Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting

Abstract

Purpose of review: The use of selective 5-hydroxytryptamine type 3 receptor antagonists has improved the management of postoperative nausea and vomiting, but has not completely eliminated it. In this article, we discuss the pharmacology of 5-hydroxytryptamine type 3 receptor antagonists and the impact of pharmacogenetics on postoperative nausea and vomiting.

Recent findings: Dolasetron, granisetron, ondansetron, palonosetron, and tropisetron have similar mechanisms of action but different pharmacokinetic and pharmacodynamic properties. Genetic polymorphism in the cytochrome P450 mono-oxygenase system, drug efflux transporter adenosine triphosphate-binding cassette subfamily B member 1 and 5-hydroxytryptamine type 3 receptor subunits also contribute to the interindividual variation in response to different 5-hydroxytryptamine type 3 receptor antagonists. These differences account for differences in the duration of action and clinical efficacy of these agents.

Summary: Pharmacogenetics testing in patients may help differentiate responders to 5-hydroxytryptamine type 3 receptor antagonists from non-responders and allow the anesthesiologist to individualize antiemetic therapy. The cost-effectiveness of such screening in postoperative nausea and vomiting management has, however, not been evaluated. Given the multifactorial nature of postoperative nausea and vomiting, a multimodal approach to reduce or eliminate risk factors will be most successful in its management.