fewer extrapyramidal side effect

High doses of thioridazine cause pigmentary retinopathy and cardiac


arrythmia

Fluphenazine and trifluoperazine

In compare with thioridazine, cause fewer autonomic side effect and more
extrapyramidal side effects

Fluphenazine is available in long-term depot preparation

Thioxanthenes

Thiothixene has pharmacological effects similar to trifluoperazine

It is used for schizophrenia

(Other thiothixenes in BNF are flupentixol [depixol] zuclopentixol [clopixol].

Butyrophenones

Haloperidol has pharmacological effects similar to fluphenazine.

It is available in a long-acting depot.

It is used for schizophrenia and Tourettes syndrome (corprolalia and


echolalia).

Azepines

Loxapine (typical), clozapine, olanzapine (atypical)

Loxapine properties are similar to phenothiazines

Clozapine has fewer extrapyramidal side effect and greater activity against
negative symptoms and its use is with 1.3% first year incidence of
potentially fatal agranulocytosis.

Other atypical drugs are amisulpride, quetiapine, risperidone and zotepine.

continued

Olanzapine is:
As effective as haloperidol in alleviating of positive symptoms.
Superior to haloperidol in alleviating of negative symptoms.
Fewer extrapyramidal side effects
At high doses may cause akathisia, pseudoparkinsonism, and
dystonias.

Risperidone

Its pharmacological effects are similar to olanzapine.

But less sedation more orthostatic hypotension, higher incidence of


extrapyramidal side effcts.