Influence of <scp>UGT</scp>2B7,<scp>OPRM</scp>1 and <scp>ABCB</scp>1 Gene Polymorphisms on Postoperative Morphine Consumption

Bastami, Salumeh; Gupta, Anil; Zackrisson, Anna-Lena; Ahlner, Johan; Osman, Abdimajid; Uppugunduri, Srinivas

doi:10.1111/bcpt.12248

Cited by 58 publications

(45 citation statements)

References 26 publications

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“…It has been speculated that the absorption of morphine is reduced in the CC carriers due to the effective efflux by P-gp in gut and/or through the blood brain barrier and consequently reducing the bioavailability of morphine for the receptors in brain. Conversely the TT carriers with abnormal function of P-gp should have a higher concentration of morphine [16]. The C3435T ABCB1 SNP has recently been associated with a different need for morphine in humans.…”

Section: Discussionmentioning

confidence: 99%

Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid Sensitivity in Treatment of Postoperative Pain

Nojkov

Карталов

Кузмановска

et al. 2016

Prilozi

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Background:The minimal effective analgesic concentration of opioids required for satisfactory analgesia may differ significantly among the patients. Genetic factors may contribute to the variable response to opioids by affecting their pharmacokinetics or pharmacodynamics. Methods: Ninety nine patients undergoing abdominal surgery with colorectal anastomosis because of colorectal carcinoma were enrolled in the present study. C34535T was genotyped in all subjects and the patients were divided into three groups according to their genotype: CC-wild type homozygous, CT-mutant heterozygous and TT-mutant homozygous. Intravenous fentanyl, patient controlled analgesia was provided postoperatively for pain control in the first 24 hour after surgery. Opioid consumption, pain scores and the adverse side effects were evaluated. Results: Our main result is that the patients in the CC genotype group consumed significantly more fentanyl (375.0 µg ± 43.1) than the patients in the TT group (295.0 µg ± 49.1) and the CT (356.4 µg ± 41.8) group in the treatment of postoperative pain. The patients in the TT group had lower VAS scores at 6h, 12h, 18 h and 24h postoperatively. There were no significant differences in the side effects among the three groups regarding the vomiting and the sedation score. The patients in the TT group had more frequently nausea score 1, than the patients in the other two groups. Conclusion: Our study indicates that the C3435T SNPs of the ABCB1 gene is associated with differences in the opioid sensitivity. The ABCB1 polymorphism may serve as an important genetic predictor to guide the acute pain therapy in postoperative patients.

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Section: Discussionmentioning

confidence: 99%

Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid Sensitivity in Treatment of Postoperative Pain

Nojkov

Карталов

Кузмановска

et al. 2016

Prilozi

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“…It has been suggested that genetic polymorphisms of drug transporters are the cause for variations in pain sensitivity shown not just in animal studies but also in humans . There are very few, if any, reported studies of pain sensitivity, especially of cold pain, among healthy subjects in association with the ABCB1 gene.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of P‐gp activity enhanced the analgesic effects of opioids due to its increase in the brain concentration . Bastami et al showed that ABCB1 gene polymorphisms were significantly associated with variability in morphine drug requirements in 40 patients undergoing abdominal hysterectomy. It was found that patients homozygous for 1236T and 3435T alleles required lower doses of morphine for pain relief.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic variations may partly explain the observed variability in pain; for example, genetic mechanisms of pain perception accounted for approximately 60% of the variability in cold‐pressor pain . Common genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses . A number of studies reported strong linkage disequilibrium (LD) between c.1236C>T and c.2677G>T/A as well as c.3435C>T polymorphism .…”

Section: Introductionmentioning

confidence: 99%

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Relationship Between ABCB1 Polymorphisms and Cold Pain Sensitivity Among Healthy Opioid‐naive Malay Males

et al. 2017

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“…However, other similar study approaches reveal no such relationship [2,3]. Moreover, no significant results have been found in human experimental pain models and controlled clinical-pain models [1,2,4]. This could be due to poor study designs lacking relevant end points (e.g., side effects and pharmacodynamic response).…”

Section: Polymorphisms Affecting Drug Transportersmentioning

confidence: 97%

Do Genes Affect Morphine Response?

Ladebo

Olesen

2017

Pharmacogenomics

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Morphine is an essential medication for treatment of severe acute and chronic pain. However, interindividual differences in pain sensitivity and analgesic response make the clinical use of morphine challenging. Approximately 10-30% of patients report an unsatisfactory pain relief or intolerable side effects, which often leads to drug withdrawal. Several confounding factors such as age, gender, mental state, polypharmacy, organ function, comorbidity and certain lifestyle habits can influence the therapeutic outcome and thus contribute to the variability seen. Genetic variation has also shown to alter the pharmacokinetics and pharmacodynamics of morphine. In the following, a brief overview will be provided on how genes encoding pharmacokinetic (drug transporters or metabolizing enzymes) and pharmacodynamic (receptors or enzymes) factors can play a vital role for the efficacy of morphine. Polymorphisms affecting drug transportersGenetic polymorphisms can alter the functionality of gene products and thus affect drug response and severity of side effects. Morphine is a substrate for P-gp, which is an efflux transporter, belonging to the ATP-binding cassette (ABC) family, encoded by the ABCB1 gene. P-gp serves as a defender against xenobiotics by limiting drug absorption over the small intestine and facilitating excretion by transporting drugs into bile -and urine ducts. Last but not least, it also transports xenobiotics out of the brain across the blood-brain barrier, thereby minimizing drug-receptor interactions.In vitro studies have found an association between polymorphisms of the ABCB1 gene and lower glycoprotein activity and expression levels in the duodenum, natural killer cells and renal parenchyma [1]. Some observational studies in cancer patients have also found an association between ABCB1 polymorphisms and altered analgesic responses and dose requirements. However, other similar study approaches reveal no such relationship [2,3]. Moreover, no significant results have been found in human experimental pain models and controlled clinical-pain models [1,2,4]. This could be due to poor study designs lacking relevant end points (e.g., side effects and pharmacodynamic response). Presently, the C3435T polymorphism is the most studied ABCB1 SNP. It is plausible that other ABCB1 SNPs have a clinical significance, although additional studies are needed to confirm this hypothesis.Another but functionally different transporter is the OCT1, which transports organic cations such as morphine into hepatocytes, thus potentially influencing morphine disposition and hepatic metabolism. Currently, no strong evidence suggests that the OCT1 reduced-function polymorphisms affect morphine response. However, one study did find a significant higher morphine AUC 0-24 h and an insignificant higher C max in healthy Caucasian carriers. Unfortunately, no pharmacodynamic end points were evaluated, wthereby the clinical impact is impossible to discuss [5].

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Influence of UGT2B7,OPRM1 and ABCB1 Gene Polymorphisms on Postoperative Morphine Consumption

Cited by 58 publications

References 26 publications

Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid Sensitivity in Treatment of Postoperative Pain

Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid Sensitivity in Treatment of Postoperative Pain

Relationship Between ABCB1 Polymorphisms and Cold Pain Sensitivity Among Healthy Opioid‐naive Malay Males

Do Genes Affect Morphine Response?

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