CYP2D6 Basic Genotyping of Patients with Chronic Pain Receiving Tramadol or Codeine. A Study in a Greek Cohort

Pain Medicine ◽  
2020 ◽  
Vol 21 (11) ◽  
pp. 3199-3204 ◽  
Author(s):  
Chrysanthi Batistaki ◽  
Eleni Chrona ◽  
Andreas Kostroglou ◽  
Georgia Kostopanagiotou ◽  
Maria Gazouli

Abstract Objective To assess CYP2D6 genotype prevalence in chronic pain patients treated with tramadol or codeine. Design Prospective cohort study. Setting General hospital, pain management unit. Subjects Patients with chronic pain, treated with codeine or tramadol. Methods Patients’ pain was assessed at baseline (numeric rating scale [NRS]; 0–10). Prescription of codeine or tramadol was selected randomly. The assessment of patients’ response to the drug in terms of pain relief and adverse effects was performed after 24 hours. Reduction of pain intensity of >50% or an NRS <4 was considered a positive response. Patients’ blood samples were collected during the first visit. Genotyping for the common variants CYP2D6 *2, *3, *4, *5, *6, *9, *10, *14, and *17 was performed, and alleles not carrying any polymorphic allele were classified as CYP2D6*1 (wild-type [wt]). Results Seventy-six consecutive patients were studied (20 males, 56 females), aged 21–85 years. Thirty-four received tramadol and 42 codeine. The main genotypes of CYP2D6 identified were the wt/wt (35.5%), the *4/wt (17.1%), and the *6/wt (10.5%). Adverse effects were common, especially in carriers of *9/*9, *5/*5, *5/*4, and *10/*10, as well as in variants including the 4 allele (*4/*1 [38.4%] and *4/*4 [42.8%]). Conclusions Genotyping can facilitate personalized pain management with opioids, as specific alleles are related to decreased efficacy and adverse effects.

2021 ◽  
Vol 10 (5) ◽  
pp. 973
Author(s):  
Shane Kaski ◽  
Patrick Marshalek ◽  
Jeremy Herschler ◽  
Sijin Wen ◽  
Wanhong Zheng

Patients with chronic pain managed with opioid medications are at high risk for opioid overuse or misuse. West Virginia University (WVU) established a High-Risk Pain Clinic to use sublingual buprenorphine/naloxone (bup/nal) plus a multimodal approach to help chronic pain patients with history of Substance Use Disorder (SUD) or aberrant drug-related behavior. The objective of this study was to report overall retention rates and indicators of efficacy in pain control from approximately six years of High-Risk Pain Clinic data. A retrospective chart review was conducted for a total of 78 patients who enrolled in the High-Risk Pain Clinic between 2014 and 2020. Data gathered include psychiatric diagnoses, prescribed medications, pain score, buprenorphine/naloxone dosing, time in clinic, and reason for dismissal. A linear mixed effects model was used to assess the pain score from the Defense and Veterans Pain Rating Scale (DVPRS) and daily bup/nal dose across time. The overall retention of the High-Risk Pain Clinic was 41%. The mean pain score demonstrated a significant downward trend across treatment time (p < 0.001), while the opposite trend was seen with buprenorphine dose (p < 0.001). With the benefit of six years of observation, this study supports buprenorphine/naloxone as a safe and efficacious component of comprehensive chronic pain treatment in patients with SUD or high-risk of opioid overuse or misuse.


2010 ◽  
Vol 1 (1) ◽  
pp. 24-33 ◽  
Author(s):  
K.K. Lemberg ◽  
T.E. Heiskanen ◽  
M. Neuvonen ◽  
V.K. Kontinen ◽  
P.J. Neuvonen ◽  
...  

AbstractOxycodone is a strong opioid and it is increasingly used in the management of acute and chronic pain. The pharmacodynamic effects of oxycodone are mainly mediated by the μ-opioid receptor. However, its affinity for the μ-opioid receptor is significantly lower compared with that of morphine and it has been suggested that active metabolites may play a role in oxycodone analgesia. Oxycodone is mainly metabolized by hepatic cytochrome (CYP) enzymes 2D6 and 3A4. Oxycodone is metabolized to oxymorphone, a potent μ-opioid receptor agonist by CYP2D6. However, CYP3A4 is quantitatively a more important metabolic pathway. Chronic pain patients often use multiple medications. Therefore it is important to understand how blocking or inducing these metabolic pathways may affect oxycodone induced analgesia. The aim of this study was to find out whether blocking CYP2D6 would decrease oxycodone induced analgesia in chronic pain patients.The effects of the antidepressant paroxetine, a potent inhibitor of CYP2D6, on the analgesic effects and pharmacokinetics of oral oxycodone were studied in 20 chronic pain patients using a randomized, double-blind, placebo-controlled cross-over study design. Pain intensity and rescue analgesics were recorded daily, and the pharmacokinetics and pharmacodynamics of oxycodone were studied on the 7th day of concomitant paroxetine (20 mg/day) or placebo administration. The patients were genotyped for CYP2D6, 3A4, 3A5 and ABCB1.Paroxetine had significant effects on the metabolism of oxycodone but it had no statistically significant effect on oxycodone analgesia or use of morphine for rescue analgesia. Paroxetine increased the dose-adjusted mean AUC0–12h of oxycodone by 19% (−23 to 113%; P = 0.003), and that of noroxycodone by 100% (5–280%; P < 0.0001) but decreased the AUC0–12 h of oxymorphone by 67% (−100 to −22%; P < 0.0001) and that of noroxymorphone by 68% (−100 to −16%; P < 0.0001).Adverse effects were also recorded in a pain diary for both 7-day periods (placebo/paroxetine). The most common adverse effects were drowsiness and nausea/vomiting. One patient out of four reported dizziness and headache during paroxetine co-administration, whereas no patient reported these during placebo administration (P = 0.0471) indicating that these adverse effects were due to paroxetine.No statistically significant associations of the CYP2D6 or CYP3A4/5 genotype of the patients and the pharmacokinetics of oxycodone or its metabolites, extent of paroxetine–oxycodone interaction, or analgesic effects were observed probably due to the limited number of patients studied.The results of this study strongly suggest that CYP2D6 inhibition does not significantly change oxycodone analgesia in chronic pain patients and that the analgesic activity of oxycodone is mainly due to the parent compound and that metabolites, e.g. oxymorphone, play an insignificant role. The clinical implication of these results is that induction of the metabolism of oxycodone may lead to inadequate analgesia while increased drug effects can be expected after addition of potent CYP3A4/5 inhibitors particularly if combined with CYP2D6 inhibitors or when administered to poor metabolizers of CYP2D6.


Author(s):  
Lupi Lestari ◽  
Elizeus Hanindito ◽  
Arie Utariani

Introduction: Effective postoperative pain management provides improved patient comfort and satisfaction, earlier mobilization, fewer pulmonary and cardiac complications, reduced risk deep vein thrombosis, fast recovery, and reduced cost of care. Preemptive analgesia, initiated before the surgical procedure to prevent pain in the early postoperative period, has the potential to be more effective than a similar analgesic treatment initiated after surgery. As a part of multimodal analgesia, the use of NSAIDs should always be considered for acute postoperative pain management. NSAIDs can be used preoperatively as a part of the preemptive regimen and for postoperative pain control to increase the efficacy of opioids and reduce its side effects. Material and Method: This research was experimental research with a case-control design of the study. The samples separated into two groups, the first group got ketoprofen suppository before the induction, and the second group didn’t get the ketoprofen suppository The intensity of pain measured with the Numeric Rating Scale (NRS) or Wong-Baker Faces Pain Scale was the variable studied at different postoperative times (30 min, 60 min, 120 min, 2-6 hours, 6-12 hours). The total amount of rescue analgesics (fentanyl) and side effects were other variables of this study. Result and Discussion: The result is ketoprofen suppository as preemptive analgesia administrations can reduce postoperative pain. Numeric Rating Scale was significantly lower in the ketoprofen group compared to the control group (p < 0,05) at 30 min, 60 min, 230 min, 2-6 hours, 6-12 hours. The number of postoperative analgesics needed in the recovery room was significant differences among both groups (p < 0,05). Conclusion: Preemptive analgesia in patients who underwent an operation with general anesthesia with ketoprofen suppository was effectively in blocking noxious stimuli and central sensitization, with subsequent prevention of acute postoperative pain.


2020 ◽  
Vol 4S;23 (8;4S) ◽  
pp. E183-S204
Author(s):  
Christopher Gharibo

Background: The COVID-19 pandemic has worsened the pain and suffering of chronic pain patients due to stoppage of “elective” interventional pain management and office visits across the United States. The reopening of America and restarting of interventional techniques and elective surgical procedures has started. Unfortunately, with resurgence in some states, restrictions are once again being imposed. In addition, even during the Phase II and III of reopening, chronic pain patients and interventional pain physicians have faced difficulties because of the priority selection of elective surgical procedures. Chronic pain patients require high intensity care, specifically during a pandemic such as COVID-19. Consequently, it has become necessary to provide guidance for triaging interventional pain procedures, or related elective surgery restrictions during a pandemic. Objectives: The aim of these guidelines is to provide education and guidance for physicians, healthcare administrators, the public and patients during the COVID-19 pandemic. Our goal is to restore the opportunity to receive appropriate care for our patients who may benefit from interventional techniques. Methods: The American Society of Interventional Pain Physicians (ASIPP) has created the COVID-19 Task Force in order to provide guidance for triaging interventional pain procedures or related elective surgery restrictions to provide appropriate access to interventional pain management (IPM) procedures in par with other elective surgical procedures. In developing the guidance, trustworthy standards and appropriate disclosures of conflicts of interest were applied with a section of a panel of experts from various regions, specialties, types of practices (private practice, community hospital and academic institutes) and groups. The literature pertaining to all aspects of COVID-19, specifically related to epidemiology, risk factors, complications, morbidity and mortality, and literature related to risk mitigation and stratification was reviewed. The evidence -- informed with the incorporation of the best available research and practice knowledge was utilized, instead of a simplified evidence-based approach. Consequently, these guidelines are considered evidence-informed with the incorporation of the best available research and practice knowledge. Results: The Task Force defined the medical urgency of a case and developed an IPM acuity scale for elective IPM procedures with 3 tiers. These included emergent, urgent, and elective procedures. Examples of emergent and urgent procedures included new onset or exacerbation of complex regional pain syndrome (CRPS), acute trauma or acute exacerbation of degenerative or neurological disease resulting in impaired mobility and inability to perform activities of daily living. Examples include painful rib fractures affecting oxygenation and post-dural puncture headaches limiting the ability to sit upright, stand and walk. In addition, urgent procedures include procedures to treat any severe or debilitating disease that prevents the patient from carrying out activities of daily living. Elective procedures were considered as any condition that is stable and can be safely managed with alternatives. Limitations: COVID-19 continues to be an ongoing pandemic. When these recommendations were developed, different stages of reopening based on geographical regulations were in process. The pandemic continues to be dynamic creating every changing evidence-based guidance. Consequently, we provided evidence-informed guidance. Conclusion: The COVID-19 pandemic has created unprecedented challenges in IPM creating needless suffering for pain patients. Many IPM procedures cannot be indefinitely postponed without adverse consequences. Chronic pain exacerbations are associated with marked functional declines and risks with alternative treatment modalities. They must be treated with the concern that they deserve. Clinicians must assess patients, local healthcare resources, and weigh the risks and benefits of a procedure against the risks of suffering from disabling pain and exposure to the COVID-19 virus. Key words: Coronavirus, COVID-19, interventional pain management, COVID risk factors, elective surgeries, interventional techniques, chronic pain, immunosuppression


2012 ◽  
Vol 3;15 (3;5) ◽  
pp. 213-223
Author(s):  
Juan Hwan Lee

Background: Epidural steroid injection has been frequently performed to treat chronic pain due to lumbosacral disc herniation (L-HIVD). However, a considerable number of patients do not achieve pain relief using this method because perineural or epidural adhesions prevent the spread of injectate into the epidural space. Percutaneous adhesiolysis (PA) is thought to be a useful method because it can eliminate the deleterious effects of adhesion. Objectives: This study aimed to evaluate the effectiveness of PA in managing chronic pain due to L-HIVD and the clinical and radiological predictive factors for the effectiveness of PA using NaviCath®. Study design: Retrospective study Setting: Spine hospital Methods: From a group of patients diagnosed with L-HIVD, we selected the 86 patients who underwent PA with NaviCath who had experienced chronic lower back or leg pain for at least 3 months and had failed to respond to anti-inflammatory medications or physical therapy of at least 1 month’s duration and fluoroscopy guided transforaminal epidural injection. We recorded the Numeric Rating Scale for back pain (NRS back) and leg pain (NRS leg) and the Oswestry Disability Index (ODI) at pretreatment, 2 weeks, and 3 months after treatment. Clinical data and magnetic resonance imaging (MRI) findings were obtained to assess the possible predictive factors for PA efficacy. Limitations: Retrospective chart review without a control group. Results: At 2 weeks after PA, significant improvement was observed in NRS back, NRS leg, and ODI compared with pretreatment. This improvement was maintained until 3 months after treatment. Among 86 patients, 61 (70.9%), 53 (61.6%) and 61 patients (70.9%) showed successful outcomes in NRS back, NRS leg, and ODI at 2 weeks, respectively. Among 74 patients who were followed up at 3 months, 47 (63.5%), 44 patients (59.5%), and 50 patients (67.6%) showed successful results in NRS back, NRS leg, and ODI at 3 months, respectively. A significantly higher proportion of patients with a history of previous lumbar surgery showed unsuccessful results on NRS back, NRS leg, and ODI scores at 2 weeks and 3 months. Co-existence of spinal stenosis was associated with a significantly higher proportion of unsuccessful results in NRS back and ODI at 2 weeks and 3 months, as well as NRS leg at 3 months. Patients with spondylolisthesis also showed a significantly higher proportion of unsuccessful results in NRS and ODI at 2 weeks. Conclusion: PA with NaviCath showed clinical effectiveness in the treatment of chronic pain due to L-HIVD that was not responsive to transforaminal epidural injection. Previous surgery and the presence of spinal stenosis or spondylolisthesis were poor prognostic predictors. This procedure may enable the physician to place the catheter tip and deliver medicine more precisely. Key words: Percutaneous adhesiolysis, lumbosacral disc herniation, Numeric Rating Scale, Oswetry Disability Index


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