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Sample records for analgesics opioid

  1. Opioid Analgesics.

    Science.gov (United States)

    Jamison, Robert N; Mao, Jianren

    2015-07-01

    Chronic pain is an international health issue of immense importance that is influenced by both physical and psychological factors. Opioids are useful in treating chronic pain but have accompanying complications. It is important for clinicians to understand the basics of opioid pharmacology, the benefits and adverse effects of opioids, and related problematic issues of tolerance, dependence, and opioid-induced hyperalgesia. In this article, the role of psychiatric comorbidity and the use of validated assessment tools to identify individuals who are at the greatest risk for opioid misuse are discussed. Additionally, interventional treatment strategies for patients with chronic pain who are at risk for opioid misuse are presented. Specific behavioral interventions designed to improve adherence with prescription opioids among persons treated for chronic pain, such as frequent monitoring, periodic urine screens, opioid therapy agreements, opioid checklists, and motivational counseling, are also reviewed. Use of state-sponsored prescription drug monitoring programs is also encouraged. Areas requiring additional investigation are identified, and the future role of abuse-deterrent opioids and innovative technology in addressing issues of opioid therapy and pain are presented. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  2. Opioid analgesics: does potency matter?

    Science.gov (United States)

    Passik, Steven D; Webster, Lynn

    2014-01-01

    Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

  3. Use of Opioid Analgesics in Older Australians.

    Science.gov (United States)

    Veal, Felicity C; Bereznicki, Luke R E; Thompson, Angus J; Peterson, Gregory M

    2015-08-01

    To identify potential medication management issues associated with opioid use in older Australians. Retrospective cross-sectional review of the utilization of analgesics in 19,581 people who underwent a medication review in Australia between 2010 and 2012. Australian residents living in the community deemed at risk for adverse medication outcomes or any resident living fulltime in an aged care facility. Patient characteristics in those taking regularly dosed opioids and not and those taking opioid doses >120 mg and ≤120 mg MEQ/day were compared. Multivariable binary logistic regression was used to analyze the association between regular opioid and high dose opioid usage and key variables. Additionally, medication management issues associated with opioids were identified. Opioids were taken by 31.8% of patients, with 22.1% taking them regularly. Several major medication management issues were identified. There was suboptimal use of multimodal analgesia, particularly a low use of non-opioid analgesics, in patients taking regular opioids. There was extensive use (45%) of concurrent anxiolytics/hypnotics among those taking regular opioid analgesics. Laxative use in those prescribed opioids regularly was low (60%). Additionally, almost 12% of patients were taking doses of opioid that exceeded Australian recommendations. A significant evidence to practice gap exists regarding the use of opioids amongst older Australians. These findings highlight the need for a quick reference guide to support prescribers in making appropriate decisions regarding pain management in older patients with persistent pain. This should also be combined with patient and caregiver education about the importance of regular acetaminophen to manage persistent pain. Wiley Periodicals, Inc.

  4. Characteristics of methadone maintenance treatment patients prescribed opioid analgesics

    Science.gov (United States)

    Glenn, Matthew C.; Sohler, Nancy L.; Starrels, Joanna L.; Maradiaga, Jeronimo; Jost, John J.; Arnsten, Julia H.; Cunningham, Chinazo O.

    2016-01-01

    Background Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them to MMT patients not prescribed opioid analgesics. Methods We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012–2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included: patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients’ report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-squared tests, t-tests, and Mann-Whitney U tests. Results Of 611 MMT patients, most reported chronic pain (62.0%), HCV infection (52.1%), and currently using illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report HIV infection (aOR=1.6, 95% CI: 1.1–2.3) and chronic pain (aOR=7.6, 95% CI: 4.6–12.6). Conclusion Among MMT patients primarily in three Bronx clinics, nearly one-third reported taking prescribed opioid analgesics. Compared to patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients. PMID:26731299

  5. Characteristics of methadone maintenance treatment patients prescribed opioid analgesics.

    Science.gov (United States)

    Glenn, Matthew C; Sohler, Nancy L; Starrels, Joanna L; Maradiaga, Jeronimo; Jost, John J; Arnsten, Julia H; Cunningham, Chinazo O

    2016-01-01

    Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them with MMT patients not prescribed opioid analgesics. We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012 to 2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients' report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-square tests, t tests, and Mann-Whitney U tests. Of 611 MMT patients, most reported chronic pain (62.0%), hepatitis C virus (HCV) infection (52.1%), and current use of illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 1.1-2.3) and chronic pain (aOR = 7.6, 95% CI: 4.6-12.6). Among MMT patients primarily in 3 Bronx clinics, nearly one third reported taking prescribed opioid analgesics. Compared with patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients.

  6. Opioid Analgesics and Nicotine: More Than Blowing Smoke.

    Science.gov (United States)

    Yoon, Jin H; Lane, Scott D; Weaver, Michael F

    2015-09-01

    Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

  7. Non-analgesic effects of opioids

    DEFF Research Database (Denmark)

    Højsted, Jette; Kurita, Geana Paula; Kendall, Sally

    2012-01-01

    Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including...... cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. Two previous systematic reviews on cancer pain and non-cancer pain...... patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient...

  8. Prescription Opioid Analgesics Commonly Unused After Surgery: A Systematic Review.

    Science.gov (United States)

    Bicket, Mark C; Long, Jane J; Pronovost, Peter J; Alexander, G Caleb; Wu, Christopher L

    2017-11-01

    Prescription opioid analgesics play an important role in the treatment of postoperative pain; however, unused opioids may be diverted for nonmedical use and contribute to opioid-related injuries and deaths. To quantify how commonly postoperative prescription opioids are unused, why they remain unused, and what practices are followed regarding their storage and disposal. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched from database inception to October 18, 2016, for studies describing opioid oversupply for adults after a surgical procedure. The primary outcome-opioid oversupply-was defined as the number of patients with either filled but unused opioid prescriptions or unfilled opioid prescriptions. Two reviewers independently screened studies for inclusion, extracted data, and assessed the study quality. Six eligible studies reported on a total of 810 unique patients (range, 30-250 patients) who underwent 7 different types of surgical procedures. Across the 6 studies, 67% to 92% of patients reported unused opioids. Of all the opioid tablets obtained by surgical patients, 42% to 71% went unused. Most patients stopped or used no opioids owing to adequate pain control, and 16% to 29% of patients reported opioid-induced adverse effects. In 2 studies examining storage safety, 73% to 77% of patients reported that their prescription opioids were not stored in locked containers. All studies reported low rates of anticipated or actual disposal, but no study reported US Food and Drug Administration-recommended disposal methods in more than 9% of patients. Postoperative prescription opioids often go unused, unlocked, and undisposed, suggesting an important reservoir of opioids contributing to nonmedical use of these products, which could cause injuries or even deaths.

  9. Non-analgesic effects of opioids: opioids and the endocrine system.

    Science.gov (United States)

    Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E

    2012-01-01

    Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

  10. Caffeine as an opioid analgesic adjuvant in fibromyalgia.

    Science.gov (United States)

    Scott, J Ryan; Hassett, Afton L; Brummett, Chad M; Harris, Richard E; Clauw, Daniel J; Harte, Steven E

    2017-01-01

    Caffeine's properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored caffeine's effects on opioid analgesia. This study assessed the effects of caffeine consumption on pain and other symptoms in opioid-using and nonusing chronic pain patients meeting the survey criteria for fibromyalgia. Patients presenting to a university-based pain clinic completed validated self-report questionnaires assessing symptoms. Patients (N=962) meeting the fibromyalgia survey criteria were stratified by opioid use and further split into groups based on caffeine amount consumed per day (no caffeine, or low, moderate, high caffeine). Analysis of covariance with Dunnett's post hoc testing compared pain and symptom severity between the no caffeine group and the caffeine consuming groups. In opioid users, caffeine consumption had modest but significant effects on pain, catastrophizing, and physical function. Lower levels of pain interference were associated with low and moderate caffeine use compared to no caffeine intake. Lower pain catastrophizing and higher physical function were observed in all caffeine dose groups, relative to the no caffeine group. Lower pain severity and depression were observed only in the moderate caffeine group. In opioid nonusers, low caffeine intake was associated with higher physical function; however, no other significant effects were observed. Caffeine consumption was associated with decreased pain and symptom severity in opioid users, but not in opioid nonusers, indicating caffeine may act as an opioid adjuvant in fibromyalgia-like chronic pain patients. These data suggest that caffeine consumption concomitant with opioid analgesics could provide therapeutic benefits not seen with opioids or caffeine alone.

  11. Caffeine as an opioid analgesic adjuvant in fibromyalgia

    Directory of Open Access Journals (Sweden)

    Scott JR

    2017-07-01

    Full Text Available J Ryan Scott,1 Afton L Hassett,1 Chad M Brummett,1 Richard E Harris,1,2 Daniel J Clauw,1,2 Steven E Harte1,2 1Chronic Pain and Fatigue Research Center, Department of Anesthesiology, 2Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA Background: Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored ca­ffeine’s effects on opioid analgesia. This study assessed the effects of caffeine consumption on pain and other symptoms in opioid-using and nonusing chronic pain patients meeting the survey criteria for fibromyalgia. Materials and methods: Patients presenting to a university-based pain clinic completed validated self-report questionnaires assessing symptoms. Patients (N=962 meeting the fibromyalgia survey criteria were stratified by opioid use and further split into groups based on caffeine amount consumed per day (no caffeine, or low, moderate, high caffeine. Analysis of covariance with Dunnett’s post hoc testing compared pain and symptom severity between the no caffeine group and the caffeine consuming groups. Results: In opioid users, caffeine consumption had modest but significant effects on pain, catastrophizing, and physical function. Lower levels of pain interference were associated with low and moderate caffeine use compared to no caffeine intake. Lower pain catastrophizing and higher physical function were observed in all caffeine dose groups, relative to the no caffeine group. Lower pain severity and depression were observed only in the moderate caffeine group. In opioid nonusers, low caffeine intake was associated with higher physical function; however, no other significant effects were observed. Conclusion: Caffeine consumption was associated with decreased pain and symptom severity in opioid users, but not in opioid nonusers, indicating caffeine may act as an

  12. Role of Dentists in Prescribing Opioid Analgesics and Antibiotics: An Overview.

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    Dana, Ralph; Azarpazhooh, Amir; Laghapour, Nima; Suda, Katie J; Okunseri, Christopher

    2018-04-01

    Opioid analgesics and antibiotics prescribed by dentists is a useful and cost-effective measure when prescribed appropriately. Common dental conditions are best managed by extracting the offending tooth, restoring the tooth with an appropriate filling material, performing root canal therapy, and/or fabricating a prosthesis for the edentulous space. Unnecessary prescription of opioid analgesics and antibiotics to treat dental pain and bacterial infection is a growing public health concern. This article highlights the state of the literature on opioid analgesic and antibiotic prescribing practices in dentistry, the impact of opioid analgesic overdose, and prevention strategies to reduce opioid analgesics and antibiotic overprescription. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Prescription of Opioid and Non-opioid Analgesics for Dental Care in Emergency Departments: Findings from the National Hospital Ambulatory Medical Care Survey

    Science.gov (United States)

    Okunseri, Christopher; Okunseri, Elaye; Xiang, Qun; Thorpe, Joshua M.; Szabo, Aniko

    2014-01-01

    Objective The aim of this study was to examine trends and associated factors in the prescription of opioid analgesics, non-opioid analgesics, opioid and non-opioid analgesic combinations and no analgesics by emergency physicians for nontraumatic dental condition (NTDC)-related visits. Our secondary aim was to investigate whether race/ethnicity is a possible predictor of receiving a prescription for either type of medication for NTDC visits in emergency departments (EDs) after adjustment for potential covariates. Methods We analyzed data from the National Hospital Ambulatory Medical Care Survey for 1997–2000 and 2003–2007, and used multinomial multivariate logistic regression to estimate the probability of receiving a prescription for opioid analgesics, non-opioid analgesics, or a combination of both compared to receiving no analgesics for NTDC-related visits. Results During 1997–2000 and 2003–2007, prescription of opioid analgesics and combinations of opioid and non-opioid analgesics increased and that of no analgesics decreased over time. The prescription rates for opioid analgesics, non-opioid analgesics, opioid and non-opioid analgesic combinations and no analgesics for NTDC-related visits in EDs were 43%, 20%, 12% and 25% respectively. Majority of patients categorized as having severe pain received prescriptions for opioids for NTDC-related visits in EDs. After adjusting for covariates, patients with self-reported dental reasons for visit and severe pain had a significantly higher probability of receiving prescriptions for opioid analgesics and opioid and non-opioid analgesic combinations. Conclusion Prescription of opioid analgesics increased over time. ED physicians were more likely to prescribe opioid analgesics and opioid and non-opioid analgesic combinations for NTDC-related visits with reported severe pain. PMID:24863407

  14. Novel Opioid Analgesics and Side Effects.

    Science.gov (United States)

    Del Vecchio, Giovanna; Spahn, Viola; Stein, Christoph

    2017-08-16

    Conventional opioids mediate analgesia as well as severe adverse effects via G-protein coupled opioid receptors (OR) in both inflamed (peripheral injured tissue) and healthy (brain, intestinal wall) environments. To exclude side effects, OR activation can be selectively achieved in damaged tissue by lowering the pK a of an opioid ligand to the acidic pH of inflammation. As a result, protonation of the ligand and consequent OR binding and activation of G-proteins is pH- and injury-specific. A novel compound (NFEPP) demonstrates the feasibility of this approach and displays blockade of pain transmission only at the peripheral site of injury, but with lack of central and gastrointestinal adverse effects. These findings suggest disease-specific receptor activation as a new strategy in drug design.

  15. Prescription Opioid Analgesics: Promoting Patient Safety with Better Patient Education.

    Science.gov (United States)

    Costello, Margaret

    2015-11-01

    Patients expect and deserve adequate postoperative pain relief. Opioid analgesics are widely used and effective in controlling postoperative pain, but their use poses risks that many patients don't understand and that all too often result in adverse outcomes. Inappropriate and often dangerous use of prescription medication has increased sharply in the past two decades in the United States. Patients and caregivers must have an adequate understanding of safe use, storage, and disposal of opioids to prevent adverse drug events in patients and others. Nurses play a key role in providing this patient education. This article provides a case study that highlights the risks and important aspects of opioid medication use in the postoperative patient.

  16. Analgesic synergy between opioid and α2 -adrenoceptors.

    Science.gov (United States)

    Chabot-Doré, A-J; Schuster, D J; Stone, L S; Wilcox, G L

    2015-01-01

    Opioid and α2 -adrenoceptor agonists are potent analgesic drugs and their analgesic effects can synergize when co-administered. These supra-additive interactions are potentially beneficial clinically; by increasing efficacy and/or reducing the total drug required to produce sufficient pain relief, undesired side effects can be minimized. However, combination therapies of opioids and α2 -adrenoceptor agonists remain underutilized clinically, in spite of a large body of preclinical evidence describing their synergistic interaction. One possible obstacle to the translation of preclinical findings to clinical applications is a lack of understanding of the mechanisms underlying the synergistic interactions between these two drug classes. In this review, we provide a detailed overview of the interactions between different opioid and α2 -adrenoceptor agonist combinations in preclinical studies. These studies have identified the spinal cord as an important site of action of synergistic interactions, provided insights into which receptors mediate these interactions and explored downstream signalling events enabling synergy. It is now well documented that the activation of both μ and δ opioid receptors can produce synergy with α2 -adrenoceptor agonists and that α2 -adrenoceptor agonists can mediate synergy through either the α2A or the α2C adrenoceptor subtypes. Current hypotheses surrounding the cellular mechanisms mediating opioid-adrenoceptor synergy, including PKC signalling and receptor oligomerization, and the evidence supporting them are presented. Finally, the implications of these findings for clinical applications and drug discovery are discussed. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

  17. Tolerance to non-opioid analgesics is opioid-sensitive in nucleus raphe magnus

    Directory of Open Access Journals (Sweden)

    Merab G Tsagareli

    2011-07-01

    Full Text Available Repeated injection of opioid analgesics can lead to a progressive loss of its effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs in the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM in the following four days result in progressively less antinociception, i.e. produce the development of tolerance to these drugs in mail rats. Special control experiments showed that post-treatment with μ-opioid antagonist naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in behavioral tail flick reflex (TF and hot plate (HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

  18. Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance.

    Science.gov (United States)

    Mercer, Susan L; Coop, Andrew

    2011-01-01

    Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.

  19. Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

    Science.gov (United States)

    2012-01-01

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

  20. Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

    Science.gov (United States)

    Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

    2012-09-19

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

  1. Non-analgesic effects of opioids: management of opioid-induced constipation by peripheral opioid receptor antagonists: prevention or withdrawal?

    Science.gov (United States)

    Holzer, Peter

    2012-01-01

    The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation (OIC) is the most disabling, with a prevalence reported to vary between 15 and 90 %. Although OIC is usually treated with laxatives, there is insufficient clinical evidence that laxatives are efficacious in this indication. In contrast, there is ample evidence from double- blind, randomized and placebo-controlled trials that peripheral opioid receptor antagonists (PORAs) counteract OIC. This specific treatment modality is currently based on subcutaneous methylnaltrexone for the interruption of OIC in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the prevention of OIC in the treatment of non-cancer and cancer pain. Both drugs counteract OIC while the analgesic effect of opioids remains unabated. The clinical studies show that more than 50 % of the patients with constipation under opioid therapy may benefit from the use of PORAs, while PORA-resistant patients are likely to suffer from non-opioid-induced constipation, the prevalence of which increases with age. While the addition of naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate defaecation by provoking an intestinal withdrawal response. The availability of PORAs provides a novel opportunity to specifically control OIC and other peripheral adverse effects of opioid analgesics (e.g., urinary retention and pruritus). The continuous dosing of a PORA has the advantage of few adverse effects, while intermittent dosing of a PORA can be associated with abdominal cramp-like pain.

  2. Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus.

    Science.gov (United States)

    Tsagareli, Merab G; Nozadze, Ivliane; Tsiklauri, Nana; Gurtskaia, Gulnaz

    2011-01-01

    Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac, and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the following 4 days result in progressively less antinociception compare to the saline control, i.e., tolerance develops to these drugs in male rats. Special control experiments showed that post-treatment with the μ-opioid antagonist naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs on the first day of testing in the tail-flick (TF) reflex and hot plate (HP) latency tests. On the second day, naloxone generally had trend effects in both TF and HP tests and impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine, and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

  3. Opioid analgesic administration in patients with suspected drug use.

    Science.gov (United States)

    Kreling, Maria Clara Giorio Dutra; Mattos-Pimenta, Cibele Andrucioli de

    2017-01-01

    To identify the prevalence of patients suspected of drug use according to the nursing professionals' judgement, and compare the behavior of these professionals in opioid administration when there is or there is no suspicion that patient is a drug user. A cross-sectional study with 507 patients and 199 nursing professionals responsible for administering drugs to these patients. The Chi-Square test, Fisher's Exact and a significance level of 5% were used for the analyzes. The prevalence of suspected patients was 6.7%. The prevalence ratio of administration of opioid analgesics 'if necessary' is twice higher among patients suspected of drug use compared to patients not suspected of drug use (p = 0.037). The prevalence of patients suspected of drug use was similar to that of studies performed in emergency departments. Patients suspected of drug use receive more opioids than patients not suspected of drug use. Identificar a prevalência de pacientes com suspeita de uso de drogas conforme opinião de profissionais de enfermagem e comparar a conduta desses profissionais na administração de opioides quando há ou não suspeita de que o paciente seja usuário de drogas. Estudo transversal com 507 pacientes e 199 profissionais de enfermagem responsáveis pela administração de medicamentos a esses pacientes. Para as análises foram utilizados os testes de Qui-Quadrado, Exato de Fisher e um nível de significância de 5%. A prevalência de pacientes suspeitos foi 6,7%. A razão de prevalência de administração de analgésicos opioides "se necessário" é duas vezes maior entre os pacientes suspeitos em relação aos não suspeitos (p=0,037). A prevalência de suspeitos foi semelhante à de estudos realizados em departamentos de emergência. Os suspeitos de serem usuários de drogas recebem mais opioides do que os não suspeitos.

  4. Personalized Medicine and Opioid Analgesic Prescribing for Chronic Pain: Opportunities and Challenges

    Science.gov (United States)

    Bruehl, Stephen; Apkarian, A. Vania; Ballantyne, Jane C.; Berger, Ann; Borsook, David; Chen, Wen G.; Farrar, John T.; Haythornthwaite, Jennifer A.; Horn, Susan D.; Iadarola, Michael J.; Inturrisi, Charles E.; Lao, Lixing; Mackey, Sean; Mao, Jianren; Sawczuk, Andrea; Uhl, George R.; Witter, James; Woolf, Clifford J.; Zubieta, Jon-Kar; Lin, Yu

    2013-01-01

    Use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy. This paper discusses the concept of data-based personalized prescribing of opioid analgesics as a means to achieve this goal. Strengths, weaknesses, and potential synergism of traditional randomized placebo-controlled trial (RCT) and practice-based evidence (PBE) methodologies as means to acquire the clinical data necessary to develop validated personalized analgesic prescribing algorithms are overviewed. Several predictive factors that might be incorporated into such algorithms are briefly discussed, including genetic factors, differences in brain structure and function, differences in neurotransmitter pathways, and patient phenotypic variables such as negative affect, sex, and pain sensitivity. Currently available research is insufficient to inform development of quantitative analgesic prescribing algorithms. However, responder subtype analyses made practical by the large numbers of chronic pain patients in proposed collaborative PBE pain registries, in conjunction with follow-up validation RCTs, may eventually permit development of clinically useful analgesic prescribing algorithms. Perspective Current research is insufficient to base opioid analgesic prescribing on patient characteristics. Collaborative PBE studies in large, diverse pain patient samples in conjunction with follow-up RCTs may permit development of quantitative analgesic prescribing algorithms which could optimize opioid analgesic effectiveness, and mitigate risks of opioid-related abuse and mortality. PMID:23374939

  5. National consumption of opioid and nonopioid analgesics in Croatia: 2007–2013

    Directory of Open Access Journals (Sweden)

    Krnic D

    2015-08-01

    Full Text Available Darko Krnic,1 Andrea Anic-Matic,2 Svjetlana Dosenovic,2 Pero Draganic,1 Sasa Zezelic,1 Livia Puljak2 1Agency for Medicinal Products and Medical Devices, Zagreb, 2Laboratory for Pain Research, School of Medicine, University of Split, Split, Croatia Background: The increased consumption of analgesics has been documented worldwide during the last 2 decades. The aim of the study was to examine the trends in opioid and nonopioid analgesic consumption in Croatia between 2007 and 2013. Methods: Data on opioid consumption were extracted from the database of the national authority. All opioid and nonopioid analgesics were included in the analysis. Data were presented as defined daily doses per 1,000 inhabitants per day. Adequacy of opioid consumption was calculated using adequacy of consumption measure. Results: During the examined 7-year period, the total consumption and total cost of all analgesics in Croatia showed continuous increase. In the M01A group (anti-inflammatory and antirheumatic products, nonsteroids, ibuprofen had an exponential increasing trend, and in 2011, it overtook diclofenac consumption. Ibuprofen and diclofenac had the highest consumption also in the M02A group of topical products for joint and muscular pain. Tramadol was by far the most consumed type of opioids (N02A group and paracetamol in the group of other analgesics and antipyretics (N02B. The adequacy of consumption measure value was 0.19, indicating that Croatia is a country with a low opioid consumption. Conclusion: Between 2007 and 2013, both consumption of analgesics and their cost in Croatia had an increasing trend. Comparisons with data from other countries, based on the published literature, indicate that analgesic consumption in Croatia is still relatively low. Calculation of the adequacy of opioid consumption indicated that Croatia is a country with low opioid consumption. Further studies are necessary for establishing whether current analgesic consumption in

  6. Non-opioid analgesics: Novel approaches to perioperative analgesia for major spine surgery.

    Science.gov (United States)

    Dunn, Lauren K; Durieux, Marcel E; Nemergut, Edward C

    2016-03-01

    Perioperative pain management is a significant challenge following major spine surgery. Many pathways contribute to perioperative pain, including nociceptive, inflammatory, and neuropathic sources. Although opioids have long been a mainstay for perioperative analgesia, other non-opioid therapies have been increasingly used as part of a multimodal analgesic regimen to provide improved pain control while minimizing opioid-related side effects. Here we review the evidence supporting the use of novel analgesic approaches as an alternative to intravenous opioids for major spine surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

    Science.gov (United States)

    Sunara, Petra; Krnic, Darko; Puljak, Livia

    2017-11-01

    Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014. HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type. In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics. Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  8. Benzodiazepines: a major component in unintentional prescription drug overdoses with opioid analgesics.

    Science.gov (United States)

    Jann, Michael; Kennedy, William Klugh; Lopez, Gaylord

    2014-02-01

    The misuse and abuse of prescription medications in the United States continues to increase despite interventions by health care professionals, regulatory, and law enforcement agencies. Opioid analgesics are the leading class of prescription drugs that have caused unintentional overdose deaths. Benzodiazepines when taken alone are relatively safe agents in overdose. However, a 5-fold increase in deaths attributed to benzodiazepines occurred from 1999 to 2009. Emergency department visits related to opioid analgesics increased by 111% followed by benzodiazepines 89%. During 2003 to 2009, the 2 prescriptions drugs with the highest increase in death rates were oxycodone 264.6% and alprazolam 233.8%. Therefore, benzodiazepines have a significant impact on prescription drug unintentional overdoses second only to the opioid analgesics. The combination prescribing of benzodiazepines and opioid analgesics commonly takes place. The pharmacokinetic drug interactions between benzodiazepines and opioid analgesics are complex. The pharmacodynamic actions of these agents differ as their combined effects produce significant respiratory depression. Physician and pharmacy shopping by patients occurs, and prescription drug-monitoring programs can provide important information on benzodiazepine and opioid analgesic prescribing patterns and patient usage. Health care professionals need to inform patients and work closely with regulatory agencies and legislatures to stem the increasing fatalities from prescription drug unintentional overdoses.

  9. Use of opioid analgesics or sleeping medication and survival of cancer patients.

    Science.gov (United States)

    Chang, Wen-Pei; Lin, Chia-Chin

    2015-06-01

    Pain and sleep disturbance have been shown to have a profound influence on the outcomes of cancer treatment. This study sought to determine whether administering opioid analgesics or sleeping medication to cancer patients during their first admission to a hospital is associated with poor prognoses. We conducted a population-based retrospective cohort study by analyzing data obtained from the National Health Insurance Research Database in Taiwan. The study population comprised cancer patients whose first admission to a hospital for initial cancer treatment was in 2004. We collected data on 2302 cancer patients. To analyze the effect of opioid analgesic and sleeping medication usage on cancer patient survival, we compared the 3-year survival rates among 4 groups of patients (no use, sleeping medications-only, opioid analgesics-only, both used). The 3-year Kaplan-Meier plots for these 4 groups show that the difference was statistically significant (log rank 48.244, p opioid analgesics-only group, and finally, the group in which both sleeping medications and opioid analgesics were used. The use of opioid analgesics or sleeping medication was shown to be negatively correlated with the survival rate of cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Prescription of opioid analgesics for nontraumatic dental conditions in emergency departments.

    Science.gov (United States)

    Okunseri, Christopher; Dionne, Raymond A; Gordon, Sharon M; Okunseri, Elaye; Szabo, Aniko

    2015-11-01

    Opioid analgesics prescribed for nontraumatic dental conditions (NTDCs) by emergency physicians continue to receive attention because of the associated potential for misuse, abuse and addiction. This study examined rates of prescription of opioid analgesics and types of opioid analgesics prescribed for NTDC visits in U.S. emergency departments. Data from the National Hospital Ambulatory Medical Care Survey from 2007 to 2010 were analyzed. Descriptive statistics and logistic regression analysis were performed and adjusted for the survey design. NTDCs made up 1.7% of all ED visits from 2007 to 2010. The prescription of opioid analgesics was 50.3% for NTDC and 14.8% for non-NTDC visits. The overall rate of opioid analgesics prescribed for NTDCs remained fairly stable from 2007 through 2010. Prescription of opioids was highest among patients aged 19-33 years (56.8%), self-paying (57.1%), and non-Hispanic Whites (53.2%). The probability of being prescribed hydrocodone was highest among uninsured patients (68.7%) and for oxycodone, it was highest among private insurance patients (33.6%). Compared to 34-52 year olds, children 0-4 years were significantly more likely to be prescribed codeine and less likely to be prescribed oxycodone. Compared to non-Hispanic Whites, non-Hispanic Blacks had significantly higher odds of been prescribed codeine and somewhat lower odds of been prescribed oxycodone, but it was not statistically significant. There was no significant change in the rates of opioid analgesics prescribed over time for NTDC visits to EDs. Age, payer type and race/ethnicity were significant predictors for the prescription of different opioid analgesics by emergency physicians for NTDC visits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Impact of a Mandatory Prescription Drug Monitoring Program on Prescription of Opioid Analgesics by Dentists

    OpenAIRE

    Rasubala, Linda; Pernapati, Lavanya; Velasquez, Ximena; Burk, James; Ren, Yan-Fang

    2015-01-01

    Prescription Drug Monitoring Programs (PDMP) are statewide databases that collect data on prescription of controlled substances. New York State mandates prescribers to consult the PDMP registry before prescribing a controlled substance such as opioid analgesics. The effect of mandatory PDMP on opioid drug prescriptions by dentists is not known. This study investigates the impact of mandatory PDMP on frequency and quantity of opioid prescriptions by dentists in a dental urgent care center. Bas...

  12. Evaluation of Analgesic Activity of Papaver libanoticum Extract in Mice: Involvement of Opioids Receptors

    Directory of Open Access Journals (Sweden)

    Mohamad Ali Hijazi

    2017-01-01

    Full Text Available Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.

  13. How resistant to tampering are codeine containing analgesics on the market? Assessing the potential for opioid extraction

    OpenAIRE

    Kimergård, Andreas; Deluca, Paolo; Hindersson, Peter; Breindahl, Torben

    2016-01-01

    IntroductionMisuse of opioid analgesics, in combination with diversion, dependence, and fatal overdoses, presents a serious problem for public health, which affects many countries worldwide. Within this context, tampering with opioids has been associated with serious harm. The aim of the present study was to assess the tampering potential of codeine combination analgesics on the market (containing codeine/non-opioid analgesics) by the extraction of codeine.MethodsCodeine was extracted from th...

  14. Recent advances in the development of 14-alkoxy substituted morphinans as potent and safer opioid analgesics.

    Science.gov (United States)

    Spetea, M; Schmidhammer, H

    2012-01-01

    Morphine and other opioid morphinans produce analgesia primarily through μ opioid receptors (MORs), which mediate beneficial but also non-beneficial actions. There is a continued search for efficacious opioid analgesics with reduced complications. The cornerstone in the development of 14-alkoxymorphinans as novel analgesic drugs was the synthesis of the highly potent MOR agonist 14-O-methyloxymorphone. This opioid showed high antinociceptive potency but also the adverse effects associated with morphine type compounds. Further developments represent the introduction of a methyl and benzyl group at position 5 of 14-O-methyloxymorphone leading to the strong opioid analgesics 14-methoxymetopon and its 5-benzyl analogue, which exhibited less pronounced side effects than morphine although interacting selectively with MORs. Introduction of arylalkyl substituents such as phenylpropoxy in position 14 led to a series of extremely potent antinociceptive agents with enhanced affinities at all three opioid receptor types. During the past years, medicinal chemistry and opioid research focused increasingly on exploring the therapeutic potential of peripheral opioid receptors by peripheralization of opioids in order to minimize the occurrence of centrally-mediated side effects. Strategies to reduce penetration to the central nervous system (CNS) include chemical modifications that increase hydrophilicity. Zwitterionic 6-amino acid conjugates of 14-Oalkyloxymorphones were developed in an effort to obtain opioid agonists that have limited access to the CNS. These compounds show high antinociceptive potency by interacting with peripheral MORs. Opioid drugs with peripheral site of action represent an important target for the treatment of severe and chronic pain without the adverse actions of centrally acting opioids.

  15. "Weak" opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine.

    Science.gov (United States)

    2016-02-01

    So-called weak opioid analgesics are often used to treat severe pain, or when paracetamol or a nonsteroidal anti-inflammatory drug (NSAID) proves inadequate. But are weak opioids any more effective than paracetamol or NSAIDs on nociceptive pain, and are they better tolerated than morphine? To answer these questions, we conducted a review of literature using the standard Prescrire methodology. The potency of codeine and tramadol is strongly influenced by the cytochrome P450 isoenzyme CYP2D6 genotype, which varies widely from one person to another. This explains reports of overdosing or underdosing after administration of standard doses of the two drugs. The potency of morphine and that of buprenorphine, an opioid receptor agonist-antagonist, appears to be independent of CYP2D6 activity. All "weak" opioids can have the same dose-dependent adverse effects as morphine. There is no evidence that, at equivalent analgesic efficacy, weak opioids carry a lower risk of addiction than low-dose morphine. Respiratory depression can occur in ultrarapid metabolisers after brief exposure to standard doses of codeine or tramadol. Similar cases have been reported with dihydrocodeine in patients with renal failure. In addition, tramadol can cause a serotonin syndrome, hypoglycaemia, hyponatraemia and seizures. Several trials have compared different weak opioids in patients with post-operative pain. A single dose of a weak opioid, possibly combined with paracetamol, has greater analgesic efficacy than paracetamol alone but is not more effective than an NSAID alone. There is a dearth of evidence on weak opioids in patients with chronic pain. Available trials fail to show that a weak opioid has markedly superior analgesic efficacy to paracetamol or an NSAID. Sublingual buprenorphine at analgesic doses appears less likely to cause respiratory depression, but it seems to have weak analgesic efficacy. In practice, when opioid therapy is needed, there is no evidence that codeine

  16. Impact of a Mandatory Prescription Drug Monitoring Program on Prescription of Opioid Analgesics by Dentists.

    Directory of Open Access Journals (Sweden)

    Linda Rasubala

    Full Text Available Prescription Drug Monitoring Programs (PDMP are statewide databases that collect data on prescription of controlled substances. New York State mandates prescribers to consult the PDMP registry before prescribing a controlled substance such as opioid analgesics. The effect of mandatory PDMP on opioid drug prescriptions by dentists is not known. This study investigates the impact of mandatory PDMP on frequency and quantity of opioid prescriptions by dentists in a dental urgent care center. Based on the sample size estimate, we collected patient records of a 3-month period before and two consecutive 3-month periods after the mandatory PDMP implementation and analyzed the data on number of visits, treatment types and drug prescriptions using Chi-square tests. For patients who were prescribed pain medications, 452 (30.6%, 190 (14.1%, and 140 (9.6% received opioid analgesics in the three study periods respectively, signifying a statistically significant reduction in the number of opioid prescriptions after implementation of the mandatory PDMP (p<0.05. Total numbers of prescribed opioid pills in a 3-month period decreased from 5096 to 1120, signifying a 78% reduction in absolute quantity. Prescriptions for non-opioid analgesics acetaminophen increased during the same periods (p<0.05. We conclude that the mandatory PDMP significantly affected the prescription pattern for pain medications by dentists. Such change in prescription pattern represents a shift towards the evidence-based prescription practices for acute postoperative pain.

  17. Opioid Analgesic Prescribing Practices of Dental Professionals in the United States.

    Science.gov (United States)

    Steinmetz, C N; Zheng, C; Okunseri, E; Szabo, A; Okunseri, C

    2017-07-01

    The prescription of opioid analgesics by dental professionals is widespread in the United States. Policy makers, government agencies, and professional organizations consider this phenomenon a growing public health concern. This study examined trends in the prescription of opioid analgesics for adults by dental professionals and associated factors in the United States. Data from the Medical Expenditure Panel Survey (1996-2013) were analyzed. Descriptive statistics were calculated separately for each year. Logistic regression analyses were conducted to estimate the overall trend during the period with and without adjusting for dental procedures and personal characteristics. Survey weights were incorporated to handle the sampling design. The prescription of opioid analgesics following dental care increased over time. After adjusting for sociodemographic factors, source of payment, and type of dental procedure, the odds ratio (OR) of prescribing opioid analgesics following a dental visit per each decade difference was 1.28 (95% confidence interval [CI], 1.19-1.38). Surgical, root canal, and implant procedures had the highest rates of opioid prescriptions and the greatest increases in rates over the study period. After adjusting for personal characteristics and type of dental procedure, the OR of receiving a prescription for opioids comparing blacks, Asians, and Hispanics to whites was 1.29 (95% CI, 1.17-1.41), 0.57 (95% CI, 0.47-0.70), and 0.84 (95% CI, 0.75-0.95), respectively. Opioid analgesic prescriptions following dental visits increased over time after adjusting for personal characteristics and type of dental procedure. The odds of receiving a prescription for opioids were higher for certain racial/ethnic minority groups. Knowledge Transfer Statement: This study highlights dental professionals prescribing practices of opioid analgesics by following dental treatments in the United States. With this knowledge, appropriate guidelines, protocols, and policies can be

  18. "Safe and effective when used as directed": the case of chronic use of opioid analgesics.

    Science.gov (United States)

    Ballantyne, Jane C

    2012-12-01

    Opioid analgesics have been used increasingly over the past 20 years for the management of chronic non-cancer pain in the USA under the assumption that they were safe and effective when used as directed. The accuracy of that assumption has not been tested against accumulated evidence. The safety of opioids used on a long-term basis has not been tested in clinical trials. Epidemiologic evidence from examinations of such use in the general population indicates that the risk of overdose increases in a dose-response manner. Such evidence also suggests increased risk of fractures and acute myocardial infarctions among elderly users of opioids for chronic pain. Experimental evidence supports short-term use of opioids, but trials of long-term use for chronic pain have not been conducted. Epidemiologic evidence suggests that long-term use does not result in improvement in function or quality of life while being associated with significant dropout rates and a high prevalence of adverse drug effects. Substantial fractions of patients are not using opioid analgesics as directed, while millions of US residents are using them without a prescription for nonmedical reasons. A prudent treatment approach consistent with the available evidence would be to reserve chronic opioid therapy for serious pain-related problems for which the effectiveness of opioids has been demonstrated and for patients whose use as directed is assured through close monitoring and for whom an explicit, informed calculation has been made that the benefits of opioids outweigh the risks.

  19. Prescription of opioid and nonopioid analgesics for dental care in emergency departments: Findings from the National Hospital Ambulatory Medical Care Survey.

    Science.gov (United States)

    Okunseri, Christopher; Okunseri, Elaye; Xiang, Qun; Thorpe, Joshua M; Szabo, Aniko

    2014-01-01

    The aim of this study was to examine trends and associated factors in the prescription of opioid analgesics, nonopioid analgesics, opioid and nonopioid analgesic combinations, and no analgesics by emergency physicians for nontraumatic dental condition (NTDC)-related visits. Our secondary aim was to investigate whether race/ethnicity is a possible predictor of receiving a prescription for either type of medication for NTDC visits in emergency departments (EDs) after adjustment for potential covariates. We analyzed data from the National Hospital Ambulatory Medical Care Survey for 1997-2000 and 2003-2007, and used multinomial multivariate logistic regression to estimate the probability of receiving a prescription for opioid analgesics, nonopioid analgesics, or a combination of both, compared with receiving no analgesics for NTDC-related visits. During 1997-2000 and 2003-2007, prescription of opioid analgesics and combinations of opioid and nonopioid analgesics increased, and that of no analgesics decreased over time. The prescription rates for opioid analgesics, nonopioid analgesics, opioid and nonopioid analgesic combinations, and no analgesics for NTDC-related visits in EDs were 43 percent, 20 percent, 12 percent, and 25 percent, respectively. Majority of patients categorized as having severe pain received prescriptions for opioids for NTDC-related visits in EDs. After adjusting for covariates, patients with self-reported dental reasons for visit and severe pain had a significantly higher probability of receiving prescriptions for opioid analgesics and opioid and nonopioid analgesic combinations. Prescription of opioid analgesics increased over time. ED physicians were more likely to prescribe opioid analgesics and opioid and nonopioid analgesic combinations for NTDC-related visits with reported severe pain. © 2014 American Association of Public Health Dentistry.

  20. Bilateral Breast Reduction Without Opioid Analgesics: A Comparative Study.

    Science.gov (United States)

    Parsa, Fereydoun Don; Cheng, Justin; Stephan, Brad; Castel, Nikki; Kim, Leslie; Murariu, Daniel; Parsa, Alan A

    2017-09-01

    Breast reduction has traditionally been performed under general anesthesia with adjunct opioid use. However, opioids are associated with a wide variety of adverse effects, including nausea, vomiting, constipation, postoperative sedation, dizziness, and addiction. This study compares bilateral breast reduction using a multimodal opioid-free pain management regimen vs traditional general anesthesia with adjunct opioids. A total of 83 female patients were enrolled in this study. Group 1 includes a retrospective series of 39 patients that underwent breast reduction via general anesthesia with adjunct opioid use. This series was compared to 2 prospective groups of patients who did not receive opioids either preoperatively or intraoperatively. In group 2, twenty-six patients underwent surgery under intravenous sedation and local anesthesia. In group 3, eighteen patients underwent surgery with general anesthesia. All patients in groups 2 and 3 received preoperative gabapentin and celecoxib along with infiltration of local anesthetics during the operation and prior to discharge to the Post-Anesthesia Care Unit (PACU). Primary outcome measures included the duration of surgery, time from end of operation to discharge home, postoperative opioid and antiemetic use, and unplanned postoperative hospitalizations. When compared to group 1, groups 2 and 3 experienced a shorter time from end of operation to discharge home (P opioid use (P opioid-free bilateral breast reduction either under local or general anesthesia as an outpatient. This method resulted in significantly less morbidity, use of opioids postoperatively, as well as unplanned hospital admissions compared to "traditional" breast reduction under general anesthesia with the use of opioids. 3. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  1. Impact of a Mandatory Prescription Drug Monitoring Program on Prescription of Opioid Analgesics by Dentists.

    Science.gov (United States)

    Rasubala, Linda; Pernapati, Lavanya; Velasquez, Ximena; Burk, James; Ren, Yan-Fang

    2015-01-01

    Prescription Drug Monitoring Programs (PDMP) are statewide databases that collect data on prescription of controlled substances. New York State mandates prescribers to consult the PDMP registry before prescribing a controlled substance such as opioid analgesics. The effect of mandatory PDMP on opioid drug prescriptions by dentists is not known. This study investigates the impact of mandatory PDMP on frequency and quantity of opioid prescriptions by dentists in a dental urgent care center. Based on the sample size estimate, we collected patient records of a 3-month period before and two consecutive 3-month periods after the mandatory PDMP implementation and analyzed the data on number of visits, treatment types and drug prescriptions using Chi-square tests. For patients who were prescribed pain medications, 452 (30.6%), 190 (14.1%), and 140 (9.6%) received opioid analgesics in the three study periods respectively, signifying a statistically significant reduction in the number of opioid prescriptions after implementation of the mandatory PDMP (pPrescriptions for non-opioid analgesics acetaminophen increased during the same periods (pprescription pattern for pain medications by dentists. Such change in prescription pattern represents a shift towards the evidence-based prescription practices for acute postoperative pain.

  2. Parenteral Opioid Analgesics Utilization Pattern in Amir-al-Momenin Hospital, Zabol-IRAN

    Directory of Open Access Journals (Sweden)

    Hossein Vatanpour

    2016-08-01

    Full Text Available Opioids are the most available medicines to get rid of any general severe pain and avoiding of any deleterious sequential that can worsen patient outcomes. Rational prescription of opioid analgesics with respect to the possibility of abuse is a big concern in the medical care costs. Zabol, where is located in eastern part of Iran and has common border with Afghanistanhas the most opioid traffic in the region. In this study the rational prescription of parenteral opioid in Amir-al-Momenin general hospital was investigated. A retrospective drug utilization review was performed on 509 in-patients who received parenteral opioids including Morphine, Pethidin, Pentazocin, Fentanyl, Alfentanil, Sufentanil and Methadone from March 21sttoSeptember 23rd, 2011. Multivariate conditional regression modeling was used to determine independent predictors for daily parenteral opioid consumption. Total daily parenteral opioid consumption was 38.63 DDDs/100bed-days for Morphine, Pethidine and Pentazocin and 84564.78 PFEQs/100bed-days for Fentanyl, Alfentanil and Sufentanil and 766 mg for Methadone. Pethidine was the most frequently prescribed parenteral opioid. Most patients who were prescribed by the intramuscular routes, ordered PRN. Daily parenteral opioid consumption was the highest in the emergency ward whereas it was considered as the lowest in the intensive care unit[ICU]. According to our findings, total daily parenteral opioid consumption was almost high in Amir-al-Momenin Hospital. Unlike to some relevant factors that can effect on the consumption of analgesic opioids like gender, age, drug-drug interaction and etc, we found no rational prescription and consumption in the mentioned hospital.

  3. Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics.

    Science.gov (United States)

    Trang, Tuan; Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W; Gutstein, Howard; Cahill, Catherine M

    2015-10-14

    Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. Copyright © 2015 the authors 0270-6474/15/3513879-10$15.00/0.

  4. Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics

    Science.gov (United States)

    Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard

    2015-01-01

    Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188

  5. Individual variability in clinical effect and tolerability of opioid analgesics - Importance of drug interactions and pharmacogenetics.

    Science.gov (United States)

    Solhaug, Vigdis; Molden, Espen

    2017-10-01

    As pain is often a comorbid condition, many patients use opioid analgesics in combination with several other drugs. This implies a generally increased risk of drug interactions, which along with inherent pharmacogenetic variability and other factors may cause differences in therapeutic response of opioids. To provide an overview of interactions and pharmacogenetic variability of relevance for individual differences in effect and tolerability of opioid analgesics, which physicians and other healthcare professionals should be aware of in clinical practice. The article was based on unsystematic searches in PubMed to identify literature highlighting the clinical impact of drug interactions and pharmacogenetics as sources of variable response of opioid analgesics. Cytochrome P450 (CYP)-mediated metabolism is an important process for both clinically relevant interactions and pharmacogenetic variability of several opioids. Concomitant use of CYP inhibitors (e.g. paroxetine, fluoxetine and bupropion) or inducers (e.g. carbamazepine, phenobarbital and phenytoin) could counteract the clinical effect or trigger side effects of analgesics in the same manner as genetically determined differences in CYP2D6-mediated metabolism of many opioids. Moreover, combination treatment with drugs that inhibit or induce P-glycoprotein (ABCB1), a blood-brain barrier efflux transporter, may alter the amount ('dose') of opioids distributed to the brain. At the pharmacodynamic level, it is crucial to be aware of the potential risk of interaction causing serotonergic syndrome when combining opioids and serotonergic drugs, in particular antidepressants inhibiting serotonin reuptake (SSRIs and SNRIs). Regarding pharmacogenetics at the receptor level of pain treatment, the knowledge is currently scarce, but an allelic variant of the μ1 opioid receptor (OPRM1) gene has been associated with higher dosage requirement to achieve analgesia. Drug interactions and pharmacogenetic differences may lead to

  6. Why patients are afraid of opioid analgesics: a study on opioid perception in patients with chronic pain.

    Science.gov (United States)

    Graczyk, Michał; Borkowska, Alina; Krajnik, Małgorzata

    2018-02-28

    INTRODUCTION    Opiophobia is deemed one of the key barriers in effective pain management. OBJECTIVES    The study aimed to assess the overall perception of opioids in cancer patients treated for chronic pain, as well as to determine the nature of their most common related fears. PATIENTS AND METHODS     The study included 100 palliative care patients who suffered from chronic cancer or noncancer pain. Initially, they had to complete a survey exploring their knowledge on analgesics and potential fear of using opioids. The second phase was based on in‑depth interviews with 10 palliative care patients suffering from cancer pain who were reluctant to use opioids. RESULTS     Of the 100 patients, 43 expressed concerns over commencing the treatment with opioids. Fear was reported more often in patients already on strong opioids, who either overtly expressed it (group C) or not (group B), as compared with patients treated with weak opioids (group A) (50%, 48%, and 19% of groups C, B, and A, respectively). The main concerns were drug addiction, fear of death or dying, and undesirable side effects. A qualitative study revealed similar types of fear among patients expressing concerns prior to being put on strong opioids. CONCLUSIONS    Opiophobia seems to be common among palliative care patients (up to 50%) treated with strong opioids. They mainly fear drug addiction, undesirable effects, and death or dying. Better awareness of patients' preconceptions about opioids may become instrumental to alleviating their suffering through enhanced pain management.

  7. High-Risk Prescribing to Medicaid Enrollees Receiving Opioid Analgesics: Individual- and County-Level Factors.

    Science.gov (United States)

    Heins, Sara E; Sorbero, Mark J; Jones, Christopher M; Dick, Andrew W; Stein, Bradley D

    2018-01-05

    Prescription opioid overdoses have increased dramatically in recent years, with the highest rates among Medicaid enrollees. High-risk prescribing includes practices associated with overdoses and a range of additional opioid-related problems. To identify individual- and county-level factors associated with high-risk prescribing among Medicaid enrollees receiving opioids. In a four-states, cross-sectional claims data study, Medicaid enrollees 18-64 years old with a new opioid analgesic treatment episode 2007-2009 were identified. Multivariate regression analyses were conducted to identify factors associated with high-risk prescribing, defined as high-dose opioid prescribing (morphine equivalent daily dose ≥100 mg for >6 days), opioid overlap, opioid-benzodiazepine overlap. High-risk prescribing occurred in 39.4% of episodes. Older age, rural county of residence, white race, and major depression diagnosis were associated with higher rates of all types of high-risk prescribing. Individuals with prior opioid, alcohol, and hypnotic/sedative use disorder diagnoses had lower odds of high-dose opioid prescribing but higher odds of opioid overlap and opioid-benzodiazepine overlap than individuals without such disorders. High-dose opioid prescribing in Massachusetts was less common than in California, Illinois, and New York, whereas the rate of benzodiazepine overlap in Massachusetts was more common than in other states. Conclusions/Importance: High-risk prescribing was common and associated with several important demographic, clinical, and community factors. Findings can be used to inform targeted interventions designed to reduce such prescribing, and given state variation observed, further research is needed to better understand the effects of state policies on high-risk prescribing.

  8. Impulsivity but not sensation seeking is associated with opioid analgesic misuse risk in patients with chronic pain.

    Science.gov (United States)

    Marino, Elise N; Rosen, Kristen D; Gutierrez, Antonio; Eckmann, Maxim; Ramamurthy, Somayaji; Potter, Jennifer Sharpe

    2013-05-01

    Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problematic opioid analgesic use. Impulsivity was assessed using the BIS, sensation seeking was measured using the SSS, and opioid analgesic misuse risk was assessed using the Current Opioid Misuse Measure (COMM). Significant bivariate associations were found between the COMM and the following predictor variables: age and the three BIS subscales: Attentional Impulsiveness, Non-planning Impulsiveness, and Motor Impulsiveness. Using a multivariate linear regression, after controlling for age, the BIS subscales accounted for 29.0% of the variance in the COMM. Attentional Impulsiveness was the only significant BIS subscale. These results suggest a potential relationship between impulsivity, but not sensation seeking, and risk for opioid analgesic misuse. Impulsivity is not a prominent trait observed in chronic pain patients; however, it may be an important risk factor for opioid analgesic misuse for a subset of individuals with chronic pain. As such, these findings suggest that additional exploration of this potential risk factor is warranted. Published by Elsevier Ltd.

  9. Increases in the Use of Prescription Opioid Analgesics and the Lack of Improvement in Disability Metrics Among Users

    Science.gov (United States)

    Sites, Brian D.; Beach, Michael L.; Davis, Matthew

    2014-01-01

    Background and Objectives In the United States, use of oral opioid analgesics has been associated with increasing rates of addiction, abuse, and diversion. However, little is known about recent national use of non-illicit prescription opioid analgesics (those prescribed in a doctor-patient relationship), the primary source of these drugs for the general US population. Our primary objective was to examine trends in the use of prescription opioid analgesics in the United States and to identify defining characteristics of patient users of prescribed opioids from 2000 to 2010. Methods We used the nationally representative Medical Expenditure Panel Survey to examine trends in prescription oral opioid analgesic use from 2000 to 2010. We used survey design methods to make national estimates of adults (18 years and older) who reported receiving an opioid analgesic prescription (referred to as opioid users) and used logistic regression to examine predictors of opioid analgesic use. Our primary outcome measures were national estimates of total users of prescription opioid analgesics and total number of prescriptions. Our secondary outcome was that of observing changes in the disability and health of the users. Results The estimated total number of opioid analgesic prescriptions in the United States increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an estimated 7.4% (95% CI, 6.9–7.9) of adult Americans were prescription opioid users compared with 11.8% (95% CI, 11.2–12.4) in 2010. Based on estimates adjusted for changes in the general population, each year was associated with a 6% increase in the likelihood of receiving an opioid prescription from 2000 to 2010. Despite the apparent increase in use, there were no demonstrable improvements in the age- or sex-adjusted disability and health status measures of opioid users. Conclusions The use of prescription opioid analgesics among adult Americans has increased in recent years, and this increase

  10. PTI-609: a novel analgesic that binds filamin A to control opioid signaling.

    Science.gov (United States)

    Burns, Lindsay H; Wang, Hoau-Yan

    2010-11-01

    Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors (MORs) so that their activation should not result in the opioid tolerance, dependence and addiction associated with current opioid painkillers. Additionally, we show that compounds that bind this site on filamin A reduce release of inflammatory cytokines. PTI-609 is a new chemical entity that binds filamin A with picomolar affinity and also activates opioid receptors via a novel binding domain. PTI-609 and analogs have similar analgesic efficacy to morphine by oral administration in mice, provide some anti-inflammatory activity in the rat collagen-induced arthritis model, and show no conditioned place preference at analgesic doses, suggesting no potential for abuse and addiction. PTI-609 was designed after discovering filamin A as the high-affinity target of naltrexone or naloxone. Combined with opiates, ultra-low-dose naloxone or naltrexone can enhance and prolong the analgesia of the opiate alone and prevent or attenuate opioid tolerance, dependence and addictive properties. We will review here the mechanism of action of ultra-low-dose naltrexone and naloxone, the discovery of filamin A as their high-affinity target, and the rationale as to why the current, dualfunction new chemical entity should not only be easier to develop but also more consistently efficacious than opioids combined with ultra-low-dose naltrexone. This new class of compounds, as well as the concept, screening assay and pharmacophore model, are covered in a family of recent patent applications.

  11. Psychological and drug abuse symptoms associated with nonmedical use of opioid analgesics among adolescents.

    Science.gov (United States)

    Boyd, Carol J; Young, Amy; McCabe, Sean E

    2014-01-01

    Approximately 18% of US adolescents engaged in prescription opioid abuse in 2013. However, this estimate may be misleading because it includes both medical misusers and nonmedical users, and there is evidence that these are 2 groups that differ relative to substance abuse and criminal risk. Thus, this study does not combine medical and nonmedical users; rather, it seeks to better understand the characteristics of nonmedical users. This was a school-based, cross-sectional study that was conducted during 2009-2010 in southeastern Michigan with a sample of 2627 adolescents using a Web-based survey. Three mutually exclusive groups were created based on responses regarding medical and nonmedical use of opioid analgesics. Group 1 had never used an opioid analgesic, Group 2 used an opioid analgesic only as prescribed, and Group 3 nonmedically used an opioid analgesic. In addition, Group 3 was divided into 2 mutually exclusive subgroups (self-treaters and sensation-seekers) based on reasons for nonmedical use. A series of multinomial logistic regressions were conducted to determine if the groups differed on the presence of pain, psychological symptoms (e.g., affective disorder, conduct disorder, attention-deficit/hyperactivity disorder [ADHD]), and drug abuse. Sixty-five percent (65.0%) of the sample was white/Caucasian and 29.5% was African American. The average age was 14.8 years (SD = 1.9). Seventy percent (70.4%; n = 1850) reported no lifetime opioid use, 24.5% (n = 644) were medical users, 3.5% (n = 92) were nonmedical users who used for pain relief only, and 1.6% (n = 41) were classified as nonmedical users for reasons other than for pain relief (e.g., to get high). Both medical users and nonmedical users reported more pain and substance abuse symptoms compared with never users. Those nonmedical users who used opioids for sensation-seeking motivations had greater odds of having psychological symptoms. These data support the need to further consider subgroups of

  12. Possible analgesic and anti-inflammatory interactions of aspartame with opioids and NSAIDs.

    Science.gov (United States)

    Sharma, Sameer; Jain, N K; Kulkarni, S K

    2005-06-01

    The purpose of the present study was to investigate analgesic and anti-inflammatory properties of aspartame, an artificial sweetner and its combination with various opioids and NSAIDs for a possible synergistic response. The oral administration of aspartame (2-16mg/kg, po) significantly increased the pain threshold against acetic acid-induced writhes in mice. Co-administration of aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po) significantly reduced acetic acid-induced writhes as compared to effects per se of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1 mg/kg, po) was co-administered with aspartame it reduced the number of writhes as compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly decreased carrageenan-induced increase in paw volume and also reversed the hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po). The study indicated that aspartame exerted analgesic and anti-inflammatory effects on its own and have a synergistic analgesic response with conventional analgesics of opioid and non-opioid type, respectively.

  13. Access to Strong Opioid Analgesics in the Context of Legal and Regulatory Barriers in Eleven Central and Eastern European Countries.

    Science.gov (United States)

    Vranken, Marjolein J M; Mantel-Teeuwisse, Aukje K; Schutjens, Marie-Hélène D B; Scholten, Willem K; Jünger, Saskia; Medic, Dr Rer; Leufkens, Hubert G M

    2018-04-06

    In 2011-2013, >95% of the global opioid analgesics consumption occurred in three regions, accounting for 15% of the world population. Despite abundant literature on barriers to access, little is known on the correlation between actual access to opioid analgesics and barriers to access, including legal and regulatory barriers. This study aimed to evaluate the correlation between access to strong opioid analgesics and barriers to access in national legislation and regulations in 11 central and eastern European countries that participated in the Access to Opioid Medication in Europe (ATOME) project. Two variables were contrasted to assess their correlation: the country level of access to strong opioid analgesics indicated by the Adequacy of Consumption Measure (ACM) and the number of potential legal and regulatory barriers identified by an external review of legislation and regulations. A linear correlation was evaluated using a squared linear correlation coefficient. Evaluation of the correlation between the ACM and the number of potential barriers produces an R 2 value of 0.023 and a correlation plot trend line gradient of -0.075, indicating no correlation between access to strong opioid analgesics and the number of potential barriers in national legislation and regulations in the countries studied. No correlation was found, which indicates that other factors besides potential legal and regulatory barriers play a critical role in withholding prescribers and patients essential pain medication in the studied countries. More research is needed toward better understanding of the complex interplay of factors that determine access to strong opioid analgesics.

  14. Comparison of two combinations of opioid and non-opioid analgesics for acute periradicular abscess: a randomized clinical trial.

    Science.gov (United States)

    Santini, Manuela Favarin; Rosa, Ricardo Abreu da; Ferreira, Maria Beatriz Cardoso; Fischer, Maria Isabel; Souza, Erick Miranda; Só, Marcus Vinícius Reis

    2017-01-01

    Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg) plus acetaminophen (500 mg), every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg) plus acetaminophen (500 mg) on the same schedule. Two factors were evaluated: (1) pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2) the occurrence of adverse effects. In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P0.05), i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.

  15. Use of opioid analgesics in the treatment of cancer pain

    DEFF Research Database (Denmark)

    Caraceni, Augusto; Hanks, Geoffrey; Kaasa, Stein

    2012-01-01

    Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared...... with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology...

  16. Caffeine as an opioid analgesic adjuvant in fibromyalgia

    OpenAIRE

    Scott JR; Hassett AL; Brummett CM; Harris RE; Clauw DJ; Harte SE

    2017-01-01

    J Ryan Scott,1 Afton L Hassett,1 Chad M Brummett,1 Richard E Harris,1,2 Daniel J Clauw,1,2 Steven E Harte1,2 1Chronic Pain and Fatigue Research Center, Department of Anesthesiology, 2Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA Background: Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored ca­ffeine&a...

  17. Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

    Science.gov (United States)

    Mora, Andrea L; Salazar, Miguel; Pablo-Caeiro, Juan; Frost, Craig P; Yadav, Yashoo; DuPont, Herbert L; Garey, Kevin W

    2012-04-01

    Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P opioid analgesics were associated with an increased risk of CDI.

  18. Key Data Gaps Regarding the Public Health Issues Associated with Opioid Analgesics

    Science.gov (United States)

    Schmidt, Teresa D.; Haddox, J. David; Nielsen, Alexandra E.; Wakeland, Wayne; Fitzgerald, John

    2014-01-01

    Most pharmaceutical opioids are used to treat pain and they have been demonstrated to be effective medications for many. Their abuse and misuse pose significant public health concerns in the United States. Research has provided much insight into the prevalence, scope, and drivers of opioid abuse, but a holistic understanding is limited by a lack of available data regarding key aspects of this public health problem. Twelve data gaps were revealed during the creation of a systems-level computer model of medical use, diversion, nonmedical use, and the adverse outcomes associated with opioid analgesics in the United States. Data specific to these gaps would enhance the validity and real-world applications of systems-level models of this public health problem, and would increase understanding of the complex system in which use and abuse occur. This paper provides an overview of these gaps, argues for the importance of closing them, and provides specific recommendations for future data collection efforts. PMID:24554390

  19. The Utilization of Opioid Analgesics Following Common Upper Extremity Surgical Procedures: A National, Population-Based Study

    Science.gov (United States)

    Waljee, Jennifer F.; Zhong, Lin; Hou, Hechuan; Sears, Erika; Brummet, Chad; Chung, Kevin C.

    2016-01-01

    Background The misuse of opioid analgesics is a major public health concern, and guidelines regarding postoperative opioid use are sparse. We examined the use of opioids following outpatient upper extremity procedures. We hypothesized that opioid use varies widely by procedure and patient factors. Methods We studied opioid prescriptions among 296,452 adults ages ≥ 18 years who underwent carpal tunnel release, trigger finger release, cubital tunnel release, and thumb carpometacarpal (CMC) arthroplasty from 2009 to 2013. We analyzed insurance claims drawn using Truven Health MarketScan Commercial Claims and Encounters, which encompasses over 100 health plans in the United States. Using multivariable regression, we compared the receipt of opioids, number of days supplied, indicators of inappropriate prescriptions, and number of refills by patient factors. Results In this cohort, 59% filled a postoperative prescription for opioid medication, and 8.8% patients had an indicator of inappropriate prescribing. The probability of filling an opioid prescription declined linearly with advancing age. In multivariate analysis, patients who had previously received opioids were more likely to fill a postoperative opioid prescription (66% vs. 59%), receive longer prescriptions (24 vs. 5 days), receive refills following surgery (24% vs. 5%), and have at least one indicator of potentially inappropriate prescribing (19% vs 6%). Conclusions Current opioid users are more likely to require postoperative opioid analgesics for routine procedures, and more likely to receive inappropriate prescriptions. More evidence is needed to identify patients who derive the greatest benefit from opioids in order to curb opioids prescriptions when alternative analgesics may be equally effective and available. PMID:26818326

  20. Reducing the default dispense quantity for new opioid analgesic prescriptions: study protocol for a cluster randomised controlled trial.

    Science.gov (United States)

    Bachhuber, Marcus A; Nash, Denis; Southern, William N; Heo, Moonseong; Berger, Matthew; Schepis, Mark; Cunningham, Chinazo O

    2018-04-20

    As opioid analgesic consumption has grown, so have opioid use disorder and opioid-related overdoses. Reducing the quantity of opioid analgesics prescribed for acute non-cancer pain can potentially reduce risks to the individual receiving the prescription and to others who might unintentionally or intentionally consume any leftover tablets. Reducing the default dispense quantity for new opioid analgesic prescriptions in the electronic health record (EHR) is a promising intervention to reduce prescribing. This study is a prospective cluster randomised controlled trial with two parallel arms. Primary care sites (n=32) and emergency departments (n=4) will be randomised in matched pairs to either a modification of the EHR so that new opioid analgesic prescriptions default to a dispense quantity of 10 tablets (intervention) or to no EHR change (control). The dispense quantity will remain fully modifiable by providers in both arms. From 6 months preintervention to 18 months postintervention, patient-level data will be analysed (ie, the patient is the unit of inference). Patient eligibility criteria are: (A) received a new opioid analgesic prescription, defined as no other opioid analgesic prescription in the prior 6 months; (B) age ≥18 years; and (C) no cancer diagnosis within 1 year prior to the new opioid analgesic prescription. The primary outcome will be the quantity of opioid analgesics prescribed in the initial prescription. Secondary outcomes will include opioid analgesic reorders and health service utilisation within 30 days after the initial prescription. Outcomes will be compared between study arms using a difference-in-differences analysis. This study has been approved by the Montefiore Medical Center/Albert Einstein College of Medicine Institutional Review Board with a waiver of informed consent (2016-6036) and is registered on ClinicalTrials.gov (NCT03003832, 6 December 2016). Findings will be disseminated through publication, conferences and meetings

  1. Use of opioids and other analgesics by older adults in the United States, 1999-2010.

    Science.gov (United States)

    Steinman, Michael A; Komaiko, Kiya D R; Fung, Kathy Z; Ritchie, Christine S

    2015-02-01

    There has been concern over rising use of prescription opioids in young and middle-aged adults. Much less is known about opioid prescribing in older adults, for whom clinical recommendations and the balance of risks and benefits differ from younger adults. We evaluated changes in use of opioids and other analgesics in a national sample of clinic visits made by older adults between 1999 and 2010. Observational study of adults aged 65 and older from the 1999-2010 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, serial cross-sectional surveys of outpatient visits in the United States. Medication use was assessed at each study visit and included medications in use prior to the visit and medications newly prescribed at the visit. Results were adjusted for survey weights and design factors to provide nationally representative estimates. Mean age was 75 ± 7 years, and 45% of visits occurred in primary care settings. Between 1999-2000 and 2009-2010, the percent of clinic visits at which an opioid was used rose from 4.1% to 9.0% (P opioid classes increased, the largest contributor to increased use was hydrocodone-containing combination opioids, which rose from 1.1% to 3.5% of visits over the study period (P opioid use was observed across a wide range of patient and clinic characteristics, including in visits for musculoskeletal problems (10.7% of visits in 1999-2000 to 17.0% in 2009-2010, P Opioid use by older adults visiting clinics more than doubled between 1999 and 2010, and occurred across a wide range of patient characteristics and clinic settings. Wiley Periodicals, Inc.

  2. Quality Improvement Initiative to Decrease Variability of Emergency Physician Opioid Analgesic Prescribing

    Directory of Open Access Journals (Sweden)

    John H. Burton

    2016-05-01

    Full Text Available Introduction: Addressing pain is a crucial aspect of emergency medicine. Prescription opioids are commonly prescribed for moderate to severe pain in the emergency department (ED; unfortunately, prescribing practices are variable. High variability of opioid prescribing decisions suggests a lack of consensus and an opportunity to improve care. This quality improvement (QI initiative aimed to reduce variability in ED opioid analgesic prescribing. Methods: We evaluated the impact of a three-part QI initiative on ED opioid prescribing by physicians at seven sites. Stage 1: Retrospective baseline period (nine months. Stage 2: Physicians were informed that opioid prescribing information would be prospectively collected and feedback on their prescribing and that of the group would be shared at the end of the stage (three months. Stage 3: After physicians received their individual opioid prescribing data with blinded comparison to the group means (from Stage 2 they were informed that individual prescribing data would be unblinded and shared with the group after three months. The primary outcome was variability of the standard error of the mean and standard deviation of the opioid prescribing rate (defined as number of patients discharged with an opioid divided by total number of discharges for each provider. Secondary observations included mean quantity of pills per opioid prescription, and overall frequency of opioid prescribing. Results: The study group included 47 physicians with 149,884 ED patient encounters. The variability in prescribing decreased through each stage of the initiative as represented by the distributions for the opioid prescribing rate: Stage 1 mean 20%; Stage 2 mean 13% (46% reduction, p<0.01, and Stage 3 mean 8% (60% reduction, p<0.01. The mean quantity of pills prescribed per prescription was 16 pills in Stage 1, 14 pills in Stage 2 (18% reduction, p<0.01, and 13 pills in Stage 3 (18% reduction, p<0.01. The group mean

  3. The Use of Opioid Analgesics following Common Upper Extremity Surgical Procedures: A National, Population-Based Study.

    Science.gov (United States)

    Waljee, Jennifer F; Zhong, Lin; Hou, Hechuan; Sears, Erika; Brummett, Chad; Chung, Kevin C

    2016-02-01

    The misuse of opioid analgesics is a major public health concern, and guidelines regarding postoperative opioid use are sparse. The authors examined the use of opioids following outpatient upper extremity procedures to discern the variation by procedure type and patient factors. The authors studied opioid prescriptions among 296,452 adults older than 18 years who underwent carpal tunnel release, trigger finger release, cubital tunnel release, or thumb carpometacarpal arthroplasty from 2009 to 2013 using insurance claims drawn from the Truven Health MarketScan Commercial Claims and Encounters, which encompasses over 100 health plans in the United States. Using multivariable regression, the authors compared the receipt of opioids, number of days supplied, indicators of inappropriate prescriptions, and number of refills by patient factors. In this cohort, 59 percent filled a postoperative prescription for opioid medication, and 8.8 percent of patients had an indicator of inappropriate prescribing. The probability of filling an opioid prescription declined linearly with advancing age. On multivariate analysis, patients who had previously received opioids were more likely to fill a postoperative opioid prescription (66 percent versus 59 percent), receive longer prescriptions (24 versus 5 days), receive refills following surgery (24 percent versus 5 percent), and have at least one indicator of potentially inappropriate prescribing (19 percent versus 6 percent). Current opioid users are more likely to require postoperative opioid analgesics for routine procedures and more likely to receive inappropriate prescriptions. More evidence is needed to identify patients who derive the greatest benefit from opioids to curb opioid prescriptions when alternative analgesics may be equally effective and available. Risk, III.

  4. Comparison of two combinations of opioid and non-opioid analgesics for acute periradicular abscess: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Manuela Favarin Santini

    Full Text Available Abstract Acute periradicular abscess is a condition characterized by the formation and propagation of pus in the periapical tissues and generally associated with debilitating pain. Objective: The aim of this study was to compare the overall analgesic effectiveness of two combinations of opioid and non-opioid analgesics for acute periradicular abscess. Material and Methods: This study included 26 patients who sought emergency care in a Brazilian dental school. The patients were randomly divided into two groups: Co/Ac - oral prescription of codeine (30 mg plus acetaminophen (500 mg, every 4 h, for 3 days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg plus acetaminophen (500 mg on the same schedule. Two factors were evaluated: (1 pain scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after treatment, using the Visual Analogue Scale; and (2 the occurrence of adverse effects. Results: In both groups, there was a reduction in pain scores over time. For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48, and 72 hours after treatment (P0.05, i.e., both treatments were effective in controlling pain caused by APA; however, the combination of Tr/Ac caused more adverse reactions as two patients had to stop using the medication. Conclusion: This study suggests that, considering both analgesic efficacy and safety, the combination of codeine and acetaminophen is more effective to control moderate to severe pain from acute periradicular abscesses.

  5. Physician-related barriers to cancer pain management with opioid analgesics

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Sjøgren, Per; Møldrup, Claus

    2007-01-01

    OBJECTIVE: The purpose of this review is to summarize the results of studies on physician-related barriers to cancer pain management with opioid analgesics. METHODS: A literature search was conducted in PUBMED, using a combined text word and MeSH heading search strategy. Those articles whose full...... texts were not available in PUBMED were retrieved from the electronic databases of specific journals. RESULTS: Sixty-five relevant articles, published in the period from 1986 to 2006, were identified. Physicians' barriers to cancer pain management were studied in questionnaire surveys and in the reviews...... of drug prescribing documents. The results of the articles found were analyzed with respect to (a) knowledge, beliefs, concerns, problems endorsed or acknowledged by physicians treating cancer pain, (b) physicians' skills in pain assessment, and (c) adequacy of opioid prescription. CONCLUSIONS...

  6. Polysubstance use and misuse or abuse of prescription opioid analgesics: a multi-level analysis of international data.

    Science.gov (United States)

    Morley, Katherine I; Ferris, Jason A; Winstock, Adam R; Lynskey, Michael T

    2017-06-01

    Increasing mortality and morbidity associated with opioid analgesics has led to concerns about their misuse and abuse, even when obtained through a prescription. These concerns have been most pronounced in the United States, but limited data make it difficult to determine whether it is a problem in other countries. We investigated opioid analgesic misuse and abuse in participants from the Global Drug Survey 2015 resident in the United States (N = 1334), United Kingdom (N = 1199), France (N = 1258), Germany (N = 866), and Australia (N = 1013) who had used at least 1 prescription opioid analgesic medication in the past year. We also investigated the relationship with polysubstance use, one of the most consistent predictors of problematic opioid analgesic use. Data included misuse and abuse of codeine, hydrocodone, oxycodone, and tramadol; ability to obtain a prescription; different sources for obtaining drugs; and past-year use of benzodiazepines and illicit drugs. In multilevel models, country of residence accounted for less than 3% of the variance in opioid analgesic misuse or abuse. Adjusting for country of residence and sociodemographic factors, use of illicit drugs and benzodiazepines was associated with 4-fold greater odds of misuse (odds ratio 4.36, 95% confidence interval 3.29-5.93) and 6-fold greater odds of abuse compared with not using either drug (odds ratio 6.49, 95% confidence interval 4.0-10.48), although the strength of the association with abuse varied by country. Misuse and abuse by those prescribed opioid analgesics seem to be a problem that is not limited to the United States and warrant attention on an international scale.

  7. Adding 75 mg pregabalin to analgesic regimen reduces pain scores and opioid consumption in adults following percutaneous nephrolithotomy

    OpenAIRE

    Aydoğan, Harun; Kucuk, Ahmet; Yuce, Hasan Husnu; Karahan, Mahmut Alp; Ciftci, Halil; Gulum, Mehmet; Aksoy, Nurten; Yalcin, Saban

    2014-01-01

    Background and objectives:Adding novel adjunctive drugs like gabapentinoids to multimodal analgesic regimen might be reasonable for lessening postoperative pain scores, total opioid consumption and side effects after percutaneous nephrolithotomy. We aimed to evaluate the effect of pregabalin on postoperative pain scores, analgesic consumption and renal functions expressed by creatinine clearance (CrCl) and blood neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (Cys C) levels i...

  8. Use of Opioids and Other Analgesics by Older Adults in the United States, 1999–2010

    Science.gov (United States)

    Steinman, Michael A.; Komaiko, Kiya D.R.; Fung, Kathy Z.; Ritchie, Christine S.

    2016-01-01

    Background & Objective There has been concern over rising use of prescription opioids in young and middle-aged adults. Much less is known about opioid prescribing in older adults, for whom clinical recommendations and the balance of risks and benefits differ from younger adults. We evaluated changes in use of opioids and other analgesics in a national sample of clinic visits made by older adults between 1999 to 2010. Design, Setting, Subjects Observational study of adults age 65 and older from the 1999–2010 National Ambulatory and National Hospital Ambulatory Medical Care Surveys, serial cross-sectional surveys of outpatient visits in the United States. Methods Medication use was assessed at each study visit and included medications in use prior to the visit and medications newly prescribed at the visit. Results were adjusted for survey weights and design factors to provide nationally representative estimates. Results Mean age was 75 +/−7 years, and 45% of visits occurred in primary care settings. Between 1999–2000 and 2009–10, the percent of clinic visits at which an opioid was used rose from 4.1% to 9.0% (Popioid classes increased, the largest contributor to increased use was hydrocodone-containing combination opioids, which rose from 1.1% to 3.5% of visits over the study period (Popioid use was observed across a wide range of patient and clinic characteristics, including in visits for musculoskeletal problems (10.7% of visits in 1999–00 to 17.0% in 2009–10, POpioid use by older adults visiting clinics more than doubled between 1999–2010, and occurred across a wide range of patient characteristics and clinic settings. PMID:25352175

  9. Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats

    Directory of Open Access Journals (Sweden)

    Angela Maria Sousa

    2015-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5 mg, naloxone 200 µg or 0.9% NaCl, rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors.

  10. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects.

    Science.gov (United States)

    Prozialeck, Walter C; Jivan, Jateen K; Andurkar, Shridhar V

    2012-12-01

    Kratom (Mitragyna speciosa) is a plant indigenous to Thailand and Southeast Asia. Kratom leaves produce complex stimulant and opioid-like analgesic effects. In Asia, kratom has been used to stave off fatigue and to manage pain, diarrhea, cough, and opioid withdrawal. Recently, kratom has become widely available in the United States and Europe by means of smoke shops and the Internet. Analyses of the medical literature and select Internet sites indicate that individuals in the United States are increasingly using kratom for the self-management of pain and opioid withdrawal. Kratom contains pharmacologically active constituents, most notably mitragynine and 7-hydroxymitragynine. Kratom is illegal in many countries. Although it is still legal in the United States, the US Drug Enforcement Administration has placed kratom on its "Drugs and Chemicals of Concern" list. Physicians should be aware of the availability, user habits, and health effects of kratom. Further research on the therapeutic uses, toxic effects, and abuse potential of kratom and its constituent compounds are needed.

  11. Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study.

    Science.gov (United States)

    Wiese, Andrew D; Griffin, Marie R; Stein, C Michael; Mitchel, Edward F; Grijalva, Carlos G

    2016-02-01

    Animal studies and in vitro human studies suggest that certain opioid analgesics impair crucial immune functions. This study was undertaken to determine whether opioid use is associated with increased risk of serious infection in patients with rheumatoid arthritis (RA). We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid in 1995-2009. Within-person comparisons of the risk of hospitalization for serious infection during periods of opioid use versus non-use were performed using conditional Poisson regression. Fixed confounders were accounted for by design; time-varying confounders included age and use of disease-modifying antirheumatic drugs, glucocorticoids, and proton-pump inhibitors. In additional analyses, risks associated with new opioid use, use of opioids known to have immunosuppressive properties, use of long-acting opioids, and different opioid dosages were assessed. Sensitivity analyses were performed to account for potential protopathic bias and confounding by indication. Among 1,790 patients with RA who had at least 1 hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared to non-use, with an incidence rate ratio (IRR) of 1.39 (95% confidence interval [95% CI] 1.19-1.62). The incidence rate was also higher during periods of long-acting opioid use, immunosuppressive opioid use, and new opioid use compared to non-use (IRR 2.01 [95% CI 1.52-2.66], IRR 1.72 [95% CI 1.33-2.23], and IRR 2.38 [95% CI 1.65-3.42], respectively). Results of sensitivity analyses were consistent with the main findings. In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection. © 2016, American College of Rheumatology.

  12. Language competence and communication skills in 3-year-old children after prenatal exposure to analgesic opioids.

    Science.gov (United States)

    Skovlund, Eva; Handal, Marte; Selmer, Randi; Brandlistuen, Ragnhild Eek; Skurtveit, Svetlana

    2017-06-01

    An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age. The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17-18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales. A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89-1.22) and OR = 1.10 (95%CI: 0.95-1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence. The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Synthesis and analysis of the opioid analgesic [[sup 14]C]-fentanyl

    Energy Technology Data Exchange (ETDEWEB)

    Bagley, J.R.; Wilhelm, J.A. (Anaquest Inc., Murray Hill, NJ (United States))

    1992-11-01

    The synthesis of [[sup 14]C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [[sup 14]C]-Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1-phenylethyl-4-piperidone and [UL-[sup 14]C]-aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [[sup 14]C]-fentanyl with the radiolabel in the aniline benzene ring. (author).

  14. Synthesis and analysis of the opioid analgesic [14C]-fentanyl

    International Nuclear Information System (INIS)

    Bagley, J.R.; Wilhelm, J.A.

    1992-01-01

    The synthesis of [ 14 C]-fentanyl, the radiolabelled congener of the potent opioid analgesic chosen for utilization in drug disposition studies, is described. [ 14 C]-Labelling was achieved in the first of two steps, a room temperature reduction of the in situ generated Schiff base from 1-phenylethyl-4-piperidone and [UL- 14 C]-aniline hydrochloride with sodium triacetoxyborohydride. A nearly instantaneous production of fentanyl was accomplished at room temperature with the addition of propionyl chloride. The overall radiochemical yield was 18%. The method described is efficiently adaptable for submicromolar scale while yielding a product of sufficient specific activity for in vivo studies. Our solvent system for thin layer chromatography was superior to the USP system reported for chromatographic analysis of fentanyl. This is the first reported preparation of [ 14 C]-fentanyl with the radiolabel in the aniline benzene ring. (author)

  15. Bias Factor and Therapeutic Window Correlate to Predict Safer Opioid Analgesics.

    Science.gov (United States)

    Schmid, Cullen L; Kennedy, Nicole M; Ross, Nicolette C; Lovell, Kimberly M; Yue, Zhizhou; Morgenweck, Jenny; Cameron, Michael D; Bannister, Thomas D; Bohn, Laura M

    2017-11-16

    Biased agonism has been proposed as a means to separate desirable and adverse drug responses downstream of G protein-coupled receptor (GPCR) targets. Herein, we describe structural features of a series of mu-opioid-receptor (MOR)-selective agonists that preferentially activate receptors to couple to G proteins or to recruit βarrestin proteins. By comparing relative bias for MOR-mediated signaling in each pathway, we demonstrate a strong correlation between the respiratory suppression/antinociception therapeutic window in a series of compounds spanning a wide range of signaling bias. We find that βarrestin-biased compounds, such as fentanyl, are more likely to induce respiratory suppression at weak analgesic doses, while G protein signaling bias broadens the therapeutic window, allowing for antinociception in the absence of respiratory suppression. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Opioid analgesics suppress male gonadal function but opioid use in males and females does not correlate with symptoms of sexual dysfunction.

    Science.gov (United States)

    Wong, Dana; Gray, Dan P; Simmonds, Mark; Rashiq, Saifee; Sobolev, Igor; Morrish, Donald W

    2011-01-01

    Opioid analgesia impairs gonadal function in men and women, but the correlation with symptoms and hormonal measurements of hypogonadism is not well established. To determine the frequency of impaired gonadal function in men and women using opioids for chronic pain, and to determine the correlation of symptoms with hormonal measurements of gonadal function. A prospective study of patients attending a multidisciplinary pain clinic was conducted. A total of 65 women (47 opioid users and 18 nonopioid analgesic controls) and 32 men (26 opioid users and six controls) were enrolled. Histories of sexual dysfunction and hormonal testing (men: total testosterone [TT], free testosterone [FT], prolactin and luteinizing hormone; women: FT, TT, prolactin, dehydroepiandrosterone sulphate, sex hormone- binding globulin, progesterone, luteinizing hormone and follicle- stimulating hormone, and estradiol) were obtained. In men, a low FT level was more common in opioid users (20⁄26; P=0.04). In men with abnormal hormone levels, there was no difference in the frequency of sexual dysfunction compared with men with normal hormone levels, and no difference in the frequency of opioid versus nonopioid use. In women, opioid users had lower FT levels (P=0.02). Low dehydroepiandrosterone sulphate was more frequent in women on opioids (P=0.03) in the menopausal group only (P=0.046). Premenopausal women taking opioids more frequently had a low TT level (P=0.03). The frequency of female sexual dysfunction was the same in opioid users (32⁄47) and controls (13⁄18; P=0.75), and also did not relate to any hormone abnormality. Men taking opioids had lower FT and higher prolactin levels, and women taking opioids had lower FT levels. Frequency of sexual dysfunction did not correlate with hormone levels in either men or women taking opioids. Opioids frequently cause low FT levels in men, but there is no relationship between abnormal hormone levels and symptoms of sexual dysfunction. Therefore, all

  17. Differential prescribing of opioid analgesics according to physician specialty for Medicaid patients with chronic noncancer pain diagnoses.

    Science.gov (United States)

    Ringwalt, Chris; Gugelmann, Hallam; Garrettson, Mariana; Dasgupta, Nabarun; Chung, Arlene E; Proescholdbell, Scott K; Skinner, Asheley Cockrell

    2014-01-01

    Despite >20 years of studies investigating the characteristics of patients seeking or receiving opioid analgesics, research characterizing factors associated with physicians' opioid prescribing practices has been inconclusive, and the role of practitioner specialty in opioid prescribing practices remains largely unknown. To examine the relationships between physicians' and other providers' primary specialties and their opioid prescribing practices among patients with chronic noncancer pain (CNCP). Prescriptions for opioids filled by 81,459 Medicaid patients with CNCP in North Carolina (USA), 18 to 64 years of age, enrolled at any point during a one-year study period were examined. χ2 statistics were used to examine bivariate differences in prescribing practices according to specialty. For multivariable analyses, maximum-likelihood logistic regression models were used to examine the effect of specialty on prescribing practices, controlling for patients' pain diagnoses and demographic characteristics. Of prescriptions filled by patients with CNCP, who constituted 6.4% of the total sample of 1.28 million individuals, 12.0% were for opioids. General practitioner⁄family medicine specialists and internists were least likely to prescribe opioids, and orthopedists were most likely. Across specialties, men were more likely to receive opioids than women, as were white individuals relative to other races⁄ethnicities. In multivariate analyses, all specialties except internal medicine had higher odds of prescribing an opioid than general practitioners: orthopedists, OR 7.1 (95% CI 6.7 to 7.5); dentists, OR 3.5 (95% CI 3.3 to 3.6); and emergency medicine physicians, OR 2.7 (95% CI 2.6 to 2.8). Significant differences in opioid prescribing practices across prescriber specialties may be reflective of differing norms concerning the appropriateness of opioids for the control of chronic pain. If so, sharing these norms across specialties may improve the care of patients with

  18. Opioid analgesics and heroin: Examining drug misuse trends among a sample of drug treatment clients in Kentucky.

    Science.gov (United States)

    Victor, Grant A; Walker, Robert; Cole, Jennifer; Logan, T K

    2017-08-01

    In an effort to mitigate Kentucky's prescription drug misuse, legislative intervention efforts were introduced in 2012 and 2013 to better regulate pain clinics, prescribed use of opioid analgesics, and to expand the monitoring of opioid prescriptions. The focus of this paper is primarily on opioid analgesics and heroin and the relationship of use/misuse patterns of these drugs to state drug policy initiatives. A secondary data analysis of drug treatment clients (N=52,360) was conducted to project illicit drug use trends in Kentucky. This study describes temporal and geographic trends of self-reported illicit drug use among individuals in state-funded treatment in Kentucky between fiscal year 2010 and fiscal year 2013. Significant reductions in the prevalence of illicit opioid use, declined from fiscal year 2010 to fiscal year 2013 (p<.01, CI=-.298 to -.215). However, heroin use rates significantly increased over the years studied, suggesting there may be a transition from prescription opioids to heroin (p<.01, CI=.143 to .178). The analysis suggests these trends may continue. Findings suggest Kentucky's legislative efforts were effective in reducing illicit prescription opioid use, but heroin use has increased. One possible explanation for this relationship is that as prescription opioids became more difficult to obtain, users turned to heroin as a substitute. The finding of rising heroin use suggests a need for further policy initiatives to reduce heroin use, but the potential effectiveness of this policy remains unclear. Understanding trends may help to guide future policy efforts and pain management treatment strategies to where they might have their greatest impact. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Use of opioid analgesics in skin disorders: Results from a nationally representative US sample.

    Science.gov (United States)

    Gupta, Madhulika A; Gupta, Aditya K; Vujcic, Branka; Piccinin, Meghan

    2015-06-01

    Increasing and inappropriate use of opioid analgesics (OA) have been declared a public health concern in the United States. There are no epidemiologic studies of OA use in skin disorders. We examined OA use in a nationally representative sample of US patient visits with only physician-diagnosed skin disorders. Retrospective cross-sectional study of 56 751 patient visits from 1995 to 2010 (International Classification of Diseases, 9th Revision, Clinical Modification codes 680-709 denoting "Diseases of the Skin and Subcutaneous Tissue"; 172, 173, 216 and 232 denoting malignant and benign skin neoplasms). An estimated 3.1% ± 0.2% of skin disorders visits were associated with OA use; 52.7% ± 5.4% were Schedule III opioids; 11.4% ± 1.4% of OA visits involved skin neoplasms and 45.4% ± 2.3% cellulitis and abscess. OA use increased from 1995 to 2010 (adjusted OR = 1.82, 95% CI: 1.49-2.22), even after controlling for increase in the frequency of skin infections from 1995 to 2010. The most frequent use OA for cellulitis and abscess is entirely consistent with their Food and Drug Administration (FDA)-approved indications for pain management. The almost two-fold increase in OA use in skin disorders from 1995 to 2010 may suggest that OA are being considered for pain management earlier in therapy. Only a minority of patient visits with OA had primary dermatologic disease. OA are being used in dermatology primarily for FDA-approved indications.

  20. Analgesic tone conferred by constitutively active mu opioid receptors in mice lacking β-arrestin 2

    Directory of Open Access Journals (Sweden)

    Hales Tim G

    2011-04-01

    Full Text Available Abstract Hedonic reward, dependence and addiction are unwanted effects of opioid analgesics, linked to the phasic cycle of μ opioid receptor activation, tolerance and withdrawal. In vitro studies of recombinant G protein coupled receptors (GPCRs over expressed in cell lines reveal an alternative tonic signaling mechanism that is independent of agonist. Such studies demonstrate that constitutive GPCR signaling can be inhibited by inverse agonists but not by neutral antagonists. However, ligand-independent activity has been difficult to examine in vivo, at the systems level, due to relatively low levels of constitutive activity of most GPCRs including μ receptors, often necessitating mutagenesis or pharmacological manipulation to enhance basal signaling. We previously demonstrated that the absence of β-arrestin 2 (β-arr2 augments the constitutive coupling of μ receptors to voltage-activated Ca2+ channels in primary afferent dorsal root ganglion neurons from β-arr2-/- mice. We used this in vitro approach to characterize neutral competitive antagonists and inverse agonists of the constitutively active wild type μ receptors in neurons. We administered these agents to β-arr2-/- mice to explore the role of constitutive μ receptor activity in nociception and hedonic tone. This study demonstrates that the induction of constitutive μ receptor activity in vivo in β-arr2-/- mice prolongs tail withdrawal from noxious heat, a phenomenon that was reversed by inverse agonists, but not by antagonists that lack negative efficacy. By contrast, the aversive effects of inverse agonists were similar in β-arr2-/- and β-arr2+/+ mice, suggesting that hedonic tone was unaffected.

  1. Effects of Ibudilast on the Subjective, Reinforcing, and Analgesic Effects of Oxycodone in Recently Detoxified Adults with Opioid Dependence.

    Science.gov (United States)

    Metz, Verena E; Jones, Jermaine D; Manubay, Jeanne; Sullivan, Maria A; Mogali, Shanthi; Segoshi, Andrew; Madera, Gabriela; Johnson, Kirk W; Comer, Sandra D

    2017-08-01

    Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and withdrawal symptoms. The effects of ibudilast on the abuse potential of opioids in humans are largely unknown. The present study was designed to examine the influence of ibudilast on subjective (including drug craving), reinforcing, and analgesic effects of oxycodone in human volunteers diagnosed with opioid dependence (equivalent to moderate-severe opioid use disorder). Non-treatment-seeking opioid-dependent male volunteers (n=11) underwent an in-patient detoxification with morphine, followed by maintenance on placebo (0 mg b.i.d.) and active ibudilast (50 mg b.i.d.). Under each maintenance dose, six experimental sample and choice sessions were completed involving oral oxycodone administration (0, 15, and 30 mg/70 kg, p.o.). Subjective effects of oxycodone and drug craving were measured with visual analog scales (VAS) and a Drug Effects Questionnaire. The cold pressor test was used to produce pain, and a modified progressive-ratio choice procedure was used to measure the reinforcing effects of oxycodone. Under the active ibudilast condition compared with the placebo condition, ratings of drug liking following 15 mg of oxycodone were decreased significantly. The mean drug breakpoint value was also significantly lower in the active vs the placebo ibudilast condition under the 15 mg oxycodone condition, but not significantly lower under the 30 mg oxycodone condition. Heroin craving was significantly reduced under active ibudilast vs placebo, and similar effects were observed for tobacco and cocaine craving. Furthermore, mean subjective ratings of pain were lower in the active ibudilast condition. Our data suggest that ibudilast may be useful for treating opioid

  2. [Opioids in chronic noncancer pain-are opioids superior to nonopioid analgesics? A systematic review and meta-analysis of efficacy, tolerability and safety in randomized head-to-head comparisons of opioids versus nonopioid analgesics of at least four week's duration].

    Science.gov (United States)

    Welsch, P; Sommer, C; Schiltenwolf, M; Häuser, W

    2015-02-01

    Some leading German pain medicine experts postulate that there is a type of chronic non-cancer pain (CNCP) with an opioid requirement. We tested whether opioids are superior to nonopioid analgesics in the management of CNCP in studies of at least 4 week's duration. We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomised controlled trials (RCTs) of opioids in CNCP. We included double-blind RTCs comparing opioids to nonopioid analgesics of at least 4 week's duration. Relative risks differences (RD) of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model. We included 10 RCTs with 3046 participants. Median study duration was 6 weeks (range 4-12 weeks). Five studies compared tramadol with nonsteroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis pain and one trial compared tramadol to flupirtine in low back pain. Morphine was compared to antidepressants (two studies), an anticonvulsant (one study) and an antiarrhythmic (one study) in different neuropathic pain syndromes. There was no significant difference between opioids and nonopioid analgesics in pain reduction (SMD 0.03 [95 % confidence interval, CI - 0.18, 0.24]; p = 0.76). Nonopioid analgesics were superior to opioids in improving physical function (SMD 0.17 [95 % CI 0.02, 0.32]; p = 0.03). Patients dropped out due to adverse events more frequently with opioids than with nonopioid analgesics (RD 0.09 [95 % CI 0.06, 0.13]; p opioids and nonopioid analgesics in terms of serious adverse events or dropout rates due to lack of efficacy. Nonopioid analgesics are superior to opioids in terms of improvement of physical function and tolerability in short-term (4-12 weeks) therapy of neuropathic, low back and osteoarthritis pain. Our results do not support the

  3. Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study.

    Science.gov (United States)

    Desai, Rishi J; Huybrechts, Krista F; Hernandez-Diaz, Sonia; Mogun, Helen; Patorno, Elisabetta; Kaltenbach, Karol; Kerzner, Leslie S; Bateman, Brian T

    2015-05-14

    To provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking. Observational cohort study. Medicaid data from 46 US states. Pregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (opioid prescriptions, corresponding to an absolute risk of 5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries in the presence of additional risk factors of known opioid misuse (220.2 (200.8 to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6)) than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0 (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000 deliveries, respectively. In propensity score matched analyses, long term prescription opioid use compared with short term use and late use compared with early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95% confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively). Use of prescription opioids during pregnancy is associated with a low absolute risk of NAS in the absence of additional risk factors. Long term use compared with short term use and late use compared with early use of prescription opioids are associated with increased NAS risk independent of additional risk factors. © Desai et al 2015.

  4. Knowledge Toward Cancer Pain and the Use of Opioid Analgesics Among Medical Students in their Integrated Clinical Clerkship

    Directory of Open Access Journals (Sweden)

    Maria Fidelis C. Manalo

    2008-01-01

    Full Text Available Introduction: Among the focal issues of barriers to pain management include the physicians’ lack of knowledge about cancer pain and negative attitudes towards opioids. Many physicians and educators attribute this, at least in part, to limited exposure to pain and palliative care education during medical school.Aim: The researcher investigated the medical students’ knowledge about cancer pain and the use of opioid analgesics.Methods: The subjects were a sample of 50 students of the University of the Philippines College of Medicine in their integrated clinical clerkship year. Descriptive statistics (frequencies, means, standard deviation, rating scales were used to determine mean knowledge score and level of confidence with opioid use. The study also identified specific areas where students exhibited good or poor knowledge of opioids.Results: Approximately sixty-nine (69% of the study respondents mentioned that pain management was given to them during their Anesthesiology lectures while a few recalled that they had these lectures during their Family Medicine rotation in Supportive, Palliative and Hospice Care. More than a third (35% of the respondents admitted to not being confident with morphine use at present. The top three reasons cited as limitations in choice of opioids for cancer pain include fear of addiction, lack of adequate knowledge and experience and fear of side effects and complications. Out of a maximum of 13 correct answers, the mean knowledge score of the medical students was 6.6 ± 2.9. Less than 16% of the respondents had adequate knowledge on cancer pain and opioid use.Conclusions: The results show that basic knowledge of the role of opioids in cancer pain management among medical students in their integrated clinical clerkship year at the University of the Philippines is poor. The findings imply a need to look into making revisions in the medical curriculum to include a training program that will enable all students to

  5. Analgesic Effects of Diluted Bee Venom Acupuncture Mediated by δ-Opioid and α2-Adrenergic Receptors in Osteoarthritic Rats.

    Science.gov (United States)

    Huh, Jeong-Eun; Seo, Byung-Kwan; Lee, Jung-Woo; Kim, Chanyoung; Park, Yeon-Cheol; Lee, Jae-Dong; Baek, Yong-Hyeon

    2017-06-23

    Context • Pain from osteoarthritis is associated with peripheral nociception and central pain processing. Given the unmet need for innovative, effective, and well-tolerated therapies, many patients, after looking for more satisfactory alternatives, decide to use complementary and alternative modalities. The analgesic mechanism of subcutaneous injections of diluted bee venom into an acupoint is thought to be part of an anti-inflammatory effect and the central modulation of pain processing. Objectives • Using the rat model of collagenase-induced osteoarthritis (CIOA), the study intended to investigate the analgesic effects of bee venom acupuncture (BVA) as they are related to the acupuncture points and dosage used and to determine whether the analgesic mechanisms of BVA for pain were mediated by opioid or adrenergic receptors. Design • Male Sprague-Dawley rats were randomly assigned to one of 19 groups, with n = 10 for each group. Setting • The study was conducted at the East-West Bone and Joint Research Institute at Kyung Hee University (Seoul, South Korea). Intervention • All rats were intra-articularly injected with collagenase solution in the left knee, followed by a booster injection performed 4 d after the first injection. For the groups receiving BVA treatments, the treatment was administered into the ST-36 acupoint, except for 1 group that received the treatment into a nonacupoint. Three BVA intervention groups received no pretreatment with agonists or antagonists; 1 of them received a dose of 1 mg/kg of bee venom into acupoint ST-36, 1 received a dose of 2 mg/kg into acupoint ST-36, and 1 received a dose of 1 mg/kg into a nonacupoint location. For the intervention groups receiving pretreatments, the opioid-receptor or adrenergic-receptor agonists or antagonists were injected 20 min before the 1-mg/kg BVA treatments. Outcome Measures • Changes in the rats' pain thresholds were assessed by evaluation of pain-related behavior, using a tail flick

  6. Use of prescribed opioid analgesics and co-medication with benzodiazepines in women before, during, and after pregnancy: a population-based cohort study.

    Science.gov (United States)

    Handal, Marte; Engeland, Anders; Rønning, Marit; Skurtveit, Svetlana; Furu, Kari

    2011-09-01

    The aim of the study was to describe the use of prescribed opioid analgesics for noncancer pain and the degree of possible concurrent co-medication with benzodiazepines to women in Norway before, during, and after pregnancy. This was a population-based cohort study based on linkage of two nationwide registries: the Medical Birth Registry of Norway, and the Norwegian Prescription Database. Prescribed opioid analgesics and benzodiazepines issued to women 3 months prior to, during, and 3 months after pregnancies were identified. The study population consisted of 194,937 singleton pregnancies beginning in March 2004 or later and ending before January 2009. About 6% of the women were dispensed opioid analgesics before, during, or after pregnancy. Almost all these women received weak opioids (99%) with short-acting codeine in combination with paracetamol (acetaminophen) as the most frequently dispensed drug. The dispensing of codeine was reduced from 24/1,000 women before pregnancy to 10/1,000 in the last trimester, increasing to 17/1,000 during the breastfeeding period. Most women were dispensed codeine once, and treatment was of short duration (about 1 week). A small group of women (n = 271) were dispensed opioids in all trimesters. Increasing benzodiazepine use was observed as the number of opioid prescriptions increased. The use of opioid analgesics in pregnant women in Norway was dominated by treatment of short duration of the weak opioid codeine. As pregnancy proceeded, opioid use was reduced. However, the increase in opioid use during the nursing period has the potential for serious adverse effects.

  7. Age and Gender Trends in Long-Term Opioid Analgesic Use for Noncancer Pain

    Science.gov (United States)

    Weisner, Constance; LeResche, Linda; Ray, G. Thomas; Saunders, Kathleen; Sullivan, Mark D.; Banta-Green, Caleb J.; Merrill, Joseph O.; Silverberg, Michael J.; Boudreau, Denise; Satre, Derek D.; Von Korff, Michael

    2010-01-01

    Objectives. We describe age and gender trends in long-term use of prescribed opioids for chronic noncancer pain in 2 large health plans. Methods. Age- and gender-standardized incident (beginning in each year) and prevalent (ongoing) opioid use episodes were estimated with automated health care data from 1997 to 2005. Profiles of opioid use in 2005 by age and gender were also compared. Results. From 1997 to 2005, age–gender groups exhibited a total percentage increase ranging from 16% to 87% for incident long-term opioid use and from 61% to 135% for prevalent long-term opioid use. Women had higher opioid use than did men. Older women had the highest prevalence of long-term opioid use (8%–9% in 2005). Concurrent use of sedative-hypnotic drugs and opioids was common, particularly among women. Conclusions. Risks and benefits of long-term opioid use are poorly understood, particularly among older adults. Increased surveillance of the safety of long-term opioid use is needed in community practice settings. PMID:20724688

  8. Receipt of opioid analgesics by HIV-infected and uninfected patients.

    Science.gov (United States)

    Edelman, E Jennifer; Gordon, Kirsha; Becker, William C; Goulet, Joseph L; Skanderson, Melissa; Gaither, Julie R; Brennan Braden, Jennifer; Gordon, Adam J; Kerns, Robert D; Justice, Amy C; Fiellin, David A

    2013-01-01

    Opioids are increasingly prescribed, but there are limited data on opioid receipt by HIV status. To describe patterns of opioid receipt by HIV status and the relationship between HIV status and receiving any, high-dose, and long-term opioids. Cross-sectional analysis of the Veterans Aging Cohort Study. HIV-infected (HIV+) patients receiving Veterans Health Administration care, and uninfected matched controls. Pain-related diagnoses were determined using ICD-9 codes. Any opioid receipt was defined as at least one opioid prescription; high-dose was defined as an average daily dose ≥ 120 mg of morphine equivalents; long-term opioids was defined as ≥ 90 consecutive days, allowing a 30 day refill gap. Multivariable models were used to assess the relationship between HIV infection and the three outcomes. Among the HIV+ (n = 23,651) and uninfected (n = 55,097) patients, 31 % of HIV+ and 28 % of uninfected (p opioids. Among patients receiving opioids, HIV+ patients were more likely to have an acute pain diagnosis (7 % vs. 4 %), but less likely to have a chronic pain diagnosis (53 % vs. 69 %). HIV+ patients received a higher mean daily morphine equivalent dose than uninfected patients (41 mg vs. 37 mg, p = 0.001) and were more likely to receive high-dose opioids (6 % vs. 5 %, p opioids than uninfected patients (median 44 vs. 60, p opioids (31 % vs. 34 %, p opioids (AOR 1.40, 95 % CI 1.35, 1.46) and high-dose opioids (AOR 1.22, 95 % CI 1.07, 1.39), but not long-term opioids (AOR 0.94, 95 % CI 0.88, 1.01). Patients with HIV infection are more likely to be prescribed opioids than uninfected individuals, and there is a variable association with pain diagnoses. Efforts to standardize approaches to pain management may be warranted in this highly complex and vulnerable patient population.

  9. Physician-related barriers to cancer pain management with opioid analgesics

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Sjøgren, Per; Møldrup, Claus

    2007-01-01

    of drug prescribing documents. The results of the articles found were analyzed with respect to (a) knowledge, beliefs, concerns, problems endorsed or acknowledged by physicians treating cancer pain, (b) physicians' skills in pain assessment, and (c) adequacy of opioid prescription. CONCLUSIONS......: This review revealed mostly general and common physician-related barriers to cancer pain management: concerns about side effects to opioids, prescription of not efficient doses of opioids, and very poor prescription for the treatment of side effects from opioids. In the future, the evaluation of the influence...

  10. Challenges Involved in the Development and Delivery of Abuse-deterrent Formulations of Opioid Analgesics.

    Science.gov (United States)

    Cohen, Joshua P; Mendoza, Mario; Roland, Carl

    2018-02-01

    This commentary examines the development, regulatory, and reimbursement challenges facing abuse-deterrent formulation (ADF) products. In January 2017, the Tufts Center for the Study of Drug Development convened a roundtable to explore clinical development, regulatory, and reimbursement challenges with respect to ADFs of opioid analgesics. Roundtable participants, who included a range of pharmaceutical industry and other experts, discussed multiple challenges. First, several key clinical development challenges were identified and discussed. These challenges pertain to prodrug development and development of deterrents against oral abuse. Second, experts suggested that more clarity is needed from regulatory authorities regarding standards for proving ADF labeling claims and for being rewarded with 3-year data exclusivity. Similarly, given the substantial burdens associated with the development of postapproval evidence generation, experts raised the need for a consistent regulatory policy related to postapproval evidence generation for all ADFs (branded and generic). Third, despite the public health benefits of certain ADF products, current coverage and access policies impede patient access. Payer justification for restrictive policies appears to be based more on budget impact considerations than cost-effectiveness. Fourth, there remains a need to further expand the evidence base regarding clinical and cost-effectiveness as well as abuse deterrence in a real-world setting for all ADF products. Clinical development challenges need to be overcome with respect to novel ADF technologies, such as prodrugs and deterrents against oral abuse. More clarity is needed from regulatory authorities on labeling claims and data exclusivity eligibility with respect to ADFs. Ensuring prescriber training and awareness of various options for treating pain, including ADF products, is an important step, as is educating payers about the public health benefits of ADFs in appropriate

  11. Analgesic

    Directory of Open Access Journals (Sweden)

    Bian Juhua

    2016-05-01

    Full Text Available This study is to establish a model of rat tibial osteocarcinoma pain, intrathecally inject specific ERK1/2 inhibitors SCH772984, observe the analgesic effect, and discuss the influence of ERK-P90RSK-Fos signal path in bone cancer pain. Forty female SD rats were randomly divided into 5 groups. Establish a bone cancer pain model after putting the intrathecal tube 5d and determine the rats’ mechanical withdrawal threshold (MWT after tube 5d; 40 SD rats with intrathecal tube back 5d were randomly divided into 5 groups. Sham Group receives no medication, the other four respectively receive 5% DMSO 10 μl, SCH 0.1, 1.0, 10 μg (SCH dissolved in 10 μl 5% DMSO intrathecally. Determine the rats’ mechanical withdrawal threshold (MWT before and after giving medication 1, 3, 6, 9, 12, 15, 18, 24 h, and 2 min spontaneous paw withdrawal. Western blot and immuno-fluorescence determine the expression condition of spinal cord dorsal horn of p-ERK, p-p90RSK and Fos protein. Intrathecal injection of SCH772984 has analgesic effects on rats with bone cancer pain, and the effects enhance with increasing dose; intrathecal injection of SCH772984 10 μg could greatly reduce the expression of spinal dorsal horn Fos protein. Injecting walker 256 tumor cells into rats’ tibia could cause behavior changes, such as idiopathic pain sensitivity and pain; the intrathecal tube almost has no effect on motor function of rats; ERK1/2 is involved in bone cancer pain, and intrathecal injection of ERK1/2 specific inhibitors SCH772984 10 μg may effectively relieve bone cancer pain.

  12. Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists

    DEFF Research Database (Denmark)

    Ebert, B; Thorkildsen, C; Andersen, S

    1998-01-01

    , in order to obtain complete analgesia, a combination of an NMDA receptor antagonist and an opioid receptor agonist is needed. Recent in vitro data have demonstrated that methadone, ketobemidone, and dextropropoxyphene, in addition to being opioid receptor agonists, also are weak noncompetitive NMDA...

  13. Efficacy and Safety of Oral and Transdermal Opioid Analgesics for Musculoskeletal Pain in Older Adults: A Systematic Review of Randomized, Placebo-Controlled Trials.

    Science.gov (United States)

    Megale, Rodrigo Z; Deveza, Leticia A; Blyth, Fiona M; Naganathan, Vasi; Ferreira, Paulo H; McLachlan, Andrew J; Ferreira, Manuela L

    2017-12-11

    This systematic review with meta-analysis was performed to evaluate the efficacy and safety of using opioid analgesics in older adults with musculoskeletal pain. We searched Cochrane Library, MEDLINE, EMBASE, Web of Science, AMED, CINAHL, and LILACS for randomized controlled trials with mean population age of 60 years or older, comparing the efficacy and safety of opioid analgesics with placebo for musculoskeletal pain conditions. Reviewers extracted data, assessed risk of bias, and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Random effects models were used to calculate standardized mean differences (when different scales were used across trials), mean differences and odds ratios with respective 95% confidence intervals (CIs). Meta-regressions were carried out to assess the influence of opioid analgesic daily dose and treatment duration on our main outcomes. We included 23 randomized placebo-controlled trials in the meta-analysis. Opioid analgesics had a small effect on decreasing pain intensity (standardized mean difference = -.27; 95% CI = -.33 to -.20) and improving function (standardized mean difference = -.27, 95% CI = -.36 to -.18), which was not associated with daily dose or treatment duration. The odds of adverse events were 3 times higher (odds ratio = 2.94; 95% CI = 2.33-3.72) and the odds of treatment discontinuation due to adverse events 4 times higher (odds ratio = 4.04; 95% CI = 3.10-5.25) in patients treated with opioid analgesics. The results show that in older adults suffering from musculoskeletal pain, using opioid analgesics had only a small effect on pain and function at the cost of a higher odds of adverse events and treatment discontinuation. For this specific population, the opioid-related risks may outweigh the benefits. The systematic review shows that, in older adults suffering from musculoskeletal conditions, opioid analgesics have only a small effect on pain and

  14. Use and Nonmedical Use of Prescription Opioid Analgesics in the General Population of Canada and Correlations with Dispensing Levels in 2009

    Directory of Open Access Journals (Sweden)

    Kevin D Shield

    2013-01-01

    Full Text Available BACKGROUND: In Canada, harm from nonmedical prescription opioid analgesic (POA use (NMPOU has increased in recent years; however, there are limitations to the current estimates of NMPOU. The 2009 Canadian Alcohol and Drug Use Monitoring Survey presents an opportunity to produce more accurate estimates of NMPOU.

  15. Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations

    Science.gov (United States)

    Turk, Dennis C.; O’Connor, Alec B.; Dworkin, Robert H.; Chaudhry, Amina; Katz, Nathaniel P.; Adams, Edgar H.; Brownstein, John S.; Comer, Sandra D.; Dart, Richard; Dasgupta, Nabarun; Denisco, Richard A.; Klein, Michael; Leiderman, Deborah B.; Lubran, Robert; Rappaport, Bob A.; Zacny, James P.; Ahdieh, Harry; Burke, Laurie B.; Cowan, Penney; Jacobs, Petra; Malamut, Richard; Markman, John; Michna, Edward; Palmer, Pamela; Peirce-Sandner, Sarah; Potter, Jennifer S.; Raja, Srinivasa N.; Rauschkolb, Christine; Roland, Carl L.; Webster, Lynn R.; Weiss, Roger D.; Wolf, Kerry

    2013-01-01

    Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Due to the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs in order to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability; (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation; (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse; and (4) post-marketing epidemiological studies. PMID:22770841

  16. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531 influences the analgesic response to the short acting opioid Remifentanil in humans

    Directory of Open Access Journals (Sweden)

    Schalling Martin

    2009-07-01

    Full Text Available Abstract Background There is evidence from animal studies that serotonin (5-HT can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531. The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS. All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG as compared to those with high expression(LA/LA, p Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of

  17. Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected?

    Science.gov (United States)

    Gnanadesigan, Nallini; Espinoza, Randall T; Smith, Rick; Israel, Michelle; Reuben, David B

    2005-01-01

    To describe the potential for interaction between opioids and serotonergic antidepressants leading to the development of serotonin syndrome (SS), mechanism of the interaction, and the spectrum of SS in elderly residents of a long-term care facility. Case series. Long-term care facility (LTCF) in California. Four elderly LTCF residents treated with serotonergic antidepressants including selective serotonin reuptake inhibitor (SSRI) or mirtazapine and opioids. Signs and symptoms suggestive of SS. We describe 4 cases of probable SS among elderly residents of a LTCF. The spectrum of serotonin toxicity ranged from visual hallucinations, muscle rigidity, myoclonus, or hypertension in patients taking an opiate with an SSRI to lethargy, hypotension, and hypoxia in a patient taking tramadol and mirtazapine. While many can benefit from coadministration of serotonergic antidepressants and opioids, it appears that some individuals are at increased risk for SS. Since SS is a clinical diagnosis, heightened clinician awareness of the possibility of SS among patients receiving SSRI or mirtazapine in combination with opioids may lead to earlier detection and avoidance of potentially lethal consequences.

  18. Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management

    Directory of Open Access Journals (Sweden)

    Feng XQ

    2017-05-01

    Full Text Available Xiu-qin Feng,1 Ling-ling Zhu,2 Quan Zhou3 1Nursing Administration Office, Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Background: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs. Method: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Results: Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8% were conducted in healthy volunteers, whereas 10 RCTs (19.2% enrolled true patients. None of the opioid–drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine–P2Y12 inhibitors, morphine–gabapentin, and methadone–zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin–opioids (morphine, tramadol, oxycodone, methadone, quinidine–opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone, antimycotics–opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol, protease inhibitors–opioids (ritonavir, ritonavir/lopinavir–oxycodone, ritonavir–fentanyl, ritonavir–tilidine, grapefruit juice–opioids (oxycodone, fentanyl, methadone, antidepressants–opioids (paroxetine–tramadol, paroxetine–hydrocodone, paroxetine–oxycodone, escitalopram–tramadol, metoclopramide–morphine, amantadine–morphine, sumatriptan

  19. Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.

    Science.gov (United States)

    Stefanucci, Azzurra; Novellino, Ettore; Mirzaie, Sako; Macedonio, Giorgia; Pieretti, Stefano; Minosi, Paola; Szűcs, Edina; Erdei, Anna I; Zádor, Ferenc; Benyhe, Sándor; Mollica, Adriano

    2017-04-13

    d-Pen 2 ,d-Pen 5 enkephalin (DPDPE) is one of the most selective synthetic peptide agonists targeting the δ-opioid receptor. Three cyclic analogues of DPDPE containing a xylene bridge in place of disulfide bond have been synthesized and fully characterized as opioid receptors agonists. The in vitro activity was investigated showing a good affinity of 7a - c for μ- and δ-receptors. In vivo biological assays revealed that 7b is the most potent analogue with the ability to maintain high level of analgesia from 15 to 60 min following intracerebroventricular (i.c.v.) administration, whereas DPDPE was slightly active until 45 min. Compound 7b induced long lasting analgesia also after subcutaneous administration, whereas DPDPE was inactive.

  20. Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements?

    Science.gov (United States)

    Shinde, Shivani; Gordon, Pamela; Sharma, Prashant; Gross, James; Davis, Mellar P

    2015-03-01

    Cancer pain is complex, and despite the introduction of the WHO cancer pain ladder, few studies have looked at the prevalence of adjuvant medication use in an inpatient palliative medicine unit. In this study, we evaluate the use of adjuvant pain medications in patients admitted to an inpatient palliative care unit and whether their use affects pain scores or opiate dosing. In this retrospective observational study, patients admitted to the inpatient palliative care unit over a 3-month period with a diagnosis of cancer on opioid therapy were selected. Data pertaining to demographics, diagnosis, oral morphine dose equivalent of the opioid at the time of discharge, adjuvant analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and pain scores as reported by nurses and physicians were collected. Seventy-seven patients were eligible over a 3-month period, out of which 65 (84 %) were taking an adjuvant medication. The most commonly prescribed adjuvant was gabapentin (70 %). Fifty-seven percent were taking more than one adjuvant. There were more women in the group receiving adjuvants (57 vs. 17%, p = 0.010). Those without adjuvants compared with those on adjuvants did not have worse pain scores on discharge as reported by physicians (0.8 ± 0.8 vs. 1.0 ± 0.7, p = 0.58) or nurses (2.0 ± 2.7 vs. 2.1 ± 2.6, p = 0.86). There was no difference in morphine equivalent doses of the opioid in both groups (median (min, max); 112 (58, 504) vs. 200 (30, 5,040)) at the time of discharge; 75-80 % of patients had improvement in pain scores as measured by a two-point reduction in numerical rating scale (NRS). This study shows that adjuvant medications are commonly used for treating pain in patients with cancer. More than half of study population were on two adjuvants or an adjuvant plus NSAID along with an opioid. We did not demonstrate any benefit in terms of improved pain scores or opioid doses with adjuvants, but this could reflect confounding variables and physician choice

  1. Associations between statewide prescription drug monitoring program (PDMP) requirement and physician patterns of prescribing opioid analgesics for patients with non-cancer chronic pain.

    Science.gov (United States)

    Lin, Hsien-Chang; Wang, Zhi; Boyd, Carol; Simoni-Wastila, Linda; Buu, Anne

    2018-01-01

    State-level prescription drug monitoring programs (PDMPs) have been implemented in most states. PDMPs enable registered prescribers to obtain real-time information on patients' prescription history to reduce non-medical use of controlled drugs. This study examined whether PDMP implementation and different levels of PDMP requirements were associated with physicians' patterns of prescribing opioid analgesics for patients with non-cancer chronic pain. This is a secondary analysis study using cross-sectional national data. Patients with non-cancer chronic pain from the 2012 National Ambulatory Medical Care Survey were included (weighted N=81,018,131; unweighted N=3295). Heckman two-step selection procedure employing two logistic regressions was used to explore the associations between PDMP requirements and physicians' prescribing behaviors, controlling for physician characteristics, patient characteristics, physician-healthcare system interaction, and physician-patient relationship, guided by the Eisenberg's model of physician decision making. State PDMP implementation status and requirement levels were not associated with physician opioid prescribing for non-cancer chronic pain treatment (p's ranged 0.30-0.32). Patients with Medicare coverage were more likely to be prescribed opioid analgesics than those with private health insurance (OR=1.55, pprescription opioids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Opioid Analgesic Use in Patients with Ankylosing Spondylitis: An Analysis of the Prospective Study of Outcomes in an Ankylosing Spondylitis Cohort.

    Science.gov (United States)

    Dau, Jonathan D; Lee, MinJae; Ward, Michael M; Gensler, Lianne S; Brown, Matthew A; Learch, Thomas J; Diekman, Laura A; Tahanan, Amirali; Rahbar, Mohammad H; Weisman, Michael H; Reveille, John D

    2018-02-01

    Opioid analgesics may be prescribed to ankylosing spondylitis (AS) patients with pain that is unresponsive to antirheumatic treatment. Our study assessed factors associated with opioid usage in AS. A prospective cohort of 706 patients with AS meeting modified New York criteria followed at least 2 years underwent comprehensive clinical evaluation of disease activity and functional impairment. These were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). Radiographic severity was assessed by the Bath Ankylosing Spondylitis Radiology Index and modified Stokes Ankylosing Spondylitis Scoring System. Medications taken concurrently with opioids, as well as C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), were determined at each study visit, performed every 6 months. Analyses were carried out at baseline, and longitudinal multivariable models were developed to identify factors independently associated with chronic and intermittent opioid usage over time. Factors significantly associated with opioid usage, especially chronic opioid use, included longer disease duration, smoking, lack of exercise, higher disease activity (BASDAI) and functional impairment (BASFI), depression, radiographic severity, and cardiovascular disease. Patients taking opioids were more likely to be using anxiolytic, hypnotic, antidepressant, and muscle relaxant medications. Multivariable analysis underscored the association with smoking, older age, antitumor necrosis factor agent use, and psychoactive drugs, as well as with subjective but not objective determinants of disease activity. Opioid usage was more likely to be associated with subjective measures (depression, BASDAI, BASFI) than objective measures (CRP, ESR), suggesting that pain in AS may derive from sources other than spinal inflammation alone.

  3. Simultaneous analysis of opioid analgesics and their metabolites in municipal wastewaters and river water by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Krizman-Matasic, Ivona; Kostanjevecki, Petra; Ahel, Marijan; Terzic, Senka

    2018-01-19

    Although published literature provides a clear demonstration of widespread occurrence of opioid analgesics (OAs) in the aquatic environment, analytical methods suitable for a systematic study of this pharmaceutical class, which would include a broad spectrum of opioid analgesics and their metabolites, are still missing. In this work, a comprehensive multiresidue method for quantitative analysis of 27 opioid analgesics and their metabolites, including 2 morphine glucuronide conjugates, was developed and validated for three matrices: raw wastewater (RW), secondary effluent (SE) and river water. The method comprised different classes of opioid analgesics, including natural opiates (morphine and codeine), their semi-synthetic derivatives (hydrocodone, hydromorphone, oxycodone, oxymorphone and buprenorphine) as well as fully synthetic opioids such as methadone, fentanyl, sufentanil, propoxyphene and tramadol. The optimized enrichment procedure involved mixed-mode, strong cation-exchange sorbent in combination with a sequential elution procedure. The extracts were analyzed by reversed-phase liquid chromatography using a Synergy Polar column coupled to electrospray ionization tandem mass spectrometry (LC-MS/MS). Accurate quantification of target OAs was achieved using 19 deuterated analogues as surrogate standards. Method accuracies for RW, SE and river water varied in the range from 91 to 126%, 74 to 120% and 75 to 116%, respectively. Careful optimization of the procedure allowed reliable determination of OAs with method quantification limits in the low ng/L range (RW: 0.3-3.5 ng/L; SE: 0.2-1.9 ng/L, river water: 0.1-0.8 ng/L. The developed method was applied for analysis of RW, SE and river water samples from Croatia. The concentrations of individual OAs in municipal wastewater varied in a wide range (from < QL to 859 ng/L) and the most prevalent representatives were tramadol, codeine, morphine and methadone and their derivatives. Elevated concentrations of

  4. The Risk of Opioid Intoxications or Related Events and the Effect of Alcohol-Related Disorders: A Retrospective Cohort Study in German Patients Treated with High-Potency Opioid Analgesics.

    Science.gov (United States)

    Jobski, K; Kollhorst, B; Schink, T; Garbe, Edeltraut

    2015-09-01

    Intoxications involving prescription opioids are a major public health problem in many countries. When taken with opioids, alcohol can enhance the effects of opioids, particularly in the central nervous system. However, data quantifying the impact of alcohol involvement in opioid-related intoxications are limited. Using claims data from the German Pharmacoepidemiological Research Database (GePaRD), we conducted a retrospective cohort study based on users of high-potency opioid (HPO) analgesics during the years 2005-2009. HPO use was classified as extended-release, immediate-release or both. We calculated incidence rates (IRs) for opioid intoxications or related events as well as adjusted IR ratios (aIRR) comparing HPO-treated patients with alcohol-related disorders (ARDs) to those without ARDs overall and within each HPO category. During the study period, 308,268 HPO users were identified with an overall IR of 340.4 per 100,000 person-years [95 % confidence interval (CI) 325.5-355.7]. The risk was highest when patients received concomitant treatment with extended- and immediate-release HPOs (IR 1093.8; 95 % CI 904.6-1310.9). ARDs increased the risk during HPO use by a factor of 1.7 and the highest aIRR was seen when comparing patients simultaneously exposed to extended- and immediate-release HPOs with ARDs to those without ARD also after excluding patients with potential improper/non-medical HPO use. Physicians should be aware of these elevated risks in HPO patients with ARDs. Active patient education by healthcare providers regarding the risk of opioid intoxications or related events due to alcohol in conjunction with HPOs is warranted.

  5. Unsolicited Reporting to Prescribers of Opioid Analgesics by a State Prescription Drug Monitoring Program: An Observational Study with Matched Comparison Group.

    Science.gov (United States)

    Young, Leonard D; Kreiner, Peter W; Panas, Lee

    2017-04-04

     State prescription drug monitoring programs (PDMPs) can help detect individuals with multiple provider episodes (MPEs; also referred to as doctor/pharmacy shopping), an indicator of prescription drug abuse and/or diversion. Although unsolicited reporting by PDMPs to prescribers of opioid analgesics is thought to be an important practice in reducing MPEs and the potential harm associated with them, evidence of its effectiveness is mixed. This exploratory research evaluates the impact of unsolicited reports sent by Massachusetts' PDMP to the prescribers of persons with MPEs.  Individuals with MPEs were identified from PDMP records between January 2010 and July 2011 as individuals having Schedule II prescriptions (at least one prescription being an opioid) from four or more distinct prescribers and four or more distinct pharmacies within six months. Based on available MA-PDMP resources, an unsolicited report containing the patient's 12-month prescription history was sent to prescribers of a subset of patients who met the MPE threshold; a comparison group closely matched on demographics and baseline prescription history, whose prescribers were not sent a report, was generated using propensity score matching. The prescription history of each group was examined for 12 months before and after the intervention.  There were eighty-four patients (intervention group) whose prescribers received an unsolicited report and 504 matched patients (comparison group) whose prescribers were not sent a report. Regression analyses indicated significantly greater decreases in the number of Schedule II opioid prescriptions ( P  prescription histories, which may improve health outcomes for patients receiving opioid analgesics from multiple providers. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  6. Prolonged release oxycodone and naloxone treatment counteracts opioid-induced constipation in patients with severe pain compared to previous analgesic treatment.

    Science.gov (United States)

    Koopmans-Klein, Gineke; Van Op den Bosch, Joeri; van Megen, Yvonne; Prenen, Hans; Huygen, Frank; Mancini, Isabelle

    2017-12-01

    Treatment with prolonged-release oxycodone/naloxone (PR OXN) has been shown to improve opioid induced constipation (OIC) in constipated patients. This publication reports on a real-life observational study investigating the efficacy of PR OXN with regard to bowel function in patients switching to PR OXN from WHO step 1, step 2 and step 3 opioids. Patients with chronic pain experiencing insufficient pain relief and/or unacceptable side effects were switched to PR OXN and monitored in this observational study with respect to efficacy regarding bowel function and efficacy regarding pain relief in comparison with previous analgesic therapy. A patient was considered a responder with respect to efficacy if this assessment was "slightly better", "better" or "much better" compared with previous therapy. Bowel function index, pain intensity, quality of life, laxative medication use, and safety analgesic were also evaluated. A total of 1338 patients (mean [SD] age 64.3 [14.9], 63% female) were observed for 43 [3-166] days (median [range]) during treatment with PR OXN. Overall response rate regarding bowel function efficacy was 82.5%. Patients with symptoms of constipation at study entry obtained a clinically relevant improvement of the bowel function index (BFI) within the first 2 weeks of PR OXN treatment. Non-constipated patients at study entry maintained normal bowel function despite switching to treatment with the opioid PR OXN. In conclusion, treatment with PR OXN results in a significant and clinically relevant improvement of bowel function. During the observation of the treatment with PR OXN patients reported an improvement of quality of life (QoL). More interestingly, non-constipated patients maintained a normal bowel function, showing prevention of constipation despite the use of an opioid.

  7. Postoperative consumption of opioid analgesics following correction of pectus excavatum is influenced by pectus severity: a single-centre study of 236 patients undergoing minimally invasive correction of pectus excavatum

    DEFF Research Database (Denmark)

    Grosen, Kasper; Pfeiffer-Jensen, Mogens; Pilegaard, Hans

    2009-01-01

    Objective: Surgical correction of pectus excavatum (PE) is primarily performed to achieve cosmetic and psychological benefits for the patient. Minimally invasive repair of PE is often associated with severe postoperative pain. This study estimates the effect of the severity of PE...... on the postoperative consumption of opioid analgesics following this procedure to optimise pain management. Methods: A retrospective study was conducted on 236 consecutive patients undergoing minimally invasive repair of PE from 2005 to 2008. The collected data included depth of preoperative pectus excavation, patient...... demographics, peri- and postoperative information, including data on pain management. The consumption of opioid analgesics was registered after discontinuation of epidural analgesia and other types of opioid analgesics used during the study period were converted to morphine equivalents. Multiple linear...

  8. Biophysical parameters of erythrocyte membranes and mechanisms of interaction with non-opioid analgesics under acute pain syndrome

    Directory of Open Access Journals (Sweden)

    Yu. I. Gubskyi

    2014-06-01

    Full Text Available Methods of fluorescent probing, spectrophotometry and microcalorimetry were applied to investigate the alterations in biophysical parameters of erythrocytes membranes, and specifically microviscosity, surface charge, molecular organization of lipid bilayer and lipid-protein interactions under conditions of acute pain syndrome produced by experimental chemical lesion. The distinctive features of non-opiod analgesics interactions and binding to the erythrocytes membranes of rats subjected to acute nociceptive pain accompanied with oxidative stress development were investigated. The abilities of analgesics under research, and namely paracetamol, aspirin, phenazone, ketorolac, pyrodazole, ketoprofenum, natrium mefenaminate, indometacin, nimesulide to make up physico-chemical complexes with lipoperoxidation modified erythrocytes surface and protein-lipid bilayer showed marked changes. The significance of oxidative damage of biophase under conditions of acute pain syndrome for analgesics effective pharmacodynamics and pharmacokinetics realization is under consideration.

  9. Spinal Tolerance and Dependence: Some Observations on the Role of Spinal N-Methyl-D-Aspartate Receptors and Phosphorylation in the Loss of Opioid Analgesic Responses

    Directory of Open Access Journals (Sweden)

    Tony L Yaksh

    2000-01-01

    Full Text Available The continuous delivery of opiates can lead to a reduction in analgesic effects. In humans, as in other animals, some component of this change in sensitivity seems likely to have a strong pharmacodynamic component. Such loss of effect, deemed to be tolerance in the present article, can be readily demonstrated in animals with repeated bolus and continuous intrathecal infusion of mu and delta opioids and alpha-2 adrenergic agonists. Research has shown that this loss of effect can be diminished by concurrent treatment with N-methyl-D-aspartate (NMDA receptor antagonists and by the suppression of the activity of spinal protein kinase C (PKC. This suggests in part the probable role of PKC-mediated phosphorylation in the right shift in the dose-effect curves observed with continuous opiate or adrenergic exposure. Importantly, this right shift is seen to occur in parallel with an increase in the phosphorylating activity in the dorsal horn and in the expression of several PKC isozymes. The target of this phosphorylation is not certain. Phosphorylation of the NMDA receptor enhances its functionality, while phosphorylation of the opioid receptor or associated channels seems to diminish their activity or to enhance internalization. While the focus is on several specific components, the accumulating data emphasize the biological complexity of these changes in spinal drug reactivity.

  10. Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

    International Nuclear Information System (INIS)

    Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min

    2011-01-01

    To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 ± 0.7, which was significantly lower than that of group A, 8.2 ± 0.7 (p 0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

  11. Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

    Energy Technology Data Exchange (ETDEWEB)

    Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min [Dept. of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2011-05-15

    To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 {+-} 0.7, which was significantly lower than that of group A, 8.2 {+-} 0.7 (p<0.05). The mean dose of intravenous pethidine was 114.3 {+-} 59.5 mg in group A and 90.5 {+-} 49.0 mg in group B, while the incidence of nausea was 67% in group A and 77% in group B. In both cases, the differences were not significantly different (p>0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

  12. prescriptions involving analgesic drugs at a secondary health facility

    African Journals Online (AJOL)

    INTRODUCTION. Analgesics are broadly divided into two classes, that is, Opioid and non-opioid drugs. Opioids are generally reserved for relieve of severe pain and are usually provided under supervision and strict control because of tendency to dependence and abuse1. On the other hand non-opioid analgesics are freely.

  13. Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request.

    Science.gov (United States)

    Hogan, William R; Hanna, Josh; Hicks, Amanda; Amirova, Samira; Bramblett, Baxter; Diller, Matthew; Enderez, Rodel; Modzelewski, Timothy; Vasconcelos, Mirela; Delcher, Chris

    2017-03-03

    The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl.obolibrary.org/obo/dron.owl . A smaller version without NDCs is available at: http://purl.obolibrary.org/obo/dron/dron-lite.owl.

  14. Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids

    Directory of Open Access Journals (Sweden)

    Hale M

    2017-01-01

    associated with opioids, such as nausea, constipation, and headache. In both rollover and de novo patients, pain intensity scores remained constant at approximately 3–4 during long-term treatment, and the dose of buprenorphine buccal film remained unchanged in 86.2% of patients.Conclusion: In appropriate patients, buprenorphine buccal film demonstrated tolerability and efficacy in the long-term management of chronic pain.Keywords: buccal drug administration, buprenorphine, chronic pain management, long-term treatment, opioid analgesics

  15. Opioid adjuvant strategy: improving opioid effectiveness.

    Science.gov (United States)

    Bihel, Frédéric

    2016-01-01

    Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

  16. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J

    2011-01-01

    studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid µ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...

  17. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  18. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J

    2011-01-01

    Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental...... studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid µ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...

  19. [Opioid Therapy and Management of Side Effects Associated with Opioids].

    Science.gov (United States)

    Nakatani, Toshihiko

    2017-04-01

    Opioids are very useful medications to reduce suffering of cancer patients such as refractory pain and dyspnea. We physicians have to use opioids to have good management of pain and suffering associated with cancer including management of side effects caused by opioids. Opioids couple opioid receptors and affect several pharmacological effects. Other than analgesic effect, opioids have some side effects of constipation, nausea and vomiting, respiratory depression. In this chapter, I take important side effects of constipation, nausea and vomiting and respiratory depression. Next, serotonin syndrome caused by tramadol combined with anti-depressants is remarked as assignable syndrome. As advancing in chemotherapy for cancer treatment, cancer survivors live longer with opioid therapy. We have to pay attention to the side effects and another dysfunction caused by long use of opioids. It is important that we physician use opioids effectively to keep activity of daily living(ADL) of patients and families as team approach.

  20. Nature's first "atypical opioids": Kratom and mitragynines.

    Science.gov (United States)

    Raffa, R B; Pergolizzi, J V; Taylor, R; Ossipov, M H

    2018-03-08

    Advances in pain research have led to an understanding that many pains are driven by more than one underlying (patho)physiologic cause (ie, they are "multimechanistic") and that better pain relief is obtained with fewer adverse effects when an analgesic is correspondingly multimechanistic. At least two of the more-modern analgesics combine opioid and non-opioid mechanisms, and have become known as "atypical opioids." Less well known is that just as Nature evolved opioids, it also evolved atypical opioids, presaging modern drug discovery efforts. Traditional (typical) opioids are extracts or analogs of substances derived from the poppy plant. They produce their analgesic and adverse effects primarily through a single, opioid mechanism (albeit with individual differences). Two most recent analgesics were developed to have both an opioid mechanism and, a second, non-opioid mechanism of action (inhibition of monoamine neurotransmitter reuptake). Little known is that Nature had already evolved a plant source of compounds with the same properties. As debate about the use and abuse potential of kratom swirls, conflicting, often contradicting, opinions are expressed. A review of the basic pharmacology of kratom reveals the explanation for the bifurcation in viewpoints: kratom has both opioid and non-opioid properties. Fascinatingly, just as the poppy plant (Papaver) evolved the typical opioids, Mitragyna evolved the mitragynines-Nature's "atypical opioids." © 2018 John Wiley & Sons Ltd.

  1. Opioid Basics: Prescription Opioids

    Science.gov (United States)

    ... Injury Violence Prevention WISQARS (Injury & Death Data) Prescription Opioids Recommend on Facebook Tweet Share Compartir Prescription opioids ... Problem Risk Factors Addiction and Overdose About Prescription Opioids Side Effects In addition to the serious risks ...

  2. Patient preference with respect to QoL and reduction in opioid-induced constipation (OIC) after treatment with prolonged-release (PR) oxycodone/naloxone compared with previous analgesic therapy [PREFER study].

    Science.gov (United States)

    van Dongen, V C P C; Vanelderen, P J L; Koopmans-Klein, G; van Megen, Y J B; Van Zundert, J; Huygen, F J P M

    2014-11-01

    The aim of this study was to assess patient preference in terms of quality of life (QoL), analgesia and bowel function for patients with moderate to severe chronic non-malignant pain, when treated with oxycodone PR/naloxone PR compared with the previous WHO-step I and/or WHO-step II analgesic treatment . This was a 3-week open-label phase 3b study conducted in Belgium and the Netherlands, after 3 weeks patients could enter an extension phase. Patient preference with respect to QoL for oxycodone PR/naloxone PR treatment compared with previous WHO-step I and/or WHO-step II analgesics was assessed. A patient was considered a responder with respect to QoL if this assessment was 'better' or 'much better' compared with previous WHO-step I or II analgesics at any time point. Response rate with respect to QoL was 59.2% (95% CI: 51.7-66.8%) for the Full Analysis (FA)-population, for the Per Protocol-population response rate was 71.7% (95% CI: 63.1-80.3%). Explorative analysis showed that response rate with respect to QoL was highest in constipated patients pretreated with WHO-step II analgesics (73.8%). Mean ± SD pain score in the FA-population at start was 74.7 ± 16.6 decreasing to 53.9 ± 24.3 after a median (range) treatment period of 173.5 (31-771) days. For constipated subjects the significant reduction in constipation [improvement of the Bowel Function Index (BFI)], was -24.8 points (95% CI: -17.1 to -32.5). BFI for non-constipated subjects remained well below 28.8. Adverse events with oxycodone PR/naloxone PR treatment were well-known opioid-related adverse events. This study shows that the studied patients previously treated with WHO-step I and/or WHO-step II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to QoL. Moreover, the study shows that treatment with oxycodone PR/naloxone PR significantly reduces OIC in constipated patients and that non-constipated patients do not develop OIC during treatment with oxycodone PR/naloxone PR.

  3. Acute Metabolic Changes Associated With Analgesic Drugs

    DEFF Research Database (Denmark)

    Hansen, Tine Maria; Olesen, Anne Estrup; Simonsen, Carsten Wiberg

    2016-01-01

    BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy (MRS) is used to measure brain metabolites. Limited data exist on the analgesic-induced spectroscopy response. This was an explorative study with the aims to investigate the central effects of two analgesic drugs, an opioid and a selective...

  4. A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain

    DEFF Research Database (Denmark)

    Kress, H.G.; Laage, D. Von der; Hoerauf, K.H.

    2008-01-01

    A new 72-hour transdermal fentanyl matrix patch has been designed, which has a 35%-50% reduction of the absolute fentanyl content compared with other currently available transdermal fentanyl patches that are using the matrix technology. The new patch has previously been shown...... to be pharmacokinetically bioequivalent to the marked fentanyl patch. To determine noninferiority in efficacy in cancer patients and to compare safety, a clinical trial comparing the new fentanyl patch with standard oral or transdermal opioid treatment was planned. The design was an open, parallel group, multicenter trial......, in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI expressed...

  5. Differences between opioids

    DEFF Research Database (Denmark)

    Drewes, Asbjørn Mohr; Jensen, Rasmus D; Møller Nielsen, Lecia

    2013-01-01

    Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids...... to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients...... who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences...

  6. Comparison of abuse, suspected suicidal intent, and fatalities related to the 7-day buprenorphine transdermal patch versus other opioid analgesics in the National Poison Data System.

    Science.gov (United States)

    Coplan, Paul M; Sessler, Nelson E; Harikrishnan, Venkatesh; Singh, Richa; Perkel, Charles

    2017-01-01

    Prescription opioid related abuse, suicide and death are significant public health problems. This study compares rates of poison center calls categorized as intentional abuse, suspected suicidal intent or fatality for the 7-day buprenorphine transdermal system/patch (BTDS) with other extended-release and long-acting (ER/LA) opioids indicated for chronic pain. Retrospective 24-month cohort study using National Poison Data System data from July 2012 through June 2014. BTDS was introduced in the United States in January 2011. Numbers and rates of calls of intentional abuse, suspected suicidal intent and fatalities were evaluated for BTDS, ER morphine, ER oxycodone, fentanyl patch, ER oxymorphone and methadone tablets/capsules, using prescription adjustment to account for community availability. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. Absolute numbers and prescription-adjusted rates of intentional abuse and suspected suicidal intent with BTDS were significantly lower (p poison center calls for intentional abuse and suspected suicidal intent events, suggesting lower rates of these risks with BTDS compared to other ER/LA opioids.

  7. High levels of opioid analgesic co-prescription among methadone maintenance treatment clients in British Columbia, Canada: results from a population-level retrospective cohort study.

    Science.gov (United States)

    Nosyk, Bohdan; Fischer, Benedikt; Sun, Huiying; Marsh, David C; Kerr, Thomas; Rehm, Juergen T; Anis, Aslam H

    2014-01-01

    The non-medical use of prescription opioids (PO) has increased dramatically in North America. Special consideration for PO prescription is required for individuals in methadone maintenance treatment (MMT). Our objective is to describe the prevalence and correlates of PO use among British Columbia (BC) MMT clients from 1996 to 2007. This study was based on a linked, population-level medication dispensation database. All individuals receiving 30 days of continuous MMT for opioid dependence were included in the study. Key measurements included the proportion of clients receiving >7 days of a PO other than methadone during MMT from 1996 to 2007. Factors independently associated with PO co-prescription during MMT were assessed using generalized linear mixed effects regression. 16,248 individuals with 27,919 MMT episodes at least 30 days in duration were identified for the study period. Among them, 5,552 individuals (34.2%) received a total of 290,543 PO co-prescriptions during MMT. The majority (74.3%) of all PO dispensations >7 days originated from non-MMT physicians. The number of PO prescriptions per person-year nearly doubled between 1996 and 2006, driven by increases in morphine, hydromorphone and oxycodone dispensations. PO co-prescription was positively associated with female gender, older age, higher levels of medical co-morbidity as well as higher MMT dosage, adherence, and retention. A large proportion of MMT clients in BC received co-occurring PO prescriptions, often from physicians and pharmacies not delivering MMT. Experimental evidence for the treatment of pain in MMT clients is required to guide clinical practice. © American Academy of Addiction Psychiatry.

  8. Effects of nalfurafine on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats.

    Science.gov (United States)

    Townsend, E Andrew; Naylor, Jennifer E; Negus, S Stevens; Edwards, Shelley R; Qureshi, Hina N; McLendon, Hunter W; McCurdy, Christopher R; Kapanda, Coco N; do Carmo, Jussara M; da Silva, Fernanda S; Hall, John E; Sufka, Kenneth J; Freeman, Kevin B

    2017-09-01

    Strategies to reduce the misuse of mu opioid agonists are critically needed. Previous work has shown that kappa opioid agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu agonists. However, use of traditional kappa agonists is limited by their dysphoric side effects. The current study examined the effects of nalfurafine, a clinically available atypical kappa agonist, on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone in male rats. To determine oxycodone/nalfurafine mixture proportions to be examined intravenously across procedures, a progressive ratio (PR) self-administration procedure compared the reinforcing effects of oxycodone (56 μg/kg/inj) available alone or as a mixture with co-administered nalfurafine (0.32, 1, or 3.2 μg/kg/inj), corresponding to oxycodone/nalfurafine proportions of 175:1, 56:1, and 18:1, respectively. Next, PR and thermal antinociception dose-effect functions were each determined for oxycodone, nalfurafine, and the same oxycodone/nalfurafine mixture proportions. Finally, the respiratory-depressant effects of equi-antinociceptive doses of oxycodone, nalfurafine, and the mixtures were compared. Nalfurafine decreased the reinforcing effects of oxycodone, and the 18:1 mixture did not function as a reinforcer. Oxycodone and nalfurafine each produced dose-dependent antinociception, and the mixtures produced additive antinociception. In addition, antinociceptive doses of the 56:1 and 18:1 mixtures did not produce respiratory depression. These results suggest that nalfurafine may augment the thermal antinociceptive effects while reducing the reinforcing and respiratory-depressant effects of oxycodone.

  9. Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids.

    Science.gov (United States)

    Hale, Martin; Urdaneta, Veronica; Kirby, M Todd; Xiang, Qinfang; Rauck, Richard

    2017-01-01

    This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids. The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients) or were recruited de novo for this study (n=61) were enrolled in this study. All patients underwent a dose titration period of ≤6 weeks, during which doses of buprenorphine buccal film were adjusted to a maximum 900 µg every 12 hours, depending on tolerability and the need for rescue medication. An optimal dose was defined as the dose that the patient found satisfactory for both pain relief and tolerability, without the need for rescue medication or with ≤2 tablets of rescue medication per day. Once the optimal dose was reached, treatment was continued for ≤48 weeks. Pain intensity was measured throughout the study using a 0-10 numerical rating scale. Of 435 patients achieving an optimal dose of buprenorphine buccal film who commenced long-term treatment, 158 (36.3%) completed 48 weeks of treatment. Treatment-related adverse events occurred in 116 patients (22.9%) during the titration phase and 61 patients (14.0%) during the long-term treatment phase, and adverse events leading to discontinuation of treatment occurred in 14 (2.8%) and 14 (3.2%) patients, respectively. The most common adverse events were those typically associated with opioids, such as nausea, constipation, and headache. In both rollover and de novo patients, pain intensity scores remained constant at approximately 3-4 during long-term treatment, and the dose of buprenorphine buccal film remained unchanged in 86.2% of patients. In appropriate patients, buprenorphine buccal film demonstrated tolerability and efficacy

  10. Adjuvant analgesics for spine surgery.

    Science.gov (United States)

    Nielsen, Rikke Vibeke

    2018-03-01

    Increasing evidence indicate that pain is insufficiently treated following surgical procedures. It is essential that pain treatment is effective with a minimum of side effects in order to promote postoperative rehabilitation. Multimodal analgesia is most likely an important strategy in reducing postoperative pain. Combinations of different analgesics with different mechanisms of action may have an additive analgesic effect with fewer side effects compared to using a single drug. However, there is still a pronounced lack of documentation for the effect and side effects of these multimodal analgesic regimes. More than 6,000 spine surgeries are performed annually in Denmark and spine surgery has been associated with high levels of pain compared to other surgical procedures. Therefore, we considered spine surgery to pose a group of well-defined surgical procedures and we used this model to investigate the efficacy of 3 adjuvant analgesics aiming to improve the multimodal approach in pain management.
 
In study I and II we hypothesized that preoperative IV dexamethasone 16 mg would reduce acute postoperative pain, opioid consumption and persistent pain after lumbar disk surgery. We found that dexamethasone significantly reduced acute pain during mobilization. The clinical relevance is however debatable and we could not demonstrate an opioid sparing effect. Further, we discovered significantly higher pain levels in the dexamethasone group compared to placebo 1 year postoperatively.
 
In study III we explored the effect of 500 mg of oral chlorzoxazone on acute postoperative pain and opioid consumption in patients with moderate to severe pain after spine surgery and found no effect of chlorzoxazone compared to placebo.
 
In study IV we hypothesized that intraoperative ketamine would reduce postoperative opioid consumption and persistent pain after spinal fusion surgery in chronic pain patients with opioid dependency. We found a significantly reduced opioid

  11. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

    Nielsen, B N; Henneberg, S W; Schmiegelow, K

    2015-01-01

    scores, consumption of supplemental analgesics and time to first analgesic were included. Trials with sample sizes of fewer than 10 patients per treatment group or trials with opioids administered intra-articularly or as peripheral nerve blocks were excluded. RESULTS: Data from 26 studies, including 1531...

  12. Efficacy of Opioid-free Anesthesia in Reducing Postoperative Respiratory Depression in Children Undergoing Tonsillectomy

    Science.gov (United States)

    2016-12-08

    Anesthesia; General Anesthesia; Analgesics, Opioid; Postoperative Complications; Pathologic Processes; Physiologic Effects of Drugs; Narcotics; Analgesics; Sleep Disordered Breathing; Obstructive Sleep Apnea of Child; Tonsillectomy; Respiratory Depression; Dexmedetomidine; Ketamine; Lidocaine; Gabapentin; Pulse Oximetry

  13. Pharmacological studies of Anti-inflammatory, Analgesic and ...

    African Journals Online (AJOL)

    Parimala Krishnan

    of analgesic drugs produce serious adverse effects, such as GI disturbances, renal damages (with NSAIDs drugs), respiratory depression and possibly dependence (with opioids). It is understandable that proposition of analgesic agents with fewer adverse effects is desirable. One of the ways to achieve this aim is the use of ...

  14. Self-treatment of opioid withdrawal with a dietary supplement, Kratom.

    Science.gov (United States)

    Boyer, Edward W; Babu, Kavita M; Macalino, Grace E; Compton, Wilson

    2007-01-01

    We examined the use of Kratom (Mitragyna sp.), a dietary supplement with mu-opioid agonist activity, by members of a cybercommunity who self-treat chronic pain with opioid analgesics from Internet pharmacies. Within one year, an increase in the number of mentions on Drugbuyers.com, a Web site that facilitates the online purchase of opioid analgesics, suggested that members began managing opioid withdrawal with Kratom. This study demonstrates the rapidity with which information on psychoactive substances disseminates through online communities and suggests that online surveillance may be important to the generation of effective opioid analgesic abuse prevention strategies.

  15. Neurobiology of opioid withdrawal: Role of the endothelin system.

    Science.gov (United States)

    Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil

    2016-08-15

    Morphine and oxycodone are potent opioid analgesics most commonly used for the management of moderate to severe acute and chronic pain. Their clinical utility is limited by undesired side effects like analgesic tolerance, dependence, and withdrawal. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. Mechanistically, G proteins and regulatory proteins such as β-arrestins have shown to play an important role in mediating opioid tolerance, dependence, and withdrawal. Recently, the involvement of central ET mechanisms in opioid withdrawal was investigated. ETA receptor antagonist was shown to block majority of the signs and symptoms associated with opioid withdrawal. This review focuses on ET as one of the potential novel strategies to manage the challenge of opioid withdrawal. An overview of additional players in this process (G proteins and β-arrestin2), and the possible therapeutic implications of these findings are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Assessment of Postoperative Analgesic Drug Efficacy

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Kloster; Gögenur, Ismail; Torup, Henrik

    2017-01-01

    BACKGROUND: Pain intensity ratings and opioid consumption (OC) are ubiquitous indicators of pain in postoperative trials of the efficacy of interventional procedures. Unfortunately, consensus on the appropriate statistical handling of these outcomes has not been reached. The aim of this article was......, therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. METHODS: Data from a randomized, double...... also included an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC0-6/0-24 h). Also, estimation of effect size, generalized odds ratio of the individual analgesic outcome variables was performed. RESULTS: Sixty-one patients were included in the final data...

  17. The evidence of neuraxial administration of analgesics for cancer-related pain

    DEFF Research Database (Denmark)

    Kurita, G P; Benthien, K S; Nordly, M

    2015-01-01

    retrieved was 2147, and 84 articles were selected for full reading. The final selection comprised nine articles regarding randomised controlled trials (RCTs) divided in four groups: neuraxial combinations of opioid and adjuvant analgesic compared with neuraxial administration of opioid alone (n = 4); single......BACKGROUND: The present systematic review analysed the existing evidence of analgesic efficacy and side effects of opioids without and with adjuvant analgesics delivered by neuraxial route (epidural and subarachnoid) in adult patients with cancer. METHODS: Search strategy was elaborated with words...... neuraxial drug in bolus compared with continuous administration (n = 2); single neuraxial drug compared with neuraxial placebo (n = 1); and neuraxial opioid combined with or without adjuvant analgesic compared with other comprehensive medical management than neuraxial analgesics (n = 2). The RCTs presented...

  18. Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

    Science.gov (United States)

    Shavit, Yehuda; Grace, Peter M.; Rice, Kenner C.; Maier, Steven F.; Watkins, Linda R.

    2011-01-01

    Vastly stimulated by the discovery of opioid receptors in the early 1970s, preclinical and clinical research was directed at the study of stereoselective neuronal actions of opioids, especially those played in their crucial analgesic role. However, during the past decade, a new appreciation of the non-neuronal actions of opioids has emerged from preclinical research, with specific appreciation for the nonclassic and nonstereoselective sites of action. Opioid activity at Toll-like receptors, newly recognized innate immune pattern recognition receptors, adds substantially to this unfolding story. It is now apparent from molecular and rodent data that these newly identified signaling events significantly modify the pharmacodynamics of opioids by eliciting proinflammatory reactivity from glia, the immunocompetent cells of the central nervous system. These central immune signaling events, including the release of cytokines and chemokines and the associated disruption of glutamate homeostasis, cause elevated neuronal excitability, which subsequently decreases opioid analgesic efficacy and leads to heightened pain states. This review will examine the current preclinical literature of opioid-induced central immune signaling mediated by classic and nonclassic opioid receptors. A unification of the preclinical pharmacology, neuroscience, and immunology of opioids now provides new insights into common mechanisms of chronic pain, naive tolerance, analgesic tolerance, opioid-induced hyperalgesia, and allodynia. Novel pharmacological targets for future drug development are discussed in the hope that disease-modifying chronic pain treatments arising from the appreciation of opioid-induced central immune signaling may become practical. PMID:21752874

  19. Spinal opioids in adult patients with cancer pain: a systematic review: a European Palliative Care Research Collaborative (EPCRC) opioid guidelines project

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Kaasa, Stein; Sjøgren, Per

    2011-01-01

    A systematic review, undertaken according to an initiative to revise European Association for Palliative Care guidelines on the use of opioids for cancer pain, which aimed to analyse analgesic efficacy and side effects of spinal opioids in adult cancer patients previously treated with systemic...... opioids....

  20. Post-Craniotomy Pain Management: Beyond Opioids.

    Science.gov (United States)

    Dunn, Lauren K; Naik, Bhiken I; Nemergut, Edward C; Durieux, Marcel E

    2016-10-01

    Craniotomy pain may be severe and is often undertreated. Pain management following craniotomy is a balancing act of achieving adequate analgesia but avoiding sedation, respiratory depression, hypercapnia, nausea and vomiting, and hypertension. Opioids are a first-line analgesic therapy; however, concern that opioid-related adverse effects (sedation, respiratory depression) may interfere with neurologic assessment and increase intracranial pressure has limited use of these drugs for intracranial surgery. Non-opioid analgesics avoid these effects and may be useful as part of a multimodal regimen for post-craniotomy pain. Regional scalp blocks, paracetamol, and non-steroidal anti-inflammatory drugs are beneficial in the early post-operative period. Recent studies suggest a role for novel analgesics: dexmedetomidine, gabapentinoids, and ketamine, though additional studies are necessary.

  1. Heterogenic control groups in randomized, controlled, analgesic trials of total hip- and knee arthroplasty.

    Science.gov (United States)

    Karlsen, Anders P; Mathiesen, Ole; Dahl, Jørgen B

    2017-11-17

    Postoperative analgesic interventions are often tested adjunct to basic non- opioid analgesics in randomized controlled trials (RCTs). Consequently, treatment in control groups, and assay sensitivity, differs between trials. We hypothesized that postoperative opioid requirements and pain intensities varies between different control groups in analgesic trials. Control groups from RCTs investigating analgesic interventions after total hip and knee arthroplasty were categorized based on standardized basic analgesic treatment. Morphine consumption 0-24h postoperatively, and resting pain scores at 6 and 24 hours for subgroups of basic treatments, were compared with ANOVA. In an additional analysis, we compared pain and opioid requirements in trials where NSAID was administered as an intervention with trial where NSAID was administered in a control group. We included 171 RCTs employing 28 different control groups with large variability in pain scores and opioid requirements. Four types of control groups (comprising 78 trials) were eligi- ble for subgroup comparisons. These subgroups received: 'opioid', 'NSAID+opioid', 'acetamino- phen+opioid', or 'NSAID+acetaminophen+opioid'. Morphine consumption and pain scores varied substantially between these groups, with no consistent superior efficacy in any subgroup. Addi- tionally, trials administering NSAID as an intervention demonstrated lower pain scores and opioid requirements than trials where NSAID was administered in a control group. Analgesic treatment in RCT control groups varies considerably. Control groups receiving various combinations of opioid, NSAID and acetaminophen did not differ consistently in pain and opioid requirements. Pain and opioid requirements were lower in trials administering NSAID as an intervention compared with trials administering NSAID in a control group.

  2. Analgesic use in patients with knee and/or hip osteoarthritis referred to an outpatient center

    DEFF Research Database (Denmark)

    Knoop, Jesper; van Tunen, Joyce; van der Esch, Martin

    2017-01-01

    use was reported by 63% of the patients, with acetaminophen, NSAIDs and opioid use reported by 50, 30 and 12%, respectively. Factors related to analgesic use were higher pain severity, longer duration of symptoms, higher radiographic hip OA severity, overweight/obesity and psychological distress...... of analgesic (yes/no) was administered and subdivided into acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs, including coxibs) and opioids. Logistic regression analyses were performed to analyze the association between analgesic use and disease-related, predisposing and enabling factors. Analgesic...

  3. Global Supply and Demand of Opioids for Pain Management.

    Science.gov (United States)

    Kunnumpurath, Sreekumar; Julien, Natasha; Kodumudi, Gopal; Kunnumpurath, Anamika; Kodumudi, Vijay; Vadivelu, Nalini

    2018-04-04

    The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management. The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries. Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.

  4. Prescription monitoring programs and emergency department visits involving opioids, 2004–2011

    Science.gov (United States)

    Maughan, Brandon C.; Bachhuber, Marcus A.; Mitra, Nandita; Starrels, Joanna L.

    2016-01-01

    Objective To determine the association between prescription drug monitoring program (PDMP) implementation and emergency department (ED) visits involving opioid analgesics. Methods Rates of ED visits involving opioid analgesics per 100,000 residents were estimated from the Drug Abuse Warning Network dataset for 11 geographically diverse metropolitan areas in the United States on a quarterly basis from 2004 to 2011. Generalized estimating equations assessed whether implementation of a prescriber-accessible PDMP was associated with a difference in ED visits involving opioid analgesics. Models were adjusted for calendar quarter, metropolitan area, metropolitan area-specific linear time trends, and unemployment rate. Results Rates of ED visits involving opioid analgesics increased in all metropolitan areas. PDMP implementation was not associated with a difference in ED visits involving opioid analgesics (mean difference of 0.8 visits [95% CI: −3.7 to 5.2] per 100,000 residents per quarter). Conclusions During 2004–2011, PDMP implementation was not associated with a change in opioid-related morbidity, as measured by emergency department visits involving opioid analgesics. Urgent investigation is needed to determine the optimal PDMP structure and capabilities to improve opioid analgesic safety. PMID:26454836

  5. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further...

  6. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further investi...

  7. Opioid research in amphibians: an alternative pain model yielding insights on the evolution of opioid receptors

    Science.gov (United States)

    Stevens, Craig W.

    2011-01-01

    This review summarizes the work from our laboratory investigating mechanisms of opioid analgesia using the Northern grass frog, Rana pipiens. Over the last dozen years, we have accumulated data on the characterization of behavioral effects after opioid administration on radioligand binding by using opioid agonist and antagonist ligands in amphibian brain and spinal cord homogenates, and by cloning and sequencing opioid-like receptor cDNA from amphibian central nervous system (CNS) tissues. The relative analgesic potency of mu, delta, and kappa opioids is highly correlated between frogs and other mammals, including humans. Radioligand binding studies using selective opioid agonists show a similar selectivity profile in amphibians and mammals. In contrast, opioid antagonists that are highly selective for mammalian mu, delta, and kappa opioid receptors were not selective in behavioral and binding studies in amphibians. Three opioid-like receptor cDNAs were cloned and sequenced from amphibian brain tissues and are orthologs to mammalian mu, delta, and kappa opioid receptors. Bioinformatics analysis of the three types of opioid receptor cDNAs from all vertebrate species with full datasets gave a pattern of the molecular evolution of opioid receptors marked by the divergence of mu, delta, and kappa opioid receptor sequences during vertebrate evolution. This divergence in receptor amino acid sequence in later-evolved vertebrates underlies the hypothesis that opioid receptors are more type-selective in mammals than in nonmammalian vertebrates. The apparent order of receptor type evolution is kappa, then delta, and, most recently, the mu opioid receptor. Finally, novel bioinformatics analyses suggest that conserved extracellular receptor domains determine the type selectivity of vertebrate opioid receptors. PMID:15464208

  8. Analgesic stairway in the treatment of oncological pain

    Directory of Open Access Journals (Sweden)

    Sarah María Regueira Betancourt

    2015-10-01

    Full Text Available Pain represents the main symptom in an important group of patients who are in active treatment for cancer and in sick people in a very advanced stage. The objective of this article is to review the basic pharmacology of the nonsteroidal antiinflammatory drugs, weak opioids, bigger opioids, as well as the different special pharmacological and non- pharmacological techniques that constitute the analgesic stairway in the management of patients who are suffering from oncological pain.

  9. Postoperative urinary retention: evaluation of patients using opioids analgesic Retención urinaria post-operatoria: evaluación de pacientes en tratamiento analgésico con opioides Retenção urinária pós-operatória: avaliação de pacientes em uso de analgesia com opióides

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Barretto de Carvalho Fernandes

    2007-04-01

    Full Text Available The study aimed to determine the occurrence of urinary retention in patients using opioid analgesic and to describe the method used for vesical relief. A prospective and consecutive series of 1,316 patients undergoing surgery from September 1999 to April 2003 and using opioids post surgery were studied. From the 1,136 patients, 594 did not use urinary catheters pre-surgery. From these 594 patients, 128 (22% suffered post operative urinary retention. Urinary retention was significantly related to the use of continuous epidural analgesia (p=0.009. About 69% of patients experiencing urinary retention post surgery returned to spontaneous micturition following a single catheterization. The incidence found of urinary retention was similar to the literature, more frequent in men who received continuous epidural analgesia. The findings suggest orientation and careful nursing team observation of post operative micturition, emphasizing the intermittent aseptically catheterization for urinary retention in order to prevent potential complications of the urinary tract.Los objetivos de este estudio fueron determinar la incidencia de retención urinaria post-operatoria en pacientes que se encontraban en uso de analgésicos opioides, así como describir el método utilizado en el vaciado vesical. Se trata de una serie prospectiva y consecutiva de 1.316 pacientes quirúrgicos, estudiados de septiembre de 1999 a abril de 2003. De ellos, 594 pacientes no usaron cateterismo de demora en el pre-operatorio. Así mismo, 128 pacientes de este grupo presentó retención urinaria, con una incidencia del 22% (128/594. Hubo una asociación estadísticamente significativa entre la ocurrencia de retención urinaria y el uso de analgesia epidural continua (p=0,009. El 69% de los pacientes presentó una micción espontánea luego de haber realizado apenas un cateterismo. La incidencia de retención urinaria encontrada es semejante a la descrita en la literatura, siendo m

  10. NATURAL AND PARTIALLY SYNTETIC ANALGESICS

    Directory of Open Access Journals (Sweden)

    Stevan Glogovac

    2005-12-01

    Full Text Available Humans have a long hystory of stimulating and mind-altering substances use. Depressive drugs, including morphine and other narcotics, barbiturates and ethanol, are strongly addictive for susceptible individuals. The phenomenon is most striking in the case of opiates. Morphine is an alkaloid of opium. Named after the Roman god of dreams, Morpheus, the compound has potent analgesic properties toward all types of pain. By supstitution of two hydroxylic groups of morphine many natural and semysyntetic derivatives with different pharmacological activity and analgesic action are obtained. Determinations and quantifications of narcotic analgesics in drug addicts are important in forensic medicine and clinical toxicology. With development of highly sensitive chromatography technique (HPLC-GC, GH-MS, more and more substances are determined, including opioid drugs: morphine, codeine, dyhydrocodeine, and heroin and 6-monoacetyl morphine. Hair analysys by HPLC/MS spectroscopy is an effective forensic tool for determining the use of abused drugs. The “fingerprint” for heroin in the mixture with the other substances(1-10 components is determined by 1D-TOCSY NMR.

  11. A Prospective Cohort Study Evaluating the Ability of Anticipated Pain, Perceived Analgesic Needs, and Psychological Traits to Predict Pain and Analgesic Usage following Cesarean Delivery

    Directory of Open Access Journals (Sweden)

    Brendan Carvalho

    2016-01-01

    Full Text Available Introduction. This study aimed to determine if preoperative psychological tests combined with simple pain prediction ratings could predict pain intensity and analgesic usage following cesarean delivery (CD. Methods. 50 healthy women undergoing scheduled CD with spinal anesthesia comprised the prospective study cohort. Preoperative predictors included 4 validated psychological questionnaires (Anxiety Sensitivity Index (ASI, Fear of Pain (FPQ, Pain Catastrophizing Scale, and Eysenck Personality Questionnaire and 3 simple ratings: expected postoperative pain (0–10, anticipated analgesic threshold (0–10, and perceived analgesic needs (0–10. Postoperative outcome measures included post-CD pain (combined rest and movement and opioid used for the 48-hour study period. Results. Bivariate correlations were significant with expected pain and opioid usage (r=0.349, anticipated analgesic threshold and post-CD pain (r=-0.349, and perceived analgesic needs and post-CD pain (r=0.313. Multiple linear regression analysis found that expected postoperative pain and anticipated analgesic needs contributed to post-CD pain prediction modeling (R2=0.443, p<0.0001; expected postoperative pain, ASI, and FPQ were associated with opioid usage (R2=0.421, p<0.0001. Conclusion. Preoperative psychological tests combined with simple pain prediction ratings accounted for 44% and 42% of pain and analgesic use variance, respectively. Preoperatively determined expected postoperative pain and perceived analgesic needs appear to be useful predictors for post-CD pain and analgesic requirements.

  12. The changing landscape of opioid prescribing: long-acting and extended-release opioid class-wide Risk Evaluation and Mitigation Strategy

    Directory of Open Access Journals (Sweden)

    Gudin JA

    2012-05-01

    Full Text Available Jeffrey A GudinEnglewood Hospital and Medical Center, Englewood, NJ, USAAbstract: Prescriptions for opioid analgesics to manage moderate-to-severe chronic noncancer pain have increased markedly over the last decade, as have postmarketing reports of adverse events associated with opioids. As an unintentional consequence of greater prescription opioid utilization, there has been the parallel increase in misuse, abuse, and overdose, which are serious risks associated with all opioid analgesics. In response to these concerns, the Food and Drug Administration announced the requirement for a class-wide Risk Evaluation and Mitigation Strategy (REMS for long-acting and extended-release (ER opioid analgesics in April 2011. An understanding of the details of this REMS will be of particular importance to primary care providers. The class-wide REMS is focused on educating health care providers and patients on appropriate prescribing and safe use of ER opioids. Support from primary care will be necessary for the success of this REMS, as these clinicians are the predominant providers of care and the main prescribers of opioid analgesics for patients with chronic pain. Although currently voluntary, future policy will likely dictate that providers undergo mandatory training to continue prescribing medications within this class. This article outlines the elements of the class-wide REMS for ER opioids and clarifies the impact on primary care providers with regard to training, patient education, and clinical practice.Keywords: long-acting opioid, extended-release opioid, risk, REMS, FDA, primary care

  13. Evaluation of the Tolerability of Switching Patients on Chronic Full ?-Opioid Agonist Therapy to Buccal Buprenorphine

    OpenAIRE

    Webster, Lynn; Gruener, Daniel; Kirby, Todd; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew

    2016-01-01

    Objective?Assess whether patients with chronic pain receiving 80 to 220?mg oral morphine sulfate equivalent of a full ?-opioid agonist could be transitioned to buccal buprenorphine at approximately 50% of their full dose without inducing opioid withdrawal or sacrificing analgesic efficacy. Methods.?A randomized, double-blind, double-dummy, active-controlled, two-period crossover study in adult patients receiving around-the-clock full opioid agonist therapy and confirmed to be opioid dependent...

  14. The impact of opioids on the endocrine system.

    Science.gov (United States)

    Katz, Nathaniel; Mazer, Norman A

    2009-02-01

    Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.

  15. Opioid intoxication

    Science.gov (United States)

    ... 2014:chap 162. Lank PM, Kusin S. Ethanol and opioid intoxication and withdrawal. In: Adams JG, ed. Emergency Medicine . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 154. National Institute on Drug Abuse. Opioids. National Institute on Drug Abuse Web site. Updated ...

  16. A preliminary investigation of remifentanil as a labor analgesic.

    Science.gov (United States)

    Olufolabi, A J; Booth, J V; Wakeling, H G; Glass, P S; Penning, D H; Reynolds, J D

    2000-09-01

    In this preliminary investigation, we evaluated the safety and analgesic efficacy of IV remifentanil for labor pain. Four women were studied, and then the trial was terminated because administration of this novel synthetic opioid produced significant maternal side effects in the absence of effective pain control.

  17. Molecular Pharmacology of δ-Opioid Receptors

    Science.gov (United States)

    Gendron, Louis; Cahill, Catherine M.; von Zastrow, Mark; Schiller, Peter W.

    2016-01-01

    Opioids are among the most effective analgesics available and are the first choice in the treatment of acute severe pain. However, partial efficacy, a tendency to produce tolerance, and a host of ill-tolerated side effects make clinically available opioids less effective in the management of chronic pain syndromes. Given that most therapeutic opioids produce their actions via µ-opioid receptors (MOPrs), other targets are constantly being explored, among which δ-opioid receptors (DOPrs) are being increasingly considered as promising alternatives. This review addresses DOPrs from the perspective of cellular and molecular determinants of their pharmacological diversity. Thus, DOPr ligands are examined in terms of structural and functional variety, DOPrs’ capacity to engage a multiplicity of canonical and noncanonical G protein–dependent responses is surveyed, and evidence supporting ligand-specific signaling and regulation is analyzed. Pharmacological DOPr subtypes are examined in light of the ability of DOPr to organize into multimeric arrays and to adopt multiple active conformations as well as differences in ligand kinetics. Current knowledge on DOPr targeting to the membrane is examined as a means of understanding how these receptors are especially active in chronic pain management. Insight into cellular and molecular mechanisms of pharmacological diversity should guide the rational design of more effective, longer-lasting, and better-tolerated opioid analgesics for chronic pain management. PMID:27343248

  18. Tolerance and withdrawal from prolonged opioid use in critically ill children.

    Science.gov (United States)

    Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol

    2010-05-01

    After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

  19. Objective methods for the assessment of the spinal and supraspinal effects of opioids

    DEFF Research Database (Denmark)

    Fischer, Iben W; Hansen, Tine M; Lelic, Dina

    2017-01-01

    by their peak latencies and amplitudes, power spectrum, scalp topographies and brain source localization. For assessment of opioid effects at the spinal level, the following methods are evaluated: the nociceptive withdrawal reflex (NWR) and spinal EPs. The nociceptive withdrawal reflex can be recorded from all......BACKGROUND AND PURPOSE: Opioids are potent analgesics. Opioids exert effects after interaction with opioid receptors. Opioid receptors are present in the peripheral- and central nervous system (CNS), but the analgesic effects are primarily mediated via receptors in the CNS. Objective methods...... for assessment of opioid effects may increase knowledge on the CNS processes responsible for analgesia. The aim of this review was to provide an overview of the most common objective methods for assessment of the spinal and supraspinal effects of opioids and discuss their advantages and limitations. METHOD...

  20. Efficacy of opioid rotation to continuous parenteral hydromorphone in advanced cancer patients failing on other opioids

    NARCIS (Netherlands)

    W.H. Oldenmenger (Wendy); P.J. Lieverse (P. J.); P.J.J.M. Janssen (Paul); W. Taal (Walter); C.C.D. van der Rijt (Carin); A. Jager (Agnes)

    2012-01-01

    textabstractPurpose: The effectiveness of an opioid rotation to parenteral hydromorphone in advanced cancer patients has never been investigated. Therefore, the purpose of this study was to investigate the analgesic efficacy and side effects of parenteral hydromorphone on serious cancer-related

  1. Drug Interaction and Serotonin Toxicity with Opioid Use: Another Reason to Avoid Opioids in Headache and Migraine Treatment.

    Science.gov (United States)

    Ansari, Hossein; Kouti, Leila

    2016-08-01

    Treatment of headache, specifically migraine attacks, has always been a challenging subject, especially for neurologist and pain specialists. Triptans are generally underutilized, despite being the gold standard abortive medication for migraine attacks. On the other hand, opioid analgesics are overused as a treatment for headache. One reason for this could be physician unfamiliarity with drug interactions between opioids and other medications, especially the possibility of serotonin toxicity. The general awareness of potential serotonin toxicity with using opioid analgesics is low. In this review, we will conduct a theoretic and evidence-based review of the potential for developing serotonin syndrome in patients who are using opioids analgesics, especially in combination with antidepressants, a common co-prescribed combination. We also review the current diagnostic criteria for serotonin syndrome and identify possible shortcomings of those criteria. Our aim is to increase the awareness of health care providers about potential drug interaction of opioid analgesics with other classes of medication. We place particular emphasis on tramadol since this drug is one of the most commonly used opioid analgesics for headache. The potential for developing serotonin syndrome is relatively high in the patients who are using opioid for pain control. The use of opioids in migraine headache is already discouraged due to the high risk of medication overuse headache and also an increase in headache-related disability (Katsarava et al. Neurology 62:788-790, 2004; Bigal and Lipton. Neurology 71:1821-8, 2008; Casucci and Cevoli. Neurol Sci. 34 Suppl 1:S125-8, 2013). This is another reason that physicians and health care providers should avoid using this class of medication for pain, specifically headache and migraine treatment.

  2. Is there a role for opioids in the treatment of fibromyalgia?

    Science.gov (United States)

    Littlejohn, Geoffrey O; Guymer, Emma K; Ngian, Gene-Siew

    2016-05-01

    The use of opioids for chronic pain has increased significantly due to a combination of the high patient burden of pain and the more widespread availability of a range of long-acting opioid preparations. This increased opioid use has translated into the care of many patients with fibromyalgia. The pain mechanism in fibromyalgia is complex but does not seem to involve disturbance of opioid analgesic functions. Hence, there is general concern about the harms in the absence of benefits of opioids in this setting. There is no evidence that pure opioids are effective in fibromyalgia but there is some evidence that opioids with additional actions on the norepinephrine-related pain modulatory pathways, such as tramadol, can be clinically useful in some patients. Novel actions of low-dose opioid antagonists may lead to better understanding of the role of opioid function in fibromyalgia.

  3. Repeated Time-to-event Analysis of Consecutive Analgesic Events in Postoperative Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Rasmussen, Sten; Kreilgaard, Mads

    2015-01-01

    BACKGROUND: Reduction in consumption of opioid rescue medication is often used as an endpoint when investigating analgesic efficacy of drugs by adjunct treatment, but appropriate methods are needed to analyze analgesic consumption in time. Repeated time-to-event (RTTE) modeling is proposed as a way...... to describe analgesic consumption by analyzing the timing of consecutive analgesic events. METHODS: Retrospective data were obtained from 63 patients receiving standard analgesic treatment including morphine on request after surgery following hip fracture. Times of analgesic events up to 96 h after surgery...... were extracted from hospital medical records. Parametric RTTE analysis was performed with exponential, Weibull, or Gompertz distribution of analgesic events using NONMEM®, version 7.2 (ICON Development Solutions, USA). The potential influences of night versus day, sex, and age were investigated...

  4. Patterns of Opioid Prescription and Use After Cesarean Delivery.

    Science.gov (United States)

    Bateman, Brian T; Cole, Naida M; Maeda, Ayumi; Burns, Sara M; Houle, Timothy T; Huybrechts, Krista F; Clancy, Caitlin R; Hopp, Stephanie B; Ecker, Jeffrey L; Ende, Holly; Grewe, Kasey; Raposo Corradini, Beatriz; Schoenfeld, Robert E; Sankar, Keerthana; Day, Lori J; Harris, Lynnette; Booth, Jessica L; Flood, Pamela; Bauer, Melissa E; Tsen, Lawrence C; Landau, Ruth; Leffert, Lisa R

    2017-07-01

    To define the amount of opioid analgesics prescribed and consumed after discharge after cesarean delivery. We conducted a survey at six academic medical centers in the United States from September 2014 to March 2016. Women who had undergone a cesarean delivery were contacted by phone 2 weeks after discharge and participated in a structured interview about the opioid prescription they received on discharge and their oral opioid intake while at home. A total of 720 women were enrolled; of these, 615 (85.4%) filled an opioid prescription. The median number of dispensed opioid tablets was 40 (interquartile range 30-40), the median number consumed was 20 (interquartile range 8-30), and leftover was 15 (interquartile range 3-26). Of those with leftover opioids, 95.3% had not disposed of the excess medication at the time of the interview. There was an association between a larger number of tablets dispensed and the number consumed independent of patient characteristics. The amount of opioids dispensed did not correlate with patient satisfaction, pain control, or the need to refill the opioid prescription. The amount of opioid prescribed after cesarean delivery generally exceeds the amount consumed by a significant margin, leading to substantial amounts of leftover opioid medication. Lower opioid prescription correlates with lower consumption without a concomitant increase in pain scores or satisfaction.

  5. Impact of opioid rescue medication for breakthrough pain on the efficacy and tolerability of long-acting opioids in patients with chronic non-malignant pain

    Science.gov (United States)

    Devulder, J.; Jacobs, A.; Richarz, U.; Wiggett, H.

    2009-01-01

    Background There is little evidence that short-acting opioids as rescue medication for breakthrough pain is an optimal long-term treatment strategy in chronic non-malignant pain. We compared clinical studies of long-acting opioids that allowed short-acting opioid rescue medication with those that did not, to determine the impact of opioid rescue medication use on the analgesic efficacy and tolerability of chronic opioid therapy in patients with chronic non-malignant pain. Methods We searched MEDLINE (1950 to July 2006) and EMBASE (1974 to July 2006) using terms for chronic non-malignant pain and long-acting opioids. Independent review of the search results identified 48 studies that met the study selection criteria. The effect of opioid rescue medication on analgesic efficacy and the incidence of common opioid-related side-effects were analysed using meta-regression. Results After adjusting for potentially confounding variables (study design and type of opioid), the difference in analgesic efficacy between the ‘rescue’ and the ‘no rescue’ studies was not significant, with regression coefficients close to 0 and 95% confidence intervals that excluded an effect of more than 18 points on a 0–100 scale in each case. There was also no significant difference between the ‘rescue’ and the ‘no rescue’ studies for the incidence of nausea, constipation, or somnolence in both the unadjusted and the adjusted analyses. Conclusions We found no evidence that rescue medication with short-acting opioids for breakthrough pain affects analgesic efficacy of long-acting opioids or the incidence of common opioid-related side-effects among chronic non-malignant pain patients. PMID:19736216

  6. Current Research on Opioid Receptor Function

    Science.gov (United States)

    Feng, Yuan; He, Xiaozhou; Yang, Yilin; Chao, Dongman; Lazarus, Lawrence H.; Xia, Ying

    2012-01-01

    The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (μ-opioid receptor, MOR; δ-opioid receptor, DOR; and κ-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes is still unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of membrane ionic homeostasis, cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders. In some species, they play an essential role in hibernation. One of the most exciting findings of the past decade is the opioid-receptor, especially DOR, mediated neuroprotection and cardioprotection. The up-regulation of DOR expression and DOR activation increase the neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers (depending on stress duration and severity) different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of homeostasis and increased pro-survival signaling (e.g., PKC-ERK-Bcl 2) and anti-oxidative capacity. In the heart, PKC and KATP channels are involved in the opioid receptor-mediated cardioprotection. The DOR-mediated neuroprotection and cardioprotection have the potential to significantly alter the clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this article

  7. The pharmacology of topical analgesics.

    Science.gov (United States)

    Barkin, Robert L

    2013-07-01

    Pain management of patients continues to pose challenges to clinicians. Given the multiple dimensions of pain--whether acute or chronic, mild, moderate, or severe, nociceptive or neuropathic--a multimodal approach may be needed. Fortunately, clinicians have an array of nonpharmacologic and pharmacologic treatment choices; however, each modality must be chosen carefully, because some often used oral agents are associated with safety and tolerability issues that restrict their use in certain patients. In particular, orally administered nonsteroidal antiinflammatory drugs, opioids, antidepressants, and anticonvulsants are known to cause systemic adverse effects in some patients. To address this problem, a number of topical therapies in various therapeutic classes have been developed to reduce systemic exposure and minimize the risks of patients developing adverse events. For example, topical nonsteroidal anti-inflammatory drug formulations produce a site-specific effect (ie, cyclo-oxygenase inhibition) while decreasing the systemic exposure that may lead to undesired effects in patients. Similarly, derivatives of acetylsalicylic acid (ie, salicylates) are used in topical analgesic formulations that do not significantly enter the patient's systemic circulation. Salicylates, along with capsaicin, menthol, and camphor, compose the counterirritant class of topical analgesics, which produce analgesia by activating and then desensitizing epidermal nociceptors. Additionally, patches and creams that contain the local anesthetic lidocaine, alone or co-formulated with other local anesthetics, are also used to manage patients with select acute and chronic pain states. Perhaps the most common topical analgesic modality is the cautious application of cutaneous cold and heat. Such treatments may decrease pain not by reaching the target tissue through systemic distribution, but by acting more directly on the affected tissue. Despite the tolerability benefits associated with avoiding

  8. Rescuing Our Warriors from Chronic Pain: A Battlefield-to-Nondeployment Means to Prevent Opioid-induced Amplification of Neuropathic Pain from Traumatic Injury

    Science.gov (United States)

    2017-10-01

    agility, suggesting that the decrease in voluntary exercise is due to loss of motivation or pain amplification rather than physical disability . We... disability 15 Sep 2016 - 14 Sep 2017 15. SUBJECT TERMS chronic pain, opioid analgesics, non-opioid analgesics, toll-like receptor 4, return to duty 16...of the project? 1. Define whether deleterious effects of opioids extend beyond neuropathic pain to other indices of disability . Determine

  9. Electrocatalytic oxidation and selective determination of an opioid analgesic methadone in the presence of acetaminophen at a glassy carbon electrode modified with functionalized multi-walled carbon nanotubes: application for human urine, saliva and pharmaceutical samples analysis.

    Science.gov (United States)

    Amiri-Aref, Mohaddeseh; Raoof, Jahan Bakhsh; Ojani, Reza

    2013-09-01

    For the first time, electrocatalytic oxidation and selective determination of methadone (Mtd), as a long-acting opioid, in the presence of acetaminophen (Ac) has been investigated at a glassy carbon electrode modified with functionalized multi-walled carbon nanotubes. This simple and sensitive electrochemical sensor was fabricated through the drop-casting of functionalized multi-walled carbon nanotubes (fMWCNT) on the surface of a glassy carbon electrode (GCE). The electrocatalytic oxidations of Ac and Mtd are both individually and simultaneously investigated at the surface of the fMWCNT modified glassy carbon electrode (fMWCNT/MGCE) through using cyclic and differential pulse voltammetric studies. The fMWCNT/MGCE offered a considerable enhancement in the anodic peak current of Ac and Mtd associated with separating their overlapping voltammetric responses with potential difference of 290 mV. The catalytic peak currents obtained from differential pulse voltammetry of Ac and Mtd increased linearly with their concentration at the ranges of 0.45-90.0 μM and 0.5-100.0 μM, respectively, and the detection limits for Ac and Mtd were sequentially 0.35 μM and 0.28 μM. Furthermore, this electrochemical sensor was successfully implemented for the quantitative determination of Ac and Mtd in human urine, saliva and pharmaceutical samples using standard addition method and the obtained results were found to be satisfactory. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Association Between Human Pain-Related Genotypes and Variability in Opioid Analgesia

    DEFF Research Database (Denmark)

    Nielsen, Lecia M; Olesen, Anne Estrup; Branford, Ruth

    2015-01-01

    On an individual level, there is a difference in the analgesic response to a given opioid. Various factors such as gender, age, and genetic variation can affect the analgesic response. The genetic variation can influence pharmacokinetics (eg drug transporters and drug-metabolizing enzymes) and...... as opioid consumption or changes in pain scores. Studies have shown promising results regarding pharmacogenetics as a diagnostic tool for predicting the individual response to a given opioid in the experimental settings; however, in the clinic, it is a more complicated task to accomplish....

  11. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics.

    Science.gov (United States)

    Johnson, Jeremy R; Lossignol, Dominique; Burnell-Nugent, Mary; Fallon, Marie T

    2013-08-01

    Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc

  12. Understanding the Opioid Epidemic

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Opioid Overdose Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Opioid Overdose Opioid Basics Understanding the Epidemic Commonly Used ...

  13. Synergistic interaction between mazindol, an anorectic drug, and swim-stress on analgesic responses in the formalin test in mice.

    Science.gov (United States)

    Vendruscolo, Leandro Franco; Takahashi, Reinaldo Naoto

    2004-01-23

    The present study examined the interaction between mazindol (MZ), an anorectic drug extensively used in Brazil and opioid/non-opioid endogenous analgesic systems activated by swim-stress. Further, the role of opioid, dopamine and N-methyl-D-aspartate (NMDA) receptors in mediating the analgesic effect was evaluated. The stress-induced analgesia of a 3-min swimming at 32 degrees C (opioid/non-opioid) and 20 degrees C (non-opioid) were assessed using the formalin test. Male Swiss mice were intraperitoneally injected with naloxone (1.0 mg/kg), sulpiride (3.0 mg/kg), MK-801 (0.075 mg/kg) or saline/vehicle 15 min prior, and with MZ (0.5 mg/kg) or saline/vehicle 5 min prior to swimming. The dose of MZ (0.5 mg/kg) did not cause analgesic effect, however, the association of MZ and swim-stress at both temperatures displayed synergistic interaction on analgesia that was blocked by sulpiride and MK-801 but not by naloxone. The present results suggest that MZ and swim-stress acted synergistically on analgesic responses, involving mainly the non-opioid component and possibly mediated by dopamine D2 receptors and NMDA receptors.

  14. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

    DEFF Research Database (Denmark)

    Dahl, J B; Nielsen, R V; Wetterslev, J

    2014-01-01

    , and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists......, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin....... Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all...

  15. Endogenous Opioid Function and Responses to Morphine: The Moderating Effects of Anger Expressiveness.

    Science.gov (United States)

    Burns, John W; Bruehl, Stephen; France, Christopher R; Schuster, Erik; Orlowska, Daria; Chont, Melissa; Gupta, Rajnish K; Buvanendran, Asokumar

    2017-08-01

    Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects. For individuals with chronic pain and healthy control participants, those with low endogenous opioid function and low anger-out scores exhibited the largest morphine analgesic responses, whereas those with high anger-out and low endogenous opioid function showed relatively weaker morphine analgesic responses. Further, individuals with chronic pain with low endogenous opioid function and low anger-out scores also reported the fewest negative effects to morphine, whereas those with low endogenous opioid function and high anger-out reported the most. Findings point toward individuals with chronic pain who may strike a favorable balance of good analgesia with few side effects, as well as those who have an unfavorable balance of poor analgesia and many side effects. We sought to identify optimal candidates for opioid pain management. Low back pain patients who express anger and also have deficient endogenous opioid function may be poor candidates for opioid therapy. In contrast, low back patients who tend not to express anger and who also have deficient endogenous opioid function may make optimal candidates for opioid therapy. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  16. Cholera toxin-B subunit blocks excitatory opioid receptor-mediated hyperalgesic effects in mice, thereby unmasking potent opioid analgesia and attenuating opioid tolerance/dependence.

    Science.gov (United States)

    Shen, K F; Crain, S M

    2001-11-16

    In a previous study we demonstrated that injection (i.p.) of low doses of GM1 ganglioside in mice rapidly attenuates morphine's analgesic effects. This result is consonant with our electrophysiologic studies in nociceptive types of dorsal root ganglion (DRG) neurons in culture, which showed that exogenous GM1 rapidly increased the efficacy of excitatory (Gs-coupled) opioid receptor functions. By contrast, treatment of DRG neurons with the non-toxic B-subunit of cholera toxin (CTX-B) which binds selectively to GM1, blocked the excitatory, but not inhibitory, effects of morphine and other bimodally-acting opioid agonists, thereby resulting in a net increase in inhibitory opioid potency. The present study provides more direct evidence that endogenous GM1 plays a physiologic role in regulating excitatory opioid receptor functions in vivo by demonstrating that cotreatment with remarkably low doses of CTX-B (10 ng/kg, s.c.) selectively blocks hyperalgesic effects elicited by morphine or by a kappa opioid agonist, thereby unmasking potent opioid analgesia. These results are comparable to the effects of cotreatment of mice with morphine plus an ultra-low dose of the opioid antagonist, naltrexone (NTX) which blocks opioid-induced hyperalgesic effects, unmasking potent opioid analgesia. Low-dose NTX selectively blocks excitatory opioid receptors at their recognition site, whereas CTX-B binds to, and interferes with, a putative allosteric GM1 regulatory site on excitatory opioid receptors. Furthermore, chronic cotreatment of mice with morphine plus CTX-B attenuates development of opioid tolerance and physical dependence, as previously shown to occur during cotreatment with low-dose NTX.

  17. Altered Frequency Distribution in the Electroencephalogram is Correlated to the Analgesic Effect of Remifentanil

    DEFF Research Database (Denmark)

    Graversen, Carina; Malver, Lasse P; Kurita, Geana P

    2015-01-01

    Opioids alter resting state brain oscillations by multiple and complex factors, which are still to be elucidated. To increase our knowledge, multi-channel electroencephalography (EEG) was subjected to multivariate pattern analysis (MVPA), to identify the most descriptive frequency bands and scalp...... remifentanil treatment. As the EEG alterations were correlated to the analgesic effect, the approach may prove to be a novel methodology for monitoring individual efficacy to opioids....

  18. ORAL OPIOIDS IN THE TREATMENT OF CANCER PAIN

    NARCIS (Netherlands)

    ZYLICZ, Z; TWYCROSS, RG

    Persistent severe cancer pain should be treated with opioid drugs, principally morphine. It can be administered orally, rectally and parenterally. Morphine is metabolised in the liver mainly to glucuronides, of which morphine-6-glucuronide is a powerful analgesic. Oral morphine should be

  19. Abuse liability, behavioral pharmacology, and physical-dependence potential of opioids in humans and laboratory animals: lessons from tramadol

    OpenAIRE

    Epstein, David H.; Preston, Kenzie L.; Jasinski, Donald R.

    2006-01-01

    Assessment of abuse potential of opioid analgesics has a long history in both laboratory animals and humans. This article reviews the methods used in animals and in humans and then presents the data collected in the evaluation of tramadol, an atypical centrally acting opioid analgesic approved for marketing in the United States in 1998. Finally, data on the abuse of tramadol from postmarketing surveillance and case reports are presented. The consistency between animal and human study results ...

  20. Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor.

    Science.gov (United States)

    Che, Tao; Majumdar, Susruta; Zaidi, Saheem A; Ondachi, Pauline; McCorvy, John D; Wang, Sheng; Mosier, Philip D; Uprety, Rajendra; Vardy, Eyal; Krumm, Brian E; Han, Gye Won; Lee, Ming-Yue; Pardon, Els; Steyaert, Jan; Huang, Xi-Ping; Strachan, Ryan T; Tribo, Alexandra R; Pasternak, Gavril W; Carroll, F Ivy; Stevens, Raymond C; Cherezov, Vadim; Katritch, Vsevolod; Wacker, Daniel; Roth, Bryan L

    2018-01-11

    The κ-opioid receptor (KOP) mediates the actions of opioids with hallucinogenic, dysphoric, and analgesic activities. The design of KOP analgesics devoid of hallucinatory and dysphoric effects has been hindered by an incomplete structural and mechanistic understanding of KOP agonist actions. Here, we provide a crystal structure of human KOP in complex with the potent epoxymorphinan opioid agonist MP1104 and an active-state-stabilizing nanobody. Comparisons between inactive- and active-state opioid receptor structures reveal substantial conformational changes in the binding pocket and intracellular and extracellular regions. Extensive structural analysis and experimental validation illuminate key residues that propagate larger-scale structural rearrangements and transducer binding that, collectively, elucidate the structural determinants of KOP pharmacology, function, and biased signaling. These molecular insights promise to accelerate the structure-guided design of safer and more effective κ-opioid receptor therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Analgesic-Related Medication Errors Reported to US Poison Control Centers.

    Science.gov (United States)

    Eluri, Madhulika; Spiller, Henry A; Casavant, Marcel J; Chounthirath, Thitphalak; Conner, Kristen A; Smith, Gary A

    2017-11-23

    This study investigates the characteristics and trends of medication errors involving analgesic medications. A retrospective analysis was conducted of analgesic-related medication errors reported to the National Poison Data System (NPDS) from 2000 through 2012. From 2000 through 2012, the NPDS received 533,763 reports of analgesic-related medication errors, averaging 41,059 medication errors annually. Overall, the rate of analgesic-related medication errors reported to the NPDS increased significantly by 82.6% from 2000 to 2009, followed by a 5.7% nonsignificant decrease from 2009 to 2012. Among the analgesic categories, rates of both acetaminophen-related and opioid-related medication errors reported to the NPDS increased during 2000-2009, but the opioid error rate leveled off during 2009-2012, while the acetaminophen error rate decreased by 17.9%. Analgesic-related medication errors involved nonsteroidal anti-inflammatory drugs (37.0%), acetaminophen (35.5%), and opioids (23.2%). Children five years or younger accounted for 38.8% of analgesics-related medication errors. Most (90.2%) analgesic-related medication errors were managed on-site, rather than at a health care facility; 1.6% were admitted to a hospital, and 1.5% experienced serious medical outcomes, including 145 deaths. The most common type of medication error was inadvertently taking/given the medication twice (26.6%). Analgesic-related medication errors are common, and although most do not result in clinical consequences, they can have serious adverse outcomes. Initiatives associated with the decrease in acetaminophen-related medication errors among young children merit additional research and potential replication as a model combining government policy and multisectoral collaboration.

  2. Analgesic effect of the aqueous and ethanolic extracts of clove

    Directory of Open Access Journals (Sweden)

    Mina Kamkar Asl

    2013-04-01

    Full Text Available Objective: The beneficial effects of clove on toothache have been well documented. We have also previously shown the analgesic effects of clove essential oil. The present work was done to investigate the analgesic effects of the aqueous extract of clove using hot plate test. The possible role of opioid receptors in the analgesic effects of clove was also investigated using naloxone. Materials and Methods: Ninety male mice were divided into nine groups: (1 Saline, (2-4 Aaqueous (Aq 50, Aq 100, and Aq 200 groups which were treated with 50, 100, and 200 mg/kg of aqueous extract of clove, respectively, (5-7 Ethanolic (Eth 50, Eth 100, and Eth 200 groups which were treated with 50, 100, and 200 mg/kg of ethanolic extract of clove, respectively, and (8-9 Aq 100- Naloxone and Aq 200- Naloxone which were pretreated with 4 mg/kg of naloxone before injection of 100 or 200 mg/kg of the aqueous extract. The hot plate test was performed as a base record 10 min before injection of drugs and consequently repeated every 10 minutes after the injection. Results: The maximal percent effect (MPE in the animal groups treated with 50, 100, and 200 mg/kg of aqueous extract was significantly higher than the control group. Pretreatment with naloxone reduced the analgesic effects of both 100 and 200 mg/kg of the aqueous extract. Administration of all three doses of the ethanloic extract also non-significantly increased the MPE. Conclusion: The results of the present study showed that aqueous extract of clove has analgesic effect in mice demonstrated by hot plate test which is reversible by naloxone. The role of opioid system in the analgesic effect of clove might be suggested. However, more investigations are needed to elucidate the exact mechanism(s.

  3. The use of analgesic drugs by South African veterinarians : continuing education

    OpenAIRE

    K.E. Joubert

    2001-01-01

    According to a survey, non-steroidal anti-inflammatory agents were the most popular analgesic used in South Africa for management of peri-operative pain, acute post-operative pain and chronic pain. The most popular non-steroidal anti-inflammatory agents are flunixin meglumine and phenylbutazone. The most popular opioid type drug is buprenorphine, followed by morphine. In the peri-operative setting, analgesic agents were not actively administered to 86.3 % of cats and 80.7 % of dogs. Analgesic...

  4. High-affinity naloxone binding to filamin a prevents mu opioid receptor-Gs coupling underlying opioid tolerance and dependence.

    Directory of Open Access Journals (Sweden)

    Hoau-Yan Wang

    Full Text Available Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs by the mu opioid receptor (MOR, although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565 as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565 abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence.

  5. High-Affinity Naloxone Binding to Filamin A Prevents Mu Opioid Receptor–Gs Coupling Underlying Opioid Tolerance and Dependence

    Science.gov (United States)

    Wang, Hoau-Yan; Frankfurt, Maya; Burns, Lindsay H.

    2008-01-01

    Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [3H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [3H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A2561-2565 as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A2561-2565 abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor–Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence. PMID:18253501

  6. High-affinity naloxone binding to filamin a prevents mu opioid receptor-Gs coupling underlying opioid tolerance and dependence.

    Science.gov (United States)

    Wang, Hoau-Yan; Frankfurt, Maya; Burns, Lindsay H

    2008-02-06

    Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3)H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3)H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565) as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565) abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence.

  7. Pregabalin for Opioid-Refractory Pain in a Patient with Ankylosing Spondylitis

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    Konstantinos A. Kontoangelos

    2013-01-01

    Full Text Available Background. Ankylosing spondylitis (AS is a systemic inflammatory disease with chronic back pain as the most common presenting symptom. We present a case of a male patient with AS reporting symptoms of severe low back pain, buttock pain, and limited spinal mobility. After chronic treatment with opioids, we administered pregabalin at a dose of 300 mg as an analgesic agent while opioids were discontinued. Findings. Pain symptoms improved progressively, and opioids were gradually discontinued without any withdrawal symptoms reported. Conclusions. Pregabalin is potentially useful in the management of pain in patients with AS while effectively managing the discontinuation of opioid treatment.

  8. Analgesic Potential of Opuntia dillenii and Its Compounds Opuntiol and Opuntioside Against Pain Models in Mice

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    Faheema Siddiqui

    2016-05-01

    Full Text Available Opuntia dillenii (Nagphana traditionally used against inflammation and also possess analgesic effect. Thus in the present study analgesic properties of O. dillenii cladode methanol extract, its fractions obtained via vacuum liquid chromatography along with isolated α-pyrones, opuntiol and its glucoside, opuntioside were analyzed. The acetic acid-induced writhes were reduced by O. dillenii test agents with opuntioside being most effective (IC 50 26 ± 0.9 mg/kg and equipotent to diclofenac and β-sitosterol. Consistently, it also elicited most potent effect (IC 50: 28 ± 1.1 and 24 ± 1.2 mg/kg during early and late phases of formalin-induced paw licking, producing effect similar to diclofenac and indomethacin. It was also most effective in hot plate test. Naloxone (opioid antagonist reversed the analgesic effects of extract and fractions but failed to antagonize the opuntiol and opuntioside analgesic effects. In conclusion, edible O. dillenii extract, its fractions, opuntiol and opuntioside reduced peripheral and centrally mediated pain via opioid dependent and independent systems. Among them opuntioside emerged as most effective analgesic possibly due to the presence of glucose moiety at position 7 of its α-pyrone ring. This is the first report of opuntiol and opuntioside analgesic effect which may serve as lead compounds in designing of new analgesics.

  9. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty

    DEFF Research Database (Denmark)

    Andersen, Lasse Østergaard; Kehlet, H

    2014-01-01

    the analgesic efficacy of LIA for early postoperative pain treatment. In addition, the analgesic efficacy of wound catheters and implications for length of hospital stay (LOS) were evaluated. Twenty-seven randomized controlled trials in 756 patients operated on with THA and 888 patients operated on with TKA...... were selected for inclusion in the review. In THA, no additional analgesic effect of LIA compared with placebo was reported in trials with low risk of bias when a multimodal analgesic regimen was administered perioperatively. Compared with intrathecal morphine and epidural analgesia, LIA was reported...... to have similar or improved analgesic efficacy. In TKA, most trials reported reduced pain and reduced opioid requirements with LIA compared with a control group treated with placebo/no injection. Compared with femoral nerve block, epidural or intrathecal morphine LIA provided similar or improved analgesia...

  10. Study of analgesic activity of ethanol extract of Phlogacanthus thyrsiflorus on experimental animal models

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    Apurba Mukherjee

    2009-06-01

    Full Text Available The aim of the study was to evaluate the central and peripheral analgesic action of Phlogacanthus thyrsiflorus in experimental animal models. The extract was prepared by percolation method and acute oral toxicity testing was performed as per OECD guidelines. Analgesic activity was assessed by tail flick method (for central action and glacial acetic acid-induced writhing test (for peripheral action. Leaves extract (500 mg/kg, p.o. and aspirin (100 mg/kg showed significant peripheral analgesic activity (p<0.05. Leaves extract (500 mg/kg, p.o. and pethidine (50 mg/kg, i.p. also showed significant central analgesic activity (p<0.05. Naloxone (1 mg/kg, s.c. was used to find the mechanism of central analgesic action. Some partial agonistic activity for the opioid receptors seems to be probable mechanism of action.

  11. Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast).

    Science.gov (United States)

    Hutchinson, Mark R; Lewis, Susannah S; Coats, Benjamen D; Skyba, David A; Crysdale, Nicole Y; Berkelhammer, Debra L; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M; Judd, Charles M; Maier, Steven F; Watkins, Linda R; Johnson, Kirk W

    2009-02-01

    Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused three-to-five-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, while improving analgesia.

  12. Analgesic effects of melatonin

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J

    2011-01-01

    has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...

  13. Neonatal opioid withdrawal syndrome.

    Science.gov (United States)

    Sutter, Mary Beth; Leeman, Lawrence; Hsi, Andrew

    2014-06-01

    Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy

    DEFF Research Database (Denmark)

    Søndergaard, Jens; Christensen, Helene Nordahl; Ibsen, Rikke

    2017-01-01

    Background and aim Opioid analgesics are often effective for pain management, but may cause constipation. The aim of this study was to determine healthcare resource use and costs in non-cancer and cancer patients with opioid-induced constipation (OIC). Methods This was a nationwide register......-based cohort study including patients ≥18 years of age initiating ≥4 weeks opioid therapy (1998–2012) in Denmark. A measure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain......, marital status, and comorbidities using Generalised Linear Model. Results We identified 97 169 eligible opioid users (77 568 non-cancer and 19 601 patients with a cancer diagnosis). Among non-cancer patients, 15% were classified with OIC, 10% had previous constipation, and 75% were without OIC. Patients...

  15. Prescription Opioids during Pregnancy

    Science.gov (United States)

    ... include codeine, morphine and oxycodone. If you take opioids during pregnancy, they can cause serious problems for your baby, like premature birth and drug withdrawal called NAS. Even if you use an opioid ...

  16. Prescription Pain Medications (Opioids)

    Science.gov (United States)

    ... who take them as prescribed by a doctor. Opioid withdrawal can cause: restlessness muscle and bone pain sleep ... View Online Download PDF Dramatic Increases in Maternal Opioid Use ... in a drug withdrawal syndrome in newborns called neonatal abstinence syndrome (NAS). ...

  17. Prediction of opioid dose in cancer pain patients using genetic profiling

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Grønlund, Debbie; Gram, Mikkel

    2018-01-01

    investigated whether data processing with support vector machine learning could predict required opioid dose in cancer pain patients, using genetic profiling. Eighteen single nucleotide polymorphisms (SNPs) within the µ and δ opioid receptor genes and the catechol-O-methyltransferase gene were selected......OBJECTIVE: Use of opioids for pain management has increased over the past decade; however, inadequate analgesic response is common. Genetic variability may be related to opioid efficacy, but due to the many possible combinations and variables, statistical computations may be difficult. This study...... for analysis. RESULTS: Data from 1237 cancer pain patients were included in the analysis. Support vector machine learning did not find any associations between the assessed SNPs and opioid dose in cancer pain patients, and hence, did not provide additional information regarding prediction of required opioid...

  18. Is mechanism and symptom-based analgesia an answer to opioid-Induced hyperalgesia?

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    Mayank Gupta

    2015-01-01

    Full Text Available "Cancer Pain" and "Pain in cancer patient" are not synonymous. Opioid-induced Hyperalgesia (OIH is a paradoxical state of nociceptive sensitization caused by exposure to opioids. Neuropathic pain is only partially responsive to opioids; injudicious increase in dose of opioids in neuropathic pain may not only result in inadequate pain relief but also OIH. Majority of literature on OIH is in non-cancer pain with systemic use of opioids. We describe the development and successful treatment of OIH in a 55-year-old male patient with Small cell Carcinoma Lung. Opioid tapering, rotation, systemic desensitization helps in combatting OIH. The use of anti-neuropathic adjuvant analgesics helps not only in preventing and treating OIH but also in understanding putative mechanisms underlying neuropathic pain and OIH.

  19. Postoperative analgesic efficacy of intravenous dexketoprofen in lumbar disc surgery.

    Science.gov (United States)

    Yazar, Mehmet Akif; Inan, Nurten; Ceyhan, Aysegul; Sut, Esra; Dikmen, Bayazit

    2011-07-01

    We investigated the postoperative analgesic efficacy and effect on total tramadol consumption of intravenous dexketoprofen trometamol, a new nonsteroidal anti-inflammatory drug, in patients that had undergone lumbar disc surgery. Sixty patients were included in this placebo-controlled, randomized, double-blind study. General anesthesia was applied to both groups. Group D (n=30) received dexketoprofen (50 mg) intravenously 30 minutes before the end of surgery and at the postoperative 12th hour, whereas group C (n=30) received 2 mL of 0.9% NaCL intravenously at the same time points. All patients received a patient controlled analgesia device with a tramadol, 25 mg bolus, 15 minutes lockout protocol, and were followed with visual analog scale, verbal rating scale, modified Aldrete recovery scoring system, and Ramsay sedation scale in the postoperative period. There was no significant difference between the groups for demographic data, duration of surgery, mean arterial pressure, and heart rate. The time to first postoperative analgesic requirement was significantly longer in group D (151.33±81.98 min) than group C (19±5.78 min) (Pdexketoprofen was an effective analgesic for postdiscectomy pain when used alone or in addition to opioids. It is easy to administer and decreases tramadol consumption and opioid-related side effects.

  20. Pain in the management of opioid use disorder

    Directory of Open Access Journals (Sweden)

    Sirohi S

    2016-11-01

    Full Text Available Sunil Sirohi,1 Amit K Tiwari21Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, 2Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USAOpioids remain the drug of choice for the clinical management of moderate to severe pain. However, in addition to their most effective analgesic actions, opioids also produce a sense of well-being and euphoria, which may trigger significant concerns associated with their use.1 In fact, there has been an alarming increase in prescription opioid use, abuse and illicit use; and according to the National Center for Health Statistics, the total number of deaths related to opioid overdose has more than tripled from 2011 to 2014.2–5 Although representing 5.0 % of the global population, studies report that Americans consume 80% of the global opioid supply,3 and the United States is experiencing an opioid abuse epidemic.6 Considering this unprecedented rise in opioid consumption, the United States Centers for Disease Control and Prevention has listed prescription opioid overdose among one of the 10 most important public health problems in all the 50 states.7

  1. Methylnaltrexone in the treatment of opioid-induced constipation

    Directory of Open Access Journals (Sweden)

    Beverley Greenwood-Van Meerveld

    2008-12-01

    Full Text Available Beverley Greenwood-Van Meerveld1, Kelly M Standifer21Veterans Affairs Medical Center, Oklahoma Center for Neuroscience, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Department of Pharmaceutical Sciences, Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: Constipation is a significant problem related to opioid medications used to manage pain. This review attempts to outline the latest findings related to the therapeutic usefulness of a μ opioid receptor antagonist, methylnaltrexone in the treatment of opioid-induced constipation. The review highlights methylnaltrexone bromide (RelistorTM; Progenics/Wyeth a quaternary derivative of naltrexone, which was recently approved in the United States, Europe and Canada. The Food and Drug Administration in the United States approved a subcutaneous injection for the treatment of opioid bowel dysfunction in patients with advanced illness who are receiving palliative care and when laxative therapy has been insufficient. Methylnaltrexone is a peripherally restricted, μ opioid receptor antagonist that accelerates oral–cecal transit in patients with opioidinduced constipation without reversing the analgesic effects of morphine or inducing symptoms of opioid withdrawal. An analysis of the mechanism of action and the potential benefits of using methylnaltrexone is based on data from published basic research and recent clinical studies.Keywords: methylnaltrexone, constipation, opioid

  2. Analysis of opioid consumption in clinical trials: a simulation based analysis of power of four approaches

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Nyberg, Joakim; Kreilgaard, Mads

    2017-01-01

    Inconsistent trial design and analysis is a key reason that few advances in postoperative pain management have been made from clinical trials analyzing opioid consumption data. This study aimed to compare four different approaches to analyze opioid consumption data. A repeated time-to-event (RTTE......) model in NONMEM was used to simulate clinical trials of morphine consumption with and without a hypothetical adjuvant analgesic in doses equivalent to 15-62% reduction in morphine consumption. Trials were simulated with duration of 24-96 h. Monte Carlo simulation and re-estimation were performed...... of potency was obtained with a RTTE model accounting for both morphine effects and time-varying covariates on opioid consumption. An RTTE analysis approach proved better suited for demonstrating efficacy of opioid sparing analgesics than traditional statistical tests as a lower sample size was required due...

  3. Trends in analgesic exposures reported to Texas Poison Centers following increased regulation of hydrocodone.

    Science.gov (United States)

    Haynes, Ashley; Kleinschmidt, Kurt; Forrester, Mathias B; Young, Amy

    2016-06-01

    In October 2014, the Drug Enforcement Administration reclassified hydrocodone to schedule II, increasing regulations on use. The impact of rescheduling hydrocodone on opioid exposures is unclear, especially in states with special restrictions required for prescribing schedule II agents. To assess whether changes in exposures to prescription opioid analgesics and heroin as reported to poison centers occurred in the 6 months after hydrocodone rescheduling. We hypothesized that hydrocodone exposures would decrease, while less tightly regulated opioids, such as codeine and tramadol, would increase. This study compares opioid analgesic exposures reported to Texas Poison Centers before and after this change in a state that requires special prescription pads for Schedule II agents. Cases included all opioid analgesic exposures reported to a statewide poison center network, comparing exposures from 6 months before to 6 months after heightened regulations. Specific opioids with large changes in reported exposures were further characterized by patient age and exposure intent. Hydrocodone exposures decreased from 1567 to 1135 (28%, p = 0.00017), decreasing for all ages. Codeine exposures increased significantly from 189 to 522 (176%, p = 0.00014), including a 263% increase for age >20 years. Codeine misuse increased 443% and adverse drug events 327%. Oxycodone exposures increased from 134 to 189 (39%, p = 0.0143), increasing only among patients age >20 years. Reported heroin exposures increased from 156 to 179 (15%, p = 0.2286) and tramadol from 666 to 708 (6%, p = 0.0193). Other opioid exposures changed little or had limited reports. The increased regulation of hydrocodone was followed temporally by a decrease in reported hydrocodone exposures, but also increases in codeine, oxycodone and tramadol exposures. This may reflect a shift in prescribing practices, changes in street availability of hydrocodone or decreased drug diversion. The increased

  4. Nanoconjugated NAP as a Potent and Periphery Selective Mu Opioid Receptor Modulator To Treat Opioid-Induced Constipation.

    Science.gov (United States)

    Xu, Guoyan G; Zolotarskaya, Olga Yu; Williams, Dwight A; Yuan, Yunyun; Selley, Dana E; Dewey, William L; Akbarali, Hamid I; Yang, Hu; Zhang, Yan

    2017-01-12

    Opioids are the mainstay for cancer and noncancer pain management. However, their use is often associated with multiple adverse effects. Among them, the most common and persistent one is probably opioid-induced constipation (OIC). Periphery selective opioid antagonists may alleviate the symptoms of OIC without compromising the analgesic effects of opioids. Recently our laboratories have identified one novel lead compound, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl)acetamido]morphinan (NAP), as a peripherally selective mu opioid receptor ligand carrying subnanomolar affinity to the mu opioid receptor and over 100-folds of selectivity over both the delta and kappa opioid receptors, with reasonable oral availability and half-life, and potential to treat OIC. Nanoparticle-based drug delivery systems are now widely considered due to their technological advantages such as good stability, high carrier capacity, low therapeutic side effects, etc. Herein we report nanoparticle supported NAP as a potential candidate for OIC treatment with improved peripheral selectivity over the original lead compound NAP.

  5. Development and validation of an Opioid Attractiveness Scale: a novel measure of the attractiveness of opioid products to potential abusers

    Directory of Open Access Journals (Sweden)

    Fernandez Kathrine C

    2006-02-01

    Full Text Available Abstract Background The growing trends in opioid abuse, assessment of the abuse liability of prescription opioid products, and growing efforts by the pharmaceutical industry to develop 'abuse-resistant' formulations highlight a need to understand the features that make one product more 'attractive' than another to potential abusers. We developed a scale to measure the 'attractiveness' of prescription opioids to potential abusers, and used the scale to measure the relative attractiveness of 14 opioid analgesic products. Methods First, the concept of attractiveness was empirically defined with a group of prescription opioid abusers and experts in opioid abuse using a process called Concept Mapping. Abuse liability consisted of two components: factors intrinsic to the drug formulation (e.g., speed of onset, duration and factors extrinsic to drug formulation (e.g., availability, availability of alternatives, cost. A 17-item Opioid Attractiveness Scale (OAS was constructed, focusing on factors intrinsic to the drug product. Results A total of 144 individuals participated in tests of validity and reliability. Internal consistency was excellent (Cronbach's α = 0.85–0.94. Drug rankings based on OAS scores achieved good inter-rater agreement (Kendall's W 0.37, p Conclusion An initial examination of the psychometric properties of the OAS suggests that it is a valid and reliable scale. The OAS may be useful in providing important guidance on product features that are attractive to potential abusers.

  6. Opioid Overdose Education for Individuals Prescribed Opioids for Pain Management: Randomized Comparison of Two Computer-Based Interventions

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    Andrew S. Huhn

    2018-02-01

    Full Text Available BackgroundOpioid overdose (OD rates in the United States have reached unprecedented levels. Current OD prevention strategies largely consist of distribution of naloxone and in-person trainings, which face obstacles to expedient, widespread dissemination. Web-based interventions have increased opioid-OD response knowledge in patients with opioid-use disorders; however, these interventions have not been tested in the larger population of individuals that are prescribed opioid analgesics. This study assessed a web-based intervention providing education across three knowledge domains: opioid effects, opioid-OD symptoms, and opioid-OD response.MethodsParticipants (N = 197 were adults recruited on Amazon Mechanical Turk from May to June 2017, who were prescribed an opioid medication for pain. Participants were randomly assigned to a Presentation (n = 97 intervention communicating relevant facts in each knowledge domain, or a Presentation + Mastery (n = 100 intervention including the same facts but requiring that participants respond correctly to ≥80% of embedded questions in each module before advancing. Participants completed the Brief Opioid Overdose Knowledge (BOOK measure before and after the interventions, and provided feedback on acceptability.ResultsBoth versions of the intervention resulted in significant pre to postintervention increases in BOOK scores across all knowledge domains (p < 0.001, with no significant knowledge differences between groups. The Presentation intervention took significantly less time to complete (p < 0.001 and was completed by significantly more participants than the Presentation + Mastery intervention (p < 0.001. Most participants rated both interventions as highly acceptable.ConclusionResults replicate a previous study (1 and suggest the web-based Presentation intervention may be a convenient, cost-effective method for disseminating crucial public health information for preventing

  7. The opioid rotation ratio of hydrocodone to strong opioids in cancer patients.

    Science.gov (United States)

    Reddy, Akhila; Yennurajalingam, Sriram; Desai, Hem; Reddy, Suresh; de la Cruz, Maxine; Wu, Jimin; Liu, Diane; Rodriguez, Eden Mae; Waletich, Jessica; Shin, Seong Hoon; Gayle, Vicki; Patel, Pritul; Dalal, Shalini; Vidal, Marieberta; Tanco, Kimberson; Arthur, Joseph; Tallie, Kimmie; Williams, Janet; Silvestre, Julio; Bruera, Eduardo

    2014-11-01

    Cancer pain management guidelines recommend initial treatment with intermediate-strength analgesics such as hydrocodone and subsequent escalation to stronger opioids such as morphine. There are no published studies on the process of opioid rotation (OR) from hydrocodone to strong opioids in cancer patients. Our aim was to determine the opioid rotation ratio (ORR) of hydrocodone to morphine equivalent daily dose (MEDD) in cancer outpatients. We reviewed the records of consecutive patient visits at our supportive care center in 2011-2012 for OR from hydrocodone to stronger opioids. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected from patients who returned for follow-up within 6 weeks. Linear regression analysis was used to estimate the ORR between hydrocodone and MEDD. Successful OR was defined as 2-point or 30% reduction in the pain score and continuation of the new opioid at follow-up. Overall, 170 patients underwent OR from hydrocodone to stronger opioid. The median age was 59 years, and 81% had advanced cancer. The median time between OR and follow-up was 21 days. We found 53% had a successful OR with significant improvement in the ESAS pain and symptom distress scores. In 100 patients with complete OR and no worsening of pain at follow-up, the median ORR from hydrocodone to MEDD was 1.5 (quintiles 1-3: 0.9-2). The ORR was associated with hydrocodone dose (r = -.52; p < .0001) and was lower in patients receiving ≥40 mg of hydrocodone per day (p < .0001). The median ORR of hydrocodone to morphine was 1.5 (n = 44) and hydrocodone to oxycodone was 0.9 (n = 24). The median ORR from hydrocodone to MEDD was 1.5 and varied according to hydrocodone dose. ©AlphaMed Press.

  8. PK20, a new opioid-neurotensin hybrid peptide that exhibits central and peripheral antinociceptive effects

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    Tsuda Yuko

    2010-12-01

    Full Text Available Abstract Background The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor. Results Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia. Conclusions The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.

  9. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

    Science.gov (United States)

    Dahl, J B; Nielsen, R V; Wetterslev, J; Nikolajsen, L; Hamunen, K; Kontinen, V K; Hansen, M S; Kjer, J J; Mathiesen, O

    2014-11-01

    In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin reduced 24 h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and ≥ 13 mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all seem to have well-documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  10. Dexmedetomidine infusion to facilitate opioid detoxification and withdrawal in a patient with chronic opioid abuse

    Directory of Open Access Journals (Sweden)

    Surjya Prasad Upadhyay

    2011-01-01

    Full Text Available Many patients are admitted to the intensive care unit (ICU for acute intoxication, serious complication of overdose, or withdrawal symptoms of illicit drugs. An acute withdrawal of drugs with addiction potential is associated with a sympathetic overactivity leading to marked psychomimetic disturbances. Acute intoxication or withdrawal of such drugs is often associated with life-threatening complications which require ICU admission and necessitate prolonged sedative analgesic medications, weaning from which is often complicated by withdrawal and other psychomimetic symptoms. Dexmedetomidine, an alpha-2 (α2 agonist, has been used successfully to facilitate withdrawal and detoxification of various drugs and also to control delirium in ICU patients. Herein, we report a case of a chronic opioid abuse (heroin patient admitted with acute overdose complications leading to a prolonged ICU course requiring sedative-analgesic medication; the drug withdrawal-related symptoms further complicated the weaning process. Dexmedetomidine infusion was successfully used as a sedative-analgesic to control the withdrawal-related psychomimetic symptoms and to facilitate smooth detoxification and weaning from opioid and other sedatives.

  11. Radioreceptor opioid assay

    International Nuclear Information System (INIS)

    Miller, R.J.; Chang, K.-J.

    1981-01-01

    A radioreceptor assay is described for assaying opioid drugs in biological fluids. The method enables the assay of total opioid activity, being specific for opioids as a class but lacking specificity within the class. A radio-iodinated opioid and the liquid test sample are incubated with an opiate receptor material. The percentage inhibition of the binding of the radio-iodinated compound to the opiate receptor is calculated and the opioid activity of the test liquid determined from a standard curve. Examples of preparing radio-iodinated opioids and assaying opioid activity are given. A test kit for the assay is described. Compared to other methods, this assay is cheap, easy and rapid. (U.K.)

  12. The SISAP: A New Screening Instrument for Identifying Potential Opioid Abusers in the Management of Chronic Nonmalignant Pain Within General Medical Practice

    Directory of Open Access Journals (Sweden)

    Robert B Coambs

    1996-01-01

    Full Text Available BACKGROUND: Many physicians are overly cautious about prescribing opioids for chronic pain because of fears of iatrogenic addiction. However, in patients with chronic pain, addiction to opioid analgesics is exceedingly rare when there is no prior history of alcohol or drug abuse.

  13. The use of analgesic drugs by South African veterinarians : continuing education

    Directory of Open Access Journals (Sweden)

    K.E. Joubert

    2001-07-01

    Full Text Available According to a survey, non-steroidal anti-inflammatory agents were the most popular analgesic used in South Africa for management of peri-operative pain, acute post-operative pain and chronic pain. The most popular non-steroidal anti-inflammatory agents are flunixin meglumine and phenylbutazone. The most popular opioid type drug is buprenorphine, followed by morphine. In the peri-operative setting, analgesic agents were not actively administered to 86.3 % of cats and 80.7 % of dogs. Analgesic premedications were frequently administered, e.g. xylazine or ketamine, but no specific drug was administered for post-operative pain. Veterinarians need to critically review their anaesthetic and analgesic practices in order to achieve balanced anaesthesia.

  14. ANALGESIC EFFICACY OF TRAMADOL IN PEDIATRIC TONSILLECTOMY WITH ADENOIDECTOMY

    Directory of Open Access Journals (Sweden)

    Janez Benedik

    2015-05-01

    Full Text Available Background: Tonsillectomy is one of the most commonly performed surgical prcedures in childhood. Acute pain after tonsillectomy and adenoidectomy can be treated with non-opioid and opioid analgesics. Our hypothesis stated that tramadol iv after induction of anaesthesia has superior analgesic effect compared to acetaminophen.Methods:  In a prospective, randomised study we compared analgesic efficacy of tramadol (group T: 2 mg/kgBW iv and acetaminophen (group A: elixir 15 mg/kgBW before op. procedure in a group of 108 children (age 3-7 years. Exclusion critheria: allergy, liver or kidney failure, epilepsy, febrile convulsions. A standard anaesthetic technique was used: propofol, alfentanil, vecuronium, positive pressure ventilation with 60% nitrous oxide in oxygen. After the procedure each child received acetaminophen suppositories (10 mg/kgBW/4-6h and combined suppositories. Monitoring: vital signs during and after op. procedure, pain intensity on the ward (facial pain score.    Results: There were no significant differences between the two groups in age distribution (mean age 5,2 years, ASA physical status, body weight, operative procedure, pain scores (VAS 6h after operative procedure; group T: 4,21±1,45; group A: 4,06±1,33, oxygen saturation, pulse frequency and the consumption of acetaminophen suppositories. Significant difference was in the consumption of combined suppositories (group T: 1,85±0,79; group A: 1,43±0,69, p=0,003.   Conclusion: Our study has shown, that tramadol is not a superior analgesic for the relief of posttonsillectomy pain in children compared to acetaminophen. 

  15. Joint pain epidemiology and analgesic usage in Madagascar.

    Science.gov (United States)

    Samison, Luc Hervé; Randriatsarafara, Fidiniaina Mamy; Ralandison, Stéphane

    2017-01-01

    To describe the epidemiology of joint pains and document analgesics usage in an African context. Patients suffering from joint pain were recruited from nine sites located in Antananarivo, Madagascar, including 6 hospital services and 3 clinics. Doctors collected information on the etiology and characteristics of the patients' pain. Analgesics prescribed by these doctors were also documented. In total, 400 patients were enrolled in the study (52.5% women, mean age of 42.34 years ± 17.7 [4-86]). Pain of mechanical type was found in 260 participants, 65%; 95% CI [60.1% to 69.6%] and inflammatory type pains in 128 cases 32%; 95% CI [27.5% to 36.9%]. Mixed pains were found in 12 patients (3%). The median duration of pain prior to the consultation was 6.5 days. The average pain intensity was 57.9 ± 19.9 mm of a total of 100 mm maximum on a visual analogue scale, VAS. The etiologies of mechanical type pains were dominated by fracture, common low back pain and tendonitis. Arthrosis was the dominant cause of inflammatory type pain, followed by rheumatoid arthritis and gout. NSAIDs (74.5%) were the most frequently prescribed analgesics followed by paracetamol (49.5%), weak opioids (23%) and corticosteroids (12.25%). Two-thirds of medical prescriptions (65.3%) were of combined analgesics. These findings demonstrated that mechanical type pains were the main reason for consultations for joint pain in these situations in Antananarivo, Madagascar. The most frequently prescribed pain-relieving medications were NSAIDs, paracetamol, weak opioids and corticosteroids. This descriptive study may be a useful starting point for further epidemiological studies of pain in the African context.

  16. Herbal medication: potential for adverse interactions with analgesic drugs.

    Science.gov (United States)

    Abebe, W

    2002-12-01

    The use of herbal supplements in the US has increased dramatically in recent years. These products are not regulated by the Food and Drug Administration (FDA) with the same scrutiny as conventional drugs. Patients who use herbal supplements often do so in conjunction with conventional drugs. This article is a review of potential adverse interactions between some of the commonly used herbal supplements and analgesic drugs. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, have the potential to interact with herbal supplements that are known to possess antiplatelet activity (ginkgo, garlic, ginger, bilberry, dong quai, feverfew, ginseng, turmeric, meadowsweet and willow), with those containing coumarin (chamomile, motherworth, horse chestnut, fenugreek and red clover) and with tamarind, enhancing the risk of bleeding. Acetaminophen may also interact with ginkgo and possibly with at least some of the above herbs to increase the risk of bleeding. Further, the incidences of hepatotoxicity and nephrotoxicity may be augmented by acetaminophen when concomitantly used with the potentially hepatotoxic herbs Echinacea and kava, and with herbs containing salicylate (willow, meadowsweet), respectively. The concomitant use of opioid analgesics with the sedative herbal supplements, valerian, kava and chamomile, may lead to increased central nervous system (CNS) depression. The analgesic effect of opioids may also be inhibited by ginseng. It is suggested that health-care professionals should be more aware of the potential adverse interactions between herbal supplements and analgesic drugs, and take appropriate precautionary measures to avoid their possible occurrences. However, as most of the interaction information available is based on individual case reports, animal studies and in vitro data, further research is needed to confirm and assess the clinical significance of these potential interactions.

  17. Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    Directory of Open Access Journals (Sweden)

    Heike L Rittner

    2009-04-01

    Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

  18. Yiguanjian cataplasm attenuates opioid dependence in a mouse

    Science.gov (United States)

    Gao, Shuai; Gao, Hong; Fan, Yuchen; Zhang, Guanghua; Sun, Fengkai; Zhao, Jing; Li, Feng; Yang, Yang; Wang, Kai

    2016-08-01

    To investigate the effect of Yiguanjian (YGJ) cataplasm on the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. One hundred Swiss albino mice, of equal male to female ratio, were randomly and equally divided into 10 groups. A portion (3 cm2) of the backside hair of the mice was removed 1 day prior to the experiment. Morphine (5 mg/kg) was intraperitoneally administered twice daily for 5 days. YGJ cataplasm was prepared and pasted on the bare region of the mice immediately before morphine administration on day 3 and subsequently removed at the end day 5. On day 6, naloxone (8 mg/kg) was intraperitoneally injected to precipitate opioid withdrawal syndrome. Behavioral observation was performed in two 30-min phases immediately after naloxone injection. The YGJ cataplasm significantly and dose-dependently attenuated morphine-naloxone- induced experimental opioid withdrawal, in terms of withdrawal severity score and the frequencies of jumping, rearing, forepaw licking, and circling behaviors. However, YGJ cataplasm treatment did not alter the acute analgesic effect of morphine. YGJ cataplasm could attenuate opioid dependence and its associated withdrawal symptoms. Therefore, YGJ cataplasm could serve as a potential therapy for opioid addiction in the future.

  19. Genetics Home Reference: opioid addiction

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Opioid addiction Opioid addiction Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Opioid addiction is a long-lasting (chronic) disease that can ...

  20. Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats

    Science.gov (United States)

    Hingne, Priyanka M.; Sluka, Kathleen A.

    2008-01-01

    Repeated daily application transcutaneous electrical nerve stimulation (TENS) results in tolerance, at spinal opioid receptors, to the anti-hyperalgesia produced by TENS. Since N-Methyl-D-Aspartate (NMDA) receptor antagonists prevent analgesic tolerance to opioid agonists we hypothesized that blockade of NMDA receptors will prevent tolerance to TENS. In rats with knee joint inflammation, TENS was applied for 20 minute daily at high frequency (100 Hz), low frequency (4 Hz), or sham TENS. Rats were treated with the NMDA antagonist MK-801 (0.01 mg/kg-0.1 mg/kg) or vehicle daily before TENS. Paw withdrawal thresholds were tested before and after inflammation, and before and after TENS treatment for 4 days. On day 1 TENS reversed the decreased mechanical withdrawal threshold induced by joint inflammation. On day 4 TENS had no effect on the decreased withdrawal threshold in the group treated with vehicle demonstrating development of tolerance. However, in the group treated with 0.1 mg/kg MK-801, TENS significantly reversed the mechanical withdrawal thresholds on day 4 demonstrating that tolerance did not develop. Vehicle treated animals developed cross-tolerance at spinal opioid receptors. Treatment with MK-801 reversed this cross-tolerance at spinal opioid receptors. In summary, blockade of NMDA receptors prevents analgesic tolerance to daily TENS by preventing tolerance at spinal opioid receptors. Perspective Tolerance observed to the clinical treatment of TENS could be prevented by administration of pharmaceutical agents with NMDA receptors activity such as ketamine or dextromethorphan. PMID:18061543

  1. Mindfulness Meditation Modulates Pain Through Endogenous Opioids.

    Science.gov (United States)

    Sharon, Haggai; Maron-Katz, Adi; Ben Simon, Eti; Flusser, Yuval; Hendler, Talma; Tarrasch, Ricardo; Brill, Silviu

    2016-07-01

    Recent evidence supports the beneficial effects of mindfulness meditation on pain. However, the neural mechanisms underlying this effect remain poorly understood. We used an opioid blocker to examine whether mindfulness meditation-induced analgesia involves endogenous opioids. Fifteen healthy experienced mindfulness meditation practitioners participated in a double-blind, randomized, placebo-controlled, crossover study. Participants rated the pain and unpleasantness of a cold stimulus prior to and after a mindfulness meditation session. Participants were then randomized to receive either intravenous naloxone or saline, after which they meditated again, and rated the same stimulus. A (3) × (2) repeated-measurements analysis of variance revealed a significant time effect for pain and unpleasantness scores (both P mindfulness meditation and after placebo, but not after naloxone. Furthermore, there was a positive correlation between the pain scores following naloxone vs placebo and participants' mindfulness meditation experience. These findings show, for the first time, that meditation involves endogenous opioid pathways, mediating its analgesic effect and growing resilient with increasing practice to external suggestion. This finding could hold promising therapeutic implications and further elucidate the fine mechanisms involved in human pain modulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Opioid Use Patterns Among Active Duty Service Members and Civilians: 2006 2014

    Science.gov (United States)

    2017-12-27

    normality in error terms using the Shapiro–Wilk test and multi-collinearity was tested using a variance inflation factor. The best-fitting model was...guest on 11 January 2018 products on opioid analgesic prescribing. JAMA Intern Med 2016; 176 (3): 399–402. 22. Mosher HJ, Krebs EE, Carrel M, Kaboli PJ

  3. Treatment of chronic pain in older people: Evidence-based choice of strong-acting opioids

    NARCIS (Netherlands)

    van Ojik, Annette L.; Jansen, Paul A. F.; Brouwers, Jacobus R. B. J.; van Roon, Eric N.

    2012-01-01

    In the treatment of chronic malignant and non-malignant pain, opioids are used as strong analgesics. Frail elderly patients often have multiple comorbidities and use multiple medicines, leading to an increased risk of clinically relevant drug-drug and drug-disease interactions. Age-related changes

  4. Liver and kidney toxicity in chronic use of opioids: An experimental ...

    Indian Academy of Sciences (India)

    Unknown

    scavenging system of plasma and liver and heart pathology in adolescence heroin users; Vopr. Med. Khim. 45 501–506. Poppers P J 1980 Hepatic drug metabolism and anesthesia;. Anaesthesist 29 55–58. Portenoy K R and Foley K M 1986 Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases; Pain.

  5. Does adding low doses of oral naltrexone to morphine alter the subsequent opioid requirements and side effects in trauma patients?

    Science.gov (United States)

    Farahmand, Shervin; Ahmadi, Omid; Dehpour, Ahmadreza; Khashayar, Patricia

    2012-01-01

    The present study aims to assess the influence of ultra-low doses of opioid antagonists on the analgesic properties of opioids and their side effects. In the present randomized, double-blind controlled trial, the influence of the combination of ultra-low-dose naltrexone and morphine on the total opioid requirement and the frequency of the subsequent side effects was compared with that of morphine alone (added with placebo) in patients with trauma in the upper or lower extremities. Although the morphine and naltrexone group required 0.04 mg more opioids during the study period, there was no significant difference between the opioid requirements of the 2 groups. Nausea was less frequently reported in patients receiving morphine and naltrexone. The combination of ultra-low-dose naltrexone and morphine in extremity trauma does not affect the opioid requirements; it, however, lowers the risk of nausea. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction - Recommendations of the Nordic Working Group

    DEFF Research Database (Denmark)

    Drewes, Asbjørn Mohr; Munkholm, Pia; Simrén, Magnus

    2016-01-01

    and OIBD, particularly OIC, will lead to better pain treatment in patients on opioid therapy. Subsequently, optimised therapy will improve quality of life and, from a socio-economic perspective, may also reduce costs associated with hospitalisation, sick leave and early retirement in these patients....... on the frequency of bowel movements. Many patients with pain receive opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus and should also be considered......, lifestyle changes, tapering the opioid dosage and alternative analgesics. Whilst opioid rotation may also improve symptoms, these remain unalleviated in a substantial proportion of patients. Should conventional treatment fail, mechanism-based treatment with opioid antagonists should be considered...

  7. Reported analgesic administration to rabbits undergoing experimental surgical procedures

    Science.gov (United States)

    2011-01-01

    Background It has become widely accepted that whenever animals are used in scientific procedures, the 3Rs principle of replacement, reduction and refinement described by William Russell and Rex Burch should be adhered to. Animals should be replaced with non-sentient alternatives if possible, the number of animals used should be reduced and experimental procedures should be refined to minimise pain, suffering and distress. Administration of analgesic agents to animals undergoing surgical procedures is a refinement used to alleviate pain. In this study, a structured literature review was carried out to examine current trends in analgesic administration to rabbits undergoing experimental surgical procedures. Results 128 papers from 51 peer-reviewed journals were selected for inclusion in this review. Reporting administration of systemic analgesia to rabbits in peer-reviewed scientific papers increased significantly from 16% to 50% between 1995-1997 and 2005-2007 (P buprenorphine was the most frequently used agent and non-steroidal anti-inflammatory drugs were used less frequently than opioids in both time periods. Conclusions Although this review provides evidence that systemic analgesic administration to rabbits undergoing surgical procedures is increasing, rabbits do not always receive analgesia when they undergo experimental surgery. Other practices in rabbit perioperative care that could be improved, highlighted by this survey include: 1) changing the timing of analgesic administration by giving systemic analgesics pre- or perioperatively rather than only postoperatively, 2) using multimodal analgesia when pain is likely to be moderate to severe and 3) increasing the use of non-steroidal anti-inflammatory drugs and use of other techniques such as epidural analgesia particularly for orthopaedic procedures. PMID:21338514

  8. Combined analysis of circulating β-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects.

    Science.gov (United States)

    Rhodin, Annica; Grönbladh, Alfhild; Ginya, Harumi; Nilsson, Kent W; Rosenblad, Andreas; Zhou, Qin; Enlund, Mats; Hallberg, Mathias; Gordh, Torsten; Nyberg, Fred

    2013-02-12

    Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the μ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide β-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls. The plasma β-endorphin levels were significantly higher in controls than in pain patients.A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found. Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.

  9. Update on prescription extended-release opioids and appropriate patient selection

    Directory of Open Access Journals (Sweden)

    Brennan MJ

    2013-07-01

    Full Text Available Michael J Brennan The Pain Center of Fairfield, Fairfield, CT, USA Abstract: Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. Keywords: chronic pain, opioid analgesics, extended release, abuse prevention

  10. Trends in opioid use and dosing among socio-economically disadvantaged patients

    Science.gov (United States)

    Gomes, Tara; Juurlink, David N; Dhalla, Irfan A; Mailis-Gagnon, Angela; Paterson, J Michael; Mamdani, Muhammad M

    2011-01-01

    Background Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. Methods Using a cross-sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario’s public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. Results Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long-acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid-related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42–1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25–11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78–25.12) among those with very-high-dose prescriptions. Interpretation Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain

  11. Opioid Overdose Crisis

    Science.gov (United States)

    ... use in helping to reduce the symptoms of opioid withdrawal (FDA, November 2017) Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in Metropolitan and Nonmetropolitan Areas — United ... opioid crisis (5:08) (Washington Post, September 2017) Contribution ...

  12. Opiate and opioid withdrawal

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000949.htm Opiate and opioid withdrawal To use the sharing features on this page, ... or withdrawing from opiates. Alternative Names Withdrawal from opioids; Dopesickness; Substance use - opiate withdrawal; Substance abuse - opiate withdrawal; Drug abuse - opiate withdrawal; ...

  13. Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty

    DEFF Research Database (Denmark)

    Lunn, Troels Haxholdt; Husted, Henrik; Laursen, Mogens Berg

    2015-01-01

    was more pronounced from days 2-6 in A vs C. More severe adverse reactions were observed in group A vs B and C. In conclusion, gabapentin may have a limited if any role in acute postoperative pain management of opioid-naive patients undergoing total knee arthroplasty and should not be recommended......Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs harm have not been clarified. In this randomized, double-blind, placebo-controlled dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized...... (1:1:1) to either gabapentin 1300 mg/d (group A), gabapentin 900 mg/d (group B), or placebo (group C) daily from 2 hours preoperatively to postoperative day 6 in addition to a standardized multimodal analgesic regime. The primary outcome was pain upon ambulation 24 hours after surgery...

  14. Risk of respiratory depression with opioids and concomitant gabapentinoids

    Directory of Open Access Journals (Sweden)

    Savelloni J

    2017-11-01

    Full Text Available Julie Savelloni,1 Heather Gunter,2 Kelly C Lee,3 Chih Hsu,1 Cassia Yi,2 Kyle P Edmonds,4 Timothy Furnish,5 Rabia S Atayee1 1Department of Pharmacy, UC San Diego Health, San Diego, CA, USA; 2Department of Nursing, UC San Diego Health, San Diego, CA, USA; 3Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA; 4Department of Medicine, UC San Diego Health Sciences, San Diego, CA, USA; 5Department of Anesthesiology, UC San Diego Health, San Diego, CA, USA Introduction: The combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration. Methods: This retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group. Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group. Results: A total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4% versus 17

  15. Opioid Use and Storage Patterns by Patients after Hospital Discharge following Surgery.

    Science.gov (United States)

    Bartels, Karsten; Mayes, Lena M; Dingmann, Colleen; Bullard, Kenneth J; Hopfer, Christian J; Binswanger, Ingrid A

    2016-01-01

    Opioid-based analgesic therapy represents a cornerstone of pain management after surgery. The recent rise in opioid sales and opioid overdoses suggests it is important to maximize the safety of opioid prescribing after surgery. Given that patients may live with other family members in the home, safe storage and appropriate disposal of excess opioids after hospital discharge are necessary to prevent unintended secondary exposures. Identifying characteristics of patients who are likely to be prescribed excess opioids after surgery may enable more targeted prescription practices and safety interventions. Our study aimed to elucidate patient-reported opioid use patterns and modes of home storage of opioids among patients discharged home after Cesarean section (C-section) and thoracic surgery. Specifically, we sought to identify characteristics of patients who reported using about half or more versus less of the opioids prescribed to them for use after hospital discharge. For this cohort study, we developed a survey on quality of analgesia following hospital discharge, amounts of opioids taken relative to the amount prescribed, reasons for not taking all prescribed medications, and storage and disposal methods for leftover opioids. Adult patients, who had C-section or thoracic surgery at a tertiary academic medical center, were given a web-based self-administered survey after discharge. Descriptive statistics (means and standard deviations, proportions) were used to describe the study sample and survey results. Comparisons between patients who reported taking about half or more versus less of the opioids prescribed to them for use after hospital discharge were made using unpaired t-tests, Mann-Whitney tests, and Chi-square tests as appropriate. The majority (53%) of respondents after C-section (N = 30) reported taking either no or very few (less than 5) prescribed opioid pills; 83% reported taking half or less; and 17% of women, reported taking all or nearly all (5 or

  16. Opioid Use and Storage Patterns by Patients after Hospital Discharge following Surgery.

    Directory of Open Access Journals (Sweden)

    Karsten Bartels

    Full Text Available Opioid-based analgesic therapy represents a cornerstone of pain management after surgery. The recent rise in opioid sales and opioid overdoses suggests it is important to maximize the safety of opioid prescribing after surgery. Given that patients may live with other family members in the home, safe storage and appropriate disposal of excess opioids after hospital discharge are necessary to prevent unintended secondary exposures. Identifying characteristics of patients who are likely to be prescribed excess opioids after surgery may enable more targeted prescription practices and safety interventions. Our study aimed to elucidate patient-reported opioid use patterns and modes of home storage of opioids among patients discharged home after Cesarean section (C-section and thoracic surgery. Specifically, we sought to identify characteristics of patients who reported using about half or more versus less of the opioids prescribed to them for use after hospital discharge.For this cohort study, we developed a survey on quality of analgesia following hospital discharge, amounts of opioids taken relative to the amount prescribed, reasons for not taking all prescribed medications, and storage and disposal methods for leftover opioids. Adult patients, who had C-section or thoracic surgery at a tertiary academic medical center, were given a web-based self-administered survey after discharge. Descriptive statistics (means and standard deviations, proportions were used to describe the study sample and survey results. Comparisons between patients who reported taking about half or more versus less of the opioids prescribed to them for use after hospital discharge were made using unpaired t-tests, Mann-Whitney tests, and Chi-square tests as appropriate.The majority (53% of respondents after C-section (N = 30 reported taking either no or very few (less than 5 prescribed opioid pills; 83% reported taking half or less; and 17% of women, reported taking all or

  17. Jurisdictional differences in opioid use, other licit and illicit drug use, and harms associated with substance use among people who tamper with pharmaceutical opioids.

    Science.gov (United States)

    Peacock, Amy; Bruno, Raimondo; Cama, Elena; Kihas, Ivana; Larance, Briony; Lintzeris, Nick; Hordern, Antonia; White, Nancy; Ali, Robert; Degenhardt, Louisa

    2015-11-01

    The harms associated with non-medical use of pharmaceutical opioid analgesics are well established; however, less is known about the characteristics and drug-use patterns of the growing and hidden populations of people using pharmaceutical opioids illicitly, including the frequency of pharmaceutical opioid injection. This paper aimed to undertake a detailed examination of jurisdictional differences in patterns of opioid use among a cohort of people who regularly tamper with pharmaceutical opioids in Australia. Data were drawn from the National Opioid Medications Abuse Deterrence study. The cohort was recruited from New South Wales (NSW; n = 303), South Australia (SA; n = 150) and Tasmania (TAS; n = 153) to participate in face-to-face structured interviews collecting data on use of pharmaceutical opioids, benzodiazepines, other sedative drugs and illicit substances, as well as the harms associated with substance use. TAS participants reported greater use and injection of certain pharmaceutical opioids (particularly morphine and methadone tablets), and limited heroin use, with lower rates of engagement in opioid substitution treatment, compared with NSW participants. NSW participants were more socially disadvantaged and more likely to report risky injecting behaviours and injecting-related injuries and diseases compared with SA and TAS participants. SA participants reported greater rates of pain conditions, greater use of pain-based services, as well as broader use of pharmaceutical opioids in regards to forms and route of administration, compared with NSW participants. Distinct jurisdictional profiles were evident for people who tamper with pharmaceutical opioids, potentially reflecting jurisdictional differences in prescribing regulatory mechanisms and addiction treatment models. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  18. Is this ?complicated? opioid withdrawal?

    OpenAIRE

    Parkar, S.R.; Seethalakshmi, R; Adarkar, S; Kharawala, S

    2006-01-01

    Seven patients with opioid dependence admitted in the de-addiction centre for detoxification developed convulsions and delirium during the withdrawal phase. After ruling out all other possible causes of these complications, opioid withdrawal seemed to emerge as the most likely explanation. The unpredictability of the course of opioid dependence and withdrawal needs to be considered when treating patients with opioid dependence.

  19. Opioid Mechanism Involvement in the Synergism Produced by the Combination of Diclofenac and Caffeine in the Formalin Model

    OpenAIRE

    Flores-Ramos, Jos? Mar?a; D?az-Reval, M. Irene

    2013-01-01

    Analgesics can be administered in combination with caffeine for improved analgesic effectiveness in a process known as synergism. The mechanisms by which these combinations produce synergism are not yet fully understood. The aim of this study was to analyze whether the administration of diclofenac combined with caffeine produced antinociceptive synergism and whether opioid mechanisms played a role in this event. The formalin model was used to evaluate the antinociception produced by the oral ...

  20. Current analgesic use predicts low emotional quality of life in youth: A cross-sectional survey among university students in Sikkim, North East India

    OpenAIRE

    Ahongshangbam, Shurmala; Chakrabarti, Amit

    2013-01-01

    Background & objectives: Occurrence of chronic physical pain is increasingly identified among youth, and medically unsupervised analgesic use is a possible risk factor for opioid dependence and other mental diseases in later life. Therefore, the present study was carried out in young student population in Sikkim, India, to explore predictors (including current chronic pain and current analgesic use) of low QoL in youth to identify a subset of population vulnerable to substance use and mental ...

  1. Management of cancer pain: 1. Wider implications of orthodox analgesics

    Directory of Open Access Journals (Sweden)

    Lee SK

    2014-01-01

    Full Text Available Susannah K Lee,1 Jill Dawson,2 Jack A Lee,3 Gizem Osman,4 Maria O Levitin,5 Refika Mine Guzel,5 Mustafa BA Djamgoz5,61Pomona College, Claremont, CA, USA; 2Healthcare Communications Consultancy, Danville, CA, USA; 3College of Arts and Sciences, Vanderbilt University, Nashville, TN, USA; 4Department of Chemical Engineering, Loughborough University, Loughborough, UK; 5Division of Cell and Molecular Biology, Neuroscience Solutions to Cancer Research Group, South Kensington Campus, Imperial College London, London, UK; 6Cyprus International University, Biotechnology Research Centre, Haspolat, North Cyprus, Mersin, TurkeyAbstract: In this review, the first of two parts, we first provide an overview of the orthodox analgesics used commonly against cancer pain. Then, we examine in more detail the emerging evidence for the potential impact of analgesic use on cancer risk and disease progression. Increasing findings suggest that long-term use of nonsteroidal anti-inflammatory drugs, particularly aspirin, may reduce cancer occurrence. However, acetaminophen may raise the risk of some hematological malignancies. Drugs acting upon receptors of gamma-aminobutyric acid (GABA and GABA “mimetics” (eg, gabapentin appear generally safe for cancer patients, but there is some evidence of potential carcinogenicity. Some barbiturates appear to slightly raise cancer risks and can affect cancer cell behavior in vitro. For cannabis, studies suggest an increased risk of squamous cell carcinoma of the tongue, larynx, and possibly lung. Morphine may stimulate human microvascular endothelial cell proliferation and angiogenesis; it is not clear whether this might cause harm or produce benefit. The opioid, fentanyl, may promote growth in some tumor cell lines. Opium itself is an emerging risk factor for gastric adenocarcinoma and possibly cancers of the esophagus, bladder, larynx, and lung. It is concluded that analgesics currently prescribed for cancer pain can

  2. Study of analgesic activity of Teucrium polium extract

    Directory of Open Access Journals (Sweden)

    2017-11-01

    Full Text Available Background and objectives: Pain is a primarily protective in nature, but often causes discomfort. Currently available analgesic drugs are not useful in all cases due to their side effects. Medicinal plants are believed to be an important source of new chemical substances with potential therapeutic effects, such as, Teucrium polium (TP used traditionally to relieve headache, rheumatic arteritis and pain during pregnancy. The aim of this study is to clarify mechanism of antinociceptive effect of TP.Methods: This review article was carried out by searching studies in Pubmed, Google Scholar, SID and Science Direct by using the search keywords. In this review, 45 articles were found and 25 of them were applied. Results: Numerous studies indicate that T. polium contains strong analgesic properties through the effect of opoidergic, H1 and H2 receptors and alpha-2-adrenergic effect.  Alpha-2-adrenergic induces analgesia through the direct effect on the spinal cord with both post-synaptic hyper polarization and restrain presynaptic transmission secretion therefore, primary afferent nerve fibers are blocked. Conclusion: The results indicated that the plant induces analgesic effects through the alpha-2-adrenergic mechanism. According to the findings, there are some evidences suggesting that the central and the peripheral effects of the plant extract may occur through the opioid and histaminergic system. Generally, present study proposes that T. polium possesses a strong antinociceptive property.

  3. Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

    Science.gov (United States)

    Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E.; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard

    2017-01-01

    Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication

  4. Medications Development for Opioid Abuse

    Science.gov (United States)

    Negus, S. Stevens; Banks, Matthew L.

    2013-01-01

    Here we describe methods for preclinical evaluation of candidate medications to treat opioid abuse and dependence. Our perspective is founded on the propositions that (1) drug self-administration procedures provide the most direct method for assessment of medication effects, (2) procedures that assess choice between opioid and nondrug reinforcers are especially useful, and (3) the states of opioid dependence and withdrawal profoundly influence both opioid reinforcement and the effects of candidate medications. Effects of opioid medications on opioid choice in nondependent and opioid-dependent subjects are reviewed. Various nonopioid medications have also been examined, but none yet have been identified that safely and reliably reduce opioid choice. Future research will focus on (1) strategies for increasing safety and/or effectiveness of opioid medications, and (2) continued development of nonopioids such as inhibitors of endocannabinoid catabolic enzymes or inhibitors of opioid-induced glial activation. PMID:23125072

  5. Stereochemical Basis for a Unified Structure Activity Theory of Aromatic and Heterocyclic Rings in Selected Opioids and Opioid Peptides

    Directory of Open Access Journals (Sweden)

    Joel S. Goldberg

    2010-02-01

    Full Text Available This paper presents a novel unified theory of the structure activity relationship of opioids and opioid peptides. It is hypothesized that a virtual or known heterocyclic ring exists in all opioids which have activity in humans, and this ring occupies relative to the aromatic ring of the drug, approximately the same plane in space as the piperidine ring of morphine. Since the rings of morphine are rigid, and the aromatic and piperidine rings are critical structural components for morphine’s analgesic properties, the rigid morphine molecule allows for approximations of the aromatic and heterocyclic relationships in subsequent drug models where bond rotations are common. This hypothesis and five propositions are supported by stereochemistry and experimental observations. Proposition #1 The structure of morphine provides a template. Proposition #2 Steric hindrance of some centric portion of the piperidine ring explains antagonist properties of naloxone, naltrexone and alvimopam. Proposition #3 Methadone has an active conformation which contains a virtual heterocyclic ring which explains its analgesic activity and racemic properties. Proposition #4 The piperidine ring of fentanyl can assume the morphine position under conditions of nitrogen inversion. Proposition #5 The first 3 amino acid sequences of beta endorphin (l-try-gly-gly and the active opioid dipeptide, l-tyr-pro, (as a result of a peptide turn and zwitterion bonding form a virtual piperazine-like ring which is similar in size, shape and location to the heterocyclic rings of morphine, meperidine, and methadone. Potential flaws in this theory are discussed. This theory could be important for future analgesic drug design.

  6. Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.

    Science.gov (United States)

    Esparza-Villalpando, Vicente; Pozos-Guillén, Amaury; Masuoka-Ito, David; Gaitán-Fonseca, César; Chavarría-Bolaños, Daniel

    2018-03-01

    Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect. © 2017 Wiley Periodicals, Inc.

  7. [Opioids and the heart].

    Science.gov (United States)

    Sokolova, N A; Ashmarin, I P

    1992-01-01

    The possible role of the opioid system in the cardiovascular function is an area that attracted significant attention in recent years. In order to clarify the possible role of opioids in cardiac regulation we have studied the myocardial effects of some opioids and their antagonists. Our results show that in vitro some opioids (dermorphin, alpha- and gamma-endorphins, dalargin and other) may exert inotropic, but not chronotropic, action and may act as modulatory agents on the cholinergic myocardial effects. Some of the opioidergic effects were blocked by naloxone and some were not. The results of pharmacological and physiological analysis show that opioidergic-cholinergic interaction may occur at the postsynaptic myocardial level via different mechanisms. It is well known that in vivo opioids play a significant role in shock and stress; sometimes they act as positive and sometimes--as a negative factor; the mechanisms of these effects are still not clear. We have shown that the endogenous opioid antagonist tetrapeptide FMRFa (Phe-Met-Arg-Phe-NH2) acted as a preservative agent to the acute hypobaric hypoxia and hemorrhagic shock, blood pressure and respiration and also the time of life. The efficacy of FMRFa was higher than that of naloxone. It was suggested that one of the possible mechanism of FMRFa preservative action was the increasing of sympathetic nervous system activity mediated by the endogenous opioid system inhibition.

  8. Effects of stress and. beta. -funal trexamine pretreatment on morphine analgesia and opioid binding in rats

    Energy Technology Data Exchange (ETDEWEB)

    Adams, J.U.; Andrews, J.S.; Hiller, J.M.; Simon, E.J.; Holtzman, S.G.

    1987-12-28

    This study was essentially an in vivo protection experiment designed to test further the hypothesis that stress induces release of endogenous opiods which then act at opioid receptors. Rats that were either subjected to restraint stress for 1 yr or unstressed were injected ICV with either saline or 2.5 ..mu..g of ..beta..-funaltrexamine (..beta..-FNA), an irreversible opioid antagonist that alkylates the mu-opioid receptor. Twenty-four hours later, subjects were tested unstressed for morphine analgesia or were sacrificed and opioid binding in brain was determined. (/sup 3/H)D-Ala/sup 2/NMePhe/sup 4/-Gly/sup 5/(ol)enkephalin (DAGO) served as a specific ligand for mu-opioid receptors, and (/sup 3/H)-bremazocine as a general ligand for all opioid receptors. Rats injected with saline while stressed were significantly less sensitive to the analgesic action of morphine 24 hr later than were their unstressed counterparts. ..beta..-FNA pretreatment attenuated morphine analgesia in an insurmountable manner. Animals pretreated with ..beta..-FNA while stressed were significantly more sensitive to the analgesic effect of morphine than were animals that received ..beta..-FNA while unstressed. ..beta..-FNA caused small and similar decreases in (/sup 3/H)-DAGO binding in brain of both stressed and unstressed animals. 35 references, 2 figures, 2 tables.

  9. Opioid Abuse after TBI

    Science.gov (United States)

    2015-09-01

    Award Number: W81XWH-11-1-0373 TITLE: “Opioid Abuse after TBI” PRINCIPAL INVESTIGATOR: Candace L. Floyd, Ph.D., and Katherine L. Nicholson...30Jun2015 4. TITLE AND SUBTITLE “Opioid Abuse after TBI” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0373 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...secondly tested the hypothesis that moderate TBI increases the susceptibility for opioid abuse as measured by an alteration in the rewarding properties of

  10. Assessment of Postoperative Analgesic Drug Efficacy: Method of Data Analysis Is Critical.

    Science.gov (United States)

    Andersen, Lars Peter Kloster; Gögenur, Ismail; Torup, Henrik; Rosenberg, Jacob; Werner, Mads Utke

    2017-09-01

    Pain intensity ratings and opioid consumption (OC) are ubiquitous indicators of pain in postoperative trials of the efficacy of interventional procedures. Unfortunately, consensus on the appropriate statistical handling of these outcomes has not been reached. The aim of this article was, therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. Data from a randomized, double-blind, placebo-controlled study investigating the analgesic efficacy of a regional anesthetic block following a major elective surgical procedure were analyzed. The original data included measurements of pain intensity (visual analog scale [VAS]) at rest and during coughing (VAS0/2/4/6/12/18/24 h) and OC0-6/0-24 h administered by patient-controlled analgesia. The statistical analyses included comparisons of discrete pain intensity scores (VAS0/2/4/6/12/18/24 h), summary measures of pain intensity ratings (area under the curve [AUC]-VAS0-6/0-24 h; mean VAS0-6/0-24 h), and OC0-6/0-24 h. Finally, the analyses also included an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC0-6/0-24 h). Also, estimation of effect size, generalized odds ratio of the individual analgesic outcome variables was performed. Sixty-one patients were included in the final data analysis. Discrete pain intensity ratings differed significantly between the treatment groups at specific postoperative time points, but appropriate correction for multiple comparisons eliminated some of these differences. AUC-VAS0-6 h differed significantly at rest and during coughing, while no difference was found for AUC-VAS0-24 h. In contrast, mean VAS0-6 h and VAS0-24 h differed significantly between treatment groups at rest and during coughing. OC0-6/0-24 h differed significantly between the

  11. Analgesic effects of lappaconitine in leukemia bone pain in a mouse model

    Directory of Open Access Journals (Sweden)

    Xiao-Cui Zhu

    2015-05-01

    Full Text Available Bone pain is a common and severe symptom in cancer patients. The present study employed a mouse model of leukemia bone pain by injection K562 cells into tibia of mouse to evaluate the analgesic effects of lappacontine. Our results showed that the lappaconitine treatment at day 15, 17 and 19 could effectively reduce the spontaneous pain scoring values, restore reduced degree in the inclined-plate test induced by injection of K562 cells, as well as restore paw mechanical withdrawal threshold and paw withdrawal thermal latency induced by injection of K562 cells to the normal levels. Additionally, the molecular mechanisms of lappaconitine’s analgesic effects may be related to affect the expression levels of endogenous opioid system genes (POMC, PENK and MOR, as well as apoptosis-related genes (Xiap, Smac, Bim, NF-κB and p53. Our present results indicated that lappaconitine may become a new analgesic agent for leukemia bone pain management.

  12. Twenty‐five years of prescription opioid use in Australia: a whole‐of‐population analysis using pharmaceutical claims

    Science.gov (United States)

    Karanges, Emily A.; Blanch, Bianca; Buckley, Nicholas A.

    2016-01-01

    Aim The aim of this paper is to investigate 25‐year trends in community use of prescribed opioid analgesics in Australia, and to map these trends against major changes to opioid registration and subsidy. Methods We obtained dispensing data from 1990 to 2014 from two sources: dispensing claims processed under Australia's national drug subsidy programme, the Pharmaceutical Benefits Scheme, including under co‐payment records from 2012; and estimates of non‐subsidized medicine use from a survey of Australian pharmacies (until 2011). Utilization was expressed in defined daily doses (DDD)/1000 population/day. Results Opioid dispensing increased almost four‐fold between 1990 and 2014, from 4.6 to 17.4 DDD/1000 pop/day. In 1990, weak, short‐acting or orally administered opioids accounted for over 90% of utilization. Use of long‐acting opioids increased over 17‐fold between 1990 and 2000, due primarily to the subsidy of long‐acting morphine and increased use of methadone for pain management. Between 2000 and 2011, oxycodone, fentanyl, buprenorphine, tramadol and hydromorphone use increased markedly. Use of strong opioids, long‐acting and transdermal preparations also increased, largely following the subsidy of various opioids for noncancer pain. In 2011, the most dispensed opioids were codeine (41.1% of total opioid use), oxycodone (19.7%) and tramadol (16.1%); long‐acting formulations comprised approximately half, and strong opioids 40%, of opioid dispensing. Conclusions Opioid utilization in Australia is increasing, although these figures remain below levels reported in the US and Canada. The increased use of opioids was largely driven by the subsidy of long‐acting formulations and opioids for the treatment of noncancer pain. PMID:26991673

  13. Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study.

    Science.gov (United States)

    Dreifuss, Jessica A; Griffin, Margaret L; Frost, Katherine; Fitzmaurice, Garrett M; Potter, Jennifer Sharpe; Fiellin, David A; Selzer, Jeffrey; Hatch-Maillette, Mary; Sonne, Susan C; Weiss, Roger D

    2013-07-01

    Prescription opioid dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome. A secondary analysis of data from a large multisite, randomized clinical trial, the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study (POATS) was undertaken to examine baseline patient characteristics (N=360) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence. Baseline predictor variables included self-reported demographic and opioid use history information, diagnoses assessed via the Composite International Diagnostic Interview, and historical opioid use and related information from the Pain And Opiate Analgesic Use History. In bivariate analyses, pre-treatment characteristics associated with successful opioid use outcome included older age, past-year or lifetime diagnosis of major depressive disorder, initially obtaining opioids with a medical prescription to relieve pain, having only used opioids by swallowing or sublingual administration, never having used heroin, using an opioid other than extended-release oxycodone most frequently, and no prior opioid dependence treatment. In multivariate analysis, age, lifetime major depressive disorder, having only used opioids by swallowing or sublingual administration, and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome. This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids. Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients' response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone. Copyright © 2012 Elsevier Ireland

  14. Randomized pilot trial measuring knowledge acquisition of opioid education in emergency department patients using a novel media platform.

    Science.gov (United States)

    Chakravarthy, Bharath; Somasundaram, Shashank; Mogi, Jennifer; Burns, Roshan; Hoonpongsimanont, Wirachin; Wiechmann, Warren; Lotfipour, Shahram

    2018-01-02

    The number of active opioid analgesic prescriptions has risen steadily, causing increases in nonmedical opioid use, addiction, and overdose. Insufficient focus on patient discharge instructions has contributed to lack of patient awareness regarding dangers of opioids. This study examines whether an educational Khan Academy-style animation discharge instruction on the dangers and safe usage of opioid analgesics elicits higher knowledge acquisition than current standard of care. Additionally, it measures the feasibility of implementing this video discharge instruction in the emergency department (ED). Fifty-two English-speaking patients aged 18 years or older receiving an opioid prescription were enrolled in this study. Patients were randomized into 2 groups. The standard of care group received verbal instruction and an informational sheet, whereas the video animation group received a 6-minute video on proper usage of opioids in addition to standard of care. Video content was sourced from samhsa.gov and administered within the ED prior to discharge. Both groups received a 26-question test regarding the dangers and safe usage of opioids immediately after education. An unpaired t test compared knowledge acquisition between the 2 groups. Fifty-four patients were approached, 52 patients enrolled; 27 in the standard group and 25 in the animation group. The standard of care group averaged 65% knowledge acquisition (16.8/26 correct), whereas the animation group averaged 82% acquisition (21.2/26 correct). The video animation significantly increased patient knowledge acquisition about opioid medications' risks and proper usage and disposal (P = .001). It can be concluded that medical knowledge acquisition is improved in the video animation group compared with the current standard of care (P = .001). It can also be concluded that it is feasible to implement a novel media platform to educate patients receiving opioid analgesics in the ED (96.1%).

  15. Sources of prescription opioids among diagnosed opioid abusers.

    Science.gov (United States)

    Shei, Amie; Rice, J Bradford; Kirson, Noam Y; Bodnar, Katharine; Birnbaum, Howard G; Holly, Pamela; Ben-Joseph, Rami

    2015-04-01

    Diversion and abuse of prescription opioids are important public health concerns in the US. This study examined possible sources of prescription opioids among patients diagnosed with opioid abuse. Commercially insured patients aged 12-64 diagnosed with opioid abuse/dependence ('abuse') were identified in OptumHealth Reporting and Insights medical and pharmacy claims data, 2006-2012, and required to have continuous eligibility over an 18 month study period surrounding the first abuse diagnosis. We examined whether abusers had access to prescription opioids through their own prescriptions and/or to diverted prescription opioids through family members' prescriptions obtained prior to the abuser's first abuse diagnosis. For comparison, we examined access to prescription opioids of a reference population of non-abusers. Sensitivity analyses focused on patients initially diagnosed with opioid dependence and, separately, abusers not previously treated with buprenorphine. Of the 9291 abusers meeting the selection criteria, 79.9% had an opioid prescription prior to their first abuse diagnosis; 20.1% of abusers did not have an opioid prescription prior to their first abuse diagnosis, of whom approximately half (50.8%) had a family member who had an opioid prescription prior to the abuser's first abuse diagnosis (compared to 42.2% of non-abusers). Similar results were found among patients initially diagnosed with opioid dependence and among abusers not previously treated with buprenorphine. The study relied on the accuracy of claims data to identify abusers, but opioid abuse is often undiagnosed. In addition, only prescription claims that were reimbursed by a health plan were included in the analysis. While most abusers had access to prescription opioids through their own prescriptions, many abusers without their own opioid prescriptions had access to prescription opioids through family members and may have obtained prescription opioids that way. Given the study design and

  16. [Toxicity of analgesics in the family doctor practice].

    Science.gov (United States)

    Kuźniar-Placek, Justyna; Szponar, Jarosław; Panasiuk, Lech

    2012-01-01

    Analgesic usage without any consultation with a physician is very common in Poland. It increases the risk of occurrence of the harmful effect or harmful interaction with other medicaments taken by the patient. The abuse of painkillers applies not only to opioid but also to nonopioid analgesics. The largest group of commonly available medicaments are NSAIDs. The most frequent undesirable effect of NSAIDs' is dyspepsia. Among the most dangerous, and very often the ones without any symptoms, are gastric and duodenum ulceration for which the bleeding and perforation may be the first manifestation. Each non steroidal anti-inflammatory drug taken in large doses can be a cause of analgesic nephropathy. Its deceitful course can delay the diagnosis leading to chronic kidney failure. A complex supplements, that include central acting substances, increase the risk of kidney damage, as well as physical and psychological addiction. NSAIDs can cause: the heart failure to be more severe, treatment resistant arterial hypertension, increase an effectiveness of anticoagulants or antidiabetic drugs. The problem is also that some medicaments are available without a prescription (acetylsalicylic acid, ibuprofen, acetaminophen), especially that they are ingredients of many complex supplements considered safe. Taking doses larger than therapeutic or simultaneously taking many supplements of the same active substance had many times led to poisoning and even death. Equally dangerous can be an abuse of tramadol, codeine and COX-2 inhibitors. Therefore, prudential prescription of NSAIDs, knowledge of risks related to therapy and informing the patients about their side effects, may decrease the number of patients abusing the analgesics which can lead to lowering the number of deaths caused by serious complications.

  17. Use of electroanalgesia and laser therapies as alternatives to opioids for acute and chronic pain management [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Paul F. White

    2017-12-01

    Full Text Available The use of opioid analgesics for postoperative pain management has contributed to the global opioid epidemic. It was recently reported that prescription opioid analgesic use often continued after major joint replacement surgery even though patients were no longer experiencing joint pain. The use of epidural local analgesia for perioperative pain management was not found to be protective against persistent opioid use in a large cohort of opioid-naïve patients undergoing abdominal surgery. In a retrospective study involving over 390,000 outpatients more than 66 years of age who underwent minor ambulatory surgery procedures, patients receiving a prescription opioid analgesic within 7 days of discharge were 44% more likely to continue using opioids 1 year after surgery. In a review of 11 million patients undergoing elective surgery from 2002 to 2011, both opioid overdoses and opioid dependence were found to be increasing over time. Opioid-dependent surgical patients were more likely to experience postoperative pulmonary complications, require longer hospital stays, and increase costs to the health-care system. The Centers for Disease Control and Prevention emphasized the importance of finding alternatives to opioid medication for treating pain. In the new clinical practice guidelines for back pain, the authors endorsed the use of non-pharmacologic therapies. However, one of the more widely used non-pharmacologic treatments for chronic pain (namely radiofrequency ablation therapy was recently reported to have no clinical benefit. Therefore, this clinical commentary will review evidence in the peer-reviewed literature supporting the use of electroanalgesia and laser therapies for treating acute pain, cervical (neck pain, low back pain, persistent post-surgical pain after spine surgery (“failed back syndrome”, major joint replacements, and abdominal surgery as well as other common chronic pain syndromes (for example, myofascial pain, peripheral

  18. Novel Oral Therapies for Opioid-induced Bowel Dysfunction in Patients with Chronic Noncancer Pain.

    Science.gov (United States)

    Holder, Renee M; Rhee, Diane

    2016-03-01

    Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid-induced constipation or opioid-induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid-induced constipation. Axelopran (TD-1211) and sustained-release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting μ-opioid receptor antagonists. Naloxone essentially functions as a peripherally acting μ-opioid receptor antagonist when administered orally in a sustained-release formulation. Lubiprostone is a locally acting chloride channel (CIC-2) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are

  19. Perioperative analgesic requirements in severely obese adolescents and young adults undergoing laparoscopic versus robotic-assisted gastric sleeve resection

    Directory of Open Access Journals (Sweden)

    Anita Joselyn

    2015-01-01

    Full Text Available Purpose: One of the major advantages for patients undergoing minimally invasive surgery as compared to an open surgical procedure is the improved recovery profile and decreased opioid requirements in the perioperative period. There are no definitive studies comparing the analgesic requirements in patients undergoing two different types of minimally invasive procedure. This study retrospectively compares the perioperative analgesic requirements in severely obese adolescents and young adults undergoing laparoscopic versus robotic-assisted, laparoscopic gastric sleeve resection. Materials and Methods: With Institutional Review Board approval, the medication administration records of all severely obese patients who underwent gastric sleeve resection were retrospectively reviewed. Intra-operative analgesic and adjuvant medications administered, postoperative analgesic requirements, and visual analog pain scores were compared between those undergoing a laparoscopic procedure versus a robotic-assisted procedure. Results: This study cohort included a total of 28 patients who underwent gastric sleeve resection surgery with 14 patients in the laparoscopic group and 14 patients in the robotic-assisted group. Intra-operative adjuvant administration of both intravenous acetaminophen and ketorolac was similar in both groups. Patients in the robotic-assisted group required significantly less opioid during the intra-operative period as compared to patients in the laparoscopic group (0.15 ± 0.08 mg/kg vs. 0.19 ± 0.06 mg/kg morphine, P = 0.024. Cumulative opioid requirements for the first 72 postoperative h were similar in both the groups (0.64 ± 0.25 vs. 0.68 ± 0.27 mg/kg morphine, P = NS. No difference was noted in the postoperative pain scores. Conclusion: Although intraoperative opioid administration was lower in the robotic-assisted group, the postoperative opioid requirements, and the postoperative pain scores were similar in both groups.

  20. Does mutual compensation of the cognitive effects induced by pain and opioids exist?

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Malver, Lasse Paludan; Andresen, Trine

    2015-01-01

    RATIONALE: Studies have demonstrated that both pain and opioids have actions on the central nervous system that may interfere with cognitive function, but their effects have mainly been analysed separately and not as an integrated process. OBJECTIVE: The objective of this study is to test two...... hypotheses: (1) the analgesic effect of opioids improves cognitive function by decreasing pain, and (2) pain antagonizes cognitive effects of opioids. METHODS: Randomized, placebo-controlled, crossover study. Three experiments were conducted with 22 healthy males. Sustained attention, memory and motor....... CONCLUSION: Pain and remifentanil seemed to have additive deleterious cognitive effects. This study represents an initial step to enhance our basic understanding of some of the cognitive effects following a painful stimulus and an opioid infusion separately and combined in a sequence comparable to clinical...

  1. Latin-American guidelines for opioid use in chronic nononcologic pain.

    Science.gov (United States)

    Lara-Solares, Argelia; Aguayo Zamora, Carlos; Amescua García, César; Garcia, João Batista Santos; Berenguel Cook, María Del Rosario; Bonilla Sierra, Patricia; Campos Kraychete, Durval; Flores Cantisani, José Alberto; Guerrero, Carlos; Guillén Núñez, María Del Rocío; Hernández Castro, John Jairo; Hernández Ortíz, Andrés; Jreige Iskandar, Aziza; Lech, Osvandré; Macías Guerra, Jacqueline; Ramírez Samayoa, Gerardo; Rangel Morillo, Edwin; Rico Pazos, María Antonieta; Sempértegui Gallegos, Manuel

    2017-05-01

    Latin-American experts in the use of opioids in patients with chronic nononcologic pain (CNOP) have updated existing recommendations to current Latin-American reality. Several key opinion leaders from Latin America participated in a face-to-face meeting in Guatemala (April 2015) to discuss the use of opioids in CNOP. Subgroups of experts worked on specific topics, reviewed the literature and shaped the final manuscript. The expert panel developed guidelines taking into consideration the utility of both opioid and nonopioid analgesics and factors pertaining to their efficacy, safety, adherence, administration and risks for abuse/addiction. Latin-American guidelines for the use of opioids in CNOP should improve pain relief and patients' quality of life by increasing access to these effective agents.

  2. The mu-opioid receptor agonist/noradrenaline reuptake inhibition (MOR-NRI) concept in analgesia: the case of tapentadol.

    Science.gov (United States)

    Tzschentke, Thomas M; Christoph, Thomas; Kögel, Babette Y

    2014-04-01

    Tapentadol is a novel, centrally-acting analgesic drug, with an analgesic efficacy comparable to that of strong opioids such as oxycodone and morphine. Its high efficacy has been demonstrated in a range of animal models of acute and chronic, nociceptive, inflammatory, and neuropathic pain as well as in clinical studies with moderate to severe pain arising from a number of different etiologies. At the same time, a favorable gastrointestinal tolerability has been demonstrated in rodents and humans, and advantages over morphine regarding tolerance development and physical dependence were shown in animal studies. Furthermore, a low level of abuse and diversion is beginning to emerge from first post-marketing data. Tapentadol acts as a μ-opioid receptor (MOR) agonist and noradrenaline reuptake inhibitor (NRI). Both mechanisms of action have been shown to contribute to the analgesic activity of tapentadol and to produce analgesia in a synergistic manner, such that relatively moderate activity at the two target sites (MOR and noradrenaline reuptake transporter) is sufficient to produce strong analgesic effects. It has been suggested that tapentadol is the first representative of a proposed new class of analgesics, MOR-NRI. This review presents the evidence that has led to this suggestion, and outlines how the pharmacology of tapentadol can explain its broad analgesic activity profile and high analgesic potency as well as its favorable tolerability.

  3. Sucrose ingestion causes opioid analgesia

    Directory of Open Access Journals (Sweden)

    F.N. Segato

    1997-08-01

    Full Text Available The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean ± SEM, N = 12 for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 ± 0.04, 0.10 ± 0.05, 0.15 ± 0.08 and 0.49 ± 0.07, respectively. One-way ANOVA indicated a significant difference (F(3,47 = 9.521, P<0.001 and the Tukey multiple comparison test (P<0.05 showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7 receiving sucrose exhibited an analgesia index of 0.20 ± 0.10 while rats receiving only sucrose (N = 7 had an index of 0.68 ± 0.11 (t = 0.254, 10 degrees of freedom, P<0.03. This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.

  4. Overlapping mechanisms of stress-induced relapse to opioid use disorder and chronic pain: Clinical implications

    Directory of Open Access Journals (Sweden)

    Udi E Ghitza

    2016-05-01

    Full Text Available Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics which have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently-available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions which may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.

  5. Association of sleep disordered breathing symptoms with early postoperative analgesic requirement in pediatric ambulatory surgical patients.

    Science.gov (United States)

    Yang, Kamie; Baetzel, Anne; Chimbira, Wilson T; Yermolina, Yuliya; Reynolds, Paul I; Nafiu, Olubukola O

    2017-05-01

    Sleep disordered breathing (SDB) symptoms are associated with increased rates of opioid-induced respiratory depression as well as enhanced nociception. Consequently, practitioners often withhold or administer lower intraoperative doses of opioids out of concern for postoperative respiratory depression. Therefore, SDB may be a critical determinant of analgesic requirement in the post-anesthesia care unit (PACU). We investigated whether preoperative SDB classification was independently associated with need for PACU analgesic intervention in a cross-sectional sample of 985 children who underwent elective, painful ambulatory surgical procedures. Using prospectively collected data, children aged 4-17yr were grouped into two categories based on whether or not they had symptoms of SDB. Perioperative variables were compared between the exposed and control groups using Chi-squared test for categorical or t-test for continuous variables. Logistic regression analysis was used to assess the association between SDB and the odds of requiring PACU IV opioids. Children with preoperative SDB symptoms (N = 325) compared with the reference group of children who did not have these symptoms had higher rates of PACU analgesic intervention (47.1% vs. 37.4%; p = 0.004) and higher mean arousal pain scores (3.7 ± 3.5 vs.1.9 ± 2.9; p children undergoing ambulatory surgery, exerts a significant influence on PACU pain behavior and analgesic requirement. Mechanisms underlying this enhanced pain experience deserve further elucidation. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Prescription Pattern of Analgesic Drugs for Patients Receiving Palliative Care in a Teaching Hospital in India.

    Science.gov (United States)

    Menezes, Vishma Hydie; Nair, Shoba N; Soumya, M S; Tarey, S D

    2016-01-01

    Drugs used in the palliative care unit for managing symptoms are major contributors toward the expenditure occurring in palliative care. This study was conducted to understand the prescription pattern of analgesic drugs in the patients who are receiving palliative care in a teaching hospital in India by a retrospective study of case records. Case record based, retrospective, descriptive study was conducted at the Pain and Palliative Care Department of St. John's Medical College Hospital, Bengaluru. Case record files of all patients referred to Pain and Palliative Care Department for the treatment of pain in the year of 2012 were studied. Patients' age, gender, diagnoses, numerical pain rating scale (0-10), drugs prescribed, dosage, frequency, route of administration were recorded. The difference in drug utilization between the genders was done using Chi-square test. Data were collected from 502 patients of which 280 (56%) were males and 222 (44%) were females. Twelve percent of patients had mild pain (1-3), 34% had moderate pain (4-6), and 54% had severe pain (7-10). The most commonly used analgesic drugs were opioids (47%), followed by nonsteroidal anti-inflammatory drugs (36%). The opioids used were tramadol (56%), and morphine (38%). Ninety percent of patients with numerical pain scale more than 6 received morphine. There was no difference in analgesic drug utilization with regards to gender. Prescription pattern differed depending on the severity of pain. Opioids were the most commonly used drugs for pain management. The study shows that prescription pattern in palliative care unit of this hospital was in accordance with WHO pain management guidelines. The study showed the current trend in prescription of analgesic drugs in the teaching hospital where the study was conducted.

  7. Genome-wide association study identifies polymorphisms associated with the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test

    Directory of Open Access Journals (Sweden)

    Kaori Takahashi

    2018-03-01

    Full Text Available Opioid analgesics are widely used for the treatment of moderate to severe pain. The analgesic effects of opioids are well known to vary among individuals. The present study focused on the genetic factors that are associated with interindividual differences in pain and opioid sensitivity. We conducted a multistage genome-wide association study in subjects who were scheduled to undergo mandibular sagittal split ramus osteotomy and were not medicated until they received fentanyl for the induction of anesthesia. We preoperatively conducted the cold pressor-induced pain test before and after fentanyl administration. The rs13093031 and rs12633508 single-nucleotide polymorphisms (SNPs near the LOC728432 gene region and rs6961071 SNP in the tcag7.1213 gene region were significantly associated with the analgesic effect of fentanyl, based on differences in pain perception latency before and after fentanyl administration. The associations of these three SNPs that were identified in our exploratory study have not been previously reported. The two polymorphic loci (rs13093031 and rs12633508 were shown to be in strong linkage disequilibrium. Subjects with the G/G genotype of the rs13093031 and rs6961071 SNPs presented lower fentanyl-induced analgesia. Our findings provide a basis for investigating genetics-based analgesic sensitivity and personalized pain control. Keywords: Opioid sensitivity, Analgesia, Fentanyl, Polymorphism, GWAS

  8. The development of new analgesics over the past 50 years: a lack of real breakthrough drugs.

    Science.gov (United States)

    Kissin, Igor

    2010-03-01

    Fifty-nine drugs identified as analgesics were introduced from 1960 to 2009 and remain in use. Seven can be regarded as having novel molecular targets; however, only one, sumatriptan, was sufficiently effective to motivate the introduction of many similar drugs acting at the same target (triptans). Publication productivity in the area of pain grew exponentially during this period. Pain-related publications on morphine were dominant among other analgesics. Very intensive research efforts directed at diverse molecular targets related to pain mechanisms produced thousands of publications, but those efforts have not yet yielded new analgesics with sufficient effectiveness to change the share of publications on opioids or nonsteroidal antiinflammatory drugs. Morphine and aspirin, introduced for the treatment of pain more than a century ago, continue to dominate biomedical publications despite their limited effectiveness in many areas (e.g., neuropathic pain) and multiple serious adverse effects. The present assessment reveals the lack of real breakthroughs in analgesic drug development despite intense research efforts. Possible factors contributing to the apparent drought of novel analgesics are discussed.

  9. Prescription History of Emergency Department Patients Prescribed Opioids

    Science.gov (United States)

    Houghland, John; Yaron, Michael; Heard, Kennon

    2013-01-01

    Introduction: To use Colorado's prescription drug monitoring program (PDMP) to describe the recent opioid prescription history of patients discharged from our emergency department (ED) with a prescription for opioid pain medications. Methods: Retrospective cohort study of 300 adult ED patients who received an opioid prescription. We abstracted prescription histories for the six months prior to the ED visit from the PDMP, and abstracted clinical and demographic variables from the chart. Results: There were 5,379 ED visits during the study month, 3,732 of which were discharged. Providers wrote 1,165 prescriptions for opioid analgesics to 1,124/3,732 (30%) of the patients. Median age was 36 years. Thirty-nine percent were male. Patients were 46% Caucasian, 26% African American, 22% Hispanic, 2% Asian and 4% other. These were similar to our overall ED population. There was substantial variability in the number of prescriptions, prescribers and total number of pills. A majority (205/296) of patients had zero or one prescription. The 90th percentile for number of prescriptions was seven, while the 10th percentile was zero. Patients in the highest decile tended to be older, with a higher proportion of Caucasians and females. Patients in the lowest decile resembled the general ED population. The most common diagnoses associated with opioid prescriptions were abdominal pain (11.5%), cold/flu symptoms (9.5%), back pain (5.4%), flank pain (5.0%) and motor vehicle crash (4.7%). Conclusion: Substantial variability exists in the opioid prescription histories of ED patients, but a majority received zero or one prescription in the preceding six months. The top decile of patients averaged more than two prescriptions per month over the six months prior to ED visit, written by more than 6 different prescribers. There was a trend toward these patients being older, Caucasian and female. PMID:23687544

  10. Prescription History of Emergency Department Patients Prescribed Opioids

    Directory of Open Access Journals (Sweden)

    Jason A Hoppe

    2013-05-01

    Full Text Available Introduction: To use Colorado’s prescription drug monitoring program (PDMP to describe the recent opioid prescription history of patients discharged from our emergency department (ED with a prescription for opioid pain medications.Methods: Retrospective cohort study of 300 adult ED patients who received an opioid prescription. We abstracted prescription histories for the six months prior to the ED visit from the PDMP, and abstracted clinical and demographic variables from the chart.Results: There were 5,379 ED visits during the study month, 3,732 of which were discharged. Providers wrote 1,165 prescriptions for opioid analgesics to 1,124/3,732 (30% of the patients. Median age was 36 years. Thirty-nine percent were male. Patients were 46% Caucasian, 26% African American, 22% Hispanic, 2% Asian and 4% other. These were similar to our overall ED population. There was substantial variability in the number of prescriptions, prescribers and total number of pills. A majority (205/296 of patients had zero or one prescription. The 90th percentile for number of prescriptions was seven, while the 10th percentile was zero. Patients in the highest decile tended to be older, with a higher proportion of Caucasians and females. Patients in the lowest decile resembled the general ED population. The most common diagnoses associated with opioid prescriptions were abdominal pain (11.5%, cold/flu symptoms (9.5%, back pain (5.4%, flank pain (5.0% and motor vehicle crash (4.7%.Conclusion: Substantial variability exists in the opioid prescription histories of ED patients, but a majority received zero or one prescription in the preceding six months. The top decile of patients averaged more than two prescriptions per month over the six months prior to ED visit, written by more than 6 different prescribers. There was a trend toward these patients being older, Caucasian and female. [West J Emerg Med. 2013;14(3:247–252.

  11. Prescription Drug Monitoring Programs Are Associated With Sustained Reductions In Opioid Prescribing By Physicians.

    Science.gov (United States)

    Bao, Yuhua; Pan, Yijun; Taylor, Aryn; Radakrishnan, Sharmini; Luo, Feijun; Pincus, Harold Alan; Schackman, Bruce R

    2016-06-01

    State prescription drug monitoring programs are promising tools to rein in the epidemic of prescription opioid overdose. We used data from a national survey to assess the effects of these programs on the prescribing of opioid analgesics and other pain medications in ambulatory care settings at the point of care in twenty-four states from 2001 to 2010. We found that the implementation of a prescription drug monitoring program was associated with more than a 30 percent reduction in the rate of prescribing of Schedule II opioids. This reduction was seen immediately following the launch of the program and was maintained in the second and third years afterward. Effects on overall opioid prescribing and prescribing of non-opioid analgesics were limited. Increased use of these programs and the adoption of new policies and practices governing their use may have contributed to sustained effectiveness. Future studies are needed to evaluate the policies' comparative effectiveness. Project HOPE—The People-to-People Health Foundation, Inc.

  12. Prevalence of and Comorbid Health Conditions Associated With Pediatric Prescription Opioid Use in the US.

    Science.gov (United States)

    Banerjee, Souvik; Roland, Carl L; Willke, Richard; Mardekian, Jack; Garrison, Louis P

    Prescription opioids are among the most effective analgesics to treat moderate to severe pain; however, little is known about the use of prescription opioids in children, particularly those receiving an extended-release formulation for the treatment of chronic pain. In this retrospective study, the authors determined the prevalence of prescription opioid use among 7-17-year-old children and associated comorbid health conditions from 2010 to 2013 using Truven Health MarketScan (MarketScan) and Optum Clinformatics DataMart (Optum). The primary end points were prevalence of using any prescription opioids, using only prescription short-acting opioids (SAOs), and at least one prescription of a long-acting opioid (LAO). The prevalence of prescription opioid use among children is non-negligible and has been trending downwards: 6.90% in 2010 and 5.93% in 2013 using MarketScan and a similar trend using Optum: 5.47% in 2010 and 4.51% in 2013. Very few children had claims for LAOs, with only 0.04% (4979 children) in MarketScan and 0.03% (1117 children) in Optum. Given the very small number of children, primarily in the 12-17 age group, who are prescribed LAOs, there is a need to focus on a better understanding of the patterns of SAO use in children.

  13. Relationship between Opioid Treatment and Rate of Healing in Chronic Wounds

    Science.gov (United States)

    Shanmugam, Victoria K.; Couch, Kara S.; McNish, Sean; Amdur, Richard L.

    2016-01-01

    Opioids are routinely used analgesics in patients with chronic wounds; however the impact of opioid exposure on wound healing is poorly understood. The purpose of this study was to investigate the association between opioid exposure and wound outcome in the WE-HEAL study. This longitudinal observational study was conducted on 450 subjects enrolled in the WE-HEAL biorepository. Data were collected prospectively including baseline characteristics, pain score, longitudinal opioid exposure, and total wound surface area (tWSA). Data were analyzed using static multivariate models, fixed-effects mixed models, and time to event analysis. Using fixed-effects models, opioid dose was significantly associated with tWSA after accounting for the effects of pain score and baseline co-variates (pwound size. Patients with opioid dose >0 to wounds; however, the data presented suggest that opioid exposure is associated with reduced likelihood of healing in patients with chronic wounds. Whether this is a causal relationship will require further study. PMID:27865036

  14. Opioid-prescribing practices in chronic cancer pain in a tertiary care pain clinic

    Directory of Open Access Journals (Sweden)

    Raghu S Thota

    2011-01-01

    Full Text Available Introduction: Under treatment of pain is a recognized global issue. Opioid analgesic medication is the mainstay of treatment in cancer patients as per the World Health Organization (WHO pain relief ladder, yet 50% of cancer patients worldwide do not receive adequate pain relief or are undertreated. Aim: The aim of this study was to audit the ongoing opioid-prescribing practices in our tertiary cancer pain clinic during January-June 2010. Materials& Methods: The prescribed type of opioid, dose, dosing interval, and laxatives details were analyzed. Results: Five hundred pain files were reviewed and 435 were found complete for audit. Three hundred forty-eight (80% patients were prescribed opioids. Two hundred fifty-nine (74.4% received weak opioids while 118 (33.9% received strong opioids. A total of 195 (45% patients had moderate and 184 (42% had severe pain. Ninety-three (26.7% patients received morphine; however, only 31.5% (58 of 184 in severe pain received morphine as per the WHO pain ladder. Only 73 of 93 (78.4% patients received an adequate dose of morphine with an adequate dosing interval and only 27 (29% were prescribed laxatives with morphine. Conclusion: This study shows that the under treatment of pain and under dosing of opioids coupled with improper side effect management are major issues.

  15. Assessment and Treatment of Abuse Risk in Opioid Prescribing for Chronic Pain

    Directory of Open Access Journals (Sweden)

    Robert N. Jamison

    2011-01-01

    Full Text Available Opioid analgesics provide effective treatment for noncancer pain, but many physicians have concerns about adverse effects, tolerance, and addiction. Misuse of opioids is prominent in patients with chronic back pain and early recognition of misuse risk could help physicians offer adequate patient care while implementing appropriate levels of monitoring to reduce aberrant drug-related behaviors. In this review, we discuss opioid abuse and misuse issues that often arise in the treatment of patients with chronic back pain and present an overview of assessment and treatment strategies that can be effective in improving compliance with the use of prescription opioids for pain. Many persons with chronic back pain have significant medical, psychiatric and substance use comorbidities that affect treatment decisions and a comprehensive evaluation that includes a detailed history, physical, and mental health evaluation is essential. Although there is no “gold standard” for opioid misuse risk assessment, several validated measures have been shown to be useful. Controlled substance agreements, regular urine drug screens, and interventions such as motivational counseling have been shown to help improve patient compliance with opioids and to minimize aberrant drug-related behavior. Finally, we discuss the future of abuse-deterrent opioids and other potential strategies for back pain management.

  16. The pharmacological basis of opioids.

    Science.gov (United States)

    Ghelardini, Carla; Di Cesare Mannelli, Lorenzo; Bianchi, Enrica

    2015-01-01

    An opioid is a chemical that binds to opioid receptors, which are widely distributed in the central and peripheral nervous system and gastrointestinal tract. The different effects elicited by activation of these receptors are due to their specific neuronal and extraneuronal distribution. The painkiller effect of opioids is induced by the synergy of the two events, namely reduction of pain threshold and emotional detachment from pain. The opioid effects transcending analgesia include sedation, respiratory depression, constipation and a strong sense of euphoria. There are opioid-like substances endogenously produced by the body. Naturally occurring peptides, called enkephalins, have opioid-like activities but are not derived from opium and exert opioid-like effects by interacting with opioid receptors on cell membranes. Yet, animals do contain the same morphine precursors and metabolites as opium poppy and are able to synthesize endogenous morphine alkaloid. Experimental and clinical studies show that opioids, at doses comparable to those of endogenous opioids, can activate pronociceptive systems, leading to pain hypersensitivity and short-term tolerance, a phenomenon encountered in postoperative pain management by acute opioid administration. Whether endogenous opioids play a role in the acute pain necessary to the survival of the individual, remains an open question.

  17. Mu receptor binding of some commonly used opioids and their metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhaorong; Irvine, R.J. (Univ. of Adelaide (Australia)); Somogyi, A.A.; Bochner, F. (Univ. of Adelaide (Australia) Royal Adelaide Hospital (Australia))

    1991-01-01

    The binding affinity to the {mu} receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with {sup 3}H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding. Decreasing the length of the alkyl group at position 3 decreased the K{sub i} values (morphine < codeine < ethylmorphine < pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 had relatively weak receptor binding, while their O-demethylated metabolites had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

  18. Design, recruitment outcomes, and sample characteristics of the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial.

    Science.gov (United States)

    Krebs, Erin E; Jensen, Agnes C; Nugent, Sean; DeRonne, Beth; Rutks, Indulis; Leverty, David; Gravely, Amy; Noorbaloochi, Siamak; Bair, Matthew J; Kroenke, Kurt

    2017-11-01

    This manuscript describes the study protocol, recruitment outcomes, and baseline participant characteristics for the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial. SPACE is a pragmatic randomized comparative effectiveness trial conducted in multiple VA primary care clinics within one VA health care system. The objective was to compare benefits and harms of opioid therapy versus non-opioid medication therapy over 12months among patients with moderate-to-severe chronic back pain or hip/knee osteoarthritis pain despite analgesic therapy; patients already receiving regular opioid therapy were excluded. Key design features include comparing two clinically-relevant medication interventions, pragmatic eligibility criteria, and flexible treat-to-target interventions. Screening, recruitment and study enrollment were conducted over 31months. A total of 4491 patients were contacted for eligibility screening; 53.1% were ineligible, 41.0% refused, and 5.9% enrolled. The most common reasons for ineligibility were not meeting pain location and severity criteria. The most common study-specific reasons for refusal were preference for no opioid use and preference for no pain medications. Of 265 enrolled patients, 25 withdrew before randomization. Of 240 randomized patients, 87.9% were male, 84.1% were white, and age range was 21-80years. Past-year mental health diagnoses were 28.3% depression, 17% anxiety, 9.4% PTSD, 7.9% alcohol use disorder, and 2.6% drug use disorder. In conclusion, although recruitment for this trial was challenging, characteristics of enrolled participants suggest we were successful in recruiting patients similar to those prescribed opioid therapy in usual care. Published by Elsevier Inc.

  19. Perioperative analgesic use by Ontario veterinarians, 2012.

    Science.gov (United States)

    Reimann, Jessica; Dewey, Cate; Bateman, Shane W; Kerr, Carolyn; Johnson, Ron

    2017-02-01

    The objectives of this study were to describe the routine use of analgesics by Ontario veterinarians for common surgeries in dogs and cats, and to compare routine use of analgesics between species and surgeries, using Chi-square analyses. In total, 239 veterinarians responded to the questionnaires; a response rate of 13.1%. Fifty-two percent to 79% of veterinarians used meloxicam for both species and all surgeries. Approximately 9% of veterinarians did not use analgesics for dog ovariohysterectomy and castration, while 16% to 22% did not use analgesics for these surgeries in cats. Veterinarians used and dispensed analgesics to dogs more often than to cats ( P veterinarians administered analgesics pre-emptively to both dogs and cats for all surgeries. Continuing education for veterinarians needs to focus on understanding of pre-emptive analgesia, preventive analgesia, and the importance of dispensing analgesic drugs after surgery for all surgeries.

  20. Opioid Prescribing PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2017-07-06

    This 60 second public service announcement is based on the July 2017 CDC Vital Signs report. Higher opioid prescribing puts patients at risk for addiction and overdose. Learn what can be done about this serious problem.  Created: 7/6/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/6/2017.

  1. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism

    Directory of Open Access Journals (Sweden)

    Coluzzi F

    2015-03-01

    Full Text Available Flaminia Coluzzi,1,2 Joseph Pergolizzi,3,4 Robert B Raffa,5 Consalvo Mattia1,2 1Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesiology, Intensive Care Medicine and Pain Therapy, Faculty of Pharmacy and Medicine – Polo Pontino, Sapienza University of Rome, Latina, Italy; 2SIAARTI Study Group on Acute and Chronic Pain, Rome, Italy; 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 4Naples Anesthesia and Pain Associates, Naples, FL, 5Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1 the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2 reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3 chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine. Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily should be monitored for the early detection of hormonal impairment and low bone mass density. Keywords: opioids side effects, bone metabolism, fractures, OPIAD, endocrine system, chronic pain

  2. The Use of Analgesic and Other Pain-Relief Drugs to Manage Chronic Low Back Pain: Results from a National Survey.

    Science.gov (United States)

    Gouveia, Nélia; Rodrigues, Ana; Ramiro, Sofia; Eusébio, Mónica; Machado, Pedro M; Canhão, Helena; Branco, Jaime C

    2017-03-01

    To analyze and characterize the intake profile of pain-relief drugs in a population-based study of adults with chronic low back pain (CLBP). EpiReumaPt was a cross-sectional Portuguese population-based study (10,661 subjects). Self-reported active CLBP was considered to be low back pain on the day of enrollment and for ≥ 90 days. Prevalence and profile of analgesic intake was characterized among those self-reporting active CLBP, taking into account the intensity of pain and the World Health Organization (WHO) analgesic ladder. We further investigated whether the presence of active CLBP was a factor independently associated with the intake of analgesics (adjusted for potential confounders). Among 1,487 subjects with active CLBP, only 18.7% were using analgesic/pain-relief drugs. Estimated prevalence was anxiolytics, 14.1%; nonsteroidal anti-inflammatory drugs (NSAIDs), 12.3%; antidepressants, 10.1%; analgesic, antipyretics, 6.6%; anticonvulsants, 3.4%; central muscle relaxants, 2.6%; and analgesic opioids, 1.6%. Most subjects with severe pain were in the first step of the WHO analgesic ladder: NSAIDs plus anxiolytics (4.6%), NSAIDs plus antidepressants (3.2%), or NSAIDs plus muscle relaxants (2.5%). The presence of active CLBP was significantly associated with the intake of all therapeutic groups: antidepressants (odds ratio [OR] = 12.56; P pain-relief drug intake in patients with active CLBP was very low, even for those with severe pain. The WHO analgesic ladder was carefully followed, with an extremely conservative use of analgesic opioids even for those with severe pain. © 2016 World Institute of Pain.

  3. Opioid regulation of mu receptor internalisation: relevance to the development of tolerance and dependence.

    Science.gov (United States)

    Lopez-Gimenez, Juan F; Milligan, Graeme

    2010-11-01

    Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence. Although aspects of this model are controversial, such observations suggest a number of approaches to further enhance the use of morphine as an analgesic.

  4. Barriers to access to opioid medicines for patients with opioid dependence: a review of legislation and regulations in eleven central and eastern European countries.

    Science.gov (United States)

    Vranken, Marjolein J M; Mantel-Teeuwisse, Aukje K; Jünger, Saskia; Radbruch, Lukas; Scholten, Willem; Lisman, John A; Subataite, Marija; Schutjens, Marie-Hélène D B

    2017-06-01

    Barriers linked to drug control systems are considered to contribute to inequitable access to controlled medicines, leaving millions of people in pain and suffering. Most studies focus on access to opioids for the treatment of severe (cancer) pain. This study aims to identify specific access barriers for patients with opioid dependence in legislation and regulations of 11 central and eastern European countries. This study builds on a previous analysis of legislation and regulations as part of the EU 7th Framework Access To Opioid Medication in Europe (ATOME) project. An in-depth analysis was undertaken to determine specific barriers for patients with opioid dependence in need of opioid analgesics or opioid agonist therapy (OAT). For each country, the number and nature of specific potential barriers for these patients were assessed according to eight categories: prescribing; dispensing; manufacturing; usage; trade and distribution; affordability; penalties; and other. An additional keyword search was conducted to minimize the omission of barriers. Barriers in an additional category, language, were recorded qualitatively. Countries included Bulgaria, Cyprus, Estonia, Greece, Hungary, Latvia, Lithuania, Serbia, Slovakia, Slovenia and Turkey. Ten of the 11 countries (all except Estonia) showed specific potential barriers in their legislation and regulations. The total number of barriers varied from two (Slovenia) to 46 (Lithuania); the number of categories varied from one (Slovenia) to five (Lithuania). Most specific potential barriers were shown in the categories 'prescribing', 'usage' and 'other'. The total number in a single category varied from one to 18 (Lithuania, prescribing). Individual differences between countries in the same specific potential barrier were shown; for example, variation in minimum age criteria for admission to OAT ranging from 15 (Lithuania, in special cases) to 20 years (Greece). All countries had stigmatizing language in their legislation

  5. Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans.

    Science.gov (United States)

    Sims-Williams, Hugh; Matthews, Julian C; Talbot, Peter S; Love-Jones, Sarah; Brooks, Jonathan Cw; Patel, Nikunj K; Pickering, Anthony E

    2017-02-01

    Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [ 11 C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [ 11 C]DPN and [ 15 O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [ 11 C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [ 11 C]DPN binding and the analgesic effect or the effect on mood (POMS SV ) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Karine Thibault

    Full Text Available Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  7. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Science.gov (United States)

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  8. Opioid Use Patterns Among Active Duty Service Members and Civilians: 2006-2014.

    Science.gov (United States)

    Kazanis, William; Pugh, Mary J; Tami, Claudina; Maddry, Joseph K; Bebarta, Vikhyat S; Finley, Erin P; McGeary, Don D; Carnahan, David H; Potter, Jennifer S

    2018-03-01

    Between 2001 and 2009, opioid analgesic prescriptions in the Military Health System quadrupled to 3.8 million. The sheer quantity of opioid analgesics available sets the stage for issues related to misuse, abuse, and diversion. To address this issue, the Department of Defense implemented several directives and clinical guidelines to improve access to appropriate pain care and safe opioid prescribing. Unfortunately, little has been done to characterize changing patterns of opioid use in active duty service members (ADSM), so little is known about how combat operations and military health care policy may have influenced this significant problem. We examined changes in opioid use for ADSM between 2006 and 2014, compared trends with the civilian population, and explored the potential role of military-specific factors in changes in opioid use in the Military Health System. After obtaining Institutional Review Board approval, administrative prescription records (Pharmacy Data Transaction Records) for non-deployed ADSM were used to determine the number of opioid prescriptions dispensed each year and the proportion of ADSM who received at least one prescription per month between 2006 and 2014. Based on the observation and the literature, we identified December 2011 as the demarcation point (the optimal point to identify the downturn in opioid use) and used it to compare opioid use trends before and after. We used an autoregressive forecast model to verify changes in opioid use patterns before and after 2011. Several interrupted time series models examined whether military system-level factors were associated with changes in opioid use. Between 2006 and 2014, 1,516,979 ADSM filled 7,119,945 opioid prescriptions, either in military treatment facilities or purchased through TRICARE. Both active duty and civilian populations showed signs of decreasing use after 2011, but this change was much more pronounced among ADSM. The forecast model showed a significant difference after

  9. Implications of prescription drug monitoring and medical cannabis legislation on opioid overdose mortality.

    Science.gov (United States)

    Phillips, Elyse; Gazmararian, Julie

    To determine whether specific state legislation has an effect on opioid overdose mortality rates compared to states without those types of legislation. Ecological study estimating opioid-related mortality in states with and without a prescription drug monitoring program (PDMP) and/or medical cannabis legislation. Opioid-related mortality rates for 50 states and Washington DC from 2011 to 2014 were obtained from CDC WONDER. PDMP data were obtained from the National Alliance for Model State Drug Laws, and data on medical cannabis legislation from the National Organization for the Reform of Marijuana Laws. The relationship between PDMPs with mandatory access provisions, medical cannabis legislation, and opioid-related mortality rates. Multivariate repeated measures analysis performed with software and services. Medical cannabis laws were associated with an increase of 21.7 percent in mean age-adjusted opioid-related mortality (p legislation produced a borderline significant decrease of 10.1 percent (p = 0.055). For every year states had both types of legislation, interaction resulted in a 0.6 percent decrease in rate (p = 0.013). When combined with the availability of medical cannabis as an alternative analgesic therapy, PDMPs may be more effective at decreasing opioid-related mortality.

  10. The role of ABC transporters of the blood-brain barrier in opioid tolerance development

    Directory of Open Access Journals (Sweden)

    Kamila Środa-Pomianek

    2018-02-01

    Full Text Available Opioids constitute an important group of drugs used in chronic pain treatment, e.g. cancer pain. Unfortunately, the development of the organism’s tolerance to the analgesic activity of opioids, the tendency to develop addictions and undesirable side effects are the main causes reducing opioid efficiency in chronic pain treatment. Among many mechanisms connected to emerging of opioid resistance the ATP-binding cassette (ABC transporters present at the blood-brain barrier may play an important role. These transporter proteins, especially P-glycoprotein (ABCB1, MDR1, affect pharmacokinetics of many drugs and xenobiotics that are their substrates. ABC transporters reduce cellular uptake of drugs and/or increase their export from brain tissue to blood. Substrate specificity of P-glycoprotein is extremely wide and comprises many structurally and functionally unrelated compounds. What is interesting, substrate specificity of P-glycoprotein overlaps to a great extent the specificity of the isoforms of cytochrome P450 involved in drug metabolism. In the present review, the ABC proteins-mediated transport of opioids was discussed as well as the mechanisms of transport regulation. Cellular metabolism of various opioid drugs and the role of ABC transporters in their absorption, distribution and elimination were also described.

  11. The analgesic effect of wound infiltration with local anaesthetics after breast surgery

    DEFF Research Database (Denmark)

    Byager, N; Hansen, Mads; Mathiesen, Ole

    2014-01-01

    significant reduction in post-operative, supplemental opioid consumption that was, however, of limited clinical relevance. CONCLUSION: Wound infiltration with local anaesthetics may have a modest analgesic effect in the first few hours after surgery. Pain after breast surgery is, however, generally mild......BACKGROUND: Wound infiltration with local anaesthetics is commonly used during breast surgery in an attempt to reduce post-operative pain and opioid consumption. The aim of this review was to evaluate the effect of wound infiltration with local anaesthetics compared with a control group on post......-operative pain after breast surgery. METHODS: A systematic review was performed by searching PubMed, Google Scholar, the Cochrane database and Embase for randomised, blinded, controlled trials of wound infiltration with local anaesthetics for post-operative pain relief in female adults undergoing breast surgery...

  12. Teens Mix Prescription Opioids with Other Substances

    Science.gov (United States)

    ... Infographics » Teens Mix Prescription Opioids with Other Substances Teens Mix Prescription Opioids with Other Substances Email Facebook ... amphetamines (10.6%, 10.3%, and 9.5%). Teens who mix prescription opioids with other drugs are ...

  13. Peripheral Opioid Analgesia

    Science.gov (United States)

    1999-07-16

    well. Morphine was isolated in 1806 and as early as 1850 it was used medicinally in conjunction with anesthesia , and it continues to be used for pain...and morphine stimulate POMC expression which is probably mediated through CRH. In the periphery of humans, rats and cows the POMC mRNA is 200-300 base...use of any copyrighted material in the dissenation entitled: "Peripheral Opioid Analgesia" beyond brief excerpts is with the pennission of the

  14. Influence of bile acid derivates on morphine analgesic effect in mice

    Directory of Open Access Journals (Sweden)

    Vasović Velibor

    2014-01-01

    Full Text Available Background/Aim. It is known that bile acids improve the absorption, bioavailability and pharmacodynamic characteristics of some drugs. Morphine analgesia is produced by activation of opioid receptors within the central nervous system (CNS at both spinal and supraspinal levels. Since a morphine molecule contains 3 polar groups and therefore hard to transfer through the blood-brain barrier, the aim of the study was to examine the potential influence of bile acids derivates, namely sodium salt of monoketocholic acid (MKH-Na and methyl ester of monoketocholic acid (MKH-Me, on analgesic effect of morphine. Methods. White male mice of NMRI-Haan strain, with body weight of 20-24 g, were used in this study. The analgesic effect of morphine (administered by subcutaneous and intramuscular route in a dose of 2 mg/kg, with and without pretreatment with MKH-Na (4 mg/kg and MKH-Me (4 mg/kg was estimated by the hot plate method. Results. Administration of MKH-Me prior to subcutaneous administration of morphine increased the morphine analgesic effect but the increase was not statistically significant. At the same time administration of MKH-Na did not affect morphine analgesic effect. The analgesic effect of morphine increased when administered intramuscularly 20 min after MKH-Me administration. When compared with the group of animals treated only with morphine, a statistically significant increase in analgesic effect was detected 10, 30, 40 and 50 min after morphine administration (p < 0.05. Pretreatment with MKH-Na did not affect morphine analgesic effect. Conclusion. According to the results of this study it can be presumed that after intramuscular morphine administration methyl ester of monoketocholic acid increases morphine transport into the central nervous system and consequently the analgesic effect, as well. Further research on bile acids-morphine interaction both in vitro and in vivo is necessary to completely elucidate the mechanism of this

  15. Pure analgesics in a rheumatological outpatient clinic

    Directory of Open Access Journals (Sweden)

    M.A. Cimmino

    2011-09-01

    Full Text Available Objective: Pure analgesics are only rarely used by Italian clinicians and this holds true also for rheumatologists. This work is concerned with an evaluation of the use of analgesics in a rheumatological outpatient clinic during the period 1989-1999. Methods: The records of 1705 patients consecutively seen at the clinic were downloaded on a specifically built website. Results: 4469 visits were considered. In 260 of them (5.8%, analgesics were prescribed to 234 (13.7% patients. The number of patients with a prescription of analgesics steadily increased during the years 1989-1999. The diagnoses in patients assuming analgesics were: osteoarthritis (47.1%, inflammatory arthritis (24.2%, soft tissue rheumatisms (13.7%, nonspecific arthralgia/myalgia (7.5%, and connective tissue diseases (2.6%. Peripheral analgesics were used in 188 (82.5% patients and central analgesics were used in the remaining 40 patients (17.5%. Analgesic drugs were used mainly in degenerative joint conditions. The indications for analgesics in the 55 patients with inflammatory arthrits were: (a partial or total remission of arthritis; for this reason non-steroidal anti-inflammatory drugs were no longer required in 18 patients; (b to increase the analgesic effect of NSAIDs in 23 patients; (c contraindications to NSAIDs in 14 patients (renal failure in 2 patients, gastritis in 10, allergy and bleeding in the remaining two. Conclusions: About 14% of our outpatients were treated with analgesics with an increasing trend in the examined period. The main indications for analgesics are degenerative conditions but they can be used also in selected patients with arthritis.

  16. Effects of Ginkgo Biloba Extract EGb-761 on Neuropathic Pain in Mice: Involvement of Opioid System.

    Science.gov (United States)

    Zhu, Chao; Li, Wei; Xu, Fan; Li, Mo; Yang, Liu; Hu, Xue-Yu; Ye, Zheng-Xu; Wang, Zhe; Luo, Zhuo-Jing

    2016-11-01

    Neuropathic pain is considered as one of the most difficult types of pain to manage with conventional analgesics. EGb-761 is extracted from leaves of Ginkgo biloba and has analgesia and anti-inflammatory properties. This study aimed to examine the effect of EGb-761 on chronic constriction injury (CCI)-induced neuropathic pain behaviors, including thermal hyperalgesia and mechanical allodynia, and to explore the possible mechanisms underlying this action. To this end, CCI mice were intraperitoneally injected with EGb-761 (10, 20, 40, and 80 mg/kg), and thermal hyperalgesia, mechanical allodynia, cytokines, and mu-opioid receptor expression were measured. Results showed that EGb-761 attenuated thermal hyperalgesia and mechanical allodynia dose-dependently and the best delivery time window was from day 7 to day 14 after CCI. Additionally, EGb-761 treatment significantly decreased pro-inflammatory cytokines and enhanced mu opioid receptor (MOR) expression in the sciatic nerve. Moreover, the opioid antagonist naloxone prevented the effect of EGb-761 on thermal hyperalgesia and mechanical allodynia but did not influence the effect of EGb-761 on inflammatory cytokines. In conclusion, this study suggests that the potential of EGb-761 as a new analgesic for neuropathic pain treatment, and opioid system may be involved in the EGb-761-induced attenuation of thermal hyperalgesia and mechanical allodynia. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Possible participation of endogenous opioid peptides on the mechanism involved in analgesia induced by vouacapan.

    Science.gov (United States)

    Duarte, I D; Ferreira-Alves, D L; Nakamura-Craig, M

    1992-01-01

    The involvement of opioid peptides in the mechanism of action of vouacapan, a new experimental compound extracted from seeds of Pterodon poligalaeflorus Benth, was investigated both in mice utilizing acetic acid writhing response and in rats utilizing inflammatory hyperalgesia induced by carrageenan and modified Randall-Selitto method. Vouacapan, in both models, caused a dose-dependent analgesia when injected p.o., s.c. and i.p. The analgesic effect was partially blocked by naloxone, nalorphine and n-methyl-nalorphine. Significant tolerance to analgesic effect was observed following repeated administration of vouacapan or morphine. On the last day of treatment, cross administration revealed symmetrical and asymmetrical cross-tolerance between vouacapan and morphine, in rats and mice, respectively. We conclude that a release of endorphins could be involved in the analgesic mechanism of vouacapan in both models tudied.

  18. Impact of Prior Therapeutic Opioid Use by Emergency Department Providers on Opioid Prescribing Decisions.

    Science.gov (United States)

    Pomerleau, Adam C; Perrone, Jeanmarie; Hoppe, Jason A; Salzman, Matthew; Weiss, Paul S; Nelson, Lewis S

    2016-11-01

    Our study sought to examine the opioid analgesic (OA) prescribing decisions of emergency department (ED) providers who have themselves used OA therapeutically and those who have not. A second objective was to determine if OA prescribing decisions would differ based on the patient's relationship to the provider. We distributed an electronic survey to a random sample of ED providers at participating centers in a nationwide research consortium. Question topics included provider attitudes about OA prescribing, prior personal therapeutic use of OAs (indications, dosing, and disposal of leftover medication), and hypothetical analgesic-prescribing decisions for their patients, family members, and themselves for different painful conditions. The total survey population was 957 individuals; 515 responded to the survey, a 54% response rate. Prior personal therapeutic OA use was reported in 63% (95% CI = [58-68]). A majority of these providers (82%; 95% CI = [77-87]) took fewer than half the number of pills prescribed. Regarding provider attitudes towards OA prescribing, 66% (95% CI = [61-71]) agreed that OA could lead to addiction even with short-term use. When providers were asked if they would prescribe OA to a patient with 10/10 pain from an ankle sprain, 21% (95% CI = [17-25]) would for an adult patient, 13% (95% CI = [10-16]) would for an adult family member, and 6% (95% CI = [4-8]) indicated they themselves would take an opioid for the same pain. When the scenario involved an ankle fracture, 86% (95% CI = [83-89]) would prescribe OA for an adult patient, 75% (95% CI = [71-79]) for an adult family member, and 52% (95% CI = [47-57]) would themselves take OA. Providers who have personally used OA to treat their pain were found to make similar prescribing decisions compared to those who had not. No consistent differences in prescribing decisions were found between ED providers based on their prior therapeutic use of OA. When making OA prescribing decisions, ED providers

  19. Impact of Prior Therapeutic Opioid Use by Emergency Department Providers on Opioid Prescribing Decisions

    Directory of Open Access Journals (Sweden)

    Adam C Pomerleau

    2016-11-01

    Full Text Available INTRODUCTION: Our study sought to examine the opioid analgesic (OA prescribing decisions of emergency department (ED providers who have themselves used OA therapeutically and those who have not. A second objective was to determine if OA prescribing decisions would differ based on the patient's relationship to the provider. METHODS: We distributed an electronic survey to a random sample of ED providers at participating centers in a nationwide research consortium. Question topics included provider attitudes about OA prescribing, prior personal therapeutic use of OAs (indications, dosing, and disposal of leftover medication, and hypothetical analgesic-prescribing decisions for their patients, family members, and themselves for different painful conditions. RESULTS: The total survey population was 957 individuals; 515 responded to the survey, a 54% response rate. Prior personal therapeutic OA use was reported in 63% (95% CI = [58-68]. A majority of these providers (82%; 95% CI = [77-87] took fewer than half the number of pills prescribed. Regarding provider attitudes towards OA prescribing, 66% (95% CI = [61-71] agreed that OA could lead to addiction even with short-term use. When providers were asked if they would prescribe OA to a patient with 10/10 pain from an ankle sprain, 21% (95% CI = [17-25] would for an adult patient, 13% (95% CI = [10-16] would for an adult family member, and 6% (95% CI = [4-8] indicated they themselves would take an opioid for the same pain. When the scenario involved an ankle fracture, 86% (95% CI = [83-89] would prescribe OA for an adult patient, 75% (95% CI = [71-79] for an adult family member, and 52% (95% CI = [47-57] would themselves take OA. Providers who have personally used OA to treat their pain were found to make similar prescribing decisions compared to those who had not. CONCLUSION: No consistent differences in prescribing decisions were found between ED providers based on their prior therapeutic use of OA

  20. Potentiation of Opioid-Induced Analgesia by L-Type Calcium Channel Blockers: Need for Clinical Trial in Cancer Pain

    Directory of Open Access Journals (Sweden)

    S Basu Ray

    2008-01-01

    Full Text Available Previous reports indicate that the analgesic effect of opioids is due to both closure of specific voltage-gated calcium channels (N- and P/Q-types and opening of G protein-coupled inwardly rectifying potassium channels (GIRKs in neurons concerned with transmission of pain. However, administration of opioids leads to unacceptable levels of side effects, particularly at high doses. Thus, current research is directed towards simultaneously targeting other voltage-gated calcium channels (VGCCs like the L-type VGCCs or even other cell signaling mechanisms, which would aug-ment opioid-mediated analgesic effect without a concurrent increase in the side effects. Unfortunately, the results of these studies are often conflicting considering the different experimental paradigms (variable drug selection and their doses and also the specific pain test used for studying analgesia adopted by researchers. The present review focuses on some of the interesting findings regarding the analgesic effect of Opioids + L-VGCC blockers and suggests that time has come for a clinical trial of this combination of drugs in the treatment of cancer pain.

  1. THE ROLE OF MULTIDRUG RESISTANCE ASSOCIATED PROTEIN (MRP) IN THE BLOOD-BRAIN BARRIER AND OPIOID ANALGESIA

    Science.gov (United States)

    Su, Wendy; Pasternak, Gavril W.

    2013-01-01

    The blood brain barrier protects the brain from circulating compounds and drugs. The ATP-binding cassette (ABC) transporter P-glycoprotein (Pgp) is involved with the barrier, both preventing the influx of agent from the blood into the brain and facilitating the efflux of compounds from the brain into the blood, raising the possibility of a similar role for other transporters. Multidrug resistance associated protein (MRP), a 190 kDa protein similar to Pgp is also ABC transport that has been implicated in the blood brain barrier. The current study explores its role in opioid action. Immunohistochemically, it is localized in the choroid plexus in ratsand can be selectively downregulated by antisense treatment at both the level of mRNA, as shown by RT-PCR, and protein, as demonstrated immunohistochemically. Behaviorally, downregulation of MRP significantly enhances the analgesic potency of systemic morphine in MRP knockout mice and in antisense-treated rats by lowering the blood brain barrier. Following intracerebroventricular administration, a number of compounds, including some opioids, are rapidly secreted from the brain into the blood where they contribute to the overall analgesic effects by activating peripheral systems. MRP plays a role in this efflux. Downregulating MRP expression leads to a corresponding decrease in the transport and a diminished analgesic response from opioids administered intracerebroventricularly. Thus, the transporter protein MRP plays a role in maintaining the blood-brain barrier and modulates the activity of opioids. PMID:23508590

  2. Assessment of Postoperative Analgesic Drug Efficacy

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Kloster; Gögenur, Ismail; Torup, Henrik

    2017-01-01

    , therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. METHODS: Data from a randomized, double......: Our analyses demonstrate that the applied statistical method may alter the statistical significance and estimates of effect size of analgesic outcome variables in postoperative pain trials. Our findings underline the importance of defining valid statistical methods for future analgesic drug trials. We...... drug efficacy....

  3. Prescriptions involving analgesic drugs at a secondary health facility ...

    African Journals Online (AJOL)

    Paracetamol was the most commonly prescribed analgesic drug accounting for 55.7% of all analgesic drugs prescribed while Dipyrone was the most commonly prescribed parenteral analgesic drug. Dipyrone accounted for 19% of total Analgesic drug prescriptions but 93% of analgesics administered by intramuscular route ...

  4. Analgesic Potential of Essential Oils

    Directory of Open Access Journals (Sweden)

    José Ferreira Sarmento-Neto

    2015-12-01

    Full Text Available Pain is an unpleasant sensation associated with a wide range of injuries and diseases, and affects approximately 20% of adults in the world. The discovery of new and more effective drugs that can relieve pain is an important research goal in both the pharmaceutical industry and academia. This review describes studies involving antinociceptive activity of essential oils from 31 plant species. Botanical aspects of aromatic plants, mechanisms of action in pain models and chemical composition profiles of the essential oils are discussed. The data obtained in these studies demonstrate the analgesic potential of this group of natural products for therapeutic purposes.

  5. Opioids and immunosupression in oncological postoperative patients

    Directory of Open Access Journals (Sweden)

    José Luis Bonilla-García

    Full Text Available Summary Introduction: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU-acquired infection after a schedule of sedoanalgesia of at least 6 days. Method: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. Results: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068. Conclusion: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

  6. Preoperative opioid use and its association with perioperative opioid demand and postoperative opioid independence in patients undergoing spine surgery.

    Science.gov (United States)

    Armaghani, Sheyan J; Lee, Dennis S; Bible, Jesse E; Archer, Kristin R; Shau, David N; Kay, Harrison; Zhang, Chi; McGirt, Matthew J; Devin, Clinton J

    2014-12-01

    Prospective cohort. To assess whether preoperative opioid use is associated with increased perioperative opioid demand and postoperative opioid independence in patients undergoing spine surgery. Previous work has demonstrated increased opioid requirements during the intraoperative and immediate postoperative period in patients with high levels of preoperative opioid use. Despite this, they remain a common agent class used for the management of pain in patients prior to spine surgery. A total of 583 patients were included. Self-reported daily opioid consumption was obtained preoperatively and converted into morphine equivalent amounts and opioid use was recorded at the 12-month postoperative time. Intraoperative and immediate postoperative opioid demand was calculated. Linear regression analyses for intraoperative and immediate postoperative opioid demand while logistic regression analyses for opioid independence at 12 months including relevant covariates such as depression and anxiety were performed. The median preoperative morphine equivalent amount for the cohort was 8.75 mg, with 55% of patients reporting some degree of opioid use. Younger age, more invasive surgery, anxiety, and primary surgery were significantly associated with increased intraoperative opioid demand (P spine surgery predicts increased immediate postoperative opioid demand and decreased incidence of postoperative opioid independence. Psychiatric diagnoses in those using preoperative opioids were predictors of continued opioid use at 12 months. Patients may benefit from preoperative counseling that emphasizes minimizing opioid use prior to undergoing spine surgery. 2.

  7. Mu Opioids and Their Receptors: Evolution of a Concept

    Science.gov (United States)

    Pan, Ying-Xian

    2013-01-01

    Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated. PMID:24076545

  8. The impact of the opioids fentanyl and morphine on nociception and bone destruction in a murine model of bone cancer pain.

    NARCIS (Netherlands)

    ElMouedden, M.; Meert, T.F.

    2007-01-01

    Chronic pain resulting from metastasis into skeleton of certain neoplastic diseases remains poorly understood and relatively resistant to analgesic treatment. Opioids are the principal axis in drug therapy for this type of pain, especially at the end stage of cancer. Our aim was to examine whether,

  9. Adherence to Analgesics for Cancer Pain: A Comparative Study of African Americans and Whites Using an Electronic Monitoring Device.

    Science.gov (United States)

    Meghani, Salimah H; Thompson, Aleda M L; Chittams, Jesse; Bruner, Deborah W; Riegel, Barbara

    2015-09-01

    Despite well-documented disparities in cancer pain outcomes among African Americans, surprisingly little research exists on adherence to analgesia for cancer pain in this group. We compared analgesic adherence for cancer-related pain over a 3-month period between African Americans and whites using the Medication Event Monitoring System (MEMS). Patients (N = 207) were recruited from outpatient medical oncology clinics of an academic medical center in Philadelphia (≥18 years of age, diagnosed with solid tumors or multiple myeloma, with cancer-related pain, and at least 1 prescription of oral around-the-clock analgesic). African Americans reported significantly greater cancer pain (P < .001), were less likely than whites to have a prescription of long-acting opioids (P < .001), and were more likely to have a negative Pain Management Index (P < .001). There were considerable differences between African Americans and whites in the overall MEMS dose adherence, ie, percentage of the total number of prescribed doses that were taken (53% vs 74%, P < .001). On subanalysis, analgesic adherence rates for African Americans ranged from 34% (for weak opioids) to 63% (for long-acting opioids). Unique predictors of analgesic adherence varied by race; income levels, analgesic side effects, and fear of distracting providers predicted analgesic adherence for African Americans but not for whites. Perspective: Despite evidence of disparities in cancer pain outcomes among African Americans, surprisingly little research exists on African Americans' adherence to analgesia for cancer pain. This prospective study uses objective measures to compare adherence to prescribed pain medications between African American and white patients with cancer pain. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

    Science.gov (United States)

    Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

    2013-01-01

    Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

  11. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

    Science.gov (United States)

    Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L

    2013-11-01

    Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Interleukin 1 beta and corticotropin-releasing factor inhibit pain by releasing opioids from immune cells in inflamed tissue.

    Science.gov (United States)

    Schäfer, M; Carter, L; Stein, C

    1994-01-01

    Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves. The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans. Here we examine in vivo and in vitro whether interleukin 1 beta (IL-1) or corticotropin-releasing factor (CRF) is capable of releasing these endogenous opioids and inhibiting pain. When injected into inflamed rat paws (but not intravenously), IL-1 and CRF produce antinociception, which is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively, and by the immunosuppressant cyclosporine A. In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, delta-, and kappa-opioid antagonists, whereas CRF effects are attenuated by all except a kappa-antagonist. Finally, IL-1 and CRF produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes. This effect is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively. These findings suggest that IL-1 and CRF activate their receptors on immune cells to release opioids that subsequently occupy multiple opioid receptors on sensory nerves and result in antinociception. beta-Endorphin, mu- and delta-opioid receptors play a major role, but IL-1 and CRF appear to differentially release additional opioid peptides. PMID:7910403

  13. An investigation into the prescribing of analgesics

    African Journals Online (AJOL)

    and anxiolytics, drugs used for psychoses and related disorders, antidepressant drugs, drugs used for nausea and vertigo, analgesics, anti-epileptics and drugs used for. Parkinsonism-related disorders. The average percentage of drugs dispensed in each of these subgroups is given in Table l. Analgesics accounted.

  14. Phytochemical Screening and Preliminary Evaluation of Analgesic ...

    African Journals Online (AJOL)

    In this study, the methanolic root extract of Cissus polyantha was subjected to preliminary phytochemical screening, analgesic and anti-inflammatory studies. Phytochemical studies was carried out using standard phytochemical protocol while the analgesic studies was carried out using acetic acid-induced writhing tests in ...

  15. Analgesic Treatment in Laparoscopic Gastric Bypass Surgery

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenberg, Jacob

    2014-01-01

    This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines...... analgesic treatment in LRYGB surgery....

  16. THE ANALGESIC EFFECTS OF CHENOPODIUM AMBROSIOIDES ...

    African Journals Online (AJOL)

    Aqueous extract of the leaf of Chenopodium ambrosides, a Nigeria traditional medicinal plant, has been evaluated for its analgesic potential in mice. The analgesic potential of the plant extract was studied using the thermal (hot plate) test. The plant extract was found effective at the dose of 0.4g/kg and 0.8g/kg in elevating ...

  17. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  18. Analgesic principle from Curcuma amada.

    Science.gov (United States)

    Faiz Hossain, Chowdhury; Al-Amin, Mohammad; Rahman, Kazi Md Mahabubur; Sarker, Aurin; Alam, Md Mahamudul; Chowdhury, Mahmudul Hasan; Khan, Shamsun Nahar; Sultana, Gazi Nurun Nahar

    2015-04-02

    The rhizome of Curcuma amada has been used as a folk medicine for the treatment of rheumatic disorders in the northern part of Bangladesh and has also used for the treatment of inflammation and fever in the Ayurvedic and Unani systems of medicine. Aim of the study was to investigate the analgesic principle of the MeOH extract of the rhizome of Curcuma amada by an in vivo bioassay guided chromatographic separation and purification, and the structure elucidation of the purified compound by spectroscopic methods. Dried powder of Curcuma amada rhizomes was extracted with MeOH. The analgesic activity of the crude extract and its chromatographic fractions as well as the purified compound itself was evaluated by the acetic acid induced writhing method and the formalin induced licking test in Swiss albino mice. The MeOH extract was separated by chromatographic methods and the pure active compound was purified by crystallization in hexanes. The structure of the pure compound was then elucidated by spectroscopic methods. The MeOH extract of Curcuma amada exhibited 41.63% and 45.53% inhibitions in the acetic acid induced writhing method at doses of 200mg/kg and 400mg/kg, respectively. It also exerted 20.43% and 28.50% inhibitions in early phase at doses of 200mg/kg and 400mg/kg, respectively, and 30.41% and 42.95% inhibitions in late phase at doses of 200mg/kg and 400mg/kg, respectively in the formalin induced licking test. Vacuum Liquid Chromatography (VLC) of crude extract yielded five fractions and Fr. 1 was found to have the most potent analgesic activity with inhibitions of 36.96% in the acetic acid induced writhing method and 47.51% (early phase), 39.50% (late phase) in the formalin induced licking test at a dose of 200mg/kg. Column chromatography of Fr. 1 on silica gel generated seven fractions (SF. 1-SF. 7). SF. 2 showed the most potent activity with inhibition of 49.81% in the acetic acid induced writhing method at a dose of 100mg/kg. Crystallization of SF. 2 yielded

  19. The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice

    OpenAIRE

    Navani, Dipesh M.; Sirohi, Sunil; Madia, Priyanka A.; Yoburn, Byron C.

    2011-01-01

    On the basis of efficacy, opioid antagonists are classified as inverse opioid agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6β-naltrexol). This study examined the interaction between naltrexone and 6β-naltrexol in the precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore, the possible contribution of constitutive opioid receptor activity to precipitated withdrawal was evaluated using increasing levels of morphine dependence. In the first experiment, ...

  20. Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated by opioid mechanism

    Directory of Open Access Journals (Sweden)

    Pirkulashvili N

    2017-07-01

    Full Text Available Natia Pirkulashvili,1 Nana Tsiklauri,1 Marina Nebieridze,2 Merab G Tsagareli1 1Laboratory of Pain and Analgesia, 2Laboratory of Brain Metabolism, Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia Abstract: Several lines of investigations have shown that in some brain areas, in particular, in the midbrain periaqueductal gray matter, rostral ventromedial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of nonsteroidal anti-inflammatory drugs (NSAIDs induce antinociception with distinct development of tolerance. The agranular insular cortex (AIC is a small region of the cerebral cortex located on the lateral area of the rat’s cerebral hemisphere that is involved in the perception and response to pain. In the present study, we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac, and xefocam microinjected into the AIC in rats. Male Wistar rats receiving NSAIDs into the AIC were tested for antinociception by tail-flick and hot plate tests. Treatment with each NSAID significantly enhanced the tail-flick and hot plate latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, ie, they developed tolerance. Pretreatment with an opioid antagonist naloxone completely prevented, and posttreatment naloxone abolished, the analgesic effects of the three NSAIDs in both behavioral assays. These findings support the notion that the development of tolerance to the antinociceptive effects of NSAIDs is mediated via an endogenous opioid system possibly involving descending pain modulatory systems. Keywords: antinociception, endogenous opioids, descending modulation, nociception, non­opioid tolerance

  1. (/sup 3/H)(D-Ala2,NMePhe4,Gly-ol5)-enkephalin (mu-opioid) binding in beige-J mice

    Energy Technology Data Exchange (ETDEWEB)

    Raffa, R.B.; Baldy, W.J. Jr.; Shank, R.P.; Mathiasen, J.R.; Vaught, J.L.

    1988-05-01

    Tritiated (D-Ala2,NMePhe4,Gly-ol5)-enkephalin ((3H)DAGO) was used to examine mu-opioid receptor number and mu-ligand binding in brain synaptic membranes (P2 fraction) from C57BL/6J-bgJ/bgJ (beige-J) mice, a strain with combined deficiencies in immunological function (resembling Chediak-Higashi syndrome) and analgesic response to mu-opioid agonists such as morphine and DAGO. As controls, white mice, beige-J littermates (normally responsive to mu-opioid agonists), and a known mu-deficient strain (CXBK) were also examined. Neither the KD (0.47 to 0.49 nM) nor the Bmax (153 to 168 fmol/mg protein) determined for beige-J mice was significantly different from values determined for littermates or white mice. In contrast, the Bmax of CXBK mice (66 fmol/mg protein) was clearly less than that of the other strains. The analgesic defect of beige-J mice, therefore, is not likely due to an insufficient number of mu-opioid receptors, as it presumably is in CXBK mice. Carbachol (200 micrograms/ml), which partly corrects the analgesic defect of beige-J mice, had no effect on (3H)DAGO binding either acutely in vitro or chronically ex vivo after administration to beige-J mice for three weeks. Hence, the analgesic defect of beige-J mice appears to be due to some defect in the mu-opioid receptor-effector coupling mechanism or to some endogenous substance that inhibits binding of mu-opioid ligands to otherwise functional receptors.

  2. [3H][D-Ala2,NMePhe4,Gly-ol5]-enkephalin (mu-opioid) binding in beige-J mice

    International Nuclear Information System (INIS)

    Raffa, R.B.; Baldy, W.J. Jr.; Shank, R.P.; Mathiasen, J.R.; Vaught, J.L.

    1988-01-01

    Tritiated [D-Ala2,NMePhe4,Gly-ol5]-enkephalin ([3H]DAGO) was used to examine mu-opioid receptor number and mu-ligand binding in brain synaptic membranes (P2 fraction) from C57BL/6J-bgJ/bgJ (beige-J) mice, a strain with combined deficiencies in immunological function (resembling Chediak-Higashi syndrome) and analgesic response to mu-opioid agonists such as morphine and DAGO. As controls, white mice, beige-J littermates (normally responsive to mu-opioid agonists), and a known mu-deficient strain (CXBK) were also examined. Neither the KD (0.47 to 0.49 nM) nor the Bmax (153 to 168 fmol/mg protein) determined for beige-J mice was significantly different from values determined for littermates or white mice. In contrast, the Bmax of CXBK mice (66 fmol/mg protein) was clearly less than that of the other strains. The analgesic defect of beige-J mice, therefore, is not likely due to an insufficient number of mu-opioid receptors, as it presumably is in CXBK mice. Carbachol (200 micrograms/ml), which partly corrects the analgesic defect of beige-J mice, had no effect on [3H]DAGO binding either acutely in vitro or chronically ex vivo after administration to beige-J mice for three weeks. Hence, the analgesic defect of beige-J mice appears to be due to some defect in the mu-opioid receptor-effector coupling mechanism or to some endogenous substance that inhibits binding of mu-opioid ligands to otherwise functional receptors

  3. Comparing Early Postoperative Period Analgesic Effect of Dexketoprofene Trometamol and Lornoxicam in Mediastinoscopy Cases

    Science.gov (United States)

    Sagiroglu, Gonul

    2011-01-01

    Objective: In this study, we aimed comparing early postoperative period analgesic effectiveness and the effects on opioid consumption of intravenous dexketoprofen and lornoxicam that are given preemptively. Materials and Methods: Forty patients, planned elective mediastinoscopy, were included in this prospective randomized study. These patients were classified in two groups, group D for dexketoprofene trometamol and group L for lornoxicam, randomly. 20 minutes before the operation 50 mg dexketoprofene trometamol and 8 mg lornoxicam were injected intravenously for group D and group L respectively. In postoperative intensive care unit, pain scores, mean arterial pressures, heart rates and peripheric O2 saturations of patients were recorded at 0, 10, 20, 60, 90 and 120th minutes. Results: When we evaluate the VAS score of the groups, there was a significant decrease in group D in all measured timesstatistically compairing to group L (p0.05). Conclusion: Since intravenous dexketoprofen, applied preemptively, has more potent analgesic effect and causing less opioid consumption in early postoperative period, is better than intravenous lornoxicam. PMID:25610155

  4. Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice.

    Science.gov (United States)

    Jang, Jae-Hwan; Park, Ji-Yeun; Oh, Ju-Young; Bae, Sun-Jeong; Jang, Hyunchul; Jeon, Songhee; Kim, Jongpil; Park, Hi-Joon

    2018-01-15

    The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, indicating the involvements of many physiological functions, but the role in pain has yet to be determined. In this study, we found that pMCH -/- mice showed lower baseline pain thresholds to mechanical and thermal stimuli than did pMCH +/+ mice, and the time to reach the maximum hyperalgesic response was also significantly earlier in both inflammatory and neuropathic pain. To examine its pharmacological properties, MCH was administered intranasally into mice, and results indicated that MCH treatment significantly increased mechanical and thermal pain thresholds in both pain models. Antagonist challenges with naltrexone (opioid receptor antagonist) and AM251 (cannabinoid 1 receptor antagonist) reversed the analgesic effects of MCH in both pain models, suggesting the involvement of opioid and cannabinoid systems. MCH treatment also increased the expression and activation of CB1R in the medial prefrontal cortex and dorsolateral- and ventrolateral periaqueductal grey. The MCH1R antagonist abolished the effects induced by MCH. This is the first study to suggest novel analgesic actions of MCH, which holds great promise for the application of MCH in the therapy of pain-related diseases.

  5. Differential analgesic effect of tenoxicam on the wound pain and uterine cramping pain after cesarean section.

    Science.gov (United States)

    Hsu, Hsing-Wen; Cheng, Ya-Jung; Chen, Li-Kuei; Wang, Yong-Ping; Lin, Chen-Jung; Lee, Chien-Nan; Sun, Wei-Zen

    2003-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to enhance opioid analgesia in the acute pain service. The question, however, of whether NSAIDs produce a similar extent of potentiation among different types of pain, has not been thoroughly investigated. A randomized, placebo-controlled, double-blind study was performed to characterize the analgesic effect of tenoxicam, a long-acting NSAID, on resting wound pain, evoked wound pain, and uterine cramping pain after cesarean section. Saline (n = 48) or 20 mg tenoxicam (n = 45) was intravenously injected immediately after clamping the umbilical cord. All patients were instructed to obtain maximal postoperative analgesia by intravenous patient-controlled morphine. RESULTS Tenoxicam profoundly reduced the intensity of uterine cramping pain (3.6 [2.0-5.6] versus 5.5 [3.4-6.6]; p pain at rest, with movement, changing position, sitting, and walking. Intraoperative injection of 20 mg tenoxicam decreased the demand ratio for patient-controlled analgesia (PCA) and 24-hour morphine consumption by approximately 30%. The data show that tenoxicam potentiates opioid analgesic effect on the somatic and visceral types of pain to different extents, and they suggest that intraoperative injection of 20 mg tenoxicam is sufficient to enhance intravenous PCA morphine on uterine cramping pain for the first 24 hours after cesarean section.

  6. The damage done by the war on opioids: the pendulum has swung too far

    Directory of Open Access Journals (Sweden)

    Atkinson TJ

    2014-05-01

    Full Text Available Timothy J Atkinson,1 Michael E Schatman,2 Jeffrey Fudin1,3–51PGY2 Pain and Palliative Care Pharmacy Residency, Stratton VA Medical Center, Albany, NY, 2Foundation for Ethics in Pain Care, Bellevue, WA, 3School of Pharmacy, University of Connecticut, Storrs, CT, 4Western New England University College of Pharmacy, Springfield, MA, 5Buffalo College of Pharmacy, State University of New York, Buffalo, NY, USAIn the United States, patterns of opioid use for the management of pain have drastically changed over the past 30 years. In the 1980s, the American pain medicine landscape was characterized by opiophobia, the fear to prescribe opioids. Around the turn of the millennium, however, we witnessed a fairly rapid shift to opiophilia, or the "overprescribing" of opioids. The ubiquitous undertreatment of pain was the catalyst for clinicians and pain societies to successfully lobby for increased use of opioids for all pain types, including non-cancer pain. The approval of new standards for pain management incorporating pain as the "fifth vital sign" by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO1 seemingly fueled this increase in opioid prescription. From 1991–2009, prescriptions for opioid analgesics tripled, with emergency department visits related to non-medical use of prescription opioid overdoses doubling from 2005–2009.2 In 2010, accidental overdose deaths associated with opioids increased for the eleventh consecutive year, highlighting the drastic shift in opioid use.3 The figurative pendulum began to swing toward opiophobia following the publication of data that demonstrated that the risk of addiction associated with chronic opioid use was likely underestimated.4 Guidelines for the use of controlled substances released by the Federation of State Medical Boards of the US in 1998 reflected this change in attitude.5 At present, there is a general consensus that opioids are over-prescribed and education among health

  7. Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain.

    Science.gov (United States)

    Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

    2005-09-01

    Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (degrees C), as well as suprathreshold tonic heat pain intensity (46.5 degrees C for 1 min) measured by 0-10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI -8.8, 42.8), P = 0.19), pressure (2.2 mmHg (-28.7, 33.2), P = 0.89) and heat (-0.3 degrees C (-1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities -0.4 NPS units (95% CI -1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the 'weak' opioid-treated subgroup and the 'strong' opioid-treated subgroup again revealed insignificant results. These results suggest that the administration of 'commonly used' dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients

  8. Kratom and Future Treatment for the Opioids Addiction and Chronic Pain: Periculo Beneficium?

    Science.gov (United States)

    Ismail, Ismaliza; Wahab, Suzaily; Sidi, Hatta; Das, Srijit; Lin, Loo Jiann; Razali, Rosdinom

    2017-04-25

    Kratom (Mitragynaspeciosa), a natural existing plant found in South-East Asia, is tradi-tionally used as an herb to help to elevate a person's energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (μ) and kappa (κ). The role of neural reward pathway linked to μ-opioid receptors and both dopaminergic and GABA-ergic interneurons that express μ-opioid receptors were deliberated. However, kratom has been reported to be abused together with other illicit substances with high risk of potential addiction. There are also anecdotes of an adverse effect and toxicity of kratom, i.e. tremor, fatigue, seizure, and death. Different countries have distinctive regulation and policy on the plantation and use of this plant when most of the countries banned the use of it because of its addiction problems and side effects. The aim of this review is to highlight on the potential use of kratom, a unique 'herbs" as a substitution therapy for chronic pain and opioid addiction, based on the neurobiological perspective of pain and the underlying mechanism of actions of drug addiction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Cancer pain in the opioid-addicted patient: can we treat it right?

    Science.gov (United States)

    Modesto-Lowe, Vania; Girard, Lisa; Chaplin, Margaret

    2012-01-01

    Although cancer elicits an array of physical and emotional symptoms, pain is often identified as the most distressing. Cancer pain may result from the primary tumor, metastasis, surgery, radiation, chemotherapy, or medical comorbidities. Although treatment with opioid analgesics is accepted as appropriate therapy for cancer-related pain, under treatment may persist among certain patients. Opioid-addicted individuals represent a challenging and heterogeneous population to treat. Addiction is linked to psychopathology and antisocial behaviors (eg, lying) which often complicate evaluation. Chronic exposure to opioids may lead to physiologic dependence and its correlates, tolerance and hyperalgesia. Given the variability and subjectivity of the cancer pain experience, there are no objective measures which capture the adequacy of pain control. Thus, when faced with complaints of uncontrolled pain, clinicians must consider a differential diagnosis of tolerance, disease progression, addiction, pseudoaddiction, chemical coping, or even criminal behavior. This article explores the cognitive, behavioral, and physiological correlates of opioid addiction that may impact cancer pain management. It also discusses risk reduction strategies for opioid misuse and research directions that may lead to improved clinical outcomes in these patients.

  10. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Khanna IK

    2015-12-01

    Full Text Available Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed µ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other µ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.Keywords: buprenorphine, opioids, opioid dependence, partial agonist, hyperalgesia, neuropathic pain

  11. Abuse-deterrent Opioid Formulations.

    Science.gov (United States)

    Litman, Ronald S; Pagán, Olivia H; Cicero, Theodore J

    2017-12-18

    Abuse-deterrent opioid formulations have been suggested as one way to decrease the abuse, addiction, and overdose of orally prescribed opioids. Ten oral opioid formulations have received abuse-deterrent labeling by the U.S. Food and Drug Administration (FDA). Their properties consist of physical and/or chemical means by which the pills resist manipulation and create a barrier to unintended administration, such as chewing, nasal snorting, smoking, and intravenous injection. In this review, we describe the mechanisms of abuse-deterrent technology, the types of premarketing studies required for FDA approval, the pharmacology of the currently approved abuse-deterrent opioid formulations, and the evidence for and against their influence on opioid abuse. We conclude that there is currently insufficient evidence to indicate that the availability of abuse-deterrent opioid formulations has altered the trajectory of opioid overdose and addiction; however, postmarketing studies are in their infancy, and novel deterrent formulations are continually being developed and submitted for marketing approval.

  12. Antinociceptive effects of pluronic lecithin organo (PLO)-opioid gels in rats with thermal injury.

    Science.gov (United States)

    Clifford, John L; Christy, Robert J; Cheppudira, Bopaiah P

    2017-12-01

    Opioids are extensively used as analgesics to control burn pain. However, systemic administration of opioids induces multiple adverse effects that are primarily CNS mediated. Alternately, topical application of low dose of opioids directly at the site of injury could attenuate pain while avoiding CNS-mediated side effects. Pluronic lecithin organogels (PLO) have been extensively used as vehicles to deliver topical drugs. In this study, we for the first time assessed the analgesic efficacy of three opioid-PLO formulations (fentanyl, methadone & morphine) in a rat full-thickness thermal injury (FTTI) pain model. Experiments were performed using 44 adult male Sprague-Dawley rats. A single 0.1mL topical application of either morphine (5mg/mL, n=6), fentanyl (10μg/mL, n=8), methadone gel (5mg/mL, n=8), ketamine (50mg/mL, n=6), saline (0.1mL, n=8) or PLO gel alone (0.1mL, n=8) was administered to the plantar surface of the injured hindpaw on days 4 and 7 following thermal injury. The anti-hyperalgesic effects were then measured (5, 15, 30, 60 and 120min post-drug application) using the Hargreaves' thermal test. All three opioids produced statistically significant increases in paw withdrawal latency (PWL), taken as a measure of anti-hyperalgesia, in comparison to saline-treated group (Pthermal hyperalgesia in a rat hindpaw FTTI model, supporting the development of topical formulations of these drugs for burn pain treatment in the clinic. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  13. Effect of intraoperative esmolol infusion on anesthetic, analgesic requirements and postoperative nausea-vomitting in a group of laparoscopic cholecystectomy patients

    OpenAIRE

    Dereli, Necla; Tutal, Zehra Baykal; Babayigit, Munire; Kurtay, Aysun; Sahap, Mehmet; Horasanli, Eyup

    2015-01-01

    PURPOSE: Postoperative pain and nausea/vomitting (PNV) are common in laparoscopic cholecystectomy patients. Sympatholytic agents might decrease requirements for intravenous or inhalation anesthetics and opioids. In this study we aimed to analyze effects of esmolol on intraoperative anesthetic-postoperative analgesic requirements, postoperative pain and PNV. METHODS: Sixty patients have been included. Propofol, remifentanil and vecuronium were used for induction. Study groups were as follows;...

  14. Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy.

    Science.gov (United States)

    Unal, Ciğdem; Cakan, Türkay; Baltaci, Bülent; Başar, Hülya

    2013-10-01

    [corrected] We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl) due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Visual Analog Scale (VAS) scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12(th) h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml) in group paracetamol (72.3 ± 38.0 ml) and dexketoprofen trometamol (69.3 ± 24.1 ml) was significantly lower than group placebo (129.3 ± 22.6 ml) (P dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Dexketoprofen trometamol and Paracetamol didn't cause significant change on pain scores, but increased patients' comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not recommended.

  15. Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy

    Directory of Open Access Journals (Sweden)

    Çiğdem Ünal

    2013-01-01

    Full Text Available Backround: We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Materials and Methods: Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Results: Visual Analog Scale (VAS scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12 th h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml in group paracetamol (72.3 ± 38.0 ml and dexketoprofen trometamol (69.3 ± 24.1 ml was significantly lower than group placebo (129.3 ± 22.6 ml (P < 0.001. Global satisfaction scores of the patients in group placebo was significantly lower than group dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Conclusion: Dexketoprofen trometamol and Paracetamol didn′t cause significant change on pain scores, but increased patients′ comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not

  16. The Global Opioid Policy Initiative (GOPI) project to evaluate the availability and accessibility of opioids for the management of cancer pain in Africa, Asia, Latin America and the Caribbean, and the Middle East: introduction and methodology.

    Science.gov (United States)

    Cherny, N I; Cleary, J; Scholten, W; Radbruch, L; Torode, J

    2013-12-01

    Opioid analgesics are critical to the effective relief of cancer pain. Effective treatment is predicated on sound assessments, individually tailored analgesic therapy, and the availability and accessibility of the required medications. In some countries, pain relief is hampered by the lack of availability or barriers to the accessibility of opioid analgesics. As the follow-up to a successful project to evaluate the availability and accessibility of opioids and regulatory barriers in Europe, the European Society for Medical Oncology (ESMO) and the European Association for Palliative Care (EAPC) undertook to expand their research to those parts of the world where data were lacking regarding these aspects of care, in particular Africa, Asia, the Middle East, Latin America and the Caribbean, and the states of India. This project has been undertaken in collaboration with the Union for International Cancer Control (UICC), the Pain and Policy Studies Group (PPSG) of the University of Wisconsin, and the World Health Organization (WHO), together with a consortium of 17 international oncology and palliative care societies. This article describes the study methodology.

  17. [Biosynthesis of opioid peptides].

    Science.gov (United States)

    Rossier, J

    1988-01-01

    The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu at their aminoterminus. Three distinct families of these peptides (endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). [Met] enkephalin, [Leu] enkephalin and the related heptapeptide [Met] enkephalin-Arg6-Phe7 and octapeptide [Met] enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structure of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. The most common scheme for enzymatic maturation of precursors proposes the action of a trypsin-like endopeptidase followed by a carboxypeptidase B-like exopeptidase. However, we have provided evidence that this combination of trypsin-like and carboxypeptidase B-like enzymes may not be the only mechanism for liberating enkephalin from low molecular weight enkephalin-containing peptides. Indeed, endo-oligopeptidase A, an enzyme, known to hydrolyze the Phe5-Ser6 bond of bradykinin and the Arg8-Arg9 bond of neurotensin, has been shown to produce, by a single cleavage, [Leu] enkephalin or [Met] enkephalin from small enkephalin-containing peptides, (Camargo et al., 1987, J. Neurochem. 48, 1258-1263).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Can anaesthetic and analgesic techniques affect cancer recurrence or metastasis?

    LENUS (Irish Health Repository)

    Heaney, A

    2012-12-01

    Summary Cancer is a leading cause of morbidity and mortality worldwide and the ratio of incidence is increasing. Mortality usually results from recurrence or metastases. Surgical removal of the primary tumour is the mainstay of treatment, but this is associated with inadvertent dispersal of neoplastic cells into the blood and lymphatic systems. The fate of the dispersed cells depends on the balance of perioperative factors promoting tumour survival and growth (including surgery per se, many anaesthetics per se, acute postoperative pain, and opioid analgesics) together with the perioperative immune status of the patient. Available evidence from experimental cell culture and live animal data on these factors are summarized, together with clinical evidence from retrospective studies. Taken together, current data are sufficient only to generate a hypothesis that an anaesthetic technique during primary cancer surgery could affect recurrence or metastases, but a causal link can only be proved by prospective, randomized, clinical trials. Many are ongoing, but definitive results might not emerge for a further 5 yr or longer. Meanwhile, there is no hard evidence to support altering anaesthetic technique in cancer patients, pending the outcome of the ongoing clinical trials.

  19. Towards safer use of opioids.

    LENUS (Irish Health Repository)

    Carson, R W R

    2009-09-01

    The main aim of our work was to improve the safety of opioid use in our institution, an acute generalhospital with 620 beds. Initially, all reported opioid errors from 2001 - 2006 were audited. The findings directed a range of multidisciplinary staff educational inputs to improve opioid prescribing and administration practice, and encourage drug error reporting. 448 drug errors were reported, of which 54 (12%) involved opioids; of these, 43 (79%) involved codeine, morphine or oxycodone. 31 of the errors (57%) were associated with administration, followed by 12 (22%) with dispensing and 11 (20%) with prescribing. There were 2 reports of definite patient harm. A subsequent audit examined a 17-month period following the introduction of the above teaching: 17 errors were noted, of which 14 (83%) involved codeine, morphine or oxycodone. Again, drug administration was most error-prone, comprising 11 (65%) of reports. However, just 2 (12%) of the reported errors now involved prescribing, which was a reduction.

  20. Gene Variants Reduce Opioid Risks

    Science.gov (United States)

    ... morphine or methadone treatment to wean them off opioid dependence, and 21 (24 percent) were treated with additional medications to alleviate withdrawal symptoms. However, those infants with a guanine rs1799971 ...

  1. Newer approaches to opioid detoxification

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar

    2012-01-01

    Full Text Available Opioid use disorders present with distressing withdrawal symptoms at the time of detoxification. The pharmacological agents and methods currently in use for detoxification mainly include buprenorphine, methadone, and clonidine. Many other pharmacological agents have been tried for opioid detoxification. This review takes a look at the newer pharmacological options, both opioid agonists and non-agonist medications that have been utilized for detoxification. Peer reviewed articles were identified using PubMed and PsychInfo databases. The keywords included for the search were a combination of ′opioid′ and ′detoxification′ and their synonyms. All the articles published in the last 10 years were screened for. Relevant data was extracted from identified studies. Many newer pharmacological agents have been tried in detoxification of opioids. However, the quest for a safe, efficacious, cost-effective pharmacological option which requires minimal monitoring still continues. The role of non-pharmacological measures and alternative medicine needs further evaluation.

  2. antipyretic and analgesic activities of sphenoceutrum jollyanum

    African Journals Online (AJOL)

    The petroleum ether and methanol extracts of Sphenoceutrum jollyanum leaves possess significant in vitro analgesstic and antipyretic activities. Key Words: Sphenocentrum jollyanum, Menispermaceae, analgesic activity, antipyretic activity. Nig. J. Nat. Prod. And Med. Vol.2 1998: 52-53 ...

  3. In vivo analgesic and anti-inflammatory effects of the essential oil from Artemisia sieberi fruit

    Directory of Open Access Journals (Sweden)

    A. Darabian

    2017-10-01

    Full Text Available Background and objectives: Drugs with analgesic properties such as opioids and NSAIDs have not been effective in all cases, because of their low potency and side effects. As a result, looking for other alternatives is necessary. Plants are important sources of new phytochemicals that possess significant therapeutic effects. Regarding the traditional use of Artemisia sieberi fruit as a natural painkiller and anti-inflammatory agent and the high content of essential oil in the fruits, we were prompted to investigate the anti-inflammatory and analgesic activities of A. sieberi fruits oil. Methods: Artemisia sieberi fruits essential oil was extracted by hydrodistillation method. The analgesic and anti-inflammatory activities of the oil were studied by formalin and carrageenan tests, respectively at the doses of 0.2, 0.4 and 0.8 mg/kg for the experimental animals. Control group received sweet almond oil as the vehicle and standard groups received morphine (2 mg/kg and indomethacin (5 mg/kg for the formalin and carrageenan tests respectively. Results: All doses of A. sieberi fruits essential oil induced antinociceptive activity during the second phase of the formalin test but the maximum effect was observed at the dose of 0.8 mg/kg. In carrageenan test all the experimental doses of theoil significantly reduced the inflammation (p

  4. Analgesic-antiinflammatory drugs inhibit orbicularis oculi reflexes in humans via a central mode of action.

    Science.gov (United States)

    Ferracuti, S; Leardi, M G; Cruccu, G; Fabbri, A; Itil, T M

    1994-01-01

    1. A cross-over single blind study examined the possible central effects of non-opioid analgesic drugs on the trigeminal reflexes. 2. The corneal reflex and blink reflex (R1, R2) were recorded electromyographically and response areas measured in healthy volunteers before and after intramuscular injection of piroxicam (40 mg); and after intravenous injection of lysine acetylsalicylate (500 mg). After the last drug recording the subjects received intravenous naloxone (2 mg) followed 5 minutes later by further reflex testing. Saline was used as a placebo in control experiments. 3. Both analgesics reduced the corneal reflex: piroxicam induced a 27% and lysine acetylsalicylate a 21% a reduction that naloxone did not reverse. Neither drug reduced the early or the late component of the blink reflex. 4. The marked inhibitory changes that the two non-narcotic analgesics produced on the corneal reflex--a nociceptive response--indicate a centrally-mediated action. 5. Naloxone's failure to reverse the induced analgesia argues against opiate receptor mediation.

  5. A Retrospective Study on the Effectiveness of Switching to Oral Methadone for Relieving Severe Cancer-Related Neuropathic Pain and Limiting Adjuvant Analgesic Use in Japan.

    Science.gov (United States)

    Sugiyama, Yosuke; Sakamoto, Nobuhiro; Ohsawa, Masahiro; Onizuka, Mami; Ishida, Kyoko; Murata, Yuki; Iio, Ayaka; Sugano, Koji; Maeno, Ken; Takeyama, Hiromitsu; Akechi, Tatsuo; Kimura, Kazunori

    2016-10-01

    Cancer-related neuropathic pain is resistant to treatment with multiple medications and results in reduced patient quality of life. The aim was to find a new curative to treat neuropathic pain without using adjuvant analgesics. This was a retrospective study that used the FACES Pain Scale (FPS) to measure pain intensity and pain relief. Twenty-eight inpatients who were treated with other strong opioids and who consulted the palliative care team about their pain relief. In 22 (78.6%) out of 28 patients who successfully switched to methadone from other strong opioids, such as oxycodone and fentanyl, within two weeks, the mean FPS score was significantly reduced from 4.43 to 1.86, and methadone switching either reduced the number of prescriptions or stopped them entirely in 12 out of 17 (70.5%) patients who had used adjuvant analgesics before switching to methadone. These results suggest that opioid switching to oral methadone not only achieves pain relief but also curtails substantial adjuvant analgesic use.

  6. Is Kratom the New 'Legal High' on the Block?: The Case of an Emerging Opioid Receptor Agonist with Substance Abuse Potential.

    Science.gov (United States)

    Chang-Chien, George C; Odonkor, Charles A; Amorapanth, Prin

    2017-01-01

    Kratom is an unscheduled opioid receptor agonist that comes in the form of dietary supplements currently being abused by chronic pain patients on prescription opioids. Active alkaloids isolated from kratom such as mitragynine and 7-hydroxymitragynine are thought to act on mu- and delta-opioid receptors as well as alpha-2 adrenergic and 5-HT2A receptors. Animal studies suggest that kratom may be more potent than morphine. Consequently, kratom consumption produces analgesic and euphoric feelings among users. In particular, some chronic pain patients on opioids take kratom to counteract the effects of opioid withdrawal. Although the Food and Drug Administration has banned its use as a dietary supplement, kratom continues to be widely available and easily accessible on the Internet at much less expensive rates than some opioid replacement therapies like buprenorphine. There are no federal regulations monitoring the sale and distribution of this drug, yet kratom has been associated with severe signs and symptoms such as hallucinations, delusions, depressions, myalgias, chills, nausea/vomiting, respiratory hepatoxicity, seizures, coma, and death. A search of the pain literature shows past research has not described the use and potential deleterious effects of this drug. Many pain physicians are not familiar with kratom and as providers who take care of high-risk chronic pain patients using prescribed opioids, knowledge of current unregulated opioid receptor agonists with abuse potential is of paramount importance. The goal of this article is to introduce kratom to pain specialists and to spur a conversation on how pain physicians may take the lead to help curb the opioid abuse and overdose epidemic. Further studies may be required to help better understand the clinical and long-term effects of kratom use among chronic pain patients.Key words: Opioid receptor agonist, Kratom, Mitragynine, opioid overdose, chronic pain, substance abuse.

  7. Acute opioid withdrawal is associated with increased neural activity in reward-processing centers in healthy men: A functional magnetic resonance imaging study.

    Science.gov (United States)

    Chu, Larry F; Lin, Joanne C; Clemenson, Anna; Encisco, Ellen; Sun, John; Hoang, Dan; Alva, Heather; Erlendson, Matthew; Clark, J David; Younger, Jarred W

    2015-08-01

    Opioid analgesics are frequently prescribed for chronic pain. One expected consequence of long-term opioid use is the development of physical dependence. Although previous resting state functional magnetic resonance imaging (fMRI) studies have demonstrated signal changes in reward-associated areas following morphine administration, the effects of acute withdrawal on the human brain have been less well-investigated. In an earlier study by our laboratory, ondansetron was shown to be effective in preventing symptoms associated with opioid withdrawal. The purpose of this current study was to characterize neural activity associated with acute opioid withdrawal and examine whether these changes are modified by ondansetron. Ten participants were enrolled in this placebo-controlled, randomized, double-blind, crossover study and attended three acute opioid withdrawal sessions. Participants received either placebo or ondansetron (8Ymg IV) before morphine administration (10Ymg/70Ykg IV). Participants then underwent acute naloxone-precipitated withdrawal during a resting state fMRI scan. Objective and subjective opioid withdrawal symptoms were assessed. Imaging results showed that naloxone-precipitated opioid withdrawal was associated with increased neural activity in several reward processing regions, including the right pregenual cingulate, putamen, and bilateral caudate, and decreased neural activity in networks involved in sensorimotor integration. Ondansetron pretreatment did not have a significant effect on the imaging correlates of opioid withdrawal. This study presents a preliminary investigation of the regional changes in neural activity during acute opioid withdrawal. The fMRI acute opioid withdrawal model may serve as a tool for studying opioid dependence and withdrawal in human participants. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Positron Emission Tomography (PET) Imaging of Opioid Receptors

    NARCIS (Netherlands)

    van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

    2014-01-01

    The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid

  9. Abuse risks and routes of administration of different prescription opioid compounds and formulations

    Directory of Open Access Journals (Sweden)

    Dailey Taryn M

    2011-10-01

    Full Text Available Abstract Background Evaluation of tamper resistant formulations (TRFs and classwide Risk Evaluation and Mitigation Strategies (REMS for prescription opioid analgesics will require baseline descriptions of abuse patterns of existing opioid analgesics, including the relative risk of abuse of existing prescription opioids and characteristic patterns of abuse by alternate routes of administration (ROAs. This article presents, for one population at high risk for abuse of prescription opioids, the unadjusted relative risk of abuse of hydrocodone, immediate release (IR and extended release (ER oxycodone, methadone, IR and ER morphine, hydromorphone, IR and ER fentanyl, IR and ER oxymorphone. How relative risks change when adjusted for prescription volume of the products was examined along with patterns of abuse via ROAs for the products. Methods Using data on prescription opioid abuse and ROAs used from 2009 Addiction Severity Index-Multimedia Version (ASI-MV® Connect assessments of 59,792 patients entering treatment for substance use disorders at 464 treatment facilities in 34 states and prescription volume data from SDI Health LLC, unadjusted and adjusted risk for abuse were estimated using log-binomial regression models. A random effects binary logistic regression model estimated the predicted probabilities of abusing a product by one of five ROAs, intended ROA (i.e., swallowing whole, snorting, injection, chewing, and other. Results Unadjusted relative risk of abuse for the 11 compound/formulations determined hydrocodone and IR oxycodone to be most highly abused while IR oxymorphone and IR fentanyl were least often abused. Adjusting for prescription volume suggested hydrocodone and IR oxycodone were least often abused on a prescription-by-prescription basis. Methadone and morphine, especially IR morphine, showed increases in relative risk of abuse. Examination of the data without methadone revealed ER oxycodone as the drug with greatest risk after

  10. Practical pharmacology of methadone: A long-acting opioid

    Directory of Open Access Journals (Sweden)

    M M Sunilkumar

    2018-01-01

    Full Text Available Methadone is a naturally long-acting analgesic with unique pharmacodynamic and pharmacokinetic properties compared to other opioids, available now in India, to treat severe pain. It has the potential to dramatically relieve suffering among patients with serious illness who are living with persistent physical pain. However, clinicians must appreciate its unique pharmacologic properties and its use in clinical practice safely and effectively. The available formulation in India is a racemic mixture of the S- and R-enantiomers, and as such, it will have a propensity for drug-drug and drug-genetic interactions that can increase the risk of Torsades de Point and respiratory depression. Appropriate patient selection, careful dosing and thorough monitoring of methadone will mitigate these risks.

  11. COMPARISON OF INTRAOPERATIVE KETAMINE VS. FENTANYL USE DECREASES POSTOPERATIVE OPIOID REQUIREMENTS IN TRAUMA PATIENTS UNDERGOING CERVICAL SPINE SURGERY.

    Science.gov (United States)

    Berkowitz, Aviva C; Ginsburg, Aryeh M; Pesso, Raymond M; Angus, George L D; Kang, Amiee; Ginsburg, Dov B

    2016-02-01

    Postoperative airway compromise following cervical spine surgery is a potentially serious adverse event. Residual effects of anesthesia and perioperative opioids that can cause both sedation and respiratory depression further increase this risk. Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that provides potent analgesia without noticeable respiratory depression. We investigated whether intraoperative ketamine administration could decrease perioperative opioid requirements in trauma patients undergoing cervical spine surgery. We retrospectively reviewed anesthesia records identifying cervical spine surgeries performed between March 2014 and February 2015. All patients received a balanced anesthetic technique utilizing sevoflurane 0.5 minimum alveolar concentration (MAC) and propofol infusion (50-100 mcg/kg/min). For intraoperative analgesia, one group of patients received ketamine (N=25) and a second group received fentanyl (N=27). Cumulative opioid doses in the recovery room and until 24 hours postoperatively were recorded. Fewer patients in the ketamine group (11/25 [44%] vs. 20/27 [74%], respectively; p = 0.03) required analgesics in the recovery room. Additionally, the total cumulative opioid requirements in the ketamine group decreased postoperatively at both 3 and 6 hours (p = 0.01). Ketamine use during cervical spine surgery decreased opioid requirements in both the recovery room and in the first 6 hours postoperatively. This may have the potential to minimize opioid induced respiratory depression in a population at increased risk of airway complications related to the surgical procedure.

  12. Opioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies?

    Science.gov (United States)

    Weber, Lena; Yeomans, David C; Tzabazis, Alexander

    2017-08-01

    This article reviews the phenomenon of opioid-induced hyperalgesia (OIH) and its implications for clinical anesthesia. The goal of this review is to give an update on perioperative prevention and treatment strategies, based on findings in preclinical and clinical research. Several systems have been suggested to be involved in the pathophysiology of OIH with a focus on the glutaminergic system. Very recently preclinical data revealed that peripheral μ-opioid receptors (MORs) are key players in the development of OIH and acute opioid tolerance (AOT). Peripheral MOR antagonists could, thus, become a new prevention/treatment option of OIH in the perioperative setting. Although the impact of OIH on postoperative pain seems to be moderate, recent evidence suggests that increased hyperalgesia following opioid treatment correlates with the risk of developing persistent pain after surgery. In clinical practice, distinction among OIH, AOT and acute opioid withdrawal remains difficult, especially because a specific quantitative sensory test to diagnose OIH has not been validated yet. Since the immediate postoperative period is not ideal to initiate long-term treatment for OIH, the best strategy is to prevent its occurrence. A multimodal approach, including choice of opioid, dose limitations and addition of nonopioid analgesics, is recommended.

  13. Repeated Quantitative Urine Toxicology Analysis May Improve Chronic Pain Patient Compliance with Opioid Therapy.

    Science.gov (United States)

    Knezevic, Nebojsa Nick; Khan, Omar M; Beiranvand, Afsaneh; Candido, Kenneth D

    2017-02-01

    Even though serious efforts have been undertaken by different medical societies to reduce opioid use for treating chronic benign pain, many Americans continue to seek pain relief through opioid consumption. Assuring compliance of these patients may be a difficult aspect of proper management even with regular behavioral monitoring. The purpose of this study was to accurately assess the compliance of chronic opioid-consuming patients in an outpatient setting and evaluate if utilizing repeated urine drug testing (UDT) could improve compliance. Retrospective analysis of prospectively collected data. Outpatient pain management clinic. After Institutional Review Board (IRB) approval, a retrospective analysis of data for 500 patients was conducted. We included patients who were aged 18 years and older who were treated with opioid analgesic medication for chronic pain. Patients were asked to provide supervised urine toxicology specimens during their regular clinic visits, and were asked to do so without prior notification. The specimens were sent to an external laboratory for quantitative testing using liquid chromatography-tandem mass spectrometry. Three hundred and eighty-six (77.2%) patients were compliant with prescribed medications and did not use any illicit drugs or undeclared medications. Forty-one (8.2%) patients tested positive for opioid medication(s) that were not prescribed in our clinic; 8 (1.6%) of the patients were positive for medication that was not prescribed by any physician and was not present in the Illinois Prescription Monitoring Program; 5 (1%) patients tested negative for prescribed opioids; and 60 (12%) patients were positive for illicit drugs (8.6% marijuana, 3.2% cocaine, 0.2% heroin). Repeated UDTs following education and disclosure, showed 49 of the 77 patients (63.6%) had improved compliance. This was a single-site study and we normalized concentrations of opioids in urine with creatinine levels while specific gravity normalization was not

  14. Illicit Opioid Intoxication: Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    A. Fareed

    2011-01-01

    Full Text Available Opioid intoxications and overdose are associated with high rates of morbidity and mortality. Opioid overdose may occur in the setting of intravenous or intranasal heroin use, illicit use of diverted opioid medications, intentional or accidental misuse of prescription pain medications, or iatrogenic overdose. In this review, we focused on the epidemiology of illict opioid use in the United States and on the mechanism of action of opioid drugs. We also described the signs and symptoms, and diagnoses of intoxication and overdose. Lastly, we updated the reader about the most recent recommendations for treatment and prevention of opioid intoxications and overdose.

  15. Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

    Directory of Open Access Journals (Sweden)

    Norma Carrillo-Munguía

    2015-01-01

    Full Text Available Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception.

  16. Postoperative Pain Management After Sternotomy In Off-Pump Coronary Artery Bypass Graft (CABG Surgery - A Comparative Study Between NSAID (Diclofenac Sodium and Opioid (Pethidine

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    Kamrul Hasan

    2011-02-01

    Full Text Available Background: Traditionally, postoperative pain has been managed either reactively with drugs given as needed or proactively with continuous infusion of analgesics. Objectives:The present prospective comparative study was carried out to find difference in efficacy between opioid and NSAID (Non-stroid anti-inflammatory drugs in the post-sternotomy pain management following off pump coronary bypass graft surgery. Methods: A total of 30 patients were randomly divided into two groups. – 15 patients were treated with NSAID (Diclofenac sodium and 15 patients with opioid (pethidine which are not commonly used in cardiac surgery. Patients ranging from 40 – 60 years with ASA Grade I & II who underwent off-pump CABG with median sternotomy were included in the study. Statistics: The test statistics used to analyze the data were Chi-square Test and repeated measure ANOVA. Result & conclusion: The study concluded that the intensity of post-sternotomy pain was inappreciably higher in the NSAID group than that in the opioid group throughout the whole period of observation suggesting that opioid (pethidine would be a promising analgesic in the post-sternotomy pain management than NSAID (diclofenac sodium (p = 0.045. Key words: Post-sternotomy pain; OPCAB; choice of analgesic. DOI: 10.3329/bsmmuj.v3i2.7059BSMMU J 2010; 3(2: 91-96

  17. Evaluation of a survey of the diplomates of the American College of Laboratory Animal Medicine on use of analgesic agents in animals used in biomedical research.

    Science.gov (United States)

    Hubbell, J A; Muir, W W

    1996-09-01

    To determine the analgesic agents administered to animals frequently used in biomedical research. Telephone survey. Diplomates of the American College of Laboratory Animal Medicine. 200 of 429 active diplomates listed in the 1993 directory of the American College of Laboratory Animal Medicine were selected at random for telephone interviews. Diplomates were asked to identify the species that they cared for and the dosages, dosing intervals, and routes of administration for analgesic agents. 90 of 200 (45%) diplomates completed the survey. Twenty-two analgesic agents were identified for use in 472 applications in 16 species. Opioid analgesics were the most frequently selected agents, with buprenorphine hydrochloride and butorphanol being most frequently used. Intramuscular and subcutaneous routes of administration were used most frequently. Among diplomates of the American College of Laboratory Animal Medicine, opioids are the most frequently selected agents used to induce analgesia in animals used in biomedical research. Dosages and dosing intervals used vary widely among animals of various species as well as for animals in each species.

  18. MEL-N16: A Series of Novel Endomorphin Analogs with Good Analgesic Activity and a Favorable Side Effect Profile.

    Science.gov (United States)

    Liu, Xin; Zhao, Long; Wang, Yuan; Zhou, Jingjing; Wang, Dan; Zhang, Yixin; Zhang, Xianghui; Wang, Zhaojuan; Yang, Dongxu; Mou, Lingyun; Wang, Rui

    2017-10-18

    Opioid peptides are neuromodulators that bind to opioid receptors and reduce pain sensitivity. Endomorphins are among the most active endogenous opioid peptides, and they have good affinity and selectivity toward the μ opioid receptor. However, their clinical usage is hindered by their inability to cross the blood-brain barrier and their poor in vivo activity after peripheral injection. In order to overcome these defects, we have designed and synthesized a series of novel endomorphin analogs with multiple site modifications. Radioligand binding, cAMP accumulation, and β-arrestin-2 recruitment assays were employed to determine the activity of synthesized endomorphin analogs toward opioid receptors. The blood-brain barrier permeability and antinociceptive effect of these analogs were determined in several rodent models of acute and persistent pain. In addition, the side effects of the analogs were examined. The radioligand binding assay and functional activity examination indicated that the MEL-N16 series of compounds were more active agonists against μ opioid receptor than were the parent peptides. Notably, the analogs displayed biased downstream signaling toward G-protein pathways over β-arrestin-2 recruitment. The analogs showed highly potent antinociceptive effects in the tested nociceptive models. In comparison with endomorphins, the synthesized analogs were better able to penetrate the blood-brain barrier and exerted their pain regulatory activity in the central nervous system after peripheral injection. These analogs also have lower tendency to cause side effects than morphine does at similar or equal antinociceptive doses. The MEL-N16 compounds have highly potent and efficacious analgesic effects in various pain models with a favorable side effect profile.

  19. The analgesic efficacy of ultrasound-guided transversus abdominis plane block for retroperitoneoscopic donor nephrectomy: A randomized controlled study

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    Beena K Parikh

    2013-01-01

    Full Text Available Background: Transversus abdominis plane (TAP block is suitable for lower abdominal surgeries. Blind TAP block has many complications and uncertainty of its effects. Use of ultrasonography increases the safety and efficacy. This study was conducted to evaluate the analgesic efficacy of ultrasound (USG-guided TAP block for retroperitoneoscopic donor nephrectomy (RDN. Methods: In a prospective randomized double-blind study, 60 patients undergoing laparoscopic donor nephrectomy were randomly divided into two groups by closed envelope method. At the end of surgery, USG-guided TAP block was given to the patients of both the groups. Study group (group S received inj. Bupivacaine (0.375%, whereas control group (group C received normal saline. Inj. Tramadol (1 mg/kg was given as rescue analgesic at visual analog scale (VAS more than 3 in any group at rest or on movement. The analgesic efficacy was judged by VAS both at rest and on movement, time to first dose of rescue analgesic, cumulative dose of tramadol, sedation score, and nausea score, which were also noted at 30 min, 2, 4, 6, 12, 18, and 24 h postoperatively. Total tramadol consumption at 24 h was also assessed. Results: Patients in group S had significantly lower VAS score, longer time to first dose of rescue analgesic (547.13±266.96 min vs. 49.17±24.95 min and lower tramadol consumption (103.8±32.18 mg vs. 235.8±47.5 mg in 24 h. Conclusion: The USG-guided TAP block is easy to perform and effective as a postoperative analgesic regimen in RDN, with opioids-sparing effect and without any complications.

  20. Hemodynamic and Behavioral Differences after Administration of Meloxicam, Buprenorphine, or Tramadol as Analgesics for Telemeter Implantation in Mice

    Science.gov (United States)

    Rätsep, Matthew T; Barrette, Valerie F; Winterborn, Andrew; Adams, Michael A; Croy, B Anne

    2013-01-01

    Cannulation of the common carotid artery for chronic, continuous radiotelemetric recording of aortic hemodynamic properties in mice is a highly invasive recovery surgery. Radiotelemetric recording, by its continuous nature, gives the most accurate measurements of hemodynamic variables in experimental animals, and is widely used in the study of cardiovascular diseases including hypertension. The American Heart Association has recommended data acquisition by radiotelemetric recording but did not provide guidelines regarding postoperative analgesic support. We assessed hemodynamic parameters, locomotor activity, food intake, and weight loss in radiotransmitter-implanted CD1 female mice receiving analgesic support during the first 48 h after surgery. The efficacy of analgesic support from the NSAID meloxicam was compared with that of the widely used opioid agonist buprenorphine and the related compound, tramadol. Meloxicam-treated mice recovered lost body weight more rapidly than did tramadol- or buprenorphine-treated mice. Furthermore, meloxicam-treated mice maintained circadian rhythm after surgery and had tighter regulation of mean arterial pressure than did tramadol- or buprenorphine-treated mice. Meloxicam was also superior with regard to food intake, locomotor activity, and limiting variance in hemodynamic parameters. This study indicates that when compared with buprenorphine and tramadol, meloxicam should be the postoperative analgesic of choice for radiotelemeter implantation in mice. PMID:24041211

  1. Opioids: The Prescription Drug & Heroin Overdose Epidemic

    Science.gov (United States)

    ... About the Epidemic Help, Resources and Information National Opioids Crisis Search Search National Helpline SAMHSA’s National Helpline ... 1-800-662-4357 Visit Helpline Website THE OPIOID EPIDEMIC IN NUMBERS 80% Nearly 80% of heroin ...

  2. Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

    Science.gov (United States)

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena

    2015-01-01

    Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

  3. Pharmacological studies of lappaconitine. Analgesic activities.

    Science.gov (United States)

    Ono, M; Satoh, T

    1988-07-01

    The analgesic activity of lappaconitine, which is contained in the root of Aconitum sinomantanum Nakai, was examined after oral and subcutaneous administration to mice or rats by using methods for screening of analgesics, i.e., hot plate, tail immersion, tail pinch, tail pressure, acetic acid-induced writhing, bradykinin-induced flexor reflex of hind limb and Randall-Selitto methods. The results were compared with those for morphine, indometacin and acetylsalicylic acid (ASA). Analgesic activities of lappaconitine were greater than those of indometacin and ASA, but generally about 2 to 5 times less than those of morphine. However, in the rat tail immersion test, orally administered lappaconitine exhibited more potent analgesic activity than morphine; in this test, lappaconitine was almost equipotent when given orally and subcutaneously, whereas the potency of orally administered morphine was only one-twentieth of that of subcutaneously administered morphine. Like morphine, lappaconitine increased the pain threshold of the normal paw as well as that of the inflamed paw when tested by the Randall-Selitto method. The results show that lappaconitine has strong analgesic activity, and further suggest that the central nervous system may be involved in the action on the pain threshold.

  4. Interactions of Opioids and HIV Infection in the Pathogenesis of Chronic Pain

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    Bolong eLiu

    2016-02-01

    Full Text Available Over 50% of HIV-1/AIDS patients suffer chronic pain. Currently, opioids are the cornerstone medications for treating severe pain in these patients. Ironically, emerging clinical data indicates that repeated use of opiate pain medicines might in fact heighten the chronic pain states in HIV patients. Both laboratory-based and clinical studies strongly suggest that opioids exacerbate the detrimental effects of HIV-1 infection on the nervous system, both on neurons and glia. The combination of opioids and HIV-1 infection may promote the damage of neurons, including those in the pain sensory and transmission pathway, by activating both caspase-dependent and caspase-independent pro-apoptotic pathways. In addition, the opiate-HIV-1 interaction may also cause widespread disturbance of glial function and elicit glial-derived pro-inflammatory responses that dysregulate neuronal function. The deregulation of neuron-glia cross-talk that occurs with the combination of HIV-1 and opioids appears to play an important role in the development of the pathological pain state. In this article, we wish to provide an overview of the potential molecular and cellular mechanisms by which opioids may interact with HIV-1 to cause neurological problems, especially in the context of HIV-associated pathological pain. Elucidating the underlying mechanisms will help researchers and clinicians to understand how chronic use of opioids for analgesia enhances HIV-associated pain. It will also assist in optimizing therapeutic approaches to prevent or minimize this significant side effect of opiate analgesics in pain management for HIV patients.

  5. Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis.

    Science.gov (United States)

    Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Jimenez-Vargas, Nestor N; Lopez-Lopez, Cintya; Jaramillo-Polanco, Josue; Okamoto, Takanobu; Nasser, Yasmin; Bunnett, Nigel W; Lomax, Alan E; Vanner, Stephen J

    2017-12-01

    Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways. Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca 2+ imaging techniques. Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca 2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits. Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Inhibition of tolerance to spinal morphine antinociception by low doses of opioid receptor antagonists.

    Science.gov (United States)

    McNaull, Benjamin; Trang, Tuan; Sutak, Maaja; Jhamandas, Khem

    2007-04-10

    Ultra-low doses of opioid receptor antagonists inhibit development of chronic spinal morphine tolerance. As this phenomenon mechanistically resembles acute tolerance, the present study examined actions of opioid receptor antagonists on acute spinal morphine tolerance. In adult rats, administration of three intrathecal injections of morphine (15 microg) at 90 min intervals produced a significant decline of the antinociceptive effect and loss of agonist potency in both the tail-flick and paw-pressure tests. These reduced responses, indicative of acute tolerance, were blocked by co-injection of morphine (15 microg) with naltrexone (NTX, 0.05 ng), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTAP, 0.001 ng), naltrindole (0.06 ng), or nor-binaltorphimine (0.1 ng). Repeated injections of CTAP, naltrindole, or nor-binaltorphimine without morphine elicited a delayed weak antinociceptive response which was blocked by a high dose of naltrexone (2 microg). In another set of experiments, administration of low dose spinal (0.05 ng) or systemic (0.01 microg/kg) morphine produced a sustained thermal hyperalgesia. This response was blocked by opioid receptor antagonists at doses inhibiting development of acute morphine tolerance. Lastly, an acute spinal injection of morphine (15 microg) with naltrexone (0.05 ng) produced a sustained analgesic response; this was antagonized by adenosine receptor antagonist, 8-phenyltheophylline (3 microg). The results show that ultra-low doses of opioid receptor antagonists block acute tolerance to morphine. This effect may result from blockade of opioid excitatory effects that produce a latent hyperalgesia that then contributes to induction of tolerance. The sustained antinociception produced by combination of morphine with an opioid receptor antagonist shows dependency on the adenosine receptor activity.

  7. Neuropathic and chronic pain stimuli downregulate central mu-opioid and dopaminergic transmission.

    Science.gov (United States)

    Niikura, Keiichi; Narita, Minoru; Butelman, Eduardo R; Kreek, Mary Jeanne; Suzuki, Tsutomu

    2010-07-01

    Although morphine and other mu-opioid agonists are the main analgesics for severe pain, these compounds have potential for abuse and/or addiction. This has complicated the use of mu-agonists in the treatment of chronic pain. However, clinical studies show that when mu-agonist analgesics are appropriately used to control pain, actual abuse or addiction does not usually occur, although some risk factors that increase vulnerability need to be considered, including genetic variation. We review recent findings on molecular adaptations in sustained pain models, and propose how these adaptations (including sustained release of the endogenous mu-agonist beta-endorphin) can result in decreased abuse potential of mu-agonists in chronic pain states. We also review data on particular gene polymorphisms (e.g. in the mu-receptor gene) that could also influence the relative abuse potential of mu-agonists in clinical pain populations. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Erectile dysfunction in patients with chronic pain treated with opioids.

    Science.gov (United States)

    Ajo, Raquel; Segura, Ana; Inda, María-Del-Mar; Margarit, César; Ballester, Pura; Martínez, Emi; Ferrández, Guillermina; Sánchez-Barbie, Ángel; Peiró, Ana M

    2017-07-21

    Chronic pain is associated with comorbidities that have an impact on the quality of life of patients and, among others, affect their sexual functioning. One of the most relevant side effects of opioid analgesics is erectile dysfunction (ED), due in part to the inhibition of the gonadal-pituitary-hypothalamic axis and the decline in testosterone levels. To evaluate ED and effectiveness of treatment in men with chronic pain treated with long-term opioids. Prospective observational study lasting 3 years, where the intensity of pain (visual analogue scale, 0-10cm), erectile function (IIEF-EF, range 1-30 points), quality of life (EQ-VAS, 0-100mm), quality of sexual life (MSLQ-QOL, 0-100 points), anxiety/depression (HAD, 0-21 points) and testosterone levels, was assessed in patients who reported sexual dysfunction (ED or libido modification). A 6-month follow-up was applied to each patient after administering the usual treatment in the Andrology Unit. The study was approved by the Clinical Research Ethics Committee and data were statistically analyzed with the GraphPad Prism 5 software. ED was observed in 27.6% of patients (n=105, 57±12.2 years, mean dose of morphine equivalent=107.1±107.9mg/day, 84.3% adjuvant analgesics). After 6 months, 42% of patients showed a significant improvement after being treated with iPDE5 (48.5%) and/or testosterone gel (81.8%), with a resolution rate of 31% (p=0.000). A positive correlation was observed between the improvement of IIEF and quality of sexual life (55.5±25.7 points, p=0.000), as well as anxiety (7.4±4.3 points, p=0.048). No significant changes were observed in the levels of testosterone, in the levels of pain nor in the quality of life, which remained moderate. Erectile function and quality of sexual life, as well as anxiety, improved in patients treated chronically with opioids after administering andrological treatment. The management of patients with pain should include a review of their sexual health history given the

  9. Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

    Directory of Open Access Journals (Sweden)

    Piechota Marcin

    2006-06-01

    Full Text Available Abstract Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q Khdrbs1 and ATPase Na+/K+ alpha2 subunit (Atp1a2 with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids.

  10. Analgesic activity of some Indian medicinal plants.

    Science.gov (United States)

    Malairajan, P; Geetha Gopalakrishnan; Narasimhan, S; Jessi Kala Veni, K

    2006-07-19

    In the present study of some of the Indian medicinal plants Sida acuta whole plant (Malvaeae), Stylosanthes fruticosa (whole plant) (Papilionaceae), Toona ciliata (heart wood) (Meliaceao), Bougainvilla spectabilis (leaves) (Nyctaginaceae), Ficus glomerata (bark, leaves) (Moraceae) and Polyalthia longifolia (leaves) (Annonaceae). The different plants were used in folklore medicine in the treatment of toothache and strengthening of gums, anthelmintic, kidney diseases, analgesic, anti-inflammatory, hepatoprotective, antihyperglycaemic, antihyperglycaemic and anticancer. The extract was prepared using powdered material with ethanol, concentrated under vacuo and were evaluated for analgesic activity by analgesiometer at three dose level (100, 300 and 500mg/kg). Analgesic activity was significant with Toona ciliata (heart wood) ethanolic extract when compared with other extracts and its activity was confirmed by tail immersion method.

  11. Analgesic effects of dexamethasone in burn injury

    DEFF Research Database (Denmark)

    Werner, Mads U; Lassen, Birgit Vibeke; Kehlet, Henrik

    2002-01-01

    BACKGROUND AND OBJECTIVES: Glucocorticoids are well-known adjuvant analgesics in certain chronic pain states. There is, however, a paucity of data on their analgesic efficacy in acute pain. Therefore, the aim of the study was to examine the analgesic effects of dexamethasone in a validated burn...... model of acute inflammatory pain in humans. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Intravenous dexamethasone 8 mg or placebo was administered on 2 separate study days. Two hours after drug administration, a first-degree burn...... and secondary hyperalgesia. RESULTS: The burn injury induced significant increases in erythema (P burn did not differ between dexamethasone and placebo treatments (P >.6). There were no significant...

  12. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.

    1986-01-01

    The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

  13. Evaluation of analgesic activity of allopurinol and febuxostat in experimental analgesic models in mice

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    Promod D Shankpal

    2015-01-01

    Full Text Available Background: Allopurinol and febuxostat are xanthine oxidase inhibitors which are used in the treatment of hyperuricemia and gout. Pain is one of the important symptoms in gout patients. The present study was to evaluate the analgesic activity of allopurinol and febuxostat in two analgesic models in mice. Materials and Methods: The analgesic activity of allopurinol (39 mg/kg and febuxostat (15.6 mg/kg was evaluated using central analgesic model of Eddy′s hot plate and peripheral analgesic model of acetic acid induced writhing. Both drugs were compared with the positive control, pentazocine for a hot plate method and aspirin for the writhing method. Furthermore, both allopurinol and febuxostat were compared with each other. Results: Both allopurinol and febuxostat showed significant increase in reaction time at various time periods in hot plate method and also showed significant delay in onset of writhing as well as decrease in number of writhes in writhing method. As compared to positive control result, allopurinol and febuxostat result were lower. Febuxostat shows better analgesic activity as compared to that of allopurinol. Conclusion: Allopurinol and febuxostat exhibited analgesic activity in both central and peripheral models of pain.

  14. The role of surfactants in the formulation of elastic liposomal gels containing a synthetic opioid analgesic

    Directory of Open Access Journals (Sweden)

    Singh S

    2016-04-01

    Full Text Available Sima Singh,1,* Harsh Vardhan,1,* Niranjan G Kotla,2 Balaji Maddiboyina,3 Dinesh Sharma,4 Thomas J Webster5,6 1School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India; 2Center for Research in Medical Devices, National University of Ireland, Galway, Ireland; 3Department of Pharmaceutics, Vishwabharathi College of Pharmaceutical Sciences, Guntur, India; 4Ranbaxy Laboratory Ltd, Gurgaon, India; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 6Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia *These authors contributed equally to this work Abstract: Transdermal drug delivery systems have made significant contributions to the medical community, but have yet to completely substitute oral or parenteral delivery. Recently, various strategies have been used to augment the transdermal delivery of therapeutics. Primarily, they include iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, microneedles, and vesicular systems. Among these strategies, elastic liposomes appear promising. Elastic vesicle scaffolds have been developed and evaluated as novel topical and transdermal delivery systems, with an infrastructure consisting of hydrophobic and hydrophilic moieties together, and as a result, such scaffolds can accommodate drug molecules with a wide range of solubility. High deformability of these vesicles provides for better penetration of intact vesicles. This system is much more efficient at delivering low- and high-molecular-weight drugs to the skin in terms of quantity and depth. In this work, elastic liposomes of Tramadol HCl were prepared using a solvent evaporation method with different surfactants and were characterized using microscopy, and particle size, shape, drug content, ex vivo release, and zeta potential were also calculated. The prepared elastic liposomes were found to be in the range of 152.4 nm with a zeta potential of -22.4 mV; the entrapment efficiencies of the selected formulation was found to be 79.71%±0.27%. All formulations in the form of a gel were evaluated for physicochemical properties and were found to be homogeneous with no grittiness, and the pH of all formulations was found to be neutral. The optimized selected elastic liposomal formulation followed the Higuchi equation and Fickian diffusion and released the drug for a period of 24 hours. The overall results provide much promise for the continued investigation of deformable vesicles as transdermal drug carriers. Keywords: elastic liposome, skin delivery, occlusion, hydration-gradient, hydrogel

  15. Contribution of positron emission tomography for the study of response variability to opioid drugs

    International Nuclear Information System (INIS)

    Auvity, Sylvain

    2017-01-01

    There is a high variability between patients in the initial analgesic response to opioid drugs. The chronic use of opioids leads to tolerance and may induce dependence or addiction. Current Positron Emission Tomography (PET) imaging methods, focusing on the impact of opioids on neuronal and synaptic functions, have failed to elucidate the parameters that control this variability of therapeutic response. A wealth of preclinical studies has addressed the possibility for neuro-immune or neuro-pharmacokinetic parameters to control the response to opioid drugs. Dedicated tools are thus required to investigate their impact on the pharmacology of opioid drugs in vivo and test their implication for variability in therapeutic response. The aim of this PhD project was to develop or to evaluate original methods to study the neuro-immune and neuro-pharmacokinetic components of the variability of response to opioid drugs. Opioid drugs were shown to interact with the innate immune System in the central nervous System (CNS) and to modulate the activity of glial cells. Glial cell activity is often hypothesized to modulate the analgesic efficacy of opioids and account for the development of tolerance and dependence. PET imaging using TSPO (Translocator protein 18 kDa) radioligands such as 18 F-DPA-714 is the most advanced approach to non-invasively study glial cell activation. In nonhuman primates, we showed that acute morphine exposure increased the brain distribution of 18 F-DPA-714, suggesting glial cell activation. The extent of the increase was linked to the baseline brain distribution of 18 F-DPA-714, suggesting the presence of priming parameters in controlling the neuro-immune response to morphine exposure. In healthy rats, we showed that morphine-induced tolerance and withdrawal did not detectably increase the brain distribution of 18 F-DPA-714 as well as the expression of other bio-markers of glial/micro-glial activation. Dedicated methods were then proposed to investigate

  16. Opioid antagonists with minimal sedation for opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M

    2017-05-29

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications. We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies. We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants. We used standard methodological procedures expected by Cochrane. Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha 2 -adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient

  17. Pain Treatment Continues To Be Inaccessible for Many Patients Around the Globe: Second Phase of Opioid Price Watch, a Cross-Sectional Study To Monitor the Prices of Opioids.

    Science.gov (United States)

    Pastrana, Tania; Wenk, Roberto; Radbruch, Lukas; Ahmed, Ebtesam; De Lima, Liliana

    2017-04-01

    Strong opioids are a cornerstone of pain treatment, of which morphine is considered an essential analgesic by the World Health Organization. Access to opioids is limited, due to restrictive laws, limited education, and high prices. This is the second phase of a global project to monitor and report the dispensing price of opioids with the specific aim to expand and increase the information and allow further analysis of the challenges in their availability and affordability. Participants were asked to provide the lowest dispensing price of the smallest selling unit and lowest strength of five opioids in 13 formulations from a licensed pharmacy located closest to a public facility that provides diagnosis/treatment for life-threatening conditions. Data were collected from July 2015 to March 2016. Average availability, median (Me), and interquartile range (IQR) price were calculated for four gross national income (GNI) categories: higher income countries (HIC), upper middle income countries (UMIC), low middle income countries (LMIC), and low income countries (LIC). Affordability for one month of treatment with morphine immediate release (IR) tablet was also calculated. Data were submitted by 67 participants from 43 countries. Availability is strongly related to GNI level (Kruskal-Wallis tests p opioid medications. This highlights the need to continue efforts at improving access, availability, and affordability.

  18. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.

    Directory of Open Access Journals (Sweden)

    Kathleen Hempenstall

    2005-07-01

    Full Text Available BACKGROUND: Postherpetic neuralgia (PHN is a complication of acute herpes zoster, which is emerging as a preferred clinical trial model for chronic neuropathic pain. Although there are published meta-analyses of analgesic therapy in PHN, and neuropathic pain in general, the evidence base has been substantially enhanced by the recent publication of several major trials. Therefore, we have conducted a systematic review and meta-analysis for both efficacy and adverse events of analgesic therapy for PHN. METHODS AND FINDINGS: We systematically searched databases (MEDLINE 1966-2004, EMBASE 1988-2004, CINAHL 1982-2002, and PubMed [29 October 2004] for trials of PHN. We also searched references of retrieved studies and review articles for further trials. We included trials that examined adult patients with PHN of greater duration than 3 mo, that were blinded, randomised, and had at least one measure of pain outcome. Dichotomous pain outcome data were extracted for 50% decrease in baseline pain using a hierarchy of pain/pain-relief measurement tools. Where available, dichotomous data were also collected for adverse events. Calculated estimates of efficacy included relative benefit and number needed to treat. Of 62 studies identified, 35 were randomised controlled trials. Of these, 31 were placebo controlled and suitable for meta-analysis, from which it was possible to extract dichotomous efficacy outcome data from 25. This meta-analysis revealed that there is evidence to support the use of the following orally administered therapies: tricyclic antidepressants, "strong" opioids, gabapentin, tramadol, and pregabalin. Topical therapies associated with efficacy were lidocaine 5% patch and capsaicin. Finally, a single study of spinal intrathecal administration of lidocaine and methyl prednisolone demonstrated efficacy, although this has yet to be replicated. Data suggest that the following therapies are not associated with efficacy in PHN: certain NMDA

  19. Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer.

    Science.gov (United States)

    Katakami, Nobuyuki; Harada, Toshiyuki; Murata, Toru; Shinozaki, Katsunori; Tsutsumi, Masakazu; Yokota, Takaaki; Arai, Masatsugu; Tada, Yukio; Narabayashi, Masaru; Boku, Narikazu

    2017-12-01

    Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids-common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting μ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned on a 1:1 basis to receive once-daily oral naldemedine 0.2 mg or placebo. The primary end point was the proportion of spontaneous bowel movement (SBM) responders (≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline). The primary end point of COMPOSE-5 was safety. Results In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96). The proportion of SBM responders in COMPOSE-4 was significantly greater with naldemedine than with placebo (71.1% [69 of 97 patients] v 34.4% [33 of 96 patients]; P opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.

  20. Use of analgesic drugs and risk of ovarian cancer

    DEFF Research Database (Denmark)

    Ammundsen, Henriette B; Faber, Mette T; Jensen, Allan

    2012-01-01

    The role of analgesic drug use in development of ovarian cancer is not fully understood. We examined the association between analgesic use and risk of ovarian cancer. In addition, we examined whether the association differed according to histological types.......The role of analgesic drug use in development of ovarian cancer is not fully understood. We examined the association between analgesic use and risk of ovarian cancer. In addition, we examined whether the association differed according to histological types....

  1. Feeding Releases Endogenous Opioids in Humans.

    Science.gov (United States)

    Tuulari, Jetro J; Tuominen, Lauri; de Boer, Femke E; Hirvonen, Jussi; Helin, Semi; Nuutila, Pirjo; Nummenmaa, Lauri

    2017-08-23

    The endogenous opioid system supports a multitude of functions related to appetitive behavior in humans and animals, and it has been proposed to govern hedonic aspects of feeding thus contributing to the development of obesity. Here we used positron emission tomography to investigate whether feeding results in hedonia-dependent endogenous opioid release in humans. Ten healthy males were recruited for the study. They were scanned with the μ-opioid-specific ligand [ 11 C]carfentanil three times, as follows: after a palatable meal, a nonpalatable meal, and after an overnight fast. Subjective mood, satiety, and circulating hormone levels were measured. Feeding induced significant endogenous opioid release throughout the brain. This response was more pronounced following a nonpalatable meal versus a palatable meal, and independent of the subjective hedonic responses to feeding. We conclude that feeding consistently triggers cerebral opioid release even in the absence of subjective pleasure associated with feeding, suggesting that metabolic and homeostatic rather than exclusively hedonic responses play a role in the feeding-triggered cerebral opioid release. SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic and homeostatic functions. It has been proposed that overeating and concomitant opioid release could downregulate opioid receptors and promote the development of obesity. However, it remains unresolved whether feeding leads to endogenous opioid release in humans. We used in vivo positron emission tomography to test whether feeding triggers cerebral opioid release and whether this response is associated with pleasurable sensations. We scanned volunteers using the μ-opioid receptor-specific radioligand [ 11 C]carfentanil three times, as follows: after an overnight fast, after consuming a palatable meal, and after consuming a nonpalatable meal. Feeding led to significant endogenous opioid release, and this occurred also in the absence of feeding

  2. ANALGESIC AND ANTIPYRETIC ACTIONS OF ENANTIA ...

    African Journals Online (AJOL)

    ANALGESIC AND ANTIPYRETIC ACTIONS OF ENANTIA CHLORANTHA EXTRACT IN SOME LABORATORY ANIMALS. ... Abstract. Aqueous extract of the bark of Enantia chlorantha administered intraperitoneally (i.p) into healthy adult albino mice at does of 1.0 and 5.0g/kg resulted in elevation of pain threshold.

  3. Comparative analgesic effects of paracetamol with paracetamol ...

    African Journals Online (AJOL)

    This study was designed to evaluate the contribution of caffeine to analgesia in paracetamol-caffeine preparation. Analgesic properties were evaluated in mice using acetic acid-induced writhing and hot plate methods. In the acetic acid method, the test drugs were administered orally to the mice. After 30 min. all the mice ...

  4. Analgesic Effect and Immunomodulation Response on Pro ...

    African Journals Online (AJOL)

    In order to determine qualitatively the chemical components of the extract, thin layer chromatography (TLC) was used. The analgesic activity of the extract at various doses (25, 50, 100 and 200 mg/kg, i.p) was assessed using formalin test while pro-inflammatory cytokines were measured by enzyme-linked immunosorbent ...

  5. Antisecretory and analgesic activities of Terminalia bellerica

    African Journals Online (AJOL)

    STORAGESEVER

    2010-05-03

    May 3, 2010 ... This study describes the antisecretory and analgesic activities of the crude extract of Terminalia bellerica (Tb.Cr). T. bellerica extract inhibited the castor oil-induced intestinal fluid secretion in mice at the dose range of 300 - 1000 mg/kg. The extract also dose-dependently (50 - 100 mg/kg) reduced the.

  6. Central Nervous System Depressant, Analgesic and Antidiarrheal ...

    African Journals Online (AJOL)

    In CNS depressant test, diazepam (1 mg/kg) was used as reference drug while indomethacin (10 mg/kg) and loperamide(2 mg/kg) were used as standard drugs in analgesic and antidiarrheal tests, respectively. Results: In hole cross method, EALS showed the most effective depressant effect, viz, 1.17±0.17 for 200 mg/kg ...

  7. Chemical Characterization, Anti inflammatory and Analgesic ...

    African Journals Online (AJOL)

    Chemical Characterization, Anti inflammatory and Analgesic Properties of Jatropha Multifida Root Bark. ... Phytochemical investigations reveal the presence of alkaloids, tannins, glycosides, saponins and flavonoids. The extract at a dose of 400 mg/kg significantly (P < 0.01) reduced paw thickness in rat compared to control.

  8. Antipyretic, analgesic, anti-inflammatory and cytotoxic effects of four ...

    African Journals Online (AJOL)

    ... and 2-acetamido-5-sulfonamidobenzoic acid (AMSABA, 4) were synthesized and evaluated for their analgesic, antipyretic, anti-inflammatory and cytotoxic activities. HASBA, AASBA and AMASBA showed higher analgesic activity than aspirin (ASA) at 100 mg/kg dose, while AMSABA showed the least analgesic property.

  9. Evaluation of analgesic and anti-inflammatory effects of ethanol ...

    African Journals Online (AJOL)

    This study was undertaken to investigate the leaf part of the plant for analgesic and anti-inflammatory. The ethanol extract of Ficus iteophylla leaves (100, 200, and 400mgkg-1, i.p) was evaluated for analgesic and anti-inflammatory activities. The analgesic effect was studied using acetic acid-induced abdominal constriction ...

  10. An investigation into the prescribing of analgesics | Truter | South ...

    African Journals Online (AJOL)

    Data were obtained from a medical aid which used a formulary system. Main outcome measures: Percentage of central nervous system drugs that analgesics comprised; proportion of patients using combination analgesics; cost of analgesics. Results: On average, 83.3% of all central nervous system drugs dispensed were ...

  11. The effectiveness of analgesic electrotherapy in the control of pain ...

    African Journals Online (AJOL)

    The change in pain perceived was assessed after a course of analgesic electrotherapy using a visual analogue scale as well as changes in use of analgesics and walking ability. Results: The level of pain reported and use of analgesics dropped significantly after the electrotherapy course, compared to the control group.

  12. Evaluation Of Analgesic And Anti-Inflammatory Activity Of Diospyros ...

    African Journals Online (AJOL)

    Evaluation Of Analgesic And Anti-Inflammatory Activity Of Diospyros Cordifolia Extract. S Das, PK Haldar, G Pramanik, SP Panda, S Bera. Abstract. In this study we evaluated the analgesic and anti- inflammatory activities of the methanol extract of stem bark of Diospyros cordifolia (MEDC) Roxb. The analgesic effects of the ...

  13. Factors influencing use of analgesics among construction workers in ...

    African Journals Online (AJOL)

    BACKGROUND: Analgesics also known as painkillers are widely used for pain relief. There are severe health implications associated with excessive use of analgesics. This paper examines factors influencing the use of analgesics among construction workers in the Ga-East Municipality (GEM) of the Greater Accra region of ...

  14. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Vanita Ahuja

    2015-01-01

    Full Text Available Background and Aims: Flupirtine maleate is a centrally acting, non-opioid analgesic with unique muscle relaxant properties as compared to common analgesics. The aim of this study was to compare post-operative analgesic efficacy of flupirtine maleate and ibuprofen in patients undergoing gynaecological ambulatory surgeries. Methods: This prospective, randomised controlled study was conducted in 60 women of American Society of Anesthesiologists physical status I/II, 18-70 years of age and scheduled to undergo gynaecological ambulatory surgeries. The participants were randomised to receive either 100 mg oral flupirtine maleate (group flupirtine, n = 30 or 800 mg oral ibuprofen (group ibuprofen, n = 30, 1 h prior to surgery and then every 8 h for 48 h. Verbal Numerical Rating Scale (VNRS on movement was assessed at 0, 2, 4, 6 and 8 h following surgery. Following discharge from hospital, the patients were interviewed telephonically at 12, 24 and 48 h post-operatively. VNRS was statistically analysed using Mann-Whitney test. Results: VNRS on movement was statistically reduced at 2 h after surgery (P = 0.04 in group flupirtine as compared to group ibuprofen. The analgesic efficacy was similar in both the groups at 4, 6, 8, 12, 24 and 48 h after surgery. The satisfaction scores at 24 and 48 h post-operatively were superior in group flupirtine as compared to group ibuprofen (P < 0.001. Conclusion: Analgesic efficacy of flupirtine maleate was comparable with ibuprofen in patients in ambulatory gynaecological patients up to 48 h postoperatively with superior satisfaction scores.

  15. Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer

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    Ehrnrooth, E.; Grau, C.; Zachariae, R.; Andersen, Joern [Aarhus Univ. Hospital (Denmark). Dept. of Oncology

    2001-11-01

    Patients who receive radiotherapy for head and neck cancer are likely to develop painful mucositis. The pain is characterized by a burning or stinging sensation similar to neuropathic pain sensations. The purpose of the present study was to compare the analgesic effect of a tricyclic antidepressant (TC), commonly used in the treatment of neuropathic pain, with the effect of opioids on radiation-induced mucositis pain. Forty-three patients receiving 66-68 Gy external radiation according to the DAHANCA guidelines (the Danish Head and Neck Cancer Study Group) were randomized to either morphine or TC when mucositis pain was insufficiently managed with weak analgesics. Patients with insufficient pain control in either treatment arm received supplementary medication from the opposite treatment arm. Pain was evaluated weekly using a VAS scale and the McGill Pain Questionnaire. The degree of mucositis and the degree of depression were measured at the same time intervals. Twenty-two patients entered the opioid arm and 21 the TC arm. Two patients in each arm were non-evaluable. VAS pain scores were significantly reduced in the opioid treatment arm one week after randomization (p=0.01). Eight patients in the TC arm were managed with TC alone, but for 11 patients it was necessary to add morphine. The 20 evaluable patients in the morphine arm required no additional treatment. There were no significant differences in side effects between the two groups. Higher pain scores in the TC arm, but not in the opioid arm, were significantly correlated with higher BDI scores. Some head and neck cancer patients with radiation-induced nucositis pain may have sufficient pain control on TC alone. This might be useful in patients with relative counter-indications to opioid treatment.

  16. Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer

    International Nuclear Information System (INIS)

    Ehrnrooth, E.; Grau, C.; Zachariae, R.; Andersen, Joern

    2001-01-01

    Patients who receive radiotherapy for head and neck cancer are likely to develop painful mucositis. The pain is characterized by a burning or stinging sensation similar to neuropathic pain sensations. The purpose of the present study was to compare the analgesic effect of a tricyclic antidepressant (TC), commonly used in the treatment of neuropathic pain, with the effect of opioids on radiation-induced mucositis pain. Forty-three patients receiving 66-68 Gy external radiation according to the DAHANCA guidelines (the Danish Head and Neck Cancer Study Group) were randomized to either morphine or TC when mucositis pain was insufficiently managed with weak analgesics. Patients with insufficient pain control in either treatment arm received supplementary medication from the opposite treatment arm. Pain was evaluated weekly using a VAS scale and the McGill Pain Questionnaire. The degree of mucositis and the degree of depression were measured at the same time intervals. Twenty-two patients entered the opioid arm and 21 the TC arm. Two patients in each arm were non-evaluable. VAS pain scores were significantly reduced in the opioid treatment arm one week after randomization (p=0.01). Eight patients in the TC arm were managed with TC alone, but for 11 patients it was necessary to add morphine. The 20 evaluable patients in the morphine arm required no additional treatment. There were no significant differences in side effects between the two groups. Higher pain scores in the TC arm, but not in the opioid arm, were significantly correlated with higher BDI scores. Some head and neck cancer patients with radiation-induced nucositis pain may have sufficient pain control on TC alone. This might be useful in patients with relative counter-indications to opioid treatment

  17. Current analgesic use predicts low emotional quality of life in youth: a cross-sectional survey among university students in Sikkim, North East India.

    Science.gov (United States)

    Ahongshangbam, Shurmala; Chakrabarti, Amit

    2013-06-01

    Occurrence of chronic physical pain is increasingly identified among youth, and medically unsupervised analgesic use is a possible risk factor for opioid dependence and other mental diseases in later life. Therefore, the present study was carried out in young student population in Sikkim, India, to explore predictors (including current chronic pain and current analgesic use) of low QoL in youth to identify a subset of population vulnerable to substance use and mental diseases in later life. The study was conducted in a health university setting in Sikkim, North East India. In this cross-sectional study, 156 participants were enrolled with almost equal number of males and females. Generic instruments for demographics and current analgesic use and SF - 36, for assessment of quality of life (QoL), were used. QoL was measured in general, physical and emotional domains. Presence of chronic physical pain during past four weeks was captured using SF - 36. Almost two-third participants reported presence of current physical pain (69%, n=108); and (14%, n=22) reported current analgesic use for pain. In logistic regression model controlled for age, ethnicity, gender and residence, higher body mass index (BMI) (β=-0.16, P=0.02) and current analgesic use (β=1.6, P=0.006) predicted low QoL in emotional domain (less accomplishment due to emotional problem). Current analgesic use also predicted low QoL in another measure of emotional domain (depressed β=2.0, P=0.001). This study identified a subset of participants in their youth with low QoL in emotional domain predicted by current analgesic use and possible overweight problem. Low QoL in more than one emotional domain also identifies possibility of later psychiatric impairment. However, chronic pain did not emerge as a significant predictor of low QoL in emotional domain.

  18. Patients at Risk: Preoperative Opioid Use Affects Opioid Prescribing, Refills, and Outcomes After Total Knee Arthroplasty.

    Science.gov (United States)

    Hernandez, Nicholas M; Parry, Joshua A; Mabry, Tad M; Taunton, Michael J

    2018-01-16

    The purpose of this study was to evaluate the effect of preoperative opioid use on opioid prescriptions, refills, and clinical outcomes after total knee arthroplasty (TKA). A retrospective review identified 53 patients on preoperative opioids who were matched 1:2 to 106 opioid-naive patients undergoing primary TKA with at least 2-year follow-up. Opioid refills, Knee Society Score (preoperative and follow-up), morphine equivalent dose (MED) prescribed, and persistent opioid use were compared between groups. The average total MED prescribed at discharge was 1248 mg, ranging from 0 to 5600 mg. The average daily MED used before discharge was greater in the preoperative opioid group compared to the opioid-naive group (90 ± 75 mg vs 54 ± 42 mg; P = .001). The preoperative opioid group and opioid-naive group differed in terms of refills (1.3 ± 1.6 vs 0.4 ± 0.6; P = .0001), persistent opioid use (21 [39%] vs 5 [4%], P = .0001), postoperative KSS (85 ± 11 vs 90 ± 13; P = .01), and manipulations under anesthesia (4 [8%] vs 1 [1%], P = .03). Preoperative tramadol users had the same risk of refills, persistent opioid use, reduced KSS, and manipulation under anesthesia as those taking other opioids. Preoperative opioid users were discharged with less opioids, required more refills, were more likely to remain on opioids, and required more manipulations under anesthesia than opioid-naive patients. These risks extended to preoperative tramadol users. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Using behavioral economics to predict opioid use during prescription opioid dependence treatment.

    Science.gov (United States)

    Worley, Matthew J; Shoptaw, Steven J; Bickel, Warren K; Ling, Walter

    2015-03-01

    Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, peconomic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids.

    Science.gov (United States)

    Uekuzu, Yoshihiro; Higashiguchi, Takashi; Futamura, Akihiko; Ito, Akihiro; Mori, Naoharu; Murai, Miyo; Ohara, Hiroshi; Awa, Hiroko; Chihara, Takeshi

    2017-03-01

    There have been few detailed reports on respiratory depression due to overdoses of opioids in terminal cancer patients. We investigated the situation of treatment with opioid antagonists for respiratory depression that occurred after administration of opioid at optimal doses in terminal cancer patients, to clarify pathological changes as well as causative factors. In 2443 terminal cancer patients receiving opioids, 7 patients (0.3%) received opioid antagonists: 6, morphine (hydrochloride, 5; sulfate, 1); 1, oxycodone. The median dosage of opioids was 13.3 mg/d, as converted to morphine injection. Respiratory depression occurred on this daily dose in 4 patients and after changed dose and route in 3 patients. Opioids were given through the vein in 6 patients and by the enteral route in 1 patient. Concomitant drugs included nonsteroidal anti-inflammatory drugs in 3 patients and zoledronic acid in 2 patients. In morphine-receiving patients, renal functions were significantly worsened at the time of administration of an opioid antagonist than the day before the start of opioid administration. These findings indicate that the proper use of opioids was safe and acceptable in almost all terminal cancer patients. In rare cases, however, a risk toward respiratory depression onset is indicated because morphine and morphine-6-glucuronide become relatively excessive owing to systemic debility due to disease progression, especially respiratory and renal dysfunctions. At the onset of respiratory depression, appropriate administration of an opioid antagonist mitigated the symptoms. Thereafter, opioid switching or continuous administration at reduced dosages of the same opioids prevented the occurrence of serious adverse events.

  1. Hydroxyurea and acute painful crises in sickle cell anemia: effects on hospital length of stay and opioid utilization during hospitalization, outpatient acute care contacts, and at home.

    Science.gov (United States)

    Ballas, Samir K; Bauserman, Robert L; McCarthy, William F; Castro, Oswaldo L; Smith, Wally R; Waclawiw, Myron A

    2010-12-01

    Exploratory findings from the randomized, double-blind, placebo-controlled, multicenter study of hydroxyurea (MSH) in sickle cell anemia (SS). Recurrent acute painful crises may be mild, moderate, or severe in nature and often require treatment at home, in acute care facilities as outpatients, and in the hospital with oral and/or parenteral opioids. The objectives of this study were to determine the effects of hydroxyurea (HU) on length of stay (LOS) in hospital and opioid utilization during hospitalization, outpatient acute care contacts, and at home. Data from patient diaries, follow-up visit forms, and medical contact forms for the 299 patients enrolled in the MSH were analyzed. Types and dosages of at home, acute care, and in-hospital analgesic usage were explored descriptively. At-home analgesics were used on 40% of diary days and 80% of two-week follow-up periods, with oxycodone and codeine the most frequently used. Responders to HU used analgesics on fewer days. During hospitalization, 96% were treated with parenteral opioids, with meperidine the most frequently used; oxycodone was the most commonly used oral medication. The average LOS for responders to HU was about two days less than for other groups, and their cumulative time hospitalized during the trial was significantly less than for nonresponders or placebo groups (P<0.022). They also had the lowest doses of parenteral opioids during acute care crises (P=0.015). Beneficial effects of HU include shortening the duration of hospitalization because of acute painful episodes and reducing the net amount of opioid utilization. Copyright © 2010 U.S. Cancer Pain Relief Committee. All rights reserved.

  2. The Analgesic Effects of Different Extracts of Aerial Parts of Coriandrum Sativum in Mice

    Science.gov (United States)

    Fatemeh Kazempor, Seyedeh; Vafadar langehbiz, Shabnam; Hosseini, Mahmoud; Naser Shafei, Mohammad; Ghorbani, Ahmad; Pourganji, Masoomeh

    2015-01-01

    Regarding the effects of Coriandrum sativum (C. sativum) on central nervous system, in the present study analgesic properties of different extracts of C. sativum aerial partswere investigated. The mice were treated by saline, morphine, three doses (20, 100 and 500 mg/kg) of aqueous, ethanolic, choloroformic extracts of C. sativum and one dose (100 mg/kg) of aqueous, two doses of ethanolic (100 and 500 mg/kg) and one dose of choloroformic (20 mg/kg) extracts of C. sativum pretreated by naloxone. Recording of the hot plate test was performed 10 min before injection of the drugs as a base and it was consequently repeated every 10 minutes after the extracts injection. The maximal percent effect (MPE) in the groups treated by three doses of aqueous, ethanolic and chloroformic extracts were significantly higher than saline group which were comparable to the effect of morphine. The effects of most effective doses of extracts were reversed by naloxone. The results of present study showed analgesic effect of aqueous, ethanolic and chloroformic extracts of C. sativum extract. These effects of the extracts may be mediated by opioid system. However, more investigations are needed to elucidate the exact responsible mechanism(s) and the effective compound(s).

  3. Evaluation of the analgesic effect of 4-anilidopiperidine scaffold containing ureas and carbamates.

    Science.gov (United States)

    Monti, Ludovica; Stefanucci, Azzurra; Pieretti, Stefano; Marzoli, Francesca; Fidanza, Lorenzo; Mollica, Adriano; Mirzaie, Sako; Carradori, Simone; De Petrocellis, Luciano; Schiano Moriello, Aniello; Benyhe, Sándor; Zádor, Ferenc; Szűcs, Edina; Ötvös, Ferenc; Erdei, Anna I; Samavati, Reza; Dvorácskó, Szabolcs; Tömböly, Csaba; Novellino, Ettore

    2016-12-01

    Fentanyl is a powerful opiate analgesic typically used for the treatment of severe and chronic pain, but its prescription is strongly limited by the well-documented side-effects. Different approaches have been applied to develop strong analgesic drugs with reduced pharmacologic side-effects. One of the most promising is the design of multitarget drugs. In this paper we report the synthesis, characterization and biological evaluation of twelve new 4-anilidopiperidine (fentanyl analogues). In vivo hot-Plate test, shows a moderate antinociceptive activity for compounds OMDM585 and OMDM586, despite the weak binding affinity on both μ and δ-opioid receptors. A strong inverse agonist activity in the GTP-binding assay was revealed suggesting the involvement of alternative systems in the brain. Fatty acid amide hydrolase inhibition was evaluated, together with binding assays of cannabinoid receptors. We can conclude that compounds OMDM585 and 586 are capable to elicit antinociception due to their multitarget activity on different systems involved in pain modulation.

  4. Reduced consumption of analgesics in patients with diabetes mellitus admitted to hospital for acute myocardial infarction

    DEFF Research Database (Denmark)

    Nielsen, F E; Gram-Hansen, P; Christensen, J H

    1991-01-01

    In a case-control study, the consumption of analgesics was analysed in 39 patients with diabetes, admitted with acute myocardial infarction (MI). The control group comprised of non-diabetics with MI was computer-matched to the diabetic group with respect to age and sex as well as enzyme......-estimated size of the infarction. The median number of injections of opioid analgesics in the diabetes and non-diabetes groups was 2 and 5, respectively (0.01 less than P less than 0.05), and the median consumption of morphine was 20 mg and 35 mg, respectively (0.01 less than P less than 0.......05). There was no statistically significant trend for the duration of pain to be shorter in the diabetes group. There was no difference between the two groups with respect to number of patients with Q-wave infarct, initial heart rate-blood pressure product or body weight, all of which are possible confounders. We conclude...

  5. Results of forty years Yellow Card reporting for commonly used perioperative analgesic drugs.

    Science.gov (United States)

    Richardson, Jennifer; Holdcroft, Anita

    2007-06-01

    A variety of analgesics are used perioperatively and associated adverse drug reactions (ADRs) may complicate anaesthesia and recovery. We aimed to measure the demographics of reported suspected ADRs to alfentanil, fentanyl, ketorolac, morphine, nalbuphine, papaveretum, pethidine and remifentanil. We report a retrospective analysis of Yellow Card reports of suspected ADRs from 1965-2004 as classified in the Adverse Drug Reaction On-line Tracking database (ADROIT) of the Medicines and Healthcare products Regulatory Agency (MHRA). In total, 1312 reactions were retrieved. A single drug was reported in 908, 39 were fatal and 219 categorised as 'allergic'. Allergic phenomenon varied from 2/33 (6%) for remifentanil to 11/53 (21%) for alfentanil. 'Cardiovascular' reactions were reported frequently with remifentanil (18/33, 55%) and alfentanil (19/53, 36%) and these generated a signal for possible hazards from proportional reporting ratios (PRRs). The opioid fentanyl was associated with similar hazard signals for muscular and psychiatric ADRs. Perioperative vigilance may reduce morbidity and mortality from preventable ADRs to analgesic drugs. Denominator and diagnostic data are essential for prospective studies. Copyright (c) 2007 John Wiley & Sons, Ltd.

  6. Opioid-taking self-efficacy as influencing emotional status in patients with cancer pain.

    Science.gov (United States)

    Ding, She-Anne; Liang, Shu-Yuan; Wu, Wei-Wen; Liu, Chieh-Yu; Cheng, Su-Fen

    2016-12-01

    The purpose of this study was to evaluate how much of the variance in emotional status amongst Taiwanese cancer patients could be accounted for by opioid-taking self-efficacy. This cross-sectional study included 109 cancer patients who had taken prescribed opioid analgesics for cancer related pain in the past week and completed the Opioid-Taking Self-Efficacy Scale-CA (OTSES-CA) and Hospital Anxiety and Depression Scale. There was a significant and negative correlation between scores on anxiety and self-efficacy total scale (r = -0.29, p self-efficacy communication subscale (r = -0.37, p self-efficacy acquiring help subscale (r = -0.22, p self-efficacy managing treatment related concerns subscale (r = -0.32, p self-efficacy total scale was not significant (r = -0.18, p > 0.05); only the self-efficacy communication subscale was significantly and negatively associated with depression (r = -0.27, p self-efficacy total scale accounted for 8% of predicting the patients' anxiety. Opioid-taking self-efficacy subscales accounted for 20% (R 2  = 0.20, p = 0.000) of the variance in predicting anxiety and 10% (R 2  = 0.10, p = 0.02) of the variance in predicting depression. This study highlights the potential importance of a patient's opioid-taking self-efficacy beliefs in their emotional status, which is relevant to cancer pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Opioid use after total hip arthroplasty surgery is associated with revision surgery.

    Science.gov (United States)

    Inacio, Maria C S; Pratt, Nicole L; Roughead, Elizabeth E; Paxton, Elizabeth W; Graves, Stephen E

    2016-03-10

    Pain is an indication for total hip arthroplasty (THA) and it should be resolved post-surgery. Because patients' pain is typically treated pharmacologically we tested whether opioid use can be used as a surrogate for patient-reported pain and as an indicator for early surgical failure. Specifically, we evaluated whether the amount of opioids taken within the year after THA was associated with one and five years risk of revision surgery. A cohort of 9943 THAs (01/2001-12/2012) was evaluated. Post-operative opioid use was the exposure of interest and cumulative daily oral morphine equivalent (OME) amounts were calculated. Total OMEs/90-day periods were categorised into quartiles. Revisions within one and five years were the outcomes of interest. Of the THAs, 2.0 % (N = 200) were revised within one year and 4.2 % (N = 413) within five years. After adjustments for gender, age, surgical indication, co-morbidities, and other analgesics, revision was associated with amount of OMEs in the second quarter after THA (days 91-180 after discharge). Patients on medium-high amounts of OME (400-1119 mg) had higher risk of one (hazard ratio (HR) = 2.22, 95 % CI 1.08-4.56) and five year (HR = 1.66, 95 % CI 1.08-2.56) revision than a patient not taking opioids. During the same period, patients taking the highest amounts of OMEs (≥1120 mg) had a 2.64 (95 % CI 1.03-6.74) times higher risk of one year and a 2.11 (95 % CI 1.13-3.96) times higher risk of five year revision. Opioid use 91-180 days post-surgery is associated with higher risk of revision surgery and therefore is an early and useful indicator for surgical failure.

  8. Prevalence of prescription opioid use disorder among chronic opioid therapy patients after health plan opioid dose and risk reduction initiatives.

    Science.gov (United States)

    Von Korff, Michael; Walker, Rod L; Saunders, Kathleen; Shortreed, Susan M; Thakral, Manu; Parchman, Michael; Hansen, Ryan N; Ludman, Evette; Sherman, Karen J; Dublin, Sascha

    2017-08-01

    No studies have assessed the comparative effectiveness of guideline-recommended interventions to reduce risk of prescription opioid use disorder among chronic opioid therapy (COT) patients. We compared the prevalence of prescription opioid use disorder among COT patients from intervention clinics that had implemented opioid dose and risk reduction initiatives for more than 4 years relative to control clinics that had not. After a healthcare system in Washington State implemented interventions to reduce opioid dose and risks, we surveyed 1588 adult primary care COT patients to compare the prevalence of prescription opioid use disorder among COT patients from the intervention and control clinics. Intervention clinics managed COT patients at lower COT doses and with more consistent use of risk reduction practices. Control clinics cared for similar COT patients but prescribed higher opioid doses and used COT risk reduction practices inconsistently. Prescription opioid use disorder was assessed with the Psychiatric Research Interview for Substance and Mental Disorders. The prevalence of prescription opioid use disorder was 21.5% (95% CI=18.9% to 24.4%) among COT patients in the intervention clinics and 23.9% (95% CI=20.5% to 27.6%) among COT patients in the control clinics. The adjusted relative risk of prescription opioid use disorder was 1.08 (95% CI=0.89, 1.32) among the control clinic patients relative to the intervention clinic patients. Long-term implementation of opioid dose and risk reduction initiatives was not associated with lower rates of prescription opioid use disorder among prevalent COT patients. Extreme caution should be exercised by clinicians considering COT for patients with chronic non-cancer pain until benefits of this treatment and attendant risks are clarified. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Update on the role of non-opioids for postoperative pain treatment.

    Science.gov (United States)

    Schug, Stephan A; Manopas, Andreas

    2007-03-01

    Non-opioids play an ever increasing role in the treatment of postoperative pain; either on their own for mild to moderate pain or in combination with other analgesic approaches, in particular opioids, as a component of multimodal analgesia. The analgesics paracetamol (acetaminophen) and dipyrone (metamizole) as well as compounds with an additional anti-inflammatory effect (non-selective non-steroidal anti-inflammatory drugs and selective cyclo-oxygenase-2 inhibitors) are used widely in the perioperative period. Paracetamol is gaining renewed interest in this setting due to its minimal adverse effects and recent availability in a parenteral preparation, but its benefits are insufficiently studied. Dipyrone continues to be used in many countries despite the ongoing debate on the incidence and relevance of its ability to cause agranulocytosis. Among the anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors have the most supportive data for their beneficial effects as a component of multimodal analgesia and offer benefits with regard to their adverse effect profile.

  10. Reasons for opioid use among patients with dependence on prescription opioids: the role of chronic pain.

    Science.gov (United States)

    Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; McHugh, R Kathryn; Haller, Deborah; Jacobs, Petra; Gardin, John; Fischer, Dan; Rosen, Kristen D

    2014-08-01

    The number of individuals seeking treatment for prescription opioid dependence has increased dramatically, fostering a need for research on this population. The aim of this study was to examine reasons for prescription opioid use among 653 participants with and without chronic pain, enrolled in the Prescription Opioid Addiction Treatment Study, a randomized controlled trial of treatment for prescription opioid dependence. Participants identified initial and current reasons for opioid use. Participants with chronic pain were more likely to report pain as their primary initial reason for use; avoiding withdrawal was rated as the most important reason for current use in both groups. Participants with chronic pain rated using opioids to cope with physical pain as more important, and using opioids in response to social interactions and craving as less important, than those without chronic pain. Results highlight the importance of physical pain as a reason for opioid use among patients with chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Postoperative opioid sparing with injectable hydroxypropyl-β-cyclodextrin-diclofenac: pooled analysis of data from two Phase III clinical trials

    Directory of Open Access Journals (Sweden)

    Gan TJ

    2016-12-01

    Full Text Available Tong J Gan,1 Neil Singla,2 Stephen E Daniels,3 Douglas A Hamilton,4,5 Peter G Lacouture,6,7 Christian RD Reyes,8 Daniel B Carr4,9 1Department of Anesthesiology, Stony Brook University, NY, 2Lotus Clinical Research, LLC, Pasadena, CA, 3Premier Research, Austin, TX, 4Javelin Pharmaceuticals, Inc., Cambridge, MA, 5New Biology Ventures, LLC, San Mateo, CA, 6Magidom Discovery, LLC, St Augustine, FL, 7Department of Emergency Medicine, Brown University School of Medicine, Providence, RI, 8Hospira Inc., Lake Forest, IL, 9Department of Anesthesiology, Tufts Medical Center, Boston, MA, USA Purpose: Use of nonopioid analgesics (including nonsteroidal anti-inflammatory drugs for postoperative pain management can reduce opioid consumption and potentially prevent opioid-related adverse events. This study examined the postoperative opioid-sparing effect of repeated-dose injectable diclofenac formulated with hydroxypropyl-β-cyclodextrin (HPβCD-diclofenac. Patients and methods: Pooled data from two double-blind, randomized, placebo- and active comparator-controlled Phase III trials were analyzed. Patients received HPβCD-diclofenac, placebo, or ketorolac by intravenous injection every 6 hours for up to 5 days following abdominal/pelvic or orthopedic surgery. Rescue opioid use was evaluated from the time of first study drug administration to up to 120 hours following the first dose in the overall study population and in subgroups defined by baseline pain severity, age, and HPβCD-diclofenac dose. Results: Overall, 608 patients received ≥1 dose of study medication and were included in the analysis. While 93.2% of patients receiving placebo required opioids, the proportion of patients requiring opioids was significantly lower for patients receiving HPβCD-diclofenac (18.75, 37.5, or 50 mg or ketorolac (P<0.005 for all comparisons. Mean cumulative opioid dose and number of doses were significantly lower among patients receiving HPβCD-diclofenac versus placebo

  12. Tramadol reduces the 5-HTP-induced head-twitch response in mice via the activation of mu and kappa opioid receptors.

    Science.gov (United States)

    Sun, Hong-Lei; Zheng, Ji-Wang; Wang, Keng; Liu, Rui-Ke; Liang, Jian-Hui

    2003-01-31

    Tramadol, an atypical opioid analgesic, stimulates both opiatergic and serotonergic systems. Here we have investigated the effect of tramadol in mice on 5-hydroxyptrytophan (5-HTP)-induced head twitch response (HTR), which is an animal model for the activation of the CNS 5-HT(2A) receptors in mice. Tramadol attenuated 5-HTP-induced HTR in a dose-dependent manner as morphine. Furthermore, the nonselective opioid receptor antagonists, naloxone and diprenorphine (M5050), reversed the effect of tramadol on 5-HTP-induced HTR dose-dependently. Interestingly, in contrast to the selective delta opioid receptor antagonist NTI, beta-FNA, a selective mu receptor antagonist, and nor-BNI, a selective kappa opioid receptor antagonist, antagonized the attenuation of 5-HTP-induced HTR by tramadol. In conclusion, administration of tramadol systemically inhibits 5-HTP-induced HTR in mice by activating opiatergic system in the CNS. Our findings show that mu and kappa opioid receptors, but not delta opioid receptor, play an important role in the regulation of serotonergic function in the CNS.

  13. Pre-Irradiation of blood by gallium aluminum arsenide (830 nm) low-level laser enhances peripheral endogenous opioid analgesia in rats.

    Science.gov (United States)

    Hagiwara, Satoshi; Iwasaka, Hideo; Hasegawa, Akira; Noguchi, Takayuki

    2008-09-01

    Low-level laser therapy (LLLT) has been reported to relieve pain, free of side effects. However, the mechanisms underlying LLLT are not well understood. Recent studies have also demonstrated that opioid-containing immune cells migrate to inflamed sites and release beta-endorphins to inhibit pain as a mode of peripheral endogenous opioid analgesia. We investigated whether pre-irradiation of blood by LLLT enhances peripheral endogenous opioid analgesia. The effect of LLLT pretreatment of blood on peripheral endogenous opioid analgesia was evaluated in a rat model of inflammation. Additionally, the effect of LLLT on opioid production was also investigated in vitro in rat blood cells. The expression of the beta-endorphin precursors, proopiomelanocortin and corticotrophin releasing factor, were investigated by reverse transcription polymerase chain reaction. LLLT pretreatment produced an analgesic effect in inflamed peripheral tissue, which was transiently antagonized by naloxone. Correspondingly, beta-endorphin precursor mRNA expression increased with LLLT, both in vivo and in vitro. These findings suggest that that LLLT pretreatment of blood induces analgesia in rats by enhancing peripheral endogenous opioid production, in addition to previously reported mechanisms.

  14. Investigation of the Practices, Legislation, Supply Chain, and Regulation of Opioids for Clinical Pain Management in Southern Africa: A Multi-sectoral, Cross-National, Mixed Methods Study.

    Science.gov (United States)

    Namisango, Eve; Allsop, Matthew J; Powell, Richard A; Friedrichsdorf, Stefan J; Luyirika, Emmanuel B K; Kiyange, Fatia; Mukooza, Edward; Ntege, Chris; Garanganga, Eunice; Ginindza-Mdluli, Mavis Ntombifuthi; Mwangi-Powell, Faith; Mondlane, Lidia Justino; Harding, Richard

    2018-03-01

    Sub-Saharan Africa faces an increasing incidence and prevalence of life-limiting and life-threatening conditions. These conditions are associated with a significant burden of pain linked to high morbidity and disability that is poorly assessed and undertreated. Barriers to effective pain management partly relate to lack of access to opioid analgesia and challenges in their administration. To identify country-specific and broader regional barriers to access, as well as the administration of opioids, and generate recommendations for advancing pain management in Southern Africa. A parallel mixed methods design was used across three countries: Mozambique, Swaziland, and Zimbabwe. Three activities were undertaken: 1) a review of regulatory and policy documentation, 2) group interviews, and 3) a self-administered key informant survey. Barriers to accessing opioid analgesics for medical use include overly restrictive controlled medicines' laws; use of stigmatizing language in key documents; inaccurate actual opioid consumption estimation practices; knowledge gaps in the distribution, storage, and prescription of opioids; critical shortage of prescribers; and high out-of-pocket financial expenditures for patients against a backdrop of high levels of poverty. Policies and relevant laws should be updated to ensure that the legislative environment supports opioid access for pain management. Action plans for improving pain treatment for patients suffering from HIV or non-communicable diseases should address barriers at the different levels of the supply chain that involve policymakers, administrators, and service providers. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  15. Low doses of cyclic AMP-phosphodiesterase inhibitors rapidly evoke opioid receptor-mediated thermal hyperalgesia in naïve mice which is converted to prominent analgesia by cotreatment with ultra-low-dose naltrexone.

    Science.gov (United States)

    Crain, Stanley M; Shen, Ke-Fei

    2008-09-22

    Systemic (s.c.) injection in naïve mice of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors, e.g. 3-isobutyl-1-methylxanthine [(IBMX) or caffeine, 10 mg/kg] or the more specific cAMP-PDE inhibitor, rolipram (1 mug/kg), rapidly evokes thermal hyperalgesia (lasting >5 h). These effects appear to be mediated by enhanced excitatory opioid receptor signaling, as occurs during withdrawal in opioid-dependent mice. Cotreatment of these mice with ultra-low-dose naltrexone (NTX, 0.1 ng/kg-1 pg/kg, s.c.) results in prominent opioid analgesia (lasting >4 h) even when the dose of rolipram is reduced to 1 pg/kg. Cotreatment of these cAMP-PDE inhibitors in naïve mice with an ultra-low-dose (0.1 ng/kg) of the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) or the mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA) also results in opioid analgesia. These excitatory effects of cAMP-PDE inhibitors in naïve mice may be mediated by enhanced release of small amounts of endogenous bimodally-acting (excitatory/inhibitory) opioid agonists by neurons in nociceptive networks. Ultra-low-dose NTX, nor-BNI or beta-FNA selectively antagonizes high-efficacy excitatory (hyperalgesic) Gs-coupled opioid receptor-mediated signaling in naïve mice and results in rapid conversion to inhibitory (analgesic) Gi/Go-coupled opioid receptor-mediated signaling which normally requires activation by much higher doses of opioid agonists. Cotreatment with a low subanalgesic dose of kelatorphan, an inhibitor of multiple endogenous opioid peptide-degrading enzymes, stabilizes endogenous opioid agonists released by cAMP-PDE inhibitors, resulting in conversion of the hyperalgesia to analgesia without requiring selective blockade of excitatory opioid receptor signaling. The present study provides a novel pharmacologic paradigm that may facilitate development of valuable non-narcotic clinical analgesics utilizing cotreatment with ultra-low-dose rolipram plus ultra-low-dose NTX or related

  16. Opioid-Induced Esophageal Dysfunction (OIED) in Patients on Chronic Opioids.

    Science.gov (United States)

    Ratuapli, Shiva K; Crowell, Michael D; DiBaise, John K; Vela, Marcelo F; Ramirez, Francisco C; Burdick, George E; Lacy, Brian E; Murray, Joseph A

    2015-07-01

    Bowel dysfunction has been recognized as a predominant side effect of opioid use. Even though the effects of opioids on the stomach and small and large intestines have been well studied, there are limited data on opioid effects on esophageal function. The aim of this study was to compare esophageal pressure topography (EPT) of patients taking opioids at the time of the EPT (≤24 h) with chronic opioid users who were studied off opioid medications for at least 24 h using the Chicago classification v3.0. A retrospective review identified 121 chronic opioid users who completed EPT between March 2010 and August 2012. Demographic and manometric data were compared between the two groups using general linear models or χ(2). Of the 121 chronic opioid users, 66 were studied on opioid medications (≤24 h) and 55 were studied off opioid medications for at least 24 h. Esophagogastric junction (EGJ) outflow obstruction was significantly more prevalent in patients using opioids within 24 h compared with those who did not (27% vs. 7%, P=0.004). Mean 4 s integrated relaxation pressure was also significantly higher in patients studied on opioids (10.71 vs. 6.6 mm Hg, P=0.025). Resting lower esophageal sphincter pressures tended to be higher on opioids (31.61 vs. 26.98 mm Hg, P=0.25). Distal latency was significantly lower in patients studied on opioids (6.15 vs. 6.74 s, P=0.044). Opioid use within 24 h of EPT is associated with more frequent EGJ outflow obstruction and spastic peristalsis compared with when opioid use is stopped for at least 24 h before the study.

  17. To take or not to take: the association between perceived addiction risk, expected analgesic response and likelihood of trying novel pain relievers in self-identified chronic pain patients.

    Science.gov (United States)

    Tompkins, D Andrew; Huhn, Andrew S; Johnson, Patrick S; Smith, Michael T; Strain, Eric C; Edwards, Robert R; Johnson, Matthew W

    2018-01-01

    Probability discounting refers to the effect of outcome uncertainty on decision making. Using probability discounting, we examined the degree to which self-identified chronic pain patients (CPP) were likely to try a novel analgesic medication given increasing addiction risk. We postulated that propensity for opioid misuse, trait impulsivity and previous opioid experience would be associated positively with likelihood of risky medication use. This cross-sectional on-line study determined state/trait associations with addiction-related medication decisions in CPP. US-based CPP participated via Amazon Mechanical Turk; data were collected and analyzed in Baltimore, Maryland. A total of 263 CPP (70.6% female) participated in the study from 12-13 December 2014. CPP responded to the Benefit versus Addiction Risk Questionnaire (BARQ) assessing likelihood of taking a hypothetical once-daily oral analgesic medication as a function of two factors: risk of addiction (0-50%) and duration of expected complete pain relief (3, 30 or 365 days). The primary outcome was the BARQ, quantified as area under the curve (AUC). Grouping of CPP at high or low risk for opioid misuse was based on the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Predictors included previous experience with opioids, as well as various measures of chronic pain and mental health. Across hypothetical addiction risk assessed in the BARQ, the likelihood of taking a novel analgesic medication was elevated significantly in patients with high (≥18; n = 137) versus low (<18; n = 126) SOAPP-R scores [P < 0.001; 3-day: Cohen's d = 0.66, 95% confidence interval (CI) = 0.63, 0.69; 30-day: d = 0.74, 95% CI = 0.71, 0.78; 365-day: d = 0.75, 95% CI = 0.72, 0.79]. In the United States, self-identified chronic pain patients (CPP) at higher risk for opioid misuse were more likely to report willingness to try a novel analgesic despite increasing addiction risk than CPP with low risk

  18. Effect of intraoperative lidocaine on anesthetic consumption, and bowel function, pain intensity, analgesic consumption and hospital stay after breast surgery.

    Science.gov (United States)

    Choi, Soo Joo; Kim, Myung Hee; Jeong, Hui Yeon; Lee, Jeong Jin

    2012-05-01

    Perioperative lidocaine infusion improves postoperative outcomes, mostly after abdominal and urologic surgeries. Knowledge of the effect of lidocaine on peripheral surgeries is limited. Presently, we investigated whether intraoperative lidocaine infusion reduced anesthetic consumption, duration of ileus, pain intensity, analgesic consumption and hospital stay after breast plastic surgeries. Sixty female patients, aged 20-60 years, enrolled in this prospective study were randomly and equally divided to two groups. One group (n = 30) received a 1.5 mg/kg bolus of lidocaine approximately 30 min before incision followed by continuous infusion of lidocaine (1.5 mg/kg/h) until skin closure (lidocaine group). The other group (n = 30) was untreated (control group). Balanced inhalation (sevoflurane) anesthesia and multimodal postoperative analgesia were standardized. End tidal sevoflurane concentration during surgery, time to the first flatus and defecation, visual analog pain scale (0-10), analgesic consumption and associated side effects at 24, 48, and 72 h after surgery, hospital stay, and patient's general satisfaction were assessed. Compared to the control group, intraoperative lidocaine infusion reduced by 5% the amount of sevoflurane required at similar bispectral index (P = 0.014). However, there were no significant effects of lidocaine regarding the return of bowel function, postoperative pain intensity, analgesic sparing and side effects at all time points, hospital stay, and level of patient's satisfaction for pain control. Low dose intraoperative lidocaine infusion offered no beneficial effects on return of bowel function, opioid sparing, pain intensity and hospital stay after various breast plastic surgeries.

  19. Adding pregabalin to a multimodal analgesic regimen does not reduce pain scores following cosmetic surgery: a randomized trial.

    Science.gov (United States)

    Chaparro, Luis Enrique; Clarke, Hance; Valdes, Paola A; Mira, Mauricio; Duque, Lorena; Mitsakakis, Nicholas

    2012-12-01

    Multimodal analgesia increases the chance of successful discharge and pain control after surgery, and pregabalin is being promoted as an effective analgesic, based on placebo-controlled studies. We investigated whether adding pregabalin improved pain control and reduced opioid requests when it was added to a multimodal analgesic regimen for cosmetic surgery. One hundred and ten women who underwent same-day cosmetic surgery were randomized to receive oral pregabalin, 75 mg q12 h for five consecutive days starting the night before surgery, or identical placebos. Participants, outcomes assessors, and the statistician were blinded. The primary outcome was postoperative numerical movement-evoked pain scores at 2, 24, 48, 72, and 96 h after surgery. The secondary outcomes included pain scores at rest; incidence of moderate to severe pain; and analgesic and antiemetic requirements; as well as the incidence of nausea, vomiting, and somnolence. Based on 99 patients who completed the study, we found no difference between the groups in the primary outcome; 72 h after surgery, movement-evoked median pain scores were cosmetic surgery. Several factors could explain our findings, including the possibility of publication bias in the current literature.

  20. Opioid Therapy for Chronic Nonmalignant Pain

    Directory of Open Access Journals (Sweden)

    Russell K Portenoy

    1996-01-01

    Full Text Available Long term administration of an opioid drug for chronic nonmalignant pain continues to be controversial, but is no longer uniformly rejected by pain specialists. This is true despite concerns that the regulatory agencies that oversee physician prescribing of opioid drugs continue to stigmatize the practice. The changing clinical perspective has been driven, in part, by widespread acknowledgement of the remarkably favourable outcomes achieved during opioid treatment of cancer pain. These outcomes contrast starkly with popular teaching about chronic opioid therapy and affirm the potential for prolonged efficacy, tolerable side effects, enhanced function associated with improved comfort and minimal risk of aberrant drug-related behaviours consistent with addiction. A large anecdotal experience in populations with nonmalignant pain suggests that these patients are more heterogeneous and that opioid therapy will greatly benefit some and will contribute to negative outcomes for others. The few controlled clinical trials that have been performed support the safety and efficacy of opioid therapy, but have been too limited to ensure generalization to the clinical setting. A critical review of the medical literature pertaining to chronic pain, opioid pharmacology and addiction medicine can clarify misconceptions about opioid therapy and provide a foundation for patient selection and drug administration. The available data support the view that opioids are no panacea for chronic pain, but should be considered in carefully selected patients using clinically derived guidelines that stress a structured approach and ongoing monitoring of efficacy, adverse effects, functional outcomes and the occurrence of aberrant drug-related behaviours.

  1. America's Opioid Epidemic: Supply and Demand Considerations.

    Science.gov (United States)

    Clark, David J; Schumacher, Mark A

    2017-11-01

    America is in the midst of an opioid epidemic characterized by aggressive prescribing practices, highly prevalent opioid misuse, and rising rates of prescription and illicit opioid overdose-related deaths. Medical and lay public sentiment have become more cautious with respect to prescription opioid use in the past few years, but a comprehensive strategy to reduce our reliance on prescription opioids is lacking. Addressing this epidemic through reductions in unnecessary access to these drugs while implementing measures to reduce demand will be important components of any comprehensive solution. Key supply-side measures include avoiding overprescribing, reducing diversion, and discouraging misuse through changes in drug formulations. Important demand-side measures center around educating patients and clinicians regarding the pitfalls of opioid overuse and methods to avoid unnecessary exposure to these drugs. Anesthesiologists, by virtue of their expertise in the use of these drugs and their position in guiding opioid use around the time of surgery, have important roles to play in reducing patient exposure to opioids and providing education about appropriate use. Aside from the many immediate steps that can be taken, clinical and basic research directed at understanding the interaction between pain and opioid misuse is critical to identifying the optimal use of these powerful pain relievers in clinical practice.

  2. Buprenorphine for the treatment of opioid dependence.

    Science.gov (United States)

    Boothby, Lisa A; Doering, Paul L

    2007-02-01

    The clinical issues surrounding the use of buprenorphine for the treatment of opioid dependence are reviewed. Opioids continue to be some of the most frequently reported prescription medications in substance abuse- related cases. A semisynthetic derivative of thebaine, buprenorphine hydrochloride is a partial mu-opioid receptor agonist and kappa-receptor antagonist with a long duration of action. The pharmacokinetic and pharmacodynamic profiles of buprenorphine are not well characterized. The ethical and legal issues associated with the maintenance treatment of opioid dependence are complex. Clinical trials have compared the efficacy of methadone, buprenorphine, and buprenorphine-naloxone for the detoxification and maintenance treatment of opioid dependence. Based on the available literature, it appears that buprenorphine, buprenorphine-naloxone, and methadone are similarly efficacious for the treatment of opioid-dependent patients. Buprenorphine-naloxone has less potential for abuse and diversion. The adverse-effect profiles for buprenorphine, buprenorphine-naloxone, and methadone are similar. Once-weekly office visits for patient evaluation and dispensing of buprenorphine seem feasible and convenient for both practitioners and patients. The three phases of opioid maintenance treatment are induction, stabilization, and maintenance. It is good practice for the admitting physician to consult with the patient's addiction treatment provider, when possible, to obtain the patient's treatment history. Buprenorphine is an attractive option for the pharmacologic treatment of opioid dependence. Compliance and adherence to buprenorphine therapy for opioid-dependent patients remain clinical issues. Future research efforts should focus on improving compliance and adherence to buprenorphine therapy.

  3. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).

    Science.gov (United States)

    Pergolizzi, Joseph; Böger, Rainer H; Budd, Keith; Dahan, Albert; Erdine, Serdar; Hans, Guy; Kress, Hans-Georg; Langford, Richard; Likar, Rudolf; Raffa, Robert B; Sacerdote, Paola

    2008-01-01

    SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional

  4. Antinociceptive tolerance to NSAIDs in the rat formalin test is mediated by the opioid mechanism.

    Science.gov (United States)

    Tsiklauri, Nana; Nozadze, Ivliane; Gurtskaia, Gulnaz; Tsagareli, Merab G

    2017-02-01

    In the past decade it has been shown that tolerance develops to the antinociceptive effect of repeated systemic administration of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) in acute pain models using rats. This is similar to the tolerance observed with opioid-induced analgesia. In the present study, we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac and xefocam in a chronic inflammatory pain model, the formalin test. Male Wistar rats receiving intraplantar formalin were tested for antinociception following intraperitoneal injection of NSAIDs in thermal paw withdrawal (Hargreaves) test and mechanical paw withdrawal (von Frey) test. Repeated measures analysis of variance with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluations. Treatment with each NSAID significantly elevated the thermal paw withdrawal latency and mechanical paw withdrawal threshold on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, i.e., tolerance developed. With daily intraplantar injections of formalin, there was a trend toward reduced antinociceptive effects of diclofenac and ketorolac while xefocam exhibited a significant reduction (tolerance). It is noteworthy that the NSAID tolerant groups of rats still exhibited a strong hyperalgesia during phase I formalin following administration of each NSAID, an effect not observed in non-tolerant rats. Pretreatment with naloxone completely prevented the analgesic effects of these three NSAIDs in both behavioral assays. The present findings support the notion that the development of tolerance to the antinociceptive effects of NSAIDs in an inflammatory pain model is mediated via an endogenous opioid system possibly involving descending pain modulatory systems. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Factors associated with primary care prescription of opioids for joint pain.

    Science.gov (United States)

    Green, D J; Bedson, J; Blagojevic-Burwell, M; Jordan, K P; van der Windt, D

    2013-02-01

    Opioids are commonly prescribed in primary care and can offer pain relief but may also have adverse effects. Little is known about the characteristics of people likely to receive an opioid prescription in primary care. The aim is to identify what factors are associated with primary care prescribing of high-strength analgesics in a community sample of older people with joint pain. A prospective two-stage postal survey completed at baseline and 3-year follow-up in a population aged 50 and over registered with eight general practitioner (GP) practices in North Staffordshire (North Staffordshire Osteoarthritis Project cohorts) linked with data from medical records. Participants were selected who reported joint pain in one or more joints at baseline. Outcome measures were the number of prescriptions for high-strength pain medication (opioids) in the following 3 years. Socio-demographic and health status factors associated with prescription were assessed using a zero-inflated Poisson model. 873 (19%) people were prescribed opioids (out of 4652 providing complete data) ranging from 1 to 76 prescriptions over 3 years. Baseline factors significantly associated with increased rates of prescription were younger age group [65-74 group: incidence rate ratio (IRR) = 1.26 (1.18-1.35)], male gender [IRR = 1.17 (1.12-1.23)], severe joint pain [IRR = 1.19 (1.12-1.26)] poor physical function [IRR = 0.99 (0.99-0.99)] and lower frequency of alcohol consumption [once/twice a year: IRR = 1.13 (1.06-1.21), never: IRR = 1.14 (1.06-1.22)]. Restricting the analysis to those without prior prescriptions for strong opioids showed similar results. Poor physical function and participation restrictions were strongly associated with prescriptions of stronger opioids in addition to several socio-demographic and lifestyle factors. Given the uncertainties over the effectiveness and risks of opioid use, future research could investigate decision making of GPs, exploring reasons for prescribing them.

  6. Birth and Neonatal Outcomes following Opioid Use in Pregnancy: A Danish Population-Based Study

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    Mette Nørgaard

    2015-01-01

    increased prevalence of adverse birth outcomes, and this increase could only be explained to a smaller extent by increased prevalence of smoking. The risk of NAS was eight-fold higher in methadone-exposed neonates than that in buprenorphine-exposed neonates, but this difference may at least partly be explained by differences in underlying indications (analgesic versus opioid maintenance treatment between the two groups.

  7. Validation of a computer case definition for sudden cardiac death in opioid users

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    Kawai Vivian K

    2012-08-01

    Full Text Available Abstract Background To facilitate the use of automated databases for studies of sudden cardiac death, we previously developed a computerized case definition that had a positive predictive value between 86% and 88%. However, the definition has not been specifically validated for prescription opioid users, for whom out-of-hospital overdose deaths may be difficult to distinguish from sudden cardiac death. Findings We assembled a cohort of persons 30-74 years of age prescribed propoxyphene or hydrocodone who had no life-threatening non-cardiovascular illness, diagnosed drug abuse, residence in a nursing home in the past year, or hospital stay within the past 30 days. Medical records were sought for a sample of 140 cohort deaths within 30 days of a prescription fill meeting the computer case definition. Of the 140 sampled deaths, 81 were adjudicated; 73 (90% were sudden cardiac deaths. Two deaths had possible opioid overdose; after removing these two the positive predictive value was 88%. Conclusions These findings are consistent with our previous validation studies and suggest the computer case definition of sudden cardiac death is a useful tool for pharmacoepidemiologic studies of opioid analgesics.

  8. Gestational and ovarian sex steroid antinociception: synergy between spinal kappa and delta opioid systems.

    Science.gov (United States)

    Dawson-Basoa, M; Gintzler, A R

    1998-05-25

    Pain thresholds are elevated during gestation and following the simulation of pregnancy blood levels of estrogen and progesterone (hormone simulated pregnancy; HSP). The analgesia associated with both conditions is opioid-mediated and results from the activation of spinal cord kappa and delta (but not mu) opiate receptors. Blockade of spinal kappa or delta opiate receptors, individually, can abolish the antinociception associated with either gestational day 20 or day 19 of HSP. Surprisingly, during either physiological pregnancy or HSP, the magnitude of reduction in the increment in jump thresholds following the combined intrathecal application of suboptimum concentrations of kappa and delta antagonists is indistinguishable from that observed following their individual intrathecal application. These data indicate that gestational and ovarian sex steroid-induced antinociception is not simply the sum of the independent analgesic effects of spinal kappa and delta opioid systems but requires their coincident activation. It is suggested that the synergy that has been reported following the exogenous intrathecal application of kappa and delta opioids also occurs between their endogenous counterparts and underlies the intrinsic analgesia associated with each condition. Utilization of such a mechanism allows for significant physiological effects (analgesia) to be achieved with doses of relevant substrates (dynorphin and enkephalin) which alone would produce minimal receptor activation (and analgesia). This would minimize tolerance and dependence formation. Copyright 1998 Elsevier Science B.V. All rights reserved.

  9. Cell-Autonomous Regulation of Mu-Opioid Receptor Recycling by Substance P

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    Shanna L. Bowman

    2015-03-01

    Full Text Available How neurons coordinate and reprogram multiple neurotransmitter signals is an area of broad interest. Here, we show that substance P (SP, a neuropeptide associated with inflammatory pain, reprograms opioid receptor recycling and signaling. SP, through activation of the neurokinin 1 (NK1R receptor, increases the post-endocytic recycling of the mu-opioid receptor (MOR in trigeminal ganglion (TG neurons in an agonist-selective manner. SP-mediated protein kinase C (PKC activation is both required and sufficient for increasing recycling of exogenous and endogenous MOR in TG neurons. The target of this cross-regulation is MOR itself, given that mutation of either of two PKC phosphorylation sites on MOR abolishes the SP-induced increase in recycling and resensitization. Furthermore, SP enhances the resensitization of fentanyl-induced, but not morphine-induced, antinociception in mice. Our results define a physiological pathway that cross-regulates opioid receptor recycling via direct modification of MOR and suggest a mode of homeostatic interaction between the pain and analgesic systems.

  10. Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone

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    Atefeh Aminian

    2016-07-01

    Full Text Available Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg, animals received intraperitoneal injections of morphine (5 mg/kg/day and/or naltrexone (20 mg/kg/day, an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy.

  11. Effects of opioids on local anesthesia in the rat: a codeine and tramadol study

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    Talita Girio Carnaval

    2013-12-01

    Full Text Available Opioids are central analgesics that act on the CNS (central nervous system and PNS (peripheral nervous system. We investigated the effects of codeine (COD and tramadol (TRAM on local anesthesia of the sciatic nerve. Eighty Wistar male rats received the following SC injections in the popliteal fossa: local anesthetic with epinephrine (LA; local anesthetic without vasoconstrictor (LA WV; COD; TRAM; LA + COD; LA + TRAM; COD 20 minutes prior to LA (COD 20' + LA or TRAM 20 minutes prior to LA (TRAM 20' + LA. As a nociceptive function, the blockade was considered the absence of a paw withdraw reflex. As a motor function, it was the absence of claudication. As a proprioceptive function, it was the absence of hopping and tactile responses. All data were compared using repeated-measures analysis of variance (ANOVA. Opioids showed a significant increase in the level of anesthesia, and the blockade duration of LA + COD was greater than that of the remaining groups (p < 0.05. The associated use of opioids improved anesthesia efficacy. This could lead to a new perspective in controlling dental pain.

  12. Adult emergency department patients with sickle cell pain crisis: results from a quality improvement learning collaborative model to improve analgesic management.

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    Tanabe, Paula; Hafner, John W; Martinovich, Zoran; Artz, Nicole

    2012-04-01

    The aims of this study were to 1) estimate differences in pain management process and patient-reported outcomes, pre- and postimplementation of analgesic protocols for adults with sickle cell disease (SCD), and 2) examine the effects of site and visit frequency on changes in pain scores and time to analgesic. A multicenter, prospective, longitudinal study enrolled patients from three academic medical centers between October 2007 and September 2009. All ED patients 18 years or older with a chief complaint of a sickle cell pain episode were enrolled. Sites formed a SCD quality improvement (QI) team and implemented standard nurse-initiated emergency department (ED) analgesic protocols; outcomes were compared between study periods defined as pre- and postimplementation of protocols. Medical record review was conducted to measure time to administration of initial analgesic, opioids used, route of opioid administration, the change in pain scores from arrival to discharge (negative numbers reflect a decrease in pain scores), and the number of ED visits per individual patient during the study period at each site. On day 7 after the ED visit, a follow-up phone interview was conducted. Patients were queried about their ED pain management using a scale from 1 to 10 (1 = outstanding, 10 = worst). Descriptive statistics are used to report the results. Ordinary least-squares regression models were constructed to measure the effect of time period, site, and number of visits per patient on change in pain score. During the study period, 342 unique patients (57% female, mean ± SD age = 32 ± 11 years) were enrolled and had a total of 2,934 visits. There was no difference in time to administration of the initial analgesic between study periods. Overall, there was a significant decrease in pain scores from arrival to discharge between the pre- and postintervention study periods: the average difference in arrival to discharge pain scores (cm) was greater during the postimplementation

  13. Evaluation of the relationship between opioid exposure in extremely low birth weight infants in the neonatal intensive care unit and neurodevelopmental outcome at 2 years.

    Science.gov (United States)

    Kocek, Melissa; Wilcox, Roger; Crank, Christopher; Patra, Kousiki

    2016-01-01

    Extremely low birth weight (ELBW) infants are exposed to many painful procedures while in the neonatal intensive care unit (NICU), such as catheter insertion and endotracheal intubation. Exposure of ELBW infants to repetitive pain and stress in the NICU can lead to cardiovascular instability and may alter neuronal and synaptic organization. Opioid analgesics are administered to reduce pain, stress and to potentially reduce poor neurologic outcomes. They may also be utilized as sedation for mechanically ventilated ELBW infants. There is limited data in regards to neurodevelopmental outcomes of preterm infants exposed to opioids, and available studies have conflicting results. To examine the relationship between cumulative opioid dose in ELBW infants in the NICU and neurodevelopmental outcomes at 20 months corrected age (CA). 100 ELBW infants who had complete neurodevelopmental assessments at 20 months CA were categorized by cumulative opioid exposure during the NICU stay (high vs. low/no opioid). Outcome measures included cognitive, motor and language scores from the Bayley Scales of Infant and Toddler Development-III (BSITD-III). Multiple regression analyses adjusted for the impact of social and neonatal risk factors on outcome. There were 60 patients with high and 40 with low/no opioid exposure. Infants in the high dose group had a higher number of median ventilator days (53.5 vs. 45.6 days, p=0.046) and a higher incidence of necrotizing enterocolitis (5% vs. 21.7%, p=0.022). There were no significant differences in BSITD-III scores between the two opiate groups. In multivariate analysis cumulative opioid dose was associated with lower cognitive scores on the BSITD-III even after adjusting for social and neonatal risk factors (β=-0.247, p=0.012). Cumulative opioid dose is associated with worse cognitive scores at 20 months CA even after adjusting for social and neonatal risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Craving and subsequent opioid use among opioid dependent patients who initiate treatment with buprenorphine

    Science.gov (United States)

    Tsui, Judith I.; Anderson, Bradley J.; Strong, David R.; Stein, Michael D.

    2016-01-01

    Background Few studies have directly assessed associations between craving and subsequent opioid use among treated patients. Our objective was to prospectively evaluate the relative utility of two craving questionnaires to predict opioid use among opioid dependent patients in treatment. Method Opioid dependent patients (n=147) initiating buprenorphine treatment were assessed for three months. Craving was measured using: 1) the Desires for Drug Questionnaire (DDQ) and 2) the Penn Alcohol-Craving Scale adapted for opioid craving (PCS) for this study. Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use after adjusting for gender, age, ethnicity, education, opioid of choice, frequency of use, pain and depression. In these analyses craving assessed at time t was entered as a time-varying predictor of opioid use at time t+1. Results In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p .05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > .05) scores. Conclusion Self-reported craving for opioids was associated with subsequent lapse to opioid use among a cohort of patients treated with buprenorphine. PMID:24521036

  15. Toward safe accessibility of opioid pain medicines in Vietnam and other developing countries: a balanced policy method.

    Science.gov (United States)

    Krakauer, Eric L; Nguyen, Thi Phuong Cham; Husain, Syeda Asra; Nguyen, Thi Hai Yen; Joranson, David E; Luong, Ngoc Khue; Maurer, Martha A

    2015-05-01

    Moderate or severe pain is common among people with advanced cancer and other life-threatening illnesses. Yet despite agreement that pain relief is a human right, the poorest 80% of the world's population rarely have access to strong opioid analgesics. Excessively restrictive opioid policies, especially in developing countries, both stem from and propagate misguided fears about opioids, so-called opiophobia. Because opiophobia, like any norm, is historically, socially, and culturally situated, efforts to change opiophobic policies will be most effective if guided by awareness of their historical, social, and cultural determinants. We describe some of these determinants in Vietnam and report on results of an ongoing project there to allay opiophobia and improve safe access to opioids for medical uses. We used a method that entails working with committed local partners, including a high-level official from the Ministry of Health, to review all Vietnamese policies governing opioid accessibility to identify the barriers; devising an action plan to safely reduce or circumnavigate the barriers; obtaining buy-in for the plan from all stakeholders, including drug regulators and the police; and assisting the Ministry of Health to implement the plan. Since the start of the project, morphine consumption has increased each year and as of 2010 was ninefold greater than in 2003, and the number of hospitals offering palliative care has increased from three to 15. We conclude that this balanced policy method appears to be helping to reduce barriers to opioid access in Vietnam and should be used in other developing countries. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  16. Health care resource use and cost differences by opioid therapy type among chronic noncancer pain patients

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    Landsman-Blumberg PB

    2017-07-01

    Full Text Available Pamela B Landsman-Blumberg,1 Nathaniel Katz,2,3 Kavita Gajria,4 Anna O D’Souza,1 Sham L Chaudhari,1 Paul P Yeung,5 Richard White6 1Real-World Evidence, Xcenda LLC, Palm Harbor, FL, 2Analgesic Solutions, Natick, MA, 3Tufts University School of Medicine, Boston, MA, 4Global Health Economics Outcomes Research, Teva Pharmaceuticals, Inc., Frazer, PA, 5Migraine and Headache Clinical Development, Teva Pharmaceuticals, Inc., Frazer, PA, 6Neuroscience, Angarrack Value Solutions, West Chester, PA, USA Abstract: The study assessed 12-month chronic pain (CP-related health care utilization and costs among chronic noncancer pain (CNCP patients who initiated various long-term opioid treatments. Treatments included monotherapy with long-acting opioids (mono-LAOs, monotherapy with short-acting opioids (mono-SAOs, both LAOs and SAOs (combination, and opioid therapy initiated with SAO or LAO and switched to the other class (switch. Using MarketScan® claims databases (2006–2012, we identified CNCP patients with ≥90 days opioid supply after pain diagnosis and continuous enrollment 12 months before pain diagnosis (baseline period and 12 months after opioid start (post-index period. Outcomes included CP-related health care utilization and costs. Among CNCP patients (n=21,203, the cohort distribution was 74% mono-SAOs, 22% combination, 2% mono-LAOs, and 2% switch. During follow-up, the average daily morphine equivalent dose was highest in mono-LAO patients (96.4 mg compared with combination patients (89.8 mg, switch patients (64.3 mg, and mono-SAO patients (36.2 mg. After adjusting for baseline differences, the mono-LAO cohort had lower total CP-related costs ($4,933 compared with the mono-SAO ($8,604, switch ($10,470, and combination ($15,190 cohorts (all: P<0.05. Mono-LAO patients had greater CP-related prescription costs but lower medical costs than the other cohorts during the follow-up period, including lower CP-related hospitalizations (1% vs 11%–20

  17. Conversion of chronic pain patients from full-opioid agonists to sublingual buprenorphine.

    Science.gov (United States)

    Daitch, Jonathan; Frey, Michael E; Silver, David; Mitnick, Carol; Daitch, Danielle; Pergolizzi, Joseph

    2012-07-01

    Sublingual buprenorphine-naloxone (buprenorphine SL) is a preparation that is used to treat opioid dependence. In addition, the Drug Enforcement Administration (DEA) has acknowledged the legality of an off-label use to treat pain with a sublingual buprenorphine preparation. Buprenorphine SL is unique among the opioid class of analgesics; this compound has a high affinity for the mu-receptor, yet only partially activates it. Thus, buprenorphine SL can provide analgesia, yet minimize opioid side effects. Many patients on high doses of traditional opioid medication develop tolerance. Despite escalating medication dosage, a subset of patients had a paradoxical increase in pain, which has been characterized as opioid-induced hyperalgesia (OIH).  Buprenorphine SL, on the other hand, may even be anti-hyperalgesic and may have utility in treating these challenging patients. To determine the effectiveness of converting patients from traditional full agonist opioid medication to sublingual buprenorphine, as well as to identify patient groups that are most likely to benefit from this therapy. Patients who underwent conversion either had developed tolerance with diminished analgesia or were experiencing side effects on their opioid medications. An observational report of outcomes assessment. An interventional pain management practice setting in the United States. Retrospective data from clinical records was compiled on 104 de-identified chronic pain patients whose personal information had been redacted (60 men and 44 women, aged 21-78) and who had previously been treated with opioid-agonist drugs; they were converted to buprenorphine SL in tablet form during the study. Chronic pain was defined as persistent pain for at least 6 months. Data collected from patient profiles included age, sex, diagnosis, medication history, pre-induction opioid intake, reason for detoxification, pre-induction Clinical Opiate Withdrawal Score (COWS), and if applicable, cause of buprenorphine SL

  18. Retrospective Chart Review of Skin-to-Skin Contact in the Operating Room and Administration of Analgesic and Anxiolytic Medication to Women After Cesarean Birth.

    Science.gov (United States)

    Wagner, Debra L; Lawrence, Stephen; Xu, Jing; Melsom, Janice

    2018-04-01

    Transporting a newborn out of the operating room after cesarean birth can contribute to maternal awareness of discomfort, anxiety, and the need for administration of analgesics and anxiolytics for relief. This retrospective study analyzed the association between skin-to-skin contact in the operating room and administration of analgesics and anxiolytics to women in the operating and recovery rooms after cesarean birth. Our results indicated a trend toward decreased medication administration for women who experienced skin-to-skin contact and add to evidence supporting the incorporation of skin-to-skin contact in the operating room as the standard of care for cesarean birth. This practice has the potential to enhance the birth experience, promote breastfeeding, and provide greater safety with less exposure to opioids and benzodiazepines for women and their newborns. © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  19. Physicians Experience with and Expectations of the Safety and Tolerability of WHO-Step III Opioids for Chronic (Low Back Pain: Post Hoc Analysis of Data from a German Cross-Sectional Physician Survey

    Directory of Open Access Journals (Sweden)

    Michael A. Ueberall

    2015-01-01

    Full Text Available Objective. To describe physicians’ daily life experience with WHO-step III opioids in the treatment of chronic (low back pain (CLBP. Methods. Post hoc analysis of data from a cross-sectional online survey with 4.283 Germany physicians. Results. With a reported median use in 17% of affected patients, WHO-step III opioids play a minor role in treatment of CLBP in daily practice associated with a broad spectrum of positive and negative effects. If prescribed, potent opioids were reported to show clinically relevant effects (such as ≥50% pain relief in approximately 3 of 4 patients (median 72%. Analgesic effects reported are frequently related with adverse events (AEs. Only 20% of patients were reported to remain free of any AE. Most frequently reported AE was constipation (50%, also graded highest for AE-related daily life restrictions (median 46%. Specific AE countermeasures were reported to be necessary in approximately half of patients (median 45%; nevertheless AE-related premature discontinuation rates reported were high (median 22%. Fentanyl/morphine were the most/least prevalently prescribed potent opioids mentioned (median 20 versus 8%. Conclusion. Overall, use of WHO-step III opioids for CLBP is low. AEs, especially constipation, are commonly reported and interfere significantly with analgesic effects in daily practice. Nevertheless, beneficial effects outweigh related AEs in most patients with CLBP.

  20. Natural Flavonoids as Promising Analgesic Candidates: A Systematic Review.

    Science.gov (United States)

    Xiao, Xiao; Wang, Xiaoyu; Gui, Xuan; Chen, Lu; Huang, Baokang

    2016-11-01

    Due to the chemical structural diversity and various analgesic mechanisms, an increasing number of studies indicated that some flavonoids from medicinal plants could be promising candidates for new natural analgesic drugs, which attract high interests of advanced users and academic researchers. The aim of this systematic review is to report flavonoids and its derivatives as new analgesic candidates based on the pharmacological evidences. Sixty-four papers were found concerning the potential analgesic activity of 46 flavonoids. In this case, the evidence for analgesic activity of flavonoids and total flavonoids was investigated. Meanwhile, the corresponding analgesic mechanism of flavonoids was discussed by generalizing and analyzing the current publications. Based on this review, the conclusion can be drawn that some flavonoids are promising candidates for painful conditions and deserve particular attention in further research and development. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

  1. Use of prescription opioids with abuse-deterrent technology to address opioid abuse.

    Science.gov (United States)

    Michna, Edward; Kirson, Noam Y; Shei, Amie; Birnbaum, Howard G; Ben-Joseph, Rami

    2014-08-01

    The development of new formulations of extended-release (ER) opioids with abuse-deterrent technology attempts to deter prescription opioid abuse while maintaining appropriate access to care for pain patients. This study examined the degree to which some patients may avoid switching to reformulated ER opioids with abuse-deterrent technology and the extent to which those patients are more likely to be abusers. We analyzed Truven MarketScan pharmacy and medical claims data following the introduction of two reformulated ER opioids with abuse-deterrent technology. Adults aged 18-64 who were continuous users of extended-release oxycodone HCl (ER oxycodone) or extended-release oxymorphone HCl (ER oxymorphone) in a 6 month period prior to the introduction of the respective reformulations of those products were identified and categorized based on whether they switched to the reformulation, switched to other ER/long-acting (LA) opioids (without abuse-deterrent technology), or discontinued ER/LA opioid treatment in a 6 month post-reformulation period. Abusers were identified using ICD-9-CM diagnosis codes for opioid abuse/dependence. Pearson's chi-squared tests and Fisher's exact tests were then used to compare rates of abuse between patients who avoided switching to a reformulated ER opioid. Sensitivity analyses examined several definitions used in this analysis. ER/LA opioid utilization; rates of diagnosed opioid abuse. A total of 31%-50% of patients avoided switching to reformulated ER opioids. Rates of diagnosed opioid abuse were higher among these patients compared to patients who transitioned to the reformulated ER opioids. Due to the observational research design, caution is warranted in causal interpretation of the findings. The study was conducted among commercially insured continuous ER oxycodone or ER oxymorphone users; future research should consider additional patient populations, such as non-continuous users and those without commercial insurance (i.e., Medicare

  2. The opioid overdose epidemic: opportunities for pharmacists

    Directory of Open Access Journals (Sweden)

    Wu LT

    2017-07-01

    Full Text Available Li-Tzy Wu,1–4 Udi E Ghitza,5 Anne L Burns,6 Paolo Mannelli,1 1Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University School of Medicine, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, 5Center for Clinical Trials Network, National Institute on Drug Abuse, Bethesda, MD, 6American Pharmacists Association, Washington, DC, USA The USA is experiencing an opioid overdose epidemic. It has been driven largely by prescription opioids and intensified by a surge of illicit opioids (e.g., heroin and fentanyl.1,2 Drug-involved overdose, mainly opioids (e.g., prescription opioids and heroin, is a leading cause of accidental death in the USA. The opioid overdose epidemic has been escalating consistently for over a decade.2 Every day, an estimated 91 Americans die from opioid-related overdose.3 Opioid overdose appears to have disproportionally affected men, adults aged 25–64 years, and non-Hispanic whites.2

  3. Opioid-taking self-efficacy affects the quality of life of Taiwanese patients with cancer pain.

    Science.gov (United States)

    Liang, Shu-Yuan; Ding, She-Anne; Wu, Wei-Wen; Liu, Chieh-Yu; Lin, Chia-Chin

    2015-07-01

    Quality of life is an important indicator for evaluating the outcome of treatment for patients with cancer pain. Perceived self-efficacy has been reported to play an important role in controlling quality of life (QOL). Limited studies have focused on opioid-taking self-efficacy effects on the patients' QOL, which is caused by cancer pain. The purpose of this study was to evaluate how much of the variance in QOL among Taiwanese cancer patients with pain could be accounted for by opioid-taking self-efficacy. This cross-sectional study included 109 cancer patients who had taken prescribed opioid analgesics for cancer-related pain in the past week and completed the Opioid-Taking sSelf-Efficacy Scale and European Organization for Research and Treatment of Cancer Quality of Life Group Questionnaire. There was a significant correlation between scores on self-efficacy total scale and functional QOL (r = 0.30, p self-efficacy total scale accounted for 8% (R (2) = 0.08, p self-efficacy beliefs in their quality of life, which is relevant to cancer pain.

  4. δ-opioid receptor and somatostatin receptor-4 heterodimerization: possible implications in modulation of pain associated signaling.

    Directory of Open Access Journals (Sweden)

    Rishi K Somvanshi

    Full Text Available Pain relief is the principal action of opioids. Somatostatin (SST, a growth hormone inhibitory peptide is also known to alleviate pain even in cases when opioids fail. Recent studies have shown that mice are prone to sustained pain and devoid of analgesic effect in the absence of somatostatin receptor 4 (SSTR4. In the present study, using brain slices, cultured neurons and HEK-293 cells, we showed that SSTR4 and δ-Opioid receptor (δOR exist in a heteromeric complex and function in synergistic manner. SSTR4 and δOR co-expressed in cortical/striatal brain regions and spinal cord. Using cultured neuronal cells, we describe the heterogeneous complex formation of SSTR4 and δOR at neuronal cell body and processes. Cotransfected cells display inhibition of cAMP/PKA and co-activation of SSTR4 and δOR oppose receptor trafficking induced by individual receptor activation. Furthermore, downstream signaling pathways either associated with withdrawal or pain relief are modulated synergistically with a predominant role of SSTR4. Inhibition of cAMP/PKA and activation of ERK1/2 are the possible cellular adaptations to prevent withdrawal induced by chronic morphine use. Our results reveal direct intra-membrane interaction between SSTR4 and δOR and provide insights for the molecular mechanism for the anti-nociceptive property of SST in combination with opioids as a potential therapeutic approach to avoid undesirable withdrawal symptoms.

  5. Exploring the relationship between analgesic event rate and pain intensity in kidney stone surgery: A Repeated Time to Event Pilot Study

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Pedersen, Katja Venborg; Christrup, Lona Louring

    III-60 Rasmus Juul Exploring the relationship between analgesic event rate and pain intensity in kidney stone surgery: A Repeated Time to Event Pilot Study RV Juul(1), KV Pedersen(2, 4), LL Christrup(1), AE Olesen(1, 3), AM Drewes(3), PJS Osther(4), TM Lund(1) 1) Department of Drug Design...... model well described both morphine and oxycodone consumption data. RTTE modelling is a promising tool to investigate correlations between opioid consumption and pain intensity in time, but appropriate methods needs to be applied to study this relationship. References: 1) Pedersen KV, et al. Urolithiasis...

  6. Gut Homeostasis, Microbial Dysbiosis, and Opioids.

    Science.gov (United States)

    Wang, Fuyuan; Roy, Sabita

    2017-01-01

    Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

  7. Anti-inflammatory and analgesic activities: Chemical constituents of ...

    African Journals Online (AJOL)

    Anti-inflammatory and analgesic activities: Chemical constituents of essential oils of Ocimum gratissimum , Eucalyptus citriodora and Cymbopogon giganteus inhibited lipoxygenase L-1 and cyclooxygenase of PGHS.

  8. Paracetamol and analgesic nephropathy: Are you kidneying me?

    Directory of Open Access Journals (Sweden)

    Waddington F

    2014-12-01

    Full Text Available Freya Waddington, Mark Naunton, Jackson Thomas Faculty of Health, University of Canberra, Canberra, ACT, Australia Introduction: Analgesic nephropathy is a disease resulting from the frequent use of combinations of analgesic medications over many years, leading to significant impairment of renal function. The observation of a large number of cases of renal failure in patients abusing analgesic mixtures containing phenacetin led to the initial recognition of the nephrotoxicity from the use of analgesics. Phenacetin was subsequently exclusively blamed for this disease. However, the role of a single analgesic as a sole cause of analgesic nephropathy was challenged, and a number of researchers have since attempted to determine the extent of involvement of other analgesics including nonsteroidal anti-inflammatory drugs (NSAIDs, aspirin, and paracetamol. Case presentation: We present the case of an 83-year-old woman with a history of NSAID-induced nephropathy with poor pain control and reluctance to use paracetamol. We attempt to briefly review the evidence of paracetamol being implicated in the development of analgesic-induced nephropathy. Conclusion: There is a lack of concrete data regarding causative analgesics, including paracetamol. Patients should therefore not be withheld paracetamol, an effective and commonly recommended agent, for fear of worsening renal function. Keywords: kidney, paracetamol, nephropathy, phenacetin

  9. Pain treatment after tonsillectomy: advantages of analgesics regularly given compared with analgesics on demand.

    Science.gov (United States)

    Thorneman, G; Akervall, J

    2000-10-01

    The aim of the present prospective study was to evaluate pain treatment during the first postoperative 24 h for 40 patients (age over 18) undergoing tonsillectomy. Patients were divided into two groups: group A (n = 20) received analgesics on demand and group B (n = 20) on a regular basis. Basic pain treatment consisted of paracetamol 750 mg x 6 and diclofenac 50 mg x 3. Pain measurement was performed using a visual analogue scale (VAS): a 10 cm line with 0 cm equalling no pain and 10 cm equalling the worst pain ever felt. The following parameters were studied: VAS values, the need for rescue analgesics, intra- and postoperative bleeding, nausea and vomiting, postoperative food intake and hospital time. Only 4 of 20 (20%) patients in group B needed rescue analgesics in the postoperative ward compared with 15 of 20 (75%) in group A (p values were generally rather low in both groups. The mean value for all observed VAS values was less than 4 in both study groups. However, no significant difference in VAS values was observed between the two study groups. Our results suggest that regularly given postoperative pain treatment after tonsillectomy, starting intraoperatively with paracetamol and diclofenac, has significant advantages compared with a regimen in which patients receive analgesics only on demand.

  10. Changes in pain and concurrent pain medication use following compounded topical analgesic treatment for chronic pain: 3- and 6-month follow-up results from the prospective, observational Optimizing Patient Experience and Response to Topical Analgesics study

    Directory of Open Access Journals (Sweden)

    Gudin JA

    2017-10-01

    Full Text Available Jeffrey A Gudin,1 Michael J Brennan,2 E Dennis Harris,3 Peter L Hurwitz,3 Derek T Dietze,4 James D Strader5 1Pain Medicine and Palliative Care, Englewood Hospital and Medical Center, Englewood, NJ, 2The Pain Center of Fairfield, Fairfield, CT, 3Clarity Science, Austin, TX, 4Metrics for Learning, LLC, Queen Creek, AZ, 5Safe Harbor Compliance and Clinical Services, LLC, Austin, TX, USA Background: Opioids and other controlled substances prescribed for chronic pain are associated with abuse, addiction, and death, prompting national initiatives to identify safe and effective pain management strategies including topical analgesics.Methods: This prospective, observational study evaluated changes from baseline in overall mean severity and interference scores on the Brief Pain Inventory scale and the use of concurrent pain medications at 3- and 6-month follow-up assessments in chronic pain patients treated with topical analgesics. Changes in pain severity and interference and medication usage were compared between treated patients and unmatched and matched controls.Results: The unmatched intervention group (unmatched-IG included 631 patients who completed baseline and 3-month follow-up surveys (3-month unmatched-IG and 158 who completed baseline and 6-month follow-up assessments (6-month unmatched-IG. Baseline and 3-month follow-up data were provided by 76 unmatched controls and 76 matched controls (3-month unmatched-CG and matched-CG, and 51 unmatched and 36 matched patients completed baseline and 6-month follow-up surveys (6-month unmatched-CG and matched-CG. Baseline demographic characteristics and mean pain severity and interference scores were similar between groups. There were statistically significant decreases from baseline in mean pain severity and interference scores within the 3- and 6-month unmatched-IG (all P<0.001. Significantly greater decreases in the mean change from baseline in pain severity and interference scores were evident for the

  11. Physician Introduction to Opioids for Pain Among Patients with Opioid Dependence and Depressive Symptoms

    Science.gov (United States)

    Tsui, Judith I.; Herman, Debra S.; Kettavong, Malyna; Alford, Daniel; Anderson, Bradley J.; Stein, Michael D.

    2011-01-01

    This study determined the frequency of reporting being introduced to opioids by a physician among opioid dependent patients. Cross-sectional analyses were performed using baseline data from a cohort of opioid addicts seeking treatment with buprenorphine. The primary outcome was response to the question: “Who introduced you to opiates?” Covariates included sociodemographics, depression, pain, current and prior substance use. Of 140 participants, 29% reported that they had been introduced to opioids by a physician. Of those who were introduced to opioids by a physician, all indicated that they had initially used opioids for pain, versus only 11% of those who did not report being introduced to opioids by a physician (p<0.01). There was no difference in current pain (78% vs. 85%, p=0.29), however participants who were introduced to opioids by a physician were more likely to have chronic pain (63% vs. 43%, p=0.04). A substantial proportion of individuals with opioid dependence seeking treatment may have been introduced to opioids by a physician. PMID:20727704

  12. Impact of a Psychological Opioid-Risk Evaluation on Opioid Prescribing in Primary Care.

    Science.gov (United States)

    Vargovich, Alison M; McNeil, Daniel W; Foley, Kimberly P; Sperry, Jeannie

    2016-07-01

    The misuse and abuse of opioids has increased across the United States in recent years, associated with a rise in opioid-related overdose deaths. Physicians report having difficulty discerning substance abuse or drug diversion, which can lead to over- or under-prescribing of opioids and poor pain management. Additionally, research suggests that patient characteristics (eg, sex, ethnicity/race, age) may unduly influence the pain management decisions of health care providers. This investigation aimed to assist in physicians' prescribi