D2 receptor antagonism

Centrally acting D2 blockade and post-synaptic GABA antagonism

D2 receptor antagonism, 5HT-R antagonism, H1-R/M-R/alpha1-R antagonism

D2<5-HT2a and H1-R antagonism

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

CVS: Orthostatic hypotension

CNS: Somnolence. Lowers seizure threshold

GIT: Dysphagia

Metabolic/Other: Hyperglycaemia and increased risk of developing diabetes

sedating

well absorbed orally with bioavailability of 60-80% orally

Good oral absorption

Good oral absorption

92%

98%

Protein bound

18-30L/kg

extensively hepatically metabolized

Hepatic metabolism. Smoking induces the CYP1A2 metabolism of olanzapine

Active metabolite norquetiapine which has anticholinergic effects

mainly biliary, some urine

11ml/min/kg

elimination T1/2 is 10-38hours

Terminal T1/2 is 33 hours

Elimination t1/2 is 7 hours, active metabolite elimination T1/2 is 12 hours

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

First Generation Antipsychotics (D2-Antagonism)

Second Generation Antipsychotics/Atypical (D2-Antagonism/5-HT2a)

Second Generation Antipsychotics/Atypical (D2-Antagonism/5-HT2a)

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

- Psychosis
- Bipolar and acute mania

1. Psychosis
2. Bipolar disorder
3. Agitation

Atypical antipsychotic

Level 3

Level 3

Level 3

Oral tablets, syrup and clear colourless solution for injection

Oral wafer, tablet

IR and SR tablets
Start 50mg nocte and uptitrate to 300mg nocte
Dose reduce by 30-50% in elderly