Pharmacology

Most antipsychotics are thought to work at least partly through blocking dopamine receptors in the brain. Serum prolactin level is a measure of this dopaminergic blockade. However, different antipsychotic drugs have different effects at the various subtypes of dopamine receptors. Most antipsychotics also have anti-adrenergic, anticholinergic, and antihistaminic actions.

Chlorpromazine is regarded pharmacologically as a 'dirty' drug; that is, it has actions on several neurotransmitter systems. As indicated above, its antihista-mine action produces sedation, which is often useful in acute psychiatric presentations. By contrast, haloperidol is a 'cleaner' drug, with actions predominantly on the dopamine system. Because it does not have actions on the histamine and acetylcholine systems, it may not be strongly sedative in some patients; it may therefore need to be supplemented in clinical use by prescription of minor tranquillizers such as the benzodiazepines.

Recently, 'atypical' antipsychotics have been introduced and have rapidly become popular. They were initially promoted as being free from side-effects, but, inevitably, after a few years, their side-effects have become apparent. Risperidone can cause extrapyramidal side-effects. Olanzepine, especially, but also other atypicals are associated with weight gain and diabetes. They also carry a specific risk of stroke, causing them to be discouraged in the elderly.

Prescribers must remain alert to sudden changes in medication availability and indications. Lack of a sufficient market caused the company concerned suddenly to stop supplying droperidol. Action by the Committee on the Safety of

Medicines caused the very useful and gentle drug thioridazine (Melleril) to be abruptly withdrawn as a first-line treatment of schizophrenia, on the basis of reported cardiovascular problems. And more recently, as indicated above, the supposedly safe atypicals have been warned against in the elderly, in whom they may cause stroke.

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