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Biomedicine & Pharmacotherapy =... Jun 2024Opioid receptor agonists are often used when cancer patients undergo surgery or analgesic treatment. As analgesics in clinical care, opioids can provide intraoperative... (Review)
Review
Opioid receptor agonists are often used when cancer patients undergo surgery or analgesic treatment. As analgesics in clinical care, opioids can provide intraoperative or to chronic cancer pain relief. Immune function plays an important role in anti-cancer therapy, with cellular immunity, comprised principally of T-lymphocytes and natural killer cells, representing the primary anti-cancer immune response. However, it remains unclear whether immune function is further affected with the use of opioids in already immunocompromised cancer patients. This article provides a review of the effects of commonly used clinical opioids, including morphine, oxycodone, fentanyl and tramadol, on immune function in cancer patients. It provides a summary of current evidence regarding the immunomodulatory effects of opioids in the cancer setting and mechanisms underlying these interactions.
Topics: Humans; Analgesics, Opioid; Neoplasms; Cancer Pain; Animals; T-Lymphocytes; Immune System
PubMed: 38701564
DOI: 10.1016/j.biopha.2024.116665 -
JAMA Health Forum Oct 2023Insurers are increasingly limiting the duration of opioid prescriptions for acute pain. Among patients undergoing surgery, it is unclear whether implementation of these...
IMPORTANCE
Insurers are increasingly limiting the duration of opioid prescriptions for acute pain. Among patients undergoing surgery, it is unclear whether implementation of these limits is associated with changes in opioid prescribing and patient-reported outcomes, such as pain.
OBJECTIVE
To assess changes in surgical opioid prescribing and patient-reported outcomes after implementation of an opioid prescribing limit by a large commercial insurer in Michigan.
DESIGN, SETTING, AND PARTICIPANTS
This was a cross-sectional study with an interrupted time series analysis. Data analyses were conducted from October 1, 2022, to February 28, 2023. The primary data source was the Michigan Surgical Quality Collaborative, a statewide registry containing data on opioid prescribing and patient-reported outcomes from adults undergoing common general surgical procedures. This registry is linked to Michigan's prescription drug monitoring program database, allowing observation of opioid dispensing. The study included 6045 adults who were covered by the commercial insurer and underwent surgery from January 1, 2017, to October 31, 2019.
EXPOSURE
Policy limiting opioid prescriptions to a 5-day supply in February 2018.
MAIN OUTCOMES AND MEASURES
Among all patients, segmented regression models were used to assess for level or slope changes during February 2018 in 3 patient-reported outcomes: pain in the week after surgery (assessed on a scale of 1-4: 1 = none, 2 = minimal, 3 = moderate, and 4 = severe), satisfaction with surgical experience (scale of 0-10, with 10 being the highest satisfaction), and amount of regret regarding undergoing surgery (scale of 1-5, with 1 being the highest level of regret). Among patients with a discharge opioid prescription and a dispensed opioid prescription (prescription filled within 3 days of discharge), additional outcomes included total morphine milligram equivalents in these prescriptions, a standardized measure of opioid volume.
RESULTS
Among the 6045 patients included in the study, mean (SD) age was 48.7 (12.6) years and 3595 (59.5%) were female. Limit implementation was not associated with changes in patient-reported satisfaction or regret and was associated with only a slight level decrease in patient-reported pain score (-0.15 [95% CI, -0.26 to -0.03]). Among 4396 patients (72.7%) with a discharge and dispensed opioid prescription, limit implementation was associated with a -22.3 (95% CI, -32.8 to -11.9) and -26.1 (95% CI, -40.9 to -11.3) level decrease in monthly mean total morphine milligram equivalents of discharge and dispensed opioid prescriptions, respectively. These decreases corresponded approximately to 3 to 3.5 pills containing 5 mg of oxycodone.
CONCLUSIONS
This cross-sectional analysis of data from adults undergoing general surgical procedures found that implementation of an insurer's limit was associated with modest reductions in opioid prescribing but not with worsened patient-reported outcomes. Whether these findings generalize to other procedures warrants further study.
Topics: Adult; Humans; Female; Middle Aged; Male; Analgesics, Opioid; Cross-Sectional Studies; Insurance Carriers; Pain, Postoperative; Practice Patterns, Physicians'; Oxycodone; Patient Reported Outcome Measures
PubMed: 37831460
DOI: 10.1001/jamahealthforum.2023.3541 -
Cureus Sep 2023Beaver tail liver is a rare hepatic anatomical variant in which the left hepatic lobe extends into the left upper quadrant and surrounds the spleen. This extension of...
Beaver tail liver is a rare hepatic anatomical variant in which the left hepatic lobe extends into the left upper quadrant and surrounds the spleen. This extension of the left hepatic lobe consists of normal hepatic parenchyma with no functional liver impairment. In trauma cases, however, the extended left hepatic lobe is vulnerable to injury and confused for a splenic injury due to similar echogenicities and densities on ultrasound and CT. It is also misdiagnosed as a splenic subcapsular hematoma, perisplenic hemorrhage, or mass. Usually, the beaver tail liver is encountered incidentally in patients. We present a 67-year-old male with a history of chronic obstructive lung disease, coronary artery disease, myocardial infarction, and aortic valve replacement. The patient was admitted for further evaluation and placed under the Baker Act for attempting to overdose on oxycodone to commit suicide. Initial imaging identified an ill-defined lesion on CT angiography, which raised concerns for potential malignancy of the liver. Ultimately, an MRI of the abdomen ruled out a malignant lesion due to a lack of abnormal contrast enhancement over the circumscribed region. Consequently, further imaging of the liver led to the incidental discovery of the beaver tail liver in this patient. Due to the rarity of this variant, available literature regarding beaver tail liver is limited to several case reports describing it as an incidental finding. This case highlights the rare nature and unique challenges the beaver tail liver presents for emergency medicine physicians, surgeons, and radiologists interpreting imaging studies without knowledge of its existence. It is important to emphasize how the unexpected presence of the left hepatic lobe in the upper left quadrant of the abdomen can lead to misinterpretations in FAST (focused assessment with sonography in trauma) exams and CT scans. Using non-invasive tools, such as color Doppler, is one way to reduce the incorrect diagnosis of hepatic anatomic variants.
PubMed: 37789993
DOI: 10.7759/cureus.44579 -
European Journal of Pharmaceutical... Mar 2024Oxycodone is one of the most commonly used opioids to treat moderate to severe pain. It is metabolized mainly by CYP3A4 and CYP2D6, while only a small fraction of the...
Exploring the impact of CYP2D6 and UGT2B7 gene-drug interactions, and CYP-mediated DDI on oxycodone and oxymorphone pharmacokinetics using physiologically-based pharmacokinetic modeling and simulation.
Oxycodone is one of the most commonly used opioids to treat moderate to severe pain. It is metabolized mainly by CYP3A4 and CYP2D6, while only a small fraction of the dose is excreted unchanged into the urine. Oxymorphone, the metabolite primarily formed by CYP2D6, has a 40- to 60-fold higher mu-opioid receptor affinity than the parent compound. While CYP2D6-mediated gene-drug-interactions (GDIs) and drug-drug interactions (DDIs) are well-studied, they only account for a portion of the variability in oxycodone and oxymorphone exposure. The combined impact of CYP2D6-mediated GDIs and DDIs, CYP3A4-mediated DDIs, and UGT2B7 GDIs is not fully understood yet and hard to study in head-to-head clinical trials given the relatively large number of scenarios. Instead, we propose the use of a physiologically-based pharmacokinetic model that integrates available information on oxycodone's metabolism to characterize and predict the impact of DDIs and GDIs on the exposure of oxycodone and its major, pharmacologically-active metabolite oxymorphone. To this end, we first developed and verified a PBPK model for oxycodone and its metabolites using published clinical data. The verified model was then applied to determine the dose-exposure relationship of oxycodone and oxymorphone stratified by CYP2D6 and UGT2B7 phenotypes respectively, and administered perpetrators of CYP-based drug interactions. Our simulations demonstrate that the combination of CYP2D6 UM and a UGT2B7Y (268) mutation may lead to a 2.3-fold increase in oxymorphone exposure compared to individuals who are phenotyped as CYP2D6 NM / UGT2B7 NM. The extent of oxymorphone exposure increases up to 3.2-fold in individuals concurrently taking CYP3A4 inhibitors, such as ketoconazole. Inhibition of the CYP3A4 pathway results in a relative increase in the partial metabolic clearance of oxycodone to oxymorphone. Oxymorphone is impacted to a higher extent by GDIs and DDIs than oxycodone. We predict oxymorphone exposure to be highest in CYP2D6 UMs/UGT2B7 PMs in the presence of ketoconazole (strong CYP3A4 index inhibitor) and lowest in CYP2D6 PMs/UGT2B7 NMs in the presence of rifampicin (strong CYP3A4 index inducer) covering a 55-fold exposure range.
Topics: Humans; Oxycodone; Oxymorphone; Cytochrome P-450 CYP2D6; Ketoconazole; Cytochrome P-450 CYP3A; Drug Interactions; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 CYP3A Inducers; Guanine Nucleotide Dissociation Inhibitors; Glucuronosyltransferase
PubMed: 38171419
DOI: 10.1016/j.ejps.2023.106689 -
BMC Pharmacology & Toxicology Nov 2023Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced...
OBJECTIVE
Adverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.
METHODS
Evidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.
RESULTS
Based on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.
CONCLUSION
Polymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.
Topics: Humans; Analgesics, Opioid; Oxycodone; Case-Control Studies; Polymorphism, Single Nucleotide; Genotype; Drug-Related Side Effects and Adverse Reactions
PubMed: 37990344
DOI: 10.1186/s40360-023-00708-4 -
Laryngoscope Investigative... Aug 2023To identify changes in otolaryngologists' opioid prescribing trends for Medicare beneficiaries associated with the enactment of state laws that limit the duration of...
OBJECTIVES
To identify changes in otolaryngologists' opioid prescribing trends for Medicare beneficiaries associated with the enactment of state laws that limit the duration of prescriptions to 3-7 days in the years 2016 and 2017 in the United States.
METHODS
Through the Centers for Medicare and Medicaid Services (CMS) database, we retrieved data on Medicare enrollment and on the total days prescribed and total number of beneficiaries for the drugs codeine/acetaminophen, hydrocodone/acetaminophen, oxycodone HCl, oxycodone/acetaminophen, and tramadol HCl, by each otolaryngologist prescriber in 13 states from January 2013 to December 2019. We modeled trends using linear spline regression models that controlled for Medicare beneficiaries' state-level socio-demographic characteristics' fixed effects.
RESULTS
Across the 13 states, the number of days of all five opioids prescribed per beneficiary declined by 8.35 (SD = 12.61). The most commonly prescribed opioid type by otolaryngologists during the 5-year study period was tramadol HCl (28.72 days/beneficiary) followed by oxycodone HCl (19.99 days/beneficiary). All opioids had declines in prescription days over this time window and higher rates of decline in the years following law passage. Four states experienced statistically significant declines in the prescriptions of all opioids after the year of legislation passage ( < .05). Some states that had the greatest inclines in opioid prescriptions in the years prior to law enactment also experienced the greatest reductions in the time after legislation enactment.
CONCLUSIONS
Opioid prescribing practices of otolaryngologists may have been affected by opioid prescription duration limiting laws passed in 13 states in 2016 and 2017.
LEVEL OF EVIDENCE
Level 4.
PubMed: 37621267
DOI: 10.1002/lio2.1085 -
Frontiers in Psychiatry 2024
PubMed: 38544850
DOI: 10.3389/fpsyt.2024.1382894 -
Frontiers in Pharmacology 2023The drug overdose crisis has spawned serious health consequences, including the increased incidence of substance use disorders (SUDs), conditions manifested by...
The drug overdose crisis has spawned serious health consequences, including the increased incidence of substance use disorders (SUDs), conditions manifested by escalating medical and psychological impairments. While medication management is a key adjunct in SUD treatment, this crisis has crystallized the need to develop additional therapeutics to facilitate extended recovery from SUDs. The "hunger hormone" ghrelin acts by binding to the growth hormone secretagogue receptor 1α (GHS1αR) to control homeostatic and hedonic aspects of food intake and has been implicated in the mechanisms underlying SUDs. Preclinical studies indicate that GHS1αR antagonists and inverse agonists suppress reward-related signaling associated with cocaine and opioids. In the present study, we found that the GHS1αR antagonist JMV2959 was efficacious to suppress both cue-reinforced cocaine and oxycodone drug-seeking, but not cocaine or oxycodone self-administration in male Sprague-Dawley rats. These data suggest a role of the ghrelin-GHS1αR axis in mediating overlapping reward-related aspects of cocaine and oxycodone and premises the possibility that a GHS1αR antagonist may be a valuable therapeutic strategy for relapse vulnerability in SUDs.
PubMed: 37795028
DOI: 10.3389/fphar.2023.1268366 -
BMJ Open Mar 2024This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. (Observational Study)
Observational Study
OBJECTIVES
This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021.
DESIGN
This is an observational study.
SETTING
More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them.
METHODS
The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics.
RESULTS
There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics.
CONCLUSIONS
Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.
Topics: Humans; Analgesics, Opioid; Drug Overdose; Heroin; Narcotics; Opiate Overdose; Oxycodone; Tennessee; United States
PubMed: 38453203
DOI: 10.1136/bmjopen-2023-073765 -
Journal of Personalized Medicine May 2024Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid... (Review)
Review
Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone's prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients' quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations.
PubMed: 38793067
DOI: 10.3390/jpm14050483