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Journal of Medical Toxicology :... Apr 2022
Topics: Analgesics, Opioid; Humans; Opiate Alkaloids; Opioid-Related Disorders
PubMed: 34780053
DOI: 10.1007/s13181-021-00864-1 -
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 -
Expert Review of Clinical Pharmacology Feb 2017A wide range of medications have been studied for posttraumatic stress disorder (PTSD) and a number are registered for this indication. Nevertheless, current... (Review)
Review
A wide range of medications have been studied for posttraumatic stress disorder (PTSD) and a number are registered for this indication. Nevertheless, current pharmacotherapies are only partially effective in some patients, and are minimally effective in others. Thus novel treatment avenues need to be explored. Areas covered: In considering novel pharmacological agents for the treatment of PTSD, this paper takes a translational approach. We outline how advances in our understanding of the underlying neurobiology of PTSD may inform the identification of potential new treatment targets, including glutamatergic, noradrenergic and opioid pathways. Expert commentary: Continued investigation of the neural substrates and signalling pathways involved in responses to trauma may inform the development of novel treatment targets for future drug development for PTSD. However, the translation of preclinical findings to clinical practice is likely to be complex and gradual.
Topics: Excitatory Amino Acid Agents; Humans; Opiate Alkaloids; Psychotherapy; Psychotropic Drugs; Stress Disorders, Post-Traumatic; Sympathomimetics
PubMed: 27835034
DOI: 10.1080/17512433.2017.1260001 -
Journal of Psychosocial Nursing and... Sep 2020
Topics: Analgesics, Opioid; Depression; Fathers; Firearms; Humans; Opiate Alkaloids; Opioid-Related Disorders; Pain; Veterans; Vietnam Conflict
PubMed: 32853388
DOI: 10.3928/02793695-20200616-01 -
Journal of Opioid Management 2022To examine the role of Targin® (oral oxycodone:naloxone combination) in the perioperative setting. (Observational Study)
Observational Study
OBJECTIVE
To examine the role of Targin® (oral oxycodone:naloxone combination) in the perioperative setting.
DESIGN
A single center prospective observational pilot study at a regional hospital.
SETTING
Thirty-eight eligible patients undergoing major general surgical operations were recruited. Thirty-two patients completed the study.
INTERVENTIONS
Participants were given Targin twice daily from day 2 post-operatively with twice daily measures of pain scores, gut function, and mobility.
MAIN OUTCOME MEASURES
The primary end points were analgesic efficacy and the rate of ileus. Secondary end points were gastrointestinal (GI) recovery and the need for opioid requirement on discharge, at 1 week and 1 month.
RESULTS
Average pain score over 5 days at rest was one and on movement was four out of 10. All patients mobilized to a chair by day 3. Twenty-six participants (81.3 percent) experienced nausea at some point during the study, and four participants (12.5 percent) were diagnosed with a post-operative ileus (POI). There was no serious adverse event reported. Only two patients were on opioids at 1-month discharge. This was due to them having Orthopaedic surgery not related to this study.
Topics: Analgesia; Analgesics, Opioid; Humans; Ileus; Narcotic Antagonists; Opiate Alkaloids; Oxycodone; Pain; Pain, Postoperative; Prospective Studies
PubMed: 35666485
DOI: 10.5055/jom.2022.0721 -
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 -
Medical Science Monitor : International... May 2018Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important... (Review)
Review
Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important for mediating essential biological activities. The prototype opiate alkaloid morphine represents a low molecular mass heterocyclic compound that has been evolutionarily fashioned from a relatively restricted role as a secreted antimicrobial phytoalexin into a broad spectrum regulatory molecule. As an essential corollary, positive evolutionary pressure has driven the development of a cognate 6-transmembrane helical (TMH) domain μ3 opiate receptor that is exclusively responsive to morphine and related opiate alkaloids. A key aspect of "morphinergic" signaling mediated by μ3 opiate receptor activation is its functional coupling with regulatory pathways utilizing constitutive nitric oxide (NO) as a signaling molecule. Importantly, tonic and phasic intra-mitochondrial NO production exerts profound inhibitory effects on the rate of electron transport, H+ pumping, and O2 consumption. Given the pluripotent role of NO as a selective, temporally-defined chemical regulator of mitochondrial respiration and cellular bioenergetics, the expansion of prokaryotic denitrification systems into mitochondrial NO/nitrite cycling complexes represents a series of evolutionary modifications of existential proportions. Presently, our short review provides selective discussion of evolutionary development of morphine, opiate alkaloids, μ3 opiate receptors, and NO systems, within the perspectives of enhanced mitochondrial function, cellular bioenergetics, and the human microbiome.
Topics: Alkaloids; Biological Evolution; Energy Metabolism; Humans; Microbiota; Nitric Oxide; Nitrite Reductases
PubMed: 29756604
DOI: 10.12659/MSM.909409 -
Advances in Neuroimmunology 1994Receptor interactions of morphine are reviewed, with particular attention given to a recently discovered opiate receptor, designated mu 3, with unique selectivity for... (Review)
Review
Receptor interactions of morphine are reviewed, with particular attention given to a recently discovered opiate receptor, designated mu 3, with unique selectivity for morphine and certain other opiate alkaloids. Morphine, other opiate alkaloids and related analogs are known to bind to the classical delta, mu and kappa opioid receptor subtypes. Each of these subtypes also binds one or more of the endogenous opioid peptides with high affinity. Immunocytes have recently been found to contain a unique receptor for morphine, capable of binding morphine and certain other opiate alkaloids, but with essentially no or exceedingly low affinity for the naturally occurring endogenous opioid peptides or peptide analogs. This putative mu 3 (morphine/opiate alkaloid) receptor is present in invertebrate immunocytes as well as in human peripheral blood monocytes (macrophages). More recently this same receptor has been found in certain established macrophage cell lines and in human peripheral blood granulocytes. Finally, the same or closely related opiate alkaloid-selective (mu 3) receptor has been found to be present in a neuroblastoma and in a hybrid neural cell line. Studies indicate that in the immunocytes the receptor mediates inhibitory effects of morphine on cellular chemotaxis. While the functional coupling of this receptor in neurons is not known, it is postulated that the receptor may mediate effects of opiates on neuronal differentiation and cell division as well as neuronal transmission. Both for the immune system and the nervous system, the mu 3 receptor may constitute a major site of action for putative endogenous morphine or morphine-like substances. This receptor system also provides an additional pharmacological site of action for exogenously administered opiate alkaloid drugs. The mu 3 receptor is proposed to be an important neuro-immune link. This system is likely to play a significant role in a variety of responses involving the immune system, including the response of the organism to stress, infection and malignant transformation.
Topics: Animals; Bivalvia; Cell Movement; Granulocytes; Humans; Immune System; Immune Tolerance; Leukocytes; Macrophages; Morphine; Narcotics; Neurons; Opioid Peptides; Rats; Receptors, Opioid; Receptors, Opioid, mu; Vertebrates
PubMed: 7952830
DOI: 10.1016/s0960-5428(05)80002-6 -
Surgical Endoscopy Mar 2023The ongoing epidemic of prescription opiate abuse is one of the most pressing health issues in the United States today. Consequently, analgesic adjuncts, such as...
BACKGROUND
The ongoing epidemic of prescription opiate abuse is one of the most pressing health issues in the United States today. Consequently, analgesic adjuncts, such as multimodal drug regimens and regional anesthetic blocks (like transversus abdominis plane (TAP) block), have been introduced to the perioperative period in hopes of decreasing postoperative opiate use. However, the effect of these interventions on intraoperative opiate use has not been examined. We hypothesized that preoperative TAP block would be associated with decreased intraoperative opiate use during minimally invasive cholecystectomy.
METHODS
This was a retrospective review of patients undergoing minimally invasive cholecystectomy between June 2018 and January 2021. Perioperative data, operative times, and medication administration data were collected. Intraoperative opiate use was calculated in total morphine equivalent doses (MED) for each patient and adjusted for operative time. Univariate analysis and multivariate linear regression were performed to determine factors affecting intraoperative opiate requirements.
RESULTS
261 patients were included in this study, of which 62 (23.8%) received preoperative TAP block and 199 (76.2%) did not. Preoperative TAP block was associated with decreased intraoperative opiate use (0.199 vs 0.312, p < 0.001), while there were no statistically significant differences associated with other analgesic adjuncts including preoperative acetaminophen (p = 0.485), celecoxib (p = 0.112), gabapentin (p = 0.165), or intraoperative ketorolac (p = 0.200). On multivariate analysis, preoperative TAP block was independently associated with decreased intraoperative opiate use (< 0.001), while chronic cholecystitis on final pathology was associated with increased intraoperative opiate use (p = 0.002).
CONCLUSION
The use of preoperative TAP block was associated with decreased intraoperative opiate use during minimally invasive cholecystectomy and should be considered for routine use. Future research should investigate whether preoperative TAP blocks and a subsequent decrease of intraoperative opiates, also result in a decrease in postoperative opiate use and improvements in postoperative outcomes.
Topics: Humans; Opiate Alkaloids; Analgesics, Opioid; Pain, Postoperative; Cholecystectomy; Morphine; Analgesics; Abdominal Muscles
PubMed: 35864354
DOI: 10.1007/s00464-022-09445-x -
The Journal of Neuroscience : the... Jan 2022We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin...
We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin (Hcrt)-producing neurons. However, it remains unknown how this increase affects target areas of the hypocretin system involved in opioid withdrawal, including norepinephrine containing structures locus coeruleus (LC) and A1/A2 medullary regions. Using a combination of immunohistochemical, biochemical, imaging, and behavioral techniques, we now show that the increase in detected hypocretin cell number translates into a significant increase in hypocretin innervation and tyrosine hydroxylase (TH) levels in the LC without affecting norepinephrine-containing neuronal cell number. We show that the increase in TH is completely dependent on Hcrt innervation. The A1/A2 regions were unaffected by morphine treatment. Manipulation of the Hcrt system may affect opioid addiction and withdrawal. Previously, we have shown that the hypothalamic hypocretin system undergoes profound anatomic changes in human heroin addicts and in mice exposed to morphine, suggesting a role of this system in the development of addictive behaviors. The locus coeruleus plays a key role in opioid addiction. Here we report that the hypothalamic hypocretin innervation of the locus coeruleus increases dramatically with morphine administration to mice. This increase is correlated with a massive increase in tyrosine hydroxylase expression in locus coeruleus. Elimination of hypocretin neurons prevents the tyrosine hydroxylase increase in locus coeruleus and dampens the somatic and affective components of opioid withdrawal.
Topics: Animals; Locus Coeruleus; Mice; Morphine; Motor Activity; Neurons; Norepinephrine; Opiate Alkaloids; Orexins; Substance Withdrawal Syndrome; Tyrosine 3-Monooxygenase
PubMed: 34853083
DOI: 10.1523/JNEUROSCI.1557-21.2021