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Nature Sep 2019
Topics: Analgesics, Opioid; Humans; Opioid Epidemic; Opioid-Related Disorders; Pain
PubMed: 31511676
DOI: 10.1038/d41586-019-02681-7 -
Current Opinion in Pulmonary Medicine Nov 2020Summarize the effects of opioids on sleep including sleep architecture, sleep disordered breathing (SDB) and restless legs syndrome. (Review)
Review
PURPOSE OF REVIEW
Summarize the effects of opioids on sleep including sleep architecture, sleep disordered breathing (SDB) and restless legs syndrome.
RECENT FINDINGS
Opioids are associated with the development of central sleep apnea (CSA) and ataxic breathing. Recent reports suggest that adaptive servo-ventilation may be an effective treatment for CSA associated with opioids.
SUMMARY
Opioids have multiple effects on sleep, sleep architecture and SDB. Although originally described with methadone use, most commonly used opioids have also been shown to affect sleep. In patients on chronic methadone, sleep architecture changes include decreases in N3 and REM sleep. However, in patients with chronic nonmalignant pain, opioids improve sleep quality and sleep time. Opioids, generally at a morphine equivalent dose more than 100 mg/day, are associated with an increased incidence of CSA and ataxic breathing as well as obstructive sleep apnea. Other risk factors may include concomitant use of other medications such as antidepressants, gabapentinoids and benzodiazepines. Opioid-induced CSA can be potentially treated with adaptive servo-ventilation. Finally, opioids are a potential therapeutic option for restless legs syndrome unresponsive to dopamine agonists and other medications. However, use in patients with restless legs syndrome should proceed with caution, taking into account the risk for dependence and development of SDB.
Topics: Analgesics, Opioid; Humans; Noninvasive Ventilation; Restless Legs Syndrome; Sleep; Sleep Apnea Syndromes; Sleep Apnea, Central; Sleep Apnea, Obstructive
PubMed: 32925368
DOI: 10.1097/MCP.0000000000000733 -
Current Opinion in Supportive and... Jun 2020Opioids are potent drugs for the treatment of severe pain, but they are burdened by detrimental side-effects, such as respiratory depression, addiction, sedation and... (Review)
Review
PURPOSE OF REVIEW
Opioids are potent drugs for the treatment of severe pain, but they are burdened by detrimental side-effects, such as respiratory depression, addiction, sedation and constipation. Their clinical application is undisputed in acute (e.g. perioperative) and cancer pain, but their use in chronic nonmalignant pain has met increasing scrutiny and has contributed to the opioid crisis. Thus, novel analgesics with reduced side-effects are badly needed.
RECENT FINDINGS
Current research topics include enkephalinase inhibitors, allosteric and multivalent ligands, biased opioid receptor signaling and selective activation of peripheral opioid receptors in injured tissues.
SUMMARY
Opioids still appear to be most promising among current approaches in the development of analgesics. Basic knowledge about pathophysiology of clinical pain and novel insights in pharmacology suggest that the most interesting perspectives are augmenting endogenous opioid actions and selectively targeting peripheral opioid receptors. The latter approach is additionally supported by evidence from clinical studies. Some biased, multivalent and peripherally selective agonists have advanced to phase III trials, but novel drugs have not become available for clinical application. Future strategies in analgesic drug development might include public-private partnerships and nonprofit pharmaceutical companies, as exemplified by the AIDS crisis and proposals to combat antibiotic resistance.
Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Chronic Pain; Drug Tolerance; Humans; Neprilysin; Opioid-Related Disorders; Receptors, Opioid; Signal Transduction
PubMed: 32304400
DOI: 10.1097/SPC.0000000000000495 -
Molecular and Cellular Neurosciences Jun 2023The opioids are potent and widely used pain management medicines despite also possessing severe liabilities that have fueled the opioid crisis. The pharmacological... (Review)
Review
The opioids are potent and widely used pain management medicines despite also possessing severe liabilities that have fueled the opioid crisis. The pharmacological properties of the opioids primarily derive from agonism or antagonism of the opioid receptors, but additional effects may arise from specific compounds, opioid receptors, or independent targets. The study of the opioids, their receptors, and the development of remediation strategies has benefitted from derivatization of the opioids as chemical tools. While these studies have primarily focused on the opioids in the context of the opioid receptors, these chemical tools may also play a role in delineating mechanisms that are independent of the opioid receptors. In this review, we describe recent advances in the development and applications of opioid derivatives as chemical tools and highlight opportunities for the future.
Topics: Humans; Analgesics, Opioid; Receptors, Opioid
PubMed: 36948231
DOI: 10.1016/j.mcn.2023.103845 -
Anesthesiology Clinics Jun 2023Advances in opioid pharmacology promise to bring a "better opioid." Biased opioid agonists, designed to recruit G protein over β-arrestin signaling, may provide... (Review)
Review
Advances in opioid pharmacology promise to bring a "better opioid." Biased opioid agonists, designed to recruit G protein over β-arrestin signaling, may provide analgesia without adverse effects of traditional opioids. Oliceridine, the first biased opioid agonist, was approved in 2020. In vitro and in vivo data present a complicated picture, with decreased gastrointestinal and respiratory adverse effects but similar abuse potential. Advances in pharmacology will result in new opioids brought to market. However, lessons learned from the past implore appropriate safeguards to patient safety and critical evaluation of the data and science behind new drugs.
Topics: Humans; Analgesics, Opioid; Receptors, Opioid, mu; Pain; Pain Management; Analgesia
PubMed: 37245944
DOI: 10.1016/j.anclin.2023.02.001 -
Current Treatment Options in Oncology Feb 2020Opioids are the gold standard for the treatment of cancer-related pain. Preclinical studies have associated opioids with cancer progression and overall survival. In mice... (Review)
Review
Opioids are the gold standard for the treatment of cancer-related pain. Preclinical studies have associated opioids with cancer progression and overall survival. In mice models, opioids have been shown to possess pro-tumor activity secondary to immunosuppression, migration of tumor cells, increased activity of vascular endothelial growth factor receptors, and angiogenesis leading to tumor progression. In contrast, opioids have also been associated with having antitumor activity by activation of apoptosis and phagocytosis. However, high-quality randomized controlled trials in humans that are focused on the association between opioids and survival in cancer patients are lacking, which underscores the importance of being cautious when interpreting the results of the preclinical studies. Cancer-related pain is complex and multifactorial and may worsen as the disease progresses leading to higher opioid utilization. Moreover, cancer pain by itself has been associated with poor survival. The survival in these advanced cancer patients taking opioids may be more likely to be associated with cancer progression and not the opioid use. Adequate treatment of cancer pain has the potential to improve quality of life and performance status, highlighting the importance of continuing to use opioids to manage pain efficiently. More research is clearly needed.
Topics: Analgesics, Opioid; Antineoplastic Combined Chemotherapy Protocols; Cancer Pain; Disease Progression; Humans; Immunosuppressive Agents; Morphine; Mortality; Neoplasms; Perioperative Care; Receptors, Opioid
PubMed: 32095929
DOI: 10.1007/s11864-020-0713-7 -
Molecular Pharmacology Oct 2020In the past 50 years, scientists have made considerable strides toward understanding how opioids act. This special issue of celebrates these 50 years of opioid research...
In the past 50 years, scientists have made considerable strides toward understanding how opioids act. This special issue of celebrates these 50 years of opioid research and the role that the International Narcotics Research Conference has played in driving this research, by bringing together review and original research articles that present historical highlights, the current state of the art, and perspectives on the future of opioid research. SIGNIFICANCE STATEMENT: Opioids have been used for thousands of years to manage pain and cause euphoria, but their use has been highly limited due to serious side effects. Deciphering the mechanisms of how opioids mediate beneficial and adverse physiological outcomes is essential for developing better treatments for pain and for opioid addiction.
Topics: Analgesics, Opioid; Biomedical Research; Congresses as Topic; Drug Design; Humans; Opioid-Related Disorders; Pain
PubMed: 32788221
DOI: 10.1124/molpharm.120.000132 -
Physical Medicine and Rehabilitation... May 2020Numerous guidelines targeting safe use of opioids for chronic pain have been published but substantial challenges persist in clinical application of best practice... (Review)
Review
Numerous guidelines targeting safe use of opioids for chronic pain have been published but substantial challenges persist in clinical application of best practice recommendations. This article describes a pragmatic approach to clinical care of adults with chronic pain receiving long-term opioid therapy. Three components of care are emphasized: (1) medical and mental health assessment before initiating opioid therapy, (2) clinical surveillance during the course of long-term opioid therapy, and (3) clinical considerations and strategies governing opioid tapering. A pressing need exists for ongoing research to further clarify the optimal role that long-term opioid therapy has in treatment of chronic pain.
Topics: Analgesics, Opioid; Chronic Pain; Drug Tapering; Humans; Opioid-Related Disorders; Pain Management
PubMed: 32279729
DOI: 10.1016/j.pmr.2020.01.006 -
Seminars in Nephrology Jan 2021
Topics: Analgesics, Opioid; Humans; Kidney
PubMed: 33896467
DOI: 10.1016/j.semnephrol.2021.03.001 -
Archives of Toxicology Feb 2023Insights into the pathophysiology of many non-immune-mediated drug reactions referred to as toxicities, sensitivities, intolerances, or pseudoallergies have resulted... (Review)
Review
Insights into the pathophysiology of many non-immune-mediated drug reactions referred to as toxicities, sensitivities, intolerances, or pseudoallergies have resulted from research identifying the mastocyte-related G-protein-coupled receptor (GPCR) member X2 (MRGPRX2), a human mast cell receptor mediating adverse reactions without the involvement of antibody priming. Opioid-induced degranulation of mast cells, particularly morphine, provoking release of histamine and other preformed mediators and causing hemodynamic and cutaneous changes seen as flushing, headache and wheal and flare reactions in the skin, is an example of results of MRGPRX2 activation. Opioids including morphine, codeine, dextromethorphan and metazocine as well as endogenous prodynorphin opioid peptides activate MRGPRX2 at concentrations causing mast cell degranulation. Unlike the canonical opioid receptors, MRGPRX2 shows stereochemical recognition preference for dextro rather than levo opioid enantiomers. Opioid analgesic drugs (OADs) display a range of histamine-releasing potencies from the strong releaser morphine to doubtful releasers like hydromorphone and the non-releaser fentanyl. Whether there is a correlation between histamine release by individual OADs, MRGPRX2 activation, and presence or absence of adverse cutaneous effects is not known. To investigate the question, ongoing research with recently pursued methodologies and strategies employing basophil and mast cell tests resulting from MRGPRX2 insights should help to elucidate whether or not an opioid's histamine-releasing potency, and its property of provoking an adverse reaction, are each a reflection of its activation of MRGPRX2.
Topics: Humans; Analgesics, Opioid; Histamine; Receptors, Neuropeptide; Hypersensitivity; Receptors, G-Protein-Coupled; Morphine Derivatives; Mast Cells; Cell Degranulation; Nerve Tissue Proteins
PubMed: 36344690
DOI: 10.1007/s00204-022-03402-2