Opiates are among the most common causes of medication-induced nausea and vomiting. Twenty-seven percent of patients with noncancer pain managed with opiates reported nausea in one recent study, while 9 % noted vomiting [20]. In a systematic review of randomized trials of opiate medications for pain control, nausea and vomiting were experienced by 32 and 15 % of patients, respectively [21]. Opiate drugs are believed to elicit these symptoms by actions within the central and peripheral nervous systems. These effects include binding to μ-opioid receptors in the area postrema, the nucleus tractus solitarius, the vestibular apparatus, and the gut myenteric and submucosal plexi where they stimulate uncoordinated contractile activity. Other receptor subtypes may participate in opiate-induced nausea and vomiting including k and δ-opioid, D₂, 5-HT₃, and NK₁ receptors. Furthermore, morphine can increase synthesis, release, and metabolism of serotonin [22]. Most investigators observe similar degrees of nausea and vomiting from use of all opiate medications when adjusted for potency. However, some reports suggest that some agents such as tapentadol and hydromorphone may elicit less nausea and/or vomiting compared to morphine or oxycodone [23].

Nausea and vomiting are very common complications of cancer chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) is classified as acute, delayed, and anticipatory. Chemotherapy drugs have been stratified into four risk categories for CINV including those that are at high (90 % risk of CINV without antiemetic therapy), moderate (30–90 %), low (10–30 %), and minimal (<10 %) risk. Highly emetogenic agents include cisplatin, high-dose cyclophosphamide, streptozotocin, carmustine, and dacarbazine. Even with antiemetic prophylaxis, acute and delayed vomiting are reported by 35 and 50 % of patients receiving highly emetogenic drugs, respectively [24]. Anticipatory nausea and vomiting occur in 25–34 % of individuals within the first four courses of chemotherapy, especially in younger patients. Risk scores have been developed to predict the risk of CINV and include poor social functioning, nausea before administration of chemotherapy, female sex, age <50 years, delivery of these highly emetogenic drugs, and prior history of CINV [25]. Compared to those at low risk, patients at high risk are three to four times more likely to experience CINV. Patients under treatment for hematologic malignancies appear to be a higher risk of CINV, perhaps secondary to their younger age and the emetogenicity of the chemotherapeutic agents employed in this setting [25].

Pathways underlying CINV have been extensively characterized in animal and human models and provide the rational basis for its prophylaxis and treatment. Acute vomiting after highly emetogenic agents like cisplatin is associated with elevations in plasma and ileal tissue serotonin, serotonin immunoreactive mucosal cells, and urinary levels of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) within hours of chemotherapy administration. Conversely, milder chemotherapeutic drugs do not increase plasma serotonin or urinary 5-HIAA concentrations. Mechanistic studies have observed release of serotonin from intestinal mucosal enterochromaffin cells which then bind to vagal afferent 5-HT₃ receptors projecting to the area postrema. Highly emetogenic agents like cisplatin also increase serotonin turnover in the brain and activate several structures including the dorsal vagal nuclei and central amygdala. The risk for acute CINV development is increased with some 5-HT₃ receptor gene polymorphisms, reflecting participation of serotonin pathways. Conversely, delayed CINV is mostly mediated by serotonin-independent pathways as there is little 5-HIAA excretion in the urine and poor responses to 5-HT₃ receptor antagonists. Rather, evidence suggests an important role for central NK₁ receptor-mediated mechanisms as suggested by the capability of central but not peripheral NK₁ receptor antagonists to reduce delayed CINV [3]. However, studies observing reductions in delayed CINV after treatment with the long-acting 5-HT₃ receptor antagonist palonosetron suggest there may be interactions between 5-HT₃ and NK₁ receptor pathways in this emetic phase [26]. In contrast to acute CINV, delayed emesis is prevented by ablation of the area postrema but is unaffected by vagotomy. Other pathways which may participate in delayed CINV include 5-HT₄ receptor, adrenoceptor, and peripheral muscarinic receptor pathways.

Postoperative nausea and vomiting (PONV) occurs after 17–37 % of operations. Drug risk factors for this condition include general anesthesia with volatile agents or nitrous oxide, intraoperative neostigmine, and intra- and postoperative opiate use. Indeed, opiate use after anesthesia is one of 5 factors in a recently developed risk score predicting rates of PONV [27]. Non-medication-related risk factors for PONV include abdominal or orthopedic surgery, female sex, older age, obesity, anxiety previous PONV, histories of migraines or motion sickness, and prior Helicobacter pylori infection. Mechanisms underlying PONV have not been completely defined; however, some reports suggest that inhalational anesthestics (e.g., halothane, isoflurane) can modify 5-HT₃ receptor function [28]. A range of variants of genes encoding M₃, D₂, 5-HT₃, μ-opioid receptors, and α₂-adrenoceptors have been associated with PONV which may underlie susceptibility to this complication. Other polymorphisms associated with PONV may influence transport and metabolism of opiates or antiemetics like the 5-HT₃ receptor antagonist ondansetron.

Several medications elicit nausea and vomiting by mechanisms unrelated to receptor activation or neurotransmitter release. Salicylates and nonsteroidal anti-inflammatory drugs are proposed to produce these symptoms by local mucosal irritation in the stomach and duodenum with subsequent activation of vagal afferent pathways. Similar local effects may be involved in nausea and vomiting after ingestion of potassium supplements or vitamin preparations. Medication effects on ion channels may mediate nausea and vomiting evoked by some cardiac antiarrhythmics, antihypertensives, anticonvulsants, calcium channel antagonists, and diuretics.

Medications prescribed to treat or prevent nausea and vomiting include antiemetic agents acting on an assortment of receptor pathways in the central or peripheral nervous systems, prokinetic drugs that increase motor activity or accelerate transit in the stomach or small bowel, and medications that modulate neural activity to reduce noxious gut sensations.