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THE ASSOCIATION OF CYP2D6 AND mu-OPIOID RECEPTOR GENOTYPESAND POSTOPERATIVE NAUSEA AND VOMITING IN ADULT ORTHOPEDIC PATIENTS WITH SINGLE EXTREMITY FRACTURES

Wesmiller, Susan Watters (2010) THE ASSOCIATION OF CYP2D6 AND mu-OPIOID RECEPTOR GENOTYPESAND POSTOPERATIVE NAUSEA AND VOMITING IN ADULT ORTHOPEDIC PATIENTS WITH SINGLE EXTREMITY FRACTURES. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Often considered the big little problem, postoperative nausea and vomiting (PONV) is a common surgical complication. Treatment of pain with opioids is the primary cause of PONV although other risk factors include female gender, non smoking status and history of PONV or motion sickness. Research has focused on medications to prevent or treat PONV, and risk factors that contribute to PONV. Genetics may also play a role. The purpose of this study was to explore the association of CYP2D6 and mu-opioid receptor genotypes with PONV in patients with single extremity fractures. Subjects (n=143), aged 18-70 were recruited for this exploratory, descriptive study. Informed consent was obtained. PONV was collected by self-report and chart audit. Saliva samples were collected for DNA extraction. Results of Taqman® allele discrimination were used to assign a CYP2D6 classification of poor metabolizer (PM), intermediate metabolizer (IM) extensive metabolizer (EM) and ultrarapid metabolizer (UM). Two SNPS of the mu-opioid receptor gene were analyzed, A118G and C17T by Polymerace Chain Reaction (PCR). Due to genetic differences within ethnic groups, only Caucasians (n=112) were included in the CYP2D6 analysis. The incidence of PONV in the PACU was 38%, increasing to 50% when assessed for 48 hours. CYP2D6 classification results were: 7 (6%) PM group; 34 (30%) IM group; 71 (63%), EM group; and no ultrarapid metabolizers. Gender and history of PONV were significant risk factors in this study (p<.05). There was a trend for age (p=.071), but smoking was not significant (p=.505). The CYP2D6 EM group served as the reference for binary logistic regression analysis which revealed a significant difference with the CYP2D6 PM group for presence of PONV (p =.003). The sample size for the mu-opioid receptor genotype analysis was 82, the genotype distribution was 58 (70%) AA or CC (wild type) and 24 (30%) polymorphism (AG, GG, CT, or TT were combined). No statistical differences were found in the mu-opioid receptor genotype groups for PONV. Ultimately personalized medicine will allow health care providers to treat all patients individually, so it is important for clinical genetic research to identify those risks that may lead to a negative outcome.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wesmiller, Susan Wattersswe100@pitt.eduSWE100
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairHenker, Richard Arhe001@pitt.eduRHE001
Committee MemberDonovan, Heidi Sdonovanh@pitt.eduDONOVANH
Committee MemberMeng, Limengl@anes.upmc.edu
Committee MemberSereika, Susan Mssereika@pitt.eduSSEREIKA
Committee MemberConley, Yvette Pyconley@pitt.eduYCONLEY
Date: 2 May 2010
Date Type: Completion
Defense Date: 14 April 2010
Approval Date: 2 May 2010
Submission Date: 29 April 2010
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: ; CYP2D6; mu-opioid; opioids; Postoperative nausea and vomiting
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04292010-153827/, etd-04292010-153827
Date Deposited: 10 Nov 2011 19:43
Last Modified: 15 Nov 2016 13:42
URI: http://d-scholarship.pitt.edu/id/eprint/7732

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