The Influence of OPRM1 A118G Polymorphism on the Dosage of Morphine in Patients with Advanced Liver Cancer

Cheng, Hongzhen; Chu, Xiao‐Yan; Yi, Shenghua

doi:10.29271/jcpsp.2021.11.1375

Cited by 3 publications

(2 citation statements)

References 2 publications

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“…Additionally, the analgesic effects of morphine and fentanyl are mediated by the µ-opioid receptor. There is evidence that the G allele found in our patient is associated with increased morphine or fentanyl consumption [ 53 , 54 , 55 , 56 , 57 , 58 ].…”

Section: Discussion and Pharmaceutical Assessmentmentioning

confidence: 82%

Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy

Wiss

Stäuble

Schwabedissen

et al. 2023

JPM

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Patients suffering from chronic pain may respond differently to analgesic medications. For some, pain relief is insufficient, while others experience side effects. Although pharmacogenetic testing is rarely performed in the context of analgesics, response to opiates, non-opioid analgesics, and antidepressants for the treatment of neuropathic pain can be affected by genetic variants. We describe a female patient who suffered from a complex chronic pain syndrome due to a disc hernia. Due to insufficient response to oxycodone, fentanyl, and morphine in addition to non-steroidal anti-inflammatory drug (NSAID)-induced side effects reported in the past, we performed panel-based pharmacogenotyping and compiled a medication recommendation. The ineffectiveness of opiates could be explained by a combined effect of the decreased activity in cytochrome P450 2D6 (CYP2D6), an increased activity in CYP3A, and an impaired drug response at the µ-opioid receptor. Decreased activity for CYP2C9 led to a slowed metabolism of ibuprofen and thus increased the risk for gastrointestinal side effects. Based on these findings we recommended hydromorphone and paracetamol, of which the metabolism was not affected by genetic variants. Our case report illustrates that an in-depth medication review including pharmacogenetic analysis can be helpful for patients with complex pain syndrome. Our approach highlights how genetic information could be applied to analyze a patient’s history of medication ineffectiveness or poor tolerability and help to find better treatment options.

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Section: Discussion and Pharmaceutical Assessmentmentioning

confidence: 82%

Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy

Wiss

Stäuble

Schwabedissen

et al. 2023

JPM

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“…OPRM1 A118G mutation is the most common and reported functional gene. Some studies have shown that its gene mutation reduces the efficacy of various opioids, and patients with GG need more opioids to relieve pain [ 10 – 13 ].On the other hand, some studies have shown that OPRM1 A118G mutation can enhance the analgesic effect of patients [ 14 – 16 ].…”

Section: Discussionmentioning

confidence: 99%

Is OPRM1 genotype a valuable predictor of VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl?

et al. 2023

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Objective This study was conducted to examine the association between the A118G polymorphism of the OPRM1 gene and the risk of increased VAS scores in patients with colorectal cancer who underwent laparoscopic radical resection for which fentanyl was used. Methods The OPRM1 A118G genotype in subjects were detected. The relationship between the A118G polymorphism of the OPRM1 gene and increased Visual Analogue Scale (VAS) scores throughout the perioperative period was explored. A total of 101 patients receiving fentanyl anesthesia undergoing laparoscopic radical resection of colon tumors at Zhongshan Hospital, Fudan University between July 2018 and December 2020 were investigated in the present study. The relative risk between the A118G polymorphism of the OPRM1 gene and VAS ≥ 4 in the PACU was estimated using the adjusted effect relationship diagram, baseline characteristic analysis, and multiple logistic regression analysis. The relationship between the A118G polymorphism of the OPRM1 gene and VAS in the PACU, as well as perioperative fentanyl usage, was examined after confounders were adjusted. Results Subjects with OPRM1 A118G wild gene A were less sensitive to fentanyl, which was a risk factor for PACU VAS ≥ 4. Before the model was adjusted, the odds ratio (OR) was 14.73 (P = 0.001). After adjusting for age, sex, weight, height, and the duration of surgery, the OR increased to 16.55 (P = 0.001). When adjusting for age, sex, weight, height, surgery duration, COMT Val158Met gene polymorphism, CYP3A4 *1G gene polymorphism, and CYP3A5 *3gene polymorphism, the OR was 19.94 (P = 0.002). Moreover, OPRM1 A118G wild type gene A was found to be a risk factor for increased dosage of fentanyl in the PACU. Before the model was adjusted, the OR reached 16.90 (P = 0.0132). After adjusting for age, sex, body weight, intraoperative fentanyl dosage, surgery duration, and height, the OR was 13.81, (P = 0.0438). When adjusting for age, sex, weight, height, intraoperative fentanyl dosage, surgery duration, COMT Val158Met gene polymorphism, CYP3A4 *1G gene polymorphism, and CYP3A5 *3 gene polymorphism, the OR reached 15.23, (P = 0.0205). Conclusion The A118G polymorphism of the OPRM1 gene carrying wild gene A was a risk factor for VAS ≥ 4 in the PACU. Moreover, it is a risk factor for increased dosage of fentanyl in the PACU.

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Pharmacogenetics of Biochemically Verified Abstinence in an Opioid Agonist Therapy Randomized Clinical Trial of Methadone and Buprenorphine/Naloxone

Kazi,

Chenoweth,

Jutras‐Aswad

et al. 2023

Clin Pharma and Therapeutics

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Methadone and buprenorphine/naloxone are opioid agonist therapies for opioid use disorder treatment. Genetic factors contribute to individual differences in opioid response; however, little is known regarding genetic associations with clinical outcomes in people receiving opioid agonist therapies. Participants diagnosed with opioid use disorder, principally consisting of prescription opioids (licit or illicit), were randomized to methadone or buprenorphine/naloxone for 24 weeks of daily treatment (NCT03033732). Urine was collected at 12 biweekly study visits and analyzed for non‐treatment opioids. Variants in genes involved in methadone metabolism (CYP2B6, CYP2C19, and CYP3A4), buprenorphine metabolism (CYP3A4 and UGT2B7), and μ‐opioid receptor function (OPRM1) were genotyped and analyzed for their association with the number of non‐treatment opioid‐free urine screens. Primary analyses focused on the last 12 weeks (6 study visits, post‐titration) of treatment among those reporting White ethnicity. Additional sensitivity and exploratory analyses were performed. Among methadone‐treated participants (n = 52), the OPRM1 rs1799971 AA genotype (vs. G‐genotypes, i.e., having one or two G alleles) was associated with greater opioid‐free urine screens (incidence rate ratio = 5.24, 95% confidence interval (CI) = 2.43–11.26, P = 0.000023); longitudinal analyses showed a significant genotype‐by‐time interaction over the full 24 weeks (12 study visits, β = −0.28, 95% CI = −0.45 to −0.11, P = 0.0015). Exploratory analyses suggest an OPRM1 rs1799971 genotype effect on retention. No evidence of association was found between other genetic variants, including in metabolic variants, and non‐treatment opioid‐free urine screens in the methadone or buprenorphine/naloxone arms. Those with the OPRM1 rs1799971 G‐genotypes may have a poorer response to methadone maintenance treatment, an effect that persisted through 24 weeks of treatment.

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The Influence of OPRM1 A118G Polymorphism on the Dosage of Morphine in Patients with Advanced Liver Cancer

Cited by 3 publications

References 2 publications

Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy

Pharmacogenetic Analysis Enables Optimization of Pain Therapy: A Case Report of Ineffective Oxycodone Therapy

Is OPRM1 genotype a valuable predictor of VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl?

Pharmacogenetics of Biochemically Verified Abstinence in an Opioid Agonist Therapy Randomized Clinical Trial of Methadone and Buprenorphine/Naloxone

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