Opioids In Clinical Practice Research Articles

HSD4 Opioid Use Among Migraine Patients Treated with Acute and Preventive Treatment

Opioids are not part of guideline-recommended treatment regimen for migraine; however, migraine patients are still prescribed opioids in clinical practice. The study assesses the real-world opioid utilization among migraine patients initiating on newer acute (ubrogepant, rimegepant, lasmiditan) and preventive (galcanezumab, erenumab, fremanezumab) migraine therapies and on standard of care (triptans).

A Retrospective Study of the Efficacy and Safety of Naldemedine for Treatment of Opioid-Induced Constipation in Patients with Hepatobiliary Pancreatic Cancer.

Background and Objectives: Opioid analgesics, which are used for cancer-related pain management, cause opioid-induced constipation (OIC). Naldemedine, a peripheral opioid receptor antagonist, is an OIC-modifying agent, but no focused efficacy and safety analysis has been conducted for its use in hepatobiliary pancreatic cancers. We performed a multi-institutional study on the efficacy and safety of naldemedine in patients with hepatobiliary pancreatic cancer using opioids in clinical practice. Materials and Methods: We retrospectively evaluated patients with hepatobiliary pancreatic cancer (including liver, biliary tract, and pancreatic cancers) treated with opioids and naldemedine during hospitalization at ten institutions in Japan from June 2017 to August 2019. We assessed the frequency of bowel movements before and after the initiation of naldemedine therapy. Responders were defined as patients who defecated ≥3 times/week, with an increase from a baseline of ≥1 defecations/week over seven days after the initiation of naldemedine administration. Results: Thirty-four patients were observed for one week before and one week after starting naldemedine. The frequency of bowel movements increased by one over the baseline frequency or to at least thrice per week in 21 patients. The response rate was 61.7% (95% confidence interval: 45.4-78.0%). The median number of weekly bowel movements before and after naldemedine treatment was 2 (range: 0-9) and 6 (range: 1-17), respectively, in the overall population (n = 34); the increase in the number of bowel movements following naldemedine administration was statistically significant (Wilcoxon signed-rank test, p < 0.0001). Diarrhea was the predominant gastrointestinal symptom, and 10 (29.4%) patients experienced grade 1, grade 2, or grade 3 adverse events. The only other adverse event included fatigue in one patient; grade 2-4 adverse events were absent. Conclusions: Naldemedine is effective, and its use may be safe in clinical practice for patients with hepatobiliary pancreatic cancer receiving opioid analgesics.

Relationship of Substance Abuse and Living Situation on Burn Survivors

Burn injuries are associated with high morbidity and fatality. Severe burns are complicated by an inflammatory and immunological response, metabolic abnormalities, and distributive shock that can cause multiple organ failure and be difficult to manage. Burns pose a considerate impact on patient's quality of life, mental and physical health. A burn injury frequently necessitates a lifelong healing procedure. Changes in survivors' mobility, appearance, and capacity to carry out activities of daily living have an influence on them. Burn injury trauma can persist for years, giving survivors anxiety and making daily life more difficult. Evidence points to substance-abuse disorders and psychiatric comorbidities as having an effect on social reintegration postburn, in addition to damage severity and physical comorbidities. Additionally, increased prevalence of substance addiction and psychiatric illnesses are reported among burn patients and survivors. Long-term and frequently complex hospital care as well as prolonged and unsuccessful postburn rehabilitation have been linked to substance misuse and psychiatric illnesses. Psychiatric rehabilitation is impacted by the stigma attached to burns, substance abuse, mental illness, and pain. Burn patients are commonly prescribed opioids in clinical practice for the management of pain. However, long-term opioid use, albeit beneficial, leads to opioid dependence and may also be associated with other mental health problems. Psychological assessments of burn survivors can also help in prevention of substance abuse. The purpose of this research is to review the available information about relationship of substance abuse and living situation of burn survivors.

The Persistent Pain Transcriptome: Identification of Cells and Molecules Activated by Hyperalgesia

During persistent pain, the dorsal spinal cord responds to painful inputs from the site of injury, but the molecular modulatory processes have not been comprehensively examined. Using transcriptomics and multiplex in situ hybridization, we identified the most highly regulated receptors and signaling molecules in rat dorsal spinal cord in peripheral inflammatory and post-surgical incisional pain models. We examined a time course of the response including acute (2 hours) and longer term (2 day) time points after peripheral injury representing the early onset and instantiation of hyperalgesic processes. From this analysis, we identify a key population of superficial dorsal spinal cord neurons marked by somatotopic upregulation of the opioid neuropeptide precursor prodynorphin, and 2 receptors: the neurokinin 1 receptor, and anaplastic lymphoma kinase. These alterations occur specifically in the glutamatergic subpopulation of superficial dynorphinergic neurons. In addition to specific neuronal gene regulation, both models showed induction of broad transcriptional signatures for tissue remodeling, synaptic rearrangement, and immune signaling defined by complement and interferon induction. These signatures were predominantly induced ipsilateral to tissue injury, implying linkage to primary afferent drive. We present a comprehensive set of gene regulatory events across 2 models that can be targeted for the development of non-opioid analgesics. PerspectiveThe deadly impact of the opioid crisis and the need to replace morphine and other opioids in clinical practice is well recognized. Embedded within this research is an overarching goal of obtaining foundational knowledge from transcriptomics to search for non-opioid analgesic targets. Developing such analgesics would address unmet clinical needs.

Opioid free anesthesia: evidence for short and long-term outcome.

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.

Opioids in clinical practice

The treatment of pain improves quality of life. Opioids are commonly prescribed painkillers. The side effects of opioids depend on the route of administration, dosage, drug metabolism, comorbid diseases and the patient’s general condition. Despite many beneficial effects, opioids can lead to increased mortality in heart failure, myocardial infarction, pulmonary oedema, and COPD. This article reviews specific uses of opioid medications. Opioids induce immunosuppression, and may undergo drug-drug interactions, especially during polytherapy or polypragmasia.

Opioids and chronic pain: using what we know to change what we do.

The review draws together firm conclusions about effectiveness and harms of prolonged opioid treatment and explores the complex nature of chronic pain. The literature may now explain why long-term opioid treatment has failed to live up to its late 20th century promise. An understanding of sources of bias in clinical trials has allowed a more detailed and accurate picture of the role of opioids in chronic pain to emerge and there is recognition that populations in clinical trials differ in very important ways to those given opioids in clinical practice. The prevalence of psychiatric and emotional comorbidities in patients with long-term pain is identified in clinical populations and the influence of these on the experience of pain and the outcomes of therapy are well described. This improved understanding of the role of opioids and the complexity of the pain experience should allow more appropriate assessment of patients and better focused treatment planning, but the influences on prescriber behaviour are many and varied and change in prescribing practice may be difficult to achieve. Clinicians treating patients with chronic pain need to understand the many contributors to the reported experience of pain. A shared understanding of this complexity helps to set prescriber and patient expectations appropriately. If medications are used as part of the treatment plan they should only be prescribed if they produce useful pain relief and meaningful improvements in quality of life.

Opioid-Induced Endocrinopathy in Cancer Patients: An Underestimated Clinical Problem

The impact of both endogenous and exogenous opioids on the endocrine system has been known for many years. With the increased use of opioids in chronic pain treatment, the research focuses mainly on their effects on the endocrine system in patients with chronic non-malignant pain. Despite the wide dissemination of cancer, there has been little research on the possible effects of opioids on the endocrine system in cancer patients. For the growing number of cancer survivors and patients in long-term remission who take opioids, other aspects of endocrine disorders caused or exacerbated by opioids will have practical and clinical importance. Conversely, this problem may be less relevant for patients in active cancer treatment or in the advanced stage of disease. This article presents the available research on the effects of opioids on the endocrine system and the clinical consequences resulting from opioid use in cancer patients. Clinicians who use opioids in clinical practice should be aware of the existence of the endocrine symptoms of opioid therapy. There is still a need for more research in this area to maintain the best possible quality of life for cancer patients treated with opioid analgesics.

Prescribing Practices, Knowledge, and Use of Prescription Drug Monitoring Programs (PDMP) by a National Sample of Medical Toxicologists, 2012

Prescription opioid analgesic misuse and addiction are a significant public health concern in the USA. Through their concurrent roles as prescribers and public health stewards, medical toxicologists (MTs) have a unique perspective on this issue. They represent a physician group with a particular interest in prescription drug monitoring programs (PDMPs) because of their subspecialty knowledge of the negative consequences of opioid overprescribing in terms of misuse, diversion, addiction, and overdose death. This study surveyed a national sample of MTs about their opioid prescribing patterns and their knowledge and use of PDMPs. A link to a Web-based survey was disseminated by email to the physician membership of the American College of Medical Toxicology. The survey assessed the circumstances and details of the respondents prescribing practices for opioids and their knowledge and use of PDMPs. This included focused questions regarding their perceived limitation of their current PDMP. Responses were received from 205/445 surveys (46 %), representing responses from 35 states. The majority (78 %) of MTs responding to the survey reported that they primarily practice emergency medicine. Although awareness of PDMPs, in general, was high, approximately 25 % reported no knowledge of or did not have access to their state's PDMP. Barriers to use included time and complexity required to access relevant information. MTs prescribe opioids primarily to patients in the Emergency Department (ED) for acute pain or acute exacerbations of chronic pain. MTs are generally aware of PDMPs, although many were unaware of or not using their state-based PDMPs when prescribing opioids in clinical practice.

Sevoflurane Inhibits the µ-Opioid Receptor Function Expressed in Xenopus Oocytes

Sevoflurane is widely used for anesthesia, and is commonly used together with opioids in clinical practice. However, the effects of sevoflurane on µ-opioid receptor (µOR) functions is still unclear. In this study, the effects of sevoflurane on µOR functions were analyzed by using Xenopus oocytes expressing a µOR fused to chimeric Gα protein G_qi5 (µOR-G_qi5). Sevoflurane by itself did not elicit any currents in oocytes expressing µOR-G_qi5, whereas sevoflurane inhibited the [D-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin (DAMGO)-induced Cl^– currents at clinically used concentrations. Sevoflurane did not affect the Cl^– currents induced by AlF₄^–, which directly led to activation of G proteins. The inhibitory effects of sevoflurane on the DAMGO-induced currents were not observed in oocytes pretreated with the protein kinase C (PKC) inhibitor GF109203X. These findings suggest that sevoflurane would inhibit µOR function. Further, the mechanism of inhibition by sevoflurane would be mediated by PKC.

Response to baca

To the Editor:—We appreciate the opportunity to respond to the letter by Baca et al. While our figure did show that the intervention group more often reported that they were “more likely to prescribe opioids” after the training (intervention 30% vs control 10%), this occurred in a minority of both groups, was not a statistically significant difference, and was not the intended purpose of the training. The training was intended to improve the quality of opioid care when deemed clinically appropriate. It did not address the appropriateness of opioid use (other than to discourage it in the presence of substance abuse), because this is a highly controversial area of practice with a rapidly evolving database. Long clinical tradition and a substantial research literature supports our assertion that methadone is “the long-acting opioid least prone to abuse.”1 Increased rates of opioid-related deaths in recent years have been reported in various states, including our own.2 These have occurred as prescription opioid availability has increased. Abuse of opioids has generally increased, but abuse is most prevalent with Oxycontin and hydrocodone, not methadone.3 There may be special problems with methadone safety due to the need for complicated dose conversion from other opioids and due to the fact that patients may not understand that “as needed” dosing is not safe or effective with methadone.4 We agree that the efficacy and safety of long-term opioid therapy for chronic pain remains to be demonstrated, especially for the psychiatrically vulnerable patients who are likely to receive long-term opioids in clinical practice. We have recently shown using population-based data that patients with psychiatric disorders are significantly more likely to receive opioids for chronic pain.5 While it is likely not permissible to deny opioid treatment to all patients with chronic nonmalignant pain, more research is clearly necessary to define when and how to use opioids to maximize benefit for patients with this pain.

Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids

Adverse events of opioids may restrict their use in non-cancer pain. Analysis of the incidence of common adverse events in trials conducted in non-cancer pain has usually been limited to opioids used to treat severe pain according to the WHO three-step ladder. To examine the incidence of common adverse events of opioids in non-cancer pain, a systematic review and meta-analysis of information from randomised trials of all opioids in non-cancer pain was undertaken. Studies used were published randomised trials of oral opioid in non-cancer pain, with placebo or active comparator. Thirty-four trials with 5,546 patients were included with 4,212 patients contributing some information on opioid adverse events. Most opioids used (accounting for 90% of patients) were for treating moderate rather than severe pain. Including trials without a placebo increased the amount of information available by 1.4 times. Because of clinical heterogeneity in condition, opioid, opioid dose, duration, and use of titration, only broad results could be calculated. Use of any oral opioid produced higher rates of adverse events than did placebo. Dry mouth (affecting 25% of patients), nausea (21%), and constipation (15%) were the most common adverse events. A substantial proportion of patients on opioids (22%) withdrew because of adverse events. Because most trials were short, less than four weeks, and because few titrated the dose, these results have limited applicability to longer-term use of opioids in clinical practice. Suggestions for improved studies are made.

Bedside perspectives on the use of opioids: transferring results of clinical research into practice.

1. Transference of research findings to clinical practice has been a challenge for those managing chronic pain. Generally, pain is not well controlled in hospitals and steps need to be taken to make pain control more effective. 2. Clinical trials of opioids have shown that pain can be controlled in the great majority of patients. Apart from the use of the World Health Organization Analgesic Ladder, a 'pain diagnosis' should be made and a comprehensive view of pain needs to be considered by the clinician. This would include pain and other physical symptoms, psychological issues and social and spiritual stresses. 3. Respiratory depression and tolerance for opioids are often seen as negative aspects of opioids and, therefore, may lead to inadequate control of pain. The evidence cited suggests that, in the long-term treatment of cancer pain, respiratory depression almost never occurs. The only situation that warrants caution is when an anaesthetic block or similar procedure relieves pain treated by opioids, when that patient has been receiving large doses of opioids. Long-term studies with opioids show that tolerance may occur, but is not a clinical problem and should not impair their use in adequate doses to relieve the patient's pain. 4. The active morphine metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) do need to be considered when administering morphine. There seems to be considerable interindividual variation in the production and elimination of metabolites. In cases of renal failure or in the elderly, the ratios of M3G and M6G to morphine accumulate exponentially, making opioid toxicity more likely. Even different routes of administration seem to be associated with different ratios of metabolites. A knowledge of these sources of pharmacokinetic variability may lead to more effective use of the opioids in clinical practice.