These may be classified as shown in Table 31.1.
Antiemetics that act on the vomiting centre have antimuscarinic (their principal mode) and anti-histaminic action (hyoscine, promethazine); they alleviate vomiting from any cause. In contrast, drugs that act on the CTZ (haloperidol, ondansetron) are effective only for vomiting mediated by stimulation of the chemoreceptors (by morphine, digoxin, cytotoxics, uraemia). The most efficacious drugs act at more than one site (Table 31.1).
Antimuscarinic drugs (including those classed primarily as histamine H1 receptor antagonists) are described in Chapters 21 and 29. Drugs with antimuscarinic activity probably act both centrally
TABLE 31.1 Classification of anttemesis drugs
Drug Site of action/comment
Dopamine D2 receptor antagonists domperidone metoclopramide haloperidol phenothiaiines, e.g. c hi or promazine, prochlorperazine, thiethylperazine 5-HTj receptor antagonists ondansetron granisetron tropisetron Antimuscarinics hyoscine and some drugs also classed as histamine H receptor antagonists, e.g. cyclizine, dimenhydrinate, promethazine Other agents corticosteroids (dexamethasone. Gut (vomiting due to methyl prednisolone) cytotoxics)
cannabinoids (nabilone) benzodiazepines (lorazepam)
and in the gastrointestinal tract. Phenothiazines and butyrophenones owe their antiemetic efficacy to blockade of dopamine D2 receptors but they readily penetrate the brain and may produce unwanted extrapyramidal effects by blocking D2 receptors in the basal ganglia; many also have antimuscarinic effects.
Metoclopramide acts centrally by blocking dopamine D2 receptors in the CTZ, and peripherally by enhancing the action of acetylcholine at muscarinic nerve endings in the gut. It raises the tone of the lower oesophageal sphincter, relaxes the pyloric antrum and duodenal cap and increases peristalsis and emptying of the upper gut. The peripheral actions are utilised to empty the stomach before emergency anaesthesia and in labour. If an opioid has been given, metoclopramide may fail to overcome the opioid-induced inhibition of gastric emptying and thus the risk of vomiting and inhaling gastric contents remains. The direct effects on the gut are antagonised by antimuscarinic drugs. The action of metoclopramide is terminated by metabolism in the liver (t'/i, 4 h).
CTZ and gut CT2 and gut
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