Copyright Dr Garry KJ Pettet 2005 - 2009

Copyright Dr Garry KJ Pettet 2005 - 2009

Antipsychotics (neuroleptics)
The dopamine hypothesis of psychosis:
Psychotic symptoms result from dopamine neurotransmission
Dopamine receptors:
o D1-like:

D1 and D5
Are post-synaptic
Stimulate adenylate cyclase and cAMP
o D2-like:

D2, D3 and D4
Are both pre- and post-synaptic
Inhibit adenylate cyclase and cAMP
Dopaminergic pathways:
o Mesolimbic / mesocortical:
Concerned with mood and emotional stability
Ventral tegmental area:
Ventral striatum and the frontal cortex
o Nigrostriatal:
Concerned with movement
Substantia nigra and the dorsal striatum
Neuroleptics block D2 receptors:
o Explains why they cause movement disorders as a side effect

Clinical classification of neuroleptics:

Typical:
o Produce extrapyramidal symptoms (EPS)
Atypical:
o So-called because they have a low incidence of EPS
o However, all apart from clozapine can cause EPS at high doses
Chemical classification of neuroleptics:
Typical:
o Phenothiazines:
Propylamines (chlorpromazine):
Sedation ++
Anticholinergic ++
EPS ++
Piperidines (thioridazine):
Sedation ++
Anticholinergic ++
EPS +
Can cause torsade de pointes
Piperazines (fluphenazine):
Sedation +
Anticholinergic +
EPS +++
o Thioxanthines (flupenthixole):
Sedation +
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Anticholinergic +
EPS ++
o Butyrophenones (haloperidol):
Sedation Anticholinergic EPS +++
Atypical:
o True:
Clozapine:
Sedation ++
Anticholinergic +
EPS o Apparent:
Sulpiride:
Sedation +
Anticholinergic
EPS +
Risperidone:
Sedation ++
Anticholinergic +
EPS +

General effects of the neuroleptics:

Early (hours):
o Desired:
Sedation (histamine / -receptor blockade)
Tranquilisation (dopamine blockade)
o Unwanted:
Acute dystonic reactions
Medium (daysweeks):
o Desired:
Suppression of:
Delusions
Disordered thinking
Hallucinations
o Unwanted:
Akathisia
Parkinsonism
Late (monthsyears):
o Desired:
Prevention of relapse
o Unwanted:

Tardive dyskinesia
Any time:
o Neuroleptic malignant syndrome
Chlorpromazine:
Indications:
o Psychotic disorders (e.g. schizophrenia / mania)
o Labyrinthine disorders / vertigo

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Copyright Dr Garry KJ Pettet 2005 - 2009

Copyright Dr Garry KJ Pettet 2005 - 2009

o Nausea / vomiting
o Chronic hiccups
Adverse effects:
o Common:
Sedation
Anticholinergic effects:
Blurred vision
Dry mouth
Postural hypotension
Constipation
Urinary retention
Extrapyramidal effects:
Acute dystonia
Akathisia
Parkinsonism
Tardive dyskinesia
Hyperprolactinaemia:
Amenorrhoea
Galactorrhoea
Impotence
o Uncommon:
Neuroleptic malignant syndrome
Agranulocytosis
Cholestatic jaundice
Interactions:
o ACE inhibitors:
Can cause severe hypotension

Fluoxetine:
plasma levels of haloperidol

Clozapine:
Regarded by many as the only true atypical neuroleptic:
o EPS is not evident even at high doses
o Effective in patients refractory to other neuroleptics
o Can treat the negative symptoms of schizophrenia
Mechanism of action:
o Blocks D4 and 5-HT2 receptors
o Weak blockade of striatal D2 receptors
Adverse effects:
o Agranulocytosis (requires regular blood monitoring)
o Myocarditis / cardiomyopathy
o Ileus
Contraindications:
o Severe cardiac disorders
o History of neutropenia / agranulocytosis
Interactions:
o Avoid concomitant use with drugs that have a high risk of
causing agranulocytosis (e.g. carbimazole)

Haloperidol:
Indications:
o Psychosis
o Motor tics
Adverse effects:
o Common:
Extrapyramidal effects:
Acute dystonia
Akathisia
Parkinsonism
Postural hypotension
o Uncommon:
Convulsions
Neuroleptic malignant syndrome
Tardive dyskinesia
Weight loss
Interactions:
o Amiodarone:
risk of ventricular arrhythmias
o Carbamazepine:
plasma levels of haloperidol (metabolism accelerated)

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