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American Family Physician Mar 2016
Review
Topics: Acetaminophen; Acute Pain; Analgesics, Opioid; Drug Combinations; Extremities; Humans; Hydrocodone; Oxycodone; Pain Measurement
PubMed: 26926980
DOI: No ID Found -
The Cochrane Database of Systematic... Jun 2016Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense... (Review)
Review
BACKGROUND
Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense symptoms. Patients complain of unpleasant sensations in the legs, at or before bedtime, and feel an urge to move the legs, which improves with movement, such as walking. Symptoms start with the patient at rest (e.g. sitting or lying down), and follow a circadian pattern, increasing during the evening or at night. Many pharmacological intervention are available for RLS, including drugs used to treat Parkinson's disease (L-Dopa and dopaminergic agonists), epilepsy (anticonvulsants), anxiety (benzodiazepines), and pain (opioids). Dopaminergic drugs are those most frequently used for treatment of RLS, but some patients do not respond effectively and require other medication. Opioids, a class of medications used to treat severe pain, seem to be effective in treating RLS symptoms, and are recommended for patients with severe symptoms, because RLS and pain appear to share the same mechanism in the central nervous system. All available drugs are associated to some degree with side effects, which can impede treatment. Opioids are associated with adverse events such as constipation, tolerance, and dependence. This justifies the conduct of a systematic review to ascertain whether opioids are safe and effective for treatment of RLS.
OBJECTIVES
To asses the effects of opioids compared to placebo treatment for restless legs syndrome in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled trials, CENTRAL 2016, issue 4 and MEDLINE, EMBASE, and LILACS up to April 2016, using a search strategy adapted by Cochraneto identify randomised clinical trials. We checked the references of each study and established personal communication with other authors to identify any additional studies. We considered publications in all languages.
SELECTION CRITERIA
Randomised controlled clinical trials of opioid treatment in adults with idiopathic RLS.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened articles, independently extracted data into a standard form, and assessed for risk of bias. If necessary, they discussed discrepancies with a third researcher to resolve any doubts.
MAIN RESULTS
We included one randomised clinical trial (N = 304 randomised; 204 completed; 276 analysed) that evaluated opioids (prolonged release oxycodone/naloxone) versus placebo. After 12 weeks, RSL symptoms had improved more in the drug group than in the placebo group (using the IRLSSS: MD -7.0; 95% CI -9.69 to -4.31 and the CGI: MD -1.11; 95% CI -1.49 to -0.73). More patients in the drug group than in the placebo group were drug responders (using the IRLSSS: RR 1.82; 95% CI 1.37 to 2.42 and the CGI: RR1.92; 95% ICI 1.49 to 2.48). The proportion of remitters was greater in the drug group than in the placebo group (using the IRLSSS: RR 2.14; 95% CI 1.45 to 3.16). Quality of life scores also improved more in the drug group than in the placebo group (MD -0.73; 95% CI -1.1 to -0.36). Quality of sleep was improved more in the drug group measured by sleep adequacy (MD -0.74; 95% CI -1.15 to -0.33), and sleep quantity (MD 0.89; 95% CI 0.52 to 1.26).There was no difference between groups for daytime somnolence, trouble staying awake during the day, or naps during the day. More adverse events were reported in the drug group (RR 1.22; 95% CI 1.07 to 1.39). The major adverse events were gastrointestinal problems, fatigue, and headache.
AUTHORS' CONCLUSIONS
Opioids seem to be effective for treating RLS symptoms, but there are no definitive data regarding the important problem of safety. This conclusion is based on only one study with a high dropout rate (moderate quality evidence).
Topics: Analgesics, Opioid; Disorders of Excessive Somnolence; Humans; Naloxone; Oxycodone; Randomized Controlled Trials as Topic; Restless Legs Syndrome
PubMed: 27355187
DOI: 10.1002/14651858.CD006941.pub2 -
British Journal of Clinical Pharmacology Sep 2022Tapentadol, an opioid with mu-opioid receptor agonism and noradrenaline reuptake inhibition, has been increasingly used in Australia since 2011. However, data on...
AIMS
Tapentadol, an opioid with mu-opioid receptor agonism and noradrenaline reuptake inhibition, has been increasingly used in Australia since 2011. However, data on hospital prescribing trends and indications are scarce. This study aimed to investigate hospital prescribing trends of tapentadol, oxycodone and tramadol in a Sydney local health district (LHD) and the indications for tapentadol hospital prescriptions in an Australian tertiary hospital.
METHODS
We analysed 5-year patient dispensing for tapentadol, oxycodone and tramadol from four hospitals in a Sydney LHD with data expressed as oral morphine equivalents (OME). We also conducted a retrospective review of 140 and 54 patients prescribed tapentadol at a tertiary hospital's surgical and spinal units in 2020.
RESULTS
Over 5 years in the Sydney LHD, there was a 19.5% reduction in total dispensing of these opioids from 1 225 210 to 986 477.5 OME milligrams. Decreases were specifically for oxycodone (-37.8% immediate-release, -65.2% sustained-release) and tramadol (-74.6% immediate-release, -70.1% sustained-release). Contrastingly, hospital prescriptions of tapentadol immediate-release increased by 223.2% between 2018-19 and 2020-21 while sustained-release increased by 17.9% from 2016-17 to 2020-21. By 2020-21, tapentadol overtook oxycodone to become the most prescribed opioid in the Sydney LHD (51.4%). At the hospital's surgical units, 137 (97.9%) patients were prescribed tapentadol for acute post-operative pain with the majority (54.0%) prescribed both immediate-release and sustained-release tapentadol, while 71.1% were prescribed for neuropathic pain in the spinal units.
CONCLUSION
In a Sydney LHD, tapentadol prescriptions increased significantly to become the preferred opioid analgesic. At the hospital's surgical units, off-label prescriptions of tapentadol sustained-release for acute post-operative pain were observed.
Topics: Analgesics, Opioid; Australia; Delayed-Action Preparations; Humans; Morphine; Oxycodone; Pain, Postoperative; Phenols; Tapentadol; Tramadol
PubMed: 35763675
DOI: 10.1111/bcp.15448 -
CMAJ : Canadian Medical Association... Feb 2013
Topics: Analgesics, Opioid; Canada; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drugs, Generic; Humans; Opioid-Related Disorders; Oxycodone; Practice Patterns, Physicians'; Prescription Drug Misuse
PubMed: 23296585
DOI: 10.1503/cmaj.122099 -
Neuropharmacology May 2020The increasing abuse of opioids - such as oxycodone - poses major challenges for health and socioeconomic systems. Human prescription opioid abuse is marked by chronic,...
The increasing abuse of opioids - such as oxycodone - poses major challenges for health and socioeconomic systems. Human prescription opioid abuse is marked by chronic, voluntary, oral intake and sex differences. To develop interventions, the field would benefit from a preclinical paradigm that similarly provides rodents with chronic, continuous, oral, voluntary and free-choice access to oxycodone. Here we show female and male rats voluntarily ingest and choose oxycodone over water and show both dependence and motivation to take oxycodone during a chronic oral voluntary, two-bottle choice, continuous access paradigm. Adult female and male Long-Evans rats were given unlimited, continuous homecage access to two bottles containing water (Control) or one bottle of water and one bottle of oxycodone dissolved in water (Experimental). Virtually all experimental rats voluntarily drank oxycodone (~10 mg/kg/day) and escalated their intake over 22 weeks. Females self-administered twice as much oxycodone by body weight (leading to higher blood levels of oxycodone) and engaged in more gnawing behavior of wooden blocks relative to males. Precipitated withdrawal revealed high levels of dependence in both sexes. Reflecting motivation to drink oxycodone, ascending concentrations of citric acid suppressed the intake of oxycodone (Experimental) and the intake of water (Control); however, Experimental rats returned to pre-citric acid preference levels whereas Controls rats did not. Pre-screening behaviors of rats on open field exploration predicted oxycodone intake. Thus, rats consumed and preferred oxycodone over time in this chronic two-bottle oral choice paradigm and both sexes displayed many features of human oxycodone abuse.
Topics: Administration, Oral; Analgesics, Opioid; Animals; Choice Behavior; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Male; Opioid-Related Disorders; Oxycodone; Rats; Rats, Long-Evans; Self Administration; Sex Characteristics; Substance Withdrawal Syndrome; Water
PubMed: 32001238
DOI: 10.1016/j.neuropharm.2020.107978 -
Neuropsychopharmacology : Official... Sep 2018Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing... (Randomized Controlled Trial)
Randomized Controlled Trial
Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5, and 5.0 mg, PO) with smoked cannabis (0.0, 5.6% Δ tetrahydrocannabinol [THC]) and analgesia was assessed using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4 °C); times to report pain (pain threshold) and withdraw the hand from the water (pain tolerance) were recorded. Abuse-related effects were measured and effects of oxycodone on cannabis self-administration were determined. Alone, 5.0 mg oxycodone increased pain threshold and tolerance (p ≤ 0.05). Although active cannabis and 2.5 mg oxycodone alone failed to elicit analgesia, combined they increased pain threshold and tolerance (p ≤ 0.05). Oxycodone did not increase subjective ratings associated with cannabis abuse, nor did it increase cannabis self-administration. However, the combination of 2.5 mg oxycodone and active cannabis produced small, yet significant, increases in oxycodone abuse liability (p ≤ 0.05). Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis's abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.
Topics: Adult; Analgesia; Analgesics, Opioid; Double-Blind Method; Dronabinol; Drug Synergism; Female; Humans; Male; Marijuana Smoking; Middle Aged; Opioid-Related Disorders; Oxycodone; Pain Measurement; Young Adult
PubMed: 29463913
DOI: 10.1038/s41386-018-0011-2 -
Bioengineered Apr 2022Endothelial dysfunction is an important mechanism involved in myocardial ischemia-reperfusion (I/R) injury. We aimed to explore the effects of Oxycodone on myocardial...
Endothelial dysfunction is an important mechanism involved in myocardial ischemia-reperfusion (I/R) injury. We aimed to explore the effects of Oxycodone on myocardial I/R injury in vivo and in vitro to reveal its mechanisms related to Sigma-1 Receptor (SIGMAR1). A rat model of I/R-induced myocardial injury was developed. The ischemic area and myocardial histopathological changes after oxycodone addition were evaluated by TTC staining and H&E staining. LDH, CK-MB and cTnI levels were used to assess myocardial function. Then, the endothelial integrity was reflected by the expressions of ZO-1, Claudin-1 and Occludin. Afterward, ELISA, RT-qPCR, western blot and immunofluorescence assays were adopted for the detection of inflammation-related genes. SIGMAR1 expression in myocardial tissues induced by I/R and cardiac microvascular endothelial cells (CMECs) under hypoxic/reoxygenation (H/R) was determined using RT-qPCR and western blotting. Subsequently, after SIGMAR1 silencing or BD1047 addition (a SIGMAR1 antagonist), cell apoptosis and endothelial integrity were analyzed in the presence of Oxycodone in H/R-stimulated CMECs. Results indicated that Oxycodone decreased the ischemic area and improved myocardial function in myocardial I/R injury rat. Oxycodone improved myocardial histopathological injury and elevated endothelial integrity, evidenced by upregulated ZO-1, Claudin-1 and Occludin expressions. Moreover, inflammatory response was alleviated after Oxycodone administration. Molecular docking suggested that SIGMAR1 could directly bind to Oxycodone. Oxycodone elevated SIGMAR1 expression and SIGMAR1 deletion or BD1047 addition attenuated the impacts of Oxycodone on apoptosis and endothelial integrity of CMECs induced by H/R. Collectively, Oxycodone alleviates myocardial I/R injury in vivo and in vitro by binding to SIGMAR1.
Topics: Animals; Apoptosis; Claudin-1; Endothelial Cells; Molecular Docking Simulation; Myocardial Reperfusion Injury; Myocytes, Cardiac; Occludin; Oxycodone; Rats; Receptors, sigma; Sigma-1 Receptor
PubMed: 35412431
DOI: 10.1080/21655979.2022.2057632 -
Journal of Pain and Symptom Management Jul 2010The use of patient-controlled analgesia (PCA) allows patients to be managed at home and may increase the quality of life of patients with regard to drug administration....
CONTEXT
The use of patient-controlled analgesia (PCA) allows patients to be managed at home and may increase the quality of life of patients with regard to drug administration. To ensure that intact drug is delivered to the patient in this setting, it is important to study its microbiological and physicochemical stability. Although these factors have been widely studied for many parenteral opioids, very few authors have investigated oxycodone stability associated with long-duration infusion in cancer patients.
OBJECTIVES
The aim of this study was to assess the microbiological and physicochemical stability of oxycodone hydrochloride solution in PCA devices and thereby to determine the feasibility of extending the expiration dates after mixing.
METHODS
Sixteen CADD reservoirs and 32 Rythmic reservoirs were filled aseptically with pure (10 mg/mL) and diluted (1 mg/mL) oxycodone solution. Three different vehicles (0.9% sodium chloride, water for injection, and 5% dextrose) were used for dilution. Among the PCA systems stored over 28 days at room temperature, 16 Rythmic reservoirs were protected from light. Microbiological stability was assessed by performing sterility tests. The physicochemical study was performed by determining aspect, pH, osmolality evolution, and weight. Drug concentrations were determined using the stability-indicating high performance liquid chromatography combined to ultraviolet detection technique.
RESULTS
There was no significant change in pH, weight, and osmolality values of any solutions. No precipitation or change in color was observed in any of the sample solutions. There was no significant loss of oxycodone, and no trace of degradation products was detected.
CONCLUSION
This study indicates that pure and diluted oxycodone solutions in the PCA systems are stable for 28 days at room temperature when prepared aseptically.
Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Bacteria; Calibration; Drug Contamination; Drug Delivery Systems; Drug Stability; Fungi; Oxycodone; Pharmaceutical Solutions; Sterilization
PubMed: 20570483
DOI: 10.1016/j.jpainsymman.2009.11.323 -
Journal of Managed Care Pharmacy : JMCP 2003Although use of long-acting opioid analgesics has increased for chronic nonmalignant pain management, little is known about patient-reported utilization patterns.
BACKGROUND:
Although use of long-acting opioid analgesics has increased for chronic nonmalignant pain management, little is known about patient-reported utilization patterns.
OBJECTIVES:
To assess patient-reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride (HCl) controlled-release among patients with chronic nonmalignant pain and to compare these patterns to standard dose administration guidelines recommended in the manufacturers' prescribing information (PI).
METHODS:
Cross-sectional, observational, multicenter study of English-speaking patients who were seeking chronic nonmalignant pain management from 6 outpatient pain clinics. The inclusion criteria for the study were (1) diagnosis of chronic nonmalignant pain, (2) prescription for and current use of either transdermal fentanyl or oxycodone HCl controlled-release, and (3) duration of use for either transdermal fentanyl or oxycodone HCl controlled-release of at least 6 weeks. Patients completed either an oxycodone HCl controlled-release or transdermal fentanyl utilization questionnaire. A conversion table was used to standardize opioid analgesic doses from transdermal fentanyl or oxycodone HCl controlled-release to daily oral morphine equivalents. The principal outcome measures were the average interval between oxycodone HCl controlled-release administrations, the number of days the current transdermal fentanyl patch would be worn, and the percentage of oxycodone HCl controlled-release and transdermal fentanyl patients whose administration frequency exceeded the standard recommendation in the manufacturer's PI (every 12 hours for oxycodone HCl controlled-release or every 72 hours for transdermal fentanyl). Other outcome measures included the number of oxycodone HCl controlled-release tablets per administration, the daily dose of long-acting opioid, the duration of adequate pain relief, and the difference in daily oral morphine equivalents between transdermal fentanyl and oxycodone HCl controlled-release patients, after adjusting in a multivariate regression model for demographic and clinical characteristics.
RESULTS:
A total of 690 patients were enrolled in this study; 437 (63.4%) received oxycodone HCl controlled- release and 253 (36.6%) received transdermal fentanyl. Oxycodone HCl controlled-release patients reported taking a median of 1 tablet 3 times per day or a median of 3 tablets per day. A mean of 1.6 tablets per administration and 4.6 tablets per day were taken. The average interval between administrations of oxycodone HCl controlled-release was 7.8 hours, and the median daily dose was 80.0 mg (mean 155.6 mg). Among oxycodone HCl controlled-release patients, 17.5% had an average interval between administrations of 12 or more hours, whereas 1.9% reported the duration of pain relief as 12 or more hours. Transdermal fentanyl patients reported wearing the patch, on average, for 2.5 days (median 2.5), and 41.2% reported wearing the patch for at least 3 days, whereas 14.1% reported the duration of pain relief as at least 3 days. The median daily dosage strength of transdermal fentanyl was 75.0 mcg/hour. In the multivariate regression analysis, oxycodone HCl controlled-release patients had, on average, roughly 22 mg additional oral morphine equivalents per day relative to transdermal fentanyl patients (not statistically significant); the probability that oxycodone HCl controlled-release patients had higher oral morphine equivalents was 82.6%, which suggests a trend toward higher oral morphine equivalents per day in the oxycodone HCl controlled-release group.
CONCLUSIONS:
Transdermal fentanyl and oxycodone HCl controlled-release both appear to be used by patients in a manner that is inconsistent with the standard recommendation in the manufacturers' PI; however, the difference between patient-reported utilization and the PI recommendation is more pronounced with oxycodone HCl controlled-release.
Topics: Analgesics, Opioid; Delayed-Action Preparations; Female; Fentanyl; Humans; Male; Oxycodone; Pain
PubMed: 14613448
DOI: 10.18553/jmcp.2003.9.5.457 -
Journal of Palliative Medicine Nov 2022Equianalgesic tools are commonly utilized to guide dose of analgesic therapy, but there is no national consensus on equianalgesic calculations in the United States. To...
Equianalgesic tools are commonly utilized to guide dose of analgesic therapy, but there is no national consensus on equianalgesic calculations in the United States. To propose a summary of current opioid equianalgesic data that include variations and trends among national institutions. Opioid equianalgesic tools were obtained between May and September 2021. For meperidine, tramadol, codeine, hydrocodone, morphine, oxycodone, oxymorphone, hydromorphone, levorphanol, fentanyl, and tapentadol, details of adjustment for incomplete tolerance, opioid equianalgesic ratios, and formulation types were collected and analyzed. Baseline opioid pharmaco kinetic data were obtained through manufacturer labels on FDA databases, including half-life (), volume of distribution (), clearance (Cl), area under the curve (AUC), max concentration (), and time to max concentration (). Thirty-two institutions' equianalgesic tools were included with each study opioid appearing on an average of 23 institutions' tools. Few tools contained guidance on levorphanol or tapentadol; or included minimum and maximum recommended doses. All tools included guidance on fentanyl, hydromorphone, oxycodone, morphine, and hydrocodone. A minority of tools included guidance on cross-tolerance considerations ( = 12, 37.5%). Oral-tramadol-to-oral-morphine and oral-hydromorphone-to-intravenous (IV)-hydromorphone had the largest variances across equianalgesic tools (6.7 ± 2.8 and 4.06 ± 1.2 mg, respectively). Opioid equianalgesia tools from across the United States demonstrated significant variation in their inclusion of guidance on adjustment for incomplete cross-tolerance, oral-to-IV, and oral-to-oral opioid equianalgesic ratios, and which opioids and formulations were listed. Tramadol and hydromorphone had the most variation in their equianalgesic guidance among the opioids.
Topics: Humans; Analgesics, Opioid; Hydromorphone; Oxycodone; Tapentadol; Tramadol; Levorphanol; Hydrocodone; Administration, Oral; Fentanyl; Morphine
PubMed: 35559657
DOI: 10.1089/jpm.2021.0678