Antipsychotic butyrophenones also possess antiemetic properties due to their central dopaminergic blockade (see Chapter 29). The main agent used is droperidol, which can be given by intramuscular or intravenous injection. In antiemetic doses, droperidol is extremely sedating. Previously, it was used extensively for postoperative nausea and vomiting, in conjunction with opiates and benzodiazepines for sedation for surgical and endoscopic procedures, for neuroleptanalgesia, and for induction and maintenance of general anesthesia. Extrapyramidal effects and hypotension may occur. Droperidol may prolong the QT interval, rarely resulting in fatal episodes of ventricular tachycardia including torsades de pointes. Therefore, droperidol should not be used in patients with QT prolongation and should be used only in patients who have not responded adequately to alternative agents.
Substituted benzamides include metoclopramide (discussed previously) and trimethobenzamide. Their primary mechanism of antiemetic action is believed to be dopamine-receptor blockade. Trimethobenzamide also has weak antihistaminic activity. For prevention and treatment of nausea and vomiting, metoclopramide may be given in the relatively high dosage of 10–20 mg orally or intravenously every 6 hours. The usual dose of trimethobenzamide is 300 mg orally, or 200 mg by intramuscular injection. The principal adverse effects of these central dopamine antagonists are extrapyramidal: restlessness, dystonias, and parkinsonian symptoms.
The pharmacology of anticholinergic agents is discussed in Chapter 8 and that of H1 antihistaminic agents in Chapter 16. As single agents, these drugs have weak antiemetic activity, although they are particularly useful for the prevention or treatment of motion sickness. Their use may be limited by dizziness, sedation, confusion, dry mouth, cycloplegia, and urinary retention. Diphenhydramine and one of its salts, dimenhydrinate, are first-generation histamine H1 antagonists that also have significant anticholinergic properties. Because of its sedating properties, diphenhydramine is commonly used in conjunction with other antiemetics for treatment of emesis due to chemotherapy. Meclizine is an H1 antihistaminic agent with minimal anticholinergic properties that also causes less sedation. It is used for the prevention of motion sickness and the treatment of vertigo due to labyrinth dysfunction.
Hyoscine (scopolamine), a prototypic muscarinic receptor antagonist, is one of the best agents for the prevention of motion sickness. However, it has a very high incidence of anticholinergic effects when given orally or parenterally. It is better tolerated as a transdermal patch. Superiority to dimenhydrinate has not been proved.
Benzodiazepines such as lorazepam or diazepam are used before the initiation of chemotherapy to reduce anticipatory vomiting or vomiting caused by anxiety. The pharmacology of these agents is presented in Chapter 22.