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Expert Review of Clinical Pharmacology May 2021: Chronic low back pain (LBP) is common, and some patients require opiates therapy. This Bayesian network meta-analysis (NMA) analyzed available randomized clinical... (Meta-Analysis)
Meta-Analysis
: Chronic low back pain (LBP) is common, and some patients require opiates therapy. This Bayesian network meta-analysis (NMA) analyzed available randomized clinical trials (RCTs) on the use of opioids for LBP.: All RCTs comparing two or more opioids for chronic LBP and reporting results under the Numeric Rating Scale were included. The following drugs were analyzed: fentanyl, morphine, tapentadol, oxycodone, buprenorphine, oxymorphone, tramadol. The NMA was performed through the STATA routine for Bayesian hierarchical random-effects model analysis, with standardized mean difference (SMD) effect measure. Data regarding the rate of adverse events and different drug formulations were also reported.: Data from 2933 patients were obtained, with a mean age of 53.30 ± 6.95 years. The mean duration of symptoms prior to beginning the trial was 95.16 ± 47.29 months. The mean follow-up was 3.29 ± 1.72 months. Among the analyzed compounds, oxymorphone, tapentadol and fentanyl showed the highest efficacy in terms of pain reduction.: According to published level I evidence, oxymorphone, tapentadol and fentanyl were the most effective drugs in the treatment of chronic LBP. However, different formulation and pharmacokinetic characteristics need to be taken into consideration when choosing the ideal compound for a given patient.
Topics: Analgesics, Opioid; Bayes Theorem; Chronic Pain; Humans; Low Back Pain; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 33706636
DOI: 10.1080/17512433.2021.1903316 -
Data in Brief Apr 2021Here we describe the dataset of the first report of pharmacogenomics profiling in an outpatient spine setting with the primary aims to catalog: 1) the genes, alleles,...
Here we describe the dataset of the first report of pharmacogenomics profiling in an outpatient spine setting with the primary aims to catalog: 1) the genes, alleles, and associated rs Numbers (accession numbers for specific single-nucleotide polymorphisms) analysed and 2) the genotypes and corresponding phenotypes of the genes involved in metabolizing 37 commonly used analgesic medications. The present description applies to analgesic medication-metabolizing enzymes and may be especially valuable to investigators who are exploring strategies to optimize pharmacologic pain management (e.g., by tailoring analgesic regimens to the genetically identified sensitivities of the patient). Buccal swabs were used to acquire tissue samples of 30 adult patients who presented to an outpatient spine clinic with the chief concern of axial neck and/or back pain. Array-based assays were then used to detect the alleles of genes involved in the metabolism of pain medications, including all common (wild type) and most rare variant alleles with known clinical significance. Both CYP450 isozymes - including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 - and the phase II enzyme UDP-glucuronosyltransferase-2B7 (UGT2B7) were examined. Genotypes/phenotypes were then used to evaluate each patient's relative ability to metabolize 37 commonly used analgesic medications. These medications included both non-opioid analgesics (i.e., aspirin, diclofenac, nabumetone, indomethacin, meloxicam, piroxicam, tenoxicam, lornoxicam, celecoxib, ibuprofen, flurbiprofen, ketoprofen, fenoprofen, naproxen, and mefenamic acid) and opioid analgesics (i.e., morphine, codeine, dihydrocodeine, ethylmorphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, alfentanil, fentanyl, sufentanil, meperidine, ketobemidone, dextropropoxyphene, levacetylmethadol, loperamide, methadone, buprenorphine, dextromethorphan, tramadol, tapentadol, and tilidine). The genes, alleles, and associated rs Numbers that were analysed are provided. Also provided are: 1) the genotypes and corresponding phenotypes of the genes involved in metabolizing 37 commonly used analgesic medications and 2) the mechanisms of metabolism of the analgesic medications by primary and ancillary pathways. In supplemental spreadsheets, the raw and analysed pharmacogenomics data for all 30 patients evaluated in the primary research article are additionally provided. Collectively, the presented data offer significant reuse potential in future investigations of pharmacogenomics for pain management.
PubMed: 33644270
DOI: 10.1016/j.dib.2021.106832 -
British Journal of Clinical Pharmacology Apr 2021Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated the need new analytical strategies and techniques to understand the...
AIMS
Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated the need new analytical strategies and techniques to understand the medications involved, user characteristics and other factors needed to address the epidemic.
METHODS
A strategy of mosaic surveillance has evolved. Using real world evidence, the goal is to paint a more complete profile of a drug's real world misuse using triangulation-integrating results from multiple sources, where each approach has unrelated sources of bias.
RESULTS
Research findings have been remarkably consistent across multiple data sources. The most commonly misused opioid medications: hydrocodone = oxycodone > methadone = buprenorphine = tramadol = fentanyl (prescription form) > morphine > hydromorphone = oxymorphone > tapentadol. This rank order is similar to the number of prescriptions dispensed for each product in the USA. In the USA, prescription opioid misuse started to decrease about 2011. Typically, multiple drugs are misused together, particularly in lethal cases. Immediate release formulations are more commonly misused than extended release formulations. The introduction of tamper resistant formulations to resist crushing were followed by a decrease in misuse of those products.
CONCLUSIONS
The rapid expansion of opioid prescribing was accompanied by increasing misuse and mortality. Interventions such as prescription drug monitoring programmes, increased law enforcement and abuse deterrent formulations have been followed by decreases in misuse of most opioid analgesics.
Topics: Analgesics, Opioid; Humans; Opioid-Related Disorders; Oxycodone; Practice Patterns, Physicians'; Prescription Drug Misuse
PubMed: 33606888
DOI: 10.1111/bcp.14791 -
Annals of Palliative Medicine Mar 2021Cancer patients often require feeding or venting gastrostomy-tubes (G-tubes) for enteral nutrition or symptom palliation. The administration of most extended-release...
BACKGROUND
Cancer patients often require feeding or venting gastrostomy-tubes (G-tubes) for enteral nutrition or symptom palliation. The administration of most extended-release (ER) opioids via the G-tube or orally followed by clamping of the venting G-tube is contraindicated. Oxymorphone immediate release (IR) may be useful because of its longer half-life compared to other IR opioids. We examined the use of oxymorphone IR administered every 8 hours in patients with G-tubes.
METHODS
This was a retrospective chart review of 40 consecutive cancer patients with G-tubes who underwent opioid rotation (OR) to oxymorphone. Demographics, symptoms, morphine equivalent daily dose (MEDD), and oxymorphone dose were collected. Successful OR was defined as a 2-point or 30% reduction in pain score and continued use of oxymorphone at follow-up in outpatient setting, or discharge in inpatient setting. Opioid rotation ration (ORR) between MEDD and oxymorphone in patients with successful OR was calculated as MEDD before the OR divided by total oxymorphone dose/day at follow-up or discharge.
RESULTS
The median age was 56 years, 57.5% were white, 68% male, 47.5% (n=19) had head and neck cancer, 90% had advanced disease, 67.5% (n=27) were inpatient, and 15% (n=6) had venting G-tubes. 25/40 (62.5%) patients had successful OR to oxymorphone. The median ORR from MEDD to oxymorphone was 3.5 (IQR, 3.1-4). There were no independent predictors for successful OR, and ORR did not significantly differ among various groups.
CONCLUSIONS
Oxymorphone IR can be used successfully in cancer patients with G-tubes using an ORR of 3.5 to calculate dose from MEDD.
Topics: Analgesics, Opioid; Female; Gastrostomy; Humans; Male; Middle Aged; Neoplasms; Oxymorphone; Pain; Retrospective Studies
PubMed: 33549000
DOI: 10.21037/apm-20-969 -
Pain Physician Jan 2021Chronic low back pain (CLBP) incurs huge costs owing to increased healthcare expenditure, disability, insurance, and work absenteeism. Opioid analgesics are commonly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic low back pain (CLBP) incurs huge costs owing to increased healthcare expenditure, disability, insurance, and work absenteeism. Opioid analgesics are commonly used for the management of CLBP.
OBJECTIVE
To compare and rank the opioids used in the management of CLBP, in terms of efficacy and safety.
STUDY DESIGN
Systematic review and network meta-analyses (NMA).
METHOD
The search was conducted in Embase, PubMed, Cochrane databases for randomized controlled trials (RCTs) that had evaluated the efficacy and safety of opioids in CLBP. Two authors independently performed data extraction and quality assessment. The proportion of patients reporting either 30% or 50% reduction in pain from baseline to follow-up on the numeric rating scale, was measured as efficacy outcome. Pairwise meta-analyses and Bayesian NMA, within the random-effects model, were used to synthesize data. Effect estimates from Bayesian NMA were presented as odds ratio (OR) with 95% credible intervals (CrI). Heterogeneity and convergence were assessed by using I 2 and deviation information criteria.
RESULTS
Twenty-three RCTs with a total of 8,420 patients, evaluating 13 different opioids were included in this NMA. For 30% pain reduction, oxymorphone (OR: 5.36; 95% CrI: 1.02-30.3), tramadol with acetaminophen (OR: 2.37; 95% CrI: 1.08-5.17), and buprenorphine (OR: 2.29; 95% CrI: 1.05-5.07) shown statistically significant more effective than placebo. For 50% pain reduction, the statistically significant difference is observed with buprenorphine (OR: 2.38 95% CrI: 1.08-5.24), oxymorphone (OR: 5.10; 95% CrI: 1.31-20.41), and tramadol with acetaminophen (OR: 2.11; 95% CrI: 1.07-4.21). Hydrocodone (OR: 0.33; 95% CrI: 0.14-0.77) was found statistically safer compared to the other opioids.
LIMITATIONS
Only 5 trials had more than a 12-week study duration. We need clinical trials with longer follow-up as CLBP management requires a longer duration, and long-term prescribing of opioids associated with severe adverse event profile, development of tolerance, and dependence.
CONCLUSIONS
Oxymorphone has an advantage over other opioids to reduce pain by 30% and 50% in patients with CLBP.
Topics: Analgesics, Opioid; Bayes Theorem; Chronic Pain; Humans; Low Back Pain; Network Meta-Analysis
PubMed: 33400430
DOI: No ID Found -
Journal of Analytical Toxicology Feb 2022The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG),...
The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG), oxymorphone-3β-D-glucuronide (NOMG), noroxymorphone (NOM), oxymorphone (OM), 6α-oxycodol (αOCL), 6β-oxycodol (βOCL), noroxycodone (NOC) and oxycodone (OC) in urine by liquid chromatography tandem mass spectrometry to be used in a human study. The method was validated according to the Academy Standards Board Standard Practices for Method Development in Forensic Toxicology. The method was then applied to a single-dose pilot study of a subject. Urine samples were collected from the subject after ingesting 10-mg OC as an immediate-release tablet. Additionally, urine specimens (n = 15) that had previously been confirmed positive for OC were analyzed using the validated method. The calibration range for NOMG and OMG was 0.05-10 μg/mL; for all other analytes, it was 0.015-10 μg/mL. Validation parameters such as bias, precision, carryover and dilution integrity, all met the validation criteria. After the method was validated, urine samples from the first subject in the controlled dose study were analyzed. It was observed that OC, NOC and OMG contained the highest concentrations and were present in either the 0.5 or 1 h void. NOC and OMG were detected until the 48 h collection, while OC was detectable till the 24 h collection. Time to reach maximum concentration (Tmax) in the urine was achieved within 1.5 h for OC and within 3 h for NOC and OMG. Maximum concentration (Cmax) in the urine for OC, NOC and OMG was 3.15, 2.0 and 1.56 μg/mg, respectively. OC concentrations in authentic urines ranged from 0.015 to 12 μg/mL. Ranges for NOMG and OMG were 0.054-9.7 μg/mL and 0.14-67 μg/mL, respectively. A comprehensive method for the quantification of NOMG, OMG, NOM, OM, αOCL, βOCL, NOC and OC in urine was optimized and met the validation criteria. The concentrations of NOMG and OMG presented in this study provide the details needed in the forensic community to better comprehend OC pharmacokinetics.
Topics: Chromatography, Liquid; Humans; Oxycodone; Oxymorphone; Pilot Projects; Tandem Mass Spectrometry
PubMed: 33270113
DOI: 10.1093/jat/bkaa186 -
Molecules (Basel, Switzerland) Sep 2020Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not...
Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the -carboxymethyl- and -carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were -alkylated with -(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the -carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests.
Topics: Analgesics, Opioid; Demethylation; Esters; Haptens; Morphine; Protons; Titrimetry
PubMed: 32887468
DOI: 10.3390/molecules25174009 -
Psychopharmacology Dec 2020Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects often limit use. Drugs acting concomitantly as agonists at μ opioid...
RATIONALE
Opioids remain the drugs of choice for treating moderate to severe pain, although adverse effects often limit use. Drugs acting concomitantly as agonists at μ opioid receptors and antagonists at δ opioid receptors produce antinociceptive effects with a reduced profile of adverse effects; one such drug, benzylideneoxymorphone (BOM), might further limit adverse effects because it appears to have lower pharmacological efficacy than other μ opioid receptor agonists.
OBJECTIVES
The current study compared the acute behavioral effects of BOM with the effects of other μ opioid receptor agonists.
METHODS
Discriminative stimulus and rate-decreasing effects were studied in 1 group of 7 rats discriminating 3.2 mg/kg morphine while responding under a fixed-ratio 10 schedule of food presentation. Antinociceptive effects were determined in a second group of 8 rats using a warm water tail withdrawal procedure. Reinforcing effects were evaluated in a third group of 12 rats with a history of remifentanil self-administration.
RESULTS
BOM produced morphine-lever responding and both discriminative stimulus and rate-decreasing effects were antagonized by naltrexone. BOM did not markedly increase tail-withdrawal latencies from water maintained at 50 °C and did not substantially attenuate the antinociceptive effects of morphine. BOM was not self-administered and did not change remifentanil self-administration.
CONCLUSIONS
Some effects of BOM (e.g., discriminative stimulus effects) appear to be mediated by μ opioid receptors; however, BOM is not self-administered by rats, suggesting that it might have limited abuse liability and a reduced profile of adverse effects compared with currently prescribed opioids.
Topics: Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Male; Morphine; Naltrexone; Narcotic Antagonists; Oxymorphone; Pain; Pain Measurement; Rats; Receptors, Opioid, delta; Receptors, Opioid, mu; Reinforcement, Psychology; Self Administration
PubMed: 32820390
DOI: 10.1007/s00213-020-05638-1