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The Medical Letter on Drugs and... Dec 2022
Topics: Humans; Analgesics, Opioid; Pain; Oxycodone; Morphine
PubMed: 36541938
DOI: No ID Found -
Clinical Biochemistry Feb 2023Urine drug testing (UDT) monitors prescription compliance and/or drug abuse. However, interpretation of UDT results obtained by liquid chromatography-tandem mass...
BACKGROUND
Urine drug testing (UDT) monitors prescription compliance and/or drug abuse. However, interpretation of UDT results obtained by liquid chromatography-tandem mass spectrometry (LC-MS-MS) can be complicated by the presence of drug impurities that are detected by highly sensitive methods. Hydrocodone is a drug impurity that can be found as high as 1% in oxycodone pills.
OBJECTIVES
We evaluated the frequency and concentration of hydrocodone and its metabolite, hydromorphone, in patients taking oxycodone to check if the ratio of hydrocodone or hydromorphone to oxycodone could distinguish between oxycodone only use from those consuming additional opiates.
DESIGN & METHODS
We correlated LC-MS/MS results with medication records of 319 patients with positive oxycodone results over 7 months (4/2021-11/2021).
RESULTS
Fifteen of 319 patients with positive oxycodone results were taking oxycodone only. For these 15 patients, the mean ratio of hydrocodone to oxycodone was 0.57% (range 0.05%-3.35%), and the mean ratio of hydromorphone to oxycodone was 0.81% (range 0.18-3.51%).
CONCLUSIONS
Hydrocodone and/or hydromorphone are detectable in patients taking only oxycodone and can likely be identified as an impurity if their calculated ratio to oxycodone is <1 %. Further validation of the ratios in a larger sample size is recommended.
Topics: Humans; Hydrocodone; Hydromorphone; Oxycodone; Analgesics, Opioid; Chromatography, Liquid; Oxymorphone; Tandem Mass Spectrometry; Opioid-Related Disorders
PubMed: 36535386
DOI: 10.1016/j.clinbiochem.2022.12.009 -
Journal of Opioid Management 2022To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables.
DESIGN
Frequentist network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing opioids in patient-controlled analgesia (PCA).
SETTING
A systematic review.
DATA SOURCES
A systematic search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified relevant RCTs from start of recording to 2019.
ELIGIBILITY CRITERIA
RCTs comparing opioids via intravenous PCA in acute pain, with comparable resulting pain scores and identical treatment with coanalgesics at study level. The quality of studies was assessed using the Cochrane risk of bias tool with six items.
RESULTS
52 RCTs were identified with data for 16 opioids. Primary endpoint was the inverted ratio of means of the total consumption administered via PCA, which resembles the analgesic potency. The calculated analgesic potencies were sufentanil 423 [95 percent CI 334.99; 532.96], fentanyl 58 [48.22; 68.60], buprenorphine 37 [26.66; 50.81], remifentanil 13 [9.37; 19.13], alfentanil 7 [4.02; 11.01], hydromorphone 6 [4.96; 8.43], oxymorphone 6 [4.46; 8.84], butorphanol 4.5 [3.05; 6.73], diamorphine 2.2 [1.16; 4.10], morphine 1, oxycodone 0.9 [0.65; 1.34], piritramide 0.9 [0.55; 1.56], nalbuphine 0.7 [0.54; 0.95], pethidine 0.12 [0.10; 0.15], meptazinol 0.08 [0.03; 0.20], and tramadol 0.08 [0.07; 0.10].
CONCLUSIONS
The results in part contradict the values from the literature, which have been criticized for their imprecision. From clinical experience however, our findings seem very plausible. Short-acting opioids are less potent compared to longer acting drugs, eg, morphine, probably due to shorter intervals for -readministration.
Topics: Humans; Analgesia, Patient-Controlled; Analgesics, Opioid; Network Meta-Analysis; Tramadol; Morphine
PubMed: 36523208
DOI: 10.5055/jom.2022.0751 -
Circulation Research Aug 2022To clarify the mechanisms underlying physical activity (PA)-related cardioprotection, we examined the association of PA with plasma bioactive lipids (BALs) and... (Clinical Trial)
Clinical Trial
BACKGROUND
To clarify the mechanisms underlying physical activity (PA)-related cardioprotection, we examined the association of PA with plasma bioactive lipids (BALs) and cardiovascular disease (CVD) events. We additionally performed genome-wide associations.
METHODS
PA-bioactive lipid associations were examined in VITAL (VITamin D and OmegA-3 TriaL)-clinical translational science center (REGISTRATION: URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT01169259; N=1032) and validated in JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)-NC (REGISTRATION: URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT00239681; N=589), using linear models adjusted for age, sex, race, low-density lipoprotein-cholesterol, total-C, and smoking. Significant BALs were carried over to examine associations with incident CVD in 2 nested CVD case-control studies: VITAL-CVD (741 case-control pairs) and JUPITER-CVD (415 case-control pairs; validation).
RESULTS
We detected 145 PA-bioactive lipid validated associations (false discovery rate <0.1). Annotations were found for 6 of these BALs: 12,13-diHOME, 9,10-diHOME, lysoPC(15:0), oxymorphone-3b-D-glucuronide, cortisone, and oleoyl-glycerol. Genetic analysis within JUPITER-NC showed associations of 32 PA-related BALs with 22 single-nucleotide polymorphisms. From PA-related BALs, 12 are associated with CVD.
CONCLUSIONS
We identified a PA-related bioactive lipidome profile out of which 12 BALs also had opposite associations with incident CVD events.
Topics: Cardiovascular Diseases; Cholesterol, LDL; Exercise; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Risk Factors; Rosuvastatin Calcium
PubMed: 35862024
DOI: 10.1161/CIRCRESAHA.122.320952 -
The Journal of Pharmacology and... Aug 2022Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success, as mutations can dramatically alter therapeutic efficacy and...
Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success, as mutations can dramatically alter therapeutic efficacy and addiction liability. We found robust, sex-dependent BALB/c substrain differences in oxycodone behaviors and whole brain concentration of oxycodone metabolites. BALB/cJ females showed robust state-dependent oxycodone reward learning as measured via conditioned place preference when compared with the closely related BALB/cByJ substrain. Accordingly, BALB/cJ females also showed a robust increase in brain concentration of the inactive metabolite noroxycodone and the active metabolite oxymorphone compared with BALB/cByJ mice. Oxymorphone is a highly potent, full agonist at the mu opioid receptor that could enhance drug-induced interoception and state-dependent oxycodone reward learning. Quantitative trait locus (QTL) mapping in a BALB/c F2 reduced complexity cross revealed one major QTL on chromosome 15 underlying brain oxymorphone concentration that explained 32% of the female variance. BALB/cJ and BALB/cByJ differ by fewer than 10,000 variants, which can greatly facilitate candidate gene/variant identification. Hippocampal and striatal cis-expression QTL (eQTL) and exon-level eQTL analysis identified , a candidate gene coding for a transcriptional repressor with a private BALB/cJ retroviral insertion that reduces expression and sex-dependent dysregulation of cytochrome P450 enzymes. Whole brain proteomics corroborated the eQTL and identified upregulated CYP2D11 that could increase brain oxymorphone in BALB/cJ females. To summarize, is a highly promising candidate gene underlying brain oxycodone metabolite levels. Future studies will validate and its site of action using reciprocal gene editing and tissue-specific viral manipulations in BALB/c substrains. SIGNIFICANCE STATEMENT: Our findings show that genetic variation can result in sex-specific alterations in whole brain concentration of a bioactive opioid metabolite after oxycodone administration, reinforcing the need for sex as a biological factor in pharmacogenomic studies. The cooccurrence of female-specific increased oxymorphone and state-dependent reward learning suggests that this minor yet potent and efficacious metabolite of oxycodone could increase opioid interoception and drug-cue associative learning of opioid reward, which has implications for cue-induced relapse of drug-seeking behavior and for precision pharmacogenetics.
Topics: Analgesics, Opioid; Animals; Brain; Female; Homeodomain Proteins; Male; Mice; Mice, Inbred BALB C; Oxycodone; Oxymorphone; Reward
PubMed: 35688478
DOI: 10.1124/jpet.122.001217 -
Journal of Analytical Toxicology Oct 2022A rapid, simple extraction method followed by qualitative screening using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for drugs in oral fluid is presented....
A rapid, simple extraction method followed by qualitative screening using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for drugs in oral fluid is presented. The decision points were selected to be at, or lower, than those recommended as Tier I compounds by the National Safety Council's Alcohol, Drugs and Impairment Division for toxicological investigation of driving under the influence of drug (DUID) cases and were also at, or lower, than those recommended by Substance Abuse and Mental Health Service Administration and the Department of Transportation for Federal workplace drug testing programs. The method included 30 drugs: delta-9-tetrahydrocannabinol, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, cocaine, benzoylecgonine, carisoprodol, meprobamate, zolpidem, alprazolam, clonazepam, 7-aminoclonazepam, diazepam, nordiazepam, lorazepam, oxazepam, temazepam, codeine, morphine, 6-acetylmorphine, buprenorphine, fentanyl, hydrocodone, hydromorphone, oxycodone, oxymorphone, methadone, tramadol and phencyclidine. Phencyclidine was included because it is in the Federal workplace program even though it is considered a Tier II drug for DUID cases. A liquid-liquid extraction method using isopropanol, hexane and ethyl acetate to extract drugs from the oral fluid-buffer mix collected in a Quantisal™ device, followed by LC-MS-MS screening, was developed and validated according to ANSI/ASB 2019 Standard Practices for Method Validation in Forensic Toxicology. Interference studies, limit of detection, precision at the decision point, ionization suppression/enhancement and processed sample stability were determined for each drug. The method was successfully applied to proficiency specimens and routine samples received in the laboratory.
Topics: 2-Propanol; 3,4-Methylenedioxyamphetamine; Alprazolam; Amphetamines; Buprenorphine; Carisoprodol; Clonazepam; Cocaine; Codeine; Dronabinol; Fentanyl; Hexanes; Hydrocodone; Hydromorphone; Lorazepam; Meprobamate; Methadone; Methamphetamine; Morphine Derivatives; N-Methyl-3,4-methylenedioxyamphetamine; Nordazepam; Oxazepam; Oxycodone; Oxymorphone; Pharmaceutical Preparations; Phencyclidine; Tandem Mass Spectrometry; Temazepam; Tramadol; Zolpidem
PubMed: 35640884
DOI: 10.1093/jat/bkac031 -
Journal of Analytical Toxicology Aug 2022To avoid a positive urine drug test, donors might try to subvert the test, either by adulterating the specimen with a product designed to interfere with testing or by...
To avoid a positive urine drug test, donors might try to subvert the test, either by adulterating the specimen with a product designed to interfere with testing or by substituting the specimen for a synthetic urine. A market search conducted in December of 2020 identified 3 adulterants and 32 synthetic urines, and a selection was procured based on specific criteria. Samples prepared with the 3 adulterants and 10 synthetic urines were submitted for testing at five forensic drug testing laboratories to perform immunoassay screening, chromatographic confirmation analysis and specimen validity testing (SVT). One adulterant determined to contain iodate reduced THC-COOH concentrations by 65% and the concentrations of 6-acetylmorphine, morphine, oxycodone, oxymorphone, hydrocodone and hydromorphone by 6-27%. Another adulterant determined to contain nitrite reduced THC-COOH concentrations by 22%, while the third did not affect drug screening or confirmatory testing. Both active adulterants could be identified through positive oxidant screens as well as through signal suppression in cloned enzyme donor immunoassay (CEDIA). The synthetic urines could not be identified either through traditional SVT or by the AdultaCheck10 dipstick. The Synthetic UrineCheck dipstick produced a difference in response between the authentic urine specimen and the synthetic urine samples, but the difference was small and difficult to observe. While most synthetic urines now contain uric acid, magnesium and caffeine, the results indicated that a biomarker panel including endogenous and exogenous markers of authentic urine performed well and clearly demonstrated the absence of biomarkers in the synthetic urines. The SVT assay also offers potential targets for future screening assays.
Topics: Dronabinol; Hydrocodone; Immunoassay; Oxymorphone; Substance Abuse Detection
PubMed: 35639619
DOI: 10.1093/jat/bkac029 -
American Health & Drug Benefits Mar 2022The opioid epidemic and drug abuse are critical public health challenges in the United States. The number of deaths from exceeding the recommended opioid dose is...
BACKGROUND
The opioid epidemic and drug abuse are critical public health challenges in the United States. The number of deaths from exceeding the recommended opioid dose is increasing.
OBJECTIVE
To describe the recent trends in utilization, spending, and cost of opioid medications in the US Medicaid population between 1991 and 2019.
METHODS
This retrospective, descriptive study was designed to evaluate the utilization of, spending on, and cost of opioids from 1991 to 2019 in the Medicaid population. We extracted data from the Centers for Medicare & Medicaid Services national Medicaid pharmacy files. The opioids received included fentanyl, meperidine, morphine, hydromorphone, oxymorphone, hydrocodone, hydrocodone plus acetaminophen, oxycodone, oxycodone plus acetaminophen, tapentadol, and tramadol. The number of prescriptions and reimbursement spending were calculated for each medication per quarter year. The average per-prescription reimbursement as a proxy of drug price was calculated as the reimbursement amount divided by the number of prescriptions per quarter year. The market shares by spending and utilization were also calculated for each opioid medication.
RESULTS
The number of all opioid prescriptions in Medicaid increased from approximately 2.1 million in 1991 to approximately 41.6 million in 2015, and then reduced to approximately 19.1 million in 2019. During this 29-year study period, the opioid medications that were used as monotherapy were hydrocodone (246.8 million prescriptions), oxycodone (111.9 million prescriptions), and tramadol (75.2 million prescriptions). The total spending in the Medicaid population on opioids was $19.4 billion, including approximately $7.3 billion spending on oxycodone, approximately $3.7 billion on fentanyl, and approximately $3.3 billion on hydrocodone. The majority of opioid prices increased over time, and the highest average costs per opioid prescription in 2019 were $1188 for oxymorphone, $641 for tapentadol, and $198 for fentanyl.
CONCLUSIONS
The utilization of and spending on opioid medications in Medicaid increased over time, peaked in 2015, and then declined with the initiation of nationwide programs to combat the opioid epidemic. Effective cost-containment strategies and programs to combat the abuse of opioids are warranted in Medicaid programs.
PubMed: 35586617
DOI: No ID Found -
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 -
Drug and Alcohol Dependence Jun 2022Prior research demonstrates a high prevalence of substance use, including opioid use, among those who have had personal or vicarious contact with the correctional...
BACKGROUND
Prior research demonstrates a high prevalence of substance use, including opioid use, among those who have had personal or vicarious contact with the correctional system. Relatedly, alongside patterns of rising opioid use in general, opioid use during pregnancy is becoming a growing public health concern. Still, risk factors for prescription opioid use during pregnancy remain understudied. This study is the first to assess the connection between a women's personal or vicarious exposure to incarceration in the 12 months prior to birth and patterns of prenatal opioid use.
METHODS
Data are from the Pregnancy Risk Assessment Monitoring System (PRAMS) in 2019 (N = 17,551 mothers). Logistic and multinomial logistic regression are used to assess the association between incarceration exposure and patterns of opioid use during pregnancy.
RESULTS
Incarceration-exposed women were more likely to use all eight types of prescription opioids assessed in this study (Hydrocodone, Codeine, Oxycodone, Tramadol, Hydromorphone/Meperidine, Oxymorphone, Morphine, and Fentanyl). After adjustment for control variables, incarceration-exposed women were significantly more likely to report any prescription opioid use during pregnancy (OR = 1.745, 95% CI = 1.194, 2.554). Furthermore, relative to no opioid use, incarceration exposure was also associated with illicit prescription opioid use (RRR = 2.979, 1.533, 5.791).
CONCLUSIONS
Incarceration exposure in the year prior to birth is associated with higher odds of prescription opioid use. These findings add to the burgeoning literature that details a women's exposure to incarceration is a risk marker for substance use and engagement in health risk behaviors that can jeopardize maternal and infant wellbeing.
Topics: Analgesics, Opioid; Female; Humans; Opioid-Related Disorders; Oxycodone; Pregnancy; Prescriptions; Tramadol
PubMed: 35405460
DOI: 10.1016/j.drugalcdep.2022.109434