Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


23611.pdf (2.99 MB)

ETD Abstract Container

Abstract Header

Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents

Chidambaran, Vidya
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491317932872925

Abstract Details

2017, MS, University of Cincinnati, Medicine: Clinical and Translational Research.
Background: Genetic susceptibility for morphine induced adverse effects like respiratory depression (RD), resulting from opioid-cannabinoid interactions, has not been studied. Anandamide, an endogenous cannabinoid, is degraded by Fatty Acid Amide Hydrolase, coded by gene FAAH. We hypothesized that FAAH variants will be associated with altered susceptibility to opioid adverse effects. Methods: We prospectively recruited 101 White adolescents with idiopathic scoliosis/kyphoscoliosis undergoing spine fusion using standardized anesthesia and postoperative morphine patient-controlled analgesia. Blood samples were collected for genotyping FAAH variants and morphine pharmacokinetics. We measured hypercapnic response to 5% CO2 (HCVR) before and after morphine administration, and followed subjects for morphine associated RD and post-operative nausea/vomiting (PONV) on postoperative day one. Results: We found significant (p<0.0001) interaction for FAAH variants rs11576941, rs2295632, rs2295633, rs324420, rs6699322, rs3766246, rs45586133, rs6699322 and rs4141964 with morphine induced depression of HCVR, adjusted for morphine concentrations. Variant rs11576941 was significantly associated with PONV (OR 2.14; 95% CI 1.06-4.33; p = 0.0339), while rs11576941, rs2295632, rs45586133 and rs6699322 were marginally associated with RD after adjusting for sex, morphine and diazepam doses. HCVR was significantly more depressed in patients who developed RD compared to those who did not (p=0.0034). Thus, FAAH-HCVR association indirectly predicts risk of impending clinical RD in children receiving morphine. Using curated databases, we show that rs324420 is a missense variant, while most of the others are regulatory. Conclusion: We have identified novel genetic predictors for opioid-endocannabinoid interactions leading to opioid adverse outcomes, supporting preemptive genotyping for RD risk prediction and safer optimization of opioid analgesia.
Erin Haynes, Dr.P.H. (Committee Chair)
Lisa Martin, Ph.D. (Committee Member)
Senthilkumar Sadhasivam (Committee Member)
37 p.
Genetics
Fatty acid amide hydrolase; hypercapnic ventilatory response; opioid induced respiratory depression; pharmacogenetics; opioid-cannabinoid interaction; Postoperative vomiting

Recommended Citations

Citations

  • Chidambaran, V. (2017). Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491317932872925

    APA Style (7th edition)

  • Chidambaran, Vidya. Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents. 2017. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491317932872925.

    MLA Style (8th edition)

  • Chidambaran, Vidya. "Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents." Master's thesis, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491317932872925

    Chicago Manual of Style (17th edition)

ucin1491317932872925
219
© 2017, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.