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BioRxiv : the Preprint Server For... Jul 2023Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol would influence intake of...
Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol would influence intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with access to either alcohol (20% v/v) and water or only water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent extinction training and brains were processed for c-fos mRNA expression immediately following a cue-primed reinstatement test. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, female oxycodone+alcohol rats exhibited decreased demand elasticity for intravenous oxycodone and increased cue-primed reinstatement while male rats did not. Spontaneous withdrawal signs were correlated with oxycodone intake while alcohol intake was correlated with anxiety-like behavior. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor containing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and alters the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.
PubMed: 37546763
DOI: 10.1101/2023.07.20.549769 -
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 -
Oncology Letters Aug 2023There have been few studies on predictive biomarkers that may be useful to select the most suitable opioids to optimize therapeutic efficacy in individual patients with...
There have been few studies on predictive biomarkers that may be useful to select the most suitable opioids to optimize therapeutic efficacy in individual patients with cancer pain. We recently investigated the efficacy of morphine and oxycodone using single nucleotide polymorphisms (SNPs) of the catechol-O-methyltransferase () rs4680 gene as a biomarker (RELIEF study). To explore additional biomarkers that may enable the selection of an appropriate opioid for individual patients with cancer pain, three SNPs were examined: C-C motif chemokine ligand 11 (; rs17809012), histamine N-methyltransferase (; rs1050891) and transient receptor potential V1 (; rs222749), which were screened from 74 pain-related SNPs. These SNPs, which were identified as being significantly associated with the analgesic effect of morphine, were then used to genotype the 135 patients in the RELIEF study who had been randomized into a morphine group (n=69) or an oxycodone group (n=66). The present study then assessed whether the SNPs could also be used as selective biomarkers to predict which opioid(s) might be the most suitable to provide pain relief for patients with cancer. Oxycodone tended to provide superior analgesic effects over morphine in patients carrying the genotype AA for the rs17809012 SNP (P=0.012 for interaction), suggesting that it could serve as a potential biomarker for personalized analgesic therapy for patients suffering with cancer pain.
PubMed: 37545623
DOI: 10.3892/ol.2023.13941 -
Scientific Reports Nov 2023Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of...
Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with homecage access to alcohol (20% v/v) and/or water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent a cue-primed reinstatement test and brains were processed for c-fos mRNA expression. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, only female oxycodone + alcohol rats exhibited decreased demand elasticity and increased cue-primed reinstatement. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor expressing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.
Topics: Female; Rats; Male; Animals; Oxycodone; Motivation; Sucrose; Alcohol Drinking; Ethanol; Receptors, Dopamine; Neurons; Water; Self Administration; Extinction, Psychological
PubMed: 37932476
DOI: 10.1038/s41598-023-46111-1 -
Medicine Jul 2023To evaluate the efficacy and safety of perioperative cryotherapy combined with intra-articular injection of tranexamic acid (TXA) in total knee arthroplasty (TKA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the efficacy and safety of perioperative cryotherapy combined with intra-articular injection of tranexamic acid (TXA) in total knee arthroplasty (TKA) and explore a new strategy of enhanced recovery after TKA.
METHODS
We randomly divided 200 patients into 4 groups: normal saline (10 mL) by drainage (Group A, placebo); intra-articular injection of TXA (1 g, 10 mL, Group B); normal saline (10 mL) and continuous cryotherapy postoperatively (Group C) and intra-articular injection of TXA (1 g, 10 mL) and continuous cryotherapy postoperatively (Group D). Primary outcomes were blood loss volume, postoperative pain and circumference variation. We also recorded consumption of analgesics, postoperative length of stay (p-LOS), range of motion (ROM), function score (Hospital for Special Surgery) and severe complications.
RESULTS
There were statistically significant differences in postoperative drainage volume, total blood loss, hidden blood loss, and visual analogue scale at rest and walking on postoperative day 1 (POD1), POD2, POD3, ROM (POD3, 7, discharge, postoperative month), circumference variation (POD3, 7), p-LOS, Hospital for Special Surgery score (discharge) and drop of hemoglobin on POD3 (P < .05) among 4 groups, but there were no significant differences in intraoperative blood loss, postoperative prothrombin, activated partial thromboplastin time, overall number of patients or total consumption of oxycodone and perioperative complications (e.g., incidence of surgical site infection, deep venous thrombosis, and cold injury) among them (P > .05).
CONCLUSION
Continuous cryotherapy combined with intra-articular injection of TXA provides short-term advantages in reducing blood loss, pain, postoperative swelling, p-LOS and increasing ROM and joint function in the early postoperative period after TKA without increasing any severe complications.
Topics: Humans; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Injections, Intra-Articular; Postoperative Hemorrhage; Saline Solution; Tranexamic Acid
PubMed: 37478271
DOI: 10.1097/MD.0000000000034381 -
The Science of the Total Environment Dec 2023Wastewater-based epidemiology (WBE) relies on representative sampling that is typically achieved with autosamplers that collect time, flow, or volume proportional...
Wastewater-based epidemiology (WBE) relies on representative sampling that is typically achieved with autosamplers that collect time, flow, or volume proportional samples. The expense, resources and operational know-how associated with autosampler operation means they are only typically available at major wastewater treatment plants (WWTPs). This results in a lack of data on consumption levels in regional and remote areas, or in countries that lack the financial means. The aim of this study was to estimate and investigate trends in drug consumption across varying levels of remoteness in Australia. Field-calibrated, microporous polyethylene passive samplers were deployed over 2 periods (Aug/Sept 2019 and 2020) at 43 treatment plants covering all five categories of remoteness, as per Australian Bureau of Statistics definitions (Major cities, Inner regional, Outer regional, Remote, and Very remote). The per capita consumption of cocaine, methylamphetamine, nicotine, oxycodone and MDMA were estimated. No spatial trends between remoteness and drug consumption were observed, except for cocaine, where Major cities had a 5-to-10-fold higher consumption compared to the other levels of remoteness in 2019 and 2020, respectively. Outer regional sites had the highest and lowest methylamphetamine consumption. The variance in drug use among sites was much higher in Remote (and Inner/Outer regional) sites when compared with Major cities. A significant and consistent decrease in oxycodone consumption was observed at all sites between 2019 and 2020, possibly related to regulatory changes and the COVID-19 pandemic where elective surgeries were suspended. The majority of sites experienced a decrease in cocaine and methylamphetamine consumption, possibly due to border restrictions or changes in supply and demand dynamics. This was the first extensive passive sampling study to assess drug consumption in urban, regional, and remote locations, demonstrating that passive samplers can facilitate extension of wastewater-based drug monitoring programs to sites where other representative sampling options are very difficult to implement.
PubMed: 37574069
DOI: 10.1016/j.scitotenv.2023.166163 -
Journal of Chromatography. B,... May 2024Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics...
Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics of oxycodone and its metabolites in horses, as well as to detect the illegal use of oxycodone in racehorses, a method for quantification and confirmation of oxycodone and its metabolites is needed. In this study, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that can simultaneously quantify and confirm oxycodone and eight metabolites in equine urine. Samples were subjected to enzymatic hydrolysis and then liquid-liquid extraction using ethyl acetate. The analyte separation was achieved on a Hypersil Gold C18 sub-2 µm column and analytes were detected on a triple quadrupole mass spectrometer. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 25-50 pg/mL and 100 pg/mL, respectively. Excellent linearity of the calibration curves was observed over a range of 100-10000 pg/mL for all nine analytes. Retention time, signal-to-noise ratio, and product ion ratios were utilized as confirmation criteria, with the limits of confirmation (LOC) ranging from 100 to 250 pg/mL. The data from a pilot pharmacokinetic (PK) study suggested that oxycodone metabolites have longer detection periods in equine urine compared to oxycodone itself; thus, the detection of metabolites in equine urine extends the ability to detect oxycodone exposure in racehorses.
Topics: Animals; Horses; Tandem Mass Spectrometry; Oxycodone; Chromatography, High Pressure Liquid; Limit of Detection; Reproducibility of Results; Linear Models
PubMed: 38615430
DOI: 10.1016/j.jchromb.2024.124125 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
The Israel Medical Association Journal... Jan 2024
Topics: Humans; Acetaminophen; Oxycodone; Drug Combinations; Analgesics, Opioid; Double-Blind Method; Analgesics, Non-Narcotic; Pain, Postoperative
PubMed: 38420645
DOI: No ID Found -
Anesthesiology and Pain Medicine Feb 2024Total hip replacement (THR) is frequently associated with intense post-surgical pain. Effective pain management is of crucial importance to improving patient's condition...
BACKGROUND
Total hip replacement (THR) is frequently associated with intense post-surgical pain. Effective pain management is of crucial importance to improving patient's condition and increasing his/her satisfaction in the post-operative time.
OBJECTIVES
This study aimed to compare the analgesic effect and safety of oxycodone and fentanyl after THR.
METHODS
Seventy-two cases scheduled for elective THR were included in this randomized, triple-blind trial. The patients were equally randomized into 2 groups: Fentanyl group (50 ug of fentanyl) and oxycodone group (oxycodone 4 mg). Drugs were received 20 min prior to the end of the operation.
RESULTS
Post-operative visual analog scale (VAS) measurements at rest and movement at the post-anesthesia care unit (PACU) and in the ward, 2 h, 4 h, and 8 h post-operatively exhibited a significantly reduced value in the oxycodone group compared to the fentanyl group (P-value < 0.05). Time to first rescue for analgesia was delayed significantly in the oxycodone compared to the fentanyl group (P-value < 0.001). Fentanyl consumption (ug) in the 1st post-operative 12 h, 24 h, and 48 h decreased significantly in the oxycodone group compared to the fentanyl group (P-value < 0.001). Post-operative nausea, vomiting, headache, and pruritus were matched between the 2 groups (P > 0.05).
CONCLUSIONS
A bolus dose of 4 mg of oxycodone provided superior analgesic efficacy than 50 ug fentanyl as evidenced by significantly lower pain score, delayed onset to first request for analgesia, and the smaller amount of fentanyl consumption at 12, 24, and 48 h post-total hip arthroplasty compared to fentanyl. The incidence of adverse events was comparable between the 2 groups.
PubMed: 38725916
DOI: 10.5812/aapm-142710