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Addiction Biology Mar 2022Neuronal ensembles within the infralimbic cortex (IL) and their projections to the nucleus accumbens (NAc) mediate opiate seeking in well-trained rats. However, it is...
Neuronal ensembles within the infralimbic cortex (IL) and their projections to the nucleus accumbens (NAc) mediate opiate seeking in well-trained rats. However, it is unclear how early this circuitry is recruited during oxycodone self-administration. Here, we used retrograde labelling (CTb) and immunohistochemistry to identify NAc-projecting neurons in the IL that were activated during initial oxycodone seeking. Next, we sought to determine the role of IL neuronal ensembles in initial oxycodone self-administration. We used the Daun02 procedure in male and female Fos-LacZ rats to chemogenetically inactivate IL Fos-expressing neurons at different time points in oxycodone self-administration training: immediately after meeting criteria for acquisition of behaviour and following nine daily sessions with increasing schedules of reinforcement (FR1, FR2 and FR3) in which rats demonstrated stable oxycodone intake under increasing effort to self-administer. We found that Daun02 infusions attenuated oxycodone seeking at both the initial learning and well-trained time points. These results suggest that IL neuronal ensembles are formed during initial learning of oxycodone self-administration and required for the maintenance and expression of oxycodone seeking.
Topics: Animals; Female; Male; Neurons; Nucleus Accumbens; Oxycodone; Rats; Rats, Transgenic; Self Administration
PubMed: 35229934
DOI: 10.1111/adb.13148 -
The Cochrane Database of Systematic... Aug 2017Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well-tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated version of the original Cochrane review published in 2015, Issue 2 on oxycodone for cancer-related pain.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2016. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions.
SELECTION CRITERIA
We included randomised controlled trials (parallel group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall quality of the evidence using GRADE.
MAIN RESULTS
For this update, we identified six new studies (1258 participants) for inclusion. In total, we included 23 studies which enrolled/randomised 2648 participants, with 2144 of these analysed for efficacy and 2363 for safety. The studies examined a number of different drug comparisons.Pooled analysis of three of the four studies comparing controlled-release (CR) oxycodone to immediate-release (IR) oxycodone showed that the ability of CR and IR oxycodone to provide pain relief were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). Pooled analyses of adverse events showed no significant differences between CR and IR oxycodone for asthenia (risk ratio (RR) 0.58, 95% CI 0.2 to 1.68), confusion (RR 0.78, 95% CI 0.2 to 3.02), constipation (RR 0.71, 95% CI 0.45 to 1.13), dizziness/lightheadedness (RR 0.74, 95% CI 0.4 to 1.37), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), dry mouth (RR 1.14, 95% CI 0.48 to 2.75), insomnia (RR 1.04, 95% CI 0.31 to 3.53), nausea (RR 0.85, 95% CI 0.56 to 1.28), nervousness (RR 0.57, 95% CI 0.2 to 1.64), pruritus (RR 1.46, 95% CI 0.65 to 3.25), vomiting (RR 0.66, 95% CI 0.38 to 1.15), and discontinuation due to adverse events (RR 0.6, 95% CI 0.29 to 1.22). The quality of the evidence was very low for all these adverse events. Three of the four studies found similar results for treatment acceptability.Pooled analysis of seven of the nine studies comparing CR oxycodone to CR morphine indicated that pain relief was significantly better after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; low quality evidence). However, sensitivity analysis did not corroborate this result (SMD 0.12, 95% CI -0.02 to 0.26).Pooled analyses of adverse events showed no significant differences between CR oxycodone and CR morphine for confusion (RR 1.01 95% CI 0.78 to 1.31), constipation (RR 0.98, 95% CI 0.82 to 1.16), dizziness/lightheadedness (RR 0.76, 95% CI 0.33 to 1.76), drowsiness/somnolence (RR 0.9, 95% CI 0.75 to 1.08), dry mouth (RR 1.01, 95% CI 0.8 to 1.26), dysuria (RR 0.71, 95% CI 0.4 to 1.26), nausea (RR 1.02, 95% CI 0.82 to 1.26), pruritus (RR 0.81, 95% CI 0.51 to 1.29), vomiting (RR 0.94, 95% CI 0.68 to 1.29), and discontinuation due to adverse events (RR 1.06, 95% CI 0.43 to 2.6). However, the RR for hallucinations was significantly lower after treatment with CR oxycodone compared to CR morphine (RR 0.52, 95% CI 0.28 to 0.97). The quality of the evidence was very low for all these adverse events. There were no marked differences in treatment acceptability or quality of life ratings.The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability.The quality of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes.
AUTHORS' CONCLUSIONS
The conclusions have not changed since the previous version of this review. The data suggest that oxycodone offers similar levels of pain relief and overall adverse events to other strong opioids including morphine. Although we identified a clinically insignificant benefit on pain relief in favour of CR morphine over CR oxycodone, this did not persist following sensitivity analysis and so we do not consider this important. However, in this updated analysis, we found that hallucinations occurred less often with CR oxycodone than with CR morphine, but the quality of this evidence was very low so this finding should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.
Topics: Aged; Analgesics, Opioid; Cancer Pain; Constipation; Delayed-Action Preparations; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morphine; Nausea; Neoplasms; Oxycodone; Pain Measurement; Quality of Life; Randomized Controlled Trials as Topic; Sleep Stages; Vomiting
PubMed: 28829910
DOI: 10.1002/14651858.CD003870.pub6 -
Addiction (Abingdon, England) Sep 2021To establish and quantify the association between abuse-deterrent formulation (ADF) oxycodone and 1-year risk of opioid-related harm.
AIM
To establish and quantify the association between abuse-deterrent formulation (ADF) oxycodone and 1-year risk of opioid-related harm.
DESIGN
Propensity score-matched cohort study of electronic medical records for years 2014-18, with patients followed up for 1 year after their index health-care visit.
SETTING
More than 70 million patients from 56 US health-care organizations.
PARTICIPANTS
Patients aged 18-64 years at index health-care visit with any indication for an oral opioid analgesic, with no past 12-month history of oral oxycodone use or substance use disorder, and who were alive at the end of the 1-year follow-up (new episode of prescription oral ADF oxycodone [OxyContin], n = 45 045; new episode of non-ADF oxycodone opioid preparation, n = 1 377 359).
MEASUREMENTS
International Classification of Diseases diagnoses of any opioid-related disorder or non-fatal opioid poisoning within 1 year of the index health-care visit. Pooled odds ratios (OR) with 95% confidence intervals (95% CI).
FINDINGS
After propensity score matching, 89 802 patients with a mean age of 44 [standard deviation (SD) = 11] years (62% women, 68% white) were included. During 1-year follow-up, 1445 diagnoses of opioid use disorder or opioid poisoning occurred in the ADF oxycodone cohort (34.8/1000 person-years) and 765 occurred in the non-ADF oxycodone cohort (18.2/1000 person-years). The odds of opioid-related adverse outcomes were increased in the ADF oxycodone cohort compared with the non-ADF oxycodone opioid cohort, including for opioid use disorders (OR = 2.02; 95% CI = 1.83, 2.23) and opioid poisoning (OR = 1.64 95% CI = 1.35, 1.99).
CONCLUSIONS
Patients with a new prescription of abuse-deterrent formulation oxycodone may be at increased risk of opioid-related harm.
Topics: Analgesics, Opioid; Child; Cohort Studies; Delayed-Action Preparations; Electronic Health Records; Female; Humans; Male; Opioid-Related Disorders; Oxycodone
PubMed: 33394528
DOI: 10.1111/add.15392 -
BMJ Supportive & Palliative Care Jun 2018To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI,... (Review)
Review
OBJECTIVES
To assess the efficacy, tolerability and acceptability of oxycodone for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In-Process, Embase, SCI, Conference Proceedings Citation Index-Science, BIOSIS, PsycINFO and four trials registries to November 2016.
RESULTS
We included 23 randomised controlled trials with 2144 patients analysed for efficacy and 2363 for safety. Meta-analyses showed no significant differences between controlled-release (CR) and immediate-release oxycodone in pain intensity or adverse events but did show significantly better pain relief after treatment with CR morphine compared with CR oxycodone. However, sensitivity analysis did not corroborate this result. Meta-analyses of the adverse events showed a significantly lower risk of hallucinations after treatment with CR oxycodone compared with CR morphine, but no other differences. The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone in pain relief or adverse events. The quality of this evidence base was limited by the high/unclear risk of bias of the studies and the low event rates for many outcomes.
CONCLUSIONS
Oxycodone offers similar levels of pain relief and adverse events to other strong opioids. However, hallucinations occurred less with CR oxycodone than with CR morphine, but the quality of this evidence was very low, so this finding should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that oxycodone can be used first line as an alternative to morphine. However, because it is cheaper, morphine generally remains the first-line opioid of choice.
Topics: Analgesics, Opioid; Cancer Pain; Humans; Oxycodone; Pain Management; Patient Preference; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29331953
DOI: 10.1136/bmjspcare-2017-001457 -
JMIR Public Health and Surveillance Dec 2021Opioid use disorder and its consequences are a persistent public health concern for Australians. Web activity has been used to understand the perception of drug safety...
BACKGROUND
Opioid use disorder and its consequences are a persistent public health concern for Australians. Web activity has been used to understand the perception of drug safety and diversion of drugs in contexts outside of Australia. The anonymity of the internet offers several advantages for surveilling and inquiring about specific covert behaviors, such as diversion or discussion of sensitive subjects where traditional surveillance approaches might be limited.
OBJECTIVE
This study aims to characterize the content of web posts and compare reports of illicit sales of tapentadol and oxycodone from sources originating in Australia. First, post content is evaluated to determine whether internet discussion encourages or discourages proper therapeutic use of the drugs. Second, we hypothesize that tapentadol would have lower street price and fewer illicit sales than oxycodone.
METHODS
Web posts originating in Australia between 2017 and 2019 were collected using the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program. Using a manual coding process, unstructured post content from social media, blogs, and forums was categorized into topics of discussion related to the harms and behaviors that could lead to harm. Illicit sales data in a structured format were collected through a crowdsourcing website between 2016 and 2019 using the Researched Abuse, Diversion, and Addiction-Related Surveillance System StreetRx Program. In total, 2 multivariable regression models assessed the differences in illicit price and number of sales.
RESULTS
A total of 4.7% (28/600) of tapentadol posts discussed an adverse event, whereas 10.27% (95% CI 9.32-11.21) of oxycodone posts discussed this topic. A total of 10% (60/600) of tapentadol posts discussed unsafe use or side effects, whereas 20.17% (95% CI 18.92-21.41) of oxycodone posts discussed unsafe use or side effects. There were 31 illicit sales reports for tapentadol (geometric mean price per milligram: Aus $0.12 [US $0.09]) and 756 illicit sales reports for oxycodone (Aus $1.28 [US $0.91]). Models detected no differences in the street price or number of sales between the drugs when covariates were included, although the potency of the pill significantly predicted the street price (P<.001) and availability predicted the number of sales (P=.03).
CONCLUSIONS
Australians searching the web for opinions could judge tapentadol as safer than oxycodone because of the web post content. The illicit sales market for tapentadol was smaller than that of oxycodone, and drug potency and licit availability are likely important factors influencing the illicit market.
Topics: Analgesics, Opioid; Australia; Humans; Internet; Oxycodone; Tapentadol
PubMed: 34932012
DOI: 10.2196/29187 -
The Cochrane Database of Systematic... Feb 2015Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids are, however, not effective for pain in all patients, nor are they well-tolerated by all patients. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for patients with cancer pain.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), EMBASE (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), PsycINFO (Ovid) and PubMed to March 2014. We also searched Clinicaltrials.gov, metaRegister of Controlled Trials (mRCT), EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform (ICTRP). We checked the bibliographic references of relevant identified studies and contacted the authors of the included studies to find additional trials not identified by the electronic searches. No language, date or publication status restrictions were applied to the search.
SELECTION CRITERIA
We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted study data (study design, participant details, interventions and outcomes) and independently assessed the quality of the included studies according to standard Cochrane methodology. Where possible, we meta-analysed the pain intensity data using the generic inverse variance method, otherwise these data were summarised narratively along with the adverse event and patient preference data. The overall quality of the evidence for each outcome was assessed according to the GRADE approach.
MAIN RESULTS
We included 17 studies which enrolled/randomised 1390 patients with 1110 of these analysed for efficacy and 1170 for safety. The studies examined a number of different drug comparisons. Four studies compared controlled release (CR) oxycodone to immediate release (IR) oxycodone and pooled analysis of three of these studies showed that the effects of CR and IR oxycodone on pain intensity after treatment were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). This was in line with the finding that none of the included studies reported differences in pain intensity between the treatment groups. Three of the four studies also found similar results for treatment acceptability and adverse events in the IR and CR groups; but one study reported that, compared to IR oxycodone, CR oxycodone was associated with significantly fewer adverse events.Six studies compared CR oxycodone to CR morphine and pooled analysis of five of these studies indicated that pain intensity did not differ significantly between the treatments (SMD 0.14, 95% CI -0.04 to 0.32; low quality evidence). There were no marked differences in adverse event rates, treatment acceptability or quality of life ratings.The remaining seven studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None of them found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability.The quality of this evidence base was limited by the risk of bias of the studies and by small sample sizes for many outcomes. Random sequence generation and allocation concealment were under-reported, and the results were substantially compromised by attrition with data missing from more than 20% of the enrolled/randomised patients for efficacy and from more than 15% for safety.
AUTHORS' CONCLUSIONS
Overall, the data included within this review suggest that oxycodone offers similar levels of pain relief and adverse events to other strong opioids including morphine, which is commonly considered the gold standard strong opioid. Our conclusions are consistent with other recent reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine will be justified. This means that for clinical purposes oxycodone or morphine can be used as first line oral opioids for relief of cancer pain.
Topics: Analgesics, Opioid; Delayed-Action Preparations; Drug Administration Schedule; Humans; Morphine; Neoplasms; Oxycodone; Pain; Pain Management; Randomized Controlled Trials as Topic
PubMed: 25723351
DOI: 10.1002/14651858.CD003870.pub5 -
Psychopharmacology Dec 2022Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like...
RATIONALE
Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway.
OBJECTIVES
Compare the respiratory effects of oral mitragynine to oral oxycodone in rats with the study design previously published by US Food and Drug Administration (FDA) scientists for evaluating the respiratory effects of opioids (Xu et al., Toxicol Rep 7:188-197, 2020).
METHODS
Blood gases, observable signs, and mitragynine pharmacokinetics were assessed for 12 h after 20, 40, 80, 240, and 400 mg/kg oral mitragynine isolate and 6.75, 60, and 150 mg/kg oral oxycodone hydrochloride.
FINDINGS
Oxycodone administration produced significant dose-related respiratory depressant effects and pronounced sedation with one death each at 60 and 150 mg/kg. Mitragynine did not yield significant dose-related respiratory depressant or life-threatening effects. Sedative-like effects, milder than produced by oxycodone, were evident at the highest mitragynine dose. Maximum oxycodone and mitragynine plasma concentrations were dose related.
CONCLUSIONS
Consistent with mitragynine's pharmacology that includes partial µ-opioid receptor agonism with little recruitment of the respiratory depressant activating β-arrestin pathway, mitragynine produced no evidence of respiratory depression at doses many times higher than known to be taken by humans.
Topics: Animals; Rats; Analgesics, Opioid; Mitragyna; Oxycodone; Plant Extracts; Receptors, Opioid; Secologanin Tryptamine Alkaloids
PubMed: 36308562
DOI: 10.1007/s00213-022-06244-z -
The Cochrane Database of Systematic... Oct 2016Cancer pain is an important and distressing symptom that tends to increase in frequency and intensity as the cancer advances. For people with advanced cancer, the... (Review)
Review
BACKGROUND
Cancer pain is an important and distressing symptom that tends to increase in frequency and intensity as the cancer advances. For people with advanced cancer, the prevalence of pain can be as high as 90%. It has been estimated that 30% to 50% of people with cancer categorise their pain as moderate to severe, with between 75% and 90% of people with cancer experiencing pain that they describe as having a major impact on their daily life. Epidemiological studies suggest that approximately 15% of people with cancer pain fail to experience acceptable pain relief with conventional management. Uncontrolled pain can lead to physical and psychological distress and can, consequently, have a drastic effect on people's quality of life.
OBJECTIVES
To determine the analgesic efficacy of hydromorphone in relieving cancer pain, as well as the incidence and severity of any adverse events.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and clinical trials registers up to April 2016. There were no language, document type or publication status limitations applied in the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared hydromorphone with placebo or other active pain medication for cancer pain in both adults and children. The four main outcomes selected have previously been identified as important to people with cancer; pain no worse than mild pain, and the impact of the treatment on consciousness, appetite and thirst. We did not consider physician-, nurse- or carer-reported measures of pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We used a random-effects model and assessed the risk of bias for all included studies. A meta-analysis was not completed on any of the primary outcomes in this review due to the lack of data. We assessed the evidence using GRADE and created two 'Summary of findings' tables.
MAIN RESULTS
We included four studies (604 adult participants), which compared hydromorphone to oxycodone (two studies) or morphine (two studies). Overall, the included studies were at low or unclear risk of bias, rated unclear due to unknown status of blinding of outcome assessment; we rated three studies at high risk of bias for potential conflict of interest. Data for 504 participants were available for analysis. We collected data on endpoint participant-reported pain intensity measured with a visual analogue scale (VAS) (mean ± standard deviation (SD): hydromorphone 28.86 ± 17.08, n = 19; oxycodone 30.30 ± 25.33, n = 12; scale from 0 to 100 with higher score indicating worse pain), and Brief Pain Inventory (BPI) 24 hours worst pain subscale (mean ± SD: hydromorphone 3.5 ± 2.9, n = 99; morphine 4.3 ± 3.0, n = 101, scale from 0 to 10 with higher score indicating worse pain). The data demonstrated a similar effect between groups with both comparisons. The pain intensity data showed that participants in all four trials achieved no worse than mild pain. There were several adverse events: some were the expected opioid adverse effects such as nausea, constipation and vomiting; others were not typical opioid adverse effects (for example, decreased appetite, dizziness and pyrexia, as shown in Table 1 in the main review), but generally showed no difference between groups. There were three deaths in the morphine group during the trial period, considered to be due to disease progression and unrelated to the drug. Three trials had over 10% dropout, but the reason and proportion of dropout was balanced between groups. The overall quality of evidence was very low mainly due to high risk of bias, imprecision of effect estimates and publication bias. There were no data available for children or for several participant-important outcomes, including participant-reported pain relief and treatment impact on consciousness, appetite or thirst.
AUTHORS' CONCLUSIONS
This review indicated little difference between hydromorphone and other opioids in terms of analgesic efficacy. Data gathered in this review showed that hydromorphone had a similar effect on participant-reported pain intensity as reported for oxycodone and morphine. Participants generally achieved no worse than mild pain after taking hydromorphone, which is comparable with the other drugs. It produced a consistent analgesic effect through the night and could be considered for use in people with cancer pain experiencing sleep disturbance. However, the overall quality of evidence was very low mainly due to risk of bias, imprecision of effect estimates and publication bias. This review only included four studies with limited sample size and a range of study designs. Data for some important outcomes, such as impact of the treatment on consciousness, appetite or thirst, were not available. Therefore, we were unable to demonstrate superiority or inferiority of hydromorphone in comparison with other analgesics for these outcomes. We recommend that further research with larger sample sizes and more comprehensive outcome data collection is required.
Topics: Adult; Analgesics, Opioid; Female; Humans; Hydromorphone; Male; Morphine; Neoplasms; Oxycodone; Pain; Pain Measurement; Randomized Controlled Trials as Topic
PubMed: 27727452
DOI: 10.1002/14651858.CD011108.pub2 -
British Journal of Clinical Pharmacology Feb 2017This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and... (Clinical Trial)
Clinical Trial
AIMS
This prospective study aimed to characterize the population pharmacokinetics of intravenous oxycodone and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of oxycodone for major open intra-abdominal surgery.
METHODS
In the pharmacokinetic study, patients were administered intravenous oxycodone (0.1 mg kg ), and arterial blood was sampled at pre-set intervals. In the analgesic-potency study, patients were administered intravenous oxycodone (0.1 mg kg ) 30 min before the end of the surgery, were placed in the postoperative anaesthesia care unit (PACU), and were asked to rate their pain every 10 min using a visual analogue scale (0 = no pain, 10 = most severe pain). On the first occasion that wound pain at rest and during compression was rated as ≥3 or ≥5, respectively, the first blood sample was obtained to determine the MEC. A second blood sample was obtained after titration with 2 mg of oxycodone to yield wound pain <3 at rest and <5 during wound compression, and MEAC was determined. MEC and MEAC were determined again in each patient.
RESULTS
In the population pharmacokinetic study (n = 54), oxycodone plasma concentration over time was well described by a three-compartment mammillary model. Lean body mass and age were significant covariates for the volume of distribution and metabolic clearance of the pharmacokinetic model of oxycodone, respectively. The analgesic-potency study (n = 50) showed that the median (95% CI) MEC and MEAC were 31.5 (19.2-42.8) and 74.1 (29.2-128.3) ng ml (first measurements) and 63.4 (15.6-120.1) and 76.1 (32.9-132.7) ng ml (second measurements), respectively.
CONCLUSIONS
In major intra-abdominal open surgery, the MEAC and analgesic potency of oxycodone were 75 ng ml and 60 ng ml , respectively.
Topics: Abdomen; Administration, Intravenous; Aged; Analgesics, Opioid; Female; Humans; Male; Middle Aged; Models, Biological; Oxycodone; Pain Measurement; Pain, Postoperative; Prospective Studies
PubMed: 27558774
DOI: 10.1111/bcp.13101 -
Behavioural Pharmacology Sep 2022The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those...
The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those without one. Therefore, oxycodone might be misused for its anxiolytic properties. We investigated if oxycodone affects anxiety-like behavior in adult male and female rats. The rats were treated with oxycodone (0.178, 0.32, 0.56, or 1 mg/kg), and anxiety-like behavior was investigated in the elevated plus-maze test. Immediately after the elevated plus-maze test, a small open field test was conducted to determine the effects of oxycodone on locomotor activity. In the elevated plus-maze test, oxycodone increased the percentage of time spent on the open arms, the percentage of open arm entries, time on the open arms, open arm entries, and the distance traveled. The males treated with vehicle had a lower percentage of open arm entries than the females treated with vehicle, and oxycodone treatment led to a greater increase in the percentage of open arm entries in the males than females. Furthermore, the females spent more time on the open arms, made more open arm entries, spent less time in the closed arms, and traveled a greater distance than the males. In the small open field test, treatment with oxycodone did not affect locomotor activity or rearing. Sex differences were observed; the females traveled a greater distance and displayed more rearing than the males. In conclusion, oxycodone decreases anxiety-like behavior in rats, and oxycodone has a greater anxiolytic-like effect in males than females.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Elevated Plus Maze Test; Female; Humans; Locomotion; Male; Maze Learning; Oxycodone; Rats
PubMed: 35947068
DOI: 10.1097/FBP.0000000000000690