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Arthritis & Rheumatology (Hoboken, N.J.) May 2018
Topics: Dextropropoxyphene; Interrupted Time Series Analysis
PubMed: 29439284
DOI: 10.1002/art.40449 -
Fundamental & Clinical Pharmacology Jun 2018Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a... (Comparative Study)
Comparative Study
Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified prescriptions collected during three periods from 2001 to 2012. The data recorded in a national program which records all falsified prescriptions presented to community pharmacies were studied. Included data regarded: subjects, prescription forms, and drugs. Description of the dataset in three periods (2001-2004, 2005-2008, and 2009-2012) was completed with clustering analyses to characterize profiles of prescriptions and subjects associated with the most reported drugs. The 4469 falsified prescriptions concerned most often females (51.6%). Average age was 46.5 years. Zolpidem, bromazepam, and buprenorphine were the most frequent drugs. Alone, 13 drugs (1.7%, 13/772) represented more than 40% of the total reports (3055/7272). They were associated with three diversion profiles: (i) buprenorphine, flunitrazepam, and morphine were mentioned on overlapping secure prescription forms presented by young men; (ii) alprazolam, bromazepam, zolpidem, codeine/acetaminophen were mentioned on simple prescription forms presented by experienced women; and (iii) acetaminophen and lorazepam were mentioned on modified prescription forms presented by elderly subjects. Clonazepam, clorazepate, dextropropoxyphene, zopiclone moved between those profiles. The patterns of falsified prescriptions provided in this study contribute to enhance the scientific knowledge on the most diverted prescription drugs. The latter follow distinct trajectories across time depending on their pharmacology (including their abuse/addiction potential) and on their regulation's history. The close and continuous analysis of falsified prescriptions is an excellent way to monitor prescription drug diversion.
Topics: Adult; Age Factors; Cluster Analysis; Community Pharmacy Services; Drug Prescriptions; Female; France; Fraud; Humans; Male; Middle Aged; Patients; Prescription Drug Diversion; Prescription Drug Misuse; Prescription Drug Monitoring Programs; Program Evaluation; Sex Factors; Time Factors
PubMed: 29436015
DOI: 10.1111/fcp.12356 -
Toxicology Communications 2018The emergency department (ED) at Louisiana State University-Health Science Center in Shreveport (LSUHSC-S) serves an urban population with a large rural catchment area....
The emergency department (ED) at Louisiana State University-Health Science Center in Shreveport (LSUHSC-S) serves an urban population with a large rural catchment area. This study focuses on demographic variables in substance abuse trends in this region based on urine drug screen (UDS) results. A database of de-identified UDSs ordered in the ED at LSUHSC-S between 1998 and 2011 was analyzed. Samples were tested for the presence of amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, 3,4-methylenedioxymethamphetamine (MDMA), methadone, methamphetamine, opiates, phencyclidine, and propoxyphene. The patient population was categorized by age group, gender, and race. The majority of tests were performed on African-American and Caucasian patients ages 18 to 54 followed by the 0 to 11-year-old group. Of the drugs tested, cannabinoids represented the highest percentage of positive results in both the African-American and Caucasian populations. Opiates returned the highest percent of positive results among all prescription drugs. The Caucasian population predominated in positive tests for prescription drugs (opiates and benzodiazepines), while the African-American population predominated in results positive for illicit drugs (cannabinoids and cocaine). The increasing presence of opiates and cannabinoids, particularly in very young patients, should prompt policy makers and healthcare providers to develop intervention strategies to protect the most vulnerable populations.
PubMed: 30906915
DOI: 10.1080/24734306.2018.1468539 -
Journal of Chromatography. A Jan 2018Although published literature provides a clear demonstration of widespread occurrence of opioid analgesics (OAs) in the aquatic environment, analytical methods suitable...
Although published literature provides a clear demonstration of widespread occurrence of opioid analgesics (OAs) in the aquatic environment, analytical methods suitable for a systematic study of this pharmaceutical class, which would include a broad spectrum of opioid analgesics and their metabolites, are still missing. In this work, a comprehensive multiresidue method for quantitative analysis of 27 opioid analgesics and their metabolites, including 2 morphine glucuronide conjugates, was developed and validated for three matrices: raw wastewater (RW), secondary effluent (SE) and river water. The method comprised different classes of opioid analgesics, including natural opiates (morphine and codeine), their semi-synthetic derivatives (hydrocodone, hydromorphone, oxycodone, oxymorphone and buprenorphine) as well as fully synthetic opioids such as methadone, fentanyl, sufentanil, propoxyphene and tramadol. The optimized enrichment procedure involved mixed-mode, strong cation-exchange sorbent in combination with a sequential elution procedure. The extracts were analyzed by reversed-phase liquid chromatography using a Synergy Polar column coupled to electrospray ionization tandem mass spectrometry (LC-MS/MS). Accurate quantification of target OAs was achieved using 19 deuterated analogues as surrogate standards. Method accuracies for RW, SE and river water varied in the range from 91 to 126%, 74 to 120% and 75 to 116%, respectively. Careful optimization of the procedure allowed reliable determination of OAs with method quantification limits in the low ng/L range (RW: 0.3-3.5 ng/L; SE: 0.2-1.9 ng/L, river water: 0.1-0.8 ng/L. The developed method was applied for analysis of RW, SE and river water samples from Croatia. The concentrations of individual OAs in municipal wastewater varied in a wide range (from < QL to 859 ng/L) and the most prevalent representatives were tramadol, codeine, morphine and methadone and their derivatives. Elevated concentrations of morphine glucuronides (up to 370 ng/L) found in raw municipal wastewater indicated their importance in the overall morphine mass balance.
Topics: Analgesics, Opioid; Chromatography, Liquid; Environmental Monitoring; Rivers; Tandem Mass Spectrometry; Wastewater
PubMed: 29274731
DOI: 10.1016/j.chroma.2017.12.025 -
Forensic Science International Feb 2018Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are...
Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry. Drugs were extracted from hair by incubation in a buffer:solvent mixture at 37°C during 18h. Analysis was performed on a chromatographic system comprised of an Agilent 6550 QTOF coupled to a 1290 Infinity UHPLC system. High resolution accurate mass data were acquired in the All Ions mode and exported into Mass Hunter Quantitative software for quantitation and identification using qualifier fragment ions. Validation included selectivity, matrix effects, calibration range, within day and between day precision and accuracy. The analytes were 7-amino-flunitrazepam, 7-amino-clonazepam, 7-amino-nitrazepam, acetylmorphine, alimemazine, alprazolam, amphetamine, benzoylecgonine, buprenorphine, diazepam, ethylmorphine, fentanyl, hydroxyzine, ketobemidone, codeine, cocaine, MDMA, methadone, methamphetamine, morphine, oxycodone, promethazine, propiomazine, propoxyphene, tramadol, zaleplone, zolpidem, and zopiclone. As proof of concept, hair from 29 authentic post mortem cases were analysed. The calibration range was established between 0.05ng/mg to 5.0ng/mg for all analytes except fentanyl (0.02-2.0), buprenorphine (0.04-2.0), and ketobemidone (0.05-4.0) as well as for alimemazine, amphetamine, cocaine, methadone, and promethazine (0.10-5.0). For all analytes, the accuracy of the fortified pooled hair matrix was 84-108% at the low level and 89-106% at the high level. The within series precisions were between 1.4 and 6.7% and the between series precisions were between 1.4 and 10.1%. From the 29 autopsy cases, 121 positive findings were encountered from 23 of the analytes in concentrations similar to those previously published. We conclude that the developed method proved precise and accurate and that it had sufficient performance for the purpose of detecting regular use of drugs or treatment with prescription drugs. To identify a compound we recommend the use of ion ratios as a complement to instrument software "matching scores".
Topics: Chromatography, High Pressure Liquid; Forensic Toxicology; Hair; Humans; Mass Spectrometry; Narcotics; Pharmaceutical Preparations; Reproducibility of Results
PubMed: 29241093
DOI: 10.1016/j.forsciint.2017.12.001 -
Clinical Toxicology (Philadelphia, Pa.) Aug 2018Since the banning of dextropropoxyphene from the market, overdoses, and fatalities attributed to tramadol, a WHO step-2 opioid analgesic, have increased markedly....
CONTEXT
Since the banning of dextropropoxyphene from the market, overdoses, and fatalities attributed to tramadol, a WHO step-2 opioid analgesic, have increased markedly. Tramadol overdose results not only in central nervous system (CNS) depression attributed to its opioid properties but also in seizures, possibly related to non-opioidergic pathways, thus questioning the efficiency of naloxone to reverse tramadol-induced CNS toxicity.
OBJECTIVE
To investigate the most efficient antidote to reverse tramadol-induced seizures and respiratory depression in overdose.
MATERIALS AND METHODS
Sprague-Dawley rats overdosed with 75 mg/kg intraperitoneal (IP) tramadol were randomized into four groups to receive solvent (control group), diazepam (1.77 mg/kg IP), naloxone (2 mg/kg intravenous bolus followed by 4 mg/kg/h infusion), and diazepam/naloxone combination. Sedation depth, temperature, number of seizures, and intensity, whole-body plethysmography parameters and electroencephalography activity were measured.
RESULTS
Naloxone reversed tramadol-induced respiratory depression (p < .05) but significantly increased seizures (p < .01) and prolonged their occurrence time. Diazepam abolished seizures but significantly deepened rat sedation (p < .05) without improving ventilation. Diazepam/naloxone combination completely abolished seizures, significantly improved rat ventilation by reducing inspiratory time (p < .05) but did not worsen sedation. None of these treatments significantly modified rat temperature.
CONCLUSIONS
Diazepam/naloxone combination is the most efficient antidote to reverse tramadol-induced CNS toxicity in the rat.
Topics: Analgesics, Opioid; Animals; Antidotes; Drug Overdose; Naloxone; Rats; Rats, Sprague-Dawley; Respiratory Insufficiency; Seizures; Tramadol
PubMed: 29148295
DOI: 10.1080/15563650.2017.1401080 -
Rapid Communications in Mass... Dec 2017
Simultaneous quantitation of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma using solid-phase extraction and gas chromatography/mass spectrometry: Method validation and application to cardiovascular safety of therapeutic doses.
PubMed: 29108129
DOI: 10.1002/rcm.7976 -
Southern Medical Journal Nov 2017Opioid abuse is a growing problem in civilian communities, and it has developed in the military as well. Telephone calls to poison centers requesting pill identification... (Observational Study)
Observational Study
OBJECTIVES
Opioid abuse is a growing problem in civilian communities, and it has developed in the military as well. Telephone calls to poison centers requesting pill identification (ID) is a marker of drug abuse. This study identifies the number of pill ID calls made to the poison centers from areas containing and surrounding three Texas military bases during an 8-year period.
METHODS
We performed a retrospective observational study identifying calls to certified poison centers in Texas from 2002 to 2009 that identified hydrocodone tablets and other pain medications. We noted the calls made from ZIP codes containing and surrounding the three largest military bases in Texas.
RESULTS
We reviewed 75,537 drug ID calls for any drug from the ZIP codes of interest. Total drug ID calls increased 105% and the number of calls for hydrocodone increased 463%.
CONCLUSIONS
In our study most of the drug ID calls from military communities in Texas were for hydrocodone. The rate of calls for hydrocodone increased more than the rate of calls for other analgesics from 2002 to 2009. Using drug ID calls as a surrogate of drug abuse, our results suggest that hydrocodone abuse has increased within military communities and that poison center data can be a reliable surrogate for prescription drug abuse near military bases. Future studies are needed to further understand the extent of this problem in military and civilian communities. We can use this information to heighten awareness, influence prescription practices, establish practice guidelines, and develop educational programs to mitigate the increasing rate of prescription analgesic abuse in the United States.
Topics: Analgesics, Opioid; Dextropropoxyphene; Humans; Hydrocodone; Military Facilities; Opioid-Related Disorders; Poison Control Centers; Retrospective Studies; Substance-Related Disorders; Tablets; Telephone; Texas; Tramadol
PubMed: 29100223
DOI: 10.14423/SMJ.0000000000000718 -
The Cochrane Database of Systematic... Oct 2017Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'.
OBJECTIVES
To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults.
METHODS
We searched the Cochrane Database of Systematic Reviews (the Cochrane Library) Issue 3, 2017 on 8 March 2017 to identify all Cochrane Reviews of studies of medium- or long-term opioid use (2 weeks or more) for CNCP in adults aged 18 and over. We assessed the quality of the reviews using the AMSTAR criteria (Assessing the Methodological Quality of Systematic Reviews) as adapted for Cochrane Overviews. We assessed the quality of the evidence for the outcomes using the GRADE framework.
MAIN RESULTS
We included a total of 16 reviews in our overview, of which 14 presented unique quantitative data. These 14 Cochrane Reviews investigated 14 different opioid agents that were administered for time periods of two weeks or longer. The longest study was 13 months in duration, with most in the 6- to 16-week range. The quality of the included reviews was high using AMSTAR criteria, with 11 reviews meeting all 10 criteria, and 5 of the reviews meeting 9 out of 10, not scoring a point for either duplicate study selection and data extraction, or searching for articles irrespective of language and publication type. The quality of the evidence for the generic adverse event outcomes according to GRADE ranged from very low to moderate, with risk of bias and imprecision being identified for the following generic adverse event outcomes: any adverse event, any serious adverse event, and withdrawals due to adverse events. A GRADE assessment of the quality of the evidence for specific adverse events led to a downgrading to very low- to moderate-quality evidence due to risk of bias, indirectness, and imprecision.We calculated the equivalent milligrams of morphine per 24 hours for each opioid studied (buprenorphine, codeine, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, tapentadol, tilidine, and tramadol). In the 14 Cochrane Reviews providing unique quantitative data, there were 61 studies with a total of 18,679 randomised participants; 12 of these studies had a cross-over design with two to four arms and a total of 796 participants. Based on the 14 selected Cochrane Reviews, there was a significantly increased risk of experiencing any adverse event with opioids compared to placebo (risk ratio (RR) 1.42, 95% confidence interval (CI) 1.22 to 1.66) as well as with opioids compared to a non-opioid active pharmacological comparator, with a similar risk ratio (RR 1.21, 95% CI 1.10 to 1.33). There was also a significantly increased risk of experiencing a serious adverse event with opioids compared to placebo (RR 2.75, 95% CI 2.06 to 3.67). Furthermore, we found significantly increased risk ratios with opioids compared to placebo for a number of specific adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting.There was no data on any of the following prespecified adverse events of interest in any of the included reviews in this overview of Cochrane Reviews: addiction, cognitive dysfunction, depressive symptoms or mood disturbances, hypogonadism or other endocrine dysfunction, respiratory depression, sexual dysfunction, and sleep apnoea or sleep-disordered breathing. We found no data for adverse events analysed by sex or ethnicity.
AUTHORS' CONCLUSIONS
A number of adverse events, including serious adverse events, are associated with the medium- and long-term use of opioids for CNCP. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event. Based on the adverse events identified, clinically relevant benefit would need to be clearly demonstrated before long-term use could be considered in people with CNCP in clinical practice. A number of adverse events that we would have expected to occur with opioid use were not reported in the included Cochrane Reviews. Going forward, we recommend more rigorous identification and reporting of all adverse events in randomised controlled trials and systematic reviews on opioid therapy. The absence of data for many adverse events represents a serious limitation of the evidence on opioids. We also recommend extending study follow-up, as a latency of onset may exist for some adverse events.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Patient Dropouts; Randomized Controlled Trials as Topic; Review Literature as Topic; Time Factors
PubMed: 29084357
DOI: 10.1002/14651858.CD012509.pub2 -
Forensic Science International Nov 2017The synthetic opioid propoxyphene was a schedule IV controlled substance with multiple reported health risks before the US Food and Drug Administration issued a request...
The synthetic opioid propoxyphene was a schedule IV controlled substance with multiple reported health risks before the US Food and Drug Administration issued a request for voluntary market withdrawal in November 2010. The purpose of this study is to investigate the characteristics and occurrences of propoxyphene-related deaths in Florida before and after voluntary market removal. Decedent-level toxicology data from Florida's Medical Examiners Commission was used to compare the temporal, polysubstance use, sociodemographic, and geographic profiles associated with propoxyphene-involved deaths for a pre-withdrawal (November 2008-November 2010) and post-withdrawal (December 2010-December 2012) period. Sensitivity analyses using multiple data sources, including Florida's Prescription Drug Monitoring Program and other states' data, were conducted to examine potential reporting bias. Results showed that the number of propoxyphene-involved deaths declined by 84% from 580 deaths to 92 deaths after market withdrawal. The co-occurrence of other prevalent drugs, such as oxycodone (17.2% to 26.1%, p=0.0422) increased significantly in the post-withdrawal study period. A larger proportion of the propoxyphene-related deaths were reported from South Florida after the withdrawal (28.4% to 56.5%, p<0.0001). No significant changes in age and race/ethnicity were observed. Sensitivity analyses revealed that several deaths occurred in other states after market withdrawal, as recently as 2016. Our findings are consistent with previous studies that propoxyphene was still available after removal from the US market. Continued surveillance is recommended after highly abused opioids are withdrawn from the market due to on-going safety risks.
Topics: Accidents; Adult; Age Distribution; Aged; Analgesics, Opioid; Dextropropoxyphene; Drug Overdose; Female; Florida; Humans; Male; Middle Aged; Poisoning; Safety-Based Drug Withdrawals; Sex Distribution; Suicide
PubMed: 29080523
DOI: 10.1016/j.forsciint.2017.10.008