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Sample records for higher opioid doses

  1. Defined daily doses (DDD) do not accurately reflect opioid doses used in contemporary chronic pain treatment.

    Science.gov (United States)

    Nielsen, Suzanne; Gisev, Natasa; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Larance, Briony; Campbell, Gabrielle; Shanahan, Marian; Blyth, Fiona; Lintzeris, Nicholas; Pearson, Sallie; Mattick, Richard; Degenhardt, Louisa

    2017-05-01

    To assess how well the defined daily dose (DDD) metric reflects opioid utilisation among chronic non-cancer pain patients. Descriptive, cross-sectional study, utilising a 7-day medication diary. Community-based treatment settings, Australia. A sample of 1101 people prescribed opioids for chronic non-cancer pain. Opioid dose data was collected via a self-completed 7-day medication diary capturing names, strengths and doses of each medication taken in the past week. Median daily dose was calculated for each opioid. Comparisons were made to the World Health Organization's (WHO) DDD metric. WHO DDDs ranged from 0.6 to 7.1 times the median opioid doses used by the sample. For transdermal fentanyl and oral hydromorphone, the median dose was comparable with the DDD. The DDD for methadone was 0.6 times lower than the median doses used by this sample of chronic pain patients. In contrast, the DDD for oxycodone and transdermal buprenorphine, the most commonly used strong opioids for chronic pain in Australia, was two to seven times higher than actual doses used. For many opioids, there are key differences between the actual doses used in clinical practice and the WHO's DDDs. The interpretation of opioid utilisation studies using population-level DDDs may be limited, and a recalibration of the DDD for many opioids or the reporting of opioid utilisation in oral morphine equivalent doses is recommended. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. The impact of opioid prescription dose and duration during a workers compensation claim, on post-claim continued opioid use: A retrospective population-based study.

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    Shafer, Leigh Anne; Raymond, Colette; Ekuma, Okechukwu; Kraut, Allen

    2015-06-01

    Workers Compensation Board (WCB) recipients are a group commonly prescribed opioids. We explored factors influencing post-claim opioid dose and duration by linking data from 22,451 claims with the Manitoba Center for Population Health registry. On average, the WCB paid for 94.55% of opioids prescribed during a claim. The amount paid for by the WCB varied significantly by total opioids prescribed. The main predictors of high opioid dosage (120 + morphine equivalents (ME)/day) during the first year post-claim (logistic regression), and of longer post-claim opioid usage (survival analysis), included opioid dosage during the final month of the claim both paid for and not paid for by the WCB. Amongst low dose opioid claims, the WCB covers most opioids prescribed. Higher opioid dose WCB recipients are often prescribed opioids not covered by the WCB. Both opioids paid for and not paid for by the WCB are associated with post-claim opioid use. © 2015 Wiley Periodicals, Inc.

  3. Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study.

    Science.gov (United States)

    Kaplovitch, Eric; Gomes, Tara; Camacho, Ximena; Dhalla, Irfan A; Mamdani, Muhammad M; Juurlink, David N

    2015-01-01

    The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown. We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy. Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated.

  4. Novel Measure of Opioid Dose and Costs of Care for Diabetes Mellitus: Opioid Dose and Health Care Costs.

    Science.gov (United States)

    Gautam, Santosh; Franzini, Luisa; Mikhail, Osama I; Chan, Wenyaw; Turner, Barbara J

    2016-03-01

    Diabetes mellitus (DM) has well known costly complications but we hypothesized that costs of care for chronic pain treated with opioid analgesic (OA) medications would also be substantial. In a statewide, privately insured cohort of 29,033 adults aged 18 to 64 years with DM and noncancer pain who filled OA prescription(s) from 2008 to 2012, our outcomes were costs for specific health care services and total costs per 6-month intervals after the first filled OA prescription. Average daily OA dose (4 categories) and total dose (quartiles) in morphine-equivalent milligrams were calculated per 6-month interval after the first OA prescription and combined into a novel OA dose measure. Associations of OA measures with costs of care (n = 126,854 6-month intervals) were examined using generalized estimating equations adjusted for clinical conditions, psychotherapeutic drugs, and DM treatment. Incremental costs for each type of health care service and total cost of care increased progressively with average daily and total OA dose versus no OAs. The combined OA measure identified the highest incremental total costs per 6-month interval that were increased by $8,389 for 50- to 99-mg average daily dose plus >900 mg total dose and, by $9,181 and $9,958 respectively, for ≥100 mg average daily dose plus 301- to 900-mg or >900 mg total dose. In this statewide DM cohort, total health care costs per 6-month interval increased progressively with higher average daily OA dose and with total OA dose but the greatest increases of >$8,000 were distinguished by combinations of higher average daily and total OA doses. The higher costs of care for opioid-treated patients appeared for all types of services and likely reflects multiple factors including morbidity from the underlying cause of pain, care and complications related to opioid use, and poorer control of diabetes as found in other studies. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Clinical characteristics of veterans prescribed high doses of opioid medications for chronic non-cancer pain.

    Science.gov (United States)

    Morasco, Benjamin J; Duckart, Jonathan P; Carr, Thomas P; Deyo, Richard A; Dobscha, Steven K

    2010-12-01

    Little is known about patients prescribed high doses of opioids to treat chronic non-cancer pain, though these patients may be at higher risk for medication-related complications. We describe the prevalence of high-dose opioid use and associated demographic and clinical characteristics among veterans treated in a VA regional healthcare network. Veterans with chronic non-cancer pain prescribed high doses of opioids (≥ 180 mg/day morphine equivalent; n=478) for 90+ consecutive days were compared to two groups with chronic pain: Traditional-dose (5-179 mg/day; n=500) or no opioid (n=500). High-dose opioid use occurred in 2.4% of all chronic pain patients and in 8.2% of all chronic pain patients prescribed opioids long-term. The average dose in the high-dose group was 324.9 (SD=285.1)mg/day. The only significant demographic difference among groups was race (p=0.03) with black veterans less likely to receive high doses. High-dose patients were more likely to have four or more pain diagnoses and the highest rates of medical, psychiatric, and substance use disorders. After controlling for demographic factors and VA facility, neuropathy, low back pain, and nicotine dependence diagnoses were associated with increased likelihood of high-dose prescriptions. High-dose patients frequently did not receive care consistent with treatment guidelines: there was frequent use of short-acting opioids, urine drug screens were administered to only 25.7% of patients in the prior year, and 32.0% received concurrent benzodiazepine prescriptions, which may increase risk for overdose and death. Further study is needed to identify better predictors of high-dose usage, as well as the efficacy and safety of such dosing. Published by Elsevier B.V.

  6. Easing Opioid Dose May Improve Pain and Quality of Life

    Science.gov (United States)

    ... html Easing Opioid Dose May Improve Pain and Quality of Life Slowly lowering the drug amount also helps people ... improve pain and function, as well as boost quality of life. "As many as 10 million Americans use long- ...

  7. Trends in high-dose opioid prescribing in Canada.

    Science.gov (United States)

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

    2014-09-01

    To describe trends in rates of prescribing of high-dose opioid formulations and variations in opioid product selection across Canada. Population-based, cross-sectional study. Canada. Retail pharmacies dispensing opioids between January 1, 2006, and December 31, 2011. Opioid dispensing rates, reported as the number of units dispensed per 1000 population, stratified by province and opioid type. The rate of dispensing high-dose opioid formulations increased 23.0%, from 781 units per 1000 population in 2006 to 961 units per 1000 population in 2011. Although these rates remained relatively stable in Alberta (6.3% increase) and British Columbia (8.4% increase), rates in Newfoundland and Labrador (84.7% increase) and Saskatchewan (54.0% increase) rose substantially. Ontario exhibited the highest annual rate of high-dose oxycodone and fentanyl dispensing (756 tablets and 112 patches per 1000 population, respectively), while Alberta's rate of high-dose morphine dispensing was the highest in Canada (347 units per 1000 population). Two of the highest rates of high-dose hydromorphone dispensing were found in Saskatchewan and Nova Scotia (258 and 369 units per 1000 population, respectively). Conversely, Quebec had the lowest rate of high-dose oxycodone and morphine dispensing (98 and 53 units per 1000 population, respectively). We found marked interprovincial variation in the dispensing of high-dose opioid formulations in Canada, emphasizing the need to understand the reasons for these differences, and to consider developing a national strategy to address opioid prescribing. Copyright© the College of Family Physicians of Canada.

  8. Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality.

    Science.gov (United States)

    Dasgupta, Nabarun; Funk, Michele Jonsson; Proescholdbell, Scott; Hirsch, Annie; Ribisl, Kurt M; Marshall, Steve

    2016-01-01

    Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality. Prospective observational cohort with one year follow-up. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data. Residential population of North Carolina (n = 9,560,234), with 2,182,374 opioid analgesic patients. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person-years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9). Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk. Published by

  9. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    Introduction: The combination of reduced dose of local anesthetics (LA) and highly lipid‑soluble synthetic opioids for patients undergoing transurethral surgery could reduce block duration and side‑effects. However, it remains unclear what are the most appropriate levels of low dose and the extent to which the side‑effects ...

  10. Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Eric Kaplovitch

    Full Text Available The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown.We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8% escalated to high dose therapy and n = 59 (0.2% died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70 and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53. These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy.Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated.

  11. Nonopioid substance use disorders and opioid dose predict therapeutic opioid addiction.

    Science.gov (United States)

    Huffman, Kelly L; Shella, Elizabeth R; Sweis, Giries; Griffith, Sandra D; Scheman, Judith; Covington, Edward C

    2015-02-01

    Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment. This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  12. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    2014-09-24

    Sep 24, 2014 ... stay of the patients. Therefore, reducing the side effects associated with intrathecal anesthesia is quite helpful to support better postoperative management. Combined low dose local anesthetics and opioids versus single use of LA for transurethral urological surgery: A meta‑analysis. Y Ding, M Li, L Chen1, ...

  13. Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering

    Science.gov (United States)

    Greenwald, Mark K.

    2008-01-01

    A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

  14. The use of opioids for breakthrough pain in acute palliative care unit by using doses proportional to opioid basal regimen.

    Science.gov (United States)

    Mercadante, Sebastiano; Villari, Patrizia; Ferrera, Patrizia; Mangione, Salvatore; Casuccio, Alessandra

    2010-05-01

    To determine the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain (BP). In 66 patients consecutive patients admitted to a pain relief and palliative care unit, the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain (BP) were assessed. The choice of the opioid to be administered as rescue medication was based on the characteristics of patients, clinical stability, compliance, preference, and so on. For each episode, nurses were instructed to routinely collect changes in pain intensity and emerging problems when pain became severe (T0), and to re-assess the patient 15 minutes after the opioid given as a rescue medication (T15). Six hundred twenty four episodes of BP were recorded during admission. Intravenous morphine (IV-MO) and oral transmucosal fentanyl (OTFC) were most frequently administered. Of 503 events available, 427 episodes were defined as successfully treated, while 76 episodes required a further administration of opioids. Pain intensity significantly decreased at T15 in all the groups (Popioids for BP proportional to the basal opioid regimen, are very effective and safe in clinical practice, regardless the opioid and modality used.

  15. Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: An observational case-control study.

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    Hina, Nabil; Fletcher, Dominique; Poindessous-Jazat, Frédérique; Martinez, Valéria

    2015-04-01

    Chronic pain and opioid consumption may trigger diffuse hyperalgesia, but their relative contributions to pain vulnerability remain unclear. To assess preoperative opioid-induced hyperalgesia and its postoperative clinical consequences in patients with chronic pain scheduled for orthopaedic surgery. A prospective observational study. Raymond Poincare teaching hospital. Adults with or without long-term opioid treatment, scheduled for orthopaedic surgery. Preoperative hyperalgesia was assessed with eight quantitative sensory tests, in a pain-free zone. Postoperative morphine consumption and pain intensity were evaluated using a numerical rating scale (NRS) in the recovery room and during the first 72 h. We analysed results from 68 patients (28 opioid-treated patients and 40 controls). Mean daily opioid consumption was 42 ± 25 mg of morphine equivalent. The opioid-treated group displayed significantly higher levels of preoperative hyperalgesia in three tests: heat tolerance threshold (47.1°C vs. 48.4°C; P = 0.045), duration of tolerance to a 47°C stimulus (40.2 vs. 51.1 s; P = 0.03) and mechanical temporal summation [1.79 vs. 1.02 (ΔNRS10-1); P = 0.036]. Patients in the opioid-treated group consumed more morphine (19.1 vs. 9.38 mg; P = 0.001), had a higher pain intensity (7.6 vs. 5.5; P = 0.001) in the recovery room and a higher cumulative morphine dose at 72 h (39.8 vs. 25.6 mg; P = 0.02). Chronic pain patients treated with low doses of opioid had hyperalgesia before surgery. These results highlight the need to personalise the management of patients treated with opioids before surgery. ID-RCB 2011-A00304-37.

  16. 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

  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

    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...... 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...... dose using genetic profiling....

  18. Opioid analgesic dose and the risk of misuse, overdose, and death: A narrative review.

    Science.gov (United States)

    Coyle, David Tyler; Pratt, Chih-Ying; Ocran-Appiah, Josephine; Secora, Alex; Kornegay, Cynthia; Staffa, Judy

    2017-12-15

    Despite the rise in serious adverse events paralleling increased prescription opioid analgesic use in the United States over the past 2 decades, the association between opioid analgesic dose and the risk of serious adverse health outcomes is incompletely characterized. We sought to synthesize the medical literature for observational studies examining the association between opioid analgesic dose and the risk of serious adverse health outcomes, with particular attention to the outcomes of misuse, abuse, addiction, overdose, and death. Searching MEDLINE using PubMed and bibliography review, we identified 22 observational studies published between 2000 and 2015 that assessed the association between opioid analgesic dose and the risk of serious adverse health outcomes. Some of these studies had significant methodological limitations. Twelve reviewed studies examined the outcomes of misuse, overdose, or death; no studies examining the risk of addiction or abuse met our criteria for inclusion. The results of multiple studies clearly indicate an increasing risk of serious adverse health outcomes associated with increasing opioid analgesic dose. In particular, the risk of misuse, overdose, and death increases with increasing opioid analgesic dose. However, there is no opioid dose inflection point beyond which the risk of these adverse health outcomes increases. No opioid analgesic dose is without risk. The reviewed studies show an increasing risk of serious adverse health outcomes-including misuse, overdose, and death-associated with increasing opioid analgesic dose. Further research is needed to characterize the relationship between opioid analgesic dose and the risk of addiction and abuse. This analysis could inform policy actions for regulators and clinical decision making for providers. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  19. Potential drug interaction with opioid agonist in the setting of chronic low-dose opioid antagonist use.

    Science.gov (United States)

    Leonard, James B; Nair, Vidya; Diaz, Christopher J; Penoyar, Jonathan B; Goode, Penelope A

    2017-08-01

    Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis. The patient received a single dose of oxycodone 5mg that resulted in obtundation unresponsive to painful stimuli necessitating the administration of naloxone boluses and infusion along with admission to the intensive care unit for 1 night. The patient responded well to naloxone therapy. He was discharged in satisfactory condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The use of sublingual fentanyl for breakthrough pain by using doses proportional to opioid basal regimen.

    Science.gov (United States)

    Mercadante, Sebastiano; Prestia, Giovanna; Casuccio, Alessandra

    2013-11-01

    The aim of this study was to prospectively assess the efficacy and safety of sublingual fentanyl (SLF) in doses proportional to opioid doses used for background analgesia for the treatment of BTP of cancer patients. A sample of patients admitted to an acute palliative care unit, presenting breakthrough pain (BTP) episodes and receiving stable doses of opioids for background pain was selected to assess the efficacy and safety of SLF used in doses proportional to the basal opioid regimen used for the management of BTP. For each patient, data from four consecutive episodes were collected. For each episode, nurses collected changes in pain intensity and adverse effects when pain got severe (T0), and 5, 10, and 15 minutes after SLF was given (T15). Seventy patients were recruited for the study. The mean age was 61.7 (±11.5). Forty-one patients were males. A total of 173 episodes of BTP were recorded (mean 2.5 episodes/patient). In 19 events, documentation regarding changes in pain intensity was incomplete. Of the 154 evaluable episodes, 143 were successfully treated (92%). Mean doses of SLF were 637 µg (SD 786), and 51 patients (72.8%) received SLF doses ≥800 µg. When compared to younger adult patients, older patients received significantly lower doses of SLF (p opioid regimen. Pain intensity significantly decreased at T5, 10 and T15 (p opioid regimen for the management of BTP is safe and effective in clinical practice.

  1. Pain treatment with opioids : achieving the minimal effective and the minimal interacting dose.

    Science.gov (United States)

    Geppetti, Pierangelo; Benemei, Silvia

    2009-01-01

    Appropriate and successful management of pain with opioid analgesics is based on tailoring pharmacologic treatment to the individual and identifying the minimal effective dose at which pain is controlled with minimal adverse effects. Morphine and morphine-like-agonists exhibit similar pharmacodynamic profiles, but substantially different receptor affinities and pharmacokinetic properties, which dictate the dosage, route and regimen required to achieve analgesic effect. Opioids exhibit differences in drug elimination resulting in marked variations in the plasma half-life value. Although fentanyl is more potent than morphine, with a shorter duration of action than parenteral morphine, its oral bioavailability is poor and it is administered transdermally. Morphine, with a short half-life and a time to steady-state plasma concentrations of 10-12 hours is better suited than transdermal fentanyl for initial opioid therapy and for the treatment of unstable pain, which requires a fluctuating opioid dose. International guidelines recommend normal-release morphine for initial optimization of individual dose because its pharmacokinetics allow 'real-time' dose regimen changes and rapid identification of the dose required for pain control. Once an effective normal-release morphine dosage is achieved, other administration routes, formulations and opioids can be considered as required. Despite guidelines advocating that transdermal fentanyl should only be used in patients who are shown to be tolerant to strong opioid therapy, in Italy and other European countries, controlled-release or transdermal opioids are often used when starting opioid therapy. Opioids are associated with a wide range of adverse reactions, but these can be minimized with careful drug titration and maintenance. A major challenge with pain control is polypharmacy and the risk of pharmacokinetic or pharmacodynamic drug-drug interactions. Prevention and management of interactions rely on careful and timely

  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. Miotic and subject-rated effects of therapeutic doses of tapentadol, tramadol, and hydromorphone in occasional opioid users.

    Science.gov (United States)

    Stoops, William W; Glaser, Paul E A; Rush, Craig R

    2013-07-01

    Tapentadol is a novel analgesic that activates mu-opioid receptors and blocks norepinephrine reuptake. There is very little information available regarding the non-analgesic pharmacodynamic effects of tapentadol. This outpatient study evaluated the physiological, subject-rated, and performance effects of therapeutic doses of tapentadol compared to two control drugs in humans. This double-blind, within-subject study examined the effects of oral placebo, tapentadol (25, 50, and 75 mg), tramadol (50, 100, and 150 mg), and hydromorphone (2, 4, and 6 mg). Nine occasional opioid users completed the study. Pharmacodynamic drug effects were measured before and for 6 h after drug administration. All three doses of the tested drugs produced comparable, time-dependent decreases in pupil diameter, but the effects were generally not dose dependent. The high dose of tapentadol, as well as all three doses of tramadol and hydromorphone, increased positive subject-rated effects (e.g., "Good Effects" and "Like the Drug") as a function of time. Only tramadol increased negative subject-rated effects (e.g., "Bad Effects" and "Nauseous"); however, these were of low magnitude. The highest tested dose of tapentadol produced a profile of positive effects comparable to that of hydromorphone, whereas tramadol produced positive and negative subject-rated effects. The mixed findings for tramadol are consistent with previous findings indicating that it has a distinct profile of effects relative to prototypic opioids. Future research should examine the effects of higher tapentadol doses, as well as the factors contributing to the different subject-rated profile of effects observed for tramadol relative to tapentadol and hydromorphone.

  4. DOSE-RESPONSE RELATIONSHIP BETWEEN METHADONE DOSE AND ADHERENCE TO ANTIRETROVIRAL THERAPY AMONG HIV-POSITIVE PERSONS WHO USE ILLICIT OPIOIDS

    Science.gov (United States)

    Lappalainen, Leslie; Nolan, Seonaid; Dobrer, Sabina; Puscas, Cathy; Montaner, Julio; Ahamad, Keith; Dong, Huiru; Kerr, Thomas; Wood, Evan; Milloy, M-J

    2015-01-01

    Background and Aims For HIV-positive individuals who use illicit opioids, engagement in methadone maintenance therapy (MMT) can contribute to improved HIV treatment outcomes. However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated. We sought to examine the relationship between methadone dose and ART adherence among a cohort of persons who use illicit opioids. Design and Setting We used data from the ACCESS study, an ongoing prospective observational cohort of HIV-positive persons who use illicit drugs in Vancouver, Canada, confidentially linked to comprehensive HIV treatment data in a setting of universal no-cost medical care including medications. We evaluated the longitudinal relationship between methadone dose and the likelihood of ≥ 95% adherence to ART among ART-exposed participants during periods of engagement in MMT. Participants 297 ART-exposed individuals on MMT were recruited between December 2005 and May 2013 and followed for a median of 42.1 months. Measurements We measured methadone dose at ≥ 100 vs methadone maintenance therapy, those receiving higher doses of methadone (≥ 100 mg/day) are more likely to achieve ≥ 95% adherence to antiretroviral therapy than those receiving lower doses. PMID:25940906

  5. Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy: A Systematic Review.

    Science.gov (United States)

    Frank, Joseph W; Lovejoy, Travis I; Becker, William C; Morasco, Benjamin J; Koenig, Christopher J; Hoffecker, Lilian; Dischinger, Hannah R; Dobscha, Steven K; Krebs, Erin E

    2017-08-01

    Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts. Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain. Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events. Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies). Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs. Very low quality evidence suggests that several types of interventions may be effective to reduce or

  6. Population prevalence of high dose paracetamol in dispensed paracetamol/opioid prescription combinations: an observational study

    Science.gov (United States)

    2012-01-01

    Background Paracetamol (acetaminophen) is generally considered a safe medication, but is associated with hepatotoxicity at doses above doses of 4.0 g/day, and even below this daily dose in certain populations. Methods The Nova Scotia Prescription Monitoring Program (NSPMP) in the Canadian province of Nova Scotia is a legislated organization that collects dispensing information on all out-of-hospital prescription controlled drugs dispensed for all Nova Scotia residents. The NSPMP provided data to track all paracetamol/opioids redeemed by adults in Nova Scotia, from July 1, 2005 to June 30, 2010. Trends in the number of adults dispensed these prescriptions and the numbers of prescriptions and tablets dispensed over this period were determined. The numbers and proportions of adults who filled prescriptions exceeding 4.0 g/day and 3.25 g/day were determined for the one-year period July 1, 2009 to June 30, 2010. Data were stratified by sex and age (paracetamol/opioid prescription was lower in each successive one-year period. From July 2009 to June 2010, one in 12 adults (n = 59,197) filled prescriptions for over 13 million paracetamol/opioid tablets. Six percent (n = 3,786) filled prescriptions that exceeded 4.0 g/day and 18.6% (n = 11,008) exceeded 3.25 g/day of paracetamol at least once. These findings exclude non-prescription paracetamol and paracetamol–only prescribed medications. Conclusions A substantial number of individuals who redeem prescriptions for paracetamol/opioid combinations may be at risk of paracetamol-related hepatotoxicity. Healthcare professionals must be vigilant when prescribing and dispensing these medications in order to reduce the associated risks. PMID:22709372

  7. Assessing risk for drug overdose in a national cohort: role for both daily and total opioid dose?

    Science.gov (United States)

    Liang, Yuanyuan; Turner, Barbara J

    2015-04-01

    Current research on the risk of opioid analgesics with drug overdose does not account for the total morphine equivalent dose (MED) of opioids filled by a patient. In this study, time from first opioid prescription until drug overdose was examined for 206,869 privately insured patients aged 18 to 64 with noncancer pain and ≥2 filled prescriptions for Schedule II or III opioids from January 2009 to July 2012. Opioid therapy was examined in 6-month intervals including 6 months before an overdose and categorized as mean daily MED (0, 1-19, 20-49, 50-99, ≥100 mg) and total MED divided at top quartile (0, 1-1,830, >1,830 mg). Survival analysis was used, adjusting for demographics, clinical conditions, and psychoactive drugs. Relative to no opioid therapy, persons at highest risk for overdose (adjusted hazard ratios of 2-3) received a daily MED of ≥100 mg regardless of total dose or a daily MED of 50 to 99 mg with a high total MED (>1,830 mg). The hazard ratio was significantly lower (1.43, 95% confidence interval = 1.15-1.79) for 50 to 99 mg daily MED with a lower total MED (≤1,830 mg), whereas hazard ratios for lower daily MEDs did not differ by total dose. This analysis suggests that clinicians should consider total MED to assess risk of overdose for persons prescribed 50 to 99 mg daily MED. When addressing risks for drug overdose, this analysis supports the need for clinicians, administrators, and policy makers to monitor not only daily opioid dose but also total dose for patients receiving 50 to 99 mg daily MED. Published by Elsevier Inc.

  8. Switching from high doses of pure μ-opioid agonists to transdermal buprenorphine in patients with cancer

    DEFF Research Database (Denmark)

    Lundorff, Lena; Sjøgren, Per; Hansen, Ole Bo

    2013-01-01

    BACKGROUND: Several myths on buprenorphine's pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain...

  9. The Opioid Epidemic: By the Numbers

    Science.gov (United States)

    ... in partnership with the U.S. Department of Justice. Naloxone Overdose deaths involving synthetic opioids, including fentanyl, increased by ... access to overdose reversal drugs, multiple doses of naloxone may be ... fentanyl overdose, given its higher potency compared with other opioids. ...

  10. Opioid Dose Reduction in a VA Health Care System--Implementation of a Primary Care Population-Level Initiative.

    Science.gov (United States)

    Westanmo, Anders; Marshall, Peter; Jones, Elzie; Burns, Kevin; Krebs, Erin E

    2015-05-01

    To describe processes and outcomes of a health system quality improvement initiative designed to reduce opioid-related harms. The initiative was a primary care population-level intervention to reduce high-dose opioid prescribing, which was locally defined as >200 morphine-equivalent mg (MED) daily. We describe the implementation process and report prescribing rates and primary care provider (PCP) attitudes and beliefs before and after implementation. A VA health care system comprising one large, urban teaching hospital and 11 outpatient clinics in surrounding suburban and rural locations. All patients who received any prescription from the outpatient pharmacy (unique pharmacy patients) were included in the population. PCPs at the main hospital were surveyed. Prescribing outcomes were determined from merged VA databases by examining rates of opioid dispensing within 90-day time windows before and after implementation. PCP beliefs and attitudes were evaluated with preimplementation and postimplementation surveys. Following implementation, the number of patients prescribed >200 MED daily decreased from 342 (0.65% of unique pharmacy patients) to 65 (0.12%). Overall, the number of unique pharmacy patients who received at least one opioid prescription within 90 days decreased from 6,942 (13.7%) on April 1, 2011 to 5,981 (11.0%) on October 1, 2014 (13.8% decrease). Most PCPs agreed it was reasonable for the medical center to set a 200 MED limit (76% at baseline and 87% at follow up). Opioid Safety Initiative implementation was associated with a substantial reduction in high-dose opioid prescribing. Factors that contributed to initiative success included leadership support and active clinical pharmacy engagement. Wiley Periodicals, Inc.

  11. Revised Dose Schema of Sublingual Buprenorphine in the Treatment of the Neonatal Opioid Abstinence Syndrome

    Science.gov (United States)

    Kraft, Walter K.; Dysart, Kevin; Greenspan, Jay S.; Gibson, Eric; Kaltenbach, Karol; Ehrlich, Michelle E.

    2010-01-01

    AIMS Over half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacologic therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS. DESIGN Randomized, phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine. SETTING Large, urban, tertiary care hospital. PARTICIPANTS Twenty-four term infants requiring pharmacological treatment for NAS. MEASUREMENTS Outcomes were neonatal safety, length of treatment, and length of hospitalization. FINDINGS Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (p=0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (p=0.05). CONCLUSIONS Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine. PMID:20925688

  12. Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

    OpenAIRE

    Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip

    2011-01-01

    Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher const...

  13. Peripartum pain management in opioid dependent women.

    Science.gov (United States)

    Höflich, A S; Langer, M; Jagsch, R; Bäwert, A; Winklbaur, B; Fischer, G; Unger, A

    2012-04-01

    Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experiencedby opioid maintained pregnantwomenduring delivery and the perinatal period. Theaim of the present study was to investigate differences in pain management of opioid maintained compared to nondependent pregnant women during delivery and the postpartum period. 40 deliveries of 37 opioid dependent women enrolled in a double-blind, double-dummy randomized controlled trial (RCT) examining the safety and efficacy of methadone (mean dose at the time of delivery = 63.89 mg) and buprenorphine (mean dose at the time of delivery = 14.05 mg) during pregnancy were analyzed and participants were matched to a non-dependent comparison group of 80 pregnant women. Differences in pain management (opioid and non-opioid analgesic medication) during delivery and perinatal period were analyzed. Following cesarean delivery opioid maintained women received significantly less opioid analgesics (day of delivery p = 0.038; day 1: p = 0.02), NSAIDs were administered more frequently to opioid dependent patients than to the comparison group during cesarean section and on the third day postpartum. Significantly higher nicotine consumption in the group of opioid dependentwomenhad a strong influence onthe retrieved results, and might be considered as an independent factor of altered pain experience. Differences in pain treatment became evident when comparing opioid maintained women to healthy controls. These differences might be based on psychosocial consequences of opioid addiction along with the lack of an interdisciplinary consensus on pain treatment protocols for opioid dependent patients. © 2011 European Federation of International Association for the Study of Pain Chapters.

  14. The Effect of a Payer-Mandated Decrease in Buprenorphine Dose on Aberrant Drug Tests and Treatment Retention Among Patients with Opioid Dependence.

    Science.gov (United States)

    Accurso, Anthony J; Rastegar, Darius A

    2016-02-01

    The optimal dose for office-based buprenorphine therapy is not known. This study reports on the effect of a change in payer policy, in which the insurer of a subset of patients in an office-based practice imposed a maximum sublingual buprenorphine dose of 16 mg/day, thereby forcing those patients on higher daily doses to decrease their dose. This situation created conditions for a natural experiment, in which treatment outcomes for patients experiencing this dose decrease could be compared to patients with other insurance who were not challenged with a dose decrease. Subjects were 297 patients with opioid use disorder in a primary care practice who were prescribed buprenorphine continuously for at least 3 months. Medical records were retrospectively reviewed for urine drug test results and treatment retention. Rates of aberrant urine drug tests were calculated in the period before the dose decrease and compared to rate after it with patients serving as their own controls. Comparison groups were formed from patients with the same insurance on buprenorphine doses of 16 mg/day or lower, patients with different insurance on 16 mg/day or lower, and patients with different insurance on greater than 16 mg/day. Rates of aberrant drug tests and treatment retention of patients on 16 mg/day or less of buprenorphine were compared to that of patients on higher daily doses. The rate of aberrant urine drug tests among patients who experienced a dose decrease rose from 27.5% to 34.2% (p=0.043). No comparison group showed any significant change in aberrant drug test rates. Moreover, all groups who were prescribed buprenorphine doses greater than 16 mg/day displayed lower rates of aberrant urine drug tests than groups prescribed lower doses. Retention in treatment was also highest among those prescribed greater than 16 mg/day (100% vs. 86.8%, 90.1%, and 84.4% p=0.010). An imposed buprenorphine dose decrease was associated with an increase in aberrant drug tests. Patients in a

  15. Opioid intoxication

    Science.gov (United States)

    Intoxication - opioids; Opioid abuse - intoxication; Opioid use - intoxication ... Saunders; 2013:chap 154. National Institute on Drug Abuse. Opioids. National Institute on Drug Abuse Web site. Updated ...

  16. Depression and prescription opioid misuse among chronic opioid therapy recipients with no history of substance abuse.

    Science.gov (United States)

    Grattan, Alicia; Sullivan, Mark D; Saunders, Kathleen W; Campbell, Cynthia I; Von Korff, Michael R

    2012-01-01

    Opioid misuse in the context of chronic opioid therapy (COT) is a growing concern. Depression may be a risk factor for opioid misuse, but it has been difficult to tease out the contribution of co-occurring substance abuse. This study aims to examine whether there is an association between depression and opioid misuse in patients receiving COT who have no history of substance abuse. A telephone survey was conducted at Group Health Cooperative and Kaiser Permanente of Northern California. We interviewed 1,334 patients on COT for noncancer pain who had no history of substance abuse. Patients were asked about 3 forms of opioid misuse: (1) self-medicating for symptoms other than pain, (2) self-increasing doses, and (3) giving to or getting opioids from others. Depression was evaluated by the 8-item Patient Health Questionnaire (PHQ-8). Compared with patients who were not depressed (PHQ-8 score 0 to 4), patients with moderate depression (PHQ-8 score 10 to 14) and severe depression (PHQ-8 score 15 or higher) were 1.8 and 2.4 times more likely, respectively, to misuse their opioid medications for non-pain symptoms. Patients with mild (PHQ-8 score 5 to 9), moderate, and severe depression were 1.9, 2.9, and 3.1 times more likely, respectively, to misuse their opioid medications by self-increasing their dose. There was no statistically significant association between depression and giving opioids to or getting them from others. In patients with no substance abuse history, depressive symptoms are associated with increased rates of some forms of self-reported opioid misuse. Clinicians should be alert to the risk of patients with depressive symptoms using opioids to relieve these symptoms and thereby using more opioids than prescribed.

  17. Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial.

    Science.gov (United States)

    Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S; Swartz, Marvin S; Woody, George E

    2014-05-01

    The approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine. Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month. Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded. Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Endogenous opioids and smoking: a review of progress and problems.

    Science.gov (United States)

    Pomerleau, O F

    1998-02-01

    The present report examines efforts to elucidate the role of opioid mechanisms in the reinforcement of smoking. A number of approaches have been used to evaluate nicotine-opioid interactions. Opiate agonists such as heroin or methadone have been found to increase cigarette smoking reliably in humans, and morphine has been shown to increase the potency and efficacy of nicotine in rats. There is also an extensive literature documenting the nicotine-stimulated release of endogenous opioids in various brain regions involved in the mediation of opiate reinforcement. Blockade studies using opioid antagonists have not been as conclusive. Although animal models have demonstrated commonalities between nicotine withdrawal and the opiate abstinence syndrome, including reversibility by morphine, and although the impact of nicotine on certain response systems such as respiratory reflexes has clearly been shown to involve opioid mediation, attempts to demonstrate opioid modulation for the key indicators of smoking reinforcement--cigarette consumption and nicotine self-administration--have been fraught with difficulty. Resolution of the apparent contradictions will require taking into account: (a) the biphasic properties of nicotine-opioid effects at higher doses and anti-opioid effects at lower doses; (b) the contributions of the opioid receptor populations--mu, kappa, sigma--stimulated at various dose levels; (c) the possibility that endogenous-opioid activity is entrained primarily during the acquisition or re-acquisition of nicotine self-administration; (d) the possibility that the endogenous opioid response does contribute to nicotine reinforcement but only as a delimited component of the neuroregulatory cascade of nicotine; and (e) the possibility that opioids contribute primarily to nicotine reinforcement under special conditions such as stress. Taking these considerations into account should allow studies on endogenous opioid effects to begin to do justice to the

  19. Antinociceptive effects of mixtures of mu opioid receptor agonists and cannabinoid receptor agonists in rats: impact of drug and fixed-dose ratio.

    Science.gov (United States)

    Maguire, David R; France, Charles P

    2017-11-25

    Pain is a significant clinical problem, and there is a need for effective pharmacotherapies with fewer adverse effects than currently available drugs (e.g., mu opioid receptor agonists). Cannabinoid receptor agonists enhance the antinociceptive effects of mu opioid receptor agonists, but it remains unclear which drugs and in what proportion will yield the most effective and safest treatments. The antinociceptive effects of the mu opioid receptor agonists etorphine and morphine alone and in combination with the cannabinoid receptor agonists Δ9-THC and CP55940 were studied in male Sprague-Dawley rats (n=16) using a warm water tail withdrawal procedure. The ratio of opioid to cannabinoid (3:1, 1:1, and 1:3) varied for each mixture. Drugs administered alone or as pairwise mixtures of an opioid and a cannabinoid dose-dependently increased tail withdrawal latency. Mixtures with morphine produced supra-additive (CP55940) and additive (Δ9-THC) effects, whereas mixtures with etorphine and either cannabinoid were sub-additive. The interactions were not different among ratios for a particular mixture. The nature of the interaction between opioids and cannabinoids with regard to antinociceptive effects varies with the particular drugs in the mixture, which can have implications for designing combination therapies for pain. Copyright © 2017. Published by Elsevier B.V.

  20. Overdose and prescribed opioids: Associations among chronic non-cancer pain patients

    Science.gov (United States)

    Dunn, Kate M; Saunders, Kathleen W; Rutter, Carolyn M; Banta-Green, Caleb J; Merrill, Joseph O; Sullivan, Mark D; Weisner, Constance M; Silverberg, Michael J; Campbell, Cynthia I; Psaty, Bruce M; Von Korff, Michael

    2010-01-01

    Background Chronic opioid therapy for chronic non-cancer pain (CNCP) is increasingly common in community practice. Concomitant with this practice change, rates of fatal opioid overdose have increased. It is not known to what extent overdose risks are elevated among patients receiving medically prescribed chronic opioid therapy. Objective To estimate rates of opioid overdose and their association with average prescribed daily opioid dose among patients receiving medically prescribed chronic opioid therapy. Design Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at time of overdose. Setting Health maintenance organization. Patients Individuals (n=9940) who received 3+ opioid prescriptions within 90-days for CNCP between 1997 and 2005. Measurements Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes, non-fatal and fatal overdoses, were identified through diagnostic codes from inpatient and outpatient care and death certificates and confirmed by medical record review. Results Fifty-one opioid-related overdoses were identified, including six deaths. Compared to patients receiving 1-20mg of opioids per day (0.2% annual overdose rate), patients receiving 50-99 mg had a 3.7 fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7% annual overdose rate. Patients receiving 100mg or more per day had an 8.9 fold increase in overdose risk (95% C.I. 4.0, 19.7) and a 1.8% annual overdose rate. Limitations Increased overdose risk among patients on higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation. Conclusions Patients receiving higher doses of prescribed opioids are at increased risk of opioid overdose, underscoring the need for close supervision of these patients. PMID:20083827

  1. Combination of Low-dose Nalbuphine and Morphine in Patient-controlled Analgesia Decreases Incidence of Opioid-related Side Effects

    Directory of Open Access Journals (Sweden)

    Yu-Chang Yeh

    2009-07-01

    Conclusion: Combination of low-dose nalbuphine and morphine in PCA decreases the incidence of opioid-related nausea, without affecting the analgesia and PCA requirement. This novel combination can improve the quality of PCA used for postoperative pain control after gynecological surgery.

  2. Efficacy, Tolerability, and Dose-Dependent Effects of Opioid Analgesics for Low Back Pain: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Abdel Shaheed, Christina; Maher, Chris G; Williams, Kylie A; Day, Richard; McLachlan, Andrew J

    2016-07-01

    Opioid analgesics are commonly used for low back pain, however, to our knowledge there has been no systematic evaluation of the effect of opioid dose and use of enrichment study design on estimates of treatment effect. To evaluate efficacy and tolerability of opioids in the management of back pain; and investigate the effect of opioid dose and use of an enrichment study design on treatment effect. Medline, EMBASE, CENTRAL, CINAHL, and PsycINFO (inception to September 2015) with citation tracking from eligible randomized clinical trials (RCTs). Placebo-controlled RCTs in any language. Two authors independently extracted data and assessed risk of bias. Data were pooled using a random effects model with strength of evidence assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The primary outcome measure was pain. Pain and disability outcomes were converted to a common 0 to 100 scale, with effects greater than 20 points considered clinically important. Of 20 included RCTs of opioid analgesics (with a total of 7925 participants), 13 trials (3419 participants) evaluated short-term effects on chronic low back pain, and no placebo-controlled trials enrolled patients with acute low back pain. In half of these 13 trials, at least 50% of participants withdrew owing to adverse events or lack of efficacy. There was moderate-quality evidence that opioid analgesics reduce pain in the short term; mean difference (MD), -10.1 (95% CI, -12.8 to -7.4). Meta-regression revealed a 12.0 point greater pain relief for every 1 log unit increase in morphine equivalent dose (P = .046). Clinically important pain relief was not observed within the dose range evaluated (40.0-240.0-mg morphine equivalents per day). There was no significant effect of enrichment study design. For people with chronic low back pain who tolerate the medicine, opioid analgesics provide modest short-term pain relief but the effect is not likely to be clinically important

  3. The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial.

    Science.gov (United States)

    Bornemann-Cimenti, Helmar; Wejbora, Mischa; Michaeli, Kristina; Edler, Alexander; Sandner-Kiesling, Andreas

    2016-10-01

    Evidence confirms that perioperative ketamine administration decreases opioid usage. To reduce the risk for potential psychodysleptic side effects, however, ketamine dosing tends to be limited to low-dose regimens. We hypothesized that even lower doses of ketamine would be sufficient, with minimal side effects, when used as a component of multimodal perioperative pain management. In this triple-blinded, randomized, active- and placebo-controlled clinical trial, patients undergoing elective major abdominal surgery were randomized to one of three treatment groups: low-dose S-ketamine (a 0.25 mg/kg bolus and 0.125 mg/kg/h infusion for 48 hours), minimal-dose S-ketamine (a 0.015 mg/kg/h infusion following a saline bolus), and placebo (saline bolus and infusion). Opioid consumption, pain levels, hyperalgesia at the incision site, and delirium scores were assessed 48 h postoperatively. Patients in the placebo group had the highest cumulative piritramide consumption and the largest normalized areas of hyperalgesia at the incisional site, while those in the low-dose group had the highest delirium scores. Postoperative pain levels did not differ significantly between the treatment groups. Our data demonstrate that minimal-dose S-ketamine was comparable to the conventional low-dose regimen in reducing postoperative opioid consumption and hyperalgesia. Postoperative delirium, however, was less frequent with the minimal-dose regimen. We therefore suggest that minimal-dose S-ketamine may be a useful low-risk component of balanced perioperative analgesia.

  4. Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum.

    Science.gov (United States)

    Johnson, Matthew W; MacLean, Katherine A; Reissig, Chad J; Prisinzano, Thomas E; Griffiths, Roland R

    2011-05-01

    Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2(A)) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. The Role of Program Directors in Treatment Practices: The Case of Methadone Dose Patterns in U.S. Outpatient Opioid Agonist Treatment Programs.

    Science.gov (United States)

    Frimpong, Jemima A; Shiu-Yee, Karen; D'Aunno, Thomas

    2017-10-01

    To describe changes in characteristics of directors of outpatient opioid agonist treatment (OAT) programs, and to examine the association between directors' characteristics and low methadone dosage. Repeated cross-sectional surveys of OAT programs in the United States from 1995 to 2011. We used generalized linear regression models to examine associations between directors' characteristics and methadone dose, adjusting for program and patient factors. Data were collected through telephone surveys of program directors. The proportion of OAT programs with an African American director declined over time, from 29 percent in 1995 to 16 percent in 2011. The median percentage of patients in each program receiving methadone doses than other programs. This association was even stronger in programs with an African American director who served populations with higher percentages of African American patients. Demographic characteristics of OAT program directors (e.g., their race) may play a key role in explaining variations in methadone dosage across programs and patients. Further research should investigate the causal pathways through which directors' characteristics affect treatment practices. This may lead to new, multifaceted managerial interventions to improve patient outcomes. © Health Research and Educational Trust.

  6. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy.

    Science.gov (United States)

    Miller, Matthew; Barber, Catherine W; Leatherman, Sarah; Fonda, Jennifer; Hermos, John A; Cho, Kelly; Gagnon, David R

    2015-04-01

    The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past 2 decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury. Few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others. To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action (ie, long-acting vs short-acting formulations). A propensity score-adjusted cohort study was conducted using population-based health care utilization data from the Veterans Administration Healthcare System. The patients were veterans with chronic painful conditions who began therapy with opioid analgesics between January 1, 2000, and December 31, 2009. Unintentional overdoses that are explicitly coded using International Classification of Disease, Ninth Revision codes as drug or medication poisonings of accidental intent (E850.x-860.x) or undetermined intent (E980.x or drug poisoning [960.x-980.x] without an accompanying external cause of injury code). A total of 319 unintentional overdose events were observed. Patients initiating therapy with long-acting opioids were more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury than did those receiving short-acting opioids (hazard ratio [HR], 2.33; 95% CI, 1.26-4.32). The risk associated with long-acting agents was particularly marked during the first 2 weeks after initiation of treatment (HR, 5.25; 1.88-14.72). To our knowledge, the findings of the present study provide the first evidence

  7. CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction.

    Science.gov (United States)

    Levran, Orna; Peles, Einat; Hamon, Sara; Randesi, Matthew; Adelson, Miriam; Kreek, Mary Jeanne

    2013-07-01

    Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter-individual variability in dose-response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6 and CYP2D6. The CYP2B6*6 allele [single nucleotide polymorphisms (SNPs) 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well-characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co-medication that may affect methadone metabolism were included. The stabilizing daily methadone dose in this sample ranges between 13 and 260mg (mean 140±52mg). The mean methadone doses required by subjects homozygous for the variant alleles of the CYP2B6 SNPs 785A>G and 516G>T (88, 96mg, respectively) were significantly lower than those of the heterozygotes (133, 129mg, respectively) and the non-carriers (150, 151mg, respectively) (nominal P=0.012, 0.048, respectively). The results remain significant after controlling for age, sex and the ABCB1 SNP 1236C>T (rs1128503), which was previously shown to be associated with high methadone dose requirement in this population (P=0.006, 0.030, respectively). An additional 77 CYP2B6, CYP3A4 and CYP2D6 SNPs were genotyped. Of these, 24 SNPs were polymorphic and none showed significant association with methadone dose. Further studies are necessary to replicate these preliminary findings in additional subjects and other populations. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  8. Misuse of Opioids in Orthopaedic Postoperative Patients.

    Science.gov (United States)

    Gangavalli, Anup; Malige, Ajith; Terres, George; Rehman, Saqib; Nwachuku, Chinenye

    2017-04-01

    In light of the recent uptrend in the prescription of opioids, this study seeks to identify patterns of opioid misuse among orthopaedic postoperative patients and principal external sources in obtaining these medications. Ten-month survey-based study. Two Level I trauma centers (urban and suburban). Two hundred seven patients between the ages of 18 and 89 years who underwent surgical fixation of fractures involving the pelvis, long bones, or periarticular regions of the knee, ankle, elbow, and wrist. Patients who believed they were undermedicated, used prescribed opioids at higher than recommended doses, and took extra opioids in addition to their prescribed analgesics were analyzed by age, employment, income, education, controlled substance use, pain interference with activities of daily living, and anatomic surgical site. One hundred eighty-two patients completed the survey; 19.2% of patients (n = 35) felt undermedicated [unemployed (P higher dose than prescribed [unemployed (P graduates (P unemployed patients (P Unemployed and lower-income patients were significantly more likely to believe that their surgeon was not prescribing them enough pain medications as well as use their prescribed opioid medications at a higher than recommended dose compared with their employed counterparts with higher incomes. Unemployed patients were also significantly more likely to use additional opioid analgesics in addition to those prescribed to them by their primary surgeon. Surgeon awareness of a patient's socioeconomic background and associated risk of opioid misuse is crucial to prescribe the safest most effective pain regimen. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

  9. Evaluating the Impact of a Clinical Decision Support Tool to Reduce Chronic Opioid Dose and Decrease Risk Classification in a Veteran Population.

    Science.gov (United States)

    Patel, Shardool; Carmichael, Jan M; Taylor, Janice M; Bounthavong, Mark; Higgins, Diana T

    2017-10-01

    Chronic opioid therapy-clinical reminder (COT-CR) is a decision support tool to prompt providers to carefully assess patients prescribed chronic opioids. This tool was developed to address inappropriate opioid prescribing. To determine COT-CR's impact on reducing morphine equivalent monthly dose (MEMD) and risk index for overdose or serious prescription opioid-induced respiratory depression (RIOSORD) values in veterans receiving chronic opioids. This retrospective cohort review matched patients with a complete COT-CR to patients with an incomplete COT-CR using propensity scores. In the primary aim, an interrupted time series design evaluated for changes in MEMD 12 months before and 6 months after the index date. The index date was the first pain or primary care provider visit post COT-CR installation. In the secondary aims, a retrospective cohort design was used to evaluate the changes in RIOSORD index score and risk class 6 months after the index date. After matching, 3801 patients were included in the complete and incomplete COT-CR groups, respectively. Greater average reduction in MEMD (-11.6 MEMD; 95% CI = -0.97 to -22.25 MEMD; P = 0.032) and RIOSORD index score (-0.53 RIOSORD index score; 95% CI = -1.00, -0.05 RIOSORD index score; P = 0.030) was observed in patients with a complete COT-CR compared to patients with an incomplete COT-CR. Differences in RIOSORD risk class were insignificant. Completing the COT-CR was associated with reduced MEMD and RIOSORD values. This suggests that active monitoring can change prescribing patterns, thereby, reducing the overall risk of opioid overdose in at-risk veterans.

  10. Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors

    Science.gov (United States)

    Hipólito, Lucia; Wilson-Poe, Adrianne; Campos-Jurado, Yolanda; Zhong, Elaine; Gonzalez-Romero, Jose; Virag, Laszlo; Whittington, Robert; Comer, Sandra D.; Carlton, Susan M.; Walker, Brendan M.; Bruchas, Michael R.

    2015-01-01

    Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. SIGNIFICANCE STATEMENT This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between

  11. Fentanyl Buccal Tablet vs. Oral Morphine in Doses Proportional to the Basal Opioid Regimen for the Management of Breakthrough Cancer Pain: A Randomized, Crossover, Comparison Study.

    Science.gov (United States)

    Mercadante, Sebastiano; Adile, Claudio; Cuomo, Arturo; Aielli, Federica; Cortegiani, Andrea; Casuccio, Alessandra; Porzio, Giampiero

    2015-11-01

    Fentanyl products have shown superiority to oral opioids for the management of breakthrough cancer pain (BTcP). However, these studies did not use appropriate patient selection, and drugs have been compared by using different rationales. The aim of this randomized, crossover, controlled study was to compare efficacy and safety of fentanyl buccal tablets (FBTs) and oral morphine (OM), given in doses proportional to opioid daily doses. Cancer patients with pain receiving ≥60 mg or more of oral morphine equivalents per day and presenting with ≤3 episodes of BTcP per day were included. In a randomized, crossover manner, patients received FBT or OM at doses proportional to the daily opioid regimen in four consecutive episodes of BTcP. Pain intensity was measured before (T0) and 15 (T15) and 30 minutes (T30), after study drugs. In total, 263 episodes of BTcP were treated. A statistical difference in changes in pain intensity-decrease of ≥33% and ≥50%-between the two groups was observed at T15 and T30 (P medication. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  12. The effect of opioid and acepromazine premedication on the anesthetic induction dose of propofol in cats.

    Science.gov (United States)

    Hall, T L; Duke, T; Townsend, H G; Caulkett, N A; Cantwell, S L

    1999-01-01

    The median effective dosage (ED50) for induction of anesthesia with propofol was determined by using the up-and-down method in 31 unpremedicated cats, in 30 cats premedicated with butorphanol, 0.4 mg/kg body weight (BW), and acepromazine, 0.1 mg/kg BW, intramuscularly, and in 30 cats premedicated with morphine, 0.2 mg/kg BW, and acepromazine, 0.1 mg/kg BW, intramuscularly. The dose required for a satisfactory anesthetic induction in 50% of unpremedicated cats (ED50) was 7.22 mg/kg BW and of premedicated cats was 5.00 mg/kg BW. The reduction in dose was statistically significant in both premedicated groups compared with no premedication. There was no significant difference in ED50 between premedication regimes. Cyanosis was the most common adverse effect observed in all groups following anesthetic induction with propofol. PMID:10646062

  13. Chronic non-cancer pain and the epidemic prescription of opioids in the Danish population

    DEFF Research Database (Denmark)

    Birke, H; Kurita, G P; Sjøgren, P

    2016-01-01

    prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non-Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used...... higher doses than men. Concurrent use of BZD/BZD-related drugs decreased (13%) from 2010 to 2013, still one-third of long-term opioid user were co-medicated with these drugs. CONCLUSIONS: The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD...

  14. Opioids for chronic pain: new evidence, new strategies, safe prescribing.

    Science.gov (United States)

    de Leon-Casasola, Oscar A

    2013-03-01

    In the United States, the prevalence and burden of chronic pain is large and still growing. Older adults (aged ≥65 years) make up a large portion of the population with chronic pain, and their presentation, diagnosis, and treatment tends to be more complicated because of age-related physiological changes and comorbidities. Guidelines on treating patients with severe back pain recommend opioids as an option for those who do not find adequate pain relief from acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). For older adult patients at higher risk for NSAID-related adverse effects, such as those who have gastrointestinal or cardiovascular disease, diabetes mellitus, or who are taking low-dose aspirin, opioids are recommended instead. Opioids may also be an appropriate option for patients with neuropathic pain who have not achieved adequate analgesia from maximum doses of first- and second-line antineuropathic agents. Still, opioids are not appropriate for all patients; rather, a differential diagnosis, consideration of other comorbidities, and the potential for opioid-related adverse effects and substance abuse are required to confirm the value of opioid treatment for each individual. For nonresponders to opioid therapy, opioid rotation should be considered before discontinuation is pursued. Copyright © 2013. Published by Elsevier Inc.

  15. Impact of Family History of Substance Abuse on Admission Opioid Dose, Depressive Symptoms, and Pain Catastrophizing in Patients with Chronic Pain.

    Science.gov (United States)

    Pestka, Elizabeth L; Craner, Julia; Evans, Michele; Nash, Virginia; Kimondo, Njoki; Pestka, Deborah; Loukianova, Larissa; Sperry, Jeannie

    2017-11-15

    The objectives of this study were to examine association between a family history of substance abuse and admission morphine equivalent dose, depression and pain catastrophizing screening scores, as well as reported personal history of substance use. The retrospective research was completed in an interdisciplinary three-week pain rehabilitation center. The subject cohort included admissions from January through December 2014 with 351 datasets for family history of substance abuse and oral morphine equivalency and 341 for depression, pain catastrophizing and use of substances. Outcome measures included admission self-reported data on family history of substance abuse and past and current substance use, admission morphine equivalency dose, and scores on the Center for Epidemiologic Studies-Depression Scale and the Pain Catastrophizing Scale. One hundred forty-seven patients were using opioid medications on admission and those with a positive family history of substance abuse had an oral morphine equivalency (M = 92.12, SD = 95.32) compared to a negative history (M = 80.34, SD = 64.86); the difference was not statistically significant, t (120.01) =.87, p = .39. Patients with a positive family history reported higher levels of both depression, t (327.40) = 3.15, p = .002 and pain catastrophizing, t (338) = 2.76, p = .01. Those with a positive family history endorsed greater frequency of past alcohol use χ(2) (1, N = 326) = 6.67, p = 0.1 and marijuana use χ(2) (1, N = 341) = 4.23, p = .04 and past χ(2) (1, N = 329) = 9.90, p = .002 and current tobacco use χ(2) (1, N = 327) = 8.81, p = .003. Use of family history of substance abuse information may help provide data for multimodal treatments of chronic non-cancer-pain. The findings from this study can be used to guide future research. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  16. Classification and identification of opioid addiction in chronic pain patients

    DEFF Research Database (Denmark)

    Højsted, Jette; Nielsen, Per Rotbøll; Guldstrand, Sally Kendall

    2010-01-01

    Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction, to investi......Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction...... as addicted were treated with significantly higher opioid doses, drank more alcohol, smoked more tobacco, used benzodiazepines and had higher levels of depression. According to ICD-10 patients classified as addicted used higher doses of opioids, drank more alcohol and had higher scores of anxiety...... and depression. High opioid doses, concomitant use of alcohol and younger age were risk factors. The risk profile for PC was different to ICD-10 by adding risk factors as concomitant use of benzodiazepines, having depression and low educational level. PC seems to be appropriate for diagnosing addiction in opioid...

  17. Dyspnea, relative youth and low daily doses of opioids predict increased opioid dosage in the last week of a terminal cancer patient's life.

    Science.gov (United States)

    Miura, Tomofumi; Matsumoto, Yoshihisa; Motonaga, Shinya; Hasuo, Hideaki; Abe, Keiko; Kinoshita, Hiroya

    2014-11-01

    Most cancer patients become increasingly anxious toward the end of their life. The objective of this study was to identify predictors of increased opioid dosage in the last week of a terminal cancer patient's life. We retrospectively reviewed charts of patients who died in our palliative care unit. We assigned the patients to increased group or decreased group according to changes in oral morphine equivalent dosage in their last 7 days. Logistic regression analysis was used to identify predictors of increased oral morphine equivalent dosage. We analyzed data of 158 patients (female: 43.7%, median age: 64 years). The median oral morphine equivalent dosages on Days 7 and 1 before death were 50 mg (interquartile range: 24-122) and 61 mg (28-129), respectively. Independent predictors of increased oral morphine equivalent dosage included dyspnea (odds ratio: 11.5, 95% confidence interval: 4.98-28.83, P confidence interval: 1.04-5.26, P = 0.04) and oral morphine equivalent dosage confidence interval: 1.68-8.89, P youth and oral morphine equivalent dosage <50 mg on Day 7 before death were predictive of increased oral morphine equivalent dosage in the last 7 days. Our findings may help oncologists to more accurately inform patients about expected opioid requirements and thus relieve their end-of-life anxiety. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Opioid Addiction

    Science.gov (United States)

    ... drug.Opioid drugs include:opiumcodeinefentanylheroinhydrocodonehydromorphonemethadonemorphineoxycodoneoxymorphoneparegoricsufentaniltramadol. Symptoms of opioid addiction The first step toward recovery is recognizing that you have a problem with ...

  19. Cholestasis and endogenous opioids: liver disease and exogenous opioid pharmacokinetics.

    Science.gov (United States)

    Davis, Mellar

    2007-01-01

    A class of endogenous opioids is upregulated in liver disease particular to cholestasis, which contributes to symptoms in liver disease such as pruritus, hypotension and encephalopathy. Symptoms associated with cholestasis are reversed or at least ameliorated by mu opioid receptor antagonists. Palliation of symptoms related to cholestatic liver disease also involves bile acid binding agents. Opioid receptor antagonists, unlike bile acid binding agents, have been reported to relieve multiple symptoms, except for pruritus, and improve liver function as demonstrated in experimental cholestasis. Exogenous opioid pharmacology is altered by liver disease. Dose reduction or prolongation of dose intervals is necessary depending on the severity of liver disease.

  20. Opioid Drugs in Patients With Liver Disease: A Systematic Review

    Science.gov (United States)

    Soleimanpour, Hassan; Safari, Saeid; Shahsavari Nia, Kavous; Sanaie, Sarvin; Alavian, Seyed Moayed

    2016-01-01

    Context The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients. Evidence Acquisition This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles. Results In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered. Conclusions Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased

  1. Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice

    Directory of Open Access Journals (Sweden)

    Jennifer Mecklenburg

    2017-02-01

    Conclusion:. As in humans, baseline nociception was lower in aged vs adult mice, while postoperative hypersensitivity magnitudes were comparable between groups. Unlike in humans, adult mice were more sensitive to mu-opioids, although higher doses of mixed mu-opioids were more effective for postoperative antihypersensitivity in aged mice.

  2. Fentanyl Pectin Nasal Spray Versus Oral Morphine in Doses Proportional to the Basal Opioid Regimen for the Management of Breakthrough Cancer Pain: A Comparative Study.

    Science.gov (United States)

    Mercadante, Sebastiano; Aielli, Federica; Adile, Claudio; Costanzi, Andrea; Casuccio, Alessandra

    2016-07-01

    Fentanyl products have shown superiority over oral opioids for the management of breakthrough cancer pain (BTcP). However, these studies did not use an appropriate patient selection, and drugs have been compared using a different rationale. The aim of this randomized, crossover, controlled study was to compare the efficacy and safety of fentanyl pectin nasal spray (FPNS) and oral morphine (OM), given in doses proportional to opioid daily doses. Cancer patients with pain receiving ≥60 mg of OM equivalents/day and presenting with ≤3 episodes of BTcP/day were included. Patients received, in a randomized, crossover manner, FPNS or OM at doses proportional to the daily opioid regimen in four consecutive episodes of BTcP. Pain intensity was measured before (T0), 15 (T15), and 30 minutes (T30) after study drugs. A total of 167 episodes were treated, 82 with FNPS and 85 with OM. A statistical difference in pain intensity between the two groups was observed at T15, but not at T30 (P = 0.018 and P = 0.204, respectively). In a greater number of episodes treated with FPNS, there was a pain decrease of ≥33% in comparison with OM after 15 and 30 minutes (76.5% vs. 32.8%, and 89% vs. 54.9%, respectively). Similar differences were found in the decrease in pain intensity of ≥50% after 15 and 30 minutes (52.3% vs. 11.4%, and 75% vs. 45.8%, respectively). The difference was highly significant at T15 (P pain difference at T15 of FPNS and OM were 3.24 (1.7) and 2.70 (1.2), respectively, whereas the mean (SD) SPIDs30 of FPNS and OM were 4.87 (1.7) and 4.54 (1.5), respectively. The difference was highly significant at T15 (P = 0.019). No severe adverse effects after study drug administration were observed. When used in doses proportional to the basal opioid regimen, FPNS showed a superior analgesic effect over OM for the management of BTcP. Only minor adverse effects were found with both medications. Copyright © 2016 American Academy of Hospice and Palliative Medicine

  3. 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.

  4. Effects of exercise and supraphysiological dose of nandrolone decano-ate on the rat plasma opioid level: a brief report

    Directory of Open Access Journals (Sweden)

    Mehdi Mohebi

    2014-06-01

    Conclusion: In the present study we show that chronic nandrolone decanoate admin-istration attenuates effects of two weeks swimming exercise on serum opioid peptide and reduces the level of beta-endorphin and met-enkephalin. Keeping in mind that opi-oidergic system play an important role in behavior, athletes abusing anabolic steroid drugs may potentially experience changes in mood and behavior.

  5. More Dose-dependent Side Effects with Mercaptopurine over Azathioprine in IBD Treatment Due to Relatively Higher Dosing.

    Science.gov (United States)

    Broekman, Mark M T J; Coenen, Marieke J H; van Marrewijk, Corine J; Wanten, Geert J A; Wong, Dennis R; Verbeek, Andre L M; Klungel, Olaf H; Hooymans, Piet M; Guchelaar, Henk-Jan; Scheffer, Hans; Derijks, Luc J J; de Jong, Dirk J

    2017-10-01

    There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients with inflammatory bowel disease for the frequency of side effects and efficacy. Post hoc analysis of the "Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics" (TOPIC) trial, in which thiopurine-naive patients with inflammatory bowel disease with an indication for a thiopurine were randomized for a genotype-based dose versus standard of care. For this study, Cox proportional hazard ratios (HRs) were calculated to compare AZA and MP for discontinuation rates within 5 months, incidence of hepatotoxicity, leukopenia, and gastrointestinal side effects. Treatment efficacy was compared by logistic regression. Patient characteristics were similar for patients treated with AZA (n = 494, 64.4%) and MP (n = 273, 35.6%), yet patients with MP were relatively higher dosed compared with those on AZA. Discontinuation rates within 5 months were not different, 39.3% (AZA) and 38.1% (MP), HR 0.92 (95% confidence interval, 0.72-1.17; P = 0.50); however, patients on MP were more often subjected to dose reductions (30% versus 14%, P < 0.01). Higher rates of hepatotoxicity, HR 1.93 (95% confidence interval, 1.35-2.76; P < 0.01) and leukopenia, HR 2.55 (95% confidence interval, 1.51-4.30; P < 0.01) were observed with MP, which annulled in a secondary analysis with adjustment for the higher dose and metabolite levels. Patients treated with MP were relatively higher dosed, which resulted in more dose-dependent side effects and a higher rate of dose reductions.

  6. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, O; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

  7. Defining clinical issues around tolerance, hyperalgesia, and addiction: a quantitative and qualitative outcome study of long-term opioid dosing in a chronic pain practice.

    Science.gov (United States)

    Schneider, Jennifer P; Kirsh, Kenneth L

    2010-01-01

    Treatment with opioid medications has grown over the past decades, but has been surrounded by some ongoing controversy and debate to whether it is causing more harm than good for patients. To this end, the field of pain management has suffered from a lack of clarity about some basic definitions on concepts such as tolerance and hyperalgesia. Some characterize these issues as inevitable parts of opioid therapy while other schools of thought look at these issues as relatively rare occurrences. Unfortunately, most of the rhetoric around these topics has occurred with very little in the realm of real world data. To this end, the authors have reviewed the charts of 197 patients treated by a pain specialist for at least 1 year to better illustrate whether notions of tolerance and hyperalgesia are common occurrences and, more importantly, whether they occur within any type of specified timeframe. A total of 197 patient charts were reviewed. The sample had an average age of 49.39 years (range = 19-87 years; standard deviation [SD] = 12.48) and comprised 66 men (33.5 percent) and 131 women (66.5 percent). The patients were seen in the pain practice for an average of 56.52 months (range = 12-155 months; SD = 31.26). On average, the patients maintained an average daily dose of 180 mg morphine equivalents for a period of 35.1 months (range = 3-101 months; SD = 21.3). Looking at the pattern of medication usage change over time, 34.5 percent experienced dose stabilization after the initial titration, 13.2 percent had early dose stabilization within one dose change, and an additional 14.7 percent actually had dose decreases after surgeries or other interventional procedures. Only 6.6 percent of the sample had to be discharged or weaned from controlled substances over time in the clinic. Thus, it appears that tolerance and hyperalgesia are not foregone conclusions when considering placing a patient on long-term opioid therapy.

  8. Compulsivity in opioid dependence.

    Science.gov (United States)

    Tolomeo, Serenella; Matthews, Keith; Steele, Douglas; Baldacchino, Alex

    2018-02-02

    This study aimed to investigate the relationship between compulsivity versus impulsivity and structural MRI abnormalities in opioid dependence. We recruited 146 participants: i) patients with a history of opioid dependence due to chronic heroin use (n=24), ii) heroin users stabilised on methadone maintenance treatment (n=48), iii) abstinent participants with a history of opioid dependence due to heroin use (n=24) and iv) healthy controls (n=50). Compulsivity was measured using Intra/Extra-Dimensional (IED) Task and impulsivity was measured using the Cambridge Gambling Task (CGT). Structural Magnetic Resonance Imaging (MRI) data were also obtained. As hypothesised, compulsivity was negatively associated with impulsivity (p<0.02). Testing for the neural substrates of compulsivity versus impulsivity, we found a higher compulsivity/impulsivity ratio associated with significantly decreased white matter adjacent to the nucleus accumbens, bed nucleus of stria terminalis and rostral cingulate in the abstinent group, compared to the other opioid dependent groups. In addition, self-reported duration of opioid exposure correlated negatively with bilateral globus pallidus grey matter reductions. Our findings are consistent with Volkow & Koob's addiction models and underline the important role of compulsivity versus impulsivity in opioid dependence. Our results have implications for the treatment of opioid dependence supporting the assertion of different behavioural and biological phenotypes in the opioid dependence and abstinence syndromes. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Regulation of human sperm motility by opioid receptors.

    Science.gov (United States)

    Agirregoitia, E; Subiran, N; Valdivia, A; Gil, J; Zubero, J; Irazusta, J

    2012-05-01

    The endogenous opioid system has been reported to have important functions in human reproduction. Practically all the components of this peptide system have been discovered in human sperm cells, but their functions in these cells are far from being well understood. In the present work, we report the effects of opioid agonism and antagonism on human sperm motility, a parameter which is crucially associated with male fertility. Morphine (10(-7) M), a μ- opioid receptor agonist, decreased both the percentage of motile progressive sperm and three measured velocities without altering the linearity, straightness or vigour of sperm cells. This effect was reversed by naloxone. Higher doses of morphine did not have further effects on the measured parameters. The incubation of sperm cells with the δ-opioid receptor agonist D-penicillamine (2,5)-enkephalin did not affect sperm cell motility. However, naltrindole, a specific δ-receptor antagonist, reduced the linear and curvilinear velocities, as well as linearity, straightness and the amplitude of head displacement, and beat frequency. In summary, our results indicate that the endogenous opioid system may regulate opioid motility in vitro. These finding suggest that the endogenous opioid system could be useful as a biochemical tool for the diagnosis and treatment of male infertility. © 2011 Blackwell Verlag GmbH.

  10. The use of paracetamol (acetaminophen) among a community sample of people with chronic non-cancer pain prescribed opioids.

    Science.gov (United States)

    Hoban, B; Larance, B; Gisev, N; Nielsen, S; Cohen, M; Bruno, R; Shand, F; Lintzeris, N; Hall, W; Farrell, M; Degenhardt, L

    2015-11-01

    The regular use of simple analgesics in addition to opioids such as paracetamol (or acetaminophen) is recommended for persistent pain to enhance analgesia. Few studies have examined the frequency and doses of paracetamol among people with chronic non-cancer pain including use above the recommended maximum daily dose. To assess (i) the prevalence of paracetamol use among people with chronic non-cancer pain prescribed opioids, (ii) assess the prevalence of paracetamol use above the recommended maximum daily dose and (iii) assess correlates of people who used paracetamol above the recommended maximum daily dose including: age, gender, income, education, pain severity and interference, use of paracetamol/opioid combination analgesics, total opioid dose, depression, anxiety, pain self-efficacy or comorbid substance use, among people prescribed opioids for chronic non-cancer pain. This study draws on baseline data collected for the Pain and Opioids IN Treatment (POINT) study and utilises data from 962 interviews and medication diaries. The POINT study is national prospective cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited from randomly selected pharmacies across Australia. Sixty-three per cent of the participants had used paracetamol in the past week (95% CI = 59.7-65.8). Among the paracetamol users 22% (95% CI = 19.3-24.6) had used paracetamol/opioid combination analgesics and 4.8% (95% CI = 3.6-6.3) had used paracetamol above the recommended maximum daily dose (i.e. > 4000 mg/day). Following binomial logistic regression (χ(2) = 25.98, df = 10, p = 0.004), people who had taken above the recommended maximum daily dose were less likely to have low income (AOR = 0.52, 95% CI = 0.27-0.99), more likely to use paracetamol/opioid combination analgesics (AOR = 2.01, 95% CI = 1.02-3.98) and more likely to take a higher opioid dose (AOR = 1.00, 95% CI = 1.00-1.01). The majority of people with chronic non-cancer pain prescribed

  11. 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.

  12. [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.

  13. Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

    Science.gov (United States)

    Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J.; Weiner, Debra L.

    2015-01-01

    Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents, mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI and in the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI 0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage. PMID:21953763

  14. Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

    Science.gov (United States)

    Dampier, Carlton D; Smith, Wally R; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C; Minniti, Caterina P; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A Kyle; McClish, Donna; McKinlay, Sonja M; Miller, Scott T; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J; Weiner, Debra L

    2011-12-01

    Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

  15. Opioid rotation with extended-release opioids: where should we begin?

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2011-12-01

    Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

  16. Identifying and assessing the risk of opioid abuse in patients with cancer: an integrative review

    Directory of Open Access Journals (Sweden)

    Carmichael AN

    2016-06-01

    Full Text Available Ashley-Nicole Carmichael,1 Laura Morgan,1 Egidio Del Fabbro2 1School of Pharmacy, 2Division of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA Background: The misuse and abuse of opioid medications in many developed nations is a health crisis, leading to increased health-system utilization, emergency department visits, and overdose deaths. There are also increasing concerns about opioid abuse and diversion in patients with cancer, even at the end of life. Aims: To evaluate the current literature on opioid misuse and abuse, and more specifically the identification and assessment of opioid-abuse risk in patients with cancer. Our secondary aim is to offer the most current evidence of best clinical practice and suggest future directions for research. Materials and methods: Our integrative review included a literature search using the key terms “identification and assessment of opioid abuse in cancer”, “advanced cancer and opioid abuse”, “hospice and opioid abuse”, and “palliative care and opioid abuse”. PubMed, PsycInfo, and Embase were supplemented by a manual search. Results: We found 691 articles and eliminated 657, because they were predominantly noncancer populations or specifically excluded cancer patients. A total of 34 articles met our criteria, including case studies, case series, retrospective observational studies, and narrative reviews. The studies were categorized into screening questionnaires for opioid abuse or alcohol, urine drug screens to identify opioid misuse or abuse, prescription drug-monitoring programs, and the use of universal precautions. Conclusion: Screening questionnaires and urine drug screens indicated at least one in five patients with cancer may be at risk of opioid-use disorder. Several studies demonstrated associations between high-risk patients and clinical outcomes, such as aberrant behavior, prolonged opioid use, higher morphine-equivalent daily dose

  17. Medical and psychological risks and consequences of long-term opioid therapy in women.

    Science.gov (United States)

    Darnall, Beth D; Stacey, Brett R; Chou, Roger

    2012-09-01

    Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. To review the medical and psychological risks and consequences of long-term opioid therapy in women. Scientific literature containing relevant keywords and content were reviewed. Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted. Wiley Periodicals, Inc.

  18. Human psychopharmacology and dose-effects of salvinorin A, a kappa-opioid agonist hallucinogen present in the plant Salvia divinorum

    Science.gov (United States)

    Johnson, Matthew W.; MacLean, Katherine A.; Reissig, Chad J.; Prisinzano, Thomas E.; Griffiths, Roland R.

    2010-01-01

    Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. Salvia divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 minutes for 60 minutes after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 minutes (first time point) and definite subjective effects were no longer present at approximately 20 minutes after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2A) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects. PMID:21131142

  19. Increases in seizure latencies induced by subcutaneous docosahexaenoic acid are lost at higher doses.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Taha, Ameer Y; Mantha, Rebecca L; Ciobanu, Flaviu A; Zeng, Qiudi H; Tchkhartichvili, George M; Domenichiello, Anthony F; Bazinet, Richard P; Burnham, W M

    2012-05-01

    Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid (PUFA) which has been found to have anticonvulsant properties. Our group has previously reported in a pilot study that the acute administration of subcutaneous (s.c.) DHA increases seizure latencies in the maximal pentylenetetrazole (PTZ) seizure test, however it loses its effect at higher doses. The purpose of the present experiments was (1) to confirm that DHA loses its effect at higher doses, (2) to correlate the anticonvulsant properties of DHA with DHA levels in the different lipid pools of serum and (3) to evaluate whether an anticonvulsant dose of DHA resulted in an increase in DHA release from the brain phospholipids following induction of seizure. In the first experiment, male Wistar rats were injected s.c. with 200, 300, 400 or 600 mg/kg of DHA, or 400mg/kg oleic acid (OA, isocaloric control), and seizure tested with the maximal PTZ test 1h post injection (Experiment 1). In a second experiment, subjects received either: (1) an effective dose of DHA (400mg/kg), (2) a higher, non-effective dose (600 mg/kg; based on the findings of Experiment 1), or (3) OA (400mg/kg). Subjects were sacrificed 1h post injection and blood was collected for fatty acid analysis (Experiment 2). In the third experiment, subjects were injected with either the effective dose of DHA (400mg/kg) or OA (400mg/kg). One hour post lipid injection, animals received either PTZ or saline, and animals were euthanized via microwave fixation. Brain were extracted and unesterified fatty acid concentrations were measured (Experiment 3). Experiment 1 confirmed that DHA loses its effects at higher doses in the maximal PTZ test. The 400mg/kg dose was maximally effective but effects were lost at 600 mg/kg. Experiment 2 showed that only the unesterified DHA pool in serum was statistically increased by an acute injection of s.c. DHA (P0.05). Curiously, unesterified DHA levels were similar in both the 400mg/kg and 600 mg/kg dosage groups

  20. Determining pharmacological selectivity of the kappa opioid receptor antagonist LY2456302 using pupillometry as a translational biomarker in rat and human.

    Science.gov (United States)

    Rorick-Kehn, Linda M; Witcher, Jennifer W; Lowe, Stephen L; Gonzales, Celedon R; Weller, Mary Ann; Bell, Robert L; Hart, John C; Need, Anne B; McKinzie, Jamie H; Statnick, Michael A; Suico, Jeffrey G; McKinzie, David L; Tauscher-Wisniewski, Sitra; Mitch, Charles H; Stoltz, Randall R; Wong, Conrad J

    2014-10-31

    Selective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression. The kappa opioid receptor antagonist, LY2456302, exhibits ~30-fold higher affinity for kappa opioid receptors over mu opioid receptors, which is the next closest identified pharmacology. Here, we determined kappa opioid receptor pharmacological selectivity of LY2456302 by assessing mu opioid receptor antagonism using translational pupillometry in rats and humans. In rats, morphine-induced mydriasis was completely blocked by the nonselective opioid receptor antagonist naloxone (3mg/kg, which produced 90% mu opioid receptor occupancy), while 100 and 300 mg/kg LY2456302 (which produced 56% and 87% mu opioid receptor occupancy, respectively) only partially blocked morphine-induced mydriasis. In humans, fentanyl-induced miosis was completely blocked by 50mg naltrexone, and LY2456302 dose-dependently blocked miosis at 25 and 60 mg (minimal-to-no blockade at 4-10mg). We demonstrate, for the first time, the use of translational pupillometry in the context of receptor occupancy to identify a clinical dose of LY2456302 achieving maximal kappa opioid receptor occupancy without evidence of significant mu receptor antagonism. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  1. Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study.

    Science.gov (United States)

    Ekström, Magnus P; Bornefalk-Hermansson, Anna; Abernethy, Amy P; Currow, David C

    2014-01-30

    To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD). Population based longitudinal consecutive cohort study. Centres prescribing long term oxygen therapy in Sweden. 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register. Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs. 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤ 30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia. Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.

  2. Chronic pain and use of opioids: a population-based pharmacoepidemiological study from the Norwegian prescription database and the Nord-Trøndelag health study.

    Science.gov (United States)

    Fredheim, Olav Magnus S; Mahic, Milada; Skurtveit, Svetlana; Dale, Ola; Romundstad, Pål; Borchgrevink, Petter C

    2014-07-01

    In previous studies on prescription patterns of opioids, accurate data on pain are missing, and previous epidemiological studies of pain lack accurate data on opioid use. The present linkage study, which investigates the relationship between pain and opioid use, is based on accurate individual data from the complete national Norwegian prescription database and the Nord-Trøndelag health study 3, which includes about 46,000 people. Baseline data were collected in 2006 to 2008, and the cohort was followed up for 3 years. Of 14,477 people who reported chronic nonmalignant pain, 85% did not use opioids at all, 3% used opioids persistently, and 12% used opioids occasionally. Even in the group reporting severe or very severe chronic pain, the number not using opioids (2680) was far higher than the number who used opioids persistently (304). However, three quarters of people using opioids persistently reported strong or very strong pain in spite of the medication. Risk factors for the people with chronic pain who were not persistent opioid users at baseline to use opioids persistently 3 years later were occasional use of opioids, prescription of >100 defined daily doses per year of benzodiazepines, physical inactivity, reports of strong pain intensity, and prescription of drugs from 8 or more Anatomical Therapeutic Chemical groups. The study showed that most people having chronic nonmalignant pain are not using opioids, even if the pain is strong or very strong. However, the vast majority of patients with persistent opioid use report strong or very strong pain in spite of opioid treatment. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  3. 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.

  4. Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans

    Science.gov (United States)

    Qureshi, Asaf A; Khan, Dilshad A; Silswal, Neerupma; Saleem, Shahid; Qureshi, Nilofer

    2016-01-01

    Background Tocotrienols has been known to lower serum lipid parameters below 500 mg/d, while increase lipid parameters at higher dose of 750 mg/d. δ-Tocotrienol has a novel inflammatory property of concentration-dependent inhibition and activation. Therefore, inhibition (anti-inflammatory) property of tocotrienols at low doses is useful for cardiovascular disease, whereas, activation (pro-inflammatory) property using high dose is found effective for treatments of various types of cancer. We have recently described plasma bioavailability of 125 mg/d, 250 mg/d and 500 mg/d doses of δ-tocotrienol in healthy fed subjects, which showed dose-dependent increases in area under the curve (AUC) and maximum concentration (Cmax). Hence, in the current study, higher doses of tocotrienols have used to analyze its effect on plasma pharmacokinetic parameters. Aims To evaluate the safety and bioavailability of higher doses (750 mg and 1000 mg) of annatto-based tocotrienols in healthy fed subjects. All four isomers (α-, β-, γ-, δ-) of tocols (tocotrienols and tocopherols) present in the plasmas of subjects were quantified and analyzed for various pharmacokinetic parameters. Study design An open-label, randomized study was performed to analyze pharmacokinetics and bioavailability of δ-tocotrienol in 6 healthy fed subjects. All subjects (3/dose) were randomly assigned to one of each dose of 750 mg or 1000 mg. Blood samples were collected at 0, 1, 2, 4, 6, 8 h intervals and all isomers of α-,β-,γ-,δ-tocotrienols, and tocopherols in plasmas were quantified by HPLC. Results Oral administration of 750 and 1000 mg/d of tocotrienols resulted in dose-dependent increases in plasmas (ng/ml) AUCt0-t8 6621, 7450; AUCt0-∞ 8688, 9633; AUMC t0-∞ 52497, 57199; MRT 6.04, 5.93; Cmax 1444, 1592 (P<0.05), respectively, of δ-tocotrienol isomer. Moreover, both doses also resulted in plasmas Tmax 3.33–4 h; elimination half-life (t1/2 h) 2.74, 2.68; time of clearance (Cl-T, l/h) 0.086, 0

  5. Opioid addiction in pregnancy.

    Science.gov (United States)

    Shainker, Scott A; Saia, Kelley; Lee-Parritz, Aviva

    2012-12-01

    The purpose of this review is to discuss the incidence, risks, pregnancy complications, and maintenance options for treatment of opioid addiction in pregnancy. Opioid dependence in pregnancy carries clear identifiable maternal and fetal risk. Providing care for patients with dependence is best done in a multidisciplinary care model addressing the particular needs of this population. There are limited data on maternal detoxification, with data still emerging surrounding the safety profile of this practice. Historically, methadone has been the recommended maintenance treatment; however, recent data on buprenorphine identify this as a safe and effective option. The majority of births from women with opioid dependence result in neonatal abstinence syndrome requiring prolonged neonatal hospitalization. Intrapartum pain management should not differ from the general obstetric population. Postpartum pain is magnified in this population, and particular attention should be focused on this issue. Breast-feeding is recommended regardless of maintenance dose, unless other conditions restricting breast-feeding are present. Comprehensive postpartum care and transition of care to addiction specialists are highly recommended. Obstetricians and gynecologists, family physicians, addiction specialists. After completing this CME activity, physicians should be better able to assess the treatment options available to patients with opioid addiction during pregnancy, compare the risk/safety profiles of methadone and buprenorphine, and evaluate the recommendations and current data surrounding breast-feeding while on opioid maintenance treatment.

  6. 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

  7. Reducing opioid analgesic deaths in America: what health providers can do.

    Science.gov (United States)

    Agarin, Taghogho; Trescot, Andrea M; Agarin, Aniefiok; Lesanics, Doreena; Decastro, Claricio

    2015-01-01

    Available data have shown steady increases of drug overdose deaths between 1992 and 2011. We review evidenced-based recommendations provided by a few prominent North American pain societies and suggest ways on how health providers might help reduce opioid analgesic deaths by implementing these practices. To identify health care providers' roles in reducing opioid analgesic deaths. A comprehensive review of current literature. The review included relevant literature identified through searches of MEDLINE, Cochran reviews, and Google Scholar, PubMed and EMBASE from January 1998 to January 2014. The level of evidence was classified as I (good), II (fair), and III (limited) based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Several practices such as too high doses overall, giving too high doses to opioid naive patients, too fast opioid titration, insufficient use and knowledge of urine drug testing, not updating knowledge of drug metabolism/interactions, and inadequate patient monitoring are associated with higher risks of opioid analgesic deaths. Suboptimal risk stratification of patients, rotation practices, and use of opioids analgesics in chronic noncancer pain are also associated factors. There were a paucity of good evidence studies which show recommendations reduce death. Providers should be aware of all associated factors with opiate analgesic deaths and apply the available evidence in reducing opioid analgesic deaths.

  8. Toward a systematic approach to opioid rotation

    Directory of Open Access Journals (Sweden)

    Smith HS

    2014-10-01

    Full Text Available Howard S Smith,1,† John F Peppin2,3 1Department of Anesthesiology, Albany Medical College, Albany, NY, USA; 2Global Scientific Affairs, Mallinckrodt Pharmaceuticals, St Louis, MO, USA; 3Center for Bioethics, Pain Management and Medicine, St Louis, MO, USA†Author deceased May 18, 2013 Abstract: Patients requiring chronic opioid therapy may not respond to or tolerate the first opioid prescribed to them, necessitating rotation to another opioid. They may also require dose increases for a number of reasons, including worsening disease and increased pain. Dose escalation to restore analgesia using the primary opioid may lead to increased adverse events. In these patients, rotation to a different opioid at a lower-than-equivalent dose may be sufficient to maintain adequate tolerability and analgesia. In published trials and case series, opioid rotation is performed either using a predetermined substitute opioid with fixed conversion methods, or in a manner that appears to be no more systematic than trial and error. In clinical practice, opioid rotation must be performed with consideration of individual patient characteristics, comorbidities (eg, concurrent psychiatric, pulmonary, renal, or hepatic illness, and concurrent medications, using flexible dosing protocols that take into account incomplete opioid cross-tolerance. References cited in this review were identified via a search of PubMed covering all English language publications up to May 21, 2013 pertaining to opioid rotation, excluding narrative reviews, letters, and expert opinion. The search yielded a total of 129 articles, 92 of which were judged to provide relevant information and subsequently included in this review. Through a review of this literature and from the authors' empiric experience, this review provides practical information on performing opioid rotation in clinical practice. Keywords: chronic pain, opioid rotation, opioid analgesics

  9. 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.

  10. Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access

    Science.gov (United States)

    2015-01-01

    Opioid overdose and mortality have increased at an alarming rate prompting new public health initiatives to reduce drug poisoning. One initiative is to expand access to the opioid antidote naloxone. Naloxone has a long history of safe and effective use by organized healthcare systems and providers in the treatment of opioid overdose by paramedics/emergency medicine technicians, emergency medicine physicians and anesthesiologists. The safety of naloxone in a prehospital setting administered by nonhealthcare professionals has not been formally established but will likely parallel medically supervised experiences. Naloxone dose and route of administration can produce variable intensity of potential adverse reactions and opioid withdrawal symptoms: intravenous administration and higher doses produce more adverse events and more severe withdrawal symptoms in those individuals who are opioid dependent. More serious adverse reactions after naloxone administration occur rarely and may be confounded by the effects of other co-intoxicants and the effects of prolonged hypoxia. One component of the new opioid harm reduction initiative is to expand naloxone access to high-risk individuals (addicts, abusers, or patients taking high-dose or extended-release opioids for pain) and their close family or household contacts. Patients or their close contacts receive a naloxone prescription to have the medication on their person or in the home for use during an emergency. Contacts are trained on overdose recognition, rescue breathing and administration of naloxone by intramuscular injection or nasal spraying of the injection prior to the arrival of emergency medical personnel. The safety profile of naloxone in traditional medical use must be considered in this new context of outpatient prescribing, dispensing and treatment of overdose prior to paramedic arrival. New naloxone delivery products are being developed for this prehospital application of naloxone in treatment of opioid

  11. Psychiatric Comorbidity Is Associated Prospectively with Diminished Opioid Analgesia and Increased Opioid Misuse in Patients with Chronic Low Back Pain.

    Science.gov (United States)

    Wasan, Ajay D; Michna, Edward; Edwards, Robert R; Katz, Jeffrey N; Nedeljkovic, Srdjan S; Dolman, Andrew J; Janfaza, David; Isaac, Zach; Jamison, Robert N

    2015-10-01

    Opioids are frequently prescribed for chronic low back pain (CLBP), but there are little prospective data on which patient subgroups may benefit. Psychiatric comorbidity, such as high levels of depression and anxiety symptoms (termed comorbid negative affect [NA]), is a common presentation and may predict diminished opioid analgesia and/or increased opioid misuse. The authors conducted a 6½-month prospective cohort study of oral opioid therapy, with an active drug/placebo run-in period, in 81 CLBP patients with low, moderate, and high levels of NA. Treatment included an opioid titration phase with a prescribing physician blinded to NA group assignment and a 4-month continuation phase, during which subjects recorded daily pain levels using an electronic diary. The primary outcome was the percent improvement in average daily pain, summarized weekly. There was an overall 25% dropout rate. Despite the high NA group being prescribed a higher average daily dose of morphine equivalents, linear mixed model analysis revealed that the 24 study completers in each of the high NA and low NA groups had an average 21 versus 39% improvement in pain, respectively (P < 0.01). The high NA group also had a significantly greater rate of opioid misuse (39 vs. 8%, P < 0.05) and significantly more and intense opioid side effects (P < 0.01). These results indicate that the benefit and risk considerations in CLBP patients with high NA versus low NA are distinctly different. Thus, NA is an important phenotypic variable to characterize at baseline, before deciding whether to prescribe opioids for CLBP.

  12. Classification and identification of opioid addiction in chronic pain patients

    DEFF Research Database (Denmark)

    Højsted, Jette; Nielsen, Per Rotbøll; Guldstrand, Sally Kendall

    2010-01-01

    Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction, to investi......Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction......, to investigate whether PC were applicable and to compare these criteria with the ICD-10 criteria. The study was cross-sectional and included 253 patients with chronic pain at a tertiary pain centre. Patients were screened for addiction by a physician and a nurse. The addiction prevalence was 14.4% according...... as addicted were treated with significantly higher opioid doses, drank more alcohol, smoked more tobacco, used benzodiazepines and had higher levels of depression. According to ICD-10 patients classified as addicted used higher doses of opioids, drank more alcohol and had higher scores of anxiety...

  13. Respiratory depression in the intoxicated trauma patient: are opioids to blame?

    Science.gov (United States)

    Shenk, Eleni; Barton, Cassie A; Mah, Nathan D; Ran, Ran; Hendrickson, Robert G; Watters, Jennifer

    2016-02-01

    Providing effective pain management to acutely intoxicated trauma patients represents a challenge of balancing appropriate pain management with the risk of potential respiratory depression from opioid administration. The objective of this study was to quantify the incidence of respiratory depression in trauma patients acutely intoxicated with ethanol who received opioids as compared with those who did not and identify potential risk factors for respiratory depression in this population. Retrospective medical record review was conducted for subjects identified via the trauma registry who were admitted as a trauma activation and had a detectable serum ethanol level upon admission. Risk factors and characteristics compared included demographics, Injury Severity Score, Glasgow Coma Score, serum ethanol level upon arrival, urine drug screen results, incidence of respiratory depression, and opioid and other sedative medication use. A total of 233 patients were included (78.5% male). Patients who received opioids were more likely to have a higher Injury Severity Score and initial pain score on admission as compared with those who did not receive opioids. Blood ethanol content was higher in patients who did not receive opioids (0.205 vs 0.237 mg/dL, P = .015). Patients who did not receive opioids were more likely to be intubated within 4 hours of admission (1.7% vs 12.1%, P = .02). Opioid administration was not associated with increased risk of respiratory depression (19.7% vs 22.4%, P = .606). Increased cumulative fentanyl dose was associated with increased risk of respiratory depression. Increased cumulative fentanyl dose, but not opioid administration alone, was found to be a risk factor for respiratory depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Computational opioid prescribing: a novel application of clinical pharmacokinetics.

    Science.gov (United States)

    Linares, Oscar A; Linares, Annemarie L

    2011-01-01

    We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist prescribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety.

  15. Prescription and administration of opioids to hospital in-patients, and barriers to effective use.

    Science.gov (United States)

    Murnion, Bridin P; Gnjidic, Danijela; Hilmer, Sarah N

    2010-01-01

    This study aimed to describe prescribing and administration of opioids in a tertiary referral teaching hospital. Secondary aims were assessment of staff knowledge of opioid pharmacology and available preparations, and of perceived barriers limiting opioid use. A cross-sectional survey of in-patients requiring opioid analgesia was performed. An anonymous semi-structured questionnaire was administered to medical and nursing staff. Australian tertiary referral teaching hospital. All patients prescribed opioids on study wards over 3 months (N = 190). Oxycodone was the most frequently prescribed opioid (51.4%). The majority (64.7%) of participants had incomplete pain relief, which was significantly associated with having opioid related side effects. There was no association between pain relief and prescribed daily dose or received daily dose of opioids. Limited understanding of opioid preparations, tolerance, and dependence was demonstrated by staff. The most common perceived barriers to opioid use included difficulties in identifying the right dose, staff time required to prescribe and monitor, and large numbers of preparations. While prescription of inadequate doses was perceived as a barrier, this study identified that submaximal doses were administered. An opioid educational session improved knowledge of opioid formulations. The majority of participants had incomplete pain relief and the maximum prescribed doses of opioids were not administered. Reported barriers included staff knowledge of opioid dose titration and opioid preparations, and time constraints. Identified barriers included poor knowledge of opioid preparations.

  16. Safety profile of injectable hydromorphone and diacetylmorphine for long-term severe opioid use disorder.

    Science.gov (United States)

    Oviedo-Joekes, Eugenia; Brissette, Suzanne; MacDonald, Scott; Guh, Daphne; Marchand, Kirsten; Jutha, Salima; Harrison, Scott; Janmohamed, Amin; Zhang, Derek Z; Anis, Aslam H; Krausz, Michael; Marsh, David C; Schechter, Martin T

    2017-07-01

    To review the safety profile of injectable hydromorphone and diacetylmorphine and explore if adverse events (AEs) or serious adverse events (SAEs) were associated with dose and patterns of attendance. This was a non-inferiority randomized double-blind controlled trial (Vancouver, Canada) testing hydromorphone (n=100) and diacetylmorphine (n=102) for the treatment of severe opioid use disorder. Medications were delivered under the supervision of trained Registered Nurses up to three times daily. AEs were described using MedDRA codes. Most common related AEs included immediate post-injection reaction or injection site pruritus reactions, somnolence and opioid overdoses. Adjusted analysis indicated that participants in the hydromorphone group were less likely to have any related AE or SAE compared to the diacetylmorphine group. Related somnolence and opioid overdose events were distributed throughout the six months treatment period. In the diacetylmorphine group, five of the eleven related SAE opioid overdoses (requiring naloxone) occurred in the first 30days since most recent treatment initiation. Analysis of somnolence and opioid overdose (AEs and SAEs) event rates by received dose suggested a non-linear relationship. However, in the diacetylmorphine group higher event rates per person days were recorded at lower doses. When injectable hydromorphone and diacetylmorphine are individually dosed and monitored, their opioid-related side effects, including potential fatal overdoses, are safely mitigated and treated by health care providers. In the midst of an opioid overdose epidemic, injectable options are timely to reach a very important minority of people who inject street opioids and are not attracted to other treatments. Copyright © 2017. Published by Elsevier B.V.

  17. Perioperative opioid usage: avoiding adverse effects.

    Science.gov (United States)

    Funk, Robert D; Hilliard, Paul; Ramachandran, Satya Krishna

    2014-10-01

    Opioids remain the most common analgesic tool for the surgeon, owing to their cost-effectiveness in both the inpatient and outpatient setting. Aside from these attributes, opioids have significant side effects that are associated with morbidity and mortality. Specifically, obese patients, patients with sleep apnea, and the elderly may be at an increased risk of experiencing sedation and respiratory depression in response to opioids. Opioid reduction strategies prove useful for decreasing total opioid dose and, in turn, their associated adverse effects. Such strategies may include adjuvant nonopioid analgesics such as α-2 agonists, gabapentinoids, and N-methyl-D-aspartate receptor agonists as well as local, regional, or neuraxial anesthesia and modification of surgical technique where possible for operative patients. Patients may also present to surgeons while taking chronic opioids, including high-dose opioids and opioid agonist/antagonists. These clinical scenarios are associated with extreme challenges in postoperative analgesic management. With all opioid prescribing, other sedative medications should be limited or avoided as the risk for additive sedation is significant. This review aims to describe systematic methods to reduce opioid side effects and identify specific risk-reduction strategies within each risk group.

  18. Long-term Prescription of Opioids and/or Benzodiazepines and Mortality Among HIV-Infected and Uninfected Patients.

    Science.gov (United States)

    Weisberg, Daniel F; Gordon, Kirsha S; Barry, Declan T; Becker, William C; Crystal, Stephen; Edelman, Eva J; Gaither, Julie; Gordon, Adam J; Goulet, Joseph; Kerns, Robert D; Moore, Brent A; Tate, Janet; Justice, Amy C; Fiellin, David A

    2015-06-01

    Increased long-term prescription of opioids and/or benzodiazepines necessitates evaluating risks associated with their receipt. We sought to evaluate the association between long-term opioids and/or benzodiazepines and mortality in HIV-infected patients receiving antiretroviral therapy and uninfected patients. Prospective analysis of all-cause mortality using multivariable methods and propensity score matching among HIV-infected patients receiving antiretroviral therapy and uninfected patients. Of 64,602 available patients (16,989 HIV-infected and 47,613 uninfected), 27,128 (exposed and unexposed to long-term opioids and/or benzodiazepines) were 1:1 matched by propensity score. The hazard ratio for death was 1.40 [95% confidence interval (CI): 1.22 to 1.61] for long-term opioid receipt, 1.26 (95% CI: 1.08 to 1.48) for long-term benzodiazepine receipt, and 1.56 (95% CI: 1.26 to 1.92) for long-term opioid and benzodiazepine receipt. There was an interaction (P = 0.01) between long-term opioid receipt and HIV status with mortality. For long-term opioid receipt, the hazard ratio was 1.46 (95% CI: 1.15 to 1.87) among HIV-infected patients, and 1.25 (95% CI: 1.05 to 1.49) among uninfected patients. Mortality risk was increased for patients receiving both long-term opioids and benzodiazepines when opioid doses were ≥ 20 mg morphine-equivalent daily dose and for patients receiving long-term opioids alone when doses were ≥ 50 mg morphine-equivalent daily dose. Long-term opioid receipt was associated with an increased risk of death; especially with long-term benzodiazepine receipt, higher opioid doses, and among HIV-infected patients. Long-term benzodiazepine receipt was associated with an increased risk of death regardless of opioid receipt. Strategies to mitigate risks associated with these medications, and caution when they are coprescribed, are needed particularly in HIV-infected populations.

  19. 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.

  20. Additional benefit of higher dose green tea in lowering postprandial blood glucose

    Directory of Open Access Journals (Sweden)

    Rita Lahirin

    2015-07-01

    Full Text Available Background: Green tea contains catechins that have inhibitory effects on amylase, sucrase, and sodium-dependent glucose transporter (SGLT which result in lowering of postprandial blood glucose (PBG. This beneficial effect has been widely demonstrated using the usual dose (UD of green tea preparation. Our study was aimed to explore futher lowering of PBG using high dose (HD of green tea in healthy adolescents.Methods: 24 subjects received 100 mL infusion of either 0.67 or 3.33 grams of green tea with test meal. Fasting, PBG at 30, 60, 120 minutes were measured. Subjects were cross-overed after wash out. PBG and its incremental area under the curve (IAUC difference between groups were analyzed with paired T-test. Cathecin contents of tea were measured using high-performance liquid chromatography (HPLC.Results: The PBG of HD group was lower compared to UD (at 60 minutes =113.70 ± 13.20 vs 124.16 ± 8.17 mg/dL, p = 0.005; at 120 minutes = 88.95 ± 6.13 vs 105.25 ± 13.85 mg/dL, p < 0.001. The IAUC of HD was also found to be lower compared to UD (2055.0 vs 3411.9 min.mg/dL, p < 0.001.Conclusion: Additional benefit of lowering PBG can be achieved by using higher dose of green tea. This study recommends preparing higher dose of green tea drinks for better control of PBG.

  1. Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain.

    Science.gov (United States)

    Doehring, Alexandra; Oertel, Bruno Georg; Sittl, Reinhard; Lötsch, Jörn

    2013-01-01

    Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics. A major epigenetic mechanism is methylation or demethylation at CpG-rich DNA islands. DNA methylation triggered by drugs has largely unexplored therapeutic consequences. Here we report increased methylation at a CpG rich island in the OPRM1 gene coding for μ-opioid receptors and at a global methylation site (LINE-1) in leukocytes of methadone-substituted former opiate addicts compared with matched healthy controls. Higher DNA methylation associated with chronic opioid exposure was reproduced in an independent cohort of opioid-treated as compared to non-opioid-treated pain patients. This suggests that opioids may stimulate DNA methylation. The OPRM1 methylation had no immediate effect on μ-opioid receptor transcription and was not associated with opioid dosing requirements. However, the global DNA methylation at LINE-1 was significantly correlated with increased chronic pain. This suggests inhibitory effects on the transcription of still unspecified nocifensive gene products. It further implies that opioids may be causally associated with increased genome-wide DNA methylation, although currently there is no direct evidence of this. This has phenotypic consequences for pain and may provide a new, epigenetics-associated mechanism of opioid-induced hyperalgesia. The results indicate a potential influence of opioid analgesics on the patients' epigenome. They emphasize the need for reliable and cost-effective screening tools and may imply that high-throughput screening for lead compounds in artificial expression systems may not provide the best tools for identifying new pain medications. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Evaluating use of higher dose oxybutynin in combination with desmopressin for refractory nocturnal enuresis.

    Science.gov (United States)

    Berkenwald, Aaron; Pires, Jacqueline; Ellsworth, Pamela

    2016-08-01

    /attention-deficit hyperactivity disorder(ADD/ADHD) and CDVS with failure on monotherapy. No patients in the study reported any adverse events or side effects from the medications. The overall success rate of 96.7% with titrated doses of oxybutynin in combination with desmopressin is considerably higher than the response rates on fixed dose combination therapy quoted in the literature and supports the need for further evaluation in larger studies. Additionally, we found a statistically significant association between monotherapy failure and children with either ADD/ADHD or controlled daytime voiding symptoms. Our study is limited by small numbers and larger studies are needed to confirm these results. Our results suggest that ADCT is a safe and effective treatment option for primary nocturnal enuresis refractory to standard and low-dose combination therapy. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  3. Single-dose evaluation of safety, tolerability and pharmacokinetics of newly formulated hydromorphone immediate-release and hydrophilic matrix extended-release tablets in healthy Japanese subjects without co-administration of an opioid antagonist.

    Science.gov (United States)

    Toyama, Kaoru; Uchida, Naoki; Ishizuka, Hitoshi; Sambe, Takehiko; Kobayashi, Shinichi

    2015-09-01

    This single dose, open-label study investigated the safety, tolerability and pharmacokinetics of single oral doses of newly formulated immediate-release (IR) and hydrophilic matrix extended-release (ER) hydromorphone tablets in healthy Japanese subjects without co-administration of an opioid antagonist under fasting and fed conditions. Plasma and urinary concentrations of hydromorphone and metabolites were measured by liquid-chromatography tandem mass-spectroscopy. Following administration of the ER tablet, plasma concentrations of hydromorphone slowly increased with a median tmax of 5.0 h and the Cmax decreased to 37% of the IR tablet, while the AUC0-inf was comparable with that of the IR tablet when administered at the same dose. The degree of fluctuation in the plasma concentration for the ER tablet was much lower than that of the IR tablet and certain levels of plasma concentrations were maintained after 24 h of ER dosing. The AUC0-inf and Cmax increased with food for both IR and ER tablets. The AUC0-inf of hydromorphone-3-glucoside was one-tenth of that of hydromorphone-3-glucuronide. A single oral administration of the hydromorphone tablets would be well-tolerated in healthy Japanese subjects despite a lack of co-administration of an opioid antagonist and the newly developed ER hydromorphone tablets may have the appropriate PK characteristics for once-daily dosing. © 2015, The American College of Clinical Pharmacology.

  4. Variability in prescription opioid intake and reinforcement amongst 129 substrains.

    Science.gov (United States)

    Jimenez, S M; Healy, A F; Coelho, M A; Brown, C N; Kippin, T E; Szumlinski, K K

    2017-09-01

    Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence. All substrains exhibited a dose-dependent increase in oral oxycodone and heroin preference and intake under limited-access procedures and all, but 129S1/SvlmJ mice, exhibited oxycodone reinforcement. Relative to the other substrains, 129P3/J mice exhibited higher heroin and oxycodone intake. While 129X1/SvJ exhibited the highest anxiety-like behavior during natural opioid withdrawal, somatic and behavior signs of precipitated withdrawal were most robust in 129P3/J mice. These results demonstrate the feasibility and relative sensitivity of our oral opioid self-administration procedures for detecting substrain differences in drug reinforcement/intake among 129 mice, of relevance to the identification of genetic variants contributing to high vs. low oxycodone reinforcement and intake. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  5. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    Science.gov (United States)

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis.

    Science.gov (United States)

    Fletcher, D; Martinez, V

    2014-06-01

    Opioids can increase sensitivity to noxious stimuli and cause opioid-induced hyperalgesia. We performed a systematic review to evaluate the clinical consequences of intra-operative doses of opioid. We identified randomized controlled trials which compared intra-operative opioid to lower doses or placebo in adult patients undergoing surgery from MEDLINE, EMBASE, LILAC, Cochrane, and hand searches of trial registries. We pooled data of postoperative pain intensity, morphine consumption, incidence of opioid-related side-effects, primary and secondary hyperalgesia. For dichotomous outcomes relative risks [95% confidence intervals (CIs)] and for continuous outcomes mean differences (MDs) or standardized mean difference (SMD; 95% CI) were calculated. Twenty-seven studies involving 1494 patients were included in the analysis. Patients treated with high intra-operative doses of opioid reported higher postoperative pain intensity than the reference groups (MD: 9.4 cm; 95% CI: 4.4, 14.5) at 1 h, (MD: 7.1 cm; 95% CI: 2.8, 11.3) at 4 h, and (MD: 3 cm; 95% CI: 0.4, 5.6) at 24 h on a 100 cm visual analogue scale. They also showed higher postoperative morphine use after 24 h (SMD: 0.7; 95% CI: 0.37, 1.02). There was no difference in the incidences of nausea, vomiting, and drowsiness. These results were mainly associated with the use of remifentanil. The impact of other opioids is less clear because of limited data. This review suggests that high intra-operative doses of remifentanil are associated with small but significant increases in acute pain after surgery. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. New developments in the management of opioid dependence: focus on sublingual buprenorphine–naloxone

    Directory of Open Access Journals (Sweden)

    Soyka M

    2015-01-01

    Full Text Available Michael Soyka1,21Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany; 2Private Hospital Meiringen, Meiringen, SwitzerlandAbstract: Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine–naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed.Keywords: buprenorphine, methadone, naloxone, opioids, opioid dependence, therapy

  8. Long-term prescription opioids and/or benzodiazepines and mortality among HIV-infected and uninfected patients

    Science.gov (United States)

    Weisberg, DF; Gordon, KS; Barry, DT; Becker, WC; Crystal, S; Edelman, EJ; Gaither, J; Gordon, AJ; Goulet, J; Kerns, RD; Moore, BA; Tate, J; Justice, AC; Fiellin, DA

    2015-01-01

    Background Increased long-term prescribing of opioids and/or benzodiazepines necessitates evaluating risks associated with their receipt. We sought to evaluate the association between long-term opioids and/or benzodiazepines and mortality in HIV-infected patients receiving antiretroviral therapy and uninfected patients. Methods Prospective analysis of all-cause mortality using multivariable methods and propensity score matching among HIV-infected patients receiving antiretroviral therapy and uninfected patients. Results From 64,602 available patients (16,989 HIV-infected and 47,613 uninfected), 27,128 (long-term opioids and/or benzodiazepines exposed and unexposed) were 1:1 matched by propensity score. The hazard ratio (HR) for death was 1.40 (95% confidence interval [CI] 1.22-1.61) for long-term opioid receipt, 1.26 (95% CI 1.08-1.48) for long-term benzodiazepine receipt, and 1.56 (95% CI 1.26-1.92) for long-term opioid and benzodiazepine receipt. There was an interaction (p= 0.01) between long-term opioid receipt and HIV status with mortality. For long-term opioid receipt, the HR was 1.46 (95% CI 1.15-1.87) among HIV-infected patients, and 1.25 (95% CI 1.05 – 1.49) among uninfected patients. Mortality risk was increased for patients receiving both long-term opioids and benzodiazepines when opioid doses were ≥20mg morphine equivalent daily dose (MEDD) and for patients receiving long-term opioids alone when doses were ≥50mg MEDD. Conclusions Long-term opioid receipt was associated with an increased risk of death; especially with long-term benzodiazepine receipt, higher opioid doses and among HIV-infected patients. Long-term benzodiazepine receipt was associated with an increased risk of death regardless of opioid receipt. Strategies to mitigate risks associated with these medications, and caution when they are co-prescribed, are needed particularly in HIV-infected populations. PMID:26009831

  9. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment : a randomized controlled trial

    NARCIS (Netherlands)

    De Jong, Cor A J; Laheij, Robert J F; Krabbe, Paul F M

    AIM: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  10. General anaesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomized controlled trial.

    NARCIS (Netherlands)

    Jong, C.A.J. de; Laheij, R.J.F.; Krabbe, P.F.M.

    2005-01-01

    AIM: Opioid detoxification by administering opioid-antagonists under general anaesthesia has caused considerable controversy. This study is conducted to determine whether rapid detoxification under general anaesthesia results in higher levels of opioid abstinence than rapid detoxification without

  11. Opioid Overdose Outbreak - West Virginia, August 2016.

    Science.gov (United States)

    Massey, Joel; Kilkenny, Michael; Batdorf, Samantha; Sanders, Sarah K; Ellison, Debra; Halpin, John; Gladden, R Matthew; Bixler, Danae; Haddy, Loretta; Gupta, Rahul

    2017-09-22

    On August 15, 2016, the Mayor's Office of Drug Control Policy in Huntington, West Virginia, notified the Cabell-Huntington Health Department (CHHD) of multiple calls regarding opioid overdose received by the emergency medical system (EMS) during 3 p.m.-8 p.m. that day. A public health investigation and response conducted by the West Virginia Bureau for Public Health (BPH) and CHHD identified 20 opioid overdose cases within a 53-hour period in Cabell County; all cases included emergency department (ED) encounters. EMS personnel, other first responders, and ED providers administered the opioid antidote naloxone to 16 (80%) patients, six of whom were administered multiple doses, suggesting exposure to a highly potent opioid. No patients received referral for recovery support services. In addition to the public health investigation, a public safety investigation was conducted; comprehensive opioid toxicology testing of clinical specimens identified the synthetic opioid fentanyl* and novel fentanyl analogs, including carfentanil,† which had been used by patients who overdosed in Huntington. Results of these two investigations highlight the importance of collaboration between public health and public safety agencies to provide in-depth surveillance data from opioid overdose outbreaks that involve high-potency fentanyl analogs. These data facilitated a public health response through increased awareness of powerful opioid substances requiring multiple naloxone doses for reversal, and improved patient linkage to recovery support services and a harm reduction program from the ED after opioid overdose.

  12. Postoperative opioid analgesia: time for a reconsideration?

    DEFF Research Database (Denmark)

    Kehlet, H; Rung, G W; Callesen, T

    1996-01-01

    ;72:375-8). Many initial improvements simply involved the administration of opioid analgesics in new ways, such as continuous or on demand intravenous (i.v.) or epidural infusion. These methods allow lower total opioid dosages, provide a more stable concentration of opioid at the receptor and correspondingly...... better analgesic effects, and also fewer unwanted side effects. Although opioids have played a prominent role in postoperative analgesia for centuries and are still often administered as a matter of routine, their frequent minor side effects and the increasing availability of suitable alternatives may...... relief-what is the issue? Br J Anaesth 1994;72:375-8)] provide an opportunity for a reappraisal of opioid use in these settings. For this debate, controlled clinical studies on the opioid-sparing effect of different analgesic techniques are mentioned, and preferably studies with multiple dosing...

  13. The effect of opioids on sleep architecture.

    Science.gov (United States)

    Dimsdale, Joel E; Norman, Daniel; DeJardin, Douglas; Wallace, Mark S

    2007-02-15

    The effect of opioid medications on sleep architecture has been demonstrated in patients with comorbid pain or opioid addiction. This study examined whether commonly used opioid medications have an adverse effect on sleep architecture in healthy adults. Forty-two healthy subjects were examined with polysomnography after a bedtime dose of placebo, sustained-release morphine sulfate (15 mg), or methadone (5 mg) on each of 3 different nights in a double-blind multiple crossover study in a sleep laboratory in the General Clinical Research Center at an academic medical center. Both opioid drugs significantly reduced deep sleep and increased stage 2 sleep (both p architecture in healthy adults, and observed reductions in slow-wave sleep following opioid administration may have important implications for the pathogenesis of opioid-use related fatigue.

  14. Opioid-prescribing practices and provider confidence recognizing opioid analgesic abuse in HIV primary care settings.

    Science.gov (United States)

    Lum, Paula J; Little, Sherri; Botsko, Michael; Hersh, David; Thawley, Robert E; Egan, James E; Mitty, Jennifer; Boverman, Joshua; Fiellin, David A

    2011-03-01

    Pain syndromes are common in HIV-infected patients, who also are commonly affected by opioid-use disorders. Although opioids can treat pain, prescribers must consider the consequences of iatrogenic or missed addiction diagnoses. In an anonymous online survey, we asked a national sample of HIV providers about their demographics, experience, and patients, and their practices and attitudes about chronic opioid therapy, addiction, and confidence recognizing opioid analgesic abuse. One hundred six providers reported 28% of their patients had chronic pain; 21% received opioid analgesics; 37% were HIV infected by injecting drug use; and 12% were addicted to prescription opioids. Few providers followed recommended guidelines for chronic opioid therapy in nonmalignant pain. Mean provider confidence was 6.3 on a scale of 10. Higher confidence was associated with provider sex (P opioids (P = 0.005), and prescribing buprenorphine (P = 0.009). HIV providers seldom follow recommended guidelines for opioid prescribing and have limited confidence in their ability to recognize opioid analgesic abuse. Clinical practices developed to reduce misuse and increase early detection and treatment of opioid dependence are associated with higher confidence. The implementation of guidelines to improve the quality of opioid prescribing in HIV clinics may aid in the diagnosis of addictive disorders and prevent their adverse outcomes.

  15. Opioid errors in inpatient palliative care services: a retrospective review.

    Science.gov (United States)

    Heneka, Nicole; Shaw, Tim; Rowett, Debra; Lapkin, Samuel; Phillips, Jane L

    2018-01-04

    Opioids are a high-risk medicine frequently used to manage palliative patients' cancer-related pain and other symptoms. Despite the high volume of opioid use in inpatient palliative care services, and the potential for patient harm, few studies have focused on opioid errors in this population. To (i) identify the number of opioid errors reported by inpatient palliative care services, (ii) identify reported opioid error characteristics and (iii) determine the impact of opioid errors on palliative patient outcomes. A 24-month retrospective review of opioid errors reported in three inpatient palliative care services in one Australian state. Of the 55 opioid errors identified, 84% reached the patient. Most errors involved morphine (35%) or hydromorphone (29%). Opioid administration errors accounted for 76% of reported opioid errors, largely due to omitted dose (33%) or wrong dose (24%) errors. Patients were more likely to receive a lower dose of opioid than ordered as a direct result of an opioid error (57%), with errors adversely impacting pain and/or symptom management in 42% of patients. Half (53%) of the affected patients required additional treatment and/or care as a direct consequence of the opioid error. This retrospective review has provided valuable insights into the patterns and impact of opioid errors in inpatient palliative care services. Iatrogenic harm related to opioid underdosing errors contributed to palliative patients' unrelieved pain. Better understanding the factors that contribute to opioid errors and the role of safety culture in the palliative care service context warrants further investigation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Drug Overdose: Differing Risk Models for Women and Men among Opioid Users with Non-Cancer Pain.

    Science.gov (United States)

    Liang, Yuanyuan; Goros, Martin W; Turner, Barbara J

    2016-12-01

    To examine risk factors for drug overdose by sex reflecting differing patterns of opioid and other drug use. National privately insured cohort. 206,869 subjects filling ≥2 opioid prescriptions from January 2009 through July 2012. Sex-specific prediction models for future drug overdose developed and validated using variables measured within 6 months after starting opioids: demographics, substance use, comorbidities, opioid dose, and psychoactive drugs. Logistic regression and split-sample validation were used. Area under the receiver operating curves (AUCs) for both sex-specific risk models (0.80) were higher (P opioid dose alone. Risk factors for drug overdose were similar by sex but effects differed. For both sexes, substance use was the strongest predictor but the adjusted odds ratio (AOR) [95% CI] was 5.95 [4.33, 8.06] for women vs. 4.69 [3.24, 6.68] for men. AORs for daily opioid dose rose monotonically in men to 2.42 [1.76, 3.28] for high vs. low dose but were non-monotonic in women with 1.79 [1.35, 2.35] for high dose. AOR for 1-60 days of antidepressants vs. none was significant only in men (1.98 [1.32, 2.9]). AOR for benzodiazepine use was higher in men than women (2.75 vs 2.35, respectively). Zolpidem use was significant only in women. AUCs for sex-specific models were lower for the opposite sex and significantly lower for the men's model in the women's derivation dataset. These models reveal similar risk factors by sex for drug overdose in opioid users but significant differences in effects that, if validated in other cohorts, may inform differing risk management strategies. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. 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 ...

  18. Opioid Abuse and Addiction

    Science.gov (United States)

    Opioids, sometimes called narcotics, are a type of drug. They include strong prescription pain relievers, such as ... tramadol. The illegal drug heroin is also an opioid. Some opioids are made from the opium plant, ...

  19. Assessment of low-dose radiotoxicity in microorganisms and higher organisms

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, Muhammad Hassan

    2016-01-11

    This work was dedicated to quantify and distinguish the radio- and chemitoxic effects of environmentally relevant low doses of uranium on the metabolism of microorganisms and multicellular organisms by a modern and highly sensitive microcalorimetry. In such low-dose regime, lethality is low or absent. Therefore, quantitative assays based on survival curves cannot be employed, particularly for multicellular organisms. Even in the case of microbial growth, where individual cells may be killed by particle radiation, classical toxicity assessments based on colony counting are not only extremely time-consuming but also highly error-prone. Therefore, measuring the metabolic activity of the organism under such kinds of conditions would give an extremely valuable quantitative measure of viability that is based on life cell monitoring, rather than determining lethality at higher doses and extrapolating it to the low dose regime. The basic concept is simple as it relies on the metabolic heat produced by an organism during development, growth or replication as an inevitable byproduct of all biochemical processes. A metabolic effect in this concept is defined as a change in heat production over time in the presence of a stressor, such as a heavy metal. This approach appeared to be particular versatile for the low dose regime. Thus, the thesis attempted in this case to measure the enthalpy production of a bacterial population as a whole to derive novel toxicity concepts. In the following chapters, an introduction about the properties of ionizing radiation will be briefly presented, in addition to a review about the isothermal calorimetry and its application in studying the bacterial growth. Later in chapter 2, the effect of uranium on the metabolic activity of three different bacterial strains isolated form a uranium mining waste pile together with a reference strain that is genetically related to them will be investigated. Due to the lack of published dedicated calibration

  20. Risks for Opioid Abuse and Dependence Among Recipients of Chronic Opioid Therapy: Results from the TROUP Study

    Science.gov (United States)

    Edlund, Mark J.; Martin, Bradley C.; Fan, Ming-Yu; Devries, Andrea; Braden, Jennifer B.; Sullivan, Mark D.

    2010-01-01

    Objective To estimate the prevalence of and risk factors for opioid abuse/dependence in long-term users of opioids for chronic pain, including risk factors for opioid abuse/dependence that can potentially be modified to decrease the likelihood of opioid abuse/dependence, and non-modifiable risk factors for opioid abuse/dependence that may be useful for risk stratification when considering prescribing opioids. Methods We used claims data from two disparate populations, one national, commercially insured population (HealthCore) and one state-based, publicly insured (Arkansas Medicaid). Among users of chronic opioid therapy, we regressed claims-based diagnoses of opioid abuse/dependence on patient characteristics, including physical health, mental health and substance abuse diagnoses, sociodemographic factors, and pharmacological risk factors. Results Among users of chronic opioid therapy, 3% of both the HealthCore and Arkansas Medicaid samples had a claims-based opioid abuse/dependence diagnosis. There was a strong inverse relationship between age and a diagnosis of opioid abuse/dependence. Mental health and substance use disorders were associated with an increased risk of opioid abuse/dependence. Effects of substance use disorders were especially strong, although mental health disorders were more common. Concerning opioid exposure; lower days supply, lower average doses, and use of Schedule III-IV opioids only, were all associated with lower likelihood of a diagnosis of opioid abuse/dependence. Conclusion Opioid abuse and dependence are diagnosed in a small minority of patients receiving chronic opioid therapy, but this may underestimate actual misuse. Characteristics of the patients and of the opioid therapy itself are associated with the risk of abuse and dependence. PMID:20634006

  1. Patterns of Opioid Use and Risk of Opioid Overdose Death Among Medicaid Patients.

    Science.gov (United States)

    Garg, Renu K; Fulton-Kehoe, Deborah; Franklin, Gary M

    2017-07-01

    The Centers for Disease Control and Prevention recognizes Medicaid as a high-risk population for fatal opioid overdose. Further research is needed to identify factors that put Medicaid patients at increased risk. To determine whether patterns of opioid use are associated with risk of opioid-related mortality among opioid users. This is a retrospective cohort study. In total, 150,821 noncancer pain patients aged 18-64 years with ≥1 opioid prescription, April 2006 to December 2010, Washington Medicaid. Average daily dose (morphine equivalents), opioid schedule/duration of action, sedative-hypnotic use. Compared with patients at 1-19 mg/d, risk of opioid overdose death significantly increased at 50-89 mg/d [adjusted hazard ratio (aHR), 2.3; 95% confidence interval (CI), 1.4-4.1], 90-119 mg/d (aHR, 4.0; 95% CI, 2.2-7.3), 120-199 mg/d (aHR, 3.8; 95% CI, 2.1-6.9), and ≥200 mg/d (aHR, 4.9; 95% CI, 2.9-8.1). Patients using long-acting plus short-acting Schedule II opioids had 4.7 times the risk of opioid overdose death than non-Schedule II opioids alone (aHR, 4.7; 95% CI, 3.3-6.9). Sedative-hypnotic use compared with nonuse was associated with 6.4 times the risk of opioid overdose death (aHR, 6.4; 95% CI, 5.0-8.4). Risk was particularly high for opioids combined with benzodiazepines and skeletal muscle relaxants (aHR, 12.6; 95% CI, 8.9-17.9). Even at opioid doses 1-19 mg/d, patients using sedative-hypnotics concurrently had 5.6 times the risk than patients without sedative-hypnotics (aHR, 5.6; 95% CI, 1.6-19.3). Our findings support Federal guideline-recommended dosing thresholds in opioid prescribing. Concurrent sedative-hypnotic use even at low opioid doses poses substantially greater risk of opioid overdose.

  2. Relapse prevention medications in community treatment for young adults with opioid addiction.

    Science.gov (United States)

    Vo, Hoa T; Robbins, Erika; Westwood, Meghan; Lezama, Debra; Fishman, Marc

    2016-01-01

    Despite the well-known effectiveness and widespread use of relapse prevention medications such as extended release naltrexone (XR-NTX) and buprenorphine for opioid addiction in adults, less is known about their use in younger populations. This was a naturalistic study using retrospective chart review of N = 56 serial admissions into a specialty community treatment program that featured the use of relapse prevention medications for young adults (19-26 years old) with opioid use disorders. Treatment outcomes over 24 weeks included retention and weekly opioid-negative urine tests. Patients were of mean age 23.1, 70% male, 86% Caucasian, 82% with history of injection heroin use, and treated with either buprenorphine (77%) or XR-NTX (23%). The mean number of XR-NTX doses received was 4.1. Retention was approximately 65% at 12 weeks and 40% at 24 weeks, and rates of opioid-negative urine were 50% at 12 weeks and 39% at 24 weeks, with missing samples imputed as positive. There were no statistically significant differences in retention (t = 1.87, P = .06) or in rates of weekly opioid-negative urine tests (t = 1.96, P = .06) between medication groups, over the course of 24 weeks. The XR-NTX group had higher rates of weekly negative urine drug tests for other nonopioid substances (t = 2.83, P < .05) compared with the buprenorphine group. Males were retained in treatment longer and had higher rates of opioid-negative weeks compared with females. These results suggest that relapse prevention medications including both buprenorphine and XR-NTX can be effectively incorporated into standard community treatment for opioid addiction in young adults with good results. Specialty programming focused on opioid addiction in young adults may provide a promising model for further treatment development.

  3. The relationship between overactivity and opioid use in chronic pain: a 5-day observational study.

    Science.gov (United States)

    Andrews, Nicole Emma; Strong, Jenny; Meredith, Pamela Joy; Fleming, Julia Ann

    2016-02-01

    With increasing concerns about the potential harm of long-term opioid therapy, there is a need for the development and implementation of alternative treatment strategies for patients with chronic pain who have been using opioids for a prolonged period of time. Based on the findings from a recent qualitative investigation that suggested there may be a bidirectional association between opioid reliance and habitual overactivity behaviour (activity engagement that significantly exacerbates pain), this study was designed to quantitatively investigate the association between opioid use and habitual overactivity over a 5-day period in a group of chronic pain patients. Participants provided a list of their prescribed pain medication, completed a self-report measure of habitual overactivity, and then commenced 5 days of data collection. Data collection required participants to wear an activity monitor and to complete a diary that detailed their daily activities and the time at which they took medication. Individuals reporting higher levels of habitual overactivity were more likely to be prescribed opioids. In addition, higher levels of habitual overactivity were associated with more frequent pro re nata ("as needed") opioid use over the 5 days, and with a discrepancy between the prescribed and actual oral morphine-equivalent daily dose, where more medication was taken than was prescribed. There was no predominant context for pro re nata use. The results of this study support the idea that habitual overactivity behaviour may play a role in the development of reliance on opioid medication and that such an association may provide a potential treatment target for opioid therapy rationalisation.

  4. Higher Rates of Dose Optimisation for Infliximab Responders in Ulcerative Colitis than in Crohn's disease.

    Science.gov (United States)

    O'Donnell, Sarah; Stempak, Joanne M; Steinhart, A Hillary; Silverberg, Mark S

    2015-10-01

    Studies have demonstrated the benefit of dose optimisation in the setting of secondary loss of response to infliximab in inflammatory bowel disease. The aim of our study was to retrospectively investigate the rates of dose optimisation in an inflammatory bowel disease cohort receiving maintenance infliximab therapy to determine if there are different rates of dose optimisation between CD and UC cases and what impact this has on the durability of treatment effect. Cases receiving infliximab for treatment of IBD between January 2008 and February 2014 were identified from an infusion centre database. Cases receiving ≥ 4 infusions were included in the study. Details of infusion dosing and timing were obtained. A dose increase from 5mg/kg to 10mg/kg or a reduction in the dosing interval was considered a dose optimisation. A total of 412 cases were included in the study; 52.7% required at least one dose optimisation. Dose optimisation was more common in UC than in CD cases [67.2% vs 46.3%, p = 0.00006]. The median time to dose optimisation was 7 months (95% confidence interval [CI] 4.8-9.2) for UC cases and 27 months [95% CI 7.3-46.7] for CD cases, p = 0.00003. Here we have shown that dose optimisation is required more frequently in UC than in CD, with a significantly shorter time to dose optimisation for UC cases than CD cases. The majority of cases responding to induction therapy with infliximab will have a sustained response to therapy, but over 50% will require a dose optimisation during their treatment. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Naltrexone extended-release injection: an option for the management of opioid abuse

    Directory of Open Access Journals (Sweden)

    Taylor Jr R

    2011-12-01

    receptor antagonism by taking higher doses of an opioid agonist or if opioid receptors become "sensitized" under long-term antagonism. The focus of the present review is the current information regarding the safety and efficacy of naltrexone extended-release therapy.Keywords: opioid dependence, relapse prevention, depot injection, extended-release naltrexone

  6. Use of immediate-release opioids as supplemental analgesia during management of moderate-to-severe chronic pain with buprenorphine transdermal system

    Directory of Open Access Journals (Sweden)

    Silverman S

    2017-05-01

    Full Text Available Sanford Silverman,1,2 Robert B Raffa,3,4 Marc J Cataldo,5 Monica Kwarcinski,5 Steven R Ripa5 1Comprehensive Pain Medicine, Pompano Beach, 2Department of Integrated Medical Sciences, Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 3Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA, 4Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 5Purdue Pharma LP, Stamford, CT, US Background: The buprenorphine transdermal system (BTDS is approved in the US for the management of chronic pain. Due to its high affinity for μ-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing μ-opioid-receptor agonists, including immediate-release (IR opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable.Materials and methods: This post hoc analysis evaluated the use of IR opioids as supplemental analgesia during the management of moderate–severe chronic pain with BTDS at 52 US sites (BUP3015S, NCT01125917. Patients were categorized into IR-opioid and no-IR-opioid groups. At each visit of the extension phase, adverse events, concomitant medications, and information from the Brief Pain Inventory (BPI were recorded.Results: The most common supplemental IR opioids prescribed during BTDS treatment (n=354 were hydrocodone–acetaminophen and oxycodone–acetaminophen. The mean daily dose of IR opioids (morphine equivalents for supplemental analgesia was 22 mg. At baseline, BPI – pain intensity and BPI – interference scores were higher for patients in the IR-opioid group. In both treatment groups, scores improved by week 4, and then were maintained throughout 6 months of the open-label extension trial. The incidence of treatment-emergent adverse events was similar in

  7. Survey of Ontario primary care physicians’ experiences with opioid prescribing

    Science.gov (United States)

    Wenghofer, Elizabeth Francis; Wilson, Lynn; Kahan, Meldon; Sheehan, Carolynn; Srivastava, Anita; Rubin, Ava; Brathwaite, Joanne

    2011-01-01

    Abstract Objective To measure physicians’ experiences with opioid-related adverse events and their perceived level of confidence in their opioid prescribing skills and practices. Design Mailed survey. Setting The province of Ontario. Participants A total of 1000 primary care physicians randomly selected from the College of Physicians and Surgeons of Ontario registration database. Main outcome measures Opioid-related adverse events and concerns (eg, number of patients, type of opioid, cause of the event or concern); physicians’ confidence, comfort, and satisfaction with opioid prescribing; physicians’ opinions on strategies to optimize their prescribing; and physicians’ perspectives of their interactions with pharmacists and nurses. Results The response rate was close to 66%, for a total of 658 participants. Almost all respondents reported prescribing opioids for chronic pain in the past 3 months. Eighty-six percent of respondents reported being confident in their prescribing of opioids, but 42% of respondents indicated that at least 1 patient had experienced an adverse event related to opioids in the past year, usually involving oxycodone, and 16.3% of respondents did not know if their patients had experienced any opioid-related adverse events. The most commonly cited factors leading to adverse events were that the patient took more than prescribed, the prescribed dose was too high, or the patient took alcohol or sedating drugs with the opioids. Most physicians had concerns about the opioid use of 1 or more of their patients; concerns included running out of opioids early, minimal access to pain and addiction treatment, and addiction and overdose. The reported number of physicians’ patients taking opioids was positively associated with their confidence and comfort levels in opioid prescribing and negatively associated with their belief that many patients become addicted to opioids. Conclusion Most physicians have encountered opioid-related adverse events

  8. Survey of Ontario primary care physicians' experiences with opioid prescribing.

    Science.gov (United States)

    Wenghofer, Elizabeth Francis; Wilson, Lynn; Kahan, Meldon; Sheehan, Carolynn; Srivastava, Anita; Rubin, Ava; Brathwaite, Joanne

    2011-03-01

    To measure physicians' experiences with opioid-related adverse events and their perceived level of confidence in their opioid prescribing skills and practices. Mailed survey. Setting The province of Ontario. A total of 1000 primary care physicians randomly selected from the College of Physicians and Surgeons of Ontario registration database. Opioid-related adverse events and concerns (eg, number of patients, type of opioid, cause of the event or concern); physicians' confidence, comfort, and satisfaction with opioid prescribing; physicians' opinions on strategies to optimize their prescribing; and physicians' perspectives of their interactions with pharmacists and nurses. The response rate was close to 66%, for a total of 658 participants. Almost all respondents reported prescribing opioids for chronic pain in the past 3 months. Eighty-six percent of respondents reported being confident in their prescribing of opioids, but 42% of respondents indicated that at least 1 patient had experienced an adverse event related to opioids in the past year, usually involving oxycodone, and 16.3% of respondents did not know if their patients had experienced any opioid-related adverse events. The most commonly cited factors leading to adverse events were that the patient took more than prescribed, the prescribed dose was too high, or the patient took alcohol or sedating drugs with the opioids. Most physicians had concerns about the opioid use of 1 or more of their patients; concerns included running out of opioids early, minimal access to pain and addiction treatment, and addiction and overdose. The reported number of physicians' patients taking opioids was positively associated with their confidence and comfort levels in opioid prescribing and negatively associated with their belief that many patients become addicted to opioids. Most physicians have encountered opioid-related adverse events. Comprehensive strategies are required to promote safe prescribing of opioids, including

  9. The clinical implications of cytochrome p450 interactions with opioids and strategies for pain management.

    Science.gov (United States)

    Brennan, Michael J

    2012-12-01

    Pharmacokinetic differences among opioids influence a patient's response to opioid treatment. An important element affecting a drug's pharmacokinetics, its metabolism, may be altered under various circumstances, thereby enhancing or mitigating a patient's response to opioids. The genetic background of the metabolic enzymes involved in opioid metabolism, comorbid medical conditions, older age, and the presence of other drugs that influence metabolism are such factors that can cause the response to opioid therapy to vary greatly from the expected response to a standard dose. As a result of the variability in individual responses to opioids, clinical management of pain with opioids must be empirical. Copyright © 2012. Published by Elsevier Inc.

  10. Low-dose combination therapy: the rationalization for an ACE inhibitor and a calcium channel blocker in higher risk patients.

    Science.gov (United States)

    Kaplan, N M

    2001-05-01

    As more high-risk hypertensives are treated and the need for more intensive antihypertensive therapy is recognized, combination therapies are increasingly used. For initial therapy, particularly for relatively low-risk patients, low-dose combinations are often appropriate. For those who require additional therapy, higher doses of combinations may provide further efficacy while minimizing dose-dependent side effects of monotherapy, thereby improving adherence to therapy. Those combination agents should provide 24-h control with one daily dose, thereby ensuring protection in the early morning hours. Combining an angiotensin converting enzyme inhibitor and a calcium channel blocker is a rational approach to treating hypertension. Not only does it provide significantly better blood pressure control than individual components used as monotherapy, it also minimizes dose-dependent side effects. Also, combining agents from different classes results in complementary mechanisms of action that provide other cardiovascular protective benefits.

  11. 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.

  12. Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa.

    Science.gov (United States)

    Matsumoto, Kenjiro; Horie, Syunji; Ishikawa, Hayato; Takayama, Hiromitsu; Aimi, Norio; Ponglux, Dhavadee; Watanabe, Kazuo

    2004-03-12

    Mitragynine is an indole alkaloid isolated from the Thai medicinal plant Mitragyna speciosa. We previously reported the morphine-like action of mitragynine and its related compounds in the in vitro assays. In the present study, we investigated the opioid effects of 7-hydroxymitragynine, which is isolated as its novel constituent, on contraction of isolated ileum, binding of the specific ligands to opioid receptors and nociceptive stimuli in mice. In guinea-pig ileum, 7-hydroxymitragynine inhibited electrically induced contraction through the opioid receptors. Receptor-binding assays revealed that 7-hydroxymitragynine has a higher affinity for micro-opioid receptors relative to the other opioid receptors. Administration of 7-hydroxymitragynine (2.5-10 mg/kg, s.c.) induced dose-dependent antinociceptive effects in tail-flick and hot-plate tests in mice. Its effect was more potent than that of morphine in both tests. When orally administered, 7-hydroxymitragynine (5-10 mg/kg) showed potent antinociceptive activities in tail-flick and hot-plate tests. In contrast, only weak antinociception was observed in the case of oral administration of morphine at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid agonist that is structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.

  13. Does Association of Opioid Use with Pain and Function Differ by Fibromyalgia/Widespread Pain Status?

    Science.gov (United States)

    Turner, Judith A.; Shortreed, Susan M.; Saunders, Kathleen W.; LeResche, Linda; Thielke, Stephen; Von Korff, Michael

    2016-01-01

    Many consider chronic opioid therapy (COT) to be ineffective for fibromyalgia, but empirical evidence is limited. Among patients identified as initiating COT, we examined whether fibromyalgia was associated with different relationships of opioid use to pain and activity interference outcomes 12 months later. We obtained electronic data on diagnoses and opioid prescriptions. We obtained patient self-report data, including pain and activity interference measures, at baseline, 4 months, and 12 months. Among 1,218 patients, 429 (35%) met our definition of fibromyalgia. Patients with and without fibromyalgia who had intermittent/lower-dose or regular/higher-dose opioid use at 12 months had similar 12-month pain intensity scores. However, among patients with minimal/no opioid use at 12 months, 12-month pain intensity was greater for those with fibromyalgia (adjusted mean = 5.15 [95% CI = 4.80, 5.51]; 0-10 scale) than for those without (4.44 [4.15, 4.72]). Similar patterns were observed for 12-month activity interference. Among patients who discontinued opioids by 12 months, those with fibromyalgia were more likely to report bothersome side effects and less likely to report pain improvement as important reasons for discontinuation (P-values fibromyalgia had worse outcomes and were less likely to have discontinued due to pain improvement. Among patients continuing COT, pain and activity interference outcomes were worse than those of patients with minimal/no opioid use and did not differ for those with fibromyalgia versus those with diverse other chronic pain conditions. PMID:27643834

  14. Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

    Science.gov (United States)

    Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Elayi, Samy Claude; Walsh, Sharon L

    2016-07-01

    The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21h before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance. Oxycodone produced prototypic opioid agonist effects (i.e. suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10mg produced effects most similar to placebo, while the 20 and 30mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose. CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.

    Science.gov (United States)

    Sehgal, Nalini; Colson, James; Smith, Howard S

    2013-11-01

    Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

  16. ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy.

    Science.gov (United States)

    2012-05-01

    Opioid use in pregnancy is not uncommon, and the use of illicit opioids during pregnancy is associated with an increased risk of adverse outcomes. The current standard of care for pregnant women with opioid dependence is referral for opioid-assisted therapy with methadone, but emerging evidence suggests that buprenorphine also should be considered. Medically supervised tapered doses of opioids during pregnancy often result in relapse to former use. Abrupt discontinuation of opioids in an opioid-dependent pregnant woman can result in preterm labor, fetal distress, or fetal demise. During the intrapartum and postpartum period, special considerations are needed for women who are opioid dependent to ensure appropriate pain management, to prevent postpartum relapse and a risk of overdose, and to ensure adequate contraception to prevent unintended pregnancies. Patient stabilization with opioid-assisted therapy is compatible with breastfeeding. Neonatal abstinence syndrome is an expected and treatable condition that follows prenatal exposure to opioid agonists.

  17. Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

    Science.gov (United States)

    Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

    2017-10-01

    Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHDvitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Solhaug, Vigdis; Molden, Espen

    2017-10-17

    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

  19. Potential misuse and inappropriate prescription practices involving opioid analgesics.

    Science.gov (United States)

    Liu, Ying; Logan, Joseph E; Paulozzi, Leonard J; Zhang, Kun; Jones, Christopher M

    2013-08-01

    Opioid misuse and abuse are growing concerns among the medical and public health communities. To examine the prevalence of indicators for potential opioid misuse in a large, commercially insured adult population. We adapted existing indicators developed by expert panels to include having overlapping opioid prescriptions, overlapping opioid and benzodiazepine prescriptions, long-acting/ extended release (LA/ER) opioids for acute pain,and high daily doses of opioids (>100 morphine milligram equivalents). These indicators were assessed among continuously enrolled individuals aged 18-64 years from the 2009 Truven Health MarketScan databases. Analyses were stratified by sex. We identified 3,391,599 eligible enrollees who received at least 1 opioid prescription. On average, enrollees obtained 3.3 opioid prescriptions, and the average annual days of supply was 47 days. Twice as many enrollees received opioid prescriptions for acute pain as for chronic pain. About a quarter of the enrollees had at least 1 indicator of either potential misuse by patients or inappropriate prescription practices by providers. About 15% of enrollees had high daily doses;7.8% had opioid overlap; and 7.9% had opioid and benzodiazepine overlap. Among those prescribed LA/ER opioids, 24.3% were treated for acute pain. Overlap indicators were more common among women. Our findings underscore the critical need to develop programs aimed at promoting appropriate use of opioids. Retrospective opioid utilization reviews similar to our analyses can potentially help managed care organizations and healthcare providers improve patient care and reduce the risk of adverse outcomes related to these medications.

  20. Mechanism of the Interaction of Cannabinoid System in Central Amygdale with Opioid System

    Directory of Open Access Journals (Sweden)

    S. Sarahroodi

    2008-01-01

    Full Text Available Background and objectivesCannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.MethodsIn the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala (intra-Amyg microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety. ResultsIntraperitoneal injection of morphine (3, 6 and 9 mg/kg increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced %OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA (at the dose of 1.25 and 5 ng/rat increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine (6 mg/kg, i.p. without any interaction. Naloxone also reduced ACPA effects. Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 (2.5, 25 and 100 ng/rat did not alter %OAT and %OAE but higher doses of drug (25 and 100 ng/rat reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety.ConclusionThe results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid system may have interaction with cannabinoid receptor in the amygdale. Keywords: Cannabinoids, Morphine; Naloxone, Anxiety, Elevated Plus-Maze

  1. Higher Chest Wall Dose Results in Improved Locoregional Outcome in Patients Receiving Postmastectomy Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Panoff, Joseph E.; Takita, Cristiane [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Hurley, Judith [Department of Medicine, Division of Hematology and Oncology, Miller School of Medicine, University of Miami, Miami, Florida (United States); Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Reis, Isildinha M. [Department of Epidemiology and Public Health and Sylvester Division of Biostatistics, University of Miami Miller School of Medicine, Miami, Florida (United States); Sylvester Division of Biostatistics and Bioinformatics Core, University of Miami Miller School of Medicine, Miami, Florida (United States); Zhao, Wei [Sylvester Division of Biostatistics and Bioinformatics Core, University of Miami Miller School of Medicine, Miami, Florida (United States); Rodgers, Steven E. [Department of Medicine, Division of Hematology and Oncology, Miller School of Medicine, University of Miami, Miami, Florida (United States); Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Gunaseelan, Vijayalakshmi [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Wright, Jean L., E-mail: Jwright3@med.miami.edu [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States)

    2012-03-01

    Purpose: Randomized trials demonstrating decreased locoregional recurrence (LRR) and improved overall survival (OS) in women receiving postmastectomy radiation therapy (PMRT) used up to 50 Gy to the chest wall (CW), but in practice, many centers boost the CW dose to {>=}60 Gy, despite lack of data supporting this approach. We evaluated the relationship between CW dose and clinical outcome. Methods and Materials: We retrospectively reviewed medical records of 582 consecutively treated patients who received PMRT between January 1999 and December 2009. We collected data on patient, disease, treatment characteristics, and outcomes of LRR, progression-free survival (PFS) and OS. Results: Median follow-up from the date of diagnosis was 44.7 months. The cumulative 5-year incidence of LRR as first site of failure was 6.2%. CW dose for 7% (43 patients) was {<=}50.4 Gy (range, 41.4-50.4 Gy) and 93% received >50.4 Gy (range, 52.4-74.4 Gy). A CW dose of >50.4 Gy vs. {<=}50.4 Gy was associated with lower incidence of LRR, a 60-month rate of 5.7% (95% confidence interval [CI], 3.7-8.2) vs. 12.7% (95% CI, 4.5-25.3; p = 0.054). Multivariate hazard ratio (HR) for LRR controlling for race, receptor status, and stage was 2.62 (95% CI, 1.02-7.13; p = 0.042). All LRR in the low-dose group occurred in patients receiving 50 to 50.4 Gy. Lower CW dose was associated with worse PFS (multivariate HR, 2.73; 95% CI, 1.64-4.56; p < 0.001) and OS (multivariate HR, 3.88; 95% CI, 2.16-6.99; p < 0.001). Conclusions: The addition of a CW boost above 50.4 Gy resulted in improved locoregional control and survival in this cohort patients treated with PMRT for stage II-III breast cancer. The addition of a CW boost to standard-dose PMRT is likely to benefit selected high-risk patients. The optimal technique, target volume, and patient selection criteria are unknown. The use of a CW boost should be studied prospectively, as has been done in the setting of breast conservation.

  2. 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.

  3. Prescription opioid epidemic and infant outcomes.

    Science.gov (United States)

    Patrick, Stephen W; Dudley, Judith; Martin, Peter R; Harrell, Frank E; Warren, Michael D; Hartmann, Katherine E; Ely, E Wesley; Grijalva, Carlos G; Cooper, William O

    2015-05-01

    Although opioid pain relievers are commonly prescribed in pregnancy, their association with neonatal outcomes is poorly described. Our objectives were to identify neonatal complications associated with antenatal opioid pain reliever exposure and to establish predictors of neonatal abstinence syndrome (NAS). We used prescription and administrative data linked to vital statistics for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. A random sample of NAS cases was validated by medical record review. The association of antenatal exposures with NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant characteristics. Of 112,029 pregnant women, 31,354 (28%) filled ≥ 1 opioid prescription. Women prescribed opioid pain relievers were more likely than those not prescribed opioids (P < .001) to have depression (5.3% vs 2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%). Infants with NAS and opioid-exposed infants were more likely than unexposed infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a multivariable model, higher cumulative opioid exposure for short-acting preparations (P < .001), opioid type (P < .001), number of daily cigarettes smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio: 2.08 [95% confidence interval: 1.67-2.60]) were associated with greater risk of developing NAS. Prescription opioid use in pregnancy is common and strongly associated with neonatal complications. Antenatal cumulative prescription opioid exposure, opioid type, tobacco use, and selective serotonin reuptake inhibitor use increase the risk of NAS. Copyright © 2015 by the American Academy of Pediatrics.

  4. Sleep quality in opioid-naive and opioid-dependent patientson methadone maintenance therapy in Malaysia.

    Science.gov (United States)

    Zahari, Zalina; Inrahim, Muslih Abdulkarim; Tan, Soo Choon; Mohamad, Nasir; Ismail, Rusli

    2016-12-20

    Sleep disturbances may contribute to poor treatment outcomes in opioid-dependent patients. The extent to which the sleep profiles of opioid-dependent patients differ from those of the general Malaysian population is not documented. This study compared opioid-naive subjects and opioid-dependent patients on methadone maintenance therapy (MMT) in terms of their sleep quality. Participants comprised Malay male opioid-naive subjects (n = 159) and opioid-dependent patients (n = 160) from MMT clinics in Kelantan, Malaysia, between March and October 2013. Sleep quality was evaluated using the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI). The opioid-dependent patients exhibited higher global PSQI scores [adjusted mean (95% CI) = 5.46 (5.02, 5.90)] than the opioid-naive group [4.71 (4.26, 5.15)] [F (1, 313) = 4.77, P = 0.030]. This study confirmed the poorer sleep quality among opioid-dependent patients on MMT, as manifested by their higher global PSQI scores. The sleep complaints in this patient population are a factor to consider and, when necessary, sleep evaluation and treatment should be undertaken to improve MMT patients' quality of sleep and overall treatment outcome.

  5. 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

  6. Opioid use in the elderly.

    NARCIS (Netherlands)

    Wilder-Smith, O.H.G.

    2005-01-01

    Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in

  7. Survey of intrathecal opioid usage in the UK.

    Science.gov (United States)

    Giovannelli, M; Bedforth, N; Aitkenhead, A

    2008-02-01

    Intrathecal opioids are now used routinely in the UK for intra- and postoperative analgesia. The opioids of choice have altered over recent years and the dosage regimens used can vary between institutions. Concerns over safety have been reduced probably because much lower doses of opioids are now being used. This survey explored the practice of intrathecal opioid usage in the UK. We sent a questionnaire survey to 270 anaesthetic departments and received 199 replies, a response rate of 73.7%. Intrathecal opioids were used in 175 (88.4%) departments. Of these departments, 107 (61.1%) had local guidelines or protocols in place. Opioids such as diamorphine (used in 136 (78.2%) of departments) and fentanyl (129 (74.1%)) with a shorter duration of action are now more commonly used than morphine (37 (21.3%)) for intrathecal analgesia. In 96 (54.5%) departments, patients were nursed on regular surgical wards following administration of spinal opioids. The use of low-dose lipophilic intrathecal opioids for postoperative analgesia is widespread in the UK. Patients are commonly nursed in low-dependency post-anaesthetic care areas. The low incidence of adverse events reported by the respondents along with the popularity of the technique suggests that low-dose spinal opioid administration is safe.

  8. 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.

  9. Prescription Opioids during Pregnancy

    Science.gov (United States)

    ... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... safe? > Prescription opioids during pregnancy Prescription opioids during pregnancy E-mail to a friend Please fill in ...

  10. Broader Considerations of Higher Doses of Donepezil in the Treatment of Mild, Moderate, and Severe Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Camryn Berk

    2012-01-01

    Full Text Available Donepezil, a highly selective acetylcholinesterase inhibitor (AChEI, is approved as a symptomatic treatment mild, moderate, and severe Alzheimer's disease (AD. Donepezil exerts its treatment effect through multiple mechanisms of action including nicotinic receptor stimulation, mitigation of excitotoxicity, and influencing APP processing. The use of donepezil at higher doses is justified given the worsening cholinergic deficit as the disease advances. Donepezil has been investigated in several clinical trials of subjects with moderate-to-severe AD. While the side effects are class specific (cholinergically driven, demonstrable benefit has been shown at the 10 mg dose and the 23 mg doses. Here, we review the clinical justification, efficacy, safety, and tolerability of use of donepezil in the treatment of moderate-to-severe AD.

  11. 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

    neuropathic pain: The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4. The use of opioids in elderly patients with impaired hepatic and renal function: Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that--except for buprenorphine--doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5. Opioids and respiratory depression: Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6. Opioids and immunosuppression: Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The

  12. Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone.

    Science.gov (United States)

    Fishman, Marc

    2008-08-01

    Background There has been increasing interest in the use of extended release injectable naltrexone for the treatment of opioid dependence. Case description We report a case of precipitated withdrawal in a 17-year-old adolescent female receiving extended release naltrexone (Vivitrol) for opioid dependence, following her third serial monthly dose of the medication, several days after using oxycodone with mild intoxication. Conclusions This case suggests that, in some circumstances, the opioid blockade may be overcome when naltrexone levels drop towards the end of the dosing interval, producing vulnerability to subsequent naltrexone-induced withdrawal. This may provide cautionary guidance for clinical management and dosing strategies.

  13. Overdose deaths demand a new paradigm for opioid rotation.

    Science.gov (United States)

    Webster, Lynn R; Fine, Perry G

    2012-04-01

    An increasing number of deaths have been inferred to be associated with current opioid rotation practices and evidence is mounting that the use of widely accepted protocols for opioid rotation is an important contributing factor. Based on the findings of a literature review published in conjunction with this article, we propose a new paradigm for a potentially safer method of opioid rotation and present a case study illustrating the paradigm. This new paradigm suggests three easy-to-remember steps in opioid rotation and obviates the need to use a conversion table. Report of a clinical case of a patient undergoing opioid rotation using this new paradigm. The patient was successfully rotated from extended-release oxycodone to extended-release hydromorphone. The dose of oxycodone was slowly decreased, while the hydromorphone dose was slowly titrated. A critical element to this approach involved providing sufficient immediate-release opioid to treat breakthrough pain and to reverse acute abstinence signs and symptoms if the dosing changes prove insufficient. A safer new paradigm for opioid rotation may provide an important incremental step forward in reducing adverse public health consequences of inappropriate opioid dosing. Wiley Periodicals, Inc.

  14. 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.

  15. Dosing antibiotic prophylaxis during cardiopulmonary bypass-a higher level of complexity? A structured review.

    Science.gov (United States)

    Paruk, Fathima; Sime, Fekade B; Lipman, Jeffrey; Roberts, Jason A

    2017-04-01

    In highly invasive procedures such as open heart surgery, the risk of post-operative infection is particularly high due to exposure of the surgical field to multiple foreign devices. Adequate antibiotic prophylaxis is an essential intervention to minimise post-operative morbidity and mortality. However, there is a lack of clear understanding on the adequacy of traditional prophylactic dosing regimens, which are rarely supported by data. The aim of this structured review is to describe the relevant pharmacokinetic/pharmacodynamic (PK/PD) considerations for optimal antibiotic prophylaxis for major cardiac surgery including cardiopulmonary bypass (CPB). A structured review of the relevant published literature was performed and 45 relevant studies describing antibiotic pharmacokinetics in patients receiving extracorporeal CPB as part of major cardiac surgery were identified. Some of the studies suggested marked PK alterations in the peri-operative period with increases in volume of distribution (V d ) by up to 58% and altered drug clearances of up to 20%. Mechanisms proposed as causing the PK changes included haemodilution, hypothermia, retention of the antibiotic within the extracorporeal circuit, altered physiology related to a systemic inflammatory response, and maldistribution of blood flow. Of note, some studies reported no or minimal impact of the CPB procedure on antibiotic pharmacokinetics. Given the inconsistent data, ongoing research should focus on clarifying the influence of CPB procedure and related clinical covariates on the pharmacokinetics of different antibiotics during cardiac surgery. Traditional prophylactic dosing regimens may need to be re-assessed to ensure sufficient drug exposures that will minimise the risk of surgical site infections. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  16. Outpatient non-opioid detoxification for opioid withdrawal. Who is likely to benefit?

    Science.gov (United States)

    McCann, M J; Miotto, K; Rawson, R A; Huber, A; Shoptaw, S; Ling, W

    1997-01-01

    The authors examined characteristics of successful completers of an outpatient clonidine/oxazepam detoxification procedure for opioid dependence. Of 215 initial applicants, 167 received medication, and 65 successfully completed by taking a dose of naltrexone. Those who completed were more likely to have last used an opioid other than heroin, to be heroin smokers, rather than intravenous users, to have used benzodiazepines in the 30 days before treatment, and to have abstained from opioids for a longer time before presenting for treatment. New users (for less than 2 years) did no better than those using longer than 2 years. These findings may help in the continued refinement of patient placement criteria.

  17. Nurses' opinions on appropriate administration of PRN range opioid analgesic orders for acute pain.

    Science.gov (United States)

    Gordon, Debra B; Pellino, Teresa A; Higgins, Gerry Ann; Pasero, Chris; Murphy-Ende, Kathleen

    2008-09-01

    The use of "as needed" or "pro re nata" (PRN) range opioid analgesic orders is a common clinical practice in the management of acute pain, designed to provide flexibility in dosing to meet an individual's unique needs. Range orders enable necessary adjustments in doses based on individual response to treatment. However, PRN range opioid orders have recently come under scrutiny as a source of confusion and as a medication management safety issue. How nurses administer range orders may vary based on their interpretation of the intent of an order, inadequate knowledge of analgesic titration, or exaggerated concerns about opioid safety. The purpose of this study was to investigate nurses' opinions of the appropriate implementation of range orders. Six hundred two nurses from one large academic medical center and one multihospital system completed an online survey using theoretic clinical vignettes to examine their opinions of appropriate analgesic administration practices. The majority of participants chose appropriate responses to the vignettes; however, there was a great deal of variability in responses. Those who had attended pain management courses were more likely to have a higher percentage of appropriate responses than those who had not attended courses. Years in practice and educational level were not significantly related to percentage of appropriate responses; however, there was a trend for nurses with a master's degree to have a higher percentage than nurses with other educational preparation. Consideration of opioid pharmacokinetics can provide logic to develop a new paradigm where range orders are replaced with orders that provide more explicit instructions to titrate an opioid to the most effective dose.

  18. Buprenorphine and methadone for opioid addiction during pregnancy.

    Science.gov (United States)

    Mozurkewich, Ellen L; Rayburn, William F

    2014-06-01

    Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The impact of epidural analgesia compared to systemic opioid-based analgesia with regard to length of hospital stay and recovery of bowel function: retrospective evaluation of 1555 patients undergoing thoracotomy.

    Science.gov (United States)

    Kampe, Sandra; Weinreich, Gerhard; Darr, Christopher; Eicker, Kolja; Stamatis, Georgios; Hachenberg, Thomas

    2014-11-23

    To assess the protocols of epidural analgesia versus systemic opioid-based analgesia retrospectively in 1555 thoracotomies in our thoracic centre during 2011-2013. Pain therapy is aggressive and standardized in our thoracic centre thoughout the complete postoperative stay. Patients receive either standardized epidural analgesia with ropivacaine + sufentanil 4-8 mls/h (500 mls bag) and are bridged when the epidural bag is finished to a standardized controlled-release oxycodone protocol with non opioid every 6 hours (EDA Group), or patients receive immediately postoperative standardized oral analgesic protocol with controlled-released oxycodone and non opioid every 6 h (Opioid Group). All patients are visited daily by a pain specialist throughout the whole stay. Data of 1555 thoracotomies from 2011-2013 were analysed, 838 patients in the EDA Group and 717 patients in the Opioid Group. There was no difference with regard to sex or age between groups. 7.5% of patients in the EDA Group and 13% in the Oxy Group had a preexisting pain therapy (p = 0.001). In the EDA Group epidural analgesia was performed for 4.6 ± 1.5 days. Length of hospital stay was the same in both groups (EDA: 9.9.6 ± 4.9 vs Opioid: 9.6 ± 5.8 days). 84.7% of patients in the EDA Group and 79.1% of patients of the Oxy Group were dismissed with oral opioid (p < 0.004). When patients were dismissed with opioid medication patients in the EDA Group were dismissed with higher oxycodone opioid doses than patients in the Opioid Group (29.5 ± 15.2 mg vs 26.9 ± 15.2 mg, p = 0.01). There was no difference with regard to dejection time between the two groups (EDA: 3.8 ± 2.2 days vs Opioid: 3.7 ± 1.6 days, n.s.). We first present data monitoring postoperative analgesic protocols after thoracotomies throughout the whole stay in hospital until dismission. Our retrospective data indicate that patients with epidural analgesia stay as long in hospital as

  20. Opioid complications and side effects.

    Science.gov (United States)

    Benyamin, Ramsin; Trescot, Andrea M; Datta, Sukdeb; Buenaventura, Ricardo; Adlaka, Rajive; Sehgal, Nalini; Glaser, Scott E; Vallejo, Ricardo

    2008-03-01

    Medications which bind to opioid receptors are increasingly being prescribed for the treatment of multiple and diverse chronic painful conditions. Their use for acute pain or terminal pain is well accepted. Their role in the long-term treatment of chronic noncancer pain is, however, controversial for many reasons. One of the primary reasons is the well-known phenomenon of psychological addiction that can occur with the use of these medications. Abuse and diversion of these medications is a growing problem as the availability of these medications increases and this public health issue confounds their clinical utility. Also, the extent of their efficacy in the treatment of pain when utilized on a chronic basis has not been definitively proven. Lastly, the role of opioids in the treatment of chronic pain is also influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications. It is these phenomena that are the focus of this review. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioid usage are constipation (which has a very high incidence) and nausea. These 2 side effects can be difficult to manage and frequently tolerance to them does not develop; this is especially true for constipation. They may be severe enough to require opioid discontinuation, and contribute to under-dosing and inadequate analgesia. Several clinical trials are underway to identify adjunct therapies that may mitigate these side effects. Switching opioids and/or routes of administration may also provide benefits

  1. [Use of opioids in the elderly -- pharmacokinetic and pharmacodynamic considerations].

    Science.gov (United States)

    Freye, E; Levy, J V

    2004-09-01

    of fear of complications associated with treating perioperative pain. Although it is known that inadequate analgesia may delay recovery, the treatment of perioperative pain in the geriatric patient remains inadequate, even relative to younger patients. It is well established that there is increased responsiveness to the effects of opioids in the elderly. This may result in an increased risk of respiratory depression, while especially the elderly female patient demonstrates an increase in the duration of effects, but the risk of nausea is not augmented. Increased sensitivity of older patients to systemic opioids mostly involves pharmacokinetic factors such as a higher proportion of unbound and active substances as well as changes in drug redistribution. Because of a 40 % reduction in stroke volume in the elderly, there is a protracted redistribution of opioids to the liver. This results in a prolonged metabolisation, a lesser inactivation over time followed by an increase in duration of effects, mainly impairment of respiration. To a much lesser extent, pharmacodynamic factors with an increased response at opioid receptor sites have to be considered. Although the mechanisms causing differences of opioid action in the elderly may be complex, the clinical implications are not. They include slow titration of opioids to allow for long circulation times, lower total doses because of increased sensitivity, and anticipation of a longer duration of action because of reduced clearance. Since elderly patients present multimorbidity, therapy of chronic pain has to be considered in the light of multidrug intake, which, due to interaction, results in marked side-effects, and a prolonged duration of action. Those opioids should be used which, due to their pharmacokinetic properties, have a reduced volume of distribution, present a low plasma protein binding and finally result in the formation of no pharmacologically active metabolites.

  2. Understanding opioid overdose characteristics involving prescription and illicit opioids: A mixed methods analysis.

    Science.gov (United States)

    Yarborough, Bobbi Jo H; Stumbo, Scott P; Janoff, Shannon L; Yarborough, Micah T; McCarty, Dennis; Chilcoat, Howard D; Coplan, Paul M; Green, Carla A

    2016-10-01

    Opioid abuse and misuse are significant public health issues. The CDC estimated 72% of pharmaceutical-related overdose deaths in the US in 2012 involved opioids. While studies of opioid overdoses have identified sociodemographic characteristics, agents used, administration routes, and medication sources associated with overdoses, we know less about the context and life circumstances of the people who experience these events. We analyzed interviews (n=87) with survivors of opioid overdoses or family members of decedents. Individuals experiencing overdoses were members of a large integrated health system. Using ICD codes for opioid overdoses and poisonings, we identified participants from five purposefully derived pools of health-plan members who had: 1) prescriptions for OxyContin(®) or single-ingredient sustained-release oxycodone, 2) oxycodone single-ingredient immediate release, 3) other long-acting opioids, 4) other short-acting opioids, or 5) no active opioid prescriptions. Individuals who experienced opioid overdoses abused and misused multiple medications/drugs; experienced dose-related miscommunications or medication-taking errors; had mental health and/or substance use conditions; reported chronic pain; or had unstable resources or family/social support. Many had combinations of these risks. Most events involved polysubstance use, often including benzodiazepines. Accidental overdoses were commonly the result of abuse or misuse, some in response to inadequately treated chronic pain or, less commonly, medication-related mistakes. Suicide attempts were frequently triggered by consecutive negative life events. To identify people at greater risk of opioid overdose, efforts should focus on screening for prescribed and illicit polysubstance use, impaired cognition, and changes in life circumstances, psychosocial risks/supports, and pain control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Pharmacogenomics-guided policy in opioid use disorder (OUD management: An ethnically-diverse case-based approach

    Directory of Open Access Journals (Sweden)

    Earl B. Ettienne

    2017-12-01

    Full Text Available Introduction: Opioid use disorder (OUD is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse. Clinical pharmacogenomics studies the effect that inherited genetic variations have on drug response. Our objective is to demonstrate the impact of pharmacogenetic testing on OUD management outcomes. Methods: We analyzed a patient who reported discomfort at daily buprenorphine dose of 24mg, which was a mandated daily maximum by the pharmacy benefits manager. Regular urine screenings were conducted to detect the presence of unauthorized substances, and pharmacogenetic testing was used to determine the appropriate dose of buprenorphine for OUD management. Results: At the 24mg buprenorphine daily dose, the patient had multiple relapses with unauthorized substances. Pharmacogenetic testing revealed that the patient exhibited a cytochrome P450 3A4 ultrarapid metabolizer phenotype, which necessitated a higher than recommended daily dose of buprenorphine (32mg for adequate OUD management. The patient exhibited a reduction in the number of relapses on the pharmacogenetic-based dose recommendation compared to standard dosing. Conclusion: Pharmacogenomic testing as clinical decision support helped to individualize OUD management. Collaboration by key stakeholders is essential to establishing pharmacogenetic testing as standard of care in OUD management. Keywords: Opioid use disorder, Opioid agonist treatment, Buprenorphine, Pharmacogenomics, Policy

  4. Opioid Prescribing and Potential Overdose Errors Among Children 0 to 36 Months Old.

    Science.gov (United States)

    Basco, William T; Ebeling, Myla; Garner, Sandra S; Hulsey, Thomas C; Simpson, Kit

    2015-07-01

    To estimate the frequency of potential overdoses among outpatient opioid-containing prescriptions. Using 11 years of outpatient Medicaid prescription data, we compared opioid dose dispensed (observed) versus expected dose to estimate overdose error frequencies. A potential overdose was defined as any preparation dispensed that was >110% of expected based on imputed, 97th percentile weights. There were 59 536 study drug prescriptions to children 0 to 36 months old. Overall, 2.7% of the prescriptions contained potential overdose quantities, and the average excess amount dispensed was 48% above expected. Younger ages were associated with higher frequencies of potential overdose. For example, 8.9% of opioid prescriptions among infants 0 to 2 months contained potential overdose quantities, compared with 5.7% among infants 3 to 5 months old, 3.6% among infants 6 to 11 months old, and 2.3% among children >12 months (P Opioid prescriptions for infants and children routinely contained potential overdose quantities. © The Author(s) 2015.

  5. Psychological factors as predictors of opioid abuse and illicit drug use in chronic pain patients.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Giordano, James; Boswell, Mark V; Fellows, Bert; Manchukonda, Rajeev; Pampati, Vidyasagar

    2007-01-01

    Psychopathology (depression, anxiety, somatization disorder) and substance abuse (opioid misuse and illicit drug use) are common in patients with chronic pain and present problems for public health and clinical management. Despite a body of literature describing various methods for identifying psychopathology, opioid misuse, and illicit drug use in chronic pain patients, the relationship between psychopathologies, substance abuse, and chronic pain has not been well characterized. This report describes a total of 500 consecutive pain patients prescribed and receiving stable doses of opioids. The patients were evaluated for psychopathology, opioid abuse, and illicit drug use during the course of regular pain management treatment. The relationships between psychopathology and drug abuse and/or illicit drug use in chronic pain patients were examined, and psychological evaluation for depression, anxiety, and somatization disorder was performed. Depression, anxiety, and somatization disorder were documented in 59, 64, and 30 percent of chronic pain patients, respectively. Drug abuse was significantly higher in patients with depression as compared to patients without depression (12 percent with depression versus 5 percent without). Current illicit drug use was higher in women with depression (22 percent) than women without depression (14 percent) and in men with or without depression (12 percent). Current illicit drug use was also higher in men with somatization disorder (22 percent) than men without (9 percent). This study demonstrated that the presence of psychological features of depression and somatization disorder may be markers of substance abuse diathesis in chronic pain patients.

  6. Phorbol ester suppression of opioid analgesia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, L.J.; Wang, X.J.; Han, J.S. (Beijing Medical Univ. (China))

    1990-01-01

    Protein kinase C (PKC) has been shown to be an important substrate in intracellular signal transduction. Very little is known concerning its possible role in mediating opiate-induced analgesia. In the present study, 12-O-tetradecanoylphorbol 13-acetate (TPA), a selective activator of PKC, was injected intrathecally (ith) to assess its influence on the analgesia induced by intrathecal injection of the mu opioid agonist PL017, the delta agonist DPDPE and the kappa agonist 66A-078. Radiant heat-induced tail flick latency (TFL) was taken as an index of nociception. TPA in the dose of 25-50 ng, which did not affect the baseline TFL, produced a marked suppression of opioid antinociception, with a higher potency in blocking mu and delta than the kappa effect. In addition, mu and delta agonists induced remarkable decreases in spinal cyclic AMP (cAMP) content whereas the kappa effect was weak. The results suggest a cross-talk between the PKC system and the signal transduction pathway subserving opioid analgesia.

  7. Comparison of Low-Dose Higher-Relaxivity and Standard-Dose Lower-Relaxivity Contrast Media for Delayed-Enhancement MRI: A Blinded Randomized Crossover Study.

    Science.gov (United States)

    Cheong, Benjamin Y C; Duran, Cihan; Preventza, Ourania A; Muthupillai, Raja

    2015-09-01

    The gadolinium-based MRI contrast agent gadobenate dimeglumine has nearly twice the MR relaxivity of gadopentetate dimeglumine at 1.5 T. The purpose of this study was to determine whether a lower dose (0.1 mmol/kg) of gadobenate dimeglumine can be used to obtain delayed-enhancement MR images comparable to those obtained with a standard dose (0.2 mmol/kg) of gadopentetate dimeglumine. In this blinded randomized crossover study, 20 patients with known myocardial infarction underwent two separate delayed-enhancement MRI examinations after receiving 0.1 mmol/kg gadobenate dimeglumine and 0.2 mmol/kg gadopentetate dimeglumine (random administration). The conspicuity of lesion enhancement 5, 10, and 20 minutes after contrast administration was quantified as relative enhancement ratio (RER). With either gadolinium-based contrast agent, damaged myocardium had higher signal intensity than normal remote myocardium (RER > 4) on delayed-enhancement MR images, and the blood RER declined over time after contrast administration. The blood RER was not significantly higher for gadobenate dimeglumine than for gadopentetate dimeglumine at 5 and 10 minutes. Nevertheless, there was a larger reduction in blood RER for gadobenate dimeglumine than for gadopentetate dimeglumine between 5 and 10 minutes and between 10 and 20 minutes. The volumes of enhancement were similar for gadobenate dimeglumine (13.6 ± 8.8 cm(3)) and gadopentetate dimeglumine (13.5 ± 8.9 cm(3)) (p = 0.98). The mean difference in Bland-Altman analysis for delayed-enhancement volume between the agents was 0.1 cm(3). Qualitatively and quantitatively, delayed-enhancement MR images of ischemic myocardium obtained with 0.1 mmol/kg gadobenate dimeglumine are comparable to those obtained with 0.2 mmol/kg gadopentetate dimeglumine 5, 10, and 20 minutes after contrast administration.

  8. Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse: Part 1.

    Science.gov (United States)

    Kaye, Alan D; Jones, Mark R; Kaye, Adam M; Ripoll, Juan G; Galan, Vincent; Beakley, Burton D; Calixto, Frank; Bolden, Jamie L; Urman, Richard D; Manchikanti, Laxmaiah

    2017-02-01

    Chronic pain and prescription opioid abuse are extremely prevalent both in this country and worldwide. Consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. Individuals with chronic pain and co-occurring substance use disorders and/or mental health disorders, are at a higher risk for misuse of prescribed opioids. Opioid abuse and misuse occurs for a variety of reasons, including self-medication, use for reward, compulsive use because of addiction, and diversion for profit. There is a significant need for treatment approaches that balance treating chronic pain; while minimizing risks for opioid abuse, misuse, and diversion. The use of chronic opioid therapy for chronic non-cancer pain has increased dramatically in the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument which provides an effective and rational method of selecting patients for opioid therapy, predicting risk, and identifying problems once they arise could be of enormous benefit in clinical practice. Such an instrument could potentially curb the risk of iatrogenic addiction. Although several screening instruments and strategies have been introduced in recent years, there is no single test or instrument which can reliably and accurately predict those patients not suitable for opioid therapy or identify those who need increased vigilance or monitoring during therapy. At present, screening for opioid abuse includes assessment of premorbid and comorbid substance abuse; assessment of aberrant drug-related behaviors; risk factor stratification; and utilization of opioid assessment screening tools. Multiple opioid assessment screening tools and instruments have been developed by various authors. In addition, urine drug testing, monitoring of prescribing practices, prescription monitoring

  9. [An appropriate opioid rotation method for treatment of cancer pain--nationwide usage survey of opioid analgesics].

    Science.gov (United States)

    Watanabe, Norio; Yasumura, Mikio; Yamamura, Keiko; Yasuda, Kimio

    2009-09-01

    The use of opioid for treatment of cancer pain has become common with the spread of the WHO method for relief of cancer pain. However, it cannot yet be said whether such usage is appropriate. To understand how opioid analgesics are actually used, we conducted a nationwide mail-based questionnaire survey of doctors dealing with cancer pain treatment. Results indicate that at opioid rotation to fentanyl patch due to insufficient effect, the second opioid is used in a potency equianalgesic or less of the first, so the efficacy of the second is often insufficient. In cases where previous medication had an insufficient effect, taking rescue doses into account, we believe it is important to rotate opioid at 30- 50% above the equianalgesic dose.

  10. Buprenorphine-Mediated Transition from Opioid Agonist to Antagonist Treatment: State of the Art and New Perspectives

    Science.gov (United States)

    Mannelli, Paolo; Peindl, Kathleen S.; Lee, Tong; Bhatia, Kamal S.; Wu, Li-Tzy

    2012-01-01

    Constant refinement of opioid dependence (OD) therapies is a condition to promote treatment access and delivery. Among other applications, the partial opioid agonist buprenorphine has been studied to improve evidence-based interventions for the transfer of patients from opioid agonist to antagonist medications. This paper summarizes PubMed-searched clinical investigations and conference papers on the transition from methadone maintenance to buprenorphine and from buprenorphine to naltrexone, discussing challenges and advances. The majority of the 26 studies we examined were uncontrolled investigations. Many small clinical trials have demonstrated the feasibility of in- or outpatient transfer to buprenorphine from low to moderate methadone doses (up to 60–70 mg). Results on the conversion from higher methadone doses, on the other hand, indicate significant withdrawal discomfort, and need for ancillary medications and inpatient treatment. Tapering high methadone doses before the transfer to buprenorphine is not without discomfort and the risk of relapse. The transition buprenorphine-naltrexone has been explored in several pilot studies, and a number of treatment methods to reduce withdrawal intensity warrant further investigation, including the co-administration of buprenorphine and naltrexone. Outpatient transfer protocols using buprenorphine, and direct comparisons with other modalities of transitioning from opioid agonist to antagonist medications are limited. Given its potential salience, the information gathered should be used in larger clinical trials on short and long-term outcomes of opioid agonist-antagonist transition treatments. Future studies should also test new pharmacological mechanisms to help reduce physical dependence, and identify individualized approaches, including the use of pharmacogenetics and long-acting opioid agonist and antagonist formulations. PMID:22280332

  11. Opioid effect on lungs.

    Science.gov (United States)

    Yamanaka, Travis; Sadikot, Ruxana T

    2013-02-01

    Opioids are widely used for their analgesic properties for the management of acute and chronic pain related to a variety of illnesses. Opioid usage is associated with adverse effects on respiration which are often attributed to depression of the central nervous system. Recent data indicate that opioid use has increased over the last two decades. There is also increasing evidence that opioids have a variety of effects on the lungs besides suppression of respiration. Opioids can affect immune cells function, increase histamine release causing bronchospasm, vaso-constriction and hypersensitivity reactions. Together, these actions have a variety of effects on lung function. Here, we provide a comprehensive review of the effects of opioids on the lungs including the respiratory centre, immune function, airways and pulmonary vasculature. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

  12. Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk

    Directory of Open Access Journals (Sweden)

    Elizabeth Huber

    2016-05-01

    Full Text Available Beginning in the late 1990s, a movement began within the pain management field focused upon the underutilization of opioids, thought to be a potentially safe and effective class of pain medication. Concern for addiction and misuse were present at the start of this shift within pain medicine, and an emphasis was placed on developing reliable and valid methods and measures of identifying those at risk for opioid misuse. Since that time, the evidence for the safety and effectiveness of chronic opioid therapy (COT has not been established. Rather, the harmful, dose-dependent deleterious effects have become clearer, including addiction, increased risk of injuries, respiratory depression, opioid induced hyperalgesia, and death. Still, many individuals on low doses of opioids for long periods of time appear to have good pain control and retain social and occupational functioning. Therefore, we propose that the question, “Who is at risk of opioid misuse?” should evolve to, “Who may benefit from COT?” in light of the current evidence.

  13. Intraoperative Use of Remifentanil and Opioid Induced Hyperalgesia/Acute Opioid Tolerance - Systematic review

    Directory of Open Access Journals (Sweden)

    Sang Hun eKim

    2014-05-01

    Full Text Available IntroductionThe use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT and opioid-induced hyperalgesia (OIH in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. ObjectivesSearch of the available literature to assess remifentanil AOT and OIH based on available published data.MethodsWe reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey. ResultsOur results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research.Discussions and ConclusionsAOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold, should be suspected with any unexplained pain report unassociated with the disease progression.The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug’s effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion.Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.

  14. The cognitive and psychomotor effects of opioid analgesics. I. A randomized controlled trial of single doses of dextropropoxyphene, lorazepam and placebo in healthy subjects.

    Science.gov (United States)

    O'Neill, W M; Hanks, G W; White, L; Simpson, P; Wesnes, K

    1995-01-01

    Twelve subjects (3 male) took part in a randomised double-blind four way crossover study designed to examine the cognitive and psychomotor effects of single doses of dextroproxyphene. On four study days one week apart each subject received each study product (i) dextropropoxyphene napsylate 100 mg, (ii) dextropropoxyphene napsylate 200 mg, (iii) lorazepam 2 mg and (iv) placebo. Performance measures were simple reaction time, choice reaction time, number vigilance, memory scanning, word recall (immediate and delayed), word recognition, picture recognition, critical flicker fusion threshold (CFFT) and visual analogue scales of alertness, calmness and contentment. Lorazepam had a marked effect on the range of tests used illustrating the sensitivity of the best battery. This was in contrast to the effects of dextropropoxyphene. A dose related effect in CFFT was detected, the 200 mg dose producing a significant decrease in CFFT throughout the testing period. Dextropropoxyphene also showed a tendency to improve scores on the verbal memory tasks. These data indicate that dextropropoxyphene in the usual doses does not produce significant impairment of cognitive and psychomotor function.

  15. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, Ola; Sjøgren, P

    2017-01-01

    BACKGROUND: Longitudinal population-based studies of long-term opioid therapy (L-TOT) in chronic non-cancer pain (CNCP) patients are sparse. Our study investigated incidence and predictors for initiating L-TOT and changes in self-rated health, pain interference and physical activities in long......-term opioid users. METHODS: Data were obtained from the national representative Danish Health and Morbidity Surveys and The Danish National Prescription Registry. Respondents with no dispensed opioids the year before the survey were followed from 2000 and from 2005 until the end of 2012 (n = 12...... defined as those who were dispensed at least one opioid prescription in six separate months within a year. RESULTS: The incidence of L-TOT was substantially higher in CNCP patients at baseline than in others (9/1000 vs. 2/1000 person-years). Smoking behaviour and dispensed benzodiazepines were...

  16. Hiperalgesia induzida por opioides (HIO

    Directory of Open Access Journals (Sweden)

    Plínio da Cunha Leal

    2010-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Opioides são medicamentos frequentemente usados para o controle da dor que, contudo, podem causar hiperalgesia. A circunstância pela qual esse fenômeno pode ocorrer não está inteiramente esclarecida. O objetivo desta revisão foi descrever os mecanismos, os fatores implicados e a modulação por medicamentos. CONTEÚDO: Foram descritos os fatores implicados no desenvolvimento da hiperalgesia induzida por opioides (HIO, como duração de uso, dose e tipo de opioide. Os mecanismos incluem o sistema glutamatérgico e receptores N-metil-D-aspartato (NMDA, ativação de ciclo-oxigenase (COX espinal, aminoácidos excitatórios, dinorfina, citocinas e quimocinas; prostaglandinas e facilitação descendente. A modulação de hiperalgesia pode ser feita com antagonistas de receptores NMDA, agonistas adrenérgicos-alfa2 e inibidores de COX. CONCLUSÕES: O assunto é bastante complexo, envolvendo uma série de mecanismos fisiopatológicos que podem contribuir para a HIO e o desconforto do paciente, trazendo consequências que podem ser danosas.

  17. A Case-Based Approach to Integrating Opioid Pharmacokinetic and Pharmacodynamic Concepts in Cancer Pain Management.

    Science.gov (United States)

    Lam, Lisa H; Pirrello, Rosene D; Ma, Joseph D

    2016-07-01

    Opioids are prescribed for cancer pain. Over the past decade, the annual increase in opioid prescriptions has been accompanied by an increase in opioid-associated deaths. Health care professionals must be proficient in proper dosing, titrating, and monitoring of opioid medications. With the numerous opioid medications and formulations available, an understanding of pharmacokinetic (PK) and pharmacodynamic (PD) concepts is necessary to appropriately individualize opioid-based cancer pain regimens. The purpose of this review is to highlight PK/PD concepts that are clinically relevant to the use of opioids. By way of a cancer pain patient case scenario, PK/PD concepts that are relevant in the initiation, titration, and rotation of an opioid regimen are discussed. © 2015, The American College of Clinical Pharmacology.

  18. Genetics Home Reference: opioid addiction

    Science.gov (United States)

    ... This Page American Society of Addiction Medicine: Opioid Addiction 2016 Facts and Figures (PDF) Centers for Disease Control and Prevention: Prescription Opioid Overdose Data Crist RC, Berrettini WH. ...

  19. Parenteral opioids for maternal pain relief in labour.

    Science.gov (United States)

    Ullman, Roz; Smith, Lesley A; Burns, Ethel; Mori, Rintaro; Dowswell, Therese

    2010-09-08

    Parenteral opioids are used for pain relief in labour in many countries throughout the world. To assess the acceptability, effectiveness and safety of different types, doses and modes of administration of parenteral opioids given to women in labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2010) and reference lists of retrieved studies. We included randomised controlled trials examining the use of intramuscular or intravenous opioids (including patient controlled analgesia) for women in labour. We looked at studies comparing an opioid with placebo or another opioid. At least two review authors independently assessed study eligibility, collected data and assessed risk of bias. We included 54 studies involving more than 7000 women that compared an opioid with placebo or another opioid administered intramuscularly or intravenously. The 54 studies reported on 27 different comparisons, and for many outcomes only one study contributed data. Overall the evidence was of poor quality regarding the analgesic effect of opioids, satisfaction with analgesia, adverse effects and harm to women and babies. There were few statistically significant results. Many of the studies had small sample sizes, and low statistical power. Overall, findings indicated that parenteral opioids provided some pain relief and moderate satisfaction with analgesia in labour, although up to two-thirds of women who received opioids reported moderate or severe pain and/or poor or moderate pain relief one or two hours after administration. Opioid drugs were associated with maternal nausea, vomiting and drowsiness, although different opioid drugs were associated with different adverse effects. There was no clear evidence of adverse effects of opioids on the newborn. We did not have sufficient evidence to assess which opioid drug provided the best pain relief with the least adverse effects. Parenteral opioids provide some relief from pain in labour but are associated

  20. Acquired pharmaco-dynamic opioid tolerance: a concept analysis.

    Science.gov (United States)

    Middleton, Carolyn; Harden, Jane

    2014-02-01

    To report an analysis of the concept of acquired pharmaco-dynamic opioid tolerance. Acquired pharmaco-dynamic opioid tolerance is a complex and poorly understood phenomenon associated with strong opioid therapy for managing pain. Critical review of the concept provides greater clarification of the attributes, assisting healthcare professionals in addressing pain and functional management of patients, particularly those with non-malignant pain. Concept analysis. A systematic literature search was undertaken using electronic data bases: CINAHL, British Nursing Index, EMBase, Medline, Pubmed and AMED. All literature reviewed was in English and published between 1976 and 2012. The key search terms were 'chronic non-malignant pain', 'strong opioid therapy' and 'development of acquired pharmaco-dynamic opioid tolerance'; all possible variant terms were also searched. The Walker and Avant approach was used to guide the concept analysis. The concept analysis revealed four empirical referents: plasticity, drug administration, reduced analgesic efficacy and increased drug dosing. Tachyphylexia was identified as a borderline case, opioid induced hyperalgesia as a related case and pseudo-tolerance as a contrary case. The antecedent is administration of an opioid analgesic drug and the consequences, increasing opioid drug dose to maintain analgesic effect. Untangling the antecedents, empirical referents and consequences of tolerance help healthcare professionals understand its complexities. Improved knowledge may ultimately influence patient outcomes through the construction of better monitoring systems. This concept analysis may also provide insights for policy change and give empirical direction for future research. © 2013 Blackwell Publishing Ltd.

  1. Primary care management of opioid use disorders: Abstinence, methadone, or buprenorphine-naloxone?

    Science.gov (United States)

    Srivastava, Anita; Kahan, Meldon; Nader, Maya

    2017-03-01

    To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance. PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included. Both methadone and buprenorphine-naloxone are substantially more effective than abstinence-based treatment. Methadone has higher treatment retention rates than buprenorphine-naloxone does, while buprenorphine-naloxone has a lower risk of overdose. For all patient groups, physicians should recommend methadone or buprenorphine-naloxone treatment over abstinence-based treatment (level I evidence). Methadone is preferred over buprenorphine-naloxone for patients at higher risk of treatment dropout, such as injection opioid users (level I evidence). Youth and pregnant women who inject opioids should also receive methadone first (level III evidence). If buprenorphine-naloxone is prescribed first, the patient should be promptly switched to methadone if withdrawal symptoms, cravings, or opioid use persist despite an optimal buprenorphine-naloxone dose (level II evidence). Buprenorphine-naloxone is recommended for socially stable prescription oral opioid users, particularly if their work or family commitments make it difficult for them to attend the pharmacy daily, if they have a medical or psychiatric condition requiring regular primary care (level IV evidence), or if their jobs require higher levels of cognitive functioning or psychomotor performance (level III evidence). Buprenorphine-naloxone is also recommended for patients at high risk of methadone toxicity, such as the elderly, those taking high doses of benzodiazepines or other sedating drugs, heavy drinkers, those with a lower level of opioid tolerance, and those at high risk of

  2. The infusion of opioids during terminal withdrawal of mechanical ventilation in the medical intensive care unit.

    Science.gov (United States)

    Mazer, Mark A; Alligood, Chad M; Wu, Qiang

    2011-07-01

    Most deaths in intensive care units occur after limitation or withdrawal of life-sustaining therapies. Often these patients require opioids to assuage suffering; yet, little has been documented concerning their use in the medical intensive care unit. To determine the dose and factors influencing the use of opioids in patients undergoing terminal withdrawal of mechanical ventilation in this setting. Data were prospectively collected from 74 consecutive patients expected to die soon after extubation. The doses of morphine, effect on time to death, and relation of dose to diagnostic categories were analyzed. The mean (±standard deviation) dose of morphine given to patients during the last hour of mechanical ventilation was 5.3mg/hour. Patients dying after extubation received 10.6 mg/hour just before death. Immediately before extubation, the dose correlated directly with chronic medical opioid use and sepsis with respiratory failure and inversely with coma after cardiopulmonary resuscitation or a primary neurological event. After terminal extubation, the final morphine dose correlated directly with the presence of sepsis with respiratory failure and chronic pulmonary disease. The mean time to death after terminal extubation was 152.7 ± 229.5 minutes without correlation with premorbid diagnoses. After extubation, each 1mg/hour increment of morphine infused during the last hour of life was associated with a delay of death by 7.9 minutes (P = 0.011). Premorbid conditions may influence the dose of morphine given to patients undergoing terminal withdrawal of mechanical ventilation. Higher doses of morphine are associated with a longer time to death. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  3. Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse (Part 2).

    Science.gov (United States)

    Kaye, Alan D; Jones, Mark R; Kaye, Adam M; Ripoll, Juan G; Jones, Donald E; Galan, Vincent; Beakley, Burton D; Calixto, Frank; Bolden, Jamie L; Urman, Richard D; Manchikanti, Laxmaiah

    2017-02-01

    Chronic pain and prescription opioid abuse are extremely prevalent in the United States and worldwide. The consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. The risk for misuse of prescribed opioids is much higher in patients with chronic pain, especially those with concurrent substance use and /or mental health disorders. Several reasons can account for the occurrence of opioid abuse and misuse, including self-medication, use for reward, compulsive use related to addiction, and diversion for profit. There is a need, therefore, for therapeutic approaches that balance treating chronic pain, while minimizing risks for opioid abuse, misuse, and diversion. Chronic opioid therapy for chronic non-cancer pain has seen a dramatic increase throughout the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument that provides an effective and rational method for selecting patients for opioid therapy, predicting risk, and identifying problems once they have arisen, could be of enormous benefit in clinical practice. An instrument as such has the potential to attenuate the risk of iatrogenic addiction. Despite the recent introduction of various screening strategies and instruments, no single test or instrument can reliably and accurately predict those patients unsuitable for opioid therapy or pinpoint those requiring heightened degrees of surveillance and monitoring throughout their therapy. Current opioid abuse screening tactics include assessing premorbid and comorbid substance abuse; assessing aberrant drug-related behaviors; stratification of risk factors; and utilizing opioid assessment screening tools. Several authors have contributed numerous screening tools and instruments to aid the assessment of appropriate opioid therapy. Additional essential measures

  4. Pharmacogenomic considerations in opioid analgesia

    Directory of Open Access Journals (Sweden)

    Vuilleumier PH

    2012-08-01

    Full Text Available Pascal H Vuilleumier,1 Ulrike M Stamer,1 Ruth Landau21Klinik für Anästhesiologie und Schmerztherapie, Inselspital Universität Bern, Switzerland; 2Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA, USAAbstract: Translating pharmacogenetics to clinical practice has been particularly challenging in the context of pain, due to the complexity of this multifaceted phenotype and the overall subjective nature of pain perception and response to analgesia. Overall, numerous genes involved with the pharmacokinetics and dynamics of opioids response are candidate genes in the context of opioid analgesia. The clinical relevance of CYP2D6 genotyping to predict analgesic outcomes is still relatively unknown; the two extremes in CYP2D6 genotype (ultrarapid and poor metabolism seem to predict pain response and/or adverse effects. Overall, the level of evidence linking genetic variability (CYP2D6 and CYP3A4 to oxycodone response and phenotype (altered biotransformation of oxycodone into oxymorphone and overall clearance of oxycodone and oxymorphone is strong; however, there has been no randomized clinical trial on the benefits of genetic testing prior to oxycodone therapy. On the other hand, predicting the analgesic response to morphine based on pharmacogenetic testing is more complex; though there was hope that simple genetic testing would allow tailoring morphine doses to provide optimal analgesia, this is unlikely to occur. A variety of polymorphisms clearly influence pain perception and behavior in response to pain. However, the response to analgesics also differs depending on the pain modality and the potential for repeated noxious stimuli, the opioid prescribed, and even its route of administration.Keywords: pain perception, opioid analgesia, genetic variation, pharmacogenetics

  5. Preference for an Opioid/Benzodiazepine Mixture over an Opioid Alone Using a Concurrent Choice Procedure in Rhesus Monkeys.

    Science.gov (United States)

    Weed, Peter F; France, Charles P; Gerak, Lisa R

    2017-07-01

    Increased abuse of opioids is contributing to an escalation in overdose deaths. Benzodiazepines are frequently abused with opioids, possibly because they increase the potency and/or effectiveness of opioids to produce reinforcing effects. This study used a concurrent-choice procedure to determine whether monkeys would choose to self-administer a mixture of the opioid remifentanil and the benzodiazepine midazolam over remifentanil alone. Initially, three monkeys could respond on one lever for saline and on a second lever for either remifentanil alone or midazolam alone. Thereafter, monkeys chose between a dose of remifentanil (0.32 µ g/kg/infusion) that did not change and a dose of remifentanil that varied across sessions; for some sessions, midazolam was combined with varying doses of remifentanil. All monkeys received more infusions of remifentanil (0.0032-0.32 µ g/kg/infusion) than saline, whereas only two monkeys responded more for midazolam than for saline. When 0.32 µ g/kg/infusion remifentanil was available on one lever and a dose of remifentanil that varied across sessions (0.1-1 µ g/kg/infusion) was available on the other lever, monkeys chose the larger dose. Combining 3.2 µ g/kg/infusion midazolam with 0.32 µ g/kg/infusion remifentanil increased responding for the mixture over 0.32 µ g/kg/infusion remifentanil alone, although monkeys chose remifentanil alone over mixtures containing smaller doses of remifentanil. When 10 µ g/kg/infusion midazolam was combined with 0.1 µ g/kg/infusion remifentanil, monkeys chose the mixture over 0.32 µ g/kg/infusion remifentanil alone. Thus, monkeys prefer some opioid/benzodiazepine mixtures to larger doses of the opioid alone, suggesting that opioid/benzodiazepine coabuse might be due to increased potency (and possibly effectiveness) of opioids to produce reinforcing effects. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus higher dose ICS for adults with asthma.

    Science.gov (United States)

    Evans, David J W; Kew, Kayleigh M; Anderson, Debbie E; Boyter, Anne C

    2015-07-21

    Long-acting muscarinic antagonists (LAMA), a class of drugs with proven effectiveness in chronic obstructive pulmonary disease (COPD), are being considered as an add-on option for adults with asthma whose condition is uncontrolled on inhaled corticosteroids (ICS). It is important to assess the safety and efficacy of LAMA add-on as an alternative to the prolonged use of higher doses of ICS, which are known to cause undesirable side effects in some people. To compare the effects of adding a LAMA to any dose of ICS versus increasing the dose of ICS, for uncontrolled asthma in adults. We searched the Cochrane Airways Group Specialised Register (CAGR) from its inception in 1995 to April 2015, imposing no restriction on language of publication. We also handsearched trial registries, reference lists of primary studies and existing reviews, as well as manufacturers' websites. We looked for parallel or cross-over randomised controlled trials lasting at least 12 weeks, in which adults whose asthma was not well controlled on ICS alone were randomised to treatment with LAMA add-on to ICS or with an increased dose of ICS. Trials were excluded if patients were taking long-acting beta2-agonists during the study period. Two review authors independently screened the searches and extracted data from studies meeting all the inclusion criteria. We used Covidence to manage duplicate screening, data extraction and risk of bias judgements, and to form a consensus where discrepancies arose. We used standard methods expected by The Cochrane Collaboration.The pre-specified primary outcomes were exacerbations requiring a course of oral corticosteroids (OCS), effects on quality of life and serious adverse events. One cross-over randomised controlled trial met the inclusion criteria. The trial was performed in 210 patients with moderate to severe asthma and compared the use of the LAMA tiotropium bromide with double dose beclomethasone (an ICS) using a cross-over design and 14-week treatment

  7. Peripheral Opioid Analgesia

    Science.gov (United States)

    1999-07-16

    4 . Basbaum AI, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annual Review of Neuroscience 7...include endorphin , enkephalin and dynorphin which are differentially processed from precursor peptides depending on the site of their production. These...Introduction of Text 1-2 Opioid Peptides and Opioid Receptors ................ ..................... ............. . 2-14 Pain Pathways and Central

  8. State variation in opioid and benzodiazepine prescriptions between independent and nonindependent advanced practice registered nurse prescribing states.

    Science.gov (United States)

    Schirle, Lori; McCabe, Brian E

    2016-01-01

    Many people lack access to primary care services in the United States. One possible solution is to increase utilization of advanced practice registered nurses (APRNs). A common patient safety concern about independent prescribing by APRNs is that prescribers will increase prescriptions for medications with abuse/dependence potential, such as opioids or benzodiazepines. The purpose was to investigate the relationship in opioid- and benzodiazepine-prescribing rates between independent vs. nonindependent APRN prescribing states. Tertiary analysis of a Centers for Disease Control and Prevention study reporting state variation in prescribing rates of opioids and benzodiazepines using 2012 Intercontinental Marketing Services Health retail prescription data representing 259,000,000 prescriptions. Analyses were performed using different definitions for independent states: (a) states allowing at least one APRN type independent prescribing and (b) states allowing all APRN types independent prescribing. ANOVA tests were used to test for differences in mean number of opioid- and benzodiazepine-prescribing rates per 100 residents. Analysis of Covariance tests were employed controlling for state characteristics previously determined to affect controlled substance-prescribing rates (e.g., Medicare rates, race, socioeconomic status, number of physicians/capita). There were significantly higher opioid and benzodiazepine prescriptions in states with nonindependent APRN prescribing laws than those in states with independent APRN prescribing laws and no significant differences in long-acting opioids or high-dose opioids. This study found no evidence to support the argument that independent prescribing increases prescriptions with abuse potential. Independent prescriptive authority, only one piece of APRN practice, has been one of the most controversial issues but one with great potential to help ease access to U.S. health care problems. Empirical evidence demonstrating the safety of

  9. Opioid epidemic in the United States.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Helm, Standiford; Fellows, Bert; Janata, Jeffrey W; Pampati, Vidyasagar; Grider, Jay S; Boswell, Mark V

    2012-07-01

    Over the past two decades, as the prevalence of chronic pain and health care costs have exploded, an opioid epidemic with adverse consequences has escalated. Efforts to increase opioid use and a campaign touting the alleged undertreatment of pain continue to be significant factors in the escalation. Many arguments in favor of opioids are based solely on traditions, expert opinion, practical experience and uncontrolled anecdotal observations. Over the past 20 years, the liberalization of laws governing the prescribing of opioids for the treatment of chronic non-cancer pain by the state medical boards has led to dramatic increases in opioid use. This has evolved into the present stage, with the introduction of new pain management standards by the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) in 2000, an increased awareness of the right to pain relief, the support of various organizations supporting the use of opioids in large doses, and finally, aggressive marketing by the pharmaceutical industry. These positions are based on unsound science and blatant misinformation, and accompanied by the dangerous assumptions that opioids are highly effective and safe, and devoid of adverse events when prescribed by physicians. Results of the 2010 National Survey on Drug Use and Health (NSDUH) showed that an estimated 22.6 million, or 8.9% of Americans, aged 12 or older, were current or past month illicit drug users, The survey showed that just behind the 7 million people who had used marijuana, 5.1 million had used pain relievers. It has also been shown that only one in 6 or 17.3% of users of non-therapeutic opioids indicated that they received the drugs through a prescription from one doctor. The escalating use of therapeutic opioids shows hydrocodone topping all prescriptions with 136.7 million prescriptions in 2011, with all narcotic analgesics exceeding 238 million prescriptions. It has also been illustrated that opioid analgesics are now

  10. Differences between opioids

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......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...

  11. Drug Overdose in a Retrospective Cohort with Non-Cancer Pain Treated with Opioids, Antidepressants, and/or Sedative-Hypnotics: Interactions with Mental Health Disorders.

    Science.gov (United States)

    Turner, Barbara J; Liang, Yuanyuan

    2015-08-01

    Opioid analgesics and other psychoactive drugs may pose an even greater risk for drug overdose in persons with mental health disorders. The purpose of this study was to examine interactions of filled prescriptions for opioids, benzodiazepines, antidepressants, and zolpidem with mental health disorders in regard to drug overdose. The study was a retrospective cohort review. Subjects were national HMO beneficiaries aged 18-64 years, enrolled at least 1 year (01/2009 to 07/2012), who filled at least two prescriptions for Schedule II or III opioids for non-cancer pain. The outcome was the first inpatient or outpatient drug overdose after the first filled opioid prescription. Predictors were calculated in 6-month intervals and exactly 6 months before a drug overdose: opioid use (mean daily morphine-equivalent dose), benzodiazepine use (days' supply), antidepressant use (days' supply), zolpidem use (days' supply), mental health disorders (depression, anxiety/PTSD, psychosis), pain-related conditions, and substance use disorders (alcohol, other drug). A total of 1,385 (0.67%) subjects experienced a drug overdose (incidence rate 421/100,000 person-years). The adjusted odds ratios (AOR) for overdose among all subjects rose monotonically with daily opioid dose, but highest (AOR = 7.06) for persons with depression and a high opioid dose (≥100 mg) versus no depression or opioid use. Longer-term antidepressants (91-180 days) were protective for persons with depression, with 20% lower AORs for overdose versus short-term (1-30 days) or none. For persons without depression, the AORs of overdose were increased for antidepressant use, but greatest (AOR = 1.98) for short-term use versus none. The AORs of overdose increased with the duration of benzodiazepine therapy among all subjects, with over 2.5-fold higher AORs for 91-180 days versus none. Opioids and longer-duration benzodiazepines were associated with drug overdose among all subjects, but opioid risk was greatest for

  12. [Long-term pediatric opioid based pain control. Case reports].

    Science.gov (United States)

    Zernikow, B; Schiessl, C; Wamsler, C; Griessinger, N; Sittl, R

    2005-10-01

    Based on 4 case reports we focus on the peculiarities of long-term pediatric opioid based pain control. Case report #1, emphasizing the importance of adequate opioid dosing with reference to body weight, illustrates that with adequate management oral sustained-release opioid therapy is safe even in infants less than one year old. Case report #2 is the first report on the usage of buccal fentanyl citrate for pediatric break-through pain control. Case report #3 focuses on the adverse effects of opioid pain control in an infant with neurological impairment. Case report #4 reports on the successful tumor pain control using transdermal buprenorphine. We conclude that proven therapeutic strategies for opioid pain control as applied in adults may be adopted for the usage on children in pediatrics. However, it is mandatory to take into account both the pharmacokinetic and pharmacodynamic peculiarities of childhood.

  13. Pressure Pain Sensitivity in Patients With Suspected Opioid-Induced Hyperalgesia.

    Science.gov (United States)

    Wasserman, Ronald A; Hassett, Afton L; Harte, Steven E; Goesling, Jenna; Malinoff, Herbert L; Berland, Daniel W; Zollars, Jennifer; Moser, Stephanie E; Brummett, Chad M

    2015-01-01

    This study was designed to test whether a brief quantitative sensory testing assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia (OIH). Twenty patients on long-term opioid therapy with suspected OIH were recruited along with 20 healthy controls. Pressure pain threshold, Pain50, a measure of intermediate suprathreshold pressure pain sensitivity, and tolerance levels were evaluated. As a secondary outcome, changes in pressure pain sensitivity after intravenous administration of placebo (saline) and fentanyl (1.5 μg/kg) were assessed. There were no significant differences in pain measures between healthy controls and patients. However, there was an association between higher doses of opioids and having a lower pain tolerance (r = -0.46, P = 0.041) and lower Pain50 (r = -0.46, P = 0.044), which was consistent with the hypothesis. Patients on more than 100 mg oral morphine equivalents displayed decreased pressure pain tolerance compared with patients taking less than 100 mg oral morphine equivalents (P = 0.042). In addition, male patients showed a hyperalgesic response to fentanyl administration, which was significant for the Pain50 measure (P = 0.002). Whereas there were no differences between patients suspected of having OIH and the healthy controls, the finding that higher doses of opioids were associated with more sensitivity suggests that dose might be an important factor in the development of hyperalgesia. In addition, male patients demonstrated a hyperalgesic response after a bolus of fentanyl. Future studies are needed to develop better diagnostics for detecting hyperalgesia in the clinical setting.

  14. Influence from genetic variability on opioid use for cancer pain: a European genetic association study of 2294 cancer pain patients

    DEFF Research Database (Denmark)

    Klepstad, P; Fladvad, T; Skorpen, F

    2011-01-01

    mechanisms. The patients' mean age was 62.5 years, and the average pain intensity was 3.5. The patients' primary opioids were morphine (n=830), oxycodone (n=446), fentanyl (n=699), or other opioids (n=234). Pain intensity, time on opioids, age, gender, performance status, and bone or CNS metastases predicted...... variability with opioid doses in a large population using a confirmatory validation population was warranted. We recruited 2294 adult European patients using a World Health Organization (WHO) step III opioid and analyzed single nucleotide polymorphisms (SNPs) in genes with a putative influence on opioid......C, HTR3D, HTR3E, HTR1, or CNR1 showed significant associations with opioid dose in both the development and the validation analyzes. These findings do not support the use of pharmacogenetic analyses for the assessed SNPs to guide opioid treatment. The study also demonstrates the importance...

  15. Health care resource use and cost differences by opioid therapy type among chronic noncancer pain patients

    Directory of Open Access Journals (Sweden)

    Landsman-Blumberg PB

    2017-07-01

    %, emergency department visits (4% vs 11%–18%, and diagnostic radiology use (21% vs 54%–61% (all: P<0.001. Use of pain-related medications and other treatment modalities was also significantly lower in the mono-LAO cohort relative to the other cohorts. CNCP patients using long-term monotherapy with LAOs had the lowest CP-related total health care costs in the 12 months after opioid initiation compared with mono-SAO, switch, or combination patients despite higher opioid daily doses and higher prescription costs. Future research accounting for severity and duration of pain would aid in determining the optimal long-term opioid regimen for CNCP patients. Keywords: chronic pain, long-acting opioids, short-acting opioids, health care claims, database study

  16. OPIOIDS IN DENTISTRY: A LITERARY REVIEW

    Directory of Open Access Journals (Sweden)

    António H. S. Delgado

    2015-07-01

    Full Text Available The use and prescription of opioids in dentistry is a relevant and current issue given that this class of drugs is still widely used in the treatment of pain, and dentists play a major role in knowing how to properly prescribe them. In this article the aim was to summarize modern literature, scientific articles and textbooks of pharmacology and pharmacology for dentistry in order to provide the dentist with theory and evidence regarding the use of opioids, that can be transported into future clinical judgement. The opioids most commonly used in today’s practice are codeine and oxycodon, they can both be prescribed to manage acute pain when all else fails, and they should be administered in association with paracetamol. The prescription of these drugs is made only when the benefits outweigh the risks and whenever strong analgesia is procured. In children, the use of codeine is compared to morphine and, according to the guidelines, the use of morphine should be considered instead, but in Portugal codeine is still prescribed. In the elderly and during pregnancy, use of opioids should be avoided and needs dose adjustments. This way we conclude that the pharmacotherapy of opioids in the practice of dentistry is common, breaking the prejudice that can arise from the prescription of this class of drugs.

  17. Correlates of overdose risk perception among illicit opioid users.

    Science.gov (United States)

    Rowe, Christopher; Santos, Glenn-Milo; Behar, Emily; Coffin, Philip O

    2016-02-01

    Opioid-related mortality continues to increase in the United States. The current study assesses demographic and behavioral predictors of perceived overdose risk among individuals who use opioids illicitly. By examining these correlates in the context of established overdose risk factors, we aim to assess whether characteristics and behaviors that have been associated with actual overdose risk translate to higher perception of risk. We conducted a cross-sectional survey of 172 adult illicit opioid users in San Francisco, CA and used multivariable logistic regression to identify predictors of perception of high risk for opioid overdose. Age (aOR=0.96, 95%CI=0.93-1.00) and number of injection days per month (0.91, 0.86-0.97) were associated with a lower odds of perceived high overdose risk. There was no independent association between use of opioid analgesics, concurrent use of opioids and benzodiazepines or cocaine, or HIV status and overdose risk perception. Opioid users who injected more frequently and those who were older were less likely to perceive themselves as being at risk of overdose, notwithstanding that those who inject more are at higher risk of overdose and those who are older are at higher risk overdose mortality. In addition, despite being established overdose risk factors, there was no relationship between use of opioid analgesics, concurrent use of opioids and cocaine or benzodiazepines, or self-reported HIV status and overdose risk perception. These findings highlight key populations of opioid users and established risk factors that may merit focused attention as part of education-based overdose prevention and opioid management strategies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Examination of opioid prescribing in Australia from 1992 to 2007.

    Science.gov (United States)

    Leong, M; Murnion, B; Haber, P S

    2009-10-01

    Opioid prescribing is controversial with evidence of both significant under-utilization and over-utilization. There is some evidence to support efficacy for chronic non-malignant pain, but community and individual harms are increasingly reported. To review availability of opioid preparations and prescription patterns of opioids through the subsidized Pharmaceutical Benefits Scheme in Australia from 1992 to 2007. Interrogation of the Health Insurance Commission database from 1992 to 2007. Item numbers for all available opioid preparations were identified, and frequency of dispensing was collected and collated. The number of opioids on the Pharmaceutical Benefits Scheme (PBS) increased from 11 preparations of four medications to 70 preparations of eight medications during this period. The total number of PBS opioid prescriptions increased from 2 397 006 in 1992 to 6 998 556 in 2007. We identified a dramatic and continuing increase in prescription of oxycodone in all dose ranges. Fentanyl prescribing is increasing to a lesser degree. Morphine and tramadol prescribing appears to have plateaued. Opioid use is increasing. There is a pressing need for co-ordinated assessment of efficacy and harms to facilitate quality usage of opioids.

  19. Somatization is associated with non-adherence to opioid prescriptions.

    Science.gov (United States)

    Trafton, Jodie A; Cucciare, Michael A; Lewis, Eleanor; Oser, Megan

    2011-05-01

    Non-adherence to opioid prescriptions can decrease the safety and efficacy of opioid therapy. Identifying factors associated with over- and under-use of opioids in patients presenting with pain may improve prescribing and pain management. Patients presenting with pain often also present with somatization, and somatization is associated with both excessive use of and non-adherence to medications. This study examines the relationship between somatization and non-adherence (over- and under-use) to opioid prescriptions in the Veteran sample. One hundred and ninety-one Veterans who received an opioid prescription at a Veterans Affairs Palo Alto Health Care System in the prior year participated by completing a 1.5 hour semistructured interview which included assessments of depressive symptoms, somatization, medication side effects, and opioid pain medication usage. The percentage of patients non-adherent to opioid prescriptions increased as a function of somatization: Compared to no somatization, all levels of somatization were associated with higher rates of underuse, while severe somatization was associated with increased rates of overuse. Consistent with previous studies of medication non-adherence, increased depression and medication side effects were associated with decreased adherence to opioid prescriptions. However, in exploratory analyses, somatization mediated the relationship between depressive symptoms and opioid-use patterns as well as medication side effects and opioid use patterns. This article sought to explore the relationship between somatization and adherence to prescription opioid medications. Our findings suggest that pain management treatment plans may be optimized by addressing patient distress about physical symptoms when considering the use of prescription opioid medications. Published by Elsevier Inc.

  20. Buprenorphine dosing choices in specific populations: review of expert opinion.

    Science.gov (United States)

    Maremmani, Icro; Rolland, Benjamin; Somaini, Lorenzo; Roncero, Carlos; Reimer, Jens; Wright, Nat; Littlewood, Richard; Krajci, Peter; Alho, Hannu; D'Agnone, Oscar; Simon, Nicolas

    2016-09-01

    Treatment of opioid dependence with buprenorphine improves outcomes. Typical dosing ranges for all patients from clinical evidence and as defined in the product information are wide. For specific groups with complex clinical scenarios, there is no clear consensus on dosing choices to achieve best possible outcomes. The doses of buprenorphine used in 6 European countries was reviewed. A review of published evidence supported rapid induction with buprenorphine and the benefits of higher doses but did not identify clearly useful guidance on dosing choices for groups with complex clinical scenarios. An expert group of physicians with experience in addiction care participated in a discussion meeting to share clinical practice experience and develop a consensus on dosing choices. There was general agreement that treatment outcomes can be improved by optimising buprenorphine doses in specific subgroups. Specific groups in whom buprenorphine doses may be too low and who could have better outcomes with optimised dosing were identified on the basis of clinical practice experience. These groups include people with severe addiction, high tolerance to opioids, and psychiatric comorbidities. In these groups it is recommended to review dosing choices to ensure buprenorphine dosing is sufficient.

  1. Reducing the harm of opioid overdose with the safe use of naloxone : a pharmacologic review.

    Science.gov (United States)

    Kim, Hong K; Nelson, Lewis S

    2015-07-01

    Opioid overdose fatality has increased threefold since 1999. As a result, prescription drug overdose surpassed motor vehicle collision as the leading cause of unintentional injury-related death in the USA. Naloxone , an opioid antagonist that has been available for decades, can safely reverse opioid overdose if used promptly and correctly. However, clinicians often overestimate the dose of naloxone needed to achieve the desired clinical outcome, precipitating acute opioid withdrawal syndrome (OWS). This article provides a comprehensive review of naloxone's pharmacologic properties and its clinical application to promote the safe use of naloxone in acute management of opioid intoxication and to mitigate the risk of precipitated OWS. Available clinical data on opioid-receptor kinetics that influence the reversal of opioid agonism by naloxone are discussed. Additionally, the legal and social barriers to take home naloxone programs are addressed. Naloxone is an intrinsically safe drug, and may be administered in large doses with minimal clinical effect in non-opioid-dependent patients. However, when administered to opioid-dependent patients, naloxone can result in acute opioid withdrawal. Therefore, it is prudent to use low-dose naloxone (0.04 mg) with appropriate titration to reverse ventilatory depression in this population.

  2. Oxycodone recycling: a novel hypothesis of opioid tolerance development in humans.

    Science.gov (United States)

    Linares, Oscar A; Fudin, Jeffrey; Schiesser, William E; Linares, Annemarie Daly; Boston, Raymond C

    2014-09-01

    We hypothesize that oxycodone (OC) recycling promotes sustained synaptic OC content, which prolongs OC's exposure to local μ-opioid receptors (μORs). In that way, OC recycling gives rise to OC tolerance in humans. To pilot test our hypothesis, we developed a whole-body OC mass transport tolerance recovery model. The model derived quantifiable measure of tolerance is TΩ. TΩ estimates OC's tolerance recovery in days; It is defined as the rate of recovery of OC's pharmacologic response after OC is stopped. We studied a random sample of five opioid intolerant healthy male subjects with no history of opioid or illicit drug use, or comorbidities in silico. Subjects were age 24.5 ± 2.3 yr (all values mean ± SD), weight 93 ± 20 kg, and CYP2D6 EM phenotype. Each subject was studied under two experimental conditions: (1) administration of a single oral dose of OC 12 ± 7 mg; and, after complete washout of OC from the intravascular pool, (2) administration of repetitive oral OC doses every 4h for 5 half-lives (t1/2 = 4.5h)-after which time steady-state was assumed. Repetitive OC dose TΩ fell 61% compared to single OC dose TΩ (5.2 ± 1.1 vs. 3.5 ± 0.7 days, p = 0.001). The fall in TΩ was associated with a significant 3-fold increase in extravascular OC content, which was accompanied by 2-fold increase in OC spillover from the extravascular pool, into the intravascular pool. Thus, the model predicted that a single dose of orally administered OC could give rise to tolerance. This is consistent with the widely held view of acute opioid tolerance. In addition, the dynamic changes accompanying repetitive OC dosing suggested that local unbound OC gave rise to both higher extravascular OC content and increased OC spillover. This reflects that OC stimulated endocytosis of μORs was accompanied by a reduction in the availability OC responsive neuroeffector cell surface μOR binding sites. We conclude that our hypothesis extends current concepts of opioid tolerance

  3. 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.

  4. Mechanism of the Interaction of Cannabinoid System in Central Amygdale with Opioid System

    Directory of Open Access Journals (Sweden)

    S Sarahroodi

    2012-05-01

    Full Text Available

    Background and objectives

    Cannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.

                                                                                                                             

    Methods

    In the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala (intra-Amyg microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety.

     

    Results

    Intraperitoneal injection of morphine (3, 6 and 9 mg/kg increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced %OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA (at the dose of 1.25 and 5 ng/rat increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine (6 mg/kg, i.p. without any interaction. Naloxone also reduced ACPA effects.  

    Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 (2.5, 25 and 100 ng/rat did not alter %OAT and %OAE but higher doses of drug (25 and 100 ng/rat reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety.

    Conclusion

    The results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid

  5. Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics.

    Science.gov (United States)

    Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Gray, Andrew; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Howes, John; Weis, Holger; Friedhoff, Lawrence

    2016-08-01

    The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine. © 2016, The American College of Clinical Pharmacology.

  6. Impact of the combined use of benzodiazepines and opioids on workers' compensation claim cost.

    Science.gov (United States)

    Lavin, Robert A; Tao, Xuguang Grant; Yuspeh, Larry; Bernacki, Edward J

    2014-09-01

    Study the use patterns and claim cost impact of prescription opioids and benzodiazepines in workers' compensation. A cohort of 11,394 lost time claims filed with the Louisiana Workers' Compensation Corporation from 1999 to 2002 was observed for 7 years post injuries. We found that benzodiazepines are almost always prescribed in combination with opioids. The odds ratios of benzodiazepines used alone, with short-acting opioids and with long-acting opioids for claims ≥$100,000, were 2.74, 4.69, and 14.24, respectively (after controlling for gender, low back pain, marital status, attorney involvement, and each other). Average benzodiazepine daily dose increased to year 3 postinjury and plateaued thereafter, whereas the average opioid dose escalated each year postinjury. The addition of benzodiazepines to an opioid treatment regimen significantly increases workers' compensation costs.

  7. Partial characterization of a novel endogenous opioid in human cerebrospinal fluid

    Energy Technology Data Exchange (ETDEWEB)

    Miller, B.E.; Lipman, J.J.; Byrne, W.L.

    1987-12-07

    Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated Peak B has previously been shown to be related to the pain status of chronic pain patients. The authors now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (< 1.0 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.

  8. Experience of adjunctive cannabis use for chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study.

    Science.gov (United States)

    Degenhardt, Louisa; Lintzeris, Nicholas; Campbell, Gabrielle; Bruno, Raimondo; Cohen, Milton; Farrell, Michael; Hall, Wayne D

    2015-02-01

    There is increasing debate about cannabis use for medical purposes, including for symptomatic treatment of chronic pain. We investigated patterns and correlates of cannabis use in a large community sample of people who had been prescribed opioids for chronic non-cancer pain. The POINT study included 1514 people in Australia who had been prescribed pharmaceutical opioids for chronic non-cancer pain. Data on cannabis use, ICD-10 cannabis use disorder and cannabis use for pain were collected. We explored associations between demographic, pain and other patient characteristics and cannabis use for pain. One in six (16%) had used cannabis for pain relief, 6% in the previous month. A quarter reported that they would use it for pain relief if they had access. Those using cannabis for pain on average were younger, reported greater pain severity, greater interference from and poorer coping with pain, and more days out of role in the past year. They had been prescribed opioids for longer, were on higher opioid doses, and were more likely to be non-adherent with their opioid use. Those using cannabis for pain had higher pain interference after controlling for reported pain severity. Almost half (43%) of the sample had ever used cannabis for recreational purposes, and 12% of the entire cohort met criteria for an ICD-10 cannabis use disorder. Cannabis use for pain relief purposes appears common among people living with chronic non-cancer pain, and users report greater pain relief in combination with opioids than when opioids are used alone. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Trends in heroin and pharmaceutical opioid overdose deaths in Australia.

    Science.gov (United States)

    Roxburgh, Amanda; Hall, Wayne D; Dobbins, Timothy; Gisev, Natasa; Burns, Lucinda; Pearson, Sallie; Degenhardt, Louisa

    2017-10-01

    There has been international concern over the rise in fatal pharmaceutical opioid overdose rates, driven by increased opioid analgesic prescribing. The current study aimed to examine trends in opioid overdose deaths by: 1) opioid type (heroin and pharmaceutical opioids); and 2) age, gender, and intent of the death assigned by the coroner. Analysis of data from the National Coronial Information System (NCIS) of opioid overdose deaths occurring between 2001 and 2012. Deaths occurred predominantly (98%) among Australians aged 15-74 years. Approximately two-thirds of the decedents (68%) were male. The heroin overdose death rate remains unchanged over the period; these were more likely to occur among males. Pharmaceutical opioid overdose deaths increased during the study period (from 21.9 per million population in 2001-36.2), and in 2012 they occurred at 2.5 times the incident rate of heroin overdose deaths. Increases in pharmaceutical opioid deaths were largely driven by accidental overdoses. They were more likely to occur among males than females, and highest among Australians aged 45-54 years. Rates of fentanyl deaths in particular showed an increase over the study period (from a very small number at the beginning of the period) but in 2012 rates of morphine deaths were higher than those for oxycodone, fentanyl and tramadol. Given the increase in rates of pharmaceutical opioid overdose deaths, it is imperative to implement strategies to reduce pharmaceutical opioid-related mortality, including more restrictive prescribing practices and increasing access to treatment for opioid dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Changes of QTc interval after opioid switching to oral methadone.

    Science.gov (United States)

    Mercadante, Sebastiano; Prestia, Giovanna; Adile, Claudio; Casuccio, Alessandra

    2013-12-01

    A consecutive sample of patients who were switched from strong opioids to methadone in a period of 1 year was surveyed. QTc was assessed before switching (T0) and after achieving adequate analgesia and an acceptable level of adverse effects (Ts). Twenty-eight of 33 patients were switched to methadone successfully. The mean initial methadone doses at T0 were 67.1 mg/day (SD ±80.2, range 12-390). The mean QTc interval at T0 was 400 ms (SD ±30, range 330-450). The mean QTc interval at Ts (median 5 days) was 430 ms (SD ±26, range 390-500). The difference (7.7 %) was significant (p opioid doses expressed as oral morphine equivalents and QTc at T0 (p = 0.428), nor between mean methadone doses and QTc at Ts (p = 0.315). No age differences were found with previous opioid doses (p = 0.917), methadone doses (p = 0.613), QTc at T0 (p = 0.173), QTc at Ts (p = 0.297), and final opioid-methadone conversion ratio (p = 0.064). While methadone used for opioids switching seems to be an optimal choice to improve the opioid response in patients poorly responsive to the previous opioid, the possible QTc prolongation should be of concern despite not producing clinical consequences in this group of patients. A larger number of patients should be assessed to quantify the risk of serious arrhythmia.

  11. Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5α expression in PBMC.

    Science.gov (United States)

    Aamer, Hadega A; Rajakumar, Premeela; Nyaundi, Julia; Murphey-Corb, Michael

    2014-05-23

    At least six host-encoded restriction factors (RFs), APOBEC3G, TRIM5α, tetherin, SAMHD1, schlafen 11, and Mx2 have now been shown to inhibit HIV and/or SIV replication in vitro. To determine their role in vivo in the resistance of macaques to mucosally-acquired SIV, we quantified both pre-exposure (basal) and post-exposure mRNA levels of these RFs, Mx1, and IFNγ in PBMC, lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal exposures to the primary isolate, SIV/DeltaB670. Repetitive challenge divided the monkeys into two groups with respect to their susceptibility to infection: highly susceptible (2-3 challenges, 5 monkeys) and poorly susceptible (≥6 challenges, 3 monkeys). Basal RF and Mx1 expression varied among the three tissues examined, with the lowest expression generally detected in duodenal tissues, and the highest observed in PBMC. The one exception was A3G whose basal expression was greatest in lymph nodes. Importantly, significantly higher basal expression of TRIM5α and Mx1 was observed in PBMC of animals more resistant to mucosal infection. Moreover, individual TRIM5α levels were stable throughout a year prior to infection. Post-exposure induction of these genes was also observed after virus appearance in plasma, with elevated levels in PBMC and duodenum transiently occurring 7-10 days post infection. They did not appear to have an effect on control of viremia. Interestingly, minimal to no induction was observed in the resistant animal that became an elite controller. These results suggest that constitutively expressed TRIM5α appears to play a greater role in restricting mucosal transmission of SIV than that associated with type I interferon induction following virus entry. Surprisingly, this association was not observed with the other RFs. The higher basal expression of TRIM5α observed in PBMC than in duodenal tissues emphasizes the understated role of the second barrier to systemic infection involving the transport of

  12. Opioid switching from and to tapentadol extended release in cancer patients: conversion ratio with other opioids.

    Science.gov (United States)

    Mercadante, Sebastiano; Porzio, Giampiero; Aielli, Federica; Adile, Claudio; Verna, Lucilla; Ficorella, Corrado; Giarratano, Antonello; Casuccio, Alessandra

    2013-06-01

    The aim of this exploratory study was to assess the conversion ratios between tapentadol and other opioids in patients requiring an opioid switching. A prospective study was carried out in a convenience sample of consecutive patients admitted to an acute palliative care unit and a home care unit for a period of 1 year. Patients who were switched from/to tapentadol were selected. The initial ratio between tapentadol and other opioids, expressed as oral morphine equivalents was 1:3.3. The subsequent doses were flexible and were changed to fit the patients' needs. Pain intensity and distress score were recorded until opioid doses were stable. In all, 37 patients were examined; 24 and 13 patients were switched from and to tapentadol, respectively. The most frequent sequences were tapentadol-morphine (18 patients) in one direction, and morphine-tapentadol (8 patients) in the other direction. In the sequence tapentadol-morphine and morphine-tapentadol, the mean final tapentadol-morphine ratios were 3.9:1 (SD 2.3), and 1:4.5 (SD 3.2), respectively, which did not differ significantly from the initial established conversion ratio. A minority of patients were switched from/to tapentadol to/from other opioids. Globally, the initial ratio did not change after switching took place. Data suggest that a conversion ratio between tapentadol and other opioids, expressed in oral morphine equivalents could be 1:3.3 in both direction, particularly in patients who are switched in conditions of equianalgesia. The limited number of patients prevents a definitive conclusion to be drawn, and data should be interpreted with caution, given the exploratory nature of the study and the question of the low number of patients should be addressed in future studies.

  13. 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......, 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...... characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31% versus 19%) compared to those without OIC (P 

  14. Association of Overall Opioid Prescriptions on Adolescent Opioid Abuse.

    Science.gov (United States)

    Sheridan, David C; Laurie, Amber; Hendrickson, Robert G; Fu, Rongwei; Kea, Bory; Horowitz, B Zane

    2016-11-01

    Opioid abuse is a public health epidemic in the United States. Much literature has focused on the prescribing practices of physicians and opioid misuse by adults. However, there are limited data on the effect of opioid prescriptions on adolescent recreational ingestion of these medications. The objective of this study was to assess for a relationship between opioid prescribing practices across the United States and adolescent opioid ingestion calls to poison centers. This was an observational study using the National Poison Data System. The study population consisted of poison center calls regarding adolescents between 2005 and 2010 in the database with a coding of "intentional abuse" and an opioid ingestion. National opioid prescription estimates were generated using nationally representative outpatient and inpatient databases. There were 4186 adolescent opioid ingestion calls during the study period. There was a general increase between 2005 and 2010 in both teen opioid abuse calls (617 in 2005 to 782 in 2010) and national opioid prescriptions (approximately 78 million in 2005 to 108 million in 2010). For each opioid prescription increase per 100 persons per year, the annual teen opioid abuse calls increased by 1.8% (95% confidence interval 0.9-2.8%), equivalent to an absolute increase of about 0.04 to 0.05 calls per 100,000 teens annually. There appears to be an association between opioid prescriptions nationally and poison center calls for adolescent opioid ingestions. This is particularly important in this patient population because of impulsivity and early exposure to substance abuse. Providers should be aware of the nonmedical use of opioids by adolescents and educate patients accordingly. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Opioid neurotransmission modulates defensive behavior and fear-induced antinociception in dangerous environments.

    Science.gov (United States)

    Coimbra, Norberto Cysne; Calvo, Fabrício; Almada, Rafael Carvalho; Freitas, Renato Leonardo; Paschoalin-Maurin, Tatiana; Dos Anjos-Garcia, Tayllon; Elias-Filho, Daoud Hibrahim; Ubiali, Walter Adriano; Lobão-Soares, Bruno; Tracey, Irene

    2017-06-23

    The effects of endogenous opioid peptide antagonists on panic-related responses are controversial. Using elevated mazes and a prey-versus-predator paradigm, we investigated the involvement of the endogenous opioid peptide-mediated system in the modulation of anxiety- and panic attack-induced responses and innate fear-induced antinociception in the present work. Wistar rats were intraperitoneally pretreated with either physiological saline or naloxone at different doses and were subjected to either the elevated plus- or T-maze test or confronted by Crotalus durissus terrificus. The defensive behaviors of the rats were recorded in the presence of the predator and at 24h after the confrontation, when the animals were placed in the experimental enclosure without the rattlesnake. The peripheral non-specific blockade of opioid receptors had a clear anxiolytic-like effect on the rats subjected to the elevated plus-maze but not on those subjected to the elevated T-maze; however, a clear panicolytic-like effect was observed, i.e., the defensive behaviors decreased, and the prey-versus-predator interaction responses evoked by the presence of the rattlesnakes increased. A similar effect was noted when the rats were exposed to the experimental context in the absence of the venomous snake. After completing all tests, the naloxone-treated groups exhibited less anxiety/fear-induced antinociception than the control group, as measured by the tail-flick test. These findings demonstrate the anxiolytic and panicolytic-like effects of opioid receptor blockade. In addition, the fearlessness behavior displayed by preys treated with naloxone at higher doses enhanced the defensive behavioral responses of venomous snakes. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. 77 FR 75177 - Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments

    Science.gov (United States)

    2012-12-19

    ... between minimizing opioid drug abuse and misuse, while simultaneously enabling appropriate access to pain..., such as those pertaining to drug product composition, specific abuse-deterrence properties, and... establish a maximum daily dose of opioid drugs? d. What effect(s), if any, would a maximum daily dose for...

  17. [TEN YEARS OF OPIOID CONSUMPTION BY CHILDREN (2001-2010)].

    Science.gov (United States)

    Freud, Tamar; Sherf, Michael; Battat, Erez; Vardy, Daniel; Shvartzman, Pesach

    2015-09-01

    Opioids are considered a cornerstone in the treatment of pain. They are rarely used in almost half of the countries of the world, especially in children. The aim of this study was to assess opioid use over a ten-year study period from 2001-2010, among children 0-18 years old who are members of Clalit Health Services (CHS), the largest HMO in Israel Data on the purchase of opioids, authorized for use in Israel, was obtained from the computerized databases of CHS. In addition, the patient's demographic details and cancer morbidity were also extracted. The data was analyzed after all the doses of all opioids consumed (fentanyl patch, oxycodone, methadone, hydromorphone, oral transmucosal fentanyl) were converted into oral morphine equivalents (OME). In all, 1,098 children purchased at least one opioid prescription during the study period. Of them, 27.3% had a diagnosis of cancer and 55.5% were female. A 42% decrease in total annual OME (mg) purchased, from 209,443 mg to 122,048 mg, was observed from 2001 to 2010. There was no specific pattern or trend in the annual number of pediatric and adolescent patients who purchased at least one opioid drug during the study period. In 86.5% of the cases, children with a non-cancer cause of pain purchased opioids for only one month. There is a low and inconsistent rate of opioid consumption among pediatric and adolescent members of the CHS. Further study is needed to explore the reasons for this low opioid consumption rate in this population group.

  18. Changes in opioid prescribing for chronic pain in Washington State.

    Science.gov (United States)

    Franklin, Gary M; Fulton-Kehoe, Deborah; Turner, Judith A; Sullivan, Mark D; Wickizer, Thomas M

    2013-01-01

    To conduct a survey of primary care physicians and advanced registered nurse practitioners (ARNPs) in Washington State (WA) focused on changes in practice patterns and use of support tools in the prescription of opioids for the treatment of chronic noncancer pain (CNCP). A convenience sample of primary care providers in WA was obtained from diverse geographic regions and health care organizations. The web-based anonymous survey was conducted in March-August 2011. Among 856 provider respondents, 623 reported treating patients with CNCP and served as the analysis sample. Most providers (72%) reported concern about opioid overdose, addiction, dependence, or diversion. Only 25% indicated concern about regulatory scrutiny. Only a small proportion of providers overall (3.3%) reported that they had stopped prescribing opioids for CNCP, but twice as many ARNPs (5.8%) as physicians (MDs and osteopaths) (2.1%) reported this. A greater proportion of physicians (70.9%) than ARNPs (40.1%) reported familiarity with the Washington State opioid dosing guidelines. Physicians in a large health plan with substantial infrastructure support reported less concern about opioids compared with providers in other settings. Of providers in Spokane (the largest city in Eastern Washington), 45% reported very low capacity to access pain specialty consultation. The vast majority of providers reported a need to access more efficient, innovative means of support and education related to treating patients with CNCP, such as telemedicine consultation. Overall, prescribing providers in WA reported ongoing concerns regarding opioid use for CNCP, but those affiliated with a health care organization with opioid prescribing guidelines and access to pain consultation were less likely to report being concerned about opioid-related problems or to have discontinued prescribing opioids.

  19. Effects of cold pressor pain on the abuse liability of intranasal oxycodone in male and female prescription opioid abusers

    Science.gov (United States)

    Lofwall, Michelle R.; Nuzzo, Paul A.; Walsh, Sharon L.

    2012-01-01

    Background Approximately 1.9 million persons in the U.S. have prescription opioid use disorders often with concomitant bodily pain, but systematic data on the impact of pain on abuse liability of opioids is lacking. The purpose of this study was to determine whether pain alters the intranasal abuse liability of oxycodone, a commonly prescribed and abused analgesic, in males and females. Methods Sporadic prescription opioid abusers (10 females, 10 males) participated in this mixed (between and within-subject), randomized inpatient study. Experimental sessions (n=6) tested intranasal placebo, oxycodone 15 or 30 mg/70 kg during cold pressor testing (CPT) and a warm water control. Observer- and subject-rated drug effect measures, analgesia, physiologic and cognitive effects were assessed. Results The CPT significantly increased blood pressure, heart rate, pain, stress, and “opiate desire” compared to the no-pain control but did not alter opioid liking, high or street value. Intranasal oxycodone produced effects within 10 minutes, significantly decreasing pain and significantly increasing subjective measures of abuse liability (e.g., high). Females had higher ratings of street value, high, and liking for one or both active doses. Conclusions The CPT was a reliably painful and stressful stimulus that did not diminish the abuse liability of intranasal Oxycodone®. Females were more sensitive to oxycodone on several abuse liability measures that warrant further follow-up. Snorting oxycodone rapidly produced psychoactive effects indicative of substantial abuse liability. PMID:22209386

  20. New Developed DR Detector Performs Radiographs of Hand, Pelvic and Premature Chest Anatomies at a Lower Radiation Dose and/or a Higher Image Quality

    DEFF Research Database (Denmark)

    Precht, Helle; Outzen, Claus Bjørn; Tingberg, Anders

    2013-01-01

    using Visual Grading Analysis (VGA). The results from the technical phantom studies showed that the image quality expressed as IQFINV values was on average approximately 45 % higher with the CXDI-70C detector compared to the CXDI-55C detector. Consistently, the VGA results from the anatomical phantom......A newly developed Digital Radiography (DR) detector has smaller pixel size and higher fill factor than earlier detector models. These technical advantages should theoretically lead to higher sensitivity and higher spatial resolution, thus making dose reduction possible without scarifying image...... quality compared to previous DR detector versions. To examine whether the newly developed Canon CXDI-70C DR detector provides an improved image quality and/or allows for dose reductions in hand and pelvic bone examinations as well as premature chest examinations, compared to the previous (CXDI-55C) DR...

  1. Opioid overdose in a child: case report and discussion with emphasis on neurosurgical implications.

    Science.gov (United States)

    Reisner, Andrew; Hayes, Laura L; Holland, Christopher M; Wrubel, David M; Kebriaei, Meysam A; Geller, Robert J; Baum, Griffin R; Chern, Joshua J

    2015-12-01

    In environments in which opioids are increasingly abused for recreation, children are becoming more at risk for both accidental and nonaccidental intoxication. In toxic doses, opioids can cause potentially lethal acute leukoencephalopathy, which has a predilection for the cerebellum in young children. The authors present the case of a 2-year-old girl who suffered an accidental opioid overdose, presenting with altered mental status requiring cardiorespiratory support. She required emergency posterior fossa decompression, partial cerebellectomy, and CSF drainage due to cerebellar edema compressing the fourth ventricle. To the authors' knowledge, this is the first report of surgical decompression used to treat cerebellar edema associated with opioid overdose in a child.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Diagnostic I-131 scintigraphy in patients with differentiated thyroid cancer : no additional value of higher scan dose

    NARCIS (Netherlands)

    Phan, TTH; van Tol, KM; Links, TP; Piers, DA; de Vries, EGE; Dullaart, RPF; Jager, PL

    2004-01-01

    Objective: After initial treatment with total thyroidectomy and radioiodine ablation, most follow-up protocols for patients with differentiated thyroid carcinoma contain cyclic diagnostic I-131 imaging and serum thyroglobulin measurements. The applied diagnostic I-131 doses vary between 37 and 370

  4. Smoking history, nicotine dependence and opioid use in patients with chronic non-malignant pain

    DEFF Research Database (Denmark)

    Plesner, K; Jensen, H I; Højsted, J

    2016-01-01

    BACKGROUND: Previous studies have demonstrated a positive association between smoking and addiction to opioids in patients with chronic non-malignant pain. This could be explained by a susceptibility in some patients to develop addiction. Another explanation could be that nicotine influences both...... pain and the opioid system. The objective of the study was to investigate whether smoking, former smoking ± nicotine use and nicotine dependence in patients with chronic non-malignant pain were associated with opioid use and addiction to opioids. METHODS: The study was a cross-sectional study carried...... as in the general population. The prevalence of patients using opioids was 54% and the prevalence of addiction to opioids was 6%. No significant differences in addiction were found between the different smoking groups, but smokers and former smokers using nicotine tended to use opioids more frequently and at higher...

  5. Evaluating the abuse potential of opioids and abuse-deterrent -opioid formulations: A review of clinical study methodology.

    Science.gov (United States)

    Setnik, Beatrice; Schoedel, Kerri A; Levy-Cooperman, Naama; Shram, Megan; Pixton, Glenn C; Roland, Carl L

    With the development of opioid abuse-deterrent formulations (ADFs), there is a need to conduct well-designed human abuse potential studies to evaluate the effectiveness of their deterrent properties. Although these types of studies have been conducted for many years, largely to evaluate inherent abuse potential of a molecule and inform drug scheduling, methodological approaches have varied across studies. The focus of this review is to describe current "best practices" and methodological adaptations required to assess abuse-deterrent opioid formulations for regulatory submissions. A literature search was conducted in PubMed® to review methodological approaches (study conduct and analysis) used in opioid human abuse potential studies. Search terms included a combination of "opioid," "opiate," "abuse potential," "abuse liability," "liking," AND "pharmacodynamic," and only studies that evaluated single doses of opioids in healthy, nondependent individuals with or without prior opioid experience were included. Seventy-one human abuse potential studies meeting the prespecified criteria were identified, of which 21 studies evaluated a purported opioid ADF. Based on these studies, key methodological considerations were reviewed and summarized according to participant demographics, study prequalification, comparator and dose selection, route of administration and drug manipulation, study blinding, outcome measures and training, safety, and statistical analyses. The authors recommend careful consideration of key elements (eg, a standardized definition of a "nondependent recreational user"), as applicable, and offer key principles and "best practices" when conducting human abuse potential studies for opioid ADFs. Careful selection of appropriate study conditions is dependent on the type of ADF technology being evaluated.

  6. Impact of ABCB1 and CYP2B6 Genetic Polymorphisms on Methadone Metabolism, Dose and Treatment Response in Patients with Opioid Addiction: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Dennis, Brittany B.; Bawor, Monica; Thabane, Lehana; Sohani, Zahra; Samaan, Zainab

    2014-01-01

    Background Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse. Objectives To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment). Methods Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms. Results We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05–1.00, p = 0.03) with minimal heterogeneity (I2 = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27–2.61, p = 0.02) however significant heterogeneity was observed (I2 = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response. Conclusion Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers. PMID:24489693

  7. Opioid metabolism and clinical aspects.

    Science.gov (United States)

    Mercadante, Sebastiano

    2015-12-15

    Opioids are are commonly used for the management of acute and chronic pain. Opioids have different physicochemical and pharmacokinetic characteristics, which explain the profound changes in the clinical effect in several clinical conditions. Pharmacokinetics influences the opioid response affecting bioavailability, production of metabolites with residual clinical activity, and elimination. Generality of opioid metabolism and clinical implications for specific opioids in different clinical conditions were reviewed to bridge the gap between pharmacokinetics and clinical response. The knowledge of opioid metabolism is essential, particularly for older and complicated patients who receive multiple medications and may have impaired of renal and hepatic function. The recognition of possible metabolic problems and the consideration of adverse drug-drug interactions are fundamental to optimize the use of opioids in clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong.

    Science.gov (United States)

    Cheung, C W; Chan, T Cw; Chen, P P; Chu, M C; Chui, W Cm; Ho, P T; Lam, F; Law, S W; Lee, J Ly; Wong, S Hs; Wong, V Kc

    2016-10-01

    Opioids are increasingly used to control chronic non-cancer pain globally. International opioid guidelines have been issued in many different countries but a similar document is not generally available in Hong Kong. Chronic opioid therapy has a role in multidisciplinary management of chronic non-cancer pain despite insufficient evidence for its effectiveness and safety for long-term use. This document reviews the current literature to inform Hong Kong practitioners about the rational use of chronic opioid therapy in chronic non-cancer pain. It also aims to provide useful recommendations for the appropriate, effective, and safe use of such therapy in the management of chronic non-cancer pain in adults. Physicians should conduct a comprehensive biopsychosocial evaluation of patients prior to the commencement of opioid therapy. When opioid use is deemed appropriate, the patient should provide informed consent within an agreement that specifies treatment goals and expectations. A trial of opioid can be commenced and, provided there is progress towards treatment goals, then chronic therapy can be considered at a dose that minimises harm. Monitoring of effectiveness, safety, and drug misuse should be continued. Treatment should be stopped when opioids become ineffective, intolerable, or misused. The driving principles for opioid prescription in chronic pain management should be: start with a low dose, titrate slowly, and maintain within the shortest possible time.

  9. The Economic Impact of Opioid Use in the Management of Chronic Nonmalignant Pain.

    Science.gov (United States)

    Lipman, Arthur; Webster, Lynn

    2015-10-01

    Chronic nonmalignant pain (CNMP), defined as persistent pain that is not attributable to a potentially life-limiting condition and has a duration of at least 3 months, is widespread in the United States. Moderate-to-severe CNMP often is treated with opioid analgesics, and there is ongoing debate regarding appropriate allocation of opioids to treat CNMP because long-term treatment can result in problematic side effects, drug misuse, or abuse leading to detrimental medical, social, and economic consequences. Furthermore, therapeutic strategies arising from concerns about the misuse of opioids may impede the treatment of patients who require strong analgesics for adequate pain relief. While current CNMP management includes nonpharmacologic and pharmacologic approaches, including acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids, there is debate regarding the risk-benefit profile of opioids for chronic pain treatment. Mitigation of opioid misuse and abuse and proper administration of opioid analgesics must be balanced against providing appropriate analgesia. To accomplish this, managed care policies could implement guidelines that focus on evaluating risk characteristics for opioid misuse and abuse, use opioid dose-sparing strategies, and encourage the use of alternative analgesics or nonpharmacologic therapy when appropriate. The purpose of this review is to examine challenges and costs associated with CNMP management using opioids and to summarize alternative therapeutic approaches.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Opioid Misuse Trends in Treatment Seeking Populations: Revised Prescription Opioid Policy and Temporally Corresponding Changes.

    Science.gov (United States)

    Hoffman, Lauren A; Lewis, Ben; Nixon, Sara Jo

    2017-12-06

    Over the last two decades, U.S. rates of prescription opioid (PO) misuse have risen drastically. In response, federal and state governments have begun to implement new PO policies. Recent legislative changes warrant up-to-date assessments of today's misuse rates. To explore potential changes in opioid misuse trends among substance-using treatment seekers, in temporal relation to legislative response. Substance-use data were collected from two cross-sectional Florida-based inpatient cohorts during periods preceding (pre-policy; n = 647) and following (post-policy; n = 396) statewide PO policy initiatives. Participants provided information concerning their most frequently used drugs before treatment. PO and illicit opioid (IO) use prevalence, frequency and route of administration were examined for pre-policy vs. post-policy cohort differences. Relative to the pre-policy cohort, a greater percentage of the post-policy cohort reported recent misuse, daily use, and intravenous administration of POs. IO use was also more frequently reported post-policy. Non-opioid drug use prevalence did not significantly differ between cohorts. Among the opioid-using subsample, equivalent percentages of the pre- and post-policy cohorts reported the use of POs without IOs, IOs without POs, and POs/IOs concurrently. Conclusions/Importance: Florida's PO policy amendments were temporally accompanied by a higher prevalence of PO misuse and IO use among treatment-seekers assessed in this study. Whether our data reflect increased awareness of and treatment seeking for opioid use disorders or insufficient efficacy of new policies to reduce opioid misuse remains in question. Regardless, findings suggest the need for enhanced emphasis on mitigating hazardous PO-use behaviors (e.g., IV use).

  12. APA national audit of pediatric opioid infusions.

    Science.gov (United States)

    Morton, Neil S; Errera, Agata

    2010-02-01

    , use of concurrent sedatives or opioids by different routes and overgenerous dosing in infants. Early respiratory depression in patients with specific risk factors, such as young age, neurodevelopmental, respiratory, or cardiac comorbidities, who are receiving nurse-controlled analgesia or continuous opioid infusion suggests that closer monitoring for at least 2 h is needed for these cases. As a result of this audit, we can provide parents with better information on relative risks to help the process of informed consent.

  13. Opioids, survival, and advanced cancer in the hospice setting.

    Science.gov (United States)

    Azoulay, Daniel; Jacobs, Jeremy M; Cialic, Ron; Mor, Eliana Ein; Stessman, Jochanan

    2011-02-01

    Although pain is common among advanced cancer patients, it can be controlled in a large proportion of patients. Several barriers hinder this, including the concern that opioids hasten death. We examined whether opioids influence survival among advanced cancer patients. Retrospective observational study from September 2006 to October 2007. In-patient hospice unit. Participants were 114 consecutive hospice patients (mean age 71.7 ± 13.9 years). Analysis of survival (days) following admission, according to opioid usage. Standardized Oral Morphine Equivalents (OME mg/d) were calculated. On admission 74.6% received opioids, rising to 92.1% at death. Mean opioid dosage was OME of 146 ± 245 mg/d, and mean survival was 12.3 ± 12.15 days. Mean survival, according to opioid dosage of 0, 1 to 119, and greater than or equal to 120 OME mg/d respectively at admission, was 16.7 ± 13.4, 11.2 ± 12.1, 10.0 ± 10.2 (P = .009), and according to dose at death was 17.0 ± 15.1, 12.3 ± 12.1, 11.1 ± 11.3 (P = ns). Increasing overall opioid dosage was associated with improved survival compared with no change or decreasing overall dosage (mean survival 14.0 ± 12.7 days versus 9.3 ± 9.8 versus 9.1 ± 11.4, days respectively, P = .01). Adjusting for clinical variables in Cox proportional hazards models, no significant association was found between mortality and of the following aspects of opioid usage: (1) dose on admission (Hazard Ratio [HR] 1.009, 95% confidence interval [CI] 0.999-1.019); (2) dose at death (HR 1.004, 95% CI 0.996-1.013); (3) mean dose (HR 1.006, 95% CI 0.997-1.016); (4) overall dose increase (HR 0.733, 95% CI 0.417-1.288) and decrease (HR 0.967, 95% CI 0.472-1.984); (5) day-by-day dosage changes (HR 1.005, 95% CI 0.996-1.013). Opioid usage, even at high dosages, had no effect on survival among advanced cancer patients in a hospice setting. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

  14. Improving Adherence to Long-term Opioid Therapy Guidelines to Reduce Opioid Misuse in Primary Care A Cluster-Randomized Clinical Trial

    Science.gov (United States)

    Liebschutz, Jane M.; Xuan, Ziming; Shanahan, Christopher W.; LaRochelle, Marc; Keosaian, Julia; Beers, Donna; Guara, George; O’Connor, Kristen; Alford, Daniel P.; Parker, Victoria; Weiss, Roger D.; Samet, Jeffrey H.; Crosson, Julie; Cushman, Phoebe A.; Lasser, Karen E.

    2017-01-01

    IMPORTANCE Prescription opioid misuse is a national crisis. Few interventions have improved adherence to opioid-prescribing guidelines. OBJECTIVE To determine whether a multicomponent intervention, Transforming Opioid Prescribing in Primary Care (TOPCARE; http://mytopcare.org/), improves guideline adherence while decreasing opioid misuse risk. DESIGN, SETTING, AND PARTICIPANTS Cluster-randomized clinical trial among 53 primary care clinicians (PCCs) and their 985 patients receiving long-term opioid therapy for pain. The study was conducted from January 2014 to March 2016 in 4 safety-net primary care practices. INTERVENTIONS Intervention PCCs received nurse care management, an electronic registry, 1-on-1 academic detailing, and electronic decision tools for safe opioid prescribing. Control PCCs received electronic decision tools only. MAIN OUTCOMES AND MEASURES Primary outcomes included documentation of guideline-concordant care (both a patient-PCC agreement in the electronic health record and at least 1 urine drug test [UDT]) over 12 months and 2 or more early opioid refills. Secondary outcomes included opioid dose reduction (ie, 10% decrease in morphine-equivalent daily dose [MEDD] at trial end) and opioid treatment discontinuation. Adjusted outcomes controlled for differing baseline patient characteristics: substance use diagnosis, mental health diagnoses, and language. RESULTS Of the 985 participating patients, 519 were men, and 466 were women (mean [SD] patient age, 54.7 [11.5] years). Patients received a mean (SD) MEDD of 57.8 (78.5) mg. At 1 year, intervention patients were more likely than controls to receive guideline-concordant care (65.9% vs 37.8%; P opioid treatment discontinuation (AOR, 1.6; 95% CI, 1.3–2.1; P opioid refills. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01909076 PMID:28715535

  15. Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study.

    Directory of Open Access Journals (Sweden)

    Tara Gomes

    2017-10-01

    Full Text Available Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality.We conducted a population-based nested case-control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily, moderate (900 to 1,799 mg daily, or high (≥1,800 mg daily. A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256 and 6.8% of controls (313 of 4,619 were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI

  16. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain.

    Science.gov (United States)

    Labianca, Roberto; Sarzi-Puttini, Piercarlo; Zuccaro, Stefano Maria; Cherubino, Paolo; Vellucci, Renato; Fornasari, Diego

    2012-02-01

    Chronic pain is a debilitating condition that is associated with many common diseases; this places a major burden on the healthcare system. There are currently numerous analgesic agents available for the treatment of chronic pain. In general, the oral non-opioid analgesic, paracetamol, is recommended for the initial treatment of mild to moderate pain. Therapeutic doses of paracetamol do not appear to result in hepatotoxicity, although overdose may lead to acute liver failure. Current data suggest that paracetamol has acceptable gastrointestinal tolerability. Another class of non-opioid analgesic with confirmed efficacy for the treatment of chronic mild to moderate pain are non-steroidal anti-inflammatory drugs (NSAIDs), although this efficacy is offset by the potential of adverse gastrointestinal events. In particular, non-selective NSAIDs, also known as cyclooxygenase (COX) inhibitors, carry an increased risk of serious upper gastrointestinal complications, including ulcers, perforation and bleeding. The introduction of COX-2 inhibitors provided a NSAID-based option with improved gastrointestinal safety, but increased risk of cardiovascular effects. Opioids are powerful analgesic agents used to treat moderate to severe chronic pain. However, treatment with opioids is associated with a number of common adverse effects, including constipation, nausea or vomiting, pruritus, somnolence or cognitive impairment, dry mouth, tolerance or dependence and urinary retention. Although there are multiple strategies in place to manage adverse events that arise from both non-opioid and opioid analgesic therapy, a better understanding of the mechanisms involved in the development of specific drug-related adverse effects is required along with proper prescribing practices and adequate physician/patient education. Balanced against the adverse effects of pain management medications, there is a need to be mindful of the widespread, often serious, adverse consequences of poorly managed

  17. Opioid Antagonist Impedes Exposure.

    Science.gov (United States)

    Merluzzi, Thomas V.; And Others

    1991-01-01

    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  18. Opiate and opioid withdrawal

    Science.gov (United States)

    ... of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med . 2015 Sep-Oct;9(5):358-367. PMID: 26406300 www.ncbi.nlm.nih.gov/pubmed/26406300 . Review Date 4/20/2016 Updated by: Jacob L. ...

  19. Correlates and Consequences of Opioid Misuse among High-Risk Young Adults

    Directory of Open Access Journals (Sweden)

    Sheree M. Schrager

    2014-01-01

    Full Text Available Background. Prescription opioids are the most frequently misused class of prescription drug among young adults aged 18–25, yet trajectories of opioid misuse and escalation are understudied. We sought to model opioid misuse patterns and relationships between opioid misuse, sociodemographic factors, and other substance uses. Methods. Participants were 575 young adults age 16–25 who had misused opioids in the last 90 days. Latent class analysis was performed with models based on years of misuse, recency of misuse, and alternate modes of administration within the past 12 months, 3 months, and 30 days. Results. Four latent classes emerged that were differentially associated with heroin, cocaine, and methamphetamine use, tranquilizer misuse, daily opioid misuse, and opioid withdrawal. Alternate modes of administering opioids were associated with increased risk for these outcomes. Sociodemographic factors, homelessness, prescription history, and history of parental drug use were significantly associated with riskier opioid misuse trajectories. Conclusion. Young adults who reported more debilitating experiences as children and adolescents misused opioids longer and engaged in higher risk alternate modes of administering opioids. Data on decisions both to use and to alter a drug’s form can be combined to describe patterns of misuse over time and predict important risk behaviors.

  20. Use of prescribed opioids by children and adolescents: Differences between Denmark, Norway and Sweden.

    Science.gov (United States)

    Mahic, M; Fredheim, O M; Borchgrevink, P C; Skurtveit, S

    2015-09-01

    There are few studies on the use of opioids among children and adolescents. The aim of this study was to determine the 1-year prevalence of prescribed opioid dispensing in Denmark, Norway and Sweden, and to compare gender and age differences in the use of weak and strong opioids between the three countries. Data on the dispensing of opioids were collected from the websites of the complete national prescription databases in the three countries. All individuals aged 0-19 with at least one prescription of opioids during the study period were included. The 1-year prevalence of opioid use among young individuals aged 0-19 years increased during the study period (2006-2012) in Denmark from 2.5 to 3.4 per thousand, in Norway from 10.7 to 13.4 per thousand and in Sweden from 5.9 to 7.1 per thousand. In all three countries, more boys than girls used opioids between the ages of 0 and 10, whereas girls were the major users in the age range 11-19. Use of opioids in all three countries was dominated by weak opioids, codeine being the most dominant in Norway and Sweden and tramadol in Denmark. The 1-year prevalence of prescribed opioid use among children and adolescents in Norway was far higher than in Denmark and Sweden. During the study period, an increasing use of opioids among children and adolescents was observed in all three countries. © 2014 European Pain Federation - EFIC®

  1. Effects of immediate-release opioid on memory functioning: a randomized-controlled study in patients receiving sustained-release opioids.

    Science.gov (United States)

    Kamboj, S K; Conroy, L; Tookman, A; Carroll, E; Jones, L; Curran, H V

    2014-11-01

    The effects of opioid medication on cognitive functioning in patients with cancer and non-cancer pain remain unclear. In this mechanistic randomized, double-blind, placebo-controlled, cross-over study of patients (n = 20) receiving sustained-release and immediate-release opioid medication as part of their palliative care, we examine memory effects of an additional dose of participants' immediate-release medication (oxycodone or morphine) or placebo. Immediate prose recall and recall of related and unrelated word pairs was assessed pre-and post-drug (placebo or immediate-release opioid). Memory for these stimuli was also tested after a delay on each testing occasion. Finally, performance on an 'interference' word pair task was assessed on the two testing occasions since proactive interference has been posited as a mechanism for acute opioid-induced memory impairment. Unlike previous work, we found no evidence of memory impairment for material presented before or after individually tailored, 'breakthrough' doses of immediate-release opioid. Furthermore, immediate-release opioid did not result in increased memory interference. On the other hand, we found enhanced performance on the interference word pair task after immediate-release opioid, possibly indicating lower levels of interference. These results suggest that carefully titrated immediate-release doses of opioid drugs may not cause extensive memory impairment as previously reported, and in fact, may improve memory in certain circumstances. Importantly, our findings contrast strikingly with those of a study using the same robust design that showed significant memory impairment. We propose that factors, such as depressive symptoms, education level and sustained-release opioid levels may influence whether impairment is observed following immediate-release opioid treatment. © 2014 European Pain Federation - EFIC®

  2. The opioid ketobemidone has a NMDA blocking effect

    DEFF Research Database (Denmark)

    Andersen, S; Dickenson, A H; Kohn, M

    1996-01-01

    . The present study was therefore made to evaluate the effects of ketobemidone. The study consists of two parts. (1) Single unit recordings were made from dorsal horn neurones in the halothane-anaesthetised rat. Neurones were activated by transcutaneous electrical stimulation of their receptive fields at C......There are clinical observations that neurogenic pain can respond well to the opioid ketobemidone, in contrast to pethidine and morphine. This has led us to the hypothesis that the analgesic effect of ketobemidone in neurogenic pain may be due to both opioid as well as additional non-opioid effects......, dose-dependently and selectively reduced C-fibre evoked responses. Ketobemidone was also found to block wind-up more effectively than morphine at equieffective doses, but unlike morphine in a non-naloxone-reversible manner. (2) In a binding study ketobemidone was shown to inhibit [3H]MK-801 binding...

  3. Risk Factors for Opioid-Use Disorder and Overdose.

    Science.gov (United States)

    Webster, Lynn R

    2017-11-01

    Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.

  4. Pain, alcohol use disorders and risky patterns of drinking among people with chronic non-cancer pain receiving long-term opioid therapy.

    Science.gov (United States)

    Larance, Briony; Campbell, Gabrielle; Peacock, Amy; Nielsen, Suzanne; Bruno, Raimondo; Hall, Wayne; Lintzeris, Nicholas; Cohen, Milton; Degenhardt, Louisa

    2016-05-01

    The utilisation of pharmaceutical opioids has increased internationally, and there is evidence of increasing risky alcohol consumption with ageing. This study examines the patterns and correlates of risky drinking among people with chronic non-cancer pain (CNCP) prescribed opioids, and the associations between alcohol consumption and pain. The Pain and Opioids IN Treatment cohort comprises 1514 people in Australia prescribed pharmaceutical opioids for CNCP. Participants reported lifetime, past year and past month alcohol use, as well as mental and physical health, other substance use, pain characteristics, and current opioid dose. Less than one-tenth of the sample were 'lifetime abstainers' (7%); 34% were 'former drinkers'; 34% were 'non-risky drinkers' (i.e., past 12 month use ≤4 standard drinks); 16% were 'occasional risky drinkers'; and 8% were 'regular risky drinkers' (i.e., ≥weekly use of >4 standard drinks). Males reported greater levels of alcohol use, and a third (33%) of the total sample reported a lifetime alcohol use disorder. Controlling for demographics, mental health, physical health and substance use disorder history, 'former drinkers' (cf. 'non-risky drinkers') reported higher pain severity and interference ratings, and lower pain coping. 'Occasional risky drinkers' and 'regular risky drinkers' (cf. 'non-risky drinkers') reported higher levels of pain interference. Among people with CNCP, those who abstained from alcohol or drank at risky levels reported poorer pain outcomes compared with moderate drinkers. Early identification and intervention for risky drinking among people is critical, particularly given the risks associated with co-administration of alcohol and opioids. Copyright © 2016. Published by Elsevier Ireland Ltd.

  5. Differential effects of exercise on brain opioid receptor binding and activation in rats.

    Science.gov (United States)

    Arida, Ricardo Mario; Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Cavalheiro, Esper Abrão; Zavala-Tecuapetla, Cecilia; Brand, Serge; Rocha, Luisa

    2015-01-01

    Physical exercise stimulates the release of endogenous opioid peptides supposed to be responsible for changes in mood, anxiety, and performance. Exercise alters sensitivity to these effects that modify the efficacy at the opioid receptor. Although there is evidence that relates exercise to neuropeptide expression in the brain, the effects of exercise on opioid receptor binding and signal transduction mechanisms downstream of these receptors have not been explored. Here, we characterized the binding and G protein activation of mu opioid receptor, kappa opioid receptor or delta opioid receptor in several brain regions following acute (7 days) and chronic (30 days) exercise. As regards short- (acute) or long-term effects (chronic) of exercise, overall, higher opioid receptor binding was observed in acute-exercise animals and the opposite was found in the chronic-exercise animals. The binding of [(35) S]GTPγS under basal conditions (absence of agonists) was elevated in sensorimotor cortex and hippocampus, an effect more evident after chronic exercise. Divergence of findings was observed for mu opioid receptor, kappa opioid receptor, and delta opioid receptor receptor activation in our study. Our results support existing evidence of opioid receptor binding and G protein activation occurring differentially in brain regions in response to diverse exercise stimuli. We characterized the binding and G protein activation of mu, kappa, and delta opioid receptors in several brain regions following acute (7 days) and chronic (30 days) exercise. Higher opioid receptor binding was observed in the acute exercise animal group and opposite findings in the chronic exercise group. Higher G protein activation under basal conditions was noted in rats submitted to chronic exercise, as visible in the depicted pseudo-color autoradiograms. © 2014 International Society for Neurochemistry.

  6. Polydrug abuse: A review of opioid and benzodiazepine combination use

    Science.gov (United States)

    Jones, Jermaine D.; Mogali, Shanthi; Comer, Sandra D.

    2012-01-01

    This paper reviews studies examining the pharmacological interactions and epidemiology of the combined use of opioids and benzodiazepines (BZD). A search of English language publications from 1970 - 2012 was conducted using PubMed and PsycINFO®. Our search found approximately 200 articles appropriate for inclusion in this paper. While numerous reports indicate that the co-abuse of opioids and BZDs is ubiquitous around the world, the reasons for the co-abuse of these medications are not entirely clear. Though the possibility remains that opioid (ab)users are using BZDs therapeutically to self-medicate anxiety, mania or insomnia, the data reviewed in this paper suggest that BZD use is primarily recreational. For example, co-users report seeking BZD prescriptions for the purpose of enhancing opioid intoxication or “high,” and use doses that exceed the therapeutic range. Since there are few clinical studies investigating the pharmacological interaction and abuse liability of their combined use, this hypothesis has not been extensively evaluated in clinical settings. As such, our analysis encourages further systematic investigation of BZD abuse among opioid users. The co-abuse of BZDs and opioids is substantial and has negative consequences for general health, overdose lethality, and treatment outcome. Physicians should address this important and underappreciated problem with more cautious prescribing practices, and increased vigilance for abusive patterns of use. PMID:22857878

  7. Cancer pain management: safe and effective use of opioids.

    Science.gov (United States)

    Bruera, Eduardo; Paice, Judith A

    2015-01-01

    Pain remains a serious consequence of cancer and its treatment. Although significant advances have been made in providing effective cancer pain control, barriers persist. Lack of knowledge, limited time, financial restrictions, and diminished availability of necessary medications serve as significant obstacles. Safe and effective opioid use in a patient with cancer requires skill to overcome these challenges. Understanding the mechanism of action, along with the pharmacokinetics and pharmacodynamics, of opioids will lead to appropriate selection, dosing, and titration of these agents. Rotation from one opioid or route to another is an essential proficiency for oncologists. As opioid-related adverse effects often occur, the oncology team must be expert in preventing and managing constipation, nausea, sedation, and neurotoxicities. An emerging concern is overtreatment-the excessive and prolonged use of opioids in patients when these agents may produce more harm than benefit. This can occur when opioids are used inappropriately to treat comorbid psychologic issues such as anxiety and depression. Recognizing risk factors for overuse along with key components of universal precautions will promote safe use of these medications, supporting adherence and preventing diversion, thereby protecting the patient, the prescriber, and the community. Because substance use disorders are not rare in the oncology setting, attention must be given to the balance of providing analgesia while limiting harm. Caring for patients with substance misuse requires compassionate, multidisciplinary care, with input from supportive oncology/palliative care as well as addiction specialists.

  8. Polydrug abuse: a review of opioid and benzodiazepine combination use.

    Science.gov (United States)

    Jones, Jermaine D; Mogali, Shanthi; Comer, Sandra D

    2012-09-01

    This paper reviews studies examining the pharmacological interactions and epidemiology of the combined use of opioids and benzodiazepines (BZDs). A search of English language publications from 1970 to 2012 was conducted using PubMed and PsycINFO(®). Our search found approximately 200 articles appropriate for inclusion in this paper. While numerous reports indicate that the co-abuse of opioids and BZDs is ubiquitous around the world, the reasons for the co-abuse of these medications are not entirely clear. Though the possibility remains that opioid abusers are using BZDs therapeutically to self-medicate anxiety, mania or insomnia, the data reviewed in this paper suggest that BZD use is primarily recreational. For example, co-users report seeking BZD prescriptions for the purpose of enhancing opioid intoxication or "high," and use doses that exceed the therapeutic range. Since there are few clinical studies investigating the pharmacological interaction and abuse liability of their combined use, this hypothesis has not been extensively evaluated in clinical settings. As such, our analysis encourages further systematic investigation of BZD abuse among opioid abusers. The co-abuse of BZDs and opioids is substantial and has negative consequences for general health, overdose lethality, and treatment outcome. Physicians should address this important and underappreciated problem with more cautious prescribing practices, and increased vigilance for abusive patterns of use. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Investigation of sinonasal anatomy via low-dose multidetector CT examination in chronic rhinosinusitis patients with higher risk for perioperative complications.

    Science.gov (United States)

    Fraczek, Marcin; Guzinski, Maciej; Morawska-Kochman, Monika; Krecicki, Tomasz

    2017-02-01

    The aim of the study was to compare visualisation of the surgically relevant anatomical structures via low- and standard-dose multidetector CT protocol in patients with chronic rhinosinusitis (CRS) and higher risk for perioperative complications (i.e. presence of bronchial asthma, history of sinus surgery and advanced nasal polyposis). 135 adult CRS patients were divided randomly into standard-dose (120 kVp, 100 mAs) or low-dose CT groups (120 kVp, 45 mAs). The detectability of the vital anatomical structures (anterior ethmoid artery, optic nerve, cribriform plate and lamina papyracea) was scored using a five-point scale (from excellent to unacceptable) by a radiologist and sinus surgeon. Polyp sizes were quantified endoscopically according to the Lildholdt's scale (LS). Olfactory function was tested with the "Sniffin' Sticks" test. On the low-dose CT images, detectability ranged from 2.42 (better than poor) for cribriform plate among anosmic cases to 4.11 (better than good) for lamina papyracea in cases without nasal polyps. Identification of lamina papyracea on low-dose scans was significantly worse in each group and the same was the case with cribriform plates in patients with advanced polyposis and anosmia. Cribriform plates were the most poorly identified (between poor and average) among all the structures on low-dose images. Identification of anterior ethmoid artery (AEA) with reduced dose was insignificantly worse than with standard-dose examination. The AEA was scored as an average-defined structure and was the second weakest visualised. In conclusion, preoperatively, low-dose protocols may not sufficiently visualise the surgically relevant anatomical structures in patients with CRS and bronchial asthma, advanced nasal polyps (LS > 2) and history of sinus surgery. Low mAs value enables comparable detectability of sinonasal landmarks with standard-dose protocols in patients without analysed risk factors. In the context of planned surgery, the current

  10. Opioids for the management of breakthrough pain in cancer patients.

    Science.gov (United States)

    Zeppetella, Giovambattista; Davies, Andrew N

    2013-10-21

    ) in the management of breakthrough pain. Two studies examined the titration of OTFC, one study compared OTFC versus normal-release morphine and one study compared OTFC versus placebo.Fifteen studies (1699 participants) met the inclusion criteria for this update. All studies reported on the utility of seven different transmucosal fentanyl formulations, five of which were administered orally and two nasally. Eight studies compared the transmucosal fentanyl formulations versus placebo, four studies compared them with another opioid, one study was a comparison of different doses of the same formulation and two were randomised titration studies. Oral and nasal transmucosal fentanyl formulations were an effective treatment for breakthrough pain. When compared with placebo or oral morphine, participants gave lower pain intensity and higher pain relief scores for transmucosal fentanyl formulations at all time points. Global assessment scores also favoured transmucosal fentanyl preparations. One study compared intravenous with the transmucosal route and both were effective. Oral and nasal transmucosal fentanyl is an effective treatment in the management of breakthrough pain. The RCT literature for the management of breakthrough pain is relatively small. Given the importance of this subject, more trials, including head-to-head comparisons of the available transmucosal fentanyl formulations are required.

  11. Low dose growth hormone treatment in infants and toddlers with Prader-Willi syndrome is comparable to higher dosage regimens.

    Science.gov (United States)

    Scheermeyer, Elly; Harris, Mark; Hughes, Ian; Crock, Patricia A; Ambler, Geoffrey; Verge, Charles F; Bergman, Phil; Werther, George; Craig, Maria E; Choong, Catherine S; Davies, Peter S W

    2017-06-01

    Evaluate benefit and risk of low dose growth hormone treatment (GHT, 4.5mg/m2/week) in very young children with Prader-Willi Syndrome (PWS). Prospective longitudinal clinical intervention. We evaluated 31 infants (aged 2-12months) and 42 toddlers (13-24months) from the PWS-OZGROW database for height, weight and BMI using the World Health Organization standard deviation scores (SDSWHO) and PWS specific BMI (SDSPWS), bone age, insulin-like growth factor 1 (IGF-I) levels and adverse events over 3years of GHT. At commencement of GHT infants had a lower BMI SDSWHO (-0.88 vs 0.40) than toddlers, while toddlers had a lower height SDSWHO (-1.44 vs -2.09) (both P<0.05). All increased height SDSWHO (2year delta height infants +1.26 SDS, toddlers+1.21 SDS), but infants normalised height sooner, achieving a height SDS of -0.56 within 1year, while toddlers achieved a height SDS of -0.88 in two years. BMI SDSWHO increased, while BMI SDSPWS decreased (both P<0.0001) and remained negative. The GHT response did not differ with gestation (preterm 23%) or genetic subtype (deletion vs maternal uniparental disomy). Bone age advancement paralleled chronological age. All children had low serum IGF-I at baseline which increased, but remained within the age-based reference range during GHT (for 81% in first year). Four children had spinal curvature at baseline; two improved, two progressed to a brace and two developed an abnormal curve over the observation period. Mild to severe central and/or obstructive sleep apnoea were observed in 40% of children prior to GHT initiation; 11% commenced GHT on positive airway pressure (PAP), oxygen or both. Eight children ceased GHT due to onset or worsening of sleep apnoea: 2 infants in the first few months and 6 children after 6-24months. Seven resumed GHT usually after adjusting PAP but five had adenotonsillectomy. One child ceased GHT temporarily due to respiratory illness. No other adverse events were reported. Two children substantially improved

  12. Advances in the delivery of buprenorphine for opioid dependence

    Directory of Open Access Journals (Sweden)

    Rosenthal RN

    2017-08-01

    Full Text Available Richard N Rosenthal,1 Viral V Goradia2 1Department of Psychiatry, Addiction Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 2Department of Psychiatry, Upstate Medical University, Syracuse, NY, USA Abstract: Opioid use disorders (OUDs have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD. Keywords: opioid use disorder, buprenorphine, drug diversion, drug implants, depot medications, maintenance therapy, treatment adherence

  13. When Is an Opioid Safe to Take?

    Science.gov (United States)

    ... gov/news/fullstory_166872.html When Is an Opioid Safe to Take? Doctors say it can treat ... Society of Anesthesiologists (ASA): Why was I prescribed opioids? Did the doctor assume opioids are the strongest ...

  14. "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

  15. Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain.

    Science.gov (United States)

    Gong, Xiao-Di; Wang, Jiong-Yi; Liu, Feng; Yuan, Hai-Hua; Zhang, Wen-Ying; Guo, Yue-Hui; Jiang, Bin

    2013-01-01

    Polymorphisms of OPRM1 A118G and ABCB1 C3435T have been suggested to contribute to inter-individual variability regarding pain sensitivity, opioid usage, tolerance and dependence and incidence of adverse effects in patients with chronic pain. This study aimed to investigate the association of both two polymorphisms with opioid requirements in Chinese patients with cancer pain. The genotypes of rs1799971 (OPRM1) and rs1045642 (ABCB1) were determined by PCR-RFLP and direct sequencing methods respectively in 112 patients with cancer-related pain. Comparisons between the different genotype or allele groups were performed with t-tests or one-way ANOVA tests, as appropriate. The potential relationship of allele number with opioid response was performed with a trend Jonckheere-Terpstra test. In the 112 subjects, the frequencies of variant 118 G and 3435T allele were 38.4% and 37.9%, respectively. Significant higher 24h-opioid doses were observed in patients with GG (P=0.0004) and AG + GG (P=0.005) genotypes than the AA carriers. The dominant mutant 118G allele tended to be associated with progressively increasing 24h-opioiddoses (P=0.001). Compared with CC/CT, patients with ABCB1 TT genotype received higher 24h- and weight-surface area-adjusted-24h- opioids doses (P=0.057 and 0.028, respectively). The OPRM1 A118G single nucleotide polymorphism (SNP) is a key contributor for the inter-individual variability in opioidrequirements in Chinese cancer pain patients. This may possibly extend to the ABCB1 C3435T SNP.

  16. Buprenorphine for managing opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M; Mbewe, Dalitso

    2017-02-21

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment. To assess the effects of buprenorphine versus tapered doses of methadone, alpha 2 -adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha 2 -adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens. We used standard methodological procedures expected by Cochrane. We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to

  17. New opioid receptor antagonist: Naltrexone-14-O-sulfate synthesis and pharmacology.

    Science.gov (United States)

    Zádor, Ferenc; Király, Kornél; Váradi, András; Balogh, Mihály; Fehér, Ágnes; Kocsis, Dóra; Erdei, Anna I; Lackó, Erzsébet; Zádori, Zoltán S; Hosztafi, Sándor; Noszál, Béla; Riba, Pál; Benyhe, Sándor; Fürst, Susanna; Al-Khrasani, Mahmoud

    2017-08-15

    Opioid antagonists, naloxone and naltrexone have long been used in clinical practice and research. In addition to their low selectivity, they easily pass through the blood-brain barrier. Quaternization of the amine group in these molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In addition, zwitterionic compounds have been reported to have limited CNS access. The current study, for the first time gives report on the synthesis and the in vitro [competition binding, G-protein activation, isolated mouse vas deferens (MVD) and mouse colon assay] pharmacology of the zwitterionic compound, naltrexone-14-O-sulfate. Naltrexone, naloxone, and its 14-O-sulfate analogue were used as reference compounds. In competition binding assays, naltrexone-14-O-sulfate showed lower affinity for µ, δ or κ opioid receptor than the parent molecule, naltrexone. However, the μ/κ opioid receptor selectivity ratio significantly improved, indicating better selectivity. Similar tendency was observed for naloxone-14-O-sulfate when compared to naloxone. Naltrexone-14-O-sulfate failed to activate [ 35 S]GTPγS-binding but inhibit the activation evoked by opioid agonists (DAMGO, Ile 5,6 deltorphin II and U69593), similarly to the reference compounds. Schild plot constructed in MVD revealed that naltrexone-14-O-sulfate acts as a competitive antagonist. In mouse colon, naltrexone-14-O-sulfate antagonized the inhibitory effect of morphine with lower affinity compared to naltrexone and higher affinity when compared to naloxone or naloxone-14-O-sulfate. In vivo (mouse tail-flick test), subcutaneously injected naltrexone-14-O-sulfate antagonized morphine's antinociception in a dose-dependent manner, indicating it's CNS penetration, which was unexpected from such zwitter ionic structure. Future studies are needed to evaluate it's pharmacokinetic profile. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse.

    Directory of Open Access Journals (Sweden)

    M D Raleigh

    Full Text Available Among vaccines aimed at treating substance use disorders, those targeting opioids present several unique medication development challenges. 1 Opioid overdose is a common complication of abuse, so it is desirable for an opioid vaccine to block the toxic as well as the addictive effects of opioids. 2 It is important that an opioid vaccine not interfere with the action of opioid antagonists used to reverse opioid overdose or treat addiction. 3 Some opioids are immunosuppressive and chronic ongoing opioid use could interfere with vaccine immunogenicity. 4 Although antibody-bound oxycodone is unable to enter the brain because of its size, it might still be able to activate peripheral opioid receptors. To assess vaccine impact on opioid toxicity, rats vaccinated with oxycodone conjugated to keyhole limpet hemocyanin subunit dimer (OXY-dKLH adsorbed to alum or controls vaccinated with dKLH were compared with regard to oxycodone-induced hotplate analgesia and oxycodone-induced respiratory depression and bradycardia. Vaccination shifted the dose-response curves to the right, representing protection, for each of these endpoints. Naloxone was equally effective in both OXY-dKLH and control groups, providing complete and rapid reversal of respiratory depression. The administration of a long-acting naltrexone formulation during vaccination did not impair vaccine immunogenicity in mice. Similarly, serum anti-oxycodone antibody titers were not altered by continuous morphine infusion during vaccination compared to opioid-naïve controls. Competitive ELISA assay showed negligible or low affinity of immune antiserum for endogenous opioids or opioid antagonists. In vitro receptor binding assays showed that antibody-bound oxycodone does not activate mu opioid receptors. These data support further study of OXY-dKLH as a potential treatment for oxycodone abuse and suggest that vaccination might also reduce the severity of oxycodone overdose.

  19. Single dose oral analgesics for postoperative pain have few adverse events.

    Science.gov (United States)

    Wong, Yin J

    2016-09-01

    Data sourcesThe Cochrane Database of Systematic Reviews on the Cochrane Library.Study selectionAll Cochrane reviews of RCTs between 1999 to 2015, conducted in adults examining the adverse events associated with single dose oral analgesics used for acute post-operative pain were considered.Data extraction and synthesisStudies were searched, reviewed and assessed independently by two reviewers and standard data items extracted. Methodological quality was assessed using criteria adapted from AMSTAR (Assessing the Methodological Quality of Systematic Reviews).ResultsData from 39 Cochrane reviews of 41 different analgesics or analgesic combinations involving a total of 350 studies involving 35,000 adults were included. Most analgesics were tested in a narrow dose range. For most NSAIDs, paracetamol (acetaminophen), and combinations not containing opioids, the rates of adverse events were similar to that of placebos (NSAID 3% - 44% vs 4 - 46%; paracetamol 7-18% vs 6-16%; combination 11-30% vs 6-48%). However, for higher dosages, like 1000 mg aspirin, 1000 mg diflunisal, and opioids or drug combinations containing opioids, there was a statistically significant difference in the incidence of adverse events reported (NNH 7.7(95%CI; 4.8 - 20) for 1000 mg aspirin; 7.5(95%CI; 4.8-17) for 1000 mg diflunisal; 3.5-8.6 for opioids and combinations). Serious adverse events were rare, occurring at about 1 in 3,200.ConclusionsDespite ongoing problems with the measurement, recording and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.

  20. Defining risk of prescription opioid overdose: pharmacy shopping and overlapping prescriptions among long-term opioid users in medicaid.

    Science.gov (United States)

    Yang, Zhuo; Wilsey, Barth; Bohm, Michele; Weyrich, Meghan; Roy, Kakoli; Ritley, Dominique; Jones, Christopher; Melnikow, Joy

    2015-05-01

    Use of multiple pharmacies concurrently (pharmacy shopping) and overlapping prescriptions may be indicators of potential misuse or abuse of prescription opioid medications. To evaluate strategies for identifying patients at high risk, we first compared different definitions of pharmacy shopping and then added the indicator of overlapping opioid prescriptions. We identified a cohort of 90,010 Medicaid enrollees who used ≥ 3 opioid prescriptions for ≥ 90 days during 2008 to 2010 from a multistate Medicaid claims database. We compared the diagnostic odds ratios for opioid overdose events of 9 pharmacy shopping definitions. Within a 90-day interval, a threshold of 4 pharmacies had the highest diagnostic odds ratio and was used to define pharmacy shopping. The overdose rate was higher in the subgroup with overlapping prescriptions (18.5 per 1,000 person-years [PYs]) than in the subgroup with pharmacy shopping as the sole indicator (10.7 per 1,000 PYs). Among the subgroup with both conditions, the overdose rate was 26.3 per 1,000 PYs, compared with 4.3 per 1,000 PYs for those with neither condition. Overlapping opioid prescriptions and pharmacy shopping measures had adjusted hazard ratios of 3.0 and 1.8, respectively, for opioid overdose. Using these measures will improve accurate identification of patients at highest risk of opioid overdose, the first step in implementing targeted prevention policies. Long-term prescription opioid use may lead to adverse events, including overdose. Both pharmacy shopping and overlapping opioid prescriptions are associated with adverse outcomes. This study demonstrates that using both indicators will better identify those at high risk of overdose. Published by Elsevier Inc.

  1. Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States.

    Science.gov (United States)

    Iwanicki, Janetta L; Severtson, S Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J; Ellis, Matthew S; Kurtz, Steven P; Buttram, Mance E; Dart, Richard C

    2016-01-01

    Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (popioids (pOpioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (popioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

  2. Endogenous opioid peptides in uterine fluid.

    Science.gov (United States)

    Petraglia, F; Facchinetti, F; M'Futa, K; Ruspa, M; Bonavera, J J; Gandolfi, F; Genazzani, A R

    1986-08-01

    The present study demonstrates the presence of the endogenous opioid peptides beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), in the uterine fluid of fertile women and normally cycling and superovulated cows. The two peptides are undetectable in the uterine fluid of untreated postmenopausal women, whereas they are present following estrogen-progesterone treatment. Immunoreactive (IR) MET-ENK concentrations were higher in the secretory than in the proliferative phase of the menstrual cycle. IR beta-EP and IR MET-ENK are present also in the follicular, oviductal, and uterine fluid of cows, and in the uterine fluid, concentrations of IR MET-ENK are higher in the superovulated than in the control animals. Because opioids play important roles on endocrine and immune functions, the present data support the potential physiologic role of endometrial secretions.

  3. The cognitive effects of opioids.

    Science.gov (United States)

    Ersek, Mary; Cherrier, Monique M; Overman, Steven S; Irving, Gordon A

    2004-06-01

    Successful opioid therapy often depends on achieving a balance between analgesic effectiveness and side effects. The risk of opioid-induced cognitive impairment often hinders clinicians and patients from initiating or optimizing opioid therapy. Despite subjective experiences of mental dullness and sedation, objective tests of cognitive functioning do not always demonstrate marked changes following opioid administration. To guide clinical practice, as well as patient and family teaching, pain management nurses should be familiar with literature regarding this topic. The purpose of this article is to review the empiric literature on opioids and cognitive functioning, including the relationships among pain, cognition, delirium, and opioids. In general, research reflects minimal to no significant impairments in cognitive functioning. If impairment does occur, it is most often associated with parenteral opioids administered to opioid-naive individuals. Some evidence suggests that opioids may actually enhance cognitive function and decrease delirium in some patient populations. This article describes this research and explores the clinical implications of the research in this area.

  4. Pain management of opioid-treated cancer patients in hospital settings in Denmark.

    Science.gov (United States)

    Lundorff, L; Peuckmann, V; Sjøgren, P

    2008-01-01

    To evaluate the performance and quality of cancer pain management in hospital settings. Anaesthesiologists specialised in pain and palliative medicine studied pain management in departments of oncology and surgery. Study days were randomly chosen and patients treated with oral opioids were included. Information regarding pain aetiology and mechanisms, pain medications and opioid side effects were registered from the medical records and by examining patients. Pain intensity was assessed using the Brief Pain Inventory. In total, 59 cancer patients were included. In 49 (83%) patients pain aetiology was assessed by the physicians of the departments of oncology and surgery. In only 19 (32%) patients they assessed pain mechanisms. The median oral morphine dose was 120 mg/day (range: 10-720 mg/day). Seventy-eight per cent of patients received opioids at adequate regular intervals according to the duration of action. In 88% of the patients supplemental short-acting oral opioids were given on demand and the median supplemental oral dose was 16.5% of the daily dose. Seven patients with neuropathic pain received adjuvant drugs, whereas six patients with non-neuropathic pain received adjuvant drugs. Regarding opioid side effects only constipation and nausea were treated in the majority of the patients. Average pain intensity in the last 24 h for the total number of patients (n=59) Cancer pain was prevalent in opioid-treated patients in hospital settings: however, focussing on average pain intensity, the outcome seems favourable compared with other countries. Pain mechanisms were seldom examined and adjuvant drugs were not specifically used for neuropathic pain. Opioid dosing intervals and supplemental opioid doses were most often adequate. However, opioid side effects were highly prevalent and most side effects were left untreated.

  5. Purified cell wall from the probiotic bacterium Lactobacillus gasseri activates systemic inflammation and, at higher doses, produces lethality in a rat model.

    Science.gov (United States)

    Xu, Xinhui; Hicks, Caitlin; Li, Yan; Su, Junwu; Shiloach, Joseph; Kaufman, Jeanne B; Fitz, Yvonne; Eichacker, Peter Q; Cui, Xizhong

    2014-07-02

    One proposed benefit of probiotic therapy is that probiotic bacterial cell-wall binding to intestinal cell pathogen-recognition receptors activates protective innate immunity. However, in critically ill patients, intestinal epithelium disruption by shock or other insults may compromise this compartmentalized response and cause systemic bacteria and cell-wall translocation. The effects of intravascular introduction of probiotic bacterial cell wall are unclear. We investigated 24-hour infusions of purified cell wall from Lactobacillus gasseri ATC33323 (L. gasseri), a probiotic bacterium, in Sprague-Dawley rats (n = 49). Increasing cell-wall doses (0 (control), 10, 20, 40, 80, or 160 mg/kg over 24 hours) produced dose-ordered decreases in survival measured after 168 hours (11 survivors/11 total (100%), seven of seven (100%), seven of seven (100%), six of eight (75%), five of eight (63%), and one of nine (11%), respectively, P gasseri cell wall was equally or more lethal than Staphylococcus aureus cell wall, which was previously studied (100% to 88% survival with the same increasing doses). During challenge, compared with controls, L. gasseri cell wall produced increases in blood IL-1β, IL-10, tumor necrosis factor-α, migratory inhibitory protein-1α, monocyte chemotactic protein-1, and nitric oxide, and decreases in neutrophils, lymphocytes, and platelets that were greater with higher versus lower doses (P ≤ 0.05). Medium-dose cell wall (40 and 80 mg/kg combined) progressively decreased blood pressure and increased heart rate, and all doses increased lactate, hepatic transaminases, and creatinine phosphokinase (P ≤ 0.05). Although L. gasseri, like other probiotic bacteria, is considered safe, its cell wall can stimulate the maladaptive inflammatory response associated with pathogenic bacteria. Such effects deserve study, especially regarding critically ill patients.

  6. Pharmacotherapy of Pain in the Older Population: The Place of Opioids.

    Science.gov (United States)

    Prostran, Milica; Vujović, Katarina Savić; Vučković, Sonja; Medić, Branislava; Srebro, Dragana; Divac, Nevena; Stojanović, Radan; Vujović, Aleksandar; Jovanović, Lepa; Jotić, Ana; Cerovac, Nataša

    2016-01-01

    Pain is a common symptom in older people. It is possible that pain is underreported in older persons due to an incorrect belief that it is an inevitable part of aging. Opioid analgesics are potent medications, with confirmed efficacy for the treatment of moderate to severe pain. These drugs are commonly used in older persons. However, there is insufficient evidence regarding safety of opioids in older patients. One of the reasons for this is the lack of randomized, controlled clinical trials. People of advanced age often have comorbidites and use other prescription drugs, as well as over-the-counter (OTC) compounds, thus making them more suceptible to the risk of interactions with opioids. Significant pharmacokinetic and pharmacodynamic changes that occur with advancing age increase the risk of adverse effects of opioids. There are also some discrepancies between guidelines, which recommend the use of lower doses of opioids in older patients, and the findings in the literature which suggest that pain is often undertreated in this age group. It seems that there are significant variations in the tolerability of different opioid analgesics in older people. Morphine, fentanyl, oxycodone, and buprenorphine are still the preferred evidence-based choices for add-on opioid therapy for these patients. However, the safety and efficacy of other opioids in older patients, especially if comorbidities and polypharmacy are present, is still questionable. This review addresses the most important aspects of the use of opioids in older persons, focusing on pharmacokinetics, pharmacodynamics, adverse effects, and interactions.

  7. Is tapentadol different from classical opioids? A review of the evidence

    Science.gov (United States)

    Langford, Richard M; Knaggs, Roger; Farquhar-Smith, Paul; Dickenson, Anthony H

    2016-01-01

    Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain. The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action. The reduced incidence of some of the typical opioid-induced side effects, compared to equianalgesic doses of classical opioids, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms. Both the pre-clinical and clinical profiles appear to be differentiated from those of classical opioids. PMID:27867511

  8. Is tapentadol different from classical opioids? A review of the evidence.

    Science.gov (United States)

    Langford, Richard M; Knaggs, Roger; Farquhar-Smith, Paul; Dickenson, Anthony H

    2016-11-01

    Tapentadol is a single molecule able to deliver analgesia by two distinct mechanisms, a feature which differentiates it from many other analgesics. Pre-clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist activity and noradrenaline re-uptake inhibition. From these, one may predict that tapentadol would be applicable across a broad spectrum of pain from nociceptive to neuropathic. The evidence in animal models suggests that norepinephrine re-uptake inhibition (NRI) is a key mechanism and may even predominate over opioid actions in chronic (and especially neuropathic) pain states, reinforcing that tapentadol is different to classical opioids and may, therefore, be an a priori choice for the treatment of neuropathic and mixed pain. The clinical studies and subsequent practice experience and surveillance support the concept of opioid and non-opioid mechanisms of action. The reduced incidence of some of the typical opioid-induced side effects, compared to equianalgesic doses of classical opioids, supports the hypothesis that tapentadol analgesia is only partially mediated by opioid agonist mechanisms. Both the pre-clinical and clinical profiles appear to be differentiated from those of classical opioids.

  9. CDC Vital Signs: Opioid Painkiller Prescribing

    Science.gov (United States)

    ... Health Services Administration Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends Opioid Overdose Prevention Toolkit Buprenorphine Treatment Locator Mental Health Treatment Locator ...

  10. Physicians' beliefs and likelihood of prescribing opioid tamper-resistant formulations for chronic noncancer pain patients.

    Science.gov (United States)

    Turk, Dennis C; Dansie, Elizabeth J; Wilson, Hilary D; Moskovitz, Bruce; Kim, Myoung

    2014-04-01

    Tamper-resistant opioid formulations (TRFs) have recently been the target of active development in an effort to deter opioid misuse and abuse. To understand factors that are predictive of physicians' likelihoods of prescribing TRFs to patients with chronic noncancer pain (CNCP). A cross-sectional survey was conducted, utilizing a questionnaire of clinicians' attitudes and opinions about opioids for CNCP (Clinicians' Attitudes about Opioids Scale) to explore beliefs about and likelihood of prescribing TRFs. A nationally representative sample of 1,535 practicing physicians throughout the United States. A stepwise hierarchical multiple linear regression analysis was conducted to estimate if physician characteristics, opinions, or geographic region categorized according to state rates of mortality by drug overdose and milligrams of opioids prescribed by state were predictive of the likelihood of prescribing TRFs. Board certification in Pain Medicine and prescribing opioids to a higher volume of CNCP patients were significantly predictive of a reported likelihood of prescribing TRFs, in addition to concerns about possible misuse and abuse of opioids, beliefs in the effectiveness of opioids for CNCP, and greater satisfaction with education and training in pain management this set of factors accounted for 21% of the model variance. Rates of mortality by drug overdose and opioid prescription volume by location were not predictive of TRF usage. Reducing physician concerns about potential misuse and abuse of opioids through additional education in pain management and dissemination of information about the potential benefits and availability of TRFs should influence physicians' attitudes about and the adoption of TRFs. Wiley Periodicals, Inc.

  11. Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

    Science.gov (United States)

    Cepeda, M Soledad; Fife, Daniel; Kihm, Mary A; Mastrogiovanni, Greg; Yuan, Yingli

    2014-12-01

    This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

  12. 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.

  13. Higher toxicity with 42 Gy in 10 fractions as a total dose for 3D-conformal accelerated partial breast irradiation: results from a dose escalation phase II trial.

    Science.gov (United States)

    Bourgier, Celine; Acevedo-Henao, Catalina; Dunant, Ariane; Rossier, Christine; Levy, Antonin; El Nemr, Mohamed; Dumas, Isabelle; Delaloge, Suzette; Mathieu, Marie-Christine; Garbay, Jean-Remi; Taghian, Alphonse; Marsiglia, Hugo

    2012-08-22

    Recent recommendations regarding indications of accelerated partial breast irradiation (APBI) have been put forward for selected breast cancer (BC) patients. However, some treatment planning parameters, such as total dose, are not yet well defined. The Institut Gustave Roussy has initiated a dose escalation trial at the 40 Gy/10 fractions/5 days and at a further step of total dose (TD) of 42 Gy/10 fractions/ 5 days. Here, we report early results of the latest step compared with the 40 Gy dose level. From October 2007 to March 2010, a total of 48 pT1N0 BC patients were enrolled within this clinical trial: 17 patients at a TD of 42 Gy/10f/5d and 31 at a TD of 40 Gy/10f/5d. Median follow-up was 19 months (min-max, 12-26). All the patients were treated by APBI using a technique with 2 minitangents and an "enface" electrons delivering 20% of the total dose. Toxicities were systematically assessed at 1; 2; 6 months and then every 6 months. Patients' recruitment of 42 Gy step was ended owing to persistent grade 3 toxicity 6 months after APBI completion (n = 1). Early toxicities were statistically higher after a total dose of 42 Gy regarding grade ≥2 dry (p = 0.01) and moist (p = 0.05) skin desquamation. Breast pain was also statistically higher in the 42 Gy step compared to 40 Gy step (p = 0.02). Other late toxicities (grade ≥2 fibrosis and telangectasia) were not statistically different between 42 Gy and 40 Gy. Early toxicities were more severe and higher rates of late toxicities were observed after 42 Gy/10 fractions/5 days when compared to 40 Gy/10 fractions/5 days. This data suggest that 40 Gy/10 fractions/ 5 days could potentially be the maximum tolerance for PBI although longer follow-up is warranted to better assess late toxicities.

  14. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children

    Science.gov (United States)

    Wong, Ivan; St John-Green, Celia; Walker, Suellen M

    2013-01-01

    Background and Objectives Perioperative pain in children can be effectively managed with systemic opioids, but addition of paracetamol or nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce opioid requirements and potentially improve analgesia and/or reduce adverse effects. Methods A systematic literature search was conducted to identify trials evaluating postoperative opioid requirements in children and comparing NSAID and/or paracetamol with placebo. Studies were stratified according to design: continuous availability of intravenous opioid (PCA/NCA) vs intermittent ‘as needed’ bolus; and single vs multiple dose paracetamol/NSAIDs. Primary outcome data were extracted, and the percentage decrease in mean opioid consumption was calculated for statistically significant reductions compared with placebo. Secondary outcomes included differences in pain intensity, adverse effects (sedation, respiratory depression, postoperative nausea and vomiting, pruritus, urinary retention, bleeding), and patient/parent satisfaction. Results Thirty-one randomized controlled studies, with 48 active treatment arms compared with placebo, were included. Significant opioid sparing was reported in 38 of 48 active treatment arms, across 21 of the 31 studies. Benefit was most consistently reported when multiple doses of study drug were administered, and 24 h PCA or NCA opioid requirements were assessed. The proportion of positive studies was less with paracetamol, but was influenced by dose and route of administration. Despite availability of opioid for titration, a reduction in pain intensity by NSAIDs and/or paracetamol was reported in 16 of 29 studies. Evidence for clinically significant reductions in opioid-related adverse effects was less robust. Conclusion This systematic review supports addition of NSAIDs and/or paracetamol to systemic opioid for perioperative pain management in children. PMID:23570544

  15. Hypothesizing that a Pro-Dopaminergic Regulator (KB220z(™) Liquid Variant) can Induce "Dopamine Homeostasis" and Provide Adjunctive Detoxification Benefits in Opiate/Opioid Dependence.

    Science.gov (United States)

    Blum, Kenneth; Whitney, Debra; Fried, Lye; Febo, Marcelo; Waite, Roger L; Braverman, Eric R; Dushaj, Kristina; Li, Mona; Giordano, John; Demetrovics, Zsolt; Badgaiyan, Rajendra D

    2016-01-01

    In order to explore the initiation of detoxification of addictive patients to opiates/opioids (along with some other anti-withdrawal agents), we developed a protocol to be utilized in treatment centers particularly with heavily dependent opiate/opioid subjects. Out of 17 subjects, only three received Buprenorphine/Naloxone (Bup/nx) along with KB220Z. In this pilot, we first used a dose of KB220Z of 2 oz twice daily before meals along with clonidine and benzodiazepines and other anti-nausea and sleep aids including Gabapentin. The dose of KB220Z was maintained for 6 days in five individuals. In a second scenario, we utilized a higher dose of 4 oz every 6 hours, over a 6-day period. The higher dose was employed in another 12 patients. It is noteworthy that only 3 people have relapsed utilizing these two protocols during the first two weeks of the study, allowing for the remaining 82% to be maintained on KB220Z. The patients have been maintained without any additional Bup/nx for a minimum of 120 days and in one subject, 214 days. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates utilizing data from the Clinical opiate Withdrawal Scale (COWS) pre and post KB220Z. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates. While this does not constitute an acceptable controlled experiment, it does provide some preliminary evidence that agrees with an earlier study. Moreover, because of the utilization of standard detoxifying agents in this detoxification protocol, we cannot make any inference to KB220Z's effects. However, out of 17 subjects, only three required Bup/nx suggesting an interesting finding. If further confirmed in larger studies, the utilization for opiate/opioid detoxification may provide a novel way to eliminate the need for addictive opioids during withdrawal and detoxification. This paradigm shift may translate to a reduction in utilizing powerful and

  16. The effects of food on opioid-induced nausea and vomiting and pharmacological parameters: a systematic review.

    Science.gov (United States)

    Raffa, Robert B; Colucci, Robert; Pergolizzi, Joseph V

    2017-09-01

    Opioids remain the standard of care for treating moderate to severe pain resulting from surgery or injury in cases of acute pain, and are recommended for patients who have not responded to nonopioid analgesics. Effective management of pain has an impact on clinical course and often depends on achieving an acceptable balance between opioid efficacy, safety, and tolerability. Common opioid-related adverse events such as nausea and vomiting are associated with an overall lower achievement of effective pain management and patient satisfaction. However, in practice, clinicians employ various strategies to maximize efficacy, minimize these adverse effects, and ensure the careful, judicious, and evidence-based use of opioids for patients who require them. Typical strategies for management and minimization of these types of adverse events include dose reduction, dose titration, opioid rotation, prescription for an antiemetic, and recommending the patient take opioids with food. Overall, the most straightforward approach that clinicians tend to employ that does not require additional visits or adjustment of prescriptions, is to recommend patients take opioids with food. However, given the current climate with opioids, it is critical and imperative that decisions for use of opioids be grounded in a solid and thorough evidence-base. In fact, several opioids are recommended to be taken explicitly with or without food because of interactions with abuse-deterrent technologies that can cause increased adverse events or inadequate analgesia. Therefore, we sought to review, synthesize, and summarize the literature for randomized, controlled trials and other studies to support the hypothesis that taking opioids with food reduces opioid-related events such as nausea and vomiting. Based on the current evidence we surveyed, the recommendation to take opioids with food does not appear to consistently and unequivocally reduce nausea and vomiting and, in many cases, increases the

  17. Differences and over-time changes in levels of prescription opioid analgesic dispensing from retail pharmacies in Canada, 2005-2010.

    Science.gov (United States)

    Fischer, Benedikt; Jones, Wayne; Krahn, Murray; Rehm, Jürgen

    2011-12-01

    To examine qualitative and quantitative levels and trends of prescription opioid analgesics ("opioids") use and the potential impact of prescription monitoring programs (PMPs), in the 10 Canadian provinces, for 2005-2010. Opioid dispensing data from a representative sample of 2700 retail pharmacies were obtained. Individual opioid dispensing values were translated into defined daily doses per day/1000 population and categorized into "weak opioids" and "strong opioids" by standardized methods. Opioid prescription rates between provinces and over time, as well as the impact of PMPs, were examined using regression analyses techniques (i.e., Poisson, ANOVAs). Significant differences between provinces in the overall standardized rates of dispensing for total opioids, as well as for "weak opioids" and "strong opioids" categories, were found. The majority of provinces featured increases or curvilinear trends in the standardized amounts of opioids dispensed over time, mainly driven by increases in "strong opioids" use. In addition, significant inter-provincial differences in the levels of dispensing of individual opioids were found. Comparisons of changes in opioid dispensing between provinces with and without PMPs did not indicate significant differences. Opioid use featured significant quantitative and qualitative differences between provinces in Canada and showed an overall increasing trend mainly driven by changes in "strong opioids" in the study period. Reasons for the observed differences are not clear yet require systematic examination to allow evidence-based interventions in the interest of equitable pain treatment as well as the reduction of high levels of opioid-related morbidity and mortality in Canada. Copyright © 2011 John Wiley & Sons, Ltd.

  18. Opioid use in palliative care

    African Journals Online (AJOL)

    Repro

    Prejudice, fear and lack of core knowledge contribute to present-day poor opioid administration by doctors caring for patients with intolerable symptoms and pain at the end of life.The core knowl- edge required for using opioids is relative- ly simple, but myths and misconceptions regarding morphine still abound in both.

  19. Effects of Combined Opioids on Pain and Mood in Mammals

    Directory of Open Access Journals (Sweden)

    Richard H. Rech

    2012-01-01

    Full Text Available The authors review the opioid literature for evidence of increased analgesia and reduced adverse side effects by combining mu-opioid-receptor (MOR agonists, kappa-opioid-receptor (KOR agonists, and nonselective low-dose-opioid antagonists (LD-Ant. We tested fentanyl (MOR agonist and spiradoline (KOR agonist, singly and combined, against somatic and visceral pain models. Combined agonists induced additive analgesia in somatic pain and synergistic analgesia in visceral pain. Other investigators report similar effects and reduced tolerance and dependence with combined MOR agonist and KOR agonist. LD-Ant added to either a MOR agonist or KOR agonist markedly enhanced analgesia of either agonist. In accordance with other place-conditioning (PC studies, our PC investigations showed fentanyl-induced place preference (CPP and spiradoline-induced place aversion (CPA. We reduced fentanyl CPP with a low dose of spiradoline and reduced spiradoline CPA with a low dose of fentanyl. We propose combined MOR agonist, KOR agonist, and LD-Ant to produce superior analgesia with reduced adverse side effects, particularly for visceral pain.

  20. Dose-dependent effects of higher methionine levels on the transcriptome and metabolome of transgenic Arabidopsis seeds.

    Science.gov (United States)

    Cohen, Hagai; Amir, Rachel

    2017-05-01

    Higher methionine levels in transgenic Arabidopsis seeds trigger the accumulation of stress-related transcripts and primary metabolites. These responses depend on the levels of methionine within seeds. Methionine, a sulfur-containing amino acid, is a key metabolite in plant cells. To reveal the regulatory role of the Arabidopsis thaliana CYSTATHIONINE γ-SYNTHASE (AtCGS), methionine main regulatory enzyme, in the synthesis of methionine in seeds, we generated transgenic RNAi seeds with targeted repression of AtCGS during late developmental stages of seeds. Unexpectedly, these seeds accumulated 2.5-fold more methionine than wild-type seeds. To study the nature of these seeds, transcriptomic and primary metabolite profiling were employed using Affymetrix ATH1 microarray and gas chromatography-mass spectrometry analyses, respectively. The results were compared to transgenic Arabidopsis seeds expressing a feedback-insensitive form of AtCGS (named SSE-AtD-CGS) that were previously showed to accumulate up to sixfold more soluble methionine than wild-type seeds. Statistical assessments showed that the nature of transcriptomic and metabolic changes that occurred in RNAi::AtCGS seeds were relatively similar, but to lesser extents, to those previously reported for SSE-AtD-CGS seeds, and linked to the induction of global transcriptomic and metabolic responses associated with stronger desiccation stress. As transgenic seeds obtained by both manipulations exhibited higher, but different methionine levels, the data strongly suggest that these changes depend on the absolute amounts of methionine within seeds and much less to the expression level of AtCGS.

  1. Opioids for cancer pain - an overview of Cochrane reviews.

    Science.gov (United States)

    Wiffen, Philip J; Wee, Bee; Derry, Sheena; Bell, Rae F; Moore, R Andrew

    2017-07-06

    Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol. To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use. We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events. We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low

  2. Macroeconomic conditions and opioid abuse.

    Science.gov (United States)

    Hollingsworth, Alex; Ruhm, Christopher J; Simon, Kosali

    2017-12-01

    We examine how deaths and emergency department (ED) visits related to use of opioid analgesics (opioids) and other drugs vary with macroeconomic conditions. As the county unemployment rate increases by one percentage point, the opioid death rate per 100,000 rises by 0.19 (3.6%) and the opioid overdose ED visit rate per 100,000 increases by 0.95 (7.0%). Macroeconomic shocks also increase the overall drug death rate, but this increase is driven by rising opioid deaths. Our findings hold when performing a state-level analysis, rather than county-level; are primarily driven by adverse events among whites; and are stable across time periods. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 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...

  4. Nebulized opioids to treat dyspnea.

    Science.gov (United States)

    Chandler, S

    1999-01-01

    Breathlessness secondary to cancer and nonmalignant disease is very distressing and exhausting to patients and families. Patient quality of life and functionality can be greatly improved with effective management. The pathophysiology and treatment of dyspnea are where the science of pain management was 20 years ago. While the optimal therapy for dyspnea would be to treat the underlying cause, this is frequently not possible. Research results evaluating dosages and effectiveness of nebulized morphine are conflicting. Some researchers have reported dramatic benefit to patients in relieving the symptoms of dyspnea, increasing exercise endurance, and improving function. Other studies have reported no significant differences between nebulized morphine and saline with or without oxygen. Studies that administer single predetermined doses that are not titrated to relief in patients that do not have end-stage lung or cardiac disease may report false-negative results. Other factors such as the placebo effect of saline and oxygen, if not controlled, may cause false-positive results. The dramatic positive benefits documented warrant further investigation on the appropriate patient selection criteria and therapeutic potential. Clearly, large scale randomized trials on opioid nebulized treatments for patients with severe dyspnea need to be published to reach a clear consensus outlining efficacy and administration parameters. Until that time, we must rely on anecdotal reports for treatment options. Such reports of the effectiveness of nebulized morphine as an alternative to hospital or hospice admission are encouraging for patients and family members managing severe dyspnea in the home.

  5. Nonmedical use of prescription opioids and stimulants among student pharmacists.

    Science.gov (United States)

    Lord, Sarah; Downs, George; Furtaw, Paul; Chaudhuri, Anamika; Silverstein, Amy; Gammaitoni, Arnold; Budman, Simon

    2009-01-01

    To examine the prevalence and patterns of nonmedical use of prescription opioid analgesics and stimulants among student pharmacists. Descriptive, nonexperimental, cross-sectional study. Private urban college of pharmacy in the United States in fall 2006. 1,538 PharmD students. Online survey. Lifetime and past-year nonmedical prescription opioid and stimulant use. Response rate for the survey was 62%. Lifetime prevalence of opioid misuse was 8%, and 5% of students had misused in the past year. Lifetime prevalence of stimulant misuse was 7%, and 5% had misused in the past year. Whites and fraternity or sorority members were more likely than their peers to have ever misused opioids. Past-year opioid misuse was more likely among whites, men, and low academic achievers compared with their peers. Lifetime stimulant misuse was more likely among students who were white, older, and fraternity or sorority members, while past-year misuse was more likely among whites and low academic achievers. Common motives for opioid misuse were to have fun, to relax, and to deal with chronic pain. Stimulants were used to improve concentration and academic performance. Friends were the most common source of prescription opioids and stimulants. Nonmedical prescription use was associated with greater likelihood of alcohol and other illicit substance use. The prevalence of prescription medication misuse among student pharmacists was lower than (opioids) or comparable with (stimulants) reported rates in college populations. Subgroups of students demonstrated higher rates of nonmedical use, including whites, students involved with fraternities or sororities, and low academic achievers. That friends were the primary source of misused medications indicates that diversion of prescription-only controlled substances likely occurs among student pharmacists. Nonmedical prescription medication use should be considered in the context of other substance use.

  6. Does Prescription Opioid Shopping Increase Overdose Rates in Medicaid Beneficiaries?

    Science.gov (United States)

    Sun, Benjamin C; Lupulescu-Mann, Nicoleta; Charlesworth, Christina J; Kim, Hyunjee; Hartung, Daniel M; Deyo, Richard A; McConnell, K John

    2017-11-23

    The link between prescription opioid shopping and overdose events is poorly understood. We test the hypothesis that a history of prescription opioid shopping is associated with increased risk of overdose events. This is a secondary analysis of a linked claims and controlled substance dispense database. We studied adult Medicaid beneficiaries in 2014 with prescription opioid use in the 6 months before an ambulatory care or emergency department visit with a pain-related diagnosis. The primary outcome was a nonfatal overdose event within 6 months of the cohort entry date. The exposure of interest (opioid shopping) was defined as having opioid prescriptions by different prescribers with greater than or equal to 1-day overlap and filled at 3 or more pharmacies in the 6 months before cohort entry. We used a propensity score to match shoppers with nonshoppers in a 1:1 ratio. We calculated the absolute difference in outcome rates between shoppers and nonshoppers. We studied 66,328 patients, including 2,571 opioid shoppers (3.9%). There were 290 patients (0.4%) in the overall cohort who experienced a nonfatal overdose. In unadjusted analyses, shoppers had higher event rates than nonshoppers (rate difference of 4.4 events per 1,000; 95% confidence interval 0.8 to 7.9). After propensity score matching, there were no outcome differences between shoppers and nonshoppers (rate difference of 0.4 events per 1,000; 95% confidence interval -4.7 to 5.5). These findings were robust to various definitions of opioid shoppers and look-back periods. Prescription opioid shopping is not independently associated with increased risk of overdose events. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  7. Long-acting injectable naltrexone for the management of patients with opioid dependence.

    Science.gov (United States)

    Kjome, Kimberly L; Moeller, F Gerard

    2011-01-01

    Opioid dependence is a condition with serious clinical ramifications. Treatment has focused on detoxification, agonist therapy with methadone or buprenorphine, or remission maintenance with the opioid antagonist, naltrexone. Treatment with oral naltrexone has been limited by poor treatment adherence and relapse. Studies with long-acting formulations have shown increased treatment adherence. Extended-release injectable naltrexone has been used for the treatment of alcohol dependence, and has recently received an indication for treatment of opioid dependence from the US Food and Drug Administration. Dosing occurs once monthly and existing data with long-acting naltrexone supports efficacy of treatment for opioid dependence; however published data is sparse. Treatment with long-acting naltrexone should be monitored for hepatotoxicity, and patients should be made aware of increased risk of overdose with administration of opioids during and immediately after discontinuation of long-acting naltrexone.

  8. A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.

    Science.gov (United States)

    Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza

    2013-01-01

    Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.

  9. What do different databases tell about the use of opioids in seven European countries in 2002?

    DEFF Research Database (Denmark)

    Hamunen, K.; Laitinen-Parkkonen, P.; Paakkari, P.

    2008-01-01

    Objective: The objective of this paper was to analyse opioid consumption in a number European countries using different sources of data. Methods: Data were extracted from the United Nations' International Narcotics Control Board Report (INCB) 2003 and from the registers of the national health...... authorities in seven countries where data were available for 2002. The amount of opioid used was calculated as daily defined doses per 1000 inhabitants per day (DDD/1000/day). Danish Register of Medicinal Products Statistics was further explored for characteristics of opioid consumption (age, gender, type...... and significant discrepancies in the amounts Of opioids consumed between the national data and the INCB report. The source of data for the national registers on drug consumption varied (pharmacies or wholesale). The INCB data provide information oil opioid import and estimated need rather than on medical...

  10. Opioid therapy for chronic low back pain: prescribing considerations for advanced practice registered nurses.

    Science.gov (United States)

    Lall, Maureen Patricia

    2014-12-01

    Chronic low back pain is a common, disabling, and costly condition, and advanced practice registered nurses (APRNs) must carefully evaluate patients before considering long-term opioid therapy as a management strategy. APRNs should refer patients suspected of having a serious condition, or identifiable etiology, for specialist evaluation, as many patients improve with physical therapy, interventional pain management procedures, or surgical intervention. For patients unresponsive to nonopioid treatment, APRNs with an understanding of opioids, and the experience to assess and manage the risks of opioid misuse, abuse, and diversion, may consider long-term opioid therapy as part of a multimodal management plan. Such prescribing necessitates careful patient selection; informed consent; prudent opioid dosing and titration; and monitoring for response to treatment, adverse effects, and aberrant drug-taking behavior. Treatment and regulatory guidelines can assist APRNs in providing safe and effective care to patients with chronic low back pain.

  11. Long-Acting Injectable naltrexone for the Management of patients with Opioid Dependence

    Directory of Open Access Journals (Sweden)

    Kimberly L. Kjome

    2011-01-01

    Full Text Available Opioid dependence is a condition with serious clinical ramifications. Treatment has focused on detoxification, agonist therapy with methadone or buprenorphine, or remission maintenance with the opioid antagonist, naltrexone. Treatment with oral naltrexone has been limited by poor treatment adherence and relapse. Studies with long-acting formulations have shown increased treatment adherence. Extended-release injectable naltrexone has been used for the treatment of alcohol dependence, and has recently received an indication for treatment of opioid dependence from the US Food and Drug Administration. Dosing occurs once monthly and existing data with long-acting naltrexone supports efficacy of treatment for opioid dependence; however published data is sparse. Treatment with long-acting naltrexone should be monitored for hepatotoxicity, and patients should be made aware of increased risk of overdose with administration of opioids during and immediately after discontinuation of long-acting naltrexone.

  12. The Economic Burden of Opioid Abuse: Updated Findings.

    Science.gov (United States)

    Kirson, Noam Y; Scarpati, Lauren M; Enloe, Caroline J; Dincer, Aliya P; Birnbaum, Howard G; Mayne, Tracy J

    2017-04-01

    Opioid pain relievers can be highly effective in providing relief for patients suffering from pain. At the same time, prescription opioid abuse, dependence, overdose, and poisoning (hereinafter "abuse") have become a national public health concern. Opioid abuse is also costly: previous estimates of the annual excess costs of opioid abuse to payers range from approximately $10,000 to $20,000 per patient. To (a) provide a comprehensive, current estimate of the economic burden of opioid abuse to commercial payers and (b) explore the drivers of these excess costs of abuse. Administrative claims from beneficiaries covered by large self-insured companies throughout the United States were used to identify patients diagnosed with opioid abuse, dependence, and overdose/poisoning ("abuse") between 2012 and 2015. Sample selection criteria identified patients most likely to be misusing opioids. Abusers and nonabuser controls were matched using propensity scores. Excess health care costs were assessed over the 18-month study period. Drivers of excess costs were then evaluated by place of service and medical condition (identified as 3-digit ICD-9-CM groupings). 9,342 matched abuser/nonabuser pairs were analyzed. Relative to nonabusers, abusers had significantly higher annual health care resource utilization, leading to $14,810 in per-patient incremental annual health care costs. Excess costs began accumulating 5 months before the formal, incident diagnosis of abuse, driven by alcohol and nonopioid substance abuse. Major drivers of excess costs of abuse included opioid and other substance abuse disorders, mental health conditions, and painful conditions. Many patients had diagnoses for other substance abuse that predated their opioid abuse diagnoses. Opioid abuse imposes a substantial economic burden on payers and often occurs in the context of other substance abuse. Poly-substance abuse often precedes the diagnosis of opioid abuse. This study was funded by Purdue Pharma. Mayne

  13. Medication-assisted therapy for opioid addiction

    OpenAIRE

    Tai, Betty; Saxon, Andrew J.; Ling, Walter

    2013-01-01

    The “Medication-Assisted Therapy for Opioid Addiction” session was chaired by Dr. Betty Tai and had three presenters. The presenters (and their topics) were: Dr. Andrew J. Saxon (Methadone and Buprenorphine for Treatment of Opioid Addiction and HIV Risk Reduction), Dr. Walter Ling (Opioid Antagonist Treatment for Opioid Addiction), and Dr. Betty Tai (Chronic Care Model for Substance Use Disorder).

  14. How do prescription opioid users differ from users of heroin or other drugs in psychopathology: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

    Science.gov (United States)

    Wu, Li-Tzy; Woody, George E.; Yang, Chongming; Blazer, Dan G.

    2010-01-01

    Objectives To study substance use and psychiatric disorders among prescription opioid users, heroin users, and non-opioid drug users in a national sample of adults. Methods Analyses of data from the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions (N=43,093). Results Four groups were identified among 9140 illicit or non-prescribed drug users: heroin-other opioid users (1.0%; used heroin and other opioids), other opioid-only users (19.8%; used other opioids but never heroin), heroin-only users (0.5%; used heroin but never other opioids), and non-opioid drug users (78.7%; used drugs but never heroin or other opioids). After adjusting for variations in socioeconomic characteristics, history of substance abuse treatment, and familial substance abuse, heroin-other opioid users had greater odds of several substance use disorders (cocaine, hallucinogen, sedative, amphetamine, and tranquilizer) as compared with the other groups; heroin-only users had reduced odds of sedative and tranquilizer use disorders as compared with other opioid-only users. Non-opioid drug users had reduced odds of all substance use disorders and other mental disorders (mood, anxiety, pathological gambling, and personality) as compared with other opioid-only users. Past-year other opioid-only users also reported slightly lower scores on quality of life than past-year non-opioid drug users. Conclusions All opioid use groups had higher rates of substance use disorders than non-opioid drug users, and these rates were particularly elevated among heroin-other opioid users. Findings suggest the need to distinguish between these four groups in research and treatment as they may have different natural histories and treatment needs. PMID:21532972

  15. Opioid analgesic and benzodiazepine prescribing among Medicaid-enrollees with opioid use disorders: The influence of provider communities.

    Science.gov (United States)

    Stein, Bradley D; Mendelsohn, Joshua; Gordon, Adam J; Dick, Andrew W; Burns, Rachel M; Sorbero, Mark; Shih, Regina A; Liccardo Pacula, Rosalie

    2017-01-01

    Opioid analgesic and benzodiazepine use in individuals with opioid use disorders can increase the risk for medical consequences and relapse. Little is known about rates of use of these medications or prescribing patterns among communities of prescribers. The goal of this study was to examine rates of prescribing to Medicaid-enrollees in the calendar year after an opioid use disorder diagnosis, and to examine individual, county, and provider community factors associated with such prescribing. 2008 Medicaid claims data were used from 12 states to identify enrollees diagnosed with opioid use disorders, and 2009 claims data were used to identify rates of prescribing of each drug. Social network analysis was used to identify provider communities, and multivariate regression analyses was used to to identify patient, county, and provider community level factors associated with prescribing these drugs. The authors also examined variation in rates of prescribing across provider communities. Among Medicaid-enrollees identified with an opioid use disorder, 45% filled a prescription for an opioid analgesic, 37% filled a prescription for a benzodiazepine, and 21% filled a prescription for both in the year following their diagnosis. Females, older individuals, individuals with pain syndromes, and individuals residing in counties with higher rates of poverty were more likely to fill prescriptions. Prescribing rates varied substantially across provider communities, with rates in the highest quartile of prescribing communities over 2.5 times the rates in the lowest prescribing communities. Prescribing opioid analgesics and benzodiazepines to individuals diagnosed with opioid use disorders may increase risk of relapse and overdose. Interventions should be considered that target provider communities with the highest rates of prescribing and individuals at the highest risk.

  16. [Management of opioid maintenance treatments when analgesic treatments are required].

    Science.gov (United States)

    Laprevote, Vincent; Geoffroy, Pierre A; Rolland, Benjamin; Leheup, Benoît F; Di Patrizio, Paolo; Cottencin, Olivier; Schwan, Raymund

    2013-01-01

    Opioid maintenance treatments (OMT) reduce illicit opiate use and its associated risks. They are often prescribed on a long-term basis. Physiological changes induced by long-term OMT may cause hyperalgesia and cross-tolerance to opioid agonists, which suggests that the dosage of analgesic treatment should be modified in cases of acute pain, especially when an opioid-based analgesia is required. When treatment with analgesics is necessary, OMT must be maintained, except in exceptional cases. If a split-dosing schedule is temporarily employed during OMT, the daily dosage should not be increased for analgesic purposes. Analgesic treatment must be managed differently in case of treatment with buprenorphine or methadone. With buprenorphine, non-opioid analgesics should be introduced first, if possible. If this strategy is inefficient or contraindicated, a temporary or definitive switch to methadone should be considered. In the case of methadone-based OMT, opioid analgesics should be added directly and the dosage should be adapted according to the level of pain reported by the patient. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Antitussive activity of Withania somnifera and opioid receptors.

    Science.gov (United States)

    Nosálová, Gabriela; Sivová, Veronika; Ray, Bimalendu; Fraňová, Soňa; Ondrejka, Igor; Flešková, Dana

    2015-01-01

    Arabinogalactan is a polysaccharide isolated from the roots of the medicinal plant Withania somnifera L. It contains 65% arabinose and 18% galactose. The aim of the present study was to evaluate the antitussive activity of arabinogalactan in conscious, healthy adult guinea pigs and the role of the opioid pathway in the antitussive action. A polysaccharide extract was given orally in a dose of 50 mg/kg. Cough was induced by an aerosol of citric acid in a concentration 0.3 mol/L, generated by a jet nebulizer into a plethysmographic chamber. The intensity of cough response was defined as the number of cough efforts counted during a 3-min exposure to the aerosol. The major finding was that arabinogalactan clearly suppressed the cough reflex; the suppression was comparable with that of codeine that was taken as a reference drug. The involvement of the opioid system was tested with the use of a blood-brain barrier penetrable, naloxone hydrochloride, and non-penetrable, naloxone methiodide, to distinguish between the central and peripheral mu-opioid receptor pathways. Both opioid antagonists acted to reverse the arabinogalactan-induced cough suppression; the reversion was total over time with the latter antagonist. We failed to confirm the presence of a bronchodilating effect of the polysaccharide, which could be involved in its antitussive action. We conclude that the polysaccharide arabinogalactan from Withania somnifera has a distinct antitussive activity consisting of cough suppression and that this action involves the mu-opioid receptor pathways.

  18. Buprenorphine implants in medical treatment of opioid addiction.

    Science.gov (United States)

    Chavoustie, Steven; Frost, Michael; Snyder, Ole; Owen, Joel; Darwish, Mona; Dammerman, Ryan; Sanjurjo, Victoria

    2017-08-01

    Opioid use disorder is a chronic, relapsing disease that encompasses use of both prescription opioids and heroin and is associated with a high annual rate of overdose deaths. Medical treatment has proven more successful than placebo treatment or psychosocial intervention, and the partial µ-opioid receptor agonist and κ-opioid receptor antagonist buprenorphine is similar in efficacy to methadone while offering lower risk of respiratory depression. However, frequent dosing requirements and potential for misuse and drug diversion contribute to significant complications with treatment adherence for available formulations. Areas covered: This review describes the development of and preliminary data from clinical trials of an implantable buprenorphine formulation. Efficacy and safety data from comparative studies with other administrations of buprenorphine, including tablets and sublingual film, will be described. Key premises of the Risk Evaluation and Mitigation Strategy program for safely administering buprenorphine implants, which all prescribing physicians must complete, are also discussed. Expert commentary: Long-acting implantable drug formulations that offer consistent drug delivery and lower risk of misuse, diversion, or accidental pediatric exposure over traditional formulations represent a promising development for the effective treatment of opioid use disorder.

  19. Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors.

    Science.gov (United States)

    Mollica, Adriano; Pelliccia, Sveva; Famiglini, Valeria; Stefanucci, Azzurra; Macedonio, Giorgia; Chiavaroli, Annalisa; Orlando, Giustino; Brunetti, Luigi; Ferrante, Claudio; Pieretti, Stefano; Novellino, Ettore; Benyhe, Sandor; Zador, Ferenc; Erdei, Anna; Szucs, Edina; Samavati, Reza; Dvrorasko, Szalbolch; Tomboly, Csaba; Ragno, Rino; Patsilinakos, Alexandros; Silvestri, Romano

    2017-12-01

    Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH 2 . The bivalent compound (9) has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.

  20. Dose calculation for photon-emitting brachytherapy sources with average energy higher than 50 keV: Report of the AAPM and ESTRO

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Calatayud, Jose; Ballester, Facundo; Das, Rupak K.; DeWerd, Larry A.; Ibbott, Geoffrey S.; Meigooni, Ali S.; Ouhib, Zoubir; Rivard, Mark J.; Sloboda, Ron S.; Williamson, Jeffrey F. [Radiotherapy Department, La Fe Polytechnic and University Hospital, Valencia 46026 (Spain); Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Department of Human Oncology, University of Wisconsin, Madison, Wisconsin 53792 (United States); Department of Medical Physics and Accredited Dosimetry and Calibration Laboratory, University of Wisconsin, Madison, Wisconsin 53706 (United States); Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 (United States); Department of Radiation Oncology, Comprehensive Cancer Center of Nevada, Las Vegas, Nevada 89169 (United States); Radiation Oncology, Lynn Regional Cancer Center, 16313 South Military Trail, Delray Beach, Florida 33484 (United States); Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States); Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2 (Canada); Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States)

    2012-05-15

    Purpose: Recommendations of the American Association of Physicists in Medicine (AAPM) and the European Society for Radiotherapy and Oncology (ESTRO) on dose calculations for high-energy (average energy higher than 50 keV) photon-emitting brachytherapy sources are presented, including the physical characteristics of specific {sup 192}Ir, {sup 137}Cs, and {sup 60}Co source models. Methods: This report has been prepared by the High Energy Brachytherapy Source Dosimetry (HEBD) Working Group. This report includes considerations in the application of the TG-43U1 formalism to high-energy photon-emitting sources with particular attention to phantom size effects, interpolation accuracy dependence on dose calculation grid size, and dosimetry parameter dependence on source active length. Results: Consensus datasets for commercially available high-energy photon sources are provided, along with recommended methods for evaluating these datasets. Recommendations on dosimetry characterization methods, mainly using experimental procedures and Monte Carlo, are established and discussed. Also included are methodological recommendations on detector choice, detector energy response characterization and phantom materials, and measurement specification methodology. Uncertainty analyses are discussed and recommendations for high-energy sources without consensus datasets are given. Conclusions: Recommended consensus datasets for high-energy sources have been derived for sources that were commercially available as of January 2010. Data are presented according to the AAPM TG-43U1 formalism, with modified interpolation and extrapolation techniques of the AAPM TG-43U1S1 report for the 2D anisotropy function and radial dose function.

  1. Dose calculation for photon-emitting brachytherapy sources with average energy higher than 50 keV: report of the AAPM and ESTRO.

    Science.gov (United States)

    Perez-Calatayud, Jose; Ballester, Facundo; Das, Rupak K; Dewerd, Larry A; Ibbott, Geoffrey S; Meigooni, Ali S; Ouhib, Zoubir; Rivard, Mark J; Sloboda, Ron S; Williamson, Jeffrey F

    2012-05-01

    Recommendations of the American Association of Physicists in Medicine (AAPM) and the European Society for Radiotherapy and Oncology (ESTRO) on dose calculations for high-energy (average energy higher than 50 keV) photon-emitting brachytherapy sources are presented, including the physical characteristics of specific (192)Ir, (137)Cs, and (60)Co source models. This report has been prepared by the High Energy Brachytherapy Source Dosimetry (HEBD) Working Group. This report includes considerations in the application of the TG-43U1 formalism to high-energy photon-emitting sources with particular attention to phantom size effects, interpolation accuracy dependence on dose calculation grid size, and dosimetry parameter dependence on source active length. Consensus datasets for commercially available high-energy photon sources are provided, along with recommended methods for evaluating these datasets. Recommendations on dosimetry characterization methods, mainly using experimental procedures and Monte Carlo, are established and discussed. Also included are methodological recommendations on detector choice, detector energy response characterization and phantom materials, and measurement specification methodology. Uncertainty analyses are discussed and recommendations for high-energy sources without consensus datasets are given. Recommended consensus datasets for high-energy sources have been derived for sources that were commercially available as of January 2010. Data are presented according to the AAPM TG-43U1 formalism, with modified interpolation and extrapolation techniques of the AAPM TG-43U1S1 report for the 2D anisotropy function and radial dose function.

  2. Fixed dose of long-acting erythropoietic stimulating agents at higher frequency improves appetite, reduces inflammation and corrects anaemia in patients on haemodialysis.

    Science.gov (United States)

    Liu, Wen-Sheng; Chu, Da-Chen; Chan, Hsiang-Lin; Li, Szu-Yuan; Liu, Chih-Kuang; Yang, Chih-Yu; Chen, Yu-Wei; Lee, Pui-Ching; Lai, Yen-Ting; Lin, Chih-Ching

    2016-10-01

    Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 μg once monthly for 2 months, 50 μg twice monthly for 2 months and then 100 μg once monthly for two months. The effectiveness was determined by comparing haematocrit, nutritional status (serum protein and albumin) and inflammatory markers (tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and Hepcidin) at the beginning of the study with those at the end of the study. Forty-seven out of 67 patients completed the trial. At the end, haematocrit was significantly higher (34.51 vs 33.22%, P=.004), levels of inflammatory markers were significantly lower (TNF-α (30.71 vs 35.67 ng/mL, P=.007), IL-6 (5.12 vs 7.95 ng/mL, P=.033), hepcidin (60.39 vs 74.39 ng/mL, P=.002)), blood glucose levels were significantly lower (112.40 vs 139.02 mg/dL, P=.003) and albumin was significantly higher (4.11 vs 3.98, P=.001). Patients with a better than average response had a lower initial number of red blood cells (3.3 vs 3.6 × 10(6) /mm(3) , P=.025) and a lower IL-1 (3.8 vs 12.9 ng/mL, P=.01). They also had significantly lower blood glucose levels at the end. (91.3 vs 124.0 mg/dL, P=.03). We demonstrate that a fixed monthly dose of CERA at a twice monthly dosing schedule improves nutrition, reduces the inflammation and corrects anaemia in patients on haemodialysis. This finding may provide a new strategy for treating CKD-related anaemia. © 2016 John Wiley & Sons Australia, Ltd.

  3. Are Physicians Safely Prescribing Opioids for Chronic Noncancer Pain? A Systematic Review of Current Evidence.

    Science.gov (United States)

    Tournebize, Juliana; Gibaja, Valérie; Muszczak, Amandine; Kahn, Jean-Pierre

    2016-03-01

    With rising prescription of opioid medications for chronic noncancer pain (CNCP) in the past years, opioid abuse and overdose deaths have increased in parallel. To ensure adequate treatment outcomes and reduce the risks linked with the chronic use of opioids, practitioner's adherence to treatment guidelines is essential. This study summarizes published recommendations about the strategies to reduce the risks associated with the chronic use of opioids and evaluates the adherence of physicians to these recommendations. A systematic literature search was undertaken in May 2014 using major databases. Studies were included if they examined the adherence of practitioners with at least one form of opioid risk reduction strategy. Benchmark guidelines cited in these studies were also reviewed. The search yielded 683 records, 14 of which were found to evaluate adherence of physicians to opioid risk reduction strategies. Nine benchmark guidelines were found. Almost all physicians consider opioid therapy only when other safer approaches have failed and do not prescribe opioids at doses greater than 200 mg/day of morphine equivalent. Unfortunately, less than 50% assess pain intensity using a pain scale; they often consider transdermal fentanyl safe for opioid-naïve patients and fail to discontinue opioids if they were ineffective in relieving patients' pain. Substantial practice and knowledge gaps were identified, including the use of pain scales and prescription of transdermal fentanyl in opioid-naïve patients, which have important implications for patient's safety. Guidelines more practical to physicians' settings and further education of physicians are warranted. © 2015 World Institute of Pain.

  4. Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades?

    Science.gov (United States)

    Bujalska-Zadrożny, Magdalena; Tatarkiewicz, Jan; Kulik, Kamila; Filip, Małgorzata; Naruszewicz, Marek

    2017-03-01

    Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden deaths due to overdosing, attempts have been made to introduce co-analgesics. Due to an increasing amount of data concerning a potential enhance of opioid analgesia by the physiological antagonist of N-methyl-d-aspartate receptors, magnesium ions (Mg2+), a concomitant use of such a combination seems to be interesting from a clinical point of view. Therefore, the aim of this review is to provide an analysis of existing preclinical and clinical studies in the context of the benefits of using this combination in clinical practice. A potential mechanism of magnesium - opioid interaction is also suggested. The potential influence of Mg on opioid adverse/side effects as well as conclusions on the safety of combined administration of magnesium and opioid drugs were also summarized. Data from animal studies indicate that magnesium increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well as acute pain. In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids. However, more clinical studies are needed concerning an influence of Mg on opioid activity in other difficult to treat types of pain, especially neuropathic and inflammatory. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Wide Variation and Excessive Dosage of Opioid Prescriptions for Common General Surgical Procedures.

    Science.gov (United States)

    Hill, Maureen V; McMahon, Michelle L; Stucke, Ryland S; Barth, Richard J

    2017-04-01

    To examine opioid prescribing patterns after general surgery procedures and to estimate an ideal number of pills to prescribe. Diversion of prescription opioids is a major contributor to the rising mortality from opioid overdoses. Data to inform surgeons on the optimal dose of opioids to prescribe after common general surgical procedures is lacking. We evaluated 642 patients undergoing 5 outpatient procedures: partial mastectomy (PM), partial mastectomy with sentinel lymph node biopsy (PM SLNB), laparoscopic cholecystectomy (LC), laparoscopic inguinal hernia repair (LIH), and open inguinal hernia repair (IH). Postoperative opioid prescriptions and refill data were tabulated. A phone survey was conducted to determine the number of opioid pills taken. There was a wide variation in the number of opioid pills prescribed to patients undergoing the same operation. The median number (and range) prescribed were: PM 20 (0-50), PM SLNB 20 (0-60), LC 30 (0-100), LIH 30 (15-70), and IH 30 (15-120). Only 28% of the prescribed pills were taken. This percentage varied by operation: PM 15%, PM SLNB 25%, LC 33%, LIH 15%, and IH 31%. Less than 2% of patients obtained refills.We identified the number of pills that would fully supply the opioid needs of 80% of patients undergoing each operation: PM 5, PM SLNB 10, LC 15, LIH 15, and IH 15. If this number were prescribed, the number of opioid initially prescribed would be 43% of the actual number prescribed. There is wide variability in opioid prescriptions for common general surgery procedures. In many cases excess pills are prescribed. Using our ideal number, surgeons can adequately treat postoperative pain and markedly decrease the number of opioids prescribed.

  6. Novel approaches for the treatment of psychostimulant and opioid abuse - focus on opioid receptor-based therapies.

    Science.gov (United States)

    Bailey, Chris P; Husbands, Stephen M

    2014-11-01

    Psychostimulant and opioid addiction are poorly treated. The majority of abstinent users relapse back to drug-taking within a year of abstinence, making 'anti-relapse' therapies the focus of much current research. There are two fundamental challenges to developing novel treatments for drug addiction. First, there are three key stimuli that precipitate relapse back to drug-taking: stress, presentation of drug-conditioned cue, taking a small dose of drug. The most successful novel treatment would be effective against all three stimuli. Second, a large number of drug users are poly-drug users: taking more than one drug of abuse at a time. The ideal anti-addiction treatment would, therefore, be effective against all classes of drugs of abuse. In this review, the authors discuss the clinical need and animal models used to uncover potential novel treatments. There is a very broad range of potential treatment approaches and targets currently being examined as potential anti-relapse therapies. These broadly fit into two categories: 'memory-based' and 'receptor-based' and the authors discuss the key targets here within. Opioid receptors and ligands have been widely studied, and research into how different opioid subtypes affect behaviours related to addiction (reward, dysphoria, motivation) suggests that they are tractable targets as anti-relapse treatments. Regarding opioid ligands as novel 'anti-relapse' medication targets, research suggests that a 'non-selective' approach to targeting opioid receptors will be the most effective.

  7. Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project

    Directory of Open Access Journals (Sweden)

    Arvind Chopra

    2012-01-01

    Full Text Available Background: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination-based formulations in the treatment of Osteoarthritis (OA Knees. These formulations were "platform combination+Withania somnifera+Tribulus terrestris0" (formulation B and "platform combination+Emblica officinale" (formulation C. This paper reports safety of these formulations when used in higher doses (1.5-2 times along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation. Materials and Methods: Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I formulation B, 2 t.i.d.; (II formulation B, 2 q.i.d.; (III platform combination+Sallaki Guggul; (IV Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5 was used for analysis. Results: None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut-related (mostly epigastric burning AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT, serum glutamic oxaloacetic transaminase (SGOT] without any other hepatic abnormality was reported in 2 patients (group IV. Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5-2.22, WOMAC (functional activity questionnaire pain score (1.37, CI 0.22-2.5, and urinary C-TAX (cartilage collagen breakdown product assay was maximum (NS in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II. Conclusion: The

  8. Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project.

    Science.gov (United States)

    Chopra, Arvind; Saluja, Manjit; Tillu, Girish; Venugopalan, Anuradha; Narsimulu, Gumdal; Sarmukaddam, Sanjeev; Patwardhan, Bhushan

    2012-01-01

    Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were "platform combination+Withania somnifera+Tribulus terrestris" (formulation B) and "platform combination+Emblica officinale" (formulation C). This paper reports safety of these formulations when used in higher doses (1.5-2 times) along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation). Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5) was used for analysis. None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut-related (mostly epigastric burning) AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group IV). Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5-2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI 0.22-2.5), and urinary C-TAX (cartilage collagen breakdown product) assay was maximum (NS) in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II. The results suggested that despite higher doses, standardized

  9. Illicit Opioid Intoxication: Diagnosis and Treatment

    OpenAIRE

    Fareed, A.; Stout, S.; J. Casarella; Vayalapalli, S.; Cox, J; Drexler, K

    2011-01-01

    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 diag...

  10. Sleep-disordered breathing decreases after opioid withdrawal: results of a prospective controlled trial.

    Science.gov (United States)

    Schwarzer, Andreas; Aichinger-Hinterhofer, Marie; Maier, Christoph; Vollert, Jan; Walther, Jörg Werner

    2015-11-01

    An increased cardiovascular event rate in elderly patients under opioid medications was recently reported. One reason for this increase could be the occurrence of nocturnal apnea and hypoxia, as a consequence of sleep-disordered breathing (SDB). Using a controlled study, we prospectively analyzed SDB using polysomnography in a total of 18 patients before and after opioid withdrawal (opioid withdrawal group [OG]) and 14 patients before and after comprehensive pain management (without any strong-acting opioids) who served as the control group (CG). To analyze the differences, unpaired/paired t tests and Mann-Whitney U tests/Wilcoxon rank tests were used. At baseline, the OG presented more nocturnal apneas/hypopneas than the CG with an apnea-hypopnea index (AHI) of 41.4 ± 27.8 vs 21.8 ± 15.9 (P = 0.018). After treatment, the AHI decreased significantly only in the withdrawal group (OG: 16.7 ± 8.9; CG: 20.1 ± 12.9) (P opioid withdrawal and in none of the patients after withdrawal (P opioid intake; these findings may explain the opioid-associated cardiovascular morbidity. Thus, SDB may be a risk at lower opioid doses than hitherto described, and particular caution should be exercised in patients with comorbidities that might make them vulnerable to the consequences of SDB.

  11. CYP2D6 in the metabolism of opioids for mild to moderate pain.

    Science.gov (United States)

    Leppert, Wojciech

    2011-01-01

    In most cancer patients, pain is successfully treated with pharmacological measures using opioid analgesics for moderate to severe pain (strong opioids) alone or in combination with adjuvant analgesics (coanalgesics). Opioids for mild to moderate pain (weak opioids) are usually recommended in the treatment of cancer pain of mild to moderate intensity. There is a debate whether the second step of the WHO analgesic ladder comprising weak opioids such as tramadol, codeine and dihydrocodeine is still needed for the treatment of cancer and chronic pain since low doses of strong opioids show similar efficacy. However, many patients with mild, moderate and in some cases strong pain intensity are still successfully treated with weak opioids. All these drugs are metabolized through CYP2D6, an important enzyme for approximately 25% of all drugs administered in clinical practice. The aim of this review is to summarize data on the impact of CYP2D6 polymorphism on pharmacokinetics, pharmacodynamics and adverse effects of weak opioids. Copyright © 2011 S. Karger AG, Basel.

  12. 14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity.

    Science.gov (United States)

    Zádor, Ferenc; Balogh, Mihály; Váradi, András; Zádori, Zoltán S; Király, Kornél; Szűcs, Edina; Varga, Bence; Lázár, Bernadette; Hosztafi, Sándor; Riba, Pál; Benyhe, Sándor; Fürst, Susanna; Al-Khrasani, Mahmoud

    2017-11-05

    14-O-methyl (14-O-Me) group in morphine-6-O-sulfate (M6SU) or oxymorphone has been reported to be essential for enhanced affinity, potency and antinociceptive effect of these opioids. Herein we report on the pharmacological properties (potency, affinity and efficacy) of the new compound, 14-O-methylmorphine (14-O-MeM) in in vitro. Additionally, we also investigated the antinociceptive effect of the novel compound, as well as its inhibitory action on gastrointestinal transit in in vivo. The potency and efficacy of test compound were measured by [(35)S]GTPγS binding, isolated mouse vas deferens (MVD) and rat vas deferens (RVD) assays. The affinity of 14-O-MeM for opioid receptors was assessed by radioligand binding and MVD assays. The antinociceptive and gastrointestinal effects of the novel compound were evaluated in the rat tail-flick test and charcoal meal test, respectively. Morphine, DAMGO, Ile(5,6) deltorphin II, deltorphin II and U-69593 were used as reference compounds. 14-O-MeM showed higher efficacy (Emax) and potency (EC50) than morphine in MVD, RVD or [(35)S]GTPγS binding. In addition, 14-O-MeM compared to morphine showed higher affinity for μ-opioid receptor (MOR). In vivo, in rat tail-flick test 14-O-MeM proved to be stronger antinociceptive agent than morphine after peripheral or central administration. Additionally, both compounds inhibited the gastrointestinal peristalsis. However, when the antinociceptive and antitransit doses for each test compound are compared, 14-O-MeM proved to have slightly more favorable pharmacological profile. Our results affirm that 14-O-MeM, an opioid of high efficacy and affinity for MOR can be considered as a novel analgesic agent of potential clinical value. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B

    2015-01-01

    UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development...... of chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P ... naloxone dose (0.021 mg/kg). However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future...

  14. An examination of global and regional opioid consumption trends 1980-2011.

    Science.gov (United States)

    Hastie, Barbara A; Gilson, Aaron M; Maurer, Martha A; Cleary, James F

    2014-09-01

    Despite expert recognition that strong opioid analgesics are the cornerstone of treatment for moderate to severe pain, most of the world's population lacks adequate availability of opioids. Moreover, great disparities in availability of opioids continue to exist between higher- and lower-to-middle-income countries. This study examined more than 30 years of consumption data reported to the International Narcotics Control Board, from 1980 to 2011, for five opioids that are indicated for the treatment of moderate to severe pain: fentanyl, hydromorphone, morphine, oxycodone, and pethidine. As such, this study offers a regional and global perspective on opioid consumption, providing an indication of preparedness for treating moderate to severe pain. Countries are categorized according to the World Health Organization's six geographical regions. Morphine equivalence (ME) statistics were calculated for each study drug, allowing for equianalgesic comparisons between consumption of the study opioids and well as the ability to aggregate all study opioids (Total ME). The ME statistic is adjusted for country population, which allows for uniform global-, regional-, and country-level equianalgesic comparisons of consumption of morphine with other opioids. Although overall trend lines revealed general increases by region, profound inequities in opioid consumption continue to abound globally.

  15. Opioid-related adverse drug events: do parents recognize the signals?

    Science.gov (United States)

    Voepel-Lewis, Terri; Zikmund-Fisher, Brian; Smith, Ellen L; Zyzanski, Sarah; Tait, Alan R

    2015-03-01

    Evidence of unrelieved childhood pain, adverse drug events (ADE), and deaths suggest that parents may inadequately respond to pain and opioid-related ADE signals. This study examined parents' recognition and response to pain and ADE signals using both dynamic hypothetical scenarios and real at-home opioid decisions. A total of 514 parents whose children required prescription opioids after discharge were surveyed. Parents made analgesic decisions for 4 hypothetical scenarios wherein the child's pain level and ADE symptoms were altered. After discharge, parents recorded their child's real pain levels, ADEs, and their analgesic decisions. Mixed-effects logistic regression examined the influence of pain and ADE signals on parents' opioid decisions. Pain intensity had a main effect on parents' hypothetical and real decisions to give opioids (P≤0.001). Nausea/vomiting influenced the decision to give the prescribed opioid dose (β=-1.48 [95% confidence interval (CI): -1.78, -1.19], Popioid administration compared with other ADEs (OR=4.41 [95% CI: 1.91, 10.18], Popioid dose for oversedation, suggesting a lack of awareness regarding this potentially serious ADE. Strategies to improve parents' recognition of oversedation and its potential consequences are warranted to improve opioid safety.

  16. Abuse-deterrent formulations of prescription opioid analgesics in the management of chronic noncancer pain.

    Science.gov (United States)

    Hale, Martin E; Moe, Derek; Bond, Mary; Gasior, Maciej; Malamut, Richard

    2016-10-01

    Misuse, abuse and diversion of prescription opioid analgesics represent a global public health concern. The development of abuse-deterrent formulations (ADFs) of prescription opioid analgesics is an important step toward reducing abuse and diversion of these medications, as well as potentially limiting medical consequences when misused or administered in error. ADFs aim to hinder extraction of the active ingredient, prevent administration through alternative routes and/or make abuse of the manipulated product less attractive, less rewarding or aversive. However, opioid ADFs may still be abused via the intended route of administration by increasing the dose and/or dosing frequency. The science of abuse deterrence and the regulatory landscape are still relatively new and evolving. This paper reviews the current status of opioid ADFs, with particular focus on different approaches that can be used to deter abuse, regulatory considerations and implications for clinical management.

  17. Nalfurafine hydrochloride, a selective κ opioid receptor agonist, has no reinforcing effect on intravenous self-administration in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Kaoru Nakao

    2016-01-01

    Full Text Available Nalfurafine hydrochloride [(E-N-[17-(cyclopropylmethyl-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3-(furan-3-yl-N-methylprop-2-enamide monohydrochloride; nalfurafine] is used in Japan as an antipruritic for the treatment of intractable pruritus in patients undergoing hemodialysis or with chronic liver disease. It is a potent and selective agonist at the κ opioid receptor, but also has weak and partial agonist activity at μ opioid receptors. Opioids, especially those acting at μ receptors, carry a risk of abuse. This is an important factor in the consideration of therapeutic risk vs. benefit in clinical use and the potential for misuse as a public health problem. It is therefore necessary to carefully evaluate the reinforcing effects of nalfurafine. To this end, we investigated intravenous self-administration of nalfurafine in rhesus monkeys. The number of self-administration of nalfurafine at doses of 0.0625, 0.125 and 0.25 μg/kg/infusion was not higher than that of saline in rhesus monkeys that frequently self-administered pentazocine (0.25 mg/kg/infusion. These results indicate that nalfurafine has no reinforcing effect in rhesus monkeys in the intravenous self-administration paradigm.

  18. Factors in the choice of oral transmucosal fentanyl citrate dose for adult burns dressings.

    Science.gov (United States)

    Shah, H; Smythe, J; Hanafiah, Z; Williams, G J P; Holdcroft, A

    2009-09-01

    Factors that influenced the choice of dose of oral transmucosal fentanyl at the time of burns dressing change were investigated in a prospective study. After Ethics committee approval, data was analysed from 29 consecutive patients who had been recruited and consented for a study of pain associated with burns dressings. Patients had completed an 11-point verbal pain intensity score (VRS) prior to and after the dressing change. Analgesic use during for this period was documented. Doses of 600 to 1200 mcg of transmucosal fentanyl (Actiq) were given based on individual assessment. The pre-dressing VRS (median [range]) in the 15 patients who received 600 mcg was 8 [3-10] and was higher than the VRS of 6 [2-9] in the 800-1200 mcg group. The time since the burn was longer in the low dose group at 7 [1-22] days compared with 5 [0-50] days in the higher dose group. In addition 73% of the low dose group was prescribed opioids regularly prior to the dressing compared with 57% of the high dose group. The choice of a lower transmucosal fentanyl dose was based on prior use of opioids and the age of the burn rather than on the patient's pain intensity.

  19. The effects of indomethacin, diclofenac, and acetaminophen suppository on pain and opioids consumption after cesarean section

    Directory of Open Access Journals (Sweden)

    Godrat Akhavanakbari

    2013-01-01

    Full Text Available Background: Cesarean section is one of the common surgeries of women. Acute post-operative pain is one of the recognized post-operative complications. Aims: This study was planned to compare the effects of suppositories, indomethacin, diclofenac and acetaminophen, on post-operative pain and opioid usage after cesarean section. Materials and Methods: In this double-blind clinical trial study, 120 candidates of cesarean with spinal anesthesia and American Society of Anesthesiologists (ASA I-II were randomly divided into four groups. Acetaminophen, indomethacin, diclofenac, and placebo suppositories were used in groups, respectively, after operation and the dosage was repeated every 6 h and pain score and opioid usage were compared 24 h after the surgery. The severity of pain was recorded on the basis of Visual Analog Scale (VAS and if severe pain (VAS > 5 was observed, 0.5 mg/kg intramuscular pethidine had been used. Statistical Analysis Used: The data were analyzed in SPSS software version 15 and analytical statistics such as ANOVA, Chi-square, and Tukey′s honestly significant difference (HSD post-hoc. Results : Pain score was significantly higher in control group than other groups, and also pain score in acetaminophen group was higher than indomethacin and diclofenac. The three intervention groups received the first dose of pethidine far more than control group and the distance for diclofenac and indomethacin were significantly longer (P < 0.001. The use of indomethacin, diclofenac, and acetaminophen significantly reduces the amount of pethidine usage in 24 h after the surgery relation to control group. Conclusions : Considering the significant decreasing pain score and opioid usage especially in indomethacin and diclofenac groups rather than control group, it is suggested using of indomethacin and diclofenac suppositories for post-cesarean section analgesia.

  20. Chronic pain, opioid prescriptions, and mortality in Denmark

    DEFF Research Database (Denmark)

    Ekholm, Ola; Kurita, Geana Paula; Højsted, Jette

    2014-01-01

    This study aimed to investigate the risk of death, development of cancer, and hospital inpatient admissions resulting from injuries and toxicity/poisoning among opioid users with chronic noncancer pain. A population-based cohort of 13,127 adults, who have participated in the Danish Health Interview...... Surveys in 2000 or 2005 and have been followed up prospectively by registers until the end of 2011, were classified according to the absence or presence of chronic pain (ie, pain lasting ⩾ 6 months) and long-term or short-term opioid use (individuals using at least 1 prescription per month for 6 months...... in the previous year and at least 1 prescription in the previous year, respectively). The risk of all-cause mortality was 1.72 (95% confidence interval [CI]=1.23-2.41) times higher among long-term opioid users than among individuals without chronic pain. The risk of death was lower, but still significantly higher...

  1. Depressive effects of mu and delta opioid receptor agonists on activities of dorsal horn neurones are enhanced by dibencozide.

    Science.gov (United States)

    Villanueva, L; Bing, Z; Bouhassira, D; Le Bars, D

    1991-06-01

    The effects on C fiber evoked activity in lumbar dorsal horn convergent neurones of i.v. morphine alone, of Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) alone or of either of these drugs in association with 5-deoxyadenosylcobalamine (dibencozide) were investigated in anesthetized rats. Both morphine and DTLET depressed the neuronal responses in a dose-related fashion, with the former requiring lower doses. Although dibencozide alone was devoid of any effect, it significantly enhanced the depressive effects of all doses of morphine tested and of the lower two doses of DTLET. It is concluded that dibencozide enhances the spinal depression of nociceptive information elicited by mu and delta opioid agonists. This drug could provide a useful tool for the study of interactions between opioids and opioids receptors. It is also suggested that dibencozide could be useful in clinical practice for reducing the dosage of opioids.

  2. Respiratory \\(\\mu\\)-Opioid and benzodiazepine interactions in the understrained rat

    OpenAIRE

    Paakkari, P.; Paakkari, I.; Landes, P.; Sirén, Anna-Leena; Feuerstein, G

    2012-01-01

    lnteractions of p-opioid receptors with the benzodiazepine system were studied by examining the modulatory effects of flumazenil (a benzodiazepine antagonist) and alprazolam (a benzodiazepine agonist) on the respiratory effects ofthe opioid peptide dermorphin. Dermorphin, 1-30 nmol administered i.c.v., to conscious, unrestrained rats decreased ventilation rate (VR) and minute volume (MV) dose-dependently. The ventilatory depression was antagonized by naloxone and by the benzodiazepine antagon...

  3. Involvement of opioid peptides in the regulation of reproduction in the prawn Penaeus indicus

    Science.gov (United States)

    Sreenivasula Reddy, P.

    The possible involvement of an endogenous opioid system in the regulation of ovarian development in the prawn Penaeus indicus was investigated. Injection of leucine-enkephalin significantly increased the ovarian index and oocyte diameter in a dose-dependent manner. In contrast, injection of methionine-enkephalin significantly decreased the ovarian index and oocyte diameters. These results provide evidence to support the hypothesis that an opioid system is involved in the regulation of reproduction in crustaceans.

  4. [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)

  5. Transplantation with higher dose of natural killer cells associated with better outcomes in terms of non-relapse mortality and infectious events after allogeneic peripheral blood stem cell transplantation from HLA-matched sibling donors.

    Science.gov (United States)

    Kim, Dong Hwan; Sohn, Sang Kyun; Lee, Nan Young; Baek, Jin Ho; Kim, Jong Gwang; Won, Dong Il; Suh, Jang Soo; Lee, Kyu Bo; Shin, Im Hee

    2005-10-01

    Little is known about the role of the CD56+ natural killer (NK) cell dose on the outcome of allogeneic peripheral blood stem cell transplantation (PBSCT). Recently, higher dose of NK cells has been associated with a lower incidence of severe graft-versus-host disease (GVHD). The current study attempted to evaluate the effect of the NK cell dose on transplant outcomes in allogeneic PBSCT setting. Sixty-one cytokine mobilized PBSC recipients were analyzed according to the infused dose of CD34+ cells and NK cells in relation to overall survival (OS), non-relapse mortality (NRM), GVHD, and infectious events. The group received a higher dose of NK cells (> or =5 x 10(7)/kg) showed a lower incidence of NRM (P = 0.0186) and infectious events (P = 0.0107). In a multivariate analysis, a higher dose of NK cells was correlated to better transplant outcomes for NRM (P = 0.042) with CD34+ cell dose (P = 0.018), and for infectious events (P = 0.013) with CD34+ cell dose (P = 0.016). Higher NK cell infusion group also showed a faster immune recovery in serial measurements at days +90, +180, and +365. High dose of NK cells may play an important role in improving transplant outcomes, in terms of reducing NRM and infectious events together with CD34+ cells.

  6. Opioid Considerations for Emergency Practice

    Directory of Open Access Journals (Sweden)

    Thomas Terndrup

    2015-12-01

    Full Text Available On a backdrop of increasingly distressing opioid misuse in our communities, and safety concerns expressed by The Joint Commission and others, emergency physicians are further increasing their utilization of these important agents in our patients.

  7. Medication for Opioid Overdose: Naloxone

    Science.gov (United States)

    ... Updated: 03/03/2016 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...

  8. 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.

  9. 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.

  10. Behavioral intervention to reduce opioid overdose among high-risk persons with opioid use disorder: A pilot randomized controlled trial.

    Science.gov (United States)

    Coffin, Phillip Oliver; Santos, Glenn-Milo; Matheson, Tim; Behar, Emily; Rowe, Chris; Rubin, Talia; Silvis, Janelle; Vittinghoff, Eric

    2017-01-01

    The United States is amidst an opioid epidemic, including synthetic opioids that may result in rapid death, leaving minimal opportunity for bystander rescue. We pilot tested a behavioral intervention to reduce the occurrence of opioid overdose among opioid dependent persons at high-risk for subsequent overdose. We conducted a single-blinded randomized-controlled trial of a repeated dose motivational interviewing intervention (REBOOT) to reduce overdose versus treatment as usual, defined as information and referrals, over 16 months at the San Francisco Department of Public Health from 2014-2016. Participants were 18-65 years of age, had opioid use disorder by Structured Clinical Interview, active opioid use, opioid overdose within 5 years, and prior receipt of naloxone kits. The intervention was administered at months 0, 4, 8, and 12, preceded by the assessment which was also administered at month 16. Dual primary outcomes were any overdose event and number of events, collected by computer-assisted personal interview, as well as any fatal overdose events per vital records. A total of 78 persons were screened and 63 enrolled. Mean age was 43 years, 67% were born male, 65% White, 17% African-American, and 14% Latino. Ninety-two percent of visits and 93% of counseling sessions were completed. At baseline, 33.3% of participants had experienced an overdose in the past four months, with a similar mean number of overdoses in both arms (p = 0.95); 29% overdosed during follow-up. By intention-to-treat, participants assigned to REBOOT were less likely to experience any overdose (incidence rate ratio [IRR] 0.62 [95%CI 0.41-0.92, p = 0.019) and experienced fewer overdose events (IRR 0.46, 95%CI 0.24-0.90, p = 0.023), findings that were robust to sensitivity analyses. There were no differences between arms in days of opioid use, substance use treatment, or naloxone carriage. REBOOT reduced the occurrence of any opioid overdose and the number of overdoses. clinicaltrials.gov NCT

  11. A Detailed Exploration Into the Association of Prescribed Opioid Dosage and Overdose Deaths Among Patients With Chronic Pain.

    Science.gov (United States)

    Bohnert, Amy S B; Logan, Joseph E; Ganoczy, Dara; Dowell, Deborah

    2016-05-01

    High opioid dosage has been associated with overdose, and clinical guidelines have cautioned against escalating dosages above 100 morphine-equivalent mg (MEM) based on the potential harm and the absence of evidence of benefit from high dosages. However, this 100 MEM threshold was chosen somewhat arbitrarily. To examine the association of prescribed opioid dosage as a continuous measure in relation to risk of unintentional opioid overdose to identify the range of dosages associated with risk of overdose at a detailed level. In this nested case-control study with risk-set sampling of controls, cases (opioid overdose decedents) and controls were identified from a population of patients of the Veterans Health Administration who were prescribed opioids and who have a chronic pain diagnosis. Unintentional fatal opioid analgesic overdose was measured from National Death Index records and prescribed opioid dosage from pharmacy records. The average prescribed opioid dosage was higher (Popioid overdose death, indicating that, on average, overdose cases had a prescribed opioid dosage higher than 71% of controls. A clear cut-point in opioid dosage to distinguish between overdose cases and controls was not found. However, lowering the recommended dosage threshold below the 100 MEM used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose.

  12. Nurses' Role in Preventing Prescription Opioid Diversion.

    Science.gov (United States)

    Manworren, Renee C B; Gilson, Aaron M

    2015-08-01

    Prescription opioid abuse is at epidemic levels. Opioids diverted from friends and family members who have legitimate prescriptions are a major source of abused prescription opioids. Nurses are vital to any effort to combat this public health crisis because they have the opportunity to provide essential anticipatory guidance every time a patient receives prescription medication. The purpose of this article is to inform nurses of the magnitude of opioid diversion, the nonmedical use of opioids, and opioids' inappropriate disposal. The authors propose three potential interventions in which nurses can play a critical role: teaching patients about the risks of opioid diversion, providing patients with information on the safekeeping and proper disposal of opioids, and tracking patients' analgesic use to improve our knowledge of prescription analgesic requirements for pain management. Nurses are in an ideal position to help reverse the occurrence and potentially fatal consequences of prescription opioid diversion.

  13. Opioids in Chronic Musculoskeletal Conditions

    OpenAIRE

    Calvo-Alén, Jaime

    2010-01-01

    The use of opioids for benign disorders has been limited by concerns about these compounds' potential adverse events and their possible misuse. However, during the last few years an increased use in nonmalignant disorders, including rheumatologic diseases, has been observed. Herein, we review the scientific evidence for opioid therapy in three common scenarios in clinical rheumatology. Low back pain is a very frequent reason for consultation. Overall, the large majority of studies show a posi...

  14. Chronic pain, opioid prescriptions, and mortality in Denmark: A population-based cohort study.

    Science.gov (United States)

    Ekholm, Ola; Kurita, Geana Paula; Højsted, Jette; Juel, Knud; Sjøgren, Per

    2014-12-01

    This study aimed to investigate the risk of death, development of cancer, and hospital inpatient admissions resulting from injuries and toxicity/poisoning among opioid users with chronic noncancer pain. A population-based cohort of 13,127 adults, who have participated in the Danish Health Interview Surveys in 2000 or 2005 and have been followed up prospectively by registers until the end of 2011, were classified according to the absence or presence of chronic pain (ie, pain lasting ⩾ 6 months) and long-term or short-term opioid use (individuals using at least 1 prescription per month for 6 months in the previous year and at least 1 prescription in the previous year, respectively). The risk of all-cause mortality was 1.72 (95% confidence interval [CI]=1.23-2.41) times higher among long-term opioid users than among individuals without chronic pain. The risk of death was lower, but still significantly higher in short-term (1.36, 95% CI=1.07-1.72) and non-opioid users with chronic pain (1.39, 95% CI=1.22-1.59) than in the background population. There was no statistically significant association between long-term opioid use and cardiovascular and cancer mortality. No deaths among opioid users were caused by accidents or suicides, although opioid users had higher risks of injuries and toxicity/poisoning resulting in hospital inpatient admissions than individuals without chronic pain. The risk of all-cause mortality was significantly higher among long-term opioid users, but no obvious associations between long-term opioid use and cause-specific mortality were observed. However, opioid use increased the risk of injuries and toxicity/poisoning resulting in hospital inpatient admissions. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. Five-factor model personality traits in opioid dependence

    Directory of Open Access Journals (Sweden)

    Nordvik Hilmar

    2007-08-01

    Full Text Available Abstract Background Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence. Methods We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R, a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores. Results The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores. Conclusion We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers.

  16. 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

  17. Recovering from Opioid Overdose: Resources for Overdose Survivors & Family Members

    Science.gov (United States)

    SAMHSA Opioid Overdose Prevention TOOLKIT: Recovering From Opioid Overdose – Resources for Overdose Survivors & Family Members TABLE OF CONTENTS Recovering From Opioid Overdose Recovering from Opioid Overdose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Resources for Overdose Survivors ...

  18. Opioids in chronic musculoskeletal conditions.

    Science.gov (United States)

    Calvo-Alén, Jaime

    2010-10-01

    The use of opioids for benign disorders has been limited by concerns about these compounds' potential adverse events and their possible misuse. However, during the last few years an increased use in nonmalignant disorders, including rheumatologic diseases, has been observed. Herein, we review the scientific evidence for opioid therapy in three common scenarios in clinical rheumatology. Low back pain is a very frequent reason for consultation. Overall, the large majority of studies show a positive, yet rather moderate, effect of opioids in pain control, as well as in other outcomes including mood, work disability and anxiety. Similarly, opioids seem to have a role in the management of hip and knee osteoarthritis; indeed, they have been included in all international guidelines for the treatment of these conditions. However, clinical studies addressing opioid use in clinical situations are plagued by methodological limitations; furthermore, the large majority of these studies only provide short-term information about opiod utilization in these patients. Finally, opioids are currently being used as complementary therapy in inflammatory joint conditions whereby they may significantly improve the quality of life of some of these patients. Regarding their safety, severe adverse events, including abnormal drug-seeking behaviour, are very rare, but mild adverse events are frequent leading to drug discontinuation in a significant number of cases.

  19. Lack of experimental evidence to support mcr-1-positive Escherichia coli strain selection during oral administration of colistin at recommended and higher dose given by gavage in weaned piglets.

    Science.gov (United States)

    Viel, Alexis; Henri, Jérôme; Perrin-Guyomard, Agnès; Laroche, Julian; Couet, William; Grégoire, Nicolas; Laurentie, Michel

    2017-06-28

    In this study, we assessed the selective effect of colistin administered orally to healthy weaned piglets harbouring an intestinal mcr-1-positive Escherichia coli strain. Maximum recommended dose and a higher dose often used in European pig farms were given by gavage. No selection of the mcr-1-positive strain was observed in our controlled conditions, irrespective of the dose. Further investigations in real farming conditions seem necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  20. Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health Administration patients.

    Science.gov (United States)

    Zedler, Barbara; Xie, Lin; Wang, Li; Joyce, Andrew; Vick, Catherine; Kariburyo, Furaha; Rajan, Pradeep; Baser, Onur; Murrelle, Lenn

    2014-11-01

    Prescription opioid use and deaths related to serious toxicity, including overdose, have increased dramatically in the United States since 1999. However, factors associated with serious opioid-related respiratory or central nervous system (CNS) depression or overdose in medical users are not well characterized. The objective of this study was to examine the factors associated with serious toxicity in medical users of prescription opioids. Retrospective, nested, case-control analysis of Veterans Health Administration (VHA) medical, pharmacy, and health care resource utilization administrative data. Patients dispensed an opioid by VHA between October 1, 2010 and September 30, 2012 (N=8,987). Cases (N=817) experienced life-threatening opioid-related respiratory/CNS depression or overdose. Ten controls were randomly assigned to each case (N=8,170). Logistic regression was used to examine associations with the outcome. The strongest associations were maximum prescribed daily morphine equivalent dose (MED)≥ 100 mg (odds ratio [OR]=4.1, 95% confidence interval [CI], 2.6-6.5), history of opioid dependence (OR=3.9, 95% CI, 2.6-5.8), and hospitalization during the 6 months before the serious toxicity or overdose event (OR=2.9, 95% CI, 2.3-3.6). Liver disease, extended-release or long-acting opioids, and daily MED of 20 mg or more were also significantly associated. Substantial risk for serious opioid-related toxicity and overdose exists at even relatively low maximum prescribed daily MED, especially in patients already vulnerable due to underlying demographic factors, comorbid conditions, and concomitant use of CNS depressant medications or substances. Screening patients for risk, providing education, and coprescribing naloxone for those at elevated risk may be effective at reducing serious opioid-related respiratory/CNS depression and overdose in medical users of prescription opioids. Wiley Periodicals, Inc.

  1. Decreasing Opioid Utilization in Rehabilitation Patients Using a Clinical Nurse Specialist Pain Consultant Program.

    Science.gov (United States)

    Urton, Michael S; Rohlik, Elaine; Farrell, Meagan; Ng, Wing; Woodard, Elizabeth K

    2017-12-01

    To investigate whether access to a clinical nurse specialist (CNS) with expertise in pain management will result in more rapid decline in opioid use across the rehabilitation hospitalization. Retrospective chart review of patients discharged during 6 months prior to and 6 months after introduction of the CNS role. Not-for-profit 98-bed community inpatient rehabilitation hospital. Two population-based samples of adult, inpatient rehabilitation patients (N=72) with daily opioid use ≥30mg morphine equivalent dose (MED) per day on admission and length of stay ≥24 days. Implementation of a CNS pain consult program. Change in average daily opioid use (milligrams of MED per day), measured at admission, week 1, week 2, and week 3. Linear mixed modeling was used to estimate individual and group average opioid trajectories, including individual patient intercepts (opioid use at admission) and slopes (change in opioid use over time). There was a significant interaction between group and time (b=5.75, t=2.52, Popioid use for the CNS group (quadratic slope, -5.91) compared with the no CNS group (quadratic slope, -.16). Quadratic change in the CNS group reflected an initial increase in opioid use from admission to week 1, followed by a steady decline. Conversely, there was virtually no change in the no CNS group. Random effects revealed considerable variability in opioid trajectories across patients. Addition of a CNS pain consultant program to an inpatient rehabilitation hospital supported a distinct pattern of opioid tapering that promoted more rapid titration of daily opioid use across the rehabilitation hospitalization. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. 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.

  3. Identifying prescription opioid use disorder in primary care: diagnostic characteristics of the Current Opioid Misuse Measure (COMM).

    Science.gov (United States)

    Meltzer, Ellen C; Rybin, Denis; Saitz, Richard; Samet, Jeffrey H; Schwartz, Sonia L; Butler, Stephen F; Liebschutz, Jane M

    2011-02-01

    The Current Opioid Misuse Measure (COMM), a self-report assessment of past-month aberrant medication-related behaviors, has been validated in specialty pain management patients. The performance characteristics of the COMM were evaluated in primary care (PC) patients with chronic pain. It was hypothesized that the COMM could identify patients with prescription drug use disorder (PDD). English-speaking adults awaiting PC visits at an urban, safety-net hospital, who had chronic pain and had received any opioid analgesic prescription in the past year, were administered the COMM. The Composite International Diagnostic Interview served as the "gold standard," using DSM-IV criteria for PDD and other substance use disorders (SUDs). A receiver operating characteristic (ROC) curve demonstrated the COMM's diagnostic test characteristics. Of the 238 participants, 27 (11%) met DSM-IV PDD criteria, whereas 17 (7%) had other SUDs, and 194 (82%) had no disorder. The mean COMM score was higher in those with PDD than among all others (ie, those with other SUDs or no disorder, mean 20.4 [SD 10.8] vs 8.4 [SD 7.5], PCOMM score of⩾13 had a sensitivity of 77% and a specificity of 77% for identifying patients with PDD. The area under the ROC curve was 0.84. For chronic pain patients prescribed opioids, the development of PDD is an undesirable complication. Among PC patients with chronic pain-prescribed prescription opioids, the COMM is a promising tool for identifying those with PDD. Among primary care patients with chronic pain-prescribed opioids, the validated Current Opioid Misuse Measure (COMM) is a promising tool for identifying patients with prescription opioid use disorder. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  4. Involvement of endogenous opioid peptides in the peripheral antinociceptive effect induced by the coffee specific diterpene kahweol.

    Science.gov (United States)

    Guzzo, Luciana S; Romero, Thiago R L; Queiroz-Junior, Celso M; Caliari, Marcelo V; Azevedo, Adolfo O; Perez, Andréa C; Duarte, Igor D G

    2015-10-01

    Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect. The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2μg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of β-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws. Intraplantar injection of kahweol (40 and 80μg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100μg/paw) prevented action of kahweol (80μg/paw) and the aminopeptidases inhibitor bestatin (400μg/paw) potentiated the antinociceptive effect of kahweol (40μg/paw). Furthermore, kahweol treatment increased the intensity of β-endorphin immunoreactivity in the epithelium of rat paws. The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Structured Management of Chronic Nonmalignant Pain with Opioids in a Rural Primary Care Office.

    Science.gov (United States)

    McCann, Kevin S; Barker, Shawndra; Cousins, Raymond; Franks, Adam; McDaniel, Clinton; Petrany, Stephen; Riley, Eric

    2018-01-01

    substance regulations and is associated with a reduced number of opioid prescriptions. Patients who were on lower doses of opioid medication are more likely to wean their use with this model. © Copyright 2018 by the American Board of Family Medicine.

  6. Lubiprostone for Opioid-Induced Constipation Does Not Interfere with Opioid Analgesia in Patients with Chronic Noncancer Pain.

    Science.gov (United States)

    Spierings, Egilius L H; Brewer, Randall P; Rauck, Richard L; Losch-Beridon, Taryn; Mareya, Shadreck M

    2017-03-01

    To determine whether lubiprostone 24 μg twice daily (BID), administered to relieve opioid-induced constipation (OIC), affects opioid analgesia in patients with chronic noncancer pain. Data were pooled from 3 randomized, double-blind, placebo-controlled trials of lubiprostone in adults with chronic noncancer pain receiving stable opioid analgesia and who had documented OIC. In each study, lubiprostone 24 μg BID or placebo was administered for 12 weeks for relief of OIC using a common protocol. The Brief Pain Inventory short form (BPI-SF) was administered, and opioid use (expressed as morphine-equivalent daily dose [MEDD]) was recorded at baseline and months 1, 2, and 3. The BPI-SF provided patient scores for pain severity, the worst pain experienced in the past 24 hours, and pain interference with daily life. The pooled patient population (N = 1300) was predominately female (62.5%) and white (82.1%), with a mean age of 50.5 years. The MEDD was 97.5 mg (range, 5 to 3656 mg) in patients receiving placebo and 112.5 mg (range, 4 to 7605 mg) in patients treated with lubiprostone. Lubiprostone 24 μg BID treatment did not appear to affect opioid use or pain scores; changes from baseline were not significantly different with placebo vs. lubiprostone 24 μg BID at months 1, 2, and 3 for MEDD (P ≥ 0.435) and for BPI-SF scores for pain interference, pain severity, and worst pain (P ≥ 0.402). Lubiprostone 24 μg BID administered for relief of OIC in patients with chronic noncancer pain does not interfere with opioid analgesia. © 2016 World Institute of Pain.

  7. Benzodiazepine-opioid co-prescribing in a national probability sample of ED encounters.

    Science.gov (United States)

    Kim, Howard S; McCarthy, Danielle M; Mark Courtney, D; Lank, Patrick M; Lambert, Bruce L

    2017-03-01

    Benzodiazepine-opioid combination therapy is potentially harmful due to the risk of synergistic respiratory depression, and the rate of death due to benzodiazepine-opioid overdose is increasing. Little is known about the prevalence and characteristics of benzodiazepine-opioid co-prescribing from the ED setting. Secondary analysis of data from the National Hospital Ambulatory Medical Care Survey, using sample weights to generate population estimates. The primary objective was to describe the annual prevalence of benzodiazepine-opioid co-prescribing from 2006 to 2012, using 95% confidence intervals (95% CI) to compare adjacent years. The secondary objective was to compare characteristics of ED encounters receiving a benzodiazepine-opioid co-prescription versus those receiving an opioid prescription alone, using a multivariable logistic regression. The prevalence of benzodiazepine-opioid co-prescribing did not significantly change from 2006 to 2012. During this period, 2.7% (95% CI: 2.5-2.8%) of ED encounters prescribed an opioid were also prescribed a benzodiazepine. Relative to encounters receiving an opioid prescription alone, encounters receiving a co-prescription were more likely to represent a follow-up rather than initial visit (Odds Ratio [OR] 1.52), receive more medications (OR 1.41) and fewer procedures (OR 0.48) while in the ED, and more likely to have a diagnosis related to mental disorder (OR 20.60) or musculoskeletal problem (OR 3.71). From 2006 to 2012, almost 3% of all ED encounters receiving an opioid prescription also received a benzodiazepine co-prescription. The odds of benzodiazepine-opioid co-prescribing were significantly higher in ED encounters representing a follow-up visit and in diagnoses relating to a mental disorder or musculoskeletal problem. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms.

    Science.gov (United States)

    Schreiber, Shaul; Rigai, Tova; Katz, Yeshayahu; Pick, Chaim G

    2002-09-30

    The antinociceptive effects of the noradrenergic and specific serotonergic antidepressant (NaSSA) drug mirtazapine and its interaction with various opioid receptor subtypes were evaluated in mice with a hotplate analgesicmeter. Mirtazapine elicited an antinociceptive effect in a dose-dependent manner following doses from 1 to 7.5mg/kg. As the mirtazapine dose increased beyond 10mg/kg latencies returned to baseline, yielding a biphasic dose-response curve. The effect of opioid, adrenergic, and serotonergic receptor antagonists was examined as to their ability to block mirtazapine antinociception. Mirtazapine (at 10mg/kg)-induced antinociception was significantly inhibited by naloxone, nor-BNI, and naltrindole, but neither by beta-FNA nor by naloxonazine, implying the involvement of kappa(1)- and delta-opioid mechanisms. When adrenergic and serotonergic antagonists were used, both metergoline and yohimbine, decreased antinociception elicited by mirtazapine, implying a combined serotonergic and noradrenergic mechanism of antinociception. When mirtazapine was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated only by kappa(3)-opioid receptor subtypes. Summing up these results we conclude that the antinociceptive effect of mirtazapine is mainly influenced by the kappa(3)-opioid receptor subtype combined with both serotonergic and noradrenergic receptors. These results suggest a potential use of mirtazapine in the management of some pain syndromes, and raise questions regarding a possible indirect opioid-dependence induced by mirtazapine. However, further research is needed in order to establish both the exact clinical indications and the effective doses of mirtazapine when prescribed for pain.

  9. Quantifying the burden of opioid medication errors in adult oncology and palliative care settings: A systematic review.

    Science.gov (United States)

    Heneka, Nicole; Shaw, Tim; Rowett, Debra; Phillips, Jane L

    2016-06-01

    Opioids are the primary pharmacological treatment for cancer pain and, in the palliative care setting, are routinely used to manage symptoms at the end of life. Opioids are one of the most frequently reported drug classes in medication errors causing patient harm. Despite their widespread use, little is known about the incidence and impact of opioid medication errors in oncology and palliative care settings. To determine the incidence, types and impact of reported opioid medication errors in adult oncology and palliative care patient settings. A systematic review. Five electronic databases and the grey literature were searched from 1980 to August 2014. Empirical studies published in English, reporting data on opioid medication error incidence, types or patient impact, within adult oncology and/or palliative care services, were included. Popay's narrative synthesis approach was used to analyse data. Five empirical studies were included in this review. Opioid error incidence rate was difficult to ascertain as each study focussed on a single narrow area of error. The predominant error type related to deviation from opioid prescribing guidelines, such as incorrect dosing intervals. None of the included studies reported the degree of patient harm resulting from opioid errors. This review has highlighted the paucity of the literature examining opioid error incidence, types and patient impact in adult oncology and palliative care settings. Defining, identifying and quantifying error reporting practices for these populations should be an essential component of future oncology and palliative care quality and safety initiatives. © The Author(s) 2015.

  10. National study of discontinuation of long-term opioid therapy among veterans.

    Science.gov (United States)

    Vanderlip, Erik R; Sullivan, Mark D; Edlund, Mark J; Martin, Bradley C; Fortney, John; Austen, Mark; Williams, James S; Hudson, Teresa

    2014-12-01

    Veterans have high rates of chronic pain and long-term opioid therapy (LTOT). Understanding predictors of discontinuation from LTOT will clarify the risks for prolonged opioid use and dependence among this population. All veterans with at least 90 days of opioid use within a 180-day period were identified using national Veteran's Health Affairs (VHA) data between 2009 and 2011. Discontinuation was defined as 6 months with no opioid prescriptions. We used Cox proportional hazards analysis to determine clinical and demographic correlates for discontinuation. A total of 550,616 veterans met criteria for LTOT. The sample was primarily male (93%) and white (74%), with a mean age of 57.8 years. The median daily morphine equivalent dose was 26 mg, and 7% received high-dose (>100mg MED) therapy. At 1 year after initiation, 7.5% (n=41,197) of the LTOT sample had discontinued opioids. Among those who discontinued (20%, n=108,601), the median time to discontinuation was 317 days. Factors significantly associated with discontinuation included both younger and older age, lower average dosage, and having received less than 90 days of opioids in the previous year. Although tobacco use disorders decreased the likelihood of discontinuation, co-morbid mental illness and substance use disorders increased the likelihood of discontinuation. LTOT is common in the VHA system and is marked by extended duration of use at relatively low daily doses with few discontinuation events. Opioid discontinuation is more likely in veterans with mental health and substance use disorders. Further research is needed to delineate causes and consequences of opioid discontinuation. Published by Elsevier B.V.

  11. Personality Disorders Classification and Symptoms in Cocaine and Opioid Addicts.

    Science.gov (United States)

    Malow, Robert M.; And Others

    1989-01-01

    Examined extent to which personality disorders and associated symptom criteria were found among 117 cocaine- and opioid-dependent men in drug dependence treatment unit. Drug groups were distinguished by higher rates of antisocial and borderline symptomatology rather than by features associated with other personality disorders. Different…

  12. CDC Vital Signs–Opioid Prescribing

    Centers for Disease Control (CDC) Podcasts

    2017-07-06

    This podcast 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.

  13. Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes.

    Science.gov (United States)

    Spierings, Egilius L H; Drossman, Douglas A; Cryer, Byron; Mazen Jamal, M; Losch-Beridon, Taryn; Mareya, Shadreck M; Wang, Martin

    2017-07-17

    The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response. In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks. In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups ( P  =   0.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids ( P  =   0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone ( P  =   0.692). The safety profile of lubiprostone was unaffected by methadone use. The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.

  14. Adverse Selection? A Multi-Dimensional Profile of People Dispensed Opioid Analgesics for Persistent Non-Cancer Pain

    Science.gov (United States)

    Rogers, Kris D.; Kemp, Anna; McLachlan, Andrew J.; Blyth, Fiona

    2013-01-01

    Objectives This study investigates utilisation patterns for prescription opioid analgesics in the Australian community and how these are associated with a framework of individual-level factors related to healthcare use. Methods Self-reported demographic and health information from participants in the 45 and Up Study cohort were linked to pharmaceutical claims from 2006–2009. Participants comprised 19,816 people with ≥1 opioid analgesic dispensing in the 12-months after recruitment to the cohort and 79,882 people not dispensed opioid analgesics. All participants were aged ≥45 years, were social security pharmaceutical beneficiaries, with no history of cancer. People dispensed opioid analgesics were classified as having acute (dispensing period osteoarthritis treatment, paracetamol use, and poor physical function were the strongest predictors for all opioid analgesic users. Conclusions People dispensed opioid analgesics were in poorer health, reported higher levels of distress and poorer functioning than people not receiving opioid analgesics. Varying dispensing profiles were evident among people dispensed opioid analgesics for persistent pain, with those receiving episodic and long-term treatment dispensed the strongest opioid analgesics. The findings highlight the broad range of factors associated with longer term opioid analgesics use. PMID:24312456

  15. Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581

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    Ahmadi-Abhari Seyed Ali

    2003-11-01

    Full Text Available Abstract Background Results of preclinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. Methods A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Results Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence.

  16. Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

    Science.gov (United States)

    Wachholtz, Amy; Gonzalez, Gerardo

    2014-12-01

    Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's opioid maintenance compared to active methadone patients (p opioid naïve control group participants (p's opioid abstinence increased (R = .37; p opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Economic burden of prescription opioid misuse and abuse.

    Science.gov (United States)

    Strassels, Scott A

    2009-09-01

    abuse or misuse prescription opioids incur higher costs and health care resource use, differences in methods used to explore this question make estimating the actual societal burden imposed by this problem difficult. Efforts to establish and maintain a balance between access to these drugs for legitimate pain management while decreasing the risk of abuse and misuse are critically important and include such tools as patient and provider education, patient screening, and use of technology.

  18. Risk factors for severe respiratory depression from prescription opioid overdose.

    Science.gov (United States)

    Fox, Lindsay M; Hoffman, Robert S; Vlahov, David; Manini, Alex F

    2018-01-01

    Prescription opioid overdose is a leading cause of injury-related morbidity and mortality in the United States. We aimed to identify characteristics associated with clinical severity in emergency department patients with prescription opioid overdose. This was a secondary data analysis of adult prescription opioid overdoses from a large prospective cohort of acute overdoses. We examined elements of a typical emergency department evaluation using a multivariable model to determine which characteristics were associated with clinical severity, specifically severe respiratory depression (SRD). This study was conducted at two urban academic emergency departments in New York City, USA. Adult patients who presented with acute prescription opioid overdose between 2009 and 2013 were included in the current study. We analyzed 307 patients (mean age = 44.7, 42% female, 2.0% mortality). Patient demographics, reported substances ingested, suspected intent for ingesting the substance, vital signs, laboratory data, treatments including antidotes and intubation and outcome of death were recorded by trained research assistants. Intent was categorized into four mutually exclusive categories: suicide, misuse, therapeutic error and undetermined. The primary outcome was SRD, defined as administration of either (a) naloxone or (b) endotracheal intubation (ETI). A total of 109 patients suffered SRD with 90 patients receiving naloxone alone, nine ETI alone and 10 both naloxone and ETI. The most common opioids were oxycodone (n = 124) and methadone (n = 116). Mean age was higher in patients with SRD (51.1 versus 41.1, P < 0.001). Opioid misuse was associated with SRD in the multivariable analysis [odds ratio (OR) = 2.07, 95% confidence interval (CI) = 1.21-3.55]. The unadjusted relative risk of SRD was high for fentanyl (83.3% SRD) and lowest for codeine (3.6% SRD). In emergency department patients in the United States with prescription opioid overdose, worse clinical severity

  19. Opioid drug abuse and modulation of immune function: consequences in the susceptibility to opportunistic infections.

    Science.gov (United States)

    Roy, Sabita; Ninkovic, Jana; Banerjee, Santanu; Charboneau, Richard Gene; Das, Subhas; Dutta, Raini; Kirchner, Varvara A; Koodie, Lisa; Ma, Jing; Meng, Jingjing; Barke, Roderick A

    2011-12-01

    Infection rate among intravenous drug users (IDU) is higher than the general public, and is the major cause of morbidity and hospitalization in the IDU population. Epidemiologic studies provide data on increased prevalence of opportunistic bacterial infections such as TB and pneumonia, and viral infections such as HIV-1 and hepatitis in the IDU population. An important component in the intravenous drug abuse population and in patients receiving medically indicated chronic opioid treatment is opioid withdrawal. Data on bacterial virulence in the context of opioid withdrawal suggest that mice undergoing withdrawal had shortened survival and increased bacterial load in response to Salmonella infection. As the body of evidence in support of opioid dependency and its immunosuppressive effects is growing, it is imperative to understand the mechanisms by which opioids exert these effects and identify the populations at risk that would benefit the most from the interventions to counteract opioid immunosuppressive effects. Thus, it is important to refine the existing animal model to closely match human conditions and to cross-validate these findings through carefully controlled human studies. Better understanding of the mechanisms will facilitate the search for new therapeutic modalities to counteract adverse effects including increased infection rates. This review will summarize the effects of morphine on innate and adaptive immunity, identify the role of the mu opioid receptor in these functions and the signal transduction activated in the process. The role of opioid withdrawal in immunosuppression and the clinical relevance of these findings will also be discussed.

  20. Obtaining adequate data to determine causes of opioid-related overdose deaths.

    Science.gov (United States)

    Webster, Lynn R; Dasgupta, Nabarun

    2011-06-01

    Current data collected by medical examiners and coroners are incomplete and inadequate to evaluate the factors that lead to fatalities involving prescription opioids. Determining cause of death is critically important. Two methods are proposed to improve consistency and accuracy in the collection and analysis of decedent data in opioid-related poisoning deaths. First, an improved death certificate is needed to collect evaluative data, including: extent to which opioids were judged to 1) cause, 2) contribute to, or 3) be present in investigated deaths; extent to which opioids as a cause of death were found 1) alone, 2) combined with other prescription drugs, 3) combined with alcohol, or 4) combined with illicit drugs; the time of death; the presence or absence of a valid prescription; and the estimated quantity of opioids taken proximal to death. Patient characteristics for analysis include age, gender, race/ethnicity, geographic area (particularly whether urban or rural), body mass index, duration of opioid usage and daily average dose during the last 2 weeks of life, and histories of chronic pain/medical conditions, substance abuse, and mental illness/psychiatric diagnoses. Second, expanding the scope of opioid toxicology categories used to classify and code cause-of-death data reported by death investigators would improve identification of individual drugs and classes most often associated with overdose deaths. Formulation-specific codes should be added to facilitate consistent recording of findings by death investigators and entry into national vital statistics databases. Wiley Periodicals, Inc.

  1. Evaluation of Parenteral Opioid Analgesics Utilization in Patients Hospitalized in a Referral Teaching Hospital

    Directory of Open Access Journals (Sweden)

    Rasool Soltani

    2016-05-01

    Full Text Available Background: Opioid drugs are the most effective drugs for the treatment of moderate to severe pain. Rates of opioid use are influenced by a variety of factors. The aim of this study was to determine the pattern of use of parenteral opioid drugs in hospitalized patients in a referral teaching hospital. Methods: In a retrospective study, required data were extracted from medical records of adult patients who had received any parenteral opioid analgesic in the 6-month period from March 2013 to September 2013. The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD system method was used for evaluation of opioid analgesic use in patients.Results: The overall usage of parenteral opioid analgesics was 730.51 DDDs with meperidine (Pethidine having the most amounts of use (588.69 DDDs and 33.23 DDDs/100 bed-days. Overall, the male surgery ward and emergency department had the most amounts of use based on the number of DDDs (445.8 DDDs and per 100 bed-days (1046 DDDs/100 bed-days, respectively. Methadone use was most in the infectious diseases ward.Conclusion: The trend of parenteral opioid analgesics consumption is increasing in this hospital. Therefore, better adherence to pain treatment guidelines by medical staff is necessary for rational use of these drugs.

  2. Parenthood and opioid dependence

    Directory of Open Access Journals (Sweden)

    Pihkala H

    2015-02-01

    Full Text Available Heljä Pihkala, Mikael Sandlund Institution of Clinical Sciences/Psychiatry, Umeå University, Umeå, Sweden Introduction: Many patients in maintenance treatment programs for opioid dependence are parents to underage children. Objective: The aim of this study was to explore how parents who are regular patients in maintenance treatment perceive their parenthood. Methods: The study used a qualitative approach. The informants were recruited by staff at a substance abuse clinic in Sweden. Criteria for inclusion were participation in the local maintenance treatment program, having a child or children younger than 18 years, and being in contact with the child or children. Data were collected in 2012–2013 by in-depth interviews of seven fathers and five mothers and analyzed using concepts and procedures of qualitative content analysis. Results: The central findings of the study were: 1 the parents’ concerns about possible future discrimination against their children, ie, stigma by association; and 2 the patients’ own parents’ role as the most important support in parenthood. Conclusion: The issue of anticipated discrimination against the children of parents undergoing maintenance treatment might be an aspect to consider in the development of interventions and support. Considering the role of the patients' own parents also seems important. Keywords: parenthood, opiod dependence, maintenance treatment, qualitative analysis, anticipated stigma, stigma by association

  3. Higher dose intra-arterial milrinone and intra-arterial combined milrinone-nimodipine infusion as a rescue therapy for refractory cerebral vasospasm.

    Science.gov (United States)

    Duman, Enes; Karakoç, Fatma; Pinar, H Ulas; Dogan, Rafi; Fırat, Ali; Yıldırım, Erkan

    2017-12-01

    Background Cerebral vasospasm (CV) is a major cause of delayed morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Various cerebral protectants have been tested in patients with aneurysmal SAH. We aimed to research the success rate of treatment of CV via intra-arterial milrinone injection and aggressive pharmacological therapy for refractory CV. Methods A total of 25 consecutive patients who received intra-arterial milrinone and nimodipine treatment for CV following SAH between 2014 and 2017 were included in the study. Patients who underwent surgical clipping were excluded. Refractory vasospasm was defined as patients with CV refractory to therapies requiring ≥3 endovascular interventions. Overall, six patients had refractory CV. Long-term neurological outcome was assessed 6-18 months after SAH using a modified Rankin score and Barthel index. Results The median modified Rankin scores were 1 (min: 0, max: 3) and Barthel index scores were 85 (min: 70, max: 100) From each vasospastic territory maximal 10-16 mg milrinone was given to patients; a maximum of 24 mg milrinone was given to each patient in a session and a maximum of 42 mg milrinone was given to a patient in a day. Both milrinone and nimodipine were given to three patients. There was a large vessel diameter increase after milrinone and nimodipine injections. No patient died due to CV; only one patient had motor dysfunction on the right lower extremity. Conclusion Higher doses of milrinone can be used effectively to control refractory CV. For exceptional patients with refractory CV, high dose intra-arterial nimodipine and milrinone infusion can be used as a rescue therapy.

  4. Beyond Opioids: Mind and Body Practices

    Science.gov (United States)

    ... turn JavaScript on. Feature: Understanding Opioids Beyond Opioids: Mind and Body Practices Past Issues / Fall 2016 Table ... research shows that some non-drug approaches—including mind and body practices such as tai chi and ...

  5. Opioid pharmacokinetic drug-drug interactions.

    Science.gov (United States)

    Overholser, Brian R; Foster, David R

    2011-09-01

    Pharmacokinetic drug-drug interactions (DDIs) involving opioid analgesics can be problematic. Opioids are widely used, have a narrow therapeutic index, and can be associated with severe toxicity. The purpose of this review is to describe pharmacokinetic DDIs associated with opioids frequently encountered in managed care settings (morphine, codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, tramadol, and methadone). An introduction to the pharmacokinetic basis of DDIs is provided, and potential DDIs associated with opioids are reviewed. Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects. Conversely, opioids that are not metabolized by that system (morphine, oxymorphone, and hydromorphone) tend to be involved in fewer CYP450-associated pharmacokinetic DDIs.

  6. Buprenorphine Sublingual and Buccal (opioid dependence)

    Science.gov (United States)

    ... and naloxone are used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic painkillers). ... are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking or using ...

  7. Opioid Use and Neural Tube Defects

    Science.gov (United States)

    ... CDC.gov . Error processing SSI file Key Findings: Opioid Use and Neural Tube Defects Recommend on Facebook ... new study that looked at the use of opioids during pregnancy and their relationship to having a ...

  8. 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 ... 1-800-622-4357 Visit Helpline Website THE OPIOID EPIDEMIC IN NUMBERS 80% Nearly 80% of heroin ...

  9. Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain.

    Science.gov (United States)

    Feingold, Daniel; Goor-Aryeh, Itay; Bril, Silviu; Delayahu, Yael; Lev-Ran, Shaul

    2017-02-01

    To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain. Cross-sectional study. Two leading pain clinics in Israel. Our sample included 888 individuals receiving treatment for chronic pain, of whom 99.4% received treatment with prescription opioids or MC. Problematic use of prescription opioids and MC was assessed using DSM-IV criteria, Portenoy’s Criteria (PC), and the Current Opioid Misuse Measure (COMM) questionnaire. Additional sociodemographic and clinical correlates of problematic use were also assessed. Among individuals treated with prescription opioids, prevalence of problematic use of opioids according to DSM-IV, PC, and COMM was 52.6%, 17.1%, and 28.7%, respectively. Among those treated with MC, prevalence of problematic use of cannabis according to DSM-IV and PC was 21.2% and 10.6%, respectively. Problematic use of opioids and cannabis was more common in individuals using medications for longer periods of time, reporting higher levels of depression and anxiety, and using alcohol or drugs. Problematic use of opioids was associated with higher self-reported levels of pain, and problematic use of cannabis was more common among individuals using larger amounts of MC. Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC. Pain patients should be screened for risk factors for problematic use before initiating long-term treatment for pain-control.

  10. Incidental dose to coronary arteries is higher in prone than in supine whole breast irradiation. A dosimetric comparison in adjuvant radiotherapy of early stage breast cancer

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    Wuerschmidt, Florian; Stoltenberg, Solveigh; Kretschmer, Matthias; Petersen, Cordula

    2014-06-15

    Sparing of normal lung is best achieved in prone whole breast irradiation (WBI). However, exposure of the heart and coronary arteries might increase due to anterior movement of the heart in prone WBI. Treatment plans of 46 patients with large breasts irradiated for mammary cancer after breast-conserving surgery were retrospectively analyzed. The average treated breast volume of right-sided breasts (n = 33) was 1,804 ccm and 1,500 ccm for left-sided breasts (n = 13). The majority had invasive cancer (96 %) of which 61 % were pT1 and 39 % pT2 tumors. All patients received radiation therapy to the breast only. For three-dimensional (3D) treatment planning, all patients underwent a noncontrast-enhanced CT in the supine position with a wingboard and a second CT in the prone position using a prone breastboard. Nontarget volumes of the lung, heart, and coronary arteries were contoured. A total dose of 50.4 Gy was prescribed to the breast only. Differences were calculated for each patient and compared using the Wilcoxon signed-rank test. Treatment of left-sided breasts resulted in similar average mean heart doses in prone versus supine WBI (4.16 vs. 4.01 Gy; p = 0.70). The left anterior descending artery (LAD) had significantly higher dose exposure in left versus right WBI independent of position. Prone WBI always resulted in significantly higher exposures of the right circumflex artery (RCA) and LAD as compared to supine WBI. In left WBI, the mean LADprone was 33.5 Gy vs. LADsupine of 25.6 Gy (p = 0.0051). The V20prone of the LAD was 73.6 % vs. V20supine 50.4 % (p = 0.0006). The heart dose is not different between supine and prone WBI. However, in left WBI the incidental dose to the LAD with clinically relevant doses can be significantly higher in prone WBI. This is discussed controversially in the literature as it might depend on contouring and treatment techniques. We recommend contouring of LAD if patients are treated in prone WBI and evaluation of alternative

  11. [Survey on patients' satisfaction with opioid rescue guidance by pharmacists].

    Science.gov (United States)

    Takase, Hisamitsu; Kawade, Yoshihiro; Iwata, Hiromi; Endo, Rika; Itoh, Toshimasa; Shiokawa, Mitsuru; Shibasaki, Yumiko; Nakamura, Masumi; Hisada, Atsuo; Sano, Motohiko; Kokubun, Hideya; Kagaya, Hajime; Suzuki, Tsutomu

    2008-05-01

    To examine the influence of drug therapy guidance by pharmacists on the use of a rescue dose (RD) for opioid analgesics (opioids) and pain as well as drug therapy guidance in cancer pain treatment, we conducted a patient satisfaction survey. The subjects were 56 cancer patients undergoing opioid therapy in hospitals belonging to the Symptom Control Research Group (SCORE-G). The survey period was 2 months (from November 1 until December 31, 2006). Drug therapy guidance regarding the use of RD was performed twice in each patient to evaluate the patients' satisfaction. RD was prescribed in 87.8% of the patients in the first guidance and in 80.5% in the second guidance periods. The proportion of patients who used RD significantly increased from 63.8% to 87.5%. Five items significantly improved in the second guidance period: "marked analgesic effects," "satisfaction with current treatment," "correct understanding of RD usage," "relief through RD," and "appropriate use of RD." On comprehensive evaluation following the second round of guidance, 81% of the patients reported overall satisfaction, and 78% reported the usefulness of guidance in pain treatment. These results suggest that positive guidance by pharmacists increases patients' satisfaction. In providing guidance, it was important to confirm the characteristics and side effects of opioids as well as the necessity of RD to patients accurately and repeatedly.

  12. Opioids Switching with Transdermal Systems in Chronic Cancer Pain

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    Barbarisi M

    2009-05-01

    Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

  13. Micronized Organic Magnesium Salts Enhance Opioid Analgesia in Rats.

    Directory of Open Access Journals (Sweden)

    Magdalena Bujalska-Zadrożny

    Full Text Available As previously reported, magnesium sulphate administered parenterally significantly increased an opioid antinociception in different kinds of pain. Since the typical form of magnesium salts are poorly and slowly absorbed from the gastrointestinal tract we examined whether their micronized form could increase opioids induced antinociception.In behavioural studies on rats morphine, tramadol and oxycodone together with magnesium (lactate dihydrate, hydroaspartate, chloride in micronized (particles of size D90 < 50 μm and conventional forms were used. Changes in pain thresholds were determined using mechanical stimuli. The intestinal absorption of two forms of magnesium lactate dihydrate (at the doses of 7.5 or 15 mg ions in the porcine gut sac model were also compared.Micronized form of magnesium lactate dihydrate or hydroaspartate but not chloride (15 mg of magnesium ions kg-1 enhanced the analgesic activity of orally administered opioids, significantly faster and more effective in comparison to the conventional form of magnesium salts (about 40% for oxycodone administered together with a micronized form of magnesium hydroaspartate. Moreover, in vitro studies of transport across porcine intestines of magnesium ions showed that magnesium salts administered in micronized form were absorbed from the intestines to a greater extent than the normal form of magnesium salts.The co-administration of micronized magnesium organic salts with opioids increased their synergetic analgesic effect. This may suggest an innovative approach to the treatment of pain in clinical practice.

  14. Endocrine consequences of opioid therapy.

    Science.gov (United States)

    Aloisi, Anna Maria; Aurilio, Caterina; Bachiocco, Valeria; Biasi, Giovanni; Fiorenzani, Paolo; Pace, Maria Caterina; Paci, Valentina; Pari, Gilberto; Passavanti, Giandomenico; Ravaioli, Laura; Sindaco, Gianfranco; Vellucci, Renato; Ceccarelli, Ilaria

    2009-12-01

    Gonadal hormones are known to be affected by morphine and other opioids. In this paper, we summarize data collected in recent years which clearly indicate that the opioid-induced effects on steroid hormones depend on the opioid used and in some cases on the sex of the subject. Indeed morphine is able to reduce hormones like testosterone and cortisol in both male and female subjects in just a few hours, probably acting directly on peripheral glands. These depressant effects of morphine on hormones are also present in the treatment of surgical pain and are quickly reversible once opioid administration is suspended. Similar actions were also found to occur in experimental animals and in vitro in glial cells, further confirming the morphine-induced reduction of testosterone cell content. Testosterone and its metabolites are well known substances involved in the development and maintenance of the brain and all body structures. Thus when treating pain with opioids, their effects on hypothalamo-pituitary-gonadal and hypothalamo-pituitary-adrenal-related hormones must be considered and, where possible, hormone replacement therapy should be started.

  15. Transdermal opioids for cancer pain.

    Science.gov (United States)

    Cachia, Elaine; Ahmedzai, Sam H

    2011-03-01

    Cancer patients with moderate-to-severe pain require opioids for analgesia. Whereas early guidelines recommend oral morphine as the 'drug of choice', newer synthetic opioids can be given by a reliable and effective nonoral transdermal route. We examine the mode of action of transdermal patches and we review the evidence on two drugs, which are currently available in this formulation - buprenorphine and fentanyl - covering physicochemical characteristics and pharmacokinetics of the patches, clinical efficacy data and adverse effects. Both buprenorphine and fentanyl possess ideal characteristics for transdermal delivery, being small molecules with high lipophilicity. Studies of buprenorphine patches show benefits but there is poor randomized controlled trial evidence comparing them with oral opioids. Fentanyl patches have been used for longer and have a larger body of evidence supporting their use, with data to suggest improved pain relief and reduced opioid side effects compared with sustained release oral morphine. Patients who have used both oral morphine and transdermal fentanyl express a preference for the patch drug. Transdermal buprenorphine and fentanyl are now established for moderate-to-severe cancer pain. There is still a need for further comparative studies with other opioids, especially for buprenorphine.

  16. Peripartum pain management in opioid dependent women

    OpenAIRE

    Höflich, Anna S.; Langer, Martin; Jagsch, Reinhold; Bäwert, Andjela; Winklbaur, Bernadette; Fischer, Gabriele; Unger, Annemarie

    2012-01-01

    Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experienced by opioid maintained pregnant women during delivery and the perinatal period. The aim of the present study was to investigate differences in pain management of opioid maintained compared to non-dependent pregnant women during delivery and the postpartum period. 40 deliveries of 37 opioid dependent women enrolled in a double-blind, double-dummy randomized controlled trial (RCT) exami...

  17. Dependence and Addiction During Chronic Opioid Therapy

    OpenAIRE

    David N Juurlink; Dhalla, Irfan A.

    2012-01-01

    The use of opioids for chronic noncancer pain has increased dramatically over the past 25 years in North America and has been accompanied by a major increase in opioid addiction and overdose deaths. The increase in opioid prescribing is multifactorial and partly reflects concerns about the effectiveness and safety of alternative medications, particularly the nonsteroidal anti-inflammatory drugs. However, much of the rise in opioid prescribing reflects the assertion, widely communicated to phy...

  18. Opioid Peptides: Potential for Drug Development

    OpenAIRE

    Aldrich, Jane V.; McLaughlin, Jay P.

    2012-01-01

    Opioid receptors are important targets for the treatment of pain and potentially for other disease states (e.g. mood disorders and drug abuse) as well. Significant recent advances have been made in identifying opioid peptide analogs that exhibit promising in vivo activity for treatment of these maladies. This review focuses on the development and evaluation of opioid peptide analogs demonstrating activity after systemic administration, and recent clinical evaluations of opioid peptides for po...

  19. Assessment of extended-release opioid analgesics for the treatment of chronic pain.

    Science.gov (United States)

    Gudin, Jeffrey A

    2013-03-01

    Approximately 3.8 million patients annually receive extended-release (ER) or long-acting opioid prescriptions in the outpatient setting, around half of which are written by primary care physicians. Compared with short-acting, immediate-release (IR) formulations, ER and oral long-acting opioid analgesics are associated with clinical advantages, such as extended periods of time during which drug plasma levels are within the therapeutic range, decreased peak-to-trough fluctuations, and prolonged analgesia over the dosing period. Additionally, ER opioids offer a more convenient, less frequent dosing regimen to chronic pain patients who are often taking several concomitant medications. The increased utilization of ER opioids has been accompanied by a rise in the misuse and abuse of these formulations. Certain pharmacokinetic parameters (e.g., longer time to maximum drug plasma concentration, lower maximum drug plasma concentration) may decrease the abuse potential of intact ER opioids by limiting the positive subjective and reinforcing effects relative to IR formulations. Putative abuse-deterrent formulations have also recently been introduced to impede physical manipulation of these formulations, or reduce the harm resulting from such behavior. Such formulations may represent an incremental advance to reduce non-oral forms of abuse. This article reviews the pharmacokinetic profiles and abuse-deterrent features of newer ER opioid analgesics for the treatment of moderate to severe chronic pain.

  20. Life-threatening adverse events following therapeutic opioid administration in adults: is pharmacogenetic analysis useful?

    Science.gov (United States)

    Madadi, Parvaz; Sistonen, Johanna; Silverman, Gregory; Gladdy, Rebecca; Ross, Colin J; Carleton, Bruce C; Carvalho, Jose C; Hayden, Michael R; Koren, Gideon

    2013-01-01

    Systemic approaches are needed to understand how variations in the genes associated with opioid pharmacokinetics and response can be used to predict patient outcome. The application of pharmacogenetic analysis to two cases of life-threatening opioid-induced respiratory depression is presented. The usefulness of genotyping in the context of these cases is discussed. A panel of 20 functional candidate polymorphisms in genes involved in the opioid biotransformation pathway (CYP2D6, UGT2B7, ABCB1, OPRM1, COMT) were genotyped in these two patients using commercially available genotyping assays. In case 1, the patient experienced adverse outcomes when administered codeine and morphine, but not hydromorphone. Genetic test results suggested that this differential response may be due to an inherent propensity to generate active metabolites from both codeine and morphine. These active metabolites are not generated with hydromorphone. In case 2, the patient experienced severe respiratory depression during postoperative recovery following standard doses of morphine. The patient was found to carry genetic variations that result in decreased morphine efflux transporter activity at the blood-brain barrier and increased sensitivity to opioids. Knowledge of the relative contribution of pharmacogenetic biomarkers and their influence on opioid response are continually evolving. Pharmacogenetic analysis, together with clinical history, has the potential to provide mechanistic insight into severe respiratory depressive events in patients who receive opioids at therapeutic doses.

  1. Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

    Science.gov (United States)

    Larochelle, Marc R; Zhang, Fang; Ross-Degnan, Dennis; Wharam, J Frank

    2015-06-01

    In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown. To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates. Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012). Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010. Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions. Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, -32.2 mg morphine-equivalent dose per member per quarter [95% CI, -38.1 to -26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was -11.3 (95% CI, -12.4 to -10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, -8.19 (95% CI, -9.30 to -7.08) for propoxyphene, and -16.2 (95% CI, -18.8 to -13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, -1.10 per 100,000 members per quarter [95% CI, -1.47 to -0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100

  2. Opioids in Preclinical and Clinical Trials

    Science.gov (United States)

    Nagase, Hiroshi; Fujii, Hideaki

    Since 1952, when Gates determined the stereo structure of morphine, numerous groups have focused on discovering a nonnarcotic opioid drug [1]. Although several natural, semisynthetic, and synthetic opioid ligands (alkaloids and peptides) have been developed in clinical studies, very few were nonnarcotic opioid drugs [2]. One of the most important studies in the opioid field appeared in 1976, when Martin and colleagues [3] established types of opioid receptors (these are now classified into μ, δ, and κ types). Later, Portoghese discovered a highly selective μ type opioid receptor antagonist, β-funaltrexamine [4]. This led to the finding that the μ type opioid receptor was correlated to drug dependence [5]. Consequently, δ, and particularly κ, opioid agonists were expected to lead to ideal opioid drugs. Moreover, opioid antagonists were evaluated for the treatment of symptoms related to undesirable opioid system activation. In this chapter, we provide a short survey of opioid ligands in development and describe the discovery of the two most promising drugs, TRK-851 [6] and TRK-820 (nalfurafine hydrochloride) [7].

  3. 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.

  4. Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction

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    Leppert W

    2015-04-01

    Full Text Available Wojciech Leppert Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland Abstract: Opioid-induced bowel dysfunction (OIBD comprises gastrointestinal (GI symptoms, including dry mouth, nausea, vomiting, gastric stasis, bloating, abdominal pain, and opioid-induced constipation, which significantly impair patients’ quality of life and may lead to undertreatment of pain. Traditional laxatives are often prescribed for OIBD symptoms, although they display limited efficacy and exert adverse effects. Other strategies include prokinetics and change of opioids or their administration route. However, these approaches do not address underlying causes of OIBD associated with opioid effects on mostly peripheral opioid receptors located in the GI tract. Targeted management of OIBD comprises purely peripherally acting opioid receptor antagonists and a combination of opioid receptor agonist and antagonist. Methylnaltrexone induces laxation in 50%–60% of patients with advanced diseases and OIBD who do not respond to traditional oral laxatives without inducing opioid withdrawal symptoms with similar response (45%–50% after an oral administration of naloxegol. A combination of prolonged-release oxycodone with prolonged-release naloxone (OXN in one tablet (a ratio of 2:1 provides analgesia with limited negative effect on the bowel function, as oxycodone displays high oral bioavailability and naloxone demonstrates local antagonist effect on opioid receptors in the GI tract and is totally inactivated in the liver. OXN in daily doses of up to 80 mg/40 mg provides equally effective analgesia with improved bowel function compared to oxycodone administered alone in patients with chronic non-malignant and cancer-related pain. OIBD is a common complication of long-term opioid therapy and may lead to quality of life deterioration and undertreatment of pain. Thus, a complex assessment and management that addresses underlying

  5. Estimating State Transitions for Opioid Use Disorders.

    Science.gov (United States)

    Krebs, Emanuel; Min, Jeong E; Evans, Elizabeth; Li, Libo; Liu, Lei; Huang, David; Urada, Darren; Kerr, Thomas; Hser, Yih-Ing; Nosyk, Bohdan

    2017-07-01

    The aim was to estimate transitions between periods in and out of treatment, incarceration, and legal supervision, for prescription opioid (PO) and heroin users. We captured all individuals admitted for the first time for publicly funded treatment for opioid use disorder (OUD) in California (2006 to 2010) with linked mortality and criminal justice data. We used Cox proportional hazards and competing risks models to assess the effect of primary PO use (v. heroin) on the hazard of transitioning among 5 states: (1) opioid detoxification treatment; (2) opioid agonist treatment (OAT); (3) legal supervision (probation or parole); (4) incarceration (jail or prison); and (5) out-of-treatment. Transitions were conditional on survival, and death was modeled as an absorbing state. Both primary PO (n = 11,733) and heroin (n = 19,926) users spent most of their median 2.3 y of observation out of treatment. Primary PO users were significantly younger (median age 30 v. 34 y), and a higher percentage were female (43.1% v. 31.5%; P < 0.001), white (74.6% v. 63.1%; P < 0.001), and had completed high school (31.8% v. 18.9%; P < 0.001). When compared to primary heroin users, PO users had a higher hazard of transitioning from detoxification to OAT (Hazard Ratio (HR), 1.65; 95% CI, 1.54 to 1.77), and had a lower hazard of transitioning from out-of-treatment to either detoxification (0.75 [0.70, 0.81]) or OAT (0.90 [0.85, 0.96]). Our findings can be applied directly in state transition modeling to improve the validity of health economic evaluations. Although PO users tended to remain in treatment for longer durations than heroin users, they also tended to remain out of treatment for longer after transitioning to an out-of-treatment state. Despite the proven effectiveness of time-unlimited treatment, individuals with OUD spend most of their time out of treatment.

  6. 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...

  7. [Treatment of pain with opioid analgesics and the role of TTS-fentanyl (Durogesic)].

    Science.gov (United States)

    Persoli-Gudelj, M

    2001-01-01

    Current opinions in chronic pain treatment with opioid analgesics are presented in this review. Justified use of opioid analgesics in treatment of chronic non-malignant pain in inflammatory and degenerative processes is emphasised. Advantages of opioid analgesics compared with non-opiod analgesics are stressed. New form of opioid--a patch, Durogesic TTS, recently registered in Croatia, is described. After brief review of pharmacodynamics and pharmacokinetics of Durogesic, authors experiences in both chronic malignant pain and chronic non-malignant pain treatment with this analgesic are described. Trial was performed in Pain clinic of Karlovac General Hospital as a part of international multicentric clinical trial. Regarding efficacy, compared to the previous therapy, TTS fentanyl was evaluated positively by patients, both in pain control and ease of use, and by the author, for around the clock, non-invasive administration. Slow dose adjustment in rapid illness progression was recognised as disadvantage.

  8. Long-term use of opioids in 210 officially registered patients with chronic noncancer pain in Taiwan: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Tso-Chou Lin

    2017-04-01

    Conclusion: This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose.

  9. 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.

    2015-01-01

    Objective Animal and in vitro studies suggest that certain opioid analgesics impair crucial immune functions. We sought to determine if opioid use is associated with an increased risk of serious infections in patients with rheumatoid arthritis (RA). Methods We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid (1995–2009). We performed within-person comparisons of the risk of hospitalizations for serious infections during periods of opioid use compared with non-use using conditional Poisson regression. Fixed confounders were accounted for by design, and time-varying confounders included age, the use of disease-modifying anti-rheumatic drugs, glucocorticoids and proton-pump inhibitors. Additional analyses examined new opioid use, use of opioids known to have immunosuppressive properties, long acting opioid use, and different opioid dosages. Sensitivity analyses accounted for potential protopathic bias and confounding by indication. Results Among 1,790 patients with RA who had at least one hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared with non-use [incidence rate ratio (IRR): 1.39 (95% confidence interval (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 with non-use [IRR: 2.01 (95% CI: 1.52–2.66); IRR: 1.72 (95% CI: 1.33–2.23); IRR: 2.38 (95% CI: 1.65–3.42), respectively]. Results of sensitivity analyses were consistent with the main findings. Conclusions In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalizations for serious infection. PMID:26473742

  10. Methadone-Related Overdose Deaths in a Liberal Opioid Maintenance Treatment Programme.

    Science.gov (United States)

    Tjagvad, Christian; Skurtveit, Svetlana; Linnet, Kristian; Andersen, Ljubica Vukelic; Christoffersen, Dorte J; Clausen, Thomas

    2016-01-01

    Increasing rates of overdose deaths involving opioid maintenance treatment (OMT) medications and particularly methadone have been observed concurrently with the implementation of liberal OMT strategies (i.e. minimum of control and high doses prescribed). This study examined methadone-related overdose deaths in a liberal OMT programme. Drug-overdose deaths (n = 130) with detection of methadone in Copenhagen, Aarhus, and Odense Municipality, Denmark, during the period 2008-2011 were identified from a registry. Cases with and without prescribed methadone as OMT were compared. Treatment delivery strategy among OMT-prescribed methadone cases was investigated. Methadone was detected in 130 overdose deaths (71.4% of all overdose deaths). Among these, 63.1% were receiving methadone maintenance treatment. Of these, 79.3% had co-detection of benzodiazepines. Concomitant detection of heroin, non-prescribed benzodiazepines, and younger age were associated with having non-prescribed methadone in the toxicological findings (adjusted OR 3.1, 4.0 and 9.5, respectively). Of the decedents, 43.8% were prescribed a higher methadone dose than recommended (>120 mg daily), of which 80.0% did not have supervised intake of methadone. Liberal OMT access does not necessarily prevent overdose deaths overall. Prescription of higher doses of methadone combined with benzodiazepines may result in an increased risk of overdose for individuals in as well as outside OMT. © 2016 S. Karger AG, Basel.

  11. The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.

    Science.gov (United States)

    Ripley, Tamzin L; Sanchez-Roige, Sandra; Bullmore, Edward T; Mugnaini, Manolo; Maltby, Kay; Miller, Sam R; Wille, David R; Nathan, Pradeep; Stephens, David N

    2015-09-01

    Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding. Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75% receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone.

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

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    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

  13. Role of opioid peptides in the regulation of cytokine production by murine CD4+ T cells.

    Science.gov (United States)

    van den Bergh, P; Dobber, R; Ramlal, S; Rozing, J; Nagelkerken, L

    1994-03-01

    The presence of the opioid peptides alpha- and beta-endorphin (-End) but not methionine enkephalin (Met-enk) in in vitro cultures of purified CD4+ T cells, stimulated with concanavalin A in the presence of irradiated spleen cells, resulted in a threefold stimulation of IL-2, IL-4, and IFN-gamma production. The stimulating effect was dependent on the concentration of the peptides and reached optimal values in the dose range from 10(-12) to 10(-10) M. Similar results were obtained when purified CD4+ T cells were stimulated with immobilized anti-CD3, indicating a direct effect of opioid peptides on CD4+ T cells. Moreover, in this system a twofold enhancement of IL-6, but not IL-1, secretion was observed. These stimulatory effects were not mediated through opioid receptors since the peptide fragment beta-End6-31 that lacks the N-terminal opioid receptor binding part was still stimulatory. This is in agreement with our finding that beta-End did not affect cAMP, as described for the triggering of classical opioid receptors. Experiments undertaken to reveal the mechanism of action of opioid peptides suggest an overall enhancement of lymphokine production: (1) enhancement of IL-4 production occurred also in the presence of excess IL-2; and (2) neither IL-1 receptor-antagonizing protein nor anti-IL-6 were capable to abrogate the stimulatory effect on IL-2 and IL-4 production. Finally, the presence and activity of opioid receptors in cultures of CD4+ T cells were substantiated by the fact that the opioid receptor antagonist naloxone by itself enhanced cytokine synthesis, which points to the endogenous production by lymphocytes of down-regulating opioid peptides.

  14. In-hospital resuscitation: opioids and other factors influencing survival

    Directory of Open Access Journals (Sweden)

    Karamarie Fecho

    2009-12-01

    Full Text Available Karamarie Fecho1, Freeman Jackson1, Frances Smith1, Frank J Overdyk21Department of Anesthesiology, University of North Carolina, Chapel Hill, North Carolina, USA; 2Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina, USAPurpose: “Code Blue” is a standard term used to alertt hospital staff that a patient requires resuscitation. This study determined rates of survival from Code Blue events and the role of opioids and other factors on survival.Methods: Data derived from medical records and the Code Blue and Pharmacy databases were analyzed for factors affecting survival.Results: During 2006, rates of survival from the code only and to discharge were 25.9% and 26.4%, respectively, for Code Blue events involving cardiopulmonary resuscitation (CPR; N = 216. Survival rates for events not ultimately requiring CPR (N = 77 were higher, with 32.5% surviving the code only and 62.3% surviving to discharge. For CPR events, rates of survival to discharge correlated inversely with time to chest compressions and defibrillation, precipitating event, need for airway management, location and age. Time of week, witnessing, postoperative status, gender and opioid use did not influence survival rates. For non-CPR events, opioid use was associated with decreased survival. Survival rates were lowest for patients receiving continuous infusions (P < 0.01 or iv boluses of opioids (P < 0.05.Conclusions: One-quarter of patients survive to discharge after a CPR Code Blue event and two-thirds survive to discharge after a non-CPR event. Opioids may influence survival from non-CPR events.Keywords: code blue, survival, opioids, cardiopulmonary resuscitation, cardiac arrest, patient safety

  15. Prescription History of Emergency Department Patients Prescribed Opioids

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    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.

  16. Nurses' willingness to maximize opioid analgesia for severe cancer pain, and its predictor.

    Science.gov (United States)

    Chang, Yoon Jung; Yun, Young Ho; Park, Sang Min; Lee, So Woo; Park, Hyeoun-Ae; Ro, You-Ja; Huh, Bong Yul

    2005-09-01

    The effectiveness of cancer pain management (CPM) is influenced by nurses' willingness to maximize opioid analgesia for severe cancer pain. The purposes of this study were to identify the willingness of nurses to provide maximum-dose opioids whenever needed for CPM and to determine its associated predictors. This multicenter study was conducted among the entire total of registered nurses in seven large hospitals in Korea. Its overall response rate was 41.6%, and the data from 930 who responded (40.1%) were analyzed. We utilized a three-step, multidimensional, multiple logistic regression to identify the predictors of nurses' willingness. Only 255 nurses (27.4%) indicated that they recommended the maximum dose of opioids whenever it was needed. The respondents who were more likely to recommend morphine showed the following characteristics: older nurses (odds ratio, OR, 1.57; confidence interval, CI, 1.13-2.19); they knew the effectiveness of opioids for CPM (OR 1.53; CI 1.06-2.20); rarely concerned about a patient's addiction to opioids (OR 2.16; CI 1.48-3.15), or to a family member's addiction (OR 1.81; CI 1.20-2.73); prior experience with pain assessment tools (OR 1.62; CI 1.11-2.37); practical experience caring for cancer patients with pain over 51% (OR 1.55; CI 1.09-2.19). Our multicenter study suggested that in order to improve nurses' willingness to recommend opioids liberally in CPM: (1) attitudes about fear of opioid addiction must be changed; (2) the efficiency of opioids in CPM must be taught; and (3) implementation of pain assessment tools must be undertaken.

  17. Breastfeeding among Mothers on Opioid Maintenance Treatment: A Literature Review.

    Science.gov (United States)

    Tsai, Lillian C; Doan, Therese Jung

    2016-08-01

    Although there is an abundance of interventional studies to increase breastfeeding rates, little is known about how to support and promote breastfeeding among mothers on opioid maintenance treatment (OMT). The studies on maternal OMT mainly focus on medication excreted in breast milk and breastfeeding benefits for infants with neonatal abstinence syndrome (NAS). We aim to review interventions to improve breastfeeding outcomes among mothers on OMT to make recommendations for practice and future research. We searched CINAHL, PubMed, PsycINFO, and the Cochrane Database of Systematic Reviews for articles, preferably experimental/quasi-experimental studies published within the past 10 years, that examined interventions to increase rates of breastfeeding initiation and duration among mothers on OMT. Nine studies met our inclusion criteria, comprising 5 categories: 4 combined obstetric and addiction care, 1 rooming-in, 1 Baby-Friendly hospital, 2 inpatient/outpatient NAS treatment, and 1 divided methadone dose. Breastfeeding rates were relatively higher for divided methadone dose (81% initiated any breastfeeding) and rooming-in (62% initiated any breastfeeding); lower in Baby-Friendly hospital (24%) and inpatient/outpatient NAS treatment (45% and 24%, respectively); and mixed in combined obstetric and addiction care programs (2 studies reported 70% and 76%; 2 studies reported 17% and 28%). Studies that included both methadone and buprenorphine did not specify breastfeeding results by medication. We recommend future research to differentiate breastfeeding types and duration by OMT medication. Qualitative studies are needed to explore maternal view on breastfeeding regarding need, barrier, and motivating factors in order to develop effective interventions to promote breastfeeding among mothers on OMT. © The Author(s) 2016.

  18. Opioid and noradrenergic contributions of tapentadol in experimental neuropathic pain.

    Science.gov (United States)

    Meske, Diana S; Xie, Jennifer Y; Oyarzo, Janice; Badghisi, Hamid; Ossipov, Michael H; Porreca, Frank

    2014-03-06

    Tapentadol is a dual action molecule with mu opioid agonist and norepinephrine (NE) reuptake blocking activity that has recently been introduced for the treatment of moderate to severe pain. The effects of intraperitoneal (i.p.) morphine (10mg/kg), tapentadol (10 or 30 mg/kg) or duloxetine (30 mg/kg), a norepinephrine/serotonin (NE/5HT) reuptake inhibitor, were evaluated in male, Sprague-Dawley rats with spinal nerve ligation (SNL) or sham surgery. Additionally, the effects of these drugs on spinal cerebrospinal fluid (CSF) NE levels were quantified. Response thresholds to von Frey filament stimulation decreased significantly from baseline in SNL, but not sham, operated rats. Duloxetine, tapentadol and morphine produced significant and time-related reversal of tactile hypersensitivity. Duloxetine significantly increased spinal CSF NE levels in both sham and SNL rats and no significant differences were observed in these groups. Tapentadol (10 mg/kg) produced a significant increase in spinal NE levels in SNL, but not in sham, rats. At the higher dose (30 mg/kg), tapentadol produced a significant increase in spinal CSF NE levels in both SNL and sham groups; however, spinal NE levels were elevated for an extended period in the SNL rats. This could be detected 30 min following tapentadol (30 mg/kg) in both sham and SNL groups. Surprisingly, while the dose of morphine studied reversed tactile hypersensitivity in nerve-injured rats, CSF NE levels were significantly reduced in both sham- and SNL rats. The data suggest that tapentadol elicits enhanced elevation in spinal NE levels in a model of experimental neuropathic pain offering a mechanistic correlate to observed clinical efficacy in this pain state. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Prescription opioid use and non-fatal overdose in a cohort of injection drug users.

    Science.gov (United States)

    Lake, Stephanie; Wood, Evan; Buxton, Jane; Dong, Huiru; Montaner, Julio; Kerr, Thomas

    2015-05-01

    There is growing concern regarding rising rates of prescription drug-related deaths among the general North American population as well as increasing availability of illicitly obtained prescription opioids. Concurrently among people who inject drugs (IDU), illicit prescription opioid use has increased while non-fatal overdose remains a major source of morbidity. To evaluate whether the use of prescription opioids was associated with non-fatal overdose among IDU in Vancouver, Canada. Data was obtained from two open prospective cohorts of IDU between December 2005 and May 2013. We used generalized estimating equation (GEE) logistic regression to evaluate the association between prescription opioid use and non-fatal overdose, adjusting for various social, demographic, and behavioral factors. There were 1614 IDU, including 541 (33.5%) women, who were recruited and included in this analysis. At baseline, 526 (32.6%) reported using prescription opioids and 118 (7.3%) reported experiencing an overdose in the previous six months. In a multivariable analysis, prescription opioid use remained independently associated with non-fatal overdose (adjusted odds ratio: 1.61, 95% confidence interval: 1.32-1.95), after adjusting for confounders. We observed relatively high rates of prescription opioid use among IDU in this setting, and found an independent association between prescription opioid use and non-fatal overdose. Our data is likely representative of riskier substance use associated with those who use prescription opioids within our sample. Interventions to prevent and respond to overdoses should consider the higher risk profiles of IDU who use prescription opioids.

  20. The stigma of low opioid prescription in the hospitalized multimorbid elderly in Italy.

    Science.gov (United States)

    Marengoni, Alessandra; Nobili, Alessandro; Corli, Oscar; Djade, Codjo Djignefa; Bertoni, Diana; Tettamanti, Mauro; Pasina, Luca; Corrao, Salvatore; Salerno, Francesco; Marcucci, Maura; Mannucci, Pier Mannuccio

    2015-04-01

    The primary aim of this study was to evaluate the prevalence of opioid prescriptions in hospitalized geriatric patients. Other aims were to evaluate factors associated with opioid prescription, and whether or not there was consistency between the presence of pain and prescription. Opioid prescriptions were gathered from the REgistro POliterapie Societa` Italiana di Medicina Interna (REPOSI) data for the years 2008, 2010 and 2012. 1,380 in-patients, 65+ years old, were enrolled in the first registry run, 1,332 in the second and 1,340 in the third. The prevalence of opioid prescription was calculated at hospital admission and discharge. In the third run of the registry, the degree of pain was assessed by means of a numerical scale. The prevalence of patients prescribed with opioids at admission was 3.8% in the first run, 3.6% in the second and 4.1% in the third, whereas at discharge rates were slightly higher (5.8, 5.3, and 6.6%). The most frequently prescribed agents were mild opioids such as codeine and tramadol. The number of total prescribed drugs was positively associated with opioid prescription in the three runs; in the third, dementia and a better functional status were inversely associated with opioid prescription. Finally, as many as 58% of patients with significant pain at discharge were prescribed no analgesic at all. The conservative attitude of Italian physicians to prescribe opioids in elderly patients changed very little between hospital admission and discharge through a period of 5 years. Reasons for such a low opioid prescription should be sought in physicians' and patients' concerns and prejudices.

  1. Predicting the Risk of Opioid Use Disorder Based on Early Maladaptive Schemas.

    Science.gov (United States)

    Zamirinejad, Somayeh; Hojjat, Seyed Kaveh; Moslem, Alireza; MoghaddamHosseini, Vahideh; Akaberi, Arash

    2018-03-01

    Substance use is a globally devastating social problem. Early maladaptive schemas (EMSs) are inefficient mechanisms leading directly or indirectly to psychological distress. The current study aimed to assess the role of EMSs in predicting opioid use disorder. The cross-sectional study was conducted in 2013 in Bojnurd at northeast of Iran on 60 male opioid users who received Methadone Maintenance Treatment (MMT) and 60 control males. The opioid users were selected randomly from MMT clinics and control subjects were selected and matched with opioid users using demographic variables. The subjects completed the Young Schema Questionnaire-Short Form (YSQ-SF). Except for SS (self-sacrifice), EG (entitlement/grandiosity), US (unrelenting standards), and FA (Failure to Achieve), the mean of other maladaptive schemas in the opioid user group were significantly higher than that of the control group, adjusted for multiple comparisons. Multivariate analysis of variance (MANOVA) indicated significant differences in maladaptive schemas between the two groups. Logistic regression identified that Emotional Deprivation, Mistrust/Abuse, and Unrelenting Standards can predict opioid use. As a result, the risk of opioid-related disorders in people with higher YSQ-SF scores in these schemas is higher. The findings conclude that the existence of underlying EMS may constitute a vulnerability factor for developing opioid use disorders later on in life. Provided the vast amount of scientific literature in evidence-based treatments focusing on EMSs, maladaptive schemas and related core beliefs can be detected and treated in adolescence to prevent the enactment of the schema and psychological distress likely to induce opioid use.

  2. The opioid systems--panacea and nemesis.

    Science.gov (United States)

    Terenius, Lars; Johansson, Björn

    2010-05-21

    This mini-review outlines the opioid systems and their roles primarily as related to reward and compulsive drug/alcohol intake. The central role is taken by the mu-opioid receptor, target for opiate analgesics and also a central target in compulsive alcohol abuse, alcoholism. The mu-opioid receptor and the cognate opioid neuropeptides from proenkephalin and proopiomelancortin are members of a superfamily of opioid systems, each with unique and still to be defined roles in the central nervous system. 2010. Published by Elsevier Inc.

  3. Kappa-opioid receptors mediate the antidepressant-like activity of hesperidin in the mouse forced swimming test.

    Science.gov (United States)

    Filho, Carlos B; Del Fabbro, Lucian; de Gomes, Marcelo G; Goes, André T R; Souza, Leandro C; Boeira, Silvana P; Jesse, Cristiano R

    2013-01-05

    The opioid system has been implicated as a contributing factor for major depression and is thought to play a role in the mechanism of action of antidepressants. This study investigated the involvement of the opioid system in the antidepressant-like effect of hesperidin in the mouse forced swimming test. Our results demonstrate that hesperidin (0.1, 0.3 and 1 mg/kg; intraperitoneal) decreased the immobility time in the forced swimming test without affecting locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) in the forced swimming test was prevented by pretreating mice with naloxone (1 mg/kg, a nonselective opioid receptor antagonist) and 2-(3,4-dichlorophenyl)-Nmethyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl] acetamide (DIPPA (1 mg/kg), a selective κ-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, a peripherally acting opioid receptor antagonist), naltrindole (3 mg/kg, a selective δ-opioid receptor antagonist), clocinnamox (1 mg/kg, a selective μ-opioid receptor antagonist) or caffeine (3 mg/kg, a nonselective adenosine receptor antagonist). In addition, a sub-effective dose of hesperidin (0.01 mg/kg) produced a synergistic antidepressant-like effect in the forced swimming test when combined with a sub-effective dose of morphine (1 mg/kg). The antidepressant-like effect of hesperidin in the forced swimming test on mice was dependent on its interaction with the κ-opioid receptor, but not with the δ-opioid, μ-opioid or adenosinergic receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like properties and may be of interest as a therapeutic agent for the treatment of depressive disorders. Published by Elsevier B.V.

  4. Pain Sensitivity and Opioid Analgesia: A Pharmacogenomic Twin Study

    Science.gov (United States)

    Angst, Martin S.; Phillips, Nicholas G.; Drover, David R.; Tingle, Martha; Ray, Amrita; Swan, Gary E.; Lazzeroni, Laura C.; Clark, J. David

    2012-01-01

    Opioids are the cornerstone medication for the management of moderate to severe pain. Unfortunately, vast inter-individual differences in dose requirements complicate their effective and safe clinical use. Mechanisms underlying such differences are incompletely understood, are likely multifactorial, and include genetic and environmental contributions. While accumulating evidence suggests that variants of several genes account for some of the observed response variance, the relative contribution of these factors remains unknown. This study used a twin paradigm to provide a global estimate of the genetic and environmental contributions to inter-individual differences in pain sensitivity and analgesic opioid effects. Eighty one monozygotic and 31 dizygotic twin pairs successfully underwent a computer-controlled infusion with the muopioid agonist alfentanil in a single occasion, randomized, double-blind and placebo-controlled study design. Pain sensitivity and analgesic effects were assessed with experimental heat and cold pressor pain models along with important covariates including demographic factors, depression, anxiety, and sleep quality. Significant heritability was detected for cold pressor pain tolerance and opioid-mediated elevations in heat and cold pressor pain thresholds. Genetic effects accounted for 12–60% of the observed response variance. Significant familial effects accounting for 24–32% of observed variance were detected for heat and cold pressor pain thresholds and opioid-mediated elevation in cold pressor pain tolerance. Significant covariates included age, gender, race, education, and anxiety. Results provide a strong rationale for more detailed molecular genetic studies to elucidate mechanisms underlying inter-individual differences in pain sensitivity and analgesic opioid responses. Such studies will require careful consideration of the studied pain phenotype. PMID:22444188

  5. Opioid use in knee arthroplasty after receiving intravenous acetaminophen.

    Science.gov (United States)

    Kelly, Jennifer S; Opsha, Yekaterina; Costello, Jennifer; Schiller, Daryl; Hola, Eric T

    2014-12-01

    Intravenous (IV) acetaminophen may be an effective component of multimodal postoperative pain management. The primary objective of this study was to evaluate the impact of IV acetaminophen on total opioid use in postoperative patients. The secondary objective was to evaluate the effect of IV acetaminophen on hospital length of stay. This retrospective, case-control study evaluated the impact of IV acetaminophen on total opioid use in surgical patients. Patients were included if they received at least one perioperative dose of IV acetaminophen and underwent a surgical knee procedure. Controls were matched and randomly selected based on procedure type, age, and severity of illness. Postoperative opioids were converted into oral morphine equivalents, and overall use was compared between groups. One hundred patients were enrolled, with 25 patients receiving IV acetaminophen and 75 matched controls. A total of 135 mg versus 112.5 mg oral morphine equivalents were used in the IV acetaminophen group and control group, respectively (p=0.987). There were 45 mg/day oral morphine equivalents used in the IV acetaminophen group versus 37.5 mg in the control group (p=0.845). The median hospital length of stay in both groups was 3 days (p=0.799). IV acetaminophen did not significantly decrease postoperative opioid use in patients who underwent surgical knee procedures. In addition, there was a nonsignificant trend toward increased opioid use in the IV acetaminophen group. There was no significant difference in hospital length of stay between the IV acetaminophen group and the control group. These findings require further study in larger patient populations and in other orthopedic procedures that typically require longer hospital stays. © 2014 Pharmacotherapy Publications, Inc.

  6. Opioid Basics: Fentanyl

    Science.gov (United States)

    ... without the user’s knowledge—to increase its euphoric effects. Learn More: Fentanyl Data The Problem Illicitly-made fentanyl use is on the ... other drug users, 9 or family and friend bystanders who have obtained the medication. 10 Health Care Providers: Multiple doses of ...

  7. It’s MORe exciting than mu: Crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system

    Directory of Open Access Journals (Sweden)

    Elena H Chartoff

    2014-05-01

    Full Text Available Opioids selective for the G-protein coupled mu opioid receptor (MOR produce potent analgesia and euphoria. Heroin, a synthetic opioid, is considered one of the most addictive substances, and the recent exponential rise in opioid addiction and overdose deaths has made treatment development a national public health priority. Existing medications (methadone, buprenorphine, and naltrexone, when combined with psychosocial therapies, have proven efficacy in reducing aspects of opioid addiction. Unfortunately, these medications have critical limitations including those associated with opioid agonist therapies (e.g., sustained physiological dependence and opioid withdrawal leading to high relapse rates upon discontinuation, nonadherence to daily dosing, and non-renewal of monthly injection with extended-release naltrexone. Furthermore, current medications fail to ameliorate key aspects of addiction such as powerful conditioned associations that trigger relapse (e.g., cues, stress, the drug itself. Thus, there is a need for developing novel treatments that target neural processes corrupted with chronic opioid use. This requires a basic understanding of molecular and cellular mechanisms underlying effects of opioids on synaptic transmission and plasticity within reward-related neural circuits. The focus of this review is to discuss how crosstalk between MOR-associated G-protein signaling and glutamatergic neurotransmission leads to immediate and long-term effects on emotional states (e.g., euphoria, depression and motivated behavior (e.g., drug-seeking, relapse. Our goal is to integrate findings on how opioids modulate synaptic release of glutamate and postsynaptic transmission via AMPA and NMDA receptors in the nucleus accumbens (NAc and ventral tegmental area (VTA with the clinical (neurobehavioral progression of opioid dependence, as well as to identify gaps in knowledge that can be addressed in future studies.

  8. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial.

    NARCIS (Netherlands)

    Pechoux, C. Le; Dunant, A.; Senan, S.; Wolfson, A.; Quoix, E.; Faivre-Finn, C.; Ciuleanu, T.; Arriagada, R.; Jones, R.; Wanders, R.; Lerouge, D.; Laplanche, A.; Bussink, J.

    2009-01-01

    BACKGROUND: The optimum dose of prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC) is unknown. A meta-analysis suggested that the incidence of brain metastases might be reduced with higher PCI doses. This randomised clinical trial compared the effect of standard

  9. Dependence and addiction during chronic opioid therapy.

    Science.gov (United States)

    Juurlink, David N; Dhalla, Irfan A

    2012-12-01

    The use of opioids for chronic noncancer pain has increased dramatically over the past 25 years in North America and has been accompanied by a major increase in opioid addiction and overdose deaths. The increase in opioid prescribing is multifactorial and partly reflects concerns about the effectiveness and safety of alternative medications, particularly the nonsteroidal anti-inflammatory drugs. However, much of the rise in opioid prescribing reflects the assertion, widely communicated to physicians in the 1990s, that the risks of dependence and addiction during chronic opioid therapy were low, predictable, and could be minimized by the use of controlled-release opioid formulations. In this narrative review, we offer a critical appraisal of the publications most frequently cited as evidence that the risk of addiction during chronic opioid therapy is low. We conclude that very few well-designed studies support the notion that opioid addiction is rare during chronic opioid therapy and that none can be readily generalized to present-day practice. Despite serious methodological limitations, these studies have been repeatedly mischaracterized as showing that the risk of addiction during chronic opioid therapy is rare. These studies are countered by a larger, more rigorous and contemporary body of evidence demonstrating that dependence and addiction are relatively common consequences of chronic opioid therapy, occurring in up to one-third of patients in some series.

  10. The opioid epidemic: impact on orthopaedic surgery.

    Science.gov (United States)

    Morris, Brent J; Mir, Hassan R

    2015-05-01

    The past few decades have seen an alarming rise in opioid use in the United States, and the negative consequences from diversion of opioids for nontherapeutic use are dramatically increasing. A significant number of orthopaedic patients are at risk for repercussions from both therapeutic and nontherapeutic opioid use. Orthopaedic surgeons are the third highest prescribers of opioid prescriptions among physicians in the United States. Thus, it is important for orthopaedic surgeons to understand the detrimental effects of opioid abuse on individuals and society and to recognize objective measures to identify patients at risk for nontherapeutic opioid use. These measures include elements of the patient history, recognition of aberrant behaviors, prescription drug monitoring programs, and opioid risk-assessment tools. Copyright 2015 by the American Academy of Orthopaedic Surgeons.

  11. Adjusting Bowel Regimens When Prescribing Opioids in Women Receiving Palliative Care in the Acute Care Setting.

    Science.gov (United States)

    Gonzales, Lucia K; Delmastro, Margaret A; Boyd, Denise M; Sterling, Melvyn L; Aube, Patricia A; Le, Rosemary N; Traucht, Lisa; Quinal, Leonida R; Georges, Jane M; Glaser, Dale N

    2016-08-01

    In palliative medicine, constipation is the third most common symptom after pain and anorexia, causing some patients to discontinue opioid therapy. Women experience higher incidence of constipation than men. The prevalence of infrequent bowel movements (opioids were studied. Referral to the palliative care team decreased the prevalence of infrequent bowel movements from 72% to 45%, and algorithm adherence increased from 38% to 78%. Education of oncology nurses decreased the prevalence of infrequent bowel movements among patients with cancer from 71% to 60%, and algorithm adherence increased from 0% to 10%. Patients benefit from stool softeners and stimulants when receiving opioids. © The Author(s) 2015.

  12. Risk Factors of Prescription Opioid Overdose Among Colorado Medicaid Beneficiaries.

    Science.gov (United States)

    Dilokthornsakul, Piyameth; Moore, Gina; Campbell, Jonathan D; Lodge, Robert; Traugott, Cathy; Zerzan, Judy; Allen, Richard; Page, Robert L

    2016-04-01

    This study aims to determine risk factors of opioid overdose among the Colorado Medicaid population. A retrospective nested case-control study was undertaken. Medicaid beneficiaries who had ≥1 medical claim for an emergency department visit or a hospitalization associated with an opioid overdose from July 2009 to June 2014 were defined as cases. Controls were selected using a nearest neighbor matching without replacement. The matched controls were selected on the basis of age, sex, and opioid prescription. One case was matched with three controls. Multivariate conditional logistic regression was used to compare risk factors. A total of 816 cases with 2,448 controls were included. Six factors were associated with opioid overdose: mean morphine dose equivalent (>50 mg/d; odds ratio [OR] = 1.986 [95% confidence interval [CI], 1.509-2.614]), methadone use (switching opioid to methadone vs. no methadone use; OR = 7.230 [95% CI, 2.346-22.286]), drug/alcohol abuse (OR = 3.104 [95% CI, 2.195-4.388]), other psychiatric illness (OR = 1.730 [95% CI, 1.307-2.291]), benzodiazepine use (OR = 2.005 [95% CI, 1.516-2.652]), and the number of pharmacies used by the beneficiary (≥4 pharmacies vs. 1 pharmacy; OR = 1.514 [95% CI, 1.003-2.286]). In conclusion, several factors are associated with opioid overdose. States and communities should ensure the availability of at-home intranasal naloxone for overdose rescue on the basis of the presence of risk factors. This article presents the risk factors of opioid overdose among the Colorado Medicaid population. On the basis of study findings, Colorado Medicaid is currently working with physicians, hospitals, and other health system stakeholders to continue to develop policies to identify and assist this subset of our population. One such policy will be to provide at-home intranasal naloxone for overdose rescue. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. The effects of opioids and opioid analogs on animal and human endocrine systems.

    Science.gov (United States)

    Vuong, Cassidy; Van Uum, Stan H M; O'Dell, Laura E; Lutfy, Kabirullah; Friedman, Theodore C

    2010-02-01

    Opioid abuse has increased in the last decade, primarily as a result of increased access to prescription opioids. Physicians are also increasingly administering opioid analgesics for noncancer chronic pain. Thus, knowledge of the long-term consequences of opioid use/abuse has important implications for fully evaluating the clinical usefulness of opioid medications. Many studies have examined the effect of opioids on the endocrine system; however, a systematic review of the endocrine actions of opioids in both humans and animals has, to our knowledge, not been published since 1984. Thus, we reviewed the literature on the effect of opioids on the endocrine system. We included both acute and chronic effects of opioids, with the majority of the studies done on the acute effects although chronic effects are more physiologically relevant. In humans and laboratory animals, opioids generally increase GH and prolactin and decrease LH, testosterone, estradiol, and oxytocin. In humans, opioids increase TSH, whereas in rodents, TSH is decreased. In both rodents and humans, the reports of effects of opioids on arginine vasopressin and ACTH are conflicting. Opioids act preferentially at different receptor sites leading to stimulatory or inhibitory effects on hormone release. Increasing opioid abuse primarily leads to hypogonadism but may also affect the secretion of other pituitary hormones. The potential consequences of hypogonadism include decreased libido and erectile dysfunction in men, oligomenorrhea or amenorrhea in women, and bone loss or infertility in both sexes. Opioids may increase or decrease food intake, depending on the type of opioid and the duration of action. Additionally, opioids may act through the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion. In this review, recent information regarding endocrine disorders among opioid abusers is presented.

  14. Nausea and vomiting side effects with opioid analgesics during treatment of chronic pain: mechanisms, implications, and management options.

    Science.gov (United States)

    Porreca, Frank; Ossipov, Michael H

    2009-01-01

    Gastrointestinal (GI) side effects such as nausea and vomiting are common following opioid analgesia and represent a significant cause of patient discomfort and treatment dissatisfaction. This review examines the mechanisms that produce these side effects, their impact on treatment outcomes in chronic pain patients, and counteractive strategies. A number of mechanisms by which opioids produce nausea and vomiting have been identified. These involve both central and peripheral sites including the vomiting center, chemoreceptor trigger zones, cerebral cortex, and the vestibular apparatus of the brain, as well as the GI tract itself. Nausea and vomiting have a negative impact on treatment efficacy and successful patient management because they limit the effective analgesic dosage that can be achieved and are frequently reported as the reason for discontinuation of opioid pain medication or missed doses. While various strategies such as antiemetic agents or opioid switching can be employed to control these side effects, neither option is ideal because they are not always effective and incur additional costs and inconvenience. Opioid-sparing analgesic agents may provide a further alternative to avoid nausea and vomiting due to their reduced reliance on mu-opioid signalling pathways to induce analgesia. Nausea and vomiting side effects limit the analgesic efficiency of current opioid therapies. There is a clear need for the development of improved opioid-based analgesics that mitigate these intolerable effects.

  15. Role of the informed consent, from mesotherapy to opioid therapy.

    Science.gov (United States)

    Mammucari, M; Lazzari, M; Maggiori, E; Gafforio, P; Tufaro, G; Baffini, S; Maggiori, S; Palombo, E; de Meo, B; Sabato, A F

    2014-01-01

    Informed consent is part of a process of communication useful to obtain an agreement (conscious, voluntary and free) between doctors and patients. Mesotherapy is based on the introduction of drugs by intradermal route in order to obtain a dose-sparing effect with respect to deeper administration. Opioids are the most appropriate therapy for patients who do not respond to other therapies. Proper communication between doctor and patient, including an explanation of the potential benefits, limitations and risks (even mild), is recommended both in clinical practice and research. Active participation of the patient has the advantage of better control of adverse events, both of mesotherapy and opioid-based therapy. This information-education process returns to the fundamental concept of "first do no harm" and set a "therapeutic partnership" with patients.

  16. Neighborhood-Level and Spatial Characteristics Associated with Lay Naloxone Reversal Events and Opioid Overdose Deaths.

    Science.gov (United States)

    Rowe, Christopher; Santos, Glenn-Milo; Vittinghoff, Eric; Wheeler, Eliza; Davidson, Peter; Coffin, Philip O

    2016-02-01

    There were over 23,000 opioid overdose deaths in the USA in 2013, and opioid-related mortality is increasing. Increased access to naloxone, particularly through community-based lay naloxone distribution, is a widely supported strategy to reduce opioid overdose mortality; however, little is known about the ecological and spatial patterns of the distribution and utilization of lay naloxone. This study aims to investigate the neighborhood-level correlates and spatial relationships of lay naloxone distribution and utilization and opioid overdose deaths. We determined the locations of lay naloxone distribution sites and the number of unintentional opioid overdose deaths and reported reversal events in San Francisco census tracts (n = 195) from 2010 to 2012. We used Wilcoxon rank-sum tests to compare census tract characteristics across tracts adjacent and not adjacent to distribution sites and multivariable negative binomial regression models to assess the association between census tract characteristics, including distance to the nearest site, and counts of opioid overdose deaths and naloxone reversal events. Three hundred forty-two opioid overdose deaths and 316 overdose reversals with valid location data were included in our analysis. Census tracts including or adjacent to a distribution site had higher income inequality, lower percentage black or African American residents, more drug arrests, higher population density, more overdose deaths, and more reversal events (all p < 0.05). In multivariable analysis, greater distance to the nearest distribution site (up to a distance of 4000 m) was associated with a lower count of Naloxone reversals [incidence rate ratio (IRR) = 0.51 per 500 m increase, 95% CI 0.39-0.67, p < 0.001] but was not significantly associated with opioid overdose deaths. These findings affirm that locating lay naloxone distribution sites in areas with high levels of substance use and overdose risk facilitates reversals of opioid overdoses in those

  17. Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy.

    Science.gov (United States)

    Jones, Hendrée E; Dengler, Erin; Garrison, Anna; O'Grady, Kevin E; Seashore, Carl; Horton, Evette; Andringa, Kim; Jansson, Lauren M; Thorp, John

    2014-01-01

    Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes. The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5 min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial. (1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001). (1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. 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.

  19. Root cause analysis of prescription opioid overdoses.

    Science.gov (United States)

    Wawrzyniak, Kelly M; Sabo, Alex; McDonald, Ann; Trudeau, Jeremiah J; Poulose, Mon; Brown, Mary; Katz, Nathaniel P

    2015-01-01

    Overdoses (ODs) of prescription opioids (RxOs) have become a major public health issue in the United States. To determine the root causes of accidental prescription opioid overdoses (RxO-OD). The authors conducted a root cause analysis using the Antecedent Target-Measurement method, interviewing three types of key informants: survivors of RxO-ODs, family members, and clinical experts. Ten survivors, five family members, and three experts were interviewed. Proximal causes of RxO-ODs described by survivors and family members were recent RxO dose escalation (n = 9), polysubstance use (n = 5), and polypharmacy use (n = 3). Proximal causes were elicited by the following six antecedent causes: wanting to feel good/high (n = 9), perceived tolerance to RxO (n = 6), didn't know/believe it was dangerous (n = 5), wanting to reduce psychosocial pain (n = 5), wanting to reduce physical pain (n = 4), and wanting to avoid discomfort due to withdrawal symptoms (n = 4). RxOs involved in the OD were either prescribed by a doctor (n = 7), purchased from a dealer (n = 6), given/purchased from family/friends (n = 3), or stolen from family (n = 1). Psychosocial stressors (n = 9), chronic recurrent depression (n = 3), and chronic substance abuse/addiction (n = 4) were also distal and proximal causes of OD. Experts cited similar causes but added prescriberrelated causes (eg, inadequate training) and healthcare system and culture. Patients at risk for OD can be identified and ODs potentially prevented. Opportunities for intervention include routine screening of patients using RxOs for psychosocial distress and coping, flagging of high-risk patients, care pathways for high-risk patients, clinician and patient training on OD prevention, and developing abuse-deterrent formulations of RxOs.

  20. Use of opioid pain relievers following extraction of third molars.

    Science.gov (United States)

    Weiland, Breanna M; Wach, Anthony G; Kanar, Brent P; Castele, Matthew T; Sosovicka, Mark F; Cooke, Matthew R; Moore, Paul A

    2015-02-01

    Following extraction of third molars, it is common practice for oral and maxillofacial surgeons to provide a prescription for an opioid-containing analgesic such as hydrocodone with acetaminophen. Because the instructions for use most often indicate that these analgesics are to be taken "as needed for pain," it is unknown how many of the prescribed postoperative analgesic tablets are needed and actually taken. Therefore, an assessment of patient pain experiences and actual opioid analgesic usage was carried out using structured telephone interviews of patients performed 1 and 7 days following their thirdmolar extraction surgery. Forty-eight adolescents and young adults, ages 15 to 30 years, participated in this assessment. A review of the surgeon's notes indicated that the median number of prescribed opioid-containing analgesics (ie, Vicodin®, Norco®, Lorcet®, Percocet®) was 20 tablets (range 10 to 40). The median consumption during the first 24 hours was reported to be three tablets (range 0 to 10), and the total consumption for all 7 days was eight tablets (range 0 to 34). Four patients reported nausea or vomiting in the first 24 hours, and six patients reported nausea or vomiting during the following 6 days of recovery. The initial prescriptions provided adequate relief for 45 of the 48 patients. Higher consumption of opioid pain relievers (OPRs) was associated with a longer duration of surgery and the occurrence of postoperative infections.

  1. Exploring Opioid-Sparing Multimodal Analgesia Options in Trauma: A Nursing Perspective.

    Science.gov (United States)

    Sullivan, Denise; Lyons, Mary; Montgomery, Robert; Quinlan-Colwell, Ann

    Challenges with opioids (e.g., adverse events, misuse and abuse with long-term administration) have led to a renewed emphasis on opioid-sparing multimodal management of trauma pain. To assess the extent to which currently available evidence supports the efficacy and safety of various nonopioid analgesics and techniques to manage trauma pain, a literature search of recently published references was performed. Additional citations were included on the basis of authors' knowledge of the literature. Effective options for opioid-sparing analgesics include oral and intravenous (IV) acetaminophen; nonsteroidal anti-inflammatory drugs available via multiple routes; and anticonvulsants, which are especially effective for neuropathic pain associated with trauma. Intravenous routes (e.g., IV acetaminophen, IV ketorolac) may be associated with a faster onset of action than oral routes. Additional adjuvants for the treatment of trauma pain are muscle relaxants and alpha-2 adrenergic agonists. Ketamine and regional techniques play an important role in multimodal therapy but require medical and nursing support. Nonpharmacologic treatments (e.g., cryotherapy, distraction techniques, breathing and relaxation, acupuncture) supplement pharmacologic analgesics and can be safe and easy to implement. In conclusion, opioid-sparing multimodal analgesia addresses concerns associated with high doses of opioids, and many pharmacologic and nonpharmacologic options are available to implement this strategy. Nurses play key roles in comprehensive patient assessment; administration of patient-focused, opioid-sparing, multimodal analgesia in trauma; and monitoring for safety concerns.

  2. Trends in opioid analgesics sales to community pharmacies and hospitals in Italy (2000-2010).

    Science.gov (United States)

    Caraceni, A T; Brunelli, C; Rocco, P; Minghetti, P

    2013-08-01

    Opioid consumption data in Italy have been widely studied. However, only aggregate data can be found in the published literature, and differences are expected by distribution setting (community pharmacies and hospitals). The aim of our paper is to analyse opioids sales trends in Italy in the decade 2000-2010, in an effort to explore such differences. Quarterly sales data of opioid medicinal products sold by wholesalers to both community pharmacies (retail) and to hospitals (non-retail) during the time period 2000-2010 were supplied by IMS Italy. Data were standardized using the Defined Daily Doses per day per 1000 inhabitants (DDDd/1000). Opioid sales have steadily increased during the time period considered going from 1.04 DDDd/1000 in 2000 to 4.9 in 2010 (+292%). Nonetheless relevant differences can be found both by distribution setting and drug type. In particular retail sales have increased by 286 % for WHO Step II opioids and by 575% for WHO Step III drugs, while non-retail sales have increased by 48% and 263%, respectively. In 2010, fentanyl and buprenorphine transdermal patches and oxycodone are more widely prescribed than morphine, in the retail setting, with fentanyl at large in the first position. In hospitals morphine and fentanyl almost equally share the 75% of the market. Data suggest that morphine is no more the opioid of first choice for severe pain in Italy, at least for outpatients. This is contradicting most international guidelines available in the 2000-2010 decade.

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

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    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.

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

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    El-Mallah, Ahmed; Aboul-Ela, Maha; Ellakany, Abdalla

    2017-01-01

    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. PMID:28280516

  5. Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

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    Renata Cristina Mendes Ferreira

    2017-01-01

    Full Text Available Background. Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Methods. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2 μg. Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE2 injection. Results. Aripiprazole (100 μg/paw injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 μg/paw, a nonselective opioid receptor antagonist. The role of μ-, δ-, and κ-opioid receptors was investigated using the selective antagonists, clocinnamox (40 μg/paw, naltrindole (15, 30, and 60 μg/paw, and nor-binaltorphimine (200 μg/paw, respectively. The data indicated that only the δ-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 μg, an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 μg/paw aripiprazole-induced peripheral antinociception. Conclusion. The results suggest the participation of the opioid system via δ-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.

  6. The "other" respiratory effect of opioids: suppression of spontaneous augmented ("sigh") breaths.

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    Bell, Harold J; Azubike, Elizabeth; Haouzi, Philippe

    2011-11-01

    The purpose of this study was to examine the effects of a clinically relevant opioid on the production of augmented breaths (ABs) in unanesthetized animals breathing normal room air, using a dosage which does not depress breathing. To do this we monitored breathing noninvasively, in unrestrained animals before and after subcutaneous injection of either morphine, or a saline control. The effect of ketamine/xylazine was also studied to determine the potential effect of an alternative sedative agent. Last, the effect of naloxone was studied to determine the potential influence of endogenous opioids in regulating the normal incidence of ABs. Morphine (5 mg/kg) had no depressive effect on breathing, but completely eliminated ABs in all animals in room air (P = 0.027). However, when animals breathed hypoxic air (10% O(2)), animals did express ABs, although their incidence was still reduced by morphine (P ABs continued at their normal rate in room air during sedation with ketamine. Naloxone had no effect on breathing or AB production, and so endogenous opioids are not likely involved in regulating their rate of production under normal conditions. Our results show that in unanesthetized animals breathing normal room air, a clinically relevant opioid eliminates ABs, even at a dose that does not cause respiratory depression. Despite this, hypoxia-induced stimulation of breathing can facilitate the production of ABs even with the systemic opioid present, indicating that peripheral chemoreceptor stimulation provides a potential means of overcoming the opioid-induced suppression of these respiratory events.

  7. Delay discounting of the mu opioid receptor agonist remifentanil in rhesus monkeys

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    Maguire, David R.; Gerak, Lisa R.; France, Charles P.

    2015-01-01

    Although increased impulsivity (delay discounting) is an important risk factor for drug abuse, the impact of delay on drug taking has received relatively little attention. This study examined delay discounting of the mu opioid receptor agonist remifentanil in rhesus monkeys (n=4) responding for intravenous (i.v.) infusions under a concurrent choice procedure. Dose-effect curves for remifentanil were determined by varying the dose available on one lever (0.001-0.32 μg/kg/infusion) while keeping the dose available on the other lever (0.1 μg/kg/infusion) the same. Dose-effect curves were determined when both infusions were delivered immediately and when delivery of the fixed dose was delayed (15-180 s). When both doses of remifentanil were delivered immediately, monkeys chose the large dose. Delaying delivery of the fixed dose reduced choice of that dose and increased choice of small immediately available doses. Extending previous studies these results show that the effects of delay on choice between two doses of a mu opioid receptor agonist are consistent with hyperbolic discounting. Delaying delivery of a preferred reinforcer (e.g., large dose of drug) reduces its effectiveness and increases the effectiveness of small immediately available doses. This effect of delay, particularly on drug self-administration, might contribute to drug abuse. PMID:26397761

  8. Delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys.

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    Maguire, David R; Gerak, Lisa R; France, Charles P

    2016-04-01

    Although increased impulsivity (delay discounting) is an important risk factor for drug abuse, the impact of delay on drug taking has received relatively little attention. This study examined delay discounting of the μ-opioid receptor agonist remifentanil in rhesus monkeys (n=4) responding for intravenous infusions under a concurrent choice procedure. Dose-effect curves for remifentanil were determined by varying the dose available on one lever (0.001-0.32 μg/kg/infusion) while keeping the dose available on the other lever (0.1 μg/kg/infusion) the same. Dose-effect curves were determined when both infusions were delivered immediately and when delivery of the fixed dose was delayed (15-180 s). When both doses of remifentanil were delivered immediately, monkeys chose the large dose. Delaying delivery of the fixed dose reduced choice of that dose and increased choice of small immediately available doses. Extending previous studies, these results show that the effects of delay on choice between two doses of a μ-opioid receptor agonist are consistent with hyperbolic discounting. Delaying delivery of a preferred reinforcer (e.g. large dose of drug) reduces its effectiveness and increases the effectiveness of small immediately available doses. This effect of delay, particularly on drug self-administration, might contribute to drug abuse.

  9. Trends in major opioid analgesic consumption in Taiwan, 2002-2014.

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    Kang, Kai-Hsiang; Kuo, Li-Fen; Cheng, I-Chen; Chang, Chih-Shiuh; Tsay, Wen-Ing

    2017-07-01

    According to WHO guideline, the consumption of opioids is an important sign of national progress in cancer pain relief. However, precise data on the consumption of opioid analgesics consumption in Taiwan has not been published. We investigate opioid analgesic consumption in Taiwan between 2002 and 2014 compare the results with those in other countries to see what we could learn about other methods of pain management. To find out the different patterns between Taiwan and other country, improves the quality of pain management. We extracted from the Controlled Drugs Management Information System (CDMIS) database, the consumption data of morphine, fentanyl, and pethidine, three strong opioids, and of codeine and buprenorphine, two weak ones. Data were presented as defined daily doses for statistical purposes per million inhabitants per day (S-DDD/m/d). The number of inhabitants was extracted from the Taiwan Ministry of Interior Statistics population database. During the thirteen studied years, the total consumption of opioids markedly increased in Taiwan. By category, the consumption of morphine, fentanyl and buprenorphine increased, but the use of pethidine and codeine decreased. Compared with the selected regions and countries, the use of opioid in Taiwan progressed in Asia, but it was still lower than in Western countries. Opioid analgesics are probable addictive; however, they can improve a patients' quality of life if properly used. The Taiwan FDA continuously introduces new opioid analgesics and educates physicians on how to use them correctly. These measures will improve the quality of pain management in Taiwan. Copyright © 2016. Published by Elsevier B.V.

  10. Postoperative Opioid Consumption and Its Relationship to Cognitive Function in Elderly Hip Fracture Patients

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    Sieber, Frederick E.; Mears, Simon; Lee, Hochang; Gottschalk, Allan

    2011-01-01

    OBJECTIVES To determine the relationship between opioid consumption and cognitive impairment following hip fracture repair. DESIGN Prospective study of consecutive patients. SETTING Johns Hopkins Bayview Medical Center; Baltimore, Maryland. PARTICIPANTS Two hundred thirty-six patients ≥65 years old undergoing hip fracture repair. MEASUREMENTS Elderly patients without preoperative delirium who underwent hip fracture repair between April 2005 and July 2009 were followed for pain, opioid consumption, and postoperative delirium. Patients were tested for delirium with the confusion assessment method preoperatively and mid-morning on postoperative day 2. Pain was assessed by the nursing staff with a numeric 0–10 verbal scale. Opioid analgesia was provided in response to pain at rest to achieve scores of ≤3. Opioid consumption was analyzed with respect to the occurrence of incident postoperative delirium, presence of dementia, and other demographic variables. RESULTS Of the 236 patients, 66 (28%) had dementia with 213 (90%) receiving opioids postoperatively; including 55 (83%) demented patients and 158 (93%) non-demented patients. There was no association between the use of any postoperative opioid and incident delirium (P=0.615) in both demented (p=0.333) and non-demented patients (P=0.398). Dementia, but not postoperative delirium, was associated with less opioid use (Popioid dose (P≥0.591) on postoperative days 1 and 2 was not predictive of incident delirium. Dementia (Popioid consumption, were the most important predictors of incident postoperative delirium. CONCLUSION Concern for postoperative delirium should not prevent the use of opioid analgesic therapy sufficient to achieve a generally accepted level of comfort in patients with or without preexisting cognitive impairment. PMID:22092232

  11. Electroacupuncture-Induced Dynamic Processes of Gene Expression Levels of Endogenous Opioid Peptide Precursors and Opioid Receptors in the CNS of Goats

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    Li-Li Cheng

    2013-01-01

    Full Text Available In order to investigate the dynamic processes of mRNA levels of proenkephalin, proopiomelanocortin, prodynorphin, and opioid receptors (δ-, μ-, and κ-receptor induced by electroacupuncture (EA in the central nerve system, goats were stimulated by EA of 60 Hz for 0.5 h at a set of Baihui, Santai, Ergen, and Sanyangluo points. The pain threshold was measured using the method of potassium iontophoresis. The mRNA levels of the three opioid peptide precursors and three opioid receptors were determined with quantitative real-time PCR and the levels of Met-enkephalin with SABC immunohistochemistry at 0.5 h before and at 0, 2, 4, 6, 8, 12, and 24 h after EA. The results showed that the pain threshold correlated (P<0.01 with Met-enkephalin immunoactivities in the measured nuclei and areas of goats. The analgesic aftereffect lasted for 12 h at least. The mRNA levels of the three opioid peptide precursors and three opioid receptors began to increase at 0 h, reached the peak during the time from 4 h to 6 h or at 12 h, and remained higher at 24 h after EA was discontinued. These results suggested that the initiation of gene expression of opioid peptides and the three receptors may be associated with EA-induced analgesic aftereffect.

  12. Long-term neuropsychological effects of opioid use in children: a descriptive literature review.

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    Jain, Gaurav; Mahendra, Vijaita; Singhal, Sarita; Dzara, Kristina; Pilla, Trinadha R; Manworren, Renee; Kaye, Alan D

    2014-01-01

    Use of opioids in the management of pain and its consequences in children presents a substantial challenge. A significant concern in pediatric pain management is the long-term neuropsychological consequences of opioids. The authors aim to provide a descriptive review of the current literature surrounding the neuropsychological impact of opioid use in children, along with possible extrapolations from their use in adults and animal models. Systematic review of published literature. Various universities in the United States. The electronic review for papers published between January 1992 and December 2012 was conducted using Medline/Pubmed, PsychInfo, CINAHL, the Cochrane Library database, and Google Scholar. Findings assessing pediatric pain patients treated with opioids demonstrated no significant differences in intelligence, behavior, vocabulary, or motor skills. One study reported a decrease in a visuo-constructional ability, which measured higher order executive function. Studies from prenatal illicit opioid exposure found poorer performance on measures of language, verbal ability, mathematics, reading, impulse control, and school readiness skills. The