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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 -
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 -
Journal of Pain & Palliative Care... Mar 2024Opioids refer to chemicals that agonize opioid receptors in the body resulting in analgesia and sometimes, euphoria. Opiates include morphine and codeine; semi-synthetic... (Review)
Review
Opioids refer to chemicals that agonize opioid receptors in the body resulting in analgesia and sometimes, euphoria. Opiates include morphine and codeine; semi-synthetic opioids include heroin, hydrocodone, oxycodone, and buprenorphine; and fully synthetic opioids include tramadol, fentanyl and methadone. In 2021, an estimated 5.6 million individuals met criteria for opioid use disorder. This article provides an overview of the pharmacology of heroin and non-prescription fentanyl (NPF) and its synthetic analogues, and summarizes the literature related to the management of opioid use disorder, overdose, and withdrawal. This is followed by a description of barriers to treatment and best practices for management with a discussion on recent updates and their potential impact on this patient population. This is followed by a description of barriers to treatment and best practices for management with a discussion on recent updates and their potential impact on this patient population.
Topics: Humans; Heroin; Opioid-Related Disorders; Analgesics, Opioid; Methadone; Fentanyl
PubMed: 38100521
DOI: 10.1080/15360288.2023.2290565 -
JDR Clinical and Translational Research Oct 2023In the United States, dentists frequently prescribe hydrocodone. In October 2014, the US Drug Enforcement Administration rescheduled hydrocodone from controlled...
INTRODUCTION
In the United States, dentists frequently prescribe hydrocodone. In October 2014, the US Drug Enforcement Administration rescheduled hydrocodone from controlled substance schedule III to II, introducing more restricted prescribing and dispensing regulations, which may have changed dental prescribing of opioids.
OBJECTIVE
The study aim was to evaluate the impact of the hydrocodone rescheduling on dental prescribing of opioids in the United States.
METHODS
This was a cross-sectional study of opioids prescribed by dentists between October 2012 and October 2016, using the IQVIA Longitudinal Prescription Dataset. Monthly dentist-based opioid prescribing rate (opioid prescription [Rx]/1,000 dentists) and monthly average opioid dosages per prescription (mean morphine milligram equivalent per day [MME/d]) were measured in the 24 mo before and after hydrocodone rescheduling in October 2014 (index or interruption). An interrupted time-series analysis was conducted using segmented ordinary least square regression models, with Newey-West standard errors to handle autocorrelation.
RESULTS
Dentists prescribed 50,412,942 opioid prescriptions across the 49 mo. Hydrocodone was the most commonly prescribed opioid pre- and postindex (74.9% and 63.8%, respectively), followed by codeine (13.8% and 21.6%), oxycodone (8.1% and 9.5%), and tramadol (2.9% and 4.8%). At index, hydrocodone prescribing immediately decreased by -834.8 Rx/1,000 dentists (95% confidence interval [CI], -1,040.2 to -629.4), with increased prescribing of codeine (421.9; 95% CI, 369.7-474.0), oxycodone (85.3; 95% CI, 45.4-125.2), and tramadol (111.8; 95% CI, 101.4-122.3). The mean MME increased at index for all opioids except for hydrocodone, and dosages subsequently decreased during the postindex period.
CONCLUSION
Following the rescheduling, dentist prescribing of hydrocodone declined while prescribing of nonhydrocodone opioids increased. Understanding the impact of this regulation informs strategies to ensure appropriate prescribing of opioids for dental pain.
KNOWLEDGE TRANSFER STATEMENT
The study findings can be used by policy makers to make informed decisions in developing future risk mitigation strategies aimed to regulate opioid prescribing behaviors. Furthermore, dentist-specific resources and guidelines are needed subsequent to these policies in order to meet the dental population needs.
Topics: United States; Analgesics, Opioid; Hydrocodone; Tramadol; Oxycodone; Cross-Sectional Studies; Practice Patterns, Dentists'; Codeine; Drug Prescriptions
PubMed: 35708454
DOI: 10.1177/23800844221102830 -
Drug and Alcohol Dependence Sep 2023Increased telehealth use has led to greater interest in remote drug testing. The speed, acceptability, and ability to observe oral fluids testing makes it the best...
BACKGROUND
Increased telehealth use has led to greater interest in remote drug testing. The speed, acceptability, and ability to observe oral fluids testing makes it the best candidate for remote drug testing, but its validity and reliability compared to gold-standard urine drug testing have not been established.
METHODS
Veterans (N = 99) recruited from mental health clinics completed in-person and remote oral fluids testing and in-person urine drug testing. The validity of oral fluids versus urine drug testing and reliability of in-person versus remote oral fluids testing were evaluated.
RESULTS
Validity of oral fluids testing was similar for samples collected in-person and virtually. Oral fluids testing had good specificity (0.93-1.00) and negative predictive value (0.85-1.00), but lower sensitivity and positive predictive value. Sensitivity (0.21-0.93) was highest for methadone and oxycodone, followed by cocaine and then amphetamine and opiates. Positive predictive value (0.14-1.00) was highest for cocaine, opiates, and methadone, followed by oxycodone and then amphetamine. Validity for cannabis was low, likely because of differences in detection windows for oral fluids versus urine drug screens. Reliability of remote oral fluids testing was adequate for opiates, cocaine, and methadone, but not oxycodone, amphetamine, or cannabis.
CONCLUSIONS
Oral fluids testing identifies most negative, but not most positive, drug test results. While oral fluids testing is appropriate in some circumstances, its limitations should be acknowledged. Remote drug testing addresses many barriers, but also generates new barriers related to self-administration and remote interpretation. Limitations include a small sample and low base rates for some drugs.
Topics: Humans; Reproducibility of Results; Substance Abuse Detection; Methadone; Amphetamine; Hallucinogens; Cocaine; Opiate Alkaloids
PubMed: 37429052
DOI: 10.1016/j.drugalcdep.2023.110876 -
Pharmacology, Biochemistry, and Behavior Aug 2023The opioid epidemic remains a pressing public health crisis in the United States. Most of these overdose deaths are a result of lethal respiratory depression. In recent...
RATIONALE
The opioid epidemic remains a pressing public health crisis in the United States. Most of these overdose deaths are a result of lethal respiratory depression. In recent years the increasing incidence of opioid-involved overdose deaths has been driven by fentanyl, which is more resistant to adequate reversal by naloxone (NARCAN ®) than semi-synthetic or classical morphinan predecessors like oxycodone and heroin. For this and other reasons (e.g., precipitating withdrawal) non-opioidergic pharmacotherapies to reverse opioid-depressed respiration are needed. Methylxanthines are a class of stimulant drugs including caffeine and theophylline which exert their effects primarily via adenosine receptor antagonism. Evidence suggests methylxanthines can stimulate respiration by enhancing neural activity in respiratory nuclei in the pons and medulla independent of opioid receptors. This study aimed to determine whether caffeine and theophylline can stimulate respiration in mice when depressed by fentanyl and oxycodone.
METHODS
Whole-body plethysmography was used to characterize fentanyl and oxycodone's effects on respiration and their reversal by naloxone in male Swiss Webster mice. Next, caffeine and theophylline were tested for their effects on basal respiration. Finally, each methylxanthine was evaluated for its ability to reverse similar levels of respiratory depression induced by fentanyl or oxycodone.
RESULTS AND CONCLUSIONS
Oxycodone and fentanyl dose-dependently reduced respiratory minute volume (ml/min; MVb) that was reversible by naloxone. Caffeine and theophylline each significantly increased basal MVb. Theophylline, but not caffeine, completely reversed oxycodone-depressed respiration. In contrast, neither methylxanthine elevated fentanyl-depressed respiration at the doses tested. Despite their limited efficacy for reversing opioid-depressed respiration when administered alone, the methylxanthines safety, duration, and mechanism of action supports further evaluation in combination with naloxone to augment its reversal of opioid-depressed respiration.
Topics: Male; Animals; Mice; Analgesics, Opioid; Theophylline; Oxycodone; Caffeine; Fentanyl; Naloxone; Respiratory Insufficiency; Narcotic Antagonists
PubMed: 37414364
DOI: 10.1016/j.pbb.2023.173601 -
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 -
Acta Obstetricia Et Gynecologica... Aug 2023Opioids are used for pain relief during the first stage of labor. Oxycodone can cause maternal hypotension that may modify utero- and fetoplacental circulatory... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Opioids are used for pain relief during the first stage of labor. Oxycodone can cause maternal hypotension that may modify utero- and fetoplacental circulatory physiology. We hypothesized that maternal intravenous (i.v.) oxycodone has no detrimental effect on utero- and fetoplacental hemodynamics during the early first stage of labor.
MATERIAL AND METHODS
Twenty-two parturients requiring pain relief during the first stage of labor were randomized in a double-blinded and placebo-controlled study. By Doppler ultrasonography, both uterine artery (Ut) and umbilical vein (UV) volume blood flows (Q), Ut pulsatility index (PI), and Ut vascular resistance (RUt) were calculated. Blood flow velocity waveforms were obtained between uterine contractions. After baseline measurements, women received oxycodone 0.05 mg/kg or a placebo intravenous. Doppler ultrasonography was repeated up to 120 min after the first drug administration. The second dose of oxycodone 0.05 mg/kg was allowed at 60 min to all parturients with contraction pain ≥5/10. Maternal plasma samples were collected at each study phase and after delivery with umbilical cord plasma samples, to measure oxycodone concentrations.
CLINICALTRIALS
gov identifier (NCT no. NCT02573831).
RESULTS
At baseline, mean QUt and QUV did not differ significantly between the placebo-first (478 mL/min and 57 mL/min/kg) and the oxycodone-first (561 mL/min and 71 mL/min/kg) groups. In addition, RUt and Ut PI were comparable between the groups. Following oxycodone at 60 min, mean QUt and QUV (714 mL/min and 52 mL/min/kg) were similar to the placebo-first (520 mL/min and 55 mL/min/kg) group. Furthermore, all the measured parameters were comparable to the baseline values. At 60 min after the first study drug administration, all the parturients in the placebo-first group needed intravenous oxycodone 0.05 mg/kg. At 120 min, we found no statistically significant change in any of the measured parameters. No significant correlation was found between maternal oxycodone concentration and QUt or QUV. Furthermore, newborn oxycodone concentration did not correlate with QUV.
CONCLUSIONS
Oxycodone did not have any detrimental effect on either utero- or fetoplacental circulatory physiology during the early first stage of labor. Maternal plasma oxycodone did not correlate with utero- and fetoplacental hemodynamics. No correlation was found between newborn oxycodone concentration and fetoplacental hemodynamics.
Topics: Humans; Female; Adult; Oxycodone; Placenta; Labor Stage, First; Injections, Intravenous; Pregnancy
PubMed: 37344997
DOI: 10.1111/aogs.14603 -
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