Serotonin 5HT₃ receptors are present in the CTZ, the medullary vomiting center, and peripherally in vagal and spinal afferent nerves. 5HT₃ receptor antagonists are common antiemetics used for both the prevention and treatment of PONV. The most commonly used 5HT₃ receptors available in the United States are ondansetron, dolasetron, granisetron, and palonosetron. Ondansetron, dolasetron, and granisetron are available in oral and intravenous (IV) preparations, whereas palonosetron is available for administration by IV route only.

5HT₃ receptor antagonists have fewer side effects compared to other available antiemetics; however, they have been known to cause constipation, headache, dizziness, QTc prolongation, and cardiac arrhythmias. Palonosetron has greater 5HT₃ receptor affinity, which results in its longer half-life of 40 h (compared to a half-life of 4–9 h for the other drugs in this class), and it is not associated with QTc prolongation. Administering a 5HT₃ receptor antagonist with a corticosteroid at the induction of general anesthesia may provide better PONV prophylaxis than either drug class alone.

Ondansetron, the most commonly used 5HT₃ receptor antagonist, is generally administered in doses ranging from 4 to 16 mg IV prophylactically at the induction of anesthesia or for the treatment of PONV postoperatively. Other research has demonstrated increased efficacy when ondansetron is given at the end of surgery but prior to leaving the operating room. Some studies have shown that 4 mg of ondansetron IV is effective for the prevention and treatment of PONV, whereas other studies have demonstrated 8 mg IV to be the minimum effective dose in adults.

There are three classes of dopamine receptor antagonists commonly used as antiemetics: phenothiazines, butyrophenones, and benzamides. The antiemetic properties of these drugs are due to inhibition of dopaminergic receptors in the CTZ. The use of this class of medications is limited by side effects, especially sedation and extrapyramidal symptoms, and should be avoided in patients with Parkinson’s disease.

The most commonly used phenothiazines are perphenazine, promethazine, and prochlorperazine. Perphenazine is available only in an oral form and it is recommended that it be given preoperatively. The typical dose is 4–8 mg, which has been shown to result in effective control of PONV while producing limited side effects. Studies have demonstrated that perphenazine given preoperatively enhances the antiemetic effects of ondansetron and dolasetron. Promethazine is used for both prophylaxis and treatment of PONV. It also has anticholinergic and antihistaminic properties, which can result in substantial sedation, thus limiting its use.

The most commonly used butyrophenone as an antiemetic is droperidol. Droperidol acts through the same mechanism as the phenothiazines and is also typically used as prophylaxis against PONV. Studies have demonstrated that droperidol is equally effective in preventing PONV as the combination of ondansetron and dexamethasone. However, droperidol is still most effective when used in combination with other antiemetics. The recommended dose of droperidol is 0.625–1.25 mg IV. A “black box” warning on droperidol does exist for higher doses (>/=2.5 mg IV) due to cases of QTc prolongation and torsades de pointes, so discretion should be exercised when using droperidol in patients taking other medications that may prolong the QTc interval. Haloperidol, another butyrophenone, has also been shown to have antiemetic properties in low doses (1–2 mg IV), but it has a shorter duration of action than droperidol.

Metoclopramide, a benzamide used as an antiemetic, works by inhibiting dopaminergic receptors in the CTZ and by increasing gastric motility through peripheral activity as a cholinomimetic. Prophylactic and treatment doses of metoclopramide usually range 10–20 mg by mouth or IV every 6 h. Many recent studies comparing metoclopramide and other antiemetics, such as ondansetron and droperidol, have shown that metoclopramide is less effective in the prevention of PONV.

Dexamethasone and methylprednisolone are two corticosteroids used as antiemetics. As described above, dexamethasone has been shown to have enhanced antiemetic properties when combined with ondansetron. Corticosteroids are well known for their anti-inflammatory properties, but the basis behind their use as antiemetics is not well understood. Dexamethasone is generally administered in doses of 4–10 mg IV at the induction of anesthesia. It is recommended that dexamethasone not be routinely given as PONV prophylaxis in patients with diabetes mellitus. No convincing data has shown that adrenal suppression or inhibition of wound healing occurs with a single dose preoperatively.