Adverse events in analgesic treatment with tramadol associated with CYP2D6 extensive-metaboliser and OPRM1 high-expression variants

Kim, Eunkyung; Choi, Chan Bum; Kang, Chang Won; Bae, S.-C.

doi:10.1136/ard.2009.124347

Cited by 28 publications

(11 citation statements)

References 9 publications

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“…Those patients who required the most opioids (PMs) required the least amount of ondansetron, and those who required the most ondansetron required the lowest amount of opioids for pain (Figure 1). These findings are consistent with the recent findings of Kim, Choi, Kang, and Bae (2010), who reported that subjects with knee osteoarthritis taking tramadol for less than 14 days and classified as EM had significantly more nausea and vomiting than similar subjects taking tramadol and classified as IM. Investigators in two other studies reported results for postoperative patients who required more opioids for pain but experienced less PONV.…”

Section: Discussionsupporting

confidence: 93%

The Association of CYP2D6 Genotype and Postoperative Nausea and Vomiting in Orthopedic Trauma Patients

Wesmiller

Henker

Sereika

et al. 2012

Biological Research For Nursing

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The CYP2D6 gene encodes for an enzyme that is involved in the metabolism of more than 25% of all medications, including many opioids and antiemetics. It may contribute to the risk of postoperative nausea and vomiting (PONV), a common surgical complication. However, little research has been conducted in this area. The purpose of this study was to explore the association of CYP2D6 genotypes with PONV in adult surgical trauma patients. Data from 112 patients (28% female) with single extremity fractures, aged 18–70 years, were analyzed. PONV was defined as present if patients reported nausea, were observed vomiting, or received medication for PONV. Saliva samples collected for DNA extraction and Taqman®allele discrimination and quantitative real time polymerase chain reaction (qRT-PCR) were used to collect genotype data that were then used to assign CYP2D6 phenotype classification. The incidence of PONV was 38% in the postanesthesia care unit and increased to 50% when assessed at 48 hr. CYP2D6 classification results were 7 (6%) poor metabolizers, 34 (30%) intermediate metabolizers, and 71 (63%) extensive metabolizers. No ultrarapid metabolizers were identified. Patients who were classified as poor metabolizers had less PONV and higher pain scores. Gender and history of PONV, but not smoking, were also significant risk factors. Findings suggest variability in CYP2D6 impacts susceptibility to PONV.

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Section: Discussionsupporting

confidence: 93%

The Association of CYP2D6 Genotype and Postoperative Nausea and Vomiting in Orthopedic Trauma Patients

Wesmiller

Henker

Sereika

et al. 2012

Biological Research For Nursing

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“…1. Simplified diagram of nausea and vomiting pathways including published genetic associations (24,47,54,67,94). CHRM3 (cholinergic receptor, muscarinic 3 gene), HRT3B [5-HT (serotonin) receptor 3B gene], OPRM1 (mu opioid receptor gene), CYP2D6 (cytochrome P450 2D6), UGT2B7 (UDP-glucuronosyltransferase 2B7), and ABCB1 (multidrug resistance gene encoding P-glycoprotein).…”

Section: Cytochrome P450 2d6mentioning

confidence: 99%

“…Two studies of morphine in the post-operative period and one of tramadol for osteoarthritis have reported an association with the variant G allele of rs1799971 and less nausea/vomiting (24,47,54). The A118G genotype was not associated with fentanyl-induced post-operative nausea and vomiting in another similar sized study of 165 Chinese women who had undergone gynecological surgery (55).…”

Section: Mu Opioid Receptormentioning

confidence: 99%

Opioid genetics: the key to personalized pain control?

2012

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There are now several strong opioids available to choose from for the relief of moderate to severe pain. On a population level, there is no difference in terms of analgesic efficacy or adverse reactions between these drugs; however, on an individual level there is marked variation in response to a given opioid. The genetic influences to this variation are complex, and although current research has shown some promising results, these have not been replicated across larger studies and as such the ultimate aim of personalized prescribing remains elusive. If personalized prescribing could be achieved this would have a major impact at an individual level to facilitate safe, effective and rapid symptom control. This review presents some of the recent positive advances in opioid pharmacogenetic studies, focusing on associations between candidate genes and the three main elements of opioid response: analgesic, upper gastrointestinal and central adverse reactions.

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“…Genetic variations of CYP2D6 have been shown to affect not only the pharmacokinetics of tramadol and M1 but also the analgesic efficacy in volunteer and patient studies as well as pharmacodynamic responses [18,21,23–25,45]. In addition to CYP2D6, a few other studies have explored the role of drug transporters and pharmacological targets in tramadol efficacy or toxicity [42,43,46]. …”

Section: Pharmacogenomicsmentioning

confidence: 99%

“…However, the results have been controversial, with both positive and negative associations reported for this SNP on various opioid phenotypes, for example, dose requirement, analgesic efficacy, and side effects [65]. In a study of 160 Korean patients treated with tramadol, the A118G variant has been associated with ADRs [46]. Korean patients carrying the GG genotype were less likely to develop nausea/vomiting (6.3-fold lower odds) when treated with tramadol as compared with patients with the AA genotype, suggesting that a high risk of nausea/vomiting may be linked to high levels of μ-opioid receptor expression.…”

Section: Pharmacogenomicsmentioning

confidence: 99%