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Biomedicine & Pharmacotherapy =... Jun 2024Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive...
BACKGROUND
Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes.
MATERIALS AND METHODS
An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded.
RESULTS
The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present.
CONCLUSION
The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.
PubMed: 38876046
DOI: 10.1016/j.biopha.2024.116882 -
Biomedicine & Pharmacotherapy =... Jun 2024The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be...
The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.
PubMed: 38870630
DOI: 10.1016/j.biopha.2024.116931 -
World Journal of Emergency Medicine 2024To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments (EDs) in the USA from...
BACKGROUND
To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments (EDs) in the USA from 2007 to 2018.
METHODS
Data were gathered from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2007 to 2018. The study population included individuals of all ages presenting to USA EDs. The NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back pain. The main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time period.
RESULTS
There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007 (244,000 visits) to 2018 (92,000 visits). The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older (from 43.8% to 57.6%), female patients (from 54.5% to 62.0%), black patients (from 22.5% to 30.4%), and Hispanic/Latino patients (from 9.4% to 19.6%). Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007, with a decrease to 68.5% in 2018. Pure oxycodone was the second most prescribed medication, accounting for 6.1% in 2007 and 31.5% in 2018.
CONCLUSION
The overall number of oxycodone-containing analgesics decreased significantly from 2007 to 2018. However, that number trended upward in 45-year-old and older, female, black, or Hispanic/Latino patients from 2007 to 2018. The total amount of pure oxycodone increased significantly from 2007 to 2008.
PubMed: 38855375
DOI: 10.5847/wjem.j.1920-8642.2024.002 -
Biomedicine & Pharmacotherapy =... Jun 2024The association between polymorphisms of the human ATP binding cassette subfamily B member 1 (ABCB1) gene and opioid response has attracted intense attention recently....
The association between polymorphisms of the human ATP binding cassette subfamily B member 1 (ABCB1) gene and opioid response has attracted intense attention recently. As the ABCB1 gene encodes for the transporter P-glycoprotein in the brain and intestine involved in the pharmacokinetics of opioids, we investigated the effects of ABCB1 genetic polymorphisms on doses of opioids for pain relief and determined which pharmacokinetic process was affected in cancer pain patients. Sixty-eight cancer pain patients admitted for intrathecal therapy (ITT) were included. The association between ABCB1 genetic polymorphisms (C3435T, C1236T, G2677T/A and A61G) and systemic doses of opioids before ITT were investigated. Concentrations of oxycodone in plasma and cerebrospinal fluid (CSF) were determined by HPLC-MS/MS in 17 patients treated with oral oxycodone before ITT, and the influences of ABCB1 genetic polymorphisms on plasma-concentration to oral-dose ratios and CSF-concentration to plasma-concentration ratios of oral oxycodone were further analyzed. ABCB1 C3435T and G2677T/A polymorphisms were significantly associated with systemic doses of opioids before ITT, which coincided with the influences of ABCB1 C3435T and G2677T/A polymorphisms on the ratios of plasma-concentration to oral-dose. However, no significant difference was found in ratios of CSF-concentration to plasma-concentration among ABCB1 SNP genotypes. The present study provided the first evidence that ABCB1 C3435T and G2677T/A polymorphisms affect opioid requirement in cancer pain patients via altering transportation function of P-glycoprotein in the intestine, which will further expand our knowledge about pharmacokinetics of opioids and could contribute to the individualization of opioids use.
PubMed: 38850645
DOI: 10.1016/j.biopha.2024.116897 -
Journal of Orthopaedic Surgery and... Jun 2024Continuous peripheral nerve blocks are widely used for anesthesia and postoperative analgesia in lower limb surgeries. The authors aimed to develop a novel continuous...
BACKGROUND
Continuous peripheral nerve blocks are widely used for anesthesia and postoperative analgesia in lower limb surgeries. The authors aimed to develop a novel continuous sacral plexus block procedure for analgesia during total knee arthroplasty.
METHODS
The study comprised two stages. In Stage I, the authors built upon previous theories and technological innovations to develop a novel continuous sacral plexus block method, ultrasound-guided continuous parasacral ischial plane block (UGCPIPB) and subsequently conducted a proof-of-concept study to assess its effectiveness and feasibility. Stage II involved a historical control study to compare clinical outcomes between patients undergoing this new procedure and those receiving the conventional procedure.
RESULTS
The study observed a 90% success rate in catheter placement. On postoperative day (POD) 1, POD2, and POD3, the median visual analog scale (VAS) scores were 3 (range, 1.5-3.5), 2.5 (1.6-3.2), and 2.7 (1.3-3.4), respectively. Furthermore, 96.3% of the catheters remained in place until POD3, as confirmed by ultrasound. The study revealed a significant increase in skin temperature and peak systolic velocity of the anterior tibial artery on the blocked side compared with those on the non-blocked side. Complications included catheter clogging in one patient and leakage at the insertion site in two patients. In Stage II, the novel technique was found to be more successful than conventional techniques, with a lower catheter displacement rate than the conventional procedure for continuous sciatic nerve block.
CONCLUSION
UGCPIPB proved to be an effective procedure and safe for analgesia in total knee arthroplasty.
CHINESE CLINICAL TRIAL REGISTRY NUMBER
ChiCTR2300068902.
Topics: Humans; Pain, Postoperative; Arthroplasty, Replacement, Knee; Nerve Block; Male; Female; Aged; Ultrasonography, Interventional; Middle Aged; Proof of Concept Study; Lumbosacral Plexus; Feasibility Studies; Pain Management; Aged, 80 and over; Ischium; Pain Measurement
PubMed: 38849964
DOI: 10.1186/s13018-024-04822-9 -
Trials Jun 2024Obese patients undergoing laparoscopic sleeve gastrectomy (LSG) are particularly at risk of opioid-related side effects. To reduce patient exposure to opioids,...
The effect of pre-emptive oral pregabalin on opioid consumption in patients undergoing laparoscopic sleeve gastrectomy with an analysis of intraoperative hemodynamic stability and quality of recovery: study protocol for a randomized, prospective, double-blind study.
BACKGROUND
Obese patients undergoing laparoscopic sleeve gastrectomy (LSG) are particularly at risk of opioid-related side effects. To reduce patient exposure to opioids, multimodal analgesia, which involves the use of drugs of different classes, may be utilized. One of the drugs under consideration is pregabalin. Despite an opioid-sparing potential, few studies assess the role of pregabalin as an element of multimodal analgesia in LSG. Considering the limited number and inconsistent results of available studies, we decided to conduct a randomized, prospective study on the effect of preemptive pregabalin administration in obese patients on opioid consumption, pain scores, the incidence of opioid side effects, and hemodynamical stability.
METHODS
The study is designed as a prospective randomized controlled trial with double-blinding. Randomization will be performed in a block with a parallel 1:1 allocation. The intervention will involve receiving a pregabalin 150 mg capsule 1-2 h before the surgery, whereas the control group will receive an identically looking placebo. The primary outcome measure will be total oxycodone consumption in the first 24 h following surgery. Secondary outcome measures will be pain severity assessed using the Numerical Rating Scale (NRS) 1, 6, 12, and 24 h after surgery, postoperative sedation on the Ramsay scale, PONV impact scale, the incidence of desaturation episodes < 94%, and episodes of blurred vision at 1, 6, 12, and 24 h after surgery, intraoperative hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), total fluid volume, and total ephedrine dose. Patient comfort will be additionally assessed using the QoR-40 questionnaire at discharge.
DISCUSSION
The study will explore the efficacy and safety of preemptive pregabalin in a dose of 150 mg as a co-analgesic used in multimodal analgesia for LSG. As studies on opioid-sparing regimes concern the safety of obese patients, we aim to contribute objective data with a relatively large study sample size. The result of the present clinical trial may support the reassessment of recommendations to use pregabalin in the studied population.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05804591. Registered on 07.04.2023.
Topics: Humans; Pregabalin; Double-Blind Method; Prospective Studies; Analgesics, Opioid; Gastrectomy; Pain, Postoperative; Laparoscopy; Hemodynamics; Randomized Controlled Trials as Topic; Adult; Treatment Outcome; Pain Measurement; Administration, Oral; Analgesics; Middle Aged; Male; Time Factors; Female; Young Adult; Recovery of Function; Oxycodone
PubMed: 38849875
DOI: 10.1186/s13063-024-08225-3 -
Scandinavian Journal of Pain Jan 2024Addressing the challenges of ambulatory surgery involves balancing effective pain relief with minimizing the side effects of pain medication. Due to the heightened risk...
OBJECTIVES
Addressing the challenges of ambulatory surgery involves balancing effective pain relief with minimizing the side effects of pain medication. Due to the heightened risk of opioid abuse, Helsinki University Hospital (Finland) has had a stringent oxycodone prescription policy. This policy prompts an exploration into whether ambulatory surgery patients experience severe post-surgical pain and whether an increase in prescribed opioids would cause elevation in adverse effects.
METHODS
This prospective cohort study, with a 1-week follow-up, included 111 adult ambulatory surgery patients (orthopaedics, urology). The patients documented their pain levels within the first postoperative week (using a numerical rating scale [NRS] of 0-10) and pain medication intake up to two days postoperatively. Furthermore, they completed a questionnaire assessing their satisfaction with pain relief, medication-related adverse effects, and adherence to instructions. Medication intake was cross-referenced with the provided instructions and prescriptions.
RESULTS
A notable 56% of patients reported experiencing intense pain (NRS ≥5) within a week following surgery. Of these, 52% received a single dose of slow-release oxycodone (5-20 mg) at discharge for use on the night of surgery. Predominantly prescribed pain medications included a combination of paracetamol and codeine (64%) or ibuprofen (62%). Satisfaction rates were high, with 87% expressing satisfaction with pain medication given at hospital discharge and 90% expressing contentment with the prescribed medication. The most common adverse effects were tiredness/grogginess (45%), sleep disturbances (38%), nausea (37%), and constipation (27%). Also, 24% of patients self-reported deviations from medication instructions. A comparison of self-reported and instructed medications revealed that 14% exceeded prescribed dosages, and 28% opted for preparations different from those prescribed. Notably, patients who self-reported deviations from instructions differed from those objectively deviating from instructions.
CONCLUSIONS
Although 56% of patients had intense pain, the majority expressed satisfaction with the provided pain relief. Instances of non-adherence to medication instructions were prevalent, often going unnoticed by the patients themselves.
Topics: Humans; Male; Female; Patient Satisfaction; Middle Aged; Pain, Postoperative; Prospective Studies; Ambulatory Surgical Procedures; Adult; Oxycodone; Analgesics, Opioid; Aged; Finland; Medication Adherence; Pain Measurement
PubMed: 38843006
DOI: 10.1515/sjpain-2023-0133 -
Journal of Pain and Symptom Management Jun 2024Strong opioids are the cornerstone in the treatment of cancer-related pain.
CONTEXT
Strong opioids are the cornerstone in the treatment of cancer-related pain.
OBJECTIVES
This study aims to compare analgesic effectiveness of different strong opioids for the treatment of cancer-related pain.
METHODS
PubMed and Embase were searched for RCTs that compared strong opioids for treatment of cancer-related pain against one another. A network meta-analysis was conducted and the related Surface Under the Cumulative RAnking (SUCRA)-based treatment ranks were calculated. Primary outcome was pain intensity (numerical rating scale (NRS)) and/or the percentage of patients with ≥50% pain reduction, after 1 and 2-4 weeks.
RESULTS
Sixteen RCTs (1813 patients) were included. Methadone showed, with a high certainty of evidence, increased ORs for treatment success at 1 week, compared with morphine, buprenorphine, fentanyl, and oxycodone, range 3.230-36.833. Methadone had the highest likelihood to be the treatment of preference (ToP) (SUCRA 0.9720). For fentanyl, ORs were lower, however significant and with high certainty. After 2-4 weeks, methadone again showed the highest likelihood for ToP, however, with moderate certainty and non-significant ORs. The combination of morphine/methadone, compared with morphine, buprenorphine, fentanyl, hydromorphone, methadone, and oxycodone achieved a treatment effect of mean NRS difference after 2-4 weeks between -1.100 and -1.528 and had the highest likelihood for ToP.
CONCLUSION
The results suggest that methadone possibly deserves further promotion as first-line treatment for the treatment of cancer-related pain.
PubMed: 38838946
DOI: 10.1016/j.jpainsymman.2024.05.022 -
PloS One 2024In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences...
BACKGROUND
In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences short-term clinician prescribing practices. We sought to understand the long-term impact on postoperative opioid prescribing habits after an opioid default pill count reduction.
MATERIALS AND METHODS
A retrospective electronic medical record system (EMRS) review was conducted in a healthcare system comprised of seven affiliated hospitals. Patients who underwent a surgical procedure and were prescribed an opioid on discharge between 2017-2021 were evaluated. All prescriptions were converted into morphine equivalents (MME). Analyses were performed with the chi-square test and Bonferonni adjusted t-test.
RESULTS
191,379 surgical procedures were studied. The average quantity of opioids prescribed decreased from 32 oxycodone 5 mg tablets in 2017 to 21 oxycodone 5 mg tablets in 2021 (236 MME to 154 MME, p<0.001). The percentage of patients obtaining a refill within 90 days of surgery varied between 18.3% and 19.9% (p<0.001). Patients with a pre-existing opioid prescription and opioid-naïve patients both had significant reductions in prescription quantities above the default MME (79.7% to 60.6% vs. 65.3% to 36.9%, p<0.001). There was no significant change in refills for both groups (pre-existing 36.7% to 38.3% (p = 0.1) vs naïve 15.0% to 15.3% (p = 0.29)).
CONCLUSIONS
The benefits of decreasing the default opioid pill count continue to accumulate long after the original change. Physician uptake of small changes to default EMRS practices represents a sustainable and effective intervention to reduce the quantities of postoperative opioids prescribed without deleterious effects on outpatient opiate requirements.
Topics: Humans; Male; Female; Analgesics, Opioid; Middle Aged; Retrospective Studies; Pain, Postoperative; Drug Prescriptions; Practice Patterns, Physicians'; Adult; Aged; Electronic Health Records; Oxycodone
PubMed: 38833500
DOI: 10.1371/journal.pone.0304100 -
Drug Design, Development and Therapy 2024Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
PURPOSE
Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery.
METHODS
In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1.
RESULTS
All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; =0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; =0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups.
CONCLUSION
For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2100052085).
Topics: Humans; Oxycodone; Double-Blind Method; Middle Aged; Male; Female; Laparoscopy; Pain, Postoperative; Visceral Pain; Aged; Analgesics, Opioid; Adult; Digestive System Surgical Procedures; Dexmedetomidine; Sufentanil; Analgesia, Patient-Controlled; Flurbiprofen
PubMed: 38828025
DOI: 10.2147/DDDT.S464518