1st Generation antipsychotics
- Phenothiazines - Chlorpromazine, Prochlorperazine
- Thioxanthenes - Flupenthixol, Clopentixol
- Haloperidol
2nd generation antipsychotics
- Atypical antipsychotics - Risperidone, Clozapine, Olanzapine, Quetiapine
Contraindications
Caution
- Hepatic impairment
- Renal impairment
- Cardiac disease
- Urinary retention
- Closed angle glaucoma
- Hypotension
- Parkinsonian symptoms
- Elderly
Patients with delirium and dementia are often sedated with anti-psychotics. It is now recognised that this increases the risk of stroke and death. In addition, the elderly are more sensitive to the side effects of these drugs. The risk-benefit ratio should be carefully considered.
All of these drugs are dopamine receptor type 2 antagonists. This is the most likely explanation for their sedative / tranquilizing effect. The antipsychotic effect is probably an adaptive response to the antidopaminergic actions.
The atypical antipsychotic drugs have greater effects on other receptors than the dopamine receptor (including 5HT2 receptor, histamine receptor).
Extrapyramidal effects (see ADRs) are caused primarily by 1st generation antipsychotics as a result of their greater action on dopamine receptors than the 2nd generation drugs.
The drugs also have anticholinergic and α-adrenergic effects.
Note - the sedative levels of drugs vary and the greater the sedative effect of the drug the less the extrapyramidal or anticholinergic side effects.
- Oral
- Intramuscular - short-acting
- Intramuscular - long-acting ("depot" medication)
Much smaller doses are required for anti-emetic effects.
Warn the drugs may cause sedation and interfere with skilled motor tasks (e.g. driving). The drugs may cause a photosensitive rash so sun-block should be worn. Patients taking Clozapine should be advised to seek medical attention if they develop an unexplained fever or infection.
The antipsychotics are well absorbed across the gut and are mostly broken down by hepatic mechanisms. A number of biologically active metabolites are produced in metabolism of the drugs. Excretion is both faecal and renal.
