Association between ABCB1 gene polymorphisms and fentanyl's adverse effects in Turkish patients undergoing spinal anesthesia

Kesimci, Elvin; Engin, Ayşe Başak; Kanbak, Orhan; Karahalıl, Bensu

doi:10.1016/j.gene.2011.11.040

Cited by 28 publications

(19 citation statements)

References 23 publications

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“…In a different population of 83 Turkish adult patients receiving spinal anesthesia and intravenous fentanyl, significant respiratory acidosis was observed in patients with c.1236TT. 33 In another small adult study, the homozygous diplotype (GG-CC at c.2677G4T/A and c.3435C4T) was shown to have borderline association with morphine's side effects in terms of decreased need for ondansetron to treat postoperative nausea or vomiting. 34 In an Italian adult study of 145 patients treated with morphine, a combined effect of 3435T of ABCB1 and 80A of OPRM1 was associated with significantly increased pain relief but had no influence on incidence of side effects.…”

Section: Discussionmentioning

confidence: 99%

Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics

et al. 2014

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Opioid-related respiratory depression (RD) is a serious clinical problem as it causes multiple deaths and anoxic brain injuries. Morphine is subject to efflux via P-glycoprotein transporter encoded by ABCB1, also known as MDR1. ABCB1 polymorphisms may affect blood-brain barrier transport of morphine and therefore individual response to its central analgesic and adverse effects. This study aimed to determine specific associations between common ABCB1 genetic variants and clinically important outcomes including RD and RD resulting in prolonged stay in hospital with intravenous morphine in a homogenous pediatric surgical pain population of 263 children undergoing tonsillectomy. Children with GG and GA genotypes of ABCB1 polymorphism rs9282564 had higher risks of RD resulting in prolonged hospital stays; adding one copy of the minor allele (G) increased the odds of prolonged hospital stay due to postoperative RD by 4.7-fold (95% confidence interval: 2.1-10.8, P=0.0002).

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Section: Discussionmentioning

confidence: 99%

Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics

et al. 2014

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“…In neonatal mice, activation of cannabinoid CB1 receptor with anandamide had been shown to depress the medullary respiratory rhythm generator [47]. Variations in ABCB1 efflux pump P-gp transporter at the blood brain barrier can significantly alter cerebral pharmacokinetics and respiratory depressive effects of opioids [11,48]. Additional associations with RD are independently observed for SNPs in the ABCB1 gene, which encodes a key transporter involved in opioids’ (including morphine) central analgesic and adverse effects [49].…”

Section: Discussionmentioning

confidence: 99%

Genetic Risk Signatures of Opioid-Induced Respiratory Depression Following Pediatric Tonsillectomy

et al. 2014

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Background Respiratory depression is a clinically and economically important but preventable complication of opioids. Genetic factors can help identify patients with high risk for respiratory depression. Methods In this prospective genotype blinded clinical study, we evaluated the effect of a panel of variants in candidate genes on opioid-related respiratory depression in 347 children following tonsillectomy. Results Using unsupervised hierarchical clustering and a combination of candidate genotypes and clinical variables, we identified several distinct clusters of patients at high risk (36–38%) and low risk (10–17%) of respiratory depression; the relative risk of respiratory depression for high versus low risk clusters was 2.1–3.8 (p = 0.003). Conclusion Genetic risk predictions (genetic signatures) along with clinical risk factors effectively identify children at higher and lower risks of opioid-induced respiratory depression. Genetic signatures of respiratory depression offer strategies for improved clinical decision support to guide clinicians to balance the risks of opioid adverse effects with analgesia.

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“…Patients with the genotypes 1236TT, 2677TT, and 3435TT were found to have early and profound respiratory depression (65-73% of initial respiratory rate) following intravenous fentanyl administration, suggesting ABCB1 polymorphisms may have important clinical implications in fentanyl safety (132). However, another clinical study of 83 patients also undergoing intravenous fentanyl treatment for spinal anesthesia concluded that ABCB1 polymorphisms had no effect on fentanyl-induced sedation or respiratory depression (133). ABCB1 and ABCG2 polymorphisms were also found to have no relation with the clinical manifestations of fentanylinduced delirium or coma (134).…”

Section: Fentanylmentioning

confidence: 99%

“…A number of in vivo studies have concluded that fentanyl is a P-gp substrate while one suggested it is rather an Oatp substrate (136). Clinical results are not in consensus either, with some suggesting P-gp function has a significant role in the pharmacodynamics of fentanyl (131,132), while others suggest otherwise (133,134). Clinical evidence also suggests fentanyl is not an OATP substrate, implying fentanyl may be safely concomitantly administered with OATP substrates or inhibitors (135).…”

Section: Fentanylmentioning

confidence: 99%

“…As with morphine, there does not appear to be a clear consensus on the role of ABCB1 polymorphisms in the PK and PD of oxycodone (113)(114)(115), fentanyl (132)(133)(134), or methadone (155-162, 164, 165). The reasons behind this apparent lack of clarity may be complex, and possibly involve the geographic distribution of patients enrolled as well as the polymorphisms selected for investigation.…”

Section: Transporter Polymorphismsmentioning

confidence: 99%

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Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

et al. 2015

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Opioid-related deaths, abuse, and drug interactions are growing epidemic problems that have medical, social, and economic implications. Drug transporters play a major role in the disposition of many drugs, including opioids; hence they can modulate their pharmacokinetics, pharmacodynamics and their associated drug-drug interactions (DDIs). Our understanding of the interaction of transporters with many therapeutic agents is improving; however, investigating such interactions with opioids is progressing relatively slowly despite the alarming number of opioids-mediated DDIs that may be related to transporters. This review presents a comprehensive report of the current literature relating to opioids and their drug transporter interactions. Additionally, it highlights the emergence of transporters that are yet to be fully identified but may play prominent roles in the disposition of opioids, the growing interest in transporter genomics for opioids, and the potential implications of opioid-drug transporter interactions for cancer treatments. A better understanding of drug transporters interactions with opioids will provide greater insight into potential clinical DDIs and could help improve opioids safety and efficacy.

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Association between ABCB1 gene polymorphisms and fentanyl's adverse effects in Turkish patients undergoing spinal anesthesia

Cited by 28 publications

References 23 publications

Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics

Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics

Genetic Risk Signatures of Opioid-Induced Respiratory Depression Following Pediatric Tonsillectomy

Transporter-Mediated Disposition of Opioids: Implications for Clinical Drug Interactions

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