Neuroleptics (Antipsychotics)

Dr S. A Jayaratne
Senior Lecturer
Dept of Pharamacology

Definition of Neuroleptics
A group of drugs that have been used mainly
for treating schizophrenia but are also effective
in some other psychotic diseases and agitated
states

(Experiments of I.P.Pavlove for psychopharmacology)

 Psychosis-loss of contact with reality

Psychotics may suffer from hallucinations and
delusions and impaired insight
Schizophrenia- is a mental disorder that
makes it difficult to tell the difference between
real and unreal experiences, to think logically,
to have normal emotional responses, and to
behave normally in social situations.

 The term neuroleptics indicates dopamine

receptors (central) antagonists active in the
treatment of psychoses.
The central effects of neuroleptics prevail over
their peripheral effects which exist however.
The therapeutic use of neuroleptics, is the
treatment of psychoses.

Psychosis
Psychoses, schizophrenia in particular, are
very complex diseases involving
negative symptoms:- poverty of speech and
expression, indifference, carelessness
positive symptoms: -hallucinations, delusion,
unsuited behavior, aggressiveness.
Neuroleptics, also called antipsychotics,
improve most of these symptoms, especially
the productive ones

Positive symptoms
Delusions:paranoid, of reference,somatic, grandeur
Hallucinations-auditory, visual, tactile olfactory, gustatory
Disorganized speech
Negative symptoms
Poverty of speech
lack of emotion - the inability to enjoy regular activities (visiting with
friends, etc.) as much as before
Low energy - the person tends to sit around and sleep much more than
normal
lack of interest in life, low motivation
Affective flattening - a blank, blunted facial expression or less lively facial
movements, flat voice (lack of normal intonations and variance) or
physical movements.
Alogia (difficulty or inability to speak)
Inappropriate social skills or lack of interest or ability to socialize with
other people
Inability to make friends or keep friends, or not caring to have friends
Social isolation - person spends

Classification :-Chemical groups of

antipsychotics
Three principal groups:phenothiazines

butyrophenones
.
benzamides

Antipsychotics :-modern day classification

Classical agents- chlorpromazine
haloperidol
prochlorperazine
Atypical agents-clozapine
risperidone
olanzapine
quetiapine

Mechanism of action
They act on brain pathways in which
dopamine is the neurotransmitter
Pathways are-tuberoinfundibular pathway
(moderate prolactin release from hypothalamus)
-nigrostriatal pathway
(involved in motor control)
- mesolimbic

(overactive in psychotic illness)

pathway

Mechanism of action contd--

All antipsychotics block D2 receptors

Therefore they prevent activation of these
receptors
Thus it was postulated the deficit in schizopherenia
was increased dopaminergic activity due to a rise in
number of brain dopamine D2 receptors or receptor
supersensitivity to excess availability of dopamine
for D2 receptor activation from overproduction or
reduced destruction through enzyme deficiency

Pharmacokinetics
Given orally well absorbed & distributed
Can be given im for rapid relief of symptoms
Metabolised by cytochrome 450 isoenzymes in
liver
Long plasma half lives so that once daily
administration is possible
Depot im injections are available (drug
released over 2-4 weeks)

Clinical uses
Pychoses. They reduce manic states (excitation,
aggressiveness, insomnia), delirious states (delusion,
hallucinations) and to a lesser degree the severity of
the negative symptoms of the psychosis.
They do not cure the psychotic patient but attenuate
considerably the symptoms of his disease.
Nausea & vomiting
Intractable hiccup
Controlling severely agitated patients

Preparations
Oral
Im ( chlorpromazine, haloperidone)
Depot preparations given at intervals of 24weeks
Withdrawal
Should always start with the lowest dose &
gradually titrated up
After long term use withdrawal should be
gradual

Adverse effects
Classical antipsychotics
Sedation, drowsiness.
Extrapyrimidal symptoms
Acute dyskinesia -( intermittent muscular spasms
of the affecting especially face and neck:
torticollis, trismus, tongue protrusion, occulogyric
attack, opistothonos. These symptoms, linked to
inhibition of D2 dopaminergic receptors of the
striatum.Controlled by anticholinergic drugs eg
benztropin

Adverse effects continued

-Akathisia- (restlessness, impossibility of

remaining motionless)
-Tardive dyskinesia (abnormal movements of
tongue, lip samcking, facial grimacing,
twisting & gyratnig of the whole body)
usually difficult to control, stop or reduce the
dose

Adverse effects continued

Cardiovascular effects-postural hypotension.

(blockade of adrenoceptors) Prolongation of the
QT interval ventricular arrhythmias
Endocrine -hyperprolactinemia galactorrhoea,
gynecomastia, amenorrhoea, decreased libido
Weight gain
Allergic reactions
Photosensitization
Blood disorders: thrombopenia, agranulocytosis
particulaly with clozapine
Jaundice

Adverse effects continued

Retinal pigmentation, corneal opacities,lens

opacities
Osteoporosis

Atypical antipsychotics
Fewer extrapryramidal effects due to less D2
receptor blockade
Sexual dysfunction & skin problems are rare
Risperidone raise prolactin levels and cause
galactorrhoea
More effective than typical psychotics against
negative symptoms

Clozapine
Used in resistant schizophrenia
Causes postural hypotension, tachycardia, provoke
seizures
Agranulocytosis- differential blood should be
monitored
before starting R , every 2weeks for 18weeks

every 4weeks after 1year

If WBC/DC-is < 3000/mm3 stop treatment
Patient should report immediately symptoms of
infection (sore throat, influenza like symptoms)

Clozapine contd--

Myocarditis, & cardiomyopathy can be fatal

(most commonly in the first 2mths)
Gastrointestinal obstruction reaction
resembling obstruction. Used cautiously with
drugs causing constipation

Neuroleptic malignant syndrome