Core pharmacology

Class Group

First Generation Antipsychotics (D2-Antagonism)

Legacy Cicm Level

-

Indications Uses

1. Antipsychotic
2. Nausea and vomiting associated with terminal illness
3. Intractable hiccups

Presentation

Tablets, syrup, suppositories, straw coloured solution for injection (IM)

Mechanism of action

Central D2 blockade. Antagonism of serotonergic, histaminergic muscarinic and alpha-adrenergic receptors

Physiological effects

CVS
- - Negatively inotropic and has alpha-adrenergic blockade. This causes postural hypotension and reflex tachycardia
- Increased CBF
- PR and QTc prolongation

CNS
- Neurolepsis, sedation and anxiolysis
- Lowers seizure threshold
- Increases sleep time but majority is REM sleep

Resp
- Respiratory depressant
- Decreased bronchial secretions

Renal: Anticholinergic activity may produce urinary retention

GIT: Antiemetic. Increased appetite

Metabolic/other
- Insulin release is impaired
- ADH released is impaired
- Prolactin release is increased

Absorption

well absorbed orally but bioavailability of 30% due to first pass metabolism in liver and gut wall

Protein binding

95%

Volume of distribution

12-30L/kg

Metabolism

extensively hepatically metabolized. At least 168 metabolites described, many of which are active

Excretion

Equal quantities in urine and faeces.

Clearance

6-11ml/min/kg

Half-life

elimination T1/2 is 30 hours