- Trends in severe opioid-related poisonings and fatalities reported to the Paris poison control center - a 10-year retrospective observational study. [Journal Article]Fundam Clin Pharmacol 2020FC
- France is experiencing an increase in the number of opioid prescriptions and related fatalities. We carried out a retrospective observational study using data from the Paris PCC over a 10-year period. The main objective was to obtain an epidemiological description of the severe reported cases. The secondary objectives were to assess the evolution of the number of these cases and their severity de…
France is experiencing an increase in the number of opioid prescriptions and related fatalities. We carried out a retrospective observational study using data from the Paris PCC over a 10-year period. The main objective was to obtain an epidemiological description of the severe reported cases. The secondary objectives were to assess the evolution of the number of these cases and their severity defined by the use of fentanyl and its derivatives, the use of the opioid-poisoning treatment naloxone and the number of fatalities. During 2008-2017, 268,511 cases were recorded, including 1,122 cases of opioid-related poisoning that required medical management. These poisonings involved tramadol (43%), codeine (25%), dextropropoxyphene (13%) and morphine (8%); most resulted from self-exposure (60%). During the 10-year study period, 130 opioid-related fatalities were recorded in the Paris area, mainly resulting from suicides (39%) in men and were attributed to morphine (27%), tramadol (24%) and methadone (21%). We did not identify an increase in the number of severe opioid-related poisonings or fatalities or in the use of fentanyl or its derivatives. Conversely, we observed an increase in the use of naloxone, suggesting an increase in the severity of opioid poisonings. Our findings show that, until 2017, the opioid overdose epidemiology in the Paris area is different to that in the USA. The systematic analysis of data from the PCCs could be a good tool for health monitoring. To assess trends in France, a national study over a longer period would also be useful.
- Opioids and frequency counts in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database: a quantitative view of the epidemic. [Journal Article]Drug Healthc Patient Saf 2019; 11:65-70DH
- CONCLUSIONS: The FAERS database represents an important source for detection and reporting of adverse drug events (ADEs), in particular the opioids and related drugs. It remains a challenge to estimate the true incidence of ADEs for this class of drugs in the general population.
- Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events. [Journal Article]Med Care 2020; 58(1):4-12MC
- CONCLUSIONS: After propoxyphene market withdrawal, many individuals experienced abrupt discontinuation of opioids. Policymakers might consider supporting appropriate treatment transitions and monitoring responses following drug withdrawals.
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury: Opioids [BOOK]National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda (MD)BOOK
- The opioids are a large class of medications related in structure to the natural plant alkaloids found in opium that are derived from the resin of the opium poppy, Papaver somniferum. The natural alkaloids are also referred to as opiates and include morphine and codeine. Synthetic derivatives include heroin, fentanyl, hydromorphone, methadone, buprenorphine and others. The opioids are highly pote…
The opioids are a large class of medications related in structure to the natural plant alkaloids found in opium that are derived from the resin of the opium poppy, Papaver somniferum. The natural alkaloids are also referred to as opiates and include morphine and codeine. Synthetic derivatives include heroin, fentanyl, hydromorphone, methadone, buprenorphine and others. The opioids are highly potent and effective analgesics, but most have a high potential for dependency and abuse. Opioids act by engagement of specific cell surface receptors; the opiate receptors, which are designated µ [mu], κ [kappa] and δ [delta]. These receptors are found predominantly in the central nervous system, brain and spinal column, but are also present on vascular, cardiac, lung, gut and even peripheral blood mononuclear cells. Engagement of the opiate receptors generates a series of intracellular signals, including inhibition of adenylate cyclase, decreased opening of calcium channels, increased potassium currents and activation of protein kinase C (PKC). The major effect of these pathways is reduction in cell excitability and neurotransmission. The natural ligands for the opiate receptors are the so-called endogenous opioid peptides such as the enkephalins, endorphins and endomorphins. The opioids have a variety of clinical effects, but are predominantly known and used for their profound pain relieving effects. Other effects that are often linked to opiate analgesia include euphoria, changes in mood, drowsiness and mental clouding. However, the distinctive feature of the analgesia induced by the opioids is the lack of loss of consciousness. The pain is often described as less intense, but still present although better tolerated. Thus, the opioids do not decrease or treat the cause of the painful stimulus, but rather decrease its perception. Other effects of opioids include respiratory depression, decreased gastrointestinal motility, sedation, nausea, vomiting, constipation and intestinal bloating. Opioids also have direct cardiovascular effects, decreasing blood pressure, causing vasodilation and decreasing cardiac work. Most opioids have similar effects and side effects, although pharmacokinetic differences, tissue distribution, and receptor type specificity probably account for the variation in effects of the various synthetic and semisynthetic derivatives of morphine. Morphine is considered the prototype opiate, against which other agents are measured for their analgesic effects as well as adverse side effects. The opioids can be categorized into subclasses on the basis of their chemical structure as opium alkaloids (opiates: codeine, morphine), semisynthetic derivatives of the natural alkaloids (hydrocodone, hydromorphone, oxycodone, buprenorphine), and various classes of synthetic opioids such as the anililopiperidines (fentanyl, alfentanil, sufentanil, remifentanil), diphenylpropylamine derivatives (propoxyphene, dextropropoxyphene, methadone, diphenoxylate, loperamide), and others (pentazocine, butorphanol, nalbupine, levorphanol, tramadol), and, the opioid antagonists (nalmefene, naloxone and naltrexone). They can also be informally classified based upon their major use such as anesthesia (fentanyl, alfentanil, remifentanil, sufentanil), severe pain (morphine, hydromorphone, levorphanol, merperidine), moderate to severe acute or chronic pain (transdermal or transbuccal fentanyl, codeine, oxycodone, hydrocodone, levorphanol, methadone), diarrhea (loperamide, diphenoxylate), and cough (codeine, hydrocodone). Finally, opioids can be categorized on the basis of their action as full agonists, partial agonists or mixed agonists/antagonists, and antagonists of opiate receptors. Opioid receptor antagonists are used to reverse the effects of opioids and are invaluable in the management of opioid overdose (naloxone, naltrexone, nalmifene). Specialized opioid antagonists can be used to reverse unwanted opioid effects, such as constipation in patients with chronic pain on long-term opioids. These agents (naldemedine, naloxegol) are generally modified so as not to cross the blood brain and reverse the central nervous system effects of opiates. Opioids are rare causes of drug induced liver disease and are not mentioned in large case series of clinically apparent liver injury caused by medications. In physiological, pain relieving doses, opioids have not been implicated in causing clinically apparent liver injury, acute liver failure, chronic hepatitis or vanishing bile duct syndrome. However, overdoses of the more potent opioids have been linked to cases of acute liver injury, usually with a precipitous onset and pattern of acute toxicity with marked elevations in serum aminotransferase levels and early onset of signs of hepatic failure. This syndrome has been best characterized after buprenorphine overdose or abuse, but likely occurs with others. It is possible that the implicated opioids are not directly toxic to the liver, but cause ischemic liver injury due to respiratory failure, cardiovascular collapse, shock and anoxia that can occur with severe opioid overdose. The clinical syndrome resembles acute hepatic necrosis and liver failure, but is rapidly reversible and rarely the primary cause of death from overdose. A special form of liver injury linked to opioid use occurs with their fixed drug combinations with acetaminophen. These combinations are commonly used for moderate to moderately severe pain and can lead to abuse. If taken too frequently, acetaminophen doses may reach toxic levels, particularly with overuse for several days in the face of malnutrition, alcohol abuse or intercurrent illness. These other stresses can lower hepatic glutathione levels and predispose to acetaminophen hepatotoxicity. This constellation of events is referred to as inadvertent or unintended acetaminophen overdose or more colloquially as a “therapeutic misadventure”. For this reason, the FDA has recommended that physicians not use opioid combinations in which the dose of acetaminophen is greater than 325 mg per tablet or unit dose. References to the safety and hepatotoxic potential of the various opiate agonists are given together at the end of this Overview section. References to the opioids and the opiate antagonists used to treat substance abuse are given separately with each agent (buprenorphine, methadone, nalmefene, naloxone, naltrexone). The opioids are discussed individually or as groups of agents and links to each are given below. Full and partial agonists: Alfentanil. Butorphanol. Codeine. Diphenoxylate. Fentanyl. Heroin. Hydrocodone. Hydromorphone. Levorphanol. Loperamide. Meperidine. Methadone. Morphine. Opium. Oxycodone. Oxymorphone. Pentazocine. Remifentanil. Sufentanil. Tramadol. Opiate antagonists: Naldemedine. Nalmefene. Naloxegol. Naloxone. Naltrexone.
- Salt stress alleviation in Pennisetum glaucum through secondary metabolites modulation by Aspergillus terreus. [Journal Article]Plant Physiol Biochem 2019; 144:127-134PP
- The growth promoting activities of the isolated endophyte Aspergillus terreus from Aloe barbendsis was studied in the salt stressed Pennisetum glaucum (pearl millet). A significant (P = 0.05) increase in the root-shoot lengths, fresh and dry weights and chlorophyll content of pearl millet seedlings was noticed after colonization by A. terreus under normal conditions. At 100 mM NaCl stress and A. …
The growth promoting activities of the isolated endophyte Aspergillus terreus from Aloe barbendsis was studied in the salt stressed Pennisetum glaucum (pearl millet). A significant (P = 0.05) increase in the root-shoot lengths, fresh and dry weights and chlorophyll content of pearl millet seedlings was noticed after colonization by A. terreus under normal conditions. At 100 mM NaCl stress and A. terreus inoculation, the growth rate of pearl millet seedlings were significantly (P = 0.05) inhibited. Furthermore, the IAA production, relative water content (RWC), chlorophyll, soluble sugar, phenol and flavonoid contents were significantly decreased, whereas proline content and lipid peroxidation were increased. On the contrary, pearl millet seedlings inoculated with A. terreus retained significantly (P = 0.05) higher amounts of RWC, chlorophyll, soluble sugar, phenol and flavonoid contents under 100 mM salt stress. The higher IAA production in A. terreus associated seedlings rescued the plant growth and development under salt stress. Moreover, the LC MS/MS analysis of A. terreus cultural filtrate revealed the presence of quinic acid, ellagic acid, calycosin, wogonin, feruloylquinic acid, caffeic acid phenylethyl ester, D-glucoside, myricetin, propoxyphene and aminoflunitrazepam. The results of the study conclude that innoculation of A. terreus improves the NaCl tolerance in pearl millet by ameliorating the physicochemical attributes of the host plants.
- Prescription drug suicide in non-abusers: A 6-year forensic survey. [Journal Article]Asian J Psychiatr 2019; 44:133-137AJ
- CONCLUSIONS: It is reassuring that the absolute number of prescription drug suicides in non-abusers was small; the findings, however, are important because they could serve as a baseline for assessing time trends in future studies. For the present, we suggest that prescription drugs of potential abuse, especially those containing opioids and antispasmodics, should be prescribed and dispensed judiciously, especially to youth.
- Interpretation and Utility of Drug of Abuse Screening Immunoassays: Insights From Laboratory Drug Testing Proficiency Surveys. [Journal Article]Arch Pathol Lab Med 2019AP
- CONCLUSIONS: Survey results indicate strong clinical interest in urine drug testing and some adoption of new assays. However, urine drug testing availability does not parallel prevailing patterns of drug prescribing and abuse patterns. In particular, specific immunoassays for synthetic opioids and a lower positive cutoff for opiate immunoassays may be underused, whereas immunoassays for barbiturates, methadone, propoxyphene, and phencyclidine may be overused. Laboratories are encouraged to review their test menu, cutoffs, and assay performance and adjust their test offerings based on clinical needs and technical capabilities.
- Study of sociodemographic correlates, anxiety, and depression among opioid dependents admitted in treatment centres in Sikkim, India. [Journal Article]Open J Psychiatry Allied Sci 2019 Jul-Dec; 10(2):139-145OJ
- CONCLUSIONS: anxiety and depression are highly prevalent among ODS people. Treatment should not be limited to management of ODS but also the comorbid psychiatric illness.
- Identification of opioids in surface and wastewaters by LC/QTOF-MS using retrospective data analysis. [Journal Article]Sci Total Environ 2019; 664:874-884ST
- Opioids, both as prescription drugs and abuse substances, have been a hot topic and a focus of discussion in the media for the last few years. Although the literature published shows the occurrence of opioids and some of their metabolites in the aquatic environment, there are scarce data in the application of high resolution mass spectrometry (HRMS) for the analysis of these compounds in the envi…
Opioids, both as prescription drugs and abuse substances, have been a hot topic and a focus of discussion in the media for the last few years. Although the literature published shows the occurrence of opioids and some of their metabolites in the aquatic environment, there are scarce data in the application of high resolution mass spectrometry (HRMS) for the analysis of these compounds in the environment. The use of HRMS allows increasing the number of opioids that can be studied as well as the detection of unknown opioids, their metabolites and potential transformation products. In this work, a retrospective analysis for the identification of opioids and their metabolites using a curated database was applied to surface water and wastewater samples taken in the state of Minnesota (U.S.) in 2009, which were previously analyzed by liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) for antidepressants. The database comprised >200 opioids including natural opiates (e.g. morphine and codeine), their semi-synthetic derivatives (e.g. heroin, hydromorphone, hydrocodone, oxycodone, oxymorphone, meperidine and buprenorphine), fully synthetic opioids (e.g. fentanyl, methadone, tramadol, dextromethorphan and propoxyphene), as well as some of their metabolites (e.g. 6-monoacetylcodeine, dextrorphan, EDDP, normorphine and O-desmethyltramadol). Moreover, additional MS-MS experiments were performed to confirm their identification, as well as to recognize fragmentation patterns and diagnostic ions for several opioids. These data provide a better understanding of the historical occurrence of opioids and their metabolites in surface waters impacted by wastewater sources. The concentrations of individual opioids in surface water and wastewater effluent varied from 8.8 (EDDP) to 1640 (tramadol) ngL-1 and from 12 (dihydrocodeine) to 1288 (tramadol) ngL-1, respectively. The opioids with higher overall frequency detections were tramadol, dextromethorphan and its metabolite, dextrorphan.
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- Relative toxicity of analgesics commonly used for intentional self-poisoning: A study of case fatality based on fatal and non-fatal overdoses. [Multicenter Study]J Affect Disord 2019; 246:814-819JA
- CONCLUSIONS: Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.