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Anesthesiology Apr 2021Opioids form an important component of general anesthesia and perioperative analgesia. Discharge opioid prescriptions are identified as a contributor for persistent... (Review)
Review
Opioids form an important component of general anesthesia and perioperative analgesia. Discharge opioid prescriptions are identified as a contributor for persistent opioid use and diversion. In parallel, there is increased enthusiasm to advocate opioid-free strategies, which include a combination of known analgesics and adjuvants, many of which are in the form of continuous infusions. This article critically reviews perioperative opioid use, especially in view of opioid-sparing versus opioid-free strategies. The data indicate that opioid-free strategies, however noble in their cause, do not fully acknowledge the limitations and gaps within the existing evidence and clinical practice considerations. Moreover, they do not allow analgesic titration based on patient needs; are unclear about optimal components and their role in different surgical settings and perioperative phases; and do not serve to decrease the risk of persistent opioid use, thereby distracting us from optimizing pain and minimizing realistic long-term harms.
Topics: Analgesics, Opioid; Humans; Opioid-Related Disorders; Pain, Postoperative; Perioperative Care
PubMed: 32991672
DOI: 10.1097/ALN.0000000000003572 -
Molecules (Basel, Switzerland) Sep 2020Achieving effective pain management is one of the major challenges associated with modern day medicine. Opioids, such as morphine, have been the reference treatment for... (Review)
Review
Achieving effective pain management is one of the major challenges associated with modern day medicine. Opioids, such as morphine, have been the reference treatment for moderate to severe acute pain not excluding chronic pain modalities. Opioids act through the opioid receptors, the family of G-protein coupled receptors (GPCRs) that mediate pain relief through both the central and peripheral nervous systems. Four types of opioid receptors have been described, including the μ-opioid receptor (MOR), κ-opioid receptor (KOR), δ-opioid receptor (DOR), and the nociceptin opioid peptide receptor (NOP receptor). Despite the proven success of opioids in treating pain, there are still some inherent limitations. All clinically approved MOR analgesics are associated with adverse effects, which include tolerance, dependence, addiction, constipation, and respiratory depression. On the other hand, KOR selective analgesics have found limited clinical utility because they cause sedation, anxiety, dysphoria, and hallucinations. DOR agonists have also been investigated but they have a tendency to cause convulsions. Ligands targeting NOP receptor have been reported in the preclinical literature to be useful as spinal analgesics and as entities against substance abuse disorders while mixed MOR/NOP receptor agonists are useful as analgesics. Ultimately, the goal of opioid-related drug development has always been to design and synthesize derivatives that are equally or more potent than morphine but most importantly are devoid of the dangerous residual side effects and abuse potential. One proposed strategy is to take advantage of biased agonism, in which distinct downstream pathways can be activated by different molecules working through the exact same receptor. It has been proposed that ligands not recruiting β-arrestin 2 or showing a preference for activating a specific G-protein mediated signal transduction pathway will function as safer analgesic across all opioid subtypes. This review will focus on the design and the pharmacological outcomes of biased ligands at the opioid receptors, aiming at achieving functional selectivity.
Topics: Analgesics, Opioid; Arrestin; Furans; Humans; Ligands; Pain; Pyrones; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Signal Transduction
PubMed: 32948048
DOI: 10.3390/molecules25184257 -
Minerva Anestesiologica Feb 2021The introduction of synthetic opioids in clinical practice played a major role in the history of anesthesiology. For years, anesthesiologists have been thinking that...
The introduction of synthetic opioids in clinical practice played a major role in the history of anesthesiology. For years, anesthesiologists have been thinking that opioids are needed for intraoperative anesthesia. However, we now know that opioids (especially synthetic short-acting molecules) are definitely not ideal analgesics and may even be counterproductive, increasing postoperative pain. As well, opioids have revealed important drawbacks associated to poor perioperative outcomes. As a matter of fact, efforts in postoperative pain management in the last 30 years were driven by the idea of reducing/eliminating opioids from the postoperative period. However, a modern concept of anesthesia should eliminate opioids already intra-operatively towards a balanced, opioid-free approach (opioid-free anesthesia - OFA). In OFA drugs and techniques historically proven for their efficacy are combined in rational and defined protocols. They include ketamine, alpha-2 agonists, lidocaine, magnesium, anti-inflammatory drugs and regional anesthesia. Promising results have been obtained on perioperative outcome. For sure, analgesia is not reduced with OFA, but it is effective and with less opioid-related side effects. These benefits may be of particular importance in some high-risk patients, like OSAS, obese and chronic opioid-users/abusers. OFA may also increase patient-reported outcomes; despite it is difficult to specifically rule out the effect of intraoperative opioids. Finally, few data are available on long-term outcomes (persistent pain and opioid abuse, cancer outcome). New studies and data are required to elaborate the optimal approach for each patient/surgery, but interest and publication are increasing and may open the road to the wider adoption of OFA.
Topics: Analgesics, Opioid; Anesthesia, Conduction; Anesthesiology; Humans; Opioid-Related Disorders; Pain, Postoperative
PubMed: 32755088
DOI: 10.23736/S0375-9393.20.14515-2 -
The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review.British Journal of Anaesthesia Jan 2020Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin... (Review)
Review
Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5-hydroxytryptamine (5-HT) and 5-HT receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT but not 5-HT receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.
Topics: Analgesics, Opioid; Anesthesiologists; Fever; Humans; Intraoperative Complications; Serotonin Agents; Serotonin Syndrome
PubMed: 31653394
DOI: 10.1016/j.bja.2019.08.010 -
Molecules (Basel, Switzerland) Aug 2020Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their... (Review)
Review
Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their pharmacology, interactions, safety profiles, and how pharmacology is being manipulated to misuse these common medications, with the aim to expand on the subject outlined by the authors focusing on abuse prevention and prevalence rates. The reviewed literature was identified in several online databases through searches conducted with phrases created by combining the international non-proprietary names of the drugs with terms related to drug misuse. The results show that OTC opioids are misused as an alternative for illicit narcotics, or prescription-only opioids. The potency of codeine and loperamide is strongly dependent on the individual enzymatic activity of CYP2D6 and CYP3A4, as well as P-glycoprotein function. Codeine can also be utilized as a substrate for clandestine syntheses of more potent drugs of abuse, namely desomorphine ("Krokodil"), and morphine. The dangerous methods used to prepare these substances can result in poisoning from toxic chemicals and impurities originating from the synthesis procedure. OTC opioids are generally safe when consumed in accordance with medical guidelines. However, the intake of supratherapeutic amounts of these substances may reveal surprising traits of common medications.
Topics: Analgesics, Opioid; Codeine; Drug Misuse; Humans; Loperamide; Nonprescription Drugs
PubMed: 32867117
DOI: 10.3390/molecules25173905 -
Nature Reviews. Nephrology Feb 2022Chronic pain is highly prevalent among adults treated with maintenance haemodialysis (HD) and has profound negative effects. Over four decades, research has demonstrated... (Review)
Review
Chronic pain is highly prevalent among adults treated with maintenance haemodialysis (HD) and has profound negative effects. Over four decades, research has demonstrated that 50-80% of adult patients treated with HD report having pain. Half of patients with HD-dependent kidney failure (HDKF) have chronic moderate-to-severe pain, which is similar to the burden of pain in patients with cancer. However, pain management in patients with HDKF is often ineffective as most patients report that their pain is inadequately treated. Opioid analgesics are prescribed more frequently for patients receiving HD than for individuals in the general population with chronic pain, and are associated with increased morbidity, mortality and health-care resource use. Furthermore, current opioid prescribing patterns are frequently inconsistent with guideline-recommended care. Evidence for the effectiveness of opioids in pain management in general, and in patients with HDKF specifically, is lacking. Nonetheless, long-term opioid therapy has a role in the treatment of some patients when used selectively, carefully and combined with an ongoing assessment of risks and benefits. Here, we provide a comprehensive overview of the use of opioid therapy in patients with HDKF and chronic pain, including a discussion of buprenorphine, which has potential as an analgesic option for patients receiving HD owing to its unique pharmacological properties.
Topics: Adult; Analgesics, Opioid; Chronic Pain; Humans; Pain Management; Practice Patterns, Physicians'; Renal Dialysis; Renal Insufficiency
PubMed: 34621058
DOI: 10.1038/s41581-021-00484-6 -
Current Oncology (Toronto, Ont.) Jul 2023Pain is frequently reported during cancer disease, and it still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better... (Review)
Review
Pain is frequently reported during cancer disease, and it still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Therefore, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discusses the different options currently available to manage pain in (former) cancer patients in light of progress made in the last decade. Major progress in the field includes the recent development of a chronic cancer pain taxonomy now included in the International Classification of Diseases (ICD-11) and the update of the WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, with opioids being considered as the mainstay. The opioids crisis has prompted the reassessment of opioids use in cancer patients and survivors. This review focuses on the current utilization of opioids, the neuropathic pain component often neglected, and the techniques and non-pharmacological strategies available which help to personalize patient treatment. Cancer pain management is now closer to the management of chronic non-cancer pain, i.e., "an integrative and supportive pain care" aiming to improve patient's quality of life.
Topics: Humans; Analgesics, Opioid; Chronic Pain; Quality of Life; Cancer Pain; Pain Management; Neoplasms
PubMed: 37504360
DOI: 10.3390/curroncol30070500 -
British Journal of Hospital Medicine... Jan 2024Adverse effects of perioperative opioids have led to the pursuit of 'opioid-free anaesthesia'. While early studies have shown that effective analgesia can be achieved...
Adverse effects of perioperative opioids have led to the pursuit of 'opioid-free anaesthesia'. While early studies have shown that effective analgesia can be achieved without using opioids, with some reduction in unwanted effects, further research is needed to elucidate which patients may benefit most and how.
Topics: Humans; Anesthesia; Anesthesiology; Analgesia; Analgesics, Opioid; Drug-Related Side Effects and Adverse Reactions
PubMed: 38300677
DOI: 10.12968/hmed.2023.0344 -
Clinical Journal of Oncology Nursing Aug 2021Now that the SARS-CoV-2 virus and its variants have altered clinical oncology practice as we know it, let's return to a familiar focus from the Core Curriculum for...
Now that the SARS-CoV-2 virus and its variants have altered clinical oncology practice as we know it, let's return to a familiar focus from the Core Curriculum for Oncology Nursing-pain management. Much has happened during the past two years that influences the effective management of pain in patients with cancer-not the least of which is a clinical environment that has been changed by the COVID-19 pandemic.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; COVID-19; Cancer Pain; Female; Humans; Male; Medical Oncology; Middle Aged; Oncology Nursing; Opioid-Related Disorders; Pain Management; Pandemics; Practice Guidelines as Topic; SARS-CoV-2; United States
PubMed: 34269344
DOI: 10.1188/21.CJON.361-362 -
Immunology Letters Nov 2020Pathological pain is regulated by a balance between pro-algesic and analgesic mechanisms. Interactions between opioid peptide-producing immune cells and peripheral... (Review)
Review
Pathological pain is regulated by a balance between pro-algesic and analgesic mechanisms. Interactions between opioid peptide-producing immune cells and peripheral sensory neurons expressing opioid receptors represent a powerful intrinsic pain control in animal models and in humans. Therefore, treatments based on general suppression of immune responses have been mostly unsuccessful. It is highly desirable to develop strategies that specifically promote neuro-immune communication mediated by opioids. Promising examples include vaccination-based recruitment of opioid-containing leukocytes to painful tissue and the local reprogramming of pro-algesic immune cells into analgesic cells producing and secreting high amounts of opioid peptides. Such approaches have the potential to inhibit pain at its origin and be devoid of central and systemic side effects of classical analgesics. In support of these concepts, in this article, we describe the functioning of peripheral opioid receptors, migration of opioid-producing immune cells to inflamed tissue, opioid peptide release, and the consequent pain relief. Conclusively, we provide clinical evidence and discuss therapeutic opportunities and challenges associated with immune cell-mediated peripheral opioid analgesia.
Topics: Analgesia; Analgesics, Opioid; Animals; Humans; Immunity, Cellular; Inflammation; Leukocytes; Neuroimmunomodulation; Pain; Pain Management; Receptors, Opioid; Sensory Receptor Cells
PubMed: 32814155
DOI: 10.1016/j.imlet.2020.08.005