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International Journal of Epidemiology Mar 2021Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and...
BACKGROUND
Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.
METHODS
Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.
RESULTS
After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.
CONCLUSIONS
Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.
Topics: Analgesics, Opioid; Cause of Death; Cohort Studies; Diabetes Mellitus; Female; Humans; Iran; Opiate Alkaloids; Prospective Studies; Risk Factors
PubMed: 32810213
DOI: 10.1093/ije/dyaa126 -
ACS Chemical Neuroscience Sep 2017Opioids are among the most effective pain relievers; however, their abuse has been on the rise worldwide evident from an alarming increase in accidental opioid... (Review)
Review
Opioids are among the most effective pain relievers; however, their abuse has been on the rise worldwide evident from an alarming increase in accidental opioid overdoses. This demands for an urgent increase in scientific endeavors for better understanding of main cellular mechanisms and circuits involved in opiate addiction. Preclinical studies strongly suggest that memories associated with positive and negative opioid experiences are critical in promoting compulsive opiate-seeking and opiate-taking behaviors, and relapse. Particular focus on synaptic plasticity as the cellular correlate of learning and memory has rapidly evolved in drug addiction field over the past two decades. Several critical addiction-related brain areas are identified, one of which is the ventral tegmental area (VTA), an area intensively studied as the initial locus for drug reward. Here, we provide an update to our previous review on "Opiates and Plasticity" highlighting the most recent discoveries of synaptic plasticity associated with opiates in the VTA. Electrophysiological studies of plasticity of addiction to date have been invaluable in addressing learning processes and mechanisms that underlie motivated and addictive behaviors, and now with the availability of powerful technologies of transgenic approaches and optogenetics, circuit-based studies hold high promise in fostering synaptic studies of opiate addiction.
Topics: Analgesics, Opioid; Animals; Epigenesis, Genetic; Humans; Neuronal Plasticity; Opiate Alkaloids; Opioid-Related Disorders; Synapses; Ventral Tegmental Area
PubMed: 28768409
DOI: 10.1021/acschemneuro.7b00281 -
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 -
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 -
The Western Journal of Medicine May 1990Treating opiate-dependent patients can be difficult for many physicians because the patients' life-styles, values, and beliefs differ from those of the physicians.... (Review)
Review
Treating opiate-dependent patients can be difficult for many physicians because the patients' life-styles, values, and beliefs differ from those of the physicians. Primary care physicians, however, are often involved in the treatment of the medical complications of opiate abuse, and physicians must often manage a patient's opiate dependence until appropriate referral to a drug abuse treatment program can be arranged. Treatment is guided by an understanding of the patient's addictive disease, for which there are specific diagnostic criteria, and an understanding of the pharmacology of opiates of abuse and the medications used in treating opiate dependence. The opiate agonist, methadone, is useful for both detoxification and maintenance. The opiate antagonist, naloxone, is the treatment of choice for opiate overdose, and naltrexone, also an opiate antagonist, is a useful adjunct in subgroups of opiate-dependent patients for preventing relapse. New medications for the treatment of opiate dependence are being developed.
Topics: Central Nervous System; Humans; Inactivation, Metabolic; Methadone; Naloxone; Naltrexone; Narcotics; Opioid-Related Disorders; Primary Health Care; Receptors, Opioid
PubMed: 2161588
DOI: No ID Found -
Molecules (Basel, Switzerland) Apr 20226,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a... (Review)
Review
6,14-ethenomorphinans are semisynthetic opiate derivatives containing an ethylene bridge between positions 6 and 14 in ring-C of the morphine skeleton that imparts a rigid molecular structure. These compounds represent an important family of opioid receptor ligands in which the 6,14-etheno bridged structural motif originates from a [4 + 2] cycloaddition of morphinan-6,8-dienes with dienophiles. Certain 6,14-ethenomorphinans having extremely high affinity for opioid receptors are often non-selective for opioid receptor subtypes, but this view is now undergoing some revision. The agonist 20-etorphine and 20-dihydroetorphine are several thousand times more potent analgesics than morphine, whereas diprenorphine is a high-affinity non-selective antagonist. The partial agonist buprenorphine is used as an analgesic in the management of post-operative pain or in substitution therapy for opiate addiction, sometimes in combination with the non-selective antagonist naloxone. In the context of the current opioid crisis, we communicated a summary of several decades of work toward generating opioid analgesics with lesser side effects or abuse potential. Our summary placed a focus on Diels-Alder reactions of morphinan-6,8-dienes and subsequent transformations of the cycloadducts. We also summarized the pharmacological aspects of radiolabeled 6,14-ethenomorphinans used in molecular imaging of opioid receptors.
Topics: Analgesics; Analgesics, Opioid; Morphinans; Morphine; Naloxone; Receptors, Opioid; Receptors, Opioid, mu
PubMed: 35566212
DOI: 10.3390/molecules27092863 -
Journal of Forensic Sciences Mar 2020
Topics: Amphetamines; Cocaine; Humans; Ketamine; Opiate Alkaloids; Substance-Related Disorders
PubMed: 31995236
DOI: 10.1111/1556-4029.14273 -
Cold Spring Harbor Perspectives in... Jul 2012The study of neuronal adaptations induced by opiate drugs is particularly relevant today given their widespread prescription and nonprescription use. Although much is... (Review)
Review
The study of neuronal adaptations induced by opiate drugs is particularly relevant today given their widespread prescription and nonprescription use. Although much is known about the acute actions of such drugs on the nervous system, a great deal of work remains to fully understand their chronic effects. Here, we focus on longer-lasting adaptations that occur in two catecholaminergic brain regions that mediate distinct behavioral actions of opiates: ventral tegmental area (VTA) dopaminergic neurons, important for drug reward, and locus coeruleus (LC) noradrenergic neurons, important for physical dependence and withdrawal. We focus on changes in cellular, synaptic, and structural plasticity in these brain regions that contribute to opiate dependence and addiction. Understanding the molecular determinants of this opiate-induced plasticity will be critical for the development of better treatments for opiate addiction and perhaps safer opiate drugs for medicinal use.
Topics: Catecholamines; Heroin; Humans; Locus Coeruleus; Morphine; Neuronal Plasticity; Neurons; Synapses; Ventral Tegmental Area
PubMed: 22762025
DOI: 10.1101/cshperspect.a012070 -
Molecules (Basel, Switzerland) Feb 2020Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law...
Studying the origin of opiate and/or opiate metabolites in individual urine specimens after consumption of cold syrups is vital for patients, doctors, and law enforcement. A rapid liquid chromatography-tandem mass spectrometry method using "dilute-and-shoot" analysis without the need for extraction, hydrolysis and/or derivatization has been developed and validated. The approach provides linear ranges of 2.5-1000 ng mL for 6-acetylmorphine, codeine, chlorpheniramine, and carbinoxamine, 2.5-800 ng mL for morphine and morphine-3-β-d-glucuronide, and 2.5-600 ng mL for morphine-6-β-d-glucuronide and codeine-6-β-d-glucuronide, with excellent correlation coefficients (R > 0.995) and matrix effects (< 5%). Urine samples collected from the ten participants orally administered cold syrups were analyzed. The results concluded that participants consuming codeine-containing cold syrups did not routinely pass urine tests for opiates, and their morphine-codeine concentration ratios (M/C) were not always < 1. In addition, the distribution map of the clinical total concentration of the sum of morphine and codeine against the antihistamines (chlorpheniramine or carbinoxamine) were plotted for discrimination of people who used cold syrups. The 15 real cases have been studied by using M/C rule, cutoff value, and distribution map, further revealing a potential approach to determine opiate metabolite in urine originating from cold syrups.
Topics: Adult; Analgesics, Opioid; Chlorpheniramine; Codeine; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Histamine Antagonists; Humans; Male; Middle Aged; Morphine; Morphine Derivatives; Opiate Alkaloids; Pyridines; Young Adult
PubMed: 32098143
DOI: 10.3390/molecules25040972 -
The British Journal of General Practice... Apr 2017More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare...
BACKGROUND
More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare services. Naloxone is an effective overdose treatment and is now being considered for wider lay use.
AIM
To establish GPs' views and experiences of opiate addiction, overdose care, and naloxone provision.
DESIGN AND SETTING
An anonymous postal survey to GPs affiliated with the Department of Academic General Practice, University College Dublin, Ireland.
METHOD
A total of 714 GPs were invited to complete an anonymous postal survey. Results were compared with a parallel GP trainee survey.
RESULTS
A total of 448/714 (62.7%) GPs responded. Approximately one-third of GPs were based in urban, rural, and mixed areas. Over 75% of GPs who responded had patients who used illicit opiates, and 25% prescribed methadone. Two-thirds of GPs were in favour of increased naloxone availability in the community; almost one-third would take part in such a scheme. A higher proportion of GP trainees had used naloxone to treat opiate overdose than qualified GPs. In addition, a higher proportion of GP trainees were willing to be involved in naloxone distribution than qualified GPs. Intranasal naloxone was much preferred to single (<0.001) or multiple dose (<0.001) intramuscular naloxone. Few GPs objected to wider naloxone availability, with 66.1% ( = 292) being in favour.
CONCLUSION
GPs report extensive contact with people who have opiate use disorders but provide limited opiate agonist treatment. They support wider availability of naloxone and would participate in its expansion. Development and evaluation of an implementation strategy to support GP-based distribution is urgently needed.
Topics: Drug Overdose; Education, Medical, Graduate; General Practice; Health Knowledge, Attitudes, Practice; Humans; Ireland; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Practice Patterns, Physicians'; Preventive Health Services; Program Development; Program Evaluation
PubMed: 28246098
DOI: 10.3399/bjgp17X689857