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