Core pharmacology

Class Group

First Generation Antipsychotics (D2-Antagonism)

Legacy Cicm Level

Level 3

Indications Uses

- Schizophrenia
- Nausea and vomiting
- Motor tics and hiccupping
- Acute confusional states and delirium in intensive care
- Premedication
- Palliative care

Presentation

Oral tablets, syrup and clear colourless solution for injection

Mechanism of action

Centrally acting D2 blockade and post-synaptic GABA antagonism

Physiological effects

CVS: Minimal cardiovascular effects but has antagonistic effects at alpha adrenergic receptors that may cause hypotension in the presence of hypovolaemia

CNS: Induces neurolepsis, a state characterized by diminished motor activity, anxiolysis, and indifference to environment. Seizure threshold is raised

GIT: Powerful antiemetic

Metabolic/Other: Causes hyperprolactinaemia

Adverse Effects Toxicity

1. Extrapyramidal Reactions
- Tardive dyskinesia occurs in 20% of patients taking the drug for >1 year. Women and elderly are more susceptible
- Acute dystonic reactions occur in 2% of patients in first 72 hour especially in young men. These include torticollis, oculogyric crisis and laryngospasm

2. Neuroleptic malignant syndrome
- Typically develops over 24-72 hours ad is characterized by hyperthermia, generalized hypertonicity, autonomic instability and fluctuating LOC
- Increased muscle tone may lead to chest wall rigidity and myonecrosis. Treatment includes dantrolene and bromocriptine

3. Cardiovascular
- May prolong QTc
- Hypotension in context of hypovolaemia but this is less pronounded in oral administration

4. Hyperprolactinaemia
- Galactorrhoea and gynaecomastia
- Hypothalamic effects may lead to increased weight gain

Absorption

well absorbed orally with bioavailability of 60-80% orally

Protein binding

92%

Volume of distribution

18-30L/kg

Metabolism

extensively hepatically metabolized

Clearance

11ml/min/kg

Half-life

elimination T1/2 is 10-38hours

Excretion

mainly biliary, some urine