Sample records for tamper-resistant opioid formulations

  1. Methods and predictors of tampering with a tamper-resistant controlled-release oxycodone formulation.

    PubMed

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

    2015-12-01

    In April 2014, a tamper-resistant controlled-release oxycodone formulation was introduced into the Australian market. This study aimed to identify the level and methods of tampering with reformulated oxycodone, demographic and clinical characteristics of those who reported tampering with reformulated oxycodone, and perceived attractiveness of original and reformulated oxycodone for misuse (via tampering). A prospective cohort of 522 people who regularly tampered with pharmaceutical opioids and had tampered with the original oxycodone product in their lifetime completed two interviews before (January-March 2014: Wave 1) and after (May-August 2014: Wave 2) introduction of reformulated oxycodone. Four-fifths (81%) had tampered with the original oxycodone formulation in the month prior to Wave 1; use and attempted tampering with reformulated oxycodone amongst the sample was comparatively low at Wave 2 (29% and 19%, respectively). Reformulated oxycodone was primarily swallowed (15%), with low levels of recent successful injection (6%), chewing (2%), drinking/dissolving (1%), and smoking (<1%). Participants who tampered with original and reformulated oxycodone were socio-demographically and clinically similar to those who had only tampered with the original formulation, except the former were more likely to report prescribed oxycodone use and stealing pharmaceutical opioid, and less likely to report moderate/severe anxiety. There was significant diversity in the methods for tampering, with attempts predominantly prompted by self-experimentation (rather than informed by word-of-mouth or the internet). Participants rated reformulated oxycodone as more difficult to prepare and inject and less pleasant to use compared to the original formulation. Current findings suggest that the introduction of the tamper-resistant product has been successful at reducing, although not necessarily eliminating, tampering with the controlled-release oxycodone formulation, with lower

  2. Internet pseudoscience: Testing opioid containing formulations with tampering potential.

    PubMed

    Pascali, Jennifer P; Fais, Paolo; Vaiano, Fabio; Pigaiani, Nicola; D'Errico, Stefano; Furlanetto, Sandra; Palumbo, Diego; Bertol, Elisabetta

    2018-05-10

    Drug tampering practices, with the aim to increase availability of drug delivery and/or enhance drug effects, are accessible on Internet and are practiced by some portion of recreational drug users. Not rarely, recreational misuse may result in toxic and even fatal results. The aim of the present study was to assess the tampering risk of medicaments containing different formulations of an opioid in combination with paracetamol or dexketoprofen, following the procedures reported in dedicated forums on the web. Tablets and suppositories containing codeine, tramadol and oxycodone were extracted following the reported "Cold water extraction"; dextromethorphan was extracted from cough syrup following the procedure reported as "Acid/base extraction" and fentanyl was extracted from transdermal patches according the procedure reported in Internet. The tampered products and opportunely prepared calibrators in water were analysed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The separation of the analytes was carried on Agilent ZORBAX Eclipse Plus C18 (RRHT 2.1 mm × 50 mm, 1.8 μm) by the gradient elution of 0.01% formic acid in water and 0.01% formic acid in methanol. Acquisition was by MRM mode considering at least two transitions for compound. Declared recoveries for these home-made extractions claimed to exceed 99% for the opioid and to complete remove paracetamol, often associated to liver toxicity and thus to obtain a "safer" preparation. In this study, the authors demonstrated that rarely the recoveries for the opioid reached 90% and that up to 60% of the paracetamol amount remained in solution. Thus, high risks for health remained both for the potential lethality of the opioid content, but also for the sub-lethal chronic use of these mixtures, which contained still uncontrolled, ignored, but often important amounts of paracetamol. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Evaluation of the resistance of a geopolymer-based drug delivery system to tampering.

    PubMed

    Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne

    2014-04-25

    Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Evaluation of Abuse-Deterrent or Tamper-Resistant Opioid Formulations on Overall Health Care Expenditures in a State Medicaid Program.

    PubMed

    Keast, Shellie L; Owora, Arthur; Nesser, Nancy; Farmer, Kevin

    2016-04-01

    The development of abuse-deterrent opioid prescription medications is a priority at the national level. Pharmaceutical manufacturers have begun marketing new formulations of currently available opioids that meet higher abuse resistance standards. Little information is available regarding the impact of these formulations on overall health care expenditures. To (a) examine the relationship between health care expenditures and use of brand abuse-deterrent or tamper-resistant (ADTR) extended-release opioids versus standard dosage form (SDF) extended-release opioids in a state Medicaid population, and (b) determine whether this relationship was influenced by member-specific characteristics. The study is a cross-sectional review of Oklahoma Medicaid members (aged ≥ 21 years) with at least 1 paid pharmacy claim for long-acting opioids between September 2013 and August 2014. Members who were adherent to extended-release opioid products were classified into ADTR and SDF opioid groups. The relationship between health care expenditures (prescription, medical, and overall) and opioid groups was examined using multiple linear regression models. The impact of member-specific characteristics (age, sex, race, urban classifications, and various comorbidities) on this relationship was examined. Prescription spending ($9,265,554) accounted for 35% of overall health care expenditures ($26,304,693) among 938 members during the 12-month reference period. Total prescription expenditures were higher among ADTR than SDF user groups, and the difference in median expenditures between these 2 groups was larger among members with more comorbidities, as measured by the Charlson Comorbidity Index score. Overall, ADTR users had higher median total health care and medical expenditures, and the difference in median expenditures was dependent on whether a member had comorbidities of addiction or not (higher expenditures were observed among members with comorbidities of addiction). The abuse and

  5. Will abuse-deterrent formulations of opioid analgesics be successful in achieving their purpose?

    PubMed

    Bannwarth, Bernard

    2012-09-10

    During the last 2 decades, there has been a dramatic increase in the use of strong opioids for chronic non-cancer pain. This increase has been accompanied by a steep increase in abuse, misuse, and both fatal and non-fatal overdoses involving prescription opioids. The situation is already alarming in the US. Prescription opioid-related harm is a complex, multifactorial issue that requires a multifaceted solution. In this respect, formulations of opioid analgesics designed to resist or deter abuse may be a useful component of a comprehensive opioid risk minimization programme. Such formulations have or are being developed. Abuse-resistant opioids include those that use some kind of physical barrier to prevent tampering with the formulation. Abuse-deterrent opioids are not necessarily resistant to tampering, but contain substances that are designed to make the formulation less attractive to abusers. This article focuses on two products intended to deter abuse that were reviewed by the US Food and Drug Administration (FDA). The first (Embeda®) consists of extended-release morphine with sequestered naltrexone, an opioid antagonist that is released if the tablet is compromised by chewing or crushing. Although Embeda® exhibited abuse-deterrent features, its label warns that it can be abused in a manner similar to other opioid agonists. Furthermore, tampering with Embeda® will result in the release of naltrexone, which may precipitate withdrawal in opioid-tolerant individuals. In March 2011, all dosage forms of Embeda® were recalled because the product failed to meet routine stability standards, and its return date to the market is currently unknown. The second product (Acurox®) was intended to be both tamper resistant and abuse deterrent. It consisted of an immediate-release oxycodone tablet with subtherapeutic niacin as an aversive agent and used a gel-forming ingredient designed to inhibit inhalation and prevent extraction of the drug for injection. The new drug

  6. Changes in the dispensing of opioid medications in Canada following the introduction of a tamper-deterrent formulation of long-acting oxycodone: a time series analysis.

    PubMed

    Gomes, Tara; Mastorakos, Andrea; Paterson, J Michael; Sketris, Ingrid; Caetano, Patricia; Greaves, Simon; Henry, David

    2017-11-22

    In February 2012, a reformulated tamper-deterrent form of long-acting oxycodone, OxyNeo, was introduced in Canada. We investigated the impact of the introduction of OxyNeo on patterns of opioid prescribing. We conducted population-based, cross-sectional analyses of opioid dispensing in Canada between 2008 and 2016. We estimated monthly community pharmacy dispensing of oral formulations of codeine, morphine, hydromorphone and oxycodone, and a transdermal formulation of fentanyl, and converted quantities to milligrams of morphine equivalents (MMEs) per 1000 population. We used time series analysis to evaluate the effect of the introduction of OxyNeo on these trends. National dispensing of long-acting opioids fell by 14.9% between February 2012 and April 2016, from 36 098 MMEs to 30 716 MMEs per 1000 population ( p < 0.01). This effect varied across Canada and was largest in Ontario (reduction of 22.8%) ( p = 0.01) and British Columbia (reduction of 30.0%) ( p = 0.01). The national rate of oxycodone dispensing fell by 46.4% after the introduction of OxyNeo ( p < 0.001); this was partially offset by an increase of 47.8% in hydromorphone dispensing ( p < 0.001). Although dispensing of immediate-release opioids was a substantial contributor to overall population opioid exposure across Canada, it was unaffected by the introduction of OxyNeo ( p > 0.05 in all provinces). The findings suggest that the introduction of a tamper-deterrent formulation of long-acting oxycodone in Canada, against a background of changing public drug benefits, was associated with sustained changes in selection of long-acting opioids but only small changes in the quantity of long-acting opioids dispensed. This illustrates the limited effect a tamper-deterrent formulation and associated coverage policy can have when other, non-tamper-deterrent alternatives are readily available. Copyright 2017, Joule Inc. or its licensors.

  7. A comparison among tapentadol tamper-resistant formulations (TRF) and OxyContin® (non-TRF) in prescription opioid abusers

    PubMed Central

    Vosburg, Suzanne K.; Jones, Jermaine D.; Manubay, Jeanne M.; Ashworth, Judy B.; Shapiro, Douglas Y.; Comer, Sandra D.

    2013-01-01

    Aims To examine whether tamper-resistant formulations (TRFs) of tapentadol hydrochloride ER 50 mg (TAP50) and tapentadol hydrochloride 250 mg (TAP250) could be converted into forms amenable to intranasal (Study 1) or intravenous abuse (Study 2). Design Randomized, repeated-measures study designs were employed. A non-TRF of OxyContin® 40 mg (OXY40) served as a positive control. No drug was taken in either study. Setting The studies took place in an outpatient setting in New York, NY. Participants 25 experienced, healthy extended-release oxycodone abusers participated in each study. Measurements The primary outcome for Study 1 was percentage of participants who indicated they would snort the tampered tablets, while the primary outcome for Study 2 was percent yield of active drug in solution. Other descriptive variables such as time spent manipulating the tablets were also examined to better characterize tampering behaviors. Findings Tampered TRF tablets were less desirable than the tampered OXY40 tablets. Few individuals were willing to snort the TRF particles (TAP50: 24%, TAP250: 16%; OXY40: 100% p<.001). There was less drug extracted from the TAP50 tablet than from the OXY40 tablet (3.5% vs. 37.0%, p=.008), and no samples from the TAP250 tablets contained analyzable solutions of the drug. It took participants longer to tamper with the TAPs (Study 1: TAP50 vs. OXY40, p<.01; TAP250 vs. OXY40, p<.01; Study 2: TAP250 vs. OXY40, p<05). Conclusions Taptentadol TRF tablets were not well-liked by individuals who regularly tampered with extended-release oxycodone tablets. Employing tamper resistant technology may be a promising approach towards reducing the abuse potential of tapentadol ER. PMID:23316699

  8. Opioid use following the introduction of an extended-release oxycodone formulation with tamper-resistant properties: Prospective historical chart review in methadone-maintained patients.

    PubMed

    Sankey, Christopher; Setnik, Beatrice; Harsanyi, Zoltan; Michalko, Ken; Yang, Zejiang; Geoffroy, Pierre

    2016-01-01

    Emerging data are demonstrating that tamper-resistant opioids may play an important role in changing prescription opioid abuse behaviors. This study was a chart review to examine if the reformulation of OxyContin® into a version with tamper-resistant properties (OxyNEO®) had an impact on oxycodone-positive urine drug screens (UDSs) in opioid-dependent patients receiving methadone maintenance therapy (MMT). The historical element of this study examined 250 eligible charts from patients on MMT who had data during the time periods when only OxyContin was available (baseline period), during the transition to OxyNEO, and when only OxyNEO was available. The prospective element included an exploratory questionnaire regarding retrospective opioid use. The study was conducted at three methadone clinics, in Oshawa, Peterborough, and Scarborough in Ontario, Canada. Male and female patients were eligible if they had a diagnosis of opioid dependency, received MMT, and had at least one oxycodone-positive UDS during the baseline period. This was a noninterventional study. The main outcome was the number of oxycodonepositive UDSs. The results demonstrated a marked reduction in oxycodone-positive UDSs that showed stepwise, statistically significant decreases during the transition and post-OxyContin periods relative to baseline. While the oxycodone-positive UDS results were decreasing, morphine-related-positive UDSs remained relatively stable during the same periods. There were no significant gender differences noted. The introduction of OxyNEO was associated with a statistically significant reduction in oxycodone exposure in a population of methadone-maintained patients.

  9. Efficiency of extraction and conversion of pseudoephedrine to methamphetamine from tamper-resistant and non-tamper-resistant formulations.

    PubMed

    Presley, Brandon; Bianchi, Bob; Coleman, John; Diamond, Fran; McNally, Gerry

    2018-07-15

    Clandestine chemists have demonstrated an ability to convert commercially available pseudoephedrine formulations to methamphetamine. Some of these formulations have properties that manufacturers claim limit or block the extraction of pseudoephedrine and its direct conversion to methamphetamine. In this study, 3 commercially available pseudoephedrine formulations were evaluated for ease of extraction and conversion to methamphetamine using a common chemistry technique called the one-pot method that is frequently employed by clandestine chemists. Two marketed pseudoephedrine formulations with claimed tamper-resistant properties - Zephrex-D ® and Nexafed ® - were compared to Sunmark ® , a comparator formulation of pseudoephedrine without tamper-resistant properties. Particle size reduction was conducted using 8 readily available tools; solubility was assessed using 2 common aqueous solutions and various reaction conditions (e.g., temperature, stirring); extractability was evaluated using 8 common organic solvents. The one-pot (single vessel) method commonly used in clandestine processes was employed; chemicals and equipment were purchased locally on the open market. Quantities and addition times of the chemicals used to carry out the procedure and the duration of the reaction were varied to determine the effect on methamphetamine yield. The procedure was appropriately scaled and conducted in a controlled environment to reduce risk and maximize yields. Pseudoephedrine and methamphetamine were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Standard quantitative procedures were used to determine the quantities of pseudoephedrine and methamphetamine recovered and produced, respectively. Particle size reduction resulted in some loss of material of each pseudoephedrine formulation; Zephrex-D tablets were broken down to a coarse material; Nexafed and Sunmark tablets were reduced to a fine powder. The solubility rates of intact and ground

  10. Ephemeral profiles of prescription drug and formulation tampering: evolving pseudoscience on the Internet.

    PubMed

    Cone, Edward J

    2006-06-01

    The magnitude of non-therapeutic use, or misuse of prescription pharmaceuticals now rivals that of illicit drug abuse. Drug and formulation tampering enables misusers to administer higher doses by intended and non-intended routes. Perceived motives appear to be a combination of interests in achieving a faster onset and enhancing psychoactive effects. Narcotic analgesics, stimulants, and depressants are widely sought, examined, and tampered with for recreational use. This review examines tampering methods reported on the Internet for selected pharmaceutical products. The Internet provides broad and varied guidance on tampering methods that are specific to drug classes and unique formulations. Instructions are available on crushing, separating, purifying and chemically altering specific formulations to allow changes in dosage, route of administration, and time course of effects. Many pharmaceutical formulations contain features that serve as "barriers" to tampering. The nature and effectiveness of formulation barriers vary widely with many being overcome by adventurous misusers. Examples of successes and failures in tampering attempts are frequently described on Internet sites that support recreational drug use. Successful tampering methods that have widespread appeal evolve into recipes and become archived on multiple websites. Examples of tampering methods include: (1) how to separate narcotic drugs (codeine, hydrocodone, oxycodone) from excipients and non-desirable actives (aspirin, acetaminophen, ibuprofen); (2) overcoming time-release formulations (beads, layers, matrices); (3) removal of active drug from high-dose formulations (patches, pills); (4) alteration of dosage forms for alternate routes of administration. The development of successful formulations that inhibit or prevent drug/formulation tampering with drugs of abuse should take into consideration the scope and practice of tampering methods available to recreational drug users on the Internet.

  11. Person-level changes in oxycodone use after the introduction of a tamper-resistant formulation in Australia.

    PubMed

    Schaffer, Andrea L; Buckley, Nicholas A; Degenhardt, Louisa; Larance, Briony; Cairns, Rose; Dobbins, Timothy A; Pearson, Sallie-Anne

    2018-03-26

    Australia introduced tamper-resistant controlled-release (CR) oxycodone in April 2014. We quantified the impact of the reformulation on dispensing, switching and poisonings. We performed interrupted time-series analyses using population-representative national dispensing data from 2012 to 2016. We measured dispensing of oxycodone CR (≥ 10 mg), discontinuation of use of strong opioids and switching to other strong opioids after the reformulation compared with a historical control period. Similarly, we compared calls about intentional opioid poisoning using data from a regional poisons information centre. After the reformulation, dispensing decreased for 10-30 mg (total level shift -11.1%, 95% confidence interval [CI], -17.2% to -4.6%) and 40-80 mg oxycodone CR (total level shift -31.5%, 95% CI -37.5% to -24.9%) in participants less than 65 years of age but was unchanged in people 65 years of age or older. Compared with the previous year, discontinuation of use of strong opioids did not increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00), but switching to oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32 to 1.79). Switching to morphine varied by age ( p < 0.001), and the greatest increase was in participants less than 45 years of age (adjusted HR 4.33, 95% CI 2.13 to 8.80). Participants switching after the reformulation were more likely to be dispensed a tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40, 95% CI 1.09 to 1.79). Calls for intentional poisoning that involved oxycodone taken orally increased immediately after the reformulation (incidence rate ratio (IRR) 1.31, 95% CI 1.05-1.64), but there was no change for injected oxycodone. The reformulation had a greater impact on opioid access patterns of people less than 65 years of age who were using higher strengths of oxycodone CR. This group has been identified as having an increased risk of problematic opioid use and warrants closer monitoring in clinical practice.

  12. The introduction of a potentially abuse deterrent oxycodone formulation: Early findings from the Australian National Opioid Medications Abuse Deterrence (NOMAD) study.

    PubMed

    Degenhardt, Louisa; Bruno, Raimondo; Ali, Robert; Lintzeris, Nicholas; Farrell, Michael; Larance, Briony

    2015-06-01

    There is increasing concern about tampering of pharmaceutical opioids. We describe early findings from an Australian study examining the potential impact of the April 2014 introduction of an abuse-deterrent sustained-release oxycodone formulation (Reformulated OxyContin(®)). Data on pharmaceutical opioid sales; drug use by people who inject drugs regularly (PWID); client visits to the Sydney Medically Supervised Injecting Centre (MSIC); and last drug injected by clients of inner-Sydney needle-syringe programmes (NSPs) were obtained, 2009-2014. A cohort of n=606 people tampering with pharmaceutical opioids was formed pre-April 2014, and followed up May-August 2014. There were declines in pharmacy sales of 80mg OxyContin(®) post-introduction of the reformulated product, the dose most commonly diverted and injected by PWID. Reformulated OxyContin(®) was among the least commonly used and injected drugs among PWID. This was supported by Sydney NSP data. There was a dramatic reduction in MSIC visits for injection of OxyContin(®) post-introduction of the new formulation (from 62% of monthly visits pre-introduction to 5% of visits, August 2014). The NOMAD cohort confirmed a reduction in OxyContin(®) use/injection post-introduction. Reformulated OxyContin(®) was cheaper and less attractive for tampering than Original OxyContin(®). These data suggest that, in the short term, introduction of an abuse-deterrent formulation of OxyContin(®) in Australia was associated with a reduction in injection of OxyContin(®), with no clear switch to other drugs. Reformulated OxyContin(®), in this short follow-up, does not appear to be considered as attractive for tampering. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product.

    PubMed

    Pergolizzi, Joseph V; Taylor, Robert; LeQuang, Jo Ann; Raffa, Robert B

    2018-01-01

    Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids) that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF). ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations.

  14. Person-level changes in oxycodone use after the introduction of a tamper-resistant formulation in Australia

    PubMed Central

    Buckley, Nicholas A.; Degenhardt, Louisa; Larance, Briony; Cairns, Rose; Dobbins, Timothy A.; Pearson, Sallie-Anne

    2018-01-01

    BACKGROUND: Australia introduced tamper-resistant controlled-release (CR) oxycodone in April 2014. We quantified the impact of the reformulation on dispensing, switching and poisonings. METHODS: We performed interrupted time-series analyses using population-representative national dispensing data from 2012 to 2016. We measured dispensing of oxycodone CR (≥ 10 mg), discontinuation of use of strong opioids and switching to other strong opioids after the reformulation compared with a historical control period. Similarly, we compared calls about intentional opioid poisoning using data from a regional poisons information centre. RESULTS: After the reformulation, dispensing decreased for 10–30 mg (total level shift −11.1%, 95% confidence interval [CI], −17.2% to −4.6%) and 40–80 mg oxycodone CR (total level shift −31.5%, 95% CI −37.5% to −24.9%) in participants less than 65 years of age but was unchanged in people 65 years of age or older. Compared with the previous year, discontinuation of use of strong opioids did not increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00), but switching to oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32 to 1.79). Switching to morphine varied by age (p < 0.001), and the greatest increase was in participants less than 45 years of age (adjusted HR 4.33, 95% CI 2.13 to 8.80). Participants switching after the reformulation were more likely to be dispensed a tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40, 95% CI 1.09 to 1.79). Calls for intentional poisoning that involved oxycodone taken orally increased immediately after the reformulation (incidence rate ratio (IRR) 1.31, 95% CI 1.05–1.64), but there was no change for injected oxycodone. INTERPRETATION: The reformulation had a greater impact on opioid access patterns of people less than 65 years of age who were using higher strengths of oxycodone CR. This group has been identified as having an increased risk of problematic opioid

  15. A Secure and Robust Approach to Software Tamper Resistance

    NASA Astrophysics Data System (ADS)

    Ghosh, Sudeep; Hiser, Jason D.; Davidson, Jack W.

    Software tamper-resistance mechanisms have increasingly assumed significance as a technique to prevent unintended uses of software. Closely related to anti-tampering techniques are obfuscation techniques, which make code difficult to understand or analyze and therefore, challenging to modify meaningfully. This paper describes a secure and robust approach to software tamper resistance and obfuscation using process-level virtualization. The proposed techniques involve novel uses of software check summing guards and encryption to protect an application. In particular, a virtual machine (VM) is assembled with the application at software build time such that the application cannot run without the VM. The VM provides just-in-time decryption of the program and dynamism for the application's code. The application's code is used to protect the VM to ensure a level of circular protection. Finally, to prevent the attacker from obtaining an analyzable snapshot of the code, the VM periodically discards all decrypted code. We describe a prototype implementation of these techniques and evaluate the run-time performance of applications using our system. We also discuss how our system provides stronger protection against tampering attacks than previously described tamper-resistance approaches.

  16. Process design and control of a twin screw hot melt extrusion for continuous pharmaceutical tamper-resistant tablet production.

    PubMed

    Baronsky-Probst, J; Möltgen, C-V; Kessler, W; Kessler, R W

    2016-05-25

    Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most efficient production technique. The focus of this study is thus to evaluate the manufacturability of the HME process for tamper-resistant formulations. Parameters such as the specific mechanical energy (SME), as well as the melt pressure and its standard deviation, are important and will be discussed in this study. In the first step, the existing process data are analyzed by means of multivariate data analysis. Key critical process parameters such as feed rate, screw speed, and the concentration of the API in the polymers are identified, and critical quality parameters of the tablet are defined. In the second step, a relationship between the critical material, product and process quality attributes are established by means of Design of Experiments (DoEs). The resulting SME and the temperature at the die are essential data points needed to indirectly qualify the degradation of the API, which should be minimal. NIR-spectroscopy is used to monitor the material during the extrusion process. In contrast to most applications in which the probe is directly integrated into the die, the optical sensor is integrated into the cooling line of the strands. This saves costs in the probe design and maintenance and increases the robustness of the chemometric models. Finally, a process measurement system is installed to monitor and control all of the critical attributes in real-time by means of first principles, DoE models, soft sensor models, and spectroscopic information. Overall, the process is very robust as long as the screw speed is kept low. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Opioid analgesics: does potency matter?

    PubMed

    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.

  18. Application of hot-melt extrusion technology in immediate-release abuse-deterrent formulations.

    PubMed

    Wening, Klaus; Schwier, Sebastian; Stahlberg, Hans-J; Galia, Eric

    Hot-melt extrusion (HME) technology has been used for manufacturing extended-release abuse-deterrent formulations (ADFs) of opioid-type analgesics with improved tamper-resistant properties. Our objective was to describe application of this technology to immediate-release (IR) ADFs. For development of a sample IR ADF (hydrocodone 10 mg/acetaminophen 325 mg) based on HME, feasibility studies were performed using different excipients. The formulation selected for further development was evaluated via in vitro test battery. Moreover, in vivo performance of IR ADF technologies was investigated in an open-label, randomized, cross-over, phase 1, relative oral bioavailability study with another opioid (model compound). Single-center bioavailability trial. Twenty-four healthy white male subjects. ADF IR formulation of an opioid and marketed IR formulation. For feasibility and in vitro studies, dissolution profiles, syringeability, particle size distribution after physical manipulation, and extractability were evaluated. For the phase 1 study, pharmacokinetic parameters were evaluated and compared for ADF IR and a marketed IR formulation. After manipulation, the majority of particles from the ADF IR formulation were >500µm and, thus, not considered suitable for intranasal abuse, while the majority of particles for the reference marketed IR formulation were <500µm. The ADF IR formulation was resistant to syringing and preparation for potential intravenous injection. In healthy subjects, pharmacokinetics of an ADF and marketed IR formulation of an opioid were nearly identical. Application of HME to IR formulations led to development of products with improved mechanical resistance to manipulation for intranasal or intravenous preparation, but similar bioavailability.

  19. Tamper-Resistant Mobile Health Using Blockchain Technology

    PubMed Central

    2017-01-01

    Background Digital health technologies, including telemedicine, mobile health (mHealth), and remote monitoring, are playing a greater role in medical practice. Safe and accurate management of medical information leads to the advancement of digital health, which in turn results in a number of beneficial effects. Furthermore, mHealth can help lower costs by facilitating the delivery of care and connecting people to their health care providers. Mobile apps help empower patients and health care providers to proactively address medical conditions through near real-time monitoring and treatment, regardless of the location of the patient or the health care provider. Additionally, mHealth data are stored in servers, and consequently, data management that prevents all forms of manipulation is crucial for both medical practice and clinical trials. Objective The aim of this study was to develop and evaluate a tamper-resistant mHealth system using blockchain technology, which enables trusted and auditable computing using a decentralized network. Methods We developed an mHealth system for cognitive behavioral therapy for insomnia using a smartphone app. The volunteer data collected with the app were stored in JavaScript Object Notation format and sent to the blockchain network. Thereafter, we evaluated the tamper resistance of the data against the inconsistencies caused by artificial faults. Results Electronic medical records collected using smartphones were successfully sent to a private Hyperledger Fabric blockchain network. We verified the data update process under conditions where all the validating peers were running normally. The mHealth data were successfully updated under network faults. We further ensured that any electronic health record registered to the blockchain network was resistant to tampering and revision. The mHealth data update was compatible with tamper resistance in the blockchain network. Conclusions Blockchain serves as a tamperproof system for m

  20. Tamper-Resistant Mobile Health Using Blockchain Technology.

    PubMed

    Ichikawa, Daisuke; Kashiyama, Makiko; Ueno, Taro

    2017-07-26

    Digital health technologies, including telemedicine, mobile health (mHealth), and remote monitoring, are playing a greater role in medical practice. Safe and accurate management of medical information leads to the advancement of digital health, which in turn results in a number of beneficial effects. Furthermore, mHealth can help lower costs by facilitating the delivery of care and connecting people to their health care providers. Mobile apps help empower patients and health care providers to proactively address medical conditions through near real-time monitoring and treatment, regardless of the location of the patient or the health care provider. Additionally, mHealth data are stored in servers, and consequently, data management that prevents all forms of manipulation is crucial for both medical practice and clinical trials. The aim of this study was to develop and evaluate a tamper-resistant mHealth system using blockchain technology, which enables trusted and auditable computing using a decentralized network. We developed an mHealth system for cognitive behavioral therapy for insomnia using a smartphone app. The volunteer data collected with the app were stored in JavaScript Object Notation format and sent to the blockchain network. Thereafter, we evaluated the tamper resistance of the data against the inconsistencies caused by artificial faults. Electronic medical records collected using smartphones were successfully sent to a private Hyperledger Fabric blockchain network. We verified the data update process under conditions where all the validating peers were running normally. The mHealth data were successfully updated under network faults. We further ensured that any electronic health record registered to the blockchain network was resistant to tampering and revision. The mHealth data update was compatible with tamper resistance in the blockchain network. Blockchain serves as a tamperproof system for mHealth. Combining mHealth with blockchain technology may

  1. Abuse-Deterrent Opioid Formulations: Pharmacokinetic and Pharmacodynamic Considerations.

    PubMed

    Walter, Carmen; Knothe, Claudia; Lötsch, Jörn

    2016-07-01

    Abuse-deterrent formulations (ADFs) are technologically sophisticated pharmaceutical formulations that impede manipulation and extraction of opioids and/or provoke unpleasant effects when they are taken in excessive quantity. This is implemented by creating physical barriers, inseparably combining the opioid with an opioid antagonist or adding aversive agents to the formulation. These pharmaceutical changes may potentially alter the pharmacokinetics and consequently the pharmacodynamics of the opioid. In this review, comparative evidence on pharmacokinetic differences between abuse-deterrent and classical formulations of the same opioids is summarized; furthermore, pharmacodynamic differences, with a focus on analgesia and abuse-related symptoms, are addressed. Most of the 12 studies comparing opioid pharmacokinetics have judged the physically intact ADF as being bioequivalent to the corresponding classical formulation. Pharmacokinetic differences have, however, been reported with physically manipulated ADFs and have ranged from moderate deviations from bioequivalence to complete changes in the pharmacokinetic profile (e.g. from a sustained-release formulation to a fast-release formulation). Pharmacodynamic effects were assessed in 14 comparative studies, which reported that intact ADFs usually provided clinically equivalent analgesia and clear advantages with respect to their addiction potential. However, withdrawal symptoms could be induced by the ADFs, although rarely and, in particular, when the ADFs had been physically altered. This evidence suggests that opioid ADFs are a working concept resulting in mostly minor pharmacokinetic and pharmacodynamic differences in comparison with classical formulations; however, they may deviate from this equivalence when physically altered.

  2. Abuse-deterrent formulations: part 1 - development of a formulation-based classification system.

    PubMed

    Mastropietro, David J; Omidian, Hossein

    2015-02-01

    Strategies have been implemented to decrease the large proportion of individuals misusing abusable prescription medications. Abuse-deterrent formulations (ADFs) have been grown to incorporate many different technologies that still lack a systematic naming and organizational nomenclature. Without a proper classification system, it has been challenging to properly identify ADFs, study and determine common traits or characteristics and simplify communication within the field. This article introduces a classification system for all ADF approaches and examines the physical, chemical and pharmacological characteristics of a formulation by placing them into primary, secondary and tertiary categories. Primary approaches block tampering done directly to the product. Secondary approaches work in vivo after the product is administered. Tertiary approaches use materials that discourage abuse but do not stop tampering. Part 2 of this article discusses proprietary technologies, patents and products utilizing primary approaches. Drug products using opioid antagonists and aversive agents have been seen over the past few decades to discourage primarily overuse and injection. However, innovation in formulation development has introduced products capable of deterring multiple forms of tampering and abuse. Often, this is accomplished using known excipients and manufacturing methods that are repurposed to prevent crushing, extraction and syringeability.

  3. Child-resistant and tamper-resistant packaging: A systematic review to inform tobacco packaging regulation.

    PubMed

    Jo, Catherine L; Ambs, Anita; Dresler, Carolyn M; Backinger, Cathy L

    2017-02-01

    We aimed to investigate the effects of special packaging (child-resistant, adult-friendly) and tamper-resistant packaging on health and behavioral outcomes in order to identify research gaps and implications for packaging standards for tobacco products. We searched seven databases for keywords related to special and tamper-resistant packaging, consulted experts, and reviewed citations of potentially relevant studies. 733 unique papers were identified. Two coders independently screened each title and abstract for eligibility. They then reviewed the full text of the remaining papers for a second round of eligibility screening. Included studies investigated a causal relationship between type of packaging or packaging regulation and behavioral or health outcomes and had a study population composed of consumers. Studies were excluded on the basis of publication type, if they were not peer-reviewed, and if they had low external validity. Two reviewers independently coded each paper for study and methodological characteristics and limitations. Discrepancies were discussed and resolved. The review included eight studies: four assessing people's ability to access the contents of different packaging types and four evaluating the impact of packaging requirements on health-related outcomes. Child-resistant packaging was generally more difficult to open than non-child-resistant packaging. Child-resistant packaging requirements have been associated with reductions in child mortality. Child-resistant packaging holds the expectation to reduce tobacco product poisonings among children under six. Published by Elsevier Inc.

  4. Child-resistant and tamper-resistant packaging: A systematic review to inform tobacco packaging regulation

    PubMed Central

    Jo, Catherine L.; Ambs, Anita; Dresler, Carolyn M.; Backinger, Cathy L.

    2017-01-01

    Objective We aimed to investigate the effects of special packaging (child-resistant, adult-friendly) and tamper-resistant packaging on health and behavioral outcomes in order to identify research gaps and implications for packaging standards for tobacco products. Methods We searched seven databases for keywords related to special and tamper-resistant packaging, consulted experts, and reviewed citations of potentially relevant studies. 733 unique papers were identified. Two coders independently screened each title and abstract for eligibility. They then reviewed the full text of the remaining papers for a second round of eligibility screening. Included studies investigated a causal relationship between type of packaging or packaging regulation and behavioral or health outcomes and had a study population composed of consumers. Studies were excluded on the basis of publication type, if they were not peer-reviewed, and if they had low external validity. Two reviewers independently coded each paper for study and methodological characteristics and limitations. Discrepancies were discussed and resolved. Results The review included eight studies: four assessing people’s ability to access the contents of different packaging types and four evaluating the impact of packaging requirements on health-related outcomes. Child-resistant packaging was generally more difficult to open than non-child-resistant packaging. Child-resistant packaging requirements have been associated with reductions in child mortality. Conclusions Child-resistant packaging holds the expectation to reduce tobacco product poisonings among children under six. PMID:27939602

  5. 21 CFR 800.12 - Contact lens solutions and tablets; tamper-resistant packaging.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-resistant retail packages, there is the opportunity for the malicious adulteration of these products with... confidence in the security of the packages of over-the-counter (OTC) health care products. The Food and Drug... used to make such a solution for retail sale that is not packaged in a tamper-resistant package and...

  6. 21 CFR 800.12 - Contact lens solutions and tablets; tamper-resistant packaging.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-resistant retail packages, there is the opportunity for the malicious adulteration of these products with... confidence in the security of the packages of over-the-counter (OTC) health care products. The Food and Drug... used to make such a solution for retail sale that is not packaged in a tamper-resistant package and...

  7. 21 CFR 800.12 - Contact lens solutions and tablets; tamper-resistant packaging.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-resistant retail packages, there is the opportunity for the malicious adulteration of these products with... confidence in the security of the packages of over-the-counter (OTC) health care products. The Food and Drug... used to make such a solution for retail sale that is not packaged in a tamper-resistant package and...

  8. 21 CFR 800.12 - Contact lens solutions and tablets; tamper-resistant packaging.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-resistant retail packages, there is the opportunity for the malicious adulteration of these products with... confidence in the security of the packages of over-the-counter (OTC) health care products. The Food and Drug... used to make such a solution for retail sale that is not packaged in a tamper-resistant package and...

  9. 21 CFR 800.12 - Contact lens solutions and tablets; tamper-resistant packaging.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-resistant retail packages, there is the opportunity for the malicious adulteration of these products with... confidence in the security of the packages of over-the-counter (OTC) health care products. The Food and Drug... used to make such a solution for retail sale that is not packaged in a tamper-resistant package and...

  10. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.25 Tamper-resistant packaging requirements for cosmetic products. (a) General. Because most cosmetic liquid...

  11. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.25 Tamper-resistant packaging requirements for cosmetic products. (a) General. Because most cosmetic liquid...

  12. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.25 Tamper-resistant packaging requirements for cosmetic products. (a) General. Because most cosmetic liquid...

  13. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.25 Tamper-resistant packaging requirements for cosmetic products. (a) General. Because most cosmetic liquid...

  14. 21 CFR 700.25 - Tamper-resistant packaging requirements for cosmetic products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Tamper-resistant packaging requirements for cosmetic products. 700.25 Section 700.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... of cosmetic product packages. The Food and Drug Administration has the authority and responsibility...

  15. In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations.

    PubMed

    Mayock, Stephen P; Saim, Said; Fleming, Alison B

    2017-12-01

    Extended-release (ER) opioids are associated with high rates of abuse. Recreational opioid users often manipulate ER formulations to achieve a high plasma concentration in a short amount of time, resulting in a more rapid and intense high. Patients may also manipulate ER tablets to facilitate swallowing, without recognizing that manipulation could increase release rate. The goal of this study was to assess the ability of oxycodone DETERx (Xtampza ® ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available ER opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting. In vitro dissolution techniques were used to compare the opioid release from a variety of ER opioid formulations. Dissolution was assessed for intact and crushed dosage forms. Opioid release was quantified using high-performance liquid chromatography. Intact formulations exhibited drug release rates characteristic of 12- or 24-h dosage forms. After crushing using commonly available household tools, only Xtampza ER maintained ER of opioid. Xtampza ER maintained its ER characteristics after crushing, unlike many other commercially available opioid formulations, including some formulated with abuse-deterrent properties. As such, Xtampza ER may be less appealing to abusers and offer a margin of safety for patients who manipulate dosage forms to facilitate swallowing.

  16. Current Impact and Application of Abuse-Deterrent Opioid Formulations in Clinical Practice.

    PubMed

    Lee, Ya-Han; Brown, Daniel L; Chen, Hsiang-Yin

    2017-11-01

    Abuse-deterrent formulations (ADFs) represent one novel strategy for curbing the potential of opioid abuse. We aim to compare and contrast the characteristics and applications of current abuse-deterrent opioid products in clinical practice. Literature searches were conducted in databases (Pubmed Medline, International Pharmaceutical Abstracts, Google Scholar) and official reports. Relevant data were screened and organized into: 1) epidemiology of opioid abuse, 2) mitigation strategies for reducing opioid abuse, 3) development of ADFs, and 4) clinical experience with these formulations. Increasing trends of opioid abuse and misuse have been reported globally. There are 5 types of abuse-deterrent opioid products: physical chemical barrier, combined agonist/antagonist, sequestered aversive agent, prodrug, and novel delivery system. The advantages and disadvantages of the 5 options are discussed in this review. A total of 9 products with abuse-deterrent labels have been approved by the Food and Drug Administration (FDA). The rates of abuse, diversion, and overdose deaths of these new products are also discussed. A framework for collecting in-time data on the efficacy, benefit and risk ratio, and cost-effectiveness of these new products is suggested to facilitate their optimal use. The present review did not utilize systematic review standards or meta-analytic techniques, given the large heterogeneity of data and outcomes reviewed. ADFs provide an option for inhibiting the abuse or misuse of oral opioid products by hindering extraction of the active ingredient, preventing alternative routes of administration, or causing aversion. Their relatively high costs, uncertain insurance policies, and limited data on pharmacoeconomics warrant collaborative monitoring and assessment by government agencies, pharmaceutical manufacturers, and data analysis services to define their therapeutic role in the future. Opioid abuse, abuse-deterrent formulations, ADF, post-marketing, FDA

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

    PubMed

    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.

  18. "Tampering to Death": A Fatal Codeine Intoxication Due to a Homemade Purification of a Medical Formulation.

    PubMed

    Fais, Paolo; Pigaiani, Nicola; Cecchetto, Giovanni; Montisci, Massimo; Gottardo, Rossella; Viel, Guido; Pascali, Jennifer Paola; Tagliaro, Franco

    2017-11-01

    Many homemade tamper processes of medical codeine formulations are available on selected "forums" on the Internet, where recreational codeine users claim to be able to purify codeine by removing additives, such as acetaminophen, to avoid or limit adverse effects. In this work, it is reported and discussed a fatal case of codeine intoxication. The findings of objects such as jars, filters, and tablets, and amounts of unknown liquid material at the death scene investigation suggested a fatal codeine intoxication after the tampering procedure called "cold water extraction." Toxicological results obtained from the analysis of both the nonbiological material and the body fluids of the decedent integrated with the information collected at the death scene investigation confirmed the above-mentioned hypothesis. This report underlines the importance of a tight interconnection between criminalistics and legal medicine to strengthen the identification of the cause of death and the reconstruction of the event. © 2017 American Academy of Forensic Sciences.

  19. The role of abuse-deterrent formulations in countering opioid misuse and abuse.

    PubMed

    Nguyen, V; Raffa, R B; Taylor, R; Pergolizzi, J V

    2015-12-01

    Pain is a prevalent, and due to the ageing population, increasing medical problem. Opioids are frequently prescribed to meet the unmet medical need. Unfortunately, with the increase in the legitimate use of opioids, there has been a corresponding increase in abuse. A practical way to retain the pain relief afforded by opioids while decreasing opportunities for abuse is to make it more difficult to extract the opioid from the product or to make it less desirable to do so by designing an abuse-deterrent formulation (ADF). We provide a brief overview of the strategies and early evidence related to opioid ADFs. Published and unpublished literature, websites, and other sources were searched for current opioid formulation options, including immediate-release and extended-release products. Each was summarized, reviewed and assessed. The strategies that have been used to design the current opioid ADFs involve one or more of four approaches: a physical barrier; incorporation of an opioid receptor antagonist (e.g. naloxone) that self-limits opioid action when taken in excess amount; inclusion of a noxious agent that is released during inappropriate use; or a pro-drug. Legitimate use of opioid analgesics carries with it certain risks, including the risk of abuse. The new ADFs utilize four major strategies and provide innovative additions to the armamentarium. They likely will become an important part of a comprehensive approach to limiting, although not eliminating, opioid misuse and abuse. © 2015 John Wiley & Sons Ltd.

  20. NKTR-181: A Novel Mu-Opioid Analgesic with Inherently Low Abuse Potential.

    PubMed

    Miyazaki, Takahiro; Choi, Irene Y; Rubas, Werner; Anand, Neel K; Ali, Cherie; Evans, Juli; Gursahani, Hema; Hennessy, Marlene; Kim, Grace; McWeeney, Daniel; Pfeiffer, Juergen; Quach, Phi; Gauvin, David; Riley, Timothy A; Riggs, Jennifer A; Gogas, Kathleen; Zalevsky, Jonathan; Doberstein, Stephen K

    2017-10-01

    The increasing availability of prescription opioid analgesics for the treatment of pain has been paralleled by an epidemic of opioid misuse, diversion, and overdose. The development of abuse-deterrent formulations (ADFs) of conventional opioids such as oxycodone and morphine represents an advance in the field and has had a positive but insufficient impact, as most opioids are still prescribed in highly abusable, non-ADF forms, and abusers can tamper with ADF medications to liberate the abusable opioid within. The abuse liability of mu-opioid agonists appears to be dependent on their rapid rate of entry into the central nervous system (CNS), whereas analgesic activity appears to be a function of CNS exposure alone, suggesting that a new opioid agonist with an inherently low rate of influx across the blood-brain barrier could mediate analgesia with low abuse liability, regardless of formulation or route of administration. NKTR-181 is a novel, long-acting, selective mu-opioid agonist with structural properties that reduce its rate of entry across the blood-brain barrier compared with traditional mu-opioid agonists. NKTR-181 demonstrated maximum analgesic activity comparable to that of oxycodone in hot-plate latency and acetic-acid writhing models. NKTR-181 was distinguishable from oxycodone by its reduced abuse potential in self-administration and progressive-ratio break point models, with behavioral effects similar to those of saline, as well as reduced CNS side effects as measured by the modified Irwin test. The in vitro and in vivo studies presented here demonstrate that NKTR-181 is the first selective mu-opioid agonist to combine analgesic efficacy and reduced abuse liability through the alteration of brain-entry kinetics. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Opioid use and harms associated with a sustained-release tapentadol formulation: a postmarketing study protocol

    PubMed Central

    Larance, Briony; Farrell, Michael; Cairns, Rose; Buckley, Nicholas; Degenhardt, Louisa

    2018-01-01

    Introduction It has been argued that tapentadol may pharmacologically have lower abuse potential than other pharmaceutical opioids currently available. However, there has been no comprehensive triangulation of data regarding use and harms associated with this formulation. A sustained-release formulation (SRF) of tapentadol (Palexia) was released in Australia in 2011 and listed for public subsidy in 2013. We summarise here the methods of a postmarketing study which will measure postintroduction: (1) population level availability, (2) extramedical use and diversion, (3) attractiveness for extramedical use and (4) associated harms, of tapentadol compared against other pharmaceutical opioids. Methods and analysis We evaluated key sources on pharmaceutical use and harms in Australia. This review indicateddata from four sources that disaggregate pharmaceutical opioid formulations and capture tapentadol SRF could be triangulated. These data sources comprised: (1) national pharmaceutical opioid community sales data from 2011 to 2017, (2) national pharmaceutical opioid poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3) number of vendors on online marketplaces listing pharmaceutical opioids for sale and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms from interviews with people who regularly inject drugs in Australia. Ethics and dissemination Ethics approval is not required for use of pharmaceutical sales data. Ethics approval has been obtained for use of national pharmaceutical opioid poisonings reported to PICs (LNR/16/SCHN/44) and for use of online marketplace data and interview data from people who inject drugs (HC12086). Key findings will be published mid-2018 in a peer-reviewed academic journal, and presented at various conferences and professional meetings. PMID:29574444

  2. Tamper indicating gold nanocup plasmonic films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    DeVetter, Brent M.; Bernacki, Bruce E.; Bennett, Wendy D.

    The spectral signature of nanoplasmonic films are both robust and tailorable with optical responses ranging from the visible to the near-infrared. We present the development of flexible, elastomeric nanoplasmonic films consisting of periodic arrays of gold nanocups as tamper indicating films. Gold nanocups have polarization-sensitive optical properties that may be manufactured into films that offer unique advantages for tamper indication. These flexible films can be made quickly and at low-cost using commercially available monodisperse polystyrene nanospheres through self-assembly followed by plasma etching, metal deposition, and lift-off from a sacrificial substrate. Polarization- and angle-dependent optical spectroscopic measurements were performed to characterizemore » the fabricated films. Furthermore, using polarization-sensitive hyperspectral imaging, we demonstrate how these films can be applied to tamper indication and counterfeit resistance applications.« less

  3. Tamper indicating gold nanocup plasmonic films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    DeVetter, Brent M.; Bernacki, Bruce E.; Bennett, Wendy D.

    2017-02-13

    The spectral signature of nanoplasmonic films are both robust and tailorable with optical responses ranging from the visible to the near-infrared. We present the development of flexible, elastomeric nanoplasmonic films consisting of periodic arrays of gold nanocups as tamper indicating films. Gold nanocups have polarization-sensitive optical properties that may be manufactured into films that offer unique advantages for tamper indication. These flexible films can be made quickly and at low-cost using commercially available monodisperse polystyrene nanospheres through self-assembly followed by plasma etching, metal deposition, and lift-off from a sacrificial substrate. Polarization- and angle-dependent optical spectroscopic measurements were performed to characterizemore » the fabricated films. Using polarization-sensitive hyperspectral imaging, we demonstrate how these films can be applied to tamper indication and counterfeit resistance applications.« less

  4. Enhanced tamper indicator

    DOEpatents

    Garcia, Anthony R.; Johnston, Roger G.

    2003-07-08

    The present invention provides an apparatus and method whereby the reliability and tamper-resistance of tamper indicators can be improved. A flexible connector may be routed through a latch for an enclosure such as a door or container, and the free ends of the flexible connector may be passed through a first locking member and firmly attached to an insert through the use of one or more attachment members such as set screws. A second locking member may then be assembled in interlocking relation with the first locking member to form an interlocked assembly around the insert. The insert may have one or more sharp projections extending toward the first or second locking member so that any compressive force applied in an attempt to disassemble the interlocked assembly results in permanent, visible damage to the first or second locking member.

  5. Heroin use onset among nonmedical prescription opioid users in the club scene.

    PubMed

    Surratt, Hilary L; Kurtz, Steven P; Buttram, Mance; Levi-Minzi, Maria A; Pagano, Maria E; Cicero, Theodore J

    2017-10-01

    Nonmedical prescription opioid use (NMPOU) is well documented among participants in the club scene, yet prior studies have not examined transition to heroin use. We prospectively examined heroin initiation among a sample of young adults with drug involvement associated with participation in the club scene, to understand factors that influence transition from NMPOU to heroin and to identify opportunities for intervention. Data were drawn from a randomized trial that enrolled 750 Miami-based club and prescription drug users through respondent driven sampling, and tested the efficacy of assessment interventions in reducing risk. Participants reported current substance use at baseline, 3, 6, and 12 month follow-ups. We examined predictors of heroin initiation among participants reporting NMPOU at baseline, with no lifetime history of heroin use (N=323). The mean age was 25.0 years; 67.5% met DSM-IV criteria for substance dependence. About 1 in 13 participants (7.7%) initiated heroin use at follow-up. In univariable comparisons, frequent LSD use, history of drug overdose, high frequency NMPOU, using oral tampering methods, and endorsing a primary medical source for prescription opioids were associated with greater likelihood of heroin initiation. LSD use, oral tampering, and primary medical source were significant predictors in a Cox regression model. Heroin initiation of 7.7% suggests a high level of vulnerability for transition among young adult NMPO users in the club scene. The importance of oral tampering methods in the trajectory of NMPOU may indicate a need to further examine the role of abuse deterrent formulations in prevention efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Opioid use and harms associated with a sustained-release tapentadol formulation: a postmarketing study protocol.

    PubMed

    Peacock, Amy; Larance, Briony; Farrell, Michael; Cairns, Rose; Buckley, Nicholas; Degenhardt, Louisa

    2018-03-23

    It has been argued that tapentadol may pharmacologically have lower abuse potential than other pharmaceutical opioids currently available. However, there has been no comprehensive triangulation of data regarding use and harms associated with this formulation. A sustained-release formulation (SRF) of tapentadol (Palexia) was released in Australia in 2011 and listed for public subsidy in 2013. We summarise here the methods of a postmarketing study which will measure postintroduction: (1) population level availability, (2) extramedical use and diversion, (3) attractiveness for extramedical use and (4) associated harms, of tapentadol compared against other pharmaceutical opioids. We evaluated key sources on pharmaceutical use and harms in Australia. This review indicateddata from four sources that disaggregate pharmaceutical opioid formulations and capture tapentadol SRF could be triangulated. These data sources comprised: (1) national pharmaceutical opioid community sales data from 2011 to 2017, (2) national pharmaceutical opioid poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3) number of vendors on online marketplaces listing pharmaceutical opioids for sale and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms from interviews with people who regularly inject drugs in Australia. Ethics approval is not required for use of pharmaceutical sales data. Ethics approval has been obtained for use of national pharmaceutical opioid poisonings reported to PICs (LNR/16/SCHN/44) and for use of online marketplace data and interview data from people who inject drugs (HC12086). Key findings will be published mid-2018 in a peer-reviewed academic journal, and presented at various conferences and professional meetings. © 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.

  7. Resisting Prescribed Opioids: A Qualitative Study of Decision Making in Patients Taking Opioids for Chronic Noncancer Pain.

    PubMed

    Paterson, Charlotte; Ledgerwood, Kay; Arnold, Carolyn; Hogg, Malcolm; Xue, Charlie; Zheng, Zhen

    2016-04-01

    Opioids are increasingly prescribed for chronic noncancer pain across the developed world. Clinical guidelines for management of these patients focus on over-use. However, research into other types of long-term medication indicates that many patients minimize drug use whenever possible. To identify the varying influences on patients' decisions about their use of prescribed opioids and explore whether concepts of resistance and minimization of intake apply to these patients. A multiprofessional team performed a qualitative interview study using the constant-comparative method. Patient's decision making was explored in depth and with a thematic analysis utilizing a published "Model of medicine-taking." A purposive sample of 20 participants drawn from two pain clinics in Melbourne, Australia. The sample was biased toward patients interested in nonmedication pain management options. Patients' needs to obtain relief from severe pain, maintain function, and minimize side effects could lead to under-use as well as over-use of prescribed opioids. In keeping with the published Model of medicine-taking, resistance to taking opioids was a common and important influence on behavior. In the face of severe chronic pain, many participants used a variety of strategies to evaluate, avoid, reduce, self-regulate, and replace opioids. Furthermore, participants perceived a resistance to opioids within the system and among some healthcare professionals. This sometimes adversely affected their adherence. Both patients and doctors exhibit aspects of resistance to the use of prescribed opioids for chronic noncancer pain, suggesting that this shared concern could be the basis of a productive therapeutic alliance to improve communication and shared decision making. Clinical guidelines for opioids use for chronic noncancer pain focus on over-use. Our qualitative interview study found that many patients resisted and minimized the use of opioids. Using a published "Model of medicine-taking," we

  8. What's holding back abuse-deterrent opioid formulations? Considering 12 U.S. stakeholders.

    PubMed

    Pergolizzi, Joseph V; Taylor, Robert; LeQuang, Jo Ann; Raffa, Robert B

    2018-06-01

    There is no greater public health threat at this time in America than the opioid abuse crisis, and a systematic, level-headed, coherent, and unified approach is needed. Among the many things that have been proposed to help reduce opioid abuse is the development of opioid analgesic products in abuse-deterrent formulations (ADFs). This seems to make perfect sense. Areas covered: In this article, the viewpoints of 12 stakeholders (physicians, pain patients, payers, manufacturers, regulators, law enforcement, hospitals, first responders, elected officials, rehabilitation centers, opioid addicts, and the general public) were considered in terms of how ADF opioids are regarded and might contribute potential impediments to more widespread use. This is a narrative review based on the literature. Stakeholders were not surveyed directly. Expert opinion: Although abuse-deterrent technology for opioid analgesics has been available for several years, ADFs have not gained widespread acceptance. ADF products serve an important but limited purpose, but their incremental costs may serve as a 'mixed message' for many of the stakeholders concerned about cost containment.

  9. Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations.

    PubMed

    Gasior, Maciej; Bond, Mary; Malamut, Richard

    2016-01-01

    Prescription opioid analgesics are an important treatment option for patients with chronic pain; however, misuse, abuse and diversion of these medications are a major global public health concern. Prescription opioid analgesics can be abused via intended and non-intended routes of administration, both intact or after manipulation of the original formulation to alter the drug-delivery characteristics. Available data indicate that ingestion (with or without manipulation of the prescribed formulation) is the most prevalent route of abuse, followed by inhalation (snorting, smoking and vaping) and injection. However, reported routes of abuse vary considerably between different formulations. A number of factors have been identified that appear to be associated with non-oral routes of abuse, including a longer duration of abuse, younger age, male sex and a rural or socially deprived location. The development of abuse-deterrent formulations of prescription opioid analgesics is an important step toward reducing abuse of these medications. Available abuse-deterrent formulations 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 even aversive. There are currently five opioid analgesics with a Food and Drug Administration abuse-deterrent label, and a number of other products are under review. A growing body of evidence suggests that introduction of abuse-deterrent opioid analgesics in the USA has been associated with decreased rates of abuse of these formulations. The availability of abuse-deterrent formulations therefore appears to represent an important step toward curbing the epidemic of abuse of prescription opioid analgesics, while ensuring the availability of effective pain medications for patients with legitimate medical need.

  10. Experience with an extended-release opioid formulation designed to reduce abuse liability in a community-based pain management clinic

    PubMed Central

    Rubino, Daniel

    2011-01-01

    Context With the growing public health concern over rising rates of opioid abuse, physicians have a responsibility to incorporate safeguards into their practice to minimize the potential for opioid misuse, abuse, and diversion. Patient-specific treatment regimens should include steps to monitor treatment success with regard to optimal pain management as well as inappropriate use of opioids and other substances. Opioid formulations designed to be less attractive for abuse are also being developed. While future studies are needed to determine the impact of such formulations in addressing the issue of opioid misuse in the community as a whole, the experience of practitioners who have utilized these formulations can highlight the practical steps to incorporate such formulations into the everyday patient-care setting. Purpose The purpose of this report is to describe experience in managing patients with chronic, moderate-to-severe pain using morphine sulfate and naltrexone hydrochloride extended release capsules (MS-sNT) (EMBEDA®, King Pharmaceuticals® Inc, Bristol, TN, which was acquired by Pfizer Inc, New York, NY, in March 2011), a formulation designed with features to deter abuse/misuse, in a community-based pain management clinic. Case presentations Case reports demonstrating a clinical management plan for assessment, initial interview procedures, explanation/discussion of proposed therapies, patients’ treatment goals, conversion to MS-sNT, and titration and treatment outcomes are provided. Results The management approach yielded successful outcomes including pain relief, improved quality of life, treatment satisfaction, and patient acceptance of a formulation designed to deter abuse/misuse. Discussion The cases presented demonstrate that the communication accompanying complete pretreatment assessment, goal-setting and expectations, and attention to individual patient needs can enable optimization of pain-related outcomes, resulting in improved quality of life

  11. The effect of an abuse‐deterrent opioid formulation (OxyContin) on opioid abuse‐related outcomes in the postmarketing setting

    PubMed Central

    Chilcoat, HD; Butler, SF; Sellers, EM; Kadakia, A; Harikrishnan, V; Haddox, JD; Dart, RC

    2016-01-01

    An extended‐release opioid analgesic (OxyContin, OC) was reformulated with abuse‐deterrent properties to deter abuse. This report examines changes in abuse through oral and nonoral routes, doctor‐shopping, and fatalities in 10 studies 3.5 years after reformulation. Changes in OC abuse from 1 year before to 3 years after OC reformulation were calculated, adjusted for prescription changes. Abuse of OC decreased 48% in national poison center surveillance systems, decreased 32% in a national drug treatment system, and decreased 27% among individuals prescribed OC in claims databases. Doctor‐shopping for OC decreased 50%. Overdose fatalities reported to the manufacturer decreased 65%. Abuse of other opioids without abuse‐deterrent properties decreased 2 years later than OC and with less magnitude, suggesting OC decreases were not due to broader opioid interventions. Consistent with the formulation, decreases were larger for nonoral than oral abuse. Abuse‐deterrent opioids may mitigate abuse and overdose risks among chronic pain patients. PMID:27170195

  12. Tamper-indicating barcode and method

    DOEpatents

    Cummings, Eric B.; Even, Jr., William R.; Simmons, Blake A.; Dentinger, Paul Michael

    2005-03-22

    A novel tamper-indicating barcode methodology is disclosed that allows for detection of alteration to the barcode. The tamper-indicating methodology makes use of a tamper-indicating means that may be comprised of a particulate indicator, an optical indicator, a deformable substrate, and/or may be an integrated aspect of the barcode itself. This tamper-indicating information provides greater security for the contents of containers sealed with the tamper-indicating barcodes.

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

    PubMed

    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 (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid 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 (p<0.001). Between 2009 and 2015, IR opioids 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.

  14. Opioids Resistance in Chronic Pain Management

    PubMed Central

    Morrone, Luigi A.; Scuteri, Damiana; Rombolà, Laura; Mizoguchi, Hirokazu; Bagetta, Giacinto

    2017-01-01

    Abstract: Chronic pain management represents a serious healthcare problem worldwide. Chronic pain affects approximately 20% of the adult European population and is more frequent in women and older people. Unfortunately, its management in the community remains generally unsatisfactory and rarely under the control of currently available analgesics. Opioids have been used as analgesics for a long history and are among the most used drugs; however, while there is no debate over their short term use for pain management, limited evidence supports their efficacy of long-term treatment for chronic non-cancer pain. Therapy with opioids is hampered by inter-individual variability and serious side effects and some opioids often result ineffective in the treatment of chronic pain and their use is controversial. Accordingly, for a better control of chronic pain a deeper knowledge of the molecular mechanisms underlying resistance to opiates is mandatory. PMID:28503117

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

    PubMed

    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.

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

    PubMed Central

    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

    Background 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. Methods 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. Results 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 (p<0.001). In the Drug Diversion Program, population-adjusted rates of diversion were 6.1 fold higher for IR than ER opioids (p<0.001). In the Opioid 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 (p<0.001). Conclusions Between 2009 and 2015, IR opioids 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. PMID:27936038

  17. Establishing "abuse-deterrence equivalence" for generic abuse-deterrent opioid formulations: A proposed development framework.

    PubMed

    Setnik, Beatrice; Cone, Edward J

    2016-01-01

    Abuse-deterrent formulations are one strategy for mitigating the epidemic of prescription opioid abuse. Regulatory guidance documents describe the requirements for developing abuse-deterrent formulations of novel drugs and formulations; however, they do not address "abuse-deterrence equivalence" for generic formulations. As generics may be produced with different excipients and formulations compared to reference drugs, differences in their properties may impact their abuse-deterrent features. Currently, it is unclear what specific studies are needed to support generic abuse-deterrence claims. This commentary outlines several recommendations on the in vitro and in vivo testing required, including the conditions for conducting a human abuse potential study.

  18. System for tamper identification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bobbitt, III, John Thomas; Weeks, George E.

    2017-09-05

    A system for tamper identification. A fastener has a tamper identification surface with a unique grain structure that is altered if the fastener is removed or otherwise exposed to sufficient torque. After a period of time such as e.g., shipment and/or storage of the sealed container, a determination of whether tampering has occurred can be undertaken by examining the grain structure to determine if it has changed since the fastener was used to seal the container or secure the device.

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

    PubMed Central

    Butler, Stephen F; Benoit, Christine; Budman, Simon H; Fernandez, Kathrine C; McCormick, Cynthia; Venuti, Synne Wing; Katz, Nathaniel

    2006-01-01

    Background The growing trends in opioid abuse, assessment of the abuse liability of prescription opioid products, and growing efforts by the pharmaceutical industry to develop 'abuse-resistant' formulations highlight a need to understand the features that make one product more 'attractive' than another to potential abusers. We developed a scale to measure the 'attractiveness' of prescription opioids to potential abusers, and used the scale to measure the relative attractiveness of 14 opioid analgesic products. Methods First, the concept of attractiveness was empirically defined with a group of prescription opioid abusers and experts in opioid abuse using a process called Concept Mapping. Abuse liability consisted of two components: factors intrinsic to the drug formulation (e.g., speed of onset, duration) and factors extrinsic to drug formulation (e.g., availability, availability of alternatives, cost). A 17-item Opioid Attractiveness Scale (OAS) was constructed, focusing on factors intrinsic to the drug product. Results A total of 144 individuals participated in tests of validity and reliability. Internal consistency was excellent (Cronbach's α = 0.85–0.94). Drug rankings based on OAS scores achieved good inter-rater agreement (Kendall's W 0.37, p < 0.001). Agreement on drug OAS scores between the developmental sample and a confirmation sample was good (IntraClass Correlations [ICC] of 0.65–0.69). Global ratings of overall attractiveness of the 14 selected opioid products by substance abuse counselors corresponded with the rankings based on OAS ratings of the abuser group. Finally, substance abuse counselors completed the OAS, yielding a high level of correspondence with ratings by the abuser group (ICC = 0.83, p = 0.002). The OAS differentiated attractiveness among 14 selected pharmaceutical opioid products. OxyContin, Dilaudid, and Percocet were ranked highest (most attractive); Talwin NX and Duragesic were ranked lowest (least attractive). Conclusion An

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

    PubMed

    Butler, Stephen F; Benoit, Christine; Budman, Simon H; Fernandez, Kathrine C; McCormick, Cynthia; Venuti, Synne Wing; Katz, Nathaniel

    2006-02-02

    The growing trends in opioid abuse, assessment of the abuse liability of prescription opioid products, and growing efforts by the pharmaceutical industry to develop 'abuse-resistant' formulations highlight a need to understand the features that make one product more 'attractive' than another to potential abusers. We developed a scale to measure the 'attractiveness' of prescription opioids to potential abusers, and used the scale to measure the relative attractiveness of 14 opioid analgesic products. First, the concept of attractiveness was empirically defined with a group of prescription opioid abusers and experts in opioid abuse using a process called Concept Mapping. Abuse liability consisted of two components: factors intrinsic to the drug formulation (e.g., speed of onset, duration) and factors extrinsic to drug formulation (e.g., availability, availability of alternatives, cost). A 17-item Opioid Attractiveness Scale (OAS) was constructed, focusing on factors intrinsic to the drug product. A total of 144 individuals participated in tests of validity and reliability. Internal consistency was excellent (Cronbach's alpha = 0.85-0.94). Drug rankings based on OAS scores achieved good inter-rater agreement (Kendall's W 0.37, p < 0.001). Agreement on drug OAS scores between the developmental sample and a confirmation sample was good (IntraClass Correlations [ICC] of 0.65-0.69). Global ratings of overall attractiveness of the 14 selected opioid products by substance abuse counselors corresponded with the rankings based on OAS ratings of the abuser group. Finally, substance abuse counselors completed the OAS, yielding a high level of correspondence with ratings by the abuser group (ICC = 0.83, p = 0.002). The OAS differentiated attractiveness among 14 selected pharmaceutical opioid products. OxyContin, Dilaudid, and Percocet were ranked highest (most attractive); Talwin NX and Duragesic were ranked lowest (least attractive). An initial examination of the psychometric

  1. 43 CFR 423.25 - Vandalism, tampering, and theft.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Vandalism, tampering, and theft. 423.25 Section 423.25 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION... of Conduct § 423.25 Vandalism, tampering, and theft. (a) You must not tamper or attempt to tamper...

  2. On the designing of a tamper resistant prescription RFID access control system.

    PubMed

    Safkhani, Masoumeh; Bagheri, Nasour; Naderi, Majid

    2012-12-01

    Recently, Chen et al. have proposed a novel tamper resistant prescription RFID access control system, published in the Journal of Medical Systems. In this paper we consider the security of the proposed protocol and identify some existing weaknesses. The main attack is a reader impersonation attack which allows an active adversary to impersonate a legitimate doctor, e.g. the patient's doctor, to access the patient's tag and change the patient prescription. The presented attack is quite efficient. To impersonate a doctor, the adversary should eavesdrop one session between the doctor and the patient's tag and then she can impersonate the doctor with the success probability of '1'. In addition, we present efficient reader-tag to back-end database impersonation, de-synchronization and traceability attacks against the protocol. Finally, we propose an improved version of protocol which is more efficient compared to the original protocol while provides the desired security against the presented attacks.

  3. Tamper indicating bolt

    DOEpatents

    Blagin, Sergei V.; Barkanov, Boris P.

    2004-09-14

    A tamper-indicating fastener has a cylindrical body with threads extending from one end along a portion of the body, and a tamper indicating having a transducer for converting physical properties of the body into electronic data; electronics for recording the electronic data; and means for communicating the recorded information to a remote location from said fastener. The electronics includes a capacitor that varies as a function of force applied by the fastener, and non-volatile memory for recording instances when the capacitance varies, providing an indication of unauthorized access.

  4. Tamper-indicating seal

    DOEpatents

    Fiarman, S.; Degen, M.F.; Peters, H.F.

    1982-08-13

    There is disclosed a tamper-indicating seal that permits in the field inspection and detection of tampering. Said seal comprises a shrinkable tube having a visible pattern of markings which is shrunk over th item to be sealed, and a second transparent tube, having a second visible marking pattern, which is shrunk over the item and the first tube. The relationship between the first and second set of markings produces a pattern so that the seal may not be removed without detection. The seal is particularly applicable to UF/sub 6/ cylinder valves.

  5. Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States: Lessons Learned From OxyContin.

    PubMed

    Cicero, Theodore J; Ellis, Matthew S

    2015-05-01

    In an effort to reduce wide-scale abuse of the proprietary oxycodone hydrochloride formulation OxyContin, an abuse-deterrent formulation (ADF) was introduced in 2010. Although the reformulation produced an immediate drop in abuse rates, a definite ceiling effect appeared over time, beyond which no further decrease was seen. To examine the factors that led to the initial steep decline in OxyContin abuse and the substantial levels of residual abuse that have remained relatively stable since 2012. We used data from the ongoing Survey of Key Informants' Patients program, part of the Researched Abuse, Diversion and Addiction-Related Surveillance system that collects and analyzes postmarketing data on misuse and diversion of prescription opioid analgesics and heroin. For our survey study, patients with a DSM-V diagnosis of opioid use disorder and primary drug of abuse consisting of a prescription opioid or heroin (N = 10,784) at entry to 1 of 150 drug treatment programs in 48 states completed an anonymous structured survey of opioid abuse patterns (surveys completed from January 1, 2009, through June 30, 2014). A subset of these patients (n = 244) was interviewed to add context and expand on the structured survey. In addition to key demographic measures, past-month abuse of opioids was the primary measure in the structured surveys. In the interviews, the effect of the introduction of the ADF on drug-seeking behavior was examined. Reformulated OxyContin was associated with a significant reduction of past-month abuse after its introduction (45.1% [95% CI, 41.2%-49.1%] in January to June 2009 to 26.0% [95% CI, 23.6%-28.4%] in July to December 2012; P < .001; χ(2) = 230.83), apparently owing to a migration to other opioids, particularly heroin. However, this reduction leveled off, such that 25% to 30% of the sample persisted in endorsing past-month abuse from 2012 to 2014 (at study end [January to June 2014], 26.7% [95% CI, 23.7%-29.6%]). Among the 88 participants who

  6. Current status and evolving role of abuse-deterrent opioids in managing patients with chronic pain.

    PubMed

    Webster, Lynn; St Marie, Barbara; McCarberg, Bill; Passik, Steven D; Panchal, Sunil J; Voth, Eric

    2011-01-01

    Opioids are widely used for the treatment of patients with chronic pain; yet, the increase in their abuse, misuse, and diversion is an ongoing focus of regulatory, governmental, and legal scrutiny. As a consequence, clinicians are faced with numerous challenges in an effort to use opioids in appropriate patients with pain while minimizing the potential for opioid abuse, misuse, and diversion. Policies and programs such as state prescription monitoring programs, which have been in existence for decades, are but one attempt to address some of the issues regarding the prescribing of opioids. Another is a risk evaluation and mitigation strategy for opioids under consideration by the US Food and Drug Administration. At the clinical level, a universal precautions and risk management package that includes risk assessment and patient monitoring is a recommended approach. This approach can also include the use of abuse-deterrent and abuse-resistant formulations designed to reduce the nonmedical use of opioids. Several of these opioid formulations have been approved or should soon be on the market for use in the United States; however, their role and other questions regarding their use remain unanswered. The authors offer their clinical perspective on several of these key questions.

  7. Abuse-deterrent formulations, an evolving technology against the abuse and misuse of opioid analgesics.

    PubMed

    Schaeffer, Tammi

    2012-12-01

    The increased use of opioid pain medication has been mirrored by the increased misuse and abuse of these drugs. As part of a multidisciplinary approach to this epidemic, pharmaceutical companies, with the encouragement of the Food and Drug Administration, have increased the development of abuse-deterrent formulations. While all have the goal of treating pain while mitigating misuse and abuse, there are different technologies utilized to impart the abuse-deterrent properties. The goal of this paper is to review the basis of abuse-deterrent formulations, the different types and approaches of some of the abuse-deterrent products, and their current regulatory status in the USA.

  8. Protocol: changes in rates of opioid overdose and poisoning events in an integrated health system following the introduction of a formulation of OxyContin® with abuse-deterrent properties.

    PubMed

    Janoff, Shannon L; Perrin, Nancy A; Coplan, Paul M; Chilcoat, Howard D; Campbell, Cynthia I; Green, Carla A

    2016-05-14

    Addiction, overdoses and deaths resulting from prescription opioids have increased dramatically over the last decade. In response, several manufacturers have developed formulations of opioids with abuse-deterrent properties. For many of these products, the Food and Drug Administration (FDA) recognized the formulation with labeling claims and mandated post-marketing studies to assess the abuse-deterrent effects. In response, we assess differences in rates of opioid-related overdoses and poisonings prior to and following the introduction of a formulation of OxyContin® with abuse-deterrent properties. To assess effects of this formulation, electronic medical record (EMR) data from Kaiser Permanente Northwest (KPNW) and Kaiser Permanente Northern California (KPNC) are linked to state death data and compared to chart audits. Overdose and poisoning events will be categorized by intentionality and number of agents involved, including illicit drugs and alcohol. Using 6-month intervals over a 10-year period, trends will be compared in rates of opioid-related overdoses and poisoning events associated with OxyContin® to rates of events associated with other oxycodone and opioid formulations. Qualitative interviews with patients and relatives of deceased patients will be conducted to capture circumstances surrounding events. This study assesses and tracks changes in opioid-related overdoses and poisoning events prior to and following the introduction of OxyContin® with abuse-deterrent properties. Public health significance is high because these medications are designed to reduce abuse-related behaviors that lead to important adverse outcomes, including overdoses and deaths.

  9. Long-term efficacy, safety and tolerability of Remoxy for the management of chronic pain.

    PubMed

    Pergolizzi, Joseph V; Zampogna, Gianpietro; Taylor, Robert; Raffa, Robert B

    2015-03-01

    Historically, chronic pain generally went under-treated for a variety of objective and subjective reasons, including difficulty to objectively diagnose and manage over a long period of time, potential serious adverse effects of commonly available medications, and patient, healthcare and societal concerns over opioid medications. More recently, in an effort to redress the under-treatment of pain, the number of prescriptions of opioid analgesics has risen dramatically. However, paralleling the increased legitimate use has been a concomitant increase in opioid abuse, misuse and diversion. Pharmaceutical companies have responded by developing a variety of opioid formulations designed to deter abuse by making the products more difficult to tamper with. One such product is Remoxy(®), an extended-release formulation of the strong opioid oxycodone. We review the efficacy, safety and tolerability of this formulation based on the available published literature.

  10. 40 CFR 205.58-2 - Tampering.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Tampering. 205.58-2 Section 205.58-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) NOISE ABATEMENT PROGRAMS TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.58-2 Tampering. (a) For each configuration...

  11. Shifting blame: Buprenorphine prescribers, addiction treatment, and prescription monitoring in middle-class America

    PubMed Central

    Mendoza, Sonia; Rivera-Cabrero, Allyssa S.; Hansen, Helena

    2016-01-01

    Growing nonmedical prescription opioid analgesic use among suburban and rural Whites has changed the public’s perception of the nature of opioid addiction, and of appropriate interventions. Opioid addiction has been recast as a biological disorder in which patients are victims of their neurotransmitters and opioid prescribers are irresponsible purveyors of dangerous substances requiring controls. This framing has led to a different set of policy responses than the “War on Drugs” that has focused on heroin trade in poor urban communities; in response to prescription opioid addiction, prescription drug monitoring programs and tamper-resistant opioid formulations have arisen as primary interventions in place of law enforcement. Through the analysis of preliminary findings from interviews with physicians who are certified to manage opioid addiction with the opioid pharmaceutical buprenorphine, we argue that an increase in prescriber monitoring has shifted the focus from addicted people to prescribers as a threat, paradoxically driving users to illicit markets and constricting their access to pharmaceutical treatment for opioid addiction. Prescriber monitoring is also altering clinical cultures of care, as general physicians respond to heightened surveillance and the psychosocial complexities of treating addiction with either rejection of opioid dependent patients, or with resourceful attempts to create support systems for their treatment where none exists. PMID:27488225

  12. Shifting blame: Buprenorphine prescribers, addiction treatment, and prescription monitoring in middle-class America.

    PubMed

    Mendoza, Sonia; Rivera-Cabrero, Allyssa S; Hansen, Helena

    2016-08-01

    Growing nonmedical prescription opioid analgesic use among suburban and rural Whites has changed the public's perception of the nature of opioid addiction, and of appropriate interventions. Opioid addiction has been recast as a biological disorder in which patients are victims of their neurotransmitters and opioid prescribers are irresponsible purveyors of dangerous substances requiring controls. This framing has led to a different set of policy responses than the "War on Drugs" that has focused on heroin trade in poor urban communities; in response to prescription opioid addiction, prescription drug monitoring programs and tamper-resistant opioid formulations have arisen as primary interventions in place of law enforcement. Through the analysis of preliminary findings from interviews with physicians who are certified to manage opioid addiction with the opioid pharmaceutical buprenorphine, we argue that an increase in prescriber monitoring has shifted the focus from addicted people to prescribers as a threat, paradoxically driving users to illicit markets and constricting their access to pharmaceutical treatment for opioid addiction. Prescriber monitoring is also altering clinical cultures of care, as general physicians respond to heightened surveillance and the psychosocial complexities of treating addiction with either rejection of opioid dependent patients, or with resourceful attempts to create support systems for their treatment where none exists. © The Author(s) 2016.

  13. Integrated optical tamper sensor with planar waveguide

    DOEpatents

    Carson, Richard F.; Casalnuovo, Stephen A.

    1993-01-01

    A monolithic optical tamper sensor, comprising an optical emitter and detector, connected by an optical waveguide and placed into the critical entry plane of an enclosed sensitive region, the tamper sensor having a myriad of scraps of a material optically absorbent at the wavelength of interest, such that when the absorbent material is in place on the waveguide, an unique optical signature can be recorded, but when entry is attempted into the enclosed sensitive region, the scraps of absorbent material will be displaced and the optical/electrical signature of the tamper sensor will change and that change can be recorded.

  14. Integrated optical tamper sensor with planar waveguide

    DOEpatents

    Carson, R.F.; Casalnuovo, S.A.

    1993-01-05

    A monolithic optical tamper sensor, comprising an optical emitter and detector, connected by an optical waveguide and placed into the critical entry plane of an enclosed sensitive region, the tamper sensor having a myriad of scraps of a material optically absorbent at the wavelength of interest, such that when the absorbent material is in place on the waveguide, an unique optical signature can be recorded, but when entry is attempted into the enclosed sensitive region, the scraps of absorbent material will be displaced and the optical/electrical signature of the tamper sensor will change and that change can be recorded.

  15. Non-contact tamper sensing by electronic means

    DOEpatents

    Gritton, Dale G.

    1993-01-01

    A tamper-sensing system for an electronic tag 10 which is to be fixed to a surface 11 of an article 12, the tamper-sensing system comprising a capacitor having two non-contacting, capacitively-coupled elements 16, 19. Fixing of the body to the article will establish a precise location of the capacitor elements 16 and 19 relative to each other. When interrogated, the tag will generate a tamper-sensing signal having a value which is a function of the amount of capacity of the capacitor elements. The precise relative location of the capacitor elements cannot be duplicated if the tag is removed and affixed to a surrogate article having a fiducial capacitor element 19 fixed thereto. A very small displacement, in the order of 2-10 microns, of the capacitor elements relative to each other if the tag body is removed and fixed to a surrogate article will result in the tamper-sensing signal having a different, and detectable, value when the tag is interrogated.

  16. Tamper-indicating seals : practices, problems, and standards

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnston, R. G.

    2003-01-01

    Tamper-indicating seals have been used by customs officials for over 7,000 years. Today, seals are widely used to help counter theft, smuggling, sabotage, vandalism, terrorism, and espionage. Despite their antiquity and modern widespread use, however, there remains considerable confusion about seals, as well as a lot of misconceptions, wishful thinking, sloppy terminology, and poor practice. The absence of meaningful norms and standards, together with the surprisingly limited amount of research and development (R&D) in the field of tamper detection, has also hindered the effective use of seals. The Vulnerability Assessment Team (VAT) at Los Alamos National Laboratory has intensively studiedmore » tamper-indicating seals for the last 12 years. We have engaged in vulnerability assessments, R&D, consulting, and training for over two dozen United States government agencies and private companies, as well as for the International Atomic Energy Agency (IAEA) and Euratom. The VAT has also analyzed over 200 different types of seals in detail. This paper summarizes some of our conclusions, recommendations, and warnings regarding seals and tamper detection.« less

  17. Estimating attractiveness for abuse of a not-yet-marketed "abuse-deterrent" prescription opioid formulation.

    PubMed

    Butler, Stephen F; Black, Ryan; Grimes Serrano, Jill M; Folensbee, Lesley; Chang, Alan; Katz, Nathaniel

    2010-01-01

    The present study builds on research to model abusers' perceptions of particular analgesics' attractiveness for abuse and extends these methods to derive an estimate of attractiveness for abuse of a not-yet-marketed abuse-deterrent formulation (ADF) of a prescription opioid (Remoxy), Pain Therapeutics, Inc., San Mateo, CA, and King Pharmaceuticals, Inc., Bristol, TN). In a previous study, the Opioid Attractiveness Technology Scaling (OATS) method identified, from a drug abuser's point of view, the particular features of a prescription opioid relevant to its attractiveness for recreational use. A second online sample rated the extent to which these features applied to particular products they had actually used/abused. These data were used to model the abusers' overall preference for prescription opioids they had used/abused. In the present study, this method was applied to a not-yet-marketed ADF using substance abuse counselors as proxies for prescription opioid abusers. Thirty-eight counselors were given materials describing the new ADF along with four known products. Thirty-two counselors demonstrated sufficient agreement with abusers' ratings of the overall attractiveness of these drugs. The overall model yielded a significant pseudo R(2) of 0.15 (P < 0.001), with increasing model fit based on preferred route of administration, from swallowing whole (pseudo R(2) = 0.06; P < 0.001) and best for those who preferred to inject (pseudo R(2) = 0.40; P < 0.001). Data from a cross-validation group of 16 counselors/proxies were used to calculate the OATS scores for the five rated drugs and revealed significant differences between the ADF and OxyContin (Purdue Pharma LP, Stamford, CT), Percocet (Endo Pharmaceuticals, Chadds Ford, PA), and Vicodin (Abbott Laboratories, Abbott Park, IL), but not Talwin NX (Sanofi-aventis, Bridgewater, NJ), which was identified in the prior study as a highly unattractive drug for recreational purposes. The OATS method shows promise for

  18. Buprenorphine implants in medical treatment of opioid addiction.

    PubMed

    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. 36 CFR 2.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Trespassing, tampering and... INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property...

  20. 36 CFR 2.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Trespassing, tampering and... INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property...

  1. 36 CFR 2.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Trespassing, tampering and... INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property...

  2. 36 CFR 2.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Trespassing, tampering and... INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property...

  3. 36 CFR 2.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Trespassing, tampering and... INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property...

  4. Tampered Region Localization of Digital Color Images Based on JPEG Compression Noise

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Dong, Jing; Tan, Tieniu

    With the availability of various digital image edit tools, seeing is no longer believing. In this paper, we focus on tampered region localization for image forensics. We propose an algorithm which can locate tampered region(s) in a lossless compressed tampered image when its unchanged region is output of JPEG decompressor. We find the tampered region and the unchanged region have different responses for JPEG compression. The tampered region has stronger high frequency quantization noise than the unchanged region. We employ PCA to separate different spatial frequencies quantization noises, i.e. low, medium and high frequency quantization noise, and extract high frequency quantization noise for tampered region localization. Post-processing is involved to get final localization result. The experimental results prove the effectiveness of our proposed method.

  5. 36 CFR 1002.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Trespassing, tampering and..., PUBLIC USE AND RECREATION § 1002.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property or real property not open...

  6. 36 CFR 1002.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Trespassing, tampering and..., PUBLIC USE AND RECREATION § 1002.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property or real property not open...

  7. 36 CFR 1002.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Trespassing, tampering and..., PUBLIC USE AND RECREATION § 1002.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property or real property not open...

  8. 36 CFR 1002.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Trespassing, tampering and..., PUBLIC USE AND RECREATION § 1002.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property or real property not open...

  9. DEVELOPMENT OF A TAMPER RESISTANT/INDICATING AEROSOL COLLECTION SYSTEM FOR ENVIRONMENTAL SAMPLING AT BULK HANDLING FACILITIES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sexton, L.

    2012-06-06

    Environmental sampling has become a key component of International Atomic Energy Agency (IAEA) safeguards approaches since its approval for use in 1996. Environmental sampling supports the IAEA's mission of drawing conclusions concerning the absence of undeclared nuclear material or nuclear activities in a Nation State. Swipe sampling is the most commonly used method for the collection of environmental samples from bulk handling facilities. However, augmenting swipe samples with an air monitoring system, which could continuously draw samples from the environment of bulk handling facilities, could improve the possibility of the detection of undeclared activities. Continuous sampling offers the opportunity tomore » collect airborne materials before they settle onto surfaces which can be decontaminated, taken into existing duct work, filtered by plant ventilation, or escape via alternate pathways (i.e. drains, doors). Researchers at the Savannah River National Laboratory and Oak Ridge National Laboratory have been working to further develop an aerosol collection technology that could be installed at IAEA safeguarded bulk handling facilities. The addition of this technology may reduce the number of IAEA inspector visits required to effectively collect samples. The principal sample collection device is a patented Aerosol Contaminant Extractor (ACE) which utilizes electrostatic precipitation principles to deposit particulates onto selected substrates. Recent work has focused on comparing traditional swipe sampling to samples collected via an ACE system, and incorporating tamper resistant and tamper indicating (TRI) technologies into the ACE system. Development of a TRI-ACE system would allow collection of samples at uranium/plutonium bulk handling facilities in a manner that ensures sample integrity and could be an important addition to the international nuclear safeguards inspector's toolkit. This work was supported by the Next Generation Safeguards Initiative (NGSI

  10. Development of a video tampering dataset for forensic investigation.

    PubMed

    Ismael Al-Sanjary, Omar; Ahmed, Ahmed Abdullah; Sulong, Ghazali

    2016-09-01

    Forgery is an act of modifying a document, product, image or video, among other media. Video tampering detection research requires an inclusive database of video modification. This paper aims to discuss a comprehensive proposal to create a dataset composed of modified videos for forensic investigation, in order to standardize existing techniques for detecting video tampering. The primary purpose of developing and designing this new video library is for usage in video forensics, which can be consciously associated with reliable verification using dynamic and static camera recognition. To the best of the author's knowledge, there exists no similar library among the research community. Videos were sourced from YouTube and by exploring social networking sites extensively by observing posted videos and rating their feedback. The video tampering dataset (VTD) comprises a total of 33 videos, divided among three categories in video tampering: (1) copy-move, (2) splicing, and (3) swapping-frames. Compared to existing datasets, this is a higher number of tampered videos, and with longer durations. The duration of every video is 16s, with a 1280×720 resolution, and a frame rate of 30 frames per second. Moreover, all videos possess the same formatting quality (720p(HD).avi). Both temporal and spatial video features were considered carefully during selection of the videos, and there exists complete information related to the doctored regions in every modified video in the VTD dataset. This database has been made publically available for research on splicing, Swapping frames, and copy-move tampering, and, as such, various video tampering detection issues with ground truth. The database has been utilised by many international researchers and groups of researchers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Detection of Tampering Inconsistencies on Mobile Photos

    NASA Astrophysics Data System (ADS)

    Cao, Hong; Kot, Alex C.

    Fast proliferation of mobile cameras and the deteriorating trust on digital images have created needs in determining the integrity of photos captured by mobile devices. As tampering often creates some inconsistencies, we propose in this paper a novel framework to statistically detect the image tampering inconsistency using accurately detected demosaicing weights features. By first cropping four non-overlapping blocks, each from one of the four quadrants in the mobile photo, we extract a set of demosaicing weights features from each block based on a partial derivative correlation model. Through regularizing the eigenspectrum of the within-photo covariance matrix and performing eigenfeature transformation, we further derive a compact set of eigen demosaicing weights features, which are sensitive to image signal mixing from different photo sources. A metric is then proposed to quantify the inconsistency based on the eigen weights features among the blocks cropped from different regions of the mobile photo. Through comparison, we show our eigen weights features perform better than the eigen features extracted from several other conventional sets of statistical forensics features in detecting the presence of tampering. Experimentally, our method shows a good confidence in tampering detection especially when one of the four cropped blocks is from a different camera model or brand with different demosaicing process.

  12. Triboluminescent tamper-indicating device

    DOEpatents

    Johnston, Roger G.; Garcia, Anthony R. E.

    2002-01-01

    A tamper-indicating device is described. The device has a transparent or translucent cylindrical body that includes triboluminescent material, and an outer opaque layer that prevents ambient light from entering. A chamber in the body holds an undeveloped piece of photographic film bearing an image. The device is assembled from two body members. One of the body members includes a recess for storing film and an optical assembly that can be adjusted to prevent light from passing through the assembly and exposing the film. To use the device with a hasp, the body members are positioned on opposite sides of a hasp, inserted through the hasp, and attached. The optical assembly is then manipulated to allow any light generated from the triboluminescent materials during a tampering activity that damages the device to reach the film and destroy the image on the film.

  13. A tamper-indicating quantum seal

    DOE PAGES

    Williams, Brian P.; Britt, Keith A.; Humble, Travis S.

    2016-01-04

    Technical means for identifying when tampering occurs is a critical part of many containment and surveillance technologies. Conventional fiber optic seals provide methods for monitoring enclosed inventories, but they are vulnerable to spoofing attacks based on classical physics. We address these vulnerabilities with the development of a quantum seal that offers the ability to detect the intercept-resend attack using quantum integrity verification. Our approach represents an application of entanglement to provide guarantees in the authenticity of the seal state by verifying it was transmitted coherently. We implement these ideas using polarization-entangled photon pairs that are verified after passing through amore » fiber-optic channel testbed. Using binary detection theory, we find the probability of detecting inauthentic signals is greater than 0.9999 with a false alarm chance of 10 –9 for a 10 second sampling interval. In addition, we show how the Hong-Ou-Mandel effect concurrently provides a tight bound on redirection attack, in which tampering modifies the shape of the seal. Our measurements limit the tolerable path length change to sub-millimeter disturbances. As a result, these tamper-indicating features of the quantum seal offer unprecedented security for unattended monitoring systems.« less

  14. Assessment of extended-release opioid analgesics for the treatment of chronic pain.

    PubMed

    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.

  15. The Influence of Prescription Opioid Use Duration and Dose on Development of Treatment Resistant Depression

    PubMed Central

    Scherrer, Jeffrey F.; Salas, Joanne; Sullivan, Mark D.; Schneider, F. David; Bucholz, Kathleen K.; Burroughs, Thomas; Copeland, Laurel; Ahmedani, Brian; Lustman, Patrick J.

    2016-01-01

    Long-term prescription opioid use is associated both with new-onset and recurrence of depression. Whether chronic opioid use interferes with depression management has not been reported, therefore we determined whether patients’ longer duration of opioid use and higher opioid dose are associated with new-onset treatment resistant depression (TRD) after controlling for confounding from pain and other variables. Data was obtained from Veteran Health Administration (VHA) de-identified patient medical records. We used a retrospective cohort design from 2000–2012. Eligible subjects (n=6,169) were 18–80 years of age, free of cancer and HIV, diagnosed with depression and opioid-free for the 24-month interval prior to the observation period. Duration of a new prescription for opioid analgesic was categorized as 1–30 days, 31–90 days and >90 days. Morphine-equivalent dose (MED) during follow-up categorized as ≤50 mg versus >50 mg per day. Pain and other sources of confounding were controlled by propensity scores and inverse probability of treatment weighting. Cox proportional hazard models were computed to estimate the association between duration and dose of opioid and onset of TRD. After removing confounding by weighting data, opioid use for 31–90 days and for >90 days, compared to 1–30 days, was significantly associated with new onset TRD (HR=1.25; 95%CI: 1.09–1.45 and HR=1.52; 95%CI: 1.32–1.74, respectively). MED was not associated with new onset TRD. The risk of developing TRD increased as time spent on opioid analgesics increased. Long-term opioid treatment of chronic pain may interfere with treatment of depression. PMID:27497660

  16. Blind technique using blocking artifacts and entropy of histograms for image tampering detection

    NASA Astrophysics Data System (ADS)

    Manu, V. T.; Mehtre, B. M.

    2017-06-01

    The tremendous technological advancements in recent times has enabled people to create, edit and circulate images easily than ever before. As a result of this, ensuring the integrity and authenticity of the images has become challenging. Malicious editing of images to deceive the viewer is referred to as image tampering. A widely used image tampering technique is image splicing or compositing, in which regions from different images are copied and pasted. In this paper, we propose a tamper detection method utilizing the blocking and blur artifacts which are the footprints of splicing. The classification of images as tampered or not, is done based on the standard deviations of the entropy histograms and block discrete cosine transformations. We can detect the exact boundaries of the tampered area in the image, if the image is classified as tampered. Experimental results on publicly available image tampering datasets show that the proposed method outperforms the existing methods in terms of accuracy.

  17. Opioids with abuse-deterrent properties: A regulatory and technological overview.

    PubMed

    Haddox, J David

    Three concurrent public health problems coexist in the United States: endemic nonmedical use/misuse of opioid analgesics, epidemic overdose fatalities involving opioid analgesics, and endemic chronic pain in adults. These intertwined issues comprise an opioid crisis that has spurred the development of formulations of opioids with abuse-deterrent properties and label claims (OADP). To reduce abuse and misuse of prescription opioids, the federal Food and Drug Administration (FDA) has issued a formal Guidance to drug developers that delineates four categories of testing to generate data sufficient for a description of a product's abuse-deterrent properties, along with associated claims, in its Full Prescribing Information (FPI). This article reviews the epidemiology of the crisis as background for the development of OADP, summarizes the FDA Guidance for Industry regarding abuse-deterrent technologies, and provides an overview of some technologies that are currently employed or are under study for incorporation into OADP. Such technologies include physical and chemical barriers to abuse, combined formulations of opioid agonists and antagonists, inclusion of aversive agents, use of delivery systems that deter abuse, development of new molecular entities and prodrugs, and formulation of products that include some combination of these approaches. Opioids employing these novel technologies are one part of a comprehensive intervention strategy that can deter abuse of prescription opioid analgesics without creating barriers to the safe use of prescription opioids. The maximal public health contribution of OADP will probably occur only when all opioids have FDA-recognized abuse-deterrent properties and label claims.

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

    PubMed Central

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

    2013-01-01

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

  19. 36 CFR § 1002.31 - Trespassing, tampering and vandalism.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Trespassing, tampering and... PROTECTION, PUBLIC USE AND RECREATION § 1002.31 Trespassing, tampering and vandalism. (a) The following are prohibited: (1) Trespassing. Trespassing, entering or remaining in or upon property or real property not open...

  20. 50 CFR 27.65 - Tampering with vehicles and equipment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Tampering with vehicles and equipment. 27.65 Section 27.65 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM PROHIBITED ACTS Disturbing Violations: Against Nonwildlife Property § 27.65 Tampering with...

  1. 50 CFR 27.65 - Tampering with vehicles and equipment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Tampering with vehicles and equipment. 27.65 Section 27.65 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM PROHIBITED ACTS Disturbing Violations: Against Nonwildlife Property § 27.65 Tampering with...

  2. Evidence of tampering in watermark identification

    NASA Astrophysics Data System (ADS)

    McLauchlan, Lifford; Mehrübeoglu, Mehrübe

    2009-08-01

    In this work, watermarks are embedded in digital images in the discrete wavelet transform (DWT) domain. Principal component analysis (PCA) is performed on the DWT coefficients. Next higher order statistics based on the principal components and the eigenvalues are determined for different sets of images. Feature sets are analyzed for different types of attacks in m dimensional space. The results demonstrate the separability of the features for the tampered digital copies. Different feature sets are studied to determine more effective tamper evident feature sets. The digital forensics, the probable manipulation(s) or modification(s) performed on the digital information can be identified using the described technique.

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

    PubMed

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

    2012-10-01

    Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Because of the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability, (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation, (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse, and (4) postmarketing epidemiological studies. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  4. A graphite oxide (GO)-based remote readable tamper evident seal

    DOE PAGES

    Cattaneo, Alessandro; Bossert, Jason Andrew; Guzman, Christian; ...

    2016-09-08

    Here, this paper presents a prototype of a remotely readable graphite oxide (GO) paper-based tamper evident seal. The proposed device combines the tunable electrical properties offered by reduced graphite oxide (RGO) with a compressive sampling scheme. The benefit of using RGO as a tamper evident seal material is the sensitivity of its electrical properties to the common mechanisms adopted to defeat tamper-evident seals. RGO’s electrical properties vary upon local stress or cracks induced by mechanical action (e.g., produced by shimming or lifting attacks). Further, modification of the seal’s electrical properties can result from the incidence of other defeat mechanisms, suchmore » as temperature changes, solvent treatment and steam application. The electrical tunability of RGO enables the engraving of a circuit on the area of the tamper evident seal intended to be exposed to malicious attacks. The operation of the tamper evident seal, as well as its remote communication functionality, is supervised by a microcontroller unit (MCU). The MCU uses the RGO-engraved circuitry to physically implement a compressive sampling acquisition procedure. The compressive sampling scheme provides the seal with self-authentication and self-state-of-health awareness capabilities. Finally, the prototype shows potential for use in low-power, embedded, remote-operation nonproliferation security related applications.« less

  5. Interchangeability, Safety and Efficacy of Modified-Release Drug Formulations in the USA: The Case of Opioid and Other Nervous System Drugs.

    PubMed

    Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Hansen, Richard

    2016-04-01

    Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified-release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended-release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post-marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations.

  6. Dual-opioid therapy: changing the paradigm. Introduction.

    PubMed

    Nicholson, Bruce D

    2012-03-01

    Morphine sulfate and oxycodone hydrochloride are commonly used for pain management because of their pharmacologic profile, pharmacokinetics, and analgesic potency. However, opioids are associated with a significant adverse event (AE) burden that limits their use in both the acute and the chronic pain settings. Co-administration of opioids demonstrated synergistic analgesia and reduced side effects. Thus, dual-opioid therapy has the potential to enhance the positive analgesic benefits of opioids, while limiting the burden of opioid-related AEs. This symposium proceedings was based on presentations at the 13th World Congress on Pain in August 2010. This program will review the rationale for dual-opioid therapy based on preclinical findings and data from clinical studies showing the efficacy and tolerability profile of a dual-opioid formulation when used to treat acute postoperative pain. Wiley Periodicals, Inc.

  7. Legal liability perspectives on abuse-deterrent opioids in the treatment of chronic pain.

    PubMed

    Brushwood, David B; Rich, Ben A; Coleman, John J; Bolen, Jennifer; Wong, Winston

    2010-12-01

    Abuse-deterrent opioid analgesic formulations can help reduce the risk of opioid diversion and abuse. Not all opioid analgesics are available as both extended- and immediate-release dosage forms in abuse-deterrent formulations. Clinicians may have to balance the clinical benefit of a product that does not use abuse-deterrent technology versus the regulatory benefit of using a product with this technology. There is the possibility that a health care professional may be held legally liable when a product without abuse-deterrent qualities is used and a person suffers harm that would not have occurred had an abuse-deterrent formulation been provided. This article reviews legal precedents that inform an understanding of the need to reduce malpractice exposure by identifying patients who are at high risk of opioid diversion and/or abuse and considering the use of an abuse-deterrent formulation for these patients.

  8. Do abuse deterrent opioid formulations work?

    PubMed

    Dart, Richard C; Iwanicki, Janetta L; Dasgupta, Nabarun; Cicero, Theodore J; Schnoll, Sidney H

    We performed a systematic review to answer the question, "Does the introduction of an opioid analgesic with abuse deterrent properties result in reduced overall abuse of the drug in the community?" We included opioid analgesics with abuse deterrent properties (hydrocodone, morphine, oxycodone) with results restricted to the metasearch term "delayed onset," English language, use in humans, and publication years 2009-2016. All articles that contained data evaluating misuse, abuse, overdose, addiction, and death were included. The results were categorized using the Bradford-Hill criteria. We included 44 reports: hydrocodone (n = 7), morphine (n = 5), or oxycodone (n = 32) with Food and Drug Administration-approved Categories 1, 2, or 3 abuse deterrent labeling. The data currently available support the Hill criteria of strength (effect size), consistency (reproducibility), temporality, plausibility, and coherence. There was insufficient or no information available for the criteria of biological gradient, experiment, and analogy. We also assessed confounding factors and bias, which indicated that both were present and substantial in magnitude. Our analysis found that only oxycodone extended release (ER) had information available to evaluate abuse deterrence in the community. In Australia, Canada, and the United States, reformulation of oxycodone ER was followed by marked reduction in measures of abuse. The precise extent of reduced abuse cannot be calculated because of heterogeneous data sets, but the reported reductions ranged from 10 to 90 percent depending on the measure and the duration of follow-up.

  9. 25 CFR 11.440 - Tampering with or fabricating physical evidence.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Tampering with or fabricating physical evidence. 11.440 Section 11.440 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Offenses § 11.440 Tampering with or fabricating physical evidence...

  10. 25 CFR 11.440 - Tampering with or fabricating physical evidence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Tampering with or fabricating physical evidence. 11.440 Section 11.440 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER COURTS OF INDIAN OFFENSES AND LAW AND ORDER CODE Criminal Offenses § 11.440 Tampering with or fabricating physical evidence...

  11. Tamper-indicating device having a glass body

    DOEpatents

    Johnston, Roger G.; Garcia, Anthony R. E.

    2003-04-29

    A tamper-indicating device is described. The device has a first glass body member and a second glass body member that are attached to each other through a hasp. The glass body members of the device can be tempered. The body members can be configured with hollow volumes into which powders, microparticles, liquids, gels, or combinations thereof are sealed. The choice, the amount, and the location of these materials can produce a visible, band pattern to provide each body member with a unique fingerprint identifier, which makes it extremely difficult to repair or replace once it is damaged in order to avoid tamper detection.

  12. Secure RFID tag or sensor with self-destruction mechanism upon tampering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nekoogar, Faranak; Dowla, Farid; Twogood, Richard

    A circuit board anti-tamper mechanism comprises a circuit board having a frangible portion, a trigger having a trigger spring, a trigger arming mechanism actuated by the trigger wherein the trigger arming mechanism is initially non-actuated, a force producing mechanism, a latch providing mechanical communication between the trigger arming mechanism and the force producing mechanism, wherein the latch initially retains the force producing mechanism in a refracted position. Arming pressure applied to the trigger sufficient to overcome the trigger spring force will actuate the trigger arming mechanism, causing the anti-tamper mechanism to be armed. Subsequent tampering with the anti-tamper mechanism resultsmore » in a decrease of pressure on the trigger below the trigger spring force, thereby causing the trigger arming mechanism to actuate the latch, thereby releasing the force producing mechanism to apply force to the frangible portion of the circuit board, thereby breaking the circuit board.« less

  13. Opioid Dependence Treatment: Options In Pharmacotherapy

    PubMed Central

    Stotts, Angela L.; Dodrill, Carrie L.; Kosten, Thomas R.

    2010-01-01

    The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed. PMID:19538000

  14. Opioid-Induced Constipation and Bowel Dysfunction: A Clinical Guideline.

    PubMed

    Müller-Lissner, Stefan; Bassotti, Gabrio; Coffin, Benoit; Drewes, Asbjørn Mohr; Breivik, Harald; Eisenberg, Elon; Emmanuel, Anton; Laroche, Françoise; Meissner, Winfried; Morlion, Bart

    2017-10-01

    To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inhibitory effects of opioids are not confined to the colon, but also affect higher segments of the gastrointestinal tract, leading to the coining of the term "opioid-induced bowel dysfunction." A literature search was conducted using Medline, EMBASE, and EMBASE Classic, and the Cochrane Central Register of Controlled Trials. Predefined search terms and inclusion/exclusion criteria were used to identify and categorize relevant papers. A series of statements were formulated and justified by a comment, then labeled with the degree of agreement and their level of evidence as judged by the Strength of Recommendation Taxonomy (SORT) system. From a list of 10,832 potentially relevant studies, 33 citations were identified for review. Screening the reference lists of the pertinent papers identified additional publications. Current definitions, prevalence, and mechanism of opioid-induced bowel dysfunction were reviewed, and a treatment algorithm and statements regarding patient management were developed to provide guidance on clinical best practice in the management of patients with opioid-induced constipation and opioid-induced bowel dysfunction. In recent years, more insight has been gained in the pathophysiology of this "entity"; new treatment approaches have been developed, but guidelines on clinical best practice are still lacking. Current knowledge is insufficient regarding management of the opioid side effects on the upper gastrointestinal tract, but recommendations can be derived from what we know at present. © 2016 American Academy of Pain Medicine.

  15. Opioid-Induced Constipation and Bowel Dysfunction: A Clinical Guideline

    PubMed Central

    Müller-Lissner, Stefan; Bassotti, Gabrio; Coffin, Benoit; Drewes, Asbjørn Mohr; Breivik, Harald; Eisenberg, Elon; Emmanuel, Anton; Laroche, Françoise; Meissner, Winfried; Morlion, Bart

    2017-01-01

    Abstract Objective To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. Setting Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inhibitory effects of opioids are not confined to the colon, but also affect higher segments of the gastrointestinal tract, leading to the coining of the term “opioid-induced bowel dysfunction.” Methods A literature search was conducted using Medline, EMBASE, and EMBASE Classic, and the Cochrane Central Register of Controlled Trials. Predefined search terms and inclusion/exclusion criteria were used to identify and categorize relevant papers. A series of statements were formulated and justified by a comment, then labeled with the degree of agreement and their level of evidence as judged by the Strength of Recommendation Taxonomy (SORT) system. Results From a list of 10,832 potentially relevant studies, 33 citations were identified for review. Screening the reference lists of the pertinent papers identified additional publications. Current definitions, prevalence, and mechanism of opioid-induced bowel dysfunction were reviewed, and a treatment algorithm and statements regarding patient management were developed to provide guidance on clinical best practice in the management of patients with opioid-induced constipation and opioid-induced bowel dysfunction. Conclusions In recent years, more insight has been gained in the pathophysiology of this “entity”; new treatment approaches have been developed, but guidelines on clinical best practice are still lacking. Current knowledge is insufficient regarding management of the opioid side effects on the upper gastrointestinal tract, but recommendations can be derived from what we know at present. PMID:28034973

  16. Medical Image Tamper Detection Based on Passive Image Authentication.

    PubMed

    Ulutas, Guzin; Ustubioglu, Arda; Ustubioglu, Beste; V Nabiyev, Vasif; Ulutas, Mustafa

    2017-12-01

    Telemedicine has gained popularity in recent years. Medical images can be transferred over the Internet to enable the telediagnosis between medical staffs and to make the patient's history accessible to medical staff from anywhere. Therefore, integrity protection of the medical image is a serious concern due to the broadcast nature of the Internet. Some watermarking techniques are proposed to control the integrity of medical images. However, they require embedding of extra information (watermark) into image before transmission. It decreases visual quality of the medical image and can cause false diagnosis. The proposed method uses passive image authentication mechanism to detect the tampered regions on medical images. Structural texture information is obtained from the medical image by using local binary pattern rotation invariant (LBPROT) to make the keypoint extraction techniques more successful. Keypoints on the texture image are obtained with scale invariant feature transform (SIFT). Tampered regions are detected by the method by matching the keypoints. The method improves the keypoint-based passive image authentication mechanism (they do not detect tampering when the smooth region is used for covering an object) by using LBPROT before keypoint extraction because smooth regions also have texture information. Experimental results show that the method detects tampered regions on the medical images even if the forged image has undergone some attacks (Gaussian blurring/additive white Gaussian noise) or the forged regions are scaled/rotated before pasting.

  17. Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

    PubMed

    Bucher Bartelson, Becki; Le Lait, M Claire; Green, Jody L; Cepeda, M Soledad; Coplan, Paul M; Maziere, Jean-Yves; Wedin, Gregory P; Dart, Richard C

    2017-09-01

    An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Advances in the delivery of buprenorphine for opioid dependence.

    PubMed

    Rosenthal, Richard N; Goradia, Viral V

    2017-01-01

    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.

  19. DEVELOPMENT OF A CERAMIC TAMPER INDICATING SEAL: SRNL CONTRIBUTIONS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Krementz, D.; Brinkman, K.; Martinez-Rodriguez, M.

    2013-06-03

    Savannah River National Laboratory (SRNL) and Sandia National Laboratories (SNL) are collaborating on development of a Ceramic Seal, also sometimes designated the Intrinsically Tamper Indicating Ceramic Seal (ITICS), which is a tamper indicating seal for international safeguards applications. The Ceramic Seal is designed to be a replacement for metal loop seals that are currently used by the IAEA and other safeguards organizations. The Ceramic Seal has numerous features that enhance the security of the seal, including a frangible ceramic body, protective and tamper indicating coatings, an intrinsic unique identifier using Laser Surface Authentication, electronics incorporated into the seal that providemore » cryptographic seal authentication, and user-friendly seal wire capture. A second generation prototype of the seal is currently under development whose seal body is of Low Temperature Co-fired Ceramic (LTCC) construction. SRNL has developed the mechanical design of the seal in an iterative process incorporating comments from the SNL vulnerability review team. SRNL is developing fluorescent tamper indicating coatings, with recent development focusing on optimizing the durability of the coatings and working with a vendor to develop a method to apply coatings on a 3-D surface. SRNL performed a study on the effects of radiation on the electronics of the seal and possible radiation shielding techniques to minimize the effects. SRNL is also investigating implementation of Laser Surface Authentication (LSA) as a means of unique identification of each seal and the effects of the surface coatings on the LSA signature.« less

  20. Dependence and addiction during chronic opioid therapy.

    PubMed

    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.

  1. America's Opioid Epidemic: Supply and Demand Considerations.

    PubMed

    Clark, David J; Schumacher, Mark A

    2017-11-01

    America is in the midst of an opioid epidemic characterized by aggressive prescribing practices, highly prevalent opioid misuse, and rising rates of prescription and illicit opioid overdose-related deaths. Medical and lay public sentiment have become more cautious with respect to prescription opioid use in the past few years, but a comprehensive strategy to reduce our reliance on prescription opioids is lacking. Addressing this epidemic through reductions in unnecessary access to these drugs while implementing measures to reduce demand will be important components of any comprehensive solution. Key supply-side measures include avoiding overprescribing, reducing diversion, and discouraging misuse through changes in drug formulations. Important demand-side measures center around educating patients and clinicians regarding the pitfalls of opioid overuse and methods to avoid unnecessary exposure to these drugs. Anesthesiologists, by virtue of their expertise in the use of these drugs and their position in guiding opioid use around the time of surgery, have important roles to play in reducing patient exposure to opioids and providing education about appropriate use. Aside from the many immediate steps that can be taken, clinical and basic research directed at understanding the interaction between pain and opioid misuse is critical to identifying the optimal use of these powerful pain relievers in clinical practice.

  2. Advances in the delivery of buprenorphine for opioid dependence

    PubMed Central

    Rosenthal, Richard N; Goradia, Viral V

    2017-01-01

    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. PMID:28894357

  3. Coverage of Medications That Treat Opioid Use Disorder and Opioids for Pain Management in Marketplace Plans, 2017.

    PubMed

    Huskamp, Haiden A; Riedel, Lauren E; Barry, Colleen L; Busch, Alisa B

    2018-06-01

    Efficacious medications to treat opioid use disorders (OUDs) have been slow to diffuse into practice, and insurance coverage limits may be one important barrier. To compare coverage for medications used to treat OUDs and opioids commonly prescribed for pain management in plans offered on the 2017 Health Insurance Marketplace exchanges. We identified a sample of 100 plans offered in urban and in rural counties on the 2017 Marketplaces, weighting by population. We accessed publicly available plan coverage information on healthcare.gov for states with a federally facilitated exchange, the state exchange website for state-based exchanges, and insurer websites. About 14% of plans do not cover any formulations of buprenorphine/naloxone. Plans were more likely to require prior authorization for any of the covered office-based buprenorphine or naltrexone formulations preferred for maintenance OUD treatment (ie, buprenorphine/naloxone, buprenorphine implants, injectable long-acting naltrexone) than of short-acting opioid pain medications (63.6% vs. 19.4%; P<0.0001). Only 10.6% of plans cover implantable buprenorphine, 26.1% cover injectable naltrexone, and 73.4% cover at least 1 abuse-deterrent opioid pain medication. Many Marketplace plans either do not cover or require prior authorization for coverage of OUD medications, and these restrictions are often more common for OUD medications than for short-acting opioid pain medications. Regulators tasked with enforcement of the Mental Health Parity and Addiction Equity Act, which requires that standards for formulary design for mental health and substance use disorder drugs be comparable to those for other medications, should focus attention on formulary coverage of OUD medications.

  4. 40 CFR 205.173-2 - Tampering.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... removal or puncturing the muffler, baffles, header pipes, or any other component which conducts exhaust... EQUIPMENT NOISE EMISSION CONTROLS Motorcycle Exhaust Systems § 205.173-2 Tampering. The manufacturer must... exhaust system which causes the motorcycle to exceed the Federal noise standard. Use of the motorcycle...

  5. Buprenorphine-naloxone buccal soluble film for the treatment of opioid dependence: current update.

    PubMed

    Soyka, Michael

    2015-02-01

    Opioid dependence is a severe medical disorder with a high psychiatric and somatic comorbidity and mortality rate. The opioid agonist methadone, mixed agonist-antagonist buprenorphine and the combination of buprenorphine with the opioid antagonist naloxone are the first-line maintenance treatments for opioid dependence. Risk of diversion and accidental intoxications, especially in children, are of great concern. To lower these risks, a novel buprenorphine-naloxone film has been developed and introduced in the USA and Australia. This review evaluates the available preclinical and clinical data on the novel buprenorphine-naloxone film for treatment of opioid dependence. Literature was identified through a comprehensive PubMed search. Data sources also included official FDA information and material made public by the manufacturer. Few preclinical and clinical data on safety and efficacy have been published. The pharmacological differences between the novel film and the conventional buprenorphine/naloxone are small. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal. The spectrum of adverse events seems to be similar to that of the conventional sublingual tablet. Recent data show that patients prefer the novel film over the conventional sublingual tablet. Emerging surveillance data indicate a lower risk of accidental poisoning in children compared with the conventional formulation. Further clinical and preclinical data are needed to explore additional possible advantages of the new formulation.

  6. Interpreting labels of abuse-deterrent opioid analgesics.

    PubMed

    Webster, Lynn R

    To provide an overview of available abuse-deterrent opioids (ADOs) and the labeling text that describes abuse-deterrent (AD) properties. A nonsystematic review of ADO literature and regulatory documents guiding their development. A critical assessment and discussion of common routes of opioid abuse, AD methods and properties, US Food and Drug Administration (FDA) study requirements to achieve AD labeling, and brief guide to understanding AD labels. The FDA has issued guidance as incentive and direction to industry to develop ADOs as one component of a multi-pronged public-health strategy to combat opioid abuse and misuse. The guidance describes separate categories of premarket and postmarket studies and makes recommendations for claims that may be made based on study findings. Ten ADOs have FDA-approved labeling attesting to AD properties. Available formulations that fail to conform to FDA guidance in study and labeling recommendations cannot be considered ADO. Formulations with AD properties are expected to reduce risk compared to the same agents without AD properties but cannot prevent all abuse and adverse clinical outcomes.

  7. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  8. Towards the development of tamper-resistant, ground-based mobile sensor nodes

    NASA Astrophysics Data System (ADS)

    Mascarenas, David; Stull, Christopher; Farrar, Charles

    2011-11-01

    Mobile sensor nodes hold great potential for collecting field data using fewer resources than human operators would require and potentially requiring fewer sensors than a fixed-position sensor array. It would be very beneficial to allow these mobile sensor nodes to operate unattended with a minimum of human intervention. In order to allow mobile sensor nodes to operate unattended in a field environment, it is imperative that they be capable of identifying and responding to external agents that may attempt to tamper with, damage or steal the mobile sensor nodes, while still performing their data collection mission. Potentially hostile external agents could include animals, other mobile sensor nodes, or humans. This work will focus on developing control policies to help enable a mobile sensor node to identify and avoid capture by a hostile un-mounted human. The work is developed in a simulation environment, and demonstrated using a non-holonomic, ground-based mobile sensor node. This work will be a preliminary step toward ensuring the cyber-physical security of ground-based mobile sensor nodes that operate unattended in potentially unfriendly environments.

  9. Abuse-deterrent formulations approval reform: Will clinical correctness or real-world results be used to address the nation's opioid crisis: "Noninterference" as a new approval standard.

    PubMed

    Cohen, Dan

    To further the public policy objectives of Congress and the country, legislators should now insist that abuse-deterrent formulations (ADFs) be deployed for every C-II opioid and stimulant. The need for these innovative technologies has never been greater. And to most efficiently incentivize innovators to develop and deploy the most effective and modern deterrents, a new and simpler regulatory approval standard for ADF should be adopted by the U.S. Food and Drug Administration. That standard, based on a concept of "Noninterference" increases the potential for a much earlier deployment of ADFs in a broad range of products and allows deterrence to play its most effective role in combatting the national opioid crisis.

  10. 49 CFR Appendix C to Part 218 - Statement of Agency Enforcement Policy on Tampering

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Tampering C Appendix C to Part 218 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Pt. 218, App. C Appendix C to Part 218—Statement of Agency Enforcement Policy on Tampering The Rail Safety Improvement Act...

  11. 49 CFR Appendix C to Part 218 - Statement of Agency Enforcement Policy on Tampering

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Tampering C Appendix C to Part 218 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Pt. 218, App. C Appendix C to Part 218—Statement of Agency Enforcement Policy on Tampering The Rail Safety Improvement Act...

  12. 49 CFR Appendix C to Part 218 - Statement of Agency Enforcement Policy on Tampering

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Tampering C Appendix C to Part 218 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Pt. 218, App. C Appendix C to Part 218—Statement of Agency Enforcement Policy on Tampering The Rail Safety Improvement Act...

  13. Optically resonant subwavelength films for tamper-indicating tags and seals

    NASA Astrophysics Data System (ADS)

    Alvine, Kyle J.; Suter, Jonathan D.; Bernacki, Bruce E.; Bennett, Wendy D.

    2015-05-01

    We present the design, modeling and performance of a proof-of-concept tamper indicating approach that exploits newlydeveloped subwavelength-patterned films. These films have a nanostructure-dependent resonant optical reflection that is wavelength, angle, and polarization dependent. As such, they can be tailored to fabricate overlay transparent films for tamper indication and authentication of sensitive or controlled materials not possible with currently-known technologies. An additional advantage is that the unique optical signature is dictated by the geometry and fabrication process of the nanostructures in the film, rather than on the material used. The essential structure unit in the subwavelength resonant coating is a nanoscale Open-Ring Resonator (ORR). This building block is fabricated by coating a dielectric nanoscale template with metal to form a hemispherical shell-like structure. This curved metallic shell structure has a cross-section with an intrinsic capacitance and inductance and is thus the optical equivalent to the well-known "LC" circuit where the capacitance and inductance are determined by the nanoshell dimensions. For structures with sub 100 nm scale, this resonance occurs in the visible electromagnetic spectrum, and in the IR for larger shells. Tampering of the film would be visible though misalignment of the angle-sensitive features in the film. It is additionally possible to add in intrinsic oxidation and strain sensitive matrix materials to further complicate tamper repair and counterfeiting. Cursory standoff readout would be relatively simple using a combination of a near-infrared (or visible) LED flashlight and polarizer or passively using room lighting illumination and a dispersive detector.

  14. Ranking of sabotage/tampering avoidance technology alternatives

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Andrews, W.B.; Tabatabai, A.S.; Powers, T.B.

    1986-01-01

    Pacific Northwest Laboratory conducted a study to evaluate alternatives to the design and operation of nuclear power plants, emphasizing a reduction of their vulnerability to sabotage. Estimates of core melt accident frequency during normal operations and from sabotage/tampering events were used to rank the alternatives. Core melt frequency for normal operations was estimated using sensitivity analysis of results of probabilistic risk assessments. Core melt frequency for sabotage/tampering was estimated by developing a model based on probabilistic risk analyses, historic data, engineering judgment, and safeguards analyses of plant locations where core melt events could be initiated. Results indicate the most effectivemore » alternatives focus on large areas of the plant, increase safety system redundancy, and reduce reliance on single locations for mitigation of transients. Less effective options focus on specific areas of the plant, reduce reliance on some plant areas for safe shutdown, and focus on less vulnerable targets.« less

  15. Active Time Domain Reflectometry for Tamper Indication in Unattended Safeguards Systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sheen, David M.; Smith, Leon E.; Tedeschi, Jonathan R.

    2015-07-14

    The International Atomic Energy Agency (IAEA) continues to expand its use of unattended measurement systems. An increasing number of systems and an expanding family of instruments create challenges in terms of deployment efficiency and the implementation of data authentication measures. In collaboration with the IAEA, tamper-indicating measures to address data-transmission authentication challenges with unattended safeguards systems are under investigation. Pacific Northwest National Laboratory is studying the viability of active time-domain reflectometry (TDR) along two parallel but interconnected paths: (1) swept-frequency TDR as the highly flexible, laboratory gold standard to which field-deployable options can be compared, and (2) a low-cost commerciallymore » available spread-spectrum TDR technology as one option for field implementation. This paper describes the TDR methods under investigation and the associated benchtop test-bed, tampering scenarios of interest,, and viability measurement results to date (e.g., comparison of relative sensitivity to tamper scenarios).« less

  16. Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

    PubMed

    Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne

    2016-11-01

    Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; p corrected =0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; p corrected =0.041) (HC vs. NOD). This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Adolescent pedometer protocols: examining reactivity, tampering and participants' perceptions.

    PubMed

    Scott, Joseph John; Morgan, Philip James; Plotnikoff, Ronald Cyril; Trost, Stewart Graeme; Lubans, David Revalds

    2014-01-01

    The aim of this study was to investigate adolescents' potential reactivity and tampering while wearing pedometers by comparing different monitoring protocols to accelerometer output. The sample included adolescents (N = 123, age range = 14-15 years) from three secondary schools in New South Wales, Australia. Schools were randomised to one of the three pedometer monitoring protocols: (i) daily sealed (DS) pedometer group, (ii) unsealed (US) pedometer group or (iii) weekly sealed (WS) pedometer group. Participants wore pedometers (Yamax Digi-Walker CW700, Yamax Corporation, Kumamoto City, Japan) and accelerometers (Actigraph GT3X+, Pensacola, USA) simultaneously for seven days. Repeated measures analysis of variance was used to examine potential reactivity. Bivariate correlations between step counts and accelerometer output were calculated to explore potential tampering. The correlation between accelerometer output and pedometer steps/day was strongest among participants in the WS group (r = 0.82, P ≤ 0.001), compared to the US (r = 0.63, P ≤ 0.001) and DS (r = 0.16, P = 0.324) groups. The DS (P ≤ 0.001) and US (P = 0.003), but not the WS (P = 0.891), groups showed evidence of reactivity. The results suggest that reactivity and tampering does occur in adolescents and contrary to existing research, pedometer monitoring protocols may influence participant behaviour.

  18. Tamper to delay motion and decrease ionization of a sample during short pulse x-ray imaging

    DOEpatents

    London, Richard A [Orinda, CA; Szoke,; Abraham, Hau-Riege [Fremont, CA; Stefan P. , Chapman; Henry, N [Livermore, CA

    2007-06-26

    A system for x-ray imaging of a small sample comprising positioning a tamper so that it is operatively connected to the sample, directing short intense x-ray pulses onto the tamper and the sample, and detecting an image from the sample. The tamper delays the explosive motion of the sample during irradiation by the short intense x-ray pulses, thereby extending the time to obtain an x-ray image of the original structure of the sample.

  19. 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... dermatological, dentifrice, insulin, or lozenge product) for retail sale that is not packaged in a tamper..., dentifrice, insulin, or lozenge product) for retail sale shall package the product in a tamper-evident...

  20. 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... dermatological, dentifrice, insulin, or lozenge product) for retail sale that is not packaged in a tamper..., dentifrice, insulin, or lozenge product) for retail sale shall package the product in a tamper-evident...

  1. 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... dermatological, dentifrice, insulin, or lozenge product) for retail sale that is not packaged in a tamper..., dentifrice, insulin, or lozenge product) for retail sale shall package the product in a tamper-evident...

  2. 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... dermatological, dentifrice, insulin, or lozenge product) for retail sale that is not packaged in a tamper..., dentifrice, insulin, or lozenge product) for retail sale shall package the product in a tamper-evident...

  3. 21 CFR 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... dermatological, dentifrice, insulin, or lozenge product) for retail sale that is not packaged in a tamper..., dentifrice, insulin, or lozenge product) for retail sale shall package the product in a tamper-evident...

  4. Detecting Test Tampering Using Item Response Theory

    ERIC Educational Resources Information Center

    Wollack, James A.; Cohen, Allan S.; Eckerly, Carol A.

    2015-01-01

    Test tampering, especially on tests for educational accountability, is an unfortunate reality, necessitating that the state (or its testing vendor) perform data forensic analyses, such as erasure analyses, to look for signs of possible malfeasance. Few statistical approaches exist for detecting fraudulent erasures, and those that do largely do not…

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

    PubMed Central

    Su, Wendy; Pasternak, Gavril W.

    2013-01-01

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

  6. The prescription opioid epidemic: an overview for anesthesiologists.

    PubMed

    Alam, Asim; Juurlink, David N

    2016-01-01

    The objectives for preparing this article were to review the historical context and epidemiology surrounding the North American prescription opioid crisis, to summarize the evidence regarding the benefits and harms of long-term opioid therapy for non-cancer pain, and to outline ways in which anesthesiologists may help ameliorate the problem. We searched PubMed, Google Scholar, and EMBASE™ for relevant articles using various search terms, including pain, opioid epidemic, history of opioid use, perioperative care, and addiction. Related citations were further explored and searched depending on the specific subtopic of interest. In the 1980s and early 1990s, opioids were infrequently used for the treatment of chronic pain. Thereafter, however, physicians were gradually inculcated with the message that long-term opioid therapy was a safe and effective treatment option for patients with chronic non-cancer pain. Pharmaceutical companies supported this growing movement and employed aggressive and sometimes misleading marketing strategies for new opioid formulations. As a result, the practice of prescribing opioids flourished in the late 1990s. The surge in prescribing opioids was accompanied by a marked increase in opioid-related morbidity and mortality. This change in practice transpired despite the absence of randomized trials showing clinically significant benefit from the long-term use of opioids. Subsequently, however, a large and growing body of evidence has emerged quantifying the harms associated with long-term opioid therapy. Anesthesiologists widely prescribe opioids for acute and chronic pain; yet, as a group, they may be largely unaware of the current state of this growing epidemic and what role they can play to rectify this problem. Anesthesiologists are well positioned to take a leadership role in the management of postoperative discharge opioid therapy in an effort to curb the overutilization of opioids. Furthermore, anesthesiologists who regularly

  7. Test-Tampering Found Rampant in Atlanta System

    ERIC Educational Resources Information Center

    Samuels, Christina A.

    2011-01-01

    The author reports on a state investigation into Atlanta's impressive gains on state tests which finds that test-tampering was rampant in the much-praised school system. The report unveiled by the Georgia governor's office states that Atlanta teachers and principals for years methodically altered answer sheets for students taking state tests,…

  8. Using Focus Groups to Study Consumer Understanding and Experiences with Tamper-Evident Packaging Devices

    ERIC Educational Resources Information Center

    Pascall, Melvin A.; Lee, Ken; Fraser, Angela; Halim, Linna

    2009-01-01

    A focus group with an educational component was used to help initiate a new research hypothesis. Early-stage development of a new tamper-evident invention was improved with input from a consumer focus group. The focus group comprised consumers who were shown several tamper-evident devices, including a new color-changing cap under active…

  9. Injectable and implantable sustained release naltrexone in the treatment of opioid addiction

    PubMed Central

    Kunøe, Nikolaj; Lobmaier, Philipp; Ngo, Hanh; Hulse, Gary

    2014-01-01

    Sustained release technologies for administering the opioid antagonist naltrexone (SRX) have the potential to assist opioid-addicted patients in their efforts to maintain abstinence from heroin and other opioid agonists. Recently, reliable SRX formulations in intramuscular or implantable polymers that release naltrexone for 1–7 months have become available for clinical use and research. This qualitative review of the literature provides an overview of the technologies currently available for SRX and their effectiveness in reducing opioid use and other relevant outcomes. The majority of studies indicate that SRX is effective in reducing heroin use, and the most frequently studied SRX formulations have acceptable adverse events profiles. Registry data indicate a protective effect of SRX on mortality and morbidity. In some studies, SRX also seems to affect other outcomes, such as concomitant substance use, vocational training attendance, needle use, and risk behaviour for blood-borne diseases such as hepatitis or human immunodeficiency virus. There is a general need for more controlled studies, in particular to compare SRX with agonist maintenance treatment, to study combinations of SRX with behavioural interventions, and to study at-risk groups such as prison inmates or opioid-addicted pregnant patients. The literature suggests that sustained release naltrexone is a feasible, safe and effective option for assisting abstinence efforts in opioid addiction. PMID:23088328

  10. Injectable and implantable sustained release naltrexone in the treatment of opioid addiction.

    PubMed

    Kunøe, Nikolaj; Lobmaier, Philipp; Ngo, Hanh; Hulse, Gary

    2014-02-01

    Sustained release technologies for administering the opioid antagonist naltrexone (SRX) have the potential to assist opioid-addicted patients in their efforts to maintain abstinence from heroin and other opioid agonists. Recently, reliable SRX formulations in intramuscular or implantable polymers that release naltrexone for 1-7 months have become available for clinical use and research. This qualitative review of the literature provides an overview of the technologies currently available for SRX and their effectiveness in reducing opioid use and other relevant outcomes. The majority of studies indicate that SRX is effective in reducing heroin use, and the most frequently studied SRX formulations have acceptable adverse events profiles. Registry data indicate a protective effect of SRX on mortality and morbidity. In some studies, SRX also seems to affect other outcomes, such as concomitant substance use, vocational training attendance, needle use, and risk behaviour for blood-borne diseases such as hepatitis or human immunodeficiency virus. There is a general need for more controlled studies, in particular to compare SRX with agonist maintenance treatment, to study combinations of SRX with behavioural interventions, and to study at-risk groups such as prison inmates or opioid-addicted pregnant patients. The literature suggests that sustained release naltrexone is a feasible, safe and effective option for assisting abstinence efforts in opioid addiction. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  11. Prescription opioid abuse, pain and addiction: clinical issues and implications.

    PubMed

    Ling, Walter; Mooney, Larissa; Hillhouse, Maureen

    2011-05-01

    Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  12. Prescription opioid abuse, pain and addiction: Clinical issues and implications

    PubMed Central

    LING, WALTER; MOONEY, LARISSA; HILLHOUSE, MAUREEN

    2014-01-01

    Issues Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. Approach This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial μ agonist buprenorphine in the management of concurrent pain and opioid addiction. Implications Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. Conclusions The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. PMID:21545561

  13. Research design strategies to evaluate the impact of formulations on abuse liability.

    PubMed

    McColl, Shelley; Sellers, Edward M

    2006-06-01

    Scheduling of a chemical drug substance under the Controlled Substances Act (CSA) includes an evaluation of preclinical and clinical safety, and experimental abuse liability studies, as well as information on diversion and overdose. Formulations that mitigate abuse liability, dependence potential and public health risks (e.g., altered absorption rate and tamperability, long half-life, pro-drugs and combination products) are amenable to preclinical and clinical studies to compare their abuse potential to reference compounds. For new formulations (NF) as marketed agents, direct comparison to the immediate release (IR) formulation of the reference compound is typically needed across the full range of potential studies. While the public health advantage of formulation changes in the marketplace can be conceptualized in behavioral economic terms, generating persuasive data is challenging. Study complexity increases because of additional conditions (e.g., placebo, 2-3 doses of the IR formulation, 2-3 doses of the new formulation, and 2-3 doses of the unscheduled or negative control drug), larger sample sizes (study power driven by the comparison of the new formulation versus the IR or placebo), and associated increases in study duration. However, the use of single maximal doses of well-characterized controls can reduce the number of study arms, and using incomplete block designs can reduce study duration. Less typical experimental approaches may also be useful, such as human choice or discrimination procedures, or pre-marketing consumer studies among experienced drug tamperers. New formulations that demonstrate a substantial difference from marketed or reference products have a potential marketing advantage and should require less onerous risk management. Post-marketing epidemiological data demonstrating the lack of abuse will carry the most weight from a public health and physician perspective.

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

    PubMed

    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

  15. Opioid Challenge Evaluation of Blockade by Extended-Release Naltrexone in Opioid-Abusing Adults: Dose-Effects and Time-Course

    PubMed Central

    Bigelow, George E.; Preston, Kenzie L.; Schmittner, John; Dong, Qunming; Gastfriend, David R.

    2013-01-01

    Background Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods Outpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300 mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6 mg IM in ascending order at 1-hr intervals [up to 13.5 mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) Visual Analog Scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results Blockade of the VAS “any drug effect” response to 3 mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150 and 300 mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300 mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment. PMID:22079773

  16. Persistence and healthcare utilization associated with the use of buprenorphine/naloxone film and tablet formulation therapy in adults with opioid dependence.

    PubMed

    Clay, Emilie; Khemiri, Amine; Zah, Vladimir; Aballéa, Samuel; Ruby, Jane; Asche, Carl V

    2014-09-01

    Buprenorphine/naloxone film was developed to improve retention in treatment and reduce public health risks over the tablet formulation for opioid dependence. To compare patient persistence and resource utilization between formulations for the treatment of opioid dependence. A longitudinal, retrospective cohort analysis was conducted to compare persistence and healthcare costs in a private US insurance claims database. Previously untreated patients, who initiated treatment with buprenorphine/naloxone following the introduction of the film, were classified in two groups according to the initial prescription. Persistence was defined as the proportion of patients continuing treatment for at least 6 months. Resource utilization and related costs were calculated over the 6- and 12-month periods after treatment initiation. Film and tablet groups included 2796 and 1510 patients enrolled over 9.76 and 13.76 months on average, respectively, from initiation of treatment. Patient characteristics were similar between groups. Mean prescribed doses were 14.62 and 14.26 mg/day in film and tablet groups. Among patients enrolled for at least 6 months from the initial treatment, persistence rates were 63.78% with film vs 58.13% with tablet. Time to treatment discontinuation was longer in the film group, with a hazard ratio of 0.818 (p = 0.0005, 95% CI = [0.730;0.916]) adjusted for baseline characteristics. Patients treated with film had significantly more outpatient visits (+4%, p = 0.0185) and lower probability to be hospitalized (-17%, p = 0.0158), resulting in lower total healthcare costs over the 12-month period after initiation (-27%, p < 0.0001). Patients treated with the film formulation of buprenorphine/naloxone appeared to stay longer on treatment, have a lower probability of hospital admission, and lower health care costs compared to patients treated with the tablet. This study, based on insurance claims data, has the advantage of reflecting real-world practice, but one

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

    PubMed Central

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

    2016-01-01

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

  18. Determinants of Fentanyl and other Potent μ Opioid Agonist Misuse in Opioid-Dependent Individuals

    PubMed Central

    Cicero, Theodore J.; Ellis, Matthew S.; Paradis, Alethea; Ortbal, Zachary

    2010-01-01

    Purpose Based on preclinical and clinical abuse liability assessments, fentanyl and other potent μ opioid agonists (e.g. hydromorphone and morphine) should be the most misused opioids if accessibility in the real world were not an issue. Since the latter is seldom true, we postulated that there would be a significant mismatch between actual and predicted rates of misuse. Methods We recruited 1,818 prescription-opioid dependent patients entering drug treatment programs to complete an anonymous survey, covering drug use and health related issues. Results Hydrocodone and oxycodone products were the drugs of choice in 75% of patients, whereas potent μ opioid agonists (fentanyl, hydromorphone and morphine), with the greatest predicted abuse potential, were very rarely chosen (<5% each). Most unexpectedly, the rank order of the actual drug of choice and the preferred drug in an ideal world were highly correlated. The reason most commonly given for the failure to endorse fentanyl, for example, as an actual or preferred drug, was fear of toxicity and overdose. We found few differences in drug use patterns between a subset of high-risk, impaired health care professionals (N=196) and all other patients other than source of drug, (forged prescriptions and doctors more common and dealers much less common in the HC sample). Conclusions These results indicate that it should not be assumed- particularly for new drug formulations- that a high potential for abuse will result in actual abuse; and, most importantly, that the hesitancy to use potent opioids because of fears of abuse may be misguided. PMID:20597128

  19. 50 CFR 27.65 - Tampering with vehicles and equipment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM PROHIBITED ACTS Disturbing Violations: Against... motor vehicle, boat, equipment or machinery or attempting to tamper with, enter, or start any motor vehicle, boat, equipment or machinery on any national wildlife refuge without proper authorization is...

  20. Opioid adjuvant strategy: improving opioid effectiveness.

    PubMed

    Bihel, Frédéric

    2016-01-01

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

  1. Polyglycerol-opioid conjugate produces analgesia devoid of side effects.

    PubMed

    González-Rodríguez, Sara; Quadir, Mohiuddin A; Gupta, Shilpi; Walker, Karolina A; Zhang, Xuejiao; Spahn, Viola; Labuz, Dominika; Rodriguez-Gaztelumendi, Antonio; Schmelz, Martin; Joseph, Jan; Parr, Maria K; Machelska, Halina; Haag, Rainer; Stein, Christoph

    2017-07-04

    Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation. In contrast to conventional morphine, intravenous PG-M exclusively activated peripheral opioid receptors to produce analgesia in inflamed rat paws without major side effects such as sedation or constipation. Concentrations of morphine in the brain, blood, paw tissue, and in vitro confirmed the selective release of morphine in the inflamed milieu. Thus, PG-M may serve as prototype of a peripherally restricted opioid formulation designed to forego central and intestinal side effects.

  2. Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

    PubMed Central

    Chou, Roger; Fanciullo, Gilbert J.; Fine, Perry G.; Adler, Jeremy A.; Ballantyne, Jane C.; Davies, Pamela; Donovan, Marilee I.; Fishbain, David A.; Foley, Kathy M.; Fudin, Jeffrey; Gilson, Aaron M.; Kelter, Alexander; Mauskop, Alexander; O'Connor, Patrick G.; Passik, Steven D.; Pasternak, Gavril W.; Portenoy, Russell K.; Rich, Ben A.; Roberts, Richard G.; Todd, Knox H.; Miaskowski, Christine

    2014-01-01

    Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel following a systematic review of the evidence. PMID:19187889

  3. Tamper-indicating quantum optical seals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Humble, Travis S; Williams, Brian P

    2015-01-01

    Confidence in the means for identifying when tampering occurs is critical for containment and surveillance technologies. Fiber-optic seals have proven especially useful for actively surveying large areas or inventories due to the extended transmission range and flexible layout of fiber. However, it is reasonable to suspect that an intruder could tamper with a fiber-optic sensor by accurately replicating the light transmitted through the fiber. In this contribution, we demonstrate a novel approach to using fiber-optic seals for safeguarding large-scale inventories with increased confidence in the state of the seal. Our approach is based on the use of quantum mechanical phenomenamore » to offer unprecedented surety in the authentication of the seal state. In particular, we show how quantum entangled photons can be used to monitor the integrity of a fiber-optic cable - the entangled photons serve as active sensing elements whose non-local correlations indicate normal seal operation. Moreover, we prove using the quantum no-cloning theorem that attacks against the quantum seal necessarily disturb its state and that these disturbances are immediately detected. Our quantum approach to seal authentication is based on physical principles alone and does not require the use of secret or proprietary information to ensure proper operation. We demonstrate an implementation of the quantum seal using a pair of entangled photons and we summarize our experimental results including the probability of detecting intrusions and the overall stability of the system design. We conclude by discussing the use of both free-space and fiber-based quantum seals for surveying large areas and inventories.« less

  4. Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

    PubMed

    Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard

    2005-06-01

    Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

  5. A Theorem and its Application to Finite Tampers

    DOE R&D Accomplishments Database

    Feynman, R. P.

    1946-08-15

    A theorem is derived which is useful in the analysis of neutron problems in which all neutrons have the same velocity. It is applied to determine extrapolated end-points, the asymptotic amplitude from a point source, and the neutron density at the surface of a medium. Formulas fro the effect of finite tampers are derived by its aid, and their accuracy discussed.

  6. Maximizing value in opioid utilization: Is oxycodone immediate release a good option for pain management?

    PubMed

    Pergolizzi, Joseph V; Köknel Talu, Gül; Zmponga, Gianpetrio; Erdine, Serdar; Taylor, Robert; Ayan, Burak; Raffa, Robert B

    2015-01-01

    The modern approach to the management of pain involves optimizing all aspects of the process. This includes utilization of pharmacologic and non-pharmacologic modalities, consideration of patient characteristics, proper matching of the physiology of the pain with the analgesic's mechanism of action (pharmacodynamics, PD), and the onset and duration of action (pharmacokinetics, PK). No single agent or formulation satisfies all of the requirements for all patients. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are effective options for inflammatory pain and, as is acetaminophen, for mild pain. Specialized agents are helpful for particular pains, such as for migraine headache. Opioids remain the standard option for severe pain. Although they are generally a safe and effective option, opioids can produce dose-limiting adverse effects and have abuse potential. The goal of pain therapy is thus to achieve the maximum pain relief with the least amount of opioid exposure. Against this background of measured approach to the use of analgesics, an immediate release (IR) oral formulation of the established opioid oxycodone has been developed to provide rapid onset of action and rate of titration, both of which could maximize temporal matching of dose with pain level and reduce total exposure to drug. This article considers the option of an immediate release (IR) oral formulation for the management of pain.

  7. Current and Potential Pharmacological Treatment Options for Maintenance Therapy in Opioid-Dependent Individuals

    PubMed Central

    Tetrault, Jeanette M.; Fiellin, David A.

    2013-01-01

    Opioid dependence, manifesting as addiction to heroin and pharmaceutical opioids is increasing. Internationally, there are an estimated 15.6 million illicit opioid users. The global economic burden of opioid dependence is profound both in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism and lost productivity. Opioid agonist medications, such as methadone and buprenorphine, that stabilize neuronal systems and provide narcotic blockade are the most effective treatments. Prolonged provision of these medications, defined as maintenance treatment, typically produces improved outcomes when compared with short-duration tapers and withdrawal. The benefits of opioid agonist maintenance include decreased illicit drug use, improved retention in treatment, decreased HIV risk behaviours and decreased criminal behaviour. While regulations vary by country, these medications are becoming increasingly available internationally, especially in regions experiencing rapid transmission of HIV due to injection drug use. In this review, we describe the rationale for maintenance treatment of opioid dependence, discuss emerging uses of opioid antagonists such as naltrexone, and sustained-release formulations of naltrexone and buprenorphine, and provide a description of the experimental therapies. PMID:22235870

  8. Opioid Analgesics.

    PubMed

    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.

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

    PubMed

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

    2012-01-01

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

  10. An Efficient Semi-fragile Watermarking Scheme for Tamper Localization and Recovery

    NASA Astrophysics Data System (ADS)

    Hou, Xiang; Yang, Hui; Min, Lianquan

    2018-03-01

    To solve the problem that remote sensing images are vulnerable to be tampered, a semi-fragile watermarking scheme was proposed. Binary random matrix was used as the authentication watermark, which was embedded by quantizing the maximum absolute value of directional sub-bands coefficients. The average gray level of every non-overlapping 4×4 block was adopted as the recovery watermark, which was embedded in the least significant bit. Watermarking detection could be done directly without resorting to the original images. Experimental results showed our method was robust against rational distortions to a certain extent. At the same time, it was fragile to malicious manipulation, and realized accurate localization and approximate recovery of the tampered regions. Therefore, this scheme can protect the security of remote sensing image effectively.

  11. Are Prescription Opioids Driving the Opioid Crisis? Assumptions vs Facts.

    PubMed

    Rose, Mark Edmund

    2018-04-01

    Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized. Information was obtained by searching PubMed, governmental agency websites, and conference proceedings. Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population. Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy.

  12. Extended-release intramuscular naltrexone (VIVITROL®): a review of its use in the prevention of relapse to opioid dependence in detoxified patients.

    PubMed

    Syed, Yahiya Y; Keating, Gillian M

    2013-10-01

    Naltrexone is a μ-opioid receptor antagonist that blocks the euphoric effects of heroin and prescription opioids. In order to improve treatment adherence, a once-monthly, intramuscular, extended-release formulation of naltrexone (XR-NTX) [VIVITROL(®)] has been developed, and approved in the USA and Russia for the prevention of relapse to opioid dependence, after opioid detoxification. The clinical efficacy of this formulation in patients with opioid dependence was demonstrated in a 24-week, randomized, double-blind, placebo-controlled, multicentre, phase III trial (ALK21-013; n = 250). In this trial, opioid-detoxified patients receiving XR-NTX 380 mg once every 4 weeks, in combination with psychosocial support, had a significantly higher median proportion of weeks of confirmed opioid abstinence during weeks 5-24, compared with those receiving placebo (primary endpoint). A significantly higher proportion of patients receiving XR-NTX achieved total confirmed abstinence during this period than those receiving placebo. XR-NTX was also associated with a significantly greater reduction in opioid craving and a significantly longer treatment retention period than placebo. XR-NTX was generally well tolerated in the phase III trial. The most common (incidence ≥5 %) treatment-emergent adverse events that also occurred more frequently with XR-NTX than with placebo were hepatic enzyme abnormalities, nasopharyngitis, insomnia, hypertension, influenza and injection-site pain. Thus, XR-NTX is a useful treatment option for the prevention of relapse to opioid dependence, following opioid detoxification.

  13. Attentional Bias For Prescription Opioid Cues Among Opioid Dependent Chronic Pain Patients

    PubMed Central

    Garland, Eric L.; Froeliger, Brett; Passik, Steven D.; Howard, Matthew O.

    2012-01-01

    Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioidrelated cues. Opioid-dependent chronic pain patients (n = 32) and a comparison group of non-dependent opioid users with chronic pain (n = 33) completed a dot probe task designed to measure opioid AB. Participants also rated their opioid craving and self-reported arousal associated with opioid-related and neutral images, pain severity, and relief from pain treatments. Repeated-measures ANOVA revealed a significant group (opioid-dependent vs. non-dependent opioid user) × presentation duration (200 ms. vs. 2000 ms.) interaction, such that opioid-dependent individuals evidenced a significant AB towards opioid cues presented for 200 ms but not for cues presented for 2000 ms, whereas non-dependent opioid users did not exhibit a significant mean AB at either stimulus duration. Among opioid-dependent individuals, 200 ms opioid AB was significantly associated with opioid craving, while among non-dependent opioid users, 200 ms opioid AB was significantly associated with relief from pain treatments. Furthermore, dependent and non-dependent opioid users experienced opioid cues as significantly more arousing than neutral cues. Opioid dependence among chronic pain patients appears to involve an automatic AB towards opioid-related cues. When coupled with chronic pain, attentional fixation on opioid cues may promote compulsive drug use and addictive behavior. PMID:22968666

  14. Attentional bias for prescription opioid cues among opioid dependent chronic pain patients.

    PubMed

    Garland, Eric L; Froeliger, Brett E; Passik, Steven D; Howard, Matthew O

    2013-12-01

    Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioid-related cues. Opioid-dependent chronic pain patients (n = 32) and a comparison group of non-dependent opioid users with chronic pain (n = 33) completed a dot probe task designed to measure opioid AB. Participants also rated their opioid craving and self-reported arousal associated with opioid-related and neutral images, pain severity, and relief from pain treatments. Repeated-measures ANOVA revealed a significant group (opioid-dependent vs. non-dependent opioid user) × presentation duration (200. vs. 2,000 ms.) interaction, such that opioid-dependent individuals evidenced a significant AB towards opioid cues presented for 200 ms but not for cues presented for 2,000 ms, whereas non-dependent opioid users did not exhibit a significant mean AB at either stimulus duration. Among opioid-dependent individuals, 200 ms opioid AB was significantly associated with opioid craving, while among non-dependent opioid users, 200 ms opioid AB was significantly associated with relief from pain treatments. Furthermore, dependent and non-dependent opioid users experienced opioid cues as significantly more arousing than neutral cues. Opioid dependence among chronic pain patients appears to involve an automatic AB towards opioid-related cues. When coupled with chronic pain, attentional fixation on opioid cues may promote compulsive drug use and addictive behavior.

  15. Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic

    PubMed Central

    Severino, Amie L.; Shadfar, Arash; Hakimian, Joshua K.; Crane, Oliver; Singh, Ganeev; Heinzerling, Keith; Walwyn, Wendy M.

    2018-01-01

    Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse. PMID:29740351

  16. Clinical interpretation of opioid tolerance versus opioid-induced hyperalgesia.

    PubMed

    Chen, Lucy; Sein, Michael; Vo, Trang; Amhmed, Shihab; Zhang, Yi; Hilaire, Kristin St; Houghton, Mary; Mao, Jianren

    2014-01-01

    Opioid analgesics are commonly used to manage moderate to severe pain. However, the long-term use of opioids could lead to opioid tolerance (OT) and opioid-induced hyperalgesia (OIH). Distinguishing OIH from OT would impact the practice of opioid therapy because opioid dose adjustment may differentially influence OT and OIH. Currently, there are no standard criteria of OT versus OIH causing considerable ambiguity in clinical interpretation and management of these conditions. The authors designed a practitioner-based survey consisting of 20 targeted questions. Answering these questions would require responders' actual clinical experiences with opioid therapy. The survey was conducted between 2011 and 2012 through direct mails or e-mails to 1,408 physicians who are currently practicing in the United States. The authors find that certain clinical characteristics (eg, increased pain despite opioid dose escalation) are often used by practitioners to make differential diagnosis of OT and OIH despite some overlap in their clinical presentation. A key difference in clinical outcome is that OT and OIH could be improved and exacerbated by opioid dose escalation, respectively. Our survey results revealed a significant knowledge gap in some responders regarding differential diagnosis and management of OT and OIH. The results also identified several issues, such as opioid dose adjustment and clinical comorbidities related to OT and OIH, which require future patient-based studies.

  17. Neonatal opioid withdrawal and antenatal opioid prescribing

    PubMed Central

    Gomes, Tara; Camacho, Ximena; Yao, Zhan; Guttmann, Astrid; Mamdani, Muhammad M.; Juurlink, David N.; Dhalla, Irfan A.

    2015-01-01

    Background The incidence of neonatal opioid withdrawal is increasing in both Canada and the United States. However, the degree to which the treatment of pain with opioids, rather than the misuse of prescription opioids or heroin, contributes to the prevalence of neonatal opioid withdrawal remains unknown. Methods We conducted a retrospective, population-based, cross-sectional study between 1992 and 2011 in Ontario with 2 objectives. First, we determined the annual incidence of neonatal abstinence syndrome. Second, using data from a subset of women eligible for publicly funded prescription drugs, we determined what proportion of women who deliver an infant with neonatal abstinence syndrome were given a prescription for an opioid before and during pregnancy. Results The incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births in 2011. During the final 5 years of the study, we identified 927 deliveries of infants with neonatal abstinence syndrome to mothers who were public drug plan beneficiaries. Of these mothers, 67% had received an opioid prescription in the 100 days preceding delivery, including 53.3% who received methadone, an increase from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001). Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001). Interpretation The incidence of neonatal opioid withdrawal in Ontario has increased substantially over the last 20 years. Most of the women in this cohort who delivered an infant with neonatal abstinence syndrome had received a prescription for an opioid both before and during their pregnancy. PMID:25844370

  18. A general MHD formulation for plasmas with flow and resistive walls

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guazzotto, L.; Freidberg, J. P.; Betti, R.

    2006-11-30

    Toroidal rotation, either induced by means of neutral beams (e.g. in NSTX and DIII-D) or appearing spontaneously (e.g. in Alcator C-Mod, JET and Tore Supra) is routinely observed in modem tokamak experiments. Poloidal rotation is also commonly observed, in particular in the edge region of the plasma. Plasma rotation has a major effect on plasma stability. Flow and flow shear stabilize external modes such as the resistive wall mode (as observed e.g. in DIII-D), suppress turbulence when the flow shear is large enough, and also have a significant influence on the stability and nonlinear evolution of the internal kink andmore » ballooning modes. Flow shear can in particular have both a stabilizing (by breaking up unstable structures) and destabilizing (through the Kelvin-Helmoltz mechanism) effect. A self-consistent analysis of the effect of rotation requires the use of numerical tools. In this work, we present a general eigenvalue formulation based on a variational principle stability analysis, including arbitrary (both toroidal and poloidal) plasma rotation and a thin resistive wall of arbitrary shape and resistivity. It is shown that the problem can always be reduced to a classic eigenvalue formulation of the kind i{omega}A double underbar {center_dot} {zeta}-vector = B double underbar {center_dot} {zeta}-vector, where {zeta}-vector is the unknown eigenvector related to the plasma displacement, and {omega} the (complex) evolution frequency of the perturbation. The formulation is well suited for a finite element analysis.« less

  19. Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

    PubMed Central

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N.; Khan, Mansoor A.

    2016-01-01

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

  20. A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids.

    PubMed

    Uekuzu, Yoshihiro; Higashiguchi, Takashi; Futamura, Akihiko; Ito, Akihiro; Mori, Naoharu; Murai, Miyo; Ohara, Hiroshi; Awa, Hiroko; Chihara, Takeshi

    2017-03-01

    There have been few detailed reports on respiratory depression due to overdoses of opioids in terminal cancer patients. We investigated the situation of treatment with opioid antagonists for respiratory depression that occurred after administration of opioid at optimal doses in terminal cancer patients, to clarify pathological changes as well as causative factors. In 2443 terminal cancer patients receiving opioids, 7 patients (0.3%) received opioid antagonists: 6, morphine (hydrochloride, 5; sulfate, 1); 1, oxycodone. The median dosage of opioids was 13.3 mg/d, as converted to morphine injection. Respiratory depression occurred on this daily dose in 4 patients and after changed dose and route in 3 patients. Opioids were given through the vein in 6 patients and by the enteral route in 1 patient. Concomitant drugs included nonsteroidal anti-inflammatory drugs in 3 patients and zoledronic acid in 2 patients. In morphine-receiving patients, renal functions were significantly worsened at the time of administration of an opioid antagonist than the day before the start of opioid administration. These findings indicate that the proper use of opioids was safe and acceptable in almost all terminal cancer patients. In rare cases, however, a risk toward respiratory depression onset is indicated because morphine and morphine-6-glucuronide become relatively excessive owing to systemic debility due to disease progression, especially respiratory and renal dysfunctions. At the onset of respiratory depression, appropriate administration of an opioid antagonist mitigated the symptoms. Thereafter, opioid switching or continuous administration at reduced dosages of the same opioids prevented the occurrence of serious adverse events.

  1. DYNAMICS OF OPIOID SUBSTITUTION TREATMENTIN DIFFERENT INITIAL SUBSTANCE USER OPIOID DEPENDENT PATIENTS.

    PubMed

    Todadze, Kh; Mosia, S

    2016-05-01

    figures was observed in all groups in three month period that have been continuing during 21 month of treatment process. Study revealed normalization of scores forbothstatesin groups of heroine, desomorphine, methadone and buprenorphine users. The highest scores of depression and anxiety were observed in the group of poly-drug abusers andwhile depression rate hesitated in the range of clear "no-depression", anxiety index still remained close to the clinical important threshold after 21 month of treatment. Urine-testingon psychotropic-narcotic substances indicated remarkable decrease of illegal drug abuse in all studied groups in three month and although abuse of benzodiazepine drugs was highest in desomorphine and poly-drug abusers, the difference between groups was not statistically significant. Although some disparities have been observed in dynamics of subjects with different spectrum of initial opioid substance use, including homemade desomorphine, there is no significant difference between groups and OST effectively supports to improve depression and anxiety indices, and dramatically decreases use of illegal psychotropic-narcotic drugs during treatment. However poly-drug users seems to be the most resistant to achieve stabilization and require more treatment time and targeted interventions.

  2. Opioid Analgesics for Chronic Non-Cancer Pain: A Guideline on Opioid Prescribing.

    PubMed

    Van Demark, Robert; Chang, Peter; Heinemann, Daniel

    2016-01-01

    Over the past decade, the use of opioid analgesics has risen dramatically both in the U.S. and South Dakota. Opioids have been increasingly used to treat chronic non-cancer pain; however, the utilization of opioids for this role has limited and questionable utility. The U.S. has also seen a rise of opioid abuse, addiction, misuse, and overdose. The various pharmacological and non-pharmacological strategies to help physicians manage chronic non-cancer pain and a guideline on appropriate opioid prescribing are presented. Before the decision is made to begin opioid therapy for chronic non-cancer pain, other pharmacological and non-pharmacological therapeutic strategies should be explored. The schema for responsible opioid prescribing can be dived into the following: the initial assessment, initiating opioid therapy, maintenance therapy, and the discontinuation of opioid treatment. These categories are explored, and a general approach to prescribing opioids for chronic non-cancer pain is presented. The Centers for Disease Control and Prevention (CDC) has declared opioid prescription abuse an "epidemic." There are a variety of methods clinicians can utilize to relieve chronic non-cancer pain. If opioid therapy is sought, clinicians should be mindful of the current state of opioid abuse and misuse. This guideline may aid clinicians in appropriate opioid prescribing.

  3. Tamper Indicating Device: Initial Training, Course 50112

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bonner, Stephen Ray; Sandoval, Dana M.

    Tamper Indicating Device (TID): Initial Training, course #50112, covers Los Alamos National Laboratory (LANL) Material Control & Accountability (MC&A) TID Program procedures for the application and removal of TIDs. LANL’s policy is to comply with Department of Energy (DOE) requirements for the use of TIDs consistent with the graded safeguards described in DOE Manual DOE O 474.2, Nuclear Material Control and Accountability. When you have completed this course, you will: recognize standard practices and procedures of the LANL TID Program; have hands-on experience in the application and removal of LANL TIDs, and; verify the application and removal of LANL TIDs.

  4. Pharmaceutical Formulation Facilities as Sources of Opioids and Other Pharmaceuticals to Wastewater Treatment Plant Effluents

    PubMed Central

    2010-01-01

    Facilities involved in the manufacture of pharmaceutical products are an under-investigated source of pharmaceuticals to the environment. Between 2004 and 2009, 35 to 38 effluent samples were collected from each of three wastewater treatment plants (WWTPs) in New York and analyzed for seven pharmaceuticals including opioids and muscle relaxants. Two WWTPs (NY2 and NY3) receive substantial flows (>20% of plant flow) from pharmaceutical formulation facilities (PFF) and one (NY1) receives no PFF flow. Samples of effluents from 23 WWTPs across the United States were analyzed once for these pharmaceuticals as part of a national survey. Maximum pharmaceutical effluent concentrations for the national survey and NY1 effluent samples were generally <1 μg/L. Four pharmaceuticals (methadone, oxycodone, butalbital, and metaxalone) in samples of NY3 effluent had median concentrations ranging from 3.4 to >400 μg/L. Maximum concentrations of oxycodone (1700 μg/L) and metaxalone (3800 μg/L) in samples from NY3 effluent exceeded 1000 μg/L. Three pharmaceuticals (butalbital, carisoprodol, and oxycodone) in samples of NY2 effluent had median concentrations ranging from 2 to 11 μg/L. These findings suggest that current manufacturing practices at these PFFs can result in pharmaceuticals concentrations from 10 to 1000 times higher than those typically found in WWTP effluents. PMID:20521847

  5. Accessibility of opioid analgesics and barriers to optimal chronic pain treatment in Poland in 2000-2015.

    PubMed

    Dzierżanowski, Tomasz; Ciałkowska-Rysz, Aleksandra

    2017-03-01

    Based on the international reports, consumption of opioid analgesics in Poland is relatively low. There is limited information on possible impediments to optimal opioid use. This study was aimed to identify possible barriers to access to opioid analgesics and causes of failure to comply with current clinical guidelines. Consumption data per capita in 2000-2015 were analyzed in terms of oral morphine equivalents in total, per prescription type, per reimbursement status, to identify the impact of regulations specific for Poland. The consumption of opioid analgesics has been consistently growing from 36.0 in 2000 to 103.4 mg oral morphine equivalents (OME) per capita in 2015, mainly thanks to strong opioid consumption growth. Tramadol is the most commonly used opioid in Poland. Fentanyl and buprenorphine transdermal formulations are the most frequently used strong opioid analgesics in terms of OME. The vast majority (92.8 %) of opioids were distributed upon for outpatient use in 2015, with a almost fourfold growth of consumption of strong opioids and almost threefold of weak opioids between 2000 and 2015. Strong opioids were 41 % of OME used upon prescription in 2015. Acceleration of consumption growth has been observed since 2013. The prescription pattern does not abide by the current clinical guidelines for pain treatment, and the most often used opioids in Poland are tramadol, buprenorphine, and fentanyl. The use of opioids in Poland grows fast, with acceleration since 2013. The most important legal impediments of optimal opioid analgesics use have been lack of reimbursement, special prescription forms, and complicated prescribing rules.

  6. Using behavioral economics to predict opioid use during prescription opioid dependence treatment.

    PubMed

    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, p<.001) and a greater proportion of their income on drugs (OR=1.31, p<.001) were more likely to use opioids during treatment. Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic 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.

  7. Using behavioral economics to predict opioid use during prescription opioid dependence treatment

    PubMed Central

    Worley, Matthew J.; Shoptaw, Steven J.; Bickel, Warren K.; Ling, Walter

    2015-01-01

    Background 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. Methods 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. Results 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, p < .001) and a greater proportion of their income on drugs (OR = 1.31, p < .001) were more likely to use opioids during treatment. Conclusions Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic 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. PMID:25622776

  8. Primary Care Physicians' Knowledge and Attitudes Regarding Prescription Opioid Abuse and Diversion.

    PubMed

    Hwang, Catherine S; Turner, Lydia W; Kruszewski, Stefan P; Kolodny, Andrew; Alexander, G Caleb

    2016-04-01

    Physicians are a key stakeholder in the epidemic of prescription opioid abuse. Therefore, we assessed their knowledge of opioid abuse and diversion, as well as their support for clinical and regulatory interventions to reduce opioid-related morbidity and mortality. We conducted a nationally representative postal mail survey of 1000 practicing internists, family physicians, and general practitioners in the United States between February and May 2014. The adjusted response rate was 58%, and all physicians (100%) believed that prescription drug abuse was a problem in their communities. However, only two-thirds (66%) correctly reported that the most common route of abuse was swallowing pills whole, and nearly one-half (46%) erroneously reported that abuse-deterrent formulations were less addictive than their counterparts. In addition, a notable minority of physicians (25%) reported being "not at all" or "only slightly concerned" about the potential for opioid diversion from the licit to the illicit market when this practice is common at all levels of the pharmaceutical supply chain. Most physicians supported clinical and regulatory interventions to reduce prescription opioid abuse, including the use of patient contracts (98%), urine drug testing (90%), requiring prescribers to check a centralized database before prescribing opioids (88%), and instituting greater restrictions on the marketing and promotion of opioids (77% to 82%). Despite this, only one-third of physicians (33%) believed that interventions to reduce prescription opioid abuse had a moderate or large effect on preventing patients' clinically appropriate access to pain treatment. Although physicians are unaware of some facets of prescription opioid-related morbidity, most support a variety of clinical and regulatory interventions to improve the risk-benefit balance of these therapies.

  9. Impact of abuse-deterrent OxyContin on prescription opioid utilization.

    PubMed

    Hwang, Catherine S; Chang, Hsien-Yen; Alexander, G Caleb

    2015-02-01

    We quantified the degree to which the August 2010 reformulation of abuse-deterrent OxyContin affected its use, as well as the use of alternative extended-release and immediate-release opioids. We used the IMS Health National Prescription Audit, a nationally representative source of prescription activity in the USA, to conduct a segmented time-series analysis of the use of OxyContin and other prescription opioids. Our primary time period of interest was 12 months prior to and following August 2010. We performed model checks and sensitivity analyses, such as adjusting for marketing and promotion, using alternative lag periods, and adding extra observation points. OxyContin sales were similar before and after the August 2010 reformulation, with approximately 550 000 monthly prescriptions. After adjusting for declines in the generic extended-release oxycodone market, the formulation change was associated with a reduction of approximately 18 000 OxyContin prescription sales per month (p = 0.02). This decline corresponded to a change in the annual growth rate of OxyContin use, from 4.9% prior to the reformulation to -23.8% during the year after the reformulation. There were no statistically significant changes associated with the sales of alternative extended-release (p = 0.42) or immediate-release (p = 0.70) opioids. Multiple sensitivity analyses supported these findings and their substantive interpretation. The market debut of abuse-deterrent OxyContin was associated with declines in its use after accounting for the simultaneous contraction of the generic extended-release oxycodone market. Further scrutiny into the effect of abuse-deterrent formulations on medication use and health outcomes is vital given their popularity in opioid drug development. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Review of extended-release formulations of Tramadol for the management of chronic non-cancer pain: focus on marketed formulations

    PubMed Central

    Kizilbash, Arshi; Ngô-Minh, Cường

    2014-01-01

    Patients with chronic non-malignant pain report impairments of physical, social, and psychological well-being. The goal of pain management should include reducing pain and improving quality of life. Patients with chronic pain require medications that are able to provide adequate pain relief, have minimum dosing intervals to maintain efficacy, and avoid breakthrough pain. Tramadol has proven efficacy and a favourable safety profile. The positive efficacy and safety profile has been demonstrated historically in numerous published clinical studies as well as from post-marketing experience. It is a World Health Organization “Step 2” opioid analgesic that has been shown to be effective, well-tolerated, and valuable, where treatment with strong opioids is not required. A number of extended release formulations of Tramadol are available in Canada and the United States. An optimal extended release Tramadol formulation would be expected to provide consistent pain control with once daily dosing, few sleep interruptions, flexible dosing schedules, and no limitation on taking with meals. Appropriate treatment options should be based on the above proposed attributes. A comparative review of available extended release Tramadol formulations shows that these medications are not equivalent in their pharmacokinetic profile and this may have implications for selecting the optimal therapy for patients with pain syndromes where Tramadol is an appropriate analgesic agent. Differences in pharmacokinetics amongst the formulations may also translate into varied clinical responses in patients. Selection of the appropriate formulation by the health care provider should therefore be based on the patient’s chronic pain condition, needs, and lifestyle. PMID:24711710

  11. Insecticide resistance and diminished secondary kill performance of bait formulations against German cockroaches (Dictyoptera: Blattellidae)

    PubMed Central

    Ko, Alexander E.; Bieman, Donald N.; Schal, Coby; Silverman, Jules

    2015-01-01

    BACKGROUND Bait formulations are considered the most effective method for reducing German cockroach infestations. An important property of some bait formulations is secondary kill, whereby active ingredient is translocated in insect-produced residues throughout the cockroach population, especially affecting relatively sedentary early instar nymphs. RESULTS Blattella germanica was collected from a location where baits containing hydramethylnon, fipronil, or indoxacarb became ineffective, and these AIs were topically applied to adult males. Results revealed the first evidence for hydramethylnon resistance, moderate resistance to fipronil and extremely high resistance to indoxacarb. Insecticide residues excreted by field-collected males that ingested commercial baits effectively killed nymphs of an insecticide-susceptible laboratory strain of B. germanica but failed to kill most nymphs of the field-collected strain. CONCLUSIONS We report three novel findings: 1) The first evidence for hydramethylnon resistance in any insect; 2) extremely high levels of indoxacarb resistance in a field population; and 3) reduced secondary mortality in an insecticide-resistant field-collected strain of B. germanica. We suggest that while secondary mortality is considered to be advantageous in cockroach interventions, the ingestion of sublethal doses of AI by nymphs may select for high insecticide resistance by increasing the frequency of AI resistance alleles within the population. PMID:26689433

  12. The introduction of buprenorphine-naloxone film in opioid substitution therapy in Australia: Uptake and issues arising from changing buprenorphine formulations.

    PubMed

    Larance, Briony; Dietze, Paul; Ali, Robert; Lintzeris, Nicholas; White, Nancy; Jenkinson, Rebecca; Degenhardt, Louisa

    2015-11-01

    Buprenorphine-naloxone (BNX) film for opioid dependence treatment was introduced in Australia in 2011. A key difference in State policy approaches saw transfer from BNX tablets to BNX film mandated in South Australia (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent policies. This study examined (i) how initiations and transfers were implemented, (ii) the profile and predictors of adverse effects as self-reported by BNX film clients, and (iii) dosing issues. Survey of 334 buprenorphine (BPN), BNX tablet and BNX film clients and semi-structured interviews with 39 key experts (KEs) in 2012. Comparisons are made between clients interviewed in SA versus NSW and VIC combined. Among the 180 current BNX film clients, 23% started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n = 106) reported their clinic/prescriber recommended transfer to BNX film. Among clients who were offered but refused a transfer to BNX film (n = 66), the most common reason was 'I am happy with my current treatment and do not see a reason to change' (53%). Some opioid substitution therapy clients and KE viewed transfers as 'forced' (i.e. no choice of buprenorphine formulation). Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length of current treatment episode were associated with more BNX film-attributed adverse effects but clinic/prescriber-recommended transfer was not. The introduction of BNX film in Australia varied across States. A perception of restricted choice in medication may have undermined initial acceptance in SA. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  13. Reusable, tamper-indicating seal

    DOEpatents

    Ryan, Michael J.

    1978-01-01

    A reusable, tamper-indicating seal comprises a drum confined within a fixed body and rotatable in one direction therewithin, the top of the drum constituting a tray carrying a large number of small balls of several different colors. The fixed body contains parallel holes for looping a seal wire therethrough. The base of the drums carries cams adapted to coact with cam followers to lock the wire within the seal at one angular position of the drum. A channel in the fixed body -- visible from outside the seal -- adjacent the tray constitutes a segregated location for a small plurality of the colored balls. A spring in the tray forces colored balls into the segregated location at one angular position of the drum, further rotation securing the balls in position and the wires in the seal. A wedge-shaped plough removes the balls from the segregated location, at a different angular position of the drum, the wire being unlocked at the same position. A new pattern of colored balls will appear in the segregated location when the seal is relocked.

  14. The opioid crisis: past, present and future policy climate in Ontario, Canada.

    PubMed

    Morin, Kristen A; Eibl, Joseph K; Franklyn, Alexandra M; Marsh, David C

    2017-11-02

    Addressing opioid use disorder has become a priority in Ontario, Canada, because of its high economic, social and health burden. There continues to be stigma and criticism relating to opioid use disorder and treatment options. The result has been unsystematic, partial, reactive policies and programs developed based on divergent points of view. The aim of this manuscript is to describe how past and present understandings, narratives, ideologies and discourse of opioid use, have impacted policies over the course of the growing opioid crisis. Assessing the impact of policy is complex. It involves consideration of conceptual issues of what impacts policy change. In this manuscript we argue that the development of polices and initiatives regarding opioids, opioid use disorder and opioid agonist treatment in the last decade, have been more strongly associated with the evolution of ideas, narratives and discourses rather than research relating to opioids. We formulate our argument using a framework by Sumner, Crichton, Theobald, Zulu, and Parkhurs. We use examples from the Canadian context to outline our argument such as: the anti- drug legislation from the Canadian Federal Conservative government in 2007; the removal of OxyContin™ from the drug formulary in 2012; the rapid expansion of opioid agonist treatment beginning in the early 2000s, the unilateral decision made regarding fee cuts for physicians providing opioid agonist treatment in 2015; and the most recent implementation of a narcotics monitoring system, which are all closely linked with the shifts in public opinion and discourse at the time of which these policies and programs are implemented. We conclude with recommendations to consider a multifactorial response using evidence and stakeholder engagement to address the opioid crisis, rather than a reactive policy approach. We suggest that researchers have an important role in shaping future policy by reframing ideas through knowledge translation, formation of

  15. New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability.

    PubMed

    Cortese, Samuele; D'Acunto, Giulia; Konofal, Eric; Masi, Gabriele; Vitiello, Benedetto

    2017-02-01

    Psychostimulants are the recommended first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate is one of the most commonly used psychostimulants worldwide. Given that immediate-release and/or tablet/capsule formulations may decrease adherence to methylphenidate treatment, several drug companies have been developing novel long-acting and/or liquid/chewable formulations that may improve adherence as well as (for long-acting formulations) reduce abuse potential, decrease stigma associated with multiple administrations per day, and decrease the potential for adverse effects related to dosage peak. Here, we review the pharmacokinetics, efficacy, and tolerability of novel formulations of methylphenidate that are in development or have been approved by the US FDA or European Medicines Agency (EMA) in the last 5 years. We searched the websites of the FDA, EMA, ClinicalTrials.gov, and the pertinent drug companies. We also searched PubMed, Ovid databases (MEDLINE, PsycINFO, Embase + Embase classic), and ISI Web of Knowledge (Web of Science [Science Citation Index Expanded], Biological Abstracts, Biosis, Food Science and Technology Abstracts) to retrieve any additional pertinent information. We found data from trials for the following compounds: (1) methylphenidate extended-release oral suspension (MEROS; NWP06, Quillivant™); (2) methylphenidate extended-release chewable capsules (NWP09, QuilliChew ER™); (3) methylphenidate hydrochloride extended-release capsules (Aptensio XR™); (4) methylphenidate extended-release orally disintegrating tablets (XR-ODT; NT-0102, Cotempla™); (5) ORADUR technology (once-daily tamper-resistant formulation) methylphenidate sustained release (SR); and (6) methylphenidate modified-release (HLD-200; Bejorna™). Overall, available evidence based on trials suggests these compounds have good efficacy and tolerability. Future research should further explore the effectiveness and tolerability of

  16. 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).

    PubMed

    Pergolizzi, Joseph; Böger, Rainer H; Budd, Keith; Dahan, Albert; Erdine, Serdar; Hans, Guy; Kress, Hans-Georg; Langford, Richard; Likar, Rudolf; Raffa, Robert B; Sacerdote, Paola

    2008-01-01

    SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional

  17. Wireless tamper detection sensor and sensing system

    NASA Technical Reports Server (NTRS)

    Woodard, Stanley E. (Inventor); Taylor, Bryant D. (Inventor)

    2011-01-01

    A wireless tamper detection sensor is defined by a perforated electrical conductor. The conductor is shaped to form a geometric pattern between first and second ends thereof such that the conductor defines an open-circuit that can store and transfer electrical and magnetic energy. The conductor resonates in the presence of a time-varying magnetic field to generate a harmonic response. The harmonic response changes when the conductor experiences a change in its geometric pattern due to severing of the conductor along at least a portion of the perforations. A magnetic field response recorder is used to wirelessly transmit the time-varying magnetic field and wirelessly detecting the conductor's harmonic response.

  18. Past-year Prescription Drug Monitoring Program Opioid Prescriptions and Self-reported Opioid Use in an Emergency Department Population With Opioid Use Disorder.

    PubMed

    Hawk, Kathryn; D'Onofrio, Gail; Fiellin, David A; Chawarski, Marek C; O'Connor, Patrick G; Owens, Patricia H; Pantalon, Michael V; Bernstein, Steven L

    2017-11-22

    Despite increasing reliance on prescription drug monitoring programs (PDMPs) as a response to the opioid epidemic, the relationship between aberrant drug-related behaviors captured by the PDMP and opioid use disorder is incompletely understood. How PDMP data should guide emergency department (ED) assessment has not been studied. The objective was to evaluate a relationship between PDMP opioid prescription records and self-reported nonmedical opioid use of prescription opioids in a cohort of opioid-dependent ED patients enrolled in a treatment trial. PDMP opioid prescription records during 1 year prior to study enrollment on 329 adults meeting Diagnostic and Statistical Manual IV criteria for opioid dependence entering a randomized clinical trial in a large, urban ED were cross-tabulated with data on 30-day nonmedical prescription opioid use self-report. The association among these two types of data was assessed by the Goodman and Kruskal's gamma; a logistic regression was used to explore characteristics of participants who had PDMP record of opioid prescriptions. During 1 year prior to study enrollment, 118 of 329 (36%) patients had at least one opioid prescription (range = 1-51) in our states' PDMP. Patients who reported ≥15 of 30 days of nonmedical prescription opioid use were more likely to have at least four PDMP opioid prescriptions (20/38; 53%) than patients reporting 1 to 14 days (14/38, 37%) or zero days of nonmedical prescription opioid use (4/38, 11%; p = 0.002). Female sex and having health insurance were significantly more represented in the PDMP (p < 0.05 for both). PDMPs may be helpful in identifying patients with certain aberrant drug-related behavior, but are unable to detect many patients with opioid use disorder. The majority of ED patients with opioid use disorder were not captured by the PDMP, highlighting the importance of using additional methods such as screening and clinical history to identify opioid use disorders in ED patients and the

  19. Development of Damp-Heat Resistant Self-Primed EVA and Non-EVA Encapsulant Formulations at NREL

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pern, F. J.; Jorgensen, G. J.

    2005-11-01

    Self-primed ethylene-vinyl acetate (EVA) and non-EVA (PMG) encapsulant formulations were developed that have greater resistance to damp heat exposure at 85 deg C and 85% relative humidity (RH) (in terms of adhesion strength to glass substrates) than a commonly used commercial EVA product. The self-primed EVA formulations were developed on the basis of high-performing glass priming formulations that have previously proven to significantly enhance the adhesion strength of unprimed and primed EVA films on glass substrates during damp heat exposure. The PMG encapsulant formulations were based on an ethylene-methylacrylate copolymer containing glycidyl methacrylate.

  20. High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study.

    PubMed

    Fernandes, Kimberly; Martins, Diana; Juurlink, David; Mamdani, Muhammad; Paterson, J Michael; Spooner, Luke; Singh, Samantha; Gomes, Tara

    2016-01-01

    To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity. Interventional time-series analysis. Ontario, Canada, from 2003 to 2014. Ontario Drug Benefit (ODB) beneficiaries aged 15 to 64 years from 2003 to 2014. Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010) and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011). Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions. Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03) which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43). Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7%) over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68) or enactment of the NSAA (p-value = .59). Although the Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain led

  1. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

    PubMed

    Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

    2015-01-01

    A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

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

    PubMed

    Holder, Renee M; Rhee, Diane

    2016-03-01

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

  3. Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies.

    PubMed

    Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R

    2014-10-01

    Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.

  4. Single-molecular diodes based on opioid derivatives.

    PubMed

    Siqueira, M R S; Corrêa, S M; Gester, R M; Del Nero, J; Neto, A M J C

    2015-12-01

    We propose an efficient single-molecule rectifier based on a derivative of opioid. Electron transport properties are investigated within the non-equilibrium Green's function formalism combined with density functional theory. The analysis of the current-voltage characteristics indicates obvious diode-like behavior. While heroin presents rectification coefficient R>1, indicating preferential electronic current from electron-donating to electron-withdrawing, 3 and 6-acetylmorphine and morphine exhibit contrary behavior, R<1. Our calculations indicate that the simple inclusion of acetyl groups modulate a range of devices, which varies from simple rectifying to resonant-tunneling diodes. In particular, the rectification rations for heroin diodes show microampere electron current with a maximum of rectification (R=9.1) at very low bias voltage of ∼0.6 V and (R=14.3)∼1.8 V with resistance varying between 0.4 and 1.5 M Ω. Once most of the current single-molecule diodes usually rectifies in nanoampere, are not stable over 1.0 V and present electrical resistance around 10 M. Molecular devices based on opioid derivatives are promising in molecular electronics.

  5. Ensuring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction.

    PubMed

    Francoeur, Richard B

    2011-01-01

    This article proposes and develops novel components of community-oriented programs for creating and affording access to safe medication dispensing centers in existing retail pharmacies and in permanent or travelling pharmacy clinics that are guarded by assigned or off-duty police officers. Pharmacists at these centers would work with police, medical providers, social workers, hospital administrators, and other professionals in: planning and overseeing the safe storage of controlled substance medications in off-site community safe-deposit boxes; strengthening communication and cooperation with the prescribing medical provider; assisting the prescribing medical provider in patient monitoring (checking the state prescription registry, providing pill counts and urine samples); expanding access to lower-cost, and in some cases, abuse-resistant formulations of controlled substance medications; improving transportation access for underserved patients and caregivers to obtain prescriptions; and integrating community agencies and social networks as resources for patient support and monitoring. Novel components of two related community-oriented programs, which may be hosted outside of safe medication dispensing centers, are also suggested and described: (1) developing medication purchasing cooperatives (ie, to help patients, families, and health institutions afford the costs of medications, including tamper-or abuse-resistant/deterrent drug formulations); and (2) expanding the role of inner-city methadone maintenance treatment programs in palliative care (ie, to provide additional patient monitoring from a second treatment team focusing on narcotics addiction, and potentially, to serve as an untapped source of opioid medication for pain that is less subject to abuse, misuse, or diversion).

  6. Opioids for neuropathic pain.

    PubMed

    Katz, Nathaniel; Benoit, Christine

    2005-06-01

    Whether opioids are effective for neuropathic pain has been a matter of controversy for decades. Within limits, it is clear that opioids in general are effective for neuropathic pain. Furthermore, there is no evidence that opioids are any less effective for neuropathic pain than for non-neuropathic pain, no evidence that opioids are less effective for neuropathic pain than are other medications, and no evidence that one opioid is any more effective than another for neuropathic pain. It remains uncertain whether opioids are effective for central pain, although they may have a role. Although some patients appear to enjoy long-term benefits, most studies have been short-term. Opioids have an important role in the treatment of neuropathic pain; however, skillful opioid use balances the benefits with management of side effects and prevention and treatment of abuse and addiction.

  7. Prevalence of prescription opioid use disorder among chronic opioid therapy patients after health plan opioid dose and risk reduction initiatives.

    PubMed

    Von Korff, Michael; Walker, Rod L; Saunders, Kathleen; Shortreed, Susan M; Thakral, Manu; Parchman, Michael; Hansen, Ryan N; Ludman, Evette; Sherman, Karen J; Dublin, Sascha

    2017-08-01

    No studies have assessed the comparative effectiveness of guideline-recommended interventions to reduce risk of prescription opioid use disorder among chronic opioid therapy (COT) patients. We compared the prevalence of prescription opioid use disorder among COT patients from intervention clinics that had implemented opioid dose and risk reduction initiatives for more than 4 years relative to control clinics that had not. After a healthcare system in Washington State implemented interventions to reduce opioid dose and risks, we surveyed 1588 adult primary care COT patients to compare the prevalence of prescription opioid use disorder among COT patients from the intervention and control clinics. Intervention clinics managed COT patients at lower COT doses and with more consistent use of risk reduction practices. Control clinics cared for similar COT patients but prescribed higher opioid doses and used COT risk reduction practices inconsistently. Prescription opioid use disorder was assessed with the Psychiatric Research Interview for Substance and Mental Disorders. The prevalence of prescription opioid use disorder was 21.5% (95% CI=18.9% to 24.4%) among COT patients in the intervention clinics and 23.9% (95% CI=20.5% to 27.6%) among COT patients in the control clinics. The adjusted relative risk of prescription opioid use disorder was 1.08 (95% CI=0.89, 1.32) among the control clinic patients relative to the intervention clinic patients. Long-term implementation of opioid dose and risk reduction initiatives was not associated with lower rates of prescription opioid use disorder among prevalent COT patients. Extreme caution should be exercised by clinicians considering COT for patients with chronic non-cancer pain until benefits of this treatment and attendant risks are clarified. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis

    PubMed Central

    Regan, Patrick M.; Langford, T. Dianne; Khalili, Kamel

    2015-01-01

    Despite the identification and characterization of four opioid receptor subtypes and the genes from which they are encoded, pharmacological data does not conform to the predications of a four opioid receptor model. Instead, current studies of opioid pharmacology suggest the existence of additional receptor subtypes; however, no additional opioid receptor subtype has been identified to date. It is now understood that this discrepancy is due to the generation of multiple isoforms of opioid receptor subtypes. While several mechanisms are utilized to generate these isoforms, the primary mechanism involves alternative splicing of the pre-mRNA transcript. Extensive alternative splicing patterns for opioid receptors have since been identified and discrepancies in opioid pharmacology are now partially attributed to variable expression of these isoforms. Recent studies have been successful in characterizing the localization of these isoforms as well as their specificity in ligand binding; however, the regulation of opioid receptor splicing specificity is poorly characterized. Furthermore, the functional significance of individual receptor isoforms and the extent to which opioid- and/or HIV-mediated changes in the opioid receptor isoform profile contributes to altered opioid pharmacology or the well-known physiological role of opioids in the exacerbation of HIV neurocognitive dysfunction is unknown. As such, the current review details constitutive splicing mechanisms as well as the specific architecture of opioid receptor genes, transcripts, and receptors in order to highlight the current understanding of opioid receptor isoforms, potential mechanisms of their regulation and signaling, and their functional significance in both opioid pharmacology and HIV-associated neuropathology. PMID:26529364

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

    PubMed

    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 (Mg 2+ ), 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.

  10. Work Enabling Opioid Management.

    PubMed

    Lavin, Robert A; Kalia, Nimisha; Yuspeh, Larry; Barry, Jill A; Bernacki, Edward J; Tao, Xuguang Grant

    2017-08-01

    This study describes the relationship between opioid prescribing and ability to work. The opioid prescription patterns of 4994 claimants were studied. Three groups were constructed: 1) at least 3 consecutive months prescribed (chronic opioid therapy; COT); 2) less than 3 consecutive months prescribed (acute opioid therapy; AOT); and 3) no opioids prescribed. Variables included sex, age, daily morphine equivalent dose (MED), days opioids were prescribed, temporary total days (TTDs), and medical/indemnity/total costs. The COT versus AOT claimants had higher opioid costs ($8618 vs $94), longer TTD (636.2 vs 182.3), and average MED (66.8 vs 34.9). Only 2% of the COT cohort were not released to work. Fifty-seven percent of patients in the COT category (64 of 112) were released to work while still receiving opioids. COT does not preclude ability to work when prescribing within established guidelines.

  11. National Institute on Drug Abuse International Program: improving opioid use disorder treatment through international research training.

    PubMed

    Gust, Steven W; McCormally, Judy

    2018-07-01

    For more than 25 years, the National Institute on Drug Abuse (NIDA) has supported research-training programs, establishing a global research network and expanding the knowledge base on substance use disorders. International research to inform approaches to opioid addiction is particularly important and relevant to the United States, where opioid misuse, addiction, and overdose constitute an emerging public health crisis. This article summarizes the NIDA International Program and illustrates its impact by reviewing recent articles about treatment approaches for opioid use disorders (OUD). Studies in several countries have demonstrated the effectiveness of physician office-based opioid substitution therapies. Other research has demonstrated the effectiveness of different formulations and doses of the opioid antagonist naltrexone, as well as different approaches to providing naloxone to treat opioid overdose. Continuing research into implementation of evidence-based treatment in international settings with limited resources is applicable to US regions that face similar structural, legal, and fiscal constraints. The current review describes international research on OUD treatment and opioid overdose, most coauthored by former NIDA fellows. The findings from outside the United States have important implications for best practices domestically and in other countries that are experiencing increases in OUD prevalence and related overdose deaths.

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

    PubMed Central

    Peterson, S. J.; Laudenbach, M.; Baruffaldi, F.; Carroll, F. I.; Comer, S. D.; Navarro, H. A.; Langston, T. L.; Runyon, S. P.; Winston, S.; Pravetoni, M.; Pentel, P. R.

    2017-01-01

    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. PMID:29194445

  13. Distance traveled and frequency of interstate opioid dispensing in opioid shoppers and nonshoppers.

    PubMed

    Cepeda, M Soledad; Fife, Daniel; Yuan, Yingli; Mastrogiovanni, Greg

    2013-10-01

    Little is known about how far opioid shoppers travel or how often they cross state lines to fill their opioid prescriptions. This retrospective cohort study evaluated these measures for opioid shoppers and nonshoppers using a large U.S. prescription database. Patients with ≥3 opioid dispensings were followed for 18 months. A subject was considered a shopper when he or she filled overlapping opioid prescriptions written by >1 prescriber at ≥3 pharmacies. A heavy shopper had ≥5 shopping episodes. Outcomes assessed were distance traveled among pharmacies and number of states visited to fill opioid prescriptions. A total of 10,910,451 subjects were included; .7% developed any shopping behavior and their prescriptions accounted for 8.6% of all opioid dispensings. Shoppers and heavy shoppers were younger than the nonshoppers. Shoppers traveled a median of 83.8 miles, heavy shoppers 199.5 miles, and nonshoppers 0 miles. Almost 20% of shoppers or heavy shoppers, but only 4% of nonshoppers, visited >1 state. Shoppers traveled greater distances and more often crossed state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. Sharing of data among prescription-monitoring programs will likely strengthen those programs and may decrease shopping behavior. This study shows that opioid shoppers travel greater distances and more often cross state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. The findings support the need for data sharing among prescription-monitoring programs to deter opioid shopping behavior. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    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.

  15. Physician Introduction to Opioids for Pain Among Patients with Opioid Dependence and Depressive Symptoms

    PubMed Central

    Tsui, Judith I.; Herman, Debra S.; Kettavong, Malyna; Alford, Daniel; Anderson, Bradley J.; Stein, Michael D.

    2011-01-01

    This study determined the frequency of reporting being introduced to opioids by a physician among opioid dependent patients. Cross-sectional analyses were performed using baseline data from a cohort of opioid addicts seeking treatment with buprenorphine. The primary outcome was response to the question: “Who introduced you to opiates?” Covariates included sociodemographics, depression, pain, current and prior substance use. Of 140 participants, 29% reported that they had been introduced to opioids by a physician. Of those who were introduced to opioids by a physician, all indicated that they had initially used opioids for pain, versus only 11% of those who did not report being introduced to opioids by a physician (p<0.01). There was no difference in current pain (78% vs. 85%, p=0.29), however participants who were introduced to opioids by a physician were more likely to have chronic pain (63% vs. 43%, p=0.04). A substantial proportion of individuals with opioid dependence seeking treatment may have been introduced to opioids by a physician. PMID:20727704

  16. Delay discounting in opioid use disorder: Differences between heroin and prescription opioid users.

    PubMed

    Karakula, Sterling L; Weiss, Roger D; Griffin, Margaret L; Borges, Allison M; Bailey, Allen J; McHugh, R Kathryn

    2016-12-01

    Among those with opioid use disorder, heroin use is associated with poorer prognosis relative to use of prescription opioids alone. However, relatively little is known about distinguishing features between those who use heroin relative to those who use prescription opioids. In the present study we evaluated differences in delay discounting in those with opioid use disorder based on primary opioid of use. Delay discounting is associated with a range of negative outcomes and is an important therapeutic target in this population. Treatment-seeking adults with opioid dependence completed self-report measures including past-month opioid use and the Monetary Choice Questionnaire (Kirby and Marakovic, 1996; Kirby et al., 1999), a measure of delay discounting. Participants were divided into two groups based on whether they used any heroin in the past 30days or only prescription opioids, and delay discounting scores were compared between the groups. Group differences in sociodemographic or clinical variables were included in the analysis as covariates. Results from a forward stepwise linear regression indicated that heroin use was associated with significantly higher delay discounting (B=-0.99, SE B =0.34, t=-2.88, p=0.005), even when considering covariates. Adults with opioid dependence who exclusively used prescription opioids had lower delay discounting relative to those who used heroin. This finding contributes further to the literature suggesting that heroin use is associated with greater clinical severity among those with opioid use disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Opioid dependence

    PubMed Central

    2011-01-01

    Introduction Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens. PMID:21929827

  18. Opioid dependence.

    PubMed

    Praveen, K Thyarappa; Law, Fergus; O'Shea, Jacinta; Melichar, Jan

    2011-09-20

    Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens.

  19. Uniquely identifiable tamper-evident device using coupling between subwavelength gratings

    NASA Astrophysics Data System (ADS)

    Fievre, Ange Marie Patricia

    Reliability and sensitive information protection are critical aspects of integrated circuits. A novel technique using near-field evanescent wave coupling from two subwavelength gratings (SWGs), with the input laser source delivered through an optical fiber is presented for tamper evidence of electronic components. The first grating of the pair of coupled subwavelength gratings (CSWGs) was milled directly on the output facet of the silica fiber using focused ion beam (FIB) etching. The second grating was patterned using e-beam lithography and etched into a glass substrate using reactive ion etching (RIE). The slightest intrusion attempt would separate the CSWGs and eliminate near-field coupling between the gratings. Tampering, therefore, would become evident. Computer simulations guided the design for optimal operation of the security solution. The physical dimensions of the SWGs, i.e. period and thickness, were optimized, for a 650 nm illuminating wavelength. The optimal dimensions resulted in a 560 nm grating period for the first grating etched in the silica optical fiber and 420 nm for the second grating etched in borosilicate glass. The incident light beam had a half-width at half-maximum (HWHM) of at least 7 microm to allow discernible higher transmission orders, and a HWHM of 28 microm for minimum noise. The minimum number of individual grating lines present on the optical fiber facet was identified as 15 lines. Grating rotation due to the cylindrical geometry of the fiber resulted in a rotation of the far-field pattern, corresponding to the rotation angle of moire fringes. With the goal of later adding authentication to tamper evidence, the concept of CSWGs signature was also modeled by introducing random and planned variations in the glass grating. The fiber was placed on a stage supported by a nanomanipulator, which permitted three-dimensional displacement while maintaining the fiber tip normal to the surface of the glass substrate. A 650 nm diode laser was

  20. Development of a new esomeprazole delayed release gastro-resistant pellet formulation with improved storage stability.

    PubMed

    Barmpalexis, Panagiotis; Grypioti, Agni

    2018-06-01

    This study describes the development of a new esomeprazole (ESO) delayed release gastro-resistant formulation with improved storage stability. A three-step (drug-, sub(seal)- and enteric-) coating process was employed with the aid of a fluid bed coater. Several formulation factors (namely, size and quantity of starting non-pareil sugar spheres, binder quantity during drug-layering, sub(seal)-coating polymer type, and quantity and enteric coating quantity) were evaluated and the whole process was modeled with the aid of feed-forward back-propagation artificial neural networks (ANNs). Results showed that the selection of small-sized starting spheres (45/60 mesh size) leads to pellet agglomeration, while as sub(seal)-coating weight gain increases a reduction in ESO dissolution rate is observed. The enteric-coating applied (Eudragit L30D-55) showed good gastro-resistant performance in both 0.1 N HCl and pH 4.5 media, while immediate release profiles with more than 85% of ESO being released in less than 30 min were obtained. The effect of cellulose-based sub(seal)-coating polymers, (namely, hydroxypropyl cellulose and hydroxypropylmethyl cellulose) on formulation's storage stability at 40 ± 2 °C/75 ± 5%RH indicated that only hydroxypropylmethyl cellulose was able to stabilize ESO delayed-release formulations in terms of assay, dissolution, impurities, and gastro-resistance performance. Finally, scanning electron microscopy (SEM) analysis revealed smooth and homogeneous external surface/coating layers in all three levels (drug-, sub(seal)-, and enteric- coating), while x-ray diffraction showed no polymorphic transformations.

  1. Opioid intoxication

    MedlinePlus

    ... treat severe cough or diarrhea. The illegal drug heroin is also an opioid. When abused , opioids cause ... Abuse. What are the medical complications of chronic heroin use? National Institute on Drug Abuse Web site. ...

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

    PubMed Central

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

    2016-01-01

    Background 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. Methods 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 21 hours 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. Results 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. Conclusion 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. PMID:27234658

  3. Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors

    PubMed Central

    2013-01-01

    Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed the literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant opioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also evaluated. We postulate that the sex differences partly originated from the crosstalk among the estrogen and opioid receptors when stimulated by the exogenous opioids, possibly through common secondary messengers and the downstream gene transcriptional regulators. PMID:24010861

  4. Security protection of DICOM medical images using dual-layer reversible watermarking with tamper detection capability.

    PubMed

    Tan, Chun Kiat; Ng, Jason Changwei; Xu, Xiaotian; Poh, Chueh Loo; Guan, Yong Liang; Sheah, Kenneth

    2011-06-01

    Teleradiology applications and universal availability of patient records using web-based technology are rapidly gaining importance. Consequently, digital medical image security has become an important issue when images and their pertinent patient information are transmitted across public networks, such as the Internet. Health mandates such as the Health Insurance Portability and Accountability Act require healthcare providers to adhere to security measures in order to protect sensitive patient information. This paper presents a fully reversible, dual-layer watermarking scheme with tamper detection capability for medical images. The scheme utilizes concepts of public-key cryptography and reversible data-hiding technique. The scheme was tested using medical images in DICOM format. The results show that the scheme is able to ensure image authenticity and integrity, and to locate tampered regions in the images.

  5. Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain

    PubMed Central

    Wachholtz, Amy; Gonzalez, Gerardo

    2014-01-01

    Introduction 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. Method 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. Results A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (Log rank=15.50; p<.001) and tolerance (Log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p’s<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p’s<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns). Conclusion Among individuals with a history of prolonged 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. PMID:25456326

  6. Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

    PubMed

    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 < .001) and tolerance (log rank = 20.11; p < .001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's < .01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p < .05), with the highest tolerance found among opioid naïve control group participants (p's < .001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R = .37; p < .05); but duration of abstinence did not alter sensitivity (ns). Among individuals with a history of prolonged 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.

  7. Long-Term Opioid Therapy Reconsidered

    PubMed Central

    Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A.; Chou, Roger

    2012-01-01

    In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment. PMID:21893626

  8. Opioid Utilization and Opioid-Related Adverse Events in Non-Surgical Patients in U.S. Hospitals

    PubMed Central

    Herzig, Shoshana J.; Rothberg, Michael B.; Cheung, Michael; Ngo, Long H.; Marcantonio, Edward R.

    2014-01-01

    Background Recent studies in the outpatient setting have demonstrated high rates of opioid prescribing and overdose-related deaths. Prescribing practices in hospitalized patients are unexamined. Objective To investigate patterns and predictors of opioid utilization in non-surgical admissions to U.S. hospitals, variation in use, and the association between hospital-level use and rates of severe opioid-related adverse events. Design, Setting, and Patients Adult non-surgical admissions to 286 U.S. hospitals. Measurements Opioid exposure and severe opioid-related adverse events during hospitalization, defined using hospital charges and ICD-9-CM codes. Results Of 1.14 million admissions, opioids were used in 51%. The mean ± s.d. daily dose received in oral morphine equivalents (OME) was 68 ± 185 mg; 23% of exposed received a total daily dose of ≥ 100 mg OME. Opioid prescribing rates ranged from 5% in the lowest to 72% in the highest prescribing hospital (mean 51% ± 10%). After adjusting for patient characteristics, the adjusted opioid prescribing rates ranged from 33–64% (mean 50% ± s.d. 4%). Among exposed, 0.97% experienced severe opioid-related adverse events. Hospitals with higher opioid prescribing rates had higher adjusted relative risk of a severe opioid-related adverse event per patient exposed (RR 1.23 [1.14–1.33] for highest compared to lowest prescribing quartile). Conclusions The majority of hospitalized non-surgical patients were exposed to opioids, often at high doses. Hospitals that used opioids most frequently had increased adjusted risk of a severe opioid-related adverse event per patient exposed. Interventions to standardize and enhance the safety of opioid prescribing in hospitalized patients should be investigated. PMID:24227700

  9. Strategies to Prevent Opioid Misuse, Abuse, and Diversion That May Also Reduce the Associated Costs

    PubMed Central

    Hahn, Kathryn L.

    2011-01-01

    Background The use of prescription opioid drugs has the potential to lead to patient abuse of these medications, addiction, and diversion. Such an abuse is associated with increased costs because of excessive healthcare utilization. Finding ways to minimize the risk for abuse and addiction can enhance patient outcomes and reduce costs to patients and to payers. Objective To review current strategies that may reduce the risk for misuse and abuse of opioid medications, which in turn can enhance patient outcomes and lower costs to health insurers and patients. Discussion Implementing approaches that will encourage the use of safe practices (universal precautions) in pain management by providers can reduce the risk for abuse and misuse associated with chronic pain medications, especially opioids. These approaches include, but are not limited to, extensive physician and patient education regarding these medications and their associated risks for abuse; the development of prescription monitoring programs to detect physician or pharmacy shopping; the detection of inappropriate prescribing and medical errors; the use of physician-patient contracts concerning opioid treatment; the requirement of presenting a photo identification to pick up an opioid prescription at the pharmacy; urine drug toxicology screening; provisions for safe disposal of unused opioids; referrals to pain and addiction specialists; and potentially encouraging the use of opioid formulations aimed at reducing abuse. Conclusion Supporting such approaches by health insurers and educating providers and patients on the risks associated with chronic pain medications can help minimize the risk of prescription opioid abuse, addiction, and diversion; reduce health services utilization associated with opioid abuse; improve patient outcomes; and reduce overall costs. PMID:25126342

  10. Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart

    PubMed Central

    Headrick, John P; See Hoe, Louise E; Du Toit, Eugene F; Peart, Jason N

    2015-01-01

    Ischaemic heart disease (IHD) remains a major cause of morbidity/mortality globally, firmly established in Westernized or ‘developed’ countries and rising in prevalence in developing nations. Thus, cardioprotective therapies to limit myocardial damage with associated ischaemia–reperfusion (I–R), during infarction or surgical ischaemia, is a very important, although still elusive, clinical goal. The opioid receptor system, encompassing the δ (vas deferens), κ (ketocyclazocine) and μ (morphine) opioid receptors and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears as a logical candidate for such exploitation. This regulatory system may orchestrate organism and organ responses to stress, induces mammalian hibernation and associated metabolic protection, triggers powerful adaptive stress resistance in response to ischaemia/hypoxia (preconditioning), and mediates cardiac benefit stemming from physical activity. In addition to direct myocardial actions, central opioid receptor signalling may also enhance the ability of the heart to withstand I–R injury. The δ- and κ-opioid receptors are strongly implicated in cardioprotection across models and species (including anti-infarct and anti-arrhythmic actions), with mixed evidence for μ opioid receptor-dependent protection in animal and human tissues. A small number of clinical trials have provided evidence of cardiac benefit from morphine or remifentanil in cardiopulmonary bypass or coronary angioplasty patients, although further trials of subtype-specific opioid receptor agonists are needed. The precise roles and utility of this GPCR family in healthy and diseased human myocardium, and in mediating central and peripheral survival responses, warrant further investigation, as do the putative negative influences of ageing, IHD co-morbidities, and relevant drugs on opioid receptor signalling and protective responses. PMID:25521834

  11. On subclasses of opioid analgesics.

    PubMed

    Raffa, Robert B

    2014-12-01

    The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids. A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given. By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids. An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical

  12. Combination of intrathecal opioids with bupivacaine attenuates opioid dose escalation in chronic noncancer pain patients.

    PubMed

    Veizi, I Elias; Hayek, Salim M; Narouze, Samer; Pope, Jason E; Mekhail, Nagy

    2011-10-01

    The purpose of this study was to examine the effect of intrathecal (IT) coadministration of bupivacaine with opioids during the initial phase of opioid titration and up to 1 year after implantation of an IT drug delivery system (IDDS). The study was designed as a retrospective study. OUTCOMES ANALYZED: The outcomes analyzed for this study were pain relief, oral opioid consumption, IT opioid, and bupivacaine dosage. METHODS AND PATIENT POPULATION: The patient population for this study were consecutively implanted patients over a period of 6 years in a tertiary single center with multiple practitioners. In this retrospective study, 126 consecutive noncancer intractable pain patients were implanted with IDDS and initiated with an IT opioid (O) as a single medication or an IT opioid and bupivacaine (O + B). Pain intensity, amount of oral opioids, dose, rate, and concentration of IT opioids and bupivacaine, and number and type of IT medication used were recorded at preimplant, implant, and at 3, 6, and 12 months postimplant. The intervention used for the study was the IT delivery device implant. Significant reduction in pain intensity was observed in both groups at 12 months postimplant (O group: baseline 7.42 ± 2.1 to 5.85 ± 2.8 [n = 72, P < 0.001]; O + B group 7.35 ± 2 to 5.03 ± 2.4 (n = 54; P < 0.001]). The combination of opioids with bupivacaine from the start of IT infusion treatment resulted in a reduced progression of opioid dose escalation in comparison to patients started with opioids (O group). The rate of increase of IT opioids in the O group at 12 months was 535 ± 180%, whereas in the O + B, the dose increase was significantly lower at 185 ± 85% (P < 0.004). In both groups, there was a statistically significant decrease in oral opioid consumption compared with preimplant doses. Concomitant initial coadministration of IT bupivacaine with opioids blunts the rate of IT opioid dose escalation during the first year after implant of an IDDS. More studies are

  13. Using Opioids Safely After Surgery

    MedlinePlus

    ... Adult , Geriatric Using Opioids Safely After Surgery Using Opioids Safely After Surgery Stick to the lowest dose ... need opioid pain medicine. If your doctor says opioids aren’t necessary. If your doctor thinks you ...

  14. Opioids and Opioid Maintenance Therapies: Their Impact on Monocyte-Mediated HIV Neuropathogenesis

    PubMed Central

    Jaureguiberry-Bravo, Matias; Wilson, Rebecca; Carvallo, Loreto; Berman, Joan W.

    2017-01-01

    Background HIV-1 enters the CNS within two weeks after peripheral infection and results in chronic neuroinflammation that leads to HIV associated neurocognitive disorders (HAND) in more than 50% of infected people. HIV enters the CNS by transmigration of infected monocytes across the blood brain barrier. Intravenous drug abuse is a major risk factor for HIV-1 infection, and opioids have been shown to alter the progression and severity of HAND. Methadone and buprenorphine are opioid derivates that are used as opioid maintenance therapies. They are commonly used to treat opioid dependency in HIV infected substance abusers, but their effects on monocyte migration relevant to the development of cognitive impairment are not well characterized. Conclusion Here, we will discuss the effects of opioids and opioid maintenance therapies on the inflammatory functions of monocytes and macrophages that are related to the development of neuroinflammation in the context of HIV infection. PMID:27009099

  15. Opioid Abuse and Addiction

    MedlinePlus

    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, ...

  16. Understanding the Opioid Epidemic

    MedlinePlus

    ... Opioid Overdose Deaths Preventing Overdose Deaths Opioid Overdose Deaths From 1999-2016, more than 350,000 people ... counterfeit pills, and cocaine. 1,3 Preventing Overdose Deaths Combatting the Opioid Overdose Epidemic CDC is committed ...

  17. Craving and subsequent opioid use among opioid dependent patients who initiate treatment with buprenorphine

    PubMed Central

    Tsui, Judith I.; Anderson, Bradley J.; Strong, David R.; Stein, Michael D.

    2016-01-01

    Background Few studies have directly assessed associations between craving and subsequent opioid use among treated patients. Our objective was to prospectively evaluate the relative utility of two craving questionnaires to predict opioid use among opioid dependent patients in treatment. Method Opioid dependent patients (n=147) initiating buprenorphine treatment were assessed for three months. Craving was measured using: 1) the Desires for Drug Questionnaire (DDQ) and 2) the Penn Alcohol-Craving Scale adapted for opioid craving (PCS) for this study. Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use after adjusting for gender, age, ethnicity, education, opioid of choice, frequency of use, pain and depression. In these analyses craving assessed at time t was entered as a time-varying predictor of opioid use at time t+1. Results In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p < .01). The odds of opioid use at the subsequent follow-up assessment increased significantly as DDQ desire and intention scores increased (OR = 1.25, 95%CI 1.03; 1.51, p< .05), but was not associated significantly with DDQ negative reinforcement (OR = 1.01, 95%CI 0.88; 1.17, p > .05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > .05) scores. Conclusion Self-reported craving for opioids was associated with subsequent lapse to opioid use among a cohort of patients treated with buprenorphine. PMID:24521036

  18. Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic.

    PubMed

    Fairbairn, Nadia; Coffin, Phillip O; Walley, Alexander Y

    2017-08-01

    Community-based overdose prevention programs first emerged in the 1990's and are now the leading public health intervention for overdose. Key elements of these programs are overdose education and naloxone distribution to people who use opioids and their social networks. We review the evolution of naloxone programming through the heroin overdose era of the 1990's, the prescription opioid era of the 2000's, and the current overdose crisis stemming from the synthetic opioid era of illicitly manufactured fentanyl and its analogues in the 2010's. We present current challenges arising in this new era of synthetic opioids, including variable potency of illicit drugs due to erratic adulteration of the drug supply with synthetic opioids, potentially changing efficacy of standard naloxone formulations for overdose rescue, potentially shorter overdose response time, and reports of fentanyl exposure among people who use drugs but are opioid naïve. Future directions for adapting naloxone programming to the dynamic opioid epidemic are proposed, including scale-up to new venues and social networks, new standards for post-overdose care, expansion of supervised drug consumption services, and integration of novel technologies to detect overdose and deliver naloxone. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Opioid dependence - management in general practice.

    PubMed

    Frei, Matthew

    2010-08-01

    Addiction to opioids, or opioid dependence, encompasses the biopsychosocial dysfunction seen in illicit heroin injectors, as well as aberrant behaviours in patients prescribed opioids for chronic nonmalignant pain. To outline the management of opioid dependence using opioid pharmacotherapy as part of a comprehensive chronic illness management strategy. The same principles and skills general practitioners employ in chronic illness management underpin the care of patients with opioid dependence. Opioid pharmacotherapy, with the substitution medications methadone and buprenorphine, is an effective management of opioid dependence. Training and regulatory requirements for prescribing opioid pharmacotherapies vary between jurisdictions, but this treatment should be within the scope of most Australian GPs.

  20. Opioid Attentional Bias and Cue-Elicited Craving Predict Future Risk of Prescription Opioid Misuse Among Chronic Pain Patients*

    PubMed Central

    Garland, Eric L.; Howard, Matthew O.

    2014-01-01

    Background Some chronic pain patients receiving long-term opioid analgesic pharmacotherapy are at risk for misusing opioids. Like other addictive behaviors, risk of opioid misuse may be signaled by an attentional bias (AB) towards drug-related cues. The purpose of this study was to examine opioid AB as a potential predictor of opioid misuse among chronic pain patients following behavioral treatment. Methods Chronic pain patients taking long-term opioid analgesics (N = 47) completed a dot probe task designed to assess opioid AB, as well as self-report measures of opioid misuse and pain severity, and then participated in behavioral treatment. Regression analyses examined opioid AB and cue-elicited craving as predictors of opioid misuse at 3-months posttreatment follow-up. Results Patients who scored high on a measure of opioid misuse risk following treatment exhibited significantly greater opioid AB scores than patients at low risk for opioid misuse. Opioid AB for 200 ms cues and cue-elicited craving significantly predicted opioid misuse risk 20 weeks later, even after controlling for pre-treatment opioid dependence diagnosis, opioid misuse, and pain severity (Model R2 = .50). Conclusion Biased initial attentional orienting to prescription opioid cues and cue-elicited craving may reliably signal future opioid misuse risk following treatment. These measures may therefore provide potential prognostic indicators of treatment outcome. PMID:25282309

  1. Probuphine® (buprenorphine implant): a promising candidate in opioid dependence

    PubMed Central

    Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

    2016-01-01

    Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits. PMID:28348732

  2. Probuphine® (buprenorphine implant): a promising candidate in opioid dependence.

    PubMed

    Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

    2017-03-01

    Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits.

  3. Opioids in Preclinical and Clinical Trials

    NASA Astrophysics Data System (ADS)

    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].

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

    PubMed

    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.

  5. Impact of a new palliative care consultation team on opioid prescription in a University Hospital.

    PubMed

    Centeno, Carlos; Portela, María Angustias; Noguera, Antonio; Idoate, Antonio; Rubiales, Alvaro Sanz

    2009-01-16

    There are no validated measuring tools to gauge the effectiveness of a Hospital Palliative Care Consultation Team (PCCT). One way would be to consider its effect on the consumption of opioids expressed in total amounts and different formulations administered. We perform this study to evaluate the impact of a hospital PCCT on the trends of opioid prescription in a University Hospital. A seven year retrospective study on opioid prescription was carried out in the Clínica Universidad de Navarra. The period includes three years before and three years after the PCCT was implemented. Prescription was analysed calculating yearly the Defined Daily Dose (DDD) adjusted to 1000 hospital stays (DDD/1000HS). Indicators considered were the proportion of patients treated using opioids compared to the total estimated in need of treatment (rate of effectiveness) and the proportion of patients potentially requiring opioids but not treated who were incorporated into the treatment group (rate of improvement). From 2001 to 2007, total opioid prescription was low in non-oncology Departments (range: 69-110 DDD/1000HS) while parenteral morphine and fentanyl did not register any changes. In the same period of time, total opioid prescription increased in the Oncology Department from 240 to 558 DDD/1000HS. The rate of effectiveness in the three years prior to the implantation of the consultation team was 64% and in the three following years rose to 87%. The rate of improvement prior to the palliative care consultation team was 43% and in the three following years was 64%. A change in opioid prescription was registered after the implementation of the PCCT resulting in an increase in the prescription of parenteral morphine and methadone and a decrease in transdermal fentanyl. Implementation of a PCCT in a University Hospital is associated with a higher and more adequate use of opioids.

  6. Impact of a new palliative care consultation team on opioid prescription in a University Hospital

    PubMed Central

    Centeno, Carlos; Portela, María Angustias; Noguera, Antonio; Idoate, Antonio; Rubiales, Álvaro Sanz

    2009-01-01

    Background There are no validated measuring tools to gauge the effectiveness of a Hospital Palliative Care Consultation Team (PCCT). One way would be to consider its effect on the consumption of opioids expressed in total amounts and different formulations administered. We perform this study to evaluate the impact of a hospital PCCT on the trends of opioid prescription in a University Hospital. Methods A seven year retrospective study on opioid prescription was carried out in the Clínica Universidad de Navarra. The period includes three years before and three years after the PCCT was implemented. Prescription was analysed calculating yearly the Defined Daily Dose (DDD) adjusted to 1000 hospital stays (DDD/1000HS). Indicators considered were the proportion of patients treated using opioids compared to the total estimated in need of treatment (rate of effectiveness) and the proportion of patients potentially requiring opioids but not treated who were incorporated into the treatment group (rate of improvement). Results From 2001 to 2007, total opioid prescription was low in non-oncology Departments (range: 69–110 DDD/1000HS) while parenteral morphine and fentanyl did not register any changes. In the same period of time, total opioid prescription increased in the Oncology Department from 240 to 558 DDD/1000HS. The rate of effectiveness in the three years prior to the implantation of the consultation team was 64% and in the three following years rose to 87%. The rate of improvement prior to the palliative care consultation team was 43% and in the three following years was 64%. A change in opioid prescription was registered after the implementation of the PCCT resulting in an increase in the prescription of parenteral morphine and methadone and a decrease in transdermal fentanyl. Conclusion Implementation of a PCCT in a University Hospital is associated with a higher and more adequate use of opioids. PMID:19149875

  7. Risk of Prolonged Opioid Use Among Opioid-Naïve Patients Following Common Hand Surgery Procedures.

    PubMed

    Johnson, Shepard P; Chung, Kevin C; Zhong, Lin; Shauver, Melissa J; Engelsbe, Michael J; Brummett, Chad; Waljee, Jennifer F

    2016-10-01

    To evaluate prolonged opioid use in opioid-naïve patients after common hand surgery procedures in the United States. We studied insurance claims from the Truven MarketScan databases to identify opioid-naïve adult patients (no opioid exposure 11 months before the perioperative period) who underwent an elective (carpal tunnel release, carpometacarpal arthroplasty/arthrodesis, cubital tunnel release, or trigger finger release) or trauma-related (closed distal radius fracture fixation, flexor tendon repair, metacarpal fracture fixation, or phalangeal fracture fixation) hand surgery procedure between 2010 and 2012 (N = 77,573 patients). Patients were observed for 6 months to determine the number, timing, duration, and oral morphine equivalent dosage of postoperative opioid prescriptions. We assessed prolonged postoperative opioid use, defined as patients who filled a perioperative opioid prescription followed by a prescription between 90 and 180 days after surgery, and evaluated associated risk factors using multivariable logistic regression. In this cohort, 59,725 opioid-naïve patients (77%) filled a perioperative opioid prescription. Of these, 13% of patients continued to fill prescriptions between 90 and 180 days after surgery. Elective surgery patients were more likely to continue to fill opioid prescriptions after 90 days compared with trauma patients (13.5% vs 10.5%). Younger age, female gender, lower income, comprehensive insurance, higher Elixhauser comorbidity index, mental health disorders, and tobacco dependence or abuse were associated with prolonged opioid use. Approximately 13% of opioid-naïve patients continue to fill opioid prescriptions after hand surgery procedures 90 days after surgery. Preoperative interventions centered on opioid alternatives and early cessation, particularly among patients at risk for long-term use, is critical to addressing the prescription opioid crisis in the United States. The current national opioid use epidemic requires

  8. Opioid system and human emotions.

    PubMed

    Nummenmaa, Lauri; Tuominen, Lauri

    2017-04-10

    Emotions are states of vigilant readiness that guide human and animal behaviour during survival-salient situations. Categorical models of emotions posit neurally and physiologically distinct basic human emotions (anger, fear, disgust, happiness, sadness and surprise) that govern different survival functions. Opioid receptors are expressed abundantly in the mammalian emotion circuit, and the opioid system modulates a variety of functions related to arousal and motivation. Yet, its specific contribution to different basic emotions has remained poorly understood. Here, we review how the endogenous opioid system and particularly the μ receptor contribute to emotional processing in humans. Activation of the endogenous opioid system is consistently associated with both pleasant and unpleasant emotions. In general, exogenous opioid agonists facilitate approach-oriented emotions (anger, pleasure) and inhibit avoidance-oriented emotions (fear, sadness). Opioids also modulate social bonding and affiliative behaviour, and prolonged opioid abuse may render both social bonding and emotion recognition circuits dysfunctional. However, there is no clear evidence that the opioid system is able to affect the emotions associated with surprise and disgust. Taken together, the opioid systems contribute to a wide array of positive and negative emotions through their general ability to modulate the approach versus avoidance motivation associated with specific emotions. Because of the protective effects of opioid system-mediated prosociality and positive mood, the opioid system may constitute an important factor contributing to psychological and psychosomatic resilience. © 2017 The British Pharmacological Society.

  9. Co-administration of delta- and mu-opioid receptor agonists promotes peripheral opioid receptor function

    PubMed Central

    Schramm, Cicely L.; Honda, Christopher N.

    2010-01-01

    Enhancement of peripheral opioid analgesia following tissue injury or inflammation in animal models is well-documented, but clinical results of peripheral opioid therapy remain inconsistent. Previous studies in the central nervous system have shown that co-administration of μ- and δ-opioid receptor agonists can enhance analgesic outcomes; however, less is known about the functional consequences of opioid receptor interactions in the periphery. The present study examines the effects of intraplantar injection of the μ- and δ-opioid receptor agonists, morphine and deltorphin, alone and in combination on behavioral tests of nociception in naïve rats and on potassium-evoked release of CGRP from sciatic nerves of naïve rats. Neither drug alone affected nociceptive behaviors or CGRP release. Two separate measures of mechanical nociceptive sensitivity remained unchanged after co-administration of the two drugs. In contrast, when deltorphin was co-injected with morphine, dose-dependent and peripherally-restricted increases in paw withdrawal latencies to radiant heat were observed. Similarly, concentration-dependent inhibition of CGRP release was observed when deltorphin and morphine were administered in sequence prior to potassium stimulation. However, no inhibition was observed when morphine was administered prior to deltorphin. All combined opioid effects were blocked by co-application of antagonists. Deltorphin exposure also enhanced the in vivo and in vitro effects of another μ-opioid receptor agonist, DAMGO. Together, these results suggest that under normal conditions, δ-opioid receptor agonists enhance the effect of μ-opioid receptor agonists in the periphery, and local co-administration of δ- and μ-opioid receptor agonists may improve results of peripheral opioid therapy for the treatment of pain. PMID:20970925

  10. Opioid Use Disorders

    PubMed Central

    Sharma, Bikash; Bruner, Ann; Barnett, Gabrielle; Fishman, Marc

    2016-01-01

    Opioid use and addiction in adolescents and young adults, including heroin and non-medical use of prescription opioids, is a serious and growing health problem of epidemic proportions. Opioid use has devastating consequences for youth and their families, including: progression to full addiction, severe psychosocial impairment, HCV and HIV transmission with injection use, exacerbation of co-occurring psychiatric disorders, overdose, and death. This chapter will provide an overview of opioid use disorders (OUDs) in youth, including: etiologic factors, epidemiology, consequences, clinical presentation and course, assessment and diagnosis, overdose, detoxification, and treatment. Opioid overdose is a life-threatening emergency. Respiratory depression should be treated with naloxone, and respiratory support if necessary. Overdose should always be utilized as an opportunity to initiate addiction treatment. Opioid withdrawal management (detoxification) is often a necessary, but never sufficient, component of treatment for OUDs. Medications used in the treatment of withdrawal may include buprenorphine, clonidine and others for relief of symptoms. Treatment for OUDs is effective but treatment capacity is alarmingly limited and under-developed. Although there is a limited evidence base for youth specific treatment, emerging consensus supports the incorporation of relapse prevention medications such as buprenorphine and extended release naltrexone into comprehensive psychosocial treatment including counseling and family involvement. PMID:27338968

  11. Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone.

    PubMed

    Kelty, Erin; Hulse, Gary

    2017-08-01

    Illicit opioid use is associated with high rates of fatal and non-fatal opioid overdose. This study aims to compare rates of fatal and serious but non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone, and to identify risk factors for fatal opioid overdose. Opioid dependent patients treated with methadone (n=3515), buprenorphine (n=3250) or implant naltrexone (n=1461) in Western Australia for the first time between 2001 and 2010, were matched against state mortality and hospital data. Rates of fatal and non-fatal serious opioid overdoses were calculated and compared for the three treatments. Risk factors associated with fatal opioid overdose were examined using multivariate cox proportional hazard models. No significant difference was observed between the three groups in terms of crude rates of fatal or non-fatal opioid overdoses. During the first 28days of treatment, rates of non-fatal opioid overdose were high in all three groups, as were fatal opioid overdoses in patients treated with methadone. However, no fatal opioid overdoses were observed in buprenorphine or naltrexone patients during this period. Following the first 28 days, buprenorphine was shown to be protective, particularly in terms of non-fatal opioid overdoses. After the cessation of treatment, rates of fatal and non-fatal opioid overdoses were similar between the groups, with the exception of lower rates of non-fatal opioid overdose in the naltrexone treated patients compared with the methadone treated patients. After the commencement of treatment, gender, and hospitalisations with a diagnosis of opioid poisoning, cardiovascular or mental health problems were significant predictors of subsequent fatal opioid overdose. Rates of fatal and non-fatal opioid overdose were not significantly different in patients treated with methadone, buprenorphine or implant naltrexone. Gender and prior cause-specific hospitalisations can be used to identify

  12. Genetics of Opioid Dependence: A Review of the Genetic Contribution to Opioid Dependence

    PubMed Central

    Mistry, Chetna J; Bawor, Monica; Desai, Dipika; Marsh, David C; Samaan, Zainab

    2014-01-01

    This narrative review aims to provide an overview of the impact of opioid dependence and the contribution of genetics to opioid dependence. Epidemiological data demonstrate that opioid dependence is a global trend with far-reaching effects on the social, economic, and health care systems. A review of classical genetic studies of opioid use suggests significant heritability of drug use behavior, however the evidence from molecular genetic studies is inconclusive. Nonetheless, certain genetic variants are important to consider given their role in the pathophysiology of addictive behavior. We undertook a literature review to identify the current state of knowledge regarding the role of genes in opioid dependence. Determining the association of genetic markers could change the current understanding of the various factors contributing to opioid dependence and therefore may improve recognition of individuals at risk for the disorder and prevention and treatment strategies. PMID:25242908

  13. Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects.

    PubMed

    Yuan, Chun-Su

    2007-06-01

    To review the mechanisms of action of methylnaltrexone and its effects on opioid bowel dysfunction, as well as its effects on other opioid-induced adverse effects (ADEs), and its potential roles in clinical practice. A literature search using the MEDLINE and Cochrane Collaboration databases for articles published between 1966 and March 2007 was performed. Additional data sources were obtained from manual searches of recent journal articles, book chapters, and monographs. An updated literature search showed no additional publications. Abstracts and original preclinical and clinical research reports published in the English language were identified for review. Review articles, commentaries, and news reports of this compound were excluded. Literature related to opioids, opioid receptors, opioid antagonists, methylnaltrexone, opioid-induced bowel dysfunction, constipation, nausea, and vomiting was evaluated and selected based on consideration of the support shown for the proof of concept, mechanistic findings, and timeliness. Fifty-eight original articles from preclinical studies and clinical trials using methylnaltrexone were identified. Pharmacologic action, benefits, and ADEs of methylnaltrexone were reviewed, with a focus on its effects on bowel dysfunction after opioids. Emphases were placed on its receptor binding activities and therapeutically relevant sites of action (peripheral vs central), in which peripheral opioid receptors in the body contribute to physiological and drug-induced effects. Morphine and related opioids are associated with a number of limiting ADEs, including opioid-induced bowel dysfunction. Methylnaltrexone, a quaternary derivative of naltrexone, blocks peripheral effects of opioids while sparing central analgesic effects. It is currently under late-stage clinical investigation for the treatment of opioid-induced constipation in patients with advanced illness. Reported results showed the drug to be generally well-tolerated. The rapid

  14. Association of an Opioid Standard of Practice Intervention With Intravenous Opioid Exposure in Hospitalized Patients.

    PubMed

    Ackerman, Adam L; O'Connor, Patrick G; Doyle, Deirdre L; Marranca, Sheyla M; Haight, Carolyn L; Day, Christine E; Fogerty, Robert L

    2018-06-01

    Opioids are commonly used to treat pain in hospitalized patients; however, intravenous administration carries an increased risk of adverse effects compared with oral administration. The subcutaneous route is an effective method of opioid delivery with favorable pharmacokinetics. To assess an intervention to reduce intravenous opioid use, total parenteral opioid exposure, and the rate of patients administered parenteral opioids. A pilot study was conducted in an adult general medical unit in an urban academic medical center. Attending physicians, nurse practitioners, and physician assistants who prescribed drugs were the participants. Use of opioids was compared between a 6-month control period and 3 months following education for the prescribers on opioid routes of administration. Adoption of a local opioid standard of practice, preferring the oral and subcutaneous routes over intravenous administration, and education for prescribers and nursing staff on awareness of the subcutaneous route was implemented. The primary outcome was a reduction in intravenous doses administered per patient-day. Secondary measures included total parenteral and overall opioid doses per patient-day, parenteral and overall opioid exposure per patient-day, and daily rate of patients receiving parenteral opioids. Pain scores were measured on a standard 0- to 10-point Likert scale over the first 5 days of hospitalization. The control period included 4500 patient-days, and the intervention period included 2459 patient-days. Of 127 patients in the intervention group, 59 (46.5%) were men; mean (SD) age was 57.6 (18.5) years. Intravenous opioid doses were reduced by 84% (0.06 vs 0.39 doses per patient-day, P < .001), and doses of all parenteral opioids were reduced by 55% (0.18 vs 0.39 doses per patient-day, P < .001). In addition, mean (SD) daily parenteral opioid exposure decreased by 49% (2.88 [0.72] vs 5.67 [1.14] morphine-milligram equivalents [MMEs] per patient-day). The daily rate

  15. Personality as a risk factor for illicit opioid use and a protective factor for illicit opioid dependence.

    PubMed

    Zaaijer, Eline R; Bruijel, Jessica; Blanken, Peter; Hendriks, Vincent; Koeter, Maarten W J; Kreek, Mary Jeanne; Booij, Jan; Goudriaan, Anna E; van Ree, Jan M; van den Brink, Wim

    2014-12-01

    Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users who never became dependent with dependent opioid users. This study aims to examine the role of personality as a risk factor for opioid use and as a protective factor for the development of opioid dependence. Comparing personality factors between three groups: (1) 161 never-dependent illicit opioid users who have been using illicit opioids but never became opioid dependent; (2) 402 dependent opioid users in methadone maintenance treatment or heroin-assisted treatment; and (3) 135 healthy controls who never used heroin. Personality was assessed with a short version of Cloninger's Temperament and Character Inventory. Never-dependent opioid users reported more Novelty Seeking and Harm Avoidance and less Self-Directedness and Cooperativeness than healthy controls and more Reward Dependence and Self-Directedness, and less Harm Avoidance than dependent opioid users. Furthermore, never-dependent opioid users reported more Self-Transcendence than both dependent opioid users and healthy controls. Never-dependent opioid users may have started to use opioids partly due to their tendency to seek novel and/or spiritual experiences (high Novelty Seeking, high Self-Transcendence) and their tendency to avoid aversive stimuli (high Harm Avoidance), whereas they may have been protected against the development of dependence by their need for social approval (high Reward Dependence) and their self-efficacy (high Self-Directedness). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Ensuring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction

    PubMed Central

    Francoeur, Richard B

    2011-01-01

    This article proposes and develops novel components of community-oriented programs for creating and affording access to safe medication dispensing centers in existing retail pharmacies and in permanent or travelling pharmacy clinics that are guarded by assigned or off-duty police officers. Pharmacists at these centers would work with police, medical providers, social workers, hospital administrators, and other professionals in: planning and overseeing the safe storage of controlled substance medications in off-site community safe-deposit boxes; strengthening communication and cooperation with the prescribing medical provider; assisting the prescribing medical provider in patient monitoring (checking the state prescription registry, providing pill counts and urine samples); expanding access to lower-cost, and in some cases, abuse-resistant formulations of controlled substance medications; improving transportation access for underserved patients and caregivers to obtain prescriptions; and integrating community agencies and social networks as resources for patient support and monitoring. Novel components of two related community-oriented programs, which may be hosted outside of safe medication dispensing centers, are also suggested and described: (1) developing medication purchasing cooperatives (ie, to help patients, families, and health institutions afford the costs of medications, including tamper-or abuse-resistant/deterrent drug formulations); and (2) expanding the role of inner-city methadone maintenance treatment programs in palliative care (ie, to provide additional patient monitoring from a second treatment team focusing on narcotics addiction, and potentially, to serve as an untapped source of opioid medication for pain that is less subject to abuse, misuse, or diversion). PMID:22312232

  17. Opioid Abuse and Addiction - Multiple Languages

    MedlinePlus

    ... Opioid addiction, part 8 - español (Spanish) MP4 Healthy Roads Media Comorbidity or dual diagnosis - Opioid addiction, part 9 - English PDF Comorbidity or ... addiction, part 9 - English MP4 Comorbidity or dual diagnosis - Opioid ... MP4 Healthy Roads Media Pregnancy and opioids - Opioid addiction, part 10 - ...

  18. The US Opioid Crisis: Current Federal and State Legal Issues.

    PubMed

    Soelberg, Cobin D; Brown, Raeford E; Du Vivier, Derick; Meyer, John E; Ramachandran, Banu K

    2017-11-01

    The United States is in the midst of a devastating opioid misuse epidemic leading to over 33,000 deaths per year from both prescription and illegal opioids. Roughly half of these deaths are attributable to prescription opioids. Federal and state governments have only recently begun to grasp the magnitude of this public health crisis. In 2016, the Centers for Disease Control and Prevention released their Guidelines for Prescribing Opioids for Chronic Pain. While not comprehensive in scope, these guidelines attempt to control and regulate opioid prescribing. Other federal agencies involved with the federal regulatory effort include the Food and Drug Administration (FDA), the Drug Enforcement Agency (DEA), and the Department of Justice. Each federal agency has a unique role in helping to stem the burgeoning opioid misuse epidemic. The DEA, working with the Department of Justice, has enforcement power to prosecute pill mills and physicians for illegal prescribing. The DEA could also implement use of prescription drug monitoring programs (PDMPs), currently administered at the state level, and use of electronic prescribing for schedule II and III medications. The FDA has authority to approve new and safer formulations of immediate- and long-acting opioid medications. More importantly, the FDA can also ask pharmaceutical companies to cease manufacturing a drug. Additionally, state agencies play a critical role in reducing overdose deaths, protecting the public safety, and promoting the medically appropriate treatment of pain. One of the states' primary roles is the regulation of practice of medicine and the insurance industry within their borders. Utilizing this authority, states can both educate physicians about the dangers of opioids and make physician licensure dependent on registering and using PDMPs when prescribing controlled substances. Almost every state has implemented a PDMP to some degree; however, in addition to mandating their use, increased interstate

  19. Role of opioid tone in the pathophysiology of hyperinsulinemia and insulin resistance in polycystic ovarian disease.

    PubMed

    Fulghesu, A M; Ciampelli, M; Guido, M; Murgia, F; Caruso, A; Mancuso, S; Lanzone, A

    1998-02-01

    Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of polycystic ovarian disease (PCOD). On the other hand, being generally admitted that opioids may play a role in glycoregulation and that opioid tone is altered in PCOD, an involvement of the opioids in determining the hyperinsulinemia of PCOD patients could be suggested. The aim of this study was to evaluate the effect of a chronic opioid blockade on insulin metabolism and peripheral insulin sensitivity in PCOD hyperinsulinemic patients. Twenty-three women with PCOD were studied. An oral glucose tolerance test (OGTT) and a clamp study were performed at baseline (during the follicular phase) and after 6 weeks of naltrexone administration (50 mg/d orally). Based on the insulinemic response to the OGTT, 16 women were classified as hyperinsulinemic and seven as normoinsulinemic. Naltrexone treatment significantly reduced fasting (P < .05) and area under the curve (AUC) (P < .02) plasma insulin levels only in the hyperinsulinemic group. Moreover, hyperinsulinemic patients showed similar C-peptide incremental areas after naltrexone treatment, whereas in the same patients the fractional hepatic insulin extraction calculated from the incremental areas of insulin and C-peptide was found to be increased after chronic opioid blockade by naltrexone. For peripheral insulin sensitivity, the hyperinsulinemic group showed significantly lower (P < .01) total-body glucose utilization (M) compared with the normoinsulinemic group. No change in the M value was found after treatment in both groups. These data suggest that the insulin sensitivity and hyperinsulinemia after an OGTT are two distinct deranged features of the insulin disorder of PCOD patients.

  20. Methadone, commonly used as maintenance medication for outpatient treatment of opioid dependence, kills leukemia cells and overcomes chemoresistance.

    PubMed

    Friesen, Claudia; Roscher, Mareike; Alt, Andreas; Miltner, Erich

    2008-08-01

    The therapeutic opioid drug methadone (d,l-methadone hydrochloride) is the most commonly used maintenance medication for outpatient treatment of opioid dependence. In our study, we found that methadone is also a potent inducer of cell death in leukemia cells and we clarified the unknown mechanism of methadone-induced cell killing in leukemia cells. Methadone inhibited proliferation in leukemia cells and induced cell death through apoptosis induction and activated apoptosis pathways through the activation of caspase-9 and caspase-3, down-regulation of Bcl-x(L) and X chromosome-linked inhibitor of apoptosis, and cleavage of poly(ADP-ribose) polymerase. In addition, methadone induced cell death not only in anticancer drug-sensitive and apoptosis-sensitive leukemia cells but also in doxorubicin-resistant, multidrug-resistant, and apoptosis-resistant leukemia cells, which anticancer drugs commonly used in conventional therapies of leukemias failed to kill. Depending on caspase activation, methadone overcomes doxorubicin resistance, multidrug resistance, and apoptosis resistance in leukemia cells through activation of mitochondria. In contrast to leukemia cells, nonleukemic peripheral blood lymphocytes survived after methadone treatment. These findings show that methadone kills leukemia cells and breaks chemoresistance and apoptosis resistance. Our results suggest that methadone is a promising therapeutic approach not only for patients with opioid dependence but also for patients with leukemias and provide the foundation for new strategies using methadone as an additional anticancer drug in leukemia therapy, especially when conventional therapies are less effective.

  1. Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells.

    PubMed

    Dash, Tapan K; Konkimalla, V Badireenath

    2017-02-01

    Curcumin is very well established as a chemo-therapeutic, chemo-preventive and chemo-sensitizing agent in diverse disease conditions. As the isolated pure form has poor solubility and pharmacokinetic problems, therefore it is encapsulated in to several nano-formulations to improve its bioavailability. Here in the current study, we aim to compare different nano-formulations of curcumin for their chemo-sensitizing activity in doxorubicin (DOX) resistant K562 cells. Four different curcumin formulations were prepared namely DMSO assisted curcumin nano-dispersion (CurD, 260 nm), liposomal curcumin (CurL, 165 nm), MPEG-PCL micellar curcumin (CurM, 18 nm) and cyclodextrin encapsulated curcumin (CurN, 37 nm). The formulations were subjected to particle characterizations (size, zeta potential, release studies), followed by biological assays such as cellular uptake, P-gp inhibitory activity and reversal of DOX resistance by co-treatment with DOX. Curcumin uptake in K562N and K562R cells was mildly reduced when treated with CurL and CurM, while for CurD and CurN the uptake remained equivalent. However, CurL retained P-gp inhibitory activity of curcumin and with a considerable chemo-sensitizing effect but CurM showed no P-gp inhibitory activity. CurN retained above biological activities, but requires a secondary carrier under in vivo conditions. From the results, CurM was found to be most suitable for solubilization of curcumin where as CurL can be considered as most suitable nano-formulation for reversal of DOX resistance.

  2. Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

    PubMed Central

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena

    2015-01-01

    Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

  3. Effect of new auxin herbicide formulations on control of herbicide resistant weeds and on microbial activities in the rhizosphere

    USDA-ARS?s Scientific Manuscript database

    Widespread distribution of glyphosate-resistant weeds in soybean-growing areas across Mississippi has economically affected soybean planting and follow-up crop management operations. New multiple herbicide-resistant crop (including soybean) technologies with associated formulations will soon be comm...

  4. Formulation of stable Bacillus subtilis AH18 against temperature fluctuation with highly heat-resistant endospores and micropore inorganic carriers.

    PubMed

    Chung, Soohee; Lim, Hyung Mi; Kim, Sang-Dal

    2007-08-01

    To survive the commercial market and to achieve the desired effect of beneficial organisms, the strains in microbial products must be cost-effectively formulated to remain dormant and hence survive through high and low temperatures of the environment during transportation and storage. Dormancy and stability of Bacillus subtilis AH18 was achieved by producing endospores with enhanced heat resistance and using inorganic carriers. Heat stability assays, at 90 degrees C for 1 h, showed that spores produced under a sublethal temperature of 57 degrees C was 100 times more heat-resistant than the ones produced by food depletion at the growing temperature of 37 degrees C. When these highly heat-resistant endospores were formulated with inorganic carriers of natural and synthetic zeolite or kaolin clay minerals having substantial amount of micropores, the dormancy of the endospores was maintained for 6 months at 15-25 degrees C. Meanwhile, macroporous perlite carriers with average pore diameter larger than 3.7 microm stimulated the germination of the spores and rapid proliferation of the bacteria. These results indicated that a B. subtilis AH18 product that can remain dormant and survive through environmental temperature fluctuation can be formulated by producing heat-stressed endospores and incorporating inorganic carriers with micropores in the formulation step.

  5. Pharmacists’ experiences with dispensing opioids

    PubMed Central

    Kahan, Meldon; Wilson, Lynn; Wenghofer, Elizabeth Francis; Srivastava, Anita; Resnick, Anne; Janecek, Eva; Sheehan, Carolynn

    2011-01-01

    Abstract Objective To explore pharmacists’ beliefs, practices, and experiences regarding opioid dispensing. Design Mailed survey. Setting The province of Ontario. Participants A total of 1011 pharmacists selected from the Ontario College of Pharmacists’ registration list. Main outcome measures Pharmacists’ experiences with opioid-related adverse events (intoxication and aberrant drug-related behaviour) and their interactions with physicians. Results A total of 652 pharmacists returned the survey, for a response rate of 64%. Most (86%) reported that they were concerned about several or many of their patients who were taking opioids; 36% reported that at least 1 patient was intoxicated from opioids while visiting their pharmacies within the past year. Reasons for opioid intoxication included the patient taking more than prescribed (84%), the patient using alcohol or sedating drugs along with the opioid (69.9%), or the prescribed dose being too high (34%). Participants’ most common concerns in the 3 months before the survey were patients coming in early for prescription refills, suspected double-doctoring, and requests for replacement doses for lost medication (reported frequently by 39%, 12%, and 16% of respondents, respectively). Pharmacists were concerned about physician practices, such as prescribing benzodiazepines along with opioids. Pharmacists reported difficulty in reaching physicians directly by telephone (43%), and indicated that physicians frequently did not return their calls promptly (28%). The strategies rated as most helpful for improving opioid dispensing were a provincial prescription database and opioid prescribing guidelines. Conclusion Pharmacists commonly observe opioid intoxication and aberrant drug-related behaviour in their patients but have difficulty communicating their concerns to physicians. System-wide strategies are urgently needed to improve the safety of opioid prescribing and to enhance communication between physicians and

  6. Use of Pharmacotherapies in the Treatment of Alcohol Use Disorders and Opioid Dependence in Primary Care

    PubMed Central

    Lee, Jinhee; Kresina, Thomas F.; Campopiano, Melinda; Lubran, Robert; Clark, H. Westley

    2015-01-01

    Substance-related and addictive disorders are chronic relapsing conditions that substantially impact public health. Effective treatments for these disorders require addressing substance use/dependence comprehensively as well as other associated comorbidities. Comprehensive addressing of substance use in a medical setting involves screening for substance use, addressing substance use directly with the patient, and formulating an appropriate intervention. For alcohol dependence and opioid dependence, pharmacotherapies are available that are safe and effective when utilized in a comprehensive treatment paradigm, such as medication assisted treatment. In primary care, substance use disorders involving alcohol, illicit opioids, and prescription opioid abuse are common among patients who seek primary care services. Primary care providers report low levels of preparedness and confidence in identifying substance-related and addictive disorders and providing appropriate care and treatment. However, new models of service delivery in primary care for individuals with substance-related and addictive disorders are being developed to promote screening, care and treatment, and relapse prevention. The education and training of primary care providers utilizing approved medications for the treatment of alcohol use disorders and opioid dependence in a primary care setting would have important public health impact and reduce the burden of alcohol abuse and opioid dependence. PMID:25629034

  7. [Use of opioids in palliative care of children with advanced cancer].

    PubMed

    Fernández Urtubia, Belem; Trevigno Bravo, Antonella; Rodríguez Zamora, Natalie; Palma Torres, Chery; Cid Barria, Luis

    2016-01-01

    Despite advances in the treatment of cancer in paediatric patients, 15% of children die from the illness progression in Chile, and pain is the most significant symptom in advanced stages. Although the World Health Organization guidelines demonstrate that opioids are fundamental in pain management, there is still resistance to their use. The main objective of this article was to describe the experience in the use of opioids for pain management in paediatric patients with advanced cancer in palliative care (PC). Retrospective study of patients admitted into the PC Program at the Hospital Roberto del Río between 2002 and 2013. Analysis was carried out on demographic data; oncological diagnosis; pain intensity on admission and discharge, according to validated scales; use of non-steroidal anti-inflammatory drugs; weak opioids; strong opioids; adjuvants drugs; the presence of secondary effects resulting from the use of morphine, and the need for palliative sedation. Of the 99 medical records analysed, the median age was 8 years, 64.6% were male, and there was a similar distribution in three oncological diagnosis groups. Upon admission, 43.4% presented intense to severe pain, and upon discharge there were four patients, but with a maximum VAS score of 7 in only one case. Of the 66 patients taking strong opioids, 89% required less than 0.5mg/kg/hr. Constipation was the most frequently observed secondary effect. Two thirds of the patients studied required strong opioids, with which adequate pain management was achieved, with no serious complications observed. The use of opioids in this group of patients, following a protocol, is considered effective and safe. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Opioid-Induced Bowel Dysfunction

    PubMed Central

    Cheng, Vivian; Lembo, Anthony

    2013-01-01

    Opioid-induced bowel dysfunction (OIBD) is a potentially debilitating side effect of chronic opioid use. It refers to a collection of primarily gastrointestinal motility disorders induced by opioids, of which opioid-induced constipation (OIC) is the most common. Management of OIBD is difficult, and affected patients will often limit their opioid intake at the expense of experiencing more pain, to reduce the negative impact of OIBD on their quality of life. Effective pharmacologic therapy for OIC is considered an unmet need and several agents have recently been given priority review and approval for OIC. Furthermore, multiple agents currently in development show promise in treating OIC without significant impact on analgesia or precipitation of withdrawal symptoms. The approval and availability of such medications would represent a significant improvement in the management of OIC and OIBD in patients with chronic pain. PMID:23900996

  9. The opioid manager: a point-of-care tool to facilitate the use of the Canadian Opioid Guideline.

    PubMed

    Furlan, Andrea D; Reardon, Rhoda; Salach, Lena

    2012-01-01

    The Opioid Manager is designed to be used as a point-of-care tool for providers prescribing opioids for chronic noncancer pain. It condenses the key elements from the Canadian Opioid Guideline and can be used as a chart insert. The Opioid Manager has been validated and is available for download from the Guideline's Web site http://nationalpaincentre.mcmaster.ca/opioidmanager/. The Opioid Manager is divided into the following four parts: A) before you write the first script, B) initiation trial, C) maintenance and monitoring, and D) when is it time to decrease the dose or stop the opioid completely? The Opioid Manager has been downloaded by 1,432 users: 47 percent family physicians, 18 percent pharmacists, 13 percent other physicians, and 22 percent miscellaneous. To show how to use the Opioid Manager, the authors created a 10-minute video that is available on the Internet. The Opioid Manager is being translated to French, Spanish, Portuguese, and Farsi.

  10. Current Research on Opioid Receptor Function

    PubMed Central

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

    2012-01-01

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

  11. Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic.

    PubMed

    Hah, Jennifer M; Bateman, Brian T; Ratliff, John; Curtin, Catherine; Sun, Eric

    2017-11-01

    Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

  12. Persistent opioid use following Cesarean delivery: patterns and predictors among opioid naïve women

    PubMed Central

    Bateman, Brian T.; Franklin, Jessica M.; Bykov, Katsiaryna; Avorn, Jerry; Shrank, William H.; Brennan, Troyen A.; Landon, Joan E.; Rathmell, James P.; Huybrechts, Krista F.; Fischer, Michael A.; Choudhry, Niteesh K.

    2016-01-01

    Background The incidence of opioid-related death in women has increased five-fold over the past decade. For many women, their initial opioid exposure will occur in the setting of routine medical care. Approximately 1 in 3 deliveries in the U.S. is by Cesarean and opioids are commonly prescribed for post-surgical pain management. Objective The objective of this study was to determine the risk that opioid naïve women prescribed opioids after Cesarean delivery will subsequently become consistent prescription opioid users in the year following delivery, and to identify predictors for this behavior. Study Design We identified women in a database of commercial insurance beneficiaries who underwent Cesarean delivery and who were opioid-naïve in the year prior to delivery. To identify persistent users of opioids, we used trajectory models, which group together patients with similar patterns of medication filling during follow-up, based on patterns of opioid dispensing in the year following Cesarean delivery. We then constructed a multivariable logistic regression model to identify independent risk factors for membership in the persistent user group. Results 285 of 80,127 (0.36%, 95% confidence interval 0.32 to 0.40), opioid-naïve women became persistent opioid users (identified using trajectory models based on monthly patterns of opioid dispensing) following Cesarean delivery. Demographics and baseline comorbidity predicted such use with moderate discrimination (c statistic = 0.73). Significant predictors included a history of cocaine abuse (risk 7.41%; adjusted odds ratio 6.11, 95% confidence interval 1.03 to 36.31) and other illicit substance abuse (2.36%; adjusted odds ratio 2.78, 95% confidence interval 1.12 to 6.91), tobacco use (1.45%; adjusted odds ratio 3.04, 95% confidence interval 2.03 to 4.55), back pain (0.69%; adjusted odds ratio 1.74, 95% confidence interval 1.33 to 2.29), migraines (0.91%; adjusted odds ratio 2.14, 95% confidence interval 1.58 to 2

  13. New formulations of bupivacaine for the treatment of postoperative pain: liposomal bupivacaine and SABER-Bupivacaine.

    PubMed

    Skolnik, Aaron; Gan, Tong J

    2014-08-01

    Although generally considered both safe and effective, local anesthetics are often used in conjunction with opioids postoperatively in part because of the limited duration of drug action of local anesthetics. Much interest exists in extending the duration of local anesthetics' effects, which may reduce the requirement for opioid pain medications that are frequently associated with side effects, including nausea and vomiting, pruritus and respiratory depression. This article introduces liposomal bupivacaine and SABER®-Bupivacaine, two new formulations of bupivacaine that increase the duration of analgesia postoperatively through two novel slow-release technologies. The pharmacodynamics, pharmacokinetics, efficacy and safety of both preparations of bupivacaine are reviewed. An electronic database search conducted using the Cochrane Central Register of Controlled Trials and MEDLINE/PubMed with the following search terms: 'bupivacaine,' 'liposomal bupivacaine', 'liposome bupivacaine', 'Exparel', 'SABER-Bupivacaine', 'SABER Bupivacaine', and 'SABER' yielded 90 articles (no language or date of publication restrictions were imposed). Clinical trials involving liposomal bupivacaine and SABER-Bupivacaine indicate that both safely prolong analgesia, while decreasing opioid requirements when compared with placebo. However, additional clinical studies are necessary to better determine the efficacy and cost-effectiveness of these long-acting local anesthetic formulations.

  14. Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada.

    PubMed

    Madadi, Parvaz; Hildebrandt, Doris; Lauwers, Albert E; Koren, Gideon

    2013-01-01

    The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity. This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed. Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359). Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch), 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer. These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users.

  15. Brief Opioid Overdose Knowledge (BOOK): A Questionnaire to Assess Overdose Knowledge in Individuals Who Use Illicit or Prescribed Opioids.

    PubMed

    Dunn, Kelly E; Barrett, Frederick S; Yepez-Laubach, Claudia; Meyer, Andrew C; Hruska, Bryce J; Sigmon, Stacey C; Fingerhood, Michael; Bigelow, George E

    2016-01-01

    Opioid overdose is a public health crisis. This study describes efforts to develop and validate the Brief Opioid Overdose Knowledge (BOOK) questionnaire to assess patient knowledge gaps related to opioid overdose risks. Two samples of illicit opioid users and a third sample of patients receiving an opioid for the treatment of chronic pain (total N = 848) completed self-report items pertaining to opioid overdose risks. A 3-factor scale was established, representing Opioid Knowledge (4 items), Opioid Overdose Knowledge (4 items), and Opioid Overdose Response Knowledge (4 items). The scale had strong internal and face validity. Patients with chronic pain performed worse than illicit drug users in almost all items assessed, highlighting the need to increase knowledge of opioid overdose risk to this population. This study sought to develop a brief, internally valid method for quickly assessing deficits in opioid overdose risk areas within users of illicit and prescribed opioids, to provide an efficient metric for assessing and comparing educational interventions, facilitate conversations between physicians and patients about overdose risks, and help formally identify knowledge deficits in other patient populations.

  16. Opioid Peptidomimetics: Leads for the Design of Bioavailable Mixed Efficacy Mu Opioid Receptor (MOR) Agonist/Delta Opioid Receptor (DOR) Antagonist Ligands

    PubMed Central

    Mosberg, Henry I.; Yeomans, Larisa; Harland, Aubrie A.; Bender, Aaron M.; Sobczyk-Kojiro, Katarzyna; Anand, Jessica P.; Clark, Mary J.; Jutkiewicz, Emily M.; Traynor, John R.

    2013-01-01

    We have previously described opioid peptidomimetic, 1, employing a tetrahydroquinoline scaffold and modeled on a series of cyclic tetrapeptide opioid agonists. We have recently described modifications to these peptides that confer a mu opioid receptor (MOR) agonist, delta opioid receptor (DOR) antagonist profile, which has been shown to reduce the development of tolerance to the analgesic actions of MOR agonists. Several such bifunctional ligands have been reported, but none has been demonstrated to cross the blood brain barrier. Here we describe the transfer of structural features that evoked MOR agonist/DOR antagonist behavior in the cyclic peptides to the tetrahydroquinoline scaffold and show that the resulting peptidomimetics maintain the desired pharmacological profile. Further, the 4R diastereomer of 1 was fully efficacious and approximately equipotent to morphine in the mouse warm water tail withdrawal assay following intraperitoneal administration and thus a promising lead for the development of opioid analgesics with reduced tolerance. PMID:23419026

  17. Illicit Opioid Intoxication: Diagnosis and Treatment

    PubMed Central

    Fareed, A.; Stout, S.; Casarella, J.; 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 diagnoses of intoxication and overdose. Lastly, we updated the reader about the most recent recommendations for treatment and prevention of opioid intoxications and overdose. PMID:22879747

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

    PubMed

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

    2018-02-01

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

  19. Translational approach to the pathophysiology of panic disorder: Focus on serotonin and endogenous opioids.

    PubMed

    Graeff, Frederico G

    2017-05-01

    Panic patients experience recurrent panic attacks. Two main neurochemical hypotheses have been proposed to explain this vulnerability. The first suggests that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organizes defensive reactions to cope with proximal threats as well as of sympathomotor control areas of the rostral ventrolateral medulla that generate neurovegetative symptoms of the panic attack. The second proposes that endogenous opioids buffer panic attacks in normal subjects, and their deficit results in heightened sensitivity to suffocation and separation anxiety in panic patients. Experimental results obtained in rat models of panic indicate that serotonin interacts synergistically with endogenous opioids in the dorsal periaqueductal gray through 5-HT1A and μ-opioid receptors to inhibit proximal defense and, supposedly, panic attacks. These findings allow reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology. They also indicate that endogenous opioids are likely to participate in the panicolytic action of antidepressants and suggest that exogenous opioids may be useful for treating panic patients resistant to conventional pharmacotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents.

    PubMed

    Häuser, Winfried; Schug, Stephan; Furlan, Andrea D

    2017-05-01

    A marked rise in opioid prescriptions for patients with chronic noncancer pain (CNCP) with a parallel increase in opioid abuse/misuse, and resulting deaths was noted in the Unites states in the past decade (opioid epidemic). In response, the US Center of Diseases Control (CDC) developed a guideline for prescribing of opioids for patients with CNCP. To assess (1) if there is an opioid epidemic in Australia, Canada, and Germany (2) to compare Australian, Canadian, German, and Center of Diseases Control guidelines recommendations for long-term opioid therapy for CNCP. National evidence-based guidelines and PubMed were searched for recommendations for opioid prescriptions for CNCP. There are signs of an opioid epidemic in Australia and Canada, but not in Germany. Guidelines in all 4 countries provide similar recommendations: opioids are not the first-line therapy for patients with CNCP; regular clinical assessments of benefits and harms are necessary; excessive doses should be avoided (recommended morphine equivalent daily doses range from 50 to 200 mg/d); stopping rules should be followed. All guidelines do not recommend the use of opioids in chronic pain conditions without an established nociceptive or neuropathic cause such as fibromyalgia and primary headache. Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.

  1. Desensitization and Tolerance of Mu Opioid Receptors on Pontine Kölliker-Fuse Neurons.

    PubMed

    Levitt, Erica S; Williams, John T

    2018-01-01

    Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein-coupled inwardly rectifying potassium current was measured using whole-cell voltage-clamp recordings from KF and locus coeruleus (LC) neurons contained in acute rat brain slices. A saturating concentration of the opioid agonist [Met 5 ]-enkephalin (ME) caused significantly less desensitization in KF neurons compared with LC neurons. In contrast to LC, desensitization in KF neurons was not enhanced by activation of protein kinase C or in slices from morphine-treated rats. Cellular tolerance to ME and morphine was also lacking in KF neurons from morphine-treated rats. The lack of cellular tolerance in KF neurons correlates with the relative lack of tolerance to the respiratory depressant effect of opioids. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer.

    PubMed

    Liang, Su; Bian, Xiaomei; Liang, Dong; Sivils, Jeffrey C; Neckers, Leonard M; Cox, Marc B; Xie, Huan

    2016-01-01

    MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), highly lipophilic (logP = 6.49), poorly soluble in water (0.28 µg/mL), and highly plasma protein bound (>98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for four consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls.

  3. Solution Formulation Development and Efficacy of MJC13 in a Preclinical Model of Castrate-Resistant Prostate Cancer

    PubMed Central

    Liang, Su; Bian, Xiaomei; Liang, Dong; Sivils, Jeffrey C.; Neckers, Leonard M.; Cox, Marc B.; Xie, Huan

    2015-01-01

    MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castrate-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), very lipophilic (logP = 6.49), poorly soluble in water (0.28 μg/mL), and highly plasma protein bound (> 98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for 4 consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls. PMID:25380396

  4. Characteristics of Opioid-Users Whose Death Was Related to Opioid-Toxicity: A Population-Based Study in Ontario, Canada

    PubMed Central

    Madadi, Parvaz; Hildebrandt, Doris; Lauwers, Albert E.; Koren, Gideon

    2013-01-01

    Background The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity. Methods This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed. Results Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359). Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch), 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer. Significance/Conclusion These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users. PMID:23577131

  5. Discharge prescribing of enteral opioids after initiation as a weaning strategy from continuous opioid infusions in the Intensive Care Unit.

    PubMed

    Kram, Bridgette; Weigel, Kylie M; Kuhrt, Michelle; Gilstrap, Daniel L

    To evaluate the proportion of patients receiving a hospital discharge prescription for a scheduled enteral opioid following initiation as a weaning strategy from a continuous opioid infusion in the Intensive Care Unit (ICU). Retrospective, observational study. Five adult ICUs at a large, quaternary care academic medical center. Endotracheally intubated, opioid-naive adults receiving a continuous opioid infusion with a concomitant scheduled enteral opioid initiated. Exclusion criteria were receipt of fewer than two enteral opioid doses, documentation of a long-acting opioid as a home medication, the indication for the enteral opioid was not a weaning strategy, death during hospital admission or discharge to hospice. None. The proportion of ICU and hospital survivors who received a discharge prescription for a scheduled enteral opioid, total duration of continuous opioid infusion, duration of continuous opioid infusion after initiation of an enteral opioid therapy, total duration of enteral therapy, ICU and hospital length of stay. Of 62 included patients, 19 patients (30.6 percent) received a new prescription for a scheduled enteral opioid at hospital discharge. The median duration of enteral opioid therapy was longer for patients who received a discharge prescription compared to those who did not (20.09 vs 8.89 days, p = 0.02), though the remaining endpoints were not different. Utilizing scheduled enteral opioids as a weaning strategy from continuous opioid infusions may place patients at risk of ICU-acquired physical dependence on opioids.

  6. Apparatus and method for detecting tampering in flexible structures

    DOEpatents

    Maxey, Lonnie C [Knoxville, TN; Haynes, Howard D [Knoxville, TN

    2011-02-01

    A system for monitoring or detecting tampering in a flexible structure includes taking electrical measurements on a sensing cable coupled to the structure, performing spectral analysis on the measured data, and comparing the spectral characteristics of the event to those of known benign and/or known suspicious events. A threshold or trigger value may used to identify an event of interest and initiate data collection. Alternatively, the system may be triggered at preset intervals, triggered manually, or triggered by a signal from another sensing device such as a motion detector. The system may be used to monitor electrical cables and conduits, hoses and flexible ducts, fences and other perimeter control devices, structural cables, flexible fabrics, and other flexible structures.

  7. Macroeconomic conditions and opioid abuse.

    PubMed

    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.

  8. Targinact--opioid pain relief without constipation?

    PubMed

    2010-12-01

    Targinact (Napp Pharmaceuticals Ltd) is a modified-release combination product containing the strong opioid oxycodone plus the opioid antagonist naloxone. It is licensed for "severe pain, which can be adequately managed only with opioid analgesics".1 The summary of product characteristics (SPC) states that "naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut". Advertising for the product claims "better pain relief", "superior GI [gastrointestinal] tolerability" and "improved quality of life" "compared to previous treatment in a clinical practice study (n=7836)". Here we consider whether Targinact offers advantages over using strong opioids plus laxatives where required.

  9. Prescription opioid analgesics for pain management in Australia: 20 years of dispensing.

    PubMed

    Islam, M M; McRae, I S; Mazumdar, S; Taplin, S; McKetin, R

    2016-08-01

    Opioid prescribing/dispensing data can inform policy surrounding regulation by informing trends and types of opioid prescribed and geographic variations. In Australia so far only partial data on dispensing have been published, and data for states/territories remain unknown. Using a range of measures, this study examines 20-year (1992-2011) trends in prescription opioid analgesics in Australia - both nationally and for individual jurisdictions. Dispensing data were obtained from the Drug Utilisation Sub-Committee and the Pharmaceutical Benefits Scheme (PBS) websites. Trends in numbers of prescriptions and daily defined dose (DDD)/1000 people/day were examined over time and across states/territories. Seasonal variations in PBS/Repatriation Pharmaceutical Benefits Scheme (RPBS) items for nationwide dispensing were adjusted using a centred moving smoothing technique. In two decades, 165.32 million prescriptions for opioids were dispensed, with codeine and its derivatives the most prescribed formulation (50.1%) followed by tramadol (13.5%) and oxycodone derivatives (12.7%). In terms of DDD/1000 people/day, dispensing increased from 5.38 in 1992 to 14.46 in 2011. There are significant increasing trends for total, PBS/RPBS and under co-payment prescriptions (priced below patient co-payment). The DDD/1000 people/day for items dispensed through PBS/RPBS was highest in Tasmania. Prescription opioid dispensing increased substantially over the study period. With an ageing population, this trend is likely to continue in future. A growing concern about harms associated with opioid use warrants balanced control measures so that harms could be minimised without reducing effective pain treatment. Research examining utilisation in small geographic areas may help design spatially tailored interventions. A real-time drug-monitoring programme may reduce undue prescribing and dispensing. © 2016 Royal Australasian College of Physicians.

  10. Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations*†‡

    PubMed Central

    Fields, Marcia D.; Abate, Marie A.; Hu, Lan; Long, D. Leann; Blommel, Matthew L.; Haikal, Nabila A.; Kraner, James C.

    2016-01-01

    Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored. PMID:26223761

  11. Alcohol Screening among Opioid Agonist Patients in a Primary Care Clinic and an Opioid Treatment Program.

    PubMed

    Klimas, Jan; Muench, John; Wiest, Katharina; Croff, Raina; Rieckman, Traci; McCarty, Dennis

    2015-01-01

    Problem alcohol use is associated with adverse health and economic outcomes, especially among people in opioid agonist treatment. Screening, brief intervention, and referral to treatment (SBIRT) are effective in reducing alcohol use; however, issues involved in SBIRT implementation among opioid agonist patients are unknown. To assess identification and treatment of alcohol use disorders, we reviewed clinical records of opioid agonist patients screened for an alcohol use disorder in a primary care clinic (n = 208) and in an opioid treatment program (n = 204) over a two-year period. In the primary care clinic, 193 (93%) buprenorphine patients completed an annual alcohol screening and six (3%) had elevated AUDIT scores. In the opioid treatment program, an alcohol abuse or dependence diagnosis was recorded for 54 (27%) methadone patients. Practitioner focus groups were completed in the primary care (n = 4 physicians) and the opioid treatment program (n = 11 counselors) to assess experience with and attitudes towards screening opioid agonist patients for alcohol use disorders. Focus groups suggested that organizational, structural, provider, patient, and community variables hindered or fostered alcohol screening. Alcohol screening is feasible among opioid agonist patients. Effective implementation, however, requires physician training and systematic changes in workflow.

  12. Role of opioid receptors in the reinstatement of opioid-seeking behavior: an overview.

    PubMed

    Fattore, Liana; Fadda, Paola; Antinori, Silvia; Fratta, Walter

    2015-01-01

    Opioid abuse in humans is characterized by discontinuous periods of drug use and abstinence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of heroin addicts. The major problem in the treatment of opioid dependence still remains the occurrence of relapse, to which stressful life events, renewed use of heroin, and exposure to drug-associated environmental cues are all positively correlated. To study the neurobiology of relapse, many research groups currently use the reinstatement animal model, which greatly contributed to disentangle the mechanisms underlying relapse to drug-seeking in laboratory animals. The use of this model is becoming increasingly popular worldwide, and new versions have been recently developed to better appreciate the differential contribution of each opioid receptor subtype to the relapse phenomenon. In this chapter we review the state of the art of our knowledge on the specific role of the opioid receptors as unrevealed by the reinstatement animal model of opioid-seeking behavior.

  13. The Social Construction of the Urban Use of Information Technology: The Case of Tampere, Finland

    ERIC Educational Resources Information Center

    Inkinen, Tommi

    2006-01-01

    This paper explores the social use of information and communication technologies (ICTs) in the city of Tampere, Finland. It focuses on two essential elements: the city (as the location with national context) and citizens (as members of the "local" information society). The paper also examines the question of building social networks via…

  14. Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review.

    PubMed

    Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D

    2014-01-01

    The 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. Search of the available literature to assess remifentanil AOT and OIH based on available published data. We 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). Our results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research. AOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold after chronic opioid treatment, 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.

  15. Reusable tamper-indicating security seal

    DOEpatents

    Ryan, Michael J.

    1983-01-01

    The invention teaches means for detecting unauthorized tampering or substitutions of a device, and has particular utility when applied on a "seal" device used to secure a location or thing. The seal has a transparent body wall, and a first indicia, viz., a label identification is formed on the inside surface of this wall. Second and third indicia are formed on the outside surface of the transparent wall, and each of these indicia is transparent to allow the parallax angled viewing of the first indicia through these indicia. The second indicia is in the form of a broadly uniform pattern, viz, many small spaced dots; while the third indicia is in the form of easily memorized objects, such as human faces, made on a substrate by means of halftone printing. The substrate is lapped over the outside surface of the transparent wall. A thin cocoon of a transparent material, generally of the same material as the substrate such as plastic, is formed over the seal body and specifically over the transparent wall and the second and third indicia formed thereon. This cocoon is seamless and has walls of nonuniform thickness. Both the genuineness of the seal and whether anyone has attempted to compromise the seal can thus be visually determined upon inspection.

  16. A Systematic Content Analysis of Policy Barriers Impeding Access to Opioid Medication in Central and Eastern Europe: Results of ATOME.

    PubMed

    Larjow, Eugenia; Papavasiliou, Evangelia; Payne, Sheila; Scholten, Willem; Radbruch, Lukas

    2016-01-01

    Reliable access to opioid medication is critical to delivering effective pain management, adequate treatment of opioid dependence, and quality palliative care. However, more than 80% of the world population is estimated to be inadequately treated for pain because of difficulties in accessing opioids. Although barriers to opioid access are primarily associated with restrictive laws, regulations, and licensing requirements, a key problem that significantly limits opioid access relates to policy constraints. To identify and explore policy barriers to opioid access in 12 Eastern and Central European countries involved in the Access to Opioid Medication in Europe project, funded by the European Community's Seventh Framework (FP7/2007-2013, no. 222994) Programme. A systematic content analysis of texts retrieved from documents (e.g., protocols of national problem analyses, strategic planning worksheets, and executive summaries) compiled, reviewed, approved, and submitted by either the Access to Opioid Medication in Europe consortium or the national country teams (comprising experts in pain management, harm reduction, and palliative care) between September 2011 and April 2014 was performed. Twenty-five policy barriers were identified (e.g., economic crisis, bureaucratic issues, lack of training initiatives, stigma, and discrimination), classified under four predetermined categories (financial/economic aspects and governmental support, formularies, education and training, and societal attitudes). Key barriers related to issues of funding allocation, affordability, knowledge, and fears associated with opioids. Reducing barriers and improving access to opioids require policy reform at the governmental level with a set of action plans being formulated and concurrently implemented and aimed at different levels of social, education, and economic policy change. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  17. Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial

    PubMed Central

    Comer, Sandra D.; Sullivan, Maria A.; Yu, Elmer; Rothenberg, Jami L.; Kleber, Herbert D.; Kampman, Kyle; Dackis, Charles; O'Brien, Charles P.; Chiang, C. Nora; Hawks, Richard L.

    2013-01-01

    Context Naltrexone is a medication available in oral form that can completely block the effects produced by opioid agonists, such as heroin. However, poor medication compliance with naltrexone has been a major obstacle to the effective treatment of opioid dependence. Objective To evaluate the safety and efficacy of a sustained-release depot formulation of naltrexone in treating opioid dependence. Design, Setting, and Participants Randomized, double-blind, placebo-controlled, 8-week multi-center trial of male and female heroin-dependent patients who participated in the study between September 2000 and November 2003. Participants were stratified by years of heroin use (≥5, <4.9) and gender, and then randomized to receive one of three doses: placebo, 192 mg, or 384 mg depot naltrexone. Doses were administered at the beginning of Week 1 and then again four weeks later at the beginning of Week 5. All participants received twice-weekly relapse prevention therapy, provided observed urine samples, and completed other assessments at each visit. Main Outcome Measures Primary outcome measures were retention in treatment and percentage of opioid-negative urine samples. Results A total of 60 patients were randomized at two centers. Retention in treatment was dose related with 39%, 60%, and 68% of the patients in the placebo, naltrexone 192 mg, and naltrexone 384 mg groups, respectively, remaining in treatment at the end of the two-month treatment period. Analysis of the time to dropout revealed a significant main effect of dose with mean time to dropout of 27, 36, and 48 days, respectively, for the placebo, naltrexone 192 mg, and naltrexone 384 mg groups. The percentage of urine samples negative for opioids varied significantly as a function of dose, as did the percentage of urine samples negative for methadone, cocaine, benzodiazepines, and amphetamine. The percentage of urine samples negative for cannabinoids was not significantly different across groups. When the data were

  18. The opioid systems--panacea and nemesis.

    PubMed

    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.

  19. Women who abuse prescription opioids: findings from the Addiction Severity Index-Multimedia Version Connect prescription opioid database.

    PubMed

    Green, Traci C; Grimes Serrano, Jill M; Licari, Andrea; Budman, Simon H; Butler, Stephen F

    2009-07-01

    Evidence suggests gender differences in abuse of prescription opioids. This study aimed to describe characteristics of women who abuse prescription opioids in a treatment-seeking sample and to contrast gender differences among prescription opioid abusers. Data collected November 2005 to April 2008 derived from the Addiction Severity Index Multimedia Version Connect (ASI-MV Connect) database. Bivariate and multivariable logistic regression examined correlates of prescription opioid abuse stratified by gender. 29,906 assessments from 220 treatment centers were included, of which 12.8% (N=3821) reported past month prescription opioid abuse. Women were more likely than men to report use of any prescription opioid (29.8% females vs. 21.1% males, p<0.001) and abuse of any prescription opioid (15.4% females vs. 11.1% males, p<0.001) in the past month. Route of administration and source of prescription opioids displayed gender-specific tendencies. Women-specific correlates of recent prescription opioid abuse were problem drinking, age <54, inhalant use, residence outside of West US Census region, and history of drug overdose. Men-specific correlates were age <34, currently living with their children, residence in the South and Midwest, hallucinogen use, and recent depression. Women prescription opioid abusers were less likely to report a pain problem although they were more likely to report medical problems than women who abused other drugs. Gender-specific factors should be taken into account in efforts to screen and identify those at highest risk of prescription opioid abuse. Prevention and intervention efforts with a gender-specific approach are warranted.

  20. Nurses' Role in Preventing Prescription Opioid Diversion.

    PubMed

    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.

  1. Mice lacking the G protein γ3-subunit show resistance to opioids and diet induced obesity

    PubMed Central

    Schwindinger, William F.; Borrell, Brandon M.; Waldman, Lora C.

    2009-01-01

    Contributing to the obesity epidemic, there is increasing evidence that overconsumption of high-fat foods may be analogous to drug addiction in that the palatability of these foods is associated with activation of specific reward pathways in the brain. With this perspective, we report that mice lacking the G protein γ3-subunit (Gng3−/− mice) show resistance to high-fat diet-induced weight gain over the course of a 12-wk study. Compared with Gng3+/+ controls, female Gng3−/− mice exhibit a 40% reduction in weight gain and a 53% decrease in fat pad mass, whereas male Gng3−/− mice display an 18% reduction in weight gain and no significant decrease in fat pad mass. The basis for the lowered weight gain is related to reduced food consumption for female and male Gng3−/− mice of 13% and 14%, respectively. Female Gng3−/− mice also show a lesser preference for high-fat chow than their female Gng3+/+ littermates, suggesting an attenuated effect on a reward pathway associated with overconsumption of fat. One possible candidate is the μ-opioid receptor (Oprm1) signaling cascade. Supporting a defect in this signaling pathway, Gng3−/− mice show marked reductions in both acute and chronic morphine responsiveness, as well as increases in endogenous opioid mRNA levels in reward-related regions of the brain. Taken together, these data suggest that the decreased weight gain of Gng3−/− mice may be related to a reduced rewarding effect of the high-fat diet resulting from a defect in Oprm1 signaling and loss of the G protein γ3-subunit. PMID:19759336

  2. Opioid receptor activation triggering downregulation of cAMP improves effectiveness of anti-cancer drugs in treatment of glioblastoma

    PubMed Central

    Friesen, Claudia; Hormann, Inis; Roscher, Mareike; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf; Debatin, Klaus-Michael; Miltner, Erich

    2014-01-01

    Glioblastoma are the most frequent and malignant human brain tumors, having a very poor prognosis. The enhanced radio- and chemoresistance of glioblastoma and the glioblastoma stem cells might be the main reason why conventional therapies fail. The second messenger cyclic AMP (cAMP) controls cell proliferation, differentiation, and apoptosis. Downregulation of cAMP sensitizes tumor cells for anti-cancer treatment. Opioid receptor agonists triggering opioid receptors can activate inhibitory Gi proteins, which, in turn, block adenylyl cyclase activity reducing cAMP. In this study, we show that downregulation of cAMP by opioid receptor activation improves the effectiveness of anti-cancer drugs in treatment of glioblastoma. The µ-opioid receptor agonist D,L-methadone sensitizes glioblastoma as well as the untreatable glioblastoma stem cells for doxorubicin-induced apoptosis and activation of apoptosis pathways by reversing deficient caspase activation and deficient downregulation of XIAP and Bcl-xL, playing critical roles in glioblastomas’ resistance. Blocking opioid receptors using the opioid receptor antagonist naloxone or increasing intracellular cAMP by 3-isobutyl-1-methylxanthine (IBMX) strongly reduced opioid receptor agonist-induced sensitization for doxorubicin. In addition, the opioid receptor agonist D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux, whereas doxorubicin increased opioid receptor expression in glioblastomas. Furthermore, opioid receptor activation using D,L-methadone inhibited tumor growth significantly in vivo. Our findings suggest that opioid receptor activation triggering downregulation of cAMP is a promising strategy to inhibit tumor growth and to improve the effectiveness of anti-cancer drugs in treatment of glioblastoma and in killing glioblastoma stem cells. PMID:24626197

  3. Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

    PubMed

    Anand, Kanwaljeet J S; Clark, Amy E; Willson, Douglas F; Berger, John; Meert, Kathleen L; Zimmerman, Jerry J; Harrison, Rick; Carcillo, Joseph A; Newth, Christopher J L; Bisping, Stephanie; Holubkov, Richard; Dean, J Michael; Nicholson, Carol E

    2013-01-01

    To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit. Prospective, observational study with 100% accrual of eligible patients. Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network. Four hundred nineteen children treated with morphine or fentanyl infusions. None. Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03). Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of

  4. The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

    PubMed Central

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

    2014-01-01

    Purpose. Cancer pain management guidelines recommend initial treatment with intermediate-strength analgesics such as hydrocodone and subsequent escalation to stronger opioids such as morphine. There are no published studies on the process of opioid rotation (OR) from hydrocodone to strong opioids in cancer patients. Our aim was to determine the opioid rotation ratio (ORR) of hydrocodone to morphine equivalent daily dose (MEDD) in cancer outpatients. Patients and Methods. We reviewed the records of consecutive patient visits at our supportive care center in 2011–2012 for OR from hydrocodone to stronger opioids. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected from patients who returned for follow-up within 6 weeks. Linear regression analysis was used to estimate the ORR between hydrocodone and MEDD. Successful OR was defined as 2-point or 30% reduction in the pain score and continuation of the new opioid at follow-up. Results. Overall, 170 patients underwent OR from hydrocodone to stronger opioid. The median age was 59 years, and 81% had advanced cancer. The median time between OR and follow-up was 21 days. We found 53% had a successful OR with significant improvement in the ESAS pain and symptom distress scores. In 100 patients with complete OR and no worsening of pain at follow-up, the median ORR from hydrocodone to MEDD was 1.5 (quintiles 1–3: 0.9–2). The ORR was associated with hydrocodone dose (r = −.52; p < .0001) and was lower in patients receiving ≥40 mg of hydrocodone per day (p < .0001). The median ORR of hydrocodone to morphine was 1.5 (n = 44) and hydrocodone to oxycodone was 0.9 (n = 24). Conclusion. The median ORR from hydrocodone to MEDD was 1.5 and varied according to hydrocodone dose. PMID:25342316

  5. Investigational opioid antagonists for treating opioid-induced bowel dysfunction.

    PubMed

    Mozaffari, Shilan; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2018-03-01

    Opioids have been highlighted for their role in pain relief among cancer and non-cancer patients. Novel agents have been investigated to reduce opioid-induced constipation (OIC) as the main adverse effect that may lead to treatment discontinuation. Development of peripherally acting mu-opioid receptor antagonists (PAMORA) has resulted in a novel approach to preserve the efficacy of pain control along with less OIC. Areas covered: Clinical evidence for investigational PAMORAs was reviewed and clinical trials on investigational agents to reduce OIC were included. TD-1211 is currently being evaluated in Phase II clinical trial. Oxycodone-naltrexone and ADL-5945 went through Phase III clinical trials, but have been discontinued. Expert opinion: There is a substantial need to develop agents with specific pharmacokinetic properties to meet the needs of patients with underlying diseases. Holding the efficacy of a medicine with the highest selectivity on targeted receptors and the least adverse effects is the main approach in upcoming investigations to improve patients' quality of life (QoL). Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature.

  6. Opioid management of pain: the impact of the prescription opioid abuse epidemic.

    PubMed

    Rauenzahn, Sherri; Del Fabbro, Egidio

    2014-09-01

    The greater emphasis on pain control over the last decade has been accompanied by increased opioid prescriptions and an epidemic of opioid abuse. This review examines the financial, regulatory, and clinical practice impact of the epidemic, the factors contributing to its growth, and strategies that may counter this public health crisis. Despite the call for urgent practice change and the introduction of new initiatives such as electronic prescription monitoring and additional education programs for providers and patients, the evidence for improved outcomes are limited. There are also concerns that some patients may suffer from underprescribing as an unintended consequence of more stringent state and federal regulations. There is consensus that some form of universal precautions should be adopted for all patients, including those being treated for cancer-related pain, in order to better identify and manage those at risk of opioid abuse. The opioid prescription abuse epidemic has precipitated calls for increased regulation. Clinicians can improve patient care and diminish opioid abuse by identifying patient risk factors, increasing vigilance and structure for those at risk, and providing interdisciplinary care for any patients coping in a maladaptive manner.

  7. The association between negative affect and prescription opioid misuse in patients with chronic pain: The mediating role of opioid craving

    PubMed Central

    Martel, MO; Dolman, AJ; Edwards, RR; Jamison, RN; Wasan, AD

    2013-01-01

    Over the past decade, considerable research has accumulated showing that chronic pain patients experiencing high levels of negative affect (i.e., anxiety, depression) are at increased risk for prescription opioid misuse. The primary objective of the present study was to examine the factors that underlie the association between negative affect (NA) and prescription opioid misuse among patients with chronic pain. In this study, 82 patients with chronic musculoskeletal pain being prescribed opioid medication completed the Current Opioid Misuse Measure (COMM), a well-validated self-report questionnaire designed to assess prescription opioid misuse. Patients were also asked to complete self-report measures of pain intensity, NA, and opioid craving. A bootstrapped multiple mediation analysis was used to examine the mediating role of patients’ pain intensity and opioid craving in the association between NA and prescription opioid misuse. Consistent with previous research, we found a significant association between NA and prescription opioid misuse. Interestingly, results revealed that opioid craving, but not pain intensity, mediated the association between NA and opioid misuse. Discussion addresses the potential psychological and neurobiological factors that might contribute to the inter-relationships between NA, opioid craving, and prescription opioid misuse in patients with pain. The clinical implications of our findings are also discussed. PMID:24295876

  8. Use of Opioid Analgesics in Older Australians.

    PubMed

    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.

  9. Reversible Data Hiding in FTIR Microspectroscopy Images with Tamper Indication and Payload Error Correction

    PubMed Central

    Seppänen, Tapio

    2017-01-01

    Fourier transform infrared (FTIR) microspectroscopy images contain information from the whole infrared spectrum used for microspectroscopic analyses. In combination with the FTIR image, visible light images are used to depict the area from which the FTIR spectral image was sampled. These two images are traditionally acquired as separate files. This paper proposes a histogram shifting-based data hiding technique to embed visible light images in FTIR spectral images producing single entities. The primary objective is to improve data management efficiency. Secondary objectives are confidentiality, availability, and reliability. Since the integrity of biomedical data is vital, the proposed method applies reversible data hiding. After extraction of the embedded data, the FTIR image is reversed to its original state. Furthermore, the proposed method applies authentication tags generated with keyed Hash-Based Message Authentication Codes (HMAC) to detect tampered or corrupted areas of FTIR images. The experimental results show that the FTIR spectral images carrying the payload maintain good perceptual fidelity and the payload can be reliably recovered even after bit flipping or cropping attacks. It has been also shown that extraction successfully removes all modifications caused by the payload. Finally, authentication tags successfully indicated tampered FTIR image areas. PMID:29259987

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

    PubMed Central

    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

  11. Trends and changes in prescription opioid analgesic dispensing in Canada 2005–2012: an update with a focus on recent interventions

    PubMed Central

    2014-01-01

    Background Prescription opioid analgesic (POA) utilization has steeply increased globally, yet is far higher in established market economies than elsewhere. Canada features the world’s second-highest POA consumption rates. Following increases in POA-related harm, several POA control interventions have been implemented since 2010. Methods We examined trends and patterns in POA dispensing in Canada by province for 2005–2012, including a focus on the potential effects of interventions. Data on annual dispensing of individual POA formulations – categorized into ‘weak opioids’ and ‘strong opioids’ – from a representative sub-sample of 5,700 retail pharmacies across Canada (from IMS Brogan’s Compuscript) were converted into Defined Daily Doses (DDD), and examined intra- and inter-provincially as well as for Canada (total). Results Total POA dispensing – driven by strong opioids – increased across Canada until 2011; four provinces indicated decreases in strong opioid dispensing; seven provinces indicated decreases specifically in oxycodone dispensing, 2011–2012. The dispensing ratio weak/strong opioids decreased substantively. Major inter-provincial differences in POA dispensing levels and qualitative patterns of POA formulations dispensed persisted. Previous increasing trends in POA dispensing were reversed in select provinces 2011–2012, coinciding with POA-related interventions. Conclusions Further examinations regarding the sustained nature, drivers and consequences of the recent trend changes in POA dispensing – including possible ‘substitution effects’ for oxycodone reductions – are needed. PMID:24572005

  12. Assessment of the trends in medical use and misuse of opioid analgesics from 2004 to 2011.

    PubMed

    Atluri, Sairam; Sudarshan, Gururau; Manchikanti, Laxmaiah

    2014-01-01

    690% from 1996 to 2004 and 100% from 2004 to 2011. In contrast, misuse increased more dramatically: 4,680% from 1996 to 2011, with increases of 1,372% from 1996 through 2004 and 245% from 2004 to 2011. The number of patients seeking rehabilitation for substance abuse also increased 187% for opioids, whereas it increased 87% for heroin, 40% for marijuana, and decreased 7% for cocaine. Limitations of this assessment include the lack of data from 2003, lack of data available on meperidine, and that the aggregate data systems used in the study did not identify specific formulations or commercial products. The present trend of continued increase in the medical use of opioid analgesics appears to contribute to increases in misuse, resulting in multiple health consequences.

  13. [The endogenous opioid system and drug addiction].

    PubMed

    Maldonado, R

    2010-01-01

    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  14. Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans.

    PubMed

    Bershad, Anya K; Miller, Melissa A; Norman, Greg J; de Wit, Harriet

    2018-06-01

    Both preclinical and clinical evidence suggests that the endogenous opioid system is involved in responses to stress. For example, in animal models opioid agonists reduce isolation distress whereas opioid antagonists increase isolation distress. We recently reported that the mixed mu agonist and kappa antagonist buprenorphine dampened responses to acute psychosocial stress in humans. Now we extend this to study the effects of a pure mu-opioid agonist, hydromorphone, and a non-opioid analgesic, acetaminophen, on response to social stress. We compared the effect of hydromorphone (2 and 4 mg), acetaminophen (1000 mg) to a placebo using a between subject design. Healthy adult volunteers were randomly assigned to receive placebo (N = 13), 2 mg hydromorphone (N = 12), 4 mg hydromorphone (N = 12), or 1000 mg acetaminophen (paracetamol; N = 13) under double-blind conditions before undergoing a stress task or a control task on two separate sessions. The stress task, consisting of a standardized speaking task and the non-stressful control task were presented in counterbalanced order. Dependent measures included mood ratings, subjective appraisal of the stress (or no-stress) task, salivary cortisol, pupil diameter, heart rate, and blood pressure. The stress task produced its expected increase in heart rate, blood pressure, salivary cortisol, pupil diameter, and subjective ratings of anxiety and negative mood. Hydromorphone dose-dependently dampened cortisol responses to stress, and decreased ratings of how "challenging" participants found the task. Acetaminophen did not affect physiological responses, but, like hydromorphone, decreased ratings of how "challenging" the task was. The hydromorphone results support the idea that the mu-opioid system is involved in physiological responses to acute stress in humans, in line with results from preclinical studies. The non-opioid analgesic acetaminophen did not dampen physiological responses, but did reduce

  15. Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study.

    PubMed

    Larochelle, Marc R; Bernson, Dana; Land, Thomas; Stopka, Thomas J; Wang, Na; Xuan, Ziming; Bagley, Sarah M; Liebschutz, Jane M; Walley, Alexander Y

    2018-06-19

    Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known. To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality. Retrospective cohort study. 7 individually linked data sets from Massachusetts government agencies. 17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014. Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality. In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years. Compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR], 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). No associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]) were identified. Few events among naltrexone recipients

  16. Reality and responsibility revisited: Stakeholder accountability in the effort to develop safer opioids.

    PubMed

    Passik, Steven D; Heit, Howard A; DeGeorge, Michael

    This supplement is dedicated to an exploration of the science, potential utility, and the current state of abuse-deterrent formulations (ADF) of opioid analgesics. There are many stakeholders in the search for safer pain treatments in general, and safer opioid therapy in particular. Healthcare providers, patients, third-party payors, law enforcement and government regulators, the pharmaceutical industry, and the media all have a stake in seeing pain treated and addiction and overdose avoided. As it applies to ADFs, obviously not everyone has a stake in seeing that ADFs succeed commercially; but all stakeholders certainly have a responsibility to see that any potential advance, including ADFs, in protecting the public health is fairly and thoroughly evaluated. Particularly at a time of crisis. In this article, we revisit the framework used by Passik, Heit, and Kirsh (2006) to evaluate stakeholders' responsibilities with regard to both the opioid abuse and chronic pain epidemics. After evaluating the present status of aspirations delineated over a decade ago, we discuss the updated roles and responsibilities of each stakeholder, with emphasis on the role of ADFs as this technology was unavailable when the original manuscript was written.

  17. Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain.

    PubMed

    Shurman, Joseph; Koob, George F; Gutstein, Howard B

    2010-07-01

    Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek "katifeia" for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Repeated engagement of opponent processes without time for the brain's emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

  18. A statewide effort to reduce high-dose opioid prescribing through coordinated care organizations.

    PubMed

    Hartung, Daniel M; Alley, Lindsey; Leichtling, Gillian; Korthuis, P Todd; Hildebran, Christi

    2018-05-01

    Oregon's Medicaid program is delivered through 16 Coordinated Care Organizations (CCOs) participating in a statewide performance improvement program to reduce high-dose opioid prescribing. CCOs were allowed flexibility to develop their own dose targets and any policies, trainings, guidelines, and/or materials to meet these targets. In this study, we characterize CCO strategies to reduce high-dose opioid prescribing across the 16 CCOs. We reviewed relevant CCO documents and conducted semi-structured interviews with CCO administrators to acquire opioid-related policies, practices, timelines and contextual factors. We applied a systematic coding procedure to develop a comprehensive description of each CCO's strategy. We used administrative data from the state to summarize contextual utilization data for each CCO. Most CCOs selected a target daily morphine milligram equivalent (MME) dose of 90 mg. Sixteen issued quantity limits related to dose, eight restricted specific drug formulations (short-acting or long-acting), and 11 allowed for time-limited taper plan periods for patients over threshold. Many CCOs also employed provider trainings, feedback reports, and/or onsite technical assistance. Other innovations included incentive measures, electronic health record alerts, and toolkits with materials on local alternative therapy resources and strategies for patient communication. CCOs leveraging collaborations with regional partners appeared to mount a greater intensity of interventions than independently operating CCOs. CCOs developed a diversity of interventions to confront high-risk opioid prescribing within their organization. As healthcare systems mount interventions to reduce risky opioid prescribing, it is critical to carefully describe these activities and examine their impact on process and health outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Factors associated with opioid dose increases: a chart review of patients’ first year on long-term opioids

    PubMed Central

    Bautista, Christopher A.; Iosif, Ana-Maria; Wilsey, Barth L.; Melnikow, Joy A.; Crichlow, Althea; Henry, Stephen G.

    2016-01-01

    OBJECTIVE To examine encounter-level factors associated with opioid dose increases during patients’ first year on opioid therapy for chronic pain. DESIGN Case-control study analyzing all opioid prescriptions for patients with chronic pain during their first year after opioid initiation. Cases were patients who experienced an overall dose escalation of ≥30 mg morphine equivalents over the 1-year period; controls did not experience overall dose escalation. Main measures were encounter type; opioid dose change; documented prescribing rationale; documentation of guideline-concordant opioid prescribing practices. Two coders reviewed all encounters associated with opioid prescriptions. Analysis of factors associated with dose increases and provider documentation of prescribing rationale was conducted using multiple logistic regression. RESULTS 674 encounters were coded for 66 patients (22 cases, 44 controls). Fifty-three percent of opioid prescriptions were associated with telephone encounters; 13% were associated with email encounters. No prescribing rationale was documented for 43% of all opioid prescriptions and 25% of dose increases. Likelihood of dose increase and documentation of prescribing rationale did not significantly differ for cases versus controls. Compared to face-to-face encounters, dose increases were significantly less likely for telephone (OR 0.18, 95%CI 0.11 – 0.28) and email (OR 0.23, 95%CI 0.12 – 0.47) encounters; documentation of prescribing rationale was significantly more likely for email (OR 5.06, 95%CI 1.87–13.72) and less likely for telephone (OR 0.30, 95%CI 0.18–0.51) encounters. CONCLUSION Most opioid prescriptions were written without face-to-face encounters. One quarter of dose increases contained no documented prescribing rationale. Documented encounter-level factors were not significantly associated with overall opioid dose escalation. PMID:27477581

  20. Creating opioid dependence in the emergency department.

    PubMed

    Upadhye, Suneel

    2018-01-01

    Clinical question What is the risk of creating opioid dependence from an ED opioid prescription? Article chosen Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017;376:663-73, doi:10.1056/NEJMsa1610524. This study examined the risk of creating long-term opioid dependence from a prescription written in an opioid-naive patient in the ED.

  1. The ‘mystery’ of opioid-induced diarrhea

    PubMed Central

    Bril, Silviu; Shoham, Yoav; Marcus, Jeremy

    2011-01-01

    Bowel dysfunction, mainly constipation, is a well-known and anticipated side effect of opioids. The physician prescribing an opioid frequently confronts the challenge of preventing and treating bowel dysfunction. Different strategies have emerged for managing opioid-induced constipation. These strategies include physical activity, maintaining adequate fluid intake, adhering to regular daily bowel habits, using laxatives and other anticonstipation medications and, recently, using a peripheral opioid antagonist, either as a separate drug or in the form of an opioid agonist-antagonist combination pill. What options exist for the physician when a patient receiving opioids complains of diarrhea, cramps and bloating, rather than the expected constipation? The present article describes a possible cause of opioid-induced diarrhea and strategies for management. PMID:21766071

  2. Sociodemographic profile and pattern of opioid abuse among patients presenting to a de-addiction centre in tertiary care Hospital of Kashmir

    PubMed Central

    Farhat, Samina; Hussain, Syed Sajad; Rather, Yasir Hassan; Hussain, Syed Karrar

    2015-01-01

    Background: The substances abuse has become one of the major public health problems of present society. Recently there has been an increase in the incidence of substance abuse including that of opioids throughout the world. The proper assessment of the current trends and pattern of opioid abuse can be helpful in more effective intervention of this menace. Materials and Methods: To find out various socio-demographic variables and pattern of opioid abuse, a predevised questionnaire was administered to 200 opioid patients who presented to de-addiction center for treatment. Results: Majority of the participants (75%) were of young age group (20–30 years) and the mean age of subjects was 27.6 years. More than half of participants (55%) were abusing the opioid substances for < 3 years followed by 30% of the abusers who were using the opioids for 4–6 years. Oral route was the most common route(35%)of substance administration followed by chasing(13%) and intravenous(11%) routes. Diverted pharmaceuticals emerged as one of the common substances of abuse, and peer pressure was found to be the main reason to start substance abuse. Conclusion: A comprehensive preventive program targeting young adults needs to be formulated and strict laws against sales of diverted pharmaceuticals to be implemented. PMID:26229346

  3. Characteristics of drug use among pregnant women in the United States: Opioid and non-opioid illegal drug use.

    PubMed

    Metz, Verena E; Brown, Qiana L; Martins, Silvia S; Palamar, Joseph J

    2018-02-01

    The opioid epidemic in the US is affecting pregnant women and their offspring, with rising numbers of maternal and neonatal treatment episodes. The aim of this study was to characterize pregnant drug users in order to inform intervention strategies based on sociodemographic, mental health, and substance use characteristics. Data on pregnant women aged 18-44 reporting past-year, nonmedical opioid use or use of non-opioid illegal drugs (other than marijuana) were analyzed from the National Survey on Drug Use and Health (2005-2014). Women (N = 818) were categorized into 3 groups: 1) use of opioids only (n = 281), 2) opioid-polydrug users (n = 241), and 3) other (non-opioid) illegal drug users (n = 296). Characteristics between the 3 groups of women were compared using bivariable analyses. Most women were non-Hispanic White (67.6%), had a high school diploma or less education (61.0%), a household income <$20,000/year (72.2%), and health insurance coverage (84.3%). No significant differences between the three groups were found regarding sociodemographic characteristics. Past-30-day marijuana use was less prevalent among opioid-only users (10.9%) compared to opioid-polydrug users (43.6%) and other pregnant illegal drug users (27.6%) (P < 0.001) and past-year drug/alcohol treatment was less prevalent among opioid-only users (6.3%) compared to opioid-polydrug users (20.3%) and other illegal drug users (8.3%) (P = 0.002). Opioid-only users also reported lower prevalence of past-year depression (P < 0.001) and anxiety (P = 0.039). Pregnant drug-using women were often of low socioeconomic status, with mental health and substance use patterns suggesting the need for targeted mental health/substance use screening and interventions before and during pregnancy, particularly for opioid-polydrug users. Copyright © 2017. Published by Elsevier B.V.

  4. Inhibitory effects of opioids on compound action potentials in frog sciatic nerves and their chemical structures.

    PubMed

    Mizuta, Kotaro; Fujita, Tsugumi; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2008-08-01

    An opioid tramadol more effectively inhibits compound action potentials (CAPs) than its metabolite mono-O-demethyl-tramadol (M1). To address further this issue, we examined the effects of opioids (morphine, codeine, ethylmorphine and dihydrocodeine) and cocaine on CAPs by applying the air-gap method to the frog sciatic nerve. All of the opioids at concentrations less than 10 mM reduced the peak amplitude of the CAP in a reversible and dose-dependent manner. The sequence of the CAP peak amplitude reductions was ethylmorphine>codeine>dihydrocodeine> or = morphine; the effective concentration for half-maximal inhibition (IC(50)) of ethylmorphine was 4.6 mM. All of the CAP inhibitions by opioids were resistant to a non-specific opioid-receptor antagonist naloxone. The CAP peak amplitude reductions produced by morphine, codeine and ethylmorphine were related to their chemical structures in such that this extent enhanced with an increase in the number of -CH(2) in a benzene ring, as seen in the inhibitory actions of tramadol and M1. Cocaine reduced CAP peak amplitudes with an IC(50) value of 0.80 mM. It is concluded that opioids reduce CAP peak amplitudes in a manner being independent of opioid-receptor activation and with an efficacy being much less than that of cocaine. It is suggested that the substituted groups of -OH bound to the benzene ring of morphine, codeine and ethylmorphine as well as of tramadol and M1, the structures of which are quite different from those of the opioids, may play an important role in producing nerve conduction block.

  5. Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain.

    PubMed

    Wilder, Christine M; Miller, Shannon C; Tiffany, Elizabeth; Winhusen, Theresa; Winstanley, Erin L; Stein, Michael D

    2016-01-01

    Rising overdose fatalities among U.S. veterans suggest veterans taking prescription opioids may be at risk for overdose. However, it is unclear whether veterans prescribed chronic opioids are aware of this risk. The objective of this study was to identify risk factors and determine awareness of risk for opioid overdose in veterans treated with opioids for chronic pain, using veterans treated with methadone or buprenorphine for opioid use disorder as a high-risk comparator group. In the current study, 90 veterans on chronic opioid medication, for either opioid use disorder or pain management, completed a questionnaire assessing risk factors, knowledge, and self-estimate of risk for overdose. Nearly all veterans in both groups had multiple overdose risk factors, although individuals in the pain management group had on average a significantly lower total number of risk factors than did individuals in the opioid use disorder group (5.9 versus 8.5, p < .0001). On average, participants treated for pain management scored slightly but significantly lower on knowledge of opioid overdose risk factors (12.1 versus 13.5, p < .01). About 70% of participants, regardless of group, believed their overdose risk was below that of the average American adult. There was no significant relationship between self-estimate of overdose risk and either number or knowledge of opioid overdose risk factors. Our results suggest that veterans in both groups underestimated their risk for opioid overdose. Expansion of overdose education to include individuals on chronic opioids for pain management and a shift in educational approaches to overdose prevention may be indicated.

  6. Opioid tolerance and dependence -- do they matter?

    PubMed

    Jage, Jürgen

    2005-04-01

    The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long-term therapy with short-acting opioids predisposes to tolerance and addiction. Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others. This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug-aberrant behavior, drug history, psychopathology, and somatization.

  7. Filled Prescriptions for Opioids After Vaginal Delivery.

    PubMed

    Jarlenski, Marian; Bodnar, Lisa M; Kim, Joo Yeon; Donohue, Julie; Krans, Elizabeth E; Bogen, Debra L

    2017-03-01

    To estimate the prevalence of filled opioid prescriptions after vaginal delivery. We conducted a retrospective cohort study of 164,720 Medicaid-enrolled women in Pennsylvania who delivered a liveborn neonate vaginally from 2008 to 2013, excluding women who used opioids during pregnancy or who had an opioid use disorder. We assessed overall filled prescriptions as well as filled prescriptions in the presence or absence of the following pain-inducing conditions: bilateral tubal ligation, perineal laceration, or episiotomy. Outcomes included a binary measure of whether a woman had any opioid prescription fill 5 days or less after delivery and, among those women, a second opioid prescription fill 6-60 days after delivery. Among women with no coded pain-inducing conditions at delivery, we used multivariable logistic regression with standard errors clustered to account for within-hospital correlation to assess the association between patient characteristics and odds of a filled opioid prescription. Twelve percent of women (n=18,131) filled an outpatient opioid prescription 5 days or less after vaginal delivery; among those women, 14% (n=2,592, or 1.6% of the total) filled a second opioid prescription 6-60 days after delivery. Of the former, 5,110 (28.2%) had one or more pain-inducing conditions. Predictors of filled opioid prescriptions with no observed pain-inducing condition at delivery included tobacco use (adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2-1.4) and a mental health condition (adjusted OR 1.3, 95% CI 1.2-1.4). Having a diagnosis of substance use disorder other than opioid use disorder was not associated with filling an opioid prescription 5 days or less after delivery, but was associated with having a second opioid prescription 6-60 days after delivery (adjusted OR 1.4, 95% CI 1.2-1.6). More than 1 in 10 Medicaid-enrolled women fill an outpatient opioid prescription after vaginal delivery. National opioid-prescribing recommendations for

  8. Opioid receptor trafficking and interaction in nociceptors

    PubMed Central

    Zhang, X; Bao, L; Li, S

    2015-01-01

    Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ- and δ-opioid receptors are co-expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ-opioid receptors with δ-opioid receptors in the nociceptive afferents is facilitated by the stimulus-induced cell-surface expression of δ-opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24611685

  9. First Dutch national guidelines--pharmacological care for detained opioid addicts.

    PubMed

    Arends, M T; De Haan, H A; Van 't Hoff, G I C M

    2009-01-01

    Heterogenic care of addicted detainees in the various prisons in The Netherlands triggered the National Agency of Correctional Institutions of the Ministry of Justice, to order the Dutch Institute for Health Care Improvement (CBO) to formulate the first national guideline titled 'Pharmacological care for detained addicts'. This article presents the content of this guideline, which mainly focuses on opioid-dependent addicts. In The Netherlands, approximately 50% of the detainees are problematic substance abusers, while again half of this group suffers from psychiatric co-morbidity. In addition, somatic co-morbidity, especially infectious diseases, is also common. Due to the moderate outcome seen with voluntary drug counselling regimes in prison, there is a policy shift to extent utilization of legally enforced approaches. Continuity of care is of great importance. In case of opioid addicts this, in general, means continuation of methadone maintenance treatment. Aftercare immediately after detention and optimalization of medical information transfer is crucial. This guideline aims to realize optimal and uniform management of addiction disorders in the Dutch prison system.

  10. Opioid Rotation in Cancer Pain Treatment.

    PubMed

    Schuster, Michael; Bayer, Oliver; Heid, Florian; Laufenberg-Feldmann, Rita

    2018-03-02

    Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it. This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route. 9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best. Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.

  11. Adherence Monitoring with Chronic Opioid Therapy for Persistent Pain: A Biopsychosocial-spiritual Approach to Mitigate Risk

    PubMed Central

    Matteliano, Deborah; St. Marie, Barbara J.; Oliver, June

    2013-01-01

    Opioids represent a mainstay in the pharmacological management of persistent pain. While these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a past history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing (ASPMN) Position Statement on Pain Management in Patients with Substance Use Disorders (2012) focuses on the intersection of persistent pain, SUD, and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to now include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. PMID:24602442

  12. Patterns of Opioid Use in Sickle Cell Disease

    PubMed Central

    Han, Jin; Saraf, Santosh L.; Zhang, Xu; Gowhari, Michel; Molokie, Robert E.; Hassan, Johara; Alhandalous, Chaher; Jain, Shivi; Younge, Jewel; Abbasi, Taimur; Machado, Roberto F.; Gordeuk, Victor R.

    2016-01-01

    Pain, the hallmark complication of sickle cell disease (SCD), is largely managed with opioid analgesics in the United States, but comprehensive data regarding the long-term use of opioids in this patient population is lacking. The pain medication prescription records from a cohort of 203 SCD patients were analyzed. Twenty-five percent were not prescribed opioid medications while 47% took only short-acting opioids, 1% took only long-acting opioids, and 27% took a combination of short-acting and long-acting opioids. The median (interquartile range) daily opioid dose was 6.1 mg (1.7-26.3 mg) of oral morphine equivalents, which is lower than the published opioid use among patients with other pain syndromes. The dose of opioids correlated with the number of admissions due to vaso-occlusive crisis (VOC) (r=0.53, p<0.001). When the patients were grouped into quartiles based on daily dose opioid use, a logistic regression model showed that history of avascular necrosis (AVN) (OR 2.87, 95% CI: 1.37-6.02, p=0.005), 25-OHD levels (OR 0.59, 95% CI: 0.38-0.93, p=0.024) and total bilirubin concentration (OR 0.64, 95% CI: 0.42-0.99, p=0.043) were independently associated with opioid use quartiles. In conclusion, doses and types of opioid medications used by adult SCD patients vary widely. Our findings implicate AVN and lower vitamin D levels as factors associated with higher opioid use. They also suggest an association of higher bilirubin levels, possibly suggesting higher hemolytic rate, with lower opioid use. PMID:27466799

  13. 42 CFR 8.11 - Opioid treatment program certification.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

  14. 42 CFR 8.11 - Opioid treatment program certification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

  15. 42 CFR 8.11 - Opioid treatment program certification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

  16. 42 CFR 8.11 - Opioid treatment program certification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

  17. 42 CFR 8.11 - Opioid treatment program certification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Opioid treatment program certification. 8.11... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Certification and Treatment Standards § 8.11 Opioid... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP...

  18. "Old Age and Loneliness: Cross-Sectional and Longitudinal Analyses in the Tampere Longitudinal Study on Aging"

    ERIC Educational Resources Information Center

    Jylha, Marja

    2004-01-01

    The purpose of this study was to examine whether older age is associated with increasing loneliness in people aged 60 and over. Data came from TamELSA, a population-based prospective longitudinal study in Tampere, Finland. The followup time was 20 years. Loneliness was measured by a single question--"Do you feel lonely?"--with the…

  19. The impact of opioids on the endocrine system.

    PubMed

    Katz, Nathaniel; Mazer, Norman A

    2009-02-01

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

  20. Tamper asymmetry and its effect on transmission for x-ray driven opacity simulations

    DOE PAGES

    Morris, H. E.; Tregillis, I. L.; Hoffman, N. M.; ...

    2017-08-01

    This paper reports on synthetic transmission results from Lasnex [1] radiation-hydrodynamics simulations of opacity experiments carried out at Sandia National Laboratories' recently upgraded ZR facility. The focus is on experiments utilizing disk targets composed of a half-moon Fe/Mg mixture tamped on either end with 10- m CH and an additional 35- m beryllium tamper accessory on the end facing the spectrometer. Five x-ray sources with peak power ranging from 10 to 24 TW were used in the simulations to heat and backlight the opacity target. The dominant effect is that the beryllium behind the Fe/Mg mixture is denser and moremore » opaque than the beryllium unshielded by metal during the times of greatest importance for the transmission measurement for all drives. This causes the simulated transmission to be lower than expected, and this is most pronounced for the case using the lowest drive power. While beryllium has a low opacity, its areal density is sufficiently high such that the expected reduction of the measured transmission is significant. This situation leads to an overestimate of iron opacity by 10-215% for a photon energy range of 975- 1775 eV for the 10-TW case. It is shown that if the tamper conditions are known, the transmission through each component of the target can be calculated and the resulting opacity can be corrected.« less

  1. Opioid use in gynecologic oncology in the age of the opioid epidemic: Part I - Effective opioid use across clinical settings, a society of gynecologic oncology evidence-based review.

    PubMed

    Lefkowits, Carolyn; Buss, Mary K; Ramzan, Amin A; Fischer, Stacy; Urban, Renata R; Fisher, Christine M; Duska, Linda R

    2018-05-01

    As the only oncologists that provide both medical and surgical oncologic care, gynecologic oncologists encounter an exceptionally broad range of indications for prescribing opioids, from management of acute post-operative pain to chronic cancer-related pain to end-of-life care. If we are to balance opioid efficacy, safety and accessibility for our patients, we must be intimately familiar with appropriate clinical use of opioids in a range of settings, and engage in the national conversation around opioid misuse and how associated regulations and legislation may impact us and our patients. This article examines the appropriate use of opioids across the range of clinical settings encountered in gynecologic oncology. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia: a systematic review.

    PubMed

    Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D

    2015-01-01

    The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

  3. Prescription opioid abuse based on representative postmortem toxicology.

    PubMed

    Häkkinen, Margareeta; Vuori, Erkki; Ojanperä, Ilkka

    2014-12-01

    Opioids are important medications for pain and opioid maintenance treatment. Increasing use and abuse of prescription opioids has, however, caused worldwide concern. Our aim was to estimate the ratio between prescription opioid abuse and total use, based on representative postmortem toxicology. Our material included all the medico-legally examined deaths in Finland during 2010-2011 involving positive findings involving buprenorphine, codeine, fentanyl, methadone, oxycodone, or tramadol. We studied drug abuse by age group, with "abuse" meaning licit opioids used illicitly as narcotics. Drug-abuse history, drug injecting, or laboratory findings of illicit drugs defined an abuser case. We then compared abuser cases and other opioid-related cases between the opioids with the number of fatal poisonings, accidents, suicides, alcohol findings, concomitant opioid use, and median postmortem blood opioid concentrations. Opioid findings numbered 2499 in 2088 cases. Drug abuse involved 545 opioid-positive cases, which in Finland represented 0.5% of those deceased. The proportion of abuser cases among all opioid-related cases for buprenorphine was 85.5%, for methadone 82.4%, for tramadol 29.4%, for codeine 16.3%, for fentanyl 14.5%, and for oxycodone 6.9%. Abuse in age-groups >60 was rare. Concomitant other opioid findings were more frequent in abuser- than in other cases for codeine, oxycodone, and tramadol, whereas alcohol findings were more frequent in buprenorphine, codeine, and fentanyl abuse. Buprenorphine and methadone were most often related to drug abuse. Every other opioid studied involved some abuse, and especially tramadol. Abuse and fatal poisonings were concentrated in men aged 20-49. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Opioid Stewardship in Otolaryngology: State of the Art Review.

    PubMed

    Cramer, John D; Wisler, Brad; Gouveia, Christopher J

    2018-05-01

    Objective The United States is facing an epidemic of opioid addiction. Deaths from opioid overdose have quadrupled in the past 15 years and now surpass annual deaths during the height of the human immunodeficiency virus epidemic. There is a link between opioid prescriptions after surgery, opioid misuse, opioid diversion, and use of other drugs of abuse. As surgeons, otolaryngologists contribute to this crisis. Our objective is to outline the risk of abuse from opioids in the management of acute postoperative pain in otolaryngology-head and neck surgery (OHNS) and strategies to avoid misuse. Data Sources PubMed/MEDLINE. Review Methods We conducted a review of the literature on the rate of opioid abuse after surgery, methods of safe opioid use, and strategies to minimize the dangers of opioids. Conclusions Otolaryngologists have a responsibility to treat pain. This begins preoperatively by discussing perioperative pain control and developing a personalized pain control plan. Patients should be aware that opioids carry significant risks of adverse events and abuse. Perioperative use of multimodal nonopioid agents enables pain control and avoidance of opioids in many otolaryngologic cases. When this approach is inadequate, opioids should be used in short duration under close surveillance. Institutional standards for opioid prescribing after common procedures can minimize misuse. Implications for Practice Otolaryngologists need to acknowledge the potential harm that opioids cause. It is essential that we evaluate our practices to ensure that opioids are used responsibly. Furthermore, opioid stewardship should become a priority in otolaryngology.

  5. Neuraxial Opioid-Induced Itch and Its Pharmacological Antagonism

    PubMed Central

    2015-01-01

    Given its profound analgesic nature, neuraxial opioids are frequently used for pain management. Unfortunately, the high incident rate of itch/pruritus after spinal administration of opioid analgesics reported in postoperative and obstetric patients greatly diminishes patient satisfaction and thus the value of the analgesics. Many endeavors to solve the mystery behind neuraxial opioid-induced itch had not been successful, as the pharmacological antagonism other than the blockade of mu opioid receptors remains elusive. Nevertheless, as the characteristics of all opioid receptor subtypes have become more understood, more studies have shed light on the potential effective treatments. This review discusses the mechanisms underlying neuraxial opioid-induced itch and compares pharmacological evidence in nonhuman primates with clinical findings across diverse drugs. Both nonhuman primate and human studies corroborate that mixed mu/kappa opioid partial agonists seem to be the most effective drugs in ameliorating neuraxial opioid-induced itch while retaining neuraxial opioid-induced analgesia. PMID:25861787

  6. 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.

    PubMed

    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.

  7. Something for pain: Responsible opioid use in emergency medicine.

    PubMed

    Strayer, Reuben J; Motov, Sergey M; Nelson, Lewis S

    2017-02-01

    The United States is currently experiencing a public health crisis of opioid addiction, which has its genesis in an industry marketing effort that successfully encouraged clinicians to prescribe opioids liberally, and asserted the safety of prescribing opioids for chronic non-cancer pain, despite a preponderance of evidence demonstrating the risks of dependence and misuse. The resulting rise in opioid use has pushed drug overdose deaths in front of motor vehicle collisions to become the leading cause of accidental death in the country. Emergency providers frequently treat patients for complications of opioid abuse, and also manage patients with acute and chronic pain, for which opioids are routinely prescribed. Emergency providers are therefore well positioned to both prevent new cases of opioid misuse and initiate appropriate treatment of existing opioid addicts. In opioid-naive patients, this is accomplished by a careful consideration of the likelihood of benefit and harm of an opioid prescription for acute pain. If opioids are prescribed, the chance of harm is reduced by matching the number of pills prescribed to the expected duration of pain and selecting an opioid preparation with low abuse liability. Patients who present to acute care with exacerbations of chronic pain or painful conditions associated with opioid misuse are best managed by treating symptoms with opioid alternatives and encouraging treatment for opioid addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Barriers to Using Nonpharmacologic Approaches and Reducing Opioid Use in Primary Care.

    PubMed

    Giannitrapani, Karleen F; Ahluwalia, Sangeeta C; McCaa, Matthew; Pisciotta, Maura; Dobscha, Steven; Lorenz, Karl A

    2017-10-20

    Opioid prescribing for chronic pain, including the potential for over-reliance and misuse, is a public health concern. In the context of Veterans Administration (VA) primary care team-based pain management, we aimed to understand providers' perceptions of barriers to reducing opioid use and improving the use of nonpharmacologic pain management therapies (NPTs) for chronic pain. A semistructured interview elucidated provider experiences with assessing and managing pain. Emergent themes were mapped to known dimensions of VA primary care access. Informants included 60 primary care providers, registered nurses, licensed practical nurses, clerks, psychologists, and social workers at two VA Medical Centers. Nine multidisciplinary focus groups. Provider perceptions of barriers to reducing opioids and improving use of NPTs for patients with chronic pain clustered around availability and access. Barriers to NPT access included the following subthemes: geographical (patient distance from service), financial (out-of-pocket cost to patient), temporal (treatment time delays), cultural (belief that NPTs increased provider workload, perception of insufficient training on NPTs, perceptions of patient resistance to change, confrontation avoidance, and insufficient leadership support), and digital (measure used for pain assessment, older patients hesitant to use technology, providers overwhelmed by information). Decreasing reliance on opioids for chronic pain requires a commitment to local availability and provider-facing strategies that increase efficacy in prescribing NPTs. Policies and interventions for decreasing utilization of opioids and increasing use of NPTs should comprehensively consider access barriers. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

  9. Patient-reported opioid analgesic requirements after elective inguinal hernia repair: A call for procedure-specific opioid-administration strategies.

    PubMed

    Mylonas, Konstantinos S; Reinhorn, Michael; Ott, Lauren R; Westfal, Maggie L; Masiakos, Peter T

    2017-11-01

    A better understanding of the analgesia needs of patients who undergo common operative procedures is necessary as we address the growing opioid public health crisis in the United States. The aim of this study was to evaluate patient experience with our opioid prescribing practice after elective inguinal hernia repairs. A prospective, observational study was conducted between October 1, 2015, and September 30, 2016, in a single-surgeon, high-volume, practice of inguinal hernia operation. Adult patients undergoing elective inguinal herniorrhaphy under local anesthesia with intravenous sedation were invited to participate. All patients were prescribed 10 opioid analgesic tablets postoperatively and were counseled to reserve opioids for pain not controlled by nonopioid analgesics. Their experience was captured by completing a questionnaire 2 to 3 weeks postoperatively during their postoperative visit. A total of 185 patients were surveyed. The majority of the participants were males (177, 95.7%) and ≥60 years old (96, 51.9%). Of the 185 patients, 159 (85.9%) reported using ≤4 opioid tablets; 110 patients (59.5%) reported that they used no opioid analgesics postoperatively. None of the patients was taking opioids within 7 days of their postoperative appointment. Of the 147 patients who were employed, 111 (75.5%) reported missing ≤3 work days, 57 of whom (51.4%) missed no work at all. Patients who were employed were more likely to take opioid analgesics postoperatively (P = .049). Patients who took no opioid analgesics experienced less maximum (P < .001) and persistent groin pain (P = .037). Pain interfered less with daily activities (P = .012) and leisure activities (P = .018) for patients who did not use opioids. The majority of our patients reported that they did not require any opioid analgesics, and nearly all of those who thought that they did need opioids used <5 tablets. Our data suggest that for elective inguinal hernia repair under a local

  10. The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

    PubMed Central

    2014-01-01

    Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

  11. Characterization of opioid use in sickle cell disease.

    PubMed

    Han, Jin; Zhou, Jifang; Saraf, Santosh L; Gordeuk, Victor R; Calip, Gregory S

    2018-05-01

    Opioid analgesics are commonly used to treat vaso-occlusive pain episodes in sickle cell disease (SCD), but comprehensive evidence characterizing opioid use in this patient population is limited. Our objective was to characterize opioid use patterns among SCD patients using a large nationwide database. A large, US medical claims database was utilized to identify a cohort of 3882 SCD patients, and characteristics of opioid use were analyzed. Clinical variables including age, gender, medication use, health care utilization, and medical history were evaluated for correlations with opioid use. Forty percent of patients took opioid medications during a 12-month span, and the prevalence of any opioid use was highest for 20 to 29-year-old patients (58%). The median daily opioid dose was 1.85 mg (interquartile range: 0.62-10.68 mg) oral morphine equivalents (OME). While most opioid users took between 0 and 5 mg OME daily, 3% of pediatric patients and 23% of adult patients used more than 30-mg OME daily. High-dose opioid use was associated with older age, hydroxyurea therapy, nonsteroidal anti-inflammatory drug (NSAID) use, and frequent inpatient hospitalizations. In multivariable-adjusted analyses, patients with vaso-occlusive complications such as pain crisis (OR = 3.8, 95% CI 2.7-5.3) and avascular necrosis (AVN) (OR = 3.7, 95% CI 2.7-5.1) were associated with high-dose opioid use. Our study showed that only 40% SCD patients were on opioid analgesics during a 12-month span. However, a non-trivial number of patients used a much higher dose of opioids despite a relatively low average daily opioid dose among SCD patients, particularly with vaso-occlusive complications. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Patterns of opioid use in sickle cell disease.

    PubMed

    Han, Jin; Saraf, Santosh L; Zhang, Xu; Gowhari, Michel; Molokie, Robert E; Hassan, Joharah; Alhandalous, Chaher; Jain, Shivi; Younge, Jewel; Abbasi, Taimur; Machado, Roberto F; Gordeuk, Victor R

    2016-11-01

    Pain, the hallmark complication of sickle cell disease (SCD), is largely managed with opioid analgesics in the United States, but comprehensive data regarding the long-term use of opioids in this patient population is lacking. The pain medication prescription records from a cohort of 203 SCD patients were analyzed. Twenty-five percent were not prescribed opioid medications while 47% took only short-acting opioids, 1% took only long-acting opioids, and 27% took a combination of short-acting and long-acting opioids. The median (interquartile range) daily opioid dose was 6.1 mg (1.7-26.3 mg) of oral morphine equivalents, which is lower than the published opioid use among patients with other pain syndromes. The dose of opioids correlated with the number of admissions due to vaso-occlusive crisis (VOC) (r = 0.53, P < 0.001). When the patients were grouped into quartiles based on daily dose opioid use, a logistic regression model showed that history of avascular necrosis (AVN) (OR: 2.87, 95% CI: 1.37-6.02, P = 0.005), 25-OHD levels (OR: 0.59, 95% CI: 0.38-0.93, P = 0.024) and total bilirubin concentration (OR: 0.64, 95% CI: 0.42-0.99, P = 0.043) were independently associated with opioid use quartiles. In conclusion, doses and types of opioid medications used by adult SCD patients vary widely. Our findings implicate AVN and lower vitamin D levels as factors associated with higher opioid use. They also suggest an association of higher bilirubin levels, possibly suggesting higher hemolytic rate, with lower opioid use. Am. J. Hematol. 91:1102-1106, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Relationship of opioid prescription sales and overdoses, North Carolina.

    PubMed

    Modarai, F; Mack, K; Hicks, P; Benoit, S; Park, S; Jones, C; Proescholdbell, S; Ising, A; Paulozzi, L

    2013-09-01

    In the United States, fatal drug overdoses have tripled since 1991. This escalation in deaths is believed to be driven primarily by prescription opioid medications. This investigation compared trends and patterns in sales of opioids, opioid drug overdoses treated in emergency departments (EDs), and unintentional overdose deaths in North Carolina (NC). Our ecological study compared rates of opioid sales, opioid related ED overdoses, and unintentional drug overdose deaths in NC. Annual sales data, provided by the Drug Enforcement Administration, for select opioids were converted into morphine equivalents and aggregated by zip code. These opioid drug sales rates were trended from 1997 to 2010. In addition, opioid sales were correlated and compared to opioid related ED visits, which came from a Centers for Disease Control and Prevention syndromic surveillance system, and unintentional overdose deaths, which came from NC Vital Statistics, from 2008 to 2010. Finally, spatial cluster analysis was performed and rates were mapped by zip code in 2010. Opioid sales increased substantially from 1997 to 2010. From 2008 to 2010, the quarterly rates of opioid drug overdoses treated in EDs and opioid sales correlated (r=0.68, p=0.02). Specific regions of the state, particularly in the southern and western corners, had both high rates of prescription opioid sales and overdoses. Temporal trends in sales of prescription opioids correlate with trends in opioid related ED visits. The spatial correlation of opioid sales with ED visit rates shows that opioid sales data may be a timely way to identify high-risk communities in the absence of timely ED data. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Reducing Opioid Prescribing Rates in Emergency Medicine.

    PubMed

    Guarisco, Joseph; Salup, Adam

    2018-01-01

    Pain management is one of the most common reasons patients visit the emergency department. Understanding the contributions of emergency medicine-and specifically Ochsner Health System's emergency providers-to the opioid crisis is important. Benchmark prescribing data indicated that Ochsner Health System emergency medicine providers' opioid prescription rates were significantly higher than the national average in emergency medicine. Data relevant to visit and opioid prescription counts were extracted from the organization's electronic health record system. Opioid prescription rates were calculated for each provider. A data transparency project was initiated in which provider opioid prescription rates were unblinded and distributed among the provider group. Opioid prescription rates declined in aggregate for the emergency services from 22% to 14% during the 1-year project timeline. Some physicians demonstrated a 70% reduction in prescription rates. Importantly, patient satisfaction scores were not negatively impacted by declining opioid prescription rates. Provider performance transparency using unblinded and transparent data analytics can efficiently and significantly alter provider practice.

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

    PubMed

    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.

  16. Changes in drug use patterns reported on the web after the introduction of ADF OxyContin: findings from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Web Monitoring Program.

    PubMed

    Vosburg, Suzanne K; Haynes, Colleen; Besharat, Andrea; Green, Jody L

    2017-09-01

    This qualitative study summarizes information that individuals shared online about use of OxyContin following the August 2010 introduction of the abuse deterrent formulation (ADF). The primary objective was to study online posts that endorsed continued use of OxyContin or a switch from OxyContin to another formulation of oxycodone or another substance altogether following the introduction of the ADF. A secondary objective was to determine whether posts revealed that the ADF led to cessation of OxyContin use. Data were collected with the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program, an online surveillance system that collects and organizes posts about prescription drugs from social media websites, blogs, and forums from 3Q2009 to 4Q2014 using a commercially available web platform. Posts were categorized by whether they conveyed a switch to drugs other than reformulated OxyContin or a continuation of reformulated OxyContin abuse. "Switch posts" primarily discussed switching to immediate-release opioids. "Continue abusing" posts identified tampering strategies for alternate routes of administration, oral use, and continued use although post authors were generally unhappy with the experience. No reference to OxyContin cessation as a function of the introduction of the ADF was found; however, discontinued use was discussed. Web Monitoring data are useful for capturing cross sections of Internet conversation reflecting reactions to new drug formulations. These data support the notion that users will gravitate to non-ADFs generally, and to immediate-release non-ADF opioid formulations, specifically, as long as these options remain on the market. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder.

    PubMed

    Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

    2017-01-01

    Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes.

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

    PubMed Central

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

    2011-01-01

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

  19. Secular trends in opioid prescribing in the USA.

    PubMed

    Pezalla, Edmund J; Rosen, David; Erensen, Jennifer G; Haddox, J David; Mayne, Tracy J

    2017-01-01

    Opioid abuse and misuse in the USA is a public health crisis. The use of prescription opioid analgesics increased substantially from 2002 through 2010, then plateaued and began to decrease in 2011. This study examined prescriptions of branded and generic immediate- and extended-release opioid analgesics from 1992 to 2016. This was juxtaposed against state and federal policies designed to decrease overutilization and abuse, as well as the launch of new opioid products, including opioids with abuse-deterrent properties (OADPs). The data indicate that these health policies, including the utilization and reimbursement of OADPs, have coincided with decreased opioid utilization. The hypothesis that OADPs will paradoxically increase opioid prescribing is not supported.

  20. An analysis of errors, discrepancies, and variation in opioid prescriptions for adult outpatients at a teaching hospital

    PubMed Central

    Bicket, Mark C.; Kattail, Deepa; Yaster, Myron; Wu, Christopher L.; Pronovost, Peter

    2017-01-01

    Objective To determine opioid prescribing patterns and rate of three types of errors, discrepancies, and variation from ideal practice. Design Retrospective review of opioid prescriptions processed at an outpatient pharmacy Setting Tertiary institutional medical center Patients We examined 510 consecutive opioid medication prescriptions for adult patients processed at an institutional outpatient pharmacy in June 2016 for patient, provider, and prescription characteristics. Main Outcome Measure(s) We analyzed prescriptions for deviation from best practice guidelines, lack of two patient identifiers, and noncompliance with Drug Enforcement Agency (DEA) rules. Results Mean patient age (SD) was 47.5 years (17.4). The most commonly prescribed opioid was oxycodone (71%), usually not combined with acetaminophen. Practitioners prescribed tablet formulation to 92% of the sample, averaging 57 (47) pills. We identified at least one error on 42% of prescriptions. Among all prescriptions, 9% deviated from best practice guidelines, 21% failed to include two patient identifiers, and 41% were noncompliant with DEA rules. Errors occurred in 89% of handwritten prescriptions, 0% of electronic health record (EHR) computer-generated prescriptions, and 12% of non-EHR computer-generated prescriptions. Inter-rater reliability by kappa was 0.993. Conclusions Inconsistencies in opioid prescribing remain common. Handwritten prescriptions continue to demonstrate higher associations of errors, discrepancies, and variation from ideal practice and government regulations. All computer-generated prescriptions adhered to best practice guidelines and contained two patient identifiers, and all EHR prescriptions were fully compliant with DEA rules. PMID:28345746

  1. Drug interactions: volatile anesthetics and opioids.

    PubMed

    Glass, P S; Gan, T J; Howell, S; Ginsberg, B

    1997-09-01

    Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

  2. Psychophysiology of pain and opioid use: implications for managing pain in patients with an opioid use disorder.

    PubMed

    Wachholtz, Amy; Foster, Simmie; Cheatle, Martin

    2015-01-01

    Opioid therapy is one component of an effective pain management regimen for patients with chronic pain and the majority of these patients use their medications responsibly. However, there are a growing number of these patients who develop an opioid use disorder and in some cases require opioid replacement therapy. Managing these patients is complex and the underlying mechanisms of pain and addiction are not well understood. Developing an effective interdisciplinary treatment program for the individual with pain and an opioid use disorder will depend on enhancing our knowledge of the psychophysiology of pain and addiction. Authors gathered key empirical and theoretical papers examining the psychophysiology of comorbid pain and opioid misuse disorders. This article reviews the current theory of the effect of pain on patients with pain and concomitant addiction, the psychophysiology of pain, opioid use and addiction, and future research in this area. Individuals with a history of opioid misuse have greater levels of hyperalgesia which may be due to alterations in psychophysiological pathways. More research is needed into the psychophysiological biomarkers among individuals with comorbid pain and addiction in order to develop better treatment approaches and improve outcomes among this difficult to treat population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Impact of Preoperative Opioid Use After Emergency General Surgery.

    PubMed

    Kim, Young; Cortez, Alexander R; Wima, Koffi; Dhar, Vikrom K; Athota, Krishna P; Schrager, Jason J; Pritts, Timothy A; Edwards, Michael J; Shah, Shimul A

    2018-01-16

    Preoperative exposure to narcotics has recently been associated with poor outcomes after elective major surgery, but little is known as to how preoperative opioid use impacts outcomes after common, emergency general surgical procedures (EGS). A high-volume, single-center analysis was performed on patients who underwent EGS from 2012 to 2013. EGS was defined as the seven emergent operations that account for 80% of the national burden. Preoperative opioid use was defined as having an active opioid prescription within 7 days prior to surgery. Chronic opioid use was defined as having an opioid prescription concurrent with 90 days after discharge. A total of 377 patients underwent EGS during the study period. Preoperative opioid use was present in 84 patients (22.3%). Preoperative opioid users had longer hospital LOS (10.5 vs 6 days), higher costs of care ($25,331 vs $11,454), and higher 30-day readmission rates (22.6 vs 8.2%) compared with opioid-naïve patients (p < 0.001 each). After covariate adjustment, preoperative opioid use was predictive of LOS (RR 1.19 [1.01-1.41]) and 30-day hospital readmission (OR 2.69 [1.25-5.75]) (p < 0.05 each). Total direct cost was not different after modeling. Preoperative opioid users required more narcotic refills compared with opioid-naïve patients (5 vs 0 refills, p < 0.001). After discharge, 15.4% of opioid-naïve patients met criteria for chronic opioid use, vs 77.4% in preoperative opioid users (p < 0.001). Preoperative opioid use is associated with greater resource utilization after emergency general surgery, as well as vastly different postoperative opioid prescription patterns. These findings may help to inform the impact of preoperative opioid use on patient care, and its implications on hospital and societal cost.

  4. Rational use of opioids.

    PubMed

    Mastronardi, P; Cafiero, T

    2001-04-01

    The role of analgesia and sedation in intensive care units (ICU) is ancillary to other intensive care strategies, nevertheless they permit that every other diagnostic and therapeutic procedure is safely performed by keeping the patient pain-free, anxiety-free and cooperative. Commonly used opioids in ICU include morphine, fentanyl, sufentanil and remifentanil. The choice among opioid drugs relies on their pharmacokinetics and their pharmacodynamic effects. Cardiovascular stability observed with fentanyl and sufentanil indicates their use in hemodynamically compromised patients. Short-acting remifentanil offers several advantages in patients requiring prolonged infusions. The organ-independent metabolism of this newer molecule may be valuable in patients with multiple organ failure. The main indications for opioid analgesia and sedation in ICU include: 1) Anxiety, pain and agitation: in turn, they can increase cardiac workload, myocardial oxygen consumption and rate of dysarrhythmias; 2) immediate postoperative period after major surgery; 3) short-term invasive procedures. Potential advantages offered by opioids in the ICU setting also include: a) Cardiac protection: in animal models, it has been observed that delta-opiate receptor stimulation confers a preconditioning-like protective effects against myocardial ischemia; b) Neuroprotection: recent studies suggest that mu- and kappa-opiate receptors are involved in ischemic preconditioning against seizures in the brain. During opioid therapy in the ICU, drug tolerance and withdrawal symptoms should be anticipated and the dose adjusted accordingly.

  5. Opioid epidemic in the United States.

    PubMed

    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

  6. Fatal opioid poisoning: a counterfactual model to estimate the preventive effect of treatment for opioid use disorder in England.

    PubMed

    White, Martin; Burton, Robyn; Darke, Shane; Eastwood, Brian; Knight, Jon; Millar, Tim; Musto, Virginia; Marsden, John

    2015-08-01

    A counterfactual model was used to estimate the number of fatal opioid-related poisonings prevented by public treatment services for opioid use disorder (OUD) in England between April 2008 and March 2011. Patient OUD treatment episode data recorded by the English National Drug Treatment Monitoring System were linked to data on opioid deaths recorded by the Office for National Statistics. The source population was the official estimate of non-medical opioid users (aged 15-64 years; approximately 260 000 each year). The target population was all individuals (aged 15-64 years) treated for OUD in the study period (n = 220 665). The outcome measure was fatal opioid-related poisoning (opioid death). The opioid death rate [per 100 person-years (PY)] and mortality rate ratios (MRR) were computed for study year, age group (15-24, 25-34, 35-64 years) and for three treatment-related states: time spent 'prior to treatment', 'during treatment' and 'after treatment'. Between April 2008 and March 2011, there were 3731 opioid deaths in the study: 741 during treatment (0.20 per 100 PY; referent category); 2722 prior to treatment [0.77 per 100 PY; MRR = 3.76, 95% confidence interval (CI) = 3.18-4.44]; and 268 after treatment (0.41 per 100 PY; MRR = 1.99, 95% CI = 1.64-2.41). By counterfactual estimation, national OUD treatment services prevented an average of 880 opioid deaths each year (95% CI = 702-1084). Between April 2008 and March 2011, a counterfactual model shows that the English public treatment system for opioid use disorder prevented an average of 880 deaths each year from opioid-related poisoning. Counterfactual models of mortality prevention can be used for outcome and performance monitoring of substance use disorder treatment systems. © 2015 Society for the Study of Addiction.

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

    PubMed Central

    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

  8. Imaging opioid analgesia in the human brain and its potential relevance for understanding opioid use in chronic pain

    PubMed Central

    Lee, Michael C.; Wanigasekera, Vishvarani; Tracey, Irene

    2014-01-01

    Opioids play an important role for the management of acute pain and in palliative care. The role of long-term opioid therapy in chronic non-malignant pain remains unclear and is the focus of much clinical research. There are concerns regarding analgesic tolerance, paradoxical pain and issues with dependence that can occur with chronic opioid use in the susceptible patient. In this review, we discuss how far human neuroimaging research has come in providing a mechanistic understanding of pain relief provided by opioids, and suggest avenues for further studies that are relevant to the management of chronic pain with opioids. This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’. PMID:23891639

  9. Mild opioid deprivation increases the degree that opioid-dependent outpatients discount delayed heroin and money.

    PubMed

    Giordano, Louis A; Bickel, Warren K; Loewenstein, George; Jacobs, Eric A; Marsch, Lisa; Badger, Gary J

    2002-09-01

    A growing literature suggests that excessive temporal discounting of delayed rewards may be a contributing factor in the etiology of substance abuse problems. Little is known, however, about how drug deprivation may affect temporal discounting of delayed rewards by drug-dependent individuals. To examine the extent to which opioid deprivation affects how opioid-dependent individuals discount small, medium and large quantities of delayed heroin and money. Thirteen opioid-dependent individuals maintained on buprenorphine completed a hypothetical choice task in which they choose between a constant delayed reward amount and an immediate reward amount that was adjusted until they expressed indifference between both outcomes. The task was completed for three values of heroin and money rewards during eight sessions under conditions of opioid deprivation (four sessions) and satiation (four sessions). Across conditions, hyperbolic functions provided a good fit for the discounting data. Degree of discounting was significantly higher when subjects were opioid deprived. Consistent with previous findings, degree of discounting was higher for heroin than money and inversely related to the magnitude of the reward. Opioid deprivation increased the degree to which dependent individuals discounted delayed heroin and money. Understanding the conditions that affect how drug-dependent individuals discount delayed rewards might help us understand the myopic choices made by such individuals and help improve treatment outcomes.

  10. Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder

    PubMed Central

    Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

    2017-01-01

    Background Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). Patients and methods The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes. PMID:28572737

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

    PubMed

    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. Assessing Craving and its Relationship to Subsequent Prescription Opioid Use Among Treatment-Seeking Prescription Opioid Dependent Patients

    PubMed Central

    McHugh, R. Kathryn; Fitzmaurice, Garrett M.; Carroll, Kathleen M.; Griffin, Margaret L.; Hill, Kevin P.; Wasan, Ajay D.; Weiss, Roger D.

    2014-01-01

    Background Craving is viewed as a core feature of substance use disorders and has been shown to predict future drug use, particularly over the short term. Accordingly, craving is often assessed in treatment settings as a marker of risk for subsequent drug use. The identification of the briefest measure that maintains predictive validity is of particular value for both clinical and research settings to minimize assessment burden while maintaining utility for the prediction of use. Methods Data from a multi-site clinical trial of treatment for prescription opioid dependence were examined to evaluate whether a brief, 3-item craving scale administered each week predicted urine-confirmed self report of prescription opioid use in the subsequent week. Logistic regression models examining the association between craving and presence or absence of opioid use in the following week were conducted, controlling for opioid use in the previous week, treatment condition, and lifetime history of heroin use. Results Greater craving was associated with a higher odds of prescription opioid use in the following week. For each one-unit increase on this 10-point scale, the odds of using opioids in the subsequent week was 17% higher. In addition to an item assessing urges, items assessing cue-induced craving and perceived likelihood of relapse in an environment where drugs were previously used contributed uniquely to this association. Conclusions A brief measure of prescription opioid craving predicted prescription opioid use among individuals in treatment. This measure offers an efficient strategy to inform the assessment of risk for use in this population. PMID:25454409

  13. The gut-brain interaction in opioid tolerance.

    PubMed

    Akbarali, Hamid I; Dewey, William L

    2017-12-01

    The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. mu-Opioid receptor-independent fashion of the suppression of sodium currents by mu-opioid analgesics in thalamic neurons.

    PubMed

    Hashimoto, Keisuke; Amano, Taku; Kasakura, Akiko; Uhl, George R; Sora, Ichiro; Sakai, Norio; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

    2009-03-27

    Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by mu-opioid receptor (MOR), whereas other potential targets of opioid analgesics have not been thoroughly characterized. In this study, we found that extracellular application of morphine, fentanyl or oxycodone, which are all considered to be MOR agonists, at relatively high concentrations, but not endogenous mu-opioid peptides, produced a concentration-dependent suppression of sodium currents in cultured thalamic neurons. These effects of opioids were not affected by either a MOR antagonist naloxone or a deletion of MOR gene. Among these opioids, fentanyl strongly suppressed sodium currents to the same degree as lidocaine, and both morphine and oxycodone slightly but significantly reduced sodium currents when they were present extracellularly. In contrast, the intracellular application of morphine, but not oxycodone, fentanyl or lidocaine, reduced sodium currents. These results suggest that morphine, fentanyl and oxycodone each produce the MOR-independent suppression of sodium currents by distinct mechanisms in thalamic neurons.

  15. Transitioning Florida NPs to opioid prescribing.

    PubMed

    Craig-Rodriguez, Alicia; Gordon, Glenna; Kaplan, Louise; Grubbs, Laurie

    2017-09-21

    Prior to statutory changes in prescriptive authority for controlled substances, this study examined the knowledge gaps and prescribing limitations of Florida advanced registered nurse practitioners regarding opioids. Study results revealed statistically significant knowledge gaps in the areas of federal and state guidelines; opioid classes and proper doses; risk assessment skills; monitoring of treatment; and confidence in dealing with challenges of opioid prescribing.

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

    PubMed

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

    2018-04-04

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

  17. Tamper asymmetry and its effect on transmission for x-ray driven opacity simulations

    NASA Astrophysics Data System (ADS)

    Morris, H. E.; Tregillis, I. L.; Hoffman, N. M.; Sherrill, M. E.; Fontes, C. J.; Marshall, A. J.; Urbatsch, T. J.; Bradley, P. A.

    2017-09-01

    This paper reports on synthetic transmission results from Lasnex [Zimmerman and Kruer, Comments Plasma Phys. 2, 51 (1975)] radiation-hydrodynamics simulations of opacity experiments carried out at Sandia National Laboratories' recently upgraded ZR facility. The focus is on experiments utilizing disk targets composed of a half-moon Fe/Mg mixture tamped on either end with 10-μm CH and an additional 35-μm beryllium tamper accessory on the end facing the spectrometer. Five x-ray sources with peak power ranging from 10 to 24 TW were used in the simulations to heat and backlight the opacity target. The dominant effect is that the beryllium behind the Fe/Mg mixture is denser and more opaque than the beryllium unshielded by metal during the times of greatest importance for the transmission measurement for all drives. This causes the simulated transmission to be lower than expected, and this is most pronounced for the case using the lowest drive power. While beryllium has a low opacity, its areal density is sufficiently high such that the expected reduction of the measured transmission is significant. This situation leads to an overestimate of iron opacity by 10%-215% for a photon energy range of 975-1775 eV for the 10-TW case. It is shown that if the tamper conditions are known, the transmission through each component of the target can be calculated and the resulting opacity can be corrected.

  18. Adherence monitoring with chronic opioid therapy for persistent pain: a biopsychosocial-spiritual approach to mitigate risk.

    PubMed

    Matteliano, Deborah; St Marie, Barbara J; Oliver, June; Coggins, Candace

    2014-03-01

    Opioids represent a mainstay in the pharmacologic management of persistent pain. Although these drugs are intended to support improved comfort and function, the inherent risk of abuse or addiction must be considered in the delivery of care. The experience of living with persistent pain often includes depression, fear, loss, and anxiety, leading to feelings of hopelessness, helplessness, and spiritual crisis. Collectively, these factors represent an increased risk for all patients, particularly those with a history of substance abuse or addiction. This companion article to the American Society for Pain Management Nursing "Position Statement on Pain Management in Patients with Substance Use Disorders" (2012) focuses on the intersection of persistent pain, substance use disorder (SUD), and chronic opioid therapy and the clinical implications of monitoring adherence with safe use of opioids for those with persistent pain. This paper presents an approach to the comprehensive assessment of persons with persistent pain when receiving opioid therapy by presenting an expansion of the biopsychosocial model to include spiritual factors associated with pain and SUD, thus formulating a biopsychosocial-spiritual approach to mitigate risk. Key principles are provided for adherence monitoring using the biopsychosocial-spiritual assessment model developed by the authors as a means of promoting sensitive and respectful care. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  19. Treatment of opioid dependence with buprenorphine: current update

    PubMed Central

    Soyka, Michael

    2017-01-01

    Opioid maintenance treatment is the first-line approach in opioid dependence. Both the full opioid agonist methadone (MET) and the partial agonist buprenorphine (BUP) are licensed for the treatment of opioid dependence. BUP differs significantly from MET in its pharmacology, side effects, and safety issues. For example, the risk of respiratory depression is lower than with MET. The risk of diversion and injection of BUP have been reduced by also making it available as a tablet containing the opioid antagonist naloxone. This review summarizes the clinical effects of BUP and examines possible factors that can support decisions regarding the use of BUP or MET in opioid-dependent people. PMID:29302227

  20. Parenteral opioids for maternal pain management in labour

    PubMed Central

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

    2014-01-01

    Background Parenteral opioids are used for pain relief in labour in many countries throughout the world. Objectives To assess the acceptability, effectiveness and safety of different types, doses and modes of administration of parenteral opioids given to women in labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 April 2011) and reference lists of retrieved studies. Selection criteria 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 another opioid, placebo, other non-pharmacological interventions (TENS) or inhaled analgesia. Data collection and analysis At least two review authors independently assessed study eligibility, collected data and assessed risk of bias. Main results We included 57 studies involving more than 7000 women that compared an opioid with placebo, another opioid administered intramuscularly or intravenously or compared with TENS to the back. The 57 studies reported on 29 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

  1. Detecting aberrant opioid behavior in the emergency department: a prospective study using the screener and Opioid Assessment for Patients with Pain-Revised (SOAPP®-R), Current Opioid Misuse Measure (COMM)™, and provider gestalt.

    PubMed

    Varney, Shawn M; Perez, Crystal A; Araña, Allyson A; Carey, Katherine R; Ganem, Victoria J; Zarzabal, Lee A; Ramos, Rosemarie G; Bebarta, Vikhyat S

    2018-03-03

    Emergency department (ED) providers have limited time to evaluate patients at risk for opioid misuse. A validated tool to assess the risk for aberrant opioid behavior may mitigate adverse sequelae associated with prescription opioid misuse. We sought to determine if SOAPP-R, COMM, and provider gestalt were able to identify patients at risk for prescription opioid misuse as determined by pharmacy records at 12 months. We conducted a prospective observational study of adult patients in a high volume US ED. Patients completed the SOAPP-R and COMM, and treating EM providers evaluated patients' opioid misuse risk. We performed variable-centered, person-centered, and hierarchical cluster analyses to determine whether provider gestalt, SOAPP-R, or COMM, or a combination, predicted higher misuse risk. The primary outcome was the number of opioid prescriptions at 12 months according to pharmacy records. For 169 patients (mean age 43 years, 51% female, 73% white), correlation analysis showed a strong relationship between SOAPP-R and COMM with predicting the number of opioid prescriptions dispensed at 12 months. Provider scores estimating opioid misuse were not related to SOAPP-R and only weakly associated with COMM. In our adjusted regression models, provider gestalt and SOAPP-R uniquely predicted opioid prescriptions at 6 and 12 months. Using designated cutoff scores, only SOAPP-R detected a difference in the number of opioid prescriptions. Cluster analysis revealed that provider gestalt, SOAPP-R, and COMM scores jointly predicted opioid prescriptions. Provider gestalt and self-report instruments uniquely predicted the number of opioid prescriptions in ED patients. A combination of gestalt and self-assessment scores can be used to identify at-risk patients who otherwise miss the cutoff scores for SOAPP-R and COMM.

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

    PubMed

    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.

  3. Loaded: Gun involvement among opioid users.

    PubMed

    Stein, Michael D; Kenney, Shannon R; Anderson, Bradley J; Bailey, Genie L

    2018-06-01

    Despite ample research examining how alcohol use relates to gun involvement, little is known about the relationship between opioids and gun involvement. In the current study, we examined correlates of gun possession, accessibility, and related behaviors in an opioid dependent sample. Between October 2016 and April 2017, we surveyed persons entering a brief, inpatient opioid detoxification (n = 386) and 51 contemporaneous persons seeking alcohol detoxification at the same facility in Massachusetts and recorded their lifetime experiences with gun involvement. Participants averaged 33 years of age, 74% were male, 83% were White, and 64% had a history of incarceration. Opioid users had significantly higher rates of gun involvement than persons in alcohol detoxification; for example, 31.3% (vs. 3.9%) had carried a gun for protection, 45.1% (vs. 25.5%) had been threatened with a gun, and 13.8% (vs. 2.0%) had shot at another person. Among persons misusing opioids, male and non-White respondents, and those with a history of incarceration or poorer self-control reported greater gun involvement. Opioid users, both men and women, lead gun-involved lives. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial.

    PubMed

    DeFulio, Anthony; Everly, Jeffrey J; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

    2012-01-01

    Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Theoretical modeling of PEB procedure on EUV resist using FDM formulation

    NASA Astrophysics Data System (ADS)

    Kim, Muyoung; Moon, Junghwan; Choi, Joonmyung; Lee, Byunghoon; Jeong, Changyoung; Kim, Heebom; Cho, Maenghyo

    2018-03-01

    Semiconductor manufacturing industry has reduced the size of wafer for enhanced productivity and performance, and Extreme Ultraviolet (EUV) light source is considered as a promising solution for downsizing. A series of EUV lithography procedures contain complex photo-chemical reaction on photoresist, and it causes technical difficulties on constructing theoretical framework which facilitates rigorous investigation of underlying mechanism. Thus, we formulated finite difference method (FDM) model of post exposure bake (PEB) process on positive chemically amplified resist (CAR), and it involved acid diffusion coupled-deprotection reaction. The model is based on Fick's second law and first-order chemical reaction rate law for diffusion and deprotection, respectively. Two kinetic parameters, diffusion coefficient of acid and rate constant of deprotection, which were obtained by experiment and atomic scale simulation were applied to the model. As a result, we obtained time evolutional protecting ratio of each functional group in resist monomer which can be used to predict resulting polymer morphology after overall chemical reactions. This achievement will be the cornerstone of multiscale modeling which provides fundamental understanding on important factors for EUV performance and rational design of the next-generation photoresist.

  6. Novel opioid cyclic tetrapeptides: Trp isomers of CJ-15,208 exhibit distinct opioid receptor agonism and short-acting κ opioid receptor antagonism.

    PubMed

    Ross, Nicolette C; Reilley, Kate J; Murray, Thomas F; Aldrich, Jane V; McLaughlin, Jay P

    2012-02-01

    The κ opioid receptor antagonists demonstrate potential for maintaining abstinence from psychostimulant abuse, but existing non-peptide κ-receptor selective antagonists show exceptionally long activity. We hypothesized that the L- and D-Trp isomers of CJ-15,208, a natural cyclic tetrapeptide reported to be a κ-receptor antagonist in vitro, would demonstrate short-acting, dose-dependent antagonism in vivo, preventing reinstatement of cocaine-seeking behaviour. Affinity, selectivity and efficacy of the L-Trp and D-Trp isomers for opioid receptors were assessed in vitro in radioligand and GTPγS binding assays. Opioid receptor agonist and antagonist activities were characterized in vivo following i.c.v. administration with the 55°C warm water tail-withdrawal assay. The D-Trp isomer, which demonstrated primarily κ-receptor selective antagonist activity, was further evaluated for its prevention of stress- and drug-induced reinstatement of extinguished cocaine conditioned place preference (CPP). The two isomers showed similar affinity and selectivity for κ receptors (K(i)  30-35 nM) as well as κ receptor antagonism in vitro. As expected, the D-Trp cyclic tetrapeptide exhibited minimal agonist activity and induced dose-dependent κ-receptor selective antagonism lasting less than 18 h in vivo. Pretreatment with this peptide prevented stress-, but not cocaine-induced, reinstatement of extinguished cocaine CPP. In contrast, the L-Trp cyclic tetrapeptide unexpectedly demonstrated mixed opioid agonist/antagonist activity. The L-Trp and the D-Trp isomers of CJ-15,208 demonstrate stereospecific opioid activity in vivo. The relatively brief κ opioid receptor antagonism, coupled with the prevention of stress-induced reinstatement of extinguished cocaine-seeking behaviour, suggests the D-Trp isomer could be used therapeutically to maintain abstinence from psychostimulant abuse. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological

  7. Modulation of opioid analgesia by agmatine.

    PubMed

    Kolesnikov, Y; Jain, S; Pasternak, G W

    1996-01-18

    Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. delta-Opioid receptor-mediated analgesia also is potentiated by agmatine, but kappa1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetemide) and kappa3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the delta-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the kappa3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on kappa1-opioid analgesia in the acute model, agmatine prevents kappa1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance.

  8. A Randomized Controlled Trial of the Effects of Online Pain Management Education on Primary Care Providers.

    PubMed

    Trudeau, Kimberlee J; Hildebrand, Cristina; Garg, Priyanka; Chiauzzi, Emil; Zacharoff, Kevin L

    2017-04-01

    To improve pain management practices, we developed an online interactive continuing education (CE) program for primary care providers (PCPs). This program follows the flow of clinical decision-making through simulated cases at critical pain treatment points along the pain treatment continuum. A randomized controlled trial was conducted to test the efficacy of this program. Participants were randomized to either the experimental condition or the control condition (online, text-based CE program). A total of 238 primary care providers were recruited through hospitals, professional newsletters, and pain conferences. Participants in both conditions reported significantly improved scores on knowledge (KNOW-PAIN 50), attitudes (CAOS), and pain practice behaviors (PPBS) scales over the four-month study. The experimental condition showed significantly greater change over time on the tamper-resistant formulations (TRFs) of opioids and dosing CAOS subscale compared with the control condition. Post hoc comparisons suggested that participants in the experimental condition were less likely to endorse use of opioid TRFs over time compared with the control condition. Exploratory analyses for potential moderators indicated a significant three-way interaction with time, condition, and discipline (i.e., physician vs other) for the impediments and concerns attitudes subscale and the early refill behaviors subscale. Post hoc comparisons indicated that physicians in the experimental condition exhibited the greatest change in attitudes and the nonphysicians exhibited the greatest change in reported behaviors in response to requests for early refills. Findings suggest online CE programs may positively impact PCPs' knowledge, attitudes, and pain practice behaviors but provide minimal evidence for the value of including interactivity. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  9. Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

    PubMed

    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

  10. New formulation of methadone for opioid dependence in France: acceptability and diversion/misuse liability.

    PubMed

    Eiden, Céline; Léglise, Yves; Bertomeu, Lisa; Clavel, Vivianne; Faillie, Jean-Luc; Petit, Pierre; Peyrière, Hélène

    2013-01-01

    A new formulation of methadone as capsules is marketed in France since 2008. Few data are available on the patient acceptability and the risk of misuse of this new formulation. To assess the patient acceptability after the switch methadone syrup/capsules and the diversion/misuse liability of the methadone capsule, a study through an anonymous questionnaire was conducted between March 2011 and May 2012 in two methadone centers of the region. Forty-one patients (men 75.6%) participated, with a median age of 37 years [IQR: 33-43 years]. The median duration of syrup methadone maintenance therapy was 1 year [IQR: 1-3 years]. A majority of patients (80.5%) described side-effects due to the syrup formulation. Median daily dose at the switch to methadone capsules was 75 mg [IQR: 42-105 mg]. Six patients described differences in the pharmacologic effect between the two formulations. Concerning the diversion and misuse liability of methadone capsules, 26.8% of patients reported that the medication was available at the "street market". Three patients have tried to solubilize and eight have tried to snooze it. All patients recognize the contribution of this new formulation concerning the use, side-effects and transport. None of them returned to the syrup. © 2013 Société Française de Pharmacologie et de Thérapeutique.

  11. Health-Related Quality of Life among Chronic Opioid Users, Nonchronic Opioid Users, and Nonopioid Users with Chronic Noncancer Pain.

    PubMed

    Hayes, Corey J; Li, Xiaocong; Li, Chenghui; Shah, Anuj; Kathe, Niranjan; Bhandari, Naleen Raj; Payakachat, Nalin

    2018-02-25

    Evaluate the association between opioid therapy and health-related quality of life (HRQoL) in participants with chronic, noncancer pain (CNCP). Medical Expenditure Panel Survey Longitudinal, Medical Conditions, and Prescription Files. Using a retrospective cohort study design, the Mental Health Component (MCS12) and Physical Health Component (PCS12) scores of the Short Form-12 Version 2 were assessed to measure mental and physical HRQoL. Chronic, noncancer pain participants were classified as chronic, nonchronic, and nonopioid users. One-to-one propensity score matching was employed to match chronic opioid users to nonchronic opioid users plus nonchronic opioid users and chronic opioid users to nonopioid users. A total of 5,876 participants were identified. After matching, PCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = -0.98, 95% CI: -2.07, 0.10), chronic versus nonopioid users (LSM Diff = -2.24, 95% CI: -4.58, 0.10), or chronic versus nonchronic opioid users (LSM Diff = -2.23, 95% CI: -4.53, 0.05). Similarly, MCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = 0.76, 95% CI: -0.46, 1.98), chronic versus nonopioid users (LSM Diff = 1.08, 95% CI: -1.26, 3.42), or chronic versus nonchronic opioid users (LSM Diff = -0.57, 95% CI: -2.90, 1.77). Clinicians should evaluate opioid use in participants with CNCP as opioid use is not correlated with better HRQoL. © Health Research and Educational Trust.

  12. Opioid Addiction: Social Problems Associated and Implications of Both Current and Possible Future Treatments, including Polymeric Therapeutics for Giving Up the Habit of Opioid Consumption.

    PubMed

    Benéitez, M Cristina; Gil-Alegre, M Esther

    2017-01-01

    Detoxification programmes seek to implement the most secure and compassionate ways of withdrawing from opiates so that the inevitable withdrawal symptoms and other complications are minimized. Once detoxification has been achieved, the next stage is to enable the patient to overcome his or her drug addiction by ensuring consumption is permanently and completely abandoned, only after which can the subject be regarded as fully recovered. A systematic search on the common databases of relevant papers published until 2016 inclusive. Our study of the available oral treatments for opioid dependence has revealed that no current treatment can actually claim to be fully effective. These treatments require daily oral administration and, consequently, regular visits to dispensaries, which in most cases results in a lack of patient compliance, which causes fluctuations in drug plasma levels. We then reviewed alternative treatments in the available scientific literature on polymeric sustained release formulations. Research has been done not only on release systems for detoxification but also on release systems for giving up the habit of taking opioids. These efforts have obtained the recent authorization of polymeric systems for use in patients that could help them to reduce their craving for drugs.

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

    PubMed

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

    2011-01-01

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

  14. Life-Threatening Opioid Toxicity

    DTIC Science & Technology

    1987-01-01

    mu recep- Fentanyl (Sublimaze) tor has been determined to mediate analgesia Propoxyphene (Darvon) and ventilatory depre.;sion. Furthermore, it Pure...following opioid overdose . The reduction in ventilation is accompanied by Opioids produce their major effect on the a decreased chemosensitivity to...opiates a o d F Diphenoxylate (active ingredient in Lomotil)a mperidline overdose . Fuithermore, ven- rpxhe (avnmepedinePropoxyphene Darvon) titatory

  15. An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance Patterns in Ewing Sarcoma.

    PubMed

    Lamhamedi-Cherradi, Salah-Eddine; Menegaz, Brian A; Ramamoorthy, Vandhana; Aiyer, Ramani A; Maywald, Rebecca L; Buford, Adrianna S; Doolittle, Dannette K; Culotta, Kirk S; O'Dorisio, James E; Ludwig, Joseph A

    2015-07-01

    Ewing sarcoma is a transcription factor-mediated pediatric bone tumor caused by a chromosomal translocation of the EWSR1 gene and one of several genes in the ETS family of transcription factors, typically FLI1 or ERG. Full activity of the resulting oncogenic fusion protein occurs only after binding RNA helicase A (RHA), and novel biologically targeted small molecules designed to interfere with that interaction have shown early promise in the preclinical setting. Herein, we demonstrate marked preclinical antineoplastic activity of an orally bioavailable formulation of YK-4-279 and identify mechanisms of acquired chemotherapy resistance that may be exploited to induce collateral sensitivity. Daily enteral administration of YK-4-279 led to significant delay in Ewing sarcoma tumor growth within a murine model. In advance of anticipated early-phase human clinical trials, we investigated both de novo and acquired mechanism(s) by which Ewing sarcoma cells evade YK-4-279-mediated cell death. Drug-resistant clones, formed by chronic in vitro exposure to steadily increased levels of YK-4-279, overexpressed c-Kit, cyclin D1, pStat3(Y705), and PKC isoforms. Interestingly, cross-resistance to imatinib and enzastaurin (selective inhibitors of c-Kit and PKC-β, respectively), was observed and the use of YK-4-279 with enzastaurin in vitro led to marked drug synergy, suggesting a potential role for combination therapies in the future. By advancing an oral formulation of YK-4-279 and identifying prominent mechanisms of resistance, this preclinical research takes us one step closer to a shared goal of curing adolescents and young adults afflicted by Ewing sarcoma. ©2015 American Association for Cancer Research.

  16. Peptidases prevent mu-opioid receptor internalization in dorsal horn neurons by endogenously released opioids.

    PubMed

    Song, Bingbing; Marvizón, Juan Carlos G

    2003-03-01

    To evaluate the effect of peptidases on mu-opioid receptor (MOR) activation by endogenous opioids, we measured MOR-1 internalization in rat spinal cord slices. A mixture of inhibitors of aminopeptidases (amastatin), dipeptidyl carboxypeptidase (captopril), and neutral endopeptidase (phosphoramidon) dramatically increased the potencies of Leu-enkephalin and dynorphin A to produce MOR-1 internalization, and also enhanced the effects of Met-enkephalin and alpha-neoendorphin, but not endomorphins or beta-endorphin. The omission of any one inhibitor abolished Leu-enkephalin-induced internalization, indicating that all three peptidases degraded enkephalins. Amastatin preserved dynorphin A-induced internalization, and phosphoramidon, but not captopril, increased this effect, indicating that the effect of dynorphin A was prevented by aminopeptidases and neutral endopeptidase. Veratridine (30 microm) or 50 mm KCl produced MOR-1 internalization in the presence of peptidase inhibitors, but little or no internalization in their absence. These effects were attributed to opioid release, because they were abolished by the selective MOR antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)) and were Ca(2+) dependent. The effect of veratridine was protected by phosphoramidon plus amastatin or captopril, but not by amastatin plus captopril or by phosphoramidon alone, indicating that released opioids are primarily cleaved by neutral endopeptidase, with a lesser involvement of aminopeptidases and dipeptidyl carboxypeptidase. Therefore, because the potencies of endomorphin-1 and endomorphin-2 to elicit internalization were unaffected by peptidase inhibitors, the opioids released by veratridine were not endomorphins. Confocal microscopy revealed that MOR-1-expressing neurons were in close proximity to terminals containing opioids with enkephalin-like sequences. These findings indicate that peptidases prevent the activation of extrasynaptic MOR-1 in dorsal horn neurons.

  17. Peptidases prevent μ-opioid receptor internalization in dorsal horn neurons by endogenously released opioids

    PubMed Central

    Song, Bingbing; Marvizón, Juan Carlos G.

    2008-01-01

    To evaluate the effect of peptidases on μ-opioid receptor (MOR) activation by endogenous opioids, we measured MOR-1 internalization in rat spinal cord slices. A mixture of inhibitors of aminopeptidases (amastatin), dipeptidyl carboxypeptidase (captopril), and neutral endopeptidase (phosphoramidon) dramatically increased the potencies of Leu-enkephalin and dynorphin A to produce MOR-1 internalization, and also enhanced the effects of Met-enkephalin and α-neoendorphin, but not endomorphins or β-endorphin. Omission of any one inhibitor abolished Leu-enkephalin-induced internalization, indicating that all three peptidases degraded enkephalins. Amastatin preserved dynorphin A-induced internalization, and phosphoramidon, but not captopril, increased this effect, indicating that the effect of dynorphin A was prevented by aminopeptidases and neutral endopeptidase. Veratridine (30 μM) or 50 mM KCl produced MOR-1 internalization in the presence of peptidase inhibitors, but little or no internalization in their absence. These effects were attributed to opioid release, because they were abolished by the selective MOR antagonist CTAP and were Ca2+-dependent. The effect of veratridine was protected by phosphoramidon plus amastatin or captopril, but not by amastatin plus captopril or by phosphoramidon alone, indicating that released opioids are mainly cleaved by neutral endopeptidase, with a lesser involvement of aminopeptidases and dipeptidyl carboxypeptidase. Therefore, since the potencies of endomorphin-1 and -2 to elicit internalization were unaffected by peptidase inhibitors, the opioids released by veratridine were not endomorphins. Confocal microscopy revealed that MOR-1-expressing neurons were in close proximity to terminals containing opioids with enkephalin-like sequences. These findings indicate that peptidases prevent the activation of extrasynaptic MOR-1 in dorsal horn neurons. PMID:12629189

  18. Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain.

    PubMed

    Miranda, Hugo F; Noriega, Viviana; Zanetta, Pilar; Prieto, Juan Carlos; Prieto-Rayo, Juan Carlos; Aranda, Nicolás; Sierralta, Fernando

    2014-07-15

    Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

  19. Tamper resistant magnetic stripes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Naylor, R.B.; Sharp, D.J.

    1999-11-09

    This invention relates to a magnetic stripe comprising a medium in which magnetized particles are suspended and in which the encoded information is recorded by actual physical rotation or alignment of the previously magnetized particles within the flux reversals of the stripe which are 180{degree} opposed in their magnetic polarity. The magnetized particles are suspended in a medium which is solid, or physically rigid, at ambient temperatures but which at moderately elevated temperatures, such as 40 C, is thinable to a viscosity permissive of rotation of the particles therein under applications of moderate external magnetic field strengths within acceptable timemore » limits.« less

  20. Tamper resistant magnetic stripes

    DOEpatents

    Naylor, Richard Brian; Sharp, Donald J.

    1999-01-01

    This invention relates to a magnetic stripe comprising a medium in which magnetized particles are suspended and in which the encoded information is recorded by actual physical rotation or alignment of the previously magnetized particles within the flux reversals of the stripe which are 180.degree. opposed in their magnetic polarity. The magnetized particles are suspended in a medium which is solid, or physically rigid, at ambient temperatures but which at moderately elevated temperatures, such as 40.degree. C., is thinable to a viscosity permissive of rotation of the particles therein under applications of moderate external magnetic field strengths within acceptable time limits.

  1. Clinical and demographic covariates of chronic opioid and non-opioid analgesic use in rural-dwelling older adults: the MoVIES project.

    PubMed

    Karp, Jordan F; Lee, Ching-Wen; McGovern, Jonathan; Stoehr, Gary; Chang, Chung-Chou H; Ganguli, Mary

    2013-11-01

    To describe covariates and patterns of late-life analgesic use in the rural, population-based MoVIES cohort from 1989 to 2002. Secondary analysis of epidemiologic survey of elderly people conducted over six biennial assessment waves. Potential covariates of analgesic use included age, gender, depression, sleep, arthritis, smoking, alcohol, and general health status. Of the original cohort of 1,681, this sample comprised 1,109 individuals with complete data on all assessments. Using trajectory analysis, participants were characterized as chronic or non-chronic users of opioid and non-opioid analgesics. Multivariable regression was used to model predictors of chronic analgesic use. The cohort was followed for mean (SD) 7.3 (2.7) years. Chronic use of opioid analgesics was reported by 7.2%, while non-opioid use was reported by 46.1%. In the multivariable model, predictors of chronic use of both opioid and non-opioid analgesics included female sex, taking ≥2 prescription medications, and "arthritis" diagnoses. Chronic opioid use was also associated with age 75-84 years; chronic non-opioid use was also associated with sleep continuity disturbance. These epidemiological data confirm clinical observations and generate hypotheses for further testing. Future studies should investigate whether addressing sleep problems might lead to decreased use of non-opioid analgesics and possibly enhanced pain management.

  2. Are We Still Prescribing Opioids for Osteoarthritis?

    PubMed

    DeMik, David E; Bedard, Nicholas A; Dowdle, S Blake; Burnett, Robert A; McHugh, Michael A; Callaghan, John J

    2017-12-01

    The United States is in the midst of an opioid epidemic. These medications continue to be used to manage pain associated with osteoarthritis, despite mounting evidence questioning the benefits. The rate at which opioids are prescribed for osteoarthritis is largely unknown. We sought to identify rates of opioid prescriptions for osteoarthritis and identify factors associated with higher rates of prescribing. We queried the Humana, Inc. administrative claims database from 2007 to 2014. Patients with osteoarthritis were identified using International Classification of Diseases 9th Revision codes and classified as having hip, knee, or any joint osteoarthritis. Claims data were reviewed to identify opioid prescriptions associated with a diagnosis of osteoarthritis. Rates of prescribing were trended over time and stratified by sex, age, and geographic region. From 2007 to 2014, 17.0% of patients with any joint osteoarthritis, 13.4% of patients with hip osteoarthritis, and 15.9% with knee osteoarthritis were prescribed an opioid for their condition. Yearly rates of prescription were fairly stable over this period. Patients in the South had the highest odds of opioid prescription, while those in the Northeast had the lowest. Patients ≤49 years old were more likely to receive a prescription than those ≥50 years old. This study provides important epidemiologic data about the use of opioids for osteoarthritis. Despite increasing evidence calling proposed benefits into question and increasing awareness of risks of opioids, prescribing rates remained stable between 2007 and 2014. This provides important baseline data as we work to combat excessive and inappropriate opioid use within the United States. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Dmt and opioid peptides: a potent alliance.

    PubMed

    Bryant, Sharon D; Jinsmaa, Yunden; Salvadori, Severo; Okada, Yoshio; Lazarus, Lawrence H

    2003-01-01

    The introduction of the Dmt (2',6'-dimethyl-L-tyrosine)-Tic pharmacophore into the design of opioid ligands produced an extraordinary family of potent delta-opioid receptor antagonists and heralded a new phase in opioid research. First reviewed extensively in 1998, the incorporation of Dmt into a diverse group of opioid molecules stimulated the opioid field leading to the development of unique analogues with remarkable properties. This overview will document the crucial role played by this residue in the proliferation of opioid peptides with high receptor affinity (K(i) equal to or less than 1 nM) and potent bioactivity. The discussion will include the metamorphosis between delta-opioid receptor antagonists to delta-agonists based solely on subtle structural changes at the C-terminal region of the Dmt-Tic pharmacophore as well as their behavior in vivo. Dmt may be considered promiscuous due to the acquisition of potent mu-agonism by dermorphin and endomorphin derivatives as well as by a unique class of opioidmimetics containing two Dmt residues separated by alkyl or pyrazinone linkers. Structural studies on the Dmt-Tic compounds were enhanced tremendously by x-ray diffraction data for three potent and biologically diverse Dmt-Tic opioidmimetics that led to the development of pharmacophores for both delta-opioid receptor agonists and antagonists. Molecular modeling studies of other unique Dmt opioid analogues illuminated structural differences between delta- and mu-receptor ligand interactions. The future of these compounds as therapeutic applications for various medical syndromes including the control of cancer-associated pain is only a matter of time and perseverance. Copyright 2003 Wiley Periodicals, Inc.

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

    PubMed

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

    2016-01-01

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

  5. Characteristics of methadone maintenance treatment patients prescribed opioid analgesics

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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.

  7. Service Use Preceding Opioid-Related Fatality.

    PubMed

    Olfson, Mark; Wall, Melanie; Wang, Shuai; Crystal, Stephen; Blanco, Carlos

    2017-11-28

    This study analyzed health service patterns before opioid-related death among nonelderly individuals in the Medicaid program, focusing on decedents with and without past-year diagnoses of noncancer chronic pain. The authors identified opioid-related decedents, age ≤64 years, in the Medicaid program and characterized their clinical diagnoses, filled medication prescriptions, and nonfatal poisoning events during the 30 days and 12 months before death. The study group included 13,089 opioid-related deaths partitioned by presence or absence of chronic noncancer pain diagnoses in the last year of life. Most decedents (61.5%) had received clinical diagnoses of chronic noncancer pain conditions in the last year of life. As compared with decedents without chronic pain diagnoses, those with these diagnoses were significantly more likely to have filled prescriptions for opioids (49.0% versus 17.2%) and benzodiazepines (52.1% versus 26.6%) during the last 30 days of life, while diagnoses of opioid use disorder during this period were uncommon in both groups (4.2% versus 4.3%). The chronic pain group was also significantly more likely than the nonpain group to receive clinical diagnoses of drug use (40.8% versus 22.1%), depression (29.6% versus 13.0%) or anxiety (25.8% versus 8.4%) disorders during the last year of life. Persons dying of opioid-related causes, particularly those who were diagnosed with chronic pain conditions, commonly received services related to drug use disorders and mental disorders in the last year of life, though opioid use disorder diagnoses near the time of death were rare.

  8. Delta-opioid receptors as targets for migraine therapy.

    PubMed

    Charles, Andrew; Pradhan, Amynah A

    2016-06-01

    The purpose of this review is to contrast the properties of the δ-opioid receptor with those of the μ-opioid receptor, which is the primary target of most currently available opioid analgesics. We also discuss preclinical evidence that indicates the potential efficacy of δ-opioid receptor agonists as migraine therapy. The use of currently available opioid analgesics is highly problematic for patients with migraine. Delta-opioid receptors have key differences from μ receptors; these differences make the δ receptor an attractive therapeutic target for migraine. Delta-opioid receptors are expressed in both the peripheral and central nervous system in anatomical regions and cell types that are believed to play a role in migraine. Delta-receptor agonists have also shown promising effects in multiple migraine models, including nitroglycerin evoked hyperalgesia and conditioned place aversion, and cortical spreading depression. Evidence from animal models indicates that activation of δ receptors is less likely to cause tolerance and dependence, and less likely to cause hyperalgesia. In addition, δ receptors may have antidepressant and anxiolytic properties that are distinct from those of μ receptors. In human studies investigating other conditions, δ-receptor agonists have been generally safe and well tolerated. Delta-opioid receptor agonists have promising potential as acute and/or preventive migraine therapies, without the problems associated with currently used opioid analgesics.

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

    PubMed

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

    2018-06-01

    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.

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

    PubMed Central

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

    2009-01-01

    Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused 3-to-5-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, whilst improving analgesia. PMID:18938237

  11. Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion.

    PubMed

    Tsibulnikov, S Yu; Maslov, L N; Mukhomedzyanov, A V; Krylatov, A V; Tsibulnikova, M R; Lishmanov, Yu B

    2015-10-01

    We studied the ability of the agonist of κ1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and κ-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before reperfusion 2-fold reduced the ratio of infarction to risk area. Administration of ICI 199,441 in a dose of 0.1 mg/kg 15 min before ischemia produced a potent antiarrhythmic effect. Antiarrhythmic effect of κ-opioid receptor agonists depended on activation of κ-opioid receptors.

  12. Pain management and opioid risk mitigation in the military.

    PubMed

    Sharpe Potter, Jennifer; Bebarta, Vikhyat S; Marino, Elise N; Ramos, Rosemarie G; Turner, Barbara J

    2014-05-01

    Opioid analgesics misuse is a significant military health concern recognized as a priority issue by military leadership. Opioids are among those most commonly prescribed medications in the military for pain management. The military has implemented opioid risk mitigation strategies, including the Sole Provider Program and the Controlled Drug Management Analysis and Reporting Tool, which are used to identify and monitor for risk and misuse. However, there are substantial opportunities to build on these existing systems to better ensure safer opioid prescribing and monitor for misuse. Opioid risk mitigation strategies implemented by the civilian sector include establishing clinical guidelines for opioid prescribing and prescription monitoring programs. These strategies may help to inform opioid risk mitigation in the military health system. Reducing the risk of opioid misuse and improving quality of care for our Warfighters is necessary. This must be done through evidence-based approaches with an investment in research to improve patient care and prevent opioid misuse as well as its sequelae. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  13. Forecasting the future burden of opioids for osteoarthritis.

    PubMed

    Ackerman, I N; Zomer, E; Gilmartin-Thomas, J F-M; Liew, D

    2018-03-01

    To quantify the current national burden of opioids for osteoarthritis (OA) pain in Australia in terms of number of dispensed opioid prescriptions and associated costs, and to forecast the likely burden to the year 2030/31. Epidemiological modelling. Published data were obtained on rates of opioid prescribing for people with OA and national OA prevalence projections. Trends in opioid dispensing from 2006 to 2016, and average costs for common opioid subtypes were obtained from the Pharmaceutical Benefits Scheme and Medicare Australia Statistics. Using these inputs, a model was developed to estimate the likely number of dispensed opioid prescriptions and costs to the public healthcare system by 2030/31. In 2015/16, an estimated 1.1 million opioid prescriptions were dispensed in Australia for 403,954 people with OA (of a total 2.2 million Australians with OA). Based on recent dispensing trends and OA prevalence projections, the number of dispensed opioid prescriptions is expected to nearly triple to 3,032,332 by 2030/31, for an estimated 562,610 people with OA. The estimated cost to the Australian healthcare system was $AUD25.2 million in 2015/16, rising to $AUD72.4 million by 2030/31. OA-related opioid dispensing and associated costs are set to increase substantially in Australia from 2015/16 to 2030/31. Use of opioids for OA pain is concerning given joint disease chronicity and the risk of adverse events, particularly among older people. These projections represent a conservative estimate of the full financial burden given additional costs associated with opioid-related harms and out-of-pocket costs borne by patients. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior

    PubMed Central

    Al-Hasani, Ream; Bruchas, Michael R.

    2013-01-01

    Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years, and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled, and activate inhibitory G-proteins. These receptors form homo- and hetereodimeric complexes, signal to kinase cascades, and scaffold a variety of proteins. In this review, we discuss classical mechanisms and developments in understanding opioid tolerance, opioid receptor signaling, and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. We put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, we conclude that there is a continued need for more translational work on opioid receptors in vivo. PMID:22020140

  15. Initiation into Prescription Opioid Misuse among Young Injection Drug Users

    PubMed Central

    Lankenau, Stephen E.; Teti, Michelle; Silva, Karol; Bloom, Jennifer Jackson; Harocopos, Alex; Treese, Meghan

    2011-01-01

    Background Prescription opioids are the most frequently misused class of prescription drugs among young adults. Initiation into prescription opioid misuse is an important public health concern since opioids are increasingly associated with drug dependence and fatal overdose. Descriptive data about initiation into prescription opioid misuse among young injection drug users (IDUs) are scarce. Methods An exploratory qualitative study was undertaken to describe patterns of initiation into prescription opioid misuse among IDUs aged 16 to 25 years. Those young IDUs who had misused a prescription drug at least three times in the past three months were recruited during 2008 and 2009 in Los Angeles (n=25) and New York (n=25). Informed by an ethno-epidemiological approach, descriptive data from a semi-structured interview guide were analysed both quantitatively and qualitatively. Results Initiation into prescription opioid misuse was facilitated by easy access to opioids via participant’s own prescription, family, or friends, and occurred earlier than misuse of other illicit drugs, such as heroin. Nearly all transitioned into sniffing opioids, most injected opioids, and many initiated injection drug use with an opioid. Motives for transitions to sniffing and injecting opioids included obtaining a more potent high and/or substituting for heroin; access to multiple sources of opioids was common among those who progressed to sniffing and injecting opioids. Conclusion Prescription opioid misuse was a key feature of trajectories into injection drug use and/or heroin use among this sample of young IDUs. A new pattern of drug use may be emerging whereby IDUs initiate prescription opioid misuse before using heroin. PMID:21689917

  16. Increased use of heroin as an initiating opioid of abuse.

    PubMed

    Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

    2017-11-01

    Given the relatively recent growth in access to heroin and a more permissive atmosphere surrounding its use, we hypothesized that an increasing number of persons with limited experience and tolerance to opioids would experiment with heroin as their first opioid rather than more common prescription opioid analgesics. Individuals entering substance abuse treatment for an opioid use disorder in the period 2010-2016 (N=5885) were asked about the specific opioid they first regularly used to get high. To limit long-term recall and survival bias, analyses was restricted to opioid initiation that occurred in the past ten years (2005-2015). In 2005, only 8.7% of opioid initiators started with heroin, but this sharply increased to 33.3% (p<0.001) in 2015, with no evidence of stabilization. The use of commonly prescribed opioids, oxycodone and hydrocodone, dropped from 42.4% and 42.3% of opioid initiators, respectively, to 24.1% and 27.8% in 2015, such that heroin as an initiating opioid was now more frequently endorsed than prescription opioid analgesics. Our data document that, as the most commonly prescribed opioids - hydrocodone and oxycodone - became less accessible due to supply-side interventions, the use of heroin as an initiating opioid has grown at an alarming rate. Given that opioid novices have limited tolerance to opioids, a slight imprecision in dosing inherent in heroin use is likely to be an important factor contributing to the growth in heroin-related over dose fatalities in recent years. Copyright © 2017. Published by Elsevier Ltd.

  17. Long-term Use of Opioids for Complex Chronic Pain

    PubMed Central

    Von Korff, Michael R.

    2014-01-01

    Increased opioid prescribing for back pain and other chronic musculoskeletal pain conditions has been accompanied by dramatic increases in prescription opioid addiction and fatal overdose. Opioid-related risks appear to increase with dose. While short-term randomized trials of opioids for chronic pain have found modest analgesic benefits (a one-third reduction in pain intensity on average), the long-term safety and effectiveness of opioids for chronic musculoskeletal pain is unknown. Given the lack of large, long-term randomized trials, recent epidemiologic data suggests the need for caution when considering long-term use of opioids to manage chronic musculoskeletal pain, particularly at higher dosage levels. Principles for achieving more selective and cautious use of opioids for chronic musculoskeletal pain are proposed. PMID:24315147

  18. Tolerance and Withdrawal From Prolonged Opioid Use in Critically Ill Children

    PubMed Central

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

    2012-01-01

    OBJECTIVE After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS Relevant manuscripts published in the English language were searched in Medline by using search terms “opioid,” “opiate,” “sedation,” “analgesia,” “child,” “infant-newborn,” “tolerance,” “dependency,” “withdrawal,” “analgesic,” “receptor,” and “individual opioid drugs.” Clinical and preclinical studies were reviewed for data synthesis. RESULTS Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal. PMID:20403936

  19. Risk Evaluation and Mitigation Strategies (REMS) for extended-release and long-acting opioid analgesics: considerations for palliative care practice.

    PubMed

    Gudin, Jeffrey

    2012-06-01

    Prescription opioid analgesics are an essential treatment option for patients with moderate to severe pain. Over the last decade the increased medical use of these agents has contributed to a public health epidemic of abuse, addiction, and overdose-related deaths. These medications remain mainstays in both primary care and pain management practices. As palliative services are incorporated at earlier stages of the disease process and the number of individuals with chronic illness increases, palliative care specialists may encounter an increasing number of patients with opioid abuse and addiction problems. Extended-release (ER) and long-acting (LA) opioid formulations are administered to patients with moderate to severe chronic pain requiring around-the-clock analgesia. Given the large quantity of active ingredient contained within some dosage strengths, this medication class is associated with serious risks when taken improperly. In response to growing reports of abuse and overdose deaths, the US Food and Drug Administration (FDA) announced the need for a risk mitigation strategy for the entire class of medication. The class-wide Risk Evaluation and Mitigation Strategy (REMS) for ER/LA opioids will emphasize prescriber training and patient education to ensure that the therapeutic benefits outweigh the risks of addiction, unintentional overdose, and death. As primary care, pain management, and palliative care clinicians often encounter patients who require ER/LA opioids, an understanding of the suggested requirements and potential impact of this regulation is essential.

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

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    2012-09-19

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

  2. Understanding long-term opioid prescribing for non-cancer pain in primary care: a qualitative study.

    PubMed

    McCrorie, Carolyn; Closs, S José; House, Allan; Petty, Duncan; Ziegler, Lucy; Glidewell, Liz; West, Robert; Foy, Robbie

    2015-09-11

    The place of opioids in the management of chronic, non-cancer pain is limited. Even so their use is escalating, leading to concerns that patients are prescribed strong opioids inappropriately and alternatives to medication are under-used. We aimed to understand the processes which bring about and perpetuate long-term prescribing of opioids for chronic, non-cancer pain. We held semi-structured interviews with patients and focus groups with general practitioners (GPs). Participants included 23 patients currently prescribed long-term opioids and 15 GPs from Leeds and Bradford, United Kingdom (UK). We used a grounded approach to the analysis of transcripts. Patients are driven by the needs for pain relief, explanation, and improvement or maintenance of quality of life. GPs' responses are shaped by how UK general practice is organised, available therapeutic choices and their expertise in managing chronic pain, especially when facing diagnostic uncertainty or when their own approach is at odds with the patient's wishes. Four features of the resulting transaction between patients and doctors influence prescribing: lack of clarity of strategy, including the risk of any plans being subverted by urgent demands; lack of certainty about locus of control in decision-making, especially in relation to prescribing; continuity in the doctor-patient relationship; and mutuality and trust. Problematic prescribing occurs when patients experience repeated consultations that do not meet their needs and GPs feel unable to negotiate alternative approaches to treatment. Therapeutic short-termism is perpetuated by inconsistent clinical encounters and the absence of mutually-agreed formulations of underlying problems and plans of action. Apart from commissioning improved access to appropriate specialist services, general practices should also consider how they manage problematic opioid prescribing and be prepared to set boundaries with patients.

  3. Endogenous opioids encode relative taste preference.

    PubMed

    Taha, Sharif A; Norsted, Ebba; Lee, Lillian S; Lang, Penelope D; Lee, Brian S; Woolley, Joshua D; Fields, Howard L

    2006-08-01

    Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value.

  4. Dextromethorphan differentially affects opioid antinociception in rats

    PubMed Central

    Chen, Shiou-Lan; Huang, Eagle Yi-Kung; Chow, Lok-Hi; Tao, Pao-Luh

    2005-01-01

    Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. The antinociceptive effects of the μ-opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ-opioid agonists nalbuphine (8 mg kg−1, s.c.) and U-50,488H (20 mg kg−1, s.c.) were studied using the tail-flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. It was found that DM potentiated the antinociceptive effects of some μ-opioid agonists but not codeine or κ-opioid agonists in rats. DM potentiated morphine's antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids. PMID:15655510

  5. Comparison of Downstream Health Care Utilization, Costs, and Long-Term Opioid Use: Physical Therapist Management Versus Opioid Therapy Management After Arthroscopic Hip Surgery.

    PubMed

    Rhon, Daniel I; Snodgrass, Suzanne J; Cleland, Joshua A; Greenlee, Tina A; Sissel, Charles D; Cook, Chad E

    2018-05-01

    Physical therapy and opioid prescriptions are common after hip surgery, but are sometimes delayed or not used. The objective of this study was to compare downstream health care utilization and opioid use following hip surgery for different patterns of physical therapy and prescription opioids. The design of this study was an observational cohort. Health care utilization was abstracted from the Military Health System Data Repository for patients who were 18 to 50 years old and were undergoing arthroscopic hip surgery between 2004 and 2013. Patients were grouped into those receiving an isolated treatment (only opioids or only physical therapy) and those receiving both treatments on the basis of timing (opioid first or physical therapy first). Outcomes included overall health care visits and costs, hip-related visits and costs, additional surgeries, and opioid prescriptions. Of 1870 total patients, 82.7% (n = 1546) received physical therapy only, 71.6% (n = 1339) received prescription opioids, and 1073 (56.1%) received both physical therapy and opioids. Because 24 patients received both opioids and physical therapy on the same day, they were eventually removed the final timing-of-care analysis. Adjusted hip-related mean costs were the same in both groups receiving isolated treatments (${\\$}$11,628 vs ${\\$}$11,579), but the group receiving only physical therapy had significantly lower overall total health care mean costs (${\\$}$18,185 vs ${\\$}$23,842) and fewer patients requiring another hip surgery. For patients receiving both treatments, mean hip-related downstream costs were significantly higher in the group receiving opioids first than in the group receiving physical therapy first (${\\$}$18,806 vs ${\\$}$16,955) and resulted in greater opioid use (7.83 vs 4.14 prescriptions), greater total days' supply of opioids (90.17 vs 44.30 days), and a higher percentage of patients with chronic opioid use (69.5% vs 53.2%). Claims data were limited by the accuracy of

  6. Opioid agonist efficacy predicts the magnitude of tolerance and the regulation of mu-opioid receptors and dynamin-2.

    PubMed

    Pawar, Mohit; Kumar, Priyank; Sunkaraneni, Soujanya; Sirohi, Sunil; Walker, Ellen A; Yoburn, Byron C

    2007-06-01

    It has been proposed that opioid agonist efficacy may play a role in tolerance and the regulation of opioid receptor density. To address this issue, the present studies estimated the in vivo efficacy of three opioid agonists and then examined changes in spinal mu-opioid receptor density following chronic treatment in the mouse. In addition, tolerance and regulation of the trafficking protein dynamin-2 were determined. To evaluate efficacy, the method of irreversible receptor alkylation was employed and the efficacy parameter tau estimated. Mice were injected with the irreversible mu-opioid receptor antagonist clocinnamox (0.32-25.6 mg/kg, i.p), and 24 h later, the analgesic potency of s.c. morphine, oxycodone and etorphine were determined. Clocinnamox dose-dependently antagonized the analgesic effects of morphine, etorphine and oxycodone. The shift to the right of the dose-response curves was greater for morphine and oxycodone compared to etorphine and the highest dose of clocinnamox reduced the maximal effect of morphine and oxycodone, but not etorphine. The order of efficacy calculated from these results was etorphine>morphine>oxycodone. Other mice were infused for 7 days with oxycodone (10-150 mg/kg/day, s.c.) or etorphine (50-250 microg/kg/day, s.c.) and the analgesic potency of s.c. morphine determined. The low efficacy agonist (oxycodone) produced more tolerance than the high efficacy agonist (etorphine) at equi-effective infusion doses. In saturation binding experiments, the low efficacy opioid agonists (morphine, oxycodone) did not regulate the density of spinal mu-opioid receptors, while etorphine produced approximately 40% reduction in mu-opioid receptor density. Furthermore, etorphine increased spinal dynamin-2 abundance, while oxycodone did not produce any significant change in dynamin-2 abundance. Overall, these data indicate that high efficacy agonists produce less tolerance at equi-effective doses. Furthermore, increased efficacy was associated with

  7. Suicidal Ideation and Suicide Attempt Across Stages of Nonmedical Prescription Opioid Use and Presence of Prescription Opioid Disorders Among U.S. Adults

    PubMed Central

    Kuramoto, S. Janet; Chilcoat, Howard D.; Ko, Jean; Martins, Silvia S.

    2012-01-01

    Objective: This study compares the likelihood of suicidal ideation and suicide attempt across stages of nonmedical prescription opioid use and by presence of prescription opioid disorders (dependence and/or abuse) among adult respondents. Method: In the 2009 National Survey on Drug Use and Health, 37,933 adult respondents were asked if they had thought about suicide or had attempted suicide in the past year. The likelihood of ideation and attempt were compared across the following four categories: (a) those who never used prescription opioids, (b) former users, (c) persistent users, and (d) recent-onset users. Weighted multinomial logistic regressions were used to examine if these stages and presence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for prescription opioid disorders were associated with suicidal ideation and suicide attempt. Results: Five percent of respondents (n = 2,021) reported suicidal ideation; of these, 15% (n = 310) reported attempt. Former and persistent nonmedical prescription opioid users had greater odds of suicidal ideation than those who never used these medications nonmedically. The stages of prescription opioid use were not associated with suicide attempt. Presence of prescription opioid disorders among past-year prescription opioid users was associated with suicidal ideation but not suicide attempt. Conclusions: The risk for suicidal ideation was greater in those who no longer used prescription opioids, in persistent users, and among nonmedical users who had a prescription opioid disorder compared with users without the disorder. The results suggest a need to continue monitoring for suicide risk even among those who have stopped using prescription opioids. PMID:22333325

  8. Pharmacologic Profile of Naloxegol, a Peripherally Acting µ-Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

    PubMed Central

    Floettmann, Eike; Sostek, Mark; Payza, Kemal; Eldon, Michael

    2017-01-01

    Opioid-induced constipation (OIC) is a common side effect of opioid pharmacotherapy for the management of pain because opioid agonists bind to µ-opioid receptors in the enteric nervous system (ENS). Naloxegol, a polyethylene glycol derivative of naloxol, which is a derivative of naloxone and a peripherally acting µ-opioid receptor antagonist, targets the physiologic mechanisms that cause OIC. Pharmacologic measures of opioid activity and pharmacokinetic measures of central nervous system (CNS) penetration were employed to characterize the mechanism of action of naloxegol. At the human µ-opioid receptor in vitro, naloxegol was a potent inhibitor of binding (Ki = 7.42 nM) and a neutral competitive antagonist (pA2 - 7.95); agonist effects were <10% up to 30 μM and identical to those of naloxone. The oral doses achieving 50% of the maximal effect in the rat for antagonism of morphine-induced inhibition of gastrointestinal transit and morphine-induced antinociception in the hot plate assay were 23.1 and 55.4 mg/kg for naloxegol and 0.69 and 1.14 mg/kg by for naloxone, respectively. In the human colon adenocarcinoma cell transport assay, naloxegol was a substrate for the P-glycoprotein transporter, with low apparent permeability in the apical to basolateral direction, and penetrated the CNS 15-fold slower than naloxone in a rat brain perfusion model. Naloxegol-derived radioactivity was poorly distributed throughout the rat CNS and was eliminated from most tissues within 24 hours. These findings corroborate phase 3 clinical studies demonstrating that naloxegol relieves OIC-associated symptoms in patients with chronic noncancer pain by antagonizing the µ-opioid receptor in the ENS while preserving CNS-mediated analgesia. PMID:28336575

  9. Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain

    PubMed Central

    2014-01-01

    Background Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. Results The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. Conclusion These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity. PMID:25017386

  10. Prescription practices involving opioid analgesics among Americans with Medicaid, 2010.

    PubMed

    Mack, Karin A; Zhang, Kun; Paulozzi, Leonard; Jones, Christopher

    2015-02-01

    Recent state-based studies have shown an increased risk of opioid overdose death in Medicaid populations. To explore one side of risk, this study examines indicators of potential opioid inappropriate use or prescribing among Medicaid enrollees. We examined claims from enrollees aged 18-64 years in the 2010 Truven Health MarketScan® Multi-State Medicaid database, which consisted of weighted and nationally representative data from 12 states. Pharmaceutical claims were used to identify enrollees (n=359,368) with opioid prescriptions. Indicators of potential inappropriate use or prescribing included overlapping opioid prescriptions, overlapping opioid and benzodiazepine prescriptions, long acting/extended release opioids for acute pain, and high daily doses. In 2010, Medicaid enrollees with opioid prescriptions obtained an average 6.3 opioid prescriptions, and 40% had at least one indicator of potential inappropriate use or prescribing. These indicators have been linked to opioid-related adverse health outcomes, and methods exist to detect and deter inappropriate use and prescribing of opioids.

  11. Comparison of the Risks of Shopping Behavior and Opioid Abuse Between Tapentadol and Oxycodone and Association of Shopping Behavior and Opioid Abuse

    PubMed Central

    Fife, Daniel; Kihm, Mary A.; Mastrogiovanni, Greg; Yuan, Yingli

    2014-01-01

    Objectives: 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. Materials and Methods: 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. Results: 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. Discussion: 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. PMID:24370606

  12. Pegylated liposomal formulation of doxorubicin overcomes drug resistance in a genetically engineered mouse model of breast cancer.

    PubMed

    Füredi, András; Szebényi, Kornélia; Tóth, Szilárd; Cserepes, Mihály; Hámori, Lilla; Nagy, Veronika; Karai, Edina; Vajdovich, Péter; Imre, Tímea; Szabó, Pál; Szüts, Dávid; Tóvári, József; Szakács, Gergely

    2017-09-10

    Success of cancer treatment is often hampered by the emergence of multidrug resistance (MDR) mediated by P-glycoprotein (ABCB1/Pgp). Doxorubicin (DOX) is recognized by Pgp and therefore it can induce therapy resistance in breast cancer patients. In this study our aim was to evaluate the susceptibility of the pegylated liposomal formulation of doxorubicin (PLD/Doxil®/Caelyx®) to MDR. We show that cells selected to be resistant to DOX are cross-resistant to PLD and PLD is also ineffective in an allograft model of doxorubicin-resistant mouse B-cell leukemia. In contrast, PLD was far more efficient than DOX as reflected by a significant increase of both relapse-free and overall survival of Brca1 -/- ;p53 -/- mammary tumor bearing mice. Increased survival could be explained by the delayed onset of drug resistance. Consistent with the higher Pgp levels needed to confer resistance, PLD administration was able to overcome doxorubicin insensitivity of the mouse mammary tumors. Our results indicate that the favorable pharmacokinetics achieved with PLD can effectively overcome Pgp-mediated resistance, suggesting that PLD therapy could be a promising strategy for the treatment of therapy-resistant breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. How States Are Tackling the Opioid Crisis

    PubMed Central

    Zur, Julia; Mulvaney-Day, Norah; von Klimo, Melinda Campopiano; Selmi, Elizabeth; Harwood, Henrick

    2017-01-01

    Objectives: We used data from the 2015 National Association of State Alcohol and Drug Abuse Directors Web-based questionnaire and other sources to demonstrate the range and scope of state initiatives being used to deal with the opioid crisis in the United States. Methods: State alcohol and drug agency directors and designated senior agency managers responded to the questionnaire, which asked respondents about recent opioid-related state-level public health initiatives at their agencies. Results: State alcohol and drug agencies in all 50 states and the District of Columbia responded, all of which reported that prescription drug misuse was a high priority or the highest priority area for their agencies. Of the 51 respondents, states reported initiatives to educate the general public (n = 48), prescribers (n = 31), patients and families (n = 24), and pharmacists (n = 22) about the risks of opioids. In addition, 29 states had increased funding for medication-assisted treatment of opioid addiction, 28 had expanded the availability of naloxone (an opioid antidote), 26 had established guidelines for safe opioid prescribing, 23 had launched requirements for prescriber use of prescription monitoring programs, 23 had passed Good Samaritan laws to protect those helping treat overdoses, and 14 had enacted legislation to regulate pain clinics. Conclusions: US state alcohol and drug agencies demonstrated a robust response to the opioid crisis in the United States. They have pursued and expanded on an array of evidence-based initiatives aimed at the opioid crisis. Future public health efforts should focus on maintenance and further expansion of high-quality, evidence-based practices, policies, and programs. PMID:28152337

  14. How States Are Tackling the Opioid Crisis.

    PubMed

    Wickramatilake, Shalini; Zur, Julia; Mulvaney-Day, Norah; Klimo, Melinda Campopiano von; Selmi, Elizabeth; Harwood, Henrick

    We used data from the 2015 National Association of State Alcohol and Drug Abuse Directors Web-based questionnaire and other sources to demonstrate the range and scope of state initiatives being used to deal with the opioid crisis in the United States. State alcohol and drug agency directors and designated senior agency managers responded to the questionnaire, which asked respondents about recent opioid-related state-level public health initiatives at their agencies. State alcohol and drug agencies in all 50 states and the District of Columbia responded, all of which reported that prescription drug misuse was a high priority or the highest priority area for their agencies. Of the 51 respondents, states reported initiatives to educate the general public (n = 48), prescribers (n = 31), patients and families (n = 24), and pharmacists (n = 22) about the risks of opioids. In addition, 29 states had increased funding for medication-assisted treatment of opioid addiction, 28 had expanded the availability of naloxone (an opioid antidote), 26 had established guidelines for safe opioid prescribing, 23 had launched requirements for prescriber use of prescription monitoring programs, 23 had passed Good Samaritan laws to protect those helping treat overdoses, and 14 had enacted legislation to regulate pain clinics. US state alcohol and drug agencies demonstrated a robust response to the opioid crisis in the United States. They have pursued and expanded on an array of evidence-based initiatives aimed at the opioid crisis. Future public health efforts should focus on maintenance and further expansion of high-quality, evidence-based practices, policies, and programs.

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

    PubMed

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

    2017-11-01

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

  16. Cell death sensitization of leukemia cells by opioid receptor activation

    PubMed Central

    Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

    2013-01-01

    Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

  17. Opioid Prescription, Morbidity, and Mortality in United States Dialysis Patients.

    PubMed

    Kimmel, Paul L; Fwu, Chyng-Wen; Abbott, Kevin C; Eggers, Anne W; Kline, Prudence P; Eggers, Paul W

    2017-12-01

    Aggressive pain treatment was advocated for ESRD patients, but new Centers for Disease Control and Prevention guidelines recommend cautious opioid prescription. Little is known regarding outcomes associated with ESRD opioid prescription. We assessed opioid prescriptions and associations between opioid prescription and dose and patient outcomes using 2006-2010 US Renal Data System information in patients on maintenance dialysis with Medicare Part A, B, and D coverage in each study year ( n =671,281, of whom 271,285 were unique patients). Opioid prescription was confirmed from Part D prescription claims. In the 2010 prevalent cohort ( n =153,758), we examined associations of opioid prescription with subsequent all-cause death, dialysis discontinuation, and hospitalization controlled for demographics, comorbidity, modality, and residence. Overall, >60% of dialysis patients had at least one opioid prescription every year. Approximately 20% of patients had a chronic (≥90-day supply) opioid prescription each year, in 2010 usually for hydrocodone, oxycodone, or tramadol. In the 2010 cohort, compared with patients without an opioid prescription, patients with short-term (1-89 days) and chronic opioid prescriptions had increased mortality, dialysis discontinuation, and hospitalization. All opioid drugs associated with mortality; most associated with worsened morbidity. Higher opioid doses correlated with death in a monotonically increasing fashion. We conclude that opioid drug prescription is associated with increased risk of death, dialysis discontinuation, and hospitalization in dialysis patients. Causal relationships cannot be inferred, and opioid prescription may be an illness marker. Efforts to treat pain effectively in patients on dialysis yet decrease opioid prescriptions and dose deserve consideration. Copyright © 2017 by the American Society of Nephrology.

  18. Molecular Pharmacology of δ-Opioid Receptors

    PubMed Central

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

    2016-01-01

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

  19. Caffeine as an opioid analgesic adjuvant in fibromyalgia

    PubMed Central

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

    2017-01-01

    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 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. PMID:28814895

  20. Opioid Prescriptions by Specialty in Ohio, 2010-2014.

    PubMed

    Weiner, Scott G; Baker, Olesya; Rodgers, Ann F; Garner, Chad; Nelson, Lewis S; Kreiner, Peter W; Schuur, Jeremiah D

    2018-05-01

    The current US opioid epidemic is attributed to the large volume of prescribed opioids. This study analyzed the contribution of different medical specialties to overall opioids by evaluating the pill counts and morphine milligram equivalents (MMEs) of opioid prescriptions, stratified by provider specialty, and determined temporal trends. This was an analysis of the Ohio prescription drug monitoring program database, which captures scheduled medication prescriptions filled in the state as well as prescriber specialty. We extracted prescriptions for pill versions of opioids written in the calendar years 2010 to 2014. The main outcomes were the number of filled prescriptions, pill counts, MMEs, and extended-released opioids written by physicians in each specialty, and annual prescribing trends. There were 56,873,719 prescriptions for the studied opioids dispensed, for which 41,959,581 (73.8%) had prescriber specialty type available. Mean number of pills per prescription and MMEs were highest for physical medicine/rehabilitation (PM&R; 91.2 pills, 1,532 mg, N = 1,680,579), anesthesiology/pain (89.3 pills, 1,484 mg, N = 3,261,449), hematology/oncology (88.2 pills, 1,534 mg, N = 516,596), and neurology (84.4 pills, 1,230 mg, N = 573,389). Family medicine (21.8%) and internal medicine (17.6%) wrote the most opioid prescriptions overall. Time trends in the average number of pills and MMEs per prescription also varied depending on specialty. The numbers of pills and MMEs per opioid prescription vary markedly by prescriber specialty, as do trends in prescribing characteristics. Pill count and MME values define each specialty's contribution to overall opioid prescribing more accurately than the number of prescriptions alone.

  1. Long-term evaluation of opioid treatment in fibromyalgia.

    PubMed

    Peng, Xiaomei; Robinson, Rebecca L; Mease, Philip; Kroenke, Kurt; Williams, David A; Chen, Yi; Faries, Douglas; Wohlreich, Madelaine; McCarberg, Bill; Hann, Danette

    2015-01-01

    In a 12-month observational study, we evaluated the effect of opioid use on the outcomes in 1700 adult patients with fibromyalgia. Data were evaluated using propensity score matching after patients were divided into cohorts based on their baseline medication use: (1) taking an opioid (concurrent use of tramadol was permitted); (2) taking tramadol (but no opioids); and (3) not taking opioids or tramadol. Changes in outcomes were assessed using the Brief Pain Inventory for severity and pain-related interference (BPI-S, BPI-I), Fibromyalgia Impact Questionnaire (FIQ), Patient Health Questionnaire for depression (PHQ-8), Insomnia Severity Index (ISI), Sheehan Disability Scale (SDS), 7-item Generalized Anxiety Disorder Scale (GAD-7), and economic factors. Time-to-opioid or tramadol discontinuation was analyzed using Kaplan-Meier survival analyses. Compared with the opioid cohort, the nonopioid cohort demonstrated significantly greater reductions (P<0.05) in BPI-I, FIQ, PHQ-8, SDS, and ISI; the tramadol cohort compared with the opioid group showed greater reductions on FIQ and ISI. Reductions in BPI-S and GAD-7 did not differ significantly among cohorts. Compared with the opioid cohort, patients in the tramadol cohort had fewer outpatient visits to health care providers. Few significant differences were found between the tramadol and nonopioid cohorts across outcomes. Although pain severity was reduced over time in all cohorts, opioid users showed less improvement in pain-related interference with daily living, functioning, depression, and insomnia. Overall, the findings show little support for the long-term use of opioid medications in patients with fibromyalgia given the poorer outcomes across multiple assessment domains associated with this cohort.

  2. Formulation of carbapenems loaded gold nanoparticles to combat multi-antibiotic bacterial resistance: In vitro antibacterial study.

    PubMed

    Shaker, Mohamed A; Shaaban, Mona I

    2017-06-15

    Despite the fact that carbapenems (powerful β-lactams antibiotics) were able to fight serious infectious diseases, nowadays the spread of carbapenems-resistant bacteria is considered the main challenge in antibacterial therapy. In this study, we focused on evaluating the surface conjugation of carbapenems (imipenem and meropenem) with gold nanoparticles as a delivering strategy to specifically and safely maximize their therapeutic efficacy while destroying the developing resistance of the pathogens. Different particle size formulae (35, 70 and 200nm) were prepared by citrate reduction method. The prepared nanoparticles were functionalized with imipenem (Ipm) or meropenem (Mem) and physico-chemically characterized for loading efficiency, particle size, morphology, and in-vitro release. The antibacterial efficacy was also evaluated against carbapenems resistant Gram-negative bacteria isolated from infected human, through measuring the minimum inhibitory concentration and antibiotic kill test. All the obtained gold nanoparticles showed a distinct nano-size with loading efficiency up to 72% and 74% for Ipm and Mem, respectively. The conjugation and physico-chemical stability of the formulated carbapenems were confirmed by FTIR and X-RPD. Diffusion driven release behavior was observed for both Ipm and Mem from all of the loaded gold nanoparticles. For both Ipm and Mem, formula with 35nm diameter showed the most significant enhancement in antibacterial activity against all the selected isolates including Klebsiella pneumoniae, Proteus mirabilis and Acinteobacter baumanii. Ipm loaded Gold nanoparticles demonstrated decrease in the MIC of Ipm down to four folds, whereas, Mem loaded gold nanoparticles showed decrease in the MIC of Mem down to three folds on the tested bacterial isolates. Based on these results, the formulation of carbapenems-loaded gold nanoparticles demonstrated to be a promising nano-size delivery vehicle for improving the therapeutic activity and

  3. Possible Opioid Shopping and its Correlates.

    PubMed

    Walker, Alexander M; Weatherby, Lisa B; Cepeda, M Soledad; Bradford, Daniel; Yuan, Yingli

    2017-11-01

    We created an operational definition of possible opioid shopping in US commercial health insurance data and examined its correlates. The population consisted of 264,204 treatment courses in persons with a fill for an opioid or diuretic prescription in 2012 and a second within 18 months. We examined counts of prescribers and pharmacies and the numbers of fills and overlaps for ability to discriminate courses of opioids from diuretics, which were a negative control. The most discriminatory measure, indicating possible shopping behavior, was cross-tabulated against other prescriptions filled and diagnoses as found in insurance claims. The associations between claims characteristics and shopping behavior were assessed in a logistic regression. A definition that classified possible "moderate" or "extensive" shopping when a person obtained drug through at least 3 practices and at least 3 pharmacies over 18 months was highly discriminatory between opioid and diuretic treatment. Overlaps between fills and number of fills did not improve the discrimination. Data from insurance claims strongly predicted moderate-to-extensive levels of possible shopping (c=0.82). Prominent among 20 significant predictors were: state of residence; amount of opioid dispensed; self-payment; use of nonspecialist prescribers; high use of anxiolytics, hypnotics, psychostimulants, and antipsychotics; and use of both immediate release and extended-release or long-acting opioids. The use of ≥3 prescribing practices and ≥3 dispensing pharmacies over 18 months sharply discriminated courses of opioid treatment from courses of diuretics. This pattern of fills was additionally associated with the numbers of nonspecialist and self-paid fills, the total morphine milligram equivalents dispensed, and heavier use of drugs for anxiety, sleep, attention, and psychosis.

  4. Analysis of opioid receptor subtype antagonist effects upon mu opioid agonist-induced feeding elicited from the ventral tegmental area of rats.

    PubMed

    Lamonte, Nicole; Echo, Joyce A; Ackerman, Tsippa F; Christian, Garrison; Bodnar, Richard J

    2002-03-01

    The present study examined opioid receptor(s) mediation of feeding elicited by mu opioid agonists in the ventral tegmental area using general or selective opioid antagonist pretreatment. Naltrexone as well as equimolar doses of selective mu and kappa, but not delta opioid antagonists in the ventral tegmental area significantly reduced mu agonist-induced feeding, indicating a pivotal role for these receptor subtypes in the full expression of this response.

  5. Cue-Induced Craving in Dependence Upon Prescription Opioids and Heroin

    PubMed Central

    McHugh, R. Kathryn; Park, Sara; Weiss, Roger D.

    2014-01-01

    Background and Objectives Cues associated with heroin use (e.g., needles, powder) elicit robust craving responses in individuals dependent upon heroin. Elevated cue-induced craving may be a risk factor for relapse and can persist after periods of drug abstinence. Despite the growing prevalence of opioid dependence involving prescription opioids, published studies have yet to examine whether cue-induced craving is also present in prescription opioid dependence. Methods A sample of 50 adults diagnosed with opioid dependence (20 prescription opioid users, 25 heroin users, and 5 mixed opioid users) completed a cue reactivity assessment. Participants were administered a series of 90 pictures, including heroin-specific, prescription opioid-specific, and neutral images, and were asked to rate craving and cue salience after each image. Results Both the prescription opioid and heroin groups experienced significantly more craving to drug than to neutral stimuli. The prescription opioid group reported significantly less craving to prescription opioid stimuli than the heroin group to heroin stimuli; however, this effect was smaller and non-significant when controlling for group differences in cue salience. Discussion and Conclusions This study found evidence for cue-induced craving in individuals dependent upon prescription opioids. Further research is needed to better understand the role of cue reactivity in the course and treatment of opioid dependence involving prescription opioid use. Scientific Significance As elevated craving reactivity to drug cues may reflect a risk factor for relapse, understanding the nature of cue-induced craving in individuals with opioid dependence is important to improving treatments for this population. PMID:24628912

  6. Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies.

    PubMed

    Melichar, Jan K; Hume, Susan P; Williams, Tim M; Daglish, Mark R C; Taylor, Lindsay G; Ahmad, Rabia; Malizia, Andrea L; Brooks, David J; Myles, Judith S; Lingford-Hughes, Anne; Nutt, David J

    2005-01-01

    Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [(11)C]diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone (18-90 mg daily) had an [(11)C]diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [(11)C]diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [(11)C]diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [(11)C]diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [(11)C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.

  7. Opioid and amphetamine dependence is associated with methicillin-resistant Staphylococcus aureus (MRSA): An epidemiological register study with 73,201 Swedish in- and outpatients 1997-2013.

    PubMed

    Dahlman, Disa; Berge, Jonas; Nilsson, Anna C; Kral, Alex H; Bjorkman, Per; Hakansson, Anders C

    2017-02-01

    While methicillin-resistant Staphylococcus aureus (MRSA) is increasing in prevalence globally, Sweden is still a low-prevalence country enabling studies on the natural MRSA spread in subpopulations unaffected by a surrounding highly infected population. Substance dependence and injection drug use have been risk factors for MRSA carriage and infection in other countries. In this retrospective, longitudinal register study, we investigated MRSA epidemiology 1997-2013 in opioid and amphetamine-dependent individuals, in comparison with alcohol-dependent subjects. Data from the national Swedish in- and outpatients registers included 73,201 individuals from 1997, 1999, 2004, 2009 and 2013. We analyzed substance use disorder and demographic predictors for MRSA using generalized estimating equations. The main finding was that both opioid (adjusted odds ratio [AOR] = 2.82; 95% confidence interval [CI] = 2.16, 3.67) and amphetamine dependence (AOR = 2.71; 95% CI = 1.70, 4.16) were significantly associated with MRSA diagnosis compared with alcohol dependence, when adjusting for age, sex and year. These findings are of value to understand the dynamics of MRSA epidemiology among substance dependent persons with presumably low socioeconomic status and potential injection drug use, and implicate repeated surveillance of MRSA among these patients.

  8. Opioid Use and Neural Tube Defects

    MedlinePlus

    ... 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 ...

  9. Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

    PubMed

    Larochelle, Marc R; Cocoros, Noelle M; Popovic, Jennifer; Dee, Elizabeth C; Kornegay, Cynthia; Ju, Jing; Racoosin, Judith A

    A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Retrospective cohort study. Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

  10. Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.

    PubMed

    Huang, Zhenhua; Liang, Lining; Li, Lingyu; Xu, Miao; Li, Xiang; Sun, Hao; He, Songwei; Lin, Lilong; Zhang, Yixin; Song, Yancheng; Yang, Man; Luo, Yuling; Loh, Horace H; Law, Ping-Yee; Zheng, Dayong; Zheng, Hui

    2016-03-08

    Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.

  11. Pharmacologic Profile of Naloxegol, a Peripherally Acting µ-Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation.

    PubMed

    Floettmann, Eike; Bui, Khanh; Sostek, Mark; Payza, Kemal; Eldon, Michael

    2017-05-01

    Opioid-induced constipation (OIC) is a common side effect of opioid pharmacotherapy for the management of pain because opioid agonists bind to µ -opioid receptors in the enteric nervous system (ENS). Naloxegol, a polyethylene glycol derivative of naloxol, which is a derivative of naloxone and a peripherally acting µ -opioid receptor antagonist, targets the physiologic mechanisms that cause OIC. Pharmacologic measures of opioid activity and pharmacokinetic measures of central nervous system (CNS) penetration were employed to characterize the mechanism of action of naloxegol. At the human µ -opioid receptor in vitro, naloxegol was a potent inhibitor of binding ( K i = 7.42 nM) and a neutral competitive antagonist (p A 2 - 7.95); agonist effects were <10% up to 30 μ M and identical to those of naloxone. The oral doses achieving 50% of the maximal effect in the rat for antagonism of morphine-induced inhibition of gastrointestinal transit and morphine-induced antinociception in the hot plate assay were 23.1 and 55.4 mg/kg for naloxegol and 0.69 and 1.14 mg/kg by for naloxone, respectively. In the human colon adenocarcinoma cell transport assay, naloxegol was a substrate for the P-glycoprotein transporter, with low apparent permeability in the apical to basolateral direction, and penetrated the CNS 15-fold slower than naloxone in a rat brain perfusion model. Naloxegol-derived radioactivity was poorly distributed throughout the rat CNS and was eliminated from most tissues within 24 hours. These findings corroborate phase 3 clinical studies demonstrating that naloxegol relieves OIC-associated symptoms in patients with chronic noncancer pain by antagonizing the µ -opioid receptor in the ENS while preserving CNS-mediated analgesia. Copyright © 2017 The Author(s).

  12. New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 through 2015.

    PubMed

    Chai, Grace; Xu, Jing; Osterhout, James; Liberatore, Mark A; Miller, Kathleen L; Wolff, Carolyn; Cruz, Marisa; Lurie, Peter; Dal Pan, Gerald

    2018-05-01

    The opioid epidemic, driven in part by increased prescribing, is a public health emergency. This study examines dispensed prescription patterns and approvals of new opioid analgesic products to investigate whether the introduction of these new drugs increases prescribing. Prescribing patterns based on dispensed prescription claims from the U.S. retail setting were assessed with new brand and generic opioid analgesic products approved in the United States from 1997 through 2015. From 1997 through 2015, the U.S. Food and Drug Administration (Silver Spring, Maryland) approved 263 opioid analgesic products, including 33 brand products. Dispensed prescriptions initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015. Morphine milligram equivalents dispensed per prescription increased from 486 in 1997 to a peak of 950 in 2010, before decreasing to 905 in 2015. In 2015, generic products accounted for 96% (218/228 million prescriptions) of all opioid analgesic prescriptions dispensed. The remaining prescriptions were dispensed for brand products, of which nearly half were dispensed for one brand product (OxyContin, Purdue, USA). There has been a dramatic increase in prescriptions dispensed for opioid analgesics since 1997 and an increasing number of opioid analgesic approvals; however, the number of prescriptions dispensed has declined since 2012 despite an increasing number of approvals. Examination of dispensed prescriptions shows a shifting and complex market where multiple factors likely influence prescribing; the approval of new products alone may not be sufficient to be a primary driver of increased prescribing. An online visual overview is available for this article at http://links.lww.com/ALN/B705.

  13. Pain Intensity and Opioid Utilization in Response to CPAP Therapy in Veterans with Obstructive Sleep Apnea on Chronic Opioid Treatment.

    PubMed

    Jaoude, Philippe; Lal, Ashima; Vermont, Leah; Porhomayon, Jahan; El-Solh, Ali A

    2016-08-15

    Sleep fragmentation has been linked to poor pain tolerance and lowered pain threshold. Little evidence exists on whether continuous positive airway pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA) who are taking opioids for non-malignant pain would ameliorate pain and reduce consumption of opioids. A retrospective case-control study was performed at a VA sleep center. Pain intensity was assessed using the Numerical Categorical Scale prior to CPAP treatment and 12-mo follow-up. Opioids intake was assessed using the morphine equivalent daily dose (MEDD). Adherence to CPAP was evaluated with the built-in meter. We reviewed 113 patients with OSA (apnea-hypopnea index [AHI] 35.9 ± 29.5) using a MEDD of 61.6 mg (range 5-980 mg) and a control group of 113 veterans with OSA (AHI 33.4 ± 27.3) on no opioids treatment. CPAP adherence was significantly lower at 12 mo in opioid-treated patients compared to controls (37% versus 55%; p = 0.01). Greater pain intensity was the only independent variable associated with CPAP non-adherence at 12-mo follow-up (p = 0.03). Compared to baseline, no significant difference was observed in pain intensity or consumption of opioids in CPAP adherent patients. CPAP treatment did not reduce pain intensity or consumption of opioids in veterans with chronic pain who have coexisting OSA. CPAP adherence was lower in opioid-treated veterans with OSA compared to opioid-free veterans with OSA. Pain intensity was the only determinant of CPAP adherence. Future studies are needed to evaluate pain management program on adherence to CPAP. © 2016 American Academy of Sleep Medicine.

  14. Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals

    PubMed Central

    Guest, Charlotte; Sobotka, Fabian; Karavasopoulou, Athina; Ward, Stephen; Bantel, Carsten

    2017-01-01

    Objective Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses’ mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. Material and methods A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses’ mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580) and one German (n=799) hospital between September 2014 and February 2015. Results A total of 511 (37.1%) questionnaires were returned. Mean (standard deviation) age of participants were 37 (11) years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87% did not regard opioids as drugs to help patients die, and 72% did not view them as drugs of abuse. More English (41%) than German (28%) nurses were afraid of criminal investigations and were constantly aware of side effects (UK, 94%; Germany, 38%) when using opioids. Four latent variables were identified which likely influence nurses’ mental models: “conscious decision-making”; “medication-related fears”; “practice-based observations”; and “risk assessment”. They were predicted by strength of religious beliefs and indicators of informal learning such as experience but not by indicators of formal learning such as conference attendance. Conclusion Nurses in both countries employ analytical and affective mental

  15. Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals.

    PubMed

    Guest, Charlotte; Sobotka, Fabian; Karavasopoulou, Athina; Ward, Stephen; Bantel, Carsten

    2017-01-01

    Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses' mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses' mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580) and one German (n=799) hospital between September 2014 and February 2015. A total of 511 (37.1%) questionnaires were returned. Mean (standard deviation) age of participants were 37 (11) years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87% did not regard opioids as drugs to help patients die, and 72% did not view them as drugs of abuse. More English (41%) than German (28%) nurses were afraid of criminal investigations and were constantly aware of side effects (UK, 94%; Germany, 38%) when using opioids. Four latent variables were identified which likely influence nurses' mental models: "conscious decision-making"; "medication-related fears"; "practice-based observations"; and "risk assessment". They were predicted by strength of religious beliefs and indicators of informal learning such as experience but not by indicators of formal learning such as conference attendance. Nurses in both countries employ analytical and affective mental models when administering the opioids and seem to learn from experience

  16. The Neurobiology of Opioid Dependence: Implications for Treatment

    PubMed Central

    Kosten, Thomas R.; George, Tony P.

    2002-01-01

    Opioid tolerance, dependence, and addiction are all manifestations of brain changes resulting from chronic opioid abuse. The opioid abuser’s struggle for recovery is in great part a struggle to overcome the effects of these changes. Medications such as methadone, LAAM, buprenorphine, and naltrexone act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects. Despite the effectiveness of medications, they must be used in conjunction with appropriate psychosocial treatments. PMID:18567959

  17. Controlling pain and reducing misuse of opioids

    PubMed Central

    Kotalik, Jaro

    2012-01-01

    Abstract Objective To help family physicians achieve an ethical balance in their opioid prescribing practices. Quality of evidence MEDLINE was searched for English-language articles published between 1985 and 2011. Most available evidence was level III. Main message It is essential to follow practice guidelines when prescribing opioids, except when another course of action is demonstrably justified. In addition, when considering the appropriateness of an opioid prescription, with its many ethical implications, the decision can be usefully guided by the application of the ethical principles of beneficence, nonmaleficence, respect for autonomy, and justice. As well, it is essential to keep current about legal and regulatory changes and provincial electronic registries of opioid prescriptions. Conclusion Physicians need to ensure that their patients’ pain is properly assessed and managed. Reaching optimal pain control might necessitate prescribing opioids. But the obligation to provide pain relief needs to be balanced with an equally important responsibility not to expose patients to risk of addiction and not to create opportunities for drug diversion, trafficking, and the addiction of others. Basic ethical principles can provide a framework to help physicians make ethically appropriate decisions about opioid prescribing. PMID:22611604

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

    MedlinePlus

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

  19. Opioid receptors: from binding sites to visible molecules in vivo

    PubMed Central

    Kieffer, Brigitte L.; Evans, Christopher J.

    2010-01-01

    Opioid drugs such as heroin interact directly with opioid receptors whilst other addictive drugs, including marijuana, alcohol and nicotine indirectly activate endogenous opioid systems to contribute to their rewarding properties. The opioid system therefore plays a key role in addiction neurobiology and continues to be a primary focus for NIDA-supported research. Opioid receptors and their peptide ligands, the endorphins and enkephalins, form an extensive heterogeneous network throughout the central and peripheral nervous system. In addition to reward, opioid drugs regulate many functions such that opioid receptors are targets of choice in several physiological, neurological and psychiatric disorders. Because of the multiplicity and diversity of ligands and receptors, opioid receptors have served as an optimal model for G protein coupled receptor (GPCR) research. The isolation of opioid receptor genes opened the way to molecular manipulations of the receptors, both in artificial systems and in vivo, contributing to our current understanding of the diversity of opioid receptor biology at the behavioral, cellular and molecular levels. This review will briefly summarize some aspects of current knowledge that has accumulated since the very early characterization of opioid receptor genes. Importantly, we will identify a number of research directions that are likely to develop during the next decade. PMID:18718480

  20. Comorbid Post-Traumatic Stress Disorder and Opioid Dependence.

    PubMed

    Patel, Rikinkumar S; Elmaadawi, Ahmed; Nasr, Suhayl; Haskin, John

    2017-09-03

    Post-traumatic stress disorder (PTSD) is predominant amongst individuals addicted to opioids and obscures the course of illness and the treatment outcome. We report the case of a patient with major depressive disorder and opioid dependence, who experienced post-traumatic stress disorder symptoms during a recent visit to the inpatient unit. The similarity of symptoms between post-traumatic stress disorder and opioid dependence is so high that, sometimes, it is a challenge to differentiate between these conditions. Since opioid withdrawal symptoms mimic hyper vigilance, this results in an exaggeration of the response of patients with post-traumatic stress disorder. This comorbidity is associated with worse health outcomes, as its pathophysiology involves a common neurobiological circuit. Opioid substitution therapy and psychotherapeutic medications in combination with evidence-based cognitive behavioral therapy devised for individuals with comorbid post-traumatic stress disorder and opioid dependence may improve treatment outcomes in this population. Therefore, we conclude that the screening for post-traumatic stress disorder in the opioid-abusing population is crucial. To understand the underlying mechanisms for this comorbidity and to improve the treatment response, further research should be encouraged.

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

    PubMed

    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.

  2. Will peripherally restricted kappa-opioid receptor agonists (pKORAs) relieve pain with less opioid adverse effects and abuse potential?

    PubMed

    Albert-Vartanian, A; Boyd, M R; Hall, A L; Morgado, S J; Nguyen, E; Nguyen, V P H; Patel, S P; Russo, L J; Shao, A J; Raffa, R B

    2016-08-01

    Optimal utilization of opioid analgesics is significantly limited by the central nervous system adverse effects and misuse/abuse potential of currently available drugs. It has been postulated that opioid-associated adverse effects and abuse potential would be greatly reduced if opioids could be excluded from reaching the brain. We review the basic science and clinical evidence of one such approach - peripherally restricted kappa-opioid receptor (KOR) agonists (pKORAs). Published and unpublished literature, websites and other sources were searched for basic science and clinical information related to the potential benefits and development of peripherally restricted kappa-opioid receptor agonists. Each source was summarized, reviewed and assessed. The historical development of pKORAs can be traced from the design of increasingly KOR-selective agonists, elucidation of the pharmacologic attributes of such compounds and strategies to restrict passage across the blood-brain barrier. Novel compounds are under development and have progressed to clinical trials. The results from recent clinical trials suggest that peripherally restricted opioids can be successfully designed and that they can retain analgesic efficacy with a more favourable adverse effect profile. © 2016 John Wiley & Sons Ltd.

  3. Correlates of overdose risk perception among illicit opioid users

    PubMed Central

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

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:26754425

  4. Comparative in vitro anti-tick efficacy of commercially available products and newly developed phyto-formulations against field collected and resistant tick lines of Rhipicephalus (Boophilus) microplus.

    PubMed

    Ajith Kumar, K G; Sharma, Anil Kumar; Kumar, Sachin; Ray, D D; Rawat, A K S; Srivastava, Sharad; Ghosh, Srikant

    2016-12-01

    Rhipicephalus ( Boophilus ) microplus is considered as one of the most widely distributed tick species ecto-parasitizing on livestock and causes fatal diseases with significant production loss. To address the problem of controlling acaricide resistant tick infestations on animals, attention has been paid to develop eco-friendly phyto-acaricides. The present study was undertaken to evaluate the comparative anti-tick activities of commercially available herbal and chemical products with chemically characterized phyto-formulations developed recently against field ticks and resistant tick lines of R. ( B. ) microplus . The chemical product Butox ® Vet was found nearly passive against all the tested resistant tick lines. However, one of the commercial polyherbal product, Zerokeet ® showed an efficacy (E%) of 41.8-75.4 % ([Formula: see text]) using recommended dilution (1:2) against field ticks and resistant tick lines. However, the other commercial product, Erina ® EP has very limited efficacy against all the tested tick. In comparison, the newly developed phyto-formulation, NBA/13/B/2 and NAC-01 conferred an E% of 82.4-91.3 % ([Formula: see text]) and 62.3-94.6 % ([Formula: see text]), respectively, against tested resistant ticks. Results indicated higher marketing potentiality of newly developed formulation in the existing tick problem scenario.

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

    PubMed Central

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

    2017-01-01

    Objective 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. Materials and methods 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. Results 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. Conclusions REBOOT reduced the occurrence of any opioid

  6. Access to opioids: a global pain management crisis.

    PubMed

    Buitrago, Rosa

    2013-03-01

    The lack of availability of opioids in many countries has created a pain management crisis. Because the Single Convention on Narcotic Drugs requires governments to report annual opioid statistics, there is a need for methods to calculate individual nations' opioid needs. Ways to address this need are discussed.

  7. New trends in the development of opioid peptide analogues as advanced remedies for pain relief.

    PubMed

    Gentilucci, Luca

    2004-01-01

    The search for new peptides to be used as analgesics in place of morphine has been mainly directed to develop peptide analogues or peptidomimetics having higher biological stability and receptor selectivity. Indeed, most of the alkaloid opioid counterindications are due to the scarce stability and the contemporary activation of different receptor types. However, the development of several extremely stable and selective peptide ligands for the different opioid receptors, and the recent discovery of the micro-receptor selective endomorphins, rendered this search less fundamental. In recent years, other opioid peptide properties have been investigated in the search for new pharmacological tools. The utility of a drug depends on its ability to reach appropriate receptors at the target tissue and to remain metabolically stable in order to produce the desired effect. This review deals with the recent investigations on peptide bioavailability, in particular barrier penetration and resistance against enzymatic degradation; with the development of peptides having activity at different receptors; with chimeric peptides, with propeptides, and with non-conventional peptides, lacking basic pharmacophoric features.

  8. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain

    PubMed Central

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

    2015-01-01

    Background Opioids are frequently prescribed for chronic low back pain (CLBP), but there is 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. Methods We 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. Results There was an overall 25% drop out 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 and low NA groups had an average 21% vs. 39% improvement in pain, respectively (p<.01). The high NA group also had a significantly greater rate of opioid misuse (39% vs. 8%, p<.05), and significantly more and intense opioid side effects (p<.01). Conclusions These results indicate that the benefit and risk considerations in CLBP patients with high vs. low NA are distinctly different. Thus, negative affect is an important phenotypic variable to characterize at baseline, prior to deciding whether to prescribe opioids for CLBP. PMID:26375824

  9. Treating opioid dependence. Growing implications for primary care.

    PubMed

    Krantz, Mori J; Mehler, Philip S

    2004-02-09

    Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

  10. Fiber Optic Tamper Indicating Enclosure (TIE); A Case Study in Authentication

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anheier, Norman C.; Benz, Jacob M.; Tanner, Jennifer E.

    2015-07-15

    A robust fiber optic-based tamper-indicating enclosure (TIE) has been developed by PNNL through funding by the National Nuclear Security Administration Office of Nuclear Verification over the past few years. The objective of this work is to allow monitors to have confidence in both the authenticity and integrity of the TIE and the monitoring equipment inside, throughout the time it may be located at a host facility. Incorporating authentication features into the design were the focus of fiscal year 2014 development efforts. Throughout the development process, modifications have been made to the physical TIE design based on lessons learned via exercisesmore » and expert elicitation. The end result is a robust and passive TIE which can be utilized to protect monitoring party equipment left in a host facility.« less

  11. Healthy Adult Male Facial Skin Surface Lipid Pheromone p.o. to Treat Opioid Addiction

    ClinicalTrials.gov

    2018-03-20

    Opioid Addiction; Opioid Abuse, Continuous Use; Opioid Use; Opioid-Related Disorders; Paternal Pheromone Deficiency; Opioid Dependence; Opioid Abuse; Opioid-use Disorder; Opioid Intoxication; Opioid Abuse, Episodic

  12. Immunomodulatory effects of endogenous and synthetic peptides activating opioid receptors.

    PubMed

    Pomorska, Dorota K; Gach, Katarzyna; Janecka, Anna

    2014-01-01

    The main role of endogenous opioid peptides is the modulation of pain. Opioid peptides exert their analgesic activity by binding to the opioid receptors distributed widely in the central nervous system (CNS). However, opioid receptors are also found on tissues and organs outside the CNS, including the cells of the immune system, indicating that opioids are capable of exerting additional effects in periphery. Morphine, which is a gold standard in the treatment of chronic pain, is well-known for its immunosuppressive effects. Much less is known about the immunomodulatory effects exerted by endogenous (enkephalins, endorphins, dynorphins and endomorphins) and synthetic peptides activating opioid receptors. In this review we tried to summarize opioid peptide-mediated modulation of immune cell functions which can be stimulatory as well as inhibitory.

  13. Acute pain management in opioid-tolerant patients: a growing challenge.

    PubMed

    Huxtable, C A; Roberts, L J; Somogyi, A A; MacIntyre, P E

    2011-09-01

    In Australia and New Zealand, in parallel with other developed countries, the number of patients prescribed opioids on a long-term basis has grown rapidly over the last decade. The burden of chronic pain is more widely recognised and there has been an increase in the use of opioids for both cancer and non-cancer indications. While the prevalence of illicit opioid use has remained relatively stable, the diversion and abuse of prescription opioids has escalated, as has the number of individuals receiving methadone or buprenorphine pharmacotherapy for opioid addiction. As a result, the proportion of opioid-tolerant patients requiring acute pain management has increased, often presenting clinicians with greater challenges than those faced when treating the opioid-naïve. Treatment aims include effective relief of acute pain, prevention of drug withdrawal, assistance with any related social, psychiatric and behavioural issues, and ensuring continuity of long-term care. Pharmacological approaches incorporate the continuation of usual medications (or equivalent), short-term use of sometimes much higher than average doses of additional opioid, and prescription of non-opioid and adjuvant drugs, aiming to improve pain relief and attenuate opioid tolerance and/or opioid-induced hyperalgesia. Discharge planning should commence at an early stage and may involve the use of a 'Reverse Pain Ladder' aiming to limit duration of additional opioid use. Legislative requirements may restrict which drugs can be prescribed at the time of hospital discharge. At all stages, there should be appropriate and regular consultation and liaison with the patient, other treating teams and specialist services.

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

    PubMed

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

    2017-09-01

    Breast reduction has traditionally been performed under general anesthesia with adjunct opioid use. However, opioids are associated with a wide variety of adverse effects, including nausea, vomiting, constipation, postoperative sedation, dizziness, and addiction. This study compares bilateral breast reduction using a multimodal opioid-free pain management regimen vs traditional general anesthesia with adjunct opioids. A total of 83 female patients were enrolled in this study. Group 1 includes a retrospective series of 39 patients that underwent breast reduction via general anesthesia with adjunct opioid use. This series was compared to 2 prospective groups of patients who did not receive opioids either preoperatively or intraoperatively. In group 2, twenty-six patients underwent surgery under intravenous sedation and local anesthesia. In group 3, eighteen patients underwent surgery with general anesthesia. All patients in groups 2 and 3 received preoperative gabapentin and celecoxib along with infiltration of local anesthetics during the operation and prior to discharge to the Post-Anesthesia Care Unit (PACU). Primary outcome measures included the duration of surgery, time from end of operation to discharge home, postoperative opioid and antiemetic use, and unplanned postoperative hospitalizations. When compared to group 1, groups 2 and 3 experienced a shorter time from end of operation to discharge home (P < 0.05), fewer unplanned hospital admissions (P < 0.05), and highly significant decrease in postoperative opioid use (P < 0.001). This multimodal approach allows patients to safely undergo opioid-free bilateral breast reduction either under local or general anesthesia as an outpatient. This method resulted in significantly less morbidity, use of opioids postoperatively, as well as unplanned hospital admissions compared to "traditional" breast reduction under general anesthesia with the use of opioids. 3. © 2017 The American Society for Aesthetic Plastic Surgery

  15. Neck Pain, Preoperative Opioids, and Functionality After Cervical Fusion.

    PubMed

    Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U

    2017-01-01

    The use of opioids among patients with workers' compensation claims is associated with tremendous costs, especially for patients who undergo spinal surgery. This study compared return-to-work rates after single-level cervical fusion for degenerative disk disease between patients who received opioids before surgery and patients who underwent fusion with no previous opioid use. All study subjects qualified for workers' compensation benefits for injuries sustained at work between 1993 and 2011. The study population included 281 subjects who underwent single-level cervical fusion for degenerative disk disease with International Classification of Diseases, Ninth Revision, and Current Procedural Terminology code algorithms. The opioid group included 77 subjects who received opioids preoperatively. The control group included 204 subjects who had surgery with no previous opioid use. The primary outcome was meeting return-to-work criteria within 3 years of follow-up after fusion. Secondary outcome measures after surgery, surgical details, and presurgical characteristics for each cohort also were collected. In 36.4% of the opioid group, return-to-work criteria were met compared with 56.4% of the control group. Patients who took opioids were less likely to meet return-to-work criteria compared with the control group (odds ratio, 0.44; 95% confidence interval, 0.26-0.76; P=.0028). Return-to-work rates within the first year after fusion were 24.7% for the opioid group and 45.6% for the control group (P=.0014). Patients who used opioids were absent from work for 255 more days compared with the control group (P=.0001). The use of opioids for management of diskogenic neck pain, with the possibility of surgical intervention, is a negative predictor of successful return to work after fusion in a workers' compensation population. [Orthopedics. 2017; 40(1):25-32.]. Copyright 2016, SLACK Incorporated.

  16. Provider confidence in opioid prescribing and chronic pain management: results of the Opioid Therapy Provider Survey

    PubMed Central

    Pearson, Amy CS; Moman, Rajat N; Moeschler, Susan M; Eldrige, Jason S; Hooten, W Michael

    2017-01-01

    Introduction Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics. Materials and methods The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman’s rho. Results Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (P<0.001). Provider confidence was negatively correlated with the perception that treating pain patients was a “problem in my practice” (P=0.005). Conclusion In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable competence in managing chronic pain and explore approaches to enhance appropriate levels of confidence in caring for patients with chronic pain. PMID:28652805

  17. Opioid Addiction

    MedlinePlus

    ... breathing rate nausea, vomiting constipation physical agitation poor decision making abandoning responsibilities slurred speech sleeping more or less than normal mood swings euphoria (feeling high) irritability depression lowered motivation anxiety attacks. Symptoms of opioid overdose An overdose ...

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

    PubMed

    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

    2017-09-01

    Prescription opioid misuse is a national crisis. Few interventions have improved adherence to opioid-prescribing guidelines. To determine whether a multicomponent intervention, Transforming Opioid Prescribing in Primary Care (TOPCARE; http://mytopcare.org/), improves guideline adherence while decreasing opioid misuse risk. 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. 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. 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. 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 < .001; adjusted odds ratio [AOR], 6.0; 95% CI, 3.6-10.2), to have a patient-PCC agreement (of the 376 without an agreement at baseline, 53.8% vs 6.0%; P < .001; AOR, 11.9; 95% CI, 4.4-32.2), and to undergo at least 1 UDT (74.6% vs 57.9%; P < .001; AOR, 3.0; 95% CI, 1.8-5.0). There was no difference in odds of early refill receipt between groups (20.7% vs 20.1%; AOR, 1.1; 95% CI, 0

  19. Chronic Opioid Usage in Surgical Patients in a Large Academic Center

    PubMed Central

    Jiang, Xueying; Orton, Margaret; Feng, Rui; Hossain, Erik; Malhotra, Neil R.; Zager, Eric L.; Liu, Renyu

    2017-01-01

    Objective The objective of this study is to investigate the prevalence and disparity of chronic opioid usage in surgical patients and the potential risk factors associated with chronic opioid usage. Background Chronic opioid usage is common in surgical patients; however, the characteristics of opioid usage in surgical patients is unclear. In this study, we hypothesize that the prevalence of chronic opioid usage in surgical patients is high, and that significant disparities may exist among different surgical populations. Methods Data of opioid usage in outpatients among different surgical services were extracted from the electronic medical record database. Patient demographics, clinical characteristics of sex, age, race, body mass index (BMI), specialty visited, duration of opioid use, and opioid type were collected. Chronic opioid users were defined as patients who had been recorded as taking opioids for at least 90 days determined by the first and last visit dates under opioid usage during the investigation. Results There were 79,123 patients included in this study. The average prevalence is 9.2%, ranging from 4.4% to 23.8% among various specialties. The prevalence in orthopedics (23.8%), neurosurgery (18.7%), and gastrointestinal surgery (14.4%) ranked in the top three subspecialties. Major factors influencing chronic opioid use include age, Ethnicitiy, Subspecialtiy, and multiple specialty visits. Approximately 75% of chronic users took opioids that belong to the category II Drug Enforcement Administration classification. Conclusions Overall prevalence of chronic opioid usage in surgical patients is high with widespread disparity among different sex, age, ethnicity, BMI, and subspecialty groups. Information obtained from this study provides clues to reduce chronic opioid usage in surgical patients. PMID:27163960

  20. Medication-Assisted Treatment For Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43

    ERIC Educational Resources Information Center

    Tinkler, Emily; Vallejos Bartlett, Catalina; Brooks, Margaret; Gilbert, Johnatnan Max; Henderson, Randi; Shuman, Deborah, J.

    2005-01-01

    TIP 43 provides best-practice guidelines for medication-assisted treatment of opioid addiction in opioid treatment programs (OTPs). The primary intended audience for this volume is substance abuse treatment providers and administrators who work in OTPs. Recommendations in the TIP are based on both an analysis of current research and determinations…

  1. Opioid-use disorder among patients on long-term opioid therapy: impact of final DSM-5 diagnostic criteria on prevalence and correlates.

    PubMed

    Boscarino, Joseph A; Hoffman, Stuart N; Han, John J

    2015-01-01

    Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results. Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96). In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria. The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (<2), 28.1% for mild symptoms (2-3), 9.7% for moderate symptoms (4-5), and 3.5% for severe symptoms (six or more). Thus, the lifetime prevalence of "any" prescription opioid-use disorder in this cohort was 41.3% (95% confidence interval [CI] =37.6-45.0). A comparison to the DSM-4 criteria indicated that the majority of patients with lifetime DSM-4 opioid dependence were now classified as having mild opioid-use disorder, based on the DSM-5 criteria (53.6%; 95% CI =44.1-62.8). In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age <65 years, current pain impairment, trouble sleeping, suicidal thoughts, anxiety disorders, illicit drug use, and history of substance abuse treatment. Given the final DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of craving and abuse symptoms, and introduction of a new graded severity classification, the prevalence of opioid-use disorders has changed, while many of the DSM-4 risk factors for opioid dependence were

  2. Opioid-use disorder among patients on long-term opioid therapy: impact of final DSM-5 diagnostic criteria on prevalence and correlates

    PubMed Central

    Boscarino, Joseph A; Hoffman, Stuart N; Han, John J

    2015-01-01

    Aims Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results. Methods Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96). In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria. Results The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (<2), 28.1% for mild symptoms (2–3), 9.7% for moderate symptoms (4–5), and 3.5% for severe symptoms (six or more). Thus, the lifetime prevalence of “any” prescription opioid-use disorder in this cohort was 41.3% (95% confidence interval [CI] =37.6–45.0). A comparison to the DSM-4 criteria indicated that the majority of patients with lifetime DSM-4 opioid dependence were now classified as having mild opioid-use disorder, based on the DSM-5 criteria (53.6%; 95% CI =44.1–62.8). In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age <65 years, current pain impairment, trouble sleeping, suicidal thoughts, anxiety disorders, illicit drug use, and history of substance abuse treatment. Conclusion Given the final DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of craving and abuse symptoms, and introduction of a new graded severity classification, the prevalence of opioid-use disorders has changed, while many of the DSM-4

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

    PubMed

    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.

  4. The challenge of perioperative pain management in opioid-tolerant patients

    PubMed Central

    Coluzzi, Flaminia; Bifulco, Francesca; Cuomo, Arturo; Dauri, Mario; Leonardi, Claudio; Melotti, Rita Maria; Natoli, Silvia; Romualdi, Patrizia; Savoia, Gennaro; Corcione, Antonio

    2017-01-01

    The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. PMID:28919771

  5. Endogenous opioids regulate moment-to-moment neuronal communication and excitability.

    PubMed

    Winters, Bryony L; Gregoriou, Gabrielle C; Kissiwaa, Sarah A; Wells, Oliver A; Medagoda, Danashi I; Hermes, Sam M; Burford, Neil T; Alt, Andrew; Aicher, Sue A; Bagley, Elena E

    2017-03-22

    Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear.

  6. Medical cannabis and chronic opioid therapy.

    PubMed

    Reisfield, Gary M

    2010-12-01

    Fourteen states and the District of Columbia have legalized the use of cannabis for medical purposes. A small, high-quality literature supports the efficacy of medical cannabis for the treatment of neuropathic pain. The smoked botanical product, however, is associated with a number of adverse medical and psychiatric consequences. Furthermore, experimental data indicate that acute use of cannabis results in impairment of every important metric related to the safe operation of a motor vehicle. Epidemiological data show associations between recent cannabis use and both psychomotor impairment and motor vehicle crashes, associations that are strengthened by the concomitant use of alcohol and other central nervous system depressants. Finally, data from pain clinics reveals an unusually high prevalence of cannabis use in nearly all age groups and an association between cannabis use and opioid and other substance misuse. Based on available data and expert opinion, concomitant use of cannabis and opioids is an absolute contraindication to the operation of a motor vehicle. In patients who use cannabis and are prescribed opioids, heightened vigilance for opioid- and other substance-related problems is warranted. It is appropriate to refrain from prescribing opioids to individuals using medical cannabis if there is reasonable suspicion that the combination will pose a risk to the patient or others.

  7. Trends in Opioid Utilization Before and After Total Knee Arthroplasty.

    PubMed

    Politzer, Cary S; Kildow, Beau J; Goltz, Daniel E; Green, Cynthia L; Bolognesi, Michael P; Seyler, Thorsten M

    2018-07-01

    Opioids are a mainstay in perioperative pain management among patients undergoing total knee arthroplasty (TKA). However, patterns in opioid use before and after TKA have not been well-studied. The objectives of this study are to characterize prescribing trends preoperatively and postoperatively and identify risk factors for chronic postoperative opioid use. A review of the prescription-tracking database of a large private payer from 2007 to 2013 was performed using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Chronic opioid use was defined as opioid prescriptions over 6 contiguous months postoperatively. We identified 66,950 patients who underwent TKA with minimum 2-year follow-up and medication codes. Of those taking opioids preoperatively (n = 36,668), 34.8% became chronic users postoperatively compared to only 5.0% of the opioid-naïve cohort (n = 30,282). Major risk factors for chronic postoperative opioid use included preoperative opioid use (relative risk [RR] 3.75, 95% confidence interval [CI] 3.59-3.93), female gender (RR 1.23, 95% CI 1.20-1.25), and younger age (≤44 vs ≥60: RR 1.41, 95% CI 1.32-1.49; 45-59 vs ≥60: RR 1.42, 95% CI 1.40-1.46). From 2007 to 2013, there was a significant linear increase in opioid use preoperatively (odds ratio [OR] 1.04, 95% CI 1.03-1.05, P < .001) and postoperatively (OR 1.20, 95% CI 1.18-1.21, P < .001), but chronic postoperative opioid use increased only marginally (OR 1.01, 95% CI 1.00-1.02, P = .021). The greatest risk factors for chronic postoperative opioid use were preoperative use, younger age, female gender, greater length of stay, and worse health status. Although the use of opioids continues to grow significantly preoperatively and postoperatively, chronic opioid use post-TKA has remained clinically unchanged. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Influence of intravenous opioid dose on postoperative ileus.

    PubMed

    Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

    2011-07-01

    Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p < 0.001), maximum daily hydromorphone dose of 2 mg or more (p < 0.001), and age (p = 0.005); laparoscopy (p < 0.001) was associated with a decreased LOS. Intravenous opioid therapy is significantly associated with POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain

  9. Involvement of μ- and κ-, but not δ-, opioid receptors in the peristaltic motor depression caused by endogenous and exogenous opioids in the guinea-pig intestine

    PubMed Central

    Shahbazian, Anaid; Heinemann, Akos; Schmidhammer, Helmut; Beubler, Eckhard; Holzer-Petsche, Ulrike; Holzer, Peter

    2002-01-01

    Opiates inhibit gastrointestinal propulsion, but it is not clear which opioid receptor types are involved in this action. For this reason, the effect of opioid receptor – selective agonists and antagonists on intestinal peristalsis was studied.Peristalsis in isolated segments of the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the intraluminal pressure changes associated with the peristaltic waves.μ-Opioid receptor agonists (DAMGO, morphine), κ-opioid receptor agonists (ICI-204,448 and BRL-52,537) and a δ-opioid receptor agonist (SNC-80) inhibited peristalsis in a concentration-related manner as deduced from a rise of the peristaltic pressure threshold (PPT) and a diminution of peristaltic effectiveness.Experiments with the δ-opioid receptor antagonists naltrindole (30 nM) and HS-378 (1 μM), the κ-opioid receptor antagonist nor-binaltorphimine (30 nM) and the μ-opioid receptor antagonist cyprodime (10 μM) revealed that the antiperistaltic effect of ICI-204,448 and BRL-52,537 was mediated by κ-opioid receptors and that of morphine and DAMGO by μ-opioid receptors. In contrast, the peristaltic motor inhibition caused by SNC-80 was unrelated to δ-opioid receptor activation.Cyprodime and nor-binaltorphimine, but not naltrindole and HS-378, were per se able to stimulate intestinal peristalsis as deduced from a decrease in PPT.The results show that the neural circuits controlling peristalsis in the guinea-pig small intestine are inhibited by endogenous and exogenous opioids acting via μ- and κ-, but not δ-, opioid receptors. PMID:11834622

  10. Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in India: a report from the Global Opioid Policy Initiative (GOPI).

    PubMed

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

    2013-12-01

    India is the world's largest democracy with control of opioids divided between the national and state governments. While the global consumption of opioids has increased, the consumption has not increased at the same rate. This is the first comprehensive study of opioid availability and accessibility for cancer patients in India. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 24 of the states that make up India and the Administrative area around Delhi. About 1061 million of the nation's 1189 million people (89%) are covered by this survey. Without exception, opioid availability continues to be low throughout all of India. Even when opioids are on formulary, they are often unavailable. Access is significantly impaired by widespread over-regulation that continues to be pervasive across the nation.

  11. Preventing Opioid Use Disorders among Fishing Industry Workers

    PubMed Central

    Morocho, Cesar; King, Lauren; Bartlett, John; Kelsey, Debra; DeSousa, Monica; Biesecker, Gretchen

    2018-01-01

    Fishing industry workers are at high risk for work-related musculoskeletal disorders (MSDs) and injuries. Prescription opioids used to treat pain injuries may put these workers at increased risk for developing substance disorders. Using a Community-Based Participatory Research approach, formative research was conducted to inform the eventual development of relevant interventions to prevent and reduce opioid use disorders among fishing industry workers. Qualitative interviews (n = 21) were conducted to assess: knowledge and attitudes about opioid use disorders; features of fishing work that might affect use and/or access to treatment; and community and organizational capacity for prevention and treatment. Participants reported numerous pathways connecting commercial fishing with opioid use. The combination of high stress and physically tasking job duties requires comprehensive workplace interventions to prevent chronic pain and MSDs, in addition to tailored and culturally responsive treatment options to address opioid use disorders in this population. Public health programs must integrate workplace health and safety protection along with evidence-based primary, secondary, and tertiary interventions in order to address opioid use disorders, particularly among workers in strenuous jobs. PMID:29614742

  12. Preventing Opioid Use Disorders among Fishing Industry Workers.

    PubMed

    Walter, Angela Wangari; Morocho, Cesar; King, Lauren; Bartlett, John; Kelsey, Debra; DeSousa, Monica; Biesecker, Gretchen; Punnett, Laura

    2018-03-31

    Fishing industry workers are at high risk for work-related musculoskeletal disorders (MSDs) and injuries. Prescription opioids used to treat pain injuries may put these workers at increased risk for developing substance disorders. Using a Community-Based Participatory Research approach, formative research was conducted to inform the eventual development of relevant interventions to prevent and reduce opioid use disorders among fishing industry workers. Qualitative interviews ( n = 21) were conducted to assess: knowledge and attitudes about opioid use disorders; features of fishing work that might affect use and/or access to treatment; and community and organizational capacity for prevention and treatment. Participants reported numerous pathways connecting commercial fishing with opioid use. The combination of high stress and physically tasking job duties requires comprehensive workplace interventions to prevent chronic pain and MSDs, in addition to tailored and culturally responsive treatment options to address opioid use disorders in this population. Public health programs must integrate workplace health and safety protection along with evidence-based primary, secondary, and tertiary interventions in order to address opioid use disorders, particularly among workers in strenuous jobs.

  13. Knowledge of Opioid Overdose and Attitudes to Supply of Take-Home Naloxone Among People with Chronic Noncancer Pain Prescribed Opioids.

    PubMed

    Nielsen, Suzanne; Peacock, Amy; Lintzeris, Nicholas; Bruno, Raimondo; Larance, Briony; Degenhardt, Louisa

    2018-03-01

    Take-home naloxone (THN) is recommended in response to pharmaceutical opioid-related mortality. Some health professionals are reluctant to discuss THN for fear of causing offense. The aims of this study were to assess knowledge of opioid overdose and attitudes toward THN for opioid overdose reversal in people with chronic noncancer pain (CNCP). Prospective cohort study. Australia, September to October 2015. A subset of participants (N = 208) from a cohort of people prescribed restricted opioids for CNCP. Questions added in the two-year telephone interviews examined knowledge of overdose symptoms and attitudes toward community supply of naloxone. Associations with overdose risk factors and naloxone supply eligibility criteria with attitudes toward naloxone were explored. Fourteen percent reported ever experiencing opioid overdose symptoms. Participants correctly identified fewer than half of the overdose signs and symptoms. After receiving information on naloxone, most participants (60%), thought it was a "good" or "very good" idea. Few participants reported that they would be "a little" (N = 21, 10%) or "very" offended (N = 7, 3%) if their opioid prescriber offered them naloxone. Positive attitudes toward THN were associated with male gender (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.09-3.50), past year cannabis use (OR = 2.52, 95% CI = 1.03-6.16), and past year nicotine use (OR = 2.11, 95% CI = 1.14-3.91). Most participants had positive attitudes toward THN but low knowledge about opioid overdose symptoms. Strategies for educating patients and their caregivers on opioid toxicity are needed. THN may be best targeted toward those with risk factors in terms of overdose prevention and acceptability.

  14. The challenge of international consensus: defining an opioid essential prescription package.

    PubMed

    Vignaroli, Ernesto; Wenk, Roberto

    2012-09-01

    To describe a new strategy that aimed to facilitate opioid prescription for better pain management. The International Association of Hospice and Palliative Care recently develop a single prescription package (drugs and dosing) with one opioid, one laxative, and one antiemetic for the initiation of opioid treatment in cancer pain and other life-threatening conditions, with the intention to facilitate opioid use, improve patient compliance, and reduce adverse effects. The opioid essential prescription package was an international project designed to ensure that opioids are better tolerated by reducing the adverse effects of opioids, which could lead to more sustained improvements in pain management.

  15. Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

    PubMed

    Lebin, Jacob A; Murphy, David L; Severtson, Stevan Geoffrey; Bau, Gabrielle E; Dasgupta, Nabarun; Dart, Richard C

    2018-05-15

    Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price. Copyright © 2018 John Wiley & Sons, Ltd.

  16. Impact of Internet pharmacy regulation on opioid analgesic availability.

    PubMed

    Boyer, Edward W; Wines, James D

    2008-09-01

    Access to prescription opioid analgesics has made Internet pharmacies the object of increased regulatory scrutiny, but the effectiveness of regulatory changes in curtailing availability of opioid analgesics from online sources has been not assessed. As part of an ongoing investigation into the relationship between the Internet and substance abuse, we examined the availability of prescription opioid analgesics from online pharmacies. From a pharmacy watch Web site, we constructed a data set of postings entered every 3 months beginning November 1, 2005, that were related to the purchase of prescription opioid analgesics. Trained examiners assessed whether the final post described accessibility of pain medications that was increasing or decreasing. We identified 45 threads related to the availability of opioid analgesics from Internet pharmacies. Of the 41 (91%) threads describing the declining availability of opioid analgesic agents from Internet pharmacies, 34 (82%) received posts on November 1, 2007. Despite the subjective nature of the research question, there was high interobserver agreement between coders (kappa= .845) that availability of opioid analgesics from online pharmacies had decreased. This finding was supported by a dramatic rise in the number of pageviews (an accepted measure of Web site visitor interest in a page's content) of Web pages describing decreased availability of opioid analgesics. These data suggest striking decreases in the availability of prescription opioid analgesic pharmaceuticals. This self-reported change in drug availability may be related to increased regulation of and law enforcement operations directed against Internet pharmacies.

  17. Physician Guide to Appropriate Opioid Prescribing for Noncancer Pain

    PubMed Central

    Munzing, Timothy

    2017-01-01

    Prescription opioid use for relief of noncancer pain has risen dramatically in the last 15 years, contributing to a quadrupling of opioid overdoses and prescription opioid-related deaths. This crisis is resulting in heightened attention by health care professionals and organizations, law enforcement, and the government. In this article, I highlight key topics in the management of patients using opioids (or potentially needing opioids) in outpatient clinical practice; federal and state law enforcement actions regarding physicians’ illegal prescribing of opioids; multimodal approaches to pain control; nonmedication management of pain; response strategies when suspecting a patient of diverting or misusing opioids; and warning signs for abuse or diversion. For those patients for whom opioids are appropriate, I describe key elements for prescribing, including documentation of a detailed history and examination, appropriate evaluation to arrive at a specific diagnosis, individualizing management, and ongoing monitoring (including the use of urine drug screening and a prescription drug monitoring program). In addition to individual action, when possible, the initiation of systemwide and clinicwide safe prescribing practices supports the physician and patient such that the patient’s well-being is at the heart of all pain management decisions. Physicians are encouraged to further educate themselves to treat pain safely and effectively; to screen patients for opioid use disorder and, when diagnosed, to connect them with evidence-based treatment; and to follow Centers for Disease Control and Prevention guidelines whenever possible. PMID:28488993

  18. Physician Guide to Appropriate Opioid Prescribing for Noncancer Pain.

    PubMed

    Munzing, Timothy

    2017-01-01

    Prescription opioid use for relief of noncancer pain has risen dramatically in the last 15 years, contributing to a quadrupling of opioid overdoses and prescription opioid-related deaths. This crisis is resulting in heightened attention by health care professionals and organizations, law enforcement, and the government. In this article, I highlight key topics in the management of patients using opioids (or potentially needing opioids) in outpatient clinical practice; federal and state law enforcement actions regarding physicians' illegal prescribing of opioids; multimodal approaches to pain control; nonmedication management of pain; response strategies when suspecting a patient of diverting or misusing opioids; and warning signs for abuse or diversion. For those patients for whom opioids are appropriate, I describe key elements for prescribing, including documentation of a detailed history and examination, appropriate evaluation to arrive at a specific diagnosis, individualizing management, and ongoing monitoring (including the use of urine drug screening and a prescription drug monitoring program). In addition to individual action, when possible, the initiation of systemwide and clinicwide safe prescribing practices supports the physician and patient such that the patient's well-being is at the heart of all pain management decisions. Physicians are encouraged to further educate themselves to treat pain safely and effectively; to screen patients for opioid use disorder and, when diagnosed, to connect them with evidence-based treatment; and to follow Centers for Disease Control and Prevention guidelines whenever possible.

  19. Managing Opioid Addiction Risk in Plastic Surgery during the Perioperative Period.

    PubMed

    Demsey, Daniel; Carr, Nicholas J; Clarke, Hance; Vipler, Sharon

    2017-10-01

    Opioid addiction is a public health crisis that affects all areas of medicine. Large numbers of the population across all racial and economic demographics misuse prescription opioids and use illicit opioids. The current understanding is that opioid misuse is a disease that requires treatment, and is not an issue of choice or character. Use of opioid medication is a necessary part of postoperative analgesia, but many physicians are unsure of how to do this safely given the risk of patients developing an opioid misuse disorder. This review gives an update of the current state of the opioid crisis, explains how current surgeons' prescribing practices are contributing to it, and gives recommendations on how to use opioid medication safely in the perioperative period.

  20. [Treatment of pain in cancer with systemically administered opioids].

    PubMed

    Enting, R H; van der Rijt, C C; Wilms, E B; Lieverse, P J; de Wit, R; Smitt, P A

    2001-05-19

    The World Health Organization guidelines for cancer pain relief have been proven efficacious in 90% of the patients with cancer pain. The patient's self-report of pain is the focus of treatment. When initiating treatment, controlled-release preparations of opioids are generally favoured, and are combined with immediate release morphine to prevent or treat 'breakthrough' pain and to enable the optimum opioid dosage to be calculated. (Breakthrough pain is a transient increase in pain in a patient who has stable, persistent pain treated with opioids.) In patients with an unfavourable balance between analgesia and side effects, the following strategies may be useful, together with appropriate treatment of the side effects: Sequential opioid trials (so-called opioid rotation) is an approach which is effective in 50-70% of the patients. Changing the route of opioid administration is successful in 70-95% of the patients. When selecting an invasive technique, continuous subcutaneous infusion is medically preferred. Spinal analgesia is an alternative. Knowledge of the relative potency of opioid drugs and of their biologic availability is needed to guide changes in drugs or routes of administration.