Antipsychotic drugs or Neuroleptic drugs
called antischizophrenic Major tranquilizers .
or
The term anti psychotic and neuroleptic are used to denote a group of drugs that
is used mainly for the treatment of (schizophrenia ); and also they are effective in some
other psychotic state e.g. mania and delirium .
Chemical classification of antipsychotic drugs into :-
1) Phenothiazine derivative ;which are subdivided into :-
.
R
Chlorpromazine (largactil)
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a)Aliphatic derivatives :
b)Piperidine derivatives :- Thioridazine .
c)Piperazine derivatives :- Fluphenazine and Trifluoperizine .
2)Thioxanthine derivative e,g.:- Thiothixene .
3)Butyrophenone derivatives e.g. Haloperidol.
4)Miscellaneous structures e.g. Clozapine , Olanzapine and Risperidone .
They are incompletely absorbed from intestine ;they undergo significant
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Pharmacokinetic :
first pass metabolism in liver ;they are highly binding to plasma protein with large volume of
distribution ;they are lipid soluble compound can reach to brain .
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Dopamine hypothesis of schizophrenia :
It proposes that this disorder is caused by relative excess of functional activity of the
neurotransmitter dopamine in specific neuronal tracts in the brain ; particularly in the mesolimbic
system .
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ction :
Mechanism of a
1)Dopamine receptors –blocking activity in the brain .
All the neuroleptic drugs block dopamine receptors in the brain and the periphery ;they are five
different dopamine receptors consisting 2 families D1-like receptors include D1and D5
D2-like receptors include D2;D3and D4 .
The clinical efficacy of neuroleptic drugs is correlates closely with their ability to block D2
receptors in the mesolimbic system of the brain .
2)Serotonin receptor –blocking activity in the brain .
The newer drugs Clozapine ,Olanzapine and Risperidone appear to act through inhibition of
serotonin receptors (5-HT) .
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The pharmacological action of neuroleptic drugs
All the neuroleptic drugs reduce the hallucination and delusion
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Anti psychotic actions :
1)
associated with schizophrenia by blocking dopamine receptors in the mesolimbic system of the
brain .
these effects occur with chronic treatment with neuroleptic drugs due
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Extapyramidal effects :
2)
to block dopamine receptors in the nigrostriatal pathway lead to Parkinson like symptoms
(dystonia ;akathisia and tardive dyskinesia ) .
most of the neuroleptic drugs have antiemetic effect that are mediated by
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Antiemetic effect :
3)
blocking D2 –dopaminergic receptors of the chemoreceptor trigger zone of the medulla (CTZ) ;
except Thioridazine is not effective antiemetic .
some of the neuroleptic particularly Thioridazine ; Chlorproazine
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ic effect :
Antimuscarin
4)
;Clozapine and Olanzapine ; causes antimuscarinic effects include blurred vision ;confusion ;dry
mouth ;constipation ;….etc .
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other effects :
5)
a-Blocking of alpha adrenergic receptors causes orthostatic hypotension .
b – Blocking D2 receptor in pituitary gland lead to an in increase in the prolactin release .
c- Blocking of histaminic receptors lead to sedation like with Chlorpromazine and Clozapine
.
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Therapeutic uses of neuroleptic drugs :
1:- Schizophrenia the primary indication of neuroleptic drugs
2:- manic episode in patients with bipolar effective disorder ;used in combined with
antidepressant drugs or Lithium .
3:- Neuroleptic used in combined with narcotic analgesia for treatment of chronic pain and
anxiety in cancer cases .
4:- Chlorpromazine is used to treat intractable hiccup .
5:- Prochlorperazine is useful in the treatment of disease or drugs induced nausea ; but not
due motion sickness .
6:- Senile dementia of Alzheimer disease .
7:- H1-receptor blocking action by Phenothiazine are used for the relief purities (itching ) .
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Contraindications and cautions
1:- Acute agitation due to alcohol or other drugs withdrawal may be aggravated by the neuroleptic
(it is treated by simple sedation like diazepam ) .
2:- In epileptic patients; because the neuroleptic drugs can lower seizer threshold .
3:- Development agranulocytosis from using of neuroleptic drugs .
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Side effects :
1) Extapyramidal side effects :-
it is time dependent with dystonia occur within a few days of treatment followed by
akathisia ;Parkinson symptoms of bradykinesia ; rigidity and tremor occur later on ;tardive
dyskinesia occur after months or year of treatment .
2) Antimuscarinic side effects :- Thioridazine is show strong antimuscarinic activity with
few extra pyramidal disturbances ;in contrast with Haloperidol and Fluphenazine which
have low Anticholinergic activity and produce extra pyramidal effects .
3) Neuroleptic malignant syndrome :- fatal reaction to neuroleptic drugs characterized
by muscle rigidity ; fever ;unstable blood pressure .
4) Neuroleptic drugs depress the hypothalamus causing amenorrhea and galactorrhea in
female ;decrease libido with gynecomastia in male .
5) block alpha receptors resulting in lowered blood pressure and orthostatic hypotension .
6) Significant weight gain commonly 0ccur with a typical neuroleptic drugs
(Clozapine,Olanzapine ; and Risperidone .) .