Regulation of nausea and vomiting in cancer chemotherapy. A review with emphasis on opiate mediators.
Chemotherapy-induced nausea and vomiting are primarily regulated by chemoreceptor trigger zone (CTZ)-vomiting center (VC) pathways. Dopaminergic (D2), histaminic (H1), and muscarinic cholinergic (Ach) receptors are present in these sites, and specific receptor antagonists are potent but not "universal" antiemetics when used alone or in combination. Recently, neurons containing the endogenous opiate enkephalin were also identified near the CTZ and the VC. Furthermore, opiates stimulate vomiting at the CTZ and inhibit vomiting at the VC in dogs and in cats. A dose-related increase in nausea and vomiting in response to the opiate antagonist naloxone has also been demonstrated in patients receiving cancer chemotherapy. These observations support a role for endogenous opiates in regulating chemotherapy-induced nausea and vomiting; further, they suggest that narcotic agents may be effective antiemetics in this setting.