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

Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription: a primary care data linkage study.

PubMed

Torrance, N; Mansoor, R; Wang, H; Gilbert, S; Macfarlane, G J; Serpell, M; Baldacchino, A; Hales, T G; Donnan, P; Wyper, G; Smith, B H; Colvin, L

2018-06-01

Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003-2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. χ 2 tests examined associations between individual pain severity and opioid prescriptions. The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25-40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines was common. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Functional Characteristics of the Naked Mole Rat μ-Opioid Receptor

PubMed Central

Roth, Clarisse A.

2013-01-01

While humans and most animals respond to µ-opioid receptor (MOR) agonists with analgesia and decreased aggression, in the naked mole rat (NMR) opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1) can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP) enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR's extreme reaction to opioids. PMID:24312175

Incidence of iatrogenic opioid dependence or abuse in patients with pain who were exposed to opioid analgesic therapy: a systematic review and meta-analysis.

PubMed

Higgins, C; Smith, B H; Matthews, K

2018-06-01

The prevalence and incidence of chronic conditions, such as pain and opioid dependence, have implications for policy development, resource allocation, and healthcare delivery. The primary objective of the current review was to estimate the incidence of iatrogenic opioid dependence or abuse after treatment with opioid analgesics. Systematic electronic searches utilised six research databases (Embase, Medline, PubMed, Cinahl Plus, Web of Science, OpenGrey). A 'grey' literature search and a reference search of included articles were also undertaken. The PICOS framework was used to develop search strategies and the findings are reported in accordance with the PRISMA Statement. After eligibility reviews of 6164 articles, 12 studies (involving 310 408 participants) were retained for inclusion in the meta-analyses. A random effects model (DerSimonian-Laird method) generated a pooled incidence of opioid dependence or abuse of 4.7%. There was little within-study risk of bias and no significant publication bias; however, substantial heterogeneity was found among study effects (99.78%). Sensitivity analyses indicated that the diagnostic criteria selected for identifying opioid dependence or abuse (Diagnostic Statistical Manual (DSM-IV) vs International Classification of Diseases (ICD-9)) accounted for 20% and duration of exposure to opioid analgesics accounted for 18% of variance in study effects. Longer-term opioid analgesic exposure, and prescription of strong rather than weak opioids, were associated with a significantly lower incidence of opioid dependence or abuse. The incidence of iatrogenic opioid dependence or abuse was 4.7% of those prescribed opioids for pain. Further research is required to confirm the potential for our findings to inform prevention of this serious adverse event. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Geographic Variation in Opioid Prescribing in the U.S.

PubMed Central

McDonald, Douglas C.; Carlson, Kenneth; Izrael, David

2012-01-01

Estimates of geographic variation among states and counties in the prevalence of opioid prescribing are developed using data from a large (135M) representative national sample of opioid prescriptions dispensed during 2008 by 37,000 retail pharmacies. Statistical analyses are used to estimate the extent to which county variation is explained by characteristics of resident populations, their healthcare utilization, proxy measures of morbidity, availability of healthcare resources, and prescription monitoring laws. Geographic variation in prevalence of prescribed opioids is large, greater than variation observed for other healthcare services. Counties having the highest prescribing rates for opioids were disproportionately located in Appalachia and in Southern and Western states. The number of available physicians was by far the strongest predictor of amounts prescribed, but only one-third of county variation is explained by the combination of all measured factors. Wide variation in prescribing opioids reflects weak consensus regarding the appropriate use of opioids for treating pain, especially chronic non-cancer pain. Patients’ demands for treatment have increased, more potent opioids have become available, an epidemic of abuse has emerged, and calls for increased government regulation are growing. Greater guidance, education and training in opioid prescribing are needed for clinicians to support appropriate prescribing practices. Perspective Wide geographic variation that does not reflect differences in the prevalence of injuries, surgeries, or conditions requiring analgesics raises questions about opioid prescribing practices. Low prescription rates may indicate under-treatment, while high rates may indicate overprescribing and insufficient attention to risks of misuse. PMID:23031398

The addition of tramadol as a second opioid may improve pain relief in severe osteoarthritis: a prospective study.

PubMed

Di Lorenzo, Luigi; Foti, Calogero; Forte, Alfonso Maria; Palmieri, Enzo; Formisano, Rita; Vatakencherry, Abraham; Pappagallo, Marco

2010-01-01

Opioid combination has been shown to reduce the need for escalating doses for the treatment of cancer pain. A prospective study was planned to evaluate the addition of tramadol to a stronger opioid for the treatment of severe pain as a result of osteoarthritis, previously uncontrolled by non-opioid analgesics or weak opioids. All subjects received tramadol 200 mg and tizanidine 2 mg. At 2 weeks, tramadol was discontinued for patients still reporting poor pain relief (effectiveness ≤50%), and a stronger opioid was titrated to a morphine equivalent amount (MEA) of 40-60 mg orally. After two additional weeks, patients were then divided into two groups: the Strong Opioid Group (SO) and the Tramadol plus the Strong Opioid Group (TSO). The SO group was allowed to escalate opioid dose for lack of effectiveness; the TSO group received tramadol 150 mg daily, thereafter additional strong opioid titration was allowed. A total of 74 patients were studied: SO (n = 40) and TSOG (n = 34). All patients eventually achieved pain relief quality, with both groups reporting similar Karnofsky Performance Scale effectiveness. The SO group achieved satisfactory pain relief (>50%) at an average daily oral MEA of 120 mg. TSO subjects achieved satisfactory pain relief (>50%) at an average daily oral MEA of 95 mg. The addition of tramadol provided a synergistic effect resulting in a 30-mg decrease in necessary morphine equivalents with fewer opioid-related adverse effects. © 2010 The Authors. Pain Practice © 2010 World Institute of Pain.

The antinociceptive effect of zolpidem and zopiclone in mice.

PubMed

Pick, Chaim G; Chernes, Yakov; Rigai, Tova; Rice, Kenner C; Schreiber, Shaul

2005-07-01

Zolpidem and zopiclone are two of a newer hypno-sedative class of drugs, the "Z compounds". Their use for the treatment of short-term insomnia has been expanding constantly during the last two decades. The "Z compounds" are considered to cause less significant rebound insomnia or tolerance than the conventional hypnotic benzodiazepines. Their possible antinociceptive effect and interaction with the opioid system has not been studied yet. Our results demonstrate a significant difference between the antinociceptive properties of zopiclone and zolpidem when injected s.c. in the hotplate analgesic assay in mice. Zopiclone induced a weak, dose-dependent antinociceptive effect, antagonized only by the alpha2-adrenergic receptor antagonist yohimbine. Zolpidem induced a weak, biphasic dose-dependent antinociceptive effect, antagonized primarily by the non-selective opioid antagonist naloxone and by yohimbine. The weak antinociceptive effect of both drugs, evident only at very high doses (far beyond those used clinically to induce sleep), implies no clinical use for zopiclone or zolpidem in the management of pain. However, the possible interaction of zolpidem with the opioid system should be further investigated (in behavioral models, which do not overlap with the acute-pain antinociception model we used), both for possible side effects in special populations (i.e. elderly) and for possible drug-drug interactions, in order to minimize possible hazards and maximize clinical beneficial effects of its use for sleep.

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.

Public support for safe consumption sites and syringe services programs to combat the opioid epidemic.

PubMed

McGinty, Emma E; Barry, Colleen L; Stone, Elizabeth M; Niederdeppe, Jeff; Kennedy-Hendricks, Alene; Linden, Sarah; Sherman, Susan G

2018-06-01

We examine Americans' support for two evidence-based harm reduction strategies - safe consumption sites and syringe exchange programs - and their attitudes about individuals who use opioids. We conducted a web-based survey of a nationally representative sample of U.S. adults in July-August 2017 (N = 1004). We measured respondents' support for legalizing safe consumption sites and syringe services programs in their communities and their attitudes toward people who use opioids. We used ordered logistic regression to assess how stigmatizing attitudes toward people who use opioids, political party identification, and demographic characteristics correlated with support for the two harm reduction strategies. Twenty-nine percent of Americans supported legalizing safe consumption sites and 39% supported legalizing syringe services programs. Respondents reported high levels of stigmatizing attitudes toward people who use opioids: 16% of respondents were willing to have a person using opioids marry into their family and 28% were willing to have a person using opioids start working closely with them on a job, and 27% and 10% of respondents rated persons who use opioids as deserving (versus worthless) and strong (versus weak). Stigmatizing attitudes were associated with lower support for legalizing safe consumption sites and syringe services programs. Democrats and Independents were more likely than Republicans to support both strategies. Stigmatizing attitudes toward people who use opioids are a key modifiable barrier to garnering the public support needed to fully implement evidence-based harm reduction strategies to combat the opioid epidemic. Dissemination and evaluation of stigma reduction campaigns are a public health priority. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Opioids and Breast Cancer Recurrence: A Danish population-based cohort study

PubMed Central

Cronin-Fenton, D.P.; Heide-Jørgensen, U.; Ahern, T.P.; Lash, T.L.; Christiansen, P.M.; Ejlertsen, B.; Sjøgren, P.; Kehlet, H.; Sørensen, H.T.

2015-01-01

Background Opioids may alter immune function and thereby potentially affect cancer recurrence. We investigated the association between post-diagnosis opioid use and breast cancer recurrence. Methods We identified incident early-stage breast cancer patients, diagnosed 1996-2008 in Denmark, registered in the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of breast cancer primary surgery and continued until breast cancer recurrence, death, emigration, ten years, or 31 July 2013, whichever occurred first. We used Cox regression models to compute hazard ratios (HRs) and 95% confidence intervals (95%CI) associating breast cancer recurrence with opioid prescription use overall, and by opioid type and strength, immunosuppressive effect, chronic use (>=6 months continuous exposure), and cumulative morphine-equivalent dose, adjusting for confounders. Results We identified 34,188 patients who together contributed 283,666 person-years of follow-up. There was no association between ever use of opioids and breast cancer recurrence (HRcrude=0.98, 95% CI=0.90 - 1.1, and HRadjusted=1.0, 95% CI=0.92 - 1.1), regardless of opioid type, strength, chronicity of use, and cumulative dose. Breast cancer recurrence rates were lower among users of strong but not weakly immunosuppressive opioids, possibly due to channeling bias among those with high competing risk as mortality was higher among users of this drug type. Conclusions This large prospective cohort study provided no clinically relevant evidence of an association between opioid prescriptions and breast cancer recurrence. Our findings are important to cancer survivorship, as opioids are frequently used to manage pain associated with comorbid conditions. PMID:26207518

Opioid consumption before and after the establishment of a palliative medicine unit in an Egyptian cancer centre.

PubMed

Alsirafy, Samy A; Ibrahim, Noha Y; Abou-Elela, Enas N

2012-01-01

Opioid consumption before and after the establishment of a palliative medicine unit (PMU) in an Egyptian cancer centre was reviewed. A comparison of consumption during the year before the PMU was established to consumption during the third year after the PMU's establishment revealed that morphine consumption increased by 698 percent, fentanyl by 217 percent, and tramadol by 230 percent. Expressed in defined daily dose (DDD) and adjusted for 1,000 new cancer patients, consumption increased by 460 percent, from 4,678 DDD/1,000 new patients to 26,175 DDD/1,000 new patients. Expressed in grams of oral morphine equivalent (g OME), consumption increased by 644 percent, from 233 g OME/1,000 new patients to 1,731 g OME/1,000 new patients. The establishment of the PMU was associated with an increase in opioid consumption, especially morphine, which is an indicator of improvement in cancer pain control. The expression of opioid consumption in OME in addition to DDD may provide further information, especially when weak opioids are included in the analysis.

Canadian guideline for safe and effective use of opioids for chronic noncancer pain

PubMed Central

Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

2011-01-01

Abstract Objective To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Quality of evidence Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Main message Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Conclusion Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety. PMID:22084455

Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population.

PubMed

Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

2011-11-01

To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety.

Fentanyl-related designer drugs W-18 and W-15 lack appreciable opioid activity in vitro and in vivo.

PubMed

Huang, Xi-Ping; Che, Tao; Mangano, Thomas J; Le Rouzic, Valerie; Pan, Ying-Xian; Majumdar, Susruta; Cameron, Michael D; Baumann, Michael H; Pasternak, Gavril W; Roth, Bryan L

2017-11-16

W-18 (4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide) and W-15 (4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide) represent two emerging drugs of abuse chemically related to the potent opioid agonist fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide). Here, we describe the comprehensive pharmacological profiles of W-18 and W-15, as examination of their structural features predicted that they might lack opioid activity. We found W-18 and W-15 to be without detectible activity at μ, δ, κ, and nociception opioid receptors in a variety of assays. We also tested W-18 and W-15 for activity as allosteric modulators at opioid receptors and found them devoid of significant positive or negative allosteric modulatory activity. Comprehensive profiling at essentially all the druggable GPCRs in the human genome using the PRESTO-Tango platform revealed no significant activity. Weak activity at the sigma receptors and the peripheral benzodiazepine receptor was found for W-18 (Ki = 271 nM). W-18 showed no activity in either the radiant heat tail-flick or the writhing assays and also did not induce classical opioid behaviors. W-18 is extensively metabolized, but its metabolites also lack opioid activity. Thus, although W-18 and W-15 have been suggested to be potent opioid agonists, our results reveal no significant activity at these or other known targets for psychoactive drugs.

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

PubMed

Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

2005-09-01

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

Phorbol ester suppression of opioid analgesia in rats

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

Zhang, L.J.; Wang, X.J.; Han, J.S.

1990-01-01

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

Effectiveness of opioid analgesics in chronic noncancer pain.

PubMed

Ferrari, Renata; Zanolin, Maria E; Duse, Genni; Visentin, Marco

2015-03-01

There is general agreement about the need to perform a screening test to assess the risk of opioid misuse prior to starting a long-term opioid treatment for chronic noncancer pain. The evidence supporting the effectiveness of opioid long-term treatment is weak, and no predictors of its usefulness have been assessed. The aim of this study was to assess the effect on pain and quality of life of chronic opioid treatment, and detect the possible predictors of its effectiveness. This observational, prospective study was conducted in 2 Italian Pain Relief Units on 77 patients affected by intractable chronic pain. Patients were submitted to psycho-logical tests, investigating the individual pain experience, risk of opioid misuse, mood states, quality of life, and personality characteristics prior to starting treatment and at 2,4, and 6-month follow-up. Both maximum and habitual pain, as measured with VAS, underwent a statistically significant reduction at 2, 4, and 6-month follow-up. In multivariate analysis, lower scores in the Pain Medication Questionnaire (PMQ) were predictive of a major reduction in maximum VAS (P = 0.005). Both low PMQ and MMPI-cynicism scores were predictive of habitual VAS decrease (P = 0.012 and P = 0.028, respectively). The results indicate that pain relief significantly improved over a 6-month period of opioid treatment, together with quality of life. The outcome was better in patients with a pretreatment low risk of opioid misuse, low scores in the Cynicism scale of MMPI-2, and no aberrant drug behaviors at follow-up. Therefore, a psychological screening and support is crucial for a good outcome of opioid therapy for chronic noncancer pain patients.

Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review

PubMed Central

Lind, Jennifer N.; Interrante, Julia D.; Ailes, Elizabeth C.; Gilboa, Suzanne M.; Khan, Sara; Frey, Meghan T.; Dawson, April L.; Honein, Margaret A.; Dowling, Nicole F.; Razzaghi, Hilda; Creanga, Andreea A.; Broussard, Cheryl S.

2017-01-01

CONTEXT Opioid use and abuse have increased dramatically in recent years, particularly among women. OBJECTIVES We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations. DATA SOURCES We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies. STUDY SELECTION We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process. DATA EXTRACTION Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies. RESULTS Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation. LIMITATIONS Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement. CONCLUSIONS Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age. PMID:28562278

Immunohistochemical observations of methionine-enkephalin and delta opioid receptor in the digestive system of Octopus ocellatus.

PubMed

Sha, Ailong; Sun, Hushan; Wang, Yiyan

2013-02-01

The study was designed to determine whether methionine-enkephalin (met-Enk) or delta opioid receptor was present in the digestive system of Octopus ocellatus. The results showed that they were both in the bulbus oris, esophagus, crop, stomach, gastric cecum, intestine, posterior salivary glands of O. ocellatus, one of them, met-Enk in the rectum, anterior salivary glands, digestive gland. And the distributions were extensive in the digestive system. Strong or general met-Enk immunoreactivity was observed in the inner epithelial cells of the bulbus oris, esophagus, stomach, gastric cecum, intestine, anterior salivary glands and the adventitia of the intestine and rectum, and so was the delta opioid receptor immunoreactivity in the inner epithelial cells of the bulbus oris, esophagus, and crop, however, they were weak in other parts. Combining with delta opioid receptor, met-Enk may be involved in the regulations of food intake, absorption, movement of gastrointestinal smooth muscle and secretion of digestive gland. The different densities of met-Enk and delta opioid receptor may be related to the different functions in the digestive system of O. ocellatus. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2013-01-01

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

Between a Rock and a Hard Place: Can Physicians Prescribe Opioids to Treat Pain Adequately While Avoiding Legal Sanction?

PubMed Central

Dineen, Kelly K.; DuBois, James M.

2017-01-01

Prescription opioids are an important tool for physicians in treating pain but also carry significant risks of harm when prescribed inappropriately or misused by patients or others. Recent increases in opioid related morbidity and mortality has reignited scrutiny of prescribing practices by law enforcement, regulatory agencies, and state medical boards. At the same time, the predominant 4D model of misprescribers is outdated and insufficient; it groups physician misprescribers as dated, duped, disabled, or dishonest. The weaknesses and inaccuracies of the 4D model are explored, along with the serious consequences of its application. This article calls for development of an evidence base in this area and suggests an alternate model of misprescribers, the 3C model, which more accurately characterizes misprescribers as careless, corrupt, or compromised by impairment. PMID:27263262

[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.

Dermorphin-related peptides from the skin of Phyllomedusa bicolor and their amidated analogs activate two mu opioid receptor subtypes that modulate antinociception and catalepsy in the rat.

PubMed

Negri, L; Erspamer, G F; Severini, C; Potenza, R L; Melchiorri, P; Erspamer, V

1992-08-01

Three naturally occurring dermorphin-like peptides from the skin of the frog Phyllomedusa bicolor, the related carboxyl-terminal amides, and some substituted analogs were synthesized, their binding profiles to opioid receptors were determined, and their biological activities were studied in isolated organ preparations and intact animals. The opioid binding profile revealed a very high selectivity of these peptides for mu sites and suggested the existence of two receptor subtypes, of high and low affinity. The peptides tested acted as potent mu opioid agonists on isolated organ preparations. They were several times more active in inhibiting electrically evoked contractions in guinea pig ileum than in mouse vas deferens. When injected into the lateral brain ventricle or peritoneum of rats, the high-affinity-site-preferring ligand, [Lys7-NH2]dermorphin, behaved as a potent analgesic agent. By contrast, the low-affinity-site-preferring ligand, [Trp4,Asn7-NH2]dermorphin, produced a weak antinociception but an intense catalepsy.

Dermorphin-related peptides from the skin of Phyllomedusa bicolor and their amidated analogs activate two mu opioid receptor subtypes that modulate antinociception and catalepsy in the rat.

PubMed Central

Negri, L; Erspamer, G F; Severini, C; Potenza, R L; Melchiorri, P; Erspamer, V

1992-01-01

Three naturally occurring dermorphin-like peptides from the skin of the frog Phyllomedusa bicolor, the related carboxyl-terminal amides, and some substituted analogs were synthesized, their binding profiles to opioid receptors were determined, and their biological activities were studied in isolated organ preparations and intact animals. The opioid binding profile revealed a very high selectivity of these peptides for mu sites and suggested the existence of two receptor subtypes, of high and low affinity. The peptides tested acted as potent mu opioid agonists on isolated organ preparations. They were several times more active in inhibiting electrically evoked contractions in guinea pig ileum than in mouse vas deferens. When injected into the lateral brain ventricle or peritoneum of rats, the high-affinity-site-preferring ligand, [Lys7-NH2]dermorphin, behaved as a potent analgesic agent. By contrast, the low-affinity-site-preferring ligand, [Trp4,Asn7-NH2]dermorphin, produced a weak antinociception but an intense catalepsy. PMID:1353890

Opioid needs of patients with advanced cancer and the morphine dose-limiting law in Egypt.

PubMed

Alsirafy, Samy A; El-Mesidi, Salah M; El-Sherief, Wesam A; Galal, Khaled M; Abou-Elela, Enas N; Aklan, Nahla A

2011-01-01

Morphine is the drug of choice for moderate to severe cancer pain management. The Egyptian Narcotics Control Law limits the amount of morphine prescribed in a single prescription to a maximum of 420 mg for tablets and 60 mg for ampoules. The usual practice in Egypt is to provide that limited amount of morphine on a weekly basis. The aim of this study is to estimate the extent to which Egyptian patients may be undertreated because of this law. We reviewed the medical records of advanced cancer patients referred to the first palliative care unit in Egypt over a seven-month period. Cancer pain was managed following the WHO guidelines. After modifying the internal institutional policy, patients received adequate amounts of the available opioids without any violations of the law. From 117 eligible advanced cancer patients, 58 (50%) patients required strong opioids, 32 (27%) required weak opioids, and 27 (23%) required no regular opioids. The mean last prescribed opioid dose for those who required strong opioids was 194 mg of oral morphine equivalent/24 h (± 180). For this group of patients, a single weekly prescription would supply enough oral morphine for only 26% of them. In the case of parenteral morphine, none of these patients would receive an adequate supply. In view of the current morphine dose-limiting law and practices in Egypt, the majority of patients suffering severe cancer pain would not have access to adequate morphine doses. That dose-limiting law and other restrictive regulations represent an obstacle to cancer pain control in Egypt and should be revised urgently.

Palliative Care in Latin America from the Professional Perspective: A SWOT Analysis.

PubMed

Pastrana, Tania; Centeno, Carlos; De Lima, Liliana

2015-05-01

The development of palliative care (PC) in Latin America (LA) has been slow compared to other regions. A Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis may contribute to the identification of barriers and successful strategies. The study's objective was to conduct a SWOT analysis of the development of PC in LA from the PC professional perspective. Experts from 19 countries of the region were selected in collaboration with national associations. Specific questions were included in the Latin American Association for Palliative Care (ALCP) Atlas of Palliative Care cross-survey 2012. Content analysis was conducted categorizing responses in a SWOT framework. Descriptive and correlation analyses were performed. A total of 577 statements were provided. Among the Strengths were integration into health systems and increasing number of professionals with PC training. Among weaknesses were lack of national PC programs, limited connection between policymakers and professionals, and barriers in the availability of opioids. Opportunities were increased awareness of policymakers and higher interest of students and professionals. Threats were competing funding for other services and medications, limited interest of the pharmaceutical industry in producing affordable opioid medications, and emphasis by the media on opioid diversion and abuse. Comments were categorized under (1) health policy, (2) education and research, (3) service provision, (4) opioid availability, and (5) advocacy. A moderately positive correlation was found (R=0.4 in both) between the ALCP development index and the number of positive/negative factors mentioned by country. A SWOT framework is applicable in a situational analysis and helps to identify common aspects among the countries and key elements in the development of PC in Latin America.

Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls—antagonistic effects between opioid and serotonin-related genes

PubMed Central

Tour, Jeanette; Löfgren, Monika; Mannerkorpi, Kaisa; Gerdle, Björn; Larsson, Anette; Palstam, Annie; Bileviciute-Ljungar, Indre; Bjersing, Jan; Martin, Ingvar; Ernberg, Malin; Schalling, Martin; Kosek, Eva

2017-01-01

Abstract Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH. PMID:28282362

Comparison of fatal poisonings by prescription opioids.

PubMed

Häkkinen, Margareeta; Launiainen, Terhi; Vuori, Erkki; Ojanperä, Ilkka

2012-10-10

There is a rising trend of fatal poisonings due to medicinal opioids in several countries. The present study evaluates the drug and alcohol findings as well as the cause and manner of death in opioid-related post-mortem cases in Finland from 2000 to 2008. During this period, fatal poisonings by prescription opioids (buprenorphine, codeine, dextropropoxyphene, fentanyl, methadone, oxycodone, tramadol) increased as a share of all drug poisonings from 9.5% to 32.4%, being 22.3% over the whole period. A detailed study including the most prevalent opioids was carried out for the age group of 14-44 years, which is the most susceptible age for drug abuse in Finland. Poisonings by the weak opioids, codeine and tramadol, were found to be associated with large, often suicidal overdoses resulting in high drug concentrations in blood. Methadone poisonings were associated with accidental overdoses with the drug concentration in blood remaining within a therapeutic range. The manner of death was accidental in 43%, 55% and 94% of cases in codeine, tramadol and methadone poisonings, respectively. The median concentration of codeine and the median codeine/morphine concentration ratio were higher in codeine poisonings (1.4 and 22.5 mg/l, respectively) than in other causes of death (0.09 and 5.9 mg/l, respectively). The median concentrations of tramadol and O-desmethyltramadol were higher in tramadol poisonings (5.3 and 0.8 mg/l, respectively) than in other causes of death (0.6 and 0.2 mg/l, respectively). In methadone poisonings, the median concentration of methadone (0.35 mg/l) was not different from that in other causes of death (0.30 mg/l). Sedative drugs and/or alcohol were very frequently found in fatal poisonings involving these prescription opioids. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes.

PubMed

Tour, Jeanette; Löfgren, Monika; Mannerkorpi, Kaisa; Gerdle, Björn; Larsson, Anette; Palstam, Annie; Bileviciute-Ljungar, Indre; Bjersing, Jan; Martin, Ingvar; Ernberg, Malin; Schalling, Martin; Kosek, Eva

2017-07-01

Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.

Effects of the NOP receptor agonist Ro65-6570 on the acquisition of opiate- and psychostimulant-induced conditioned place preference in rats.

PubMed

Rutten, Kris; De Vry, Jean; Bruckmann, Walter; Tzschentke, Thomas M

2010-10-25

Activation of the Nociceptin/Orphanin FQ (NOP) receptor may have anti-abuse effects. The present study examined the consequence of NOP receptor activation on the rewarding effect of opiates and psychostimulants in the conditioned place preference task in rats. First, the motivational effect of the NOP receptor agonists Ro64-6198 (0.316-3.16 mg/kg i.p.) and Ro65-6570 (1-10mg/kg i.p.) when administered alone, was assessed. Ro65-6570 was selected for further drug combination studies since, unlike Ro64-6198, it was devoid of an intrinsic motivational effect. Next, the minimal effective dose to induce reward for the opiates heroin (0.1-3.16 mg/kg i.p.), morphine (1-10mg/kg i.p.), hydrocodone (0.316-10mg/kg i.p.), tilidine (1-31.6 mg/kg i.p.), hydromorphone (0.1-10mg/kg i.p.), and oxycodone (0.0316-10mg/kg i.p.), as well as for the psychostimulants cocaine (3.16-31.6 mg/kg i.p.) and dexamphetamine (0.316-3.16 mg/kg i.p.) in combination with Ro 65-6570 (0 or 3.16 mg/kg i.p.) was determined. All drugs produced conditioned place preference, and for opiates and cocaine, but not for dexamphetamine, the minimal effective dose was higher when combined with Ro65-6570 (3.16 mg/kg i.p.). Attenuation of the rewarding effect of tilidine (3.16 mg/kg i.p.) and oxycodone (1mg/kg i.p.) by Ro65-6570 (3.16 mg/kg i.p.) could be reversed by pre-treatment with the NOP receptor antagonist J-113397 (4.64 mg/kg i.p.), suggesting that the attenuating effect of Ro65-6570 on opiates is due to activation of the NOP receptor. Taken together, the present study suggests that activation of NOP receptors effectively attenuates the rewarding effect of opiates, but may be less effective in reducing psychostimulant-induced reward. Copyright © 2010 Elsevier B.V. All rights reserved.

Comparison of efficacy between buprenorphine and tramadol in the detoxification of opioid (heroin)-dependent subjects.

PubMed

Chawla, Jatinder Mohan; Pal, Hemraj; Lal, Rakesh; Jain, Raka; Schooler, Nina; Balhara, Yatan Pal Singh

2013-01-01

Tramadol is a synthetic opiate and a centrally acting weak m-opioid receptor agonist. The potential advantages of tramadol include ease of administration, low abuse potential, and being nonscheduled. This study compared tramadol and buprenorphine for controlling withdrawal symptoms in patients with opioid dependence syndrome. Consenting male subjects between 20 and 45 years of age who fulfilled the ICD-10-DCR criteria for opiate dependence syndrome were randomly assigned in a double-blind, double-dummy placebo-controlled trial for detoxification. Those with multiple drug dependence, abnormal cardiac, renal and hepatic functions, psychosis, or organic mental illness were excluded. Assessments included Subjective Opiate Withdrawal Scale (SOWS), Objective Opiate Withdrawal Scale (OOWS), Visual Analog Scale (VAS), and Side Effect Check List. Subjects were evaluated daily and study duration was 10 days. Sixty two subjects were enrolled. The mean SOWS and OOWS and VAS were significantly lower in the buprenorphine group on second and third day of detoxification as compared to the tramadol group. Although the retention rate was higher for buprenorphine group throughout the study, when compared with tramadol the difference was not significant on any day. Three subjects in the tramadol group had seizures. Tramadol was found to have limited detoxification efficacy in moderate to severe opioid withdrawal and substantial risk of seizures as compared to buprenorphine. Further studies are warranted to examine its efficacy in mild opioid withdrawal symptoms and its potential use in outpatient settings where its administration advantages may be valuable.

Meta-analysis of the relevance of the OPRM1 118A>G genetic variant for pain treatment.

PubMed

Walter, Carmen; Lötsch, Jörn

2009-12-01

Regard of functional pharmacogenetic polymorphisms may further the success of pain therapy by adopting individualized approaches. The mu-opioid receptor gene (OPRM1) 118A>G polymorphism is a promising candidate for both opioid effects and pain because of both biological reasonability and apparent experimental and clinical evidence. We analyzed its importance for pain therapy using a meta-analytic approach to studies relating it to opioid pain therapy. Data from suitable studies selected from hits of a PubMed search for "OPRM1" were independently extracted by two authors. The meta-analysis included phenotypes by OPRM1 genotype (opioid dosing, pain, and side effects), publication year, diagnostic status, proportion of male study participants, and whether genotype frequencies agreed with Hardy-Weinberg equilibrium. We found no consistent association between OPRM1 118A>G genotypes and most of the phenotypes in a heterogeneous set of eight clinical studies. Only weak evidence of an association with less nausea (effect size, Cohen's d=-0.21, p=0.037) and of increased opioid dosage requirements (d=0.56, p=0.018) in homozygous carriers of the G allele was obtained. This indicates that despite initially promising results, available evidence of the clinical relevance of the OPRM1 118A>G polymorphism does not withhold a meta-analysis. This discourages basing personalized therapeutic concepts of pain therapy on OPRM1 118A>G genotyping at the present state of evidence.

Patients' and physicians' perspectives on opioid therapy for chronic cancer and musculoskeletal pain in Germany, Italy, and Turkey: PAin RESearch (PARES) survey.

PubMed

Müller-Schwefe, Gerhard H H; Wimmer, Antonie M; Dejonckheere, Joachim; Eggers, Antje; Vellucci, Renato

2014-03-01

Under-treatment or lack of appropriate treatment for chronic pain remains an ongoing major healthcare problem. Opioids are being increasingly recognized as an effective option for chronic pain management. The objective of this survey was to understand the perspective of patients treated with opioids on quality of treatment, preferences, and possibilities to improve treatment and communication between patients and physicians. A large-scale PAin RESearch (PARES) survey of 2860 patients (Germany, Italy, and Turkey) with chronic cancer or musculoskeletal pain prescribed opioid therapy was conducted to assess various factors such as ease of use and compliance, sleep, quality-of-life, and polymedication. A physician component was also included. Relationships between variables and differences between groups were tested using Spearman and Wilcoxon signed-rank tests, respectively. Of the patients surveyed, 61% received strong opioids (WHO III) and 39% weak opioids (WHO II). Nearly 65% of the patients were currently on a twice daily or more dosing schedule; however, 61.5% of the patients responded that they considered once-daily dosing to be the most convenient schedule. Patients' responses indicated that different dosing schedules significantly influenced the occurrence of end-of-dose pain, feeling limited by the remaining level of pain, problems in falling asleep, and episodes of waking up at night or early in the morning. Physicians' responses showed that they were not surprised by 68.5% of patient responses; they also felt the need to change some aspect of pain treatment for a third of the patients, the commonest being pain medication (52.4%). The results of the survey suggest that patients prefer a convenient dosing scheme, which may have a positive impact on compliance. Physicians may have to communicate more closely with patients about their needs.

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

PubMed

Sunara, Petra; Krnic, Darko; Puljak, Livia

2017-11-01

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

A "novel" association to treat pain: tramadol/dexketoprofen. The first drug of a "new pharmacological class".

PubMed

Fornasari, D; Allegri, M; Gerboni, S; Fanelli, Guido

2017-04-28

 Acute and chronic pain have an important socio-economical impact. In order to help physicians to choose the appropriate drug, especially for cancer pain, in 1986 WHO has developed a three-step analgesic "ladder" for cancer pain relief in adults. Later it has also been used for acute pain and chronic non-cancer pain. In step I nonsteroidal anti-inflammatory drugs (NSAIDs) are considered with or without adjuvants, in step II the use of weak opioids for mild-moderate pain, with or without NSAIDs and adjuvant, is suggested, while the step III is reserved to strong opioids for moderate-severe pain with or without non-opioids or adjuvants. In the last two decades, a better pathophysiology knowledge has improved pain management shifting our view from the pain ladder to a modern pain pyramid, in which drugs are selected not only on the basis of pain intensity, but mainly according to mechanisms underlying pain, including peripheral and spinal sensitization which is the main trigger of chronic pain. The best pharmacological approach has become multimodal, in which drugs belonging to different steps should be combined, matching the mechanisms of action with the type of pain. An important corollary of combining analgesic drugs with different mechanism of action is that proper matching achieves the same effect with lower doses, better outcome and fewer adverse effects. In this new perspective, fixed-dose pharmaceutical combinations of different drugs are very useful to fulfil pharmacodynamics, pharmacokinetics and adherence criteria, enriching the pain pyramid of half-steps between the first and second step and between the second and third step. Hence, a new fixed combination of a NSAID with peripheral and central anti-infilammatory activities, such as dexketoprofen, and a weak opioid, such as tramadol, with double analgesic activity in the spinal cord as an opioid and, at the same time, on the descending modulatory pathways, is expected to cover a wide range of acute and recurrent painful conditions, ranging from nociceptive inflammatory pain to neuropathic pain of moderate/severe intensity. In this review we evaluate the rationale that justifies its use as new class of pharmacological modality to treat pain accordingly also to a more update view of WHO pain ladder.

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

PubMed

Drewes, Asbjørn M; Munkholm, Pia; Simrén, Magnus; Breivik, Harald; Kongsgaard, Ulf E; Hatlebakk, Jan G; Agreus, Lars; Friedrichsen, Maria; Christrup, Lona L

2016-04-01

Opioid-induced bowel dysfunction (OIBD) is an increasing problem due to the common use of opioids for pain worldwide. It manifests with different symptoms, such as dry mouth, gastro-oesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation and incomplete evacuation. Opioid-induced constipation (OIC) is one of its many symptoms and probably the most prevalent. The current review describes the pathophysiology, clinical implications and treatment of OIBD. The Nordic Working Group was formed to provide input for Scandinavian specialists in multiple, relevant areas. Seven main topics with associated statements were defined. The working plan provided a structured format for systematic reviews and included instructions on how to evaluate the level of evidence according to the GRADE guidelines. The quality of evidence supporting the different statements was rated as high, moderate or low. At a second meeting, the group discussed and voted on each section with recommendations (weak and strong) for the statements. The literature review supported the fact that opioid receptors are expressed throughout the gastrointestinal tract. When blocked by exogenous opioids, there are changes in motility, secretion and absorption of fluids, and sphincter function that are reflected in clinical symptoms. The group supported a recent consensus statement for OIC, which takes into account the change in bowel habits for at least one week rather than focusing on the frequency of bowel movements. Many patients with pain receive opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus and should also be considered in this context. There are no available tools to assess OIBD, but many rating scales have been developed to assess constipation, and a few specifically address OIC. A clinical treatment strategy for OIBD/OIC was proposed and presented in a flowchart. First-line treatment of OIC is conventional laxatives, lifestyle changes, tapering the opioid dosage and alternative analgesics. Whilst opioid rotation may also improve symptoms, these remain unalleviated in a substantial proportion of patients. Should conventional treatment fail, mechanism-based treatment with opioid antagonists should be considered, and they show advantages over laxatives. It should not be overlooked that many reasons for constipation other than OIBD exist, which should be taken into consideration in the individual patient. It is the belief of this Nordic Working Group that increased awareness of adverse effects and OIBD, particularly OIC, will lead to better pain treatment in patients on opioid therapy. Subsequently, optimised therapy will improve quality of life and, from a socio-economic perspective, may also reduce costs associated with hospitalisation, sick leave and early retirement in these patients. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Synthesis and characterization of potent and selective mu-opioid receptor antagonists, [Dmt(1), D-2-Nal(4)]endomorphin-1 (Antanal-1) and [Dmt(1), D-2-Nal(4)]endomorphin-2 (Antanal-2).

PubMed

Fichna, Jakub; do-Rego, Jean-Claude; Chung, Nga N; Lemieux, Carole; Schiller, Peter W; Poels, Jeroen; Broeck, Jozef Vanden; Costentin, Jean; Janecka, Anna

2007-02-08

To synthesize potent antagonists of the mu-opioid receptor, we prepared a series of endomorphin-1 and endomorphin-2 analogues with 3-(1-naphthyl)-d-alanine (d-1-Nal) or 3-(2-naphthyl)-d-alanine (d-2-Nal) in position 4. Some of these analogues displayed weak antagonist properties. We tried to strengthen these properties by introducing the structurally modified tyrosine residue 2,6-dimethyltyrosine (Dmt) in place of Tyr1. Among the synthesized compounds, [Dmt1, d-2-Nal4]endomorphin-1, designated antanal-1, and [Dmt1, d-2-Nal4]endomorphin-2, designated antanal-2, turned out to be highly potent and selective mu-opioid receptor antagonists, as judged on the basis of two functional assays, the receptor binding assay and the hot plate test of analgesia. Interestingly, another analogue of this series, [Dmt1, d-1-Nal4]endomorphin-1, turned out to be a moderately potent mixed mu-agonist/delta-antagonist.

Bioactive peptides derived from natural proteins with respect to diversity of their receptors and physiological effects.

PubMed

Yoshikawa, Masaaki

2015-10-01

We have found various bioactive peptides derived from animal and plant proteins, which interact with receptors for endogenous bioactive peptides such as opioids, neurotensin, complements C3a and C5a, oxytocin, and formyl peptides etc. Among them, rubiscolin, a δ opioid peptide derived from plant RuBisCO, showed memory-consolidating, anxiolytic-like, and food intake-modulating effects. Soymorphin, a μ opioid peptide derived from β-conglycinin showed anxiolytic-like, anorexigenic, hypoglycemic, and hypotriglyceridemic effects. β-Lactotensin derived from β-lactoglobulin, the first natural ligand for the NTS2 receptor, showed memory-consolidating, anxiolytic-like, and hypocholesterolemic effects. Weak agonist peptides for the complements C3a and C5a receptors were released from many proteins and exerted various central effects. Peptides showing anxiolytic-like antihypertensive and anti-alopecia effects via different types of receptors such as OT, FPR and AT2 were also obtained. Based on these study, new functions and post-receptor mechanisms of receptor commom to endogenous and exogenous bioactive peptides have been clarified. Copyright © 2015 Elsevier Inc. All rights reserved.

The evidence of neuraxial administration of analgesics for cancer-related pain: a systematic review.

PubMed

Kurita, G P; Benthien, K S; Nordly, M; Mercadante, S; Klepstad, P; Sjøgren, P

2015-10-01

The present systematic review analysed the existing evidence of analgesic efficacy and side effects of opioids without and with adjuvant analgesics delivered by neuraxial route (epidural and subarachnoid) in adult patients with cancer. Search strategy was elaborated with words related to cancer, pain, neuraxial route, analgesic and side effects. The search was performed in PubMed, EMBASE, and Cochrane for the period until February 2014. Studies were analysed according to methods, results, quality of evidence, and strength of recommendation. The number of abstracts retrieved was 2147, and 84 articles were selected for full reading. The final selection comprised nine articles regarding randomised controlled trials (RCTs) divided in four groups: neuraxial combinations of opioid and adjuvant analgesic compared with neuraxial administration of opioid alone (n = 4); single neuraxial drug in bolus compared with continuous administration (n = 2); single neuraxial drug compared with neuraxial placebo (n = 1); and neuraxial opioid combined with or without adjuvant analgesic compared with other comprehensive medical management than neuraxial analgesics (n = 2). The RCTs presented clinical and methodological diversity that precluded a meta-analysis. They also presented several limitations, which reduced study internal validity. However, they demonstrated better pain control for all interventions analysed. Side effects were described, but there were few significant differences in favour of the tested interventions. Heterogeneous characteristics and several methodological limitations of the studies resulted in evidence of low quality and a weak recommendation for neuraxial administration of opioids with or without adjuvant analgesics in adult patients with cancer. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Pain in the Frail or Elderly Patient: Does Tapentadol Have a Role?

PubMed

Veal, Felicity C; Peterson, Gregory M

2015-06-01

Persistent pain affects the elderly disproportionally, occurring in 50% of elderly community-dwelling patients and 80% of aged care residents. The management of pain in the elderly and frail patient is complicated because of the risks posed by changes in pharmacokinetics and pharmacodynamics, polypharmacy, and drug-disease interactions. Trials evaluating the efficacy of analgesics have often excluded elderly patients and universally excluded frail patients; therefore, the true efficacy and side-effect profiles in these population groups are largely unknown, especially for long-term use. A stepwise approach is recommended to managing pain, commencing with paracetamol and adding on opioids when needed to manage pain. However, because of the short duration of clinical trials, exclusion of frail patients, and minimal inclusion of elderly patients, the decision as to which opioid should be added on to paracetamol is a difficult one. This article reviews the evidence surrounding a newer opioid, tapentadol. Tapentadol acts on both the mu receptors and on neuronal reuptake of noradrenaline, and has no significant analgesically active metabolites, which theoretically presents some advantages, particularly in comparison with tramadol. However, the evidence to support tapentadol is weak and the trials were often methodologically poor and sponsored almost universally by the drug company. Currently, there is insufficient evidence to support the use of tapentadol over other opioids, which have been on the market longer, are less expensive, and have better established safety profiles. As a first-line agent after the failure of paracetamol alone, morphine, oxycodone, fentanyl, or buprenorphine are still the preferred evidence-based choices for add-on opioid therapy for elderly or frail patients.

Butorphanol in perspective.

PubMed

Rosow, C E

1988-01-01

Butorphanol tartrate is a highly effective opioid agonist-antagonist analgesic with qualitative as well as quantitative differences from the pure agonists. These differences are thought to be due to interaction with a distinct subset of opioid receptors. Although it relieves severe pain, the drug does not usually elevate mood, and it may occasionally cause dysphoria. Counterbalancing its disadvantages is a wealth of clinical experience with the drug showing an impressive record of safety. Butorphanol produces limited respiratory depression and smooth muscle spasm, and both effects are reversible with naloxone. The most prominent side effect is sedation, a property that is generally quite useful in the perioperative period. Butorphanol is a weak morphine antagonist, so it may interact with agonists like morphine or fentanyl. The chief advantages of this agent are its low toxicity and very low potential for abuse.

General, kappa, delta and mu opioid receptor antagonists mediate feeding elicited by the GABA-B agonist baclofen in the ventral tegmental area and nucleus accumbens shell in rats: reciprocal and regional interactions.

PubMed

Miner, Patricia; Shimonova, Lyudmila; Khaimov, Arthur; Borukhova, Yaffa; Ilyayeva, Ester; Ranaldi, Robert; Bodnar, Richard J

2012-03-14

Food intake is significantly increased following administration of agonists of GABA and opioid receptors into the nucleus accumbens shell (NACs) and ventral tegmental area (VTA). GABA-A or GABA-B receptor antagonist pretreatment within the VTA or NACs differentially affects mu-opioid agonist-induced feeding elicited from the same site. Correspondingly, general or selective opioid receptor antagonist pretreatment within the VTA or NACs differentially affects GABA agonist-induced feeding elicited from the same site. Regional interactions have been evaluated in feeding studies by administering antagonists in one site prior to agonist administration in a second site. Thus, opioid antagonist-opioid agonist and GABA antagonist-GABA agonist feeding interactions have been identified between the VTA and NACs. However, pretreatment with GABA-A or GABA-B receptor antagonists in the VTA failed to affect mu opioid agonist-induced feeding elicited from the NACs, and correspondingly, these antagonists administered in the NACs failed to affect mu opioid-induced feeding elicited from the VTA. To evaluate whether regional and reciprocal VTA and NACs feeding interactions occur for opioid receptor modulation of GABA agonist-mediated feeding, the present study examined whether feeding elicited by the GABA-B agonist, baclofen microinjected into the NACs was dose-dependently blocked by pretreatment with general (naltrexone: NTX), mu (beta-funaltrexamine: BFNA), kappa (nor-binaltorphamine: NBNI) or delta (naltrindole: NTI) opioid antagonists in the VTA, and correspondingly, whether VTA baclofen-induced feeding was dose-dependently blocked by NACs pretreatment with NTX, BFNA, NBNI or NTI in rats. Bilateral pairs of cannulae aimed at the VTA and NACs were stereotaxically implanted in rats, and their food intakes were assessed following vehicle and baclofen (200 ng) in each site. Baclofen produced similar magnitudes of increased food intake following VTA and NACs treatment. Baclofen administration in the VTA or NACs was also preceded by administration of NTX (0.1, 1, 5 μg, 0.5 h), BFNA (0.4, 4 μg, 24 h), NBNI (0.6, 6 μg, 0.5 h) or NTI (0.4, 4 μg, 0.5 h) into the other site with intake measured 1, 2 and 4 h after agonist treatment. VTA NTX significantly reduced NACs baclofen-induced feeding. Correspondingly, NACs NTX significantly reduced VTA baclofen-induced feeding, indicating a robust and bidirectional general opioid and GABA-B receptor feeding interaction. Whereas the high, but not low VTA BFNA dose reduced NACs baclofen-induced feeding, NACs BFNA failed to affect VTA baclofen-induced feeding, indicating a unidirectional mu opioid and GABA-B receptor feeding interaction. Whereas VTA NBNI at both doses reduced NACs baclofen-induced feeding, the high, but not low NACs NBNI dose significantly reduced VTA baclofen-induced feeding, indicating a bidirectional kappa opioid and GABA-B receptor feeding interaction. Whereas VTA NTI only transiently reduced NACs baclofen-induced feeding, NACs NTI failed to affect VTA baclofen-induced feeding, indicating a weak unidirectional delta opioid and GABA-B receptor interaction. Whereas administration of NTX or BFNA into the NACs or VTA marginally reduced spontaneous food intake, NBNI or NTI into the same sites failed to alter food intake alone. Therefore, the present study suggests that GABA employs a distributed brain network in mediating its ingestive effects that is dependent upon intact opioid receptor signaling with kappa opioid receptors more involved than mu and delta opioid receptors underlying these regional effects. An alternative hypothesis to be considered is that these effects could be the sum of two independent drug effects (opioid antagonists decreasing and baclofen increasing food intake). Copyright © 2012 Elsevier B.V. All rights reserved.

Discovery of 5-substituted tetrahydronaphthalen-2yl-methyl with N-phenyl-N-(piperidin-4-yl)propionamide derivatives as potent opioid receptor ligands.

PubMed

Deekonda, Srinivas; Wugalter, Lauren; Kulkarni, Vinod; Rankin, David; Largent-Milnes, Tally M; Davis, Peg; Bassirirad, Neemah M; Lai, Josephine; Vanderah, Todd W; Porreca, Frank; Hruby, Victor J

2015-09-15

A new series of novel opioid ligands have been designed and synthesized based on the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen-2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide derivatives to study the biological effects of these substituents on μ and δ opioid receptor interactions. Recently our group reported novel 4-anilidopiperidine analogues, in which several aromatic ring-contained amino acids were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their biological activities at the μ and δ opioid receptors. In continuation of our efforts in these novel 4-anilidopiperidine analogues, we took a peptidomimetic approach in the present design, in which we substituted aromatic amino acids with tetrahydronaphthalen-2yl methyl moiety with amino, amide and hydroxyl substitutions at the 5th position. In in vitro assays these ligands, showed very good binding affinity and highly selective toward the μ opioid receptor. Among these, the lead ligand 20 showed excellent binding affinity (2 nM) and 5000 fold selectivity toward the μ opioid receptor, as well as functional selectivity in GPI assays (55.20 ± 4.30 nM) and weak or no agonist activities in MVD assays. Based on the in vitro bioassay results the lead compound 20 was chosen for in vivo assessment for efficacy in naïve rats after intrathecal administration. Compound 20 was not significantly effective in alleviating acute pain. This discrepancy between high in vitro binding affinity, moderate in vitro activity, and low in vivo activity may reflect differences in pharmacodynamics (i.e., engaging signaling pathways) or pharmacokinetics (i.e., metabolic stability). In sum, our data suggest that further optimization of this compound 20 is required to enhance in vivo activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacological characterization of the bifunctional opioid ligand H-Dmt-Tic-Gly-NH-Bzl (UFP-505).

PubMed

Dietis, N; McDonald, J; Molinari, S; Calo, G; Guerrini, R; Rowbotham, D J; Lambert, D G

2012-02-01

While producing good-quality analgesia, µ-opioid (MOP) receptor activation produces a number of side-effects including tolerance. Simultaneous blockade of δ-opioid (DOP) receptors has been shown to reduce tolerance to morphine. Here, we characterize a prototype bifunctional opioid H-Dmt-Tic-Gly-NH-Bzl (UFP-505). We measured receptor binding affinity in Chinese hamster ovary (CHO) cells expressing recombinant human MOP, DOP, k-opioid (KOP), nociceptin/orphanin (NOP) receptors. For activation, we measured the binding of GTPγ(35)S to membranes from CHO(hMOP), CHO(hDOP), rat cerebrocortex, and rat spinal cord. In addition, we assessed 'end organ' responses in the guinea pig ileum and mouse vas deferens. UFP-505 bound to CHO(hMOP) and CHO(hDOP) with (binding affinity) pK(i) values of 7.79 and 9.82, respectively. There was a weak interaction at KOP and NOP (pK(i) 6.29 and 5.86). At CHO(hMOP), UFP-505 stimulated GTPγ(35)S binding with potency (pEC(50)) of 6.37 and in CHO(hDOP) reversed the effects of a DOP agonist with affinity (pK(b)) of 9.81 (in agreement with pK(i) at DOP). UFP-505 also stimulated GTPγ(35)S binding in rat cerebrocortex and spinal cord with pEC(50) values of 6.11-6.53. In the guinea pig ileum (MOP-rich preparation), UFP-505 inhibited contractility with pEC(50) of 7.50 and in the vas deferens (DOP-rich preparation) reversed the effects of a DOP agonist with an affinity (pA(2)) of 9.15. We have shown in a range of preparations and assays that UFP-505 behaves as a potent MOP agonist and DOP antagonist; a MOP/DOP bifunctional opioid. Further studies in dual expression systems and whole animals with this prototype are warranted.

Analgesics in postoperative care in hip fracture patients with dementia - reported by nurses.

PubMed

Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi

2014-11-01

To describe the analgesic use in hip fracture patients with dementia during the first two postoperative days as reported by nurses. Nurses play a pivotal role in treating postoperative pain in patients with dementia and monitoring the effects of administered analgesics. Cross-sectional descriptive questionnaire study in seven university hospitals and 10 central hospitals in Finland. The study was conducted from March until May in 2011 in Finland. For this analysis, the focus was on the sample of nurses (n = 269) who were working in orthopaedic units. Analgesics were classified according to the Anatomical Therapeutic Chemical Classification System. Nonparametric tests were applied to find out the significant differences between analgesic use and different hospitals. Paracetamol and strong opioids administered orally or parenterally seemed to be the most typical of postoperatively used types of analgesics in patients with dementia. Nonsteroidal anti-inflammatory analgesics and weak opioids were also commonly reported to be in use. There were no statistically significant differences between hospitals in typical daily doses. The majority of the nurses reported that the primary aim of postoperative pain management in hip fracture patients with dementia was 'slight pain, which does not prevent normal functioning' (72%). The pharmacological postoperative pain treatment in acute care was commonly based on the use of strong opioids and paracetamol in hip fracture patients with dementia. The reported use of transdermal opioids and codeine combination warrants further examination. Further studies are also needed to find out whether the pain is appropriately and adequately treated. Transdermal opioids and codeine combination may not be relevant analgesics for acute pain management in older adults. It is important to create a balance between sufficient pain relief and adverse effects of analgesics to allow early mobilisation and functional recovery. © 2014 John Wiley & Sons Ltd.

A systematic review of health economic models of opioid agonist therapies in maintenance treatment of non-prescription opioid dependence.

PubMed

Chetty, Mersha; Kenworthy, James J; Langham, Sue; Walker, Andrew; Dunlop, William C N

2017-02-24

Opioid dependence is a chronic condition with substantial health, economic and social costs. The study objective was to conduct a systematic review of published health-economic models of opioid agonist therapy for non-prescription opioid dependence, to review the different modelling approaches identified, and to inform future modelling studies. Literature searches were conducted in March 2015 in eight electronic databases, supplemented by hand-searching reference lists and searches on six National Health Technology Assessment Agency websites. Studies were included if they: investigated populations that were dependent on non-prescription opioids and were receiving opioid agonist or maintenance therapy; compared any pharmacological maintenance intervention with any other maintenance regimen (including placebo or no treatment); and were health-economic models of any type. A total of 18 unique models were included. These used a range of modelling approaches, including Markov models (n = 4), decision tree with Monte Carlo simulations (n = 3), decision analysis (n = 3), dynamic transmission models (n = 3), decision tree (n = 1), cohort simulation (n = 1), Bayesian (n = 1), and Monte Carlo simulations (n = 2). Time horizons ranged from 6 months to lifetime. The most common evaluation was cost-utility analysis reporting cost per quality-adjusted life-year (n = 11), followed by cost-effectiveness analysis (n = 4), budget-impact analysis/cost comparison (n = 2) and cost-benefit analysis (n = 1). Most studies took the healthcare provider's perspective. Only a few models included some wider societal costs, such as productivity loss or costs of drug-related crime, disorder and antisocial behaviour. Costs to individuals and impacts on family and social networks were not included in any model. A relatively small number of studies of varying quality were found. Strengths and weaknesses relating to model structure, inputs and approach were identified across all the studies. There was no indication of a single standard emerging as a preferred approach. Most studies omitted societal costs, an important issue since the implications of drug abuse extend widely beyond healthcare services. Nevertheless, elements from previous models could together form a framework for future economic evaluations in opioid agonist therapy including all relevant costs and outcomes. This could more adequately support decision-making and policy development for treatment of non-prescription opioid dependence.

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

PubMed

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

2017-11-16

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

Opiate alkaloids antagonize postsynaptic glycine and GABA responses: correlation with convulsant action.

PubMed

Werz, M A; Macdonald, R L

1982-03-18

Opiate alkaloid and opioid peptide actions on spontaneous neuronal activity and postsynaptic amino acid responsiveness were assessed using intracellular recording techniques applied to murine spinal cord neurons in primary dissociated cell culture. Application of opiates was by superfusion and amino acids by iontophoresis. Glycine and GABA but not glutamate responses were antagonized by the opiate alkaloids. Since opiate effects on glycine and GABA responses were not naloxone-reversible, only weakly stereospecific, and not produced by the opioid peptide [D-Ala2]-Met-enkephalinamide, it is unlikely that these effects were mediated by opiate receptors. Opiate depression of glycine inhibition was correlated with the induction of paroxysmal depolarizations in cultured spinal cord neurons, suggesting that antagonism of inhibitory amino acid transmission may underlie the convulsant actions of high concentrations of the opiate alkaloids.

Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain.

PubMed

Aronson, M D

1997-01-01

The treatment of chronic pain is an important function of physicians. In the United States, available drug treatments for chronic pain currently include simple analgesics such as acetaminophen, salicylates and other nonsteroidal anti-inflammatory drugs, traditional opioid drugs, and adjuvant agents (eg, antidepressants, anticonvulsants). Typically, the choice of a drug is made by balancing the indications for treatment, the clinical efficacy of the drug, and its toxicity. An understanding of the mechanism of action of these drugs helps to establish their role in therapy. Tramadol is an effective analgesic that works through a combined mechanism of weak mu receptor binding and the inhibition of serotonin and norepinephrine reuptake. Tramadol has a favorable adverse-effect profile and therefore is likely to have an important role in the management of chronic pain syndromes.

Radioreceptor assay for analysis of fentanyl and its analogs in biological samples

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

Alburges, M.E.

The assay is based on the competition of these drugs with ({sup 3}H) fentanyl for opioid receptors in membrane preparations of rat forebrain in vitro. The binding in stereospecific, reversible and saturable. Scatchard plots of saturation suggest the presence of high and low affinity binding sites. Morphine and hydromorphone complete with ({sup 3}H)fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of ({sup 3}H)fentanyl. Many other commonly abused drugs do not compete with ({sup 3}H)fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, ({plus minus})-cis-3-methylfentanyl, alpha-methylfentanyl, butyrylfentanyl and benzylfentanyl were analyzed by radioreceptormore » assay, radioimmunoassay, and gas chromatography/mass spectrometry. Urinary analysis of fentanyl showed a good correlation with these three methods; however, discrepancies were observed in the analysis of fentanyl analogs. This radioreceptor assay is well-suited as an initial assay for the detection of active analogs of fentanyl in urine with good correlation with other techniques in the analysis of fentanyl; however, there is substantial disagreement between techniques in the quantitation of fentanyl analogs. The implications of these discrepancies are discussed.« less

BET 2: Low-dose ketamine for acute pain in the ED.

PubMed

Duncan, Colby; Riley, Brad

2016-12-01

A short cut review was carried out to establish whether low-dose ketamine is better than morphine at safely and effectively reducing pain scores in ED patients with acute pain who do not respond to conventional therapies. One hundred and thirty-two papers were found using the reported searches, of these three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that the evidence is limited, but that ketamine can be an effective alternative or adjunct to intravenous opioid pain medications and in some instances may provide more effective pain relief when compared with opioids. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Detection of Papaverine for the Possible Identification of Illicit Opium Cultivation.

PubMed

Mirsafavi, Rustin Y; Lai, Kristine; Kline, Neal D; Fountain, Augustus W; Meinhart, Carl D; Moskovits, Martin

2017-02-07

Papaverine is a non-narcotic alkaloid found endemically and uniquely in the latex of the opium poppy. It is normally refined out of the opioids that the latex is typically collected for, hence its presence in a sample is strong prima facie evidence that the carrier from whom the sample was collected is implicated in the mass cultivation of poppies or the collection and handling of their latex. We describe an analysis technique combining surface-enhanced Raman spectroscopy (SERS) with microfluidics for detecting papaverine at low concentrations and show that its SERS spectrum has unique spectroscopic features that allows its detection at low concentrations among typical opioids. The analysis requires approximately 2.5 min from sample loading to results, which is compatible with field use. The weak acid properties of papaverine hydrochloride were investigated, and Raman bands belonging to the protonated and unprotonated forms of the isoquinoline ring of papaverine were identified.

Phytoconstituents from Vitex agnus-castus fruits

PubMed Central

Chen, Shao-Nong; Friesen, J. Brent; Webster, Donna; Nikolic, Dejan; van Breemen, Richard B.; Wang, Z. Jim; Fong, Harry H.S.; Farnsworth, Norman R.; Pauli, Guido F.

2011-01-01

A new labdane-diterpene, viteagnusin I (1), together with 23 known phytoconstituents were isolated from the fruits of Vitex agnus-castus L, and their structures characterized by spectroscopic method (NMR and MS). The known compounds include ten flavonoids, five terpenoids, three neolignans, and four phenolic compounds, as well as one glyceride. Biological evaluation identified apigenin, 3-methylkaempferol, luteolin, and casticin as weak ligands of delta and mu opioid receptors, exhibiting dose-dependent receptor binding. PMID:21163339

The danger of imperfect regulation: OxyContin use in the United States and Canada.

PubMed

Lexchin, Joel; Kohler, Jillian Clare

2011-01-01

Drug companies aggressively market their products to increase sales and economic rewards. Different countries have different regulatory regimes for controlling promotion. In the United States control rests directly with the Food and Drug Administration whereas Canada relies on a mixture of voluntary self-regulation and an autonomous agency. Each method has significant weaknesses. We examine these weaknesses by analyzing the promotion of OxyContin (the time release version of the opioid oxycodone) by Purdue in Canada and the United States. We then look at the association between promotion and the misuse and abuse of OxyContin in both countries. Finally, we advance specific recommendations for regulating promotion for drugs that may have a high abuse potential.

A randomized, double-blind, controlled trial on non-opioid analgesics and opioid consumption for postoperative pain relief after laparoscopic cholecystectomy.

PubMed

Abdulla, S; Eckhardt, R; Netter, U; Abdulla, W

2012-01-01

Following laparoscopic cholecystectomy, an effective post-operative pain control is necessary, at least during the first 24 hours. We present a randomized, double-blind trial on the effect of the combined use of intravenous parecoxib, and metamizol or paracetamol on piritramide consumption using a patient-controlled analgesia (PCA) pump in patients recovering from laparoscopic cholecystectomy. 120 patients were randomly allocated to four patient groups treated with normal saline or one of non-opioid analgesics (parecoxib 40 mg twice daily, metamizol 1 g three times daily, paracetamol 1 g three times daily) in addition to piritramide using the PCA pump. Beginning in the post-anesthesia care unit (PACU), patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience at rest while piritramide consumption was recorded. In all groups, piritramide consumption was high in PACU. Only metamizol significantly reduced piritramide consumption compared to the others upon discharge from PACU. Overall, cumulative piritramide consumption was slightly lower in the metamizol group and higher in the NaCl group; however, these findings were statistically not significant. VAS scores were highest upon arrival in PACU and dropped almost continuously after surgery. A significantly lower postoperative pain intensity was only found in the parecoxib group at 24 h after surgery compared to the metamizol group. The efficacy of tested additive medications on piritramide consumption and pain relief is weak and there is no clear-cut difference between the non-opioid drugs used.

Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid and sweat during treatment of opioid-dependent pregnant women

PubMed Central

Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Huestis, Marilyn A.

2011-01-01

Background Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc) and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high dose (14–20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. Methods Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 h during gestation weeks 28 or 29 and 34, and 2 months after delivery. Tmax was not affected by pregnancy; however, BUP and NBUP Cmax and AUC0–24h tended to be lower during pregnancy compared to postpartum levels. Results Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations, and BUP/NBUP ratios in plasma and OF. Conclusion Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP OF/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of OF specimens. In sweat, BUP and NBUP were detected in only 4 of 25 (12 or 24 h) specimens in low concentrations (<2.4 ng/patch). These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation. PMID:21860340

The delta-selective opioid peptide dermenkephalin and the mu-selective hybrid peptide dermenkephalin-[1-4]-dermophin-[5-7] display strikingly different conformations despite identical tetrapeptide N-termini. A quantitative 2-D NMR and molecular modeling analysis.

PubMed

Riand, J; Baron, D; Nicolas, P; Benajiba, A; Teng, Y; Naim, M

1999-12-01

The selective recognition of the aminoterminal binding pharmacophore Tyr-D-Xaa-Phe of the opioid heptapeptide dermorphin, Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 (DRM)1, and of dermenkephalin, Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 (DREK), by the mu-opioid receptor and delta-opioid receptor, respectively, depends upon the constitution / conformation of the C-terminal tripeptide. The hybrid peptide DREK-[1-4]-DRM-[5-7] is very potent at, and exquisitely selective for the mu-opioid receptor, and differs only from dermenkephalin by its C-terminal tripeptide. Comparison of the structural features of DREK-[1-4]-DRM-[5-7] and dermenkephalin by nmr analysis and molecular modeling revealed striking differences, as well in the trans (Tyr5 - Pro6) isomer (population 75%) than in the cis isomer.. Whereas the folded C-terminal tail of dermenkephalin influenced the tertiary structure of the N-terminal tetrapeptide and placed the Tyr1 and Phe3 aromatic rings in definite orientations that are best suited for the delta-receptor, there were only weak contacts, as shown by NOE data, between the aminoterminal and carboxyterminal parts of the hybrid peptide. This promoted increased flexibility of the whole backbone and relaxed orientations for the side-chains of Tyr1 and Phe3 that are compatible with the mu-receptor but unsuitable for the delta-receptor. The steric hindrance introduced by Pro6 in DREK-[1-4]-DRM-[5-7], plus the absence of large hydrophobic side-chains in positions 5 and 6 may prevent close contacts between the N-terminal and C-terminal domains and reorientation of the main pharmacophoric elements Tyr1 and Phe3.

Phytoconstituents from Vitex agnus-castus fruits.

PubMed

Chen, Shao-Nong; Friesen, J Brent; Webster, Donna; Nikolic, Dejan; van Breemen, Richard B; Wang, Z Jim; Fong, Harry H S; Farnsworth, Norman R; Pauli, Guido F

2011-06-01

A new labdane-diterpene, viteagnusin I (1), together with 23 known phytoconstituents were isolated from the fruits of Vitex agnus-castus L, and their structures characterized by spectroscopic methods (NMR and MS). The known compounds include ten flavonoids, five terpenoids, three neolignans, and four phenolic compounds, as well as one glyceride. Biological evaluation identified apigenin, 3-methylkaempferol, luteolin, and casticin as weak ligands of delta and mu opioid receptors, exhibiting dose-dependent receptor binding. Copyright © 2011 Elsevier B.V. All rights reserved.

Characterization of the Antinociceptive Effects of the Individual Isomers of Methadone Following Acute and Chronic Administration

PubMed Central

Morgan, Richard W.; Nicholson, Katherine L.

2011-01-01

Methadone is a long-acting opioid used in the treatment of various pain states and substitution therapy in heroin addiction. Extensive behavioral characterization has been carried out utilizing the racemate, but limited investigation has been performed with the individual isomers. While the l-isomer is a potent opioid agonist, the d-isomer has weak μ opioid activity and has also been shown to possess N-methyl-d-aspartate (NMDA) antagonist properties in vitro. The acute antinociceptive effects of the isomers were evaluated in rats using a warm water tail withdrawal procedure at two stimulus intensities (50° and 55° C). Increasing dose ratios of d- to l-methadone were administered chronically to determine the ability of the d-isomer to modulate antinociceptive tolerance to the l-isomer. Acutely, both l- (0.1-5.6 mg/kg, sc) and d- (3.0-56.0 mg/kg, sc) methadone produced antinociception though the efficacy of the d-isomer was limited at 55° C. These effects were dose-dependently blocked by naltrexone (0.01-1.0 mg/kg, sc). Administered chronically, d-methadone (1.7-10 mg/kg, sc) dose-dependently blocked tolerance development to the l-isomer (1.7 mg/kg, sc). These findings support the antinociceptive effects of the isomers being opioid receptor mediated with the l-isomer functioning as a full efficacy agonist whereas the d-isomer appears to have lower efficacy. The ability of nonracemic doses of the d-isomer to prevent tolerance development to the l-isomer may be attributed to partial μ agonist activity however NMDA antagonist activity cannot be discounted. PMID:21836464

Incidence of high dosage buprenorphine and methadone shopping behavior in a retrospective cohort of opioid-maintained patients in France.

PubMed

Delorme, Jessica; Chenaf, Chouki; Kabore, Jean-Luc; Pereira, Bruno; Mulliez, Aurélien; Tremey, Aurore; Brousse, Georges; Zenut, Marie; Laporte, Catherine; Authier, Nicolas

2016-05-01

Opioid Substitution Treatment (OST) misuse and diversion have significantly increased worldwide. Obtaining OST prescriptions from multiple prescribers, known as doctor shopping, is a way in which opioids may be diverted. The aim of this study was to assess the incidence of OST (high dosage buprenorphine (HDB) and methadone (MTD)) shopping behavior and identify associated risk factors, and its impact on mortality. A retrospective cohort of patients treated by OST between April 1, 2004 and December 31, 2012 from a sample of the French Health Insurance database was established. Doctor shopping was defined as ≥1 day of overlapping prescriptions written by ≥2 different prescribers and filled in ≥3 different pharmacies. A total of 2043 patients were enrolled, 1450HDB and 593 MTD. The one-year incidence of shopping behavior was 8.4% (95% CI: 7.0-10.1) in HDB group and 0% in MTD group, compared to 0.2% (95% CI: 0.1-0.2) for diuretics. On multivariate analysis, factors associated with HDB shopping behavior were: male gender HR: 1.74 (95% CI: 1.20-2.54); low-income status HR: 2.95 (95% CI: 2.07-4.44); mental health disorders HR: 1.43 (95% CI: 1.06-1.94); concurrent hypnotics use HR: 1.90 (95% CI: 1.39-2.61); concurrent use of weak opioids HR: 1.48 (95% CI: 1.09-1.99) and morphine HR: 1.69 (95% CI: 1.02-2.80). HDB shoppers had a higher, yet non-significant risk of death (HR: 1.56 (95% CI: 0.64-3.81)) than non HDB shoppers. Shopping behavior was only found in high dosage buprenorphine patients and concerned almost one out ten patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pattern of pain management practices of Filipino surgeons.

PubMed

de Leon, Jose Rhoel C; Espinosa, Erwin

2008-01-01

Among all the fields of specialization in medicine, the surgeons probably encounter the highest number of pain patients, aside from 'causing' many painful conditions due to surgical procedures. It was widely presumed that surgeons in general do not pay much attention to pain management of their patients, often passing on the responsibility to other specialists. A survey was conducted among general surgeons from all the regions in the Philippines. There were 167 respondents of 200 questionnaires sent. An 18-item, multiple-choice questionnaire was developed to assess their prevailing pain management practices preoperatively, postoperatively and when the patients are recovering, as well as their preferences in medications. The majority of the respondents (58%) claim that they personally manage their patients' postoperative pain. Almost half use a combination of a nonsteroidal anti-inflammatory drug (NSAID) and a weak opioid, and only 13% use a combination of a strong opioid and an NSAID. Only 17% of the respondents start oral medications in the recovery room. The majority (90%) claim that they personally attend to their patients' pain in the wards. Almost all the respondents (98.8%) started oral medications as soon as possible. Only 20% of the respondents always use the Visual Analog Scale in pain assessment. The majority of the respondents (55%) have no narcotic license (S2). Although the majority of the respondents claim to be involved in the management of perioperative pain of their patients, an objective assessment of the patients' pain is not usually done. The use of opioids alone or in combination is still low among Filipino surgeons; the main reason could be the regulatory provisions of the government on opioid use. Copyright 2008 S. Karger AG, Basel.

Prescribing for pain--how do nurses contribute? A national questionnaire survey.

PubMed

Stenner, Karen; Carey, Nicola; Courtenay, Molly

2012-12-01

To provide information on the profile and practice of nurses in the UK who prescribe medication for pain. Pain is widely under-reported and under-treated and can have negative consequences for health and psychosocial well-being. Indications are that nurses can improve treatment and access to pain medications when they prescribe. Whilst nurses working in many practice areas treat patients with pain, little is known about the profile, prescribing practice or training needs of these nurses. A descriptive questionnaire survey. An online questionnaire was used to survey 214 nurses who prescribed for pain in the UK between May and July 2010. Data were analysed using descriptive statistics and non-parametric tests. Half the participants (50%) worked in primary care, 32% in secondary care and 14% worked across care settings. A range of services were provided, including general practice, palliative care, pain management, emergency care, walk-in-centres and out-of-hours. The majority (86%) independently prescribed 1-20 items per week. Non-opioid and weak opioids analgesics were prescribed by most (95%) nurses, whereas fewer (35%) prescribed strong opioids. Training in pain had been undertaken by 97% and 82% felt adequately trained, although 28% had problems accessing training. Those with specialist training prescribed a wider range of pain medications, were more likely to prescribe strong opioids and were more often in pain management roles. Nurses prescribe for pain in a range of settings with an emphasis on the treatment of minor ailments and acute pain. A range of medications are prescribed, and most nurses have access to training. The nursing contribution to pain treatment must be acknowledged within initiatives to improve pain management. Access to ongoing training is required to support nurse development in this area of practice to maximise benefits. © 2012 Blackwell Publishing Ltd.

Tramadol Extended-Release for the Management of Pain due to Osteoarthritis

PubMed Central

Guetti, Cristiana; Paladini, Antonella; Varrassi, Giustino

2013-01-01

Current knowledge on pathogenesis of osteoarticular pain, as well as the consequent several, especially on the gastrointestinal, renal, and cardiovascular systems, side effects of NSAIDs, makes it difficult to perform an optimal management of this mixed typology of pain. This is especially observable in elderly patients, the most frequently affected by osteoarthritis (OA). Tramadol is an analgesic drug, the action of which has a twofold action. It has a weak affinity to mu opioid receptors and, at the same time, can result in inhibition of the reuptake of noradrenaline and serotonin in nociceptorial descending inhibitory control system. These two mechanisms, “opioidergic” and “nonopioidergic,” are the grounds for contrasting certain types of pain that are generally less responsive to opioids, such as neuropathic pain or mixed OA pain. The extended-release formulation of tramadol has good efficacy and tolerability and acts through a dosing schedule that allows a high level of patients compliance to therapies with a good recovery outcome for the patients' functional status. PMID:27335872

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

The Concentration of Opioid Prescriptions by Providers and Among Patients in the Oregon Medicaid Program.

PubMed

Kim, Hyunjee; Hartung, Daniel M; Jacob, Reside L; McCarty, Dennis; McConnell, K John

2016-04-01

This study examined the distribution of opioid prescribing across providers and patients and the extent to which concentrated distribution predicts opioid misuse. Using 2013 Oregon Medicaid claims and the National Provider Identifier Registry, this study identified patients who filled at least one opioid prescription and providers who prescribed opioids for those patients (N=61,477 Medicaid beneficiaries). This study examined the distribution of opioid prescriptions by provider and patient, the extent to which high-volume opioid use was associated with potential opioid misuse, and how this association changed when patients received opioids from providers in the top decile of morphine-equivalent doses (MEQ) prescribed in 2013. This study used four indicators of opioid misuse: doctor and pharmacy shopping for opioid prescriptions, opioid prescription overlap, and opioid and benzodiazepine prescription overlap. Opioid use and prescriptions were heavily concentrated among the top 10% of opioid users and prescribers. Those high-volume opioid users and prescribers accounted for, respectively, 83.2% and 80.8% in MEQ of entire opioids prescribed. Patients' increasing use of opioids (by MEQ) was associated with most measures of opioid misuse. Patients receiving opioids from high-volume prescribers had a higher probability of opioid prescription overlap and opioid and benzodiazepine prescription overlap compared with other patients, but the difference was significant only among patients who received high doses of opioids, and the size of the difference was modest. Whereas current policies emphasize reducing opioid prescriptions across all patients and providers, study results suggest that focusing policies on high-volume opioid users and prescribers may be more beneficial.

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.

The Concentration of Opioid Prescriptions by Providers and Patients in the Oregon Medicaid Program

PubMed Central

Kim, Hyunjee; Hartung, Daniel; Jacob, Lorie; McCarty, Dennis; McConnell, K. John

2016-01-01

Objective This study seeks to understand the distribution of opioid prescribing across providers and patients, and examines how this concentration predicts opioid misuse. Methods Using 2013 Oregon Medicaid claims and National Provider ID registry, this study identified patients who filled at least one opioid prescription and providers who prescribed opioids for those patients (N=61,477 Medicaid patients). This study examined the distribution of opioid prescriptions by provider and patient, the extent to which high-volume opioid use was associated with potential opioid misuse, and how this association changes when patients received opioids from providers in the top decile of morphine equivalents (MEQ) prescribed in 2013. This study used four indicators of opioid misuse: doctor and pharmacy shopping for opioid prescriptions, opioid prescription overlap, and opioid and benzodiazepine prescription overlap. Results Opioid use and prescriptions were heavily concentrated among the top 10% opioid users and prescribers. Those high-volume opioid users and prescribers accounted for 83.2% and 80.8% in MEQ of entire opioids prescribed. Patients’ increasing use of MEQ was associated with most measures of opioid misuse. Patients receiving opioids from high-volume prescribers had a higher probability of opioid prescription overlap and opioid and benzodiazepine prescription overlap, but the increase was significant only among patients who received high doses of opioids and the size of the increase was modest. Conclusions Whereas current policies emphasize reducing opioid prescriptions across all patients and providers, study results suggest potential for policies that focus on high-volume opioid users and prescribers. PMID:26766755

Sufentanil sublingual tablet system for the management of postoperative pain.

PubMed

Babazade, Rovnat; Turan, Alparslan

2016-12-01

Intravenous patient-controlled opioid analgesia has been an important improvement in addressing insufficient management of acute postoperative pain for over 40 years. However, there are number of weaknesses for intravenous patient-controlled analgesia, including operator and device error, intravenous line patency issues, and risk of catheter-related infection, all of which contribute to the complications and increase in cost of care. The sublingual sufentanil tablet system is a major evolution in both drug and technological management of postoperative pain. Areas covered: We reviewed the use of the sublingual sufentanil tablet system in management of moderate to severe postoperative pain in hospitalized patients, with a particular focus on the pharmacological properties of sufentanil and clinical use in different surgical patients. Expert opinion: The sublingual sufentanil tablet system can decrease intravenous opioid based patient-controlled analgesia related complications and safety issues. Current clinical studies have demonstrated this noninvasive-novel system to be safe and effective in management of acute pain in the postsurgical setting. Researchers should focus on comparing it with other available patient controlled analgesia modalities and evaluating the efficiency and cost effectiveness of the sublingual sufentanil tablet system.

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

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

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.

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

Noribogaine is a G-protein biased κ-opioid receptor agonist.

PubMed

Maillet, Emeline L; Milon, Nicolas; Heghinian, Mari D; Fishback, James; Schürer, Stephan C; Garamszegi, Nandor; Mash, Deborah C

2015-12-01

Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicate that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6'-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations>1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

[17-year-old patient with neutropenia and fever during therapy with analgesics].

PubMed

Pfersdorff, M; Spes, J; Kraus, M R

2011-02-01

A 17-year-old patient was admitted to the hospital because of fever, shivering and odynophagia. After a pathologic fracture of the neck of the femur because of a preexisting bone cyst he had been taking a combined analgetic therapy with tilidin, metamizole and diclofenac for three weeks. Physical examination was completely normal. The differential blood count revealed a severe neutropenia of < 100/µl and an elevated C-reactive protein. Several blood cultures were negative. Despite multiple diagnostic procedures no focus of infection could be detected. A bone marrow biopsy showed an impaired maturation of granulocyte precursor cells with a predominance of promyelocytes. Acute leukaemia could be excluded. This finding is typical for a e. g. metamizole-induced agranulocytosis. Treatment consisted of reverse isolation, intravenous broad-spectrum antibiotics and granulocyte colony-stimulating factors. In the following days, the clinical condition of the patient improved considerably and the neutrophil blood count normalized. This case report presents the clinical course of an acute drug-induced agranulocytosis. This condition has to be considered as a rare but potentially life-threatening side effect of a variety of drugs, for example metamizole, and requires immediate treatment. © Georg Thieme Verlag KG Stuttgart · New York.

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.

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

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.

Reappraisal deficits promote craving and emotional distress among chronic pain patients at risk for prescription opioid misuse.

PubMed

Garland, Eric L; Hanley, Adam W; Bedford, Carter E; Zubieta, Jon-Kar; Howard, Matthew O; Nakamura, Yoshio; Donaldson, Gary W; Froeliger, Brett

2018-06-04

A subset of chronic pain patients misuse prescription opioids as a means of regulating negative emotions. However, opioid misuse may result in deficits in emotion regulation strategies like reappraisal by virtue of the deleterious effects of chronic opioid exposure. The aim of this study was to characterize differences in reappraisal use among chronic pain patients at risk for opioid misuse and those who report taking opioids as prescribed. A sample of 127 pain patients receiving chronic opioid analgesic pharmacotherapy were classified as at risk for opioid misuse (n = 62) or taking opioids as prescribed (n = 65) using the Current Opioid Misuse Measure (COMM). The Emotion Regulation Questionnaire (ERQ) characterized use of emotion regulation strategies including reappraisal and expressive suppression. Participants also reported levels of opioid craving, emotional distress, and pain severity. Patients at risk for opioid misuse reported significantly less reappraisal use (M = 25.31, SD = 7.33) than those who reportedly took opioids as prescribed (M = 30.28, SD = 7.50), p<.001, but did differ with regard to suppression strategies. Reduced reappraisal use was associated with higher opioid craving and emotional distress that mediated the association between reappraisal deficits and opioid misuse risk. Further, there was a significant indirect effect of opioid misuse on emotional distress via reappraisal use. Opioid misuse risk was associated with reduced use of reappraisal, which in turn was associated with dysregulated negative emotions and increased appetitive drive towards consuming opioids. Studying individual differences in emotion regulation may yield efficacious intervention and prevention approaches to stem the rising tide of the prescription opioid crisis.

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

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.

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.

Role of Urine Drug Testing in the Current Opioid Epidemic.

PubMed

Mahajan, Gagan

2017-12-01

While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.

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].

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 patients at a high risk of fatal opioid overdose. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of dorsal hippocampus κ opioid receptors in contextual aversive memory consolidation in rats.

PubMed

Vanz, Felipe; Bicca, Maíra Assunção; Linartevichi, Vagner Fagnani; Giachero, Marcelo; Bertoglio, Leandro José; Monteiro de Lima, Thereza C

2018-06-01

The main κ opioid receptors (κORs) subtypes already described (κ 1 ORs and κ 2 ORs) are expressed in brain regions involved in aversive memory consolidation, including the dorsal hippocampus (DH). However, the role of DH κORs in consolidation of aversive memories with varied intensity and specificity is still uncertain. The present study aimed to investigate this question using pharmacological agents in rats subjected to a weak, moderate or strong contextual aversive conditioning (CAC) protocol. Antagonizing DH κORs with nor-binaltorphimine (nor-BNI), immediately after, but not 6 h later, a moderate CAC leads to intensified freezing behavior in the re-exposure to the paired context. Thus, indicating that DH κORs have an inhibitory role in the consolidation of an aversive memory. Increased DH κORs expression 1 h and 3 h after the moderate CAC was also observed. This up-regulation was absent in animals only exposed to the shock or to the context, indicating that this phenomenon requires a shock-context pairing to occur. Intra-DH nor-BNI infusion induced no changes following a weak CAC, but it was able to potentiate the expression of freezing behavior in novel and unpaired context after a strong CAC, indicating that DH κORs also modulate the consolidation of a more intense and generalized memory. Moreover, infusing the κ 2 ORs agonist GR 89696, but not the κ 1 ORs agonist U-69593, into the DH reduced the conditioned freezing expression. Nor-BNI pretreatment in a sub-effective dose prevented the κ 2 ORs agonist effects. Altogether, the present findings provide convergent evidence that κORs activation negatively modulates contextual aversive memory consolidation in rat dorsal hippocampus. Copyright © 2018. Published by Elsevier Ltd.

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.

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.

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.

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.

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

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.

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

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.

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.

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

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 limitations of PDMPs to detect opioid use disorders. © 2017 by the Society for Academic Emergency Medicine.

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.

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

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.

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 - ...

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 an assessment of the prevalence of hand surgery patients who receive and fill opioid prescriptions after common hand surgery procedures. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Controlled Substance Lock-In Programs: Examining An Unintended Consequence Of A Prescription Drug Abuse Policy.

PubMed

Roberts, Andrew W; Farley, Joel F; Holmes, G Mark; Oramasionwu, Christine U; Ringwalt, Chris; Sleath, Betsy; Skinner, Asheley C

2016-10-01

Controlled substance lock-in programs are garnering increased attention from payers and policy makers seeking to combat the epidemic of opioid misuse. These programs require high-risk patients to visit a single prescriber and pharmacy for coverage of controlled substance medication services. Despite high prevalence of the programs in Medicaid, we know little about their effects on patients' behavior and outcomes aside from reducing controlled substance-related claims. Our study was the first rigorous investigation of lock-in programs' effects on out-of-pocket controlled substance prescription fills, which circumvent the programs' restrictions and mitigate their potential public health benefits. We linked claims data and prescription drug monitoring program data for the period 2009-12 for 1,647 enrollees in North Carolina Medicaid's lock-in program and found that enrollment was associated with a roughly fourfold increase in the likelihood and frequency of out-of-pocket controlled substance prescription fills. This finding illuminates weaknesses of lock-in programs and highlights the need for further scrutiny of the appropriate role, optimal design, and potential unintended consequences of the programs as tools to prevent opioid abuse. Project HOPE—The People-to-People Health Foundation, Inc.

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

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

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.

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.

Daily home opioid use in adults with sickle cell disease: The PiSCES project.

PubMed

Smith, Wally R; McClish, Donna K; Dahman, Bassam A; Levenson, James L; Aisiku, Imoigele P; de A Citero, Vanessa; Bovbjerg, Viktor E; Roberts, John D; Penberthy, Lynne T; Roseff, Susan D

2015-01-01

Although opioid prescribing in sickle cell disease (SCD) can be controversial, little is published about patterns of opioid use. To report on home opioid use among adults with SCD. Cohort study. Adults with SCD (n=219) who completed daily pain diaries for up to 6 months and had at least one home pain day. Use of long-acting or short-acting opioids, other analgesics, or adjuvants; the proportion of home days, home pain days, and home crisis days with opioid use; these two outcomes according to patient characteristics. Patients used opioids on 12,311 (78 percent) of 15,778 home pain days. Eighty-five patients (38.8 percent) used long-acting opioids with or without short-acting opioids and 103 (47.0 percent) used only short-acting opioids. Twenty-one (9.6 percent) patients used only non-opioid analgesics and 10 (4.6 percent) used no analgesics. Both pain intensity and pain frequency were higher among opioid users (analysis of variance [ANOVA], p<0.0001). Opioid users used hydroxyurea more often than nonusers, even when controlling for mean pain on pain days. Among all patients, significant relationships were found between any opioid use and somatic symptom burden, SCD stress, negative coping, and physical and mental quality of life (QOL); the relationship with SCD stress and physical QOL remained when controlled for mean pain. Among opioid users, similar associations were found between frequency of opioid use and some disease-related and psychosocial variables. In this adult SCD sample, opioids were used by the majority of patients. Pain was the overwhelming characteristic associated with use, but disease-related and psychosocial variables were also associated.

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.

Evidence that opioids may have toll-like receptor 4 and MD-2 effects.

PubMed

Hutchinson, Mark R; Zhang, Yingning; Shridhar, Mitesh; Evans, John H; Buchanan, Madison M; Zhao, Tina X; Slivka, Peter F; Coats, Benjamen D; Rezvani, Niloofar; Wieseler, Julie; Hughes, Travis S; Landgraf, Kyle E; Chan, Stefanie; Fong, Stephanie; Phipps, Simon; Falke, Joseph J; Leinwand, Leslie A; Maier, Steven F; Yin, Hang; Rice, Kenner C; Watkins, Linda R

2010-01-01

Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unresolved. The potential involvement of toll-like receptor 4 (TLR4) was examined using in vitro, in vivo, and in silico techniques. Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Pharmacological blockade of TLR4 signaling in vivo potentiated acute intrathecal morphine analgesia, attenuated development of analgesic tolerance, hyperalgesia, and opioid withdrawal behaviors. TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. A range of structurally diverse clinically-employed opioid analgesics was found to be capable of activating TLR4 signaling in vitro. Selectivity in the response was identified since morphine-3-glucuronide, a morphine metabolite with no opioid receptor activity, displayed significant TLR4 activity, whilst the opioid receptor active metabolite, morphine-6-glucuronide, was devoid of such properties. In silico docking simulations revealed ligands bound preferentially to the LPS binding pocket of MD-2 rather than TLR4. An in silico to in vitro prediction model was built and tested with substantial accuracy. These data provide evidence that select opioids may non-stereoselectively influence TLR4 signaling and have behavioral consequences resulting, in part, via TLR4 signaling.

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

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.

Evidence that opioids may have toll like receptor 4 and MD-2 effects

PubMed Central

Hutchinson, Mark R.; Zhang, Yingning; Shridhar, Mitesh; Evans, John H.; Buchanan, Madison M.; Zhao, Tina X.; Slivka, Peter F.; Coats, Benjamen D.; Rezvani, Niloofar; Wieseler, Julie; Hughes, Travis S.; Landgraf, Kyle E.; Chan, Stefanie; Fong, Stephanie; Phipps, Simon; Falke, Joseph J.; Leinwand, Leslie A.; Maier, Steven F.; Yin, Hang; Rice, Kenner C.; Watkins, Linda R.

2009-01-01

Opioid-induced proinflammatory glial activation modulates wide-ranging aspects of opioid pharmacology including: opposition of acute and chronic opioid analgesia, opioid analgesic tolerance, opioid-induced hyperalgesia, development of opioid dependence, opioid reward, and opioid respiratory depression. However, the mechanism(s) contributing to opioid-induced proinflammatory actions remains unresolved. The potential involvement of toll like receptor 4 (TLR4) was examined using in vitro, in vivo, and in silico techniques. Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Pharmacological blockade of TLR4 signaling in vivo potentiated acute intrathecal morphine analgesia, attenuated development of analgesic tolerance, hyperalgesia, and opioid withdrawal behaviors. TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. A range of structurally diverse clinically employed opioid analgesics was found to be capable of activating TLR4 signaling in vitro. Selectivity in the response was identified since morphine-3-glucuronide, a morphine metabolite with no opioid receptor activity, displayed significant TLR4 activity, whilst the opioid receptor active metabolite, morphine-6-glucuronide, was devoid of such properties. In silico docking simulations revealed ligands bound preferentially to the LPS binding pocket of MD-2 rather than TLR4. An in silico to in vitro prediction model was built and tested with substantial accuracy. These data provide evidence that select opioids may non-stereoselectively influence TLR4 signaling and have behavioral consequences resulting, in part, via TLR4 signaling. PMID:19679181

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

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.

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

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 ...

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...

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...

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...

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...

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...

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.

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

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

Deficits in Autonomic Indices of Emotion Regulation and Reward Processing Associated with Prescription Opioid Use and Misuse

PubMed Central

Garland, Eric L.; Bryan, Craig J.; Nakamura, Yoshio; Froeliger, Brett; Howard, Matthew O.

2016-01-01

Rationale Prescription opioid misuse and high dose opioid use may result in allostatic dysregulation of hedonic brain circuitry, leading to reduced emotion regulation capacity. In particular, opioid misuse may blunt the ability to experience and upregulate positive affect from natural rewards. Objectives The purpose of this study was to examine associations between opioid use/misuse and autonomic indices of emotion regulation capability in a sample of chronic pain patients receiving prescription opioid pharmacotherapy. Methods Chronic pain patients taking long-term opioid analgesics (N = 40) completed an emotion regulation task while heart rate variability (HRV) was recorded, as well as self-report measures of opioid misuse, craving, pain severity, and emotional distress. Based on a validated cut-point on the Current Opioid Misuse Measure, participants were grouped as opioid misusers or non-misusers. Opioid misuse status and morphine equivalent daily dose (MEDD) were examined as predictors of HRV and self-reports of emotion regulation. Results Opioid misusers exhibited significantly less HRV during positive and negative emotion regulation, and significantly less positive affect, than non-misusers, after controlling for confounders including pain severity and emotional distress. MEDD was inversely associated with positive emotion regulation efficacy. Conclusion Findings implicate the presence of reward processing deficits among chronic pain patients with opioid-misusing behaviors, and opioid dosage was associated with deficient emotion regulation, suggesting the presence of compromised top-down cognitive control over bottom-up hedonic processes. Emotion regulation among opioid misusers may represent an important treatment target. PMID:27933366

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.

Prescription opioid misusing chronic pain patients exhibit dysregulated context-dependent associations: Investigating associative learning in addiction with the cue-primed reactivity task.

PubMed

Garland, Eric L; Bryan, Craig J; Kreighbaum, Lydia; Nakamura, Yoshio; Howard, Matthew O; Froeliger, Brett

2018-06-01

Associative learning undergirds the development of addiction, such that drug-related cues serve as conditioned stimuli to elicit drug-seeking responses. Plausibly, among opioid misusing chronic pain patients, pain-related information may serve as a conditioned stimulus to magnify opioid cue-elicited autonomic and craving responses through a process of second-order conditioning. We utilized a novel psychophysiological probe of pain-opioid conditioned associations, the Cue-Primed Reactivity (CPR) task. In this task, participants were presented with images as primes (200 ms) and cues (6000 ms) in pairs organized in four task blocks: "control-opioid," "pain-opioid," "control-pain," and "opioid-pain." Opioid-treated chronic pain patients (N = 30) recruited from an Army base in the Western United States were classified as opioid misusers (n = 17) or non-misusers (n = 13) via a validated cutpoint on the Prescription Drug Use Questionnaire (PDUQ; Compton et al., 2008). Opioid misuse status was examined as a predictor of HRV, craving, and mood responses on the CPR task. HRV increased to a greater extent during the pain-opioid block compared to the control-opioid block for non-misusers compared to misusers (p = .003, η 2 partial  = 0.27). In contrast, craving increased to a greater extent from baseline to the pain-opioid block for misusers than for non-misusers (p = .03, η 2 partial  = .16). Findings suggest that opioid-treated chronic pain patients exhibit Pavlovian conditioned responses to opioid cues strengthened by an associative learning process of second-order conditioning when primed by pain-related images. This pain-opioid contingency appears to become disrupted among individuals who engage in opioid misuse, such that opioid-related stimuli elicit motivational responses irrespective of pain-related contextual stimuli. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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 prescribe opioids for chronic pain patients should appreciate the limited evidence base for this practice and communicate the risks of opioid therapy to their patients.

Continuous opioid treatment for chronic noncancer pain: a time for moderation in prescribing.

PubMed

Colameco, Stephen; Coren, Joshua S; Ciervo, Carman A

2009-07-01

Physicians have embraced the concept of long-term opioid treatment for chronic noncancer pain (CNCP), as evidenced by increased prescribing. Many patients have benefited from more liberal opioid prescribing, but many have not, and prescription opioid abuse has risen significantly coincident with increased prescribing. Because of the potentially serious adverse effects of opioids, physicians must balance potential benefits against risks, especially in individuals at risk for opioid misuse, abuse, or dependence. This article reviews long-term, continuous opioid treatment of CNCP, current treatment guidelines, addiction risk stratification, opioid-induced hyperalgesia, and endocrine dysfunction.

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.

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.

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.

From selective to highly selective SSRIs: a comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram.

PubMed

Schreiber, Shaul; Pick, Chaim G

2006-08-01

Most Serotonin Selective Reuptake Inhibitors (SSRIs) have been found to possess secondary binding properties, while citalopram and its S-enantiomer (escitalopram) have been reconfirmed "purest SSRIs". Using the mouse model of acute pain hotplate analgesia meter, we evaluated the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram, injected i.p. Fluvoxamine induced a dose-dependent clear antinociceptive effect (with an ED(50) value of 6.4 mg/kg). Both fluoxetine and citalopram induced (separately) only a weak antinociceptive effect with an inverse "U" shape curve. All three drug's effects were not abolished by naloxone. Escitalopram did not elicit any effect at quasi-equipotent doses. These findings show that fluoxetine, fluvoxamine and citalopram given i.p. are weak antinociceptors, (not mediated through opioid mechanisms), while escitalopram possesses no antinociceptive properties when injected i.p. This difference between citalopram and escitalopram calls for further studies in order to assess the various differences between the two enantiomers of citalopram, and between each enantiomer and the racemic mixture.

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

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.

Endogenous opiates and behavior: 2014.

PubMed

Bodnar, Richard J

2016-01-01

This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). Copyright © 2015 Elsevier Inc. All rights reserved.

N-methyl-D-aspartate receptors and large conductance calcium-sensitive potassium channels inhibit the release of opioid peptides that induce mu-opioid receptor internalization in the rat spinal cord.

PubMed

Song, B; Marvizón, J C G

2005-01-01

Endogenous opioids in the spinal cord play an important role in nociception, but the mechanisms that control their release are poorly understood. To simultaneously detect all opioids able to activate the mu-opioid receptor, we measured mu-opioid receptor internalization in rat spinal cord slices stimulated electrically or chemically to evoke opioid release. Electrical stimulation of the dorsal horn in the presence of peptidase inhibitors produced mu-opioid receptor internalization in half of the mu-opioid receptor neurons. This internalization was rapidly abolished by N-methyl-D-aspartate (IC50=2 microM), and N-methyl-D-aspartate antagonists prevented this effect. mu-Opioid receptor internalization evoked by high K+ or veratridine was also inhibited by N-methyl-D-aspartate receptor activation. N-methyl-D-aspartate did not affect mu-opioid receptor internalization induced by exogenous endomorphins, confirming that the effect of N-methyl-D-aspartate was on opioid release. We hypothesized that this inhibition was mediated by large conductance Ca2+-sensitive K+ channels BK(Ca2+). Indeed, inhibition by N-methyl-D-aspartate was prevented by tetraethylammonium and by the selective BK(Ca2+) blockers paxilline, penitrem A and verruculogen. Paxilline did not increase mu-opioid receptor internalization in the absence of N-methyl-D-aspartate, indicating that it does not produce an increase in opioid release unrelated to the inhibition by N-methyl-d-aspartate. The BK(Ca2+) involved appears to be a subtype with slow association kinetics for iberiotoxin, which was effective only with long incubations. The BK(Ca2+) opener NS-1619 also inhibited the evoked mu-opioid receptor internalization, and iberiotoxin prevented this effect. We concluded that Ca2+ influx through N-methyl-D-aspartate receptors causes the opening of BK(Ca2+) and hyperpolarization in opioid-containing dorsal horn neurons, resulting in the inhibition of opioid release. Since mu-opioid receptors in the dorsal horn mediate analgesia, inhibition of spinal opioid release could contribute to the hyperalgesic actions of spinal N-methyl-D-aspartate receptors.

N-METHYL-d-ASPARTATE RECEPTORS AND LARGE CONDUCTANCE CALCIUM-SENSITIVE POTASSIUM CHANNELS INHIBIT THE RELEASE OF OPIOID PEPTIDES THAT INDUCE μ-OPIOID RECEPTOR INTERNALIZATION IN THE RAT SPINAL CORD

PubMed Central

SONG, B.; MARVIZÓN, J. C. G.

2006-01-01

Endogenous opioids in the spinal cord play an important role in nociception, but the mechanisms that control their release are poorly understood. To simultaneously detect all opioids able to activate the μ-opioid receptor, we measured μ-opioid receptor internalization in rat spinal cord slices stimulated electrically or chemically to evoke opioid release. Electrical stimulation of the dorsal horn in the presence of peptidase inhibitors produced μ-opioid receptor internalization in half of the μ-opioid receptor neurons. This internalization was rapidly abolished by N-methyl-d-aspartate (IC50=2 μM), and N-methyl-d-aspartate antagonists prevented this effect. μ-Opioid receptor internalization evoked by high K+ or veratridine was also inhibited by N-methyl-d-aspartate receptor activation. N-methyl-d-aspartate did not affect μ-opioid receptor internalization induced by exogenous endomorphins, confirming that the effect of N-methyl-d-aspartate was on opioid release. We hypothesized that this inhibition was mediated by large conductance Ca2+-sensitive K+ channels BK(Ca2+). Indeed, inhibition by N-methyl-d-aspartate was prevented by tetraethylammonium and by the selective BK(Ca2+) blockers paxilline, penitrem A and verruculogen. Paxilline did not increase μ-opioid receptor internalization in the absence of N-methyl-d-aspartate, indicating that it does not produce an increase in opioid release unrelated to the inhibition by N-methyl-d-aspartate. The BK(Ca2+) involved appears to be a subtype with slow association kinetics for iberiotoxin, which was effective only with long incubations. The BK(Ca2+) opener NS-1619 also inhibited the evoked μ-opioid receptor internalization, and iberiotoxin prevented this effect. We concluded that Ca2+ influx through N-methyl-d-aspartate receptors causes the opening of BK(Ca2+) and hyperpolarization in opioid-containing dorsal horn neurons, resulting in the inhibition of opioid release. Since μ-opioid receptors in the dorsal horn mediate analgesia, inhibition of spinal opioid release could contribute to the hyperalgesic actions of spinal N-methyl-d-aspartate receptors. PMID:16203108

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.

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 use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.

Opioid Hypersensitivity: Predictors of Allergy and Role of Drug Provocation Testing.

PubMed

Li, Philip H; Ue, Kok Loong; Wagner, Annette; Rutkowski, Ryszard; Rutkowski, Krzysztof

True IgE-mediated hypersensitivity to opioids is rare and many reactions are due to direct mast cell degranulation. Opioid drug provocation testing (DPT) is the gold standard for diagnosis but is underutilized. The objective of this study was to evaluate the clinical characteristics and predictors of opioid hypersensitivity, as well as outcomes of opioid DPT. Patients referred for opioid DPT over the past 9 years were studied. Patient characteristics, indications for opioid use, symptoms of index reaction, and outcomes of DPT were analyzed. Association analysis was performed to study variables associated with a diagnosis of opioid hypersensitivity. Of the total of 98 patients referred with suspected opioid hypersensitivity, 15 (15%) were diagnosed with opioid allergy. Angioedema (odds ratio [OR]: 5.66; 95% confidence interval [CI]: 1.49-21.47; P = .011) and hypotension (OR: 5.00; 95% CI: 1.15-21.70; P = .032) were significantly more frequent in opioid allergic patients than those with a negative DPT. Patients who received opioids during anesthesia were significantly more likely to be opioid allergic (OR: 6.74; 95% CI: 2.05-22.13; P = .001). In contrast, a negative association was identified with patients who received opioids for analgesia (OR: 0.27; 95% CI: 0.08-0.86; P = .008). Only 15% of our cohort were diagnosed with opioid allergy, emphasizing the importance of DPT in preventing erroneous overdiagnosis. Patients with a history of angioedema or hypotension as their index reaction were significantly more likely to be opioid allergic. DPT are safe when performed by experienced clinicians after risk stratification and using individualized protocols. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

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

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

Trends in opioid prescriptions among children and adolescents in the United States: a nationally representative study from 1996 to 2012.

PubMed

Groenewald, Cornelius B; Rabbitts, Jennifer A; Gebert, J Thomas; Palermo, Tonya M

2016-05-01

Prescription opioid misuse is a major public health concern in the United States, yet little is known about national prescription patterns. We aimed to assess trends in opioid prescriptions made to children and adolescents, to their families, and to adults in the United States from 1996 to 2012. The sample was drawn from nationally representative data, the Medical Expenditure Panel Surveys. We used survey design methods to examine trends in prescription opioid use over time and a logistic regression analysis to examine predictors associated with opioid use. Findings indicated that from 1996 to 2012 opioid prescriptions to children and adolescents remained stable and low. In 1996, 2.68% of children received an opioid prescription, and in 2012, 2.91% received an opioid prescription. In contrast, opioid prescriptions to family members of children and adolescents and adults in general significantly increased during this period. The most common opioid prescriptions to children and adolescents in 2012 were codeine, hydrocodone, and oxycodone. Using multivariate logistic regression models, the white non-Hispanic race, older age, health insurance, and parent-reported fair to poor general health were associated with higher rates of opioid prescriptions in children and adolescents. Our main finding was that although the rates of opioid prescriptions have increased among adults in the United States, the rates have not changed among children and adolescents. Recent epidemiologic association studies have identified a strong link between increased opioid prescriptions and increased rates of opioid misuse and abuse in adults. Future studies should assess the association between adult opioid prescriptions and children or adolescent opioid misuse.

Patterns of Storage, Use, and Disposal of Opioids Among Cancer Outpatients

PubMed Central

de la Cruz, Maxine; Rodriguez, Eden Mae; Thames, Jessica; Wu, Jimin; Chisholm, Gary; Liu, Diane; Frisbee-Hume, Susan; Yennurajalingam, Sriram; Hui, David; Cantu, Hilda; Marin, Alejandra; Gayle, Vicki; Shinn, Nancy; Xu, Angela; Williams, Janet; Bruera, Eduardo

2014-01-01

Purpose. Improper storage, use, and disposal of prescribed opioids can lead to diversion or accidental poisoning. Our objective was to determine the patterns of storage, utilization, and disposal of opioids among cancer outpatients. Patients and Methods. We surveyed 300 adult cancer outpatients receiving opioids in our supportive care center and collected information regarding opioid use, storage, and disposal, along with scores on the CAGE (cut down, annoyed, guilty, eye-opener) alcoholism screening questionnaire. Unsafe use was defined as sharing or losing opioids; unsafe storage was defined as storing opioids in plain sight. Results. The median age was 57 years. CAGE was positive in 58 of 300 patients (19%), and 26 (9%) had a history of illicit drug use. Fifty-six (19%) stored opioids in plain sight, 208 (69%) kept opioids hidden but unlocked, and only 28 (9%) locked their opioids. CAGE-positive patients (p = .007) and those with a history of illicit drug use (p = .0002) or smoking (p = .03) were more likely to lock their opioids. Seventy-eight (26%) reported unsafe use by sharing (9%) or losing (17%) their opioids. Patients who were never married or single (odds ratio: 2.92; 95% confidence interval: 1.48–5.77; p = .006), were CAGE positive (40% vs. 21%; p = .003), or had a history of illicit drug use (42% vs. 23%; p = .031) were more likely to use opioids unsafely. Overall, 223 of 300 patients (74%) were unaware of proper opioid disposal methods, and 138 (46%) had unused opioids at home. Conclusion. A large proportion of cancer patients improperly and unsafely use, store, and dispose of opioids, highlighting the need for establishment of easily accessed patient education and drug take-back programs. PMID:24868100

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.

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 ...

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

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

PubMed

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

2013-11-01

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

Opioid Deaths in Milwaukee County, Wisconsin 2013-2017: The Primacy of Heroin and Fentanyl.

PubMed

Peterson, Brian L; Schreiber, Sara; Fumo, Nicole; Brooke Lerner, E

2018-04-23

Heroin and fentanyl are the overwhelming and increasing cause of opioid deaths in Milwaukee County, Wisconsin. We reviewed all drug and opioid deaths from 2013 to 2017 to delineate the specific opioid drugs involved and changes in their incidence. From 2013 to 2017, 980 deaths were due to opioids, rising from 184 in 2013 to 337 in 2017. In 2017, opioid deaths exceeded combined non-natural deaths from homicide and suicide. Illicit heroin and fentanyl/analogs caused 84% of opioid deaths and 80% of drug deaths, with no increase in deaths due to oral prescription drugs such as oxycodone and hydrocodone. Any approach to decreasing this dramatic increase in opioid deaths should first focus on interdicting the supply and cheap availability of these illicit opioids. Fentanyl and its analogs represent the most deadly opioids and the greatest threat to human life in our population. © 2018 American Academy of Forensic Sciences.

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.

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.

Unused opioid analgesics and drug disposal following outpatient dental surgery: A randomized controlled trial.

PubMed

Maughan, Brandon C; Hersh, Elliot V; Shofer, Frances S; Wanner, Kathryn J; Archer, Elizabeth; Carrasco, Lee R; Rhodes, Karin V

2016-11-01

Individuals who abuse prescription opioids often use leftover pills that were prescribed for friends or family members. Dental surgery has been identified as a common source of opioid prescriptions. We measured rates of used and unused opioids after dental surgery for a pilot program to promote safe drug disposal. We conducted a randomized controlled trial of opioid use patterns among patients undergoing surgical tooth extraction at a university-affiliated oral surgery practice. The primary objective was to describe opioid prescribing and consumption patterns, with the number of unused opioid pills remaining on postoperative day 21 serving as the primary outcome. The secondary aim was to measure the effect of a behavioral intervention (informing patients of a pharmacy-based opioid disposal program) on the proportion of patients who disposed or reported intent to dispose of unused opioids. (NCT02814305) Results: We enrolled 79 patients, of whom 72 filled opioid prescriptions. On average, patients received 28 opioid pills and had 15 pills (54%) left over, for a total of 1010 unused pills among the cohort. The behavioral intervention was associated with a 22% absolute increase in the proportion of patients who disposed or reported intent to dispose of unused opioids (Fisher's exact p=0.11). Fifty-four percent of opioids prescribed in this pilot study were not used. The pharmacy-based drug disposal intervention showed a robust effect size but did not achieve statistical significance. Dentists and oral surgeons could potentially reduce opioid diversion by moderately reducing the quantity of opioid analgesics prescribed after surgery. Copyright © 2016. Published by Elsevier Ireland Ltd.

Trends in Medical and Nonmedical Use of Prescription Opioids Among US Adolescents: 1976-2015.

PubMed

McCabe, Sean Esteban; West, Brady T; Veliz, Phil; McCabe, Vita V; Stoddard, Sarah A; Boyd, Carol J

2017-04-01

Most US studies of national trends in medical and nonmedical use of prescription opioids have focused on adults. Given the limited understanding in these trends among adolescents, we examine national trends in the medical and nonmedical use of prescription opioids among high school seniors between 1976 and 2015. The data used for the study come from the Monitoring the Future study of adolescents. Forty cohorts of nationally representative samples of high school seniors (modal age 18) were used to examine self-reported medical and nonmedical use of prescription opioids. Lifetime prevalence of medical use of prescription opioids peaked in both 1989 and 2002 and remained stable until a recent decline from 2013 through 2015. Lifetime nonmedical use of prescription opioids was less prevalent and highly correlated with medical use of prescription opioids over this 40-year period. Adolescents who reported both medical and nonmedical use of prescription opioids were more likely to indicate medical use of prescription opioids before initiating nonmedical use. Prescription opioid exposure is common among US adolescents. Long-term trends indicate that one-fourth of high school seniors self-reported medical or nonmedical use of prescription opioids. Medical and nonmedical use of prescription opioids has declined recently and remained highly correlated over the past 4 decades. Sociodemographic differences and risky patterns involving medical and nonmedical use of prescription opioids should be taken into consideration in clinical practice to improve opioid analgesic prescribing and reduce adverse consequences associated with prescription opioid use among adolescents. Copyright © 2017 by the American Academy of Pediatrics.

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

Specialty of prescribers associated with prescription opioid fatalities in Utah, 2002-2010.

PubMed

Porucznik, Christina A; Johnson, Erin M; Rolfs, Robert T; Sauer, Brian C

2014-01-01

Opioid adverse events are widespread, and deaths have been directly attributed to opioids prescribed by medical professionals. Little information exists on the amount of opioids various medical specialties prescribe and the opioid fatality rate that would be expected if prescription opioid-related deaths were independent of medical specialty. To compute the incidence of prescription opioid fatalities by medical specialty in Utah and to calculate the attributable risk (AR) of opioid fatality by medical specialty. Prevalence database study design linking the Utah Controlled Substance Database (CSD) for prescribing data with the Utah Medical Examiner data to identify prescription opioid fatalities. AR were calculated for each medical specialty and year. Opioid prescriptions are common with 23,302,892 recorded in the CSD for 2002-2010, 0.64% of which were associated with a fatality. We attached specialty to 90.2% of opioid prescriptions. Family medicine and internal medicine physicians wrote the largest proportion of prescriptions (24.1% and 10.8%) and were associated with the greatest number of prescription opioid fatalities. The number of active prescriptions at time of death decreased each year. The AR of fatality by provider specialty varied each year with some specialties, such as pain medicine and anesthesiology, consistently associated with more fatalities per 1,000 opioid prescriptions than internal medicine physicians the same year. Primary care providers were the most frequent prescribers and the most often associated with opioid fatalities and should be targeted for education about safe prescribing along with specialties that prescribe less frequently but are associated with a positive AR for opioid fatality. Wiley Periodicals, Inc.

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.

The risks of opioid treatment: Perspectives of primary care practitioners and patients from safety-net clinics

PubMed Central

Hurstak, Emily E.; Kushel, Margot; Chang, Jamie; Ceasar, Rachel; Zamora, Kara; Miaskowski, Christine; Knight, Kelly

2017-01-01

Background Patients with a history of substance use are more likely than those without substance use to experience chronic noncancer pain (CNCP), to be prescribed opioids, and to experience opioid misuse or overdose. Primary care practitioners (PCPs) in safety-net settings care for low-income patients with CNCP and substance use, usually without specialist consultation. To inform communication related to opioid risk, we explored PCPs’ and patients’ perceptions of the risks of chronic opioid therapy. Methods We conducted semistructured interviews with 23 PCPs and 46 of their patients, who had a history of CNCP and substance use. We recruited from 6 safety-net health care settings in the San Francisco Bay Area. We transcribed interviews verbatim and analyzed transcripts using grounded theory methodology. Results (1) PCPs feared harming patients and the community by opioid prescribing. PCPs emphasized fear of opioid overdose. (2) Patients did not highlight concerns about the adverse health consequences of opioids, except for addiction. (3) Both patients and PCPs were concerned about PCPs’ medicolegal risks related to opioid prescribing. (4) Patients reported feeling stigmatized by policies aimed at reducing opioid misuse. Conclusion We identified differences in how clinicians and patients perceive opioid risk. To improve the informed consent process for opioid therapy, patients and PCPs need to have a shared understanding of the risks of opioids and engage in discussions that promote patient autonomy and safety. As clinics implement opioid prescribing policies, clinicians must develop effective communication strategies in order to educate patients about opioid risks and decrease patients’ experiences of stigma and discrimination. PMID:28394752

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

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

PubMed Central

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

2016-01-01

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

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.

Effectiveness of ketamine as an adjuvant to opioid-based therapy in decreasing pain associated with opioid tolerance in adults undergoing orthopedic surgery: a systematic review protocol.

PubMed

Bennett, Marsha; Bonanno, Laura; Kuhn, William

2016-10-01

The objective of this systematic review is to examine the best available evidence on the clinical effectiveness of ketamine as an adjuvant to opioid-based therapy versus opioid-based therapy alone in decreasing perioperative pain associated with opioid tolerance in adult patients, aged 18-70 years, undergoing orthopedic surgical procedures.The following question guides the systematic review: does the administration of ketamine as an adjuvant to opioid-based therapy, compared to opioid-based therapy alone, improve perioperative pain relief in opioid-tolerant adult patients undergoing orthopedic surgical procedures?

The Canary in the Coal Mine Tweets: Social Media Reveals Public Perceptions of Non-Medical Use of Opioids.

PubMed

Chan, Brian; Lopez, Andrea; Sarkar, Urmimala

2015-01-01

Non-medical prescription opioid use is a growing public health concern. Social media is an emerging tool to understand health attitudes, beliefs, and behaviors. We retrieved a sample of publicly available Twitter messages in early 2014, using common opioid medication names and slang search terms. We used content analysis to code messages by user, context of message (personal vs general experiences), and key content themes. We reviewed 540 messages, of which 375 (69%) messages were related to opioid behaviors. Of these, 316 (84%) originated from individual user accounts; 125 messages expressed personal experience with opioids. The majority of personal messages referenced using opioids to obtain a "high", use for sleep, or other non-intended use (87,70%). General attitudes regarding opioid use included positive sentiment (52, 27%), comments on others peoples opioid use (57, 30%), and messages containing public health information or links (48, 25%). In a sample of social media messages mentioning opioid medications, the most common theme amongst English users related to various forms of opioid misuse. Social media can provide insights into the types of misuse of opioids that might aid public health efforts to reduce non-medical opioid use.

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 necessary to thoroughly examine IT opioid dose escalation and the effects of addition of bupivacaine to IT opioids. Blunting IT opioid dose escalation may be a beneficial long-term effect of IT bupivacaine. Wiley Periodicals, Inc.

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

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.

In vivo neurochemical evidence that delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, inhibit acetylcholine efflux in the nucleus accumbens of freely moving rats.

PubMed

Kiguchi, Yuri; Aono, Yuri; Watanabe, Yuriko; Yamamoto-Nemoto, Seiko; Shimizu, Kunihiko; Shimizu, Takehiko; Kosuge, Yasuhiro; Waddington, John L; Ishige, Kumiko; Ito, Yoshihisa; Saigusa, Tadashi

2016-10-15

Cholinergic neurons in the nucleus accumbens express delta- and mu-opioid receptors that are thought to inhibit neural activity. Delta- and mu-opioid receptors are divided into delta1- and delta2-opioid receptors and mu1- and mu2-opioid receptors, respectively. We analysed the roles of delta- and mu-opioid receptor subtypes in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. Other than naloxonazine, given intraperitoneally, delta- and mu-opioid receptor ligands were administered intracerebrally through the dialysis probe. Doses of these compounds indicate total amount (mol) over an infusion time of 30-60min. To monitor basal acetylcholine, a low concentration of physostigmine (50nM) was added to the perfusate. The delta1-opioid receptor agonist DPDPE (3 and 300pmol) and delta2-opioid receptor agonist deltorphin II (3 and 30pmol) decreased accumbal acetylcholine in a dose-related manner. DPDPE (300pmol)- and deltorphin II (3pmol)-induced reductions in acetylcholine were each inhibited by the delta1-opioid receptor antagonist BNTX (0.3pmol) and delta2-opioid receptor antagonist naltriben (15pmol), respectively. The mu-opioid receptor agonists endomorphin-1 and endomorphin-2 (6 and 30nmol) decreased acetylcholine in a dose-related manner. Endomorphin-1- and endomorphin-2 (30nmol)-induced reductions in acetylcholine were prevented by the mu-opioid receptor antagonist CTOP (3nmol). The mu1-opioid receptor antagonist naloxonazine (15mg/kg ip), which inhibits endomorphin-1 (15nmol)-induced accumbal dopamine efflux, did not alter endomorphin-1- or endomorphin-2 (30nmol)-induced reductions in acetylcholine efflux. This study provides in vivo evidence for delta1-, delta2- and mu2-opioid receptors, but not mu1-opioid receptors, that inhibit accumbal cholinergic neural activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014.

PubMed

Rudd, Rose A; Aleshire, Noah; Zibbell, Jon E; Gladden, R Matthew

2016-01-01

The United States is experiencing an epidemic of drug overdose (poisoning) deaths. Since 2000, the rate of deaths from drug overdoses has increased 137%, including a 200% increase in the rate of overdose deaths involving opioids (opioid pain relievers and heroin). CDC analyzed recent multiple cause-of-death mortality data to examine current trends and characteristics of drug overdose deaths, including the types of opioids associated with drug overdose deaths. During 2014, a total of 47,055 drug overdose deaths occurred in the United States, representing a 1-year increase of 6.5%, from 13.8 per 100,000 persons in 2013 to 14.7 per 100,000 persons in 2014. The rate of drug overdose deaths increased significantly for both sexes, persons aged 25-44 years and ≥55 years, non-Hispanic whites and non-Hispanic blacks, and in the Northeastern, Midwestern, and Southern regions of the United States. Rates of opioid overdose deaths also increased significantly, from 7.9 per 100,000 in 2013 to 9.0 per 100,000 in 2014, a 14% increase. Historically, CDC has programmatically characterized all opioid pain reliever deaths (natural and semisynthetic opioids, methadone, and other synthetic opioids) as "prescription" opioid overdoses (1). Between 2013 and 2014, the age-adjusted rate of death involving methadone remained unchanged; however, the age-adjusted rate of death involving natural and semisynthetic opioid pain relievers, heroin, and synthetic opioids, other than methadone (e.g., fentanyl) increased 9%, 26%, and 80%, respectively. The sharp increase in deaths involving synthetic opioids, other than methadone, in 2014 coincided with law enforcement reports of increased availability of illicitly manufactured fentanyl, a synthetic opioid; however, illicitly manufactured fentanyl cannot be distinguished from prescription fentanyl in death certificate data. These findings indicate that the opioid overdose epidemic is worsening. There is a need for continued action to prevent opioid abuse, dependence, and death, improve treatment capacity for opioid use disorders, and reduce the supply of illicit opioids, particularly heroin and illicit fentanyl.

Opioid utilization among pediatric patients treated for newly diagnosed acute myeloid leukemia

PubMed Central

Miller, Tamara P.; Seif, Alix E.; Li, Yimei; Huang, Yuan-Shung V.; Fisher, Brian T.; Aplenc, Richard

2018-01-01

Purpose A cohort of pediatric patients with AML treated at hospitals contributing to the Pediatric Health Information System was used to evaluate differences in opioid utilization by sex, age, race, and insurance. Methods Billing data were used to compute the prevalence of opioid exposure and to quantify rates of utilization among those exposed to opioids as days of use per 1000 inpatient days. Multivariable regressions were used to compare opioid prevalence, and rates of utilization among those exposed. Results On average across courses, 95.2% of patients were exposed to analgesics, 84.7% were exposed to non-opioid analgesics and 77.7% were exposed to opioids. The proportion of opioid-exposed patients increased with age, but did not differ by gender, race, or insurance status. Analyses limited to patients exposed to opioids revealed modest differences in days of opioid use among female patients (adjusted rate ratio (aRR) = 1.19, 95% CI: 1.11, 1.28), patients <1 year (aRR = 1.37, 95% CI: 1.21, 1.55) or ≥10 years of age (aRR = 1.63, 95% CI: 1.46, 1.82), whereas Asian patients received fewer days of opioids compared with white patients (aRR = 0.76, 95% CI: 0.61, 0.95). There was moderate hospital-level variability in both the prevalence of opioid utilization overall and preference for specific opioid medications. There was greater inconsistency in practice concerning choices for supplemental and alternative opioids than in first-line opioid utilization. Conclusion Additional work is needed to discern whether observed differences in opioid utilization by age and race reflect a difference in treatment or a difference in the experience of pain. Future studies should also explore the factors which guide decisions on opioid selections in an attempt to explain the variability across institutions. PMID:29420604

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.

Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery.

PubMed

Sultana, Adrian; Torres, David; Schumann, Roman

2017-12-01

Opioid-free anaesthesia (OFA) is a technique where no intraoperative systemic, neuraxial or intracavitary opioid is administered with the anaesthetic. Opioid-free analgesia similarly avoids opioids in the perioperative period. There are many compelling reasons to avoid opioids in the surgical population. A number of case reports and, increasingly, prospective studies from all over the world support its benefits, especially in the morbidly obese population with or without sleep apnoea. A derivative technique is opioid sparing, where the same techniques are used but some opioid use is allowed. This chapter is a review of the current knowledge regarding opioid-free or low-dose opioid anaesthetic and analgesic techniques for the following special populations: obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, acute/chronic opioid addiction and cancer surgery. Practical aspects include sympatholysis, analgesia and Minimum Alveolar Concentration (MAC) reduction with dexmedetomidine; analgesia with low-dose ketamine and co-anaesthesia; and sympatholysis with intravenous lignocaine. Non-opioid adjuvants such as NSAIDS, paracetamol, magnesium, local anaesthetic infiltration and high-dose steroids are added in the perioperative period to further achieve co-analgesia. Loco-regional anaesthesia and analgesia are also maximised. It remains to be seen whether OFA and early postoperative analgesia, which similarly avoids opioids, can prevent the development of hyperalgesia and persistent postoperative pain syndromes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015.

PubMed

Rudd, Rose A; Seth, Puja; David, Felicita; Scholl, Lawrence

2016-12-30

The U.S. opioid epidemic is continuing, and drug overdose deaths nearly tripled during 1999-2014. Among 47,055 drug overdose deaths that occurred in 2014 in the United States, 28,647 (60.9%) involved an opioid (1). Illicit opioids are contributing to the increase in opioid overdose deaths (2,3). In an effort to target prevention strategies to address the rapidly changing epidemic, CDC examined overall drug overdose death rates during 2010-2015 and opioid overdose death rates during 2014-2015 by subcategories (natural/semisynthetic opioids, methadone, heroin, and synthetic opioids other than methadone).* Rates were stratified by demographics, region, and by 28 states with high quality reporting on death certificates of specific drugs involved in overdose deaths. During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states. A multifaceted, collaborative public health and law enforcement approach is urgently needed. Response efforts include implementing the CDC Guideline for Prescribing Opioids for Chronic Pain (4), improving access to and use of prescription drug monitoring programs, enhancing naloxone distribution and other harm reduction approaches, increasing opioid use disorder treatment capacity, improving linkage into treatment, and supporting law enforcement strategies to reduce the illicit opioid supply.

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

PubMed Central

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

2015-01-01

Background The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown. Methods and Findings We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy. Conclusions Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated. PMID:26291716

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.

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

PubMed

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

2015-09-01

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

Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats.

PubMed

Richebé, Philippe; Rivalan, Bertrand; Rivat, Cyril; Laulin, Jean-Paul; Janvier, Gérard; Maurette, Pierre; Simonnet, Guy

2009-02-01

Opioids are widely used for anesthesia but paradoxically induce postoperative pain hypersensitivity via N-methyl-D: -aspartate (NMDA) receptor modulation. Sevoflurane effects on opioid-induced hyperalgesia have not been yet evaluated in vivo. Nevertheless, some experimental in vitro studies reported anti-NMDA receptor properties for sevoflurane. The aim of this study was to evaluate sevoflurane effects on fentanyl-induced hyperalgesia in opioid-naive rats and in rats with inflammatory pain. Sevoflurane effects on hyperalgesia were evaluated in Sprague-Dawley rats: opioid-naive rats, rats treated with fentanyl (4 x 60 microg kg(-1)) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 x 60 microg kg(-1)). On day zero, subcutaneous fentanyl injections were administered and inflammatory pain was induced with one carrageenan injection in one hind paw. Rats were exposed to low concentrations of sevoflurane (1.0 or 1.5%) on day zero prior to fentanyl injections and inflammatory pain induction, and for the duration of the fentanyl analgesic effect. The nociceptive threshold (Randall-Selitto test) was evaluated daily for 7 days. On day seven, naloxone was injected and the nociceptive threshold was assessed 5 min later. In rats without inflammatory pain but treated with fentanyl on day zero, sevoflurane 1.0% reversed the early (day zero) and long-lasting (day zero to day three) hyperalgesia classically described after high-doses of fentanyl (P < 0.05). This sevoflurane concentration antagonized the hyperalgesia induced by naloxone on day seven (P = 0.33). In a second experiment in rats with inflammatory pain, exposure to low concentrations of sevoflurane (1.0 and 1.5%) did not reduce fentanyl-induced hyperalgesia (P > 0.05), but nevertheless antagonized the naloxone induced hyperalgesia on day seven (P = 0.061). Relatively low sevoflurane concentrations (1.0%) reverse fentanyl-induced hyperalgesia in rats without inflammatory pain. Nevertheless, the lack of effect of sevoflurane concentrations of 1.0% and 1.5% to oppose hyperalgesia following high-dose fentanyl and inflammatory pain suggests that sevoflurane anti-hyperalgesic properties are weak.

Opioid Tapering in Fibromyalgia Patients: Experience from an Interdisciplinary Pain Rehabilitation Program.

PubMed

Cunningham, Julie L; Evans, Michele M; King, Susan M; Gehin, Jessica M; Loukianova, Larissa L

2016-09-01

Despite current guideline recommendations against the use of opioids for the treatment of fibromyalgia pain, opioid use is reported in approximately 30% of the patient population. There is a lack of information describing the process and results of tapering of chronic opioids. The purpose of this study is to describe opioid tapering and withdrawal symptoms in fibromyalgia patients on opioids. This retrospective research study included a baseline analysis of 159 patients consecutively admitted to the Mayo Clinic Pain Rehabilitation Center from 2006 through 2012 with a pain diagnosis of fibromyalgia completing a 3-week outpatient interdisciplinary pain rehabilitation program. Opioid tapering analysis included 55 (35%) patients using daily opioids. Opioid tapering was individualized to each patient based on interdisciplinary pain rehabilitation team determination. Opioid withdrawal symptoms were assessed daily, utilizing the Clinical Opioid Withdrawal Scale. Patients taking daily opioids had a morphine equivalent mean dose of 99 mg/day. Patients on < 100 mg/day were tapered off over a mean of 10 days compared with patients on > 200 mg/day over a mean of 28 days (P < 0.001). Differences in peak withdrawal symptoms were not statistically significant based on the mean equivalent dose (P = 22). Patients taking opioids for <2 years did not differ in length of tapering (P =0.63) or peak COWS score (P =0.80) compared with >2 years duration. Patients had significant improvements in pain-related measures including numeric pain scores, depression catastrophizing, health perception, interference with life, and perceived life control at program completion. Fibromyalgia patients on higher doses of opioids were tapered off over a longer period of time but no differences in withdrawal symptoms were seen based on opioid dose. Duration of opioid use did not affect the time to complete opioid taper or withdrawal symptoms. Despite opioid tapering, pain-related measures improved at the completion of the rehabilitation program. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Concomitant use of opioid medications with triptans or serotonergic antidepressants in US office-based physician visits.

PubMed

Molina, Kyle C; Fairman, Kathleen A; Sclar, David A

2018-01-01

Opioids are not recommended for routine treatment of migraine because their benefits are outweighed by risks of medication overuse headache and abuse/dependence. A March 2016 US Food and Drug Administration (FDA) safety communication warned of the risk of serotonin syndrome from using opioids concomitantly with 5-hydroxytryptamine receptor agonists (triptans) or serotonergic antidepressants: selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Epidemiological information about co-prescribing of these medications is limited. The objective of this study was to estimate the nationwide prevalence of co-prescribing of an opioid with a serotonergic antidepressant and/or triptan in US office-based physician visits made by 1) all patients and 2) patients diagnosed with migraine. National Ambulatory Medical Care Survey (NAMCS) data were obtained for 2013 and 2014. Physician office visits that included the new or continued prescribing of ≥1 opioid medication with a triptan or an SSRI/SNRI were identified. Co-prescribed opioids were stratified by agent to determine the proportion of co-prescriptions with opioids posing a higher risk of serotonergic agonism (meperidine, tapentadol, and tramadol). Of an annualized mean 903.6 million office-based physician visits in 2013-2014, 17.7 million (2.0% of all US visits) resulted in the prescribing of ≥1 opioid medication with a triptan or an SSRI/SNRI. Opioid-SSRI/SNRI was co-prescribed in 16,044,721 visits, while opioid-triptan was co-prescribed in 1,622,827 visits. One-fifth of opioid co-prescribing was attributable to higher-risk opioids, predominantly tramadol (18.6% of opioid-SSRI/SNRI, 21.8% of opioid-triptan). Of 7,672,193 visits for patients diagnosed with migraine, 16.3% included opioid prescribing and 2.0% included co-prescribed opioid-triptan. During a period approximately 2 years prior to an FDA warning about the risk of serotonin syndrome from opioid-SSRI/SNRI or opioid-triptan co-prescribing, use of these combinations was common in the USA. Studies on prescribing patterns following the March 2016 warning, and on the risk of serotonin syndrome associated with these co-prescriptions, are needed.

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.

Suicide by means of opioid overdose in patients with chronic pain.

PubMed

Madadi, Parvaz; Persaud, Nav

2014-11-01

Deaths from prescription opioid use continue to rise in North America. The main focus to date has been developing strategies to prevent nonintentional (accidental) fatalities, which constitute the majority of opioid deaths across all jurisdictions. Often overlooked is the complex group of individuals whose cause of death was suicide by opioid overdose. Although most opioid prescribing tools focus on identifying risk factors for potential abuse, diversion, and propensity for opioid addiction, physicians who consider prescribing opioids should also screen and optimize chronic pain treatment for patients at risk for suicide.

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.

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

Mood/Anxiety disorders and their association with non-medical prescription opioid use and prescription opioid use disorder: longitudinal evidence from the National Epidemiologic Study on Alcohol and Related Conditions

PubMed Central

Martins, Silvia S.; Fenton, Miriam C.; Keyes, Katherine M.; Blanco, Carlos; Zhu, Hong; Storr, Carla L.

2012-01-01

Objective Nonmedical use of prescription opioids represents a national public health concern of growing importance. Mood and anxiety disorders are highly associated with nonmedical prescription opioid use. The authors examined longitudinal associations between nonmedical prescription opioid use and opioid disorder due to nonmedical opioid use with mood/anxiety disorders in a national sample, examining evidence for precipitation, self-medication and general shared vulnerability as pathways between disorders. Method Data were drawn from face-to-face surveys of 34,653 adult participants in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic regression models explored the temporal sequence and evidence for the hypothesized pathways. Results Baseline lifetime nonmedical prescription opioid use was associated with incidence of any mood disorder, major depressive disorder (MDD), bipolar disorder, any anxiety disorder, and generalized anxiety disorder (GAD in Wave 2, adjusted for baseline demographics, other substance use, and comorbid mood/anxiety disorders). Lifetime opioid disorder was not associated with any incident mood/anxiety disorders. All baseline lifetime mood disorders and GAD were associated with incident nonmedical prescription opioid use at follow-up, adjusted for demographics, comorbid mood/anxiety disorders, and other substance use. Baseline lifetime mood disorders, MDD, dysthymia, and panic disorder, were associated with incident opioid disorder due to nonmedical prescription opioid use at follow-up, adjusted for the same covariates. Conclusions These results suggest that preciptiation, self-medication as well as shared vulnerability are all viable pathways between nonmedical prescription opioid use and opioid disorder due to nonmedical opioid use with mood/anxiety disorders. PMID:21999943

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.

Enhancing Risk Assessment in Patients Receiving Chronic Opioid Analgesic Therapy Using Natural Language Processing.

PubMed

Haller, Irina V; Renier, Colleen M; Juusola, Mitch; Hitz, Paul; Steffen, William; Asmus, Michael J; Craig, Terri; Mardekian, Jack; Masters, Elizabeth T; Elliott, Thomas E

2017-10-01

Clinical guidelines for the use of opioids in chronic noncancer pain recommend assessing risk for aberrant drug-related behaviors prior to initiating opioid therapy. Despite recent dramatic increases in prescription opioid misuse and abuse, use of screening tools by clinicians continues to be underutilized. This research evaluated natural language processing (NLP) together with other data extraction techniques for risk assessment of patients considered for opioid therapy as a means of predicting opioid abuse. Using a retrospective cohort of 3,668 chronic noncancer pain patients with at least one opioid agreement between January 1, 2007, and December 31, 2012, we examined the availability of electronic health record structured and unstructured data to populate the Opioid Risk Tool (ORT) and other selected outcomes. Clinician-documented opioid agreement violations in the clinical notes were determined using NLP techniques followed by manual review of the notes. Confirmed through manual review, the NLP algorithm had 96.1% sensitivity, 92.8% specificity, and 92.6% positive predictive value in identifying opioid agreement violation. At the time of most recent opioid agreement, automated ORT identified 42.8% of patients as at low risk, 28.2% as at moderate risk, and 29.0% as at high risk for opioid abuse. During a year following the agreement, 22.5% of patients had opioid agreement violations. Patients classified as high risk were three times more likely to violate opioid agreements compared with those with low/moderate risk. Our findings suggest that NLP techniques have potential utility to support clinicians in screening chronic noncancer pain patients considered for long-term opioid therapy. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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

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.

Opioid activation of Toll-Like receptor 4 contributes to drug reinforcement

PubMed Central

Hutchinson, M.R.; Northcutt, A.L.; Hiranita, T.; Wang, X.; Lewis, S.; Thomas, J.; van Steeg, K.; Kopajtic, T.A.; Loram, L.; Sfregola, C.; Galer, E.; Miles, N.E.; Bland, S.T.; Amat, J.; Rozeske, R.R.; Maslanik, T.; Chapman, T.; Strand, K.; Fleshner, M.; Bachtell, R.K.; Somogyi, A.A.; Yin, H.; Katz, J.L.; Rice, K.C.; Maier, S.F.; Watkins, L.R.

2012-01-01

Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, Toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the non-opioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knockouts of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4 −/− mice had reduced oxycodone-induced p38 and JNK phosphorylation, whilst displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system which amplifies opioid-induced elevations in extracellular dopamine levels and therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward. PMID:22895704

AN EXAMINATION OF CLAIMS-BASED PREDICTORS OF OVERDOSE FROM A LARGE MEDICAID PROGRAM

PubMed Central

Cochran, Gerald; Gordon, Adam J.; Lo-Ciganic, Wei-Hsuan; Gellad, Walid F.; Frazier, Winfred; Lobo, Carroline; Chang, Joyce; Zheng, Ping; Donohue, Julie M.

2016-01-01

Background Health systems may play an important role in identification of patients at-risk of opioid medication overdose. However, standard measures for identifying overdose risk in administrative data do not exist. Objective Examine the association between opioid medication overdose and 2 validated measures of non-medical use of prescription opioids within claims data. Research Design A longitudinal retrospective cohort study that estimated associations between overdose and non-medical use. Subjects Adult Pennsylvania Medicaid program 2007-2012 patients initiating opioid treatment who were: non-dual eligible, without cancer diagnosis, and not in long-term care facilities or receiving hospice. Measures Overdose (International Classification of Disease, 9th edition, prescription opioid poisonings codes), opioid abuse (opioid use disorder diagnosis while possessing an opioid prescription), opioid misuse (a composite indicator of number of opioid prescribers, number of pharmacies, and days supplied), and dose exposure during opioid treatment episodes. Results A total of 372,347 Medicaid enrollees with 583,013 new opioid treatment episodes were included in the cohort. Opioid overdose was higher among those with abuse (1.5%) compared to those without (0.2%, p<0.001). Overdose was higher among those with probable (1.8%) and possible (0.9%) misuse compared to those without (0.2%, p<0.001). Abuse (adjusted rate ratio [ARR]=1.52, 95% CI=1.10-2.10), probable misuse (ARR=1.98, 95% CI=1.46-2.67), and possible misuse (ARR=1.76, 95% CI=1.48-2.09) were associated with significantly more events of opioid medication overdose compared to those without. Conclusions Claims-based measures can be employed by health systems to identify individuals at-risk of overdose who can be targeted for restrictions on opioid prescribing, dispensing, or referral to treatment. PMID:27984346

Sex differences in opioid use and medical issues during buprenorphine/naloxone treatment.

PubMed

Barbosa-Leiker, Celestina; McPherson, Sterling; Layton, Matthew E; Burduli, Ekaterina; Roll, John M; Ling, Walter

2018-01-01

There are sex differences in buprenorphine/naloxone clinical trials for opioid use. While women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment. To test for sex differences in opioid use during a buprenorphine/naloxone clinical trial and determine if sex differences exist in the associations between addiction-related problem areas and opioid use over the course of the trial. This secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003 examined sex differences (men = 347, women = 169) in opioid-positive samples in a randomized clinical trial comparing 7-day vs. 28-day buprenorphine/naloxone tapering strategies. Addiction-related problem areas were defined by Addiction Severity-Lite (ASI-L) domain composite scores. Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial (B = .33, p = .01) and medical issues were positively related to submitting an opioid-positive sample during treatment for women (B = 1.67, p = .01). No ASI-L domain composite score was associated with opioid-positive samples during treatment for men. Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial, and medical issues predicted opioid use during treatment for women but not men. Complementary treatment for medical problems during opioid replacement therapy may benefit women.

Educational intervention for physicians to address the risk of opioid abuse.

PubMed

Pasquale, Margaret K; Sheer, Richard L; Mardekian, Jack; Masters, Elizabeth T; Patel, Nick C; Hurwitch, Amy R; Weber, Jennifer J; Jorga, Anamaria; Roland, Carl L

To evaluate the impact of a pilot intervention for physicians to support their treatment of patients at risk for opioid abuse. Patients at risk for opioid abuse enrolled in Medicare plans were identified from July 1, 2012 to April 30, 2014 (N = 2,391), based on a published predictive model, and linked to 4,353 opioid-prescribing physicians. Patient-physician clusters were randomly assigned to one of four interventions using factorial design. Physicians received one of the following: Arm 1, patient information; Arm 2, links to educational materials for diagnosis and management of pain; Arm 3, both patient information and links to educational materials; or Arm 4, no communication. Difference-in-difference analyses compared opioid and pain prescriptions, chronic high-dose opioid use, uncoordinated opioid use, and opioid-related emergency department (ED) visits. Logistic regression compared diagnosis of opioid abuse between cases and controls postindex. Mailings had no significant impact on numbers of opioid or pain medications filled, chronic high-dose opioid use, uncoordinated opioid use, ED visits, or rate of diagnosed opioid abuse. Relative to Arm 4, odds ratios (95% CI) for diagnosed opioid abuse were Arm 1, 0.95(0.63-1.42); Arm 2, 0.83(0.55-1.27); Arm 3, 0.72(0.46-1.13). While 84.7 percent had ≥1 psychiatric diagnoses during preindex (p = 0.89 between arms), only 9.5 percent had ≥1 visit with mental health specialists (p = 0.53 between arms). Although this intervention did not affect pain-related outcomes, future interventions involving care coordination across primary care and mental health may impact opioid abuse and improve quality of life of patients with pain.

Prescription drug monitoring program data tracking of opioid addiction treatment outcomes in integrated dual diagnosis care involving injectable naltrexone

PubMed Central

Sajid, Ayesha; Whiteman, Aaron; Bell, Richard L.; Greene, Marion S.; Engleman, Eric A.

2016-01-01

Background and Objectives Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university‐affiliated integrated mental health‐addiction treatment clinic. Methods Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long‐acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders. Results There were no group differences post‐injection in treatment days, injections delivered, or treatment service encounters. UDS and PDMP measures of opioid exposures were greater in opioid compared to alcohol‐only patients. Post‐first injection, UDS's positive for opioids declined (p < .05) along with PDMP measures of opioid prescriptions (p < .001), doses (p < .01), types (p < .001), numbers of dispensing prescribers (p < .001) and pharmacies (p < .001). Opioid patients without alcohol disorders showed the best outcomes with 50% to 80% reductions in PDMP‐measures of opioids, down to levels of alcohol‐only patients. Conclusions This study shows PDMP utility for measuring opioid addiction treatment outcomes, supporting the routine use of PDMPs in clinical and research settings. Scientific Significance These findings demonstrate that opioid addiction in patients with complex addictions and mental illnesses comorbidities can show effective treatment responses as measured by PDMP tracking of decreases in opioid prescriptions to those patients. (Am J Addict 2016;25:557–564) PMID:27647699

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.

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.

[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.

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.

Multiple opiate receptors: déjà vu all over again.

PubMed

Pasternak, Gavril W

2004-01-01

The concept of multiple opioid receptors has changed dramatically since their initial proposal by Martin nearly 40 years ago. Three major opioid receptor families have now been proposed: mu, kappa and delta. Most of the opioid analgesics used clinically selectively bind to mu opioid receptors. Yet, clinicians have long appreciated subtle, but significant, differences in their pharmacology. These observations suggested more than one mu opioid receptor mechanism of action and led us to propose multiple mu opioid receptors over 20 years ago based upon a range of pharmacological and receptor binding approaches. A mu opioid receptor, MOR-1, was cloned about a decade ago. More recent studies have now identified a number of splice variants of this clone. These splice variants may help explain the pharmacology of the mu opioids and open interesting directions for future opioid research.

Comparison of early maladaptive schemas and parenting origins in patients with opioid abuse and non-abusers.

PubMed

Jalali, Mohammad Reza; Zargar, Mohammad; Salavati, Mojgan; Kakavand, Ali Reza

2011-01-01

The aim of this study was to examine the difference of early maladaptive schemas and parenting origins in opioid abusers and non-opioid abusers. The early maladaptive schemas and parenting origins were compared in 56 opioid abusers and 56 non-opioids abusers. Schemas were assessed by the Young Schema Questionnaire 3rd (short form); and parenting origins were assessed by the Young Parenting Inventory. Data were analyzed by multivariate analysis of variance (MANOVA). The analysis showed that the means for schemas between opioid abusers and non-opioid abusers were different. Chi square test showed that parenting origins were significantly associated with their related schemas. The early maladaptive schemas and parenting origins in opioid abusers were more than non-opioid abusers; and parenting origins were related to their Corresponding schemas.

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.

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 to a decline in opioid prescribing rates among ODB beneficiaries these guidelines and subsequent Ontario legislation did not result in a significant change in rates of opioid-related hospitalizations. Given the prevalence of high dose opioid prescribing in this population, this suggests that improved strategies and programs for the safe prescribing of long-acting opioids are needed.

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.

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.

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.

The Canary in the Coal Mine Tweets: Social Media Reveals Public Perceptions of Non-Medical Use of Opioids

PubMed Central

Chan, Brian; Lopez, Andrea; Sarkar, Urmimala

2015-01-01

Objective Non-medical prescription opioid use is a growing public health concern. Social media is an emerging tool to understand health attitudes, beliefs, and behaviors. Methods We retrieved a sample of publicly available Twitter messages in early 2014, using common opioid medication names and slang search terms. We used content analysis to code messages by user, context of message (personal vs general experiences), and key content themes. Results We reviewed 540 messages, of which 375 (69%) messages were related to opioid behaviors. Of these, 316 (84%) originated from individual user accounts; 125 messages expressed personal experience with opioids. The majority of personal messages referenced using opioids to obtain a “high”, use for sleep, or other non-intended use (87,70%). General attitudes regarding opioid use included positive sentiment (52, 27%), comments on others peoples opioid use (57, 30%), and messages containing public health information or links (48, 25%). Conclusions In a sample of social media messages mentioning opioid medications, the most common theme amongst English users related to various forms of opioid misuse. Social media can provide insights into the types of misuse of opioids that might aid public health efforts to reduce non-medical opioid use. PMID:26252774

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.

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.

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

The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature.

PubMed

Reisfield, Gary M; Wasan, Ajay D; Jamison, Robert N

2009-11-01

Cannabis is the most widely consumed illicit drug in the United States. Its use, particularly in early initiates, is associated with subsequent development of other drug and alcohol use disorders. The authors examined the prevalence of cannabis use and the association between cannabis use and aberrant opioid-related behaviors in patients prescribed chronic opioid therapy for persistent pain. PubMed was queried for studies of chronic opioid therapy in which aberrant opioid-related behaviors were quantitatively examined and in which cannabis use data (as determined by cannabinoid-positive urine drug tests) were extricable from that of other substances of abuse. The prevalence of cannabis use among patients prescribed chronic opioid therapy in these studies ranged from 6.2% to 39%, compared with 5.8% in the general United States population. Furthermore, cannabis use in chronic opioid patients shows statistically significant associations with present and future aberrant opioid-related behaviors. Cannabis use is prevalent in patients prescribed chronic opioid therapy and is associated with opioid misuse. Further research is necessary to clarify the strength and the nature of the association between cannabis use and opioid misuse, and to address additional questions about the consequences of cannabis use in the context of chronic opioid therapy.

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

PubMed

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

2016-02-01

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

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.

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.

Characteristics of prescribers whose patients shop for opioids: results from a cohort study.

PubMed

Cepeda, M Soledad; Fife, Daniel; Berlin, Jesse A; Mastrogiovanni, Gregory; Yuan, Yingli

2012-01-01

Little is known about the prevalence of opioid shoppers in clinical practices and the relation between prescriber characteristics and the risk of having opioid shoppers. Describe the prevalence of opioid shoppers in prescribers' practices. Assess the relation between prescribers' characteristics and patient opioid shopping behavior. Retrospective cohort study using a large US retail prescription database. Patients with ≥1 opioid dispensing were followed 18 months. These patients' prescribers are the focus of the study. A patient was a "shopper" if he or she had opioid prescriptions written by ≥1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies and a "heavy shopper" if he or she had ≥5 shopping episodes. The proportions of shoppers by prescriber and the proportion of prescribers with ≥1 shopper or heavy shopper were calculated. Among 858,290 opioid prescribers, most (87 percent) had no shoppers and 98 percent had no heavy shoppers. Prescribers who were aged 70-79 years, male, or who prescribed schedule II opioids had an increased likelihood of having shoppers. As the number of patients for whom a prescriber prescribed opioids increased, the proportion of shoppers also increased. Prescribers with 66 or more patients receiving opioids, who represented 25 percent of prescribers, prescribed for 82 percent of all shoppers. The great majority of opioid prescribers appear to have no shoppers in their practice. Any educational program will be more cost effective if targeted to prescribers of schedule II opioids with a large volume of patients requiring opioids.

Trends in Opioid Prescriptions among Part D Medicare Recipients from 2007 to 2012

PubMed Central

Kuo, Yong-Fang; Raji, Mukaila A.; Chen, Nai-Wei; Hasan, Hunaid; Goodwin, James S.

2015-01-01

Background There is growing concern about potential overuse of, and toxicity from, opioid analgesics. No nationally representative study has examined inter-state variations in opioid use and impact of policy on opioid use among older adults. Methods We used national Medicare data from 2007-2012 to assess temporal and geographic trends in rates of opioid prescription and relationship to opioid toxicity and different state regulations in Part D Medicare recipients. We excluded those with a cancer diagnosis. Multilevel, multivariable regression analyses evaluated rates of prolonged prescriptions for schedule II, schedule III, and combination II/III opioid for each state, adjusting for patient characteristics. Results The percent of Part D recipients receiving prescriptions for combined schedule II/III opioid more than 90 days in a year increased from 4.62% in 2007 to 7.35% in 2012. Large variations existed among states in rates of opioid prescriptions: from 2.84% in New York to 10.93% in Utah, in 2012 data. The state variation was larger for schedule III than schedule II. Individual characteristics independently associated with prolonged use included older age, female gender, white race, low-income, living in a lower education area, and comorbidity of drug abuse, rheumatoid arthritis, depression. Only state law regulating pain clinic was associated with reduction of schedule II opioid prescriptions. Prolonged opioid prescription use increased the odds of opioid overdose-related emergency room visits or hospitalization by 60%. Conclusions Analyses of Medicare Part D data demonstrated a substantial growth in opioid prescriptions from 2007 to 2011 and large variation in opioid prescriptions across states. PMID:26522794

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 is to review the recent work done on opioids and their receptor functions. It shall provide an informative reference for better understanding the opioid system and further elucidation of the opioid receptor function from a physiological and pharmacological point of view. PMID:22204322

Frequency of unsafe storage, use, and disposal practices of opioids among cancer patients presenting to the emergency department.

PubMed

Silvestre, Julio; Reddy, Akhila; de la Cruz, Maxine; Wu, Jimin; Liu, Diane; Bruera, Eduardo; Todd, Knox H

2017-12-01

Approximately 75% of prescription opioid abusers obtain the drug from an acquaintance, which may be a consequence of improper opioid storage, use, disposal, and lack of patient education. We aimed to determine the opioid storage, use, and disposal patterns in patients presenting to the emergency department (ED) of a comprehensive cancer center. We surveyed 113 patients receiving opioids for at least 2 months upon presenting to the ED and collected information regarding opioid use, storage, and disposal. Unsafe storage was defined as storing opioids in plain sight, and unsafe use was defined as sharing or losing opioids. The median age was 53 years, 55% were female, 64% were white, and 86% had advanced cancer. Of those surveyed, 36% stored opioids in plain sight, 53% kept them hidden but unlocked, and only 15% locked their opioids. However, 73% agreed that they would use a lockbox if given one. Patients who reported that others had asked them for their pain medications (p = 0.004) and those who would use a lockbox if given one (p = 0.019) were more likely to keep them locked. Some 13 patients (12%) used opioids unsafely by either sharing (5%) or losing (8%) them. Patients who reported being prescribed more pain pills than required (p = 0.032) were more likely to practice unsafe use. Most (78%) were unaware of proper opioid disposal methods, 6% believed they were prescribed more medication than required, and 67% had unused opioids at home. Only 13% previously received education about safe disposal of opioids. Overall, 77% (87) of patients reported unsafe storage, unsafe use, or possessed unused opioids at home. Many cancer patients presenting to the ED improperly and unsafely store, use, or dispose of opioids, thus highlighting a need to investigate the impact of patient education on such practices.

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 reversal of constipation is very encouraging. Hastening postoperative discharge may also be possible. Methylnaltrexone has the potential to prevent or treat opioid-induced peripherally mediated ADEs on bowel dysfunction without interfering with central analgesia. The study of methylnaltrexone leads to a greater understanding of the mechanisms of action of opioid pharmacology.

Use of diagnosis codes for detection of clinically significant opioid poisoning in the emergency department: A retrospective analysis of a surveillance case definition.

PubMed

Reardon, Joseph M; Harmon, Katherine J; Schult, Genevieve C; Staton, Catherine A; Waller, Anna E

2016-02-08

Although fatal opioid poisonings tripled from 1999 to 2008, data describing nonfatal poisonings are rare. Public health authorities are in need of tools to track opioid poisonings in near real time. We determined the utility of ICD-9-CM diagnosis codes for identifying clinically significant opioid poisonings in a state-wide emergency department (ED) surveillance system. We sampled visits from four hospitals from July 2009 to June 2012 with diagnosis codes of 965.00, 965.01, 965.02 and 965.09 (poisoning by opiates and related narcotics) and/or an external cause of injury code of E850.0-E850.2 (accidental poisoning by opiates and related narcotics), and developed a novel case definition to determine in which cases opioid poisoning prompted the ED visit. We calculated the percentage of visits coded for opioid poisoning that were clinically significant and compared it to the percentage of visits coded for poisoning by non-opioid agents in which there was actually poisoning by an opioid agent. We created a multivariate regression model to determine if other collected triage data can improve the positive predictive value of diagnosis codes alone for detecting clinically significant opioid poisoning. 70.1 % of visits (Standard Error 2.4 %) coded for opioid poisoning were primarily prompted by opioid poisoning. The remainder of visits represented opioid exposure in the setting of other primary diseases. Among non-opioid poisoning codes reviewed, up to 36 % were reclassified as an opioid poisoning. In multivariate analysis, only naloxone use improved the positive predictive value of ICD-9-CM codes for identifying clinically significant opioid poisoning, but was associated with a high false negative rate. This surveillance mechanism identifies many clinically significant opioid overdoses with a high positive predictive value. With further validation, it may help target control measures such as prescriber education and pharmacy monitoring.

What factors are associated with increased risk for prolonged postoperative opioid usage after colorectal surgery?

PubMed

Stafford, Caitlin; Francone, Todd; Roberts, Patricia L; Ricciardi, Rocco

2018-02-06

Opioid-related deaths have increased substantially over the last 10 years placing clinician's prescription practices under intense scrutiny. Given the substantial risk of opioid dependency after colorectal surgery, we sought to analyze risk of postoperative prolonged opioid use after colorectal resections. Between 2008 and 2014, patients undergoing abdominopelvic procedure with intestinal resection at a tertiary care facility were retrospectively identified. Patient's postoperative narcotic usage including their prescriptions on discharge and their total opioid medication use was recorded. Patient variables such as demographics, surgical characteristics, and prescription use were evaluated. Finally, we developed multivariate models to identify risk factors for prolonged opioid use (> 30 days after incident surgical procedure). We identified 9423 recorded procedures of which 2173 consisted of abdominopelvic procedures with intestinal resection and survived > 1 year. Of these, 91% (n = 1981) were discharged on opioids, and 98% (n = 1955) of those patients filled only one prescription. A total of 92 (4%) patients remained on opioids beyond 30 days, and from this group, 25% (n = 23 patients) remained at 90 days. We found no association between postoperative complications, stoma formation, and patient's sex with risk of prolonged opioid use. However, younger age and history of chronic pain were associated with an increased risk of prolonged opioid use. The use of minimally invasive techniques also attenuated the risk of prolonged opioid use (Table 2). A small but considerable proportion of patients remain on opioids beyond 30 days. Predictors of opioid use for greater than 30 days include a history of chronic pain and younger age. The use of minimally invasive techniques reduced the risk of prolonged opioid use. We identified several immutable risk factors that predicted prolonged postoperative opioid use; however, surgeons may be able to attenuate prolonged opioid use through the use of minimally invasive techniques.

Heroin - Multiple Languages

MedlinePlus

... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... Spanish) PDF Heroin - Opioid addiction, part 7 - English MP3 Heroin - Opioid addiction, part 7 - español (Spanish) MP3 ...

Prescription Drug Abuse - Multiple Languages

MedlinePlus

... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... español (Spanish) PDF Pain - Opioids, part 2 - English MP3 Pain - Opioids, part 2 - español (Spanish) MP3 Pain - ...

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

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

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

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.

Structure-Activity Relationships of Bifunctional Cyclic Disulfide Peptides Based on Overlapping Pharmacophores at Opioid and Cholecystokinin Receptors

PubMed Central

Agnes, Richard S.; Ying, Jinfa; Kövér, Katalin E.; Lee, Yeon Sun; Davis, Peg; Ma, Shou-wu; Badghisi, Hamid; Porreca, Frank; Lai, Josephine; Hruby, Victor J.

2008-01-01

Prolonged opioid exposure increases the expression of cholecystokinin (CCK) and its receptors in the central nervous system, where CCK may attenuate the antinociceptive effects of opioids. The complex interactions between opioid and CCK may play a role in the development of opioid tolerance. We designed and synthesized cyclic disulfide peptides and determined their agonist properties at opioid receptors and antagonist properties at CCK receptors. Compound 1 (Tyr-c[D-Cys-Gly-Trp-Cys]-Asp-Phe-NH2) showed potent binding and agonist activities at δ and µ opioid receptors while displaying some binding to CCK receptors. The NMR structure of the lead compound displayed similar conformational features of opioid and CCK ligands. PMID:18502541

Intersection of chronic pain treatment and opioid analgesic misuse: causes, treatments, and policy strategies

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo; Boyer, Edward; Naqvi, Zafar N; Rosenbaum, Christopher; Ziedonis, Douglas

2011-01-01

Treating chronic pain in the context of opioid misuse can be very challenging. This paper explores the epidemiology and potential treatments for chronic pain and opioid misuse and identifies educational and regulation changes that may reduce diversion of opioid analgesics. We cover the epidemiology of chronic pain and aberrant opioid behaviors, psychosocial influences on pain, pharmacological treatments, psychological treatments, and social treatments, as well as educational and regulatory efforts being made to reduce the diversion of prescription opioids. There are a number of ongoing challenges in treating chronic pain and opioid misuse, and more research is needed to provide strong, integrated, and empirically validated treatments to reduce opioid misuse in the context of chronic pain. PMID:24474854

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

Anti-arrhythmic activities of opioid agonists and antagonists and their stereoisomers.

PubMed Central

Sarne, Y.; Flitstein, A.; Oppenheimer, E.

1991-01-01

1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion-induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win 44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against occlusion-induced arrhythmia as did the opioid antagonists, and the (+)-stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors. A direct effect on ionic currents in cardiac muscle is suggested as the mechanism of opioid antiarrhythmic activity. PMID:1364840

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.

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.

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

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

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.

Trends in intentional abuse or misuse of benzodiazepines and opioid analgesics and the associated mortality reported to poison centers across the United States from 2000 to 2014.

PubMed

Calcaterra, S L; Severtson, S G; Bau, G E; Margolin, Z R; Bucher-Bartelson, B; Green, J L; Dart, R C

2018-04-03

Prior works demonstrates an increased risk of death when opioid analgesics and benzodiazepines are used concomitantly to gain a high. Using poison center data, we described trends in abuse or misuse of benzodiazepines and opioid analgesics. We quantified mortality risk associated with abuse or misuse of benzodiazepines, opioid analgesics and the combination of opioid analgesics and benzodiazepines. This was a retrospective chart review of data from the National Poison Data System which collects information from 55 poison centers located across the United States. We identified reported cases of "intentional abuse or misuse" of benzodiazepine and/or opioid analgesic exposures. Poisson regression was used to compare the number of cases from each year between 2001 and 2014 to the year 2000. Logistic regression was used to determine whether cases exposed to both benzodiazepines and opioids had greater odds of death relative to cases exposed to opioid analgesics alone. From 2000 to 2014, there were 125,485 benzodiazepine exposures and 84,627 opioid exposures among "intentional abuse or misuse" cases. Of the benzodiazepine exposures, 17.3% (n = 21,660) also involved an opioid. In 2010, exposures involving both opioids and benzodiazepines were 4.26-fold (95% CI: 3.87-4.70; p < .001) higher than in 2000. The risk of death was 1.55 (95% CI: 1.01-2.37; p = .04) times greater among those who used both an opioid and a benzodiazepine compared to opioids alone. This association held after adjusting for gender and age. Intentional abuse or misuse of benzodiazepines and opioids in combination increased significantly from 2000 to 2014. Benzodiazepine abuse or misuse far exceeded cases of opioid abuse or misuse. Death was greater with co-abuse or misuse of benzodiazepines and opioids. Population-level campaigns to inform the public about the risk of death with co-abuse or misuse of benzodiazepines and opioids are urgently needed to address this overdose epidemic.

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group (mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable. © 2017 by the Society for Academic Emergency Medicine.

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 of patients administered any parenteral opioid decreased by 57% (6% vs 14%; P < .001). Doses of opioids given by oral or parenteral route were reduced by 23% (0.73 vs 0.95 doses per patient-day, P = .02), and mean daily overall opioid exposure decreased by 31% (6.30 [4.12] vs 9.11 [7.34] MMEs per patient-day). For hospital days 1 through 3, there were no significant postintervention vs preintervention differences in mean reported pain score for patients receiving opioid therapy: day 1, -0.19 (95% CI, -0.94 to 0.56); day 2, -0.49 (95% CI, -1.01 to 0.03); and day 3, -0.54 (95% CI, -1.18 to 0.09). However, significant improvement was seen in the intervention group on days 4 (-1.07; 95% CI, -1.80 to -0.34) and 5 (-1.06; 95% CI, -1.84 to -0.27). An intervention targeting the use of intravenous opioids may be associated with reduced opioid exposure while providing effective pain control to hospitalized adults.

Trends in Opioid Use Disorder Diagnoses and Medication Treatment Among Veterans With Posttraumatic Stress Disorder.

PubMed

Shiner, Brian; Leonard Westgate, Christine; Bernardy, Nancy C; Schnurr, Paula P; Watts, Bradley V

2017-01-01

Despite long-standing interest in posttraumatic stress disorder (PTSD) and opioid use disorder comorbidity, there is a paucity of data on the prevalence of opioid use disorder in patients with PTSD. Therefore, there is limited understanding of the use of medications for opioid use disorder in this population. We determined the prevalence of diagnosed opioid use disorder and use of medications for opioid use disorder in a large cohort of patients with PTSD. We obtained administrative and pharmacy data for veterans who initiated PTSD treatment in the Department of Veterans Affairs (VA) between 2004 and 2013 (N = 731,520). We identified those with a comorbid opioid use disorder diagnosis (2.7%; n = 19,998) and determined whether they received a medication for opioid use disorder in the year following their initial clinical PTSD diagnosis (29.6%; n = 5,913). Using logistic regression, we determined the predictors of receipt of opioid use disorder medications. Comorbid opioid use disorder diagnoses increased from 2.5% in 2004 to 3.4% in 2013. Patients with comorbid opioid use disorder used more health services and had more comorbidities than other patients with PTSD. Among patients with PTSD and comorbid opioid use disorder, use of medications for opioid use disorder increased from 22.6% to 35.1% during the same time period. Growth in the use of buprenorphine (2.0% to 22.7%) was accompanied by relative decline in use of methadone (19.3% to 12.7%). Patients who received buprenorphine were younger and more likely to be rural, White, and married. Patients who received methadone were older, urban, unmarried, from racial and ethnic minorities, and more likely to see substance abuse specialists. While use of naltrexone increased (2.8% to 8.6%), most (87%) patients who received naltrexone also had an alcohol use disorder. Controlling for patient factors, there was a substantial increase in the use of buprenorphine, a substantial decrease in the use of methadone, and no change in use of naltrexone across years. Opioid use disorder is an uncommon but increasing comorbidity among patients with PTSD. Patients entering VA treatment for PTSD have their opioid use disorder treated with opioid agonist treatments in large and increasing numbers. There is a need for research both on the epidemiology of opioid use disorder among patients with PTSD and on screening for opioid use disorder.

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 coding, and observational data limit inferences of causality. Physical therapy first was associated with lower hip-related downstream costs and lower opioid use than opioids first; physical therapy instead of opioids was associated with less total downstream health care utilization. These results need to be validated in prospective controlled trials.

LACK OF CORRELATION BETWEEN OPIOID DOSE ADJUSTMENT AND PAIN SCORE CHANGE IN A GROUP OF CHRONIC PAIN PATIENTS

PubMed Central

Chen, Lucy; Vo, Trang; Seefeld, Lindsey; Malarick, Charlene; Houghton, Mary; Ahmed, Shihab; Zhang, Yi; Cohen, Abigail; Retamozo, Cynthia; Hilaire, Kristen St.; Zhang, Vivian; Mao, Jianren

2013-01-01

Despite the increasing use of opioid analgesics for chronic pain management, it is unclear whether opioid dose escalation leads to better pain relief during chronic opioid therapy. In this study, we retrospectively analyzed clinical data collected from the Massachusetts General Hospital (MGH) Center for Pain Medicine over a 7-year period. We examined 1) the impact of opioid dose adjustment (increase or decrease) on clinical pain score, 2) gender and age differences in response to opioid therapy, and 3) the influence of clinical pain conditions on the opioid analgesic efficacy. A total of 109 subjects met the criteria for data collection. We found that neither opioid dose increase, nor decrease, correlated with point changes in clinical pain score in a subset of chronic pain patients over a prolonged course of opioid therapy (an average of 704 days). This lack of correlation was consistent regardless of the type of chronic pain including neuropathic, nociceptive, or mixed pain conditions. Neither gender nor age differences showed a significant influence on the clinical response to opioid therapy in these subjects. These results suggest that dose adjustment during opioid therapy may not necessarily alter long-term clinical pain score in a group of chronic pain patients and that individualized opioid therapy based on the clinical effectiveness should be considered to optimize the treatment outcome. Perspectives The study reports a relationship, or lack thereof, between opioid dose change and clinical pain score in a group of chronic pain patients. The study also calls for further investigation into the effectiveness of opioid therapy in the management of chronic non-malignant pain conditions. PMID:23452826

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

PubMed

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

2014-01-01

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

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

Long-term outcomes from the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study.

PubMed

Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; Provost, Scott E; Fitzmaurice, Garrett M; McDermott, Katherine A; Srisarajivakul, Emily N; Dodd, Dorian R; Dreifuss, Jessica A; McHugh, R Kathryn; Carroll, Kathleen M

2015-05-01

Despite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS). POATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences. At Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, p<.05). Engagement in agonist therapy was associated with a greater likelihood of illicit-opioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use. Long-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Using prescription monitoring program data to characterize out-of-pocket payments for opioid prescriptions in a state Medicaid program.

PubMed

Hartung, Daniel M; Ahmed, Sharia M; Middleton, Luke; Van Otterloo, Joshua; Zhang, Kun; Keast, Shellie; Kim, Hyunjee; Johnston, Kirbee; Deyo, Richard A

2017-09-01

Out-of-pocket payment for prescription opioids is believed to be an indicator of abuse or diversion, but few studies describe its epidemiology. Prescription drug monitoring programs (PDMPs) collect controlled substance prescription fill data regardless of payment source and thus can be used to study this phenomenon. To estimate the frequency and characteristics of prescription fills for opioids that are likely paid out-of-pocket by individuals in the Oregon Medicaid program. Cross-sectional analysis using Oregon Medicaid administrative claims and PDMP data (2012 to 2013). Continuously enrolled nondually eligible Medicaid beneficiaries who could be linked to the PDMP with two opioid fills covered by Oregon Medicaid. Patient characteristics and fill characteristics for opioid fills that lacked a Medicaid pharmacy claim. Fill characteristics included opioid name, type, and association with indicators of high-risk opioid use. A total of 33 592 Medicaid beneficiaries filled a total of 555 103 opioid prescriptions. Of these opioid fills, 74 953 (13.5%) could not be matched to a Medicaid claim. Hydromorphone (30%), fentanyl (18%), and methadone (15%) were the most likely to lack a matching claim. The 3 largest predictors for missing claims were opioid fills that overlapped with other opioids (adjusted odds ratio [aOR] 1.37; 95% confidence interval [CI], 1.34-1.4), long-acting opioids (aOR 1.52; 95% CI, 1.47-1.57), and fills at multiple pharmacies (aOR 1.45; 95% CI, 1.39-1.52). Prescription opioid fills that were likely paid out-of-pocket were common and associated with several known indicators of high-risk opioid use. Copyright © 2017 John Wiley & Sons, Ltd.

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.

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

Association of Opioids and Sedatives with Increased Risk of In-Hospital Cardiopulmonary Arrest from an Administrative Database

PubMed Central

Overdyk, Frank J.; Dowling, Oonagh; Marino, Joseph; Qiu, Jiejing; Chien, Hung-Lun; Erslon, Mary; Morrison, Neil; Harrison, Brooke; Dahan, Albert; Gan, Tong J.

2016-01-01

Background While opioid use confers a known risk for respiratory depression, the incremental risk of in-hospital cardiopulmonary arrest, respiratory arrest, or cardiopulmonary resuscitation (CPRA) has not been studied. Our aim was to investigate the prevalence, outcomes, and risk profile of in-hospital CPRA for patients receiving opioids and medications with central nervous system sedating side effects (sedatives). Methods A retrospective analysis of adult inpatient discharges from 2008–2012 reported in the Premier Database. Patients were grouped into four mutually exclusive categories: (1) opioids and sedatives, (2) opioids only, (3) sedatives only, and (4) neither opioids nor sedatives. Results Among 21,276,691 inpatient discharges, 53% received opioids with or without sedatives. A total of 96,554 patients suffered CPRA (0.92 per 1000 hospital bed-days). Patients who received opioids and sedatives had an adjusted odds ratio for CPRA of 3.47 (95% CI: 3.40–3.54; p<0.0001) compared with patients not receiving opioids or sedatives. Opioids alone and sedatives alone were associated with a 1.81-fold and a 1.82-fold (p<0.0001 for both) increase in the odds of CPRA, respectively. In opioid patients, locations of CPRA were intensive care (54%), general care floor (25%), and stepdown units (15%). Only 42% of patients survived CPRA and only 22% were discharged home. Opioid patients with CPRA had mean increased hospital lengths of stay of 7.57 days and mean increased total hospital costs of $27,569. Conclusions Opioids and sedatives are independent and additive risk factors for in-hospital CPRA. The impact of opioid sparing analgesia, reduced sedative use, and better monitoring on CPRA incidence deserves further study. PMID:26913753

Impact of Florida's prescription drug monitoring program and pill mill law on high-risk patients: A comparative interrupted time series analysis.

PubMed

Chang, Hsien-Yen; Murimi, Irene; Faul, Mark; Rutkow, Lainie; Alexander, G Caleb

2018-04-01

We quantified the effects of Florida's prescription drug monitoring program and pill mill law on high-risk patients. We used QuintilesIMS LRx Lifelink data to identify patients receiving prescription opioids in Florida (intervention state, N: 1.13 million) and Georgia (control state, N: 0.54 million). The preintervention, intervention, and postintervention periods were July 2010 to June 2011, July 2011 to September 2011, and October 2011 to September 2012. We identified 3 types of high-risk patients: (1) concomitant users: patients with concomitant use of benzodiazepines and opioids; (2) chronic users: long-term, high-dose, opioid users; and (3) opioid shoppers: patients receiving opioids from multiple sources. We compared changes in opioid prescriptions between Florida and Georgia before and after policy implementation among high-risk/low-risk patients. Our monthly measures included (1) average morphine milligram equivalent per transaction, (2) total opioid volume across all prescriptions, (3) average days supplied per transaction, and (4) total number of opioid prescriptions dispensed. Among opioid-receiving individuals in Florida, 6.62% were concomitant users, 1.96% were chronic users, and 0.46% were opioid shoppers. Following policy implementation, Florida's high-risk patients experienced relative reductions in morphine milligram equivalent (opioid shoppers: -1.08 mg/month, 95% confidence interval [CI] -1.62 to -0.54), total opioid volume (chronic users: -4.58 kg/month, CI -5.41 to -3.76), and number of dispensed opioid prescriptions (concomitant users: -640 prescriptions/month, CI -950 to -340). Low-risk patients generally did not experience statistically significantly relative reductions. Compared with Georgia, Florida's prescription drug monitoring program and pill mill law were associated with large relative reductions in prescription opioid utilization among high-risk patients. Copyright © 2018 John Wiley & Sons, Ltd.

Opioid shopping behavior: how often, how soon, which drugs, and what payment method.

PubMed

Cepeda, M Soledad; Fife, Daniel; Chow, Wing; Mastrogiovanni, Gregory; Henderson, Scott C

2013-01-01

Doctor shopping (obtaining opioid prescriptions from multiple prescribers) is one example of opioid abuse and diversion. The authors assessed how soon shopping behavior was observed after opioid exposure, number of events per shopper, preferred opioids, and method of payment. This was a cohort study. Individuals with ≤1 dispensing for any opioid in 2008 were followed for 18 months. Shopping behavior was defined as ≤2 prescriptions by different prescribers with ≤1 day of overlap and filled at ≤3 pharmacies. Of 25,161,024 subjects, 0.30% exhibited shopping behavior. Opioid-experienced subjects were 13.7 times more likely to exhibit shopping behavior and had more shopping episodes than opioid-naive subjects. Time to first shopping event was 246.90 ± 163.61 days. Number of episodes was 2.74 ± 4.66. Most subjects with shopping behavior (55.27%) had 1 shopping episode, whereas 9.52% had ≤6 episodes; 88.99% had ≤4 prescribers. Subjects with shopping behavior filled schedule II opioids more often than subjects without shopping behavior (19.51% vs 10.89%) and more often paid in cash (44.85% vs 18.54%). Three of 1000 people exposed to opioids exhibit shopping behavior, on average, 8 months after exposure. Opioid shoppers seek strong opioids, avoid combination products, often pay cash, and obtain prescriptions from few prescribers. © 2012 The Author(s).

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.

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.

Determinants of trends in prescription opioid use in British Columbia, Canada, 2005-2013.

PubMed

Smolina, Kate; Gladstone, Emilie; Morgan, Steven G

2016-05-01

To explore the determinants of total opioid consumption in a Canadian province, and to examine patterns of opioid dispensations by sex, age, and income quintile. We used population-based administrative data on prescription drug dispensations in British Columbia (BC; population ~4 million). We apply an index-based approach to examine how changes in population exposure, type of opioids used, and intensity of use contributed to changes in total morphine equivalents dispensed per 1000 population. Between 2005 and 2013 in BC, opioid consumption increased by 31%, driven by longer duration of opioid therapy and by an increase in the use of stronger opioids. Consumption increased for oxycodone, hydromorphone, fentanyl, and tramadol; and declined for morphine, codeine, and other opioids. While we did not find large sex and age differences, the total level of opioid consumption was three times as high among individuals in the lowest income quintile compared to those in the highest income quintile. Our findings on changes in the type of opioids used and changes in intensity of use suggest that modifications to clinical management of patients on opioid therapy may be warranted. Similar drug utilization statistics, derived from drug information systems, can be reproduced in other jurisdictions to enable a better understanding of the opioid crisis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis

PubMed Central

Solbrig, Marylou V.; Adrian, Russell; Wechsler, Steven L.; Koob, George F.

2010-01-01

Opioid systems in hippocampus regulate excitability and kappa opioids have a role in anticonvulsant protection, but their mechanisms of action are incompletely understood. We examined the ability of opioid and nonopioid agents with overlapping ionic mechanisms and actions similar to kappa opioid agonists, to block seizures in rat models of encephalitis due to Borna Disease virus and Herpes Simplex Virus Type-1. Naltrindole, a delta antagonist and thus a kappa opioid sparing agent, (10 mg/kg s.c.) blocked spontaneous and naloxone (opioid antagonist)-induced seizures in the models, but produced somatic signs similar to opioid withdrawal. Given that delta antagonists as well as kappa opioid agonists in hippocampus enhance potassium M currents (IM), we tested the effect of the IM augmenter flupirtine. Flupirtine (20 mg/kg i.p.) prevented seizures in Borna and herpes infected rats, without signs of withdrawal, hypotonia or sedation. The results support the efficacy of opioid and nonopioid drugs in modulating naloxone-induced seizures in critical illness due to viral encephalitis and by analogy, opioid withdrawal seizures. PMID:17126318

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-01

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

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

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

PubMed

Mercer, Susan L; Coop, Andrew

2011-01-01

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

Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine.

PubMed

Malcolm, Benjamin J; Polanco, Martin; Barsuglia, Joseph P

2018-04-02

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants' OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.

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.

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.

American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I--evidence assessment.

PubMed

Manchikanti, Laxmaiah; Abdi, Salahadin; Atluri, Sairam; Balog, Carl C; Benyamin, Ramsin M; Boswell, Mark V; Brown, Keith R; Bruel, Brian M; Bryce, David A; Burks, Patricia A; Burton, Allen W; Calodney, Aaron K; Caraway, David L; Cash, Kimberly A; Christo, Paul J; Damron, Kim S; Datta, Sukdeb; Deer, Timothy R; Diwan, Sudhir; Eriator, Ike; Falco, Frank J E; Fellows, Bert; Geffert, Stephanie; Gharibo, Christopher G; Glaser, Scott E; Grider, Jay S; Hameed, Haroon; Hameed, Mariam; Hansen, Hans; Harned, Michael E; Hayek, Salim M; Helm, Standiford; Hirsch, Joshua A; Janata, Jeffrey W; Kaye, Alan D; Kaye, Adam M; Kloth, David S; Koyyalagunta, Dhanalakshmi; Lee, Marion; Malla, Yogesh; Manchikanti, Kavita N; McManus, Carla D; Pampati, Vidyasagar; Parr, Allan T; Pasupuleti, Ramarao; Patel, Vikram B; Sehgal, Nalini; Silverman, Sanford M; Singh, Vijay; Smith, Howard S; Snook, Lee T; Solanki, Daneshvari R; Tracy, Deborah H; Vallejo, Ricardo; Wargo, Bradley W

2012-07-01

Opioid abuse has continued to increase at an alarming rate since the 1990 s. As documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration, available evidence suggests a wide variance in chronic opioid therapy of 90 days or longer in chronic non-cancer pain. Part 1 describes evidence assessment. The objectives of opioid guidelines as issued by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to produce consistency in the application of an opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion. The focus of these guidelines is to curtail the abuse of opioids without jeopardizing non-cancer pain management with opioids. 1) There is good evidence that non-medical use of opioids is extensive; one-third of chronic pain patients may not use prescribed opioids as prescribed or may abuse them, and illicit drug use is significantly higher in these patients. 2) There is good evidence that opioid prescriptions are increasing rapidly, as the majority of prescriptions are from non-pain physicians, many patients are on long-acting opioids, and many patients are provided with combinations of long-acting and short-acting opioids. 3) There is good evidence that the increased supply of opioids, use of high dose opioids, doctor shoppers, and patients with multiple comorbid factors contribute to the majority of the fatalities. 4) There is fair evidence that long-acting opioids and a combination of long-acting and short-acting opioids contribute to increasing fatalities and that even low-doses of 40 mg or 50 mg of daily morphine equivalent doses may be responsible for emergency room admissions with overdoses and deaths. 5) There is good evidence that approximately 60% of fatalities originate from opioids prescribed within the guidelines, with approximately 40% of fatalities occurring in 10% of drug abusers. 6) The short-term effectiveness of opioids is fair, whereas the long-term effectiveness of opioids is limited due to a lack of long-term (> 3 months) high quality studies, with fair evidence with no significant difference between long-acting and short-acting opioids. 7) Among the individual drugs, most opioids have fair evidence for short-term and limited evidence for long-term due to a lack of quality studies. 8) The evidence for the effectiveness and safety of chronic opioid therapy in the elderly for chronic non-cancer pain is fair for short-term and limited for long-term due to lack of high quality studies; limited in children and adolescents and patients with comorbid psychological disorders due to lack of quality studies; and the evidence is poor in pregnant women. 9) There is limited evidence for reliability and accuracy of screening tests for opioid abuse due to lack of high quality studies. 10) There is fair evidence to support the identification of patients who are non-compliant or abusing prescription drugs or illicit drugs through urine drug testing and prescription drug monitoring programs, both of which can reduce prescription drug abuse or doctor shopping. The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Adverse selection? A multi-dimensional profile of people dispensed opioid analgesics for persistent non-cancer pain.

PubMed

Rogers, Kris D; Kemp, Anna; McLachlan, Andrew J; Blyth, Fiona

2013-01-01

This study investigates utilisation patterns for prescription opioid analgesics in the Australian community and how these are associated with a framework of individual-level factors related to healthcare use. Self-reported demographic and health information from participants in the 45 and Up Study cohort were linked to pharmaceutical claims from 2006-2009. Participants comprised 19,816 people with ≥1 opioid analgesic dispensing in the 12-months after recruitment to the cohort and 79,882 people not dispensed opioid analgesics. All participants were aged ≥45 years, were social security pharmaceutical beneficiaries, with no history of cancer. People dispensed opioid analgesics were classified as having acute (dispensing period <90 days), episodic (≥90 days and <3 'authority' prescriptions for increased quantity supply) or long-term treatment (≥90 days and ≥3 authority prescriptions). Of participants dispensed opioid analgesic 52% received acute treatment, 25% episodic treatment and 23% long-term treatment. People dispensed opioid analgesics long-term had an average of 14.9 opioid analgesic prescriptions/year from 2.0 doctors compared with 1.5 prescriptions from 1.1 doctors for people receiving acute treatment. People dispensed opioid analgesics reported more need-related factors such as poorer physical functioning and higher psychological distress. Long-term users were more likely to have access-related factors such as low-income and living outside major cities. After simultaneous adjustment, association with predisposing health factors and access diminished, but indicators of need such as osteoarthritis treatment, paracetamol use, and poor physical function were the strongest predictors for all opioid analgesic users. People dispensed opioid analgesics were in poorer health, reported higher levels of distress and poorer functioning than people not receiving opioid analgesics. Varying dispensing profiles were evident among people dispensed opioid analgesics for persistent pain, with those receiving episodic and long-term treatment dispensed the strongest opioid analgesics. The findings highlight the broad range of factors associated with longer term opioid analgesics use.

Perioperative Opioid Analgesics and Hip Arthroscopy: Trends, Risk Factors for Prolonged Use, and Complications.

PubMed

Anciano Granadillo, Victor; Cancienne, Jourdan M; Gwathmey, F Winston; Werner, Brian C

2018-05-02

The purpose of this article is to (1) examine trends in preoperative and prolonged postoperative opioid analgesic use in patient undergoing hip arthroscopy, (2) characterize risk factors for prolonged opioid analgesic use following hip arthroscopy, and (3) explore preoperative and prolonged postoperative opioid analgesic use as independent risk factors for complications following hip arthroscopy. A private insurance database was queried for patients undergoing hip arthroscopy from 2007 to 2015 with a minimum of 6 months of follow-up. Independent risk factors for prolonged opioid analgesic use were determined. Preoperative and prolonged opioid analgesic use as risk factors for complications were examined. There was a significantly decreasing trend in preoperative (P = .002) and prolonged postoperative (P = .009) opioid analgesic use. The most significant risk factor for prolonged postoperative opioid analgesic use was preoperative use (odds ratio [OR], 3.61; P < .0001). Other preoperative prescriptions, including muscle relaxants (OR, 1.5; P < .0001) and anxiolytics (OR, 2.0; P < .0001), were also significant risk factors. Preoperative opioid analgesic use was a significant risk factor for postoperative complications, including emergency room visits (OR, 2.1; P < .0001) and conversion to total hip arthroplasty (THA) (OR, 1.6; P < .0001). Prolonged postoperative opioid analgesic use was associated with a higher risk of revision hip arthroscopy (OR, 1.4; P = .0004) and conversion to THA (OR, 1.8; P < .0001). More than a quarter of patients undergoing hip arthroscopy continue to receive opioid analgesic prescriptions more than 3 months postoperatively. The most significant risk factor for prolonged opioid analgesic use is preoperative opioid analgesic use. Additionally, anxiolytics, substance use or abuse, morbid obesity, and back pain were among the more notable risk factors for prolonged postoperative opioid analgesic use. Preoperative and prolonged postoperative opioid analgesic use was associated with a higher likelihood of several adverse effects/complications. Level III, retrospective comparative study. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Prescription drug monitoring program data tracking of opioid addiction treatment outcomes in integrated dual diagnosis care involving injectable naltrexone.

PubMed

Sajid, Ayesha; Whiteman, Aaron; Bell, Richard L; Greene, Marion S; Engleman, Eric A; Chambers, R Andrew

2016-10-01

Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders. There were no group differences post-injection in treatment days, injections delivered, or treatment service encounters. UDS and PDMP measures of opioid exposures were greater in opioid compared to alcohol-only patients. Post-first injection, UDS's positive for opioids declined (p < .05) along with PDMP measures of opioid prescriptions (p < .001), doses (p < .01), types (p < .001), numbers of dispensing prescribers (p < .001) and pharmacies (p < .001). Opioid patients without alcohol disorders showed the best outcomes with 50% to 80% reductions in PDMP-measures of opioids, down to levels of alcohol-only patients. This study shows PDMP utility for measuring opioid addiction treatment outcomes, supporting the routine use of PDMPs in clinical and research settings. These findings demonstrate that opioid addiction in patients with complex addictions and mental illnesses comorbidities can show effective treatment responses as measured by PDMP tracking of decreases in opioid prescriptions to those patients. (Am J Addict 2016;25:557-564). © 2016 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP).

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 common obstetrics procedures such as vaginal delivery are warranted.

When human immunodeficiency virus (HIV) treatment goals conflict with guideline-based opioid prescribing: A qualitative study of HIV treatment providers.

PubMed

Starrels, Joanna L; Peyser, Deena; Haughton, Lorlette; Fox, Aaron; Merlin, Jessica S; Arnsten, Julia H; Cunningham, Chinazo O

2016-01-01

Human immunodeficiency virus (HIV)-infected patients have a high prevalence of chronic pain and opioid use, making HIV care a critical setting for improving the safety of opioid prescribing. Little is known about HIV treatment providers' perspectives about opioid prescribing to patients with chronic pain. The authors administered a questionnaire and conducted semistructured telephone interviews with 18 HIV treatment providers (infectious disease specialists, general internists, family medicine physicians, nurse practitioners, and physician assistants) in Bronx, NY. Open-ended interview questions focused on providers' experiences, beliefs, and attitudes about opioid prescribing and about the use of guideline-based opioid prescribing practices (conservative prescribing, and monitoring for and responding to misuse). Transcripts were thematically analyzed using a modified grounded theory approach. Eighteen HIV treatment providers included 13 physicians, four nurse practitioners, and one physician assistant. They were 62% female, 56% white, and practiced as HIV treatment providers for a mean of 14.6 years. Most reported always or almost always using opioid treatment agreements (56%) and urine drug testing (61%) with their patients on long-term opioid therapy. HIV treatment providers tended to view opioid prescribing for chronic pain within the "HIV paradigm," a set of priorities and principles defined by three key themes: (1) primacy of HIV goals, (2) familiarity with substance use, and (3) the clinician as ally. The HIV paradigm sometimes supported, and sometimes conflicted with, guideline-based opioid prescribing practices. For HIV treatment providers, perceived alignment with the HIV paradigm determined whether and how guideline-based opioid prescribing practices were adopted. For example, the primacy of HIV goals superseded conservative opioid prescribing when providers prescribed opioids with the goal of retaining patients in HIV care. These findings highlight unique factors in HIV care that influence adoption of guideline-based opioid prescribing practices. These factors should be considered in future research and initiatives to address opioid prescribing in HIV care.

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

PubMed Central

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

2010-01-01

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

MMPI disability profile is associated with degree of opioid use in chronic work-related musculoskeletal disorders.

PubMed

Kidner, Cindy L; Gatchel, Robert J; Mayer, Tom G

2010-01-01

To examine the relationship between level of opioid use and Minnesota Multiphasic Personality Inventory (MMPI) findings among chronic pain patients who were about to begin a functional restoration program. A prospective cohort study of patients with chronic disabling occupational musculoskeletal disorders. A total of 768 consecutive patients with valid MMPI were divided into 2 groups: 398 patients who reported no opioid use upon admission (No); and 370 patients who reported opioid use upon admission (Yes). Average daily opioid doses (in morphine equivalents) could be determined for 287 of 370 patients, who were further divided into 4 opioid subgroups: Low (>0 to 30 mg, n=148); Medium (>30 to 60 mg, n=57); High (>60 to 120 mg, n=47); and Very High (>120 mg, n=35). Seventy-five percent of the patients who produced valid MMPI profiles could be classified into 1 of the 4 MMPI profiles. Of those patients who could be classified, approximately 7% showed a Normal profile, 15% showed a Conversion V, 9% showed a Neurotic Triad, and 69% showed the Disability Profile. Although the Disability Profile accounted for the majority of patients in all opioid subgroups, the proportions did increase with pretreatment opioid dose, as expected, indicating a relationship between degree of psychopathology and level of pretreatment opioid use. Patients who did not take pretreatment opioids showed the highest proportions of Conversion V and Normal profiles, which indicate a lesser degree or absence of psychopathology, respectively. Patients who took pretreatment opioids were more than one-and-a-half times as likely as patients who did not take pretreatment opioids to produce the Disability Profile, whereas patients taking very high doses of pretreatment opioids were nearly 3 times as likely to produce this profile as patients who took no pretreatment opioids. The results of this study support the hypothesis that increasing levels of pretreatment opioid use is associated with less desirable MMPI profiles, specifically the Disability Profile and, thus, greater levels of pretreatment psychopathology.

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.

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 opioid therapy.

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

Undertreatment of pain and low use of opioids in Latin America.

PubMed

García, César Amescua; Santos Garcia, Joao Batista; Rosario Berenguel Cook, María Del; Colimon, Frantz; Flores Cantisani, José Alberto; Guerrero, Carlos; Rocío Guillén Núnez, María Del; Hernández Castro, John Jairo; Kraychete, Durval Campos; Lara-Solares, Argelia; Lech, Osvandré; Rico Pazos, María Antonieta; Gallegos, Manuel Sempértegui; Marcondes, Lizandra Pattaro

2018-05-01

Pain is highly prevalent among the adult Latin American population. However, many patients with moderate to severe pain do not have access to effective pain management with opioids due to limited access to healthcare, overuse of nonopioid analgesics, regulatory barriers and lack of appropriate information about opioids. There is scarce training on use of opioids among physicians and other healthcare providers, which leads to misconceptions, mainly related to a fear of prescribing opioids. Although opioids are safe and effective drugs for the treatment of moderate to severe chronic pain, the use of opioids in Latin American nations is clearly below standards compared with developed countries.

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.

Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study.

PubMed

Komen, Helga; Brunt, L Michael; Deych, Elena; Blood, Jane; Kharasch, Evan D

2018-05-25

Approximately 50 million US patients undergo ambulatory surgery annually. Postoperative opioid overprescribing is problematic, yet many patients report inadequate pain relief. In major inpatient surgery, intraoperative single-dose methadone produces better analgesia and reduces opioid use compared with conventional repeated dosing of short-duration opioids. This investigation tested the hypothesis that in same-day ambulatory surgery, intraoperative methadone, compared with short-duration opioids, reduces opioid consumption and pain, and determined an effective intraoperative induction dose of methadone for same-day ambulatory surgery. A double-blind, dose-escalation protocol randomized 60 patients (2:1) to intraoperative single-dose intravenous methadone (initially 0.1 then 0.15 mg/kg ideal body weight) or conventional as-needed dosing of short-duration opioids (eg, fentanyl, hydromorphone; controls). Intraoperative and postoperative opioid consumption, pain, and opioid side effects were assessed before discharge. Patient home diaries recorded pain, opioid use, and opioid side effects daily for 30 days postoperatively. Primary outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30 days opioid consumption, pain intensity, and opioid side effects. Median (interquartile range) methadone doses were 6 (5-6) and 9 (8-9) mg in the 0.1 and 0.15 mg/kg methadone groups, respectively. Total opioid consumption (morphine equivalents) in the postanesthesia care unit was significantly less compared with controls (9.3 mg, 1.3-11.0) in subjects receiving 0.15 mg/kg methadone (0.1 mg, 0.1-3.3; P < .001) but not 0.1 mg/kg methadone (5.0 mg, 3.3-8.1; P = .60). Dose-escalation ended at 0.15 mg/kg methadone. Total in-hospital nonmethadone opioid use after short-duration opioid, 0.1 mg/kg methadone, and 0.15 mg/kg methadone was 35.3 (25.0-44.0), 7.1 (3.7-10.0), and 3.3 (0.1-5.8) mg morphine equivalents, respectively (P < .001 for both versus control). In-hospital pain scores and side effects were not different between groups. In the 30 days after discharge, patients who received methadone 0.15 mg/kg had less pain at rest (P = .02) and used fewer opioid pills than controls (P < .0001), whereas patients who received 0.1 mg/kg had no difference in pain at rest (P = .69) and opioid use compared to controls (P = .08). In same-day discharge surgery, this pilot study identified a single intraoperative dose of methadone (0.15 mg/kg ideal body weight), which decreased intraoperative and postoperative opioid requirements and postoperative pain, compared with conventional intermittent short-duration opioids, with similar side effects.

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

PubMed

Spetea, M; Schmidhammer, H

2012-01-01

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

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

PubMed

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

2018-01-05

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

Association of childhood abuse and prescription opioid use in early adulthood.

PubMed

Austin, Anna E; Shanahan, Meghan E; Zvara, Bharathi J

2018-01-01

Previous research has examined the association of childhood abuse with opioid misuse and dependence in adulthood. However, little research has focused specifically on prescription opioids, and no studies have examined associations with prescription opioid use, a potential pathway to later opioid misuse and dependence. The aim of the present study was to examine the association of childhood emotional, physical, and sexual abuse with prescription opioid use in early adulthood. We used data from Waves I (12-18years) and IV (24-32years) of the National Longitudinal Study of Adolescent to Adult Health. At Wave IV, respondents reported experiences of childhood abuse occurring prior to age 18years and prescription opioid use in the last four weeks. We conducted multivariable logistic regression to examine associations of childhood abuse with recent prescription opioid use. In multivariable models adjusted for respondent sex, race/ethnicity, age, and socioeconomic status, childhood emotional abuse (OR=1.57, 95% CI 1.29, 1.90), physical abuse (OR=1.46, 95% CI 1.14, 1.87), and any childhood abuse (OR=1.51, 95% CI 1.24, 1.82) were significantly associated with recent prescription opioid use. Given continued increases in prescription opioid use and opioid-related morbidity and mortality in the U.S., understanding upstream social and environmental factors associated with prescription opioid use is important to strengthening and expanding current prevention and intervention strategies. Future research is needed to examine factors potentially mediating the association between childhood abuse and prescription opioid use in order to provide additional insights for prevention and intervention efforts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prescription opioids for occupational injury: results from workers' compensation claims records.

PubMed

Berecki-Gisolf, Janneke; Collie, Alex; McClure, Roderick J

2014-09-01

The objective of this study is to identify the prevalence of opioid prescription use in an Australian workers' compensation population and assess predictors of long-term use. Retrospective administrative data analysis. WorkSafe Victoria (Australia) workers' compensation. Workers with a workers' compensation claim were included if the injury/illness started in 2008 or 2009 (N = 54,931). Claim payments records dating up to 2 years postinjury were analyzed to determine receipt of prescription opioids. Long-term use was defined as use of any opioid beyond 1 year postinjury. Within the follow-up period, 8,933 (16.3%) workers claimed prescription opioids: 10.0% claimed opioids in the first year only, and 6.3% claimed opioids beyond the first year. The most commonly received opioids were codeine (10.4%), oxycodone (7.5%), and tramadol (5.0%). Dextropropoxyphene, which is considered unsafe in many countries because of potentially fatal side effects, was used by 1.9% of injured workers. Progression to long-term use of opioids was common (N = 3,446; 39%): age (35-64 years; the association with age followed an inverse U-shaped curve), women, laborers, lower socioeconomic status, greater work disability, and greater hospital expense were associated with opioid use beyond the first year postinjury. Prescription opioid use for workplace injury in Australia is common but not as common as reports from U.S. workers' compensation schemes. The type of opioid and number of repeat prescriptions are factors that should be carefully considered by practitioners prescribing opioids to injured workers: progression to long-term use is common and not fully explained by injury severity. Wiley Periodicals, Inc.

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

PubMed

Oliveto, A H; Feingold, A; Schottenfeld, R; Jatlow, P; Kosten, T R

1999-09-01

Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Nonmedical opioid use and heroin use in a nationally representative sample of us high school seniors.

PubMed

Palamar, Joseph J; Shearston, Jenni A; Dawson, Eric W; Mateu-Gelabert, Pedro; Ompad, Danielle C

2016-01-01

Nonmedical use of opioids has become increasingly problematic in recent years with increases in overdoses, treatment admissions, and deaths. Use also appears to be contributing to heroin initiation, which has increased in recent years. Further research is needed to examine which adolescents are at highest risk for nonmedical use of opioids and heroin and to explore potential links between nonmedical opioid use and heroin use. Data were analyzed from a nationally representative sample of American high school seniors in the Monitoring the Future study (2009-2013, Weighted N=67,822). We examined associations between frequency and recency of nonmedical use of opioids and heroin. Sociodemographic correlates of use of each drug were also examined. 12.4% of students reported lifetime nonmedical opioid use and 1.2% reported lifetime heroin use. As frequency of lifetime nonmedical opioid use increased, so too did the odds for reporting heroin use, with over three-quarters (77.3%) of heroin users reporting lifetime nonmedical opioid use. Recent (30-day) nonmedical opioid use was a robust risk factor for heroin use and almost a quarter (23.2%) of students who reported using opioids ≥40 times reported lifetime heroin use. Black and Hispanic students were less likely to report nonmedical opioid or heroin use than white students, but they were more likely to report heroin use in absence of nonmedical opioid use. Recent and frequent nonmedical opioid use are risk factors for heroin use among adolescents. Prevention needs to be targeted to those at highest risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nonmedical Opioid Use and Heroin Use in a Nationally Representative Sample of US High School Seniors*

PubMed Central

Palamar, Joseph J.; Shearston, Jenni A.; Dawson, Eric W.; Mateu-Gelabert, Pedro; Ompad, Danielle C.

2015-01-01

Background Nonmedical use of opioids has become increasingly problematic in recent years with increases in overdoses, treatment admissions, and deaths. Use also appears to be contributing to heroin initiation, which has increased in recent years. Further research is needed to examine which adolescents are at highest risk for nonmedical use of opioids and heroin and to explore potential links between nonmedical opioid use and heroin use. Methods Data were analyzed from a nationally representative sample of American high school seniors in the Monitoring the Future study (2009–2013, Weighted N = 67,822). We examined associations between frequency and recency of nonmedical use of opioids and heroin. Sociodemographic correlates of use of each drug were also examined. Results 12.4% of students reported lifetime nonmedical opioid use and 1.2% reported lifetime heroin use. As frequency of lifetime nonmedical opioid use increased, so too did the odds for reporting heroin use, with over three-quarters (77.3%) of heroin users reporting lifetime nonmedical opioid use. Recent (30-day) nonmedical opioid use was a robust risk factor for heroin use and almost a quarter (23.2%) of students who reported using opioids ≥40 times reported lifetime heroin use. Black and Hispanic students were less likely to report nonmedical opioid or heroin use than white students, but they were more likely to report heroin use in absence of nonmedical opioid use. Discussion Recent and frequent nonmedical opioid use are risk factors for heroin use among adolescents. Prevention needs to be targeted to those at highest risk. PMID:26653341

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.

Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study

PubMed Central

Agniel, Denis; Beam, Andrew; Yorkgitis, Brian; Bicket, Mark; Homer, Mark; Fox, Kathe P; Knecht, Daniel B; McMahill-Walraven, Cheryl N; Palmer, Nathan; Kohane, Isaac

2018-01-01

Abstract Objective To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population. Design Retrospective cohort study. Setting Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016. Participants 1 015 116 opioid naive patients undergoing surgery. Main outcome measures Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose. Results 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively. Conclusions Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact. PMID:29343479

A Quality Improvement Project to Improve Education Provided by Nurses to ED Patients Prescribed Opioid Analgesics at Discharge.

PubMed

Waszak, Daria L; Mitchell, Ann M; Ren, Dianxu; Fennimore, Laura A

2017-10-27

The opioid crisis continues to take an unprecedented number of lives and is the top cause of injury death in the United States. The emergency department is a setting where patients with pain seek care and may be prescribed an opioid, yet many patients do not receive evidence-based education about taking their opioid safely. Like many communities across the country, Allegheny County, Pennsylvania, has experienced an increased rate of opioid overdoses; from 2015-2016, the number of opioid-related overdose deaths in the county increased by 44%. This quality improvement project is the implementation of a nurse-delivered, evidence-based education initiative for patients prescribed an opioid in an emergency department. Nurses were briefly trained on opioid safety and patient education, then over 12 weeks, delivered the dual-modal (verbal and written) education with a patient teach-back to verify comprehension. Nurses who completed the project training on opioid safety and patient education had a statistically significant improvement in their knowledge. Patient satisfaction surveys showed 100% of patients reported clear understanding of how to take their pain medication, and out of the patients receiving the opioid pain education for the first time, 88.2% learned something new about how to safely take, store, or dispose of their pain medication. Improving the delivery of opioid prescription education at emergency department discharge will enhance patient knowledge and promote safety, which may help mitigate the opioid crisis by reducing the rate of opioid use disorder and accidental overdoses. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Traumatic injuries and persistent opioid use in the USA: findings from a nationally representative survey.

PubMed

Alghnam, Suliman; Castillo, Renan

2017-04-01

Although opioid abuse is a rising epidemic in the USA, there are no studies to date on the incidence of persistent opioid use following injuries. Therefore, the aims of this study are: (1) to examine the incidence of persistent opioid use among a nationally representative sample of injured and non-injured populations; (2) to evaluate whether an injury is an independent predictor of persistent opioid use. Data from the Medical Expenditure Panel Survey were pooled (years 2009-2012). Adults were followed for about 2 years, during which they were surveyed about injury status and opioid use every 4-5 months. To determine whether injuries are associated with persistent opioid use, weighted multiple logistic regressions were constructed. While 2.3 million injured individuals received any opioid during the follow-up, 371 170 (15.6%) individuals became persistent opioid users (defined as opioid use across multiple time points). In a multiple logistic regression analysis adjusting for sociodemographic characteristics and self-reported health, those who sustained injuries were 1.4 times (95% CI 1.1 to 1.9) more likely to report persistent opioid use than those without injuries. We found injuries to be significantly associated with persistent opioid use in a nationally representative sample. Further investment in injury prevention may facilitate reduction of persistent opioid use and, thus, improve population health and reduce health expenditures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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.

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.

Opioid pharmaceuticals and addiction: the issues, and research directions seeking solutions.

PubMed

Walwyn, Wendy M; Miotto, Karen A; Evans, Christopher J

2010-05-01

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.

Opioid pharmaceuticals and addiction: The issues, and research directions seeking solutions

PubMed Central

Walwyn, Wendy M.; Miotto, Karen A.; Evans, Christopher J.

2011-01-01

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies. PMID:20188495

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, ...

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 ...

Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users.

PubMed

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

2014-01-01

In the United States, use of oral opioid analgesics has been associated with increasing rates of addiction, abuse, and diversion. However, little is known about the recent national use of non-illicit prescription opioid analgesics (those prescribed in a physician-patient relationship), the primary source of these drugs for the general US population. Our primary objective was to examine trends in the use of prescription opioid analgesics in the United States and to identify defining characteristics of patient users of prescribed opioids from 2000 to 2010. We used the nationally representative Medical Expenditure Panel Survey to examine trends in prescription oral opioid analgesic use from 2000 to 2010. We used survey design methods to make national estimates of adults (18 years and older) who reported receiving an opioid analgesic prescription (referred to as opioid users) and used logistic regression to examine predictors of opioid analgesic use. Our primary outcome measures were national estimates of total users of prescription opioid analgesics and total number of prescriptions. Our secondary outcome was that of observing changes in the disability and health of the users. The estimated total number of opioid analgesic prescriptions in the United States increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an estimated 7.4% (95% confidence interval, 6.9-7.9) of adult Americans were prescription opioid users compared with 11.8% (95% confidence interval, 11.2-12.4) in 2010. On the basis of estimates adjusted for changes in the general population, each year was associated with a 6% increase in the likelihood of receiving an opioid prescription from 2000 to 2010. Despite the apparent increase in use, there were no demonstrable improvements in the age- or sex-adjusted disability and health status measures of opioid users. The use of prescription opioid analgesics among adult Americans has increased in recent years, and this increase does not seem to be associated with improvements in disability and health status among users. On a public health level, these data suggest that there may be an opportunity to reduce the prescribing of opioid analgesics without worsening of population health metrics.

Epigenetic regulation of spinal cord gene expression contributes to enhanced postoperative pain and analgesic tolerance subsequent to continuous opioid exposure

PubMed Central

Liang, De-Yong; Shi, Xiao-You; Sun, Yuan; Clark, J David

2016-01-01

Background Opioids have become the mainstay for treatment of moderate to severe pain and are commonly used to treat surgical pain. While opioid administration has been shown to cause opioid-induced hyperalgesia and tolerance, interactions between opioid administration and surgery with respect to these problematic adaptations have scarcely been addressed. Accumulating evidence suggests opioids and nociceptive signaling may converge on epigenetic mechanisms in spinal cord to enhance or prolong neuroplastic changes. Epigenetic regulation of Bdnf (brain-derived neurotrophic factor) and Pdyn (prodynorphin) genes may be involved. Results Four days of ascending doses of morphine treatment caused opioid-induced hyperalgesia and reduced opioid analgesic efficacy in mice. Both opioid-induced hyperalgesia and the reduced opioid analgesic efficacy were enhanced in mice that received hindpaw incisions. The expression of Bdnf and Pdyn (qPCR) was increased after morphine treatment and incision. Chromatin immunoprecipitation assays demonstrated that the Pdyn and Bdnf promoters were more strongly associated with acetylated H3K9 after morphine plus incision than in the morphine or incision alone groups. Selective tropomyosin-related kinase B (ANA-12) and κ-opioid receptor (nor-binaltorphimine) antagonists were administered intrathecally, both reduced hyperalgesia one or three days after surgery. Administration of ANA-12 or nor-binaltorphimine attenuated the decreased morphine analgesic efficacy on day 1, but only nor-binaltorphimine was effective on day 3 after incision in opioid-exposed group. Coadministration of histone acetyltransferase inhibitor anacardic acid daily with morphine blocked the development of opioid-induced hyperalgesia and attenuated incision-enhanced hyperalgesia in morphine-treated mice. Anacardic acid had similar effects on analgesic tolerance, showing the involvement of histone acetylation in the interactions detected. Conclusions Spinal epigenetic changes involving Bdnf and Pdyn may contribute to the enhanced postoperative nociceptive sensitization and analgesic tolerance observed after continuous opioid exposure. Treatments blocking the epigenetically mediated up-regulation of these genes or administration of TrkB or κ-opioid receptor antagonists may improve the clinical utility of opioids, particularly after surgery. PMID:27094549

Epigenetic regulation of spinal cord gene expression contributes to enhanced postoperative pain and analgesic tolerance subsequent to continuous opioid exposure.

PubMed

Sahbaie, Peyman; Liang, De-Yong; Shi, Xiao-You; Sun, Yuan; Clark, J David

2016-01-01

Opioids have become the mainstay for treatment of moderate to severe pain and are commonly used to treat surgical pain. While opioid administration has been shown to cause opioid-induced hyperalgesia and tolerance, interactions between opioid administration and surgery with respect to these problematic adaptations have scarcely been addressed. Accumulating evidence suggests opioids and nociceptive signaling may converge on epigenetic mechanisms in spinal cord to enhance or prolong neuroplastic changes. Epigenetic regulation of Bdnf (brain-derived neurotrophic factor) and Pdyn (prodynorphin) genes may be involved. Four days of ascending doses of morphine treatment caused opioid-induced hyperalgesia and reduced opioid analgesic efficacy in mice. Both opioid-induced hyperalgesia and the reduced opioid analgesic efficacy were enhanced in mice that received hindpaw incisions. The expression of Bdnf and Pdyn (qPCR) was increased after morphine treatment and incision. Chromatin immunoprecipitation assays demonstrated that the Pdyn and Bdnf promoters were more strongly associated with acetylated H3K9 after morphine plus incision than in the morphine or incision alone groups. Selective tropomyosin-related kinase B (ANA-12) and κ-opioid receptor (nor-binaltorphimine) antagonists were administered intrathecally, both reduced hyperalgesia one or three days after surgery. Administration of ANA-12 or nor-binaltorphimine attenuated the decreased morphine analgesic efficacy on day 1, but only nor-binaltorphimine was effective on day 3 after incision in opioid-exposed group. Coadministration of histone acetyltransferase inhibitor anacardic acid daily with morphine blocked the development of opioid-induced hyperalgesia and attenuated incision-enhanced hyperalgesia in morphine-treated mice. Anacardic acid had similar effects on analgesic tolerance, showing the involvement of histone acetylation in the interactions detected. Spinal epigenetic changes involving Bdnf and Pdyn may contribute to the enhanced postoperative nociceptive sensitization and analgesic tolerance observed after continuous opioid exposure. Treatments blocking the epigenetically mediated up-regulation of these genes or administration of TrkB or κ-opioid receptor antagonists may improve the clinical utility of opioids, particularly after surgery. © The Author(s) 2016.

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

Kappa2 opioid receptor subtype binding requires the presence of the DOR-1 gene.

PubMed

Ansonoff, Michael A; Wen, Ting; Pintar, John E

2010-01-01

Over the past several years substantial evidence has documented that opioid receptor homo- and heterodimers form in cell lines expressing one or more of the opioid receptors. We used opioid receptor knockout mice to determine whether in vivo pharmacological characteristics of kappa1 and kappa2 opioid receptors changed following knockout of specific opioid receptors. Using displacement of the general opioid ligand diprenorphine, we observed that occupancy or knockout of the DOR-1 gene increases the binding density of kappa1 receptors and eliminates kappa2 receptors in crude membrane preparations while the total density of kappa opioid binding sites is unchanged. Further, the analgesic potency of U69,593 in cumulative dose response curves is enhanced in mice lacking the DOR-1 gene. These results demonstrate that the DOR-1 gene is required for the expression of the kappa2 opioid receptor subtype and are consistent with the possibility that a KOR-1/DOR-1 heterodimer mediates kappa2 pharmacology.

Women and the opioid crisis: historical context and public health solutions.

PubMed

Terplan, Mishka

2017-08-01

Driven by a legitimate but overly opioid-focused response to pain, the United States is currently experiencing an opioid crisis, a crisis with parallels to the first opioid epidemic at the turn of the 20th century. Women, particularly white reproductive-age women, are increasingly the face of the opioid crisis. Given the penetration of opioid misuse and addiction across all income and insurance strata, any provider who cares for women needs to be prepared to assess and evaluate opioid use, misuse, and addiction. Although responsible opioid prescribing is essential, treatment capacity must be expanded and be inclusive of the unique needs of women. However, the public and public health response to the opioid crisis must include rolling back the war on drugs. The continued criminalization of the public health issue of drug use and the medical condition of addiction is unethical, ineffective, and inhumane. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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 did not have sufficient evidence to assess which opioid drug provided the best pain relief with the least adverse effects. Authors’ conclusions Parenteral opioids provide some relief from pain in labour but are associated with adverse effects. Maternal satisfaction with opioid analgesia was largely unreported but appeared moderate at best. This review needs to be examined alongside related Cochrane reviews examining pain management in labour. More research is needed to determine which analgesic intervention is most effective, and provides greatest satisfaction to women with acceptable adverse effects for mothers and their newborn. PMID:20824859

Data Overview: Overview of an Epidemic

MedlinePlus

... the Epidemic Commonly Used Terms Prescription Opioids Heroin Fentanyl Data Opioid Data Analysis Drug Overdose Death Data ... Overdose Data Heroin Overdose Data Synthetic Opioid Data Fentanyl Encounters Data Overdose Prevention Improve Opioid Prescribing Prevent ...

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.

Effect of Peripheral μ-, δ-, and κ-Opioid Ligands on the Development of Tolerance to Ethanol-Induced Analgesia.

PubMed

Sudakov, S K; Alekseeva, E V; Nazarova, G A

2017-06-01

We studied the rate of development of tolerance to the ethanol-induced analgesia under the effect of μ-, δ-, and κ-opioid agonists and antagonists not crossing the blood-brain barrier and rapidly inactivated by gastric and duodenal proteolytic enzymes. Activation of gastric κ-opioid receptors eliminated the analgesic effect of ethanol and accelerated the development of tolerance to ethanol-induced analgesia. In contrast, activation of gastric μ-opioid receptors decelerated the development of this tolerance. Activation of gastric δ-opioid receptors produced no effect on examined tolerance. μ-Opioid receptor antagonist decelerated and δ-opioid receptor antagonist accelerated the development of tolerance to ethanol-induced analgesia. Thus, the state of gastric opioid receptors affects the manifestation of ethanol-induced analgesia and the development of tolerance to this effect.

Pill counts and pill rental: unintended entrepreneurial opportunities.

PubMed

Viscomi, Christopher M; Covington, Melissa; Christenson, Catherine

2013-07-01

Prescription opioid diversion and abuse are becoming increasingly prevalent in many regions of the world, particularly the United States. One method advocated to assess compliance with opioid prescriptions is occasional "pill counts." Shortly before a scheduled appointment, a patient is notified that they must bring in the unused portion of their opioid prescription. It has been assumed that if a patient has the correct number and strength of pills that should be present for that point in a prescription interval that they are unlikely to be selling or abusing their opioids. Two cases are presented where patients describe short term rental of opioids from illicit opioid dealers in order to circumvent pill counts. Pill renting appears to be an established method of circumventing pill counts. Pill counts do not assure non-diversion of opioids and provide additional cash flow to illicit opioid dealers.

Opioid overdose prevention and naloxone rescue kits: what we know and what we don't know.

PubMed

Kerensky, Todd; Walley, Alexander Y

2017-01-07

The opioid use and overdose crisis is persistent and dynamic. Opioid overdoses were initially driven in the 1990s and 2000s by the increasing availability and misuse of prescription opioids. More recently, opioid overdoses are increasing at alarming rates due to wider use of heroin, which in some places is mixed with fentanyl or fentanyl derivatives. Naloxone access for opioid overdose rescue is one of the US Department of Health and Human Services' three priority areas for responding to the opioid crisis. This article summarizes the known benefits of naloxone access and details unanswered questions about overdose education and naloxone rescue kits. Hopefully future research will address these knowledge gaps, improve the effectiveness of opioid overdose education and naloxone distribution programs, and unlock the full promise of naloxone rescue kits.

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals.

PubMed

Turton, Samuel; Myers, James Fm; Mick, Inge; Colasanti, Alessandro; Venkataraman, Ashwin; Durant, Claire; Waldman, Adam; Brailsford, Alan; Parkin, Mark C; Dawe, Gemma; Rabiner, Eugenii A; Gunn, Roger N; Lightman, Stafford L; Nutt, David J; Lingford-Hughes, Anne

2018-06-25

Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [ 11 C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [ 11 C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.

Epidemiologic trends and geographic patterns of fatal opioid intoxications in Connecticut, USA: 1997-2007.

PubMed

Green, Traci C; Grau, Lauretta E; Carver, H Wayne; Kinzly, Mark; Heimer, Robert

2011-06-01

The leading cause of injury death among adults in Connecticut (CT), USA is drug poisonings. We analyzed the epidemiology and geographic distribution of opioid-involved accidental drug-involved intoxication deaths ("overdoses") in CT over an 11-year period. We reviewed data from 1997 to 2007 on all adult accidental/undetermined drug intoxication deaths in CT that were referred to the Office of the Chief Medical Examiner (OCME). Regression analyses were conducted to uncover risk factors for fatal opioid-involved intoxications and to compare heroin- to prescription opioid- and methadone-involved deaths. Death locations were mapped to visualize differences in the geographic patterns of overdose by opioid type. Of the 2900 qualifying deaths, 2231 (77%) involved opioids. Trends over time revealed increases in total opioid-related deaths although heroin-related deaths remained constant. Methadone, oxycodone and fentanyl, the most frequently cited prescription opioids, exhibited significant increases in opioid deaths. Prescription opioid-only deaths were more likely to involve other medications (e.g., benzodiazepines) and to have occurred among residents of a suburban or small town location, compared to heroin-involved or methadone-involved deaths. Heroin-only deaths tended to occur among non-Whites, were more likely to involve alcohol or cocaine and to occur in public locations and large cities. The epidemiology of fatal opioid overdose in CT exhibits distinct longitudinal, risk factor, and geographic differences by opioid type. Each of these trends has implications for public health and prevention efforts. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Suicidal ideation is associated with individual differences in prescription opioid craving and cue-reactivity among chronic pain patients.

PubMed

Garland, Eric L; Riquino, Michael R; Priddy, Sarah E; Bryan, Craig J

2017-01-01

Given that chronic pain patients experience significant rates of suicidal ideation and suicide attempts, access to prescription opioids compounds the risk of death by suicide. These patients may experience heightened opioid craving and exhibit increased cue-reactivity to stimuli associated with past opioid use when suicidal ideation produces negative affective states. Because both opioids and suicidal behavior are used to alleviate emotional and physical pain through a process of negative reinforcement, elucidating factors that mediate this association may yield insight into suicide risk among chronic pain patients. This study examined the relationship between suicidal ideation and opioid craving and cue-reactivity, and tested opioid self-medication as a mediator of associations between those factors after controlling for the impact of pain severity. A sample of 115 chronic pain patients provided demographic and clinical information on the Obsessive Compulsive Drug Use Scale, the Current Opioid Misuse Measure, and the Brief Pain Inventory before completing an opioid dot probe task in which heart rate variability was recorded. As hypothesized, suicidal ideation was positively correlated with subjective opioid craving and physiological cue-reactivity. Self-medication significantly mediated the association between suicidal ideation, craving, and cue-reactivity. As opioids relieve the emotional pain linked with suicidal thoughts, chronic pain patients with higher levels of suicidal ideation may experience more intense opioid craving and exhibit heightened physiological cue-reactivity when compared to patients with low levels of suicidal ideation.

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.

A randomized, double-blind, placebo-controlled pilot study of naltrexone to counteract antipsychotic-associated weight gain: proof of concept.

PubMed

Tek, Cenk; Ratliff, Joseph; Reutenauer, Erin; Ganguli, Rohan; O'Malley, Stephanie S

2014-10-01

Patients with schizophrenia experience higher rates of obesity as well as related morbidity and mortality than the general population does. Women with schizophrenia are at particular risk for antipsychotic-associated weight gain, obesity, and related medical disorders such as diabetes and cardiovascular disease. Given preclinical studies revealing the role of the endogenous opioid systems in human appetite and the potential of antipsychotic medications to interfere with this system, we hypothesized that opioid antagonists may be beneficial in arresting antipsychotic-associated weight gain and promoting further weight loss in women with schizophrenia. In the present study, 24 overweight women with a diagnosis of schizophrenia or schizoaffective disorder were randomized to placebo or naltrexone (NTX) 25 mg/d for 8 weeks. The primary outcome measure was a change in body weight from baseline. The patients in the NTX group had significant weight loss (-3.40 kg) compared with weight gain (+1.37 kg) in the patients in the placebo group. Mainly, nondiabetic subjects lost weight in the NTX arm. These data support the need to further investigate the role of D2 blockade in reducing food reward-based overeating. A larger study addressing the weaknesses of this pilot study is currently underway.

Simulation and Prediction of the Drug-Drug Interaction Potential of Naloxegol by Physiologically Based Pharmacokinetic Modeling.

PubMed

Zhou, D; Bui, K; Sostek, M; Al-Huniti, N

2016-05-01

Naloxegol, a peripherally acting μ-opioid receptor antagonist for the treatment of opioid-induced constipation, is a substrate for cytochrome P450 (CYP) 3A4/3A5 and the P-glycoprotein (P-gp) transporter. By integrating in silico, preclinical, and clinical pharmacokinetic (PK) findings, minimal and full physiologically based pharmacokinetic (PBPK) models were developed to predict the drug-drug interaction (DDI) potential for naloxegol. The models reasonably predicted the observed changes in naloxegol exposure with ketoconazole (increase of 13.1-fold predicted vs. 12.9-fold observed), diltiazem (increase of 2.8-fold predicted vs. 3.4-fold observed), rifampin (reduction of 76% predicted vs. 89% observed), and quinidine (increase of 1.2-fold predicted vs. 1.4-fold observed). The moderate CYP3A4 inducer efavirenz was predicted to reduce naloxegol exposure by ∼50%, whereas weak CYP3A inhibitors were predicted to minimally affect exposure. In summary, the PBPK models reasonably estimated interactions with various CYP3A modulators and can be used to guide dosing in clinical practice when naloxegol is coadministered with such agents. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Substance Use and Recidivism Outcomes for Prison-Based Drug and Alcohol Interventions.

PubMed

de Andrade, Dominique; Ritchie, Jessica; Rowlands, Michael; Mann, Emily; Hides, Leanne

2018-05-04

We conducted a systematic review to examine the substance use and recidivism outcomes of prison-based substance use interventions. We searched public health, criminology, and psychology databases, and conducted forward and backward snowballing methods to identify additional studies. Studies were included if they were published between January 1, 2000 and June 30, 2017; were published in English; and reported substance use and/or recidivism outcomes of prison-based substance use interventions. Studies were reviewed for methodological rigor using the Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies. Our search returned 49 studies: 6 were methodologically strong, 20 were moderate, and 23 were weak. Results suggest therapeutic communities are effective in reducing recidivism and, to a lesser extent substance use after release. There is also evidence to suggest that opioid maintenance treatment is effective in reducing the risk of drug use after release from prison for opioid users. Furthermore, care after release from prison appears to enhance treatment effects for both types of interventions. Results provide evidence that policymakers can use to make informed decisions on best-practice approaches when addressing prisoner substance dependence and improving long-term outcomes. This comprehensive review highlights the difficulties of conducting quality research in the prison setting and suggests innovative study design for future research.

Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations

PubMed Central

Finnerup, Nanna B; Attal, Nadine; Haroutounian, Simon; McNicol, Ewan; Baron, Ralf; Dworkin, Robert H; Gilron, Ian; Haanpaa, Maija; Hansson, Per; Jensen, Troels S; Kamerman, Peter R; Lund, Karen; Moore, Andrew; Raja, Srinivasa N; Rice, Andrew SC; Rowbotham, Michael; Sena, Emily; Siddall, Philip; Smith, Blair H; Wallace, Mark

2015-01-01

Summary Background Neuropathic pain is difficult to treat. New treatments, clinical trials and standards of quality for assessing evidence justify an update of evidence-based recommendations for its pharmacological treatment. Methods The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain conducted a systematic review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites). Meta-analysis used Numbers Needed to Treat (NNT) for 50 % pain relief as primary measure and assessed publication bias. Recommendations used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Findings In total 229 studies were included. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-review journals reported greater effects than online studies (R2=9·3%, p<0·01). Trial outcomes were generally modest even for effective drugs : in particular NNTs were 3·6 (95 % CI 3·0–4·4) for tricyclic antidepressants (TCAs), 6·4 (95 % CI 5·2–8·4) for serotonin- noradrenaline reuptake inbibitor (SNRI) antidepressants duloxetine and venlafaxine, 7·7 (95 % CI 6·5–9·4) for pregabalin and 6·3 (95 % CI 5·0–8·3) for gabapentin. NNTs were higher for gabapentin ER/enacarbil and capsaicin high concentration patches, lower for opioids and botulinum toxin A (BTX-A) and undetermined for lidocaine patches. Final quality of evidence was lower for lidocaine patches and BTX-A. Tolerability/safety and values/preferences were high for lidocaine patches and lower for opioids and TCAs. This permitted a strong GRADE recommendation for use and proposal as first line for TCAs, SNRIs, pregabalin, gabapentin and gabapentin ER/enacarbil in neuropathic pain, a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin patches and tramadol, and a weak recommendations for use and proposal as third line for strong opioids (particularly oxycodone and morphine) and BTX-A. Data for cannabinoids, tapentadol, drug combinations, and several other antiepileptics, antidepressants and topical drugs were inconclusive. Interpretation Limited efficacy, large placebo responses, inadequate diagnostic criteria and poor phenotypic profiling probably account for modest trial outcomes and should be taken into account in future studies. Funding This study was funded by NeuPSIG. PMID:25575710

Nonpeptidic Delta (δ) Opioid Agonists and Antagonists of the Diarylmethylpiperazine Class: What Have We Learned?

NASA Astrophysics Data System (ADS)

Calderon, Silvia N.

The discovery of the selective delta (δ) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, represented a major advance in the field of δ-opioid ligands. Extensive research has recently been performed to uncover the structure-activity relationships (SAR) of this class of ligands, thereby providing valuable tools for the pharmacological characterization of the δ opioid receptor. This review focuses on the SAR of this unique series of ligands, and provides an overview of the various chemical routes that have been developed and optimized through the years to allow the syntheses of these ligands on a multigram scale. The search for selective δ opioid agonists and antagonists, as well as for those with mixed opioid agonist properties with potential therapeutic value, continues. Several questions regarding the interaction at the molecular level of diphenylmethylpiperazine derivatives and related analogs with opioid receptors and in particular with the δ opioid system still remain unanswered. Indeed, the development and pharmacological characterization of novel nonpeptidic δ opioid ligands remains an active area of research, as it may provide a better understanding of the role of this receptor in multiple disease states and disorders.

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.

Sex differences in analgesic, reinforcing, discriminative, and motoric effects of opioids.

PubMed

Craft, Rebecca M

2008-10-01

This review summarizes evidence for sex differences in behavioral effects of opioids, primarily in rats. Whereas micro agonists have been found to be more potent and in some cases more efficacious in producing analgesia and sedation in males than females, females are more sensitive than males to reinforcing and locomotor stimulant effects of opioids. Sex differences in motoric effects of opioids may contribute to sex differences in other behavioral effects of opioids; for example, sex differences in rats' ability to discriminate morphine from saline can be attributed entirely to greater morphine-induced sedation in males. Chronic estradiol blunts females' sensitivity to morphine's analgesic and sedative effects, but enhances females' sensitivity to the reinforcing and locomotor stimulant effects of micro opioids. The neurobiological basis for sex differences in and estradiol modulation of behavioral effects of opioids includes brain opioid receptor density (greater in males and under low-estradiol conditions in females) and dopaminergic function (greater in females and under high-estradiol conditions). Given the significant and growing use of opioids by women, both medicinally and recreationally, understanding how female biology influences analgesic and other effects of opioids is crucial. Copyright (c) 2008 APA, all rights reserved.

Metoclopramide for Acute Migraine Treatment in the Emergency Department: An Effective Alternative to Opioids.

PubMed

Najjar, Mejdi; Hall, Tyler; Estupinan, Blanca

2017-04-20

In light of recent warnings by the United States (US) Surgeon General and Centers for Disease Control (CDC) guidelines for recommending more prudent use of opioid narcotics, the search for a non-opioid alternative for aborting acute migraines is particularly relevant. The CDC also estimates the prevalence of opioid dependence may be as high as 26% among patients prescribed opioids for chronic pain, not due to cancer, in the primary care setting. Given such staggering data, it is imperative that we, as caretakers, not foster opioid dependence but rather continue to investigate non-opioid therapies for the management of acute migraines in the emergent care settings. Our literature review demonstrates that metoclopramide should be used more frequently as first-line therapy for an acute migraine over opioids. The use of opioids specifically has been discouraged as migraine treatment by the American Headache Society citing "insufficient evidence" as the main reason. Metoclopramide, specifically using the 10 mg dose, has been cited as "highly likely to be effective" by the same guidelines. Another major issue with opioids is the growing potential for abuse, thus minimizing the use of these drugs for only special circumstances would be beneficial overall.

Opioid Analgesics and P-glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

PubMed Central

Mercer, Susan L.; Coop, Andrew

2012-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationship development to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation. PMID:21050174

Tramadol for maintenance in opioid dependence: A retrospective chart review.

PubMed

Sarkar, Siddharth; Lal, Rakesh; Varshney, Mohit; Balhara, Yatan Pal Singh

Tramadol is an opioid agonist which can be potentially used for maintenance treatment of patients with opioid use disorders. This chart review presents the characteristics of individuals with an ICD 10 diagnosis of opioid dependence who were maintained on tramadol for a period of at least 6 months. Records of patients seeking treatment for opioid dependence from the outpatient clinic of the National Drug Dependence Treatment Centre, Ghaziabad, India were screened. One hundred consecutive patients who received tramadol for more than 6 months were included. The sample comprised exclusively of males and had a mean age of 40.9 years. The median dose of tramadol at initiation and continuation was 300 mg/day. Sixty-two patients achieved complete abstinence during the course of treatment. Greater age, longer duration of opioid use, and better follow-up adherence were associated with abstinent status. The rates of abstinence were higher among those presenting with natural opioid use as compared to others (prescription opioid use or heroin use). Tramadol can be an alternative medication for harm reduction in select group of patients with opioid dependence. Further research is required to strengthen the evidence base of rational use of tramadol for maintenance treatment of patients with opioid dependence.

A systematic review of opioid use after extremity trauma in orthopedic surgery.

PubMed

Koehler, Rikki M; Okoroafor, Ugochi C; Cannada, Lisa K

2018-06-01

The United States is in a prescription opioid crisis. Orthopedic surgeons prescribe more opioid narcotics than any other surgical specialty. The purpose of this study was to evaluate the state of opioid use after extremity trauma in orthopedic surgery. A computerized literature search of PubMed/MEDLINE was conducted to evaluate the status of opioids after extremity fractures. Six articles were identified and included in the review. Patients who consume more opioids communicate greater pain intensity and less satisfaction with pain control. Intraoperative multimodal drug injection and nerve blockade are viable alternatives for postoperative pain control and can help decrease systemic opioid use. Orthopedic surgeons are overprescribing opioids. Compared to other countries, the United States consumes more opioids with no better satisfaction with pain control. Orthopedic trauma surgeons should tailor their postoperative opioid prescriptions to the individual patient and utilize alternative options in order to control postoperative pain. Patients should be counseled regarding narcotic addiction and dependence. Patients unable to manage pain postoperatively should be followed closely and receive the proper chronic pain management, mental and social health services referrals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

PubMed Central

Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

2010-01-01

Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

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

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

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.

Prescription opioid misuse in the United States and the United Kingdom: cautionary lessons.

PubMed

Weisberg, Daniel F; Becker, William C; Fiellin, David A; Stannard, Cathy

2014-11-01

In the United States, opioid analgesics have increasingly been prescribed in the treatment of chronic pain, and this trend has accompanied increasing rates of misuse and overdose. Lawmakers have responded with myriad policies to curb the growing epidemic of opioid misuse, and a global alarm has been sounded among countries wishing to avoid this path. In the United Kingdom, a similar trend of increasing opioid consumption, albeit at lower levels, has been observed without an increase in reported misuse or drug-related deaths. The comparison between these two countries in opioid prescribing and opioid overdose mortality underscores important features of prescribing, culture, and health systems that may be permissive or protective in the development of a public health crisis. As access to opioid medications increases around the world, it becomes vitally important to understand the forces impacting opioid use and misuse. Trends in benzodiazepine and methadone use in the UK as well as structural elements of the National Health Service may serve to buffer opioid-related harms in the face of increasing prescriptions. In addition, the availability and price of heroin, as well as the ease of access to opioid agonist treatment in the UK may limit the growth of the illicit market for prescription opioids. The comparison between the US and the UK in opioid consumption and overdose rates should serve as a call to action for UK physicians and policymakers. Basic, proactive steps in the form of surveillance - of overdoses, marketing practices, prescribers, and patients - and education programs may help avert a public health crisis as opioid prescriptions increase. Copyright © 2014 Elsevier B.V. All rights reserved.

Lack of Association Between the Use of Nerve Blockade and the Risk of Postoperative Chronic Opioid Use Among Patients Undergoing Total Knee Arthroplasty: Evidence From the Marketscan Database.

PubMed

Sun, Eric C; Bateman, Brian T; Memtsoudis, Stavros G; Neuman, Mark D; Mariano, Edward R; Baker, Laurence C

2017-09-01

Total knee arthroplasty (TKA) is associated with high rates of prolonged opioid use after surgery (10%-34%). By decreasing opioid use in the immediate postoperative period, perioperative nerve blockade has been hypothesized to decrease the risk of persistent opioid use. Using health care utilization data, we constructed a sample of 120,080 patients undergoing TKA between 2002 and 2012 and used billing data to identify the utilization of peripheral or neuraxial blockade. We then used a multivariable logistic regression to estimate the association between nerve blockade and the risk of chronic opioid use, defined as having filled ≥10 prescriptions or ≥120 days' supply for an opioid in the first postsurgical year. Our analyses were adjusted for an extensive set of potential confounding variables, including medical comorbidities, previous opioid use, and previous use of other medications. We did not find an association between nerve blockade and the risk of postsurgical chronic opioid use across any of these 3 groups: adjusted relative risk (ARR) 0.984 for patients opioid-naïve in the year before surgery (98.3% confidence interval [CI], 0.870-1.12, P = .794), ARR 1.02 for intermittent opioid users (98.3% CI, 0.948-1.09, P = .617), and ARR 0.986 (98.3% CI, 0.963-1.01, P = .257) for chronic opioid users. Similar results held for alternative measures of postsurgical opioid use. Although the use of perioperative nerve blockade for TKA may improve short-term outcomes, the analyzed types of blocks do not appear to decrease the risk of persistent opioid use in the longer term.

Use and Misuse of Opioids in Maine: Results From Pharmacists, the Prescription Monitoring, and the Diversion Alert Programs

PubMed Central

Piper, Brian J.; Desrosiers, Clare E.; Lipovsky, John W.; Rodney, Matthew A.; Baker, Robert P.; McCall, Kenneth L.; Nichols, Stephanie D.; Martin, Sarah L.

2016-01-01

Objective: Although opioids have substantial efficacy for acute pain management, escalation to opioid misuse and abuse is a persistent concern. This report assesses the current status of the opioid epidemic in Maine using three complementary data sets. Method: A representative sample of pharmacists (N = 275) completed an online survey regarding the extent that opioids affected their practice. A county-level analysis of opioid prescriptions (N = 1.22 million) reported to the Maine Prescription Monitoring Program (M-PMP) in 2014 and the agents implicated in arrests as reported to the Maine Diversion Alert Program (DAP, N = 2,700) in 2014/15 also was completed. Results: A significantly greater number of pharmacists agreed that opioid misuse (85.9%), rather than diversion (76.8%) or access (54.2%), was a concern. Only half (56.2%) reported use of the M-PMP. Opioids were dispensed to 22.4% of residents (37.7% of women in their 80s). This was enough to supply everyone in Maine with a 16.1-day supply. Buprenorphine accounted for almost half of opioid prescriptions to young adults (46.3% women, 49.3% men). Arrests increased by 13.3% from 2014 to 2015, and the proportion of arrests that involved prescription opioids decreased while those involving stimulants and heroin were elevated. Conclusions: Pharmacists are very aware of the potential for opioid misuse, but many do not consistently use the M-PMP. There continues to be substantial legitimate use, as well as criminal activity, involving oxycodone and other prescription opioids. Continued vigilance and use of tools like the PMP and DAP are necessary to minimize nonmedical use of opioids in Maine. PMID:27340958

A longitudinal study of depression among middle-aged and senior patients initiating chronic opioid therapy.

PubMed

Von Korff, Michael; Shortreed, Susan M; LeResche, Linda; Saunders, Kathleen; Thielke, Stephen; Thakral, Manu; Rosenberg, Dori; Turner, Judith A

2017-03-15

Improved understanding how depressive symptoms change with sustained opioid use is needed. We prospectively assessed patients 45 years or older initiating chronic opioid therapy (COT) at baseline and at 4 and 12 months, differentiating recent COT initiators (n=748) and continuing users (n=468). Level of opioid use before 12-month follow-up was classified as regular/higher-dose, intermittent/lower-dose, or minimal/no use. Depressive symptoms were assessed using the Patient Health Questionnaire-8 (PHQ-8). Depressive symptoms decreased, on average, from baseline to 12 months regardless of level of opioid use. COT patients with regular/higher-dose compared to those with intermittent/lower-dose opioid use (who had similar pain outcomes) did not differ in PHQ-8 scores at 12 months (adjusted mean difference -0.14, 95% CI, -1.07, 0.78 for COT initiators). At 12 months, COT patients with intermittent/lower-dose use had higher adjusted PHQ-8 scores than did those with minimal/no opioid use (adjusted mean difference 0.77, 95% CI, 0.03-1.52 for COT initiators). However, 77% of patients who discontinued opioids cited improved pain as a reason for discontinuation, while 21% cited negative emotional effects of opioids as a reason for discontinuation. Discontinuation was more common among persons who, at baseline, attributed 3 or more depressive symptoms to opioid use. Results are relevant to older COT patients receiving low to moderate opioid doses. Depressive symptoms did not increase with sustained opioid use. Depressive symptoms were not higher with regular/higher-dose compared to intermittent/lower-dose use. Persons who perceived negative effects of opioids on emotions more often discontinued their use. Copyright © 2017. Published by Elsevier B.V.

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

Opioid use among same-day surgery patients: Prevalence, management and outcomes

PubMed Central

Wilson, Jennifer LC; Poulin, Patricia A; Sikorski, Robert; Nathan, Howard J; Taljaard, Monica; Smyth, Catherine

2015-01-01

OBJECTIVES: To determine whether the prevalence of opioid use among patients requiring elective same-day admission (SDA) surgery is greater than the 2.5% prevalence found in the general population. Secondary objectives were to assess compliance with expert recommendations on acute pain management in opioid-tolerant patients and to examine clinical outcomes. METHODS: A retrospective review of 812 systematically sampled adult SDA surgical cases between April 1, 2008 and March 31, 2009 was conducted. RESULTS: Among 798 eligible patients, 148 (18.5% [95% CI 15.9% to 21.2%]) were prescribed opioids, with 4.4% prescribed long-acting opioids (95% CI 3.0% to 5.8%). Use of opioids was most prevalent among orthopedic and neurosurgery patients. Among the 35 patients on long-acting opioids who had a high likelihood of being tolerant, anesthesiologists correctly identified 33, but only 13 (37%) took their usual opioid preoperatively while 22 (63%) had opioids continued postoperatively. Acetaminophen, nonsteroidal anti-inflammatory drugs and pregabalin were ordered preoperatively in 18 (51%), 15 (43%) and 18 (51%) cases, respectively, while ketamine was used in 15 (43%) patients intraoperatively. Acetaminophen, nonsteroidal anti-inflammatory drugs and pregabalin were ordered postoperatively in 31 (89%), 15 (43%) and 17 (49%) of the cases, respectively. No differences in length of stay, readmissions and emergency room visits were found between opioid-tolerant and opioid-naïve patients. CONCLUSION: Opioid use is more common in SDA surgical patients than in the general population and is most prevalent within orthopedic and neurosurgery patients. Uptake of expert opinion on the management of acute pain in the opioid tolerant patient population is lacking. PMID:26357683

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.

Effect of a "pill mill" law on opioid prescribing and utilization: The case of Texas.

PubMed

Lyapustina, Tatyana; Rutkow, Lainie; Chang, Hsien-Yen; Daubresse, Matthew; Ramji, Alim F; Faul, Mark; Stuart, Elizabeth A; Alexander, G Caleb

2016-02-01

States have attempted to reduce prescription opioid abuse through strengthening the regulation of pain management clinics; however, the effect of such measures remains unclear. We quantified the impact of Texas's September 2010 "pill mill" law on opioid prescribing and utilization. We used the IMS Health LRx LifeLink database to examine anonymized, patient-level pharmacy claims for a closed cohort of individuals filling prescription opioids in Texas between September 2009 and August 2011. Our primary outcomes were derived at a monthly level and included: (1) average morphine equivalent dose (MED) per transaction; (2) aggregate opioid volume; (3) number of opioid prescriptions; and (4) quantity of opioid pills dispensed. We compared observed values with the counterfactual, which we estimated from pre-intervention levels and trends. Texas's pill mill law was associated with declines in average MED per transaction (-0.57 mg/month, 95% confidence interval [CI] -1.09, -0.057), monthly opioid volume (-9.99 kg/month, CI -12.86, -7.11), monthly number of opioid prescriptions (-12,200 prescriptions/month, CI -15,300, -9,150) and monthly quantity of opioid pills dispensed (-714,000 pills/month, CI -877,000, -550,000). These reductions reflected decreases of 8.1-24.3% across the outcomes at one year compared with the counterfactual, and they were concentrated among prescribers and patients with the highest opioid prescribing and utilization at baseline. Following the implementation of Texas's 2010 pill mill law, there were clinically significant reductions in opioid dose, volume, prescriptions and pills dispensed within the state, which were limited to individuals with higher levels of baseline opioid prescribing and utilization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Non-randomized intervention study of naloxone co-prescription for primary care patients on long-term opioid therapy for pain

PubMed Central

Coffin, Phillip O.; Behar, Emily; Rowe, Christopher; Santos, Glenn-Milo; Coffa, Diana; Bald, Matthew; Vittinghoff, Eric

2018-01-01

Background Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States. Objectives To evaluate the feasibility and impact of implementing naloxone prescription to patients prescribed opioids for chronic pain. Design 2-year non-randomized intervention study. Setting 6 safety net primary care clinics in San Francisco. Participants 1985 adults receiving long-term opioids for pain. Intervention Providers and clinic staff were trained and supported in naloxone prescribing. Measurements Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review. Results 38.2% of 1,985 patients on long-term opioids were prescribed naloxone. Patients on higher doses of opioids and with a past 12-month opioid-related emergency department (ED) visit were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month six months after the receipt of the prescription (IRR=0.53, 95%CI=0.34–0.83, P=0.005) and 63% fewer visits after one year (IRR=0.37, 95%CI=0.22–0.64, P<0.001), compared to patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone compared to those who did not (IRR 1.03, 95% CI 0.91–1.27, P = 0.61). Limitations Results are observational and may not be generalizable beyond safety net settings. Conclusion Naloxone can be co-prescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients on opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits such as reducing opioid-related adverse events. Funding Source National Institutes of Health grant R21DA036776 PMID:27366987

Persistent opioid use and socio-economic factors: a population-based study in Norway.

PubMed

Svendsen, Kristian; Fredheim, Olav M; Romundstad, Pål; Borchgrevink, Petter C; Skurtveit, Svetlana

2014-04-01

A growing proportion of the population is using opioids for longer time periods, but little is known about the characteristics of patients who are persistent opioid users. We therefore studied the association between socio-economic factors and persistent vs. short-term opioid use 4 years later. The background population is the complete Norwegian population in 2001. The study population is derived from two groups aged 35 years or older in 2001 who met one of the following criteria in 2005: (1) persistent opioid users (n = 15,113) or (2) short-term opioid users (n = 214,061). The applied definition of persistent opioid use corresponds to an average daily dose indicating likely daily use of opioids during 365 consecutive days. The socio-economic factors work status, income, marital status, immigrant status and education were obtained from the Population and Housing Census of 2001, and data on opioid use in 2005 were obtained from the complete national Norwegian Prescription Database. For logistic regression analyses, the study population was stratified by gender and by age over/under 67 years. In the 35- to 67-year-old age group, receiving a disability pension was more common in persistent opioid users compared with short-term opioid users (48% vs. 16% for women, 36% vs. 9% for men). Adjusted odds ratios for receiving a disability pension were 6.51 and 5.77 for women and men, respectively. Being divorced/separated was associated with being a persistent opioid user (odds ratio of 1.4 for both genders). There were also negative associations between persistent opioid use and attained education level, an unemployed working status and income status. Disability pension, not working, divorce, low income and low education in 2001 were associated with persistent opioid use in 2005. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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.

Comparative Analysis of Inpatient Costs for Obstetrics and Gynecology Surgery Patients Treated With IV Acetaminophen and IV Opioids Versus IV Opioid-only Analgesia for Postoperative Pain.

PubMed

Hansen, Ryan N; Pham, An T; Lovelace, Belinda; Balaban, Stela; Wan, George J

2017-10-01

Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures. Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption. We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients. We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07). Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581

PubMed Central

Assadi, Seyed Mohammad; Radgoodarzi, Reza; Ahmadi-Abhari, Seyed Ali

2003-01-01

Background Results of preclinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. Methods A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day) or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Results Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence. PMID:14624703

Exploring the lived experience of adults using prescription opioids to manage chronic noncancer pain

PubMed Central

Brooks, Erica A; Unruh, Anita; Lynch, Mary E

2015-01-01

BACKGROUND: Chronic noncancer pain (CNCP) and prescription opioid use is a highly complex and growing health care issue in Canada. Many quantitative research studies have investigated the effectiveness of opioids for chronic pain; however, gaps remain in the literature regarding the personal experience of using opioids and their impact on those experiencing CNCP. OBJECTIVE: To explore the lived experience of adults using prescription opioids to manage CNCP, focusing on how opioid medication affected their daily lives. METHODS: In-depth qualitative interviews were conducted with nine adults between 40 and 68 years of age who were using prescription opioids daily for CNCP. Interviews were audiorecorded and transcribed, and subsequently analyzed using interpretive phenomenological analysis. RESULTS: Six major themes identified positive and negative aspects of opioid use associated with social, physical, emotional and psychological dimensions of pain management. These themes included the process of decision making, and physical and psychosocial consequences of using opioids including pharmacological side effects, feeling stigmatized, guilt, fears, ambivalence, self-protection and acceptance. CONCLUSION: Although there were many negative aspects to using opioids daily, the positive effects outweighed the negative for most participants and most of the negative aspects were socioculturally induced rather than caused by the drug itself. The present study highlighted the complexities involved in using prescription opioids daily for management of CNCP for individuals living with pain. PMID:25562838

Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs.

PubMed

Valverde, Alexander; Cantwell, Shauna; Hernández, Jorge; Brotherson, Celeste

2004-01-01

To evaluate the anti-emetic properties of acepromazine in dogs receiving opioids as pre-anesthetic medication. Randomized prospective clinical study. One hundred and sixteen dogs (ASA I or II), admitted for elective surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 0.25-13.4 years of age, weighing 1.8-57.7 kg. A prospective clinical trial in which the dogs were randomly assigned to one of three groups. All groups received acepromazine (0.05 mg kg(-1) intramuscularly (i.m.)). Group I received acepromazine 15 minutes prior to opioid administration. Group II received acepromazine in combination with the opioid. Group III received acepromazine 15 minutes after opioid administration. One of three different opioids was administered i.m. to each dog: morphine sulfate at 0.5 mg kg(-1); hydromorphone hydrochloride at 0.1 mg kg(-1); or oxymorphone hydrochloride at 0.075 mg kg(-1). Dogs receiving acepromazine before the opioid (group I) had a significantly lower incidence of vomiting (18%) than dogs in groups II (45%) and III (55%). The degree of sedation was significantly lower in the dogs receiving the combination of acepromazine and the opioid (group II) than in dogs receiving the opioid as the first drug (group III). Acepromazine administered 15 minutes before the opioid lowers the incidence of vomiting induced by opioids.

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.

Successful Treatment of Opioid-Refractory Cancer Pain with Short-Course, Low-Dose Ketamine.

PubMed

Waldfogel, Julie M; Nesbit, Suzanne; Cohen, Steven P; Dy, Sydney M

2016-12-01

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

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.

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

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.

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

Adverse Selection? A Multi-Dimensional Profile of People Dispensed Opioid Analgesics for Persistent Non-Cancer Pain

PubMed Central

Rogers, Kris D.; Kemp, Anna; McLachlan, Andrew J.; Blyth, Fiona

2013-01-01

Objectives This study investigates utilisation patterns for prescription opioid analgesics in the Australian community and how these are associated with a framework of individual-level factors related to healthcare use. Methods Self-reported demographic and health information from participants in the 45 and Up Study cohort were linked to pharmaceutical claims from 2006–2009. Participants comprised 19,816 people with ≥1 opioid analgesic dispensing in the 12-months after recruitment to the cohort and 79,882 people not dispensed opioid analgesics. All participants were aged ≥45 years, were social security pharmaceutical beneficiaries, with no history of cancer. People dispensed opioid analgesics were classified as having acute (dispensing period <90 days), episodic (≥90 days and <3 ‘authority’ prescriptions for increased quantity supply) or long-term treatment (≥90 days and ≥3 authority prescriptions). Results Of participants dispensed opioid analgesic 52% received acute treatment, 25% episodic treatment and 23% long-term treatment. People dispensed opioid analgesics long-term had an average of 14.9 opioid analgesic prescriptions/year from 2.0 doctors compared with 1.5 prescriptions from 1.1 doctors for people receiving acute treatment. People dispensed opioid analgesics reported more need-related factors such as poorer physical functioning and higher psychological distress. Long-term users were more likely to have access-related factors such as low-income and living outside major cities. After simultaneous adjustment, association with predisposing health factors and access diminished, but indicators of need such as osteoarthritis treatment, paracetamol use, and poor physical function were the strongest predictors for all opioid analgesic users. Conclusions People dispensed opioid analgesics were in poorer health, reported higher levels of distress and poorer functioning than people not receiving opioid analgesics. Varying dispensing profiles were evident among people dispensed opioid analgesics for persistent pain, with those receiving episodic and long-term treatment dispensed the strongest opioid analgesics. The findings highlight the broad range of factors associated with longer term opioid analgesics use. PMID:24312456

Rates and risk factors for prolonged opioid use after major surgery: population based cohort study

PubMed Central

Soneji, Neilesh; Ko, Dennis T; Yun, Lingsong; Wijeysundera, Duminda N

2014-01-01

Objective To describe rates and risk factors for prolonged postoperative use of opioids in patients who had not previously used opioids and undergoing major elective surgery. Design Population based retrospective cohort study. Setting Acute care hospitals in Ontario, Canada, between 1 April 2003 and 31 March 2010. Participants 39 140 opioid naïve patients aged 66 years or older who had major elective surgery, including cardiac, intrathoracic, intra-abdominal, and pelvic procedures. Main outcome measure Prolonged opioid use after discharge, as defined by ongoing outpatient prescriptions for opioids for more than 90 days after surgery. Results Of the 39 140 patients in the entire cohort, 49.2% (n=19 256) were discharged from hospital with an opioid prescription, and 3.1% (n=1229) continued to receive opioids for more than 90 days after surgery. Following risk adjustment with multivariable logistic regression modelling, patient related factors associated with significantly higher risks of prolonged opioid use included younger age, lower household income, specific comorbidities (diabetes, heart failure, pulmonary disease), and use of specific drugs preoperatively (benzodiazepines, selective serotonin reuptake inhibitors, angiotensin converting enzyme inhibitors). The type of surgical procedure was also highly associated with prolonged opioid use. Compared with open radical prostatectomies, both open and minimally invasive thoracic procedures were associated with significantly higher risks (odds ratio 2.58, 95% confidence interval 2.03 to 3.28 and 1.95 1.36 to 2.78, respectively). Conversely, open and minimally invasive major gynaecological procedures were associated with significantly lower risks (0.73, 0.55 to 0.98 and 0.45, 0.33 to 0.62, respectively). Conclusions Approximately 3% of previously opioid naïve patients continued to use opioids for more than 90 days after major elective surgery. Specific patient and surgical characteristics were associated with the development of prolonged postoperative use of opioids. Our findings can help better inform understanding about the long term risks of opioid treatment for acute postoperative pain and define patient subgroups that warrant interventions to prevent progression to prolonged postoperative opioid use. PMID:24519537

Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain

PubMed Central

Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.

2017-01-01

Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897

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.

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

Distress Intolerance and Prescription Opioid Misuse Among Patients With Chronic Pain.

PubMed

McHugh, R Kathryn; Weiss, Roger D; Cornelius, Marise; Martel, Marc O; Jamison, Robert N; Edwards, Robert R

2016-07-01

The risk for misuse of opioid medications is a significant challenge in the management of chronic pain. The identification of those who may be at greater risk for misusing opioids is needed to facilitate closer monitoring of high-risk subgroups, and may help to identify therapeutic targets for mitigating this risk. The aim of this study was to examine whether distress intolerance-the perceived or actual inability to manage negative emotional and somatic states-was associated with opioid misuse in those with chronic pain. A sample of 51 participants prescribed opioid analgesics for chronic back or neck pain were recruited for a 1-time laboratory study. Participants completed measures of distress intolerance and opioid misuse, and a quantitative sensory testing battery. Results suggested that distress intolerance was associated with opioid misuse, even controlling for pain severity and negative affect. Distress intolerance was not associated with pain severity, threshold, or tolerance, but was associated with self-reported anxiety and stress after noxious stimuli. This study found robust differences in distress intolerance between adults with chronic pain with and without opioid medication misuse. Distress intolerance may be a relevant marker of risk for opioid misuse among those with chronic pain. This study demonstrated that distress intolerance was associated with opioid misuse in adults with chronic pain who were prescribed opioids. Distress intolerance can be modified with treatment, and thus may be relevant not only for identification of risk for opioid misuse, but also for mitigation of this risk. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Review of Factors, Methods, and Outcome Definition in Designing Opioid Abuse Predictive Models.

PubMed

Alzeer, Abdullah H; Jones, Josette; Bair, Matthew J

2018-05-01

Several opioid risk assessment tools are available to prescribers to evaluate opioid analgesic abuse among chronic patients. The objectives of this study are to 1) identify variables available in the literature to predict opioid abuse; 2) explore and compare methods (population, database, and analysis) used to develop statistical models that predict opioid abuse; and 3) understand how outcomes were defined in each statistical model predicting opioid abuse. The OVID database was searched for this study. The search was limited to articles written in English and published from January 1990 to April 2016. This search generated 1,409 articles. Only seven studies and nine models met our inclusion-exclusion criteria. We found nine models and identified 75 distinct variables. Three studies used administrative claims data, and four studies used electronic health record data. The majority, four out of seven articles (six out of nine models), were primarily dependent on the presence or absence of opioid abuse or dependence (ICD-9 diagnosis code) to define opioid abuse. However, two articles used a predefined list of opioid-related aberrant behaviors. We identified variables used to predict opioid abuse from electronic health records and administrative data. Medication variables are the recurrent variables in the articles reviewed (33 variables). Age and gender are the most consistent demographic variables in predicting opioid abuse. Overall, there is similarity in the sampling method and inclusion/exclusion criteria (age, number of prescriptions, follow-up period, and data analysis methods). Intuitive research to utilize unstructured data may increase opioid abuse models' accuracy.

Trends in heroin and pharmaceutical opioid overdose deaths in Australia.

PubMed

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

2017-10-01

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

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

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

PubMed

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

2018-03-01

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

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

Current Perspective on the Use of Opioids in Perioperative Medicine: An Evidence-Based Literature Review, National Survey of 70,000 Physicians, and Multidisciplinary Clinical Appraisal.

PubMed

Jahr, Jonathan S; Bergese, Sergio D; Sheth, Ketan R; Bernthal, Nicholas M; Ho, Hung S; Stoicea, Nicoleta; Apfel, Christian C

2017-08-16

Opioids represent an important analgesic option for physicians managing acute pain in surgical patients. Opioid management is not without its drawbacks, however, and current trends suggest that opioids might be overused in the United States. An expert panel was convened to conduct a clinical appraisal regarding the use of opioids in the perioperative setting. The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the statement "Opioids are not overused in the United States, even though opioid adjunct therapy achieves greater pain control with less risk." The authors' evaluation of this statement was also compared with the results of a national survey of surgeons and anesthesiologists in the United States. We report the presented literature and proceedings of the panel discussion. The national survey revealed a wide range of opinions regarding opioid overuse in the United States. Current published evidence provides support for the efficacy of opioid therapy in surgical patients; however, it is not sufficient to conclude unequivocally that opioids are-or are not-overused in the management of acute surgical pain in the United States. Opioids remain a key component of multimodal perioperative analgesia, and strategic opioid use based on clinical considerations and patient-specific needs represents an opportunity to support improved postoperative outcomes and satisfaction. Future studies should focus on identifying optimal procedure-specific and patient-centered approaches to multimodal perioperative analgesia. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Attitudes and Beliefs of Working and Work-Disabled People with Chronic Pain Prescribed Long-Term Opioids.

PubMed

Robinson, James P; Dansie, Elizabeth J; Wilson, Hilary D; Rapp, Suzanne; Turk, Dennis C

2015-07-01

This study was designed to gain insight into the apparent contradiction between the perspectives of researchers and policy makers, who have questioned the efficacy and safety of chronic opioid therapy for non-cancer pain patients, and the patients themselves, who often indicate that the therapy has value. A convenience sample of 54 patients on chronic opioid therapy was studied. Participants completed a questionnaire specifically designed for the study, and also several standard instruments that addressed functional interference, emotional functioning, and possible misuse of opioids. Their treating physicians rated the participants on the severity of their disability and the success of their opioid therapy. Although participants reported significant ongoing pain, they gave positive global ratings to their opioid therapy, and reported little concern about addiction or side effects of opioids. They strongly endorsed the beliefs that opioids helped them control their pain and allowed them to participate in important activities such as work. They expressed the belief that their pain would be severe if they did not have access to opioids, and reported negative experiences with tapering or discontinuing opioids in the past. Work-disabled participants reported higher levels of affective distress, catastrophizing, and functional interference than working participants, and were judged by their physicians to be relatively less successful in managing their pain. The results of this study suggest several tentative hypotheses about why patients on chronic opioid therapy value opioids, and identified several areas for systematic investigation in the future. © 2015 American Academy of Pain Medicine.

Rationale for cannabis-based interventions in the opioid overdose crisis.

PubMed

Lucas, Philippe

2017-08-18

North America is currently in the grips of a crisis rooted in the use of licit and illicit opioid-based analgesics. Drug overdose is the leading cause of accidental death in Canada and the US, and the growing toll of opioid-related morbidity and mortality requires a diversity of novel therapeutic and harm reduction-based interventions. Research suggests that increasing adult access to both medical and recreational cannabis has significant positive impacts on public health and safety as a result of substitution effect. Observational and epidemiological studies have found that medical cannabis programs are associated with a reduction in the use of opioids and associated morbidity and mortality. This paper presents an evidence-based rationale for cannabis-based interventions in the opioid overdose crisis informed by research on substitution effect, proposing three important windows of opportunity for cannabis for therapeutic purposes (CTP) to play a role in reducing opioid use and interrupting the cycle towards opioid use disorder: 1) prior to opioid introduction in the treatment of chronic pain; 2) as an opioid reduction strategy for those patients already using opioids; and 3) as an adjunct therapy to methadone or suboxone treatment in order to increase treatment success rates. The commentary explores potential obstacles and limitations to these proposed interventions, and as well as strategies to monitor their impact on public health and safety. The growing body of research supporting the medical use of cannabis as an adjunct or substitute for opioids creates an evidence-based rationale for governments, health care providers, and academic researchers to consider the implementation and assessment of cannabis-based interventions in the opioid crisis.

Opioid Prescribing After Curative-Intent Surgery: A Qualitative Study Using the Theoretical Domains Framework.

PubMed

Lee, Jay S; Parashar, Vartika; Miller, Jacquelyn B; Bremmer, Samantha M; Vu, Joceline V; Waljee, Jennifer F; Dossett, Lesly A

2018-07-01

Excessive opioid prescribing is common after curative-intent surgery, but little is known about what factors influence prescribing behaviors among surgeons. To identify targets for intervention, we performed a qualitative study of opioid prescribing after curative-intent surgery using the Theoretical Domains Framework, a well-established implementation science method for identifying factors influencing healthcare provider behavior. Prior to data collection, we constructed a semi-structured interview guide to explore decision making for opioid prescribing. We then conducted interviews with surgical oncology providers at a single comprehensive cancer center. Interviews were recorded, transcribed verbatim, then independently coded by two investigators using the Theoretical Domains Framework to identify theoretical domains relevant to opioid prescribing. Relevant domains were then linked to behavior models to select targeted interventions likely to improve opioid prescribing. Twenty-one subjects were interviewed from November 2016 to May 2017, including attending surgeons, resident surgeons, physician assistants, and nurses. Five theoretical domains emerged as relevant to opioid prescribing: environmental context and resources; social influences; beliefs about consequences; social/professional role and identity; and goals. Using these domains, three interventions were identified as likely to change opioid prescribing behavior: (1) enablement (deploy nurses during preoperative visits to counsel patients on opioid use); (2) environmental restructuring (provide on-screen prompts with normative data on the quantity of opioid prescribed); and (3) education (provide prescribing guidelines). Key determinants of opioid prescribing behavior after curative-intent surgery include environmental and social factors. Interventions targeting these factors are likely to improve opioid prescribing in surgical oncology.

Multiple Sources of Prescription Payment and Risky Opioid Therapy Among Veterans.

PubMed

Becker, William C; Fenton, Brenda T; Brandt, Cynthia A; Doyle, Erin L; Francis, Joseph; Goulet, Joseph L; Moore, Brent A; Torrise, Virginia; Kerns, Robert D; Kreiner, Peter W

2017-07-01

Opioid overdose and other related harms are a major source of morbidity and mortality among US Veterans, in part due to high-risk opioid prescribing. We sought to determine whether having multiple sources of payment for opioids-as a marker for out-of-system access-is associated with risky opioid therapy among veterans. Cross-sectional study examining the association between multiple sources of payment and risky opioid therapy among all individuals with Veterans Health Administration (VHA) payment for opioid analgesic prescriptions in Kentucky during fiscal year 2014-2015. Source of payment categories: (1) VHA only source of payment (sole source); (2) sources of payment were VHA and at least 1 cash payment [VHA+cash payment(s)] whether or not there was a third source of payment; and (3) at least one other noncash source: Medicare, Medicaid, or private insurance [VHA+noncash source(s)]. Our outcomes were 2 risky opioid therapies: combination opioid/benzodiazepine therapy and high-dose opioid therapy, defined as morphine equivalent daily dose ≥90 mg. Of the 14,795 individuals in the analytic sample, there were 81.9% in the sole source category, 6.6% in the VHA+cash payment(s) category, and 11.5% in the VHA+noncash source(s) category. In logistic regression, controlling for age and sex, persons with multiple payment sources had significantly higher odds of each risky opioid therapy, with those in the VHA+cash having significantly higher odds than those in the VHA+noncash source(s) group. Prescribers should examine the prescription monitoring program as multiple payment sources increase the odds of risky opioid therapy.

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

An Ambitious Research Plan to Help Solve the Opioid Crisis: HEAL Initiative

MedlinePlus

... to Help Solve the Opioid Crisis An Ambitious Research Plan to Help Solve the Opioid Crisis Email ... opioid use disorders. The Focused OUD Medications Development Research Project will consist of a series of high- ...

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

PubMed Central

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

2011-01-01

Background Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. Methods Using a cross-sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario’s public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. Results Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long-acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid-related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42–1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25–11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78–25.12) among those with very-high-dose prescriptions. Interpretation Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain has increased substantially, driven primarily by the use of long-acting oxycodone and, to a lesser extent, fentanyl. The findings of our exploratory study suggested a strong association between opioid-related mortality and the dose of opioid dispensed. PMID:22046214

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

PubMed Central

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

2014-01-01

Background and Objectives In the United States, use of oral opioid analgesics has been associated with increasing rates of addiction, abuse, and diversion. However, little is known about recent national use of non-illicit prescription opioid analgesics (those prescribed in a doctor-patient relationship), the primary source of these drugs for the general US population. Our primary objective was to examine trends in the use of prescription opioid analgesics in the United States and to identify defining characteristics of patient users of prescribed opioids from 2000 to 2010. Methods We used the nationally representative Medical Expenditure Panel Survey to examine trends in prescription oral opioid analgesic use from 2000 to 2010. We used survey design methods to make national estimates of adults (18 years and older) who reported receiving an opioid analgesic prescription (referred to as opioid users) and used logistic regression to examine predictors of opioid analgesic use. Our primary outcome measures were national estimates of total users of prescription opioid analgesics and total number of prescriptions. Our secondary outcome was that of observing changes in the disability and health of the users. Results The estimated total number of opioid analgesic prescriptions in the United States increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an estimated 7.4% (95% CI, 6.9–7.9) of adult Americans were prescription opioid users compared with 11.8% (95% CI, 11.2–12.4) in 2010. Based on estimates adjusted for changes in the general population, each year was associated with a 6% increase in the likelihood of receiving an opioid prescription from 2000 to 2010. Despite the apparent increase in use, there were no demonstrable improvements in the age- or sex-adjusted disability and health status measures of opioid users. Conclusions The use of prescription opioid analgesics among adult Americans has increased in recent years, and this increase does not appear to be associated with improvements in disability and health status among users. On a public health level, these data suggest that there may be an opportunity to reduce the prescribing of opioid analgesics without worsening of population health metrics. PMID:24310049

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 anesthetic with intravenous sedation, a policy of low opioid analgesic prescribing is achievable; these findings call for further investigation of how to best prescribe opioid medications to patients after an inguinal herniorrhaphy. Copyright © 2017 Elsevier Inc. All rights reserved.

Cross-Sectional Analysis of Per Capita Supply of Doctors of Chiropractic and Opioid Use in Younger Medicare Beneficiaries.

PubMed

Weeks, William B; Goertz, Christine M

2016-05-01

The purpose of this study was to determine whether the per-capita supply of doctors of chiropractic (DCs) or Medicare spending on chiropractic care was associated with opioid use among younger, disabled Medicare beneficiaries. Using 2011 data, at the hospital referral region level, we correlated the per-capita supply of DCs and spending on chiropractic manipulative therapy (CMT) with several measures of per-capita opioid use by younger, disabled Medicare beneficiaries. Per-capita supply of DCs and spending on CMT were strongly inversely correlated with the percentage of younger Medicare beneficiaries who had at least 1, as well as with 6 or more, opioid prescription fills. Neither measure was correlated with mean daily morphine equivalents per opioid user or per chronic opioid user. A higher per-capita supply of DCs and Medicare spending on CMT were inversely associated with younger, disabled Medicare beneficiaries obtaining an opioid prescription. However, neither measure was associated with opioid dosage among patients who obtained opioid prescriptions. Copyright © 2016. Published by Elsevier Inc.

The availability of web sites offering to sell opioid medications without prescriptions.

PubMed

Forman, Robert F; Woody, George E; McLellan, Thomas; Lynch, Kevin G

2006-07-01

This study was designed to determine the availability of web sites offering to sell opioid medications without prescriptions. Forty-seven Internet searches were conducted with a variety of opioid medication terms, including "codeine," "no prescription Vicodin," and "OxyContin." Two independent raters examined the links generated in each search and resolved any coding disagreements. The resulting links were coded as "no prescription web sites" (NPWs) if they offered to sell opioid medications without prescriptions. In searches with terms such as "no prescription codeine" and "Vicodin," over 50% of the links obtained were coded as "NPWs." The proportion of links yielding NPWs was greater when the phrase "no prescription" was added to the opioid term. More than 300 opioid NPWs were identified and entered into a database. Three national drug-use monitoring studies have cited significant increases in prescription opioid use over the past 5 years, particularly among young people. The emergence of NPWs introduces a new vector for unregulated access to opioids. Research is needed to determine the effect of NPWs on prescription opioid use initiation, misuse, and dependence.

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

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 2.90), antidepressant use (1.34%; adjusted odds ratio 3.19, 95% confidence interval 2.41 to 4.23) and benzodiazepine use (1.99%; adjusted odds ratio 3.72, 95% confidence interval 2.64 to 5.26) in the year prior to Cesarean delivery. Conclusions A very small proportion of opioid-naïve women (approximately 1 in 300) become persistent prescription opioid users following Cesarean delivery. Pre-existing psychiatric comorbidity, certain pain conditions, and substance use/abuse conditions identifiable at the time of initial opioid prescribing were predictors of persistent use. PMID:26996986

Assessing opioid shopping behaviour: a large cohort study from a medication dispensing database in the US.

PubMed

Cepeda, M Soledad; Fife, Daniel; Chow, Wing; Mastrogiovanni, Gregory; Henderson, Scott C

2012-04-01

: Risks of abuse, misuse and diversion of opioids are of concern. Obtaining opioid prescriptions from multiple prescribers, known as opioid shopping, is a way in which opioids may be abused and diverted. Previous studies relied on counting the number of prescribers or number of pharmacies a subject goes to in a year to define shopping behaviour, but did not distinguish successive prescribers from concomitant prescribers. : The aim of the study was to assess the frequency of opioid overlapping prescriptions from different prescribers, compare it with diuretics and benzodiazepines, and provide a definition of shopping behaviour that differentiates opioids from diuretics, avoiding the inappropriate flagging of individuals with legitimate use of opioids. : Population-based cohort study using the IMS LRx database. This database covers 65% of all retail prescriptions in the US and includes mail service and specialty pharmacy provider prescriptions independent of the method of payment. : Ambulatory. : Subjects with at least one dispensing for any type of opioid in 2008. Similar cohorts were created for subjects exposed to benzodiazepines or diuretics. Analyses were performed separately for naïve subjects and those with prior use. : Frequency of overlapping prescriptions defined as at least 1 day of overlapping dispensing of prescriptions written by two or more different prescribers at any time during an 18-month period. : A total of 25 161 024 subjects exposed to opioids were included, of whom 13.1% exhibited at least one episode of overlapping prescriptions during 18 months of follow-up. Almost 10% of subjects exposed to benzodiazepines and 13.8% of subjects exposed to diuretics exhibited a similar behaviour. Having overlapping prescriptions dispensed by three or more pharmacies differentiates opioids from the other medication classes. Using that criterion, the overall risk of shopping behaviour was 0.18% in subjects exposed to opioids, 0.10% in subjects exposed to benzodiazepines and 0.03% in subjects exposed to diuretics. For opioids, subjects aged between 25 and 64 years exhibited shopping behaviour more commonly (0.25%) than subjects 65 years or older (0.07%), and subjects with a history of prior opioid use exhibited such behaviour more commonly (0.7%) than opioid-naïve subjects (0.07%). : Overlapping of prescriptions is not unique to opioids and therefore a criterion that incorporates number of pharmacies is needed to define shopping behaviour. Having two or more overlapping prescriptions written by different prescribers and filled at three or more pharmacies differentiates opioids from diuretics and likely constitutes shopping behaviour.

Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors

DTIC Science & Technology

2016-07-01

treat, and current opioids (i.e. mu opioid receptor agonists such as morphine) cause unacceptable side effects including addiction . Injuries suffered...treat, and current opioids that act on mu opioid receptors such as morphine generate significant side effects including addiction . War-related...slides. Slides were then processed for fluorescent in situ hybridization with RNAscope technology (ACD Biosystems) to detect Oprd1 mRNA, as described

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

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.

Efficacy of opioids versus placebo in chronic pain: a systematic review and meta-analysis of enriched enrollment randomized withdrawal trials.

PubMed

Meske, Diana S; Lawal, Oluwadolapo D; Elder, Harrison; Langberg, Valerie; Paillard, Florence; Katz, Nathaniel

2018-01-01

Opioids have been used for millennia for the treatment of pain. However, the long-term efficacy of opioids to treat chronic non-cancer pain continues to be debated. To evaluate opioids' efficacy in chronic non-cancer pain, we performed a meta-analysis of published clinical trials for μ-opioid receptor agonists performed for US Food and Drug Administration approval. MEDLINE and Cochrane trial register were searched for enriched enrollment randomized withdrawal studies (before June 2016). Selection criteria included: adults, ≥10 subjects per arm, any chronic pain condition, double-blind treatment period lasting ≥12 weeks, and all μ-agonist opioids approved in the USA. Fifteen studies met criteria. Opioid efficacy was statistically significant ( p <0.001) versus placebo for pain intensity (standardized mean difference: -0.416), ≥30% and ≥50% improvement in pain (risk difference: 0.166 and 0.137), patient global impression of change (0.163), and patient global assessment of study medication (0.194). There were minor benefits on physical function and no effect on mental function. Opioids are efficacious in the treatment of chronic non-cancer pain for up to 3 months in randomized controlled trials. This should be considered, alongside data on opioid safety, in the use of opioids for the treatment of chronic pain.

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.

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.

Pain, opioids, and sleep: implications for restless legs syndrome treatment.

PubMed

Trenkwalder, Claudia; Zieglgänsberger, Walter; Ahmedzai, Sam H; Högl, Birgit

2017-03-01

Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described. By targeting pain and its consequences, opioids are the first-line treatment in many diseases and conditions with both acute and chronic pain and have thus been used in both acute and chronic pain conditions over the last 40 years. Addiction, dependence, and tolerability of opioids show a wide variability interindividually, as the response to opioids is influenced by a complex combination of genetic, molecular, and phenotypic factors. Although several trials have now addressed opioid treatment in RLS, hyperalgesia as a complication of long-term opioid treatment, or opioid-opioid interaction have not received much attention so far. Therapeutic opioids may act not only on opioid receptors but also via histamine or N-methyl-d-aspartate (NMDA) receptors. In patients with RLS, one of the few studies investigating opioid bindings found that possible brain regions involved in the severity of RLS symptoms are similar to those known to be involved in chronic pain, such as the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex, and orbitofrontal cortex). The results of this diprenorphine positron emission tomography study suggested that the more severe the RLS, the greater the release of endogenous opioids. Since 1993, when the first small controlled study was performed with oxycodone in RLS, opioids have been considered an efficacious off-label therapy in patients with severe RLS. A recent trial has proved the efficacy of a combination of prolonged release oxycodone/naloxone in patients with severe RLS as second-line therapy, with a mean dosage of 10/5 mg twice daily (mean difference of International Restless Legs Syndrome Study Group Rating Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been licensed as the first opioid therapy in Europe. The current results from both short- and long-term trials and studies with opioids encourage optimism in alleviating RLS symptoms in patients with severe RLS, or possibly during or after augmentation. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolving paradigms in the treatment of opioid-induced bowel dysfunction.

PubMed

Poulsen, Jakob Lykke; Brock, Christina; Olesen, Anne Estrup; Nilsson, Matias; Drewes, Asbjørn Mohr

2015-11-01

In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.

Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain.

PubMed

Feingold, Daniel; Goor-Aryeh, Itay; Bril, Silviu; Delayahu, Yael; Lev-Ran, Shaul

2017-02-01

To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain. Cross-sectional study. Two leading pain clinics in Israel. Our sample included 888 individuals receiving treatment for chronic pain, of whom 99.4% received treatment with prescription opioids or MC. Problematic use of prescription opioids and MC was assessed using DSM-IV criteria, Portenoy’s Criteria (PC), and the Current Opioid Misuse Measure (COMM) questionnaire. Additional sociodemographic and clinical correlates of problematic use were also assessed. Among individuals treated with prescription opioids, prevalence of problematic use of opioids according to DSM-IV, PC, and COMM was 52.6%, 17.1%, and 28.7%, respectively. Among those treated with MC, prevalence of problematic use of cannabis according to DSM-IV and PC was 21.2% and 10.6%, respectively. Problematic use of opioids and cannabis was more common in individuals using medications for longer periods of time, reporting higher levels of depression and anxiety, and using alcohol or drugs. Problematic use of opioids was associated with higher self-reported levels of pain, and problematic use of cannabis was more common among individuals using larger amounts of MC. Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC. Pain patients should be screened for risk factors for problematic use before initiating long-term treatment for pain-control.

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.

Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016.

PubMed

Seth, Puja; Scholl, Lawrence; Rudd, Rose A; Bacon, Sarah

2018-03-30

During 1999‒2015, 568,699 persons died from drug overdoses in the United States.* Drug overdose deaths in the United States increased 11.4% from 2014 to 2015 resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an opioid. The largest rate increases from 2014 to 2015 occurred among deaths involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1). Because of demographic and geographic variations in overdose deaths involving different drugs (2,3), † CDC examined age-adjusted death rates for overdoses involving all opioids, opioid subcategories (i.e., prescription opioids, heroin, and synthetic opioids), § cocaine, and psychostimulants with abuse potential (psychostimulants) by demographics, urbanization levels, and in 31 states and the District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249 (66.4%) involved an opioid. ¶ From 2015 to 2016, deaths increased across all drug categories examined. The largest overall rate increases occurred among deaths involving cocaine (52.4%) and synthetic opioids (100%), likely driven by illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across demographics, urbanization levels, and states and DC. The opioid overdose epidemic in the United States continues to worsen. A multifaceted approach, with faster and more comprehensive surveillance, is needed to track emerging threats to prevent and respond to the overdose epidemic through naloxone availability, safe prescribing practices, harm-reduction services, linkage into treatment, and more collaboration between public health and public safety agencies.

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

PubMed

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

2017-05-01

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

A Leptin-Mediated Central Mechanism in Analgesia-Enhanced Opioid Reward in Rats

PubMed Central

Lim, Grewo; Kim, Hyangin; McCabe, Michael F.; Chou, Chiu-Wen; Wang, Shuxing; Chen, Lucy L.; Marota, John J.A.; Blood, Anne; Breiter, Hans C.

2014-01-01

Opioid analgesics are commonly used in chronic pain management despite a potential risk of rewarding. However, it remains unclear whether opioid analgesia would enhance the opioid rewarding effect thereby contributing to opioid rewarding. Utilizing a rat paradigm of conditioned place preference (CPP) combined with ankle monoarthritis as a condition of persistent nociception, we showed that analgesia induced by either morphine or the nonsteroid anti-inflammatory drug ibuprofen increased CPP scores in arthritic rats, suggesting that analgesia itself had a rewarding effect. However, arthritic rats exhibited a significantly higher CPP score in response to morphine than ibuprofen. Thus, the rewarding effect of morphine was enhanced in the presence of persistent nociception, producing a phenomenon of analgesia-enhanced opioid reward. At the cellular level, administration of morphine activated a cascade of leptin expression, glial activation, and dopamine receptor upregulation in the nucleus accumbens (NAc), while administration of ibuprofen decreased glial activation with no effect on leptin expression in the NAc. Furthermore, the morphine rewarding effect was blocked in leptin deficient ob/ob mice or by neutralizing leptin or interleukin-1β in the NAc without diminishing morphine analgesia. The data indicate that systemic opioid can activate a leptin-mediated central mechanism in the NAc that led to the enhanced opioid rewarding effect. These findings provide evidence for an interaction between opioid analgesia and opioid rewarding, which may have implications in clinical opioid dose escalation in chronic pain management. PMID:25031415

Methodologic limitations of prescription opioid safety research and recommendations for improving the evidence base.

PubMed

Ranapurwala, Shabbar I; Naumann, Rebecca B; Austin, Anna E; Dasgupta, Nabarun; Marshall, Stephen W

2018-06-03

The ongoing opioid epidemic has claimed more than a quarter million Americans' lives over the past 15 years. The epidemic began with an escalation of prescription opioid deaths and has now evolved to include secondary waves of illicit heroin and fentanyl deaths, while the deaths due to prescription opioid overdoses are still increasing. In response, the Centers for Disease Control and Prevention (CDC) moved to limit opioid prescribing with the release of opioid prescribing guidelines for chronic noncancer pain in March 2016. The guidelines represent a logical and timely federal response to this growing crisis. However, CDC acknowledged that the evidence base linking opioid prescribing to opioid use disorders and overdose was grades 3 and 4. Motivated by the need to strengthen the evidence base, this review details limitations of the opioid safety studies cited in the CDC guidelines with a focus on methodological limitations related to internal and external validity. Internal validity concerns were related to poor confounding control, variable misclassification, selection bias, competing risks, and potential competing interventions. External validity concerns arose from the use of limited source populations, historical data (in a fast-changing epidemic), and issues with handling of cancer and acute pain patients' data. We provide a nonexhaustive list of 7 recommendations to address these limitations in future opioid safety studies. Strengthening the opioid safety evidence base will aid any future revisions of the CDC guidelines and enhance their prevention impact. Copyright © 2018 John Wiley & Sons, Ltd.

Proceedings from Bridging Health Disparities to Address the Opioid Epidemic: A Symposium at the Warren Alpert Medical School of Brown University.

PubMed

Dumenco, Luba; Monteiro, Kristina; Mello, Michael; Collins, Sally; Operario, Don; Scanlan, Karen; Dollase, Richard; George, Paul

2017-04-03

In response to the unprecedented rates of illicit drug use, including opioid addiction and overdose in Rhode Island, local healthcare institutions, led by the Warren Alpert Medical School (AMS) of Brown University, collaborated to present "Bridging Health Disparities to Address the Opioid Epidemic." This symposium sought to educate a wide array of healthcare providers and professionals around opioid use disorder, including the state of the opioid crisis in Rhode Island, national efforts around opioid misuse and how providers can work together to stem the opioid crisis in the state. The symposium included a keynote session which aimed to increase knowledge and decrease stigma. This was followed by two rounds of breakout sessions which focused on various components of opioid disorder treatment. We elicited feedback from participants in order to plan further interventions to educate providers in Rhode Island around the opioid epidemic. Primary Results: Initial feedback was positive. More importantly, this workshop allowed us to identify gaps in knowledge amongst healthcare providers in Rhode Island in order to plan further interventions for healthcare providers, including physicians, around opioid misuse, in Rhode Island. This symposium is one of the first steps that a consortium of healthcare institutions, including AMS, will take to address the opioid crisis in Rhode Island. Feedback from the event was elicited to identify gaps in healthcare provider knowledge and will be used to design and implement further interventions. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

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.

Using Health Information Technology to Improve Adherence to Opioid Prescribing Guidelines in Primary Care

PubMed Central

Zlateva, Ianita; Khatri, Khushbu; Ciaburri, Nicholas

2015-01-01

Objective: To evaluate the impact of a clinical dashboard for opioid analgesic management on opioid prescribing and adherence to opioid practice guidelines in primary care. Methods: A pre/postimplementation evaluation using electronic health record (EHR) data from patients receiving chronic opioid therapy (COT) between April 1, 2011 and March 31, 2013. Measures include annual proportions of COT patients who received urine drug testing, signed an opioid treatment agreement, had a documented assessment of pain-related functional status, and had at least 1 visit with a behavioral health provider. Results: Adherence to several opioid prescribing guidelines improved in the postimplementation year compared with the preimplementation year: (1) the proportions of COT patients with a signed opioid treatment agreement and urine drug testing increased from 49% to 63% and 66% to 86%, respectively. The proportion of COT patients with a documented assessment of functional status increased from 33% to 46% and those with a behavioral health visit increased from 24% to 28%. However, there was a small decline in the proportion of patients prescribed COT from 3.4% to 3.1%. Discussion: Implementation of an opioid dashboard led to increased adherence to certain opioid practice guidelines and a decline in COT. This may be attributable to more efficient team-based pain management facilitated by the dashboard and increased transparency of opioid prescription practices. Health Information Technology solutions such as clinical dashboards can increase adherence to practice guidelines. PMID:25411860

Altered quantitative sensory testing outcome in subjects with opioid therapy.

PubMed

Chen, Lucy; Malarick, Charlene; Seefeld, Lindsey; Wang, Shuxing; Houghton, Mary; Mao, Jianren

2009-05-01

Preclinical studies have suggested that opioid exposure may induce a paradoxical decrease in the nociceptive threshold, commonly referred as opioid-induced hyperalgesia (OIH). While OIH may have implications in acute and chronic pain management, its clinical features remain unclear. Using an office-based quantitative sensory testing (QST) method, we compared pain threshold, pain tolerance, and the degree of temporal summation of the second pain in response to thermal stimulation among three groups of subjects: those with neither pain nor opioid therapy (group 1), with chronic pain but without opioid therapy (group 2), and with both chronic pain and opioid therapy (group 3). We also examined the possible correlation between QST responses to thermal stimulation and opioid dose, opioid treatment duration, opioid analgesic type, pain duration, or gender in group 3 subjects. As compared with both group 1 (n=41) and group 2 (n=41) subjects, group 3 subjects (n=58) displayed a decreased heat pain threshold and exacerbated temporal summation of the second pain to thermal stimulation. In contrast, there were no differences in cold or warm sensation among three groups. Among clinical factors, daily opioid dose consistently correlated with the decreased heat pain threshold and exacerbated temporal summation of the second pain in group 3 subjects. These results indicate that decreased heat pain threshold and exacerbated temporal summation of the second pain may be characteristic QST changes in subjects with opioid therapy. The data suggest that QST may be a useful tool in the clinical assessment of OIH.

Definition Development and Prevalence of New Persistent Opioid Use Following Hysterectomy.

PubMed

Swenson, Carolyn W; Kamdar, Neil S; Seiler, Kristian; Morgan, Daniel M; Lin, Paul; As-Sanie, Sawsan

2018-06-18

Opioids used for postoperative pain control after surgery have been associated with an increased risk of chronic opioid use. Hysterectomy is the most common major gynecologic procedure in the United States; however, we lack a data-driven definition of new persistent opioid use specific to hysterectomy. 1) Determine a data-driven definition of new persistent opioid use among opioid naïve women undergoing hysterectomy; 2) Determine the prevalence of and risk factors for new persistent opioid use. We used data from Optum Clinformatics that includes both medical and pharmacy data from a single national private health insurer. Hysterectomies performed from January 1, 2011 to December 31, 2014 were identified using Current Procedural Terminology and International Classification of Diseases, Ninth Revision codes. Inclusion criteria included: age ≤ 63 years at hysterectomy, no opioid fills for eight months preceding (excluding the 30 days immediately prior), and no additional surgical procedures within six months post-hysterectomy. The perioperative period was defined as 30 days prior to 14 days after hysterectomy. Number of opioid prescription fills, days supplied, and total oral morphine equivalents were analyzed to determine the distribution of opioid use in the perioperative and postoperative periods. We obtained demographics including age, race, educational level, and division of the country according to the U.S. Census Bureau and used International Classification of Diseases, Ninth Revision diagnosis codes to identify hysterectomy indications, surgical route, chronic pain disorders, depression/anxiety, and substance abuse. Bivariate analyses were used to compare persistent to non-persistent opioid users. A hierarchical logistic regression model controlling for regional variation was used to determine factors associated with new persistent opioid use following hysterectomy. 24,331 women were included in the analysis. "New persistent opioid use" was defined as: ≥ 2 opioid fills within six months of hysterectomy with ≥ 1 fill every three months, and either total oral morphine equivalent ≥ 1,150 or days' supplied ≥ 39. Based on this definition, the prevalence of new persistent opioid use was 0.5% (N=122). Median perioperative oral morphine equivalents (OME) prescribed to those who became new persistent users was 437.5 mg (IQR 200, 750) compared to 225 mg (IQR 150, 300) for non-persistent users (p<.0001). Factors independently associated with new persistent opioid use included: increasing age (aOR 1.04, 95% CI 1.01-1.06, p=.006), black race (ref: white, aOR 1.61 95% CI 1.02-2.55, p =.04), gynecologic malignancy (aOR 7.61, 95% CI 3.35-17.27, p<.0001), abdominal route (aOR 3.61, 95% CI 2.03-6.43, p<.0001), depression/anxiety (aOR 2.62, 95% CI 1.71-4.02, p<.0001), and preoperative opioid fill (aOR 2.76, 95% CI 1.87-4.07, p<.0001). C-statistic for this model is 0.74. Based on our definition, the prevalence of new persistent opioid use among opioid naïve women undergoing hysterectomy is low; however, two potentially modifiable risk factors are preoperative opioid prescription and abdominal route of surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

The New Kid on the Block--Incorporating Buprenorphine into a Medical Toxicology Practice.

PubMed

Wiegand, Timothy J

2016-03-01

Buprenorphine represents a safe and effective therapy for treating opioid dependence, alleviating craving and withdrawal symptoms in opioid-dependent patients. Buprenorphine has a "blocking" effect against the action of other opioids at the mu-receptor, preventing not only opioid-induced euphoria, but CNS and respiratory depressant effects as well. Buprenorphine was approved for the treatment of opioid dependence in 2002 after the passage of Drug Abuse Treatment Act 2000 (DATA 2000) which allowed clinicians to treat opioid-dependent patients with specifically named opioid agonist therapies in an office setting. Buprenorphine programs reduce the prevalence of HIV and hepatitis C and reduce criminal behaviors associated with illicit drug use. Patients stabilized on buprenorphine have increased employment, enhanced engagement with social services, and better overall health and well-being.

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, Inc. Reprints and permission: journals.permissions@oup.com

Opioid-receptor subtype agonist-induced enhancements of sucrose intake are dependent upon sucrose concentration.

PubMed

Ruegg, H; Yu, W Z; Bodnar, R J

1997-07-01

Selective mu ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO)), delta1 ([D-Pen2, D-Pen5]-enkephalin (DPDPE)), delta2 ([D-Ala2, Glu4]-Deltorphin (Delt II)), kappa1 (U50488H) and kappa3 (naloxone benzoylhydrazone (NalBzOH)) opioid agonists each stimulate food intake in rats. Whereas studies with selective opioid antagonists implicate mu and kappa1 receptors in the mediation of sucrose intake, studies with selective opioid agonists implicate mu and delta receptors in the mediation of saccharin intake. The present study determined if specific delta1, delta2, kappa1, kappa3 and mu opioid-receptor subtype agonists produced similar alterations in sucrose intake as a function of sucrose concentration (0.5%, 2.5%, 10%) across a 1-h time-course. Each of these agonists significantly increased sucrose intake with variations in pattern, magnitude, and consistency as a function of sucrose concentration. Whereas the mu opioid agonist, DAMGO, and the delta1 opioid agonist, DPDPE, each enhanced sucrose intake at higher (2.5%, 10%), but not lower (0.5%), concentrations, the delta2 opioid agonist, Delt II, increased sucrose intake at lower (0.5%, 2.5%), but not higher (10%), concentrations. Kappa opioid agonists produced less consistent effects. The kappa1 opioid agonist, U50488H, increased sucrose intake at high (10%) concentrations and decreased sucrose intake at low (0.5%) concentrations, and the kappa3 opioid agonist, NalBzOH, inconsistently increased sucrose intake at the 0.5% (20 microg) and 10% (1 microg) concentrations. Thus, these data further implicate mu, delta1, and delta2 opioid mediation of palatable intake, particularly of its orosensory characteristics.

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 pharmacists. PMID:22084475

Opioid intake prior to admission is not increased in elderly patients with low-energy fractures: a case control study in a German hospital population.

PubMed

Schwarzer, A; Kaisler, M; Kipping, K; Seybold, D; Rausch, V; Maier, C; Vollert, J

2018-05-14

Recent studies revealed an increased prescription rate of opioids for elderly patients suffering bone fractures. To gain further insight, we conducted face-to-face interviews in the present study to compare the opioid intake between patients with low energy fractures and patients suffering from internal diseases. In this case-control study, 992 patients, aged 60 years and older, were enrolled between March 2014 and February 2015. The interview comprised a fall and medication history, comorbidities, mobility and other risk factors for fractures. Odds ratios (OR) and a multiple logistic regression model were calculated. The number of patients with pre-admission opioid intake in the last 12 months was comparable in the fracture (n=399, 13.3%) and the control group (n=593, 14.7% OR: 0.89, CI: 0.62-1.29). The number of patients with current opioid intake of short duration (<3 months) was similar in both groups (14% vs. 20%; OR: 0.66, CI: 0.23-1.93). Patients with opioid intake in the fracture group reported more frequently fatigue as an adverse event of opioid medication (58% vs. 30%; OR: 3.32, CI: 1.48-7.45). Patients with opioid intake showed more severe comorbidities and significantly decreased mobility compared to those without opioids. Elderly patients internalized due to low-energy fractures did not take opioids more frequently than patients with internal admission, for both short (<3 months) and longer duration intake. Patients with opioid intake were generally in poorer physical condition. The risk of fracture might increase in patients suffering from fatigue as a side effect of opioid medication. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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.

Dose and Duration of Opioid Use in Patients with Cancer and Noncancer Pain at an Outpatient Hospital Setting in Malaysia.

PubMed

Zin, Che S; Rahman, Norny A; Ismail, Che R; Choy, Leong W

2017-07-01

There are currently limited data available on the patterns of opioid prescribing in Malaysia. This study investigated the patterns of opioid prescribing and characterized the dosing and duration of opioid use in patients with noncancer and cancer pain. This retrospective, cross-sectional study was conducted at an outpatient hospital setting in Malaysia. All prescriptions for opioids (dihydrocodeine, fentanyl, morphine, and oxycodone) issued between January 2013 and December 2014 were examined. The number of prescriptions and patients, the distribution of mean daily dose, annual total days covered with opioids, and annual total opioid dose at the individual level were calculated and stratified by noncancer and cancer groups. A total of 1015 opioid prescriptions were prescribed for 347 patients from 2013 to 2014. Approximately 41.5% of patients (N = 144/347) and 58.5% (N = 203/347) were associated with noncancer and cancer diagnosis, respectively. Oxycodone (38.0%) was the highest prescribed primarily for the noncancer group. The majority of patients in both noncancer (74.3%) and cancer (60.4%) groups were receiving mean daily doses of < 50 mg morphine equivalents. The chronic use of opioids (> 90 days per year) was associated with 21.8% of patients in the noncancer group and 17.5% in the cancer group. The finding from this study showed that 41.5% of opioid users at an outpatient hospital setting in Malaysia received opioids for noncancer pain and 21.8% of these users were using opioids for longer than 90 days. The average daily dose in the majority of patients in both groups of noncancer and cancer was modest. © 2016 World Institute of Pain.

Association of Pretransplantion Opioid Use with Graft Loss or Death in Liver Transplantation Patients with Model of End-Stage Liver Disease Exceptions.

PubMed

Fleming, James N; Taber, David J; Pilch, Nicole A; Mardis, Caitlin R; Gilbert, Rachael E; Wilson, Lytani Z; Patel, Neha; Ball, Sarah; Mauldin, Patrick; Baliga, Prabhakar K

2018-04-01

Up to 77% of liver transplantation candidates experience pain, and the majority are prescribed opioids. Previous studies have shown increased readmissions and mortality in liver transplant recipients who were prescribed opioids before transplantation. Our aim was to identify specific populations that are at the highest risk for deleterious outcomes with opioid use before transplantation. This was a single-center retrospective cohort study of adult receiving liver transplants between 2010 and 2016 to assess the impact of pretransplantation opioid use on mortality and graft loss after liver transplantation. A total of 446 liver transplant recipients were included in the study, 148 (33%) of which were identified as pretransplantation opioid users. Opioid use increased significantly during the course of the study. There were no differences in the overall cohort between opioid users and non-opioid users with regard to graft or patient outcomes. However, the influence of opioid use on outcomes varied based on Model for End-Stage Liver Disease (MELD) and functional status. In patients with any MELD exception, opioid use was an independent predictor of time to graft loss or death (adjusted hazard ratio 2.36; 95% CI 1.05 to 5.28; p = 0.037). It also independently predicted time to graft loss or death in patients with low laboratory MELD scores (adjusted hazard ratio 2.38; 95% CI 1.10 to 5.13; p = 0.027). In our 6-year retrospective cohort, pretransplantation opioid use based on medication reconciliation was independently associated with time to graft loss or mortality in liver transplant recipients with MELD exceptions and laboratory MELD scores ≤15. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis.

PubMed

Cohen, Stephen M; Vogel, Jon D; Marcet, Jorge E; Candiotti, Keith A

2014-01-01

Postsurgical pain management remains a significant challenge. Liposome bupivacaine, as part of a multimodal analgesic regimen, has been shown to significantly reduce postsurgical opioid consumption, hospital length of stay (LOS), and hospitalization costs in gastrointestinal (GI) surgery, compared with intravenous (IV) opioid-based patient-controlled analgesia (PCA). Pooled results from open-label studies comparing a liposome bupivacaine-based multimodal analgesic regimen with IV opioid PCA were analyzed. Patients (n=191) who underwent planned surgery and received study drug (IV opioid PCA, n=105; multimodal analgesia, n=86) were included. Liposome bupivacaine-based multimodal analgesia compared with IV opioid PCA significantly reduced mean (standard deviation [SD]) postsurgical opioid consumption (38 [55] mg versus [vs] 96 [85] mg; P<0.0001), postsurgical LOS (median 2.9 vs 4.3 days; P<0.0001), and mean hospitalization costs (US$8,271 vs US$10,726; P=0.0109). The multimodal analgesia group reported significantly fewer patients with opioid-related adverse events (AEs) than the IV opioid PCA group (P=0.0027); there were no significant between-group differences in patient satisfaction scores at 30 days. A liposome bupivacaine-based multimodal analgesic regimen was associated with significantly less opioid consumption, opioid-related AEs, and better health economic outcomes compared with an IV opioid PCA-based regimen in patients undergoing GI surgery. This pooled analysis is based on data from Phase IV clinical trials registered on the US National Institutes of Health www.ClinicalTrials.gov database under study identifiers NCT01460485, NCT01507220, NCT01507233, NCT01509638, NCT01509807, NCT01509820, NCT01461122, NCT01461135, NCT01534988, and NCT01507246.

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.

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

PubMed

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

2017-04-01

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

Novel fentanyl-based dual μ/δ-opioid agonists for the treatment of acute and chronic pain.

PubMed

Podolsky, Alexander T; Sandweiss, Alexander; Hu, Jackie; Bilsky, Edward J; Cain, Jim P; Kumirov, Vlad K; Lee, Yeon Sun; Hruby, Victor J; Vardanyan, Ruben S; Vanderah, Todd W

2013-12-18

Approximately one third of the adult U.S. population suffers from some type of on-going, chronic pain annually, and many more will have some type of acute pain associated with trauma or surgery. First-line therapies for moderate to severe pain include prescriptions for common mu opioid receptor agonists such as morphine and its various derivatives. The epidemic use, misuse and diversion of prescription opioids have highlighted just one of the adverse effects of mu opioid analgesics. Alternative approaches include novel opioids that target delta or kappa opioid receptors, or compounds that interact with two or more of the opioid receptors. Here we report the pharmacology of a newly synthesized bifunctional opioid agonist (RV-Jim-C3) derived from combined structures of fentanyl and enkephalin in rodents. RV-Jim-C3 has high affinity binding to both mu and delta opioid receptors. Mice and rats were used to test RV-Jim-C3 in a tailflick test with and without opioid selective antagonist for antinociception. RV-Jim-C3 was tested for anti-inflammatory and antihypersensitivity effects in a model of formalin-induced flinching and spinal nerve ligation. To rule out motor impairment, rotarod was tested in rats. RV-Jim-C3 demonstrates potent-efficacious activity in several in vivo pain models including inflammatory pain, antihyperalgesia and antiallodynic with no significant motor impairment. This is the first report of a fentanyl-based structure with delta and mu opioid receptor activity that exhibits outstanding antinociceptive efficacy in neuropathic pain, reducing the propensity of unwanted side effects driven by current therapies that are unifunctional mu opioid agonists. © 2013. Published by Elsevier Inc. All rights reserved.

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 needed to further define their role in therapy. © 2016 Pharmacotherapy Publications, Inc.

Novel fentanyl-based dual μ/δ-opioid agonists for the treatment of acute and chronic pain

PubMed Central

Podolsky, Alexander T.; Sandweiss, Alexander; Hu, Jackie; Bilsky, Edward J; Cain, Jim P; Kumirov, Vlad K.; Lee, Yeon Sun; Hruby, Victor J; Vardanyan, Ruben S.; Vanderah, Todd W.

2014-01-01

Approximately one third of the adult U.S. population suffers from some type of on-going, chronic pain annually, and many more will have some type of acute pain associated with trauma or surgery. First-line therapies for moderate to severe pain include prescriptions for common mu opioid receptor agonists such as morphine and its various derivatives. The epidemic use, misuse and diversion of prescription opioids has highlighted just one of the adverse effects of mu opioid analgesics. Alternative approaches include novel opioids that target delta or kappa opioid receptors, or compounds that interact with two or more of the opioid receptors. Aims Here we report the pharmacology of a newly synthesized bifunctional opioid agonist (RV-Jim-C3) derived from combined structures of fentanyl and enkephalin in rodents. RV-Jim-C3 has high affinity binding to both mu and delta opioid receptors. Main Methods Mice and rats were used to test RV-Jim-C3 in a tailflick test with and without opioid selective antagonist for antinociception. RV-Jim-C3 was tested for anti-inflammatory and antihypersensitivity effects in a model of formalin-induced flinching and spinal nerve ligation. To rule out motor impairment, rotarod was tested in rats. Key findings RV-Jim-C3 demonstrates potent-efficacious activity in several in vivo pain models including inflammatory pain, antihyperalgesia and antiallodynic with no significant motor impairment. Significance This is the first report of a fentanyl-based structure with delta and mu opioid receptor activity that exhibits outstanding antinociceptive efficacy in neuropathic pain, reducing the propensity of unwanted side effects driven by current therapies that are unifunctional mu opioid agonists. PMID:24084045

AMBULATORY DIAGNOSIS AND TREATMENT OF NON-MALIGNANT PAIN IN THE UNITED STATES, 2000–2010

PubMed Central

Daubresse, Matthew; Chang, Hsien-Yen; Yu, Yuping; Viswanathan, Shilpa; Shah, Nilay D.; Stafford, Randall S.; Kruszewski, Stefan P.; Alexander, G. Caleb

2013-01-01

Background Escalating rates of prescription opioid use and abuse have occurred in the context of efforts to improve the treatment of non-malignant pain. Objectives To characterize the diagnosis and management of non-malignant pain in ambulatory, office-based settings in the United States between 2000 and 2010. Design, setting, and participants Serial cross-sectional and multivariate regression analyses of the National Ambulatory Medical Care Survey (NAMCS), a nationally representative audit of office-based physician visits. Measures (1) Annual visits volume among adults with primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3) receipt of prescription opioid or non-opioid pharmacologic therapy in visits for new musculoskeletal pain. Results Primary symptoms or diagnoses of pain consistently represented one-fifth of visits, varying little from 2000 through 2010. Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%, whereas non-opioid analgesic prescribing remained unchanged (26%–29% of visits). One-half of new musculoskeletal pain visits resulted in pharmacologic treatment, though the prescribing of non-opioid pharmacotherapies decreased from 38% of visits (2000) to 29% of visits (2010). After adjusting for potentially confounding covariates, few patient, physician or practice characteristics were associated with a prescription opioid rather than a non-opioid analgesic for new musculoskeletal pain, and increases in opioid prescribing generally occurred non-selectively over time. Conclusions Increased opioid prescribing has not been accompanied by similar increases in non-opioid analgesics or the proportion of ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives to prescription opioids may be underutilized as a means of treating ambulatory non-malignant pain. PMID:24025657

Acute opioid withdrawal is associated with increased neural activity in reward-processing centers in healthy men: A functional magnetic resonance imaging study.

PubMed

Chu, Larry F; Lin, Joanne C; Clemenson, Anna; Encisco, Ellen; Sun, John; Hoang, Dan; Alva, Heather; Erlendson, Matthew; Clark, J David; Younger, Jarred W

2015-08-01

Opioid analgesics are frequently prescribed for chronic pain. One expected consequence of long-term opioid use is the development of physical dependence. Although previous resting state functional magnetic resonance imaging (fMRI) studies have demonstrated signal changes in reward-associated areas following morphine administration, the effects of acute withdrawal on the human brain have been less well-investigated. In an earlier study by our laboratory, ondansetron was shown to be effective in preventing symptoms associated with opioid withdrawal. The purpose of this current study was to characterize neural activity associated with acute opioid withdrawal and examine whether these changes are modified by ondansetron. Ten participants were enrolled in this placebo-controlled, randomized, double-blind, crossover study and attended three acute opioid withdrawal sessions. Participants received either placebo or ondansetron (8Ymg IV) before morphine administration (10Ymg/70Ykg IV). Participants then underwent acute naloxone-precipitated withdrawal during a resting state fMRI scan. Objective and subjective opioid withdrawal symptoms were assessed. Imaging results showed that naloxone-precipitated opioid withdrawal was associated with increased neural activity in several reward processing regions, including the right pregenual cingulate, putamen, and bilateral caudate, and decreased neural activity in networks involved in sensorimotor integration. Ondansetron pretreatment did not have a significant effect on the imaging correlates of opioid withdrawal. This study presents a preliminary investigation of the regional changes in neural activity during acute opioid withdrawal. The fMRI acute opioid withdrawal model may serve as a tool for studying opioid dependence and withdrawal in human participants. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Perceptions of Harm and Reasons for Misuse of Prescription Opioid Drugs and Reasons for Not Seeking Treatment for Physical or Emotional Pain Among a Sample of College Students.

PubMed

Kenne, Deric R; Hamilton, Kelsey; Birmingham, Lauren; Oglesby, Willie H; Fischbein, Rebecca L; Delahanty, Douglas L

2017-01-02

Since the early 1990s, the United States has seen a significant increase in the prevalence of prescription opioid misuse. Despite benefits prescription opioids provide, misuse can be fatal. The current study was designed to investigate the prevalence of prescription opioid misuse, perceived harm of misuse, and reasons for misuse for physical or emotional pain instead of seeking professional medical or mental health treatment. Survey data were collected in the fall of 2013 via an online survey to a random sample of 668 students from a public Midwestern university. Lifetime prevalence of prescription opioid misuse was 9.5%. Misusers of prescription opioid drugs generally reported lower ratings of perceived harm as compared to individuals not reporting misuse of prescription opioid drugs. Primary reasons for misuse of prescription opioid drugs was to relieve pain (33.9%), "to feel good/get high" (23.2%) and experimentation (21.4%). Lifetime misuse of a prescription opioid drug for physical or emotional pain was reported by 8.1% and 2.2% of respondents, respectively. Primary reasons for misuse for physical pain included because pain was temporary, immediate relief was needed, and no health insurance/financial resources. Primary reasons for misuse for emotional pain included not wanting others to find out, embarrassment and fear. Conclusions/Importance: Reasons for misuse of prescription opioid drugs vary by type of prescription opioid drug. Reasons for not seeking treatment that ultimately lead to misuse, vary by type of pain being treated and may be important considerations in the effort to stem the misuse of prescription opioid drugs among college students.

Peripheral Sensitization Increases Opioid Receptor Expression and Activation by Crotalphine in Rats

PubMed Central

Zambelli, Vanessa Olzon; Fernandes, Ana Carolina de Oliveira; Gutierrez, Vanessa Pacciari; Ferreira, Julio Cesar Batista; Parada, Carlos Amilcar; Mochly-Rosen, Daria; Cury, Yara

2014-01-01

Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the µ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective µ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. PMID:24594607

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.

Evaluation of Emergency Department Management of Opioid-Tolerant Cancer Patients With Acute Pain.

PubMed

Patel, Pina M; Goodman, Lauren F; Knepel, Sheri A; Miller, Charles C; Azimi, Asma; Phillips, Gary; Gustin, Jillian L; Hartman, Amber

2017-10-01

There are no previously published studies examining opioid doses administered to opioid-tolerant cancer patients during emergency department (ED) encounters. To determine if opioid-tolerant cancer patients presenting with acute pain exacerbations receive adequate initial doses of as needed (PRN) opioids during ED encounters based on home oral morphine equivalent (OME) use. We performed a retrospective cohort study of opioid-tolerant cancer patients who received opioids in our ED over a two-year period. The percentage of patients who received an adequate initial dose of PRN opioid (defined as ≥10% of total 24-hour ambulatory OME) was evaluated. Logistic regression was used to establish the relationship between 24-hour ambulatory OME and initial ED OME to assess whether higher home usage was associated with higher likelihood of being undertreated. Out of 216 patients, 61.1% of patients received an adequate initial PRN dose of opioids in the ED. Of patients taking <200 OMEs per day at home, 77.4% received an adequate initial dose; however, only 3.2% of patients taking >400 OMEs per day at home received an adequate dose. Patients with ambulatory 24-hour OME greater than 400 had 99% lower odds of receiving an adequate initial dose of PRN opioid in the ED compared to patients with ambulatory 24-hour OME less than 100 (OR <0.01, CI 0.00-0.02, P < 0.001). Patients with daily home use less than 200 OMEs generally received adequate initial PRN opioid doses during their ED visit. However, patients with higher home opioid usage were at increased likelihood of being undertreated. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

The evolution of chronic opioid therapy and recognizing addiction.

PubMed

Daum, Akiva M; Berkowitz, Oren; Renner, John A

2015-05-01

Chronic pain is one of the most common complaints in the United States. Opioids have become a frequently prescribed treatment for patients with chronic nonmalignant pain. Concurrently, opioid use disorders have risen to epidemic levels. Studies investigating iatrogenic opioid addiction have been of limited quality. Aberrant drug-related behaviors may be warning signs of impending addiction. Proper screening and close monitoring are essential for managing patients on opioids for chronic nonmalignant pain.

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

PubMed

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

2016-02-01

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

Effect of restricting the legal supply of prescription opioids on buying through online illicit marketplaces: interrupted time series analysis

PubMed Central

Martin, James; Décary-Hétu, David; Aldridge, Judith

2018-01-01

Abstract Objective To examine the effect on the trade in opioids through online illicit markets (“cryptomarkets”) of the US Drug Enforcement Administration’s ruling in 2014 to reschedule hydrocodone combination products. Design Interrupted time series analysis. Setting 31 of the world’s largest cryptomarkets operating from October 2013 to July 2016. Main outcome measures The proportion of total transactions, advertised and active listings for prescription opioids, prescription sedatives, prescription steroids, prescription stimulants, and illicit opioids, and the composition of the prescription opioid market between the US and elsewhere. Results The sale of prescription opioids through US cryptomarkets increased after the schedule change, with no statistically significant changes in sales of prescription sedatives, prescription steroids, prescription stimulants, or illicit opioids. In July 2016 sales of opioids through US cryptomarkets represented 13.7% of all drug sales (95% confidence interval 11.5% to 16.0%) compared with a modelled estimate of 6.7% of all sales (3.7% to 9.6%) had the new schedule not been introduced. This corresponds to a 4 percentage point yearly increase in the amount of trade that prescription opioids represent in the US market, set against no corresponding changes for comparable products or for prescription opioids sold outside the US. This change was first observed for sales, and later observed for product availability. There was also a change in the composition of the prescription opioid market: fentanyl was the least purchased product during July to September 2014, then the second most frequently purchased by July 2016. Conclusions The scheduling change in hydrocodone combination products coincided with a statistically significant, sustained increase in illicit trading of opioids through online US cryptomarkets. These changes were not observed for other drug groups or in other countries. A subsequent move was observed towards the purchase of more potent forms of prescription opioids, particularly oxycodone and fentanyl. PMID:29899119

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.

Effect of restricting the legal supply of prescription opioids on buying through online illicit marketplaces: interrupted time series analysis.

PubMed

Martin, James; Cunliffe, Jack; Décary-Hétu, David; Aldridge, Judith

2018-06-13

To examine the effect on the trade in opioids through online illicit markets ("cryptomarkets") of the US Drug Enforcement Administration's ruling in 2014 to reschedule hydrocodone combination products. Interrupted time series analysis. 31 of the world's largest cryptomarkets operating from October 2013 to July 2016. The proportion of total transactions, advertised and active listings for prescription opioids, prescription sedatives, prescription steroids, prescription stimulants, and illicit opioids, and the composition of the prescription opioid market between the US and elsewhere. The sale of prescription opioids through US cryptomarkets increased after the schedule change, with no statistically significant changes in sales of prescription sedatives, prescription steroids, prescription stimulants, or illicit opioids. In July 2016 sales of opioids through US cryptomarkets represented 13.7% of all drug sales (95% confidence interval 11.5% to 16.0%) compared with a modelled estimate of 6.7% of all sales (3.7% to 9.6%) had the new schedule not been introduced. This corresponds to a 4 percentage point yearly increase in the amount of trade that prescription opioids represent in the US market, set against no corresponding changes for comparable products or for prescription opioids sold outside the US. This change was first observed for sales, and later observed for product availability. There was also a change in the composition of the prescription opioid market: fentanyl was the least purchased product during July to September 2014, then the second most frequently purchased by July 2016. The scheduling change in hydrocodone combination products coincided with a statistically significant, sustained increase in illicit trading of opioids through online US cryptomarkets. These changes were not observed for other drug groups or in other countries. A subsequent move was observed towards the purchase of more potent forms of prescription opioids, particularly oxycodone and fentanyl. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

State Legal Restrictions and Prescription-Opioid Use among Disabled Adults

PubMed Central

Meara, Ellen; Horwitz, Jill R.; Powell, Wilson; McClelland, Lynn; Zhou, Weiping; O’Malley, A. James; Morden, Nancy E.

2016-01-01

BACKGROUND In response to rising rates of opioid abuse and overdose, U.S. states enacted laws to restrict the prescribing and dispensing of controlled substances. The effect of these laws on opioid use is unclear. METHODS We tested associations between prescription-opioid receipt and state controlled-substances laws. Using Medicare administrative data for fee-for-service disabled beneficiaries 21 to 64 years of age who were alive throughout the calendar year (8.7 million person-years from 2006 through 2012) and an original data set of laws (e.g., prescription-drug monitoring programs), we examined the annual prevalence of beneficiaries with four or more opioid prescribers, prescriptions yielding a daily morphine-equivalent dose (MED) of more than 120 mg, and treatment for nonfatal prescription-opioid overdose. We estimated how opioid outcomes varied according to eight types of laws. RESULTS From 2006 through 2012, states added 81 controlled-substance laws. Opioid receipt and potentially hazardous prescription patterns were common. In 2012 alone, 47% of beneficiaries filled opioid prescriptions (25% in one to three calendar quarters and 22% in every calendar quarter); 8% had four or more opioid prescribers; 5% had prescriptions yielding a daily MED of more than 120 mg in any calendar quarter; and 0.3% were treated for a nonfatal prescription-opioid overdose. We observed no significant associations between opioid outcomes and specific types of laws or the number of types enacted. For example, the percentage of beneficiaries with a prescription yielding a daily MED of more than 120 mg did not decline after adoption of a prescription-drug monitoring program (0.27 percentage points; 95% confidence interval, −0.05 to 0.59). CONCLUSIONS Adoption of controlled-substance laws was not associated with reductions in potentially hazardous use of opioids or overdose among disabled Medicare beneficiaries, a population particularly at risk. PMID:27332619

Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

PubMed

Long, D R; Lihn, A L; Friedrich, S; Scheffenbichler, F T; Safavi, K C; Burns, S M; Schneider, J C; Grabitz, S D; Houle, T T; Eikermann, M

2018-05-01

The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Pain outcomes in children who received intrathecal vs intravenous opioids for pain control following major urologic surgery: a retrospective review.

PubMed

Putnam, Elizabeth M; Koppera, Prabhat; Malviya, Shobha; Voepel-Lewis, Terri

2015-12-01

Intrathecal (IT) opioid administration has been associated with postoperative benefits including reduced pain and opioid use in children. However, the postoperative benefits and risks of IT opioid administration during major urologic surgery in children remain unclear. The aim of this study was to compare postoperative pain and adverse event outcomes among children who received IT vs intravenous (IV) opioids during major urologic surgery. We reviewed the medical records of children 3-17 years of age who underwent ureteroneocystostomy or pyeloplasty between 2006 and 2012. Electronically captured anesthetic and surgical data, postanesthesia care recovery unit (PACU) and nursing flowsheets, and daily progress notes through hospital discharge were reviewed. Analgesic techniques (i.e., IT or IV patient/nurse controlled opioids), all analgesic drugs and doses were recorded. Outcome measures included pain scores, need for rescue analgesics, opioid-related adverse events, and their treatments. Seventy-seven children received IT opioids and 51 received IV opioids. More children in the IV group required rescue analgesics and had higher pain scores at PACU discharge. Children in the IV group required rescue opioids more frequently than the IT group from 0 to 8 h and 8 to 16 h after PACU discharge, but rates were similar by 16-24 h 70% of children in IT group transitioned directly to oral opioids. Seven IT placements were considered as failed due to early need for rescue opioids. Four (8%) of the IV group and seven (9%) of the IT group experienced oxygen desaturation. Two of these, both in IT group required naloxone and one was admitted to ICU for observation. The IT group experienced a higher incidence of pruritus, constipation and hypotension. We observed better postoperative pain control in children who received IT vs IV opioids for the first 16 h with no discernible difference thereafter. The intrathecal group experienced higher incidences of pruritus, constipation, and hypotension. © 2015 John Wiley & Sons Ltd.

Opioid-Prescribing Patterns of Emergency Physicians and Risk of Long-Term Use

PubMed Central

Barnett, Michael L.; Olenski, Andrew R.; Jena, Anupam B.

2017-01-01

BACKGROUND Increasing overuse of opioids in the United States may be driven in part by physician prescribing. However, the extent to which individual physicians vary in opioid prescribing and the implications of that variation for long-term opioid use and adverse outcomes in patients are unknown. METHODS We performed a retrospective analysis involving Medicare beneficiaries who had an index emergency department visit in the period from 2008 through 2011 and had not received prescriptions for opioids within 6 months before that visit. After identifying the emergency physicians within a hospital who cared for the patients, we categorized the physicians as being high-intensity or low-intensity opioid prescribers according to relative quartiles of prescribing rates within the same hospital. We compared rates of long-term opioid use, defined as 6 months of days supplied, in the 12 months after a visit to the emergency department among patients treated by high-intensity or low-intensity prescribers, with adjustment for patient characteristics. RESULTS Our sample consisted of 215,678 patients who received treatment from low-intensity prescribers and 161,951 patients who received treatment from high-intensity prescribers. Patient characteristics, including diagnoses in the emergency department, were similar in the two treatment groups. Within individual hospitals, rates of opioid prescribing varied widely between low-intensity and high-intensity prescribers (7.3% vs. 24.1%). Long-term opioid use was significantly higher among patients treated by high-intensity prescribers than among patients treated by low-intensity prescribers (adjusted odds ratio, 1.30; 95% confidence interval, 1.23 to 1.37; P<0.001); these findings were consistent across multiple sensitivity analyses. CONCLUSIONS Wide variation in rates of opioid prescribing existed among physicians practicing within the same emergency department, and rates of long-term opioid use were increased among patients who had not previously received opioids and received treatment from high-intensity opioid prescribers. (Funded by the National Institutes of Health.) PMID:28199807

42 CFR 8.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID... body that has been approved by SAMHSA under § 8.3 to accredit opioid treatment programs using opioid... SAMHSA. Accreditation survey means an onsite review and evaluation of an opioid treatment program by an...

42 CFR 8.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID... body that has been approved by SAMHSA under § 8.3 to accredit opioid treatment programs using opioid... SAMHSA. Accreditation survey means an onsite review and evaluation of an opioid treatment program by an...

42 CFR 8.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID... body that has been approved by SAMHSA under § 8.3 to accredit opioid treatment programs using opioid... SAMHSA. Accreditation survey means an onsite review and evaluation of an opioid treatment program by an...

42 CFR 8.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS CERTIFICATION OF OPIOID... body that has been approved by SAMHSA under § 8.3 to accredit opioid treatment programs using opioid... SAMHSA. Accreditation survey means an onsite review and evaluation of an opioid treatment program by an...

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

Salomon, G.; Park, E.J.; Quock, R.M.

This study was conducted to identify the opioid receptor subtype(s) responsible for RFR-induced analgesia. Male Swiss Webster mice, 20-25 g, were exposed to 20 mW/cm{sup 2} RFR in a 2,450-MHz waveguide system for 10 min, then tested 15 min later in the abdominal constriction paradigm which detects {mu}- and {kappa}-opioid activity. Immediately following RFR exposure, different groups of mice were pretreated intracerebroventricularly with different opioid receptor blockers with selectivity for {mu}- or {kappa}-opioid receptors. Results show that RFR-induced analgesia was attenuated by higher but not lower doses of the non-selective antagonist naloxone, but the selective {mu}-opioid antagonist {beta}-funaltrexamine and bymore » the selective {kappa}-opioid antagonist norbinaltorphimine. RFR-induced analgesia was also reduced by subcutaneous pretreatment with 5.0 mg/kg of the {mu}-/{kappa}-opioid antagonist({minus})-5,9-diethyl-{alpha}-5,9-dialkyl-2{prime}-hydroxy-6,7-benzomorphan(MR-2266). These findings suggest that RFR-induced analgesia may be mediated by both {mu}- and {kappa}-opioid mechanisms.« less

Mandatory Provider Review And Pain Clinic Laws Reduce The Amounts Of Opioids Prescribed And Overdose Death Rates.

PubMed

Dowell, Deborah; Zhang, Kun; Noonan, Rita K; Hockenberry, Jason M

2016-10-01

To address the opioid overdose epidemic in the United States, states have implemented policies to reduce inappropriate opioid prescribing. These policies could affect the coincident heroin overdose epidemic by either driving the substitution of heroin for opioids or reducing simultaneous use of both substances. We used IMS Health's National Prescription Audit and government mortality data to examine the effect of these policies on opioid prescribing and on prescription opioid and heroin overdose death rates in the United States during 2006-13. The analysis revealed that combined implementation of mandated provider review of state-run prescription drug monitoring program data and pain clinic laws reduced opioid amounts prescribed by 8 percent and prescription opioid overdose death rates by 12 percent. We also observed relatively large but statistically insignificant reductions in heroin overdose death rates after implementation of these policies. This combination of policies was effective, but broader approaches to address these coincident epidemics are needed. Project HOPE—The People-to-People Health Foundation, Inc.

Costs and Work Loss Burden of Diagnosed Opioid Abuse Among Employees on Workers Compensation or Short-term Disability.

PubMed

Johnston, Stephen S; Alexander, Andrea H; Masters, Elizabeth T; Mardekian, Jack; Semel, David; Malangone-Monaco, Elisabetta; Riehle, Ellen; Wilson, Kathleen; Sadosky, Alesia

2016-11-01

To compare 12-month healthcare costs between employees with versus without diagnosed opioid abuse within 12 months after an injury-related workers' compensation (WC) or short-term disability (STD) claim. Retrospective study using 2003 to 2014 US insurance claims linked to administrative data on WC/STD claims. Multivariable models compared healthcare costs between employees with versus without diagnosed opioid abuse. Study included 107,975 opioid-treated employees with an injury-related WC or STD claim. Mean number of opioid prescription fills and adjusted total healthcare costs were substantially greater in employees with diagnosed opioid abuse versus without (WC: 13.4 vs. 4.5, P < 0.001; $18,073 vs. $8470, P < 0.001; STD: 13.7 vs. 4.5, P < 0.001; $25,693 vs. $14,939, P < 0.001). Opioids are commonly prescribed to employees with injury-related WC/STD claims. Employers may benefit from proactively addressing the issue of opioid abuse in these populations.

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

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.

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 Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.

Low doses of cyclic AMP-phosphodiesterase inhibitors rapidly evoke opioid receptor-mediated thermal hyperalgesia in naïve mice which is converted to prominent analgesia by cotreatment with ultra-low-dose naltrexone.

PubMed

Crain, Stanley M; Shen, Ke-Fei

2008-09-22

Systemic (s.c.) injection in naïve mice of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors, e.g. 3-isobutyl-1-methylxanthine [(IBMX) or caffeine, 10 mg/kg] or the more specific cAMP-PDE inhibitor, rolipram (1 mug/kg), rapidly evokes thermal hyperalgesia (lasting >5 h). These effects appear to be mediated by enhanced excitatory opioid receptor signaling, as occurs during withdrawal in opioid-dependent mice. Cotreatment of these mice with ultra-low-dose naltrexone (NTX, 0.1 ng/kg-1 pg/kg, s.c.) results in prominent opioid analgesia (lasting >4 h) even when the dose of rolipram is reduced to 1 pg/kg. Cotreatment of these cAMP-PDE inhibitors in naïve mice with an ultra-low-dose (0.1 ng/kg) of the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) or the mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA) also results in opioid analgesia. These excitatory effects of cAMP-PDE inhibitors in naïve mice may be mediated by enhanced release of small amounts of endogenous bimodally-acting (excitatory/inhibitory) opioid agonists by neurons in nociceptive networks. Ultra-low-dose NTX, nor-BNI or beta-FNA selectively antagonizes high-efficacy excitatory (hyperalgesic) Gs-coupled opioid receptor-mediated signaling in naïve mice and results in rapid conversion to inhibitory (analgesic) Gi/Go-coupled opioid receptor-mediated signaling which normally requires activation by much higher doses of opioid agonists. Cotreatment with a low subanalgesic dose of kelatorphan, an inhibitor of multiple endogenous opioid peptide-degrading enzymes, stabilizes endogenous opioid agonists released by cAMP-PDE inhibitors, resulting in conversion of the hyperalgesia to analgesia without requiring selective blockade of excitatory opioid receptor signaling. The present study provides a novel pharmacologic paradigm that may facilitate development of valuable non-narcotic clinical analgesics utilizing cotreatment with ultra-low-dose rolipram plus ultra-low-dose NTX or related agents.

Prospective, Observational Study of Opioid Use After Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

PubMed

Cunningham, Daniel; Lewis, Brian; Hutyra, Carolyn; Nho, Shane; Olson, Steven; Mather, Richard

2018-05-01

To provide estimates of postoperative opioid use after hip arthroscopy for femoroacetabular impingement (FAI) syndrome and to identify risk factors for increased postoperative opioid use. All patients aged at least 18 years who were undergoing hip arthroscopy for FAI syndrome performed by 1 of 2 hip-preservation surgeons between November 2015 and August 2016 were eligible for inclusion in this study. Target minimum enrollment was set at 30 patients per surgeon based on an a priori sample size calculation. Enrolled patients completed the International Hip Outcome Tool, visual analog pain scale, Pain Catastrophizing Scale, abbreviated Patient Health Questionnaire, and questions regarding demographic characteristics and opioid and anti-inflammatory use. Opioid consumption was assessed through pill counting at 2- and 6-week postoperative appointments. Of 80 patients enrolled, 67 had complete 2- and 6-week opioid use data. Patient and operative factors were correlated with outcomes in multivariate models. Opioid use in the 2 weeks before surgery was significantly associated with higher postoperative opioid use at 2 weeks postoperatively (253.8 additional oral morphine equivalents [OMEs]; 95% confidence interval [CI], 171.2-336.5 additional OMEs; P < .0001; n = 73) and 6 weeks postoperatively (385.3 additional OMEs; 95% CI, 241.6-529.0 additional OMEs; P < .0001; n = 67). By 6 weeks postoperatively, 41 of 52 patients (79%) without opioid use in the 2 weeks before surgery used 30 or fewer 5-mg oxycodone pills compared with only 2 of 15 patients (13%) with preoperative use (odds ratio, 24.9; 95% CI, 4.2-148.5; P < .0001). Among patients undergoing hip arthroscopy for FAI syndrome, any opioid use in the 2 weeks preceding surgery was the strongest predictor of opioid use after hip arthroscopy. The impact of preoperative opioid use far exceeded the impact of other baseline patient and operative factors. Assessment of preoperative opioid use could be an important factor in guiding postoperative opioid prescribing. Level II, prospective observational study. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Opioid Receptors: Toward Separation of Analgesic from Undesirable Effects

PubMed Central

Law, P.Y.; Reggio, Patricia H.; Loh, H.H.

2013-01-01

The use of opioid analgesics for pain has always been hampered by their many side effects; in particular, the addictive liability associated with chronic use. Recently, attempts to develop analgesic agents with reduced side effects have targeted either the putative opioid receptor splice variants or the receptor heterooligomers. This review discusses the potential for receptor splice variant- and the hetero-oligomer-based discovery of new opioid analgesics. We also examine an alternative approach of using receptor mutants for pain management. Finally, we discuss the role of the biased agonism observed and the recently reported opioid receptor crystal structures in guiding the future development of opioid analgesics PMID:23598157

Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults.

PubMed

Abramoff, Benjamin A; Lange, Hannah L H; Matson, Steven C; Cottrill, Casey B; Bridge, Jeffrey A; Abdel-Rasoul, Mahmoud; Bonny, Andrea E

2015-01-01

Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence.

Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults

PubMed Central

Abramoff, Benjamin A.; Lange, Hannah L. H.; Matson, Steven C.; Cottrill, Casey B.; Bridge, Jeffrey A.; Abdel-Rasoul, Mahmoud; Bonny, Andrea E.

2015-01-01

Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence. PMID:26664819

School nurse experiences with prescription opioids in urban and rural schools: A cross-sectional survey.

PubMed

Pattison-Sharp, Ella; Estrada, Robin Dawson; Elio, Alice; Prendergast, Melissa; Carpenter, Delesha M

2017-01-01

Few studies have examined the use of prescription opioids in schools. The current study aimed to: (1) describe the context within which school nurses encounter student opioid prescriptions; (2) assess school nurses' preferences for training and student education; and (3) explore urban-rural differences in school nurses' experiences and training preferences. A convenience sample of school nurses (n = 633) from North Carolina and South Carolina participated in a brief, anonymous, online survey. Qualitative data were analyzed thematically and statistical tests (t-tests and Chi-square tests) were performed to investigate urban-rural differences. Many school nurses (40.3%) had encountered a student with an opioid prescription, but only 3.6% had naloxone available in case of an overdose. Most school nurses (69.9%), especially rural school nurses, believed students would benefit from opioid education (74.9 versus 66.6%, p = 0.03). The majority of school nurses (83.9%) were interested in opioid-related training. Many school nurses encounter students with prescription opioids and would like additional opioid-related training. The potential benefits of providing naloxone access to prevent opioid-related deaths at schools should be explored.

Opioid, cannabinoid, and transient receptor potential (TRP) systems: effects on body temperature

PubMed Central

Rawls, Scott M.; Benamar, Khalid

2014-01-01

Cannabinoid and opioid drugs produce marked changes in body temperature. Recent findings have extended our knowledge about the thermoregulatory effects of cannabinoids and opioids, particularly as related to delta opioid receptors, endogenous systems, and transient receptor potential (TRP) channels. Although delta opioid receptors were originally thought to play only a minor role in thermoregulation compared to mu and kappa opioid receptors, their activation has been shown to produce hypothermia in multiple species. Endogenous opioids and cannabinoids also regulate body temperature. Mu and kappa opioid receptors are thought to be in tonic balance, with mu and kappa receptor activation producing hyperthermia and hypothermia, respectively. Endocannabinoids participate in the febrile response, but more studies are needed to determine if a cannabinoid CB1 receptor tone exerts control over basal body temperature. A particularly intense research focus is TRP channels, where TRPV1 channel activation produces hypothermia whereas TRPA1 and TRPM8 channel activation causes hyperthermia. The marked hyperthermia produced by TRPV1 channel antagonists suggests these warm channels tonically control body temperature. A better understanding of the roles of cannabinoid, opioid, and TRP systems in thermoregulation may have broad clinical implications and provide insights into interactions among neurotransmitter systems involved in thermoregulation. PMID:21622235

Distress Intolerance and Prescription Opioid Misuse among Patients with Chronic Pain

PubMed Central

McHugh, R. Kathryn; Weiss, Roger D.; Cornelius, Marise; Martel, Marc O.; Jamison, Robert N.; Edwards, Robert R.

2016-01-01

The risk for misuse of opioid medications is a significant challenge in the management of chronic pain. The identification of those who may be at greater risk for misusing opioids is needed to facilitate closer monitoring of high-risk subgroups, and may help to identify therapeutic targets for mitigating this risk. The aim of this study was to examine whether distress intolerance--the perceived or actual inability to manage negative emotional and somatic states--was associated with opioid misuse in those with chronic pain. A sample of 51 participants prescribed opioid analgesics for chronic back or neck pain were recruited for a one-time laboratory study. Participants completed measures of distress intolerance and opioid misuse, and a quantitative sensory testing battery. Results suggested that distress intolerance was associated with opioid misuse, even controlling for pain severity and negative affect. Distress intolerance was not associated with pain severity, threshold or tolerance, but was associated with self-reported anxiety and stress following noxious stimuli. This study found robust differences in distress intolerance between adults with chronic pain with and without opioid medication misuse. Distress intolerance may be a relevant marker of risk for opioid misuse among those with chronic pain. PMID:27058161

Protocol: mixed-methods study to evaluate implementation, enforcement, and outcomes of U.S. state laws intended to curb high-risk opioid prescribing.

PubMed

McGinty, Emma E; Stuart, Elizabeth A; Caleb Alexander, G; Barry, Colleen L; Bicket, Mark C; Rutkow, Lainie

2018-02-26

The U.S. opioid epidemic has been driven by the high volume of opioids prescribed by healthcare providers. U.S. states have recently enacted four types of laws designed to curb high-risk prescribing practices, such as high-dose and long-term opioid prescribing, associated with opioid-related mortality: (1) mandatory Prescription Drug Monitoring Program (PDMP) enrollment laws, which require prescribers to enroll in their state's PDMP, an electronic database of patients' controlled substance prescriptions, (2) mandatory PDMP query laws, which require prescribers to query the PDMP prior to prescribing an opioid, (3) opioid prescribing cap laws, which limit the dose and/or duration of opioid prescriptions, and (4) pill mill laws, which strictly regulate pain clinics to prevent nonmedical opioid prescribing. Some pain experts have expressed concern that these laws could negatively affect pain management among patients with chronic non-cancer pain. This paper describes the protocol for a mixed-methods study analyzing the independent effects of these four types of laws on opioid prescribing patterns and chronic non-cancer pain treatment, accounting for variation in implementation and enforcement of laws across states. Many states have enacted multiple opioid prescribing laws at or around the same time. To overcome this issue, our study focuses on 18 treatment states that each enacted a single law of interest, and no other potentially confounding laws, over a 4-year period (2 years pre-/post-law). Qualitative interviews with key leaders in each of the 18 treatment states will characterize the timing, scope, and strength of each state law's implementation and enforcement. This information will inform the design and interpretation of synthetic control models analyzing the effects of each of the two types of laws on two sets of outcomes: measures of (1) high-risk opioid prescribing and (2) non-opioid treatments for chronic non-cancer pain. Study of mandatory PDMP enrollment, mandatory PDMP query, opioid prescribing cap, and pill mill laws is timely given a dynamic policy environment in which numerous states pass, revise, implement, and enforce varied laws to address opioid prescribing each year. Findings will inform enactment, implementation, and enforcement of these laws in additional states.

Association Between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population.

PubMed

Bradford, Ashley C; Bradford, W David; Abraham, Amanda; Bagwell Adams, Grace

2018-05-01

Opioid-related mortality increased by 15.6% from 2014 to 2015 and increased almost 320% between 2000 and 2015. Recent research finds that the use of all pain medications (opioid and nonopioid collectively) decreases in Medicare Part D and Medicaid populations when states approve medical cannabis laws (MCLs). The association between MCLs and opioid prescriptions is not well understood. To examine the association between prescribing patterns for opioids in Medicare Part D and the implementation of state MCLs. Longitudinal analysis of the daily doses of opioids filled in Medicare Part D for all opioids as a group and for categories of opioids by state and state-level MCLs from 2010 through 2015. Separate models were estimated first for whether the state had implemented any MCL and second for whether a state had implemented either a dispensary-based or a home cultivation only-based MCL. The primary outcome measure was the total number of daily opioid doses prescribed (in millions) in each US state for all opioids. The secondary analysis examined the association between MCLs separately by opioid class. From 2010 to 2015 there were 23.08 million daily doses of any opioid dispensed per year in the average state under Medicare Part D. Multiple regression analysis results found that patients filled fewer daily doses of any opioid in states with an MCL. The associations between MCLs and any opioid prescribing were statistically significant when we took the type of MCL into account: states with active dispensaries saw 3.742 million fewer daily doses filled (95% CI, -6.289 to -1.194); states with home cultivation only MCLs saw 1.792 million fewer filled daily doses (95% CI, -3.532 to -0.052). Results varied by type of opioid, with statistically significant estimated negative associations observed for hydrocodone and morphine. Hydrocodone use decreased by 2.320 million daily doses (or 17.4%) filled with dispensary-based MCLs (95% CI, -3.782 to -0.859; P = .002) and decreased by 1.256 million daily doses (or 9.4%) filled with home-cultivation-only-based MCLs (95% CI, -2.319 to -0.193; P = .02). Morphine use decreased by 0.361 million daily doses (or 20.7%) filled with dispensary-based MCLs (95% CI, -0.718 to -0.005; P = .047). Medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population. This finding was particularly strong in states that permit dispensaries, and for reductions in hydrocodone and morphine prescriptions.

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 100,000 members per quarter [95% CI, -0.01 to 0.53]). Opioid dispensing and prescription opioid overdoses decreased substantially after 2 major changes in the pharmaceutical market in late 2010. Pharmaceutical market interventions may have value in combatting the prescription opioid overdose epidemic, but heroin overdose rates continue to increase. Complementary strategies to identify and treat opioid abuse and addiction are urgently needed.

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

ER/LA Opioid Analgesics REMS: Overview of Ongoing Assessments of Its Progress and Its Impact on Health Outcomes.

PubMed

Cepeda, M Soledad; Coplan, Paul M; Kopper, Nathan W; Maziere, Jean-Yves; Wedin, Gregory P; Wallace, Laura E

2017-01-01

Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids. © 2016 American Academy of Pain Medicine.

Opioid Analgesics Administered for Pain in the Inpatient Pediatric Setting.

PubMed

Walco, Gary A; Gove, Nancy; Phillips, Jennifer; Weisman, Steven J

2017-10-01

This study aimed to describe utilization of opioid medications among infants, children, and adolescents on the inpatient setting. These data are needed to guide clinical trials and improve research methodologies, as well as to inform more about possible sources of opioid misuse in the United States. A retrospective chart review was conducted covering a span of 1 year, with a special focus on the prescription of opioids for long-term treatment of chronic pain. Opioid medications were prescribed for <5 days in most (75%) patients. Among those who were prescribed opioids for >14 days, the focus was often for reasons other than pain. These data indicate that models of chronic pain that may be utilized in clinical trials of longer-term opioid usage in pediatrics are exceedingly limited. In addition, the patterns of utilization indicate that opioid administration among pediatric inpatients is not a likely contributory factor to concerns about opioid misuse in the United States. This article presents data on the administration of opioids in a major children's hospital, with a special eye toward usage beyond treatment for short-term acute pain. These data are important to better inform discussions of research strategies for chronic pain, as well as concerns for misuse in the pediatric population. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Differentiation of δ, μ, and κ opioid receptor agonists based on pharmacophore development and computed physicochemical properties

NASA Astrophysics Data System (ADS)

Filizola, Marta; Villar, Hugo O.; Loew, Gilda H.

2001-04-01

Compounds that bind with significant affinity to the opioid receptor types, δ, μ, and κ, with different combinations of activation and inhibition at these three receptors could be promising behaviorally selective agents. Working on this hypothesis, the chemical moieties common to three different sets of opioid receptor agonists with significant affinity for each of the three receptor types δ, μ, or κ were identified. Using a distance analysis approach, common geometric arrangements of these chemical moieties were found for selected δ, μ, or κ opioid agonists. The chemical and geometric commonalities among agonists at each opioid receptor type were then compared with a non-specific opioid recognition pharmacophore recently developed. The comparison provided identification of the additional requirements for activation of δ, μ, and κ opioid receptors. The distance analysis approach was able to clearly discriminate κ-agonists, while global molecular properties for all compounds were calculated to identify additional requirements for activation of δ and μ receptors. Comparisons of the combined geometric and physicochemical properties calculated for each of the three sets of agonists allowed the determination of unique requirements for activation of each of the three opioid receptors. These results can be used to improve the activation selectivity of known opioid agonists and as a guide for the identification of novel selective opioid ligands with potential therapeutic usefulness.

ER/LA Opioid Analgesics REMS: Overview of Ongoing Assessments of Its Progress and Its Impact on Health Outcomes

PubMed Central

Cepeda, M. Soledad; Kopper, Nathan W.; Maziere, Jean-Yves; Wedin, Gregory P.; Wallace, Laura E.

2017-01-01

Objective. Opioid abuse is a serious public health concern. In response, the Food and Drug Administration (FDA) determined that a risk evaluation and mitigation strategy (REMS) for extended-release and long-acting (ER/LA) opioids was necessary to ensure that the benefits of these analgesics continue to outweigh the risks. Key components of the REMS are training for prescribers through accredited continuing education (CE), and providing patient educational materials. Methods. The impact of this REMS has been assessed using diverse metrics including evaluation of prescriber and patient understanding of the risks associated with opioids; patient receipt and comprehension of the medication guide and patient counseling document; patient satisfaction with access to opioids; drug utilization and changes in prescribing patterns; and surveillance of ER/LA opioid misuse, abuse, overdose, addiction, and death. Results and Conclusions. The results of these assessments indicate that the increasing rates of opioid abuse, addiction, overdose, and death observed prior to implementation of the REMS have since leveled off or started to decline. However, these benefits cannot be attributed solely to the ER/LA opioid analgesics REMS since many other initiatives to prevent abuse occurred contemporaneously. These improvements occurred while preserving patient access to opioids as a large majority of patients surveyed expressed satisfaction with their access to opioids. PMID:27373304

Impact of the opioid system on the reproductive axis.

PubMed

Böttcher, Bettina; Seeber, Beata; Leyendecker, Gerhard; Wildt, Ludwig

2017-08-01

Endogenous opioids, first described more than 40 years ago, have long been recognized for their main role as important neuromodulators within the central nervous system. More recently endogenous opioids and their receptor have been identified in a variety of reproductive and nonreproductive tissues outside the central nervous system. Their role within these tissues and organs, however, is only incompletely understood. In the central nervous system, endogenous opioids inhibit pulsatile GnRH release, in part mediating the stress response within the central nervous-pituitary gonadal axis, resulting in hypothalamic amenorrhea. In the ovary, the presence of endogenous opioids primarily produced by granulosa cells has been demonstrated within the follicular fluid, likely influencing oocyte maturation. In hypothalamic amenorrhea, normal cycles can be restored by the administration of opioid antagonists, such as naltrexone. In polycystic ovarian syndrome, endogenous opioids have found to be elevated and may stimulate insulin secretion from the endocrine pancreas. This effect can be inhibited by opioid antagonists, resulting in a decrease of circulating insulin levels in response to glucose challenge. Endogenous opioids may also play a role in the pathogenesis of ovarian hyperstimulation syndrome. In summary, endogenous opioids exert a wide variety of actions within the reproductive system and are worthy of further scientific study. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Caring for Pregnant Women with Opioid Use Disorder in the USA: Expanding and Improving Treatment.

PubMed

Saia, Kelley A; Schiff, Davida; Wachman, Elisha M; Mehta, Pooja; Vilkins, Annmarie; Sia, Michelle; Price, Jordana; Samura, Tirah; DeAngelis, Justin; Jackson, Clark V; Emmer, Sawyer F; Shaw, Daniel; Bagley, Sarah

Opioid use disorder in the USA is rising at an alarming rate, particularly among women of childbearing age. Pregnant women with opioid use disorder face numerous barriers to care, including limited access to treatment, stigma, and fear of legal consequences. This review of opioid use disorder in pregnancy is designed to assist health care providers caring for pregnant and postpartum women with the goal of expanding evidence-based treatment practices for this vulnerable population. We review current literature on opioid use disorder among US women, existing legislation surrounding substance use in pregnancy, and available treatment options for pregnant women with opioid use disorder. Opioid agonist treatment (OAT) remains the standard of care for treating opioid use disorder in pregnancy. Medically assisted opioid withdrawal ("detoxification") is not recommended in pregnancy and is associated with high maternal relapse rates. Extended release naltrexone may confer benefit for carefully selected patients. Histories of trauma and mental health disorders are prevalent in this population; and best practice recommendations incorporate gender-specific, trauma-informed, mental health services. Breastfeeding with OAT is safe and beneficial for the mother-infant dyad. Further research investigating options of OAT and the efficacy of opioid antagonists in pregnancy is needed. The US health care system can adapt to provide quality care for these mother-infant dyads by expanding comprehensive treatment services and improving access to care.

Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

PubMed

Franchitto, Nicolas; Jullian, Benedicte; Salles, Juliette; Pelissier, Fanny; Rolland, Benjamin

2017-06-01

Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.

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.

Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis.

PubMed

Bucklin, Brenda A; Chestnut, David H; Hawkins, Joy L

2002-01-01

Some anesthesiologists contend that intrathecal opioid administration has advantages over conventional epidural techniques during labor. Randomized clinical trials comparing analgesia and obstetric outcome using single-injection intrathecal opioids versus epidural local anesthetics suggest that intrathecal opioids provide comparable analgesia with few serious side effects. This meta-analysis compared the analgesic efficacy, side effects, and obstetric outcome of single-injection intrathecal opioid techniques versus epidural local anesthetics in laboring women. Relevant clinical studies were identified using electronic and manual searches of the literature covering the period from 1989 to 2000. Searches used the following descriptors: intrathecal analgesia, spinal opioids, epidural analgesia, epidural local anesthetics, and analgesia for labor. Data were extracted from 7 randomized clinical trials comparing analgesic measures, incidence of motor block, pruritus, nausea, hypotension, mode of delivery, and/or Apgar scores. Combined test results indicated comparable analgesic efficacy 15 to 20 minutes after injection with single-injection intrathecal opioid administration. Intrathecal opioid injections were associated with a greater incidence of pruritus (odds ratio, 14.01; 99% confidence interval, 6.9 to 28.3), but there was no difference in the incidence of nausea or in the method of delivery. Published studies suggest that intrathecal opioids provide comparable early labor analgesia when compared with epidural local anesthetics. Intrathecal opioid administration results in a greater incidence of pruritus. The choice of technique does not appear to affect the method of delivery.

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

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.

Opioid interruptions, pain, and withdrawal symptoms in nursing home residents.

PubMed

Redding, Sarah E; Liu, Sophia; Hung, William W; Boockvar, Kenneth S

2014-11-01

Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for ≥1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre- and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P < 0.015). In patients with interruptions, there were statistically insignificant changes in mean (SD) pain score (difference -0.50 [2.66]; 95% CI, -3.16 to 2.16) and withdrawal score (difference -0.91 [3.12]; 95% CI, -4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with patients without interruptions, patients with interruptions experienced larger increases in pain scores during the follow-up periods (difference 0.09 points per day; 95% CI, -0.01 to 0.019; P = 0.08). In particular, patients who received the highest quartile of opioid dose before interruption experienced increases in pain scores over time that were 0.22 points per day larger (95% CI, 0.02 to 0.41; P = 0.03) than those without interruption. Withdrawal scores were not associated with opioid interruption regardless of dose before interruption. Nursing home patients often experience interruptions in opioid dosing, which can be associated with worse pain, but not withdrawal symptoms, during acute illnesses. Clinicians should be aware of the potential risks and effects of opioid interruptions during acute illnesses in this patient group. Published by Elsevier Inc.

Endogenous opiates and behavior: 2007.

PubMed

Bodnar, Richard J

2008-12-01

This paper is the thirtieth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2007 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses.

Changes in Perceptions of Opioids Before and After Admission to Palliative Care Units in Japan: Results of a Nationwide Bereaved Family Member Survey.

PubMed

Kinoshita, Satomi; Miyashita, Mitsunori; Morita, Tatsuya; Sato, Kazuki; Miyazaki, Tamana; Shoji, Ayaka; Chiba, Yurika; Tsuneto, Satoru; Shima, Yasuo

2016-06-01

This study aimed to clarify perspectives of bereaved family members regarding opioids and compare perceptions before admission and after bereavement. A cross-sectional questionnaire survey for bereaved family members in 100 inpatient palliative care units was administered. Participants were 297 bereaved family members of patients who used opioids. Many bereaved family members had misconceptions of opioids before admission. There was improvement after bereavement, but understanding remained low. Respondents less than 65 years old showed significantly greater decreases in misconceptions regarding opioids compared to older generations, after bereavement. Bereaved family members who were misinformed about opioids by physicians were significantly more likely to have misconceptions about opioids. Educational interventions for physicians are needed to ensure that they offer correct information to the general population. © The Author(s) 2015.

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.

Endogenous opioids and feeding behavior: a 30-year historical perspective.

PubMed

Bodnar, Richard J

2004-04-01

This invited review, based on the receipt of the Third Gayle A. Olson and Richard D. Olson Prize for the publication of the outstanding behavioral article published in the journal Peptides in 2002, examines the 30-year historical perspective of the role of the endogenous opioid system in feeding behavior. The review focuses on the advances that this field has made over the past 30 years as a result of the timely discoveries that were made concerning this important neuropeptide system, and how these discoveries were quickly applied to the analysis of feeding behavior and attendant homeostatic processes. The discoveries of the opioid receptors and opioid peptides, and the establishment of their relevance to feeding behavior were pivotal in studies performed in the 1970s. The 1980s were characterized by the establishment of opioid receptor subtype agonists and antagonists and their relevance to the modulation of feeding behavior as well as by the use of general opioid antagonists in demonstrating the wide array of ingestive situations and paradigms involving the endogenous opioid system. The more recent work from the 1990s to the present, utilizes the advantages created by the cloning of the opioid receptor genes, the development of knockout and knockdown techniques, the systematic utilization of a systems neuroscience approach, and establishment of the reciprocity of how manipulations of opioid peptides and receptors affect feeding behavior with how feeding states affect levels of opioid peptides and receptors. The role of G-protein effector systems in opioid-mediated feeding responses, which was the subject of the prize-winning article, is then reviewed. Copyright 2004 Elsevier Inc.

The stigma of low opioid prescription in the hospitalized multimorbid elderly in Italy.

PubMed

Marengoni, Alessandra; Nobili, Alessandro; Corli, Oscar; Djade, Codjo Djignefa; Bertoni, Diana; Tettamanti, Mauro; Pasina, Luca; Corrao, Salvatore; Salerno, Francesco; Marcucci, Maura; Mannucci, Pier Mannuccio

2015-04-01

The primary aim of this study was to evaluate the prevalence of opioid prescriptions in hospitalized geriatric patients. Other aims were to evaluate factors associated with opioid prescription, and whether or not there was consistency between the presence of pain and prescription. Opioid prescriptions were gathered from the REgistro POliterapie Societa` Italiana di Medicina Interna (REPOSI) data for the years 2008, 2010 and 2012. 1,380 in-patients, 65+ years old, were enrolled in the first registry run, 1,332 in the second and 1,340 in the third. The prevalence of opioid prescription was calculated at hospital admission and discharge. In the third run of the registry, the degree of pain was assessed by means of a numerical scale. The prevalence of patients prescribed with opioids at admission was 3.8% in the first run, 3.6% in the second and 4.1% in the third, whereas at discharge rates were slightly higher (5.8, 5.3, and 6.6%). The most frequently prescribed agents were mild opioids such as codeine and tramadol. The number of total prescribed drugs was positively associated with opioid prescription in the three runs; in the third, dementia and a better functional status were inversely associated with opioid prescription. Finally, as many as 58% of patients with significant pain at discharge were prescribed no analgesic at all. The conservative attitude of Italian physicians to prescribe opioids in elderly patients changed very little between hospital admission and discharge through a period of 5 years. Reasons for such a low opioid prescription should be sought in physicians' and patients' concerns and prejudices.

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.

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

PubMed Central

Bruchas, Michael R.; Calo', Girolamo; Cox, Brian M.; Zaveri, Nurulain T.

2016-01-01

The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor. PMID:26956246

Introduction to the College on Problems of Drug Dependence special issue: contemporary advances in opioid neuropharmacology.

PubMed

Walsh, Sharon L; Unterwald, Ellen M; Izenwasser, Sari

2010-05-01

Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular neurobiology, it has become evident that the functional activity of opioid receptors, as ligand-regulated protein complexes, is modulated by multifarious intracellular and extracellular events, that there is genetic variation in coding for receptors, and that the activity of endogenous opioid systems may underlie actions common to other addictive disorders. This supplemental issue of Drug and Alcohol Dependence, arising from an invited symposium at the 71st Annual Meeting of the College on Problems of Drug Dependence, provides a series of contemporary reviews focused on recent advances in opioid neuropharmacology. Each speaker provides herein an invited comprehensive review of the state of knowledge on a specific topic in opioid neuropharmacology. Evans and colleagues describe the multi-faceted control of the opioid G-protein coupled receptor as a dynamic "sensor" complex and identify novel targets for drug development. von Zastrow focuses on opioid receptor-mediated events regulated by endocytosis and membrane trafficking through the endocytic pathway and differential responses to opioid agonists. Blendy and colleague provide a review of human association studies on the functional relevance of the mu opioid receptor variant, A118G, and presents data from the A112G knock-in model, an analogous mouse variant to A118G. Finally, Maldonado and colleagues provide a broader systems review from genetic, pharmacologic and behavioral studies implicating the endogenous opioid systems as a substrate for the mediation of substance use disorders spanning pharmacological classes.

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.

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease

PubMed Central

Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

2012-01-01

Background: A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Methods: Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Results: Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more “normally,” observed improvements in patients’ symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Interpretation: Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment. PMID:22529167

Catastrophic thinking and increased risk for prescription opioid misuse in patients with chronic pain

PubMed Central

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

2013-01-01

Background As a consequence of the substantial rise in the prescription of opioids for the treatment of chronic noncancer pain, greater attention has been paid to the factors that may be associated with an increased risk for prescription opioid misuse. Recently, a growing number of studies have shown that patients with high levels of catastrophizing are at increased risk for prescription opioid misuse. Objective The primary objective of this study was to examine the variables that might underlie the association between catastrophizing and risk for prescription opioid misuse in patients with chronic pain. Methods Patients with chronic musculoskeletal pain (n = 115) were asked to complete the SOAPP-R, a validated self-report questionnaire designed to identify patients at risk for prescription opioid misuse. Patients were also asked to complete self-report measures of pain intensity, catastrophizing, anxiety, and depression. Results Consistent with previous research, we found that catastrophizing was associated with an increased risk for prescription opioid misuse. Results also revealed that the association between catastrophizing and risk for opioid misuse was partially mediated by patients’ levels of anxiety. Follow-up analyses, however, indicated that catastrophizing remained a significant ‘unique’ predictor of risk for opioid misuse even when controlling for patients’ levels of pain severity, anxiety and depressive symptoms. Discussion Discussion addresses the factors that might place patients with high levels of catastrophizing at increased risk for prescription opioid misuse. The implications of our findings for the management of patients considered for opioid therapy are also discussed. PMID:23618767

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.

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.

Opioid Overdose Experience, Risk Behaviors, and Knowledge in Drug Users from a Rural versus an Urban Setting.

PubMed

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

2016-12-01

Opioid use is highly prevalent in the United States and there has been an increased incidence in the rate of opioid-related overdose. While evidence suggests there are substantial differences in opioid use among rural versus urban settings, the rate of overdose and corresponding frequency of opioid overdose risk behaviors and overdose knowledge between rural and urban settings have not been examined. Individuals with opioid use disorder from rural (N=98) and urban (N=247) settings completed a self-report survey regarding their lifetime history of overdose and overdose risk behaviors. Participants also completed the Brief Opioid Overdose Knowledge (BOOK) questionnaire, a 12-item self-report measure of opioid overdose knowledge. Overall, 35.6% of participants had experienced an overdose, and prevalence of overdose was significantly higher (p<.01) among rural (45.9%) vs. urban (31.6%) participants, though fewer rural participants reported past 30-day risk behaviors. There were few differences observed between the subset of rural and urban participants who had experienced an overdose, and fewer rural participants with a history of overdose reported past 30-day risk behaviors. Both rural and urban participants performed poorly on the BOOK, though the percent of correct responses was lowest among rural participants with a history of overdose. Results demonstrate higher rates of overdose among rural opioid users, though rural participants were less likely to report recent risk behaviors. Results also suggest that knowledge regarding key factors related to opioid overdose is severely lacking, particularly among rural opioid users, which could be a potential target for future intervention efforts.

Multidisciplinary intervention decreases the use of opioid medication discharge packs from 2 urban EDs.

PubMed

Gugelmann, Hallam; Shofer, Frances S; Meisel, Zachary F; Perrone, Jeanmarie

2013-09-01

Prescription opioid overdoses and deaths constitute a public health epidemic, and recent studies show that emergency department (ED) prescribers may contribute to this crisis. We hypothesized that a multidisciplinary educational intervention would decrease ED opioid packs dispensed at discharge. This prospective study implemented a "bundle" of interdisciplinary educational modalities: lectures, journal clubs, case discussions, and an electronic medical record decision support tool. Implementation occurred in 2 urban EDs in the same health system at different times ("affiliate," September 2011; "primary," January 2012) to better distinguish its effects. The primary outcome was preintervention/postintervention change in opioid discharge packs dispensed to all patients treated and discharged through August 2012 and was assessed by 2-way analysis of variance. The secondary outcome was bivariate analysis (using Fisher exact test) of change in opioid dispensing among patients with known risk factors for prescription opioid dependence: age less than 65 years, history of substance abuse, chronic pain, or psychiatric disorders. A total of 71,512 and 45,746 patients were evaluated and discharged from primary and affiliate EDs, respectively. Orders for opioid discharge packs decreased from 13.9% to 8.4% and 4.7% to 1.9% at the primary and affiliate hospitals (P < .0001). Dispensing among individuals at risk for opioid dependence at the primary ED decreased from 21.8% to 13.9%. A staged, multidisciplinary intervention targeting nurses, residents, nurse practitioners, and attending physicians was associated with decreased orders for opioid discharge packs in 2 urban EDs. Opioid discharge pack orders decreased slightly more among patients with risk factors for prescription opioid dependence. © 2013.

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease.

PubMed

Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

2012-06-12

A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more "normally," observed improvements in patients' symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment.

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.

Oxycodone: a pharmacological and clinical review.

PubMed

Ordóñez Gallego, A; González Barón, M; Espinosa Arranz, E

2007-05-01

Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma halflife is 3-5 h (half that of morphine) and stable plasma levels are reached within 24 h (2-7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone--which is also a very potent analgesic--and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3-4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin) is marketed as 10-, 20-, 40- or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm) is also available in capsules and oral solution. Side effects are those common to opioids: mainly nausea, constipation and drowsiness. Vomiting, pruritus and dizziness are less common. The intensity of these side effects tends to decrease over the course of time. Oxycodone causes somewhat less nausea, hallucinations and pruritus than morphine.

Hot Topics in Primary Care: Management of Opioid-induced Constipation.

PubMed

Johnson, David A; Argoff, Charles E

2015-12-01

Constipation is a common complication of opioid therapy that contributes to substantial patient morbidity, decreased productivity, and opioid nonadherence. Other causes of constipation may occur concomitantly and should be investigated. Although evidence supporting their use is limited, the use of fiber, water, laxatives, and/or exercise is recommended in current guidelines as initial management. Peripherally acting μ-opioid receptor antagonists are important treatment options, are well-tolerated, and improve many signs and symptoms of OIC in patients taking an opioid for chronic noncancer pain.

Discovery of Peripheral κ-Opioid Receptor Agonists as Novel Analgesics.

PubMed

Suzuki, Shinya; Sugawara, Yuji; Inada, Hideaki; Tsuji, Riichiro; Inoue, Atsushi; Tanimura, Ryuji; Shimozono, Rieko; Konno, Mitsuhiro; Ohyama, Tomofumi; Higashi, Eriko; Sakai, Chizuka; Kawai, Koji

2017-01-01

κ-Opioid receptor agonists with high selectivity over the μ-opioid receptor and peripheral selectivity are attractive targets in the development of drugs for pain. We have previously attempted to create novel analgesics with peripheral selective κ-opioid receptor agonist on the basis of TRK-820. In this study, we elucidated the biological properties of 17-hydroxy-cyclopropylmethyl and 10α-hydroxy derivatives. These compounds were found to have better κ-opioid receptor selectivity and peripheral selectivity than TRK-820.

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

PubMed

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

2018-04-01

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

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

PubMed

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

2013-01-01

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

Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

PubMed Central

Maslov, Leonid N; Oeltgen, Peter R.; Naryzhnaya, Natalia V.; Pei, Jian‐Ming; Brown, Stephen A.; Lishmanov, Yury B.; Downey, James M.

2016-01-01

Abstract It has now been demonstrated that the μ, δ1, δ2, and κ1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct‐reducing effect with prophylactic administration and prevent reperfusion‐induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia‐induced arrhythmias. PMID:27197922

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.