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Prehospital and Disaster Medicine Apr 2023Proximal femoral fractures are characterized as one of the most common and most painful injuries sustained by patients of all ages and are associated with high rates of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Proximal femoral fractures are characterized as one of the most common and most painful injuries sustained by patients of all ages and are associated with high rates of oligoanalgesia in the prehospital setting. Current treatments include oral and parenteral opiates and sedative agents, however regional anesthesia techniques for pain relief may provide superior analgesia with lower risk of side effects during patient transportation. The fascia iliaca compartment block (FICB) is an inexpensive treatment which is performed with minimal additional equipment, ultimately making it suitable in prehospital settings.
PROBLEM
In adult patients sustaining proximal femoral fractures in the prehospital setting, what is the effect of the FICB on non-verbal pain scores (NVPS), patient satisfaction, success rate, and adverse events compared to traditional analgesic techniques?
METHODS
A librarian-assisted literature search was conducted of the Cochrane Database, Ovid MEDLINE, PubMed, Ovid EMBASE, Scopus, and Web of Science indexes. Additionally, reference lists for potential review articles from the , the , the , , and the were reviewed. Databases and journals were searched during the period from January 1, 1980 through July 1, 2022. Each study was scrutinized for quality and validity and was assigned a level of evidence as per Oxford Center for Evidence-Based Medicine guidelines.
RESULTS
Five studies involving 340 patients were included (ie, two randomized control trials [RCTs], two observational studies, and one prospective observational study). Pain scores decreased after prehospital FICB across all included studies by a mean of 6.65 points (5.25 - 7.5) on the NVPS. Out of the total 257 FICBs conducted, there was a success rate of 230 (89.3%). Of these, only two serious adverse events were recorded, both of which related to local analgesia toxicity. Neither resulted in long-term sequelae and only one required treatment.
CONCLUSION
Use of FICBs results in a significant decrease in NVPS in the prehospital setting, and they are ultimately suitable as regional analgesic techniques for proximal femur fractures. It carries a low risk of adverse events and may be performed by health care practitioners of various backgrounds with suitable training. The results suggest that FICBs are more effective for pain management than parenteral or oral opiates and sedative agents alone and can be used as an appropriate adjunct to pain management.
Topics: Adult; Humans; Nerve Block; Femoral Fractures; Proximal Femoral Fractures; Pain; Emergency Medical Services; Fascia; Opiate Alkaloids; Hip Fractures; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36912109
DOI: 10.1017/S1049023X23000298 -
Molecules (Basel, Switzerland) Feb 2021Codeine is derived from morphine, an opioid analgesic, and has weaker analgesic and sedative effects than the parent molecule. This weak opioid is commonly used in... (Review)
Review
Codeine is derived from morphine, an opioid analgesic, and has weaker analgesic and sedative effects than the parent molecule. This weak opioid is commonly used in combination with other drugs for over-the-counter cough relief medication. Due to the psychoactive properties of opioid drugs, the easily obtained codeine often becomes subject to misuse. Codeine misuse has emerged as a concerning public health issue due to its associated adverse effects such as headache, nausea, vomiting, and hemorrhage. Thus, it is very important to develop reliable analytical techniques to detect codeine for both quality control of pharmaceutical formulations and identifying drug misuse in the community. This review aims to provide critical outlooks on analytical methods applicable to the determination of codeine.
Topics: Chemistry Techniques, Analytical; Codeine; Humans
PubMed: 33557168
DOI: 10.3390/molecules26040800 -
The Cochrane Database of Systematic... Jun 2015The review represents one in a family of four reviews focusing on a range of different interventions for drug-using offenders. This specific review considers... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The review represents one in a family of four reviews focusing on a range of different interventions for drug-using offenders. This specific review considers pharmacological interventions aimed at reducing drug use or criminal activity, or both, for illicit drug-using offenders.
OBJECTIVES
To assess the effectiveness of pharmacological interventions for drug-using offenders in reducing criminal activity or drug use, or both.
SEARCH METHODS
We searched Fourteen electronic bibliographic databases up to May 2014 and five additional Web resources (between 2004 and November 2011). We contacted experts in the field for further information.
SELECTION CRITERIA
We included randomised controlled trials assessing the efficacy of any pharmacological intervention a component of which is designed to reduce, eliminate or prevent relapse of drug use or criminal activity, or both, in drug-using offenders. We also report data on the cost and cost-effectiveness of interventions.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
Fourteen trials with 2647 participants met the inclusion criteria. The interventions included in this review report on agonistic pharmacological interventions (buprenorphine, methadone and naltrexone) compared to no intervention, other non-pharmacological treatments (e.g. counselling) and other pharmacological drugs. The methodological trial quality was poorly described, and most studies were rated as 'unclear' by the reviewers. The biggest threats to risk of bias were generated through blinding (performance and detection bias) and incomplete outcome data (attrition bias). Studies could not be combined all together because the comparisons were too different. Only subgroup analysis for type of pharmacological treatment were done. When compared to non-pharmacological, we found low quality evidence that agonist treatments are not effective in reducing drug use or criminal activity, objective results (biological) (two studies, 237 participants (RR 0.72 (95% CI 0.51 to 1.00); subjective (self-report), (three studies, 317 participants (RR 0.61 95% CI 0.31 to 1.18); self-report drug use (three studies, 510 participants (SMD: -0.62 (95% CI -0.85 to -0.39). We found low quality of evidence that antagonist treatment was not effective in reducing drug use (one study, 63 participants (RR 0.69, 95% CI 0.28 to 1.70) but we found moderate quality of evidence that they significantly reduced criminal activity (two studies, 114 participants, (RR 0.40, 95% CI 0.21 to 0.74).Findings on the effects of individual pharmacological interventions on drug use and criminal activity showed mixed results. In the comparison of methadone to buprenorphine, diamorphine and naltrexone, no significant differences were displayed for either treatment for self report dichotomous drug use (two studies, 370 participants (RR 1.04, 95% CI 0.69 to 1.55), continuous measures of drug use (one study, 81 participants, (mean difference (MD) 0.70, 95% CI -5.33 to 6.73); or criminal activity (one study, 116 participants, (RR 1.25, 95% CI 0.83 to 1.88) between methadone and buprenorphine. Similar results were found for comparisons with diamorphine with no significant differences between the drugs for self report dichotomous drug use for arrest (one study, 825 participants, (RR 1.25, 95% CI 1.03 to 1.51) or naltrexone for dichotomous measures of reincarceration (one study, 44 participants, (RR 1.10, 95% CI 0.37 to 3.26), and continuous outcome measure of crime, (MD -0.50, 95% CI -8.04 to 7.04) or self report drug use (MD 4.60, 95% CI -3.54 to 12.74).
AUTHORS' CONCLUSIONS
When compared to non-pharmacological treatment, agonist treatments did not seem effective in reducing drug use or criminal activity. Antagonist treatments were not effective in reducing drug use but significantly reduced criminal activity. When comparing the drugs to one another we found no significant differences between the drug comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures. Caution should be taken when interpreting these findings, as the conclusions are based on a small number of trials, and generalisation of these study findings should be limited mainly to male adult offenders. Additionally, many studies were rated at high risk of bias.
Topics: Adult; Buprenorphine; Crime; Criminals; Female; Heroin; Humans; Male; Methadone; Naltrexone; Narcotics; Opiate Substitution Treatment; Randomized Controlled Trials as Topic; Substance-Related Disorders
PubMed: 26035084
DOI: 10.1002/14651858.CD010862.pub2 -
Molecules (Basel, Switzerland) Dec 2022The design of enantiopure stereoisomers of N-2-phenylcyclopropylmethyl-substituted ortho-c oxide-bridged phenylmorphans, the E and Z isomers of an N-cinnamyl moiety, and...
The design of enantiopure stereoisomers of N-2-phenylcyclopropylmethyl-substituted ortho-c oxide-bridged phenylmorphans, the E and Z isomers of an N-cinnamyl moiety, and N-propyl enantiomers were based on combining the most potent oxide-bridged phenylmorphan (the ortho-c isomer) with the most potent N-substituent that we previously found with a 5-(3-hydroxy)phenylmorphan (i.e., N-2-phenylcyclopropyl methyl moieties, N-cinnamyl, and N-propyl substituents). The synthesis of the eight enantiopure N-2-phenylcyclopropylmethyl ortho-c oxide-bridged phenylmorphans and six additional enantiomers of the N-substituted ortho-c oxide-bridged phenylmorphans (N-E and Z-cinnamyl compounds, and N-propyl compounds) was accomplished. The synthesis started from common intermediates (3R,6aS,11aS)-10-methoxy-1,3,4,5,6,11a-hexahydro-2H-3,6a-methano-benzofuro[2,3-c]azocine (+)-6 and its enantiomer, (3S, 6aR, 11aR)-(-)-6, respectively. The enantiomers of ±-6 were obtained through salt formation with (S)-(+)- and (R)-(-)-p-methylmandelic acid, and the absolute configuration of the (R)-(-)-p-methylmandelate salt of (3S, 6aR, 11aR)-(-)-6 was determined by single-crystal X-ray analysis. The enantiomeric secondary amines were reacted with N-(2-phenylcyclopropyl)methyl derivatives, 2-(E)-cinnamyl bromide, and (Z)-3-phenylacrylic acid. These products led to all of the desired N-derivatives of the ortho-c oxide-bridged phenylmorphans. Their opioid receptor binding affinity was measured. The compounds with MOR affinity < 50 nM were examined for their functional activity in the forskolin-induced cAMP accumulation assay. Only the enantiomer of the N-phenethyl ortho-c oxide-bridged phenylmorphan ((-)-1), and only the (3S,6aR,11aR)-2-(((1S,2S)-2-phenylcyclopropyl)methyl)-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocin-10-ol isomer ((+)-17), and the N-phenylpropyl derivative ((-)-25) had opioid binding affinity < 50 nM. Both (-)-1 and (-)-25 were partial agonists in the cAMP assay, with the former showing high potency and low efficacy, and the latter with lower potency and less efficacy. Most interesting was the N-2-phenylcyclopropylmethyl (3S,6aR,11aR)-2-(1S,2S)-enantiomer ((+)-17). That compound had good MOR binding affinity (Ki = 11.9 nM) and was found to have naltrexone-like potency as a MOR antagonist (IC50 = 6.92 nM).
Topics: Crystallography, X-Ray; Oxides; Morphinans; Isomerism; Receptors, Opioid, mu
PubMed: 36557961
DOI: 10.3390/molecules27248808 -
The Cochrane Database of Systematic... Jun 2014The scientific literature examining effective treatments for opioid-dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component.... (Review)
Review
BACKGROUND
The scientific literature examining effective treatments for opioid-dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component. Nevertheless, no reviews have been published that systematically assess the effectiveness of pharmacological maintenance treatment in adolescents.
OBJECTIVES
To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions for retaining adolescents in treatment, reducing the use of substances and improving health and social status.
SEARCH METHODS
We searched the Cochrane Drugs and Alcohol Group's Trials Register (January 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINAHL (January 1982 to January 2014), Web of Science (1991 to January 2014) and reference lists of articles.
SELECTION CRITERIA
Randomised and controlled clinical trials of any maintenance pharmacological interventions either alone or associated with psychosocial intervention compared with no intervention, placebo, other pharmacological intervention, pharmacological detoxification or psychosocial intervention in adolescents (13 to 18 years).
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included two trials involving 189 participants. One study, with 35 participants, compared methadone with levo-alpha-acetylmethadol (LAAM) for maintenance treatment lasting 16 weeks, after which patients were detoxified. The other study, with 154 participants, compared maintenance treatment with buprenorphine-naloxone and detoxification with buprenorphine. We did not perform meta-analysis because the two studies assessed different comparisons.In the study comparing methadone and LAAM, the authors declared that there was no difference in the use of a substance of abuse or social functioning (data not shown). The quality of the evidence was very low. No side effects, such as nausea, vomiting, constipation, weakness or fatigue, were reported by study participants.In the comparison between buprenorphine maintenance and buprenorphine detoxification, maintenance treatment appeared to be more efficacious in retaining patients in treatment (drop-out risk ratio (RR) 0.37; 95% confidence interval (CI) 0.26 to 0.54), but not in reducing the number of patients with a positive urine test at the end of the study (RR 0.97; 95% CI 0.78 to 1.22). Self reported opioid use at one-year follow-up was significantly lower in the maintenance group, even though both groups reported a high level of opioid use (RR 0.73; 95% CI 0.57 to 0.95). More patients in the maintenance group were enrolled in other addiction treatment programmes at 12-month follow-up (RR 1.33; 95% CI 0.94 to 1.88). The quality of the evidence was low. No serious side effects attributable to buprenorphine-naloxone were reported by study participants and no patients were removed from the study due to side effects. The most common side effect was headache, which was reported by 16% to 21% of patients in both groups
AUTHORS' CONCLUSIONS
It is difficult to draft conclusions on the basis of only two trials. One of the possible reasons for the lack of evidence could be the difficulty of conducting trials with young people for practical and ethical reasons.There is an urgent need for further randomised controlled trials comparing maintenance treatment with detoxification treatment or psychosocial treatment alone before carrying out studies that compare different pharmacological maintenance treatments. These studies should have long follow-up and measure relapse rates after the end of treatment and social functioning (integration at school or at work, family relationships).
Topics: Adolescent; Buprenorphine; Humans; Maintenance Chemotherapy; Methadone; Methadyl Acetate; Naloxone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic
PubMed: 24957634
DOI: 10.1002/14651858.CD007210.pub3 -
Therapeutic Drug Monitoring Apr 2020In the United States, drug addiction has become a nationwide health crisis. Recently, buprenorphine (BUP), a maintenance therapy approved by the Food and Drug...
BACKGROUND
In the United States, drug addiction has become a nationwide health crisis. Recently, buprenorphine (BUP), a maintenance therapy approved by the Food and Drug Administration, has been increasingly used in pregnant women for the treatment of opioid use disorder. Pregnancy is associated with various anatomic and physiological changes, which may result in altered drug pharmacokinetics (PKs). Previously, we reported that dose-adjusted plasma concentrations of BUP are lower during pregnancy than after pregnancy. The mechanism(s) responsible for this difference has not yet been defined. Our study aimed to evaluate alterations in cytochromes P450 (CYP)- and uridine diphosphate glucunosyltransferases (UGT)-mediated metabolism of BUP during pregnancy to determine the mechanism(s) responsible for this observation.
METHODS
Data from 2 clinical studies were included in the current analysis. Study 1 was a prospective, open-labeled, nonrandomized longitudinal BUP PK study in pregnant women with a singleton gestation, stabilized on twice-daily sublingual BUP opioid substitution therapy. Each subject participated in up to 3 studies during and after pregnancy (the second, third trimester, and postpartum). The design of study 2 was similar to study 1, with patients evaluated at different time points during the pregnancy (first, second-half of pregnancy), as well as during the postpartum period. In addition, the dosing frequency of BUP study 2 participants was not restricted to twice-daily dosing. At each study visit, blood samples were collected before a BUP dose, followed by multiple collection times (10-12) after the dose, for up to 12 hours or till the end of the dosing interval. Plasma concentrations of BUP and 3 metabolites were quantified using validated ultraperformance liquid chromatography-tandem mass spectrometric assays.
RESULTS
In total, 19, 18, and 14 subjects completed the PK study during 1/2 trimester, third trimester, and postpartum, respectively. The AUC ratios of norbuprenorphine and norbuprenorphine glucuronide to buprenorphine, a measure of CYP3A mediated N-demethylation, were 1.89, 1.84, and 1.33 during the first and second, third trimesters, and postpartum, respectively. The AUC ratios of buprenorphine glucuronide to BUP, indicative of UGT activity, were 0.71, 2.07, and 0.3 at first/second trimesters, third trimester, and postpartum, respectively. Linear mixed-effect modeling analysis indicated that the AUC ratios of CYP- and UGT-mediated metabolism of BUP were significantly higher during pregnancy compared with postpartum.
CONCLUSIONS
The CYP and UGT activities were significantly increased as determined by the metabolic ratios of BUP during pregnancy compared with the postpartum period. The increased UGT activity appeared to account for a substantial part of the observed change in metabolic activity during pregnancy. This is in agreement with the need for BUP dose increment in pregnant women to reach similar BUP exposure and therapeutic effect as in nonpregnant subjects.
Topics: Adult; Buprenorphine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Female; Glucuronosyltransferase; Humans; Longitudinal Studies; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Postpartum Period; Pregnancy; Pregnancy Trimesters; Young Adult
PubMed: 31929398
DOI: 10.1097/FTD.0000000000000724 -
Journal of Substance Use and Addiction... Jun 2023Conflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Conflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone.
METHODS
We analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6.
RESULTS
The mean maximum dose taken during the study was 17.3 mg/day (range = 0.5-32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10-170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aβ ± standard error (SE) = -0.06 ± 0.04; p = 0.15), craving (aβ ± SE = -0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aβ ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3).
CONCLUSIONS
The current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.
Topics: Humans; Analgesics, Opioid; Cannabis; Narcotic Antagonists; Bayes Theorem; Opiate Substitution Treatment; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Opioid-Related Disorders; Methadone; Substance Withdrawal Syndrome
PubMed: 37003540
DOI: 10.1016/j.josat.2023.209031 -
Journal of Substance Abuse Treatment Feb 2022In 2018, the Baltimore City Health Department launched a mobile clinic called Healthcare on The Spot, which offers low-threshold buprenorphine services integrated with...
INTRODUCTION
In 2018, the Baltimore City Health Department launched a mobile clinic called Healthcare on The Spot, which offers low-threshold buprenorphine services integrated with health care services to meet the needs of people who use drugs. In addition to buprenorphine management, The Spot offers testing and treatment for hepatitis C, sexually transmitted infections, and HIV, as well as pre-exposure prophylaxis for HIV, wound care, vaccinations, naloxone distribution, and case management.
METHODS AND MATERIALS
This cohort analysis includes clinical service data from the first 15 months of The Spot mobile clinic, from September 4, 2018, to November 23, 2019. The Spot co-located with the Baltimore syringe services program in five locations across the city. Descriptive data are provided for patient demographics and services provided, as well as percent of patients retained in buprenorphine treatment at one and three months. Logistic regression identified factors associated with retention at three months.
RESULTS
The Spot mobile clinic provided services to 569 individuals from September 4, 2018, to November 23, 2019, including prescribing buprenorphine to 73.8% and testing to more than 70% for at least one infectious disease. Patients receiving a prescription for buprenorphine were more likely to be tested for HIV, hepatitis C, and sexually transmitted infections, as well as receive treatment for hepatitis C and preventive services including vaccination and naloxone distribution. The Spot initiated HIV treatment for four patients and HIV pre-exposure prophylaxis for twelve patients. More than 32% of patients had hepatitis C; nineteen of these patients initiated treatment for hepatitis C with eight having a documented cure. Buprenorphine treatment retention was 56.0% at one month and 26.2% at three months. Patients who were Black or receiving treatment for hepatitis C were more likely to be retained in buprenorphine treatment at three months.
CONCLUSIONS
Increasing access to integrated medical services and drug treatment through low-threshold, community-based models of care can be an effective tool for addressing the effects of drug use.
Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Hepatitis C; Humans; Mobile Health Units; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34238629
DOI: 10.1016/j.jsat.2021.108553 -
Acta Medica Portuguesa May 2019All health professionals should be aware of the importance of evaluating pain - fifth vital sign- in cancer patients. Peripheral and central acting analgesics are widely... (Review)
Review
INTRODUCTION
All health professionals should be aware of the importance of evaluating pain - fifth vital sign- in cancer patients. Peripheral and central acting analgesics are widely used to treat moderate to severe pain, particularly cancer pain. Many guidelines have addressed this issue. However, real life patients' have other problems and comorbidities that may raise doubts when prescribing.
MATERIAL AND METHODS
Authors made a literature search, trying to clarify same specific situations: loss of oral route, renal impairment (hemodialysis), hepatic impairment, frequent opiod interactions and the availability of short-acting formulations.
RESULTS
The following medicines were included in this analysis: the natural opiates (morphine and codeine), their synthetic and semisynthetic derivatives (hydromorphone, oxycodone, and fentanyl), the partial agonist buprenorphine and finally tramadol and tapentadol. Transdermal systems are only available for buprenorphine and fentanyl. In hepatic impairment, fentanyl is safe, but with the exception of codeine and tramadol; other opioids should be used with caution. In renal failure: fentanyl, hydromorphone, and tapentadol are safe. Morphine should be avoided; other opioids should be used with caution. In hemodialysis, buprenorphine, fentanyl, hydromorphone and tramadol (at doses up to 200 mg/day) may be used.
DISCUSSION
Failure to recognize the impact of various situations described throughout this work, including the bioavailability due to loss of oral route, due to pharmacokinetics and pharmacodynamics of the various drugs, either in the context of the impaired metabolism or excretion, or in due to pharmacological interactions, conditions a serious risk of subtreatment of pain and consequent impact in terms of quality of life.
CONCLUSION
Opioid prescription is safe and effective, even in moderate to severe comorbidities such as renal and hepatic impairment and in patients with no oral route available. In this case, as when considering pharmacological interactions, an individualized therapeutic plan is the best solution and the patient should be assessed regularly. Unadjusted doses may relate to bad pain control and a higher prevalence of adverse events.
Topics: Administration, Oral; Analgesics, Opioid; Buprenorphine; Cancer Pain; Codeine; Deglutition Disorders; Fentanyl; Humans; Hydromorphone; Liver Failure; Morphine; Oxycodone; Renal Dialysis; Renal Insufficiency; Tapentadol; Tramadol
PubMed: 31166900
DOI: 10.20344/amp.10500 -
Journal of Analytical Toxicology Mar 2021Analysis of postmortem samples with the presence of morphine can sometimes be challenging to interpret. Tolerance complicates interpretation of intoxications and causes...
Analysis of postmortem samples with the presence of morphine can sometimes be challenging to interpret. Tolerance complicates interpretation of intoxications and causes of death due to overlap in therapeutic and fatal concentrations. Determination of metabolites and metabolic ratios can potentially differentiate between abstinence, continuous administration, and perhaps time of administration. The purpose of this study was to (a) develop and validate a method for quantitation of morphine-3β-D-glucuronide, morphine-6β-D-glucuronide, normorphine, codeine-6β-D-glucuronide, norcodeine, codeine, 6-acetylmorphine, and ethylmorphine in urine using liquid chromatography-tandem mass spectrometry; (b) apply the method to opiate related deaths; (c) compare metabolic ratios in urine in different causes of death (CoD) and after different drug intakes and (d) compare heroin intoxications in rapid and delayed deaths. Validation parameters such as precision, bias, matrix effects, stability, process efficiency, and dilution integrity were assessed and deemed acceptable. Lower limits of quantitation ranged from 0.01-0.2 μg/mL for all analytes. Autopsy cases (n=135) with paired blood and urine samples were analyzed. Cases were divided into three groups based on CoD; opiate intoxication, intoxication with other drugs than opiates, and other CoD. The cases were classified by intake: codeine (n=42), heroin (n=36), morphine (n=49), and ethylmorphine (n=3). Five cases were classified as mixed intakes and excluded. Heroin intoxications (n=35) were divided into rapid (n=15) or delayed (n=20) deaths. Parent drug groups were compared using metabolic ratio morphine-3β-D-glucuronide/morphine and significant differences were observed between codeine vs morphine (p=0.005) and codeine vs heroin (p≤0.0001). Urine and blood concentrations, and metabolic ratios in rapid and delayed heroin intoxications were compared and determined a significant difference for morphine (p=0.001), codeine (p=0.009), 6-acetylmorphine (p=0.02) in urine, and morphine (p=0.02) in blood, but there was no significant difference (p=0.9) between metabolic ratios. Morphine-3β-D-glucuronide results suggested a period of abstinence prior to death in 25% of the heroin intoxications.
Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; Heroin; Morphine; Morphine Derivatives; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 33031535
DOI: 10.1093/jat/bkaa157