Academic literature on the topic 'System opioids'

Opioid peptides and multiple opioid receptors are found in brain cardiovascular nuclei, autonomic ganglia, the heart, and blood vessels, and opioids induce potent cardiovascular changes. The role of endogenous opioids in normal cardiovascular homeostasis is unclear;however, current data suggest opioid involvement in stress.

SUMMARY INTRODUCTION: Opioids interact with both innate and adaptive immune systems and have direct effects on opioid receptors located on immune cells. Research on this topic has provided evidence of the opioid influence on the immune response associated with surgical stress. The immunological effects of opioids are currently being investigated, particularly whether they influence the outcome of surgery or the underlying disease regarding important aspects like infection or cancer progression. This review addresses background research related to the influence of the opioid receptor on the immune system, the immunosuppressive effect associated with major opioids during the perioperative period, and their clinical relevance. The objective of the study was to review the effects of opioids on the immune system. Methods: A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms “immunosuppression,” “immune system,” “surgical procedures,” “analgesics,” “opioids” and “perioperative care.” Results: The immunosuppressive effect of opioids was identified over 30 years ago. They include signaling and acting directly through immune cells, including B and T lymphocytes, NK cells, monocytes, and macrophages, as well as activating the downstream pathways of the hypothalamic-pituitary-adrenal (HPA) axis leading to the production of immunosuppressive glucocorticoids in the peripheral and sympathetic nervous system.

Opioids are broad-spectrum analgesics with potent pain-relieving qualities but also with potential adverse effects related to both short-term and long-term therapy. Researchers have attempted to alter existing opioid analgesics, utilize different routes/ formulations, or combine opioid analgesics with other compounds in efforts to improve analgesia while minimizing adverse effects. Exogenous opioids, administered in efforts to achieve analgesia, work by mimicking the actions of endogenous opioids. Endogenous opioids and their receptors are located in the brain (supraspinal areas), spinal cord, and periphery. Although opioids and opioid receptors in the brain and spinal cord have received much attention over many years, peripheral endogenous opioid analgesic systems have only been extensively studied during the past decade. It has been known since 1990 that following injection into the rodent hindpaw, d-Ala2 , N-Me-Phe4 , Gly5 -ol-enkephalin (DAMGO) [a muopioid receptor agonist] probably exerts its antinociceptive effects locally, since the doses administered are too low to have an effect in the central nervous system (CNS). This notion has been supported by the observation that the quaternary compound morphine methyliodide, which does not as readily cross the bloodbrain barrier and enter the CNS, produced antinociception following intradermal administration into the hindpaw, but not when the same dose was administered systemically (subcutaneously at a distant site). With a growing appreciation of peripheral endogenous opioids, peripheral endogenous opioid receptors, and peripheral endogenous opioid analgesic systems, investigators began growing hopeful that it may be possible to achieve adequate analgesics while avoiding unwanted central untoward adverse effects (e.g. respiratory depression, somnolence, addiction). Peripherally-acting opioids, which capitalize on peripheral endogenous opioid analgesic systems, may be one potential future strategy which may be utilized in efforts to achieve potent analgesia with minimal side effects. Key words: Pain, opioids, immune cells, peripherally-acting opioids (PAO), leukocytes, inflammatory pain, peripheral analgesia

e24073 Background: Between 1999-2018, the CDC reported 232,000 deaths from prescription opioids. Lung cancer patients receive many opioid and adjunctive pain medication prescriptions. The frequency, duration, and impact of these prescriptions is unknown. Methods: We used the electronic medical record to catalogue opioid and adjunctive pain medication prescriptions given to adult cancer patients at our academic and county-affiliated health systems from 2009-2016. We identified the association of opioid and adjunctive pain medication use with patient characteristics including cancer stage and radiation therapy. Results: 1510 lung cancer patients were identified, of which 1061 had opioid prescriptions (70%). Of patients with prescriptions: hydrocodone was prescribed to 90%, morphine 35%, hydromorphone 17%, fentanyl 16%, and oxycodone 13%. 330/1061 patients had adjunctive medication prescriptions, of which, gabapentin was prescribed to 90%, pregabalin 14% and carbamazepine 2%. 296/330 patients prescribed adjunctive medications also had an opioid prescription with the following frequency: hydrocodone 90%, hydromorphone 33%, fentanyl 27%, morphine 41%, and oxycodone 23% 7/1061 patients with opioids had naloxone prescribed. Opioid usage by cancer stage is shown in the table. 211/1510 patients (13%) had prescriptions for ≥3 different opioids; 97/330 (33%) patients with adjunctive prescriptions, had prescriptions for ≥3 different opioids. Of patients treated with radiation for >4 weeks, 66% received opioids, with the proportion receiving opioids increasing with each fraction of radiation up to a rate of 90% with 5 or more fractions. 87% of patients prescribed opioids alone had an active opioid prescription 3 months after their last date of radiation as did 91% of those prescribed adjunctive medications in addition to opioids. In the total dataset: 55% of patients were from the university system and 45% were from the county system and other settings. Of the lung cancer patients with opioid prescriptions: 69% were from the university system and 31% were from other settings. Conclusions: Opioids are commonly prescribed in patients with any stage of lung cancer, particularly those with stage >1 with hydrocodone being the most prescribed. In the period under study, adjunctive medications such as gabapentin were prescribed much less than and rarely without opioids. Some lung cancer patients received ≥3 distinct opioids, with higher rates seen in those with adjunctive medicine prescriptions. Further studies to evaluate system wide opioid prescribing trends and discrepancies related to demographic factors are needed.[Table: see text]

Background: Errors may be more common and more likely to be harmful with opioids than with other medications, but little research has been conducted on these errors.Methods: The authors retrospectively analyzed MEDMARX®, an anonymous national medication error reporting database, and quantitatively described harmful opioid errors on inpatient units that did not involve devices such as patient-controlled analgesia. The authors compared patterns among opioids and qualitatively analyzed error descriptions to help explain the quantitative results.Results: The authors included 644 harmful errors from 222 facilities. Eighty-three percent caused only temporary harm; 60 percent were administration errors and 21 percent prescribing errors; and 23 percent caused underdosing and 52 percent overdosing. Morphine and hydromorphone had a significantly higher proportion of improper dose errors than other opioids (40 percent and 41 percent compared with 22 percent with meperidine). Hydromorphone errors were significantly more likely to be overdoses (78 percent vs 47 percent with other opioids). Omission errors were significantly more common with fentanyl patches (36 percent compared with 12 percent for other opioids). Wrong route errors were significantly more common with meperidine (given intravenously when prescribed as intramuscular, 34 percent vs 3 percent for morphine). Oxycodone errors were significantly more likely to be wrong drug errors (24 percent vs 11 percent for other opioids), often because of confusion between immediate- and sustained-release formulations.Conclusions: Reported opioid errors are usually associated with administration and prescribing and frequently cause uncontrolled pain as well as overdoses. These patterns of errors should be considered when using opioids and incorporated into pain guidelines, education, and quality improvement programs.

There is increasing evidence to implicate the mesolimbic dopamine system in the rewarding effects of drugs of abuse such as opioids, psychostimulants, and alcohol, and in addition endogenous opioids may play a key role in the underlying adaptive mechanisms. Opioid agonists with affinity for µ and delta opioid receptors are rewarding, whereas opioid agonists with affinity for kappa receptors are aversive. These opposing motivational effects are paralleled by an increase and decrease, respectively, of dopamine release in the nucleus accumbens. Opposite effects are induced in response to selective antagonists for these different receptor types, pointing to tonically active endogenous opioid reward mechanisms. Withdrawal from chronic morphine results in sensitization for opioid reward; an effect that is counteracted by kappa opioid agonists. The rewarding effects of psychostimulants such as cocaine and amphetamine, mediated by the mesolimbic dopamine pathway, are modulated by opioid mechanisms in both directions: sensitization by morphine pretreatment, inhibition by kappa receptor agonists. A modulatory role of endogenous opioids is also suggested from biochemical data, showing increased dynorphin and kappa receptor expression after chronic cocaine treatment. Alcohol reward involves the mesolimbic reward system also, and opioids modulate this behaviour. Naltrexone as well as selective µ and delta opioid receptor antagonists decrease alcohol consumption in operant conditioning models. Biochemical approaches point to a functional deficit of endogenous opioids in genetic models exhibiting high prevalence for alcohol intake. The therapeutic implications of these data are discussed.Key words: reward mechanisms, endogenouos opioid systems, psychostimulants, alcohol.

Opioids are used in clinical practice for sedation, anesthesia, and analgesia. Their effects depend on their pharmacokinetic and pharmacodynamic characteristics. The liver is the major site for the biotransformation of most opioids. The major metabolic pathway is oxidation. Metabolism influences distribution, clearance, onset, and offset of opioid drugs. Action also depends on the coupling of opioids with the class of receptors involved and on localization of specific receptors. Three major types of opioid receptors, designated as μ, ẟ, and ϰ, present in the central nervous system, are coupled to G proteins and inhibit adenylyl cyclase. Down’s syndrome is a congenital condition characterized by mental retardation and particular physical features. Neurotransmission alterations are important. Alteration in the concentration of opioids in the cortex of these patients has been demonstrated. Neurobiological abnormalities and, in some, abnormalities in the neurotransmission systems, anxiety, and, in particular, nociception all suggest that structural and functional alterations of opioid receptors may be present. A clear knowledge of these multiple abnormalities is essential for skillful management of the perioperative period and for a good outcome for patients with Down’s syndrome.

Opioids are the most commonly used and effective analgesic treatments for severe pain, but they have recently come under scrutiny owing to epidemic levels of abuse and overdose. These compounds act on the endogenous opioid system, which comprises four G protein–coupled receptors (mu, delta, kappa, and nociceptin) and four major peptide families (β-endorphin, enkephalins, dynorphins, and nociceptin/orphanin FQ). In this review, we first describe the functional organization and pharmacology of the endogenous opioid system. We then summarize current knowledge on the signaling mechanisms by which opioids regulate neuronal function and neurotransmission. Finally, we discuss the loci of opioid analgesic action along peripheral and central pain pathways, emphasizing the pain-relieving properties of opioids against the affective dimension of the pain experience.

Abstract Introduction Opioids are known to contribute to central sleep apnea (CSA), as they depress responsiveness to carbon dioxide and hypoxia. However, the role of non-opioid medications (antihistamines, myorelaxants, neuroleptics, antidepressants, and hypnotics) in CSA remains unclear. Given the hypothesized impact of non-opioids on the central nervous system, we examined associations between opioid and non-opioid medications and CSA. Methods Among all adults who underwent polysomnography testing at the University of Michigan’s Sleep Center between 2013-2018 (n=10,479), we identified 105 cases of CSA. Of these patients, we randomly selected 300 controls. Demographic and health characteristics, use of medications were obtained from medical charts. We classified study participants into three categories based on medication use: non-opioids only, opioids alone or in combination with non-opioids, and none. CSA was defined as a binary outcome using polysomnographic criteria as per the International Classification of Sleep Disorders-Third Edition. We used logistic regression to examine associations between medication use and CSA. Results Among participants, male:female ratio was 1:1 with a mean age of 49 (±14.3 SD) years. Opioid use alone was rare (4%), but more common in combination with non-opioids (17%), while the exclusive use of non-opioids was found among 38%. In adjusted analyses for age and sex, those who used non-opioid alone were less likely to have a CSA diagnosis (OR=0.88, (95% CI 0.5-1.6); however, the use of opioids (alone or in combination with non-opioids) was associated with a 4-fold higher odds of CSA. Conclusion These data suggest that non-opioids have a protective influence on CSA. Conversely, opioids, alone, or in combination with non-opioids, were associated with increased CSA risk, that may be attributed to opioids alone, or to opioids and non-opioids interactions. However, as opioids were mostly co-prescribed with non-opioids, the sole effect of opioids from the synergistic effect with non-opioids are difficult to disentangle. Support Dr. Gavidia was supported by a T32 Post-Doctoral Fellowship in Neuroscience NIH/NINDS T32 NS 007222

In recent years, the discovery of peripheral opioid receptors has challenged the dogma of opioids interacting exclusively with the central nervous system. In this article, we describe the current understanding of the roles of opioids and opioid receptors in renal physiology and pathophysiology. The renal response to opioid exposure varies depending upon the specific opioid agonist, dose, and duration of exposure. The known acute effects of opioids on the kidney impact salt and water balance. The chronic effects of opioid exposure on kidney function are largely unknown, but collapsing glomerulopathy has been associated with chronic heroin abuse. Opioid exposure can lead to both physiological and architectural renal changes, and this may have important clinical implications. Since opioids are often used for pain management in patients with existing kidney disease, their role in kidney function warrants attention.