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Uses. Metoclopramide is used for nausea and vomiting associated with gastrointestinal disorders, and with cytotoxic drugs and radiotherapy. It is also an effective antiemetic in migraine and is used as a prokinetic agent (see above).

Adverse reactions are characteristic of dopamine receptor antagonists and include extrapyramidal dystonia (torticollis, facial spasms, trismus, oculogyric crises) which occurs more commonly in children and young adults, and in those who are concurrently receiving other dopamine receptor antagonists, e.g. phenothiazine drugs. The antimuscarinic drug, benzatropine, given i.v., rapidly abolishes the reaction. Long-term use of metoclopramide may cause tardive dyskinesia in the elderly. Metoclopramide stimulates prolactin release and may cause gynaecomastia and lactation. Restlessness and diarrhoea may also occur.

Domperidone is a selective dopamine D2 receptor antagonist; unlike metoclopramide it does not possess an acetylcholine-like effect. The t1/, is 7 h. Dopamine does not readily penetrate the blood-brain barrier; this does not limit its therapeutic efficacy, for the CTZ is functionally outwith the barrier, but there is less risk of adverse effects in the central nervous system. Domperidone is used for nausea or vomiting associated with gastrointestinal disorders and with cytotoxic and other drug treatment. It can also be helpful in management of bloating in patients with nonulcer dyspepsia (see above). It may cause gynaecomastia and galactorrhoea.

Ondansetron is a selective 5-HT3 receptor antagonist. Drugs with this activity appear to be highly effective against nausea and vomiting induced by cytotoxic agents and radiotherapy. Evidence suggests that such anticancer treatment releases serotonin (5-HT) from enterochromaffin cells in the gut mucosa (where resides > 80% of the serotonin in the body) which activates specific receptors in the gut and central nervous system to cause emesis.6 The action of ondansetron is thus partly central and partly peripheral. Ondansetron may be given by i.v.

6 Cubeddu L X et al 1990 New England Journal of Medicine 322: 810.

injection or infusion immediately prior to cancer chemotherapy (notably with cisplatin), followed by oral administration for up to 5 days (tl/2 5 h). The drug appears to be well tolerated but constipation, headache and a feeling of flushing in the head and epigastrium may occur. Granisetron and tropisetron are similar.

Nabilone is a synthetic cannabinoid and has properties similar to tetrahydrocannabinol (the active constituent of marijuana) which has an antiemetic action. It is used to relieve nausea or vomiting caused by cytotoxic drugs. Adverse effects include: somnolence, dry mouth, decreased appetite, dizziness, euphoria, dysphoria, postural hypotension, confusion and psychosis. These may be reduced if prochlorperazine is given concomitantly.

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