Fatty acid amide hydrolase–morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children. (January 2017)

• Record Type: Journal Article
• Authors: Chidambaran, Vidya; Pilipenko, Valentina; Spruance, Kristie; Venkatasubramanian, Raja; Niu, Jing; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Zhang, Kejian; Kaufman, Kenneth; Vinks, Alexander A; Martin, Lisa J; Sadhasivam, Senthilkumar
• Is Part Of: Pharmacogenomics. Volume 18:Number 2(2017)
• Page Start: 143
• Page End: 156
• Publication Date: 2017-01
• Subjects: FAAH -- fatty acid amide hydrolase -- hypercapnic ventilatory response -- morphine -- opioid–cannabinoid interactions -- postoperative -- respiratory depression; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2016-0147
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: Fatty acid amide hydrolase ( FAAH ) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid–endocannabinoid interactions.Patients & methods: In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO2 (HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics.Results: We found significant FAAH –morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH –HCVR association predicts risk of impending RD from morphine use.Conclusion: FAAH genotypes predict risk for morphine-related adverse outcomes.