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ANTI PSYCHOTIC DRUG
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Psychosis:
Describe variety of mental disorder,characterised by loss of touch with in reality usualy occurs due to
dopamine
over activiting in mesocortical,mesolimbic pathway.
**Most common psychotic disorder - schizophrenia
Schizophrenia:
Particular kind of psychosis characterised mainly by clear sensorum but a marked thinking disturbance.
Clinical Symptom:
1. a) + ve symptom
b) hallucination
c) delirium
d) thought disorder
e) abnormal behaviour
f) reality distortion
2. - ve symptom: depressive symptoms - withdrawl from social contact,flattening of emotional
response,poverty of speech.
3. defect of cognitive function: usually acute episodes ( +ve symptoms mainly ) frequently occur &
developed
into chronic schizophrenia with in predominantly -ve symptoms.
Dopamine Hypothesis:
a) describe that symptoms arise because of functional excess of dopaminergic activity in the CNS.
b) DA - responsible for + ve symptom
c) 5HT- responsible for - ve symptom
d) drugs that activate DA receptor cause psychotic symptoms.
Q: mention the dopeminergic pathway? short note: central dopeminergic system?
Ans: 5 important pathway:
a) mesolimbic & mesocortical pathway - for behaviour
b) nigrostriatal pathway - co-ordination of voluntary movement
c) tuberoinfundibular pathway - dopamin release inhibits prolactin secretion
d) medullary-periventricular pathway - eating behaviour
e) incertohypothalamic pathway - anticipatory motivational phase.
Dopamine receptors:
a) D1 & D5 - increase cAMP - increase D1 receptor group
b) D2,D3,D4 - decrease cAMP - D2
Q. Classify anti-psychotic drug/ Enumerate typical & atypical anti-psychotic drug?
Ans. Classification** Typical/traditional/1st generation
a) phenothiazine derivatives:
1. aliphatic- chlorpromazine ( proto type )
2. piperadine- thioridazine
3. piperazine- fluphenazine,prephenazine,trifluophenazine.
b) thioxanthene derivatives: thiothixene
c) butyrophenone derivatives: haloperidol,droperidol
d) miscellaneous/ others:pimozide,molindone
**Atypical or newer:
- clozapine,olanzapine,loxapine,zotepine,risperidone
Mechanism of action:
a) dopamine receptor blocking action in brains by antipsychotic drugs.Binds with in D2 receptors
mesolimbic & mesocortical region ( blocks the d2 receptor present in mesolimbic )
b) serotinin receptor blocking activity of newer atypical drugs.Exerts action through inhibition of
serotonin receptor
c) many of this agents blocks cholinergic,adrenergic,histamine receptor ( H1 ). so cause side effect.
Thioridazine
chlorpromazine
l
cholinergic
Q. write down the pharmacological effect of chlorpromazine?
Ans.
1. Antipsychotic effect:
*emotional quitening
*pschomotor slowing
decrease motor activity,hyperactivity,aggressiveness - increase social interaction
*this drug also prevent acute attack & delay subsequence attack.
*usualy takes several weeks.
2. Extrapyramidal effect: penkinsons syndrome
3. Endocrine effect:
a) Reproductive system:
"In female* amenorrhea
* galactorrhea
* false-possitive pregnancy test
* increased libido
"In male* deccreased libido
* gynacomastia
**Thus occur due to increase prolactin secretion
b) Abnormal pigmentation.
4. Antimitive effect:
a) stop vomiting by blocking D2 receptor of CT7 of the medulla
b) effecting against also
5. cardiovascular system:
* decrease PVR
* decrease maen arteriolar pressure
* orthostatic hypotension
* these are due to alpha blocking effect
* ECG-QT interval prolonged - thionidazone
6. anti cholinargic effect:
* M receptor blocking effect
* dry mouth
* blurring of vision
* sedation
* confusion
* constipation
* urinary retention
7. other effect:
* sedation - H1 blocking effect - chlorpromazine, clozapine
* weak diuretic effect
Clinical use:
a) psychiatric indication psychosis:
* schizophrenia - main stay of treatment positive symptoms are effectively treated by typical drugs.
negative symptoms are alleviated by atypical drugs.
long term treatment prevents recurrence & allowing patient to lead normal life.
* schizo-effective disorder: schizophrenia + effective disorder
* psychosis with mania
* atypical psychosis
* psychosis with depression
* tourettes syndrome - heloperidol, pimozide - to supress severe ties
b) prevention of nausea & vomiting
c) persistent prurities
d) intractable hiccough
e) as neuroleptanesthesia
Q. Mention the adverse effect of chlorpromazine/phenothiazine/thioridazine?
Ans.
A) neurological effect:
1. parkinsons syndrome - tremor , dystoxia, akinesia
due to blockage of nigrostriatal pathway.extra pyramidal reaction.
2. akathesia - uncontrolable restlessness
3. acute dystonic reaction - spastic retroedis,torticolis
4. tardive dyskinesia - most important side effect
*late syndrome
*occurs due to relative cholinergic
deficiency secondary to super sensitivity of dopamine receptor in caudate - putamen
treatment switch to newer agent,avoid all drugs with central anticholinergic activity.
5. seizure - very rare
B) CNS/ANS effect:
1. blurred vision,dry mouth,sedation,confusion,constipation
2. orthostatic hypotension,mesoridazone
C) metabolic & endocrine effect:
1. weight gain
2. hyperprolactinaemia result in
3. amenorrhea
4.galactorrhoea
5.infertility
6.loss of livido,impotency,infertility in male
7.hyperglycaemia - secondary to weight gain associated insulin resistence
D) toxic or allergic reaction:
1.agranulocytosis - clozapine
2. cholestatic jaundice
3. skin - skin eruption, pruritis, pigmentation, photo sensitivity
E) occular complication:
1. deposits in anterior portion of eye - chlorpromazine
2. increase the normal process of aging
F) cardiac toxicity:
1. major ventricular arrythmias - thioridazine
2. cardiac conduction block - thioridazine
3. Q-T prolongation, ziprasidone
** it neuroleptic malignant syndrome,,
** occurs in patient who are extremely sensitive to retropyramidal effect..
Mechanism of action:
Due to excessive rapid blockage of post synaptic dopamine receptor.
C/F: fever, muscle regidity, altered BP & pulse
Use in pregnancy: better to avoid in pregnancy.
Drug interaction: potentiates the action of
alchol,barbiturates,narcotic,analgesics,anticholinergics,anaesthetics,antihypertensive.
A)Typical Antipsychotics:
1. blocks 70-80% D2 receptor
2. alloviates mainly possitive symptoms
3. decrease motor activity
B)Atypical Antipsychotics:
1. blocks 40-60% D2 receptor & also blocks 70-90% 5HT receptor
2. alloviates both possitive & negative symptoms
3. loss extrapyramidal effect - due to loss D2 block.
4. rate of relapse - low
5. more selective D2 receptor blocker.. ( Eg - clozopine, risperidone )