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Journal of Forensic and Legal Medicine Aug 2020Several studies have shown an association between asthma and opiate abuse. This retrospective study aims to analyse the demographic, toxicological, and seasonal... (Comparative Study)
Comparative Study
Several studies have shown an association between asthma and opiate abuse. This retrospective study aims to analyse the demographic, toxicological, and seasonal differences in asthmatic and non-asthmatic subjects who died of opiates. In addition, the relationship between toxicological levels of opiates and histologic grade of lung inflammation is examined. Deaths from 2013 to 2018 involving opiates as the primary cause of death in Cook County, Illinois (USA) were reviewed. Twenty-six cases of opiate deaths of individuals with a history of asthma and lung histology slides available were identified. In comparison, 40 cases of deaths due to opiates only were analysed. A check-list system for the evaluation of the grade of microscopic inflammation in asthma was developed. We found statistically significant differences between the asthmatics and the non-asthmatics regarding demography (age and race) and toxicology (6-MAM presence). In particular, the "opiate and asthma group" was mainly composed of African-American subjects, in contrast with the "opiate group", consisting mostly of Caucasian. The mean age was significantly higher in the "opiate and asthma group" compared with the "opiate group". A greater presence of 6-MAM was detected in the "opiate group" compared with the "opiate and asthma group". While we expected to find that low opiate levels would lead to deaths in asthmatics and, in particular, that lower opiate concentrations would cause deaths in subjects with higher grades of histologic inflammation, our study suggests that the quantity of drug and the level of inflammation are not statistically significant in the determination of death. We, therefore, recommend histologic examination of the lungs to evaluate for asthma, particularly in suspected low-level opiate-related deaths, to help further clarify any relationship between asthma and opiate use.
Topics: Adult; Black or African American; Age Distribution; Asthma; Coroners and Medical Examiners; Female; Heroin Dependence; Humans; Inflammation; Lung; Male; Middle Aged; Morphine; Morphine Derivatives; Opiate Alkaloids; Opioid-Related Disorders; Organ Size; Pulmonary Edema; Retrospective Studies; United States; White People; Young Adult
PubMed: 32738646
DOI: 10.1016/j.jflm.2020.102030 -
Journal of the American College of... Jan 2020
Topics: Acute Coronary Syndrome; Clopidogrel; Coronary Angiography; Humans; Morphine; Opiate Alkaloids; Prasugrel Hydrochloride
PubMed: 31976868
DOI: 10.1016/j.jacc.2019.11.023 -
Progress in Neuro-psychopharmacology &... Dec 2021The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic... (Review)
Review
The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic medication with proven ability to attenuate drug addiction in preclinical models. However, clinical translational studies are inconsistent. In this review, we summarize preclinical evidences and clinical trials that investigated the efficacy of memantine in treating patients with alcohol, opiate, cocaine, and nicotine use disorders and discuss the results from a mechanistic point of view. Memantine has shown efficacy in reducing alcohol and opiate craving, consumption, and withdrawal severity. However, in cocaine and nicotine use disorders, memantine did not have significant effect on cravings or consumption. Additionally, memantine was associated with increased subjective effects of alcohol, cocaine, and nicotine. We discuss possible mechanisms behind this variability. Since memantine transiently blocks NMDA receptors and protects neurons from overstimulation by excessive synaptic glutamate, its efficacy should be observed in drug phases that cause hyperglutamatergic states, while hypoglutamatergic drug use states would not resolve with blocking NMDA receptors. Second, memantine pharmacokinetic studies have been done in rodents and healthy volunteers, but not in patients with substance use disorder. Memantine, opiates, cocaine, and nicotine share the same transporter family at the blood brain barrier. This shared transport mechanism could impact brain concentrations of memantine and its effects. In conclusion, memantine remains an intriguing compound in our pharmacopeia with controversial results in treating certain aspects of drug addiction. Further studies are needed to understand the clinical and biological correlates of its efficacy.
Topics: Animals; Brain; Cocaine; Ethanol; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Memantine; Neurons; Opiate Alkaloids; Receptors, N-Methyl-D-Aspartate; Substance-Related Disorders
PubMed: 34324921
DOI: 10.1016/j.pnpbp.2021.110409 -
Pain Management May 2018To provide an update on prescription of naloxone as a harm-reduction strategy, PubMed was searched to identify publications relevant to naloxone prescribing for reversal... (Review)
Review
To provide an update on prescription of naloxone as a harm-reduction strategy, PubMed was searched to identify publications relevant to naloxone prescribing for reversal of opioid overdose. Opportunities now exist to expand naloxone use, although evidence suggests these are often missed or underexploited. The US FDA has approved an intranasal naloxone spray and an autoinjector naloxone formulation for community use. Effective use of naloxone in community settings requires screening to identify patients at risk of opioid overdose, discussing naloxone use with patients and their relatives, and providing appropriate training. The tools exist to expand the use of naloxone more widely into the community, thereby creating an opportunity to reduce opioid overdose fatalities.
Topics: Administration, Intranasal; Analgesics, Opioid; Drug Overdose; Drug Prescriptions; Humans; Naloxone; Opiate Alkaloids
PubMed: 29667859
DOI: 10.2217/pmt-2017-0065 -
AANA Journal Jun 2022With the current opiate epidemic in the United States, there is renewed interest in evaluating non-opiate adjuvant medications as effective alternatives for the...
With the current opiate epidemic in the United States, there is renewed interest in evaluating non-opiate adjuvant medications as effective alternatives for the prevention and treatment of postoperative pain. A systematic review of randomized, controlled trials on Pub Med, Medline, and Embase was conducted looking on postoperative pain management from 2008 to 2018. Studies were included if they used a gabapentenoid with or without acetaminophen and evaluated supplemental opiate use. All adult (18 years or older) surgical populations were considered for inclusion, and fourteen clinical trials met inclusion criteria. Gabapentenoid dosing varied among studies. In nine of fourteen studies, there was a finding of superiority as compared to placebo in managing postoperative pain and decreasing supplemental opiate use. Pregabalin was used in twelve of the fourteen studies and gabapentin was used in two of the fourteen studies. Of the nine studies that found a benefit from using a gabapentoid, all included pregabalin. While the rate of adverse effects was low in all studies, it was found to increase as dosages increased. Results support that pregabalin has a role in decreasing postoperative pain intensity and supplemental opiate use; however, the optimal dose or dosing regimen is not yet well understood.
Topics: Acetaminophen; Adult; Analgesics; Analgesics, Opioid; Cyclohexanecarboxylic Acids; Humans; Opiate Alkaloids; Pain, Postoperative; Pregabalin; gamma-Aminobutyric Acid
PubMed: 35604860
DOI: No ID Found -
American Journal of Nephrology 2016More than 50% of American adolescents and adults report having used illicit drugs in their lifetime. We examined the association of lifetime opiate and cocaine use with...
BACKGROUND
More than 50% of American adolescents and adults report having used illicit drugs in their lifetime. We examined the association of lifetime opiate and cocaine use with reduced kidney function, albuminuria and rapid kidney function decline among urban-dwelling adults.
METHODS
Our prospective cohort included 2,286 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants who were community-dwelling adults residing in Baltimore, MD. The predictive variables were lifetime opiate and cocaine use, defined as use of opiates or crack/cocaine ≥5 times. Outcomes included prevalent reduced estimated glomerular filtration rate (eGFR; <60 ml/min/1.73 m2 by Chronic Kidney Disease (CKD)-Epidemiology Collaboration), albuminuria (albumin-to-creatinine ratio >30 mg/g, n = 1,652) and rapid kidney function decline (>3 ml/min/1.73 m2 per year over a median of 4.7 years, n = 1,660).
RESULTS
Participants' mean age was 48 years, 15% reported opiate use, and 22% reported cocaine use. A total of 115 (5.0%) participants had reduced eGFR, 190 (11.5%) had albuminuria and 230 (13.8%) experienced rapid decline in kidney function. In adjusted logistic regression analyses, both substances were associated with greater odds of reduced eGFR (OR 2.71, 95% CI 1.50-4.89 for opiates; OR 1.40, 95% CI 0.87-2.24 for cocaine). Both substances were associated with greater odds of albuminuria (OR 1.20, 95% CI 0.83-1.73 for opiates; OR 1.80, 95% CI 1.29-2.51 for cocaine). Neither substance was associated with the rapid decline of kidney function.
CONCLUSIONS
Lifetime opiate and cocaine use was associated with prevalent reduced eGFR and albuminuria, yet not with rapid kidney function decline. The use of opiate and cocaine may be an important risk factor for CKD in urban populations.
Topics: Adult; Albuminuria; Cocaine; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Illicit Drugs; Kidney; Male; Middle Aged; Opiate Alkaloids; Renal Insufficiency, Chronic; Risk Factors
PubMed: 27788520
DOI: 10.1159/000452348 -
Neuroscience and Biobehavioral Reviews Dec 2016Opiate use is associated with deficits in decision-making. However, the impact of abstinence and co-morbid factors, like head injury and poly-substance abuse, on this... (Meta-Analysis)
Meta-Analysis Review
Opiate use is associated with deficits in decision-making. However, the impact of abstinence and co-morbid factors, like head injury and poly-substance abuse, on this ability, is currently unclear. This meta-analysis aimed to assess 1) the magnitude of decision-making deficits in opiate users; 2) whether co-morbid factors moderate the severity of these deficits; 3) whether ex-opiate users demonstrate smaller decision-making deficits than current users; and 4) whether the length of abstinence is related to the magnitude of decision-making deficits. We analysed 22 studies that compared the performance of current and ex-opiate users to healthy controls on decision-making measures such as the Iowa Gambling Task. Current users demonstrated a moderately strong impairment in decision-making relative to controls, which was not significantly moderated by co-morbid factors. The magnitude of the impairment did not significantly differ between studies assessing current or ex-users, and this impairment was not related to length of abstinence. Thus, it appears that opiate users have relatively severe decision-making deficits that persist at least 1.5 years after cessation of use.
Topics: Decision Making; Gambling; Humans; Neuropsychological Tests; Opiate Alkaloids; Substance-Related Disorders
PubMed: 27649645
DOI: 10.1016/j.neubiorev.2016.09.011 -
The Alkaloids. Chemistry and Biology 2023Morphinan alkaloids have attracted constant attention since the isolation of morphine by Sertürner in 1805. However, a group of 45 compounds possessing a complete...
Morphinan alkaloids have attracted constant attention since the isolation of morphine by Sertürner in 1805. However, a group of 45 compounds possessing a complete ent-morphinan backbone can also be found in the literature. These compounds are related to the morphinandienone subgroup and display a substitution pattern which is different from the morphinans. In particular, these alkaloids could be substituted at position C-2 and C-8 either by a hydroxy function or a methoxy moiety. Four groups of ent-morphinan alkaloids can be proposed, the salutaridine, pallidine, cephasugine and erromangine series. Interestingly, the botanical distribution of the ent-morphinans is more widespread than for the morphinans and includes the Annonaceae, Berberidaceae, Euphorbiaceae, Fumariaceae, Hernandiaceae, Lauraceae, Menispermaceae, Monimiaceae, Papaveraceae, and Ranunculaceae families. To date, their exact mode of production remains elusive and their interplay with the biosynthetic pathway of other classes of benzyltetrahydroisoquinoline alkaloids, in particular aporphines, should be confirmed. Exploration of the biological and therapeutic potential of these compounds is limited to some areas, namely central nervous system (CNS), inflammation, cancer, malaria and viruses. Further studies should be conducted to identify the cellular/molecular targets in view of promoting these compounds as new scaffolds in medicinal chemistry.
Topics: Humans; Morphinans; Morphine; Annonaceae; Aporphines; Biology
PubMed: 37716795
DOI: 10.1016/bs.alkal.2023.07.001 -
Sleep Sep 2023Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found...
Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXB's mechanism of action on narcolepsy.
Topics: Humans; Mice; Animals; Dogs; Orexins; Sodium Oxybate; Cataplexy; Locus Coeruleus; Narcolepsy; Neurons; Opiate Alkaloids
PubMed: 37155728
DOI: 10.1093/sleep/zsad135 -
Accident; Analysis and Prevention Feb 2021Pharmacological differences among different drug classes influence human cognition, visual, and motor behavior in different ways. These differences impact driving...
BACKGROUND AND AIMS
Pharmacological differences among different drug classes influence human cognition, visual, and motor behavior in different ways. These differences impact driving safety, and therefore individuals who use stimulant and opioid drugs might experience different patterns in driving safety and impairment in driving performance. This study examined the effect of long-term use of stimulant drugs and of opiate drugs on driving performance, hazard perception, visual search skills and psychomotor skills related to driving.
METHODS
A total of 75 individuals, including 28 predominantly stimulant users, 22 predominantly opiate users and 25 healthy non-drug users, participated. Driving performance and psychomotor skills were assessed via a 15-minute drive in a simulator; hazard perception was assessed via a computerized task; and visual search skill was assessed by eye tracking.
RESULTS
ANOVA analyses indicate both stimulant and opiate users drove at higher speeds and experienced more crashes than the healthy non-drug users. Stimulant but not opiate users violated red light regulations more often than the healthy non-drug users. In the hazard perception task, stimulant drug users performed more poorly than both opioid drug users and healthy non-drug users. Specifically, they had lower saccade movement scores and higher average fixation times.
CONCLUSIONS
Results confirm that both stimulant drug users and opiate drug users show impaired driving performance compared to healthy non-drug users. Stimulant drug users possessed poorer hazard perception skills compared to the opiate users and the control group, perhaps as a result of cognitive deficits created by the drug use.
Topics: Accidents, Traffic; Analgesics, Opioid; Automobile Driving; Cognition; Humans; Opiate Alkaloids; Pharmaceutical Preparations; Psychomotor Performance
PubMed: 33271373
DOI: 10.1016/j.aap.2020.105885