The efficacy of 5HT3-receptor antagonists in postoperative nausea and vomiting: the role of pharmacogenetics

INTRODUCTION: Genetic variants may affect drug efficacy on postoperative nausea and vomiting (PONV). The un-derstanding of these mechanisms will help to identify the surgical patients who might benefit from specific prophylactic and therapeutic antiemetic treatment. The aim of the present review was to investigate gene polymorphisms that influence 5-hydroxytryptamine (serotonin) type 3 receptor antagonists (5HT3RA) efficacy in PONV.EVIDENCE AQUISITION: We included articles published from 2005 to 2022, utilizing the electronic databasesPUBMED, EMBASE, COHRANE Library and ScienceDirect. To explore the relationship between genetic variations and 5HT3 receptor antagonist efficacy in PONV we focused on three different gene polymorphisms: the cytochrome P450 mono-oxygenase system gene (CYP2D6), the adenosine triphosphate (ATP)-binding cassette subfamily B gene (ABCB1) as well as the 5HT3 receptor gene (5HT3R). We also explored the relationship between the above genetic variations and their impact on 5HT3RA efficacy in the context of chemotherapy induced nausea and vomiting.EVIDENCE SYNTHESIS: Our search retrieved a total of 70 articles; 29 of them were included in the present review. Regarding polymorphisms of the CYP2D6 gene and the efficacy of serotonin antagonists in PONV, the ultra-rapid me-tabolizer genotype was associated with reduced efficacy of ondansetron, dolasetron and tropisetron, with the latter pre-senting more pronounced failure in these patients, while granisetron's efficacy remained unaffected. Regarding variations in the ABCB1 gene, three polymorphisms (2677G>T/A in exon 21; 3435C>T in exon 27; C1236T in exon 12) were associated with a better response to ondansetron and ramosetron, while they did not affect palonosetron's efficacy. Additionally, polymporphisms of the 5-HT3B receptor gene were associated with ondancetron's postoperative efficacy; the 100_-102AAG deletion variant was associated with reduced efficacy, while the Y129S variant did not show any effect on the drug's antiemetic effect.CONCLUSIONS: This review highlights that inefficacy of a specific drug in managing PONV could be attributed to specific genetic profiles and patients would possibly benefit from a drug switch. (Cite this article as: Theodosopoulou P, Rekatsina M, Staikou C. The efficacy of 5HT3-receptor antagonists in postop-erative nausea and vomiting: the role of pharmacogenetics. Minerva Anestesiol 2023;89:565-76. DOI: 10.23736/S0375-9393.22.16983-X)

Automated summary

This review investigates the gene polymorphisms that influence the efficacy of 5-hydroxytryptamine (serotonin) type 3 receptor antagonists (5HT3RA) in postoperative nausea and vomiting (PONV). The study suggests that specific genetic profiles could contribute to the inefficacy of a certain drug, and patients might benefit from switching to a different drug.