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PeerJ 2019The US is experiencing an epidemic of opioid overdoses which may be at least partially due to an over-reliance on opioid analgesics in the treatment of chronic...
BACKGROUND
The US is experiencing an epidemic of opioid overdoses which may be at least partially due to an over-reliance on opioid analgesics in the treatment of chronic non-cancer pain and subsequent escalation to heroin or illicit fentanyl. As Texas was reported to be among the lowest in the US for opioid use and misuse, further examination of this state is warranted.
MATERIALS AND METHODS
This study was conducted to quantify prescription opioid use in Texas. Data was obtained from the publicly available US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) which monitors controlled substances transactions from manufacture to commercial distribution. Data for 2006-2017 from Texas for ten prescription opioids including eight primarily used to relieve pain (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, morphine, oxycodone, oxymorphone) and two (buprenorphine and methadone) for the treatment of an Opioid Use Disorder (OUD) were examined.
RESULTS
The change in morphine mg equivalent (MME) of all opioids (+23.3%) was only slightly greater than the state's population gains (21.1%). Opioids used to treat an OUD showed pronounced gains (+90.8%) which were four-fold faster than population growth. Analysis of individual agents revealed pronounced elevations in codeine (+387.5%), hydromorphone (+106.7%), and oxycodone (+43.6%) and a reduction in meperidine (-80.3%) in 2017 relative to 2006. Methadone in 2017 accounted for a greater portion (39.5%) of the total MME than hydrocodone, oxycodone, morphine, hydromorphone, oxymorphone, and meperidine, combined. There were differences between urban and rural areas in the changes in hydrocodone and buprenorphine.
CONCLUSIONS
Collectively, these findings indicate that continued vigilance is needed in Texas to appropriately treat pain and an OUD while minimizing the potential for prescription opioid diversion and misuse. Texas may lead the US in a return to pre-opioid epidemic prescription levels.
PubMed: 31824762
DOI: 10.7717/peerj.8108 -
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 -
Scientific Reports Mar 2020Morphine and structurally-derived compounds are µ opioid receptor (µOR) agonists, and the most effective analgesic drugs. However, their usefulness is limited by...
Morphine and structurally-derived compounds are µ opioid receptor (µOR) agonists, and the most effective analgesic drugs. However, their usefulness is limited by serious side effects, including dependence and abuse potential. The N-substituent in morphinans plays an important role in opioid activities in vitro and in vivo. This study presents the synthesis and pharmacological evaluation of new N-phenethyl substituted 14-O-methylmorphinan-6-ones. Whereas substitution of the N-methyl substituent in morphine (1) and oxymorphone (2) by an N-phenethyl group enhances binding affinity, selectivity and agonist potency at the µOR of 1a and 2a, the N-phenethyl substitution in 14-methoxy-N-methylmorphinan-6-ones (3 and 4) converts selective µOR ligands into dual µ/δOR agonists (3a and 4a). Contrary to N-methylmorphinans 1-4, the N-phenethyl substituted morphinans 1a-4a produce effective and potent antinociception without motor impairment in mice. Using docking and molecular dynamics simulations with the µOR, we establish that N-methylmorphinans 1-4 and their N-phenethyl counterparts 1a-4a share several essential receptor-ligand interactions, but also interaction pattern differences related to specific structural features, thus providing a structural basis for their pharmacological profiles. The emerged structure-activity relationships in this class of morphinans provide important information for tuning in vitro and in vivo opioid activities towards discovery of effective and safer analgesics.
Topics: Analgesics, Opioid; Animals; CHO Cells; Cell Line; Cricetulus; Humans; Ligands; Male; Mice; Morphinans; Morphine; Receptors, Opioid, delta; Receptors, Opioid, mu; Structure-Activity Relationship
PubMed: 32221355
DOI: 10.1038/s41598-020-62530-w -
Journal of Clinical Anesthesia 1989The safety and efficacy of two potent opiate analgesics, fentanyl and oxymorphone, used as adjuncts in general anesthesia, were studied in 39 patients undergoing... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The safety and efficacy of two potent opiate analgesics, fentanyl and oxymorphone, used as adjuncts in general anesthesia, were studied in 39 patients undergoing elective gynecologic surgery of at least 2 hours duration. Based on a potency ratio of 10:1, patients received either fentanyl 6.5 micrograms/kg or oxymorphone 65 micrograms/kg prior to a thiopental 2 to 3 mg/kg succinylcholine induction and endotracheal intubation. Additional maintenance narcotic and isoflurane were administered as required by the "blinded" anesthesiologist in response to hemodynamic alterations 15% above a presurgical baseline. Overall analysis included hemodynamic response at preset intraoperative intervals, total anesthetic requirements, and stability of vital signs in the recovery room. Blood pressure and heart rate were reliably controlled with either agent; however, less narcotic (ml) and recovery room analgesics were required in the oxymorphone-treated group (p less than 0.05). Decreased naloxone requirements (p less than 0.05) and a more rapid emergence suggested that fentanyl was a safer agent when administered in relatively unrestricted fashion.
Topics: Anesthesia, General; Double-Blind Method; Drug Evaluation; Female; Fentanyl; Genital Diseases, Female; Hemodynamics; Humans; Hydromorphone; Oxymorphone; Randomized Controlled Trials as Topic
PubMed: 2483328
DOI: 10.1016/0952-8180(89)90022-6 -
International Journal of Environmental... May 2020There have been dynamic changes in prescription opioid use in the US but the state level policy factors contributing to these are incompletely understood. We examined...
There have been dynamic changes in prescription opioid use in the US but the state level policy factors contributing to these are incompletely understood. We examined the association between the legalization of recreational marijuana and prescription opioid distribution in Colorado. Utah and Maryland, two states that had not legalized recreational marijuana, were selected for comparison. Prescription data reported to the Drug Enforcement Administration for nine opioids used for pain (e.g., fentanyl, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone) and two primarily for opioid use disorder (OUD, methadone and buprenorphine) from 2007 to 2017 were evaluated. Analysis of the interval pre (2007-2012) versus post (2013-2017) marijuana legalization revealed statistically significant decreases for Colorado ( < 0.05) and Maryland ( < 0.01), but not Utah, for pain medications. There was a larger reduction from 2012 to 2017 in Colorado (-31.5%) than the other states (-14.2% to -23.5%). Colorado had a significantly greater decrease in codeine and oxymorphone than the comparison states. The most prevalent opioids by morphine equivalents were oxycodone and methadone. Due to rapid and pronounced changes in prescription opioid distribution over the past decade, additional study with more states is needed to determine whether cannabis policy was associated with reductions in opioids used for chronic pain.
Topics: Analgesics, Opioid; Cannabis; Colorado; Humans; Legislation, Drug; Maryland; Oxycodone; Practice Patterns, Physicians'; United States
PubMed: 32392702
DOI: 10.3390/ijerph17093251 -
Therapeutics and Clinical Risk... Aug 2008Chronic cancer and nonmalignant pain (CNMP) is a common and major health problem afflicting approximately 40 million persons in the US. Most cancer patients, and many...
Chronic cancer and nonmalignant pain (CNMP) is a common and major health problem afflicting approximately 40 million persons in the US. Most cancer patients, and many patients with CNMP, require opioid analgesics to obtain adequate pain relief. Oral oxymorphone is a new formulation of an existing parenteral opioid that has become available for the treatment of significant pain: acute postoperative, chronic arthritis, chronic low back, and chronic cancer pain. Oxymorphone is a typical mu-opioid agonist that is effective in both immediate- and extended-release (IR and ER) formulations. Oxymorphone is more lipid soluble than morphine, resulting in a rapid onset of action when given in tablet formulation, with a duration of action of approximately 4-6 hours in IR and 12 hours in ER preparations. Oxymorphone provides excellent pain relief for significant pain, with typical opioid side effects that are usually mild or moderate in intensity. Multiple double-blind, prospective, placebo-controlled clinical trials have demonstrated the clinical efficacy and safety of this new oral opioid preparation. Oral oxymorphone is an effective opioid that provides a new therapeutic option for the physician.
PubMed: 19209260
DOI: 10.2147/tcrm.s1784 -
Drug and Alcohol Dependence Sep 2018For a number of fiscal and practical reasons, data on heroin use have been of poor quality, which has hampered the ability to halt the growing epidemic. Internet search...
BACKGROUND
For a number of fiscal and practical reasons, data on heroin use have been of poor quality, which has hampered the ability to halt the growing epidemic. Internet search data, such as those made available by Google Trends, have been used as a low-cost, real-time data source for monitoring and predicting a variety of public health outcomes. We aimed to determine whether data on opioid-related internet searches might predict future heroin-related admissions to emergency departments (ED).
METHODS
Across nine metropolitan statistical areas (MSAs) in the United States, we obtained data on Google searches for prescription and non-prescription opioids, as well as Substance Abuse and Mental Health Services Administration (SAMHSA) data on heroin-related ED visits from 2004 to 2011. A linear mixed model assessed the relationship between opioid-related Internet searches and following year heroin-related visits, controlling for MSA GINI index and total number of ED visits.
RESULTS
The best-fitting model explained 72% of the variance in heroin-related ED visits. The final model included the search keywords "Avinza," "Brown Sugar," "China White," "Codeine," "Kadian," "Methadone," and "Oxymorphone." We found regional differences in where and how people searched for opioid-related information.
CONCLUSIONS
Internet search-based modeling should be explored as a new source of insights for predicting heroin-related admissions. In geographic regions where no current heroin-related data exist, Internet search modeling might be a particularly valuable and inexpensive tool for estimating changing heroin use trends. We discuss the immediate implications for using this approach to assist in managing opioid-related morbidity and mortality in the United States.
Topics: Adult; Analgesics, Opioid; Emergency Service, Hospital; Female; Forecasting; Heroin Dependence; Humans; Internet; Linear Models; Male; Patient Admission; Pilot Projects; Predictive Value of Tests; Public Health; United States; United States Substance Abuse and Mental Health Services Administration
PubMed: 30036853
DOI: 10.1016/j.drugalcdep.2018.05.009 -
Psychopharmacology Sep 2021Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are available. The primary aims of this pilot study were to directly compare IV oxymorphone to IV oxycodone, morphine, and hydromorphone on a subjective measure of drug liking and to assess relative potency.
METHODS
Participants (n = 6) with opioid use disorder, physical dependence, and current IV use completed this two-site, within-subject, double-blind, placebo-controlled, inpatient pilot study. During each session, one IV dose (mg/70 kg) was administered: oxymorphone (1.8, 3.2, 5.6, 10, 18, 32), hydromorphone (1.8, 3.2, 5.6, 10, 18), oxycodone (18, 32, 56), morphine (18, 32), and placebo. Data were collected before and for 6 h after dosing. Primary outcomes included safety/physiological effects, subjective reports of drug liking, and relative potency estimates.
RESULTS
All active test drugs produced prototypical, dose-related µ opioid agonist effects (e.g., miosis). Oxymorphone was more potent than the comparator opioids on several measures, including drug liking and respiratory depression (p < 0.05). Across abuse-related subjective outcomes, oxymorphone was 2.3-2.8-fold more potent than hydromorphone and 12.5-14-fold more potent than oxycodone (p < 0.05).
CONCLUSIONS
Despite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids.
Topics: Analgesics, Opioid; Humans; Opioid-Related Disorders; Oxycodone; Oxymorphone; Pilot Projects
PubMed: 34106317
DOI: 10.1007/s00213-021-05872-1 -
Annals of Translational Medicine Dec 2022Oxycodone is a commonly used oral opioid in children for treating postoperative pain. Highly polymorphic gene metabolizes oxycodone into its more potent metabolite,...
BACKGROUND
Oxycodone is a commonly used oral opioid in children for treating postoperative pain. Highly polymorphic gene metabolizes oxycodone into its more potent metabolite, oxymorphone. We hypothesized that altered activity due to polymorphisms will influence oxycodone requirements {relative oxycodone use [oxycodone morphine equivalents (MEq)/total MEq] to maintain analgesia} (primary outcome) and risk for oxycodone induced side-effects such as respiratory depression (RD) and emesis (secondary outcomes). We also explored the influence of genotype availability and provider guidance on oral opioid prescription patterns.
METHODS
Patients who underwent Nuss procedure and spine fusion with genotyping results available preoperatively were included. Data on demographics, genotypes, oral opioids, pain scores, RD and emesis were collected. Univariate and multivariable regression for comparison of genotype predicted poor, ultrarapid, intermediate metabolizers (PM, UM and IM) phenotype with normal metabolizers (NM) for outcomes were performed. Stratified logistic regression was conducted in low (oxycodone/total MEq <0.5) and high (and oxycodone/total MEq >0.5) oxycodone use groups for RD and emesis, with application of firth correction due to quasi-complete separations. Breslow-Day test was used to evaluate odds ratios for prescribing genotype directed opioid between control group (2012-15) (where providers were alerted to genotyping results availability but not directed to use them while prescribing) and genotype directed groups (2016-18) (where providers were directed to use the genotyping results available to them while prescribing oxycodone after surgery).
RESULTS
Of 193 subjects (age 15.9±0.25 years, 28.5% female, 93.78% White; 101 NM, 76 IM, 10 PM and 6 UM), 77.72% underwent pectus surgery. phenotype was associated with oxycodone MEq/total MEq requirements (P<0.001). Both PM and UM phenotypes had lower oxycodone requirements compared to NM [-0.316 (SE 0.098), P=0.005 and -0.432 (SE 0.113), P<0.001 respectively]. phenotype was associated with RD in high use oxycodone group (P=0.018) but not low use oxycodone groups (P=0.634). No phenotype association was found for emesis. Oxycodone was prescribed to 91.24% of NM/IM 66.67% of PM/UM (P=0.129) in control group and 94.64% of NM/IM 28.57% of PM/UM (P<0.001) in the genotype-directed group. PM/UM phenotypes in genotype directed group had a lower chance of being prescribed oxycodone (effect size =-2.775; SE 1.566; P=0.076).
CONCLUSIONS
Our findings suggest genotypes are associated with oxycodone requirements for analgesia and may influence risk for RD. Genotype availability and guidance likely influence oral opioid prescription pattern after surgery. Our findings are limited by small sample size for UM/PM groups.
PubMed: 36618804
DOI: 10.21037/atm-2022-58 -
Pharmaceuticals (Basel, Switzerland) Jun 2023Opioids are considered the cornerstone of pain management: they show good efficacy as a first-line therapy for moderate to severe cancer pain. Since...
BACKGROUND
Opioids are considered the cornerstone of pain management: they show good efficacy as a first-line therapy for moderate to severe cancer pain. Since pharmacokinetic/pharmacodynamic information about the tissue-specific effect and toxicity of opioids is still scarce, their quantification in post-mortem autoptic specimens could give interesting insights.
METHODS
We describe an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method for the simultaneous quantification of methadone, morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone and fentanyl in several tissues: liver, brain, kidney, abdominal adipose tissue, lung and blood plasma. The presented method has been applied on 28 autoptic samples from different organs obtained from four deceased PLWH who used opioids for palliative care during terminal disease.
RESULTS
Sample preparation was based on tissue weighing, disruption, sonication with drug extraction medium and a protein precipitation protocol. The extracts were then dried, reconstituted and injected onto the LX50 QSight 220 (Perkin Elmer, Milan, Italy) system. Separation was obtained by a 7 min gradient run at 40 °C with a Kinetex Biphenyl 2.6 µm, 2.1 × 100 mm. Concerning the analyzed samples, higher opioids concentrations were observed in tissues than in plasma. Particularly, O-MOR and O-COD showed higher concentrations in kidney and liver than other tissues (>15-20 times greater) and blood plasma (>100 times greater).
CONCLUSIONS
Results in terms of linearity, accuracy, precision, recovery and matrix effect fitted the recommendations of FDA and EMA guidelines, and the sensitivity was high enough to allow successful application on human autoptic specimens from an ethically approved clinical study, confirming its eligibility for post-mortem pharmacological/toxicological studies.
PubMed: 37375850
DOI: 10.3390/ph16060903