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![Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents için kapak resmi Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents için kapak resmi](/client/assets/cf6e192b74af2810/ctx/images/no_image.png)
Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents
Başlık:
Study of Association of FAAH Genotypes with Clinical Outcomes and Hypercapnic Ventilatory Response Related to Morphine Administration in Post-Surgical Adolescents
Yazar:
Chidambaran, Vidya, author.
ISBN:
9780438071698
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (37 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Committee members: Erin Haynes; Lisa Martin; Senthilkumar Sadhasivam.
Özet:
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.
Notlar:
School code: 0045
Konu Başlığı:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(696233.1) | 696233-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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