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Sample records for hydrocodone hydromorphone oxycodone

  1. Evaluation of a Newly Formulated Enzyme Immunoassay for the Detection of Hydrocodone and Hydromorphone in Pain Management Compliance Testing.

    Science.gov (United States)

    Nascimento, Renata; Poklis, Alphonse; Wolf, Carl E

    2016-10-01

    A new Hydrocodone Enzyme Immunoassay (HEIA; Lin-Zhi International, Inc.) was evaluated for the detection of hydrocodone and its main metabolite, hydromorphone. All specimens were tested with two different cutoff calibrators, 100 and 300 ng/mL, on an ARCHITECT Plus c4000 Clinical Chemistry Analyzer. Controls containing -25% (negative control) and +25% (positive control) of the cutoff calibrators and a drug-free control were analyzed with each batch. All 1,025 urine specimens were previously analyzed by ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS-MS) for opiates. Approximately, 33% (337/1,019) of the specimens yielded positive results by the HEIA assay at a cutoff concentration of 100 ng/mL and 19% (190/1,025) yielded positive results at the 300 ng/mL cutoff concentration. Of these presumptive positive specimens, UPLC-MS-MS confirmed the presence of hydrocodone and/or hydromorphone >100 ng/mL in 241 specimens and >300 ng/mL in 162 specimens, for each respective cutoff. With the 100 ng/mL cutoff, the HEIA demonstrated a sensitivity of 0.959, a specificity of 0.846 and an overall agreement with the UPLC-MS-MS of 87%. At 300 ng/mL cutoff, the HEIA demonstrated a sensitivity of 0.880, a specificity of 0.966 and an overall agreement of UPLC-MS-MS results of 95%. The Lin-Zhi HEIA 100 ng/mL cutoff assay demonstrated sensitivity for the detection of hydrocodone and hydromorphone in urine. The 300 ng/mL cutoff was less sensitive, but more selective, and should be part of an initial immunoassay screen, particularly in pain management compliance testing.

  2. Factors influencing the selection of hydrocodone and oxycodone as primary opioids in substance abusers seeking treatment in the United States.

    Science.gov (United States)

    Cicero, Theodore J; Ellis, Matthew S; Surratt, Hilary L; Kurtz, Steven P

    2013-12-01

    The purpose of the present study was to identify the factors that influence the selection of hydrocodone and oxycodone as primary drugs of abuse in opioid-dependent subjects (n = 3520) entering one of 160 drug treatment programs around the country. Anonymous, self-administered surveys and direct qualitative interviews were used to examine the influence of demographic characteristics, drug use patterns, and decision-related factors on primary opioid selection. Our results showed that oxycodone and hydrocodone were the drugs of choice in 75% of all patients. Oxycodone was the choice of significantly more users (44.7%) than hydrocodone (29.4%) because the quality of the high was viewed to be much better by 54% of the sample, compared to just 20% in hydrocodone users, who cited acetaminophen as a deterrent to dose escalation to get high and hence, its low euphoric rating. Hydrocodone users were generally risk-averse women, elderly people, noninjectors, and those who prefer safer modes of acquisition than dealers (ie, doctors, friends, or family members). In contrast, oxycodone was a much more attractive euphorigenic agent to risk-tolerant young, male users who prefer to inject or snort their drugs to get high and are willing to use more aggressive forms of diversion. Prevention and treatment approaches, and pain physicians, should benefit from these results because it is clear that not all drug abusers share the same characteristics, and the decision to use one drug over another is a complex one, which is largely attributable to individual differences (eg, personality, gender, age, and other factors).

  3. Hydrocodone

    Science.gov (United States)

    ... Other examples of combination products include those containing aspirin (Lortab ASA ® ), ibuprofen (Vicoprofen ® ) and antihistamines (Hycomine ® ). Street names Hydro, Norco, Vikes Looks like Hydrocodone has a chemical structure that is related to that of codeine and ...

  4. Sensitivity of an opiate immunoassay for detecting hydrocodone and hydromorphone in urine from a clinical population: analysis of subthreshold results.

    Science.gov (United States)

    Bertholf, Roger L; Johannsen, Laura M; Reisfield, Gary M

    2015-01-01

    Urine drug testing (UDT) is an emerging standard of care in the evaluation and treatment of chronic non-cancer pain patients with opioid analgesics. UDT may be used both to verify adherence with the opioid analgesic regimen and to monitor abstinence from non-prescribed or illicit controlled substances. In the former scenario, it is vital to determine whether the drug is present in the urine, even at low concentrations, because failure to detect the drug may lead to accusations of opioid abuse or diversion. Opiate immunoassays typically are developed to detect morphine and are most sensitive to morphine and codeine. Although many opiate immunoassays also detect hydrocodone (HC) and/or hydromorphone (HM), sensitivities for these analytes are often much lower, increasing the possibility of negative screening results when the drug is present in the urine. We selected 112 urine specimens from patients who had been prescribed HC or hydromorphone but were presumptive negative by the Roche Online DAT Opiate II™ urine drug screening assay, which is calibrated to 300 ng/mL morphine. Using a GC/MS confirmatory method with a detection limit of 50 ng/mL both for HC and for HM, one or both of these opiates were detected in 81 (72.3%) of the urine specimens. Examination of the raw data from these presumptive negative opiate screens revealed that, in many cases, the turbidity signal was greater than the signal obtained for the negative control, but less than the signal for the 300 ng/mL (morphine) threshold calibrator. A receiver operating characteristic curve generated for the reciprocal of the ratio of turbidity measurements in the patient specimens and negative (drug-free) controls, against the presence or absence of HC and/or HM by confirmatory analyses, produced an area under the curve of 0.910. We conclude that this opiate immunoassay has sufficient sensitivity to detect HC and/or HM in some urine specimens that screen presumptive negative for these commonly prescribed

  5. Therapeutic monitoring of opioids: a sensitive LC-MS/MS method for quantitation of several opioids including hydrocodone and its metabolites.

    Science.gov (United States)

    Langman, Loralie J; Korman, Eric; Stauble, M Elaine; Boswell, Mark V; Baumgartner, Richard N; Jortani, Saeed A

    2013-06-01

    For pain management, opioid therapy is a mainstay for treating acute pain and relieving moderate to severe chronic pain. Quantitative measurement of opioids and their metabolites in urine is used mainly for confirmation of screened results obtained for clinical and forensic purposes. Due to limitations in interpretation of urine results for pain management testing purposes, the use of blood or serum to assess opioids and their metabolites may be of benefit. This report describes a sensitive liquid chromatography-tandem mass spectrometry method for the detection of hydrocodone and its metabolites hydromorphone, norhydrocodone, and dihydrocodeine, and other common opiates that patients may be taking, including morphine, codeine, oxycodone, and oxymorphone in a single extraction. The method uses solid-phase extraction of 500 µL of sample with quantitation by liquid chromatography-tandem mass spectrometry. The assay is linear from 1.0 to 100 ng/mL and has a between-day coefficient of variation of <10%. The major advantage of this method is that a single extraction can detect hydrocodone and its metabolites and other opiates or opioids that patients frequently use simultaneously with hydrocodone.

  6. Hydrocodone Combination Products

    Science.gov (United States)

    Codiclear DH® (as a combination product containing Guaifenesin, Hydrocodone) ... EndaCof XP® (as a combination product containing Guaifenesin, Hydrocodone) ... Entuss® (as a combination product containing Guaifenesin, Hydrocodone)

  7. Pharmacokinetics of hydrocodone and tramadol administered for control of postoperative pain in dogs following tibial plateau leveling osteotomy.

    Science.gov (United States)

    Benitez, Marian E; Roush, James K; KuKanich, Butch; McMurphy, Rose

    2015-09-01

    To evaluate the pharmacokinetics of hydrocodone (delivered in combination with acetaminophen) and tramadol in dogs undergoing tibial plateau leveling osteotomy (TPLO). 50 client-owned dogs. Dogs were randomly assigned to receive tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h; tramadol group) or hydrocodone bitartrate-acetaminophen (0.5 to 0.6 mg of hydrocodone/kg, PO, q 8 h; hydrocodone group) following TPLO with standard anesthetic and surgical protocols. Blood samples were collected for pharmacokinetic analysis of study drugs and their metabolites over an 8-hour period beginning after the second dose of the study medication. The terminal half-life, maximum serum concentration, and time to maximum serum concentration for tramadol following naïve pooled modeling were 1.56 hours, 155.6 ng/mL, and 3.90 hours, respectively. Serum concentrations of the tramadol metabolite O-desmethyltramadol (M1) were low. For hydrocodone, maximum serum concentration determined by naïve pooled modeling was 7.90 ng/mL, and time to maximum serum concentration was 3.47 hours. The terminal half-life for hydrocodone was 15.85 hours, but was likely influenced by delayed drug absorption in some dogs and may not have been a robust estimate. Serum concentrations of hydromorphone were low. The pharmacokinetics of tramadol and metabolites were similar to those in previous studies. Serum tramadol concentrations varied widely, and concentrations of the active M1 metabolite were low. Metabolism of hydrocodone to hydromorphone in dogs was poor. Further study is warranted to assess variables that affect metabolism and efficacy of these drugs in dogs.

  8. The role of OROS hydromorphone in the management of cancer pain.

    Science.gov (United States)

    Gardner-Nix, Jackie; Mercadante, Sebastiano

    2010-01-01

    The vast majority of cancer patients experience pain, and treatment with opioids offers the most effective option for pain management. Long-lasting opioid formulations are usually used as cancer pain management strategies. This review surveys the available literature on the only available once-daily sustained-release formulation of hydromorphone, and its use in cancer pain management. Sustained-release (SR) formulations have a more consistent opioid plasma concentration, thereby minimizing the peaks and troughs associated with immediate-release opioid formulations. OROS hydromorphone (Jurnista, Janssen Pharmaceuticals, NV, Beerse, Belgium) releases hydromorphone over a 24-hour dosing period. Studies comparing its efficacy with other opioids such as morphine and oxycodone found comparable results overall. Recent trials have provided evidence of decreased rescue medication use for breakthrough pain, a good safety profile, and quality of life benefits. It appears to be an efficacious and well-tolerated treatment. The pharmacokinetics of OROS hydromorphone are linear and dose-proportional, and only minimally affected by the presence or absence of food. In addition, the SR properties of OROS hydromorphone are maintained in the presence of alcohol, with no dose dumping of hydromorphone. This formulation shows promise as an addition to cancer pain management strategies, although further randomized, double-blind trials are needed to confirm this.

  9. Hydrocodone

    Science.gov (United States)

    ... works by changing the way the brain and nervous system respond to pain.This monograph only includes information ... Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as ...

  10. Two orthorhombic polymorphs of hydromorphone

    Directory of Open Access Journals (Sweden)

    Jaroslaw Mazurek

    2016-05-01

    Full Text Available Conditions to obtain two polymorphic forms by crystallization from solution were determined for the analgesic drug hydromorphone [C17H19NO3; systematic name: (4R,4aR,7aR,12bS-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one]. These two crystalline forms, designated as I and II, belong to the P212121 orthorhombic space group. In both polymorphs, the hydromorphone molecules adopt very similar conformations with some small differences observed only in the N-methyl amine part of the molecule. The crystal structures of both polymorphs feature chains of molecules connected by hydrogen bonds; however, in form I this interaction occurs between the hydroxyl group and the tertiary amine N atom whereas in form II the hydroxyl group acts as a donor of a hydrogen bond to the O atom from the cyclic ether part.

  11. Hydromorphone

    Science.gov (United States)

    ... any of the following symptoms: irritability, hyperactivity, abnormal sleep, high-pitched cry, uncontrollable shaking of a part ... palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), ...

  12. Pharmacokinetics of hydrocodone tartrate tablets in human%酒石酸氢可酮片的人体药代动力学研究

    Institute of Scientific and Technical Information of China (English)

    郝光涛; 刘泽源; 张宏; 曲恒燕; 张丽娟; 李媛媛; 高洪志; 董瑞华; 王晓芳; 梁宇光; 张媛媛

    2015-01-01

    目的:研究酒石酸氢可酮片的人体药代动力学。方法:本研究采用单次给药、平行设计试验方法,按照给药剂量5、10、15 mg(低、中、高)分为三组,每组10人。通过高效液相色谱串联质谱(HPLC-MS/MS)法测定血浆中氢可酮及其两种代谢产物(去甲基氢可酮和氢吗啡酮)的浓度。采用WinNonlin 6.1分析软件计算药代动力学参数。结果:氢可酮、去甲基氢可酮的线性范围均为0.05~50.00μg·L-1,氢吗啡酮的线性范围为0.01~10.00μg·L-1;受试者口服酒石酸氢可酮片后体内氢可酮、去甲基氢可酮的Cmax、AUC0-t和AUC0-∞随剂量增加而增加与给药剂量呈良好线性关系。研究过程中无严重不良事件发生。结论:HPLC-MS/MS测定法灵敏、准确、简便,适用于血浆中氢可酮及其代谢产物浓度的测定以及人体药代动力学研究。%Objective:To study the pharmacokinetics of hydrocodone tartrate tablets in human. Methods:We carried out single dose, parallel design study. Subjects were divided into three groups according to the dose of 5 mg, 10 mg, 15 mg (low, medium, high), and each group contained ten subjects. HPLC-MS/MS method was used for analysis of hydrocodone and its two metabolites (demethylation of hydrocodone and hydromorphone). WinNonlin 6.1 software was used to calculate the pharmacokinetic parameters. Results:Linearity was established in the range of 0.05–50.00μg·L-1 for hydrocodone and demethylation of hydrocodone, and 0.01–10.00μg·L-1 for hydromorphone. After the oral dose of hydrocodone tartrate tablets, Cmax, AUC0-t and AUC0-∞increased with the dose and showed a good linear relationship. There were no serious adverse events during the course of this study. Conclusion:HPLC-MS/MS is a sensitive and accurate method, which is suitable for the analysis of hydrocodone and its two metabolites (demethylation of hydrocodone and hydromorphone) in plasma and the

  13. Morphine: oxycodone interventions in Denmark

    DEFF Research Database (Denmark)

    Munk Mikkelsen, Camilla; Andersen, Stig Ejdrup

    2012-01-01

    In the years of the late 2000s, the use of oxycodone in both primary care and hospital care increased significantly in Denmark while the use of morphine decreased. Although oxycodone and morphine are considered equally effective and safe, oxycodone is much more expensive than morphine. Therefore...... in hospital care. On this basis, it is economically very important that drug use in both sectors …...

  14. First degree burn injury in healthy volunteers who 6-8 weeks prior have had done a Inguinal herniotomy . | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available adon, buprenorphine, codeine, tramadol, ketobemidone, oxycodone, hydromorphone, dextromethorphan...n, buprenorphin, codein, tramadol, ketobemidon, oxycodon, hydromorphon, dextromethorphan

  15. Quantitative Method for Analysis of Hydrocodone, Hydromorphone and Norhydrocodone in Human Plasma by Liquid Chromatography-tandem Mass Spectrometry

    Science.gov (United States)

    2013-03-01

    31 (1) (2007) 1. [14] R. Zhang, et al., Artif . Cells Blood Substit. Immobil. Biotechnol. 37 (5) (2009) 203. [15] J.D. Ropero-Miller, M.K. Lambing...or hydro- morphone in blood or plasma have been reported [5,10–17]; however, detection or quantitation of the nor-metabolite was not accomplished. In

  16. Extended-release hydrocodone – gift or curse?

    Directory of Open Access Journals (Sweden)

    Krashin D

    2013-01-01

    Full Text Available Daniel Krashin,1 Natalia Murinova,2 Andrea M Trescot31Department of Anesthesiology and Pain Medicine, 2Department of Neurology University of Washington, Seattle, WA, USA 3Algone Pain Center, Wasilla, AK, USAAbstract: Hydrocodone is a semisynthetic opioid, which has been used for decades as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen. Several long-acting, non-acetaminophen-containing hydrocodone formulations are undergoing trials in the US under the auspices of the US Food and Drug Administration, and may be available shortly. This article reviews some of the advantages (including drug familiarity and lack of acetaminophen toxicity and potential disadvantages (including altered use patterns and high morphine equivalent dosing of such a medication formulation. We also discuss the abuse potential of long-acting versus short-acting opioids in general and hydrocodone specifically, as well as the metabolism of hydrocodone.Keywords: hydrocodone, long-acting opioids, opioid abuse, acetaminophen toxicity, tamper-resistant opioids

  17. Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Farr SJ

    2015-01-01

    %, 20%, and 40% alcohol, respectively. Conclusion: HC-ER can be administered without regard to meals. While there was no evidence of "dose-dumping" (an unintended, rapid release in a short time period of all or most of the hydrocodone from HC-ER, even with 40% alcohol, as with all opioids, alcohol should not be ingested while using HC-ER. Keywords: opioid, food interaction, alcohol interaction, bioavailability, norhydrocodone, hydromorphone

  18. Effects of an oxycodone conjugate vaccine on oxycodone self-administration and oxycodone-induced brain gene expression in rats.

    Directory of Open Access Journals (Sweden)

    Marco Pravetoni

    Full Text Available Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY conjugated to the carrier protein keyhole limpet hemocyanin (OXY-KLH has been shown to attenuate the antinociceptive effects of oxycodone. Here, the vaccine's ability to prevent acquisition of intravenous (i.v. oxycodone self-administration was studied in rats. Effects of vaccination on oxycodone-induced changes in the expression of several genes within the mesolimbic system, which are regulated by chronic opiate use, were also examined. Vaccination with OXY-KLH reduced the proportion of rats acquiring i.v. self-administration of oxycodone under a fixed ratio (FR 3 schedule of reinforcement compared to control rats immunized with the unconjugated KLH carrier protein. Vaccination significantly reduced the mean number of infusions at FR3, total number of infusions, and total oxycodone intake during the entire protocol. Compared to oxycodone self-administering control rats immunized with the carrier alone, rats vaccinated with the OXY-KLH immunogen showed increased levels of adenylate cyclase 5 (Adcy5 and decreased levels of early growth response protein 2 (Egr2 and the early immediate gene c-Fos in the striatum. These data suggest that vaccination with OXY-KLH can attenuate the reinforcing effects of oxycodone at a clinically-relevant exposure level. Analysis of mRNA expression identified some addiction-relevant markers that may be of interest in understanding oxycodone effects or the protection provided by vaccination.

  19. [Controlled release hydromorphone for visceral, somatic and neuropathic pain].

    Science.gov (United States)

    Alon, E; Cachin, C

    2010-03-03

    The aim of this multicentre, longitudinal investigation was to document the efficacy and tolerability profiles of controlled release hydromorphone in patients with heavy visceral, somatic or neuropathic pain under practical conditions. To this end, a prospective observational study was conducted in 57 centres in Switzerland, on a total of 196 patients. After an average of 43 days of treatment with controlled release hydromorphone, the intensity of momentary pain dropped by 46.5% and that of maximum pain dropped by 41.3%, with the efficacy of the treatment being most pronounced with visceral and somatic pain. At the same time, the prevalence of sleep disorders as a result of pain decreased from initially 86.7% to 21.0%. Controlled release hydromorphone was excellently tolerated in this group of elderly (average age 70.6 years), multimorbid pain patients receiving various medical treatments (average of 2.4 drugs in addition to pain medication), even in the voluntary long-term extension study of up to 96 days. No medical interactions were reported. Six and thirteen weeks after introducing the treatment, 89.8% and 85.2%, respectively, were still taking controlled release hydromorphone. Controlled release hydromorphone is a recommendable option for practical treatment of heavy and extremely heavy pain of various genesis.

  20. LC-MS-MS Method for Analysis of Opiates in Wastewater During Football Games II.

    Science.gov (United States)

    Gul, Waseem; Stamper, Brandon; Godfrey, Murrell; Gul, Shahbaz W; ElSohly, Mahmoud A

    2016-06-01

    Continuing our previous studies analyzing drugs of abuse in municipal wastewater, a method was developed for the analysis of opiates in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Eight opiate drugs and metabolites were analyzed including codeine, hydrocodone, hydromorphone, 6-monoacetylmorphine (6-MAM, the primary urinary metabolite of heroin), morphine, norhydrocodone (the primary urinary metabolite of hydrocodone), oxycodone and oxymorphone. These drugs were chosen because of their widespread abuse. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. These wastewater samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain codeine, hydrocodone, hydromorphone, morphine, norhydrocodone, oxycodone and oxymorphone. None of the samples contained 6-MAM.

  1. Opioid Treatment Patterns Following Prescription of Immediate-Release Hydrocodone.

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    Ben-Joseph, Rami; Bell, Jill A; Brixner, Diana; Kansal, Anuraag; Paramore, Clark; Chitnis, Abhishek; Holly, Pamela; S Burgoyne, Douglas

    2016-04-01

    Immediate-release (IR) hydrocodone is the most widely prescribed opioid in the United States; however, little is known about the utilization patterns and duration of opioid use among patients prescribed IR hydrocodone. A better understanding of the use of IR hydrocodone would result in more appropriate prescribing patterns of extended-release opioids. To assess downstream length of opioid therapy and utilization patterns of extended-release/long-acting (ER/LA) opioids among patients on IR hydrocodone to provide a better understanding of how IR and ER/LA opioids are used to manage pain. Retrospective analysis using health care claims from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline period (July 2011-December 2011) and with continuous enrollment for a 12-month follow-up period (2012) post-index date (January 1, 2012) were selected. Downstream length of therapy, defined as number of days supplied with opioids, and downstream use of ER/LA opioids during follow-up were examined by average pills per month (≤ 60 vs. > 60 pills per month) and days supply ( 60 pills per month than with ≤ 60 pills per month (7.8% vs. 1.2%, respectively, P 60 pills per month than with ≤ 60 pills per month. All results were consistent when examined by levels of days supply. A majority of the population prescribed IR hydrocodone was not prescribed opioid therapy beyond 2 months on average in the 1-year follow-up period. Only a small subset of patients with increased pills per month or days supply of IR hydrocodone in the baseline period continued to be high utilizers in the following year, averaging nearly 8 months of prescribed opioid use. A limited proportion of patients prescribed IR hydrocodone converted to ER/LA opioids. This knowledge can assist policymakers and physicians, providing an opportunity to identify small subsets of patients to improve ER/LA opioid prescribing

  2. Oxycodone combinations for pain relief.

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    Raffa, R B; Pergolizzi, J V; Segarnick, D J; Tallarida, R J

    2010-06-01

    No single analgesic drug provides the perfect therapeutic/adverse effect profile for every pain condition. In addition to convenience and possibly improved compliance, a combination of analgesic drugs offers the potential, requiring verification, of providing greater pain relief and/or reduced adverse effects than the constituent drugs when used individually. We review here analgesic combinations containing oxycodone. We found surprisingly little preclinical information about the analgesic or adverse effect profiles of the combinations (with acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, morphine, gabapentin or pregabalin). Clinical experience and studies suggest that the combinations are safe and effective and may offer certain advantages. As with all combinations, the profile of adverse effects must also be determined in order to provide the clinician with the overall benefit/risk assessment.

  3. Oxycodone

    Science.gov (United States)

    ... any of the following symptoms: irritability, hyperactivity, abnormal sleep, high-pitched cry, uncontrollable shaking of a part ... palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), ...

  4. 75 FR 61503 - Determination That AZDONE (Hydrocodone Bitartrate and Aspirin) Tablet, 5 Milligrams/500...

    Science.gov (United States)

    2010-10-05

    ...The Food and Drug Administration (FDA) has determined that AZDONE (hydrocodone bitartrate and aspirin) Tablet, 5 milligrams (mg)/ 500 mg, was not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for hydrocodone bitartrate and aspirin tablet, 5 mg/500 mg, if all other legal and regulatory requirements are met.

  5. Implications of Sensorineural Hearing Loss With Hydrocodone/Acetaminophen Abuse.

    Science.gov (United States)

    Novac, Andrei; Iosif, Anamaria M; Groysman, Regina; Bota, Robert G

    2015-01-01

    Sensorineural hearing loss is an infrequently recognized side effect of pain medication abuse. Chronic pain patients treated with opiates develop different degrees of tolerance to pain medications. In many cases, the tolerance becomes the gateway to a variety of cycles of overuse and unmasking of significant psychiatric morbidity and mortality. An individualized approach utilizing combined treatment modalities (including nonopiate pharmaceuticals) is expected to become the norm. Patients can now be provided with multidisciplinary care that addresses an individual's psychiatric, social, and medical needs, which requires close cooperation between physicians of varying specialties. This report describes a patient who experienced hearing loss from hydrocodone/acetaminophen abuse.

  6. Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350.

    Science.gov (United States)

    Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie; Liao, Donghua; Gregersen, Hans; Krogh, Klaus; Drewes, Asbjørn Mohr

    2017-10-06

    Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

  7. Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users

    Science.gov (United States)

    Darwish, Mona; Ma, Yuju; Tracewell, William; Robertson, Philmore; Webster, Lynn R.

    2017-01-01

    Objective. To compare the oral abuse potential of hydrocodone extended-release (ER) tablet developed with CIMA® Abuse-Deterrence Technology with that of hydrocodone immediate release (IR). Design. Randomized, double-blind, placebo-controlled, crossover study. Setting and Patients. One study site in the United States; adult nondependent, recreational opioid users. Methods. After confirming their ability to tolerate and discriminate hydrocodone IR 45 mg from placebo, eligible participants were randomized to receive each of the following oral treatments once: finely crushed placebo, hydrocodone IR 45-mg powder, intact hydrocodone ER 45-mg tablet, and finely crushed hydrocodone ER 45-mg tablet. Primary pharmacodynamic measure was “at the moment” drug liking. Secondary measures included overall drug liking, drug effects (e.g., balance, positive, negative, sedative), pupillometry, pharmacokinetics, and safety. Results. Mean maximum effect (Emax) for “at the moment” drug liking was significantly lower for intact (53.9) and finely crushed hydrocodone ER (66.9) vs. hydrocodone IR (85.2; P < 0.001). Drug liking for intact hydrocodone ER was comparable to placebo (Emax: 53.9 vs. 53.2). Secondary measures were consistent with these results, indicating that positive, negative, and sedative drug effects were diminished with intact and crushed hydrocodone ER tablet vs. hydrocodone IR. The 72-hour plasma concentration-time profile for each treatment mimicked its respective “at the moment” drug-liking-over-time profile. Incidence of adverse events was lower with intact hydrocodone ER (53%) vs. hydrocodone IR (79%) and finely crushed hydrocodone ER (73%). Conclusions. The oral abuse potential of hydrocodone ER (intact and finely crushed) was significantly lower than hydrocodone IR in healthy, nondependent, recreational opioid users. Hydrocodone ER was generally well tolerated. PMID:27330154

  8. Degradation of Opioids and Opiates During Acid Hydrolysis Leads to Reduced Recovery Compared to Enzymatic Hydrolysis.

    Science.gov (United States)

    Sitasuwan, Pongkwan; Melendez, Cathleen; Marinova, Margarita; Mastrianni, Kaylee R; Darragh, Alicia; Ryan, Emily; Lee, L Andrew

    2016-10-01

    Drug monitoring laboratories utilize a hydrolysis process to liberate the opiates from their glucuronide conjugates to facilitate their detection by tandem mass spectrometry (MS). Both acid and enzyme hydrolysis have been reported as viable methods, with the former as a more effective process for recovering codeine-6-glucuronide and morphine-6-glucuronide. Here, we report concerns with acid-catalyzed hydrolysis of opioids, including a significant loss of analytes and conversions of oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine to morphine. The acid-catalyzed reaction was monitored in neat water and patient urine samples by liquid chromatography-time-of-flight and tandem MS. These side reactions with acid hydrolysis may limit accurate quantitation due to loss of analytes, possibly lead to false positives, and poorly correlate with pharmacogenetic profiles, as cytochrome P450 enzyme (CYP2D6) is often involved with oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine to morphine conversions. Enzymatic hydrolysis process using the purified, genetically engineered β-glucuronidase (IMCSzyme(®)) addresses many of these concerns and demonstrates accurate quantitation and high recoveries for oxycodone, hydrocodone, oxymorphone and hydromorphone.

  9. Observations on the metabolism of morphine to hydromorphone in pain patients.

    Science.gov (United States)

    Hughes, Michelle M; Atayee, Rabia S; Best, Brookie M; Pesce, Amadeo J

    2012-05-01

    Morphine is one of several opioids used to treat chronic pain. Because of its high abuse potential, urine drug tests can confirm "consistency with prescribed medications." Hydromorphone is a recently described minor metabolite of morphine, but few data exist on the characteristics of this metabolic pathway or the relationship of morphine and hydromorphone between and within subjects. Part I of this retrospective study shows that formation of hydromorphone from morphine is concentration-dependent and possibly saturated at high concentrations of morphine. In addition, the percentage of ultra-rapid metabolizers and poor metabolizers can be determined using the lower asymptote of a sigmoidal mathematical fit and are estimated to be 0.63 and 4.0%, respectively. Expected limits of morphine and hydromorphone (as a result of morphine metabolism) concentrations in the urine were established. Part II of this study used the metabolic ratio (hydromorphone-morphine) to determine the inter-patient and intra-patient variability in morphine metabolism to hydromorphone. Metabolic ratio values varied over a large range; 25-fold and 7-fold, respectively. The expected limits established in this study can assist in assessing the cause for possible variances in metabolism, such as drug interactions. The wide variability between and within subjects may explain unpredictable, adverse effects.

  10. Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy.

    Science.gov (United States)

    Davis, Mellar P; Varga, James; Dickerson, Duke; Walsh, Declan; LeGrand, Susan B; Lagman, Ruth

    2003-02-01

    Oxycodone has become one of the most popular opioids in the United States. It is superior to morphine in oral absorption and bioavailability, and similar in terms of protein binding and lipophilicity. Gender more than age influences oxycodone elimination. Unlike morphine, oxycodone is metabolized by the cytochrome isoenzyme CYP2D6, which is severely impaired by liver dysfunction. Controlled-release (CR) oxycodone has become one of the most frequently utilized sustained-release opioids in the United States. Both its analgesic benefits and its side effects are similar to those of CR morphine. CR oxycodone is similar to morphine and other opioids in its abuse potential. Deaths attributable to oxycodone are usually associated with polysubstance abuse in which oxycodone is combined with psychostimulants, other opioids, benzodiazepines or alcohol. Oxycodone's kappa receptor binding has little role in abuse or addiction. The cost of CR oxycodone is prohibitive for most American hospices.

  11. Route of administration for illicit prescription opioids: a comparison of rural and urban drug users

    Directory of Open Access Journals (Sweden)

    Havens Jennifer R

    2010-10-01

    Full Text Available Abstract Background Nonmedical prescription opioid use has emerged as a major public health concern in recent years, particularly in rural Appalachia. Little is known about the routes of administration (ROA involved in nonmedical prescription opioid use among rural and urban drug users. The purpose of this study was to describe rural-urban differences in ROA for nonmedical prescription opioid use. Methods A purposive sample of 212 prescription drug users was recruited from a rural Appalachian county (n = 101 and a major metropolitan area (n = 111 in Kentucky. Consenting participants were given an interviewer-administered questionnaire examining sociodemographics, psychiatric disorders, and self-reported nonmedical use and ROA (swallowing, snorting, injecting for the following prescription drugs: buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, OxyContin® and other oxycodone. Results Among urban participants, swallowing was the most common ROA, contrasting sharply with substance-specific variation in ROA among rural participants. Among rural participants, snorting was the most frequent ROA for hydrocodone, methadone, OxyContin®, and oxycodone, while injection was most common for hydromorphone and morphine. In age-, gender-, and race-adjusted analyses, rural participants had significantly higher odds of snorting hydrocodone, OxyContin®, and oxycodone than urban participants. Urban participants had significantly higher odds of swallowing hydrocodone and oxycodone than did rural participants. Notably, among rural participants, 67% of hydromorphone users and 63% of morphine users had injected the drugs. Conclusions Alternative ROA are common among rural drug users. This finding has implications for rural substance abuse treatment and harm reduction, in which interventions should incorporate methods to prevent and reduce route-specific health complications of drug use.

  12. Clinical efficacy of hydrocodone-acetaminophen and tramadol for control of postoperative pain in dogs following tibial plateau leveling osteotomy.

    Science.gov (United States)

    Benitez, Marian E; Roush, James K; McMurphy, Rose; KuKanich, Butch; Legallet, Claire

    2015-09-01

    To evaluate clinical efficacy of hydrocodone-acetaminophen and tramadol for treatment of postoperative pain in dogs undergoing tibial plateau leveling osteotomy (TPLO). ANIMALS 50 client-owned dogs. Standardized anesthetic and surgical protocols were followed. Each patient was randomly assigned to receive either tramadol hydrochloride (5 to 7 mg/kg, PO, q 8 h; tramadol group) or hydrocodone bitartrate-acetaminophen (0.5 to 0.6 mg of hydrocodone/kg, PO, q 8 h; hydrocodone group) for analgesia after surgery. The modified Glasgow composite measure pain scale was used to assess signs of postoperative pain at predetermined intervals by an investigator who was blinded to treatment group. Scoring commenced with the second dose of the assigned study analgesic. Pain scores and rates of treatment failure (ie, dogs requiring rescue analgesia according to a predetermined protocol) were compared statistically between groups. 12 of 42 (29%; 5/19 in the hydrocodone-acetaminophen group and 7/23 in the tramadol group) dogs required rescue analgesic treatment on the basis of pain scores. Median pain score for the hydrocodone group was significantly lower than that of the tramadol group 2 hours after the second dose of study analgesic. The 2 groups had similar pain scores at all other time points. Overall, differences in pain scores between dogs that received hydrocodone-acetaminophen or tramadol were minor. The percentage of dogs with treatment failure in both groups was considered unacceptable.

  13. Change in prescription habits after federal rescheduling of hydrocodone combination products.

    Science.gov (United States)

    Seago, Susan; Hayek, Adam; Pruszynski, Jessica; Newman, Megan Greene

    2016-07-01

    Nationally, health care providers wrote 259 million prescriptions for narcotic analgesics in 2012, or roughly one bottle of narcotics per US adult (1). In an effort to combat this ever-growing problem, the Drug Enforcement Administration changed the schedule of hydrocodone combination products from schedule III to schedule II on October 6, 2014. Fourteen Baylor Scott & White pharmacies encompassing a 200-mile radius in Central Texas were queried for prescription information on hydrocodone/acetaminophen, morphine, codeine/acetaminophen, and tramadol before and after the rescheduling to evaluate trends in prescription drug usage. While the rescheduling of hydrocodone combination products resulted in a reduced number of prescriptions and the total quantity dispensed of both the hydrocodone/acetaminophen 5/325 mg (Norco 5/325) and 10/325 mg (Norco 10/325) formulations, this was offset by a dramatic increase in alternative narcotic analgesics such as tramadol, codeine/acetaminophen 30/300 mg (Tylenol #3), and codeine/acetaminophen 60/300 mg (Tylenol #4), which do not have schedule II requirements. Additionally, there was no significant reduction in total pain medication prescribed after converting all agents to morphine equivalents.

  14. Morphine versus oxycodone analgesia after percutaneous kidney stone surgery

    DEFF Research Database (Denmark)

    Pedersen, Katja Venborg; Olesen, Anne Estrup; Drewes, Asbjørn Mohr

    2013-01-01

    effects (nausea, dizziness, sedation, respiratory effects and itching) were registered. The postoperative opioid consumption varied considerably between the patients but the mean opioid consumption in the morphine and oxycodone group was comparable (18.93 mg versus 16.15 mg, P = 0.7). Nausea...

  15. Metabolism of Oxycodone in Human Hepatocytes from Different Age Groups and Prediction of Hepatic Plasma Clearance

    Science.gov (United States)

    Korjamo, Timo; Tolonen, Ari; Ranta, Veli-Pekka; Turpeinen, Miia; Kokki, Hannu

    2012-01-01

    Oxycodone is commonly used to treat severe pain in adults and children. It is extensively metabolized in the liver in adults, but the maturation of metabolism is not well understood. Our aim was to study the metabolism of oxycodone in cryopreserved human hepatocytes from different age groups (3 days, 2 and 5 months, 4 years, adult pool) and predict hepatic plasma clearance of oxycodone using these data. Oxycodone (0.1, 1, and 10 μM) was incubated with hepatocytes for 4 h, and 1 μM oxycodone also with CYP3A inhibitor ketoconazole (1 μM). Oxycodone and noroxycodone concentrations were determined at several time points with liquid chromatography–mass spectrometry. In vitro clearance of oxycodone was used to predict hepatic plasma clearance, using the well-stirred model and published physiological parameters. Noroxycodone was the major metabolite in all batches and ketoconazole inhibited the metabolism markedly in most cases. A clear correlation between in vitro oxycodone clearance and CYP3A4 activity was observed. The predicted hepatic plasma clearances were typically much lower than the published median total plasma clearance from pharmacokinetic studies. The data suggests that there are no children-specific metabolites of oxycodone. Moreover, CYP3A activity seems to be the major determinant in metabolic clearance of oxycodone regardless of age group or individual variability in hepatocyte batches. PMID:22291644

  16. Effects of aprepitant on the pharmacokinetics of controlled-release oral oxycodone in cancer patients.

    Directory of Open Access Journals (Sweden)

    Yutaka Fujiwara

    Full Text Available PURPOSE: Oxycodone is a µ-opioid receptor agonist widely used in the treatment of cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a minor proportion undergoes 3-O-demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release (CR oxycodone. METHOD: This study design was an open-label, single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours. Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning. The steady-state trough concentrations (Css were measured from day 1 to day 3. RESULTS: Aprepitant increased the area under the plasma concentration-time curve (AUC0-8 of oxycodone by 25% (p<0.001 and of oxymorphone by 34% (p<0.001, as well as decreased the AUC0-8 of noroxycodone by 14% (p<0.001. Moreover, aprepitant increased Css of oxycodone by 57% (p = 0.001 and of oxymorphone by 36% (p<0.001 and decreased Css of noroxycodone by 24% (p = 0.02 at day 3 compared to day 1. CONCLUSIONS: The clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose. TRIAL REGISTRATION: UMIN.ac.jp UMIN000003580.

  17. Hidromorfona: una alternativa en el tratamiento del dolor Hydromorphone: an option in the treatment of pain

    Directory of Open Access Journals (Sweden)

    B. García

    2010-04-01

    Full Text Available Los analgésicos opioides constituyen uno de los pilares fundamentales en el tratamiento farmacológico del dolor moderado-grave, especialmente en el dolor agudo y el crónico oncológico. La molécula de hidromorfona es estructuralmente muy similar a la morfina, se puede administrar tanto por vía enteral como por vía parenteral, y se une principal-mente a los receptores opioides m y en menor grado a los receptores δ. La uniσn a receptores tipo u es la causa del efecto analgιsico, asν como de los efectos secundarios. La hidromorfona se encuentra disponible en presentaciones de liberaciσn inmediata y prolongada durante 12 o 24 horas. Recientemente, se ha comercializado en Espaρa una preparación de liberación sostenida durante 24 horas que utilizan el sistema OROS Puhs-Pull®. En el tratamiento del dolor agudo, la evidencia clínica demuestra que la hidromorfona presenta una equivalencia analgésica similar a otros opiodes. Respecto al tratamiento del dolor oncológico, se ha evaluado respecto a otros opioides y con diferentes formulaciones, y se ha observado que es un fármaco equivalente a la morfina en cuanto a eficacia analgésica y efectos secundarios. En el tratamiento del dolor crónico no oncológico, no hay ensayos clínicos controlados que otorguen evidencia científica a la hidromorfona en estos pacientes. Como conclusión, la hidromorfona presenta un perfil farmacológico, propiedades analgésicas y efectos secundarios similares a la morfina, todavía persisten ciertas controversias en lo referente a las dosis equianalgésicas entre la hidromorfona y la morfina y entre la dosis oral y la parenteral.The analgesics opioids are one of the fundamental props in the pharmacological treatment of the moderate and severe pain, particularly in chronic oncology pain. The hydromorphone molecule is structurally very similar to morphine and it may be administered enterally or parenterally. It binds mainly to m opioid receptors and to a

  18. Comparison of opioid doctor shopping for tapentadol and oxycodone: a cohort study.

    Science.gov (United States)

    Cepeda, M Soledad; Fife, Daniel; Vo, Lien; Mastrogiovanni, Gregory; Yuan, Yingli

    2013-02-01

    Obtaining opioids from multiple prescribers, known as doctor shopping, is 1 example of opioid abuse and diversion. The dual mechanism of action of tapentadol could make tapentadol less likely to be abused than other opioids. The aim of this retrospective cohort study was to compare the risk of shopping behavior between tapentadol immediate release (IR) and oxycodone IR. Subjects exposed to tapentadol or oxycodone with no recent opioid use were included and followed for 1 year. The primary outcome was the proportion of subjects who developed shopping behavior defined as subjects who had opioid prescriptions written by >1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies. The opioids involved in the shopping episodes were assessed. A total of 112,821 subjects were exposed to oxycodone and 42,940 to tapentadol. Shopping behavior was seen in .8% of the subjects in the oxycodone group and in .2% of the subjects in the tapentadol group, for an adjusted odds ratio of 3.5 (95% confidence interval, 2.8 to 4.4). In the oxycodone group, 28.0% of the shopping events involved exclusively oxycodone, whereas in the tapentadol group, .6% of the shopping events involved exclusively tapentadol. Results suggest that the risk of shopping behavior is substantially lower with tapentadol than with oxycodone. The risk of opioid doctor shopping, ie, obtaining opioid prescriptions from multiple prescribers, is lower with tapentadol than with oxycodone. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  19. Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia

    DEFF Research Database (Denmark)

    Zwisler, S T; Enggaard, T P; Mikkelsen, S

    2009-01-01

    Background: Oxycodone is a semi-synthetic opioid with a mu-receptor agonist-mediated effect in several pain conditions, including post-operative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O-demethylation via the polymorphic CYP2D6. The aim of this study was to investig......Background: Oxycodone is a semi-synthetic opioid with a mu-receptor agonist-mediated effect in several pain conditions, including post-operative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O-demethylation via the polymorphic CYP2D6. The aim of this study...... for the first time in patients that the oxymorphone formation depends on CYP2D6, but we found no difference in the post-operative analgesic effect of intravenous oxycodone between the two CYP2D6 genotypes....

  20. Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

    Science.gov (United States)

    Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

    2016-10-15

    Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid.

  1. Effects of l-tetrahydropalmatine on locomotor sensitization to oxycodone in mice

    Institute of Scientific and Technical Information of China (English)

    Yan-li LIU; Jian-hui LIANG; Ling-di YAN; Rui-bin SU; Chun-fu WU; Ze-hui GONG

    2005-01-01

    Aim: Recent studies have shown that 1-tetrahydropalmatine (l-THP), an active component of Corydolis yanhusuo, can inhibit the development of the condi tional place preference induced by opioid receptor agonists, but the effects of l-THP on locomotor sensitivity induced by opioid receptor agonists have not been documented. In the present study, the effects of l-THP on locomotor sensitization to oxycodone, which is an opioid receptor agonist, were studied. Methods: Mice treated daily for 7 d with 5 mg/kg oxycodone and challenged with the same dose after 5 days of washout showed locomotor sensitization. In order to study the effects of l-THP on locomotor sensitization induced by oxycodone,l-THP was administered at doses of 6.25, 12.5, and 18.75 mg/kg, 40 min prior to treatment of oxycodone. Results: l-THP per se did not affect the locomotor activity at the doses of 6.25, 12.5, and 18.75 mg/kg, but could antagonize the hyperactivity in duced by oxycodone (5 mg/kg). Co-administration of l-THP (18.75 mg/kg), 40 min prior to oxycodone, could inhibit the development of sensitization to oxycodone.In addition,l-THP (6.25, 12.5, and 18.75 mg/kg, ig) dose-dependently prevented the expression of oxycodone sensitization. Conclusion: These results suggested thatl-THP could attenuate the locomotor-stimulating effects of oxycodone and inhibit the development and expression of oxycodone behavioral sensitization.

  2. Assessment of Alcohol-Induced Dose Dumping with a Hydrocodone Bitartrate Extended-Release Tablet Formulated with CIMA® Abuse Deterrence Technology

    OpenAIRE

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

    2015-01-01

    Background Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA® Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol. Objective Assess effects of alcohol on hydrocodone ER pharmacokinetics. Study Design Open-label, crossover (January 25–April 30, 2010). Setting Single center. Participants...

  3. Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations

    Directory of Open Access Journals (Sweden)

    Gould HJ III

    2015-10-01

    Full Text Available Harry J Gould III,1,3–7 Dennis Paul1–8 1Department of Neurology, 2Department of Pharmacology and Experimental Therapeutics, 3Department of Internal Medicine, Section of Physical Medicine and Rehabilitation, 4Department of Anesthesiology, 5Neuroscience Center of Excellence, 6Center of Excellence for Oral and Craniofacial Biology, 7Pain Mastery Center of Louisiana, 8Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA Abstract: Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the “as-needed” use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended-release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain. Keywords: opioid analgesics, patient risks, patient benefits, misuse, addiction

  4. Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

    Directory of Open Access Journals (Sweden)

    Ho Vincent

    2008-05-01

    Full Text Available Abstract Introduction Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. Case presentation A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. Conclusion We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity.

  5. Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users

    Directory of Open Access Journals (Sweden)

    Webster LR

    2012-08-01

    Full Text Available Lynn R Webster,1 Robert L Rolleri,2,3 Glenn C Pixton,3 Kenneth W Sommerville31Lifetree Clinical Research, Salt Lake City, UT, USA; 2Salix Pharmaceuticals, Inc., Raleigh, NC, USA; 3Pfizer Inc, Cary, NC, USABackground: Abuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. This study compared the relative abuse potential of oral immediate-release oxycodone HCl-niacin with that of oral immediate-release oxycodone HCl and placebo in nondependent, recreational opioid users.Methods: Forty-nine participants received oxycodone HCl-niacin 40/240 mg and 80/480 mg, oxycodone 40 mg and 80 mg, and placebo in a randomized, double-blind, placebo-controlled and active-controlled, five-way crossover study. Primary endpoints based on a bipolar 100 mm visual analog scale for drug liking were area under effect curve (AUE0–1h, AUE0–2h, AUE0–3h, peak disliking, and effect at 0.5 hours post-dose (E0.5h. Other endpoints included take drug again assessment, overall drug liking, and pupillometry.Results: There were statistically significant differences between oxycodone HCl-niacin and oxycodone HCl doses for all primary endpoints (P < 0.0001, all comparisons, suggesting reduced abuse potential with oxycodone HCl-niacin. Take drug again and overall drug liking showed greater liking of oxycodone alone. Oxycodone HCl-niacin 80/480 mg had consistently lower liking assessments than oxycodone HCl-niacin 40/240 mg, suggesting a dose-response to the aversive effects of niacin. Opioid-related adverse events were similar for equivalent oxycodone doses. The treatment-emergent adverse events most specifically associated with oxycodone HCl-niacin (ie, skin-burning sensation, warmth, and flushing were consistent with the expected vasocutaneous effects of

  6. Profile of extended-release oxycodone/acetaminophen for acute pain.

    Science.gov (United States)

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations.

  7. Hydromorphone overdose

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2007:chap 33. Zhou YL. Principles of pain management. In: Daroff RB, Fenichel GM, Jankovic J, Mazziotta JC, eds. Bradley's Neurology in Clinical Practice . 6th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap ...

  8. Hydromorphone Rectal

    Science.gov (United States)

    ... any condition that affects your breathing such as asthma, chronic obstructive pulmonary disease (COPD; a group of diseases including chronic bronchitis and emphysema that affect the lungs and airways), or kyphoscoliosis ( ...

  9. Hydromorphone Injection

    Science.gov (United States)

    ... FDA is requiring several changes to reflect these risks in the opioid and benzodiazepine labeling, and new or revised patient Medication Guides. ... care professionalsshould limit prescribing opioid pain medicines with ... about the risks of slowed or difficult breathing and/or sedation, ...

  10. Controlled-Release Oxycodone Versus Naproxen at Home After Ambulatory Surgery: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Björn Stessel, MD

    2014-12-01

    Conclusions: Paracetamol/CR oxycodone and paracetamol/naproxen are equally effective in treatment of acute postoperative pain at home after ambulatory surgery with comparable patient satisfaction level. We suggest paracetamol/CR oxycodone to be a valuable alternative for the current paracetamol/naproxen gold standard, particularly in patients with a contraindication for nonsteroidal anti-inflammatory drugs. ClinicalTrials.gov identifier: NCT02152592.

  11. Oxycodone/acetaminophen at low dosage: an alternative pain treatment for patients with rheumatoid arthritis.

    Science.gov (United States)

    Raffaeli, William; Pari, Claudia; Corvetta, Angelo; Sarti, Donatella; Di Sabatino, Valentina; Biasi, Giovanni; Galeazzi, Maurizio

    2010-01-01

    To assess efficacy and safety of the association oxycodone/acetaminophen (oxycodone/acetaminophen) for pain treatment and disability improvement in patients with rheumatoid arthritis (RA). Patients with RA (n = 29), suffering from moderate to severe pain for more than 3 months, were included in the study, except those under RA therapy with biological drugs. The treatment started with oxycodone/acetaminophen at the dosage of 5 mg/325 mg, and then the dosage was titrated until the attainment of good pain relief. Antiemetic and laxative therapy was used for the prophylaxis of known opioid-related adverse events. Patients continued their RA therapy without changing the dosages, reported reduced pain intensity and disease activity, and improvement of disability. Forty-two percent of patients had a good clinical response to oxycodone/acetaminophen treatment, according to European League against Rheumatism (EULAR) assessment criteria, and 50 percent of patients reached the American College of Rheumatology 20 percent improvement criteria (ACR20). At the end of the study, the mean (+/- SD) daily effective oxycodone/acetaminophen dose was 13.8 (+/- 6.8) mg/720.4 (+/- 291.0) mg. No serious adverse event was observed. Nausea, vomiting, and stipsis of mild-moderate intensity were the most common adverse events. Oxycodone/acetaminophen at low dosages for the treatment of chronic pain in RA patients can be a good alternative to non-steroidal antiinflammatory drugs (NSAIDs), allowing the reduction of their consumption, while keeping RA therapy stable.

  12. Acute oxycodone induces the pro-emetic pica response in rats.

    Science.gov (United States)

    Batra, Vinita R; Schrott, Lisa M

    2011-12-01

    Oxycodone, a semisynthetic opioid analgesic, is frequently prescribed for the management of pain. Side effects of nausea and emesis affect patient compliance and limit its therapeutic use. The present study established that an antinociceptive dose of oxycodone (15 mg/kg; oral) induces the pica response. We found sex differences in the temporal course of pica, with females having a longer duration. Opioid receptors mediated the pica response, as 1.0 mg/kg naloxone transiently attenuated and 2.0 mg/kg naloxone blocked pica. A κ-selective antagonist failed to block the response, suggesting mediation by μ opioid receptor. For further validation, we used the well established kaolin intake model to assess pica with the chemotherapeutic drug cisplatin as a positive control. Oxycodone and cisplatin significantly increased kaolin intake 4- to 7-fold, and the wet weight of stomach was elevated 2- to 3-fold. To examine the underlying neural circuitry, we investigated c-fos activation in the area postrema and nucleus of solitary tract (NTS). Oxycodone treatment significantly increased the number of c-fos-positive neurons in the area postrema and NTS compared with water controls. As expected, cisplatin also increased the number of c-fos-positive cells in these regions. In the area postrema, the oxycodone effect was greater than cisplatin, especially at 2 h. These results indicate that an antinociceptive dose of oxycodone is associated with the expression of pica, a pro-emetic response.

  13. [Oral osmotic hydromorphone (OROS) in patients with chronic severe pain due to osteoarthritis under daily routine conditions].

    Science.gov (United States)

    Müller-Schwefe, G H H; Blimke, B; Hesselbarth, S; Giesecke, T

    2014-04-17

    Objective of this prospective, non-interventional study was to obtain data under a therapy with oral osmotic hydromorphone (OROS) in patients with chronic severe pain due to osteoarthritis under daily routineconditions. Using the Brief Pain Inventory (BPI) patients assessed pain relief as well as the impact of pain on activities of daily living. Pain control, treatment satisfaction (by patient and investigator), physical therapy capability and the WOMAC-Index (Western Ontario and McMaster Universities Osteoarthritis) were additionally evaluated. Adverse events were continuously monitored throughout the study. 206 patients with chronic severe pain due to osteoarthritis and an initial pain intensity of 6 (NRS 0-10) received oral OROS-hydromorphone for three months. Under this treatment pain relief as well as the impact of pain on activities of daily living improved significantly. At the last examination, the patients reported a mean pain reduction of 2.5 (rest)/3.0 (movement) by day and of 2.6 (rest)/3.1 (movement) bynight (p Physical therapy capability improved in 77.9% of the patients, the WOMAC index as indicator of pain and function in osteoarthritis decreased significantly from 13.3 (baseline) to 7.5 (V6). The most frequently reported adverse events were obstipation, nausea, dizziness and fatigue. 17.5% of the patients cut the study short because of adverse events. The treatment of patients with chronic pain due to osteoarthritis with oral osmotic hydromorphone resulted in a significant reduction of all documented pain related assessments.

  14. Effect of hydromorphone hydrochloride combined with ropivacaine for orthopedic postoperative PCEA on serum pain mediators and stress response

    Institute of Scientific and Technical Information of China (English)

    Ran Chen; Yuan-Hui Liu; Yan Yan; De-Xing Luo

    2016-01-01

    Objective:To study the effect of hydromorphone hydrochloride combined with ropivacaine for orthopedic postoperative patient-controlled epidural analgesia (PCEA) on serum pain mediators and stress response.Methods: A total of 84 patients who received fracture surgery under combined spinal epidural anesthesia and required postoperative analgesia in our hospital from May 2012 to December 2015 were randomly divided into two groups, the observation group received ropivacaine combined with hydromorphone hydrochloride for postoperative PCEA, and the control group accepted ropivacaine combined with morphine hydrochloride for postoperative PCEA. PCEA, serum pain mediator levels and the degree of stress response were compared between two groups.Results: The number of additional pressing on analgesia pump and the dosage of anesthetics of observation group within 24 h after operation were significantly lower than those of control group; 1 d, 3 d and 5 d after operation, serum 5-HT, NO and PGE2 as well as Cor, GH and PRL levels of observation group were significantly lower than those of control group; 1 d, 3 d, 5 d and 7 d after operation, REE levels of observation group were significantly lower than those of control group.Conclusions:Hydromorphone hydrochloride combined with ropivacaine for orthopedic postoperative PCEA can enhance analgesic effect, reduce the dosage of anesthetics, suppress the generation of pain mediators and reduce stress response.

  15. Hydromorphone in the management of cancer-related pain: an update on routes of administration and dosage forms.

    Science.gov (United States)

    Kumar, Maansi G; Lin, Senshang

    2007-01-01

    Pain is experienced by a majority of cancer patients. As life expectancy has increased in developed and developing countries, cancer-related pain has become a major health concern. Despite the use of the three-step analgesic ladder proposed by the World Health Organization, pain still remains under treated. Morphine, the gold standard against which all other opioids has been compared is considered the first choice for management of cancer-related pain. However, recently focus has shifted to the use of hydromorphone, a semi-synthetic derivative of morphine, which is more potent, more soluble and has a comparable side-effect profile. This review focuses on the use of hydromorphone for the management of cancer-related pain emphasizing on the various routes of administration as well as dosage forms, and providing a direction for the preference of a particular route depending on the need for a rapid effect and the individual's situation. Various approaches used to modify the release of hydromorphone from the drug delivery systems with the perspective of improving patient compliance are also being discussed.

  16. Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155 compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young41Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, 2Mallinckrodt Pharmaceuticals, 3Research and Development, Mallinckrodt Pharmaceuticals, 4Department of Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USAObjective: To characterize the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP, IR HB/ibuprofen, and IR tramadol HCl/APAP.Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1 a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose on day 1, followed by two tablets every 12 hours (q12h beginning on day 3; 2 a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6, followed by one tablet every 6 hours (q6h beginning on day 3; 3 a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6, followed by one tablet q6h beginning on day 3; and 4 a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.Results: The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures

  17. Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery.

    Science.gov (United States)

    Creamer, F; Balfour, A; Nimmo, S; Foo, I; Norrie, J D; Williams, L J; Fearon, K C; Paterson, H M

    2017-01-01

    Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces). Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222). High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  18. Active surveillance of abused and misused prescription opioids using poison center data: a pilot study and descriptive comparison.

    Science.gov (United States)

    Hughes, Alice A; Bogdan, Gregory M; Dart, Richard C

    2007-01-01

    Prescription opioids are abused throughout the United States. Several monitoring programs are in existence, however, none of these systems provide up-to-date information on prescription opioid abuse. This article describes the use of poison centers as a real-time, geographically specific, surveillance system for prescription opioid abuse and compares our system with an existing prescription drug abuse monitoring program, the Drug Abuse Warning Network (DAWN). Data were collected from eight geographically dispersed poison centers for a period of twelve months. Any call involving buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone was considered a case. Any case coded as intentional exposure (abuse, intentional misuse, suicide, or intentional unknown) was regarded as misuse and abuse. Comparative data were obtained from DAWN. Poison center rates of abuse and misuse were highest for hydrocodone at 3.75 per 100,000 population, followed by oxycodone at 1.81 per 100,000 population. DAWN emergency department (ED) data illustrate a similar pattern of abuse with most mentions involving hydrocodone and oxycodone. Poison center data indicate that people aged 18 to 25 had the highest rates of abuse. DAWN reported the majority of ED mentions among 35 to 44-year-olds. Geographically, Kentucky had the uppermost rates of abuse and misuse for all opioids combined at 20.69 per 100,000 population. CONCLUSIONS. Comparing poison center data to DAWN yielded mostly comparable results, including hydrocodone as the most commonly mentioned drug. Our results suggest poison center data can be used as an indicator for prescription opioid abuse and misuse and can provide timely, geographically specific information on prescription drug abuse.

  19. Effects of different dosages of oxycodone and fentanyl on the hemodynamic changes during intubation.

    Science.gov (United States)

    Park, Ki-Bum; Ann, Junggun; Lee, Haemi

    2016-08-01

    To investigate the effectiveness of oxycodone compared with fentanyl for attenuating the hemodynamic response during endotracheal intubation. This study was conducted from June 2014 to February 2015 on healthy adults undergoing general anesthesia at the Yeungnam University Hospital, Daegu, Republic of Korea. Ninety-five patients were randomly assigned to one of 3 groups to receive the following drugs; Group F: fentanyl 2 μg/kg; Group O/70: oxycodone 140 μg/kg; Group O/100: oxycodone 200 μg/kg. Five minutes after injection of the study drug, general anesthesia was induced with propofol 1.5 mg/kg and rocuronium 0.8 mg/kg. The mean blood pressure (MBP), heart rate (HR), peripheral oxygen saturation (SpO2), and bispectral index (BIS) were compared before administration of the study drug (T1), just before endotracheal intubation (T2), one minute after endotracheal intubation (T3), and 7.5 minutes after endotracheal intubation (T4). Complications were assessed. The 2 oxycodone groups showed no significant differences in MBP, HR, SpO2, and BIS compared to Group F at the time points assessed. The incidence of complications was comparable among the groups.  Oxycodone could successfully be used to attenuate the sympathetic response during anesthetic induction. The hemodynamic profiles and incidence of complications were clinically similar among the groups, but Group O/70 tended to show a lower rate of complications of apnea.

  20. The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Enggaard, Thomas P; Noehr-Jensen, Lene;

    2009-01-01

    , extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment...

  1. General Practitioners' and Hospital Physicians' Preference for Morphine or Oxycodone as First-Time Choice for a Strong Opioid

    DEFF Research Database (Denmark)

    Poulsen, Karen K; Andersen, Stig E; Moreno, Søren I

    2013-01-01

    opioid naive. The odds ratio (OR) was calculated to investigate whether general practitioners (GPs) and hospital physicians had similar preferences for oxycodone over morphine for strong opioid-naive patients. We included 69,110 first-time prescriptions, of which 59,316 (86%) were for strong opioid......-naive patients. Opioid-naive patients received 79% of the first-time prescriptions for morphine and 91% of the prescriptions for oxycodone. Hospital physicians had a greater preference for oxycodone over morphine than GPs (OR 1.34, 95% CI 1.29-1.39). However, GPs were responsible for approximately 61% of all...... first-time prescriptions for both oxycodone and morphine for strong opioid-naive patients. In conclusion, oxycodone is to a great extent prescribed as the first-choice strong opioid, and both GPs and hospital physicians seem to contribute to this prescribing pattern of strong opioids to outpatients....

  2. Modelling the PKPD of oxycodone in experimental pain - impact of opioid receptor polymorphisms

    DEFF Research Database (Denmark)

    Olsen, Rasmus; Foster, David J R; Upton, Richard N;

    2016-01-01

    BACKGROUND: Polymorphisms in the opioid receptor genes may affect the pharmacodynamics (PD) of oxycodone and be part of the reason behind the diversity in clinical response. The aim of the analysis was to model the exposure-response profile of oxycodone for three different pain variables and search...... in healthy volunteers. Pain tolerance data from muscle pressure (n=36), visceral pressure (n=54) and skin pinch (n=34) were included. Genetic associations with 18 opioid-receptor SNPs were explored using a stepwise covariate approach. Model simulations were performed using the estimated model parameters...

  3. Optimal dose of intravenous oxycodone for attenuating hemodynamic changes after endotracheal intubation in healthy patients

    Science.gov (United States)

    Park, Yong-Hee; Lee, Seung-Hyuk; Lee, Oh Haeng; Kang, Hyun; Shin, Hwa-Yong; Baek, Chong-Wha; Jung, Yong Hun; Woo, Young Cheol

    2017-01-01

    Abstract Background: Intravenous oxycodone has been used as an adjunct to anesthetic agents. This study aimed to assess the optimal dose of intravenous oxycodone for the attenuation of the hemodynamic responses to laryngoscopy and endotracheal intubation. Methods: A prospective, randomized, double-blind study was conducted. Ninety-five patients were randomly divided into 5 groups based on the oxycodone dose: 0, 0.05, 0.1, 0.15, 0.2 mg/kg. After administering the assigned dose of intravenous oxycodone, anesthesia was induced with thiopental. Heart rate (HR) and blood pressure (BP) were measured at baseline, before intubation, and 1, 2, and 3 minutes after intubation. The percentage increase of BP was calculated as (highest BP after intubation − baseline BP)/baseline BP × 100 (%). The percentage increase of HR was calculated in same formula as above. Hypertension was defined as a 15% increase of systolic BP from baseline, and probit analysis was conducted. Results: Hemodynamic data from 86 patients were analyzed. The percentage increase of mean arterial pressure after intubation in groups 0.05, 0.1, 0.15, and 0.2 was significantly different from that in the control (P < 0.001). For HR, the percentage increase was lower than control group when oxycodone was same or more than 0.1 mg/kg (P < 0.05). Using probit analysis, the 95% effective dose (ED95) for preventing hypertension was 0.159 mg/kg (95% confidence interval [CI], 0.122–0.243). In addition, ED50 was 0.020 mg/kg (95% CI, −0.037 to 0.049). However, oxycodone was not effective for maintaining the HR in our study dosage. There were no significant differences in the incidence of hypotension during induction between groups. Conclusions: Using 0.1 mg/kg of intravenous oxycodone is sufficient to attenuate the increase of BP and HR during induction period in healthy patients. The ED95, which was 0.159 mg/kg, can be useful to adjust the dosage of IV oxycodone for maintain stable BP

  4. The effects of acupuncture point Pericardium 6 on hydromorphone-induced nausea and vomiting in healthy dogs.

    Science.gov (United States)

    Scallan, Elizabeth M; Simon, Bradley T

    2016-09-01

    To evaluate the effect of needling at acupuncture point Pericardium 6 on hydromorphone-induced nausea and vomiting. Randomized controlled clinical study. Eighty-one mixed-breed, healthy dogs aged 1.8 ± 1.6 years and weighing 14.5 ± 5.6 kg, admitted for elective ovariohysterectomy (n = 75) or castration (n = 6). Dogs were randomly assigned to one of three groups: acupuncture at Pericardium 6 (AT, n = 27); alternative acupuncture at Lung 5 (ST, n = 27), and no acupuncture (CT, n = 27). During time 0-30 minutes (baseline), occurrences of hypersalivation, vomiting and licking were recorded. At 30 minutes, subjects were administered hydromorphone (0.1 mg kg(-1) ) in combination with acepromazine (0.03 mg kg(-1) ) intramuscularly. During time 30-45 minutes (post-injection), occurrences of hypersalivation, vomiting and licking were recorded by an observer unaware of group assignment. Groups were compared using a Kruskal-Wallis test followed by a Dunn's post-test, or Fisher's exact tests when appropriate. There were no significant differences in age, weight or baseline observations among groups. Vomiting incidence post-injection was higher in the CT (20/27, 74.1%) and ST (22/27, 81.5%) groups than in the AT (10/27, 37.0%) group (p = 0.0129 and p = 0.002, respectively). The number of vomiting episodes [median (range)] after opioid administration was higher in the ST [1 (1-6)] than the AT [0 (0-2)] group (p = 0.0040). There were no differences in the median number of vomiting episodes between the ST and CT [1 (0-3)] or AT and CT groups. There were no differences in hypersalivation or licking among groups after hydromorphone-acepromazine administration. Pericardium 6 acupuncture reduced the incidence of hydromorphone-induced vomiting in healthy dogs. This cost-effective technique can improve patient well-being and comfort during the perioperative period. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia

  5. Behavioral Flexibility and Response Selection Are Impaired after Limited Exposure to Oxycodone

    Science.gov (United States)

    Seip-Cammack, Katharine M.; Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on…

  6. Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users

    OpenAIRE

    Webster LR; Rolleri RL; Pixton GC; Sommerville KW

    2012-01-01

    Lynn R Webster,1 Robert L Rolleri,2,3 Glenn C Pixton,3 Kenneth W Sommerville31Lifetree Clinical Research, Salt Lake City, UT, USA; 2Salix Pharmaceuticals, Inc., Raleigh, NC, USA; 3Pfizer Inc, Cary, NC, USABackground: Abuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. T...

  7. Controlled-Release Oxycodone and Naloxone in the Treatment of Chronic Low Back Pain: A Placebo-Controlled, Randomized Study

    Directory of Open Access Journals (Sweden)

    C Cloutier

    2013-01-01

    Full Text Available BACKGROUND: For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR oxycodone/CR naloxone.

  8. Intravenous oxycodone for pain relief in the first stage of labour--maternal pharmacokinetics and neonatal exposure.

    Science.gov (United States)

    Kokki, Merja; Franco, Maria Gonzalez; Raatikainen, Kaisa; Välitalo, Pyry; Sankilampi, Ulla; Heinonen, Seppo; Neuvonen, Pertti J; Kokki, Hannu

    2012-09-01

    Physiological changes during pregnancy may change pharmacokinetics of compounds. Oxycodone is an increasingly used opioid agonist in acute pain management but its pharmacokinetics in labouring women has not been established. We studied the maternal pharmacokinetics and neonatal exposure of intravenous oxycodone for pain relief in the first stage of labour. The study was prospective, open-labelled and with a control group. After informed consent, 15 nulliparous parturients and newborns, and newborns in a control group were studied. In the study group, oxycodone boluses of 1 mg i.v., up to a cumulative dose of 5 mg, was administered when labour pain score was 5/10 or higher. As the control group, 30 other newborns after uncomplicated deliveries with no systemic opioids were assessed for the neonatal outcome. In the study group, maternal pharmacokinetics of oxycodone was measured from plasma concentrations during labour, and neonatal exposure was assessed from umbilical plasma samples using population pharmacokinetic methods. Maternal plasma oxycodone concentration decreased with a median half-life of 2.6 hr (range, 1.8-2.8). Oxycodone concentrations in the umbilical plasma 2.7 μg/l (0.3-14.5) were similar as in maternal plasma 2.4 (0.1-14.8) μg/l at the time of birth. No severe or unexpected adverse effects were noted. To conclude, firstly, maternal elimination half-life of i.v. oxycodone was significantly shorter than that reported in non-pregnant women, and secondly, maternal plasma oxycodone at the birth correlated well with neonatal umbilical concentrations and may, thus, be used as an estimate of neonatal exposure.

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

    Science.gov (United States)

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

    2017-08-01

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

  10. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).

    Science.gov (United States)

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

    2008-01-01

    SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation--fentanyl and buprenorphine--fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2. The use of opioids in noncancer-related pain: Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3. The use of opioids in neuropathic pain: The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4. The use of opioids in elderly patients with impaired hepatic and renal function: Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that--except for buprenorphine--doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5. Opioids and respiratory depression: Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6. Opioids and immunosuppression: Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7. Safety and tolerability profile of opioids: The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.

  11. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2015-09-01

    Full Text Available Martin E Hale,1 Charles Laudadio,2 Ronghua Yang,2 Arvind Narayana,2 Richard Malamut2 1Gold Coast Research, LLC, Plantation, FL, 2Teva Branded Pharmaceutical Products R & D, Inc., Frazer, PA, USA Abstract: This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15–90 mg and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable. Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst pain intensity, supplemental opioid usage, aberrant drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148 or hydrocodone ER (n=146. Weekly API did not differ significantly between hydrocodone ER and placebo at week 12 (P=0.134; although, in post hoc analyses, the change in weekly API was significantly lower with hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, –0.20 vs 0.40; P=0.032. Significantly more patients had .33% and .50% increase in weekly API with placebo (P<0.05, and mean weekly worst pain intensity was significantly lower with hydrocodone ER at week 12 (P=0.026. Supplemental medication usage was higher with placebo (86% than hydrocodone ER (79%. Incidence of aberrant drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this hydrocodone ER formulation in managing chronic low back or

  12. Stability of Fentanyl Citrate, Hydromorphone Hydrochloride, Ketamine Hydrochloride, Midazolam, Morphine Sulfate, and Pentobarbital Sodium in Polypropylene Syringes

    OpenAIRE

    Collin Anderson; Mark MacKay

    2015-01-01

    Purpose: Determine the stability of fentanyl 10 mcg/mL in 0.9% sodium chloride, fentanyl 10 mcg/mL in 5% dextrose, fentanyl 50 mcg/mL, hydromorphone 100 mcg/mL in 0.9% sodium chloride, ketamine 10 mg/mL, midazolam 0.4 mg/mL in 5% dextrose, midazolam 5 mg/mL, morphine 1 mg/mL in 0.9% sodium chloride, morphine 1 mg/mL in 5% dextrose, and pentobarbital 50 mg/mL when stored as single drug entities at room temperature in polypropylene syringes. Methods: Four 5 mL samples of each drug and concentra...

  13. The Genetic Influences on Oxycodone Response Characteristics in Human Experimental Pain

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Sato, Hiroe; Nielsen, Lecia Møller

    2015-01-01

    PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P ...Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response...... to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral...

  14. Oxycodone and dexamethasone for pain management after tonsillectomy: a placebo-controlled EMG assessed clinical trial.

    Science.gov (United States)

    Vaiman, Michael; Krakovski, Daniel; Haitov, Zoe

    2011-10-01

    Surface electromyographic (sEMG) study of post-tonsillectomy swallow-evoked muscular reactions was performed in order to evaluate the efficacy and safety of oxycodone and dexamethasone in pain management after tonsillectomy. 90 randomly chosen operated adults were divided into three groups. Group 1 (n = 30) was treated with OxyContin (Oxycodone) injections; Group 2 (n = 30) was treated with Dexacort (Dexamethasone), and Group 3 (n = 30) was a placebo group. Pain assessment included visual analogue scale (VAS) pain score and the EMG data like the timing, electric amplitude and graphic patterns of muscular activity during deglutition. We investigated masseter, infrahyoid and submental-submandibular muscles. Records from trapezius muscle were used for control. The results were compared with previously established normative database. The patients were tested 24 h after surgery. The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients. Analgesia with oxycodone smoothed the recorded sEMG swallow peaks and increases time of deglutition. Dexamethasone normalized muscular activity in deglutition in cases with edema as detected by the EMG records. Statistically significant difference in muscle reactions was detected between the two Groups and the placebo group. Application of oxycodone significantly reduces the postoperative pain. Application of dexamethasone after tonsillectomy is advisable because of the reduction of postoperative morbidity while the reduction of the postoperative pain is secondary to the reduction of edema. SEMG might be used as an adjunctive measure of pain behavior via assessment of muscular reactions to pain and to analgesia.

  15. Oxycodone versus fentanyl for intravenous patient-controlled analgesia after laparoscopic supracervical hysterectomy

    Science.gov (United States)

    Kim, Nan Seol; Lee, Jeong Seok; Park, Su Yeon; Ryu, Aeli; Chun, Hea Rim; Chung, Ho Soon; Kang, Kyou Sik; Chung, Jin Hun; Jung, Kyung Taek; Mun, Seong Taek

    2017-01-01

    Abstract Background: Oxycodone, a semisynthetic thebaine derivative opioid, is widely used for the relief of moderate to severe pain. The aim of this study was to compare the efficacy and side effects of oxycodone and fentanyl in the management of postoperative pain by intravenous patient-controlled analgesia (IV-PCA) in patients who underwent laparoscopic supracervical hysterectomy (LSH). Methods: The 127 patients were randomized to postoperative pain treatment with either oxycodone (n = 64, group O) or fentanyl group (n = 63, group F). Patients received 7.5 mg oxycodone or 100 μg fentanyl with 30-mg ketorolac at the end of anesthesia followed by IV-PCA (potency ratio 75:1) for 48 hours postoperatively. A blinded observer assessed postoperative pain based on the numerical rating scale (NRS), infused PCA dose, patient satisfaction, sedation level, and side effects. Results: Accumulated IV-PCA consumption in group O was less (63.5 ± 23.9 mL) than in group F (85.3 ± 2.41 mL) during the first 48 hours postoperatively (P = 0.012). The NRS score of group O was significantly lower than that of group F at 4 and 8 hours postoperatively (P dizziness, and drowsiness was significantly higher in group O than in group F. Patient satisfaction was lower in group O than in group F during the 48 hours after surgery (P dizziness, and drowsiness, suggests that the doses used in this study were not equipotent. PMID:28272250

  16. Venlafaxine and oxycodone effects on human spinal and supraspinal pain processing

    DEFF Research Database (Denmark)

    Lelic, D; Fischer, I W D; Olesen, A E;

    2016-01-01

    of the foot was recorded at the tibialis anterior muscle before and after 5 days of treatment. For the supraspinal activity, 61-channel electroencephalogram evoked potentials (EPs) to the electrical stimulations were simultaneously recorded. Areas under curve (AUCs) of the EMG signals were analyzed. Latencies......-cingulate-operculum network (P modulation of spinal nociceptive transmission, which may reflect changes in balance between descending inhibition and descending facilitation. Oxycodone...

  17. Decreased diversion by doctor-shopping for a reformulated extended release oxycodone product (OxyContin).

    Science.gov (United States)

    Chilcoat, Howard D; Coplan, Paul M; Harikrishnan, Venkatesh; Alexander, Louis

    2016-08-01

    Doctor-shopping (obtaining prescriptions from multiple prescribers/pharmacies) for opioid analgesics produces a supply for diversion and abuse, and represents a major public health issue. An open cohort study assessed changes in doctor-shopping in the U.S. for a brand extended release (ER) oxycodone product (OxyContin) and comparator opioids before (July, 2009 to June, 2010) versus after (January, 2011 to June, 2013) introduction of reformulated brand ER oxycodone with abuse-deterrent properties, using IMS LRx longitudinal data covering >150 million patients and 65% of retail U.S. prescriptions. After its reformulation, the rate of doctor-shopping decreased 50% (for 2+ prescribers/3+ pharmacies) for brand ER oxycodone, but not for comparators. The largest decreases in rates occurred among young adults (73%), those paying with cash (61%) and those receiving the highest available dose (62%), with a 90% decrease when stratifying by all three characteristics. The magnitude of doctor-shopping reductions increased with increasing number of prescribers/pharmacies (e.g., 75% reduction for ≥2 prescribers/≥4 pharmacies). The rate of doctor-shopping for brand ER oxycodone decreased substantially after its reformulation, which did not occur for other prescription opioids. The largest reductions in doctor-shopping occurred with characteristics associated with higher abuse risk such as youth, cash payment and high dose, and with more specific thresholds of doctor-shopping. A higher prescriber and/or pharmacy threshold also increased the magnitude of the decrease, suggesting that it better captured the effect of the reformulation on actual doctor-shoppers. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  18. Profile of extended-release oxycodone/acetaminophen for acute pain

    Directory of Open Access Journals (Sweden)

    Bekhit MH

    2015-10-01

    Full Text Available Mary Hanna Bekhit1–51David Geffen School of Medicine, 2Ronald Reagan UCLA Medical Center, 3UCLA Ambulatory Surgery Center, 4UCLA Wasserman Eye Institute, 5UCLA Martin Luther King Community Hospital, University of California Los Angeles, Los Angeles, CA, USA Abstract: This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen, are available solely in immediate-release (IR formulations. Keywords: opioid, analgesic, xartemis, acute postsurgical pain, substance abuse, acetaminophen, extended release 

  19. Comparison of relative oxycodone consumption in surgical pleth index-guided analgesia versus conventional analgesia during sevoflurane anesthesia

    Science.gov (United States)

    Won, Young Ju; Lim, Byung Gun; Lee, So Hyun; Park, Sangwoo; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon

    2016-01-01

    Abstract Background: The surgical pleth index (SPI) is proposed for titration of analgesic drugs during general anesthesia. Several reports have investigated the effect of SPI on the consumption of opioids including remifentanil, fentanyl, and sufentanil during anesthesia, but there are no reports about oxycodone. We aimed to investigate intravenous oxycodone consumption between SPI-guided analgesia and conventional analgesia practices during sevoflurane anesthesia in patients undergoing thyroidectomy. Methods: Forty-five patients undergoing elective thyroidectomy were randomly assigned to an SPI group (SPI-guided analgesia group, n = 23) or a control group (conventional analgesia group, n = 22). Anesthesia was maintained with sevoflurane to achieve bispectral index values between 40 and 60. In the SPI group, oxycodone 1 mg was administered intravenously at SPI values over 50; in the control group, oxycodone 1 mg was administered intravenously at the occurrence of tachycardia or hypertension event. Intraoperative oxycodone consumption and extubation time were recorded. The number of hemodynamic and somatic movement events was recorded, as were postoperative pain and recovery scores. Results: Patients’ characteristics were comparable between the groups. Intraoperative oxycodone consumption in the SPI group was significantly lower than the control group (3.5 ± 2.4 vs 5.1 ± 2.4 mg; P = 0.012). Extubation time was significantly shorter in the SPI group (10.6 ± 3.5 vs 13.4 ± 4.6 min; P = 0.026). Hemodynamic and somatic movement events during anesthesia were comparable between the groups, as were numeric rating scales for pain and modified Aldrete scores at postanesthesia care unit. Conclusions: SPI-guided analgesia reduces intravenous oxycodone consumption and extubation time compared with conventional analgesia based on clinical parameters during sevoflurane anesthesia in patients undergoing thyroidectomy. PMID:27583920

  20. Pharmacokinetics of guaifenesin, pseudoephedrine and hydrocodone in a combination oral liquid formulation, administered as single and multiple doses in healthy Chinese volunteers, and comparison with data for individual compounds formulated as Antuss®.

    Science.gov (United States)

    Deng, Shuhua; Huang, Wencan; Ni, Xiaojia; Zhang, Ming; Lu, Haoyang; Wang, Zhanzhang; Hu, Jinqing; Zhu, Xiuqing; Qiu, Chang; Shang, Dewei; Zhang, Yuefeng; Xiong, Linghui; Wen, Yuguan

    2017-10-01

    1. A new oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone is effective in improving the symptoms of common cold. The pharmacokinetic properties of the individual components were evaluated in a randomized, open-label, four-period study in 12 healthy Chinese volunteers following single and multiple doses. The data were compared with data for the individual ingredients in Antuss®. 2. In the single-dose period, exposure levels (AUC and Cmax) for guaifenesin, pseudoephedrine and hydrocodone increased directly as the dose of the oral liquid formulation increased from 5 to 15 mL. Only minor amounts of guaifenesin and hydrocodone were excreted in urine (∼0.10% and 4.66%, respectively). Pseudoephedrine was mainly excreted unchanged, with 44.95% of the dose excreted in urine within 24 h. After multiple dosing, there was no obvious accumulation of any drug, as assessed by AUC. When considering Cmax, there was a trend toward accumulation of hydrocodone and pseudoephedrine. The pharmacokinetic profiles of guaifenesin and pseudoephedrine in the oral liquid formulation were similar to those in the branded preparation, Antuss®. 3. The newly developed oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone was safe and well tolerated and might provide a reliable alternative to the branded formulation for patients with common colds.

  1. Cancer cachexia raises the plasma concentration of oxymorphone through the reduction of CYP3A but not CYP2D6 in oxycodone-treated patients.

    Science.gov (United States)

    Naito, Takafumi; Tashiro, Masaki; Ishida, Takuya; Ohnishi, Kazunori; Kawakami, Junichi

    2013-08-01

    This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid-induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid-induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.

  2. A microbial biomanufacturing platform for natural and semisynthetic opioids.

    Science.gov (United States)

    Thodey, Kate; Galanie, Stephanie; Smolke, Christina D

    2014-10-01

    Opiates and related molecules are medically essential, but their production via field cultivation of opium poppy Papaver somniferum leads to supply inefficiencies and insecurity. As an alternative production strategy, we developed baker's yeast Saccharomyces cerevisiae as a microbial host for the transformation of opiates. Yeast strains engineered to express heterologous genes from P. somniferum and bacterium Pseudomonas putida M10 convert thebaine to codeine, morphine, hydromorphone, hydrocodone and oxycodone. We discovered a new biosynthetic branch to neopine and neomorphine, which diverted pathway flux from morphine and other target products. We optimized strain titer and specificity by titrating gene copy number, enhancing cosubstrate supply, applying a spatial engineering strategy and performing high-density fermentation, which resulted in total opioid titers up to 131 mg/l. This work is an important step toward total biosynthesis of valuable benzylisoquinoline alkaloid drug molecules and demonstrates the potential for developing a sustainable and secure yeast biomanufacturing platform for opioids.

  3. A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2014-11-01

    Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

  4. Effect of currently approved carriers and adjuvants on the pre-clinical efficacy of a conjugate vaccine against oxycodone in mice and rats.

    Directory of Open Access Journals (Sweden)

    Marco Pravetoni

    Full Text Available Vaccination against the highly abused prescription opioid oxycodone has shown pre-clinical efficacy for blocking oxycodone effects. The current study further evaluated a candidate vaccine composed of oxycodone derivatized at the C6 position (6OXY conjugated to the native keyhole limpet hemocyanin (nKLH carrier protein. To provide an oxycodone vaccine formulation suitable for human studies, we studied the effect of alternative carriers and adjuvants on the generation of oxycodone-specific serum antibody and B cell responses, and the effect of immunization on oxycodone distribution and oxycodone-induced antinociception in mice and rats. 6OXY conjugated to tetanus toxoid (TT or a GMP grade KLH dimer (dKLH was as effective as 6OXY conjugated to the nKLH decamer in mice and rats, while the 6OXY hapten conjugated to a TT-derived peptide was not effective in preventing oxycodone-induced antinociception in mice. Immunization with 6OXY-TT s.c. absorbed on alum adjuvant provided similar protection to 6OXY-TT administered i.p. with Freund's adjuvant in rats. The toll-like receptor 4 (TLR4 agonist monophosphoryl lipid A (MPLA adjuvant, alone or in combination with alum, offered no advantage over alum alone for generating oxycodone-specific serum antibodies or 6OXY-specific antibody secreting B cells in mice vaccinated with 6OXY-nKLH or 6OXY-TT. The immunogenicity of oxycodone vaccines may be modulated by TLR4 signaling since responses to 6OXY-nKLH in alum were decreased in TLR4-deficient mice. These data suggest that TT, nKLH and dKLH carriers provide consistent 6OXY conjugate vaccine immunogenicity across species, strains and via different routes of administration, while adjuvant formulations may need to be tailored to individual immunogens or patient populations.

  5. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate- release/extended release

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young4 1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 2Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 3Research and Development, 4Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release (IR/extended-release (ER hydrocodone bitartrate (HB/acetaminophen (APAP and IR HB/APAP. Setting: The study was conducted in a contract research center. Participants: The study included healthy adults. Interventions: In a three-way crossover study, Study 1, participants received the following treatments: (A1 a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h; (B1 a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1 a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6, followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2 an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2 three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures: PK values were compared, and adverse events were assessed. Results: Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%. Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median

  6. Cost-Effectiveness of Tramadol and Oxycodone in the Treatment of Knee Osteoarthritis.

    Science.gov (United States)

    Smith, Savannah R; Katz, Jeffrey N; Collins, Jamie E; Solomon, Daniel H; Jordan, Joanne M; Suter, Lisa G; Yelin, Edward H; David Paltiel, A; Losina, Elena

    2017-02-01

    To evaluate the cost-effectiveness of incorporating tramadol or oxycodone into knee osteoarthritis (OA) treatment. We used the Osteoarthritis Policy Model to evaluate long-term clinical and economic outcomes of knee OA patients with a mean age of 60 years with persistent pain despite conservative treatment. We evaluated 3 strategies: opioid-sparing (OS), tramadol (T), and tramadol followed by oxycodone (T+O). We obtained estimates of pain reduction and toxicity from published literature and annual costs for tramadol ($600) and oxycodone ($2,300) from Red Book Online. Based on published data, in the base case, we assumed a 10% reduction in total knee arthroplasty (TKA) effectiveness in opioid-based strategies. Outcomes included quality-adjusted life years (QALYs), lifetime cost, and incremental cost-effectiveness ratios (ICERs) and were discounted at 3% per year. In the base case, T and T+O strategies delayed TKA by 7 and 9 years, respectively, and led to reduction in TKA utilization by 4% and 10%, respectively. Both opioid-based strategies increased cost and decreased QALYs compared to the OS strategy. Tramadol's ICER was highly sensitive to its effect on TKA outcomes. Reduction in TKA effectiveness by 5% (compared to base case 10%) resulted in an ICER for the T strategy of $110,600 per QALY; with no reduction in TKA effectiveness, the ICER was $26,900 per QALY. When TKA was not considered a treatment option, the ICER for T was $39,600 per QALY. Opioids do not appear to be cost-effective in OA patients without comorbidities, principally because of their negative impact on pain relief after TKA. The influence of opioids on TKA outcomes should be a research priority. © 2016, American College of Rheumatology.

  7. Intractable restless legs syndrome: role of prolonged-release oxycodone-naloxone.

    Science.gov (United States)

    de Biase, Stefano; Valente, Mariarosaria; Gigli, Gian Luigi

    2016-01-01

    Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the legs accompanied by uncomfortable sensations that occur at night or at time of rest. Pharmacological therapy should be limited to patients who suffer from clinically relevant symptoms. Chronic RLS is usually treated with either a dopamine agonist (pramipexole, ropinirole, rotigotine) or an α2δ calcium-channel ligand (gabapentin, gabapentin enacarbil, pregabalin). Augmentation is the main complication of long-term dopaminergic treatment, and frequently requires a reduction of current dopaminergic dose or a switch to non-dopaminergic medications. Opioids as monotherapy or add-on treatment should be considered when alternative satisfactory regimens are unavailable and the severity of symptoms warrants it. In a recent Phase III trial, oxycodone-naloxone prolonged release (PR) demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled by previous treatments. The adverse-event profile was consistent with the safety profile of opioids. The most frequent adverse events were fatigue, constipation, nausea, headache, hyperhidrosis, somnolence, dry mouth, and pruritus. Adverse events were usually mild or moderate in intensity. No cases of augmentation were reported. Oxycodone-naloxone PR is approved for the second-line symptomatic treatment of adults with severe to very severe idiopathic RLS after failure of dopaminergic treatment. Further studies are needed to evaluate if oxycodone-naloxone PR is equally efficacious as a first-line treatment. Moreover, long-term comparative studies between opioids, dopaminergic drugs and α2δ ligands are needed.

  8. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    Directory of Open Access Journals (Sweden)

    Kim JY

    2015-01-01

    Full Text Available Ju-Young Kim,1,* Sung-Hoon Lee,2,3,* Chun-Woong Park,4 Yun-Seok Rhee,5 Dong-Wook Kim,6 Junsang Park,3 Moonseok Lee,3 Jeong-Woong Seo,2 Eun-Seok Park2 1College of Pharmacy, Woosuk University, Wanju-gun, Republic of Korea; 2School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 3GL Pharmtech, Seongnam, Republic of Korea; 4College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea; 6Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea *These authors contributed equally to this work Abstract: The aim of present study was to design oxycodone once-a-day controlled-release (CR tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day] or once-a-day CR tablets (20 mg were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. Keywords

  9. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2013-05-01

    Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement

  10. Trends in average days' supply of opioid medications in Medicaid and commercial insurance.

    Science.gov (United States)

    Tehrani, Ali Bonakdar; Henke, Rachel Mosher; Ali, Mir M; Mutter, Ryan; Mark, Tami L

    2017-08-19

    To calculate trends in adult average days' supply for six commonly prescribed opioids: hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol to assess whether physicians changed prescribing practices at the time of the intensifying epidemic. We used 2005-2015 Truven Health MarketScan Commercial Claims and Encounters data to measure trends in opioid average days' supply among commercially insured individuals and 2005-2014 MarketScan Multi-State Medicaid data to measure trends in opioid average days' supply among Medicaid beneficiaries. For Medicaid, we found an increase in days' supply for all drugs except morphine. The largest percentage increase was for oxycodone, which increased 4.5days (37%). Opioid days' supply for individuals with commercial insurance exhibited similar but steeper trends. The largest increase was also for oxycodone, which increased 6days (56%). Between 2013 and 2015, when the opioid epidemic had begun to be widely publicized, there was no decline in the median days supplied for any of the opioids. Our results find that days' supply of opioids are increasing despite public health campaigns and media attention on the risks of opioid prescribing. More effective interventions to curb opioid prescribing are needed to reverse these trends. Published by Elsevier Ltd.

  11. Development of Oxycodone in Clinical Treatment%羟考酮临床治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    张杜枭; 葛卫红; 于锋; 谢菡

    2014-01-01

    羟考酮(oxycodone)是由蒂巴因(thebaine)改造合成的阿片类中枢神经镇痛药。近几年,随着新的羟考酮剂型的开发,该药物在急性疼痛以及慢性疼痛的控制中均广泛使用,并且出现与少量阿片类药物拮抗剂联用镇痛的方式。本文综述羟考酮的基本药理学性质以及临床应用进展。%Oxycodone is a central nervous system opioid analgesics reformed from thebaine. In recent years, with the development of the formulation of oxycodone, it has been an effective treatment for acute pain and chronic pain. In addition, oxycodone plus opioid receptor antagonist has been developed to improve analgesia in clinical. This article reviews the basic pharmacological properties of oxycodone and its clinical treatment development.

  12. Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain.

    Science.gov (United States)

    Schliessbach, Jürg; Siegenthaler, Andreas; Bütikofer, Lukas; Vuilleumier, Pascal; Jüni, Peter; Arendt-Nielsen, Lars; Curatolo, Michele

    2017-08-09

    Quantitative sensory tests (QST) can be used for profiling anti-nociceptive effects of analgesics. However, anti-nociceptive effects detected by QST are not necessarily associated with analgesic effects in pain patients. As part of a large investigation on low back pain, this paper describes the immediate analgesic and anti-nociceptive effects of oxycodone in chronic low-back pain and ranks different QST according to their ability to reflect this effect. The results are expected to support the selection of QST for future studies on potential novel opioid agonists in human pain. In this randomized, placebo-controlled and double-blinded cross-over study, 50 patients with chronic low-back pain received a single oral dose of oxycodone 15mg or active placebo, and underwent multiple QST testing. The intensity of low-back pain was recorded during 2h. The areas under the ROC curves and 95% confidence intervals were determined, whereby responder status (≥30% pain reduction) was set as reference variable and changes in QST from baseline were set as classifiers. Significant analgesic effect on low-back pain as well as anti-nociceptive effects for almost all QST parameters were observed. The QST with the highest area under the curve were heat pain detection threshold (0.65, 95%-CI 0.46 to 0.83), single-stimulus electrical pain threshold (0.64, 95%-CI 0.47 to 0.80) and pressure pain detection threshold (0.63, 95%-CI 0.48 to 0.79). The results suggest that anti-nociceptive effects assessed by QST fairly reflect clinical efficacy of oxycodone on low-back pain. Pressure pain detection threshold, heat pain detection threshold and single-stimulus electrical pain threshold may be more suitable to sort out potential non-responders rather than identifying potential responders to opioid medication. Future pre-clinical human research may consider these results when investigating the analgesic effect of opioid agonists by means of QST. Copyright © 2017 Scandinavian Association for the

  13. Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro

    DEFF Research Database (Denmark)

    Fanoe, Søren; Jensen, Gorm Boje; Sjøgren, Per

    2008-01-01

    with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some...... patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing h...... dose was associated with a 10 ms(1/2) (95% CI 2-19) longer QTc. Neither morphine nor tramadol dose was associated with the QTc. Electrophysiological testing revealed low-affinity inhibition of the potassium current through hERG channels expressed in HEK293 cells (IC(50) = 171 microM oxycodone...

  14. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone

    Science.gov (United States)

    Dhalla, Irfan A.; Mamdani, Muhammad M.; Sivilotti, Marco L.A.; Kopp, Alex; Qureshi, Omar; Juurlink, David N.

    2009-01-01

    Introduction Opioid-related mortality appears to be increasing in Canada. We examined the true extent of the problem and the impact of the introduction of long-acting oxycodone. Methods We examined trends in the prescribing of opioid analgesics in the province of Ontario from 1991 to 2007. We reviewed all deaths related to opioid use between 1991 and 2004. We linked 3271 of these deaths to administrative data to examine the patients’ use of health care services before death. Using time-series analysis, we determined whether the addition of long-acting oxycodone to the provincial drug formulary in January 2000 was associated with an increase in opioid-related mortality. Results From 1991 to 2007, annual prescriptions for opioids increased from 458 to 591 per 1000 individuals. Opioid-related deaths doubled, from 13.7 per million in 1991 to 27.2 per million in 2004. Prescriptions of oxycodone increased by 850% between 1991 and 2007. The addition of long-acting oxycodone to the drug formulary was associated with a 5-fold increase in oxycodone-related mortality (p opioid-related mortality (p = 0.02). The manner of death was deemed unintentional by the coroner in 54.2% and undetermined in 21.9% of cases. Use of health care services in the month before death was common: for example, of the 3066 patients for whom data on physician visits were available, 66.4% had visited a physician in the month before death; of the 1095 patients for whom individual-level prescribing data were available, 56.1% had filled a prescription for an opioid in the month before death. Interpretation Opioid-related deaths in Ontario have increased markedly since 1991. A significant portion of the increase was associated with the addition of long-acting oxycodone to the provincial drug formulary. Most of the deaths were deemed unintentional. The frequency of visits to a physician and prescriptions for opioids in the month before death suggests a missed opportunity for prevention. PMID:19969578

  15. Oxicodona Oxycodone

    Directory of Open Access Journals (Sweden)

    J. Sanz

    2005-12-01

    Full Text Available En el presente trabajo se realiza una revisión y puesta al día de un nuevo analgésico opioide en forma de comprimidos de administración oral de liberación controlada. Se analiza su farmacocinética, su farmacodinamia así como sus interacciones medicamentosas. Se describe el nuevo mecanismo de liberación controlada y se comparan sus características y efectos secundarios con otros preparados opioides de administración por vía oral de liberación retardada. Finalmente se dan las pautas de utilización.The present report makes a detailed revision and up date of a new pain killer recently included in Spanish handbook. It has oral route of administration and controlled liberation. Opioid analgesic mechanism and pharmacokinetic are described. The differences with other opioids are analysed. The incidence of side effects is studied and compared with other. Finally guidelines are described for being used.

  16. A single-dose, 3-way crossover pharmacokinetic comparison between immediate-release oxycodone hydrochloride with aversion technology (IRO-A, Oxecta), IRO-a with Niacin, and Oxycodone Hydrochloride (Roxicodone) in healthy adults under fasting conditions.

    Science.gov (United States)

    Leibowitz, Mark T; Zamora, Cynthia A; Brzeczko, Albert W; Stark, Jeffrey G

    2014-01-01

    Snorting and intravenous use are common routes of administration for advanced opioid abusers. A tablet form of immediate-release oxycodone (IRO) developed using Aversion Technology combines immediate release (IR) oxycodone HCl with inactive functional excipients that are intended to discourage tampering associated with intranasal and intravenous abuse (IRO-A; Oxecta, Pfizer). The purpose of this single-dose, open-label, randomized, 3-period, 3-treatment crossover study was to evaluate the bioequivalence of IRO-A to the marketed immediate-release oxycodone HCl (IRO; Roxicodone, Xanodyne Pharmaceuticals Inc., Newport, KY). IRO-A was also compared with IRO-A with niacin, a product previously developed containing the same functional excipients plus niacin as an aversive agent to discourage oral overconsumption. Healthy adults (N = 40) aged 18-55 years received single 15-mg doses of IRO-A, IRO-A with niacin (60 mg), or IRO after fasting overnight. Naltrexone was administered to diminish opioid effects. Doses were separated by a ≥7-day washout. Plasma samples taken at designated time points were analyzed using liquid chromatography with tandem mass spectrometry. Geometric mean ratios for ln-transformed parameters for IRO-A and IRO were 92%, 104%, and 104% for Cmax, AUClast (AUC is area under the concentration-time curve), and AUCinf; 90% confidence intervals were within the accepted 80%-125% range. IRO-A was also bioequivalent to IRO-A with niacin. Adverse events were mild to moderate in intensity and typical of opioid therapy (nausea, headache, vomiting). Flushing only occurred when the subjects received the IRO-A with niacin treatment (9/37 subjects). The results demonstrated that IRO-A is bioequivalent to IRO and IRO-A with niacin. With features designed to discourage tampering associated with common forms of abuse, IRO-A may provide an alternative to conventional immediate-release oxycodone formulations.

  17. Lack of Association of OPRM1 and ABCB1 Single-Nucleotide Polymorphisms to Oxycodone Response in Postoperative Pain

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Enggaard, Thomas P; Mikkelsen, Soeren

    2011-01-01

    Purpose: The aim of the study was to search for an association between the single-nucleotide polymorphisms A118G in OPRM1 and C3435T and G2677T/A in ABCB1 and the analgesic effect of intravenous oxycodone in postoperative pain. Methods: There were 268 patients with postoperative pain after......, primarily, thyroidectomy. At given times during the first 24 hours postoperatively, their pain was rated at rest and during activity according to a numeric rating scale (0 = no pain, 10 = worst possible pain) and calculated as pain time area under the curve(0-24 hours). A negative answer in a final...... the tested single-nucleotide polymorphisms in OPRM1 and ABCB1 and changes in the analgesic effect of oxycodone....

  18. [Case of acute exacerbation of neuropathic cancer pain rapidly relieved by simultaneous oral intake of immediate release oxycodone and pregabalin].

    Science.gov (United States)

    Baba, Mika; Gomwo, Ikuo

    2012-10-01

    Cancer pain consists of continuous pain lasting almost all day and transient exacerbation of pain called breakthrough pain. Breakthrough pain is classified as somatic pain and visceral pain, neuropathic pain according to the character of pain. Although the immediate release opioid is used as the first treatment of choice to breakthrough pain, the effect is not enough when it shows the character of neuropathic pain. Pregabalin has become the first medicine for the treatment of neuropathic pain, and it sometimes reveals prompt analgesic effect based on its pharmacological profile. It has also been reported that pregabalin used with oxycodine reveals analgesic effect with smaller dosage than pregabalin alone. We experienced a young patient with lung cancer suffering from sudden exacerbation of symptomatic sciatica, whose pain was markedly reduced within 30 minutes by taking immediate release oxycodone 5 mg and pregabalin 75 mg simultaneously. Conclusions : Pregabalin with immediate release oxycodone simultaneously may be able to improve acute exacerbation of neuropathic cancer pain rapidly.

  19. Evaluation of Quality of Life, Functioning, Disability, and Work/School Productivity Following Treatment with an Extended-Release Hydrocodone Tablet Formulated with Abuse-Deterrence Technology: A 12-month Open-label Study in Patients with Chronic Pain.

    Science.gov (United States)

    Hale, Martin E; Zimmerman, Thomas R; Ma, Yuju; Malamut, Richard

    2017-02-01

    This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA(®) Abuse-Deterrence Technology platform. Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF). Of 330 enrolled patients, 291 composed the full analysis population. By week 4, ≥ 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1. Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study. © 2016 World Institute of Pain.

  20. 氨酚羟考酮依赖性及滥用风险分析%Oxycodone and Acetaminophen Dependence and Abuse Risk Analysis

    Institute of Scientific and Technical Information of China (English)

    马军丽; 逄立艳; 周立新; 张黎明

    2012-01-01

    Oxycodone hydrochloride is a derivative of morphine. The pharmacological effects of the oxycodone hy— drochloride is similar to morphine. There has been animal experiments show that oxycodone and morphine are similar in strengthening effect, and they have the same potential for psychological dependence. In the United States and Australia, oxycodone products are one of the most common drugs being diverted and abused. Although the single and compound preparations of oxycodone hydrochloride are both likely to cause abuse, In China, oxycodone acetaminophen(oxycodone hydrochloride compound) is managed in accordance with prescription drug, so it is more likely to be lossed and abused compared to the single preparation of oxycodone hydrochloride which is managed in accordance with narcotic drugs. Medical institutions and drug regulatory departments shall strengthen the management and monitoring of oxycodone acetaminophen to prevent loss and abuse.%盐酸羟考酮是盐酸吗啡的衍生物,药理作用与吗啡相似,已有动物实验表明羟考酮与吗啡的强化效应相似,具有相同的精神依赖性潜力.在美国和澳大利亚等国,羟考酮类产品是最常被遭到转移和滥用的药品之一.虽然盐酸羟考酮的单方和复方制剂都有可能引发滥用,但在我国盐酸羟考酮的复方制剂即氨酚羟考酮是按照处方药管理,相对于按照麻醉药品管理的单方制剂流失和滥用的可能性更大.医疗机构和药品监管部门应当加强对氨酚羟考酮的管理和监测,积极避免流失和滥用的发生.

  1. Discriminative stimulus effects of morphine and oxycodone in the absence and presence of acetic acid in male and female C57Bl/6 mice.

    Science.gov (United States)

    Neelakantan, Harshini; Ward, Sara Jane; Walker, Ellen Ann

    2015-08-01

    The use of prescription opioids for clinical management of pain remains problematic because of concerns about addiction associated with opioid use. Another difficulty in pain management is the increasing evidence for sex differences in pain behavior and opioid-induced behavioral effects. However, few studies have documented the abuse potential of prescription opioids as a function of pain in rodents, with significant gaps in the literature pertaining to sex differences in the interaction between pain and opioid effects. The present study evaluated the effects of an experimentally induced acute pain state (acetic acid injections) on the potency of morphine and oxycodone to produce discriminative stimulus effects in male and female C57Bl/6 mice trained to discriminate 3.2 mg/kg morphine from saline. Acetic acid injections attenuated the stimulus potency of morphine by 2.2-fold but not the stimulus potency of oxycodone in male mice. Acetic acid injections did not alter the discriminative stimulus effects of either morphine or oxycodone in female mice. The antinociceptive effects of the 2 opioids were evaluated using the acetic acid-induced stretching test. For antinociceptive effects, morphine was 2.0-fold less potent relative to oxycodone in male mice, whereas morphine and oxycodone were equipotent in female mice. Taken together, these results indicate that acetic acid-induced acute pain differentially modulates the discriminative stimulus effects of morphine in male and female mice and that this change may be related to the variable antinociceptive effectiveness of these opioids across sexes.

  2. A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR.

    Science.gov (United States)

    Dupoiron, D; Stachowiak, A; Loewenstein, O; Ellery, A; Kremers, W; Bosse, B; Hopp, M

    2017-06-22

    Oxycodone/naloxone (OXN PR) is a prolonged-release formulation containing oxycodone and naloxone in a 2:1 ratio. This study aimed to evaluate the tolerability and efficacy of doses up to OXN160/80 mg PR compared with oxycodone prolonged-release formulation (OxyPR) in a randomised controlled trial. Two hundred and forty-three patients were randomised to treatment with OXN PR (n = 123) or OxyPR (n = 120) during the 5-week double-blind study. Measured were: opioid-induced constipation [bowel function index score (BFI)]; analgesic efficacy (NRS 0-10); daily laxative rescue medication use; rescue medication use, and the number of complete spontaneous bowel movements (CSBMs) per week. A subanalysis was conducted in cancer patients. Greater reductions in mean BFI scores were reported for the OXN PR group compared with OxyPR from Week 1 onwards; at Week 5 the mean change from baseline was -32.5 versus -14.2. Average 24-h pain scores were low and remained stable in the range 3-4 in both treatment groups. Analgesic rescue medication use was similar between the groups. Patients receiving OXN PR used significantly lower mean daily doses of laxative rescue medication than those receiving OxyPR (P = 0.006). The number of CSBM in the OXN PR group approximately doubled compared with a 25% decrease in the OxyPR group. Comparable results to the total study population were reported in the cancer patient subgroup. OXN PR in daily doses of up to 160/80 mg significantly improves bowel function compared with equivalent doses of OxyPR while still providing comparable analgesic efficacy. Effective analgesia can be achieved using oxycodone/naloxone PR up to 160/80 mg daily without compromising bowel function. A similar outcome was reported in cancer and non-cancer patients. © 2017 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  3. Advancement of potent narcotic anaIgesics:combination of oxycodone%强效镇痛药羟考酮复方的研究进展

    Institute of Scientific and Technical Information of China (English)

    董国明

    2014-01-01

    阿片受体激动剂羟考酮是强效麻醉性镇痛药,其镇痛作用强,但其耐受性、依赖性及其抑制胃肠道平滑肌蠕动等不良反应限制了其临床应用。自20世纪末,研究者开始分别将解热镇痛药、阿片受体激动剂、阿片受体拮抗剂、多巴胺受体拮抗剂等药物与羟考酮以不同比例进行组方,在增强镇痛作用的同时能降低羟考酮的用量并减少其不良反应,从而达到限制其滥用的目的。本文仅就羟考酮复方的发展进行较为系统的综述,以期为进一步促进其临床应用提供依据。%Oxycodone,an opioid receptor agonist,is one of potent narcotic analgesics. Despite its potent analgesic effect,the tolerant and dependent liability of oxycodone as well as its inhibition on gas-trointestinal motility strongly restricts its clinical application. Since the end of the last century,antipyretic, opioid receptor agonist,opioid receptor antagonist and dopamine receptor antagonist have been used to in combination with oxycodone at different ratios as complex prescriptions,the aim of which is to enhance the effect of oxycodone,decrease the dosage of oxycodone,and prevent the adverse effect and the tendency for misuse. Here we reviewed the development of oxycodone compositions in the recent years,hoping to provide more data for its potential clinical application.

  4. Bioequiavailability of domestic paracetamol and hydrocodone bitartrate tablets%国产氨酚氢可酮片人体生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    郝光涛; 马蒙; 曲恒燕; 李媛媛; 刘伟丽; 张丽娟; 刘泽源

    2011-01-01

    目的:评价国产与进口氛酚氢可酮片的生物等效性.方法:采用双周期自身交叉试验设计,24名健康男性志愿者分别单剂量口服国产和进口氨酚氢可酮片1片,分别于给药前及给药后0.25、0.5、1、1.5、2、4、6、8、12、16、24 h采静脉血.采用高效液相色语-质谱-质谱联用方法分别测定血浆中对乙酸氨基酚和重酒石酸氢可酮的浓度.结果:受试制剂与参比制剂中对乙酰氨基酚的tmax分别为(0.85±0.31)和(0.90±0.33)h,Cmax分别为(8.93±2.91)和(9.59±3.24)mg·L-1,t1/2分别为(3.19±0.71)和(3.20±1.48)h; AUC0-tn分别为(25.97±5.75)和(28.00±15.24)mg·L-1·h,AUC0-∞分别为(26.47±5.72)和(28.47±5.31)mg·L-1·h,受试制剂的相对生物利用度为(93.04±12.06)%.重酒石酸氢可酮的tmax分别为((1.04±0.78)和(0.96±0.751)h;Cmax分别为(22.93±6.45)和(21.49±6.19)μg·L-1; t1/2分别为(5.43±0.99)和(5.65±1.60)h; AUC0-o-tn分别为(128.59±32.75)和(116.84±29.98)μg·L-1·h; AUC0-∞分别为(135.±士34.05)和(124.7±32.3)7μg·-1'-h;受试制剂的相对生物利用度为(112.77±26.54)%.结论:国产与进口氨酚氢可酮片具有生物等效性.%Objective: To evaluate the bioequiavailability of the domestic and the imported paracetamol and hydrocodone bitartrate tablets. Methods: The blood concentrations of paracetamol and hydrocodone bitartrate in 24 healthy male volunteers were determined by HPLC-MS-MS after a single oral dose with a randomized crossover method. Results: The main pharmacokinetic parameters of the paracetamol in the test and reference preparation were as follows: tmax were (0.85 ±0.31) and (0.90 ±0.33) h, respectively; Cmax were (8.93±2.91) and (9.59±3.24) mg·L-1, respectively; t1/2 were (3.19±0.71) and (3.20± 1.48) h, respectively; AUC1-tn were (25.97±5.75) and (28.00±5.24) mg·L-1·h, AUC0-∞ were (26.47±5.72) and (28.47±5.31) mg·L-1·h, respectively; the relative bioavailability of paracetamol in the test

  5. Effect of estrogen on morphine- and oxycodone-induced antinociception in a female femur bone cancer pain model.

    Science.gov (United States)

    Ono, Hiroko; Nakamura, Atsushi; Kanemasa, Toshiyuki; Sakaguchi, Gaku; Shinohara, Shunji

    2016-02-15

    Although estrous cycle has been reported to influence antiociceptive effect of morphine in several pain conditions, its effect on cancer pain is not well established. We investigated the effect of estrogen on morphine antinociception using a bone cancer pain model and compared its potency with that of oxycodone. Female mice were ovariectomized (OVX) for preparation of a femur bone cancer pain (FBC) model. β-estradiol was subcutaneously (s.c.) administered and antinociceptive effects of opioids was assessed using the von Frey monofilament test. Although morphine (5-20mg/kg, s.c.) did have significant antinociceptive effects in the FBC-OVX group, its effects in the FBC-OVX+β-estradiol (OVX+E) group was limited. Oxycodone (1-5mg/kg, s.c.) exhibited significant effects in both groups. Expression changes in opioid-related genes (μ-, κ-, δ-opioid receptors, prodynorphin, proenkephalin, proopiomelanocortin) in the spinal and supraspinal sites were examined among the sham-OVX, sham-OVX+E, FBC-OVX, and FBC-OVX+E groups by in situ hybridization. These studies detected a significant increase in prodynorphin in the spinal dorsal horn of the FBC-OVX+E group. Spinal injection of a dynorphin-A antibody to FBC-OVX+E mice restored antinociception of morphine. In conclusion, we detected a differential effect of estrogen on morphine- and oxycodone-induced antinociception in a female FBC model. The effect of morphine was limited with estrogen exposure, which may be due to estrogen- and pain-mediated spinal expression of dynorphin-A.

  6. Rapid analysis of urinary opiates using fast gas chromatography–mass spectrometry and hydrogen as a carrier gas

    OpenAIRE

    Sumandeep Rana; Rakesh K. Garg; Anu Singla

    2014-01-01

    A sensitive and specific fast gas chromatography–mass spectrometry (FGC–MS) analytical method using hydrogen as a carrier gas is developed for the rapid simultaneous determination of morphine, codeine, hydrocodone and hydromorphone in human urine. Urine samples were spiked with deuterated internal standards, morphine-d3, codeine-d3, hydrocodone-d3 and hydro-morphone-d3, subjected to acid hydrolysis, treated with hydroxylamine to convert the keto-opiates to oximes and then extracted using a po...

  7. The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes

    DEFF Research Database (Denmark)

    Zwisler, Stine T; Enggaard, Thomas P; Noehr-Jensen, Lene

    2010-01-01

    The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subje...

  8. Fentanyl tolerance in the treatment of cancer pain: a case of successful opioid switching from fentanyl to oxycodone at a reduced equivalent dose.

    Science.gov (United States)

    Sutou, Ichiro; Nakatani, Toshihiko; Hashimoto, Tatsuya; Saito, Yoji

    2015-06-01

    Opioids are not generally deemed to have an analgesic ceiling effect on cancer pain. However, there have been occasional reports of tolerance to opioid development induced by multiple doses of fentanyl. The authors report a case of suspected tolerance to the analgesic effect of opioid, in which an increasing dose of fentanyl failed to relieve the patient's cancer pain symptoms, but opioid switching to oxycodone injections enabled a dose reduction to below the equivalent dose conversion ratio. The patient was a 60-year-old man diagnosed with pancreatic body carcinoma with multiple metastases. The base dose consisted of 12 mg/day of transdermal fentanyl patches (equivalent to 3.6 mg/day, 150 μg/h fentanyl injection), and rescue therapy consisted of 10 mg immediate-release oxycodone powders. Despite the total daily dose of fentanyl reaching 5.6 mg (equivalent to 560 mg oral morphine), the analgesic effect was inadequate; thus, an urgent adjustment was necessary. Due to the moderate dose of fentanyl, the switch to oxycodone injection was done incrementally at a daily dose equivalent to 25% of the fentanyl injection. The total dose of oxycodone was replaced approximately 53.5% of the dose of fentanyl prior to opioid switching.

  9. Economic study on the impact of side effects in patients taking oxycodone controlled-release for noncancer pain.

    Science.gov (United States)

    Anastassopoulos, Kathryn P; Chow, Wing; Tapia, Crisanta I; Baik, Rebecca; Ackerman, Stacey J; Biondi, David; Kim, Myoung S

    2012-10-01

    Chronic pain is a prevalent condition in the United States. Musculoskeletal pain, including joint and back pain, is the most common type of chronic pain, and many patients with back pain have a neuropathic component. Pain has direct economic consequences. While oxycodone controlled-release (CR) is one of the most widely used oral long-acting opioids for pain, including pain with a neuropathic component, it is often associated with bothersome side effects, resulting in additional medical resource use (MRU) and costs. To examine the impact on MRU and costs to payers of side effects in patients taking oxycodone CR alone or in combination with other pain medications for noncancer pain (including those with neuropathic pain symptoms). A nationwide convenience sample of adults in the United States, who participated in a survey research panel and reported current use of oxycodone CR for noncancer pain, completed an online survey between November 2, 2010, and December 13, 2010. Respondents were excluded if they reported current use of other extended-release or long-acting opioid prescription medications. The survey consisted of questions on demographics, clinical characteristics, pain characteristics, experience with pain medication, and MRU associated with side effects. Payer costs were calculated based on the MRU reported by the respondents multiplied by Medicare reimbursement rates for hospitalizations and outpatient visits and average wholesale price (AWP) minus 20% for medications. A subgroup of patients who reported neuropathic pain symptoms also was examined. After applying the exclusion criteria, 432 respondents completed the survey. Approximately half of the respondents (n = 219; 50.7%) reported neuropathic pain symptoms. The majority of respondents were Caucasian (88.4%) and female (63.7%) with an average age of 41.8 years (14.89). Respondents most frequently reported low back pain (41.2%), followed by osteoarthritis/rheumatoid arthritis (20.4%), neuropathic pain

  10. Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study.

    Science.gov (United States)

    Andreassen, Trine Naalsund; Eftedal, Ingrid; Klepstad, Pål; Davies, Andrew; Bjordal, Kristin; Lundström, Staffan; Kaasa, Stein; Dale, Ola

    2012-01-01

    Opioids are recommended by the World Health Organization for moderate to severe cancer pain. Oxycodone is one of the most commonly used opioids and is metabolized in the liver by CYP3A4 and CYP2D6 enzymes. The aim of this cross-sectional study was to assess the relationship between oxycodone pharmacokinetics, pharmacodynamics and the CYP2D6 genotypes "poor metaboliser" (PM), "extensive metaboliser" (EM) and "ultra-rapid metaboliser" (URM) in a cohort of patients with cancer pain. The patients were genotyped for the most common CYP2D6 variants and serum concentrations of oxycodone and metabolites were determined. Pain was assessed using the Brief Pain Inventory (BPI). The EORTC QLQ-C30 was used to assess the symptoms of tiredness and nausea. Cognitive function was assessed by the Mini Mental State (MMS) examination. Associations were examined by analyses of variance (ANOVA) and covariance (ANCOVA), or ordinal logistic regressions with and without covariates. The sample consisted of 27 PM, 413 EM (including heterozygotes) and 10 URM. PM had lower oxymorphone and noroxymorphone serum concentrations and oxymorphone to oxycodone ratios than EM and URM. No differences between PM, EM and URM in pain intensity, nausea, tiredness or cognitive function was found. CYP2D6 genotypes caused expected differences in pharmacokinetics, but they had no pharmacodynamic consequence. CYP2D6 genotypes did not influence pain control, the adverse symptoms nausea and sedation or the risk for cognitive failure in this study of patients treated with oxycodone for cancer pain.

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

    Science.gov (United States)

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

    2014-12-01

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

  12. Kids Born to Opioid-Addicted Moms Seem to Fare Poorly in School

    Science.gov (United States)

    ... of these areas. The study authors said their paper is the first to examine academic results in ... oxycodone), Vicoprofen (hydrocodone/ibuprofen), and the illegal opioid heroin are responsible for many cases of neonatal abstinence ...

  13. Reduced cognitive and psychomotor impairment with extended-release oxymorphone versus controlled-release oxycodone.

    Science.gov (United States)

    Schoedel, Kerri A; McMorn, Stephen; Chakraborty, Bijan; Zerbe, Kathleen; Sellers, Edward M

    2010-01-01

    Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). Randomized, double-blind, 5-way crossover Single inpatient research unit Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], PLSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM

  14. Determination of 4-aminophenol in hydrocodone bitartrate and acetaminophen tablets by RP-HPLC%RP-HPLC法测定复方氨酚氢可酮片中的有关物质对氨基酚

    Institute of Scientific and Technical Information of China (English)

    肖宇; 邓盛齐; 丁始安; 李楠

    2014-01-01

    Objective:To establish a method for determination of the related substance 4-aminophenol in hydrocodone bitartrate and acetaminophen tablets.Methods:An Elite Hypersil BDS Cs column (4.6 mm × 250 mm,5 μm) was adopted with a mixture of phosphate buffer and methanol as the mobile phase at the flow rate of 1 mL ·min-1 in the form of gradient elution.The detection wavelength was set at 245 nm.Results:4-aminophenol was completely separated from other substances and impurities in hydrocodone bitartrate and acetaminophen tablets with no interference by using this method.The calibration curve was in good linearity (r =0.9999,n =7) within the range of 0.21-52.45 μg · mL-1 for 4-aminophenol,the LOQ was 0.84 ng and the LOD was 0.17 ng,the RSD for repeatability was 4.4%.The recovery was within 99.1%-101.2%.Conclusion:The method is in accordance with requirements of methodology validation and reliable for determination of 4-aminophenol in hydrocodone bitartrate and acetaminophen tablets.%目的:建立复方氨酚氢可酮片中的有关物质对氨基酚的测定方法.方法:采用依利特Hypersil BDS C8色谱柱(4.6 mm×250 mm,5μm),以磷酸盐缓冲液-甲醇为流动相,进行梯度洗脱,流速1 mL·min-1,检测波长245 nm.结果:依本法进行测定,片剂中其他成分及杂质不干扰对氨基酚的测定,对照品溶液浓度在0.21~52.45μg· mL-1范围内线性关系良好(r=0.9999,n=7);定量限与检测限分别为0.84、0.17 ng;重复性试验中RSD(n =6)为4.4%;回收率在99.1%~101.2%之间.结论:本法经方法学验证可用于复方氨酚氢可酮片中有关物质对氨基酚的检查.

  15. Comparison of the Risks of Shopping Behavior and Opioid Abuse Between Tapentadol and Oxycodone and Association of Shopping Behavior and Opioid Abuse

    OpenAIRE

    Cepeda, M. Soledad; 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 ex...

  16. 氢吗啡酮联合芬太尼用于颌面部手术后镇痛效果观察%ANALGESIC EFFECTS OF HYDROMORPHONE COMBINED FENTANYL ON POSTOPERATIVE ANALGESIA OF MAXILLOFACIAL SURGERY

    Institute of Scientific and Technical Information of China (English)

    王平; 陈喜波; 李汝泓; 李艳; 杨玲

    2015-01-01

    目的::评价氢吗啡酮联合芬太尼用于颌面部手术患者术后自控静脉镇痛的效果。方法:40例择期行颌面部手术的患者随机分为氢吗啡酮+芬太尼(H)组和芬太尼(F)组,每组20例。两组术后均采用患者静脉自控镇痛的方式,F组芬太尼1.0mg;H组氢吗啡酮1.6mg+芬太尼0.5mg,记录术后2h、4h、8h、12h、24h的疼痛评分(VAS评分)和Ramsay镇静评分(RSS评分),观察恶心、呕吐、眩晕等不良反应的发生情况。结果:两组患者术后各时间点VAS评分、RSS评分比较差异无统计学意义(P>0.05)。镇痛治疗期间H组患者恶心呕吐、眩晕的发生率明显低于F组(P<0.05)。结论:氢吗啡酮联合芬太尼与单用芬太尼用于颌面部手术术后镇痛的效果相当,但不良反应发生率明显较低,更适用于颌面部手术术后镇痛。%[ABSTRACT]Objective:To evaluate the effects of hydromorphone combined fentanyl on postoperative patient control intravenous analgesia (PCIA) of maxillofacial surgery patients. Methods:40 cases selective maxillofacial surgery patients were randomly divided into hydromorphone combined fentanyl (H) group and fentanyl (F) group (n=20). These 2 groups all used PCIA:patients in H group used hydromorphone (1.6mg) combined fentanyl (0.5mg);patients in F group only used fentanyl(1.0mg). The VAS score and RSS score of patients in 2 groups were recorded 2h, 4h, 8h, 12h, 24h after operation respectively;as well as adverse effects. Results:There had no statistical signiifcance about VAS score and RSS score of 2 groups at each time point after operation (P>0.05). The incidence rate of adverse effects (nausea, vomiting and dizziness) of H group were obviously lower than that of F group (P<0.05). Conclusions:The analgesic effects of hydromorphone combined fentanyl is same as fentanyl after maxillofacial surgery, but adverse effects are fairly lower. So hydromorphone combined fentanyl is more comfortable and

  17. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain.

    Science.gov (United States)

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew

    2014-05-29

    There is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway in the UK has been criticised. In England the LCP was the subject of an independent review, commissioned by a Health Minister. The Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly, and had instead become a barrier to good care; it made over 40 recommendations, including education and training, research and development, access to specialist palliative care services, and the need to ensure care and compassion for all dying patients. In July 2013, the Department of Health released a statement that stated the use of the LCP should be "phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient".The impact of opioids was a particular concern because of their potential influence on consciousness, appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death, and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review, commissioned by the National Institute for Health Research, used standard Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone, and codeine in cancer pain studies as a close approximation to possible effects in the dying patient. To determine the impact of opioid treatment on patient consciousness, appetite and thirst in randomised controlled trials of morphine, fentanyl, oxycodone or codeine for treating cancer pain. We assessed adverse event data reported in

  18. Determination of hydromorphone concentration in human plasma by HPLC-MS/MS%高效液相色谱-质谱联用法测定人血浆中氢吗啡酮的浓度

    Institute of Scientific and Technical Information of China (English)

    曲恒燕; 郝光涛; 陈学义; 高洪志; 董瑞华; 李媛媛; 王晓芳; 刘泽源; 张宏

    2015-01-01

    Objective To determine the mass concentration in human plasma hydromorphone by established HPLC -MS/MS method.Methods The treatment of plasma with solid-phase extraction, selec-tion Kromasil 100 -5 SIL, E97915 column with 95% acetonitrile -5 mmol· L-1 ammonium acetate as the mobile phase gradient elution with positive ion, multiple reaction monitoring mode mass concentration of the sample was measured.Results The plasma samples, hydromor-phone in good ( r >0.999 8 ) 0.05 -10.00 ng · mL-1 linear relation-ship, the minimum detectable concentration was 0.05 ng· mL-1.Blood samples day and inter-day RSD were less than 15%, the average recovery >70%, and stability were good.Conclusion The method is simple, rapid, sensitive and accurate, specific, kinetics in vivo pharma-cokinetics of hydromorphone apply.%目的:建立HPLC-MS/MS法测定人血浆中氢吗啡酮的质量浓度。方法用固相萃取法处理血浆,用Kromasil 100-5SIL和E97915色谱柱,以95%乙腈-5 mmol· L-1乙酸铵为流动相,梯度洗脱,用正离子、多反应监测方式测定样品质量浓度。结果血浆样品中,氢吗啡酮在0.05~10.00 ng· mL-1内线性关系良好(r=0.9998),最低定量下限为0.05 ng· mL-1。血样日内与日间 RSD均小于15%,平均回收率>70%,且稳定性均较好。结论本方法简便快速、灵敏准确、特异性强,适用于氢吗啡酮的体内药代动力学研究。

  19. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Science.gov (United States)

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-03-15

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  20. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Directory of Open Access Journals (Sweden)

    Johan Forsgren

    Full Text Available In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  1. 盐酸氢吗啡酮注射液治疗慢性疼痛的有效性:meta分析%Efficacyof hydromorphone hydrochloride injection for treatment of chronic pain : a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    曾铮; 武庆平; 姚尚龙; 尹平; 付阿丹

    2015-01-01

    目的 采用meta分析评价盐酸氢吗啡酮注射液治疗慢性疼痛的有效性.方法 检索Web of Science Proceedings和PubMed数据库,无语种和发表时间限制.收集评价盐酸氢吗啡酮注射液治疗慢性疼痛有效性的临床研究.主要评价指标包括:VAS评分、疼痛控制率或缓解率等.由2名研究人员独立地筛选研究并提取数据,并利用Stata 10软件进行数据分析.结果 最终共11项研究符合纳入标准,共452例患者.与治疗前比较,盐酸氢吗啡酮注射液治疗后VAS评分降低(P<0.05).对于癌性疼痛患者,与其他阿片类镇痛药比较,盐酸氢吗啡酮注射液治疗后VAS评分降低,疼痛缓解率或控制率升高(P<0.05).结论 盐酸氢吗啡酮注射液可治疗慢性疼痛,其对癌性疼痛患者的治疗效果可能优于其他阿片类镇痛药物.%Objective To systematically review the efficacy of hydromorphone hydrochloride injection for treatment of chronic pain.Methods Web of Science Proceedings and PubMed were searched for clinical trials involving the efficacy of hydromorphone for treatment of chronic pain, with no language or time limit.Evaluation indexes included visual analogue scale (VAS) score and the rate of pain control or relief.The studies were screened independently, and the data were extracted by two researchers.Meta-analysis was conducted using the Stata 10 software.Results Eleven studies involving 452 patients were included in our meta-analysis.VAS score was significantly decreased after treatment compared with that before treatment.For the patients with cancer pain, VAS score was significantly decreased after treatment with hydromorphone hydrochoride injection, and the rate of pain control or relief was increased when compared with the other opioid analgesics.Conclusion Hydromorphone hydrochloride injection can treat chronic pain, and it may provide better therapeutic effect than the other opioid analgesics for the patients with cancer pain.

  2. Variability in metabolism of imipramine and desipramine using urinary excretion data.

    Science.gov (United States)

    Ramey, Kelley; Ma, Joseph D; Best, Brookie M; Atayee, Rabia S; Morello, Candis M

    2014-01-01

    Variability in imipramine and desipramine metabolism was evaluated using urinary excretion data from patients with pain. Liquid chromatography-tandem mass spectrometry was used to quantitate concentrations in urine specimens. Interpatient population contained 600 unique imipramine specimens, whereas intrapatient population had 137 patients with two or more specimens. Normal concentration ranges of imipramine, desipramine and the desipramine/imipramine metabolic ratio (MR) were established, and various factors were tested for MR impact. Geometric mean of imipramine urine concentration was 0.46 mg/g of creatinine, and desipramine was 0.67 mg/g of creatinine. Gender, concomitant known CYP2C19 inhibitor use and urine pH did not affect MR. However, proton-pump inhibitor (PPI) users had a significantly lower mean MR than those without a listed PPI. Early age group (18-36 years) had a significantly higher mean MR than middle (37-66 years) and late (67-90 years) age groups. Approximately one-third were positive for one or more of hydrocodone, oxycodone, hydromorphone or oxymorphone. Patients with no opioids reported in the medication list had a significantly lower geometric mean MR than those with prescribed opioids (1.03 vs. 1.54, P = 0.004). Patients with only one prescribed opioid had a lower MR than those with two or more prescribed opioids. Patients with younger age, prescribed opioids and no listed PPI were more likely to have a higher geometric mean urinary desipramine/imipramine MR.

  3. Drugs in hair. Part I. Metabolisms of major drug classes.

    Science.gov (United States)

    White, R M

    2017-01-01

    Currently, hair can be reliably tested for the presence of drugs. However, one major drawback to the use of parent drugs is the question of potential external or environmental contamination. The analysis of metabolites to confirm the use of the parent drugs was proposed in this short review. The development of hair as a test matrix and the incorporation of xenobiotics, in general, into the hair matrix were discussed. What constitutes an appropriate metabolite for drug testing to mirror the use of a parent drug was proposed and discussed. The use of metabolites rather than parent drugs to indicate unequivocal use rather than external exposure was also discussed for amphetamines, cannabinoids, cocaine, opiates (codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, oxymorphone), phencyclidine, fentanyl, benzodiazepines, and ethanol. This, however, was discussed in terms of class and/or individual drug. In addition, selection or potential selection of appropriate metabolites was reviewed. The actual incorporation of drug metabolites into hair versus the metabolism of drugs which was incorporated into hair were also considered.

  4. Effectiveness and safety of oxycodone/naloxone in the management of chronic pain in patients with systemic sclerosis with recurrent digital ulcers: two case reports.

    Science.gov (United States)

    Ughi, Nicola; Crotti, Chiara; Ingegnoli, Francesca

    2016-01-01

    Digital ulcers (DUs) are a severe and frequent clinical feature of patients with systemic sclerosis (SSc). The presence of DUs may cause severe pain and often lead to impairment of patient's functional activities and health-related quality of life. Moreover, poor patient cooperation during the wound care procedure due to pain may be associated with a negative outcome of DU healing. Therefore, pain management has a key role in patients with SSc. These two case reports describe the effectiveness and safety of oxycodone/naloxone in patients with SSc complicated by painful chronic DUs. Such a therapy has provided pain relief and consequently an increased compliance during redressing wounds.

  5. Modified in vivo comet assay detects the genotoxic potential of 14-hydroxycodeinone, an α,β-unsaturated ketone in oxycodone.

    Science.gov (United States)

    Pant, Kamala; Roden, Nicholas; Zhang, Charles; Bruce, Shannon; Wood, Craig; Pendino, Kimberly

    2015-12-01

    14-Hydroxycodeinone (14-HC) is an α,β-unsaturated ketone impurity found in oxycodone drug substance and has a structural alert for genotoxicity. 14-HC was tested in a combined Modified and Standard Comet Assay to determine if the slight decrease in % Tail DNA noted in a previously conducted Standard Comet Assay with 14-HC could be magnified to clarify if the response was due to cross-linking activity. One limitation of the Standard Comet Assay is that DNA cross-links cannot be reliably detected. However, under certain modified testing conditions, DNA cross-links and chemical moieties that elicit such cross-links can be elucidated. One such modification involves the induction of additional breakages of DNA strands by gamma or X-ray irradiation. To determine if 14-HC is a DNA crosslinker in vivo, a Modified Comet Assay was conducted using X-ray irradiation as the modification to visualize crosslinking activity. In this assay, 14-HC was administered orally to mice up to 320 mg/kg/day. Results showed a statistically significant reduction in percent tail DNA in duodenal cells at 320 mg/kg/day, with a nonstatistically significant but dose-related reduction in percent tail DNA also observed at the mid dose of 160 mg/kg/day. Similar decreases were not observed in cells from the liver or stomach, and no increases in percent tail DNA were noted for any tissue in the concomitantly conducted Standard Comet Assay. Taken together, 14-HC was identified as a cross-linking agent in the duodenum in the Modified Comet Assay.

  6. Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    Science.gov (United States)

    Eisenhauer, Tiffani D; Matchett, Mike; Heasley, Ralph; Morton, Terri; Devarakonda, Krishna; Giuliani, Michael; Young, Jim L; Barrett, Thomas

    2016-01-01

    Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release. To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets. IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet. IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol. IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets. IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.

  7. Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone.

    Science.gov (United States)

    Severtson, Stevan Geoffrey; Ellis, Matthew S; Kurtz, Steven P; Rosenblum, Andrew; Cicero, Theodore J; Parrino, Mark W; Gilbert, Michael K; Buttram, Mance E; Dasgupta, Nabarun; BucherBartelson, Becki; Green, Jody L; Dart, Richard C

    2016-11-01

    The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin(®)) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS(®)) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. 大剂量盐酸羟考酮治疗癌痛临床观察%Clinical Observation of Large Dose of Oxycodone Hydrochloride for the Treatment of Cancer Pain

    Institute of Scientific and Technical Information of China (English)

    李绍毅; 原玉霞; 赵红丹; 张丽慧

    2015-01-01

    目的:观察大剂量盐酸羟考酮对晚期癌症患者的镇痛效果和不良反应以及对生活质量的影响。方法通过自身对照试验,对应用大剂量盐酸羟考酮治疗的重度癌痛患者,评价疼痛程度、疼痛缓解率、不良反应及生活质量。结果应用大剂量盐酸羟考酮疼痛缓解率为95%。患者生活质量较前提高。结论大剂量盐酸羟考酮值得临床作为第三阶梯止痛药。%Objective To observe the large dose of oxycodone hydrochloride analgesic effect and adverse reaction in patients with advanced cancer and its influence on quality of life. MethodsThrough contrast test, the application of large dose of oxycodone hydrochloride treatment in patients with severe pain, evaluation of the degree of pain, pain remission rate, adverse reaction and quality of life.Results High doses of oxycodone hydrochloride pain relief rate was 95%. Patients quality of life than before.Conclusion Large dose of oxycodone hydrochloride is wort h clinical application as a third ladder painkillers.

  9. A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee

    Directory of Open Access Journals (Sweden)

    Jozef Vojtaššák

    2011-01-01

    Full Text Available Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA. Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.

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

    Science.gov (United States)

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

    2017-07-06

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

  11. Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain: an observational analysis

    Directory of Open Access Journals (Sweden)

    De Santis S

    2016-07-01

    Full Text Available Stefano De Santis,1 Cristina Borghesi,1 Serena Ricciardi,2 Daniele Giovannoni,1 Alberto Fulvi,2 Maria Rita Migliorino,2 Claudio Marcassa3 1Palliative Care and Cancer Pain Service, Oncological Pulmonary Unit, 2Oncological Pulmonary Unit, San Camillo-Forlanini Hospitals, Rome, 3Cardiologia Fondazione Maugeri IRCCS, Novara, Italy Introduction: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. Methods: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0–10 numerical rating scale and neuropathic pain (Douleur Neuropathique 4 were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form, Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. Results: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline; 46 (82.1% patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001, Brief Pain Inventory Short Form (P=0.0002, Symptom Distress Scale (P<0.0001, Hospital Anxiety and Depression Scale depression (P=0.0006 and anxiety (P<0.0001 subscales, and bowel function (P=0.0003. At study end, 37 (66.0% patients were satisfied/very satisfied with the new analgesic treatment

  12. Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial.

    Science.gov (United States)

    Löwenstein, O; Leyendecker, P; Hopp, M; Schutter, U; Rogers, P D; Uhl, R; Bond, S; Kremers, W; Nichols, T; Krain, B; Reimer, K

    2009-03-01

    This randomised, double-blind, double-dummy, parallel-group multicentre study assessed the impact of a total daily dose of 60-80 mg oral oxycodone prolonged-release (PR)/naloxone PR (OXN PR) as fixed-ratio combination for patients with opioid-induced constipation (OIC) having moderate-to-severe, non-malignant pain. During pre-randomisation patients receiving opioids for moderate-to-severe non-malignant pain were converted to oxycodone PR (OXY PR) and titrated to an effective analgesic dose. During randomisation 265 patients on a stable OXY PR dose (60-80 mg/day) and with OIC were included in the full analysis population to receive OXN PR or OXY PR alone. Primary outcome was improvement in symptoms of constipation as measured by the Bowel Function Index (BFI). Secondary/exploratory outcomes examined analgesic efficacy and other bowel function parameters. After 4 weeks of treatment, patients receiving OXN PR showed a significant improvement in bowel function compared with those in the OXY PR group (-14.9; 95% CI: -17.9, -11.9; pPR had a median number of 3.0 complete spontaneous bowel movements (CSBM) per week compared with only 1.0 for OXY PR alone. Laxative intake was lower in the OXN PR than the OXY PR group. Furthermore, improvements in bowel function were achieved without loss of analgesic efficacy; pain intensity scores were comparable between the groups and consistent for duration of the study. Most frequently reported adverse events were consistent with those reported for opioid analgesics; no new or unexpected adverse reactions attributable to OXN PR used in higher doses were observed. This study shows that the fixed-ratio combination of OXN PR is superior to OXY PR alone in terms of bowel function, while providing effective equivalent analgesia.

  13. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2014-08-01

    Full Text Available Krishna Devarakonda,1 Terri Morton,1 Rachel Margulis,2 Michael Giuliani,3 Thomas Barrett4 1Clinical Pharmacology and Pharmacokinetics, 2Clinical Operations, 3Research and Development, 4Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA Background: XARTEMIS™ XR (formerly MNK-795 is a combination oxycodone (OC and acetaminophen (APAP analgesic with both immediate-release and extended-release (ER components (ER OC/APAP. The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets versus fasted conditions on the PK of ER OC/APAP was performed. Methods: This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48 were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results: Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC] from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion: The findings from this study suggest that ER OC

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

    Science.gov (United States)

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

    2014-11-01

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

  15. Hydrochloride oxycodone sustained-release tablet for titration in cancer pain management%盐酸羟考酮缓释片用于癌痛治疗的滴定

    Institute of Scientific and Technical Information of China (English)

    杨平(综述); 王昆(审校)

    2015-01-01

    Oxycodone sustained-release tablet is a new formulation of potent opioids, which are characterized by their exact anal-gesic effect, high safety for oral administration, and slight adverse drug reaction. Oxycodone improves the quality of life of patients with cancer pains and is among the selected drugs used for controlling moderate and severe cancer pains. Relief from prolonged pain is achieved by adjusting the dose of Oxycontin (oxycodone hydrochloride) sustained-release tablet according to its pharmacological char-acteristics. The details are reviewed in this article.%盐酸羟考酮缓释片作为一种新型的强阿片类镇痛药,镇痛效果确切、口服安全性高、不良反应轻微,持续应用可提高癌痛患者的生存质量,是临床治疗中重度癌痛的首选药物之一。针对盐酸羟考酮缓释片治疗癌痛的药理特点,近年国内外将其用于癌痛治疗过程中的剂量调整,取得了很好的效果,本文对此进行综述。

  16. Bioequiavailability of domestic paracetamol and oxycodone hydrochloride capsules%国产氨酚羟考酮胶囊人体生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    郝光涛; 梁宇光; 高洪志; 刘泽源

    2011-01-01

    Objective: To evaluate the bioequiavailability of the domestic and the imported paracetamol and oxycodone hydrochloride capsules. Methods: The blood concentrations of paracetamol and oxycodone capsules in two capsules in 24 healthy male volunteers were determined by HPLC-UV and HPLC-MS-MS after a single oral dose with a randomized crossover method.Results: The main pharmacokinetic parameters of the paracetamol in the test and reference preparation were as follows: tmax were (0.75 ± 0.48) and (0.64 ± 0.43) h, respectively; Cmax were (13.45 ± 6.13)and (13.72 ± 5.24) mg·L-1, respectively; t1/2 were (1.92 ± 0.51 )and (2.24 ± 0.72) h, respectively; AUC0-tn were (39.55 ± 8.34) and (39.65 ± 8.58) mg·L-1·h, respectively; AUC0-∞ were (42.30 ± 8.85)and (42.95 ± 10.11 ) mg· L-1· h, respectively. The relative bioavailability of paracetamol in the test preparation was (101.56 ± 19.43)%.The main pharmacokinetic parameters of the oxycodone in the test and reference preparation were as follows: tmax were (0.86 ± 0.34)and (0.90 ± 0.42) h, respectively; Cmax were (25.81 ± 9.54) and (22.53 ± 7.32) μg·L-1, respectively; t1/2 were (4.51 ± 0.87) and (4.52 ± 0.73) h, respectively; AUC0-tn were (129.67 ± 37.27) and (116.78 ± 41.35) tg· L-1· h, respectively; AUC0-∞ were (134.07 ± 38.69)and (121.61 ±42.13) μg· L-1·h, respectively. The relative oxycodone bioavailability of the test preparation was (116.18±25.90)%.Conclusion: The domestic paracetamol and oxycodone hydrochloride capsules were bioequivalent to the imported ones.%目的:评价国产与进口两种氨酚羟考酮胶囊的生物等效性.方法:24名健康男性志愿者随机交叉单剂量口服2种氨酚羟考酮胶囊,采用高效液相色谱.紫外法和高效液相.质谱.质谱法分别测定血浆中对乙酰氨基酚和盐酸羟考酮的浓度.结果:受试制剂与参比制剂中时乙酰氨基酚的t,分别为(0.75 ±0.48)和(0.64±0.43)h,C分别为(13.45±6.13)和(13.72±5

  17. Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain: an observational analysis

    Science.gov (United States)

    De Santis, Stefano; Borghesi, Cristina; Ricciardi, Serena; Giovannoni, Daniele; Fulvi, Alberto; Migliorino, Maria Rita; Marcassa, Claudio

    2016-01-01

    Introduction Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. Methods This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0–10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. Results A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. Conclusion OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function. PMID:27445495

  18. A comparison of oral controlled-release morphine and oxycodone with transdermal formulations of buprenorphine and fentanyl in the treatment of severe pain in cancer patients

    Directory of Open Access Journals (Sweden)

    Nosek K

    2017-08-01

    Full Text Available Krzysztof Nosek,1 Wojciech Leppert,2,3 Hanna Nosek,4 Jerzy Wordliczek,5 Dariusz Onichimowski6 1Non–public Saint Lazarius Health Care Unit, Biskupiec, 2Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznań, 3Department of Quality of life Research, Gdańsk Medical University, Gdańsk, 4Department of Paediatrics, Regional Children Specialized Hospital, Olsztyn, 5Department of Interdisciplinary Intensive Care, Jagiellonian University College of Medicine, Kraków, 6Department of Intensive Care, Regional Hospital, Olsztyn, Poland Aim of the study: To compare analgesia and adverse effects during oral morphine and oxycodone and transdermal fentanyl and buprenorphine administration in cancer patients with pain. Patients and methods: Cancer patients treated at home and in outpatient clinics with severe pain (numerical rating scale score 6–10 fail to respond to non-opioids and/or weak opioids. All patients were randomized to either morphine, oxycodone, fentanyl or buprenorphine and divided into subgroups with predominant neuropathic and nociceptive pain component. Doses of opioids were titrated to satisfactory analgesia and acceptable adverse effects intensity. Patients were assessed at baseline and followed for 28 days. In all patient groups, immediate-release oral morphine was the rescue analgesic and lactulose 10 mL twice daily was the prophylaxis of constipation; no antiemetics were used as prophylaxis. Results: A total of 62 patients participated and 53 patients completed the study. Good analgesia was obtained for all 4 opioids, for both nociceptive and neuropathic pain. The use of co-analgesics was greater in patients with neuropathic pain. Morphine treatment was associated with less negative impact of pain on ability to walk, work and activity (trend according to Brief Pain Inventory-Short Form scores and less consumption of rescue morphine. The most common adverse effects included nausea and drowsiness

  19. Analgesic efficacy of oxycodone-acetaminophen tablets in the treatment of pain%氨酚羟考酮镇痛效果的临床观察

    Institute of Scientific and Technical Information of China (English)

    王锁良; 申小东; 王辉; 候海涛

    2009-01-01

    Objective:To observe the analgesic efficacy and side effects of oxycodone-acetaminophen tab-lets for the painful diseases and the cancer pain at middle and advanced stages. Methods: Out-patients with non-cancer pain (n = 50, painful disease) and patients with cancer pain (n = 30) were enrolled, and treated with oxyc-odone-acetaminophen 1~2 tablets, bid or tid. The analgesic effects and side effects were respectively observed 5 days after treatment in painful disease group, and 7 days after treatment cancer pain group. Results:The analgesic efficacies were satisfactory in both groups; the total pain relief rate was 100%. The complete relief rate was 87.3% in painful disease group and 70% in cancer pain group. The side effects included dizziness, lethargy, nausea, vomi-ting, and constipation. No obvious respiratory depression and psychological dependence were observed. Conclusion: oxycodone-acetaminophen has definite analgesic effect and slight adverse reactions in the treatment of painful disea-ses and cancer pain.%目的:观察氨酚羟考酮对临床常见疼痛性疾病及中晚癌痛的镇痛疗效和不良反应.方法:选取门诊非癌性疼痛病例50例,中晚期癌痛患者30例,口服氨酚羟考酮片,每次1~2片,bid或tid,非癌性疼痛组观察5 d为1个疗程,中晚期癌痛组7 d为1个疗程,观察疼痛的缓解率及不良反应.结果:两组患者均取得良好的镇痛效果,疗程结束时的总有效率达100%,在非癌性疼痛患者中疼痛的完全缓解率为87.3%,癌性疼痛患者中完全缓解率为70%.不良反应包括头晕、嗜睡、恶心、呕吐、便秘,未见明显的呼吸抑制及精神依赖性发生.结论:氨酚羟考酮用于治疗临床非癌性疼痛和中晚期癌痛,疗效确切,不良反应小.

  20. 羟考酮联合作业疗法治疗脑卒中后肩手综合征的疗效%Efficacy of oxycodone combined with occupational therapy in the treatment of shoulder hand syndrome after stroke

    Institute of Scientific and Technical Information of China (English)

    杜改焕; 刘志军; 东红; 李妍怡; 周立文

    2015-01-01

    Objective To observe the efficacy of oxycodone combined with occupational therapy in the treatment of shoulder hand syndrome after stroke phase Ⅰ.Methods Thirty patients with shoulder hand syndrome after stroke phase Ⅰ were randomly divided into oxycodone with occupational therapy group and occupational therapy group,15 cases in each group.Patients in the oxycodone with occupational therapy group were given oral oxycodone combined with occupational therapy,and the occupational therapy group received only occupational therapy.All patients were not given other oral drugs.After the treatment of 6 weeks,the motor function of limbs,pain degree and daily life ability in all patients were evaluated by Fugl-Meyer scale,visual analogue scale (VAS) and modified Barthel index (BI) before and after the treatment.Results After the treatment,the Fugl-Meyer of upper limbs motor function score,VAS and BI index improved in the two groups (P < 0.05),and those in the oxycodone combined with occupational therapy group improved significantly than those in the occupational therapy group (P < 0.05).The total effective rate in the oxycodone combined with occupational therapy group was obviously higher than that in the occupational therapy group (P< 0.05).Conclusion Oral oxycodone combined with occupational therapy is better than only occupational therapy in the treatment of shoulder hand syndrome after stroke phase I,with less adverse reaction.%目的 观察羟考酮联合作业疗法对脑卒中后肩手综合征Ⅰ期的疗效.方法 肩手综合征Ⅰ期患者30例,随机分为羟考酮加作业组和作业组(n=15),羟考酮加作业组采用羟考酮口服联合作业疗法治疗,作业组仅用作业疗法.所有患者不予其它口服药物,治疗6周后采用Fugl-Meyer法、视觉模拟评分法(VAS)、改良Barthel指数(BI)对患者治疗前后的肢体运动功能、疼痛程度、口常生活能力进行评价.结果 两组患者治疗后上肢Fugl-Meyer运动功

  1. Application of oxycodone hydrochloride in the induction of general anesthesia%羟考酮在全身麻醉诱导中的临床应用

    Institute of Scientific and Technical Information of China (English)

    朱文智; 王东信

    2016-01-01

    目的:探讨羟考酮行全麻诱导的有效性与安全性。方法择期行结直肠癌手术患者60例,年龄35~75岁,随机分为两组,每组30例。F 组静脉注射芬太尼2μg/kg、丙泊酚2 mg/kg与顺式阿曲库铵0.15 mg/kg 行全麻诱导;O 组静脉注射羟考酮0.2 mg/kg、丙泊酚2 mg/kg 与顺式阿曲库铵0.15 mg/kg 行全麻诱导。记录诱导前(T0)、插管前1 min(T1)、插管后即刻(T2)、插管后1 min(T3)、5 min(T4)的 MAP 和 HR;记录手术时间、苏醒时间、拔管时间及不良反应情况。结果与T0时比较,T1时两组 MAP 均明显降低,T2时明显升高(P <0.05),且 T1时 F 组明显低于 O 组(P<0.05);T1时 F 组 HR 明显减慢(P <0.05);T2、T3时两组 HR 均明显增快(P <0.05)。插管期间两组 HR 差异无统计学意义。两组手术时间、苏醒时间、拔管时间差异无统计学意义。F 组咳嗽发生率明显高于 O 组(P <0.05)。结论羟考酮可以安全有效地用于临床全身麻醉气管插管的诱导。%Objective To explore the clinical effect and safety of oxycodone hydrochloride in the induction of genenral anesthesia.Methods Sixty ASA Ⅰ or Ⅱ patients aged 35-75 years,sched-uled for colorectal surgery,undergoing general aneasthesia were randomly divided into two groups with 30 cases in each group:fentanyl group (group F)and oxycodone hydrochloride group (group O).Fentanyl 2 μg/kg+propofol 2 mg/kg+cisatracurium 0.1 5 mg/kg (group F)or oxycodone 0.2 mg/kg+propofol 2 mg/kg + cisatracurium 0.1 5 mg/kg (group O)was administered intravenously for general anesthesia induction.MAP and HR were monitored and recorded before the induction (T0 ),1 min before intubation (T1 ),at the time of intubation (T2 ),1 min after intubation (T3 )and 5 min after intubation (T4 ).Side-effect incidence of each group,operation time,wakening time,extuba-tion time and visual analogue scale (VAS)were recorded.Results Compared with group F,MAP in group O were lower than that of group F at

  2. The application for oxycodone in pediatric tonsillectomy,adenoidectomy children%羟考酮在小儿扁桃体、腺样体切除术中的应用

    Institute of Scientific and Technical Information of China (English)

    山淇; 王宏宇; 李春晖; 蔡巍

    2016-01-01

    Objective The experiment was designed to investigate the influence of general anesthesia intravenous oxyc-odone different programs for children. Methods Elective tonsillectomy,adenoidectomy surgical cases was 120. There were children and 3-6 years old, divided into four groups of 30 children randomly. Group A induction was given oxycodone 0. 1mg/kg;Group B induction received oxycodone 0. 2mg Group C administered during the induction was oxycodone 0. 3mg/kg;Group D induction received fentanyl 5μg/kg;If severing was intubation,added fentanyl 0. 1μg/kg. IV induction:propofol 3mg/kg,cisatracurium besilate 0. 1mg/kg. Insert an endotracheal tube for mechanical ventilation. Record the children bur-glary quiet after 5min(T0),intubation(T1) of MAP,HR;extubation time and after SpO2,and RR for extubation. Record ag-itation score after extubation,one hour after the state of consciousness alertness/sedation( OAA/S) rating,nausea,vomiting incidence and extent of bleeding after tonsillectomy. Results A group,MAP and HR for T1 to T0 was increased significant-ly(P0. 01) . Compared with group D,group C extubation time was significantly longer(P0. 01 ) . After extubation, SpO2 and RR four groups was no significant difference ( P >0. 01). Restlessness score after extubation,group A,B and C was significantly lower than that in group D(P0.01)。与D组相比,C组拔管时间明显延长(P0.01)。四组拔管后的SpO2、RR没有明显差异(P>0.01)。拔管后躁动评分,A组、B组、C组明显低于D组(P<0.01)。 D组拔管后恶心、呕吐发生率明显高于A、B两组(P<0.01),与C组无明显差异。结论对于3~6岁接受扁桃体腺样体切除术的患儿,在诱导时给予0.2mg/kg的羟考酮是比较理想的注射方案。

  3. Oxicodona en el dolor crónico no oncológico Oxycodone for the treatment of chronic noncancer pain

    Directory of Open Access Journals (Sweden)

    C. Gómez-Vega

    2007-03-01

    Full Text Available En nuestro país, más de 4 millones y medio sufren dolor crónico y de este porcentaje, más de la mitad sufren dolor intenso. La artritis reumatoide y la artrosis son las principales causas de este dolor según la Encuesta Europea del Dolor. La elección del fármaco analgésico adecuado para el control del dolor moderado-severo es importante para aumentar la calidad de vida de estos pacientes cada vez más longevos. Como nueva opción terapéutica tenemos a la Oxicodona, según la OMS la clasifica como un fármaco que se utilizaría en el segundo escalón cuando se combina con AINES (ampliamente utilizado en EEUU desde 1950 ,ya que le proporciona un efecto techo (1 y como tercer escalón cuando se utiliza sola, tanto la oxicodona de liberación. controlada como la de liberación inmediata (2. La oxicodona se usa desde 1917 y ha sido utilizada en humanos de forma intravenosa, intramuscular, intranasal, subcutánea, rectal, epidural y oral. La vía transdérmica ha sido testada en animales. Hoy en día la oxicodona de liberación prolongada es utilizada en el dolor crónico y la de liberación inmediata es usada más para el tratamiento del dolor agudo y el dolor irruptivo. La oxicodona parenteral (no disponible en nuestro país todavía parece ser una buena alternativa cuando no es posible utilizar la vía oral.Chronic pain is suffered by over 4 and a half million persons in Spain, and over half of these persons suffer intense pain. According to the European Pain Questionnaire, rheumatoid arthritis and arthrosis are the principal cause of this type of pain. It is important to choose a suitable analgesic drug for moderate-severe pain control, thus increasing the quality of life of these patients who are increasingly long living. Oxycodone offers a new therapeutic option. It is classified by the WHO as a drug to be used as a step two drug when combined with a NSAID (widely used in the US since 1950, since it has a ceiling effect (1, and as a

  4. Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly patients with cognitive impairment: an efficacy–tolerability pilot study

    Directory of Open Access Journals (Sweden)

    Petrò E

    2016-03-01

    Full Text Available Emiliano Petrò,1 Elena Ruffini,1 Melania Cappuccio,2 Valeria Guerini,2 Gloria Belotti,3 Sara Fascendini,4 Cristina Licini,4 Claudio Marcassa51Rehabiliation and Alzheimer Unit, San Pietro Polyclinic, Ponte San Pietro, 2Alzheimer Center, P. Gusmini Foundation, Vertova, 3Santa Maria Ausiliatrice Foundation, Bergamo, 4Alzheimer Center, Briolini Hospital FERB ONLUS, Gazzaniga, 5Cardiology, Maugeri Foundation IRCCS, Veruno, ItalyObjective: This pilot study evaluated the efficacy and safety of prolonged-release oxycodone/naloxone (OXN-PR in older subjects with chronic pain and mild-to-moderate cognitive impairment.Methods: This was a prospective, observational, open-label study of 45-day duration. Patients with moderate-to-severe chronic pain and naïve to strong opioids were recruited from nursing homes and Alzheimer’s disease centers. OXN-PR was initiated at low doses (5 mg od or bid and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain intensity reduction of ≥30% from baseline (T0 to 15 days after OXN-PR initiation, as assessed by a numerical rating scale or the Pain Assessment in Advanced Dementia scale. Other assessments included the Barthel activities of daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse events.Results: The analysis included 53 patients (mean age, 83.0 years; mean Mini-Mental State Examination score, 18.6 with severe pain (median Numerical Rating Scale/Pain Assessment in Advanced Dementia 6 and substantial impairment in daily functioning (mean Barthel index, 32.2. The primary endpoint was achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity from baseline to study end (numerical rating scale, 6.6±1.0 vs 2.3±1.1, P<0.0001; Pain Assessment in Advanced Dementia, 6.9±1.6 vs 0.9±0.8, P<0.0001. Substantial improvements from T0 to T45 in daily functioning (mean Barthel index, 32.2±16.8 vs 53.7±23.9, P<0.0001 and neuropsychiatric symptoms

  5. Development of a new multi-analyte assay for the simultaneous detection of opioids in serum and other body fluids using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Eckart, K; Röhrich, J; Breitmeier, D; Ferner, M; Laufenberg-Feldmann, R; Urban, R

    2015-09-15

    A liquid chromatography-tandem mass spectrometry method using electrospray ionization in positive ionization mode was developed for the simultaneous detection of multiple opioid-type drugs in plasma. The presented assay allows the quantitative determination of alfentanil, buprenorphine, codeine, desomorphine, dextromethorphan, dextrorphan, dihydrocodeine, dihydromorphine, ethylmorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, naloxone, naltrexone, oxycodone, oxymorphone, pentazocine, pethidine, pholcodine, piritramide, remifentanil, sufentanil, and tramadol as well as the metabolites 6-monoacetylmorphine, bisnortilidine, morphine-3-glucuronide, morphine-6-glucuronide, naltrexol, norbuprenorphine, norfentanyl, norpethidine, nortilidine, and O-desmethyltramadol. Serum and blood samples were purified by solid-phase extraction. The analytes were separated on a phenyl-hexyl (100mm) column by formic acid/acetonitrile gradient elution using an UPLC 1290 Infinity coupled with a 6490 Triple Quadrupole mass spectrometer. The limits of detection ranged from 0.02 to 0.6ng/mL and the lower limits of quantification ranged from 0.1 to 2.0ng/mL. The calibration curves were linear between Calibration Levels 1-6 for all 35 substances. Recovery rates ranged between 51 and 88% for all compounds except alfentanil, bisnortilidine, pethidine, and morphine-3-glucuronide. The matrix effect ranged from 86% for ethylmorphine to 105% for desomorphine. Using the validation procedure proposed by the German Society of Toxicological and Forensic Chemistry, acceptable precision and accuracy data for almost all analytes were obtained. The method was successfully applied to 206 authentic serum samples provided by the palliative and intensive care units of the University Medical Center and the police authorities. Furthermore, a suspected fatal intoxication is demonstrated by an analysis of the sufentanil in post mortem body fluids and tissues.

  6. Identification and quantitation of amphetamines, cocaine, opiates, and phencyclidine in oral fluid by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Fritch, Dean; Blum, Kristen; Nonnemacher, Sheena; Haggerty, Brenda J; Sullivan, Matthew P; Cone, Edward J

    2009-01-01

    Analytical methods for measuring multiple licit and illicit drugs and metabolites in oral fluid require high sensitivity, specificity, and accuracy. With the limited volume available for testing, comprehensive methodology is needed for simultaneous measurement of multiple analytes in a single aliquot. This report describes the validation of a semi-automated method for the simultaneous extraction, identification, and quantitation of 21 analytes in a single oral fluid aliquot. The target compounds included are amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-amphetamine, 3,4-methylenedioxyethylamphetamine, pseudoephedrine, cocaine, benzoylecgonine, codeine, norcodeine, 6-acetylcodeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, oxycodone, noroxycodone, oxymorphone, and phencyclidine. Oral fluid specimens were collected with the Intercept device and extracted by solid-phase extraction (SPE). Drug recovery from the Intercept device averaged 84.3%, and SPE extraction efficiency averaged 91.2% for the 21 analytes. Drug analysis was performed by liquid chromatography-tandem mass spectrometry in the positive electrospray mode using ratios of qualifying product ions within +/-25% of calibration standards. Matrix ion suppression ranged from -57 to 8%. The limit of quantitation ranged from 0.4 to 5 ng/mL using 0.2 mL of diluted oral fluid sample. Application of the method was demonstrated by testing oral fluid specimens from drug abuse treatment patients. Thirty-nine patients tested positive for various combinations of licit and illicit drugs and metabolites. In conclusion, this validated method is suitable for simultaneous measurement of 21 licit and illicit drugs and metabolites in oral fluid.

  7. Comparison of a triple-quadrupole and a quadrupole time-of-flight mass analyzer to quantify 16 opioids in human plasma.

    Science.gov (United States)

    Viaene, Johan; Lanckmans, Katrien; Dejaegher, Bieke; Mangelings, Debby; Vander Heyden, Yvan

    2016-08-05

    The aim of this work is to study whether a quadrupole time-of-flight (QToF) mass analyzer, coupled to an ultra high performance liquid chromatography (UHPLC) system, can be a valuable alternative for a triple-quadrupole (QqQ) mass analyzer, for quantitative toxicological purposes. The case study considered was the quantification of 16 opioids (6-monoacetylmorphine, buprenorphine, codeine, dihydrocodeine, ethylmorphine, fentanyl, hydrocodone, hydromorphone, morphine, norbuprenorphine, norcodeine, norfentanyl, oxycodone, oxymorphone, pholcodine and tilidine) in human plasma. Both methods were validated in parallel in terms of selectivity, matrix effects, extraction recovery, carry-over, bias, precision and sensitivity. Accuracy-profile methodology was used to determine the optimal calibration model, and to estimate bias, repeatability, intermediate precision and total error. Selectivity was demonstrated for all opioids and deuterated analogues, except for codeine-d3 on the UHPLC-QTOF. For most compounds, extraction recoveries were in the range 60 to 80% on both systems, except for the synthetic analogues, buprenorphine, fentanyl and tilidine, where large variability is observed. Carry-over was negligible on both systems. For different opioids, the optimal calibration model was different between the systems. The accuracy profiles of the majority of the opioids indicated that, over the entire tested concentration range, for more than 5% of the future measurements, total errors are expected to exceed the a priori defined 15% acceptance limit. For some exceptions, however, the measurements even suffer from total errors above 30%, which can be attributed to the solid phase extraction procedure that was applied as sample pretreatment technique. Sensitivity was generally tenfold better on the LC-QToF system, probably due to the difference in ion choice for quantification between both systems. In conclusion, the best performing system seemed to depend on the compound, on the

  8. A Dilute-and-Shoot LC-MS Method for Quantitating Opioids in Oral Fluid.

    Science.gov (United States)

    Enders, Jeffrey R; McIntire, Gregory L

    2015-10-01

    Opioid testing represents a dominant share of the market in pain management clinical testing facilities. Testing of this drug class in oral fluid (OF) has begun to rise in popularity. OF analysis has traditionally required extensive clean-up protocols and sample concentration, which can be avoided. This work highlights the use of a fast, 'dilute-and-shoot' method that performs no considerable sample manipulation. A quantitative method for the determination of eight common opioids and associated metabolites (codeine, morphine, hydrocodone, hydromorphone, norhydrocodone, oxycodone, noroxycodone and oxymorphone) in OF is described herein. OF sample is diluted 10-fold in methanol/water and then analyzed using an Agilent chromatographic stack coupled with an AB SCIEX 4500. The method has a 2.2-min LC gradient and a cycle time of 2.9 min. In contrast to most published methods of this particular type, this method uses no sample clean-up or concentration and has a considerably faster LC gradient, making it ideal for very high-throughput laboratories. Importantly, the method requires only 100 μL of sample and is diluted 10-fold prior to injection to help with instrument viability. Baseline separation of all isobaric opioids listed above was achieved on a phenyl-hexyl column. The validated calibration range for this method is 2.5-1,000 ng/mL. This 'dilute-and-shoot' method removes the unnecessary, costly and time-consuming extraction steps found in traditional methods and still surpasses all analytical requirements. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. The heritability of oxycodone reward and concomitant phenotypes in a LG/J × SM/J mouse advanced intercross line.

    Science.gov (United States)

    Bryant, Camron D; Guido, Michael A; Kole, Loren A; Cheng, Riyan

    2014-07-01

    The rewarding property of opioids likely contributes to their abuse potential. Therefore, determining the genetic basis of opioid reward could aid in understanding the neurobiological mechanisms of opioid addiction, provided that it is a heritable trait. Here, we characterized the rewarding property of the widely abused prescription opioid oxycodone (OXY) in the conditioned place preference (CPP) assay using LG/J and SM/J parental inbred mouse strains and 17 parent-offspring families of a LG/J × SM/J F47 /F48 advanced intercross line (AIL). Following OXY training (5 mg/kg, i.p.), SM/J mice and AIL mice, but not LG/J mice, showed an increase in preference for the OXY-paired side, suggesting a genetic basis for OXY-CPP. SM/J mice showed greater locomotor activity than LG/J mice in response to both saline and OXY. LG/J, SM/J, and AIL mice all exhibited robust OXY-induced locomotor sensitization. Narrow-sense heritability (h(2) ) estimates of the phenotypes using linear regression and maximum likelihood estimation showed good agreement (r = 0.91). OXY-CPP was clearly not a heritable trait whereas drug-free- and OXY-induced locomotor activity and sensitization were significantly and sometimes highly heritable (h(2)  = 0.30-0.84). Interestingly, the number of transitions between the saline- and OXY-paired sides emerged as a reliably heritable trait following OXY training (h(2)  = 0.46-0.66) and could represent a genetic component of drug-seeking behavior. Thus, although OXY-CPP does not appear to be amenable to genome-wide quantitative trait locus mapping, this protocol will be useful for mapping other traits potentially relevant to opioid abuse.

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

    Science.gov (United States)

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

    2017-08-14

    Treatment with prolonged-release oxycodone/naloxone (PR OXN) has been shown to improve opioid induced constipation (OIC) in constipated patients. This publication reports on a real-life observational study investigating the efficacy of PR OXN with regard to bowel function in patients switching to PR OXN from WHO-step 1, step 2 and step 3 opioids. Patients with chronic pain experiencing insufficient pain relief and/or unacceptable side effects were switched to PR OXN and monitored in this observational study with respect to efficacy regarding bowel function and efficacy regarding pain relief in comparison with previous analgesic therapy. A patient was considered responder with respect to efficacy if this assessment was 'slightly better', 'better' or 'much better' compared with previous therapy. Bowel function index, pain intensity, quality of life, laxative medication use, and safety analgesic were also evaluated. 1,338 patients (mean (sd) age 64.3 (14.9), 63% female) were observed for 43 [3-166] days (median [range]) during treatment with PR OXN. Overall response rate regarding bowel function efficacy was 82.5%. Patients with symptoms of constipation at study entry obtained a clinically relevant improvement of the bowel function index (BFI) within the first 2 weeks of PR OXN treatment. Non-constipated patients at study entry maintained normal bowel function despite switching to treatment with the opioid PR OXN. In conclusion, treatment with PR OXN results in a significant and clinically relevant improvement of bowel function. During the observation of the treatment with PR OXN patients reported an improvement of QoL. More interestingly, non-constipated patients maintained a normal bowel function, showing prevention of constipation despite the use of an opioid.

  11. A Study of Outpatient Pharmacy Utilization at Naval Hospital, Camp Lejeune

    Science.gov (United States)

    2002-07-01

    may also be placed on certain drugs based on their potential for abuse or misuse (DoD, 1999). When developing formulary management strategies, it is...FENTANYL 11 $ 2,560.24 BLOOD SUGAR DIAGNOSTIC 28 $ 2,193.86 OXYCODONE HCL/ACETAMINOPHEN 137 $ 2,076.71 METHYLPHENIDATE HCL 31 $ 1,996.63 HYDROCODONE

  12. Dosis efectiva de hidromorfona en pacientes con dolor crónico oncológico: experiencia de 4 años en el Centro Médico Nacional "20 de Noviembre" ISSSTE Effective dose of hydromorphone in patients with chronic oncologic pain: a four-year experience in the Centro Médico Nacional 20 de Noviembre, a public hospital in Mexico

    Directory of Open Access Journals (Sweden)

    E. Rionda

    2009-07-01

    Full Text Available Antecedentes: Aproximadamente 6,35 millones de nuevos casos de cáncer se diagnostican anualmente. El 90% de los pacientes con cáncer avanzado presentan dolor. El objetivo en el tratamiento del dolor oncológico es aliviar el dolor, interrumpiendo la transmisión o modulándolo a nivel cerebral o espinal. La Organización Mundial de la Salud (OMS desarrolló una escala de tres escalones para manejar el dolor oncológico. En el escalón I se incluyen analgésicos no opiáceos + coadyuvantes; en el escalón II se incluyen opiáceos leves + coadyuvantes y en el escalón III se incluyen opiáceos potentes + coadyuvantes. Material y métodos: Se revisaron 72 expedientes, en un total de 4 años, de todos los pacientes con dolor crónico oncológico que hayan estado en tratamiento con hidromorfona. En este trabajo obtuvimos la dosis promedio en la que se logró un buen control del dolor (escala analógica visual [EVA] Background: Approximately 6.35 million patients are diagnosed with cancer annually. Around 90% of patients with advanced cancer have pain. Treatment of oncologic pain aims to relieve pain by modulating or interrupting transmission in the spine or brain. The World Health Organization (WHO has developed a three-step ladder for cancer pain management. At step I, non-opioid plus adjuvant drugs are included. Step II includes opioids for mild to moderate pain plus adjuvants, and step III includes opioids for moderate to severe pain plus adjuvants. Material and methods: We reviewed 72 files corresponding to all the patients with chronic cancer pain that had been treated with hydromorphone during the previous 4 years in our hospital and calculated the mean dose at which the patients reported good pain control (Visual Analog Scale [VAS] < 4. We also studied the most common adverse effects, and whether any of the patients discontinued the treatment, and if so, the reasons for discontinuance. The type of cancer in each patient and the length

  13. BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone

    Directory of Open Access Journals (Sweden)

    Kelsey Moore

    2016-11-01

    Full Text Available Blood oxygen level dependent (BOLD imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (µ opioid receptor knock-outs (MuKO in response to oxycodone (OXY. Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high µ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala and hypothalamus, and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex and prelimbic cortex. Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala and preoptic areas. This result indicates that most effects of OXY on positive BOLD are mediated by the µ opioid receptor (on-target effects. OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122 and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum, and in some case intensified (hippocampus. Negative BOLD analysis therefore shows activation and deactivation events in the absence of the µ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects. Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY

  14. BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone

    Science.gov (United States)

    Moore, Kelsey; Madularu, Dan; Iriah, Sade; Yee, Jason R.; Kulkarni, Praveen; Darcq, Emmanuel; Kieffer, Brigitte L.; Ferris, Craig F.

    2016-01-01

    Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, and Mu (μ) opioid receptor knock-outs (MuKO) in response to oxycodone (OXY). Using a segmented, annotated MRI mouse atlas and computational analysis, patterns of integrated positive and negative BOLD activity were identified across 122 brain areas. The pattern of positive BOLD showed enhanced activation across the brain in WT mice within 15 min of intraperitoneal administration of 2.5 mg of OXY. BOLD activation was detected in 72 regions out of 122, and was most prominent in areas of high μ opioid receptor density (thalamus, ventral tegmental area, substantia nigra, caudate putamen, basal amygdala, and hypothalamus), and focus on pain circuits indicated strong activation in major pain processing centers (central amygdala, solitary tract, parabrachial area, insular cortex, gigantocellularis area, ventral thalamus primary sensory cortex, and prelimbic cortex). Importantly, the OXY-induced positive BOLD was eliminated in MuKO mice in most regions, with few exceptions (some cerebellar nuclei, CA3 of the hippocampus, medial amygdala, and preoptic areas). This result indicates that most effects of OXY on positive BOLD are mediated by the μ opioid receptor (on-target effects). OXY also caused an increase in negative BOLD in WT mice in few regions (16 out of 122) and, unlike the positive BOLD response the negative BOLD was only partially eliminated in the MuKO mice (cerebellum), and in some case intensified (hippocampus). Negative BOLD analysis therefore shows activation and deactivation events in the absence of the μ receptor for some areas where receptor expression is normally extremely low or absent (off-target effects). Together, our approach permits establishing opioid-induced BOLD activation maps in awake mice. In addition, comparison of WT and MuKO mutant mice reveals both on-target and off-target activation events, and set an OXY brain

  15. Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly patients with cognitive impairment: an efficacy–tolerability pilot study

    Science.gov (United States)

    Petrò, Emiliano; Ruffini, Elena; Cappuccio, Melania; Guerini, Valeria; Belotti, Gloria; Fascendini, Sara; Licini, Cristina; Marcassa, Claudio

    2016-01-01

    Objective This pilot study evaluated the efficacy and safety of prolonged-release oxycodone/naloxone (OXN-PR) in older subjects with chronic pain and mild-to-moderate cognitive impairment. Methods This was a prospective, observational, open-label study of 45-day duration. Patients with moderate-to-severe chronic pain and naïve to strong opioids were recruited from nursing homes and Alzheimer’s disease centers. OXN-PR was initiated at low doses (5 mg od or bid) and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain intensity reduction of ≥30% from baseline (T0) to 15 days after OXN-PR initiation, as assessed by a numerical rating scale or the Pain Assessment in Advanced Dementia scale. Other assessments included the Barthel activities of daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse events. Results The analysis included 53 patients (mean age, 83.0 years; mean Mini-Mental State Examination score, 18.6) with severe pain (median Numerical Rating Scale/Pain Assessment in Advanced Dementia 6) and substantial impairment in daily functioning (mean Barthel index, 32.2). The primary endpoint was achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity from baseline to study end (numerical rating scale, 6.6±1.0 vs 2.3±1.1, P<0.0001; Pain Assessment in Advanced Dementia, 6.9±1.6 vs 0.9±0.8, P<0.0001). Substantial improvements from T0 to T45 in daily functioning (mean Barthel index, 32.2±16.8 vs 53.7±23.9, P<0.0001) and neuropsychiatric symptoms (mean Neuropsychiatric Inventory, 25.5±27.3 vs 8.8±9.0, P<0.0001) were also reported. OXN-PR was well tolerated and did not worsen bowel function. Conclusion In this pilot study, OXN-PR was effective in improving pain and other symptoms associated with dementia, with a favorable safety and tolerability profile. Large-scale trials in people with dementia are needed to improve clinical guidance for the assessment and treatment of pain in

  16. 吗啡与羟考酮用于经皮肾镜取石术后镇痛效果比较%Comparison of Postoperative Analgesia Efficacy of Morphine Versus Oxycodone After Percuta-neous Nephrolithotomy

    Institute of Scientific and Technical Information of China (English)

    田开林; 范本祎; 秦勤; 许军; 彭波; 袁俊斌

    2015-01-01

    [Objective] To compare the analgesia efficacy of morphine versus oxycodone after percutaneous nephrolithotomy (PCNL) .[Methods] The opioid consumption ,pain relief and side effects of morphine versus oxycodone after PCNL were examined by minimizing somatic pain component .During October 2013 and Sep‐tember 2014 ,a total of 50 adult patients were recruited and randomized to receive either morphine or oxycodo‐ne intravenously as postoperative pain treatment .During the first 4 postoperative hours ,opioid consumption , pain scores and side effects (nausea ,dizziness ,respiratory effects & itching ) were recorded .[Results] The postoperative opioid consumption varied considerably .However ,the mean opioid consumption was comparable for two groups ( P>0 .05) .Nausea was significantly less frequent with morphine ( P<0 .05) .[Conclusion]Morphine and oxycodone have similar analgesia efficacies during the first 4 postoperative hours .However ,the frequency of nausea is significantly less for morphine users .%【目的】对比研究吗啡与羟考酮用于经皮肾镜碎石取石术(PCNL)后的镇痛效果。【方法】回顾性分析2013年10月至2014年9月在本院行PCNL术治疗的50名患者,根据术后给予不同的镇痛药物将患者分为吗啡组(25例)和羟考酮组(25例)。比较两组患者术后4 h镇痛药物的使用量、疼痛视觉模拟评分(VAS)及不良反应(如恶心,头晕,呼吸抑制和瘙痒)等指标。【结果】两组患者VAS评分及镇痛药的平均使用量均无统计学差异(P >0.05),吗啡组患者不良反应恶心的发生率明显少于羟考酮组(P <0.05)。【结论】吗啡与羟考酮对行PCNL术的患者镇痛效果相当,但吗啡较羟考酮可减少不良反应恶心的发生率。

  17. Razones clínicas de elección de hidromorfona OROS® para el tratamiento de pacientes con dolor crónico no oncológico: Estudio HIDOCO The clinical reason for prescribing OROS® hydromorphone in patients with chronic non-cancer: Study HIDOCO

    Directory of Open Access Journals (Sweden)

    M. D. Rodrigo Royo

    2012-06-01

    éutica, destacando su eficacia, pauta posológica y perfil de tolerabilidad como criterios principales de elección.Objective: to establish the clinical reasons for prescribing OROS® hydromorphone in patients with chronic non-cancer pain. Material and methods: an observational, retrospective, multicenter, Spanish study in patients with chronic non-cancer pain treated with OROS® hydromorphone between 1 and 5 months. The recorded information stemmed from the medical records of the patient, from the information given by the investigator of its clinical daily practice and from two questionnaires administered to the patient on adherence (Morisky-Green and quality of life (SF-36. Results: 53 investigators included data of 438 patients with a mean age of 62 years, 43.4% of them under 60 years of age. The most prevalent pathological conditions were osteoarthritis and low-back pain. Despite the time from the onset of the pain was 6.4 years, 23.3% of the patients had been experiencing pain over 10 years. Before starting treatment with OROS® hydromorphone, 62% had VAS score >7 and 33.5% had VAS score 5-7. The combination of minor opioids and NSAIDs was the most common previous treatment, and only 5% were receiving strong opioids alone. The main reason for starting OROS® hydromorphone was the lack of efficacy with the previous opioid (62.1%, and the first criterion for the choice was efficacy (81.7%, followed by dosage (60.3% and tolerability profile (47.7%. 93.4% of the patients stated that they regularly took their medicine at the right time and 57.8% considered that their current health condition was better or unchanged from the previous year. Conclusions: Undertreated pain and the lack of use of strong opioids in patients with chronic non-cancer pain are still important issues. OROS® Hydromorphone is a valid therapeutic option, with its efficacy, dosage and tolerability profile as the main reasons for its choice.

  18. 羟考酮控释片用于滴定中度癌痛的疗效观察%Effect of the Titration of Oxycodone Controlled-release Tablets on Moderate Pain

    Institute of Scientific and Technical Information of China (English)

    张颖一; 韩廷; 汪颖; 刘璐; 王宁; 王雅杰

    2011-01-01

    目的 评价盐酸羟考酮控释片对中度癌性疼痛滴定期的疗效优势.方法 本研究选取67例无阿片类药物使用史的中度癌痛患者,随机分为两组,A组(35例)使用盐酸羟考酮控释片5mg作为初始剂量对其进行滴定,B组(32例)使用硫酸吗啡控释片10mg滴定,达到疼痛明显缓解或完全缓解后进入维持期.观察期4天,以服药后1h的NRS评分(numerical rating scale,数字模拟评分法)为主要观察指标,将两组疗效进行对比.结果 给药1h后盐酸羟考酮控释片组中有1例患者疼痛获得完全缓解,12例症状明显缓解,11例达到中度缓解,总有效率高达68.6% ;硫酸吗啡控释片组有4例获得明显缓解,10例疼痛中度缓解,总有效率43.8%.服药第4天两组患者疼痛总缓解率均在90%左右.结论 在迅速缓解疼痛方面,盐酸羟考酮控释片组具有优势;而在维持期控制疼痛方面,两组疗效相当.%Objective To evaluate the efficacy advantage of oxycodone hydrochloride controlled - release tablets for moderate cancer pain. Methods This study selected 67 patients suffering from moderate pain without a history of opioid. They were randomly divided into 2 groups. A group (35 cases) used the oxycodone hydrochloride controlled - release tablets 5mg as the initial dose for titration, and B group ( 32 cases) used the morphine sulfate controlled - release tablets 10mg. All of them entered the maimenance phase after been titrated to achieve obvious relief or complete relief of pain. Within 4 - day observation period, we got the NRS score ( Numerical Rating Scale,digital analog scale) [2] the first hour after taking the pills as the main observation index to compare the two groupa. Results In the group of oxycodone hydrochloride controlled - release tablets, 1 patient achieved complete relief after 1 hour administration, 12 were obviously relieved, and 11 were moderate relieved The total efficiency was up to 68.6% . At the same time, in the

  19. 普瑞巴林联合盐酸羟考酮治疗癌性神经病理痛33例%Therapeutic Effects of Pregabalin Combined with Hydrochloric Oxycodone on 33 Casesof Malignant Neuropathic Pain

    Institute of Scientific and Technical Information of China (English)

    章必成; 章志怀; 王俊; 王志刚; 吴婷婷; 饶智国; 高建飞

    2015-01-01

    Objective To evaluate the effects of pregabalin combined with hydrochloric oxycodone on patients with ma-lignant neuropathic pain (MNP). Methods A total of 66 patients with MNP was divided into control group or treatment group randomly. The patients in control group received only hydrochloric oxycodone, and treatment group were treated with the combina-tion of pregabalin and hydrochloric oxycodone. Numeric rating scale (NRS) score was used to evaluate the analgesic effects. Med-ical outcomes study sleep scale (MOS-SS,Chinese version) was used to evaluate the improvement of sleep disorder. The changes of depression or anxiety were investigated by 17-item Hamilton Depression Rating Scale (HAMD-17) or Hamilton Anxiety Scale (HAMA), respectively. Side effects were accessed by Acute and Subacute Toxicity Grading Criteria of Anticancer Drugs (WHO). Results The pain control rate of treatment group was 87. 1% , which was superior to that of control group (58. 6% ) (P<0. 05). The improvement of sleep interference, and the quality and quantity of sleep in treatment group were also superior to that in control group (P<0. 05). After the treatment, depression and anxiety was attenuated in both groups, and the improvement degree in treatment group was higher than that in control group (P<0. 05). No obvious side effects were found in either groups. Conclusion The combination therapy of pregabalin and hydrochloric oxycodone is the better way to treat MNP.%目的:评价普瑞巴林联合盐酸羟考酮治疗癌性神经病理痛(MNP)的疗效。方法将66例 MNP 患者随机分为两组各33例,对照组接受盐酸羟考酮治疗,治疗组接受盐酸羟考酮+普瑞巴林治疗。采用数字评估法(NRS)评分比较两组患者的止痛效果,采用 MOS-SS 睡眠量表(中文版)评价和比较两组患者的睡眠改善情况,采用17项汉密尔顿抑郁量表(HAMD-17)及汉密尔顿焦虑量表(HAMA)分别评定和比较两组患者的抑郁、焦虑状态,按

  20. 羟考酮在肺切除围术期对炎症因子的影响研究%Effect of oxycodone on inflammatory factors in patients after pulmonary lobectomy

    Institute of Scientific and Technical Information of China (English)

    周本昊; 张劲松; 杜成

    2016-01-01

    目的:观察羟考酮注射液对肺叶切除术患者在围手术期对部分炎症因子的影响。方法选取40例常规肺叶切除术的患者,随机分为实验组(羟考酮组,A组,下同)和对照组(曲马多组,B组,下同)各20例。 A组术后静脉泵注羟考酮(1 mg/ml,2 mg/h),B组术后静脉泵注曲马多(0.2 mg/kg/h);采集患者麻醉诱导前(T0),术后4 h(T1),术后8 h(T2),术后24 h(T3)动脉血标本,采用酶联免疫吸附法测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)的水平;并于T0、T1、T2、T3时间点记录患者生命体征( HR、MAP、RR、SPO2),视觉模拟评分( VAS)。结果与T0比较,两组TNF-α、IL-6、IL-10浓度在T1-3明显上升(P0.05)。结论羟考酮注射液通过对血液中部分炎症因子的所起的作用,在一定程度上能减轻常规剖胸肺叶切除术术后的炎症反应,能较好地维持部分重要炎症因子的平衡,起到缓解术后免疫功能损伤的作用。%Objective To investigate the efficacy of oxycodone on partly inflammatory factors in patients af-ter pulmonary lobectomy. Methods 40 patients received pulmonary lobectomy were randomly divided into the oxyc-odone group (the group A, n=20) and the control group (the group B, n=20). The group A received oxycodone with 0. 9% sodium chloride continuous infusion (concentration 1 mg/ml, pace 2 mg/h), and the group B received tramadol with 0. 9% sodium chloride continuous infusion (pace 0. 2 mg·kg-1·h-1). The levels of TNF-α, IL-6 and IL-10 in plasma were measured immediately before induction of anesthesia ( T0 ) , 4 h ( T1 ) , 8 h ( T2 ) and 24 h ( T3 ) after operation in the two groups by using enzyme-linked immunosorbent. Their vital signs ( HR, MAP, RR, SPO2 ) and visual analogue scale ( VAS) scores were recorded at T0 ,T1 , T2 and T3 . Results The levels of TNF-α, IL-6 and IL-10 of the two groups at T1-3 increased significantly compared to T0 ( P0. 05). Conclusion

  1. Is oxycodone/naloxone effective and safe in managing chronic pain of a fragile elderly patient with multiple skin ulcers of the lower limbs? A case report 

    Directory of Open Access Journals (Sweden)

    Guerriero F

    2015-08-01

    Full Text Available Fabio Guerriero,1,2 Niccolo Maurizi,1 Matthew Francis,1 Carmelo Sgarlata,1 Giovanni Ricevuti,1,2 Mariangela Rondanelli,2,3 Simone Perna,2,3 Marco Rollone21Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, 2Azienda di Servizi alla Persona, Istituto di Cura Santa Margherita of Pavia, 3Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, University of Pavia, Pavia, Italy Abstract: Skin ulcers are a common issue in the elderly, as physiological loss of skin elasticity, alterations in microcirculation, and concomitant chronic diseases typically occur in advanced age, thereby predisposing to these painful lesions. Wound-related pain is often associated with skin ulcers and negatively impacts both the patient’s quality of life and, indirectly, wound healing. Pain management is an ongoing issue in the elderly, and remains underestimated and undertreated in this fragile population. Recent guidelines suggest the use of opioids as the frontline treatment of moderate and severe pain in nononcological pain in the elderly. However, due to the concerns of adverse reactions, drug interactions, and addiction, clinicians frequently hesitate to prescribe opioids. This case report describes an elderly diabetic patient with multiple ulcers of the lower limbs suffering wound-related pain. In our report, oxycodone/naloxone has proved to be an effective and safe drug, providing pain relief as well as increased compliance when redressing wounds and faster healing compared to that in similar patients. Our case provides anecdotal evidence, supported by other studies, to justify future, larger studies on chronic pain using this therapy. Keywords: chronic pain, skin ulcers, elderly, opioids, oxycodone, naloxone

  2. 氨酚羟考酮和盐酸曲马多治疗癌性疼痛的疗效比较%Effect Comparison of Oxycodone Acetaminophen and Tramadol Hydrochloride in the Treatment of Cancer Pain

    Institute of Scientific and Technical Information of China (English)

    王志坚; 朵珍

    2016-01-01

    目的:比较氨酚羟考酮和盐酸曲马多治疗癌性疼痛的效果。方法通过氨酚羟考酮(A组)每6 h口服1片,盐酸曲马多(B组)每12h口服1片,比较两组在治疗24h后的临床疗效以及治疗1d、2d、3 d、7 d、21 d NRS评分值。结果A组和B组在治疗24 h后临床有效率分别为86.84%和73.33%,在1 d、2 d、3 d、7 d、21 d不同时间点NRS评分两种药物差异有统计学意义,P<0.05。结论氨酚羟考酮在治疗癌性疼痛效果方面优于盐酸曲马多。%Objective Comparison of tylox and tramadol hydrochloride in treatment of cancer pain. Methods By acetaminophen oxycodone (group A) oral 1 piece every 6 hours, tramadol hydrochloride (group B) oral 1 tablet every 12 hours of observation, comparison in 24 h after treatment the clinical curative effect and treatment of 1 d, 2 d, 3 d, 7 d, 21 d of NRS score values. Results Group A and group B in the treatment of clinical effectiveness were 86.84% and 73.33% respectively after 24 h, in 1 d, 2 d, 3 d, 7 d, 21 d different NRS score two drugs have signiifcant differences, P<0.05. Conclusion Acetaminophen oxycodone in the treatment of cancer pain is better than that of tramadol hydrochloride.

  3. Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations.

    Science.gov (United States)

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

    2015-07-01

    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.

  4. Clinical report of 186 patients accepted PCIA with oxycodone after laparoscopic cholecystectomy%盐酸羟考酮在腹腔镜胆囊切除术后镇痛效果研究

    Institute of Scientific and Technical Information of China (English)

    何双亮; 甘建辉; 于虹

    2015-01-01

    Objective To explore application effect that using PCIA with oxycodone after laparoscopic cholecystectomy.Methods A total of 186 cases were included in this study,the average packet after patients were divided into A,B groups.During the maintenance of anesthesia drugs remifentanil +propofol +cis acid at-racurium,then extubation,open PCIA pump.PCIA pump recipe A group of oxycodone hydrochloride 100mg in-jection 5mg tropisetron added,increase the amount to 100 mL of normal saline;group B 100 mg of morphine sul-fate Gato alkyl granisetron 5mg,increase the amount to 100 mL of normal saline.Mian outcome:oxycodone and morphine analgesic efficacy and side effects.Record into the recovery room,wake time,extubation and cardio-vascular system parameters 5 minutes later,the pain visual analog scale,PCIA pump and whether the number of presses,vomiting,respiratory depression,nausea,or under different time points after surgery complications ac-company.Results Patients with mean arterial pressure when entering the recovery room and little difference between heart rate,immediate extubation and after extubation 5min differences in mean arterial pressure and heart rate is not the same,the difference was not statistically significant ( P >0.05).VAS scores slightly differ-ent at different times,but the difference was not statistically significant( P >0.05).All patients were awake in about 16 minutes,the average number of pressing CIA pump five times less,but the difference was not statisti-cally significant( P >0.05);the patients in group A deputy reaction rates lower than group B,and there was statistically significant ( P <0.05).Conclusion Oxycodone and morphine analgesic effect similar,effective at treating pain after laparoscopic cholecystectomy application oxycodone.%①目的探讨盐酸羟考酮在腹腔镜胆囊切除术后镇痛治疗中的应用效果。②方法选择接受腹腔镜胆囊切除术的患者186例,分为 A、B 两组。手术后拔除气管插管,开启

  5. Comparison of two different dosages of oxycodone acetaminophen used after total knee arthroplasty%不同剂量氨酚羟考酮对膝关节置换术后镇痛效果的研究

    Institute of Scientific and Technical Information of China (English)

    李锋; 张克; 刘岩; 田华; 王凤英; 娄思权

    2011-01-01

    目的 观察口服氨酚羟考酮片在膝关节置换术后患者中的镇痛疗效和安全性,选择最佳的给药剂量.方法 选择行单侧全膝关节置换患者50例,随机分为氨酚羟考酮10mg组和5mg组,均为Q8H给药,同时使用股神经阻滞(0.2%罗哌卡因),两组患者均维持镇痛5d.术后记录静息痛、康复锻炼疼痛最重时、康复锻炼结束时疼痛评分、膝关节被动活动度、膝关节主动活动度,记录功能活动时疼痛:下床、行走、即刻松拐疼痛评分,以及药物相关的并发症.结果 氨酚羟考酮10mg组患者在术后1d、3d的静息痛VAS评分及膝关节主动活动优于5mg组,不良反应发生率10mg组为26.7%,5mg组为10%.结论 氨酚羟考酮用于全膝关节置换术后康复镇痛效果良好,建议在术后早期(1~3天)使用10mg,Q8H给药,以缓解患者的静息痛、锻炼痛,之后可以减药量为5mg,Q8H,也可以达到满意的功能表现,同时减少药物的副作用.%Objective To observe the analgesic efficacy and safety of oxycodone acetaminophen tablets after total knee arthroplasty. Methods Fifty patients undergoing unilateral TKA surgery were randomly divided into two groups. The patients took oxycodone acetaminophen tablets 10mg Q8H or 5 mg Q8H after TKA. We also used continuous femoral nerve block. Measures of interest included pain ratings as determined with a visual-analog scale, changes in the range of motion of the knee, VAS scores during rest, Worst during physical therapy, transfers, walking, immediate-release climb. Results The patients who received 10mg tablets reported significantly less pain as well as significantly greater range of motion of the knee than 5mg during 1 ~3 days. Conclusion Use of oxycodone acetaminophen during rehabilitation following total knee arthroplasty leads to improved pain control, more rapid functional recovery.

  6. Clinical study on oxycodone combined with PCEA ropivacaine for labor analgesia%羟考酮联合盐酸罗哌卡因PCEA用于分娩镇痛的临床研究

    Institute of Scientific and Technical Information of China (English)

    杜建龙; 薛荣亮

    2015-01-01

    Objective To study the effect and safety of oxycodone combined with PCEA ropivacaine for labor analgesia. Methods Selected 135 cases of full-term pregnant women of ASAⅠ~Ⅱgrade. They were randomly divided into three groups:ropivacaine hydrochloride group (group L, n=45), united oxycodone hydrochloride ropivacaine group (group Q, n=45), fen-tanyl hydrochloride ropivacaine group (group F, n=45). Observed the analgesic onset time, PCEA first time and the total amount of anesthetic, sedation effect, influence of each time on maternal labor, the impact of maternal plasma catecholamines (epinephrine and norepinephrine) and cortisol, the effect on maternal blood loss, neonatal Apgar score and the incidence of adverse reactions and side effect of these groups treated by different compatibility PCEA for labor analgesia. Results There were no significant differences among the three groups on the stage of labor, blood loss and neonatal apgar score, the incidence of adverse reactions and side effect (P>0.05). Compared with group F and group L, analgesic onset time and the PCEA first time of group Q was shorter, group Q had fewer anesthetic, better sedation effect, lower concentration of plasma catecholamine and cortisol concentrations after analgesia. These differences had statistical significance (P0.05),镇痛起效时间及首次PCEA时间Q组明显短于L、F组,麻醉药总量Q组明显少于L、F组,镇痛镇静效果Q组明显优于L、F组,镇痛后血浆儿茶酚胺及皮质醇浓度Q组明显低于L、F组,差异均有统计学意义(P<0.05)。结论羟考酮联合盐酸罗哌卡因PCEA用于分娩镇痛安全有效,是一种较好的分娩镇痛新方法。

  7. Efficacy Comparison of Oxycodone Hydrochloride Controlled-release Tablets and Tramadol Hydrochloride Sustained-release Tablets in the Treatment of Moderate Cancer Pain%盐酸羟考酮缓释片与曲马多缓释片治疗中度癌痛的近期疗效比较

    Institute of Scientific and Technical Information of China (English)

    张锦丰; 杨权烈; 吴国武; 郭维新; 张英燕; 古银芳; 叶敏

    2014-01-01

    目的:比较盐酸羟考酮缓释片(奥施康定)与曲马多缓释片(奇曼丁)治疗中度癌痛的近期疗效。方法将100例伴有中度癌痛患者随机分为奥施康定组和奇曼丁组,每组50例,分别接受奥施康定和奇曼丁的治疗。结果奥施康定组治疗后第3、7、10天的NRS评分均较奇曼丁组低,且奥施康定组治疗后第3天NRS评分下降幅度较奇曼丁组明显( P﹤0.05);奥施康定组的CR率和有效率分别为34.0%和100.0%,明显高于奇曼丁组的10.0%和84.0%(P﹤0.05);2组毒副反应发生率比较差异均无统计学意义(P﹥0.05)。结论与奇曼丁相比,应用奥施康定治疗中度癌痛患者,能更快更有效缓解疼痛,而未增加毒副反应。%Objective To compare the efficacy and tolerability of oxycodone hydrochloride controlled-release tab-lets( oxycodone)and tramadol hydrochloride sustained-release tablets( tramadol)in the treatment of patients with moderate cancer pain. Methods A total of 100 patients with moderate cancer pain were randomly divided into two groups,50 patients of the oxycodone group was treated with oxycodone,and 50 patients of the tramadol group was treated with tramadol. Results The NRS scorce in the oxy-codone group had declined more significantly than the tramadol group,and the decrease was statistically significant in the first three days (P﹤0. 05). The CR rate and the response rate in the oxycodone group were significantly better than those of the tramadol group (34.0% vs10.0% and100.0% vs84.0%)(P﹤0.05).There was no statistic significant difference in the toxicity incidences be-tween the two groups(P﹥0. 05). Conclusion Compared with tramadol,oxycodone is faster and more effective to relieve pain,and don’t increase the toxicities.

  8. 盐酸羟考酮联合音乐疗法在中重度癌痛患者中的应用%Application of oxycodone hydrochloride combined with music therapy in patients with moderate to severe cancer pain

    Institute of Scientific and Technical Information of China (English)

    田会斌; 杨常清; 吴大芝; 魏利军

    2015-01-01

    Objective To investigate the effect of oxycodone hydrochloride combined the music therapy for im‐proving pain in the patients with cancer .Methods The patients with moderate to severe cancer pain admitted to our hospital were included in the study and randomly divided into two groups according to the order of admission .The two groups were respectively given different treatment methods .The group A was given oxycodone hydrochloride as the control group and the group B received the therapy of oxycodone hydrochloride combined with the music therapy as the experimental group .The clinical efficacy ,dosage ,KPS score ,QOL score and adverse drug reactions were ana‐lyzed statistically .Results The pain degree after treatment in the two groups was significantly reduced compared with before treatment ,the difference was statistically significant(P0 .05) .Conclusion In clinical treatment of the patients with moderate to severe cancer pain ,oxycodone hydrochloride combined with the music therapy has definite analgesic effect ,easy op‐eration ,few adverse reactions and high security in alleviating cancer pain ,can effectively improve the live quality of patients ,provides a new elective mode for the clinical tumor analgesia and deserves to be clinically promoted and ap‐plied .%目的:探讨盐酸羟考酮联合音乐疗法对改善癌症患者疼痛的疗效。方法将该院肿瘤科收治的中重度癌痛患者纳入研究范围,按入院先后顺序随机分为两组,分别给予不同的治疗方法,A组给予盐酸羟考酮作为对照组,B组给予盐酸羟考酮联合音乐疗法作为试验组,对其临床疗效、用药剂量、功能状态评分、生活质量评分、药物不良反应进行统计学分析。结果两组患者疼痛程度均较治疗前显著减轻,两组比较差异有统计学意义(P<0.05);A组用药剂量大于B组,两组比较差异有统计学意义(P<0.05);两组患者治疗后功能状态评分

  9. Clinical comparative study of oxycodone sustained-release tablet versus morphine tablet in dose titration therapy on moderate and severe chronic cancer pain%羟考酮缓释片和吗啡片用于中重度癌痛滴定的对比研究

    Institute of Scientific and Technical Information of China (English)

    沈俊俊; 潘月芬; 钟丽萍; 齐全

    2016-01-01

    目的:观察比较羟考酮缓释片和吗啡片用于中重度癌痛滴定的疗效及不良反应。方法选取60例既往未使用阿片类药物的中重度癌痛患者,按随机数字表法分为两组羟考酮缓释片组和吗啡片组,每组30例。羟考酮缓释片组以羟考酮缓释片10 mg/次、1次/12 h行疼痛滴定,吗啡片组以吗啡片5或10 mg作为初始剂量按需给药行疼痛滴定,24 h后均转换为羟考酮缓释片,观察1周,记录疼痛控制情况及不良反应。结果滴定期间羟考酮缓释片组日爆发痛次数、日给药次数明显少于吗啡组[(1.27±1.53)次比(4.87±1.98)次、(3.37±1.78)次比(5.10±2.20)次],差异有统计学意义(P<0.05)。滴定后第1天羟考酮缓释片组疼痛缓解率明显高于吗啡片组[83.33%(25/30)比60.00%(18/30)],差异有统计学意义(P<0.05);而滴定后第3天两组疼痛缓解率比较差异无统计学意义(P>0.05)。滴定后第1天羟考酮缓释片组爆发痛发生率明显少于吗啡片组[23.33%(7/30)比53.33%(16/30)],疼痛达到稳态率明显高于吗啡片组[86.67%(26/30)比63.33%(19/30)],差异有统计学意义(P<0.05)。而两组滴定后第3天爆发痛发生率和疼痛达到稳态率、疼痛达到稳态所需时间、不良反应发生率比较差异无统计学意义(P>0.05)。结论羟考酮缓释片用于中重度癌痛滴定的疼痛缓解率及不良反应与吗啡片类似,但较吗啡片更快止痛,并减少滴定期间爆发痛次数,减轻患者滴定过程的痛苦,具有时效优势,值得应用推广。%Objective To observe the clinical effect and adverse reaction of oxycodone sustained-release tablet and morphine tablet in dose titration therapy on moderate and severe chronic cancer pain. Methods Sixty patients suffering from moderate and severe cancer pain, without using opioid drugs, were divided into oxycodone sustained

  10. 羟考酮/对乙酰氨基酚组合药物缓解术后急性疼痛有效性和安全性的 Meta分析%Effectivity and safety of oxycodone plus acetaminophen for postoperative acute pain relief:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    肖京平; 王国俊; 罗恒丽; 杨婷; 胡功利

    2015-01-01

    目的:系统评价羟考酮/对乙酰氨基酚术后急性疼痛治疗的有效性和安全性。方法计算机检索 PubM ed、EM‐base、MEDLINE(Ovid)、Cochrane图书馆、CNKI、万方等电子数据库,查找羟考酮/对乙酰氨基酚术后疼痛治疗的随机对照试验(RCT ),检索时间均从建库至2014年9月。对符合纳入标准的RCT ,由两位评价员按 Cochrane系统评价的方法,独立进行资料提取、质量评价并交叉核对后,采用RevMan 5.2软件进行Meta分析。结果本系统评价纳入19个研究,合计2213例患者。结果显示:羟考酮/对乙酰氨基酚组在疼痛缓解有效率上明显优于安慰剂组与单用同剂量羟考酮组(P<0.01),而与单用高剂量羟考酮组及单用对乙酰氨基酚组在疼痛缓解有效率上差异无统计学意义(P>0.05)。不良反应方面发生率,组合药物与单用羟考酮组相似,多于安慰剂组及单用对乙酰氨基酚组,但程度一般为轻度到中度,无因严重不良反应而退出治疗的报道。结论目前研究表明羟考酮/对乙酰氨基酚在缓解术后急性疼痛方面效果良好且安全性高。%Objective To assess the effectivity and safety of oxycodone plus acetaminophen for postoperative acute pain re‐lief .Methods Randomized controlled trials (RCT ) on combination of oxycodone plus acetaminophen treating postoperative pain re‐lief were searched from the following data‐bases as PubMed ,EMbase ,MEDLINE(Ovid) ,the Cochrane Library ,CNKI and WAN‐FANG from the date of their establishment to September 2014 .The data of RCT meeting the inclusive criteria were extracted ac‐cording to Cochrane methods by two reviewers independently ,and after the quality was evaluated and cross checked ,meta analyses were conducted using RevMan 5 .2 sotware .Results A total of 18 studies involving 2 213 patients were included .The results of Meta‐analyses showed that compared with

  11. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.

    Science.gov (United States)

    Armstrong, Scott C; Cozza, Kelly L

    2003-01-01

    Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column. These compounds have a very similar chemical structure to morphine. Unlike morphine, which is metabolized chiefly through conjugation reactions with uridine diphosphate glucuronosyl transferase (UGT) enzymes, these five drugs are metabolized both through oxidative reactions by the cytochrome P450 (CYP450) enzyme and conjugation by UGT enzymes. There is controversy as to whether codeine, dihydrocodeine, and hydrocodone are actually prodrugs requiring activation by the CYP450 2D6 enzyme or UGT enzymes. Oxycodone and buprenorphine, however, are clearly not prodrugs and are metabolized by the CYP450 2D6 and 3A4 enzymes, respectively. Knowledge of this metabolism assists in the understanding for the potential of drug-drug interactions with these drugs. This understanding is important so that clinicians can choose the proper dosages for analgesia and anticipate potential drug-drug interactions.

  12. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    Science.gov (United States)

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

  13. Clinical studies of severe cancer pain oxycodone hydrochloride sustained-release tablets in the treatment of%盐酸羟考酮缓释片治疗中重度癌痛的临床研究

    Institute of Scientific and Technical Information of China (English)

    李成彪; 王玉珮; 齐雪花; 罗艳琴

    2015-01-01

    ObjectiveTo observe the oral oxycodone hydrochloride sustained-release tablets were administered the back-ground of moderate to severe cancer pain titration, titration analysis of efficacy and safety in order to reasonably extended release formulation of oxycodone titration improve moderate to severe cancer pain pain, improve the quality of life of patients. Methods in April 2011 to June 2013 to 116 cases with moderate to severe cancer pain patients in this study, should be completed im-mediately BPI pain scale outbreak. Taking oxycodone hydrochloride sustained-release tablets 10mg one hour after pain assess-ment, such as pain can not be controlled, preclude the use of immediate-release morphine titrated until pain control. Record achieve pain control titration number of cycles needed, while also recording the life quality improvement and evaluation of drug safety before and after treatment. Selected results of 116 cases of cancer pain, moderate pain 104 cases, 12 patients with severe cancer pain, male 80 cases, female 36 cases, in the course of treatment, pain control to compare different sex ratio, chi-square value = 0.006, P=0.938, no significant difference difference; compare pain control rate of the different nature of pain, the chi-square value = 2.377, P=0.305 comparing the difference was not significant difference varying degrees of pain Comparison of pain control rate, chi-square value = 20.135, P=0.000, there was a significant difference comparing the difference; compare different ages pain control rate, the chi-square value = 0.041, P=0.839, comparing the difference was not significant differ-ence. Comparison of different intensity of pain titration period, t=-3.683, P=0.13, the degree of pain pain control cycle impact;the groups before and after comparison of complications, chi-square =33.294, P=0.000, patient into After the set of concurrent symptoms of nausea, vomiting accounted for 6.90%, accounting for 70.69 percent of constipation, urinary

  14. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

    Directory of Open Access Journals (Sweden)

    Setnik B

    2015-07-01

    Full Text Available Beatrice Setnik,1 Carl L Roland,1 Kenneth W Sommerville,1,2 Glenn C Pixton,1 Robert Berke,3,4 Anne Calkins,5 Veeraindar Goli1,2 1Pfizer Inc, 2Duke University Medical Center, Durham, NC, USA; 3Family Health Medical Services PLLC, Mayville, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN using a standardized conversion guide. Methods: This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results: Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%. The mean (standard deviation number of days to stable dose was 20 (8.94, and number of titration steps to stable dose was 2.4 (1.37. The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion: Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of

  15. Translational Advances in Pain and Anesthesia for Cancer Patients

    Science.gov (United States)

    2012-01-01

    morphine , hydromorphone, oxycodone, fentanyl, and methadone) as well as agonist antagonists (e.g., buprenorphine, butorphanol, penta zocine, dezocine...opioids and other drugs are converted to active molecules in the body, and multiple SNPs have been identified that affect the metabolism of codeine...enzyme to metabolize drugs. Patients with two non functional alleles are poor metabolizers and exhibit decreased drug response and altered drug

  16. 盐酸羟考酮控释片联合普瑞巴林治疗癌性神经病理性疼痛的临床研究%Clinical study of oxycodone hydrochloride controlled-release tablets combined with pregabalin in the treatment of malignant neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    陈强; 李焕丽; 何斐; 郭素香

    2014-01-01

    目的:观察盐酸羟考酮控释片联合普瑞巴林治疗癌性神经病理性疼痛的临床疗效及不良反应。方法选择疼痛门诊治疗的癌性疼痛患者87例,口服盐酸羟考酮控释片1周,并进行随访调查。接受治疗患者第8天11点数字分级法评定( NRS)﹤4入A组,继续给予羟考酮治疗2周;NRS≥4随机入B1、B2组,B1组继续服用羟考酮2周, B2组联合普瑞巴林治疗2周。观察三组患者的疼痛评分及不良反应情况。结果84例(96.55%)完成第一阶段治疗。在第二阶段A组、B1组、B2组分别有28、27、26例患者。三组疼痛评分第15天均降低,第22天无改善,B2组比B1组第22天疼痛评分降低,但差异无统计学意义(P﹥0.05)。B2组羟考酮用量比B1组明显减少(P﹤0.05)。三组不良反应观察中便秘发生率最高,分别为17.9%、29.6%、34.6%。结论盐酸羟考酮控释片联合普瑞巴林治疗癌性神经病理性疼痛疗效明确,能够减少盐酸羟考酮控释片用量,是治疗癌性疼痛性价比较高的方案。%Objective To observe the clinical effect and adverse reactions of oxycodone hydro-chloride controlled-release tablets combined with pregabalin in the treatment of malignant neuropathic pain. Methods Eighty-seven patients with cancer pain admitted in pain clinic were chose,oxycodone hydro-chloride controlled-release tablets were orally given for 1 week,and the patients were followed-up. On the eighth day,patients with numeric rating scale( NRS)﹤4 were enrolled in group A,and were given oxyc-odone treatment for another 2 weeks. Patients with NRS≥4 were randomly divided into group B1 and group B2,the patients in group B1 were given oxycodone for another 2 weeks,and patients in group B2 were given combined treatment of oxycodone and pregabal for 2 weeks. The pain scores and adverse reactions were ob-served among the three groups. Results Eighty-four patients( 96. 55%)completed the

  17. Implications of Sensorineural Hearing Loss With Hydrocodone/Acetaminophen Abuse

    OpenAIRE

    Novac, Andrei; Iosif, Anamaria M.; Groysman, Regina; Bota, Robert G.

    2015-01-01

    Sensorineural hearing loss is an infrequently recognized side effect of pain medication abuse. Chronic pain patients treated with opiates develop different degrees of tolerance to pain medications. In many cases, the tolerance becomes the gateway to a variety of cycles of overuse and unmasking of significant psychiatric morbidity and mortality. An individualized approach utilizing combined treatment modalities (including nonopiate pharmaceuticals) is expected to become the norm. Patients can ...

  18. Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives.

    Science.gov (United States)

    Koopmans, Gineke; Simpson, Karen; De Andrés, Javier; Lux, Eberhard Albert; Wagemans, Michel; Van Megen, Yvonne

    2014-11-01

    The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated in patients with moderate-to-severe chronic cancer-related or non-cancer pain. All patients had opioid-induced constipation (OIC) which persisted despite substantial laxative therapy. This pooled analysis included 75 patients with OIC at study entry that was refractory to at least two laxatives with different modes of action. Patients completed randomized, double-blind treatment with OXN PR 20-120 mg/day for either 12 weeks (OXN 9001: non-cancer pain study) or 4 weeks (OXN 2001: cancer-related pain study). Analgesia and bowel function were assessed using the Brief Pain Inventory Short Form and Bowel Function Index (BFI), respectively. Use of laxative medication and safety were assessed throughout the studies. NCT00513656, EudraCT 2005-002398-57, EudraCT 2005-003510-15. Statistically and clinically significant improvements in bowel function were observed following double-blind treatment with OXN PR. Mean (SD) reduction in BFI score was 21.2 (28.8) and comparable in patients with cancer-related (19.0 [28.9]) and non-cancer pain (23.3.[29.0]; P ≤ 0.0002). Furthermore, the proportion of patients with a BFI score within normal range (≤28.8) increased from 9.5% at screening to 43.1% at Day 15 of OXN PR. While all patients used ≥2 laxatives of different classes at screening, during study treatment 36% stopped using laxatives (P PR provided effective analgesia, evidenced by stable pain scores during study treatment, and there were no unanticipated adverse events. OXN PR significantly improved bowel function and reduced the use of laxatives in patients with OIC, previously unresponsive to at least two different classes of laxatives. OXN also provided effective analgesia for patients with moderate-to-severe cancer-related pain and non-cancer-related pain.

  19. 普瑞巴林联合羟考酮治疗骨转移性癌痛临床研究%CLINICAL STUDY ON THE EFFECT OF COMBINED USE OF PREGABALIN AND OXYCODONE ON THE PAINS CAUSED BY OSSEOUS METASTATIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    上官世金

    2014-01-01

    Objective To analyze the clinical effect of the combined use of pregabalin and oxycodone on the pains caused by osseous metastatic carcinoma .Methods 92 patients with the pains caused by osseous metastatic carcinoma were randomly assigned into two groups .The contrast group was treated with oxyc‐odone ,while the experimental group was treated with the combined use of pregabalin and oxycodone .The frequency of the attacks of pain in patients ,the dosage for relieving pain and the side effects were recor‐ded .The degree of pains and the quality of patients’ life were evaluated .Results There existed significant difference in the degree of pains ,the dosage for relieving pain and the quality of patients’ life between the two groups( P <0 .05) .Conclusion The combined use of pregabalin and oxycodone can produce good clini‐cal effect on the pains caused by osseous metastatic carcinoma .%目的:探讨普瑞巴林联合羟考酮治疗骨转移性癌痛的临床效果。方法将92名骨转移性癌痛患者随机分为两组。对照组单纯应用羟考酮,试验组给予普瑞巴林联合羟考酮。记录两组患者爆发痛发生人次、解救药用量及副作用,评估疼痛程度评分及总体生活质量。结果治疗后两组患者疼痛程度评分、平均解救药用量及生活质量总体评分较治疗前差异均有统计学意义(P <0.05)。结论普瑞巴林联合羟考酮治疗转移性骨癌痛比单纯应用羟考酮治疗转移性骨癌痛更安全有效。

  20. Comparative of Therapeutic Efficacy of Oxycodone Hydrochloride Sustained-release Tablets vs. Morphine Sulfate Sustained-release Tablets for Severe Cancer Pain Control with Rectal Administration%盐酸羟考酮缓释片与硫酸吗啡缓释片直肠给药控制重度癌性疼痛的疗效比较

    Institute of Scientific and Technical Information of China (English)

    滕箭; 杨梅英; 沈季元; 王建华; 毛睿

    2012-01-01

    目的:比较盐酸羟考酮缓释片与硫酸吗啡缓释片经直肠给药治疗重度癌性疼痛的疗效和不良反应.方法:将102例伴有中、重度疼痛的癌症患者随机分为A组(50例)与B组(52例),分别经直肠给予盐酸羟考酮缓释片和硫酸吗啡缓释片,比较2组药物起效时间、癌痛类型和药品不良反应的差异.结果:A组患者治疗1、3h时的疼痛与B组同期比较,差异有统计学意义(P<0.05),2组内脏痛和躯体痛比较差异分别有统计学意义(P<0.05),2组的不良反应如恶心、呕吐、便秘比较分别有显著性差异(P<0.05),A组均优于B组.结论:盐酸羟考酮缓释片经直肠给药控制重度癌性疼痛,安全、有效、简便.%OBJECTIVE: To compare the efficacy and adverse drug reactions of oxycodone hydrochloride sustained-release tablets (Oxycontin, Oxycodone hydrochloride prolonged-release tablets) and Morphine sulfate sustained-release tablets (MS Contin, Morphine sulfate) with rectal administration in the treatment of severe cancer pain. METHODS: Clinical information of 102 cases of moderate to severe cancer pain were analyzed, and they were divided into 2 groups. 50 cases were given oxycodone hydrochloride sustained-release tablets with rectal administration group A and 52 cases were given morphine sulfate sustained-release tablets group B. The differences of onset time, the type of cancer pain and side effects were compared between 2 groups. RESULTS: There was statistical significance in the difference of cancer pain between 2 groups, after 1 h and 3 h treatment (P<0.05), there were statistical significance in the differences of visceral pain and somatic pain between 2 groups (P<0.05) ; there were significant differences in adverse drug reactions between 2 groups, such as nausea, vomiting, constipation (P<0.05), and group A was better than group B. CONCLUSION: As for non-hospitalized patients, dying patients and not oral due to various reasons, transrectal

  1. Evaluation of Patient Migration Patterns and Related Health Care Costs Within a National Medicare Advantage Prescription Drug Plan After Implementation of an Oxycodone HCl Extended-Release Access Restriction.

    Science.gov (United States)

    Chen, Chi-Chang; De, Ajita P; Sweet, Brian; Wade, Rolin L

    2017-08-01

    Health plans use formulary restrictions (e.g., prior authorization, step therapy, tier change, nonformulary status) in an effort to control cost and promote quality, safety, and appropriate prescription utilization. Some Medicare payers perceive that the inclusion of certain agents, such as branded oxycodone HCl extended-release tablets (OERs), on their formularies is associated with attracting high-cost members to the plan. To evaluate disenrollment rates, patient migration, and subsequent health care costs among OER users who disenrolled from a national Medicare Advantage Prescription Drug plan (study-MAPD) in the plan year following OER nonformulary restriction. A retrospective, longitudinal cohort study using IMS pharmacy and medical claims data between July 1, 2011, and December 31, 2014, was conducted. In the study-MAPD, adults aged ≥ 18 years who were chronic OER users with ≥ 2 OER claims 6 months before the nonformulary restriction date on January 1, 2013 (index date) and with continuous activity in pharmacy and medical claims for 6 months pre- and post-index were included in the study. Comparison years of 2012 and 2014 prerestriction/postrestriction were selected. All groups were followed for 6 months postindex. Year-to-year disenrollment rates of OER patients and the overall plan, as well as patient characteristics and costs of those who disenrolled from and those who remained with the plan, were measured. Costs were compared using a difference-in-differences approach. This study identified 2,935 eligible OER users from the study-MAPD population after imposing nonformulary restrictions on OERs on January 1, 2013. Mean age was 62.1 years, and 59.8% were female. The mean Charlson Comorbidity Index score was 1.83 for those 1,001 patients with medical claims data. For comparison years 2012 (prerestriction) and 2014 (postrestriction), 2,248 and 2,222 OER patients were identified, respectively. Patient characteristics were similar across patient cohorts in

  2. 盐酸羟考酮控释片治疗老年癌痛体会%Treatment for cancerous pain in the elderly with Oxy-Codone hydrochloride controlled-release tablets.

    Institute of Scientific and Technical Information of China (English)

    刘彦芳; 刘端祺; 李红英; 张侠

    2010-01-01

    Objective To evaluate effectiveness and side effects, as well as its safety, of Oxy-Codone hydrochloride controlled-release tablets (Oxycontin) for the elderly patients with moderate to severe cancerous pain. Methods From March 2005 to February 2009,106 elderly patients ( aged more than 60 years) suffered from moderate to severe cancerous pain were treated with Oxycontin,at initial dose of 10 mg/12 h. For the patients using making them pain-free or pain relieved mostly. Every patient was treated for 4 weeks at least. Severity of pain,sleeping status, appetite, fatigue, mental status, daily life, scores of understanding and cooperation, and side effects were .observed.Results The minimal effective dose of Oxycontin was 10 mg/d for the elderly patients with cancerous pain. Twenty-three patients (21.7%) were treated with it at dose of ≥200 mg/d,30 patients (28. 2% )at dose of 100 - 180 mg/d,and 53 patients (50. 0% ) at dose of 10 -90 mg/d. Pain was relieved in 97. 16% of the patients after treatment, with common side effects of constipation, nausea, vomiting;and drug treatment was needed for 24. 53% (26/106) of the patients with more common constipation. Conclusions Oxycontin is effective,tolerable,less side-effects for the elderly patients with moderate to severe cancerous pain, and can improve their quality of life.%目的 观察盐酸羟考酮控释片(商品名:奥施康定),治疗老年恶性肿瘤患者中、重度疼痛的临床效果及不良反应,明确该药在治疗老年癌痛中的有效性及安全性.方法 2005年3月至2009年2月中、重度疼痛老年恶性肿瘤患者(年龄≥60岁)106例,给予盐酸羟考酮控释片镇痛治疗,初始剂量10 mg/12 h,正在用吗啡类镇痛药者,按照口服吗啡1/2剂量换算,根据疼痛情况调整剂量,直至患者无痛或基本无痛,每位患者至少治疗4周以上.同时进行疼痛强度、睡眠、食欲、疲乏、精神状态、日常生活、理解配合程度评

  3. 羟考酮与舒芬太尼用于胸腔镜肺癌根治术后病人静脉镇痛效果的比较%Efficacy of oxycodone versus sufentanil for intravenous analgesia after radical resection of pulmonary carcinoma performed via video-assisted thoracoscope

    Institute of Scientific and Technical Information of China (English)

    张云霄; 陈冀衡; 范志毅; 刘英华; 姚月勤; 孔国华

    2015-01-01

    目的 比较羟考酮与舒芬太尼用于胸腔镜肺癌根治术后病人静脉镇痛的效果.方法 择期行胸腔镜肺癌根治术病人154例,年龄18 ~ 64岁,性别不限,BMI 18~25 kg/m2,ASA分级Ⅰ或Ⅱ级.采用随机数字表法,将其分为2组:舒芬太尼组(S组,n=76)和羟考酮组(O组,n=78).2组均接受静吸复合麻醉.术后当VAS评分≥4分时,2组分别静脉注射舒芬太尼5μg或羟考酮2 mg,必要时重复给药,直至VAS评分≤3分,随后进行PCIA,镇痛至术后48 h,S组PCIA泵药液配方为托烷司琼20 mg+舒芬太尼200 μg,用生理盐水稀释至100 ml;0组PCIA泵药液配方为托烷司琼20mg+羟考酮50 mg,用生理盐水稀释至100 ml,背景输注速率1 ml/h,PCA剂量2 ml,锁定时间10 min,维持VAS评分≤3分,当VAS评分≥4分时肌肉注射吗啡10 mg补救镇痛.记录补救镇痛情况、病人镇痛满意度及镇痛有关不良事件的发生情况.结果 与S组比较,O组恶心和呕吐的发生率降低(P<0.05),术后补救镇痛率、病人镇痛满意度、头晕和镇静过度的发生率差异无统计学意义(P>0.05).2组未见呼吸抑制和皮肤瘙痒发生.结论 与舒芬太尼比较,羟考酮用于胸腔镜肺癌根治术后病人静脉镇痛时可达到相似的镇痛效果,且恶心和呕吐发生率较低.%Objective To compare the efficacy of oxycodone versus sufentanil for intravenous analgesia after radical resection of pulmonary carcinoma performed via video-assisted thoracoscope.Methods One hundred fifty-four patients of both sexes, aged 18-64 yr, with body mass index of 18-25 kg/m2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , scheduled for elective radical resection of pulmonary carcinoma performed via video-assisted thoracoscope, were randomly divided into either sufentanil group (group S, n=76) or oxycodone group (group O, n =78) using a random number table.The 2 groups received combined intravenous-inhalational anesthesia.When postoperative

  4. 羟考酮注射液滴定法在急诊创伤后疼痛处理的临床观察%Clinical application of oxycodone hydrochloride injection with titration to analgesia after emergency treatment of post-trau-matic preoperative pain management

    Institute of Scientific and Technical Information of China (English)

    缪小勇; 徐葭; 曹建平

    2015-01-01

    Objective To investigate the efficacy and safety of oxycodone hydrochloride injection with titration to analgesic after emer-gency treatment of post-traumatic preoperative pain management. Methods Totally 120 cases of post-traumatic acute severe pain (VAS>80),titration of oxycodone injection to deal with the pain of patients. SBP,DBP,HR,RR,SpO2 of the patient with medication after 5,10,15,20 minutes were observed and recorded. The VAS values,ramesay sedation scores after 5,10,15,20 minutes were eval-uated and recorded. The rate of adverse reaction happened cases of patients with nausea,vomiting,respiratory depression,urinary reten-tion were Recorded. Total consumption of patients with oxycodone was calculated. Results SBP,DBP,HR had declined obviously of all time points after the treatment of,the difference was statistically significant (P0. 05). Delivery after the observation indexes were within the normal range. VAS pain score of stat-ic,dynamic to different time points after the treatment were significantly lower,the difference was statistically significant (P80)患者120例,采用羟考酮注射液滴定法对患者的疼痛进行处理,观察并记录患者给药后5、10、15、20 min各时间点的收缩压( SBP)、舒张压( DBP)、心率( HR)、呼吸频率( RR)、脉搏氧饱和度( SpO2 );评判并记录给药后5、10、15、20 min各时间点的静态、动态VAS值,Ramesay镇静评分;记录患者恶心、呕吐、呼吸抑制、尿潴留等不良反应发生率;计算患者羟考酮的总用量. 结果 与给药前比较,给药后各时间点的SBP、DBP、HR有明显下降,差异有统计学意义(P0. 05);给药后各项呼吸循环观察指标均在正常范围之内. 给药后各时间点的静态、动态VAS疼痛评分均有明显下降,差异有统计学意义( P<0. 05 );给药后10、15 min两个时间点患者的静态疼痛达到缓解标准;镇静评分有明显差异,差异有统计学意义( P <0. 05 );发生恶心6 (5. 0%)

  5. Effects of Oxycodone Hydrochloride Controlled-release Tablets on Cancer-relate Pain following Different Routes of Administration%盐酸羟考酮缓释片不同给药途径治疗癌痛的临床观察

    Institute of Scientific and Technical Information of China (English)

    尹卫华; 范惠珍; 夏红梅; 陈凤舞; 李丽华; 樊松; 何健; 庄小捷; 陈金平

    2013-01-01

    目的 观察盐酸羟考酮缓释片口服给药与直肠给药2种途径治疗癌痛的疗效和不良反应.方法 选择宜春市人民医院肿瘤科2012年2月至2013年2月收治的癌症晚期患者60例,按随机数字表法将60例患者分为口服给药组和直肠给药组,每组30例,比较2种给药途径的缓解疼痛的疗效、改善患者生活质量以及不良反应发生情况.结果 口服给药组疼痛缓解有效率为93.3%,直肠给药组有效率为90.0%,疗效和生活质量的改善相当,2组比较差异无统计学意义(P>0.05);直肠给药组消化道不良反应低于口服给药组,2组比较差异有统计学意义(P<0.05).结论 直肠给药与口服给药止痛效果相当;直肠给药不良反应少,对于胃肠道梗阻、意识障碍的患者,不失为一种简单方便、安全有效的方法.%Objective To compare the curative efficacy and side effect of orally and rectally administered oxycodone hydrochloride controlled-release tablets in cancer-relate pain.Methods Sixty advanced cancer patients treated in Yichun People's Hospital between February 2012 and February 2013 were randomly administered oxycodone hydrochloride controlled-release tablets via oral route (oral administration group,n=30) or rectal route (rectal administration group,n=30).Pain relief,quality of life and side effect were compared between the two groups.Results The effectiveness of pain relief was 93.3% in oral administration group and 90.0% in rectal administration group.There were no significant differences in the improvement in the efficacy and quality of life between the two groups (P>0.05)).However,the incidence of gastrointestinal adverse reactions in rectal administration group was significantly lower than that in oral administration group (P<0.05).Conclusion There was no obvious difference in the effectiveness of pain relief between orally and rectally administered oxycodone hydrochloride controlled-release tablets

  6. 盐酸羟考酮缓释片治疗胃癌患者中重度癌痛的临床疗效观察%Efficacy of Oxycodone Hydrochloride Controlled Release Tablet in the Treatment of Gastric Cancer Patients with Moderate to Severe Cancer Pain

    Institute of Scientific and Technical Information of China (English)

    赵松峰; 张亚玲; 张晓; 师秀琴; 张祥; 张晓坚

    2016-01-01

    Objective To observe efficacy and toxicities of oxycodone hydrochloride controlled release tablet in the treatment of gastric cancer patients with moderate to severe cancer pain. Methods The 135 cases of gastric cancer patients with moderate to severe cancer pain were was administrated with oxycodone hydrochloride controlled release tablet. The starting dose was 10 to 20 mg every 12 h,the dose was adjusted according to pain degree. Every patients were treated for two weeks. The pain relief,quality of life and toxicities were evaluated after treatment. Re-sults For the 135 patients,the NRS score after treatment(1. 68 ± 0. 98)was lower than that before treatment (7. 22 ± 2. 13)(P ﹤ 0. 05). The cancer pain relief rate was 92. 6% . The improvement rate of quality of life was 74. 1% . The main toxicities were light degree nausea and vomiting,constipation drowsiness. Conclusion Oxyc-odone hydrochloride controlled release tablet can control cancer pain and improve quality of life in the treatment of gastric cancer patients with moderate to severe cancer pain,and has good safety.%目的:探讨盐酸羟考酮缓释片用于胃癌患者中重度癌痛的临床疗效和毒副反应。方法135例胃癌中重度癌痛患者均接受口服盐酸羟考酮缓释片控制癌痛,初始剂量10~20 mg/次,q12 h,用药过程中根据疼痛评估情况进行剂量调整,直至癌痛控制良好。2周后采取 NRS 评分法进行疼痛评分,并观察疼痛缓解情况、生活质量、药物毒副反应等。结果所有135例患者治疗后 NRS 评分为(1.68±0.98)分,明显低于治疗前的(7.22±2.13)分,差异有统计学意义(P ﹥0.05)。治疗后总疼痛缓解率为92.6%。生活质量改善率为74.1%。主要毒副反应为恶心呕吐、便秘、嗜睡等,均为轻度,未影响治疗的顺利进行。结论盐酸羟考酮缓释片用于胃癌患者能够良好控制中重度癌痛,明显改善患者的生活质量,且用药较为安全。

  7. Application of Preemptive Analgesia of Transversus Abdominis Plane Blocking Combined with Oxycodo-ne Hydrochloride in Myomectomy Under Laparoscope%腹横筋膜平面阻滞联合盐酸羟考酮超前镇痛在腹腔镜子宫肌瘤核除术中的应用

    Institute of Scientific and Technical Information of China (English)

    郝晓燕; 韩利平; 高守琳

    2016-01-01

    Objective To study the application of preemptive analgesia of TAP blocking combined with oxycodone hydrochloride in myomectomy under laparoscope.Methods Our hospital selected 60 cases of patients to undergo myo-mectomy under laparoscope and randomly divided them into two groups:T and D groups.T group was treated with TAP blocking under ultrasonic guidance after anesthesia and before skin incision and intravenous injection of 0.1 mg/kg oxyc-odone hydrochloride before ending of the surgery.D group was treated with intravenous injection of 1μg/kg remifentanil before ending of the surgery.The patients’ VAS and Ramsay scores as well as the occurrence rate of adverse reaction and the satisfaction of postoperative analgesia of two group patients were recorded at 2 hours, 4 hours, 8 hours, 12 hours and 24 hours after the surgery, respectively.Results VAS of T group was significantly lower than that of D group, while Ramsay score had no statistical difference.The occurrence rate of adverse event of T group was lower than that of D group and the satisfaction rate of analgesia was higher than D group.Conclusions Preemptive analgesia of TAP blocking com-bined with oxycodone hydrochloride in myomectomy under laparoscope can mitigate the patients’ postoperative pain and increase the satisfaction of postoperative analgesia.Besides, it has lower occurrence rate of adverse reaction after opera-tions.%目的:研究腹横筋膜平面阻滞联合盐酸羟考酮超前镇痛在腹腔镜子宫肌瘤核除术中的应用。方法选择腹腔镜下子宫肌瘤核除术患者60例,随机分为两组,T组和D组。 T组在麻醉后切皮前于超声引导下行TAP阻滞和手术结束前给予盐酸羟考酮0.1 mg/kg静脉推注;D组于手术结束前给予芬太尼1μg/kg静脉推注。分别记录术后2 h、4 h、8 h、12 h、24 h患者的VAS评分和Ramsay评分,及两组患者不良反应的发生率和术后镇痛满意度。结果 T组患者的VAS评分明显低

  8. 芬太尼透皮贴剂与盐酸羟考酮缓释片治疗中重度癌痛疗效和安全性的Meta分析%Meta-analysis of Curative Effect and Safety of Transdermal Fentanyl and Oxycodone Hydrochloride Sustained-release Tablets in the Treatment of Moderate and Severe Cancer Pain

    Institute of Scientific and Technical Information of China (English)

    刘思; 余正; 胡霞

    2015-01-01

    Objective: To evaluate the curative effect and safety of transdermal fentanyl and oxycodone hy-drochloride sustained-release tablets in the treatment of moderate and severe cancer pain . Methods: Based on the literature review from CNKI and Wanfang database and med . Wanfang data , literature and information were ex-tracted according to certain inclusion and exclusion criteria. Data was analyzed using RevMan 5.3 software. Results:A total of 4 research papers involved 635 cases were included . The results of meta-analysis showed that the inci-dence of pain remission was not significantly different between the two groups using transdermal fentanyl and oxy-codone hydrochloride sustained-release tablets [ RR=0 . 99 , 95%CI ( 0 . 94 , 1 . 04 ) , P=0 . 72 ] . No significant difference was found between the two groups in the incidence of constipation [ RR=0 . 83 , 95%CI ( 0 . 53 , 1 . 28 ) , P=0 . 39 ] , dizzi-ness [ RR=0 . 85 , 95%CI ( 0 . 46 , 1 . 57 ) , P=0 . 61 ] , somnolence [ RR=0 . 49 , 95%CI ( 0 . 22 , 1 . 06 ) , P=0 . 07 ] , urinary reten-tion [ RR=0 . 53 , 95%CI ( 0 . 15 , 1 . 89 ) , P=0 . 33 ] and mental disorder [ RR=0 . 72 , 95%CI ( 0 . 29 , 1 . 78 ) , P=0 . 47 ] , except the incidence of nausea and vomitting [ RR=0 . 45 , 95%CI ( 0 . 26 , 0 . 76 ) , P=0 . 003 ] , with incidence of 6 . 03%( 17/282 ) and 11 . 33%( 40/353 ) respectively . Conclusion: Transdermal fentanyl and oxycodone hydrochloride sustained-release tablets had similar efficacy in the treatment of moderate and severe cancer pain . The incidence of nausea and vomit-ing caused by transdermal fentanyl was lower than oxycodone hydrochloride sustained-release tablets but the safety of the two drugs are similar .%目的:评价芬太尼透皮贴剂和盐酸羟考酮缓释片治疗中重度癌痛的临床疗效和安全性。方法:检索CNKI、万方数据库和万方医学网获得相关文献,按照一定的纳入和排除标准筛选文献并提取信息,采用RevMan 5.3软件进

  9. Effect of Oxycodone on multimodality postoperative analgesia and the quality of awakening in panhys-terectomy%羟考酮用于全子宫切除术后多模式镇痛的效果及对苏醒质量的影响

    Institute of Scientific and Technical Information of China (English)

    王冰; 杨海慧; 李长科

    2016-01-01

    Objective To observe the effect of Fentanyl combing with oxycodone to cure postoperative analgesia and the quality of awakening in hysterectomy and compare with fentanyl alone. Method 60 patients( ASA Ⅰ ~ Ⅱ )acceptted gyneco-logical laparoscopic hysterectomy were divided into two groups randomly:fentanyl group(F group,n = 30)and the group of oxyc-odone combined with fentanyl(OF group,n = 30). Two groups were given tracheal cannula and intravenous anesthesia. F group was given fentanyl 2μg / kg by intravenous injection,OF group were given oxycodone 0. 1mg / kg and fentanyl 1μg / kg by the same way when beginning sewing skin and the drugs given were diluted to 10 ml in 0. 9% saline. MAP 、HR 、SpO2 before drug and 10 min 、20 min、30 min after drugwere recorded;Recording the time from Discontinuation to spontaneous breathing recovery, to orientation recovery and to extubation. Scales of VAS and RASS of 1 h、2 h、4 h、8 h after operation were recorded. And degree of satisfaction and adverse reactions were recorded too. Results MAP,HR,SpO2 were no significant difference in two groups(P> 0. 05). Scales of VAS and RASS of OF group was significantly lower than that in F group(P > 0. 05),Adverse reactions were no significant difference in two groups(P > 0. 05). Degree of satisfaction in OF group were significantly higher than that in F group. Conclusion Fentanyl combined with oxycodone for postoperative analgesia of laparoscopic hysterectomy are safe and effec-tive,the degree of satisfaction of patients was higher than fentanyl.%目的:观察羟考酮联合芬太尼用于妇科腔镜下行全子宫切除术患者术后镇痛的效果及对苏醒质量的影响,并与单独使用芬太尼比较。方法:选择妇科腔镜下全子宫切除术患者60例,随机平均分为芬太组(F 组)和羟考酮联合芬太尼组(OF 组)。两组均采用气管插管、全凭静脉麻醉。开始缝皮时 F 组静脉滴注芬太尼2μg/ kg,OF

  10. 加巴喷丁联合低剂量盐酸羟考酮缓释片治疗老年糖尿病周围神经痛的随机对照研究%GABAPENTIN COMBINED WITH LOW DOSE PROLONGED-RELEASE OXYCODONE HYDROCHLORIDE FOR THE TREATMENT OF ELDERLY PATIENTS WITH DIABETIC PERIPHERAL NEUROPATHIC PAIN

    Institute of Scientific and Technical Information of China (English)

    张春驰; 李小梅; 董艳娟; 何跃

    2013-01-01

    Objective:To observe and evaluate the analgesic efficacy and safety of gabapentin combined with low dose prolonged-release oxycodone hydrochloride for the treatment of diabetic peripheral neuropathic pain (DPNP).Method:A total of 70 elderly patients with DPNP were randomized into 2 groups (each contains 35 cases),one accepted gabapentin monotherapy (G1),and the other received both gabapentin and low dose prolonged-release oxycodone hydrochloride (G2).The initial dose of gabapentin was 100 mg/d and gradually titrated.The dose of prolonged-release oxycodone hydrochloride was fixed at 10 mg/q 12 h,and the therapy keeps 2 weeks.VAS was evaluated before and at the 8th and 15th day of the treatment.Side effects were observed and recorded.Results:Totally 62 (G1 =30,G2 =32) patients completed the 2 weeks treatment.Basic characteristics have no significant difference including mean VAS scores between the 2 groups.After the treatment,the total rate of pain relief at the 8th and 15th day were significantly higher in G 1 compared with G2 (P < 0.05) and the rate of excellent pain relief in G1 was higher than G2 at the 8th day (P < 0.05).The mean daily dose of gabapentin at the 8th day have no significant difference between G1 and G2,but at the 15th day,G2 was significant higher than G1 (P < 0.05).The occurrence rate of constipation in G2 was obviously higher compared with G1 (P < 0.05).Conclusion:Gabapentin monotherapy or combined with low dose Prolongedrelease oxycodone hydrochloride could effectively release elderly patients' DPNP,and the efficacy of the combination therapy was better,but should give preventive measures to constipation.%目的:观察加巴喷丁联合低剂量盐酸羟考酮缓释片治疗老年糖尿病周围神经痛(diabeticperipheral neuropathic pain,DPNP)的疗效及安全性.方法:70例老年DPNP患者随机均分为两组(n=35),分别接受2周加巴喷丁单药(单药组)或加巴喷丁联合低剂量盐酸羟考酮缓释

  11. The clinical observation of dexmedetomidine combined with oxycodone or fentanyl during brachial plexus blockade in the thyroid surgery%右美托咪定复合羟考酮或芬太尼辅助颈丛阻滞的临床观察

    Institute of Scientific and Technical Information of China (English)

    邴彦秋; 高光洁; 徐迎阳; 尚宇

    2016-01-01

    Objective To investigate the effect of small dose of dexmedetornidine on venous continuous infusion combined with oxycodone or fentanyl during brachial plexus blockade.Methods Sixty thyroid patients (ASA Ⅰ or Ⅱ) undergone brachial plexus anesthesia for cutting or cutting thyroid tumor patients were randomly and double-blindly into three groups (n =20 in each group).Group A:single brachial plexus anesthesia;group B:dexmedetornidine combined with fentanyl;group C:dexmedetornidine combined with oxycodone.Blood pressure (Bp),heart rate (HR),the determination of plasma norepinephrine (NE),cortisol (Cor),the concentration of blood glucose (Glu),VAS,Ramsay calm score,local anesthetics dosage and side effect formation rate at the beginning operation (To),skin incision (T1),separation of the glands (T2),gland excision (T3),and the end of the surgery (T4) were recorded.Results Compared to group A,the mean arterial pressure (MAP),HR,NE,Cor,and Glu were much lower at each time point (P < 0.05) in groups B and C;Ramsay calm score and VAS score were significantly better at each time point (P < 0.05);the incidence of chills and lidocaine additional quantity were significantly lower (P <0.01).However,compared to groups A and C,choking cough response rates were much higher in group B (P < 0.01).Conclusions Small dose of dexmedetornidine on venous continuous infusion combined with oxycodone during brachial plexus blockade for thyroid patients both can eliminate the preoperative patients nervous anxiety,and effectively restrain perioperative stress response,maintain hemodynamics stable,implementation of intraoperative awaken to reduce complications.It is the new choice of anesthetic adjuvant.%目的 探析小剂量右美托咪啶静脉持续输注复合羟考酮或芬太尼辅助颈丛阻滞的应用效果.方法 60例ASA Ⅰ~Ⅱ级行甲状腺次全切或全切的甲状腺瘤患者,均行单侧颈深丛和双侧颈浅丛阻滞,随机双盲抽签方法均分为三组:

  12. 肋间神经阻滞联合盐酸羟考酮超前镇痛在胸腔镜肺叶切除术中的观察应用%Observation Application of Preemptive Analgesia with Intercostal Nerve Blocking Combined with Oxyc-odone Hydrochloride in Thoracoscopic Surgery of Pulmonary Lobectomy

    Institute of Scientific and Technical Information of China (English)

    郝晓燕; 王群超; 赵华国

    2016-01-01

    目的:研究肋间神经阻滞联合盐酸羟考酮超前镇痛在胸腔镜肺叶切除术的应用效果。方法2014年11月-2015年11月择期进行胸腔镜肺叶切除术患者60例,随机分为两组,实验组和对照组。实验组在麻醉后切皮前于超声引导下行肋间神经阻滞和手术结束前给予盐酸羟考酮0.1 mg/kg静脉推注;对照组于手术结束前给予芬太尼1μg/kg静脉推注。分别记录麻醉诱导前(T0)、手术结束时(T1)、拔管时(T2)、拔管后30 min(T3)、拔管后2 h(T4)、拔管后4 h( T5)的血压、心率、脉氧饱和度及两组患者的呼吸恢复时间,睁眼时间及气管导管的拔出时间,以及两组患者恶心呕吐等不良反应的发生率。评价患者于T3、T4、T5时视觉模拟评分( VAS)。结果对照组呼吸恢复时间、睁眼时间和气管导管拔出时间明显较实验组长,差异有显著性。两组患者在T0、T1时SBP、DBP、HR无统计学意义,T2到T5对照组SBP、DBP、HR明显升高,和实验组有显著差异;T3到T5时实验组患者的VAS评分明显低于对照组,差异有显著性。结论肋间神经阻滞联合盐酸羟考酮超前镇痛可以有效的防止胸腔镜肺叶切除术引起的术后疼痛,减少不良反应的发生。%Objective To study the application effect of preemptive analgesia with intercostal nerve blocking com-bined with oxycodone hydrochloride in thoracoscopic surgery of pulmonary lobectomy.Methods Our hospital selected 60 cases of patients to undergo thoracoscopic surgery of pulmonary lobectomy from November 2014 to November 2015 and randomly divided them into two groups:experimental group and control group.The experimental group was treated with intercostal nerve blocking under ultrasonic guidance after anesthesia and before skin incision and intravenous injec-tion of 0.1 mg/kg oxycodone hydrochloride before ending of the surgery.The control group was treated with

  13. Rewarding electrical brain stimulation in rats after peripheral nerve injury: decreased facilitation by commonly abused prescription opioids.

    Science.gov (United States)

    Ewan, Eric E; Martin, Thomas J

    2011-12-01

    Prescription opioid abuse is a significant concern in treating chronic pain, yet few studies examine how neuropathic pain alters the abuse liability of commonly abused prescription opioids. Normal and spinal nerve ligated (SNL) rats were implanted with electrodes into the left ventral tegmental area (VTA). Rats were trained to lever press for intracranial electrical stimulation (VTA ICSS), and the effects of methadone, fentanyl, hydromorphone, and oxycodone on facilitation of VTA ICSS were assessed. A second group of neuropathic rats were implanted with intrathecal catheters, and the effects of intrathecal clonidine, adenosine, and gabapentin on facilitation of VTA ICSS were assessed. The effects of electrical stimulation of the VTA on mechanical allodynia were assessed in SNL rats. Responding for VTA ICSS was similar in control and SNL rats. Methadone, fentanyl, and hydromorphone were less potent in facilitating VTA ICSS in SNL rats. Oxycodone produced a significant facilitation of VTA ICSS in control (maximum shift 24.10 ± 6.19 Hz) but not SNL rats (maximum shift 16.32 ± 7.49 Hz), but also reduced maximal response rates in SNL rats. Intrathecal administration of clonidine, adenosine, and gabapentin failed to facilitate VTA ICSS in SNL rats, and electrical stimulation of the VTA did not alter mechanical allodynia following nerve injury. The present data suggests that the positive reinforcing effects of commonly abused prescription opioids are diminished following nerve injury. In addition, alleviation of mechanical allodynia with nonopioid analgesics does not appear to stimulate limbic dopamine pathways originating from the VTA in SNL rats.

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

    Science.gov (United States)

    Feng, Xiu-qin; Zhu, Ling-ling; Zhou, Quan

    2017-01-01

    Background Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs). Method A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Results Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8%) were conducted in healthy volunteers, whereas 10 RCTs (19.2%) enrolled true patients. None of the opioid–drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine–P2Y12 inhibitors, morphine–gabapentin, and methadone–zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin–opioids (morphine, tramadol, oxycodone, methadone), quinidine–opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone), antimycotics–opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol), protease inhibitors–opioids (ritonavir, ritonavir/lopinavir–oxycodone, ritonavir–fentanyl, ritonavir–tilidine), grapefruit juice–opioids (oxycodone, fentanyl, methadone), antidepressants–opioids (paroxetine–tramadol, paroxetine–hydrocodone, paroxetine–oxycodone, escitalopram–tramadol), metoclopramide–morphine, amantadine–morphine, sumatriptan–butorphanol nasal sprays, ticlopidine–tramadol, St John’s wort–oxycodone, macrolides/ketolides–oxycodone, and levomepromazine–codeine. RCTs investigating the same combination, almost unanimously, drew consistent conclusions, except two RCTs on amantadine–intravenous morphine combination

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

    Science.gov (United States)

    Feng, Xiu-Qin; Zhu, Ling-Ling; Zhou, Quan

    2017-01-01

    Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs). A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8%) were conducted in healthy volunteers, whereas 10 RCTs (19.2%) enrolled true patients. None of the opioid-drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine-P2Y12 inhibitors, morphine-gabapentin, and methadone-zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin-opioids (morphine, tramadol, oxycodone, methadone), quinidine-opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone), antimycotics-opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol), protease inhibitors-opioids (ritonavir, ritonavir/lopinavir-oxycodone, ritonavir-fentanyl, ritonavir-tilidine), grapefruit juice-opioids (oxycodone, fentanyl, methadone), antidepressants-opioids (paroxetine-tramadol, paroxetine-hydrocodone, paroxetine-oxycodone, escitalopram-tramadol), metoclopramide-morphine, amantadine-morphine, sumatriptan-butorphanol nasal sprays, ticlopidine-tramadol, St John's wort-oxycodone, macrolides/ketolides-oxycodone, and levomepromazine-codeine. RCTs investigating the same combination, almost unanimously, drew consistent conclusions, except two RCTs on amantadine-intravenous morphine combination where a different amantadine dose was used and two RCTs on morphine

  16. 76 FR 82302 - Determination That HYCODAN (Hydrocodone Bitartrate and Homatropine Methylbromide) Tablets, 5...

    Science.gov (United States)

    2011-12-30

    .... SUPPLEMENTARY INFORMATION: In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act... March 23, 1943. In 1982, a Drug Efficacy Study Implementation review concluded that HYCODAN syrup..., among other items, drug products that have been discontinued from marketing for reasons other...

  17. Characterization of the Human Proteomic Response to Hydrocodone: A Preliminary Study

    Science.gov (United States)

    2014-05-01

    Drug testing in oral fluid, Clin Biochem Rev 27 (2006) 147-159. [24] Alcohol and Substance Abuse Measurement Instrument Collection, Addiction ...multidose administration of mixed salt amphetamine preparation, J. Anal. Toxicol. 28 (2004) 563-574. [42] A.T. Rodriguez, S. Valtier, J.T. Cody...by the National Survey of Drug Use and Health, the Drug Abuse Warning Network (DAWN) and the National Center on Addiction and Substance Abuse have

  18. Drug: D08047 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ) USP drug classification [BR:br08302] Analgesics Opioid Analgesics, Long-acting Hydromorphone D08047 Hydromorphone (INN) Opioid Anal...gesics, Short-acting Hydromorphone D08047 Hydromorphone

  19. Treatment of chronic pain in older people: evidence-based choice of strong-acting opioids.

    Science.gov (United States)

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

    2012-08-01

    In the treatment of chronic malignant and non-malignant pain, opioids are used as strong analgesics. Frail elderly patients often have multiple co-morbidities and use multiple medicines, leading to an increased risk of clinically relevant drug-drug and drug-disease interactions. Age-related changes and increased frailty may lead to a less predictable drug response, increased drug sensitivity, and potential harmful drug effects. As a result, physicians face a complex task in prescribing medication to elderly patients. In this review, the appropriateness of the strong-acting opioids buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone and tapentadol is determined for use in elderly patients. Evidence-based recommendations for prescribing strong opioids to the frail elderly are presented. A literature search was performed for all individual drugs, using a validated and published set of 23 criteria concerning effectiveness, safety, pharmacokinetics and pharmacodynamics, experience, and convenience in elderly patients. First, information on the criteria was obtained from pharmaceutical reference books and a MEDLINE search. The information obtained on the individual drugs in the class of opioids was compared with the reference drug morphine. Evidence-based recommendations were formulated on the basis of the pros and cons for the frail elderly. Using the set of 23 criteria, no differentiation can be made between the appropriateness of buprenorphine, fentanyl, hydromorphone, morphine and oxycodone for use in elderly patients. Methadone has strong negative considerations in the treatment of chronic pain in the frail elderly. Methadone has a high drug-drug interaction potential and is associated with prolongation of the QT interval and a potential risk of accumulation due to a long elimination half-life. In addition, methadone is difficult to titrate because of its large inter-individual variability in pharmacokinetics, particularly in the frail elderly

  20. Prescription Opioid Usage and Abuse Relationships: An Evaluation of State Prescription Drug Monitoring Program Efficacy

    Directory of Open Access Journals (Sweden)

    Richard M. Reisman

    2009-01-01

    Full Text Available Context: The dramatic rise in the use of prescription opioids to treat non-cancer pain has been paralleled by increasing prescription opioid abuse. However, detailed analyses of these trends and programs to address them are lacking.Objective: To study the association between state shipments of prescription opioids for medical use and prescription opioid abuse admissions and to assess the effects of state prescription drug monitoring programs (PDMPs on prescription opioid abuse admissions.Design and Setting: A retrospective ecological cohort study comparing state prescription opioid shipments (source: Automation of Reports and Consolidated Orders Systems database and inpatient admissions for prescription opioid abuse (source: Treatment Episode Data Set in 14 states with PDMPs (intervention group and 36 states without PDMPs (control group for the period 1997–2003.Results: From 1997 to 2003, oxycodone, morphine, and hydrocodone shipments increased by 479%, 100%, and 148% respectively. Increasing prescription oxycodone shipments were significantly associated with increasing prescription opioid admission rates (p 0.001. PDMP states had significantly lower oxycodone shipments than the control group. PDMP states had less increase in prescription opioid admissions per year (p = 0.063. A patient admitted to an inpatient drug abuse rehabilitation program in a PDMP state was less likely to be admitted for prescription opioid drug abuse (Odds ratio = 0.775, 95% Confidence Interval 0.764–0.785.Conclusions: PDMPs appear to decrease the quantity of oxycodone shipments and the prescription opioid admission rate for states with these programs. Overall, opioid shipments rose significantly in PDMP states during the study period indicating a negligible “chilling effect” on physician prescribing.

  1. An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.

    Science.gov (United States)

    Kimishima, Atsushi; Wenthur, Cody J; Zhou, Bin; Janda, Kim D

    2017-01-20

    Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design. Administration of these vaccines resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.

  2. Use of opioids in long-term management of temporomandibular joint dysfunction.

    Science.gov (United States)

    Bouloux, Gary F

    2011-07-01

    The long-term treatment of patients with chronic temporomandibular joint dysfunction has been challenging. The long-term use of opioids in these patients can be neither supported nor refuted based on current evidence. However, evidence is available to support the long-term use of opioids in other chronic noncancer pain states with reduced pain, improved function, and improved quality of life. One group of patients with chronic temporomandibular joint pain, for whom both noninvasive and invasive treatment has failed, might benefit from long-term opioid medication. The choices include morphine, fentanyl, oxycodone, tramadol, hydrocodone, and methadone. Adjunct medication, including antidepressant and anticonvulsant drugs, can also be used. The safety of these medications has been well established, but the potential for adverse drug-related behavior does exist, requiring appropriate patient selection, adequate monitoring, and intervention when needed.

  3. Drug: D00839 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available e (TN) C17H19NO3. HCl 321.1132 321.7986 D00839.gif Analgesic [narcotic] ATC code: N02AA03 opioids mu-opioid ...m alkaloids N02AA03 Hydromorphone D00839 Hydromorphone hydrochloride (USP) USP drug classification [BR:br08302] Analgesics Opioid Ana...hydrochloride (USP) Opioid Analgesics, Short-acting Hydromorphone D00839 Hydromorphone hydrochloride (USP) T...lgesics, Long-acting Hydromorphone D00839 Hydromorphone

  4. Drug: D02154 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02154 Mixture, Drug Aspirin - oxycodone hydrochloride - oxycodone terephthalate mi...xt; Percodan (TN) Oxycodone hydrochloride [DR:D00847], Oxycodone terephthalate [DR:D03783], Aspirin [DR:D001... and derivatives N02BA51 Acetylsalicylic acid, combinations excl. psycholeptics D02154 Aspirin - oxycodone hydrochloride - oxycodone terephthalate mixt PubChem: 7849215 ...

  5. 78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

    Science.gov (United States)

    2013-04-18

    ..., 2011. 10. CDC, ``Integrated Prevention Services for HIV Infection, Viral Hepatitis, Sexually... HIV and hepatitis B and C infection risk (Ref. 10). Further, as stated in the OxyContin labeling (see...

  6. Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer

    Science.gov (United States)

    2012-11-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  7. 77 FR 40069 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Science.gov (United States)

    2012-07-06

    ... implementation, or to review product names, to avoid look-alike and sound-alike names that may lead to medication... medication errors may have been due to the visual similarity of the container labels and carton labeling of... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND...

  8. Bioequivalence Study of Paracetamol and Hydrocodone Bitartrate Tablets%氨酚氢可酮片的生物等效性研究

    Institute of Scientific and Technical Information of China (English)

    谭广山; 郭瑞臣

    2014-01-01

    目的:评价两种氨酚氢可酮片的生物等效性.方法:以市售氨酚氢可酮片为参比制剂,以自制氨酚氢可酮片为受试制剂,采用双制剂双周期交叉试验设计,在健康男性(n=20)体内进行药动学研究,清洗期为1周.分别于每一周期给药前和给药后各时间点取肘静脉血,分离血浆.分别采用高效液相色谱(HPLC)法测定对乙酰氨基酚、液质联用(LC-MS/MS)法测定氢可酮的血药浓度,计算两者的药动学参数和相对生物利用度,评价受试制剂与参比制剂的生物等效性.结果:受试制剂l和参比制剂中对乙酰氨基酚的主要药动学参数t1/2分别为(3.900± 1.926)、(4.088±1.731)h,tmax分别为(0.775±0.197)、(0.763±0.190)h,cmax分别为(15.932±3.695)、(16.952±3.939)μ g/ml,AUC0-24h分别为(64.270 ±26.625)、(64.723±26.297)μg· h/ml,AUC0-∞分别为(67.716±33.219)、(67.661±33.150)μg· h/ml;受试制剂中对乙酰氨基酚的相对生物利用度为(100.9±14.5)%.受试制剂和参比制剂中氢可酮的主要药动学参数t1/2分别为(5.377±0.862)、(5.318±1.382)h,tmax分别为(1.438±0.590)、(1.513±0.604)h,cmax分别为(21.722±6.102)、(20.572±5.380) ng/ml,AUC0-24h分别为(135.493±33.835)、(133.009±30.810) μg· h/ml,AUC0-∞分别为(142.386±35.767)、(139.243± 31.540)μg· h/ml;受试制剂中氢可酮相对生物利用度为(102.9 ±16.9)%.结论:两种氨酚氢可酮片生物等效.

  9. Drug: D05312 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05312 Drug Oxycodone (USAN/INN) C18H21NO4 315.1471 315.3636 D05312.gif Analgesic [...ds N02AA05 Oxycodone D05312 Oxycodone (USAN/INN) USP drug classification [BR:br08302] Analgesics Opioid Analgesic...s, Long-acting Oxycodone D05312 Oxycodone (USAN/INN) Opioid Analgesics, Shor

  10. Drug Take Back in Hawai‘i: Partnership Between the University of Hawai‘i Hilo College of Pharmacy and the Narcotics Enforcement Division

    Science.gov (United States)

    Batz, Forrest; Juarez, Deborah Taira; Ladao, Lani C

    2014-01-01

    Unused/unwanted medications in households and patient care facilities expose vulnerable populations, including children, elders, and pets, to potential harm through inadvertent ingestion, as well as the potential for theft and assault. Hawai‘i Administrative Rules prohibit the return of any prescription medications to retail pharmacies after dispensing. The Hawai‘i Narcotics Enforcement Division (NED) partnered with the University of Hawai‘i at Hilo Daniel K. Inouye College of Pharmacy (CoP) in eleven Drug Take Back events throughout the state. Most participants heard of the events via newspaper and television marketing. The most common methods of medication disposal are via trash or down household drains. Over 8,000 lbs of unused/unwanted medications was collected, identified and logged from 2011 through 2012. The majority of returned drugs were non-controlled substances (90%). Commonly returned medications included prescription cardiac medications such as simvastatin and lisinopril, non-prescription analgesics such as aspirin and ibuprofen, and dietary supplements such as vitamins and iron. Commonly returned controlled substance medications included narcotics such as hydrocodone/acetaminophen combinations and oxycodone, and sedative hypnotics such as zolpidem and lorazepam. PMID:24470984

  11. Most drug overdose deaths from nonprescription opioids

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2016-12-01

    Full Text Available No abstract available. Article truncated at 150 words. The Centers for Disease Control (CDC is reporting in Morbidity and Mortality Weekly that the number of people dying from an opioid overdose rose 15.5% from 2014 to 2015, but the increase had little to do with prescription painkillers such as oxycodone or hydrocodone (1. Roughly 52,000 people died from drug overdoses in 2015 and of those deaths 33,091 involved an opioid. The increases in “death rates were driven by synthetic opioids other than methadone (72.2%, most likely illicitly-manufactured fentanyl, and heroin (20.6%”. Deaths from methadone, which is usually prescribed by physicians, decreased 9.1%. The largest increase in deaths occurred in the South and Northeast with 3% and 24% increases in deaths from synthetic opioids from 2014 to 2015. In the Midwest and West, there were more modest 17% and 9% increases during the same period. States in the Southwest with “good” to “excellent” reporting included Colorado, Nevada, and New …

  12. Detection of drugs of forensic importance in postmortem bone.

    Science.gov (United States)

    McGrath, Kelly K; Jenkins, Amanda J

    2009-03-01

    There is a paucity of literature detailing the disposition of drugs in bone and bone marrow. Infrequently, in deaths involving skeletonized remains, fragmentation, decomposition, and exsanguination, traditional specimens may be unavailable for toxicological testing. This study examined the utility of bone for the detection of benzodiazepines, opiates, cocaine and metabolites, and basic drugs in 39 cases. Cases were identified on the basis of a positive blood result. After specimen preparation, samples were assayed by liquid-liquid or solid phase extraction with gas chromatographic and gas chromatographic mass spectrometric detection. The majority of decedents were white males with 28% of individuals between the ages of 41 to 50 years. The cause of death was drug intoxication in 22 cases. The most prevalent drugs detected in the blood males and females were opiates and bases. Morphine, codeine, and oxycodone were detected in bone, whereas 6-acetylmorphine and hydrocodone were absent. For alkaline extractable drugs, in only 57% of blood positive specimens, the corresponding bone was also positive. These included antidepressants and antihistamines. Diazepam and nordiazepam were detected in the bone of all blood positive cases. Bone concentrations were higher than blood levels. Benzoylecgonine was the most common cocaine analyte detected in bone. These data demonstrated that drugs may be detected in bone using current technologies and that in general concentrations were higher than those observed in corresponding blood specimens. A negative result in bone, however, should be interpreted with caution because multiple factors determine the deposition of a drug in this matrix.

  13. The use of major analgesics in patients with renal dysfunction.

    Science.gov (United States)

    Niscola, Pasquale; Scaramucci, Laura; Vischini, Gisella; Giovannini, Marco; Ferrannini, Michele; Massa, Pasquale; Tatangelo, Paola; Galletti, Massimo; Palumbo, Roberto

    2010-06-01

    Pain in patients with impaired renal function may be a significant problem requiring treatment with opioids. However, pharmacokinetic and metabolic changes associated with an impaired renal function may raise some concerns about side effects and overdosing associated with opioid agents in this patient's population. In order to give recommendations on this issue, we review the available evidences on the pharmacokinetics and side effects of most common opioids used to treat pain. The results of this review show that the half-life of the parent opioid compounds and of their metabolites is increased in the presence of renal dysfunction, for which careful monitoring of the patient, dose reduction and a longer time interval between doses are recommended. Among opioids, morphine and codeine used with very caution and possibly avoided in renal failure/dialysis patients; tramadol, hydromorphone and oxycodone can be used with caution and close patient's monitoring, whereas transdermal buprenorphine, methadone and fentanyl/sufentanil appear to be safe to use in patients with renal failure.

  14. mu-opioid receptor-stimulated synthesis of reactive oxygen species is mediated via phospholipase D2.

    Science.gov (United States)

    Koch, Thomas; Seifert, Anja; Wu, Dai-Fei; Rankovic, Marija; Kraus, Jürgen; Börner, Christine; Brandenburg, Lars-Ove; Schröder, Helmut; Höllt, Volker

    2009-08-01

    We have recently shown that the activation of the rat mu-opioid receptor (MOPr, also termed MOR1) by the mu-agonist [D-Ala(2), Me Phe(4), Glyol(5)]enkephalin (DAMGO) leads to an increase in phospholipase D2 (PLD2) activity and an induction of receptor endocytosis, whereas the agonist morphine which does not induce opioid receptor endocytosis fails to activate PLD2. We report here that MOPr-mediated activation of PLD2 stimulates production of reactive oxygen molecules via NADH/NADPH oxidase. Oxidative stress was measured with the fluorescent probe dichlorodihydrofluorescein diacetate and the role of PLD2 was assessed by the PLD inhibitor D-erythro-sphingosine (sphinganine) and by PLD2-small interfering RNA transfection. To determine whether NADH/NADPH oxidase contributes to opioid-induced production of reactive oxygen species, mu-agonist-stimulated cells were pre-treated with the flavoprotein inhibitor, diphenylene iodonium, or the specific NADPH oxidase inhibitor, apocynin. Our results demonstrate that receptor-internalizing agonists (like DAMGO, beta-endorphin, methadone, piritramide, fentanyl, sufentanil, and etonitazene) strongly induce NADH/NADPH-mediated ROS synthesis via PLD-dependent signaling pathways, whereas agonists that do not induce MOPr endocytosis and PLD2 activation (like morphine, buprenorphine, hydromorphone, and oxycodone) failed to activate ROS synthesis in transfected human embryonic kidney 293 cells. These findings indicate that the agonist-selective PLD2 activation plays a key role in the regulation of NADH/NADPH-mediated ROS formation by opioids.

  15. [Opioids in chronic osteoarthritis pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration].

    Science.gov (United States)

    Schaefert, R; Welsch, P; Klose, P; Sommer, C; Petzke, F; Häuser, W

    2015-02-01

    The efficacy, tolerability and safety of opioid therapy in chronic osteoarthritis (OA) pain is under debate. We updated a Cochrane systematic review on the efficacy and safety of opioids in chronic OA pain published in 2009. We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in chronic osteoarthritis (OA) pain. We included double-blind randomized placebo-controlled studies lasting ≥ 4 weeks. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. We included 20 RCTs with 33 treatment arms and 8545 participants. Median study duration was 12 (4-24) weeks. Oxycodone and tramadol were each tested in six studies; buprenorphine, hydromorphone, morphine and tapentadol each in two studies and codeine, fentanyl and oxymorphone in one study each. Results are reported with 95 % confidence intervals (CIs). Opioids were superior to placebo in reducing pain intensity (SMD - 0.22 [- 0.28, - 0.17], p SpringerLink (under "Supplemental").

  16. [Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration].

    Science.gov (United States)

    Petzke, F; Welsch, P; Klose, P; Schaefert, R; Sommer, C; Häuser, W

    2015-02-01

    The efficacy and safety of opioid therapy in chronic low back pain (CLBP) is under debate. We updated a recent systematic review on the efficacy and safety of opioids in CLBP. We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CLBP. We included double-blind randomized placebo-controlled studies of at least 4 weeks duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. We included 12 RCTs with 17 treatment arms and 4375 participants. Median study duration was 12 (4-16) weeks. Of the 17 treatment arms, seven (41.2 %) used oxycodone; four (23.6 %) tramadol; buprenorphine and oxymorphone were each used in two (11.8 %) and hydromorphone and tapentadol each in one (5.8 %). The results for studies with parallel/cross-over design were as follows (with 95 % confidence interval, CI): opioids were superior to placebo in reducing pain intensity (SMD - 0.29 [- 0.37, - 0.21], p SpringerLink (under "Supplemental").

  17. The Comparative Risk of Delirium with Different Opioids: A Systematic Review.

    Science.gov (United States)

    Swart, Lieke M; van der Zanden, Vera; Spies, Petra E; de Rooij, Sophia E; van Munster, Barbara C

    2017-06-01

    There is substantial evidence that the use of opioids increases the risk of adverse outcomes such as delirium, but whether this risk differs between the various opioids remains controversial. In this systematic review, we evaluate and discuss possible differences in the risk of delirium from the use of various types of opioids in older patients. We performed a search in MEDLINE by combining search terms on delirium and opioids. A specific search filter for use in geriatric medicine was used. Quality was scored according to the quality assessment for cohort studies of the Dutch Cochrane Institute. Six studies were included, all performed in surgical departments and all observational. No study was rated high quality, one was rated moderate quality, and five were rated low quality. Information about dose, route, and timing of administration of the opioid was frequently missing. Pain and other important risk factors of delirium were often not taken into account. Use of tramadol or meperidine was associated with an increased risk of delirium, whereas the use of morphine, fentanyl, oxycodone, and codeine were not, when compared with no opioid. Meperidine was also associated with an increased risk of delirium compared with other opioids, whereas tramadol was not. The risk of delirium appeared to be lower with hydromorphone or fentanyl, compared with other opioids. Numbers used for comparisons were small. Some data suggest that meperidine may lead to a higher perioperative risk for delirium; however, high-quality studies that compare different opioids are lacking. Further comparative research is needed.

  18. Restless legs syndrome: a new entity of neuropathic pain? Treatment with prolonged release oxycodone/naloxone combination

    Directory of Open Access Journals (Sweden)

    Gemignani F

    2016-04-01

    Full Text Available Franco Gemignani,1 Andrea Melpignano,1,2 Giulia Milioli,1,2 Silvia Riccardi,1,2 Liborio Parrino1,2 1Neurology Unit, Department of Neurosciences, University of Parma, Parma, Italy; 2Sleep Disorders Center, Department of Neurosciences, University of Parma, Parma, Italy Abstract: Restless legs syndrome (RLS is a disorder of sensorimotor integration characterized by an urge to move the legs when at rest, especially at night or in the evening, which is relieved by movement. Sensory symptoms may be prominent, often exhibiting features consistent with neuropathic pain. Iron deficiency and genetic factors are implicated in RLS causation in most patients. The pathogenetic model of impaired circadian dopaminergic modulation of sensorimotor integration circuitry at the spinal level is fitting with the co-occurrence of movement disorders, sensory symptoms, and sleep disruption in RLS. Accordingly, levodopa and dopamine agonists are effective for RLS symptoms, which compensate for the impaired descending control by diencephalo-spinal dopa(minergic pathway. Dopamine agonists are usually indicated as the first-line therapy, but their use in long-term treatment is often complicated by augmentation and impulse control disorder, thus alpha-2-delta ligands also are now considered the first line of treatment. It has been recognized that endogenous opioid system is also involved in the mechanisms generating RLS, possibly through an impaired modulation of pain pathways. Opioids can be considered as an alternative therapy, particularly in patients with augmentation and/or refractory to other treatments. Recently introduced prolonged-release oxycodone–naloxone was efficacious for short-term treatment of patients with severe RLS inadequately controlled with previous treatment. It will be important to assess whether opioids, as well as other drugs, are especially effective in definite RLS subtypes such as the painful phenotype. Keywords: small fiber neuropathy, allodynia, hyperalgesia

  19. Doctor shopping reveals geographical variations in opioid abuse.

    Science.gov (United States)

    Nordmann, Sandra; Pradel, Vincent; Lapeyre-Mestre, Maryse; Frauger, Elisabeth; Pauly, Vanessa; Thirion, Xavier; Mallaret, Michel; Jouanjus, Emilie; Micallef, Joëlle

    2013-01-01

    Prescription opioid abuse is not homogeneous due to varying patterns of use and different geographic preferences. Because doctor shopping is one of the main sources of diversion, it has previously been used to estimate drug abuse. The aim of this study was to describe and compare opioid abuse in 2008 using doctor shopping to estimate abuse in 3 French regions. Data for this study came from the General Health Insurance (GHI) reimbursement database, which covers 77% of the French population. All individuals living in Provence-Alpes-Cote d'Azur-Corse (PACA), Rhone-Alpes (RA), or Midi-Pyrenees (MP) that received at least one reimbursement for oral opioids from the GHI in 2008 were included. Oral opioids under study were opioids for mild to moderate pain (dextropropoxyphene, codeine, tramadol, dihydrocodeine), opoids for moderately severe to severe pain (oral morphine, oxycodone, buprenorphine painkiller, hydromorphone), and opioid maintenance treatments (buprenorphine maintenance, methadone). For a given opioid, the Doctor Shopping Quantity (DSQ) is the quantity obtained by overlapping prescriptions from several prescribers. It is used to estimate the magnitude of abuse. The Doctor Shopping Indicator (DSI) is the DSQ divided by the total dispensed quantity. It is used to estimate the abuse corrected for use. The total DSQ for opioids in PACA (213.3 DDD/1,000 inhabitants) was twofold superior to that in RA (115.1 DDD/1,000) and in MP (106.2 DDD/1,000). The DSQ of opioids for mild to moderate pain was 75.5DDD/1000 (DSI=1.1%), 19.7DDD/1,000 (DSI=5.0%) for opioids for moderately severe to severe pain, and 55.3DDD/1,000 (DSI=6.2%) for opioid maintenance treatments. Emergent signals of abuse have been observed at a regional level for oxycodone in MP and dihydrocodeine in RA and MP. The main limitation of this study is that the GHI reimbursement database provides information about dispensed and reimbursed prescription drugs, and not necessarily the actual quantity used. These

  20. The opioid abuse and misuse epidemic: implications for pharmacists in hospitals and health systems.

    Science.gov (United States)

    Cobaugh, Daniel J; Gainor, Carl; Gaston, Cynthia L; Kwong, Tai C; Magnani, Barbarajean; McPherson, Mary Lynn; Painter, Jacob T; Krenzelok, Edward P

    2014-09-15

    The current epidemic of prescription opioid abuse and misuse in the United States is discussed, with an emphasis on the pharmacist's role in ensuring safe and effective opioid use. U.S. sales of prescription opioids increased fourfold from 1999 to 2010, with an alarming rise in deaths and emergency department visits associated with the use of fentanyl, hydrocodone, oxycodone, and other opioid medications. Signs and symptoms of opioid toxicity may include altered mental status, hypoventilation, decreased bowel motility, central nervous system and respiratory depression, peripheral vasodilation, pulmonary edema, hypotension, bradycardia, and seizures. In patients receiving long-term opioid therapy for chronic pain, urine drug testing is an important tool for monitoring and assessment of therapy; knowledge of opioid metabolic pathways and assay limitations is essential for appropriate use and interpretation of screening and confirmatory tests. In recent years, there has been an increase in federal enforcement actions against pharmacies and prescription drug wholesalers involved in improper opioid distribution, as well as increased reliance on state-level prescription drug monitoring programs to track patterns of opioid use and improper sales. Pharmacies are urged to implement or promote appropriate guidelines on opioid therapy, including the use of pain management agreement plans; policies to ensure adequate oversight of opioid prescribing, dispensing, and waste disposal; and educational initiatives targeting patients as well as hospital and pharmacy staff. Pharmacists in hospitals and health systems can play a key role in recognizing the various forms of opioid toxicity and in preventing inappropriate prescribing and diversion of opioids. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  1. Community-based opioid overdose prevention programs providing naloxone - United States, 2010.

    Science.gov (United States)

    2012-02-17

    Drug overdose death rates have increased steadily in the United States since 1979. In 2008, a total of 36,450 drug overdose deaths (i.e., unintentional, intentional [suicide or homicide], or undetermined intent) were reported, with prescription opioid analgesics (e.g., oxycodone, hydrocodone, and methadone), cocaine, and heroin the drugs most commonly involved . Since the mid-1990s, community-based programs have offered opioid overdose prevention services to persons who use drugs, their families and friends, and service providers. Since 1996, an increasing number of these programs have provided the opioid antagonist naloxone hydrochloride, the treatment of choice to reverse the potentially fatal respiratory depression caused by overdose of heroin and other opioids. Naloxone has no effect on non-opioid overdoses (e.g., cocaine, benzodiazepines, or alcohol) . In October 2010, the Harm Reduction Coalition, a national advocacy and capacity-building organization, surveyed 50 programs known to distribute naloxone in the United States, to collect data on local program locations, naloxone distribution, and overdose reversals. This report summarizes the findings for the 48 programs that completed the survey and the 188 local programs represented by the responses. Since the first opioid overdose prevention program began distributing naloxone in 1996, the respondent programs reported training and distributing naloxone to 53,032 persons and receiving reports of 10,171 overdose reversals. Providing opioid overdose education and naloxone to persons who use drugs and to persons who might be present at an opioid overdose can help reduce opioid overdose mortality, a rapidly growing public health concern.

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

    Science.gov (United States)

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

    2017-06-01

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

  3. An internet survey of 2,596 people with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Turk Dennis C

    2007-03-01

    Full Text Available Abstract Background This study explored the feasibility of using an Internet survey of people with fibromyalgia (FM, with a view to providing information on demographics, sources of information, symptoms, functionality, perceived aggravating factors, perceived triggering events, health care utilization, management strategies, and medication use. Methods A survey questionnaire was developed by the National Fibromyalgia Association (NFA in conjunction with a task force of "experts in the field". The questionnaire underwent several rounds of testing to improve its face validity, content validity, clarity and readability before it was mounted on the internet. The questionnaire consisted of 121 items and is available online at the website of the National Fibromyalgia Association. Results The questionnaire was completed by 2,569 people. Most were from the United States, with at least one respondent from each of the 50 states. Respondents were predominantly middle-aged Caucasian females, most of whom had FM symptoms for ≥ 4 years. The most common problems were morning stiffness, fatigue, nonrestorative sleep, pain, concentration, and memory. Aggravating factors included: emotional distress, weather changes, insomnia, and strenuous activity. Respondents rated the most effective management modalities as rest, heat, pain medications, antidepressants, and hypnotics. The most commonly used medications were: acetaminophen, ibuprofen, naproxen, cyclobenzaprine, amitriptyline, and aspirin. The medications perceived to be the most effective were: hydrocodone preparations, aprazolam, oxycodone preparations, zolpidem, cyclobenzaprine, and clonazepam. Conclusion This survey provides a snap-shot of FM at the end of 2005, as reported by a self-selected population of people. This descriptive data has a heuristic function, in that it identifies several issues for further research, such as the prescribing habits of FM health care providers, the role of emotional

  4. Exploring the Etiologic Factors and Dynamics of Prescription Drug Abuse in Southwest Virginia

    Directory of Open Access Journals (Sweden)

    Kerry J Redican

    2012-12-01

    Full Text Available Background: Prescription drug abuse in Southwest Virginia is a serious problem affecting indi-viduals, families, and communities. The aim of this study was to characterize and understand the extent of the prescription drug abuse problem in Southwest, Virginia as well as the dynamics that surround that abuse. More specifically, the study focused on learning the extent of the problem along with which prescription drugs are typically used prior to entering treatment, reasons for prescription drug and methadone abuse, and the sources for prescription drug use, misuse and abuse.Methods: Mixed methodology was employed which included surveying methadone clinic con-sumers at two treatment clinics in Southwest, Virginia and seven focus field interviews of key community stakeholders.Results: The extent of prescription drug abuse is high and that the demographics of prescription drug users are getting younger and now involve more males than females. Oxycodone, hydroco-done, methadone, and morphine were the most commonly used drugs prior to enrollment in the clinics with over one-half of methadone-maintained consumers reporting that they had abused benzodiazepines along with opioids. Focus groups and clinic consumer data highlighted the key etiological factors in prescription drug abuse: use (due to workforce related injuries turning to abuse, wanting to get high, overprescribing and physician issues, lack of information, and cultural acceptance of drug taking as problem solving behavior. The two most common sources for the abused prescription drugs were physicians and street dealers.Conclusions: A constellation of conditions have led to the epidemic of prescription drug abuse in Southwest Virginia, including poverty, unemployment and work-related injuries, besides, public health education programs on the dangers of prescription opiate misuse and abuse are urgently needed.

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

    Science.gov (United States)

    Cone, Edward J

    2006-06-01

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

  6. Determination of opioid analgesics in hair samples using liquid chromatography/tandem mass spectrometry and application to patients under palliative care.

    Science.gov (United States)

    Musshoff, Frank; Lachenmeier, Katrin; Trafkowski, Jens; Madea, Burkhard; Nauck, Friedemann; Stamer, Ulrike

    2007-10-01

    Hair testing procedures allow a cumulative reflection of long-term drug abuse and are useful as a test for compliance in clinical toxicology. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to determine analgesic opioid drugs in hair samples. The procedure used a simple methanolic extraction, and the evaporated extract was analyzed directly. A selective and sensitive procedure for the simultaneous determination of bisnortilidine, nortilidine, tilidine, buprenorphine, codeine, oxycodone, fentanyl, norfentanyl, hydromorphone, morphine, normorphine, oxymorphone, methadone, piritramide, and tramadol was developed and fully validated. The method fulfilled validation criteria and was shown to be sensitive, with limits of detection ranging from 0.008 to 0.017 ng/mg hair matrix, and precision ranging between 3.1% and 14.9 %. The applicability of the method was shown by analysis of authentic hair samples from patients receiving opioids for the treatment of cancer pain (eg, fentanyl was detected in concentrations up to 0.292 ng/mg, tramadol in concentrations up to 0.612 ng/mg of hair of 1 patient). Hair analysis was shown to be a complementary and useful tool in monitoring the drug-taking behavior of patients consuming opioid analgesics for the treatment of pain. In self-reports and medical records especially, the ingestion of tramadol and methadone was found to be dramatically underreported. In summary, hair analyses gave important additional information for the medical treatment of patients, the results often coming as a surprise to even the attending physicians.

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

    Science.gov (United States)

    Lauche, R; Klose, P; Radbruch, L; Welsch, P; Häuser, W

    2015-02-01

    We updated a systematic review on the comparative efficacy, tolerability and safety of opioids and of their routes of application in chronic noncancer pain (CNCP). We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CNCP. We included randomized head-to-head comparisons of opioids (opioid of the sponsor of the study versus standard opioid) of at least 4 week's duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. The quality of evidence was rated by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included 13 RCTs with 6748 participants. Median study duration was 15 weeks (range 4-56 weeks). Hydromorphone, morphine, oxymorphone and tapentadol were compared to oxycodone; fentanyl to morphine and buprenorphine to tramadol. In pooled analysis, there were no significant differences between the two groups of opioids in terms of mean pain reduction (low-quality evidence), the patient global impression to be much or very much improved outcome (low-quality evidence), physical function (very low-quality evidence), serious adverse events (moderate-quality evidence) or mortality (moderate-quality evidence). There was no significant difference between transdermal and oral application of opioids in terms of mean pain reduction, physical function, serious adverse events, mortality (all low-quality evidence) or dropout due to adverse events (very low-quality). Pooled head-to-head comparisons of opioids (opioid of the sponsor of the study versus standard opioid) provide no rational for preferring one opioid and/or administration route over another in the therapy of patients with CNCP. The English full-text version of this

  8. Amnesia Affecting Some Opioid Abusers

    Science.gov (United States)

    ... they had used opioids. These drugs include prescription painkillers, such as oxycodone (Oxycontin) and oxycodone and acetaminophen ( ... attributed to a stroke or dementia. Moreover, the brain abnormalities seen on the MRI scans appear to ...

  9. Identifying Drugs

    Science.gov (United States)

    ... Oxycodone PCP (Phencyclidine) Peyote and Mescaline Psilocybin Rohypnol Salvia Divinorum Spice/ K2, Synthetic Marijuana Steroids U-47700 Flakka ( ... Oxycodone PCP (Phencyclidine) Peyote and Mescaline Psilocybin Rohypnol Salvia Divinorum Spice/ K2, Synthetic Marijuana Steroids U-47700 Aerosol ...

  10. Drug: D02153 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02153 Mixture, Drug Acetaminophen - oxycodone hydrochloride mixt; Percocet (TN); R...oxicet 5/500 (TN); Tylox (TN) Oxycodone hydrochloride [DR:D00847], Acetaminophen [DR:D00217] Analgesic PubChem: 7849214 ...

  11. Adverse drug interactions involving common prescription and over-the-counter analgesic agents.

    Science.gov (United States)

    Hersh, Elliot V; Pinto, Andres; Moore, Paul A

    2007-01-01

    Eight analgesic preparations with approved indications for acute pain were among the top 200 drugs prescribed in the United States in 2006. In addition, an estimated 36 million Americans use over-the-counter (OTC) analgesics daily. Given this volume of use, it is not surprising that a number of drug interactions involving analgesic drugs have been reported. This article examines the pharmacologic factors that enhance the clinical relevance of potential drug interactions and reviews the literature on drug interactions involving the most commonly used analgesic preparations in the United States. A PubMed search was conducted for English-language articles published between January 1967 and July 2007. Among the search terms were drug interactions, acetaminophen, aspirin, ibuprofen, naproxen, celecoxib, NSAIDs, hydrocodone, oxycodone, codeine, tramadol, OTC analgesics, alcohol, ethanol, antihypertensive drugs, methotrexate, warfarin, SSRIs, paroxetine, fluoxetine, sertraline, citalopram, serotonin syndrome, MAOIs, and overdose. Controlled clinical trials, case-control studies, and case reports were included in the review. A number of case reports and well-controlled clinical trials were identified that provided evidence of the relatively well known drug-drug interactions between prescription/OTC NSAIDs and alcohol, antihypertensive drugs, high-dose methotrexate, and lithium, as well as between frequently prescribed narcotics and other central nervous system depressants. In contrast, the ability of recent alcohol ingestion to exacerbate the hepatotoxic potential of therapeutic doses of acetaminophen is not supported by either case reports or clinical research. Use of ibuprofen according to OTC guidelines in patients taking cardioprotective doses of aspirin does not appear to interfere with aspirin's antiplatelet activity, whereas chronic prescription use of ibuprofen and other NSAIDs may interfere. Low-dose aspirin intake appears to abolish the gastroprotective effects

  12. CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications

    Science.gov (United States)

    St Sauver, Jennifer L; Olson, Janet E; Roger, Veronique L; Nicholson, Wayne T; Black, John L; Takahashi, Paul Y; Caraballo, Pedro J; Bell, Elizabeth J; Jacobson, Debra J; Larson, Nicholas B; Bielinski, Suzette J

    2017-01-01

    Background Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients. Materials and methods We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression. Results Overall, 257 (25% of RIGHT Protocol participants) patients received at least one opioid prescription; of these, 40 (15%) were poor metabolizers, 146 (57%) were intermediate to extensive metabolizers, and 71 (28%) were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38). After adjusting for age and sex, patients with a poor or ultrarapid phenotype were 2.7 times more likely to experience either poor pain control or an adverse symptom related to the prescription compared to patients with an intermediate to extensive phenotype (odds ratio: 2.68; 95% CI: 1.39, 5.17; p=0.003). Conclusion Our results suggest that >30% of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone. These medications are frequently prescribed for pain relief, and ~39% of the US population is expected to carry one of these phenotypes, suggesting that the population-level impact of these gene

  13. Preoperative intravenous ibuprofen does not influence postoperative narcotic use in patients undergoing elective hernia repair: a randomized, double-blind, placebo controlled prospective trial

    Directory of Open Access Journals (Sweden)

    Sparber LS

    2017-07-01

    Full Text Available Lauren S Sparber,1 Christine SM Lau,1,2 Tanya S Vialet,1 Ronald S Chamberlain1–4 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 4Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Inguinal and umbilical hernia repairs are among the most common surgical procedures performed in the US. Optimal perioperative pain control regimens remain challenging and opioid analgesics are commonly used. Preoperative nonsteroidal anti-inflammatory drug (NSAID administration has been shown to reduce postoperative narcotic requirements. This study sought to evaluate the efficacy of perioperative intravenous (IV ibuprofen on postoperative pain level and narcotic use in patients undergoing open or laparoscopic inguinal and/or umbilical hernia repair.Methods: A single center, randomized, double-blind placebo-controlled trial involving patients ≥18 years undergoing inguinal and/or umbilical hernia repair was performed. Patients were randomized to receive 800 mg of IV ibuprofen or placebo preoperatively. Outcomes assessed included postoperative pain medication required and visual analog scale (VAS pain scores.Results: Forty-eight adult male patients underwent inguinal and/or umbilical hernia repair. Patients receiving IV ibuprofen used more oxycodone/acetaminophen (32% vs 13% and IV hydromorphone (12% vs 8.7%, and fewer combinations of pain medications (44% vs 65.2% in the first two postoperative hours compared to placebo (p=0.556. The IV ibuprofen group had more patients pain free (28% vs 8.7%, p=0.087 and lower VAS scores (3.08±2.14 vs 3.95±1.54, p=0.134 at 2 hours postoperatively, compared to the placebo group, however, this was not statistically significant. Similar pain levels at 1, 3, and 7 days, postoperative and similar use of rescue

  14. Pharm GKB: Cough And Cold Preparations [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available R05) Drugs And Small Molecules The following have been classified under this therapeutic category: benzonatate codeine dextromethorph...an dornase alfa guaifenesin hydrocodone l-cysteine methadone morphine pipazethate p

  15. Pharm GKB: Opium alkaloids and derivatives [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available derivatives (R05DA) Drugs And Small Molecules The following have been classified under this therapeutic category: codeine dextrometho...rphan hydrocodone methadone morphine EvidenceGene VA CHRNA3 VA CHRNA5 No related dr

  16. Drug: D00847 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available (TN) C18H21NO4. HCl 351.1237 351.8246 D00847.gif Analgesic [narcotic] Same as: C08026 ATC code: N02AA05 mu-o...ide (USP) USP drug classification [BR:br08302] Analgesics Opioid Analgesics, Long...-acting Oxycodone D00847 Oxycodone hydrochloride (USP) Opioid Analgesics, Short-acting Oxycodone D00847 Oxyc

  17. Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2010-2014.

    Science.gov (United States)

    Warner, Margaret; Trinidad, James P; Bastian, Brigham A; Minino, Arialdi M; Hedegaard, Holly

    2016-12-01

    Objectives-This report identifies the specific drugs most frequently involved in drug overdose deaths in the United States from 2010 through 2014. Methods-The 2010-2014 National Vital Statistics System mortality files were linked to electronic files containing literal text information from death certificates. Drug overdose was defined using the International Classification of Diseases, Tenth Revision underlying cause-of-death codes X40-X44 (unintentional), X60-X64 (suicide), X85 (homicide), and Y10-Y14 (undetermined intent). Among deaths with an underlying cause of death of drug overdose, the literal text in three fields of the death certificate (i.e., the cause of death from Part I, significant conditions contributing to death from Part II, and a description of how the injury occurred from Box 43) were searched to identify drug mentions. Search term lists were developed using existing drug classification systems as well as from manual review of the literal text. The search term list was then used to identify the specific drugs involved in overdose deaths. Descriptive statistics were reported for drug overdose deaths involving the 10 most frequently mentioned drugs on death certificates. Tables and figures presenting information on the specific drugs involved in deaths are based on deaths with mention of at least one specific drug on the death certificate. Results-From 2010 through 2014, the number of drug overdose deaths per year increased 23%, from 38,329 in 2010 to 47,055 in 2014. During this time period, the percentage of drug overdose deaths involving at least one specific drug increased, from 67% in 2010 to 78% in 2014. Among drug overdose deaths with at least one drug specified on the death certificate, the 10 drugs most frequently involved in overdose deaths included the following opioids: heroin, oxycodone, methadone, morphine, hydrocodone, and fentanyl; the following benzodiazepines: alprazolam and diazepam; and the following stimulants: cocaine and

  18. [Long-term opioid therapy in chronic noncancer pain. A systematic review and meta-analysis of efficacy, tolerability and safety in open-label extension trials with study duration of at least 26 weeks].

    Science.gov (United States)

    Häuser, W; Bernardy, K; Maier, C

    2015-02-01

    The efficacy and safety of long-term (≥ 6 months) opioid therapy (LtOT) in chronic noncancer pain (CNCP) is under debate. A systematic review with meta-analysis of the efficacy and harms of opioids in open-label extension studies of randomized controlled trials (RCTs) has not been conducted until now. We screened MEDLINE and clinicaltrials.gov (through to December 2013), as well as reference sections of systematic reviews of long-term RCTs of opioids in CNCP. We included open-label extension trials with a study duration ≥ 26 weeks of RCTs of ≥ 2 weeks duration. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables were calculated. We included 11 open-label extension studies with 2445 participants with nociceptive (low back, osteoarthritis) and neuropathic (radicular, polyneuropathy) pain. Median study duration was 26 (range 26-108) weeks. Four studies tested oxycodone, two studies tramadol and buprenorphine; hydromorphone, morphine, oxymorphone and tapentadol were each tested in one study. Of the patients randomized at baseline, 28.5 % (95 % confidence interval, CI, 17.9-39.2 %) finished the open-label period; 53.5 % (95 % CI 38.1-68.2 %) of patients entering the open-label period finished the open-label period. In sum, the total loss was 71.5 % (95 % CI 60.9-83.1 %) of all patients primarily included into the RCT. A total of 4.9 % (95 % CI 2.9-8.2 %) of patients dropped out due lack of efficacy; 16.8 % (95 % CI 11.0-24.8 %) dropped out to due adverse events (AE) in the open-label period and 0.08 % (95 % CI 0.001-0.05 %) of patients died during the open-label period. Only one study systematically assessed aberrant drug behavior of the patients: 5.7 % (95 % CI 3.4-9.6 %) showed aberrant drug behavior in the opinion of the investigators and 2.6 % (95 % CI 1.2-5.8 %) were judged to show

  19. Prescribing practices amid the OxyContin crisis: examining the effect of print media coverage on opioid prescribing among physicians.

    Science.gov (United States)

    Borwein, Alexandra; Kephart, George; Whelan, Emma; Asbridge, Mark

    2013-12-01

    The pain medication OxyContin (hereafter referred to as oxycodone extended release) has been the subject of sustained, and largely negative, media attention in recent years. We sought to determine whether media coverage of oxycodone extended release in North American newspapers has led to changes in prescribing of the drug in Nova Scotia, Canada. An interrupted time-series design examined the effect of media attention on physicians' monthly prescribing of opioids. The outcome measures were, for each physician, the monthly proportions of all opioids prescribed and the proportion of strong opioids prescribed that were for oxycodone extended release. The exposure of interest was media attention defined as the number of articles published each month in 27 North American newspapers. Variations in media effects by provider characteristics (specialty, prescribing volume, and region) were assessed. Within-provider changes in the prescribing of oxycodone extended release in Nova Scotia were observed, and they followed changes in media coverage. Oxycodone extended release prescribing rose steadily prior to receiving media attention. Following peak media attention in the United States, the prescribing of oxycodone extended release slowed. Likewise, following peak coverage in Canadian newspapers, the prescribing of oxycodone extended release declined. These patterns were observed across prescriber specialties and by prescriber volume, though the magnitude of change in prescribing varied. This study demonstrates that print media reporting of oxycodone extended release in North American newspapers, and its continued portrayal as a social problem, coincided with reductions in the prescribing of oxycodone extended release by physicians in Nova Scotia. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  20. Drug: D03872 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 08301] 8 Narcotics 81 Alkaloidal narcotics 811 Opium alkaloids 8119 Others D03872...r08303] N NERVOUS SYSTEM N02 ANALGESICS N02A OPIOIDS N02AA Natural opium alkaloids N02AA55 Oxycodone, combin

  1. 76 FR 60900 - Jack A. Danton, D.O.; Decision and Order

    Science.gov (United States)

    2011-09-30

    ... entitled to ``considerable weight'' given the ALJ's acknowledgment that it ``has the potential for being... taking four 15 mg oxycodone tablets a day. . 8. In diagnosing muscular-skeletal injuries, the...

  2. Opioids No Better Than Ibuprofen for Pain After Car Crash

    Science.gov (United States)

    ... Car Crash: Study But more patients prescribed powerful painkillers were still taking them 6 weeks later To ... persistent pain after a car crash, prescription opioid painkillers such as oxycodone (Oxycontin) are no more effective ...

  3. Opioids and Alcohol a Dangerous Cocktail

    Science.gov (United States)

    ... taken opioids previously. Oxycodone, an ingredient in the brand-name drugs OxyContin and Percocet, is widely prescribed ... in the journal Anesthesiology . "We hope to increase awareness regarding the dangers of prescription opioids, the increased ...

  4. Therapies for Treating Diabetic Nerve Pain

    Science.gov (United States)

    ... moderate evidence that the opioids dextromethorphan, morphine sulphate, tramadol, and oxycodone controlled- release can help treat diabetic ... have serious side effects. For example, dextromethorphan and tramadol can cause sleepiness. This may be dangerous for ...

  5. SCI with Brain Injury: Bedside to Bench Modeling for Developing Treatment and Rehabilitation Strategies

    Science.gov (United States)

    2013-10-01

    DEXTROSE 1 MICONAZOLE 2 MICONAZOLE 1 HEPARIN 1 HEPARIN 3 FENTANYL 1 FENTANYL 2 BACLOFEN 1 BACLOFEN 1 FERROUS SULFATE 1 FERROUS SULFATE 1 QUETIAPINE 1...TRAZODONE 3 TRAZADONE 5 BACLOFEN 3 BACLOFEN 3 OXYCODONE 3 OXYCODONE 2 LACTOBACILLUS 3 LACTOBACILLUS 1 MICONAZOLE 3 MICONAZOLE 1 FERROUS GLUCONATE 2 FERROUS...prescribed, together with mild analgesics and antacids, but albuterol and low molecular weight heparin have been discontinued and the use of baclofen

  6. Efficacy of opioid switching in asian 51-year-old-man with a phenomenon of pharmacokinetics tolerance: case report

    Directory of Open Access Journals (Sweden)

    Carmelo Costa

    2012-05-01

    Full Text Available Opioid switching is a therapeutic procedure used in pain management as a method to improve analgesic response and/or reduce adverse side effects. The rationale behind opioid substitution is the incomplete cross-tolerance between opioid. We report the case of an asian 51-year-old man with cancer pain unresponsive to oxycodone. In this case we hypothesize that the lack of response to oxycodone is linked to a phenomenon of pharmacokinetics tolerance.

  7. 77 FR 34051 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-06-08

    ... this meeting. Submit electronic comments to http://www.regulations.gov . Submit written comments to the... accessed at: http://www.fda.gov/AdvisoryCommittees/default.htm ; under the heading ``Resources for You... potential for abuse, of drugs containing hydrocodone either combined with other analgesics or as an...

  8. 77 FR 24988 - Manufacturer of Controlled Substances; Notice of Registration; Johnson Matthey Pharma Services

    Science.gov (United States)

    2012-04-26

    ..., verification of the company's compliance with state and local laws, and a review of the company's background... (1100) II Methylphenidate (1724) II Hydrocodone (9193) II The company plans to utilize this facility to... support of the company's primary manufacturing facility in West Deptford, New Jersey. The controlled...

  9. Pharm GKB: Cough [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available drocodone may treat Cough hydromorphone may treat Cough May Prevent benzonatate may prevent Cough dextromethorphan...ethorphan may treat Cough guaifenesin may treat Cough hy...g File - Reference Terminology (NDF-RT) May Treat benzonatate may treat Cough cocaine may treat Cough codeine may treat Cough dextrom

  10. 75 FR 44286 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2010-07-28

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Registration By Notice dated March... Enforcement Administration (DEA) to be registered as a bulk manufacturer of the basic classes of controlled... company plans to manufacture Hydromorphone HCL for sale to other manufacturers and for the manufacture...

  11. 76 FR 77850 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-12-14

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Application Pursuant to Sec. 1301... Enforcement Administration (DEA) to be registered as a bulk manufacturer of the following basic classes of... manufacture Hydromorphone HCL for sale to other manufacturers, and to manufacture other controlled...

  12. 75 FR 13304 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2010-03-19

    ... Enforcement Administration Manufacturer of Controlled Substances; Notice of Application Pursuant to Sec. 1301... renewal to the Drug Enforcement Administration (DEA) to be registered as a bulk manufacturer of the basic... commercial distribution. The company plans to manufacture Hydromorphone HCL for sale to other...

  13. Standardizing Medication Error Event Reporting in the U.S. Department of Defense

    Science.gov (United States)

    2005-01-01

    States due to medical errors is between 44,000 and 98,000. This number far exceeds the annual number of deaths resulting from AIDS, breast cancer , or...Potassium Chloride Furosemide Diazepam Fentanyl Ketorolac Potassium Chloride Furosemide Meperidine Metoprolol Ipatropium Hydromorphone Vancomycin * 2002

  14. 77 FR 16264 - Manufacturer of Controlled Substances, Notice of Registration; Halo Pharmaceutical Inc.

    Science.gov (United States)

    2012-03-20

    ... commercial distribution. ] The company plans to manufacture Hydromorphone HCL for sale to other manufacturers... the company's compliance with state and local laws, and a review of the company's background and... application by renewal to the Drug Enforcement Administration (DEA) to be registered as a bulk manufacturer of...

  15. 76 FR 10070 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-02-23

    ... intermediate in the manufacture of Hydromorphone and is not for commercial distribution. The company plans to... laws, and a review of the company's background and history. Therefore, pursuant to 21 U.S.C. 823(a... Pharmaceutical Inc., 30 North Jefferson Road, Whippany, New Jersey 07981, made application by renewal to the Drug...

  16. 77 FR 12621 - Importer of Controlled Substances; Notice of Registration; Mylan Pharmaceuticals Inc.

    Science.gov (United States)

    2012-03-01

    ... the company's compliance with state and local laws, and a review of the company's background and...) II Hydromorphone (9150) II Fentanyl (9801) II The company plans to import the listed controlled... which the foreign FDF will be compared to the company's own domestically-manufactured FDF. This analysis...

  17. 76 FR 14689 - Importer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-03-17

    ... the company's compliance with state and local laws, and a review of the company's background and... Hydromorphone (9150) II Fentanyl (9801) II The company plans to import the listed controlled substances in... foreign FDF will be compared to the company's own domestically-manufactured FDF. This analysis is required...

  18. The Effect of Propranolol on Posttraumatic Stress Disorder in Burned Service Members

    Science.gov (United States)

    2009-02-01

    administration of drugs such as protein and RNA synthesis inhibitors. Once the con- solidation process is complete, memories are stable and insensitive to...units from the operative procedures were calculated by converting opioids (morphine, hydromorphone, fenta- nyl, sufenta, and methadone ) into IV

  19. Discriminative Stimulus Effects of Tramadol in Humans

    Science.gov (United States)

    Duke, Angela N.; Bigelow, George E.; Lanier, Ryan K.

    2011-01-01

    Tramadol is an unscheduled atypical analgesic that acts as an agonist at μ-opioid receptors and inhibits monoamine reuptake. Tramadol can suppress opioid withdrawal, and chronic administration can produce opioid physical dependence; however, diversion and abuse of tramadol is low. The present study further characterized tramadol in a three-choice discrimination procedure. Nondependent volunteers with active stimulant and opioid use (n = 8) participated in this residential laboratory study. Subjects were trained to discriminate between placebo, hydromorphone (8 mg), and methylphenidate (60 mg), and tests of acquisition confirmed that all volunteers could discriminate between the training drugs. The following drug conditions were then tested during discrimination test sessions: placebo, hydromorphone (4 and 8 mg), methylphenidate (30 and 60 mg), and tramadol (50, 100, 200, and 400 mg). In addition to discrimination measures, which included discrete choice, point distribution, and operant responding, subjective and physiological effects were measured for each test condition. Both doses of hydromorphone and methylphenidate were identified as hydromorphone- and methylphenidate-like, respectively. Lower doses of tramadol were generally identified as placebo, with higher doses (200 and 400 mg) identified as hydromorphone, or opioid-like. The highest dose of tramadol increased ratings on the stimulant scale, but was not significantly identified as methylphenidate-like. Tramadol did not significantly increase subjective ratings associated with reinforcement. Taken together, these results extend previous work with tramadol as a potential medication for the treatment of opioid dependence and withdrawal, showing acute doses of tramadol exhibit a profile of effects similar to opioid agonists and may have abuse liability in certain populations. PMID:21467190

  20. O uso de opióides no tratamento da dor crônica não oncológica: o papel da metadona El uso de opioides en el tratamiento del dolor crónico no oncológica: el papel de la metadona Opioids for treating non malignant chronic pain: the role of methadone

    Directory of Open Access Journals (Sweden)

    Sady Ribeiro

    2002-09-01

    potential, mainly those refractory to conventional therapy. Morphine is the standard opioid, but other alternatives may be used such as oxycodone, hydromorphone or fentanyl. Methadone is a synthetic opioid, initially used to prevent withdrawal syndrome in addicted patients, which may be an important alternative for treating non-malignant chronic pain, especially neuropathic pain. CONCLUSIONS: Although the growing knowledge on the use of opioids for treating non-malignant chronic pain, new better controlled studies are still needed to allow a more scientific discussion about this subject. Oral methadone is cost-effective and an effective alternative for a better pain control in certain patients.

  1. Complete biosynthesis of opioids in yeast.

    Science.gov (United States)

    Galanie, Stephanie; Thodey, Kate; Trenchard, Isis J; Filsinger Interrante, Maria; Smolke, Christina D

    2015-09-04

    Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines, despite diverse market demands and uncertainty in crop yields due to weather, climate change, and pests. We engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar. All work was conducted in a laboratory that is permitted and secured for work with controlled substances. We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required the expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself. This is a proof of principle, and major hurdles remain before optimization and scale-up could be achieved. Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds.

  2. Methadone Induced Sensorineural Hearing Loss

    OpenAIRE

    Chadi Saifan; Daniel Glass; Iskandar Barakat; Suzanne El-Sayegh

    2013-01-01

    Background. Sudden sensorineural hearing loss (SSHL) caused by opiate abuse or overuse has been well documented in the medical literature. Most documented case reports have involved either heroin or hydrocodone/acetaminophen. Recently, case reposts of methadone induced SSHL have been published. Case Report. We present the case of a 31-year-old man who developed SSHL after a methadone overdose induced stupor. He was subsequently restarted on methadone at his regular dose. On follow-up audiomet...

  3. Pharmacodynamic Profile of Tramadol in Humans: Influence of Naltrexone Pretreatment

    Science.gov (United States)

    Stoops, William W.; Lofwall, Michelle R.; Nuzzo, Paul A.; Craig, Lori B.; Siegel, Anthony J.; Walsh, Sharon L.

    2012-01-01

    Rationale Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects. Objectives This study evaluated the effect of mu opioid receptor blockade with naltrexone on the pharmacodynamic action of tramadol in humans. Methods This inpatient, double-blind, randomized, within-subject study examined the effects of oral placebo, tramadol (87.5, 175 and 350 mg) and hydromorphone (4 and 16 mg; positive control) after 1 hr pretreatment with oral naltrexone (0 and 50 mg). Ten recreational opioid users completed the study. Pharmacodynamic effects were measured before and for 7 hr after initial drug administration. Results Lower doses of tramadol and hydromorphone were generally placebo-like. Hydromorphone (16 mg) produced prototypic mu opioid agonist-like effects that were blocked by naltrexone. Tramadol (350 mg) produced miosis and increased ratings of “Good Effects” and “Liking ,” but also increased ratings of “Bad Effects.” Naltrexone reversed tramadol-induced physiological effects and mydriasis emerged, but unlike results with hydromorphone, naltrexone only partially attenuated tramadol’s positive subjective effects and actually enhanced several unpleasant subjective ratings. Conclusions Naltrexone can be used to disentangle the mixed neuropharmacological actions of tramadol. High dose tramadol produces a mixed profile of effects. These data suggest that both mu and non-mu opioid actions play a role in tramadol’s subjective profile of action. PMID:22623016

  4. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids

    Directory of Open Access Journals (Sweden)

    Gorlin AW

    2016-09-01

    Full Text Available Andrew W Gorlin, David M Rosenfeld, Jillian Maloney, Christopher S Wie, Johnathan McGarvey, Terrence L Trentman Department of Anesthesiology, Mayo Clinic Arizona, Phoenix, AZ, USA Abstract: The conversion of high-dose intravenous (IV opioids to an equianalgesic epidural (EP or intrathecal (IT dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted. Keywords: intrathecal pump, epidural, cancer pain

  5. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids.

    Science.gov (United States)

    Gorlin, Andrew W; Rosenfeld, David M; Maloney, Jillian; Wie, Christopher S; McGarvey, Johnathan; Trentman, Terrence L

    2016-01-01

    The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted.

  6. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids

    Science.gov (United States)

    Gorlin, Andrew W; Rosenfeld, David M; Maloney, Jillian; Wie, Christopher S; McGarvey, Johnathan; Trentman, Terrence L

    2016-01-01

    The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted. PMID:27703394

  7. Managing pain in chronic pancreatitis:therapeutic value of opioid treatment

    DEFF Research Database (Denmark)

    Eisenberg, Elon; Ståhl, Camilla; Drewes, Asbjørn M;

    2007-01-01

    The value of opioid pharmacotherapy in the management of chronic pancreatitis pain is described. The role of kappa receptor opioid agonists and specifically oxycodone as compared to other opioid agonists is discussed. Limitations in the published studies on this topic are delineated...

  8. mu-Opioid receptor-independent fashion of the suppression of sodium currents by mu-opioid analgesics in thalamic neurons.

    Science.gov (United States)

    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.

  9. Painful Diabetic Peripheral Neuropathy: Consensus Recommendations on Diagnosis, Assessment and Management

    DEFF Research Database (Denmark)

    Tesfaye, S; Vileikyte, L; Rayman, G

    2011-01-01

    use of opiates such as the synthetic opioid tramadol, morphine and oxycodone controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated...

  10. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix

    2005-01-01

    options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics...

  11. Determination of the unbound fraction of R- and S-methadone in human brain

    DEFF Research Database (Denmark)

    Holm, Karen M D; Linnet, Kristian

    2016-01-01

    , codeine, methadone, morphine, diazepam, oxycodone, tramadol), as well as methadone enantiomers. This method was then applied to approximately 50 authentic case samples with R-methadone and S-methadone concentrations ranging from 0.03 to 13 and 0.6 to 6.8 mg/kg, respectively; median f u values (R-and S...

  12. Differential effect of opioids in patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Staahl, Camilla; Dimcevski, Georg; Andersen, Søren Due

    2007-01-01

    and morphine on experimental pain in patients with pain caused by chronic pancreatitis. MATERIAL AND METHODS: Ten patients took part in this blinded, cross-over study. The analgesic effects of morphine (30 mg, oral), oxycodone (15 mg, oral) and placebo were tested against multimodal (mechanical, thermal...

  13. Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery? A Randomized Controlled Trial?

    Directory of Open Access Journals (Sweden)

    Saddiq Mohammad Qazi

    2015-12-01

    Conclusion: The results of this study suggest that patients treated postoperatively, following cardiac surgery, are at no greater risk of harm if short term slow release ibuprofen combined with lansoprazole treatment is used when compared to an oxycodone based regimen. Renal function should, however, be closely monitored and in the event of any decrease in renal function ibuprofen must be discontinued.

  14. Recovering the Poetics of Shopping

    DEFF Research Database (Denmark)

    Jantzen, Christian; Sørensen, Sanne Dollerup

    2015-01-01

    INTRODUCTION: Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat severe and moderate pain, but for both of them the mechanisms in humans remain unclear. This study aimed to explore how oxycodone (opioid) and venlafaxine (SNR...

  15. [Post-operative pain therapy of a chronic pain patient].

    Science.gov (United States)

    Pawlik, Michael T; Ittner, Karl Peter

    2006-11-01

    Post-operative pain therapy of chronic pain patients poses a challenge. Here we report the perioperative management of a 39-year-old male under chronic therapy with oxycodon, gabapentin and tolperison. Particular the pharmacointeractions regarding premedication and postoperative dose finding of opioids with intravenous PCIA are discussed.

  16. Opioid/naloxone prolonged release combinations for opioid induced constipation

    Institute of Scientific and Technical Information of China (English)

    Shailendra Kapoor

    2012-01-01

    I read with great interest the recent article by Chen et a/in a recent issue of your esteemed journal.The article is highly thought provoking.One emerging therapeutic alternative for opioid induced constipation is the emergence of opioid/naloxone prolonged release combinations.For instance,naloxone when administered in a 1∶2 ratio with oxycodone reverses the inhibitory effect of oxycodone on the gastrointestinal tract.The advantage of oxycodone/naloxone prolonged release (OXN) is that while its anti-nociceptive efficacy is equivalent to that of oxycodone prolonged release (OXC),it significantly decreases the "Bowel Function Index" thereby ameliorating symptoms of opioid induced constipation to a large extent.Schutter et al in a recent study have reported a decrease in the bowel function index from 38.2 to 15.1.Similarly,L(o)wenstein et al in another recent study have reported that following a month of therapy,complete spontaneous bowel movements per week is increased from one in OXC therapy to three in OXN therapy.

  17. Synergistic antihypersensitive effects of pregabalin and tapentadol in a rat model of neuropathic pain.

    Science.gov (United States)

    Christoph, Thomas; De Vry, Jean; Schiene, Klaus; Tallarida, Ronald J; Tzschentke, Thomas M

    2011-09-01

    Neuropathic pain is a clinical condition which remains poorly treated and combinations of pregabalin, an antagonist of the α2δ-subunit of Ca(2+) channels, with tapentadol, a μ-opioid receptor agonist/noradrenaline reuptake inhibitor, or with classical opioids such as oxycodone and morphine might offer increased therapeutic potential. In the rat spinal nerve ligation model, a dose dependent increase in ipsilateral paw withdrawal thresholds was obtained using an electronic von Frey filament after IV administration of pregabalin (1-10mg/kg), tapentadol (0.316-10mg/kg), morphine (1-4.64 mg/kg) and oxycodone (0.316-3.16 mg/kg), with ED(50) values (maximal efficacy) of 4.21 (67%), 1.65 (94%), 1.70 (96%) and 0.63 mg/kg (100%), respectively. Equianalgesic dose combinations of pregabalin and tapentadol (dose ratio 2.5:1), morphine (2.5:1) or oxycodone (6.5:1) resulted in ED(50) values (maximal efficacy) of 0.83 (89%), 2.33 (97%) and 1.14 mg/kg (100%), respectively. The concept of dose-equivalence suggested an additive interaction of pregabalin and either oxycodone or morphine, while a synergistic interaction was obtained with pregabalin and tapentadol (demonstrated by isobolographic analysis). There was no increase in contralateral paw withdrawal thresholds and no locomotor impairment, as measured in the open field, for the combination of pregabalin and tapentadol; while a significant increase and impairment was demonstrated for the combinations of pregabalin and either morphine or oxycodone. Because combination of pregabalin and tapentadol resulted in a synergistic antihypersensitive activity, it is suggested that, beside the use of either drug alone, this drug combination may offer a beneficial treatment option for neuropathic pain.

  18. Thoracic epidural catheter for postoperative pain control following an ineffective transversus abdominis plane block using liposome bupivacaine

    Science.gov (United States)

    Terrien, Brian D; Espinoza, David; Stehman, Charles C; Rodriguez, Gabriel A; Connolly, Nicholas C

    2017-01-01

    A 24-year-old female with a history of ulcerative colitis underwent colectomy. The patient received an ineffective transversus abdominis plane (TAP) block with liposome bupivacaine (Exparel) intraoperatively and was started on a hydromorphone patient-controlled analgesia 5 hours after the TAP block, which did not relieve her pain. A continuous thoracic epidural (CTE) was then placed after blood levels of bupivacaine were drawn, and the patient immediately experienced significant pain relief. The combined use of liposome bupivacaine and bupivacaine CTE infusion in the postoperative management of this patient demonstrated no safety concerns, provided excellent analgesia and plasma concentrations of bupivacaine remained far below toxic levels. PMID:28144162

  19. Dexmedetomidine as a novel therapeutic for postoperative pain in a patient treated with buprenorphine.

    Science.gov (United States)

    Brummett, Chad M; Trivedi, Kavita A; Dubovoy, Anna V; Berland, Daniel W

    2009-01-01

    Buprenorphine is a partial agonist/antagonist used for the outpatient management of pain and addiction. It avidly binds to the opioid receptors and has a long and varied half-life. Its effects can impair the efficacy of opioids used for postoperative pain. The authors present a case of a patient managed with buprenorphine as an outpatient who presented for revision spine surgery and had significant postoperative pain that was successfully treated with hydromorphone and dexmedetomidine. This is the first reported use of dexmedetomidine for postoperative pain in a patient treated with buprenorphine.

  20. The effects of analgesics on central processing of tonic pain

    DEFF Research Database (Denmark)

    Lelic, Dina; Hansen, Tine M; Mark, Esben Bolvig

    2017-01-01

    INTRODUCTION: Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed...... decreased spectral indices in alpha band of the EEG to tonic pain, whereas oxycodone decreased the spectral indices and brain source activity in delta and theta frequency bands (all P activity predominantly decreased in the insula and inferior frontal gyrus. CONCLUSION......: The decrease of activity within insula and inferior frontal gyrus is likely involved in pain inhibition due to oxycodone treatment, whereas the decrease in alpha activity is likely involved in pain inhibition due to venlafaxine treatment....

  1. Towards safer use of opioids.

    LENUS (Irish Health Repository)

    Carson, R W R

    2009-09-01

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

  2. Opioid Abuse after TBI

    Science.gov (United States)

    2015-09-01

    VCU We continued our examination of neuronal cell death in the dentate gyrus of the hippocampus of animals in the various experimental group. An...the side of the brain contralateral to the injury. However, in the dentate gyrus ipsilateral to the injury, we saw a significant reduction in the...found no significant differences in the number of neurons in the dentate gyrus of rats from the Sham or TBI group, regardless of oxycodone

  3. Opioid Use after TBI

    Science.gov (United States)

    2013-07-01

    abused prescription pain medications is oxycodone, especially in its sustained release formulation OxyContin3. This pain medication and others in the...suggestive of increased impulsivity • No differences were detected between groups in baseline nociception or in response to the acute anti- nociceptive ...performance was stable ( 3 days >20% change) Assessment of nociception with warm water tail withdrawal: • Rats were habituated to the test apparatus

  4. General Unknown Screening by Ion Trap LC/MS/MS

    Science.gov (United States)

    2010-04-01

    specific compounds in different drug classes like various drugs of abuse , or widely prescribed pharmaceuticals such as oxycodone; however, these...Methylephedrine 7.01 180.1 135.1 1 Base Methylphenidate 9.84 234.1 84.2 1 Base Methysergide 9.44 354.2 237.1 1 Base Metoclopramide 9.00 300.2 227.1 1 Base

  5. Pharmacogenomic considerations in opioid analgesia

    Directory of Open Access Journals (Sweden)

    Vuilleumier PH

    2012-08-01

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

  6. Adjuvants for Vaccines to Drugs of Abuse and Addiction

    OpenAIRE

    Alving, Carl R.; Matyas, Gary R.; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-01-01

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, bec...

  7. The importance of communication in the management of postoperative pain.

    Science.gov (United States)

    Sugai, Daniel Y; Deptula, Peter L; Parsa, Alan A; Don Parsa, Fereydoun

    2013-06-01

    This study investigates the importance of communication in surgery and how delivering preoperative patient education can lead to better health outcomes postoperatively, via promoting tolerable pain scores and minimizing the use of narcotics after surgery. Patients who underwent outpatient surgery were randomly divided into groups to compare the pain scores of those who received preoperative patient education, the experimental group, and those who did not receive any form of patient education, the control group. Two weeks before surgery, the experimental group subjects received oral and written forms of patient education consisting of how the body responds to pain, and how endorphins cause natural analgesia. Moreover, patients were educated on the negative effects narcotics have on endorphin production and activity, as well as mechanisms of non-opioid analgesics. Of the 69 patients in the experimental group, 90% declined a prescription for hydrocodone after receiving preoperative education two weeks prior to surgery. The control group consisted of 66 patients who did not receive preoperative patient education and 100% filled their hydrocodone prescriptions. Patients in both groups were offered and received gabapentin and celecoxib preoperatively for prophylaxis of postoperative pain unless they declined. The control groups were found to have average pain scores significantly greater (P communication, which can serve as an effective means to minimize narcotic analgesia after surgery.

  8. Important drugs for cough in advanced cancer.

    Science.gov (United States)

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management.

  9. Enhanced bioavailability of opiates after intratracheal administration

    Energy Technology Data Exchange (ETDEWEB)

    Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

    1986-03-01

    Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities (codeine (84%), ethylmorphine (100%), and morphine (87%)) of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability.

  10. Pharmacological strategies to reduce pruritus during postoperative epidural analgesia after lumbar fusion surgery - a prospective randomized trial in 150 patients

    Directory of Open Access Journals (Sweden)

    Robinson Yohan

    2011-05-01

    Full Text Available Abstract Background Epidural analgesia with bupivacain, epinephrine and fentanyl provides excellent pain control after lumbar fusion surgery, but pruritus and motor block are frequent side effects. Theoretically epidural ropivacain combined with oral oxycodone could decrease the incidence of these side effects. The two regimens were compared in a prospective randomized trial. Patients and methods 150 patients (87 women treated with posterior instrumented lumbar fusion were included. The mean age was 51 +/- 11 years. 76 were randomized to bupivacain, epinephrine and fentanyl (group B and 74 to ropivacain and oxycodone (group R. Pruritus, motor block and pain were measured 6 hours after surgery, thereafter 6 times per day for 5 days. Any pain breakthrough episode was registered whenever it occurred. Results The epidural treatment could be performed in 143 patients (72 in group B and 71 in group R. Disturbing pruritus occurred in 53 patients in group B compared to 12 in group R (p Conclusions Pruritus could be reduced with a combination of epidural ropivacain and oral oxycodone, at the price of a slightly higher pain level. Ropivacaine was not found to be superior to bupivacaine with regard to motor blocks.

  11. Mu opioid mediated discriminative-stimulus effects of tramadol: an individual subjects analysis.

    Science.gov (United States)

    Strickland, Justin C; Rush, Craig R; Stoops, William W

    2015-03-01

    Drug discrimination procedures use dose-dependent generalization, substitution, and pretreatment with selective agonists and antagonists to evaluate receptor systems mediating interoceptive effects of drugs. Despite the extensive use of these techniques in the nonhuman animal literature, few studies have used human participants. Specifically, human studies have not routinely used antagonist administration as a pharmacological tool to elucidate the mechanisms mediating the discriminative stimulus effects of drugs. This study evaluated the discriminative-stimulus effects of tramadol, an atypical analgesic with monoamine and mu opioid activity. Three human participants first learned to discriminate 100 mg tramadol from placebo. A range of tramadol doses (25 to 150 mg) and hydromorphone (4 mg) with and without naltrexone pretreatment (50 mg) were then administered to participants after they acquired the discrimination. Tramadol produced dose-dependent increases in drug-appropriate responding and hydromorphone partially or fully substituted for tramadol in all participants. These effects were attenuated by naltrexone. Individual participant records indicated a relationship between mu opioid activity (i.e., miosis) and drug discrimination performance. Our findings indicate that mu opioid activity may mediate the discriminative-stimulus effects of tramadol in humans. The correspondence of generalization, substitution, and pretreatment findings with the animal literature supports the neuropharmacological specificity of the drug discrimination procedure. © Society for the Experimental Analysis of Behavior.

  12. Carprofen provides better post-operative analgesia than tramadol in dogs after enucleation: A randomized, masked clinical trial

    Science.gov (United States)

    Delgado, Cherlene; Bentley, Ellison; Hetzel, Scott; Smith, Lesley J

    2015-01-01

    Objective To compare analgesia provided by carprofen or tramadol in dogs after enucleation. Design Randomized, masked trial Animals Forty-three dogs Procedures Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for pain at baseline, and postoperatively at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥9, if there was a score ≥ 3 in any one category, or if the visual analog scale score (VAS) was ≥35 combined with a palpation score of >0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded. Characteristics between groups were compared with a Student’s t-test and Fisher’s exact test. The incidence of rescue was compared between groups using a log rank test. Pain scores and VAS scores between groups were compared using repeated measures ANOVA. Results There was no difference in age (p=0.493), gender (p=0.366) or baseline pain scores (p=0.288) between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21) compared to dogs receiving carprofen (1/22; p=0.035). Pain and VAS scores decreased linearly over time (p=0.038, ptramadol in dogs undergoing enucleation. PMID:25459482

  13. Inpatient management of sickle cell pain: a 'snapshot' of current practice.

    Science.gov (United States)

    Miller, Scott T; Kim, Hae-Young; Weiner, Debra; Wager, Carrie G; Gallagher, Dianne; Styles, Lori; Dampier, Carlton D

    2012-03-01

    The Sickle Cell Disease Clinical Research Network (SCDCRN) designed the PROACTIVE Feasibility Study (ClinicalTrials.gov NCT00951808) to determine whether elevated serum levels of secretory phospholipase A2 (sPLA2) during hospitalization for pain would permit preemptive therapy of sickle cell acute chest syndrome (ACS) by blood transfusion. While PROACTIVE was not designed to assess pain management and was terminated early due to inadequate patient accrual, collection of clinical data allowed a "snapshot" of current care by expert providers. Nearly half the patients admitted for pain were taking hydroxyurea; hydroxyurea did not affect length of stay. Providers commonly administered parenteral opioid analgesia, usually morphine or hydromorphone, to adults and children, generally by patient-controlled analgesia (PCA). Adult providers were more likely to prescribe hydromorphone and did so at substantially higher morphine equivalent doses than were given to adults receiving morphine; the latter received doses similar to children who received either medication. All subjects treated with PCA received higher daily doses of opioids than those treated by time-contingent dosing. Physicians often restricted intravenous fluids to less than a maintenance rate and underutilized incentive spirometry, which reduces ACS in patients hospitalized for pain.

  14. Pain Analysis in Patients with Pancreatic Carcinoma: Irreversible Electroporation versus Cryoablation

    Directory of Open Access Journals (Sweden)

    Jiannan Li

    2016-01-01

    Full Text Available The aim of this article is to evaluate and compare the postprocedure pain in patients with pancreatic carcinoma treated with irreversible electroporation (IRE and cryoablation (CRYO. We compared 22 patients with 22 lesions in pancreas treated with IRE and 26 patients with 27 lesions treated with cryosurgery. All the patients in the two groups were under celiac plexus block (CPB treatment to alleviate the postprocedure pain. A numerical rating scale (VAS consisting of 11-point scales and the 24 h total hydromorphone use were recorded for the analysis of the pain level in the patients who underwent these two technologies separately. Other parameters, such as the complications and the ECOG performance status, were also noted. Statistical analysis was performed by Fisher’s exact test, the Chi-square test, and Student’s t-test. All the pancreatic carcinoma patients in our study were reported to have postprocedure pain in the two groups. But there was no significant difference in the mean pain score (4.95 (IRE versus 4.85 (CRYO; P=0.52 and 24 h total hydromorphone use (3.89 mg (IRE versus 3.97 mg (CRYO; P=0.30. IRE is comparable to cryotherapy in the amount of pain that patients with pancreatic carcinoma experience.

  15. Pain Analysis in Patients with Pancreatic Carcinoma: Irreversible Electroporation versus Cryoablation

    Science.gov (United States)

    Li, Jiannan; Sheng, Shihou; Zhang, Kai

    2016-01-01

    The aim of this article is to evaluate and compare the postprocedure pain in patients with pancreatic carcinoma treated with irreversible electroporation (IRE) and cryoablation (CRYO). We compared 22 patients with 22 lesions in pancreas treated with IRE and 26 patients with 27 lesions treated with cryosurgery. All the patients in the two groups were under celiac plexus block (CPB) treatment to alleviate the postprocedure pain. A numerical rating scale (VAS) consisting of 11-point scales and the 24 h total hydromorphone use were recorded for the analysis of the pain level in the patients who underwent these two technologies separately. Other parameters, such as the complications and the ECOG performance status, were also noted. Statistical analysis was performed by Fisher's exact test, the Chi-square test, and Student's t-test. All the pancreatic carcinoma patients in our study were reported to have postprocedure pain in the two groups. But there was no significant difference in the mean pain score (4.95 (IRE) versus 4.85 (CRYO); P = 0.52) and 24 h total hydromorphone use (3.89 mg (IRE) versus 3.97 mg (CRYO); P = 0.30). IRE is comparable to cryotherapy in the amount of pain that patients with pancreatic carcinoma experience. PMID:28074177

  16. Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency

    Directory of Open Access Journals (Sweden)

    Brissette Suzanne

    2011-07-01

    Full Text Available Abstract Background Substitution with opioid-agonists (e.g., methadone has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST. In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes. Methods Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI, conducted in Vancouver and Montreal (Canada between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8 was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group. Results A total of 232 (92% and 237 (94% participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by

  17. Methadone Induced Sensorineural Hearing Loss

    Directory of Open Access Journals (Sweden)

    Chadi Saifan

    2013-01-01

    Full Text Available Background. Sudden sensorineural hearing loss (SSHL caused by opiate abuse or overuse has been well documented in the medical literature. Most documented case reports have involved either heroin or hydrocodone/acetaminophen. Recently, case reposts of methadone induced SSHL have been published. Case Report. We present the case of a 31-year-old man who developed SSHL after a methadone overdose induced stupor. He was subsequently restarted on methadone at his regular dose. On follow-up audiometry exams, he displayed persistent moderately severe sensorineural hearing loss bilaterally. Discussion. This case is notable because unlike all but one previously reported case, the patient—who was restated on methadone—did not make a complete recovery. Conclusion. Methadone overuse in rare cases causes SSHL.

  18. Efficacy of levodropropizine in pediatric cough.

    Science.gov (United States)

    De Blasio, Francesco; Dicpinigaitis, Peter V; De Danieli, Gianluca; Lanata, Luigi; Zanasi, Alessando

    2012-10-01

    Cough in children is among the most common problems managed by pediatricians, and occurs more frequently in preschool than in older children. Most acute episodes of cough are due to viral upper respiratory tract infections. The morbidity associated with acute cough in a child extends also to parents, teachers, and other family members and caregivers. Unfortunately, therapeutic options for acute cough in children are severely limited due to the absence of drugs shown to be effective antitussives with an acceptable safety profile. Agents used in the management of adult cough, such as narcotics (codeine, hydrocodone), the non-narcotic opioid dextromethorphan, first-generation, potentially sedating antihistamines, and decongestants such as pseudoephedrine, have all been deemed inadequate for treatment of acute pediatric cough on a risk/benefit basis. A growing body of evidence suggests that the peripherally acting antitussive, levodropropizine, may be an attractive alternative for the treatment of bothersome acute cough in children.

  19. Therapeutic options for acute cough due to upper respiratory infections in children.

    Science.gov (United States)

    Paul, Ian M

    2012-02-01

    Cough due to upper respiratory tract infections (URIs) is one of the most frequent complaints encountered by pediatric health-care providers, and one of the most disruptive symptoms for children and families. Despite the frequency of URIs, there is limited evidence to support the few therapeutic agents currently available in the United States (US) to treat acute cough due to URI. Published, well-designed, contemporary research supporting the efficacy of narcotics (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over-the-counter (OTC) oral antitussives and expectorants (dextromethorphan, diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated pediatric cough. Alternatively, honey and topically applied vapor rubs may be effective antitussives.

  20. Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.

    Science.gov (United States)

    Nakagawa, Akira; Matsumura, Eitaro; Koyanagi, Takashi; Katayama, Takane; Kawano, Noriaki; Yoshimatsu, Kayo; Yamamoto, Kenji; Kumagai, Hidehiko; Sato, Fumihiko; Minami, Hiromichi

    2016-02-05

    Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l(-1) from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (R)-reticuline in E. coli. Furthermore, by adding two genes to the thebaine production system, we demonstrate the biosynthesis of hydrocodone, a clinically important opioid. Improvements in opiate production in this E. coli system represent a major step towards the development of alternative opiate production systems.

  1. Methadone induced sensorineural hearing loss.

    Science.gov (United States)

    Saifan, Chadi; Glass, Daniel; Barakat, Iskandar; El-Sayegh, Suzanne

    2013-01-01

    Background. Sudden sensorineural hearing loss (SSHL) caused by opiate abuse or overuse has been well documented in the medical literature. Most documented case reports have involved either heroin or hydrocodone/acetaminophen. Recently, case reposts of methadone induced SSHL have been published. Case Report. We present the case of a 31-year-old man who developed SSHL after a methadone overdose induced stupor. He was subsequently restarted on methadone at his regular dose. On follow-up audiometry exams, he displayed persistent moderately severe sensorineural hearing loss bilaterally. Discussion. This case is notable because unlike all but one previously reported case, the patient-who was restated on methadone-did not make a complete recovery. Conclusion. Methadone overuse in rare cases causes SSHL.

  2. Abuse Liability and Reinforcing Efficacy of Oral Tramadol in Humans

    Science.gov (United States)

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

    2012-01-01

    BACKGROUND Tramadol, a monoaminergic reuptake inhibitor, is hepatically metabolized to an opioid agonist (M1). This atypical analgesic is generally considered to have limited abuse liability. Recent reports of its abuse have increased in the U.S., leading to more stringent regulation in some states, but not nationally. The purpose of this study was to examine the relative abuse liability and reinforcing efficacy of tramadol in comparison to a high (oxycodone) and low efficacy (codeine) opioid agonist. METHODS Nine healthy, non-dependent prescription opioid abusers (6 male, 3 female) participated in this within-subject, randomized, double blind, placebo-controlled study. Participants completed 14 paired sessions (7 sample, 7 self-administration). During each sample session, an oral dose of tramadol (200, 400 mg), oxycodone (20, 40 mg), codeine (100, 200 mg) or placebo was administered, and a full array of abuse liability measures was collected. During self-administration sessions, volunteers were given the opportunity to work (via progressive ratio) for the sample dose or money. RESULTS All active doses were self-administered; placebo engendered no responding. The high doses of tramadol and oxycodone were readily self-administered (70%, 59% of available drug, respectively); lower doses and both codeine doses maintained intermediate levels of drug taking. All three drugs dose-dependently increased measures indicative of abuse liability, relative to placebo; however, the magnitude and time course of these and other pharmacodynamic effects varied qualitatively across drugs. CONCLUSIONS This study demonstrates that, like other mu opioids, higher doses of tramadol function as reinforcers in opioid abusers, providing new empirical data for regulatory evaluation. PMID:23098678

  3. Hypoglycemic effects of tramadol analgesia in hospitalized patients: a case-control study.

    Science.gov (United States)

    Golightly, Larry K; Simendinger, Bonita A; Barber, Gerard R; Stolpman, Nancy M; Kick, Steven D; McDermott, Michael T

    2017-01-01

    In outpatient populations, hypoglycemia has been associated with tramadol. We sought to determine the magnitude of risk for hypoglycemia associated with tramadol use in hospitalized patients. During a 2-year period of observation, adult inpatients who received ≥1 dose of tramadol were identified and their medical records were reviewed. Patients were included if they had blood or plasma glucose (BG) concentrations measured on at least two occasions within five days after the initial administration of tramadol. A contemporary comparator group of hospitalized oxycodone recipients was similarly reviewed. Tramadol was administered to 2927 patients who met inclusion criteria. Among these, hypoglycemia (BG ≤70 mg/dL) was documented in 22 (46.8%) of 47 patients with type 1 diabetes, 113 (16.8%) of 673 patients with type 2 diabetes, and 103 (4.7%) of 2207 patients who did not have a diabetes mellitus diagnosis. In those without a diabetes diagnosis, the causality association between hypoglycemia and tramadol use was probable in 77 patients (3.5%). By comparison, hypoglycemia was documented in 8 (1.1%) of 716 matched oxycodone recipients without diabetes (p = 0.002). As compared with tramadol recipients who did not develop low BG concentrations, those who experienced tramadol-related hypoglycemia were relatively young (mean age 52.0 versus 59.8 years; p = 0.027) and predominantly female (74.0% versus 59.8%; p = 0.012). Tramadol use was causally associated with hypoglycemia in hospitalized patients. The proportion of patients without diabetes who developed hypoglycemia was higher among those who received tramadol than among those who received oxycodone. Colorado Multiple Institutional Review Board Protocol № 15-2215. Registered/approved 8 December 2015.

  4. Developments in managing severe chronic pain: role of oxycodone–naloxone extended release

    Directory of Open Access Journals (Sweden)

    Fanelli G

    2015-07-01

    Full Text Available Guido Fanelli,1 Andrea Fanelli2 1Anesthesia and Intensive Care Unit, University of Parma, Parma, 2Anesthesia and Intensive Care Unit, Policlinico S Orsola-Malpighi, Bologna, Italy Abstract: Chronic pain is a highly disabling condition, which can significantly reduce patients’ quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC. Keywords: chronic pain, opioid-induced constipation, opioids, oxycodone–naloxone

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

    Science.gov (United States)

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

    2017-08-04

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

  6. Transcriptomic and behavioural characterisation of a mouse model of burn pain identify the cholecystokinin 2 receptor as an analgesic target.

    Science.gov (United States)

    Yin, Kathleen; Deuis, Jennifer R; Lewis, Richard J; Vetter, Irina

    2016-01-01

    Burn injury is a cause of significant mortality and morbidity worldwide and is frequently associated with severe and long-lasting pain that remains difficult to manage throughout recovery. We characterised a mouse model of burn-induced pain using pharmacological and transcriptomic approaches. Mechanical allodynia elicited by burn injury was partially reversed by meloxicam (5 mg/kg), gabapentin (100 mg/kg) and oxycodone (3 and 10 mg/kg), while thermal allodynia and gait abnormalities were only significantly improved by amitriptyline (3 mg/kg) and oxycodone (10 mg/kg). The need for relatively high opioid doses to elicit analgesia suggested a degree of opioid resistance, similar to that shown clinically in burn patients. We thus assessed the gene expression changes in dorsal root ganglion neurons and pathophysiological mechanisms underpinning burn injury-induced pain using a transcriptomic approach. Burn injury was associated with significantly increased expression of genes associated with axon guidance, neuropeptide signalling, behavioural defence response and extracellular signalling, confirming a mixed neuropathic and inflammatory aetiology. Notably, among the pain-related genes that were upregulated post-injury was the cholecystokinin 2 receptor (Cckbr), a G protein-coupled receptor known as a pain target involved in reducing opioid effectiveness. Indeed, the clinically used cholecystokinin receptor antagonist proglumide (30 mg/kg) was effective at reversing mechanical allodynia, with additional analgesia evident in combination with low-dose oxycodone (1 mg/kg), including significant reversal of thermal allodynia. These findings highlight the complex pathophysiological mechanisms underpinning burn injury-induced pain and suggest that cholecystokinin-2 receptor antagonists may be useful clinically as adjuvants to decrease opioid requirements and improve analgesic management.

  7. Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction

    Directory of Open Access Journals (Sweden)

    Leppert W

    2015-04-01

    Full Text Available Wojciech Leppert Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland Abstract: Opioid-induced bowel dysfunction (OIBD comprises gastrointestinal (GI symptoms, including dry mouth, nausea, vomiting, gastric stasis, bloating, abdominal pain, and opioid-induced constipation, which significantly impair patients’ quality of life and may lead to undertreatment of pain. Traditional laxatives are often prescribed for OIBD symptoms, although they display limited efficacy and exert adverse effects. Other strategies include prokinetics and change of opioids or their administration route. However, these approaches do not address underlying causes of OIBD associated with opioid effects on mostly peripheral opioid receptors located in the GI tract. Targeted management of OIBD comprises purely peripherally acting opioid receptor antagonists and a combination of opioid receptor agonist and antagonist. Methylnaltrexone induces laxation in 50%–60% of patients with advanced diseases and OIBD who do not respond to traditional oral laxatives without inducing opioid withdrawal symptoms with similar response (45%–50% after an oral administration of naloxegol. A combination of prolonged-release oxycodone with prolonged-release naloxone (OXN in one tablet (a ratio of 2:1 provides analgesia with limited negative effect on the bowel function, as oxycodone displays high oral bioavailability and naloxone demonstrates local antagonist effect on opioid receptors in the GI tract and is totally inactivated in the liver. OXN in daily doses of up to 80 mg/40 mg provides equally effective analgesia with improved bowel function compared to oxycodone administered alone in patients with chronic non-malignant and cancer-related pain. OIBD is a common complication of long-term opioid therapy and may lead to quality of life deterioration and undertreatment of pain. Thus, a complex assessment and management that addresses underlying

  8. A compression bandage improves local infiltration analgesia in total knee arthroplasty

    DEFF Research Database (Denmark)

    Andersen, Lasse; Husted, Henrik; Otte, Niels Kristian Stahl Kri;

    2008-01-01

    BACKGROUND: High-volume local infiltration analgesia has been shown to be an effective pain treatment after knee replacement, but the role of bandaging to prolong analgesia has not been evaluated. METHODS: 48 patients undergoing fast-track total knee replacement with high-volume (170 mL) 0...... with compression bandage than in those with non-compression bandage and with a similar low use of oxycodone. Mean hospital stay was similar (2.8 days and 3.3 days, respectively). INTERPRETATION: A compression bandage is recommended to improve analgesia after high-volume local infiltration analgesia in total knee...... arthroplasty Udgivelsesdato: 2008/12...

  9. 2010年3月份美国FDA批准的NDA

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    3月份美国FDA批准的NDA如下表所示批准4月22日,委员会将讨论Acura医药公司的ACUYOX(oxycodone HCl+niacin,盐酸羟考酮+烟酸)片剂的新药申请(NDA22—451)。该药用以缓解适合使用速释口服阿片类止痛片患者的中至重度疼痛。

  10. Diencephalic storms from leptomeningeal metastases and leukoencephalopathy: a rare and clinically important complication.

    Science.gov (United States)

    Soriano, Aileen; Gutgsell, Terence L; Davis, Mellar P

    2014-02-01

    Diencephalic storms or paroxysmal sympathetic storms are characterized by episodic hyperhidrosis, hypertension, tachypnea, tachycardia, and abnormal posturing. These have been reported to occur in patients with hydrocephalus, intracranial tumors, and hypoxic, ischemic, or traumatic brain injury. They can be easily misdiagnosed as seizures, uncontrolled pheochromocytoma, drug withdrawal, thyroid storm, hypertensive crises, and sepsis or anxiety attacks. The most effective treatment to control these symptoms is yet to be identified. We present 2 individuals exhibiting these sympathetic surges; one whose symptoms were controlled with phenobarbital and the other with clonidine and oxycodone. Palliative medicine physicians should be made aware of this unusual complication.

  11. Exploring the relationship between analgesic event rate and pain intensity in kidney stone surgery: A Repeated Time to Event Pilot Study

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Pedersen, Katja Venborg; Christrup, Lona Louring;

    ). Gompertz and exponential distribution models were evaluated. Post-hoc linear mixed effect modelling was performed between estimated RTTE hazard and observed NRS using the lme4 package in R (3). Results: A Gompertz distribution model adequately described data, with a baseline event rate of 0.64h-1 (RSE 25......%) and a decline in event rate with a half-life of 1.2h-1 (RSE 22%). No significant differences were found between morphine and oxycodone. Post-hoc linear mixed effects modelling of the estimated RTTE hazard and NRS is demonstrated, but do not optimally describe the categorical nature of NRS. Conclusions: An RTTE...

  12. Suspected opioid-induced hyperalgesia in an infant.

    Science.gov (United States)

    Hallett, B R; Chalkiadis, G A

    2012-01-01

    One explanation for diminished opioid analgesic efficacy is opioid-induced hyperalgesia (OIH). We report a case of OIH in an infant with gastroschisis, requiring multiple surgical interventions and prolonged sedation for ventilation. This is the first report of OIH in an infant. On day 41 of life after nine separate surgical interventions, the patient's pain scores increased and remained elevated, despite increasing opioid administration. The patient also developed hyperalgesia, allodynia, and photophobia and became extremely irritable upon handling. Other possible causes were excluded, including interruption to opioid delivery, sepsis, acid-base and electrolyte disturbance, and ongoing surgical pathology. An opioid rotation to hydromorphone was initiated and ketamine was commenced. Sedation for ventilation was achieved with dexmedetomidine and midazolam infusions. Over a period of 24 h after opioid de-escalation, pain scores reduced rapidly and the patient became significantly less irritable with handling. All infusions were gradually weaned and eventually ceased.

  13. Ultrasound-guided paravertebral block using an intercostal approach.

    Science.gov (United States)

    Ben-Ari, Alon; Moreno, Milena; Chelly, Jacques E; Bigeleisen, Paul E

    2009-11-01

    We describe an ultrasound-guided technique of continuous bilateral paravertebral block using an intercostal approach in 12 patients undergoing elective abdominal surgery. Postoperatively, each of the patient's paravertebral catheters was bolused with 10 mL lidocaine (15 mg/mL), and each of the patient's catheters was infused with 0.2% ropivacaine at 10 mL/h. Using a pinprick test, the median number of dermatomes blocked after the initial bolus was 5 (interquartile range, 4-6), and 23 of 24 catheters produced a local anesthetic block. The median verbal pain score on postoperative day 1 was 5.5 (interquartile range, 3.5-6), and median dose of IV hydromorphone consumed during the first 24 h after surgery was 1.9 mg (interquartile range, 0.7-5.05). All catheters were removed within 72 h after surgery.

  14. Separation of Opiate Isomers Using Electrospray Ionization and Paper Spray Coupled to High-Field Asymmetric Waveform Ion Mobility Spectrometry

    Science.gov (United States)

    Manicke, Nicholas E.; Belford, Michael

    2015-05-01

    One limitation in the growing field of ambient or direct analysis methods is reduced selectivity caused by the elimination of chromatographic separations prior to mass spectrometric analysis. We explored the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS), an ambient pressure ion mobility technique, to separate the closely related opiate isomers of morphine, hydromorphone, and norcodeine. These isomers cannot be distinguished by tandem mass spectrometry. Separation prior to MS analysis is, therefore, required to distinguish these compounds, which are important in clinical chemistry and toxicology. FAIMS was coupled to a triple quadrupole mass spectrometer, and ionization was performed using either a pneumatically assisted heated electrospray ionization source (H-ESI) or paper spray, a direct analysis method that has been applied to the direct analysis of dried blood spots and other complex samples. We found that FAIMS was capable of separating the three opiate structural isomers using both H-ESI and paper spray as the ionization source.

  15. Three-dimensional solubility parameters and their use in characterising the permeation of drugs through the skin.

    Science.gov (United States)

    Groning, R; Braun, F J

    1996-05-01

    The physico-chemical properties of drug substances are major determinants of their transdermal absorption. In the present study the concept of the three-dimensional solubility parameters of Hansen was applied in conjunction with the Bagley projection to describe the permeation of drugs and model substances through the skin. Drug permeation data from the literature were compared with the calculated solubility parameters of the drugs. It was demonstrated that the permeation of drugs can be estimated by their position in the Bagley diagram. There is a linear correlation between the logarithm of the skin permeation of drugs and the exchange cohesive energy for the steroids testosterone, progesterone, hydrocortisone acetate, corticosterone, cortisone, and dexamethasone. A linear correlation can be confirmed for the permeation of glyceryl trinitrate, digitoxin, oestradiol, scopolamine, atropine, diethylcarbamazine, fentanyl, and chlorpheniramine. In the case of morphine, codeine, sufentanil, meperidine and hydromorphone there is a linear relationship, too.

  16. Alternating hemidystonia following traumatic brain injury as an unusual presentation of paroxysmal autonomic instability with dystonia syndrome.

    Science.gov (United States)

    Buerger, Kelly J; Salazar, Richard

    2014-01-01

    A 20-year-old man presented to the neurotrauma intensive care unit following blunt head injury. MRI revealed subarachnoid haemorrhage and multiple intraparenchymal haemorrhages suggesting severe brain injury. During recovery, the patient displayed intermittent episodes of alternating hemibody spasms with decerebrate/decorticate dystonic posturing. Episodes presented with autonomic dysregulation including hyperthermia, diaphoresis, tachypnoea, tachycardia and hypertension. Concern for seizure activity prompted simultaneous video monitoring and EEG testing. Results were without epileptiform activity suggesting against seizure as cause for alternating hemibody spasms. Paroxysmal autonomic instability with dystonia (PAID) was considered despite the unusual presentation. Intravenous hydromorphone was used for treatment, which relieved symptoms of autonomic dysregulation and dystonic posturing. PAID syndrome was diagnosed based on presentation with intermittent episodes of dystonia, autonomic dysregulation, absence of epileptiform activity and rapid response to opioid treatment. This case illustrates the clinical variability of this uncommon syndrome because alternating hemidystonia as main manifestation has not been previously described.

  17. Physical dependence potential of daily tramadol dosing in humans

    Science.gov (United States)

    Lofwall, Michelle R.; Mintzer, Miriam Z.; Bigelow, George E.; Strain, Eric C.

    2011-01-01

    Rationale Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence. Objectives The current study assessed the level of physical dependence and opioid blockade efficacy produced by daily maintenance on oral tramadol. Methods Nine residential opioid-dependent adults were maintained on two doses of daily oral tramadol (200 and 800 mg) for approximately 4-week intervals in a randomized, double-blind, crossover design. The acute effects of intramuscular placebo, naloxone (0.25, 0.5, and 1.0 mg), and hydromorphone (1.5, 3.0, and 6.0 mg) were tested under double-blind, randomized conditions. Outcomes included observer- and subject-rated measures and physiologic indices. Results Challenge doses of naloxone resulted in significantly higher mean peak withdrawal scores compared to placebo. Withdrawal intensity from naloxone was generally greater during 800 versus 200 mg/day tramadol maintenance. Mean peak ratings of agonist effects were elevated at higher hydromorphone challenge doses, but did not differ significantly between tramadol doses. Physiologic measures were generally affected by challenge conditions in a dose-dependent manner, with few differences between tramadol maintenance dose conditions. Conclusions Chronic tramadol administration produces dose-related opioid physical dependence, without producing dose-related attenuation of agonist challenge effects. Tramadol may be a useful treatment for patients with low levels of opioid dependence or as a treatment for withdrawal during opioid detoxification, but does not appear to be effective as a maintenance medication due to a lack of opioid cross-tolerance. PMID:20589494

  18. Pain Analysis in Patients with Hepatocellular Carcinoma: Irreversible Electroporation versus Radiofrequency Ablation-Initial Observations

    Energy Technology Data Exchange (ETDEWEB)

    Narayanan, Govindarajan, E-mail: gnarayanan@med.miami.edu; Froud, Tatiana, E-mail: tfroud@med.miami.edu [Miller School of Medicine, University of Miami, Department of Vascular and Interventional Radiology (United States); Lo, Kaming, E-mail: KLo@biostat.med.miami.edu [Miller School of Medicine, University of Miami, Department of Epidemiology and Public Health (United States); Barbery, Katuska J., E-mail: kbarbery@med.miami.edu; Perez-Rojas, Evelyn, E-mail: eprojas@med.miami.edu; Yrizarry, Jose, E-mail: jyrizarr@med.miami.edu [Miller School of Medicine, University of Miami, Department of Vascular and Interventional Radiology (United States)

    2013-02-15

    To retrospectively compare the postprocedure pain of hepatocellular carcinoma treated with irreversible electroporation (IRE) with radiofrequency ablation (RFA). This Health Insurance Portability and Accountability Act-compliant, institutional review board-approved study compared postprocedure pain in 21 patients (15 men, six women; mean age 61.5 years) who underwent IRE of 29 intrahepatic lesions (mean size 2.20 cm) in 28 IRE sessions with 22 patients (16 men, six women; mean age 60.2 years) who underwent RFA of 27 lesions (mean size 3.38 cm) in 25 RFA sessions. Pain was determined by patient-disclosed scores with an 11-point numerical rating scale and 24 h cumulative hydromorphone use from patient-controlled analgesia pump. Complications were noted. Statistical significance was evaluated by Fisher's exact test, the Chi-square test, and Student's t test. There was no significant difference in the cumulative hydromorphone dose (1.54 mg (IRE) vs. 1.24 mg (RFA); P = 0.52) and in the mean pain score (1.96 (IRE) vs. 2.25 (RFA); P = 0.70). In nine (32.14 %) of 28 IRE sessions and 11 (44.0 %) of 25 RFA sessions, patients reported no pain. Complications occurred in three (10.7 %) of 28 IRE treatments and included pneumothorax (n = 1), pleural effusion (n = 1), and bleeding in the form of hemothorax (n = 1); one (4 %) of 25 RFA treatments included burn. IRE is comparable to RFA in the amount of pain that patients experience and the amount of pain medication self-administered. Both modalities were well tolerated by patients. Prospective, randomized trials are necessary to further evaluate these findings.

  19. EMG assessment of analgesia in treatment of posttonsillectomy pain: random allocation, preliminary report.

    Science.gov (United States)

    Vaiman, Michael; Krakovski, Daniel

    2012-02-01

    Surface electromyographic (sEMG) study of posttonsillectomy swallow-evoked muscular reactions was performed to assess validity of EMG in evaluation of analgesic drugs. Sixty randomly chosen operated adults were divided into group 1 (n=30) treated with oxycodone, and group 2 (n=30) treated with placebo. Pain assessment included visual analog scale (VAS) pain score and EMG data: the timing, electric amplitude, and graphic patterns of muscular activity. We investigated masseter, infrahyoid, and submental-submandibular muscles. Records from trapezius muscle were used for control. The results were compared with previously established normative database. The sEMG data were compared with VAS score. Oxycodone significantly reduced VAS pain score and changed muscle reactions to analgesia (amplitude) as was recorded by sEMG, whereas placebo reduced VAS pain score nonsignificantly and changed the reaction of the trapezius muscle only. Analgesia smoothes the recorded swallow peaks and increases time of deglutition. Statistically significant difference in muscle reactions was detected between the 2 groups. sEMG might be used for quantitative evaluation of analgesic drugs by assessment of muscular reactions to pain and to analgesia. This method might add quantitative justification to the information obtained by VAS pain testing and clinical data.

  20. Opioid Overdose Deaths in the City and County of San Francisco: Prevalence, Distribution, and Disparities.

    Science.gov (United States)

    Visconti, Adam J; Santos, Glenn-Milo; Lemos, Nikolas P; Burke, Catherine; Coffin, Phillip O

    2015-08-01

    Drug overdose is now the leading cause of unintentional death nationwide, driven by increased prescription opioid overdoses. To better understand urban opioid overdose deaths, this paper examines geographic, demographic, and clinical differences between heroin-related decedents and prescription opioid decedents in San Francisco from 2010 to 2012. During this time period, 331 individuals died from accidental overdose caused by opioids (310 involving prescription opioids and 31 involving heroin). Deaths most commonly involved methadone (45.9%), morphine (26.9%), and oxycodone (21.8%). Most deaths also involved other substances (74.9%), most commonly cocaine (35.3%), benzodiazepines (27.5%), antidepressants (22.7%), and alcohol (19.6%). Deaths were concentrated in a small, high-poverty, central area of San Francisco and disproportionately affected African-American individuals. Decedents in high-poverty areas were significantly more likely to die from methadone and cocaine, whereas individuals from more affluent areas were more likely die from oxycodone and benzodiazepines. Heroin decedents were more likely to be within a younger age demographic, die in public spaces, and have illicit substances rather than other prescription opioids. Overall, heroin overdose death, previously common in San Francisco, is now rare. Prescription opioid overdose has emerged as a significant concern, particularly among individuals in high-poverty areas. Deaths in poor and affluent regions involve different causative opioids and co-occurring substances.

  1. Decline in drug overdose deaths after state policy changes - Florida, 2010-2012.

    Science.gov (United States)

    Johnson, Hal; Paulozzi, Leonard; Porucznik, Christina; Mack, Karin; Herter, Blake

    2014-07-04

    During 2003-2009, the number of deaths caused by drug overdose in Florida increased 61.0%, from 1,804 to 2,905, with especially large increases in deaths caused by the opioid pain reliever oxycodone and the benzodiazepine alprazolam. In response, Florida implemented various laws and enforcement actions as part of a comprehensive effort to reverse the trend. This report describes changes in overdose deaths for prescription and illicit drugs and changes in the prescribing of drugs frequently associated with these deaths in Florida after these policy changes. During 2010-2012, the number of drug overdose deaths decreased 16.7%, from 3,201 to 2,666, and the deaths per 100,000 persons decreased 17.7%, from 17.0 to 14.0. Death rates for prescription drugs overall decreased 23.2%, from 14.5 to 11.1 per 100,000 persons. The decline in the overdose deaths from oxycodone (52.1%) exceeded the decline for other opioid pain relievers, and the decline in deaths for alprazolam (35.6%) exceeded the decline for other benzodiazepines. Similar declines occurred in prescribing rates for these drugs during this period. The temporal association between the legislative and enforcement actions and the substantial declines in prescribing and overdose deaths, especially for drugs favored by pain clinics, suggests that the initiatives in Florida reduced prescription drug overdose fatalities.

  2. A national survey into perioperative anesthetic management of patients with a fractured neck of femur

    Directory of Open Access Journals (Sweden)

    Soinikoski Mirka

    2012-07-01

    Full Text Available Abstract Background We made a survey among Finnish anesthesiologists concerning the current perioperative anesthetic practice of hip fracture patients for further development in patient care. Methods All members of the Finnish Society of Anesthesiologists with a known e-mail address (786 were invited to participate in an internet-based survey. Results The overall response rate was 55% (423 responses; 298 respondents participated in the care of hip fracture patients. Preoperative analgesia was mostly managed with oxycodone and paracetamol; every fifth respondent applied an epidural infusion. Most respondents (98% employed a spinal block with or without an epidural catheter for intraoperative anesthesia. Midazolam, propofol and/or fentanyl were used for additional sedation. General anesthesia was used rarely. Postoperatively, paracetamol and non-steroidal anti-inflammatory drugs and occasionally peroral oxycodone, were prescribed in addition to epidural analgesia. Conclusions The survey suggests that the impact of more individualised analgesia regimens, both preoperatively and postoperatively, should be investigated in further studies.

  3. Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

    Directory of Open Access Journals (Sweden)

    Sachiko Fukui

    2017-03-01

    Full Text Available The purpose of this study was to develop an extended-release (ER matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS and hydroxypropylcellulose (HPC were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet. Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method, dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin. Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

  4. A Retrospective Analysis of Urine Drugs of Abuse Immunoassay True Positive Rates at a National Reference Laboratory.

    Science.gov (United States)

    Johnson-Davis, Kamisha L; Sadler, Aaron J; Genzen, Jonathan R

    2016-03-01

    Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4-methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was ∼14%, ∼34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey.

  5. Opioids in the treatment of postoperative pain: old drugs with new options?

    Science.gov (United States)

    Raeder, Johan

    2014-03-01

    New approved options with opioids in the postoperative setting may include new ways of administration, new combinations with other drugs and new opioid drugs. Newly approved devices for administration include sublingual sufentanil dispenser and transdermal iontophoretic fentanyl, with the purpose of almost mimicking the rapid and reliable onset of intravenous (IV) administration, without the problems of an ongoing IV cannula and cumbersome equipment. Still, potential problems of overdosing and misuse must be in focus when these devices come into use. Tapentadol is a new partial µ-receptor opioid agonist with a combined action on norepinephrine-induced analgesia, representing a promising drug in terms of less side effects at equianalgesic doses compared with pure agonists. The mixture of different opioids given together, such as oxycodone and morphine, for oral use may also have some analgesic synergy with an improved side-effect profile, although more studies are needed. Oral oxycodone is a reliable oral opioid option, but when combined with paracetamol in the same tablet or mixture, care should also be taken to avoid serious side effects from inadvertent paracetamol overdose.

  6. μ-Opioid receptor activation and noradrenaline transport inhibition by tapentadol in rat single locus coeruleus neurons.

    Science.gov (United States)

    Sadeghi, Mahsa; Tzschentke, Thomas M; Christie, MacDonald J

    2015-01-01

    Tapentadol is a novel analgesic that combines moderate μ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule. Both mechanisms of action are involved in producing analgesia; however, the potency and efficacy of tapentadol in individual neurons has not been characterized. Whole-cell patch-clamp recordings of G-protein-coupled inwardly rectifying K(+) (KIR 3.x) currents were made from rat locus coeruleus neurons in brain slices to investigate the potency and relative efficacy of tapentadol and compare its intrinsic activity with other clinically used opioids. Tapentadol showed agonist activity at μ receptors and was approximately six times less potent than morphine with respect to KIR 3.x current modulation. The intrinsic activity of tapentadol was lower than [Met]enkephalin, morphine and oxycodone, but higher than buprenorphine and pentazocine. Tapentadol inhibited the noradrenaline transporter (NAT) with potency similar to that at μ receptors. The interaction between these two mechanisms of action was additive in individual LC neurons. Tapentadol displays similar potency for both µ receptor activation and NAT inhibition in functioning neurons. The intrinsic activity of tapentadol at the μ receptor lies between that of buprenorphine and oxycodone, potentially explaining the favourable profile of side effects, related to μ receptors. 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. © 2013 The British Pharmacological Society.

  7. New therapy for neuropathic pain.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Watanabe, Chizuko; Yonezawa, Akihiko; Sakurada, Shinobu

    2009-01-01

    Neuropathic pain is one of the worst painful symptoms in clinic. It contains nerve-injured neuropathy, diabetic neuropathy, chronic inflammatory pain, cancer pain, and postherpes pain, and is characterized by a tactile allodynia and hyperalgesia. Neuropathic pain, especially the nerve-injured neuropathy, the diabetic neuropathy, and the cancer pain, is opioid resistant pain. Since the downregulation of mu-opioid receptors is observed in dorsal spinal cord, morphine and fentanyl could not provide marked antihyperalgesic/antiallodynic effects in the course neuropathic pain states. The downregulation of mu-opioid receptors is suggested to be mediated through the activation of NMDA receptors. Moreover, at the neuropathic pain states, the increased expression of voltage-dependent Na+ channels and Ca2+ channels are observed. Based on the above information concerned with the pathophysiology of neural changes in neuropathic pain states, new drug treatments for neuropathic pain, using ketamine, methadone, and gabapentin, have been developed. These drugs show remarkable effectiveness against hyperalgesia and allodynia during neuropathic pain states. Oxycodone is a mu-opioid receptor agonist, which has different pharmacological profiles with morphine. The remarkable effectiveness of oxycodone for neuropathic pain provides the possibility that mu-opioid receptor agonists, which have different pharmacological profile with morphine, can be used for the management of neuropathic pain.

  8. Pharmacotherapy for restless legs syndrome.

    Science.gov (United States)

    Ferini-Strambi, Luigi; Marelli, Sara

    2014-06-01

    Restless legs syndrome (RLS) is a common condition characterized by paresthesia and an urge to move. Predominantly, symptoms occur at rest in the evening or at night, and they are alleviated by moving the affected extremity. RLS prevalence in the general population has been estimated to be approximately 5%. This review presents all options for the treatment of RLS. Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS, that is, when symptoms impair the patient's quality of life, daytime functioning, social functioning or sleep. Treatment on demand is a clinical need in some RLS patients, and medications include carbidopa/levodopa, pramipexole, ropinirole, oxycodone, methadone, codeine and tramadol. Chronic RLS should be treated with either a nonergot dopamine agonist or an α-2-δ calcium channel ligand. A dopamine agonist is a more appropriate choice in the presence of depression and overweight. As α-2-δ ligands can alleviate chronic pain and may be helpful in treating anxiety and insomnia, the presence of any of these comorbidities may favor their use. For RLS present through much of the day and night, the use of long-acting agents, such as the rotigotine patch or gabapentin enacarbil should be considered. In refractory RLS, oral prolonged release oxycodone-naloxone should be considered.

  9. Targinact for restless legs syndrome.

    Science.gov (United States)

    2016-04-01

    Idiopathic restless legs syndrome (RLS)--also known as Willis-Ekbom disease--is a neurological condition characterised by an overwhelming urge to move the legs, occurring during rest or inactivity, especially at night. Symptoms are highly variable in frequency and severity, and can affect sleep and quality of life. First-line management includes addressing precipitating or aggravating factors and providing explanation, reassurance and advice on self-help strategies. Drug therapy (e.g. a dopamine agonist) is used for patients with more severe symptoms. In December 2014, the marketing authorisation for a modified-release preparation containing oxycodone and naloxone (Targinact-Napp Pharmaceuticals) was expanded to include use in the treatment of severe to very severe RLS after failure of dopaminergic therapy.(10)Here we review the management of adults with RLS, including the place of oxycodone/naloxone. 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/

  10. 中西医结合治疗中重度癌痛25例临床观察%Observation on Integrated Traditional Chinese and Western Medicine in Treating 25 Cases of Medium and Severe Cancer Induced Pain

    Institute of Scientific and Technical Information of China (English)

    王雅茹; 张岚; 田鹏娜; 宋磊; 南艳; 张向业; 张建英

    2014-01-01

    To observe the effects of external application of traditional Chinese medicine combined with oral administration of oxycodone for the treatment of medium and severe cancer ! induced pain.Methods:Fifty patients with cancer pain were randomly di-vided into treatment group (n=25 )and control group (n=25 )by the method of block randomization.Both groups gave patients oxyc-odone according to the dosage titration,and the treatment group applied traditional Chinese medicine (TCM)solution to the raw skin at the same time,3 to 5 times a day for 3 weeks.The effect in the two groups,the dosage of oxycodone and constipation condition were ob-served.Results:The pain control of the treatment group was obviously better than that of the control group (P<0.05 );the dosage of oxycontin in treatment group was decreased significantly (P<0.05 )compared with the control group;the incidence rate of constipation of the control group was higher than that of the treatment group (P<0.05 ).Conclusion:Integrated traditional Chinese and western medicine in controlling cancer ! induced pain can increase curative effect and reduce the occurrence of constipation.%目的:观察中药外用联合口服奥施康定治疗癌痛的临床疗效。方法:将50例患者采用区组随机化方法随机分为治疗组(25例)和对照组(25例);2组均按滴定剂量给予奥施康定,治疗组同时用中药药液擦于痛处皮肤,3~5次/d,3周为1个疗程。观察2组止痛效果、奥施康定用量以及2组便秘情况。结果:治疗组疼痛控制明显优于对照组(P<0.025),奥施康定用量较对照组明显减少(P<0.005),对照组便秘发生率高于治疗组(P<0.05)。结论:中西医结合控制癌性疼痛,提高疗效,减少便秘的发生。

  11. Postoperative pain management with transdermal fentanyl after forefoot surgery: a randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Merivirta R

    2015-01-01

    Full Text Available Riika Merivirta,1 Mikko Pitkänen,2 Jouko Alanen,3 Elina Haapoja,1 Mari Koivisto,4 Kristiina Kuusniemi11Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine of Turku University Hospital and University of Turku, Turku, 2Department of Anaesthesia, Hospital Orton, Invalid Foundation, Helsinki, 3Terveystalo Clinic Hospital, Helsinki, 4Department of Biostatistics, University of Turku, Turku, FinlandBackground: Quality of life is decreased in patients with hallux valgus deformity, mainly because of pain. Significant improvement is usually achieved by surgery. However, postoperative pain can be moderate to severe for 2–3 days. The aim of the present study was to evaluate the use of transdermal fentanyl for postoperative pain management after forefoot surgery.Methods: Sixty patients undergoing hallux valgus or hallux rigidus surgery were allocated to receive a patch delivering either fentanyl 12 µg/hour or placebo for postoperative pain. The consumption of rescue opioid oxycodone, the primary outcome measure, was evaluated daily until the fourth postoperative day. Total consumption of oxycodone during the study period was also assessed. Pain scores and possible adverse effects were evaluated every 6 hours during the first 24 hours and on the fourth postoperative day.Results: The use of rescue opioid was low in both groups, the median (range consumption of oxycodone being 10 (0–50 mg on the day of surgery (no difference between the groups, P=0.31 and 0 (0–35 mg thereafter. The total combined consumption was 10 (0–105 mg in the fentanyl group and 20 (0–70 mg in the placebo group (P=0.23. There were no statistically significant differences in pain scores or adverse effects between the groups.Conclusion: As a part of multimodal analgesia with ibuprofen and acetaminophen, a patch delivering fentanyl 12 µg/hour did not significantly decrease the consumption of rescue opioid or pain scores after forefoot surgery

  12. Feasibility and analgesic efficacy of the transversus abdominis plane block after single-port laparoscopy in patients having bariatric surgery

    Directory of Open Access Journals (Sweden)

    Wassef M

    2013-11-01

    Full Text Available Michael Wassef, David Y Lee, Jun L Levine, Ronald E Ross, Hamza Guend, Catherine Vandepitte, Admir Hadzic, Julio TeixeiraDepartment of Anesthesiology, St Luke's-Roosevelt Hospital Center, New York, NY, USAPurpose: The transversus abdominis plane (TAP block is a technique increasingly used for analgesia after surgery on the anterior abdominal wall. We undertook this study to determine the feasibility and analgesic efficacy of ultrasound-guided TAP blocks in morbidly obese patients. We describe the dermatomal spread of local anesthetic in TAP blocks administered, and test the hypothesis that TAP blocks decrease visual analog scale (VAS scores.Patients and methods: After ethics committee approval and informed consent, 35 patients with body mass index >35 undergoing single-port sleeve gastrectomy (SPSG were enrolled. All patients received balanced general anesthesia, followed by intravenous patient-controlled analgesia (IV-PCA; hydromorphone postoperatively; all reported VAS >3 upon arrival to the recovery room. From the cohort of 35 patients having single-port laparoscopy (SPL, a sealed envelope method was used to randomly select ten patients to the TAP group and 25 patients to the control group. The ten patients in the TAP group received ultrasound-guided TAP blocks with 30 mL of 0.2% Ropivacaine injected bilaterally. The dermatomal distribution of the sensory block (by pinprick test was recorded. VAS scores for the first 24 hours after surgery and opioid use were compared between the IV-PCA+TAP block and IV-PCA only groups.Results: Sensory block ranged from T5–L1. Mean VAS pain scores decreased from 8 ± 2 to 4 ± 3 (P=0.04 within 30 minutes of TAP block administration. Compared with patients given IV-PCA only, significantly fewer patients who received TAP block had moderate or severe pain (VAS 4–10 after block administration at 6 hours and 12 hours post-surgery. However, cumulative consumption of hydromorphone at 24 hours after SPSG surgery

  13. Cost of opioid intravenous patient-controlled analgesia: results from a hospital database analysis and literature assessment

    Directory of Open Access Journals (Sweden)

    Palmer P

    2014-06-01

    Full Text Available Pamela Palmer,1 Xiang Ji,2 Jennifer Stephens21AcelRx Pharmaceuticals, Inc., Redwood City, CA, 2Pharmerit International, Bethesda, MD, USABackground: Intravenous patient-controlled analgesia (PCA equipment and opioid cost analyses on specific procedures are lacking. This study estimates the intravenous PCA hospital cost for the first 48 postoperative hours for three inpatient surgeries.Methods: Descriptive analyses using the Premier database (2010–2012 of more than 500 US hospitals were conducted on cost (direct acquisition and indirect cost for the hospital, such as overhead, labor, pharmacy services of intravenous PCA after total knee/hip arthroplasty (TKA/THA or open abdominal surgery. Weighted average cost of equipment and opioid drug and the literature-based cost of adverse events and complications were aggregated for total costs.Results: Of 11,805,513 patients, 272,443 (2.3%, 139,275 (1.2%, and 195,062 (1.7% had TKA, THA, and abdominal surgery, respectively, with approximately 20% of orthopedic and 29% of abdominal patients having specific intravenous PCA database cost entries. Morphine (57% and hydromorphone (44% were the most frequently used PCA drugs, with a mean cost per 30 cc syringe of $16 (30 mg and $21 (6 mg, respectively. The mean number of syringes used for morphine and hydromorphone in the first 48 hours were 1.9 and 3.2 (TKA, 2.0 and 4.2 (THA, and 2.5 and 3.9 (abdominal surgery, respectively. Average costs of PCA pump, intravenous tubing set, and drug ranged from $46 to $48, from $20 to $22, and from $33 to $46, respectively. Pump, tubing, and saline required to maintain patency of the intravenous PCA catheter over 48 hours ranged from $9 to $13, from $8 to $9, and from $20 to $22, respectively. Supplemental non-PCA opioid use ranged from $56 for THA to $87 for abdominal surgery. Aggregated mean intravenous PCA equipment and opioid cost per patient were $196 (THA, $204 (TKA, and $243 (abdominal surgery. Total costs, including

  14. 14-Amino-4,5-Epoxymorphinan Derivatives and Their Pharmacological Actions

    Science.gov (United States)

    Lewis, John W.; Husbands, Stephen M.

    14-Hydroxy-7,8-dihydromorphinone (oxymorphone) and its derivatives (oxycodone, naloxone, naltrexone) have become among the most important clinical agents to have been produced from opium. 14-Aminocodeinone and its 7,8-dihydro and morphinone derivatives are of more recent origin thanks to the work of Professor Gordon Kirby and his collaborators. The 14-amino parent compounds have proved of limited interest but their 14-acylamino- and 14-alkylamino derivatives have been extensively studied. The 4'-substituted cinnamoylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones, C-CAM and M-CAM are the best available selective MOR irreversible antagonists and the related dihydrocodeinone MC-CAM, 4'-chlorocinnamoylamino-17-cyclopropylmethyl-7,8-dihydronorcodeinone, is a long-acting MOR partial agonist with extended MOR-pseudoirreversible antagonist activity that could be a candidate for pharmacotherapy of opiate abuse/dependence.

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

    DEFF Research Database (Denmark)

    Klepstad, P; Fladvad, T; Skorpen, F;

    2011-01-01

    Cancer pain patients need variable opioid doses. Preclinical and clinical studies suggest that opioid efficacy is related to genetic variability. However, the studies have small samples, findings are not replicated, and several candidate genes have not been studied. Therefore, a study of genetic...... variability with opioid doses in a large population using a confirmatory validation population was warranted. We recruited 2294 adult European patients using a World Health Organization (WHO) step III opioid and analyzed single nucleotide polymorphisms (SNPs) in genes with a putative influence on opioid...... mechanisms. The patients' mean age was 62.5 years, and the average pain intensity was 3.5. The patients' primary opioids were morphine (n=830), oxycodone (n=446), fentanyl (n=699), or other opioids (n=234). Pain intensity, time on opioids, age, gender, performance status, and bone or CNS metastases predicted...

  16. [Pain management for cancer patients with critical pathway on computer].

    Science.gov (United States)

    Hori, Natsuki; Konishi, Toshiro

    2005-02-01

    For relief from cancer pain, we developed critical pathway (CP) as an effective strategy for the medical staff treating cancer patients. This CP was made out of Microsoft Excel, and was used on personal computers. "Good sleeping" was set as the first goal and the second was "No pain in rest position." To achieve this, physicians and nurses evaluate medical efficacy and complications including nausea/vomiting, constipation, somnolence and hallucination everyday using controlled release oxycodone in addition to NSAIDs and prochlorperazine, stool softener and peristaltic stimulant for adverse effects. These outcomes lead to the medication change the next day by calculation using visual basic function due to opioid titration theory. In twelve patients this CP was acceptable, and all of them achieved the second goal within a week without severe adverse effects except constipation.

  17. [Essentials for transition of palliative care patients to palliative home care and for management of their cancer pain].

    Science.gov (United States)

    Koshikawa, Takafumi; Shimoyama, Naohito

    2006-05-01

    Multi-disciplinary team work among visiting doctors, nurses, care managers and pharmacists located close to the patient's home is essential for smooth transition of a palliative care patient from hospital care to palliative home care and should be set up prior to the patient's discharge from the hospital. Palliative home care physicians should have knowledge of the fundamental support by the government to spare excessive cost to the patients. As for cancer pain management, opioid-centered analgesic therapies have lead to better quality home care for patients. In Japan, although oxycodone SRs and fentanyl patches are available besides morphine, there is no rescue opioid other than morphine. On the other hand, some cancer pain refractory to opioids such as neuropathic cancer pain should be carefully treated by adjuvant analgesics in conjunction with non-pharmacological treatments.

  18. The Impact of Opioid Treatment on Regional Gastrointestinal Transit

    DEFF Research Database (Denmark)

    Poulsen, Jakob L; Nilsson, Matias; Brock, Christina;

    2016-01-01

    -dimensional (3D)-Transit system. METHODS: Twenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. AdverseGI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipationsymptom......BACKGROUND/AIMS: To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact ofopioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GItransit times using the 3...... questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system, and segmental transit times in the colon were determined using a custom Matlab(®) graphical user interface. RESULTS: GI symptom scores increased significantly across all applied GI questionnaires...

  19. Acura提交Acurox的新药申请

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Acura制药公司和King制药公司日前宣布,Acura已向美国食品与药品管理局(FDA)提交Acurox(oxycodone HCl/niacin,盐酸羟考酮/烟酸)片剂(Ⅰ)的新药申请(NDA),包括一个优先评审请求。Acura公司和King公司相信,如获批准,(Ⅰ)将成为第一个获得FDA批准的为制止吞服过量药片和其他误用滥用方法而设计的速释阿片类镇痛剂。

  20. A Model-Based Approach for Joint Analysis of Pain Intensity and Opioid Consumption in Postoperative Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Knøsgaard, Katrine R; Olesen, Anne E

    2016-01-01

    Joint analysis of pain intensity and opioid consumption is encouraged in trials of postoperative pain. However, previous approaches have not appropriately addressed the complexity of their interrelation in time. In this study, we applied a non-linear mixed effects model to simultaneously study pain...... intensity and opioid consumption in a 4-h postoperative period for 44 patients undergoing percutaneous kidney stone surgery. Analysis was based on 748 Numerical Rating Scale (NRS) scores of pain intensity and 51 observed morphine and oxycodone dosing events. A joint model was developed to describe...... the recurrent pattern of four key phases determining the development of pain intensity and opioid consumption in time; (A) Distribution of pain intensity scores which followed a truncated Poisson distribution with time-dependent mean score ranging from 0.93 to 2.45; (B) Probability of transition to threshold...

  1. Prehospital and En Route Analgesic Use in the Combat Setting: A Prospectively Designed, Multicenter, Observational Study

    Science.gov (United States)

    2015-03-01

    100 ) GCS 15 (6–15) 15 (15–15) 15 (14–15) 15 (15–15) 15 (15–15) 15 (14–15) 3T (n) 7 1 0 1 1 0 IQR, interquartile range; SBP , systolic blood pressure...ketorolac n = 2, oxycodone n = 1). Of the remaining 228 patients, 100 % were male, with a median age of 24 years (IQR25–75 22–30). The predominant mechanism...Morphine 34 (78/228) 42 24 — 6 6 10 mg (8–10) Fentanyl (IV) 22 (50/228) 50 — — — — 75 mcg (50– 100 ) Fentanyl (TM) 20 (45/228) — — 45 — — 800 mcg (800

  2. Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery?

    DEFF Research Database (Denmark)

    Qazi, Saddiq Mohammad; Sindby, Eske Jesper; Nørgaard, Martin Agge

    2015-01-01

    , in a short term post-cardiac surgery setting. Particular attention was given to the rate of myocardial infarction, sternal healing, gastro-intestinal complications, renal failure and all-cause mortality. METHODS: This was a single-centre, open label parallel design randomised controlled study. Patients, who...... of sternal healing, postoperative myocardial infarction or gastrointestinal bleeding. The preoperative levels of creatinine were found to increase by 100% in nine patients (9.6%) in the ibuprofen group, resulting in an acute renal injury (in accordance with the RIFLE-criteria). Eight of these patients...... returned to normal renal function within 14 days. The levels of creatinine in patients in the oxycodone group were not found to increase to the same magnitude. CONCLUSION: The results of this study suggest that patients treated postoperatively, following cardiac surgery, are at no greater risk of harm...

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

    DEFF Research Database (Denmark)

    Klepstad, P; Fladvad, T; Skorpen, F;

    2011-01-01

    Cancer pain patients need variable opioid doses. Preclinical and clinical studies suggest that opioid efficacy is related to genetic variability. However, the studies have small samples, findings are not replicated, and several candidate genes have not been studied. Therefore, a study of genetic...... mechanisms. The patients' mean age was 62.5 years, and the average pain intensity was 3.5. The patients' primary opioids were morphine (n=830), oxycodone (n=446), fentanyl (n=699), or other opioids (n=234). Pain intensity, time on opioids, age, gender, performance status, and bone or CNS metastases predicted......C, HTR3D, HTR3E, HTR1, or CNR1 showed significant associations with opioid dose in both the development and the validation analyzes. These findings do not support the use of pharmacogenetic analyses for the assessed SNPs to guide opioid treatment. The study also demonstrates the importance...

  4. Coma blisters with hypoxemic respiratory failure.

    Science.gov (United States)

    Agarwal, Abhishek; Bansal, Meghana; Conner, Kelly

    2012-03-15

    A 24-year-old woman with quadriplegia was admitted with respiratory failure because of pneumonia. She was on multiple medications including diazepam, oxycodone, and amitriptyline, known to be associated with coma blisters, though she did not overdose on any of them. On hospital day 2, she developed multiple blisters on both sides of her right forearm and hand. Skin biopsy showed eccrine gland degeneration consistent with coma blisters. It was felt that hypoxemia from her pneumonia contributed to the development of these blisters, which occurred on both pressure and non-pressure bearing areas of the arm. Coma blisters are self-limited skin lesions that occur at sites of maximal pressure, mostly in the setting of drug overdose. However, coma blisters may occur with metabolic and neurological conditions resulting in coma.

  5. The Attractiveness of Opposites: Agonists and Antagonists.

    LENUS (Irish Health Repository)

    O'Brien, Tony

    2015-02-02

    ABSTRACT Opioid-induced bowel dysfunction, of which constipation is the most common aspect, is a major limiting factor in the use of opioids for pain management. The availability of an oral, long-acting formulation of oxycodone and naloxone represents a highly significant development in pain management. The combination of an opioid analgesic with an opioid antagonist offers reliable pain control with a significant reduction in the burden of opioid-induced constipation. This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http:\\/\\/www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

  6. Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

    Science.gov (United States)

    Pergolizzi, Joseph V; Raffa, Robert B; Pappagallo, Marco; Fleischer, Charles; Pergolizzi, Joseph; Zampogna, Gianpietro; Duval, Elizabeth; Hishmeh, Janan; LeQuang, Jo Ann; Taylor, Robert

    2017-01-01

    Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include fixed-dose combination products of oxycodone analgesic together with naloxone. PMID:28176913

  7. Irreversible blockade of the high and low affinity ( sup 3 H) naloxone binding sites by C-6 derivatives of morphinane-6-ones

    Energy Technology Data Exchange (ETDEWEB)

    Krizsan, D. (EGIS Pharmaceutical Works, Budapest (Hungary)); Varga, E.; Benyhe, S.; Szucs, M.; Borsodi, A. (Biological Research Center of the Hungarian Academy of Sciences, Szeged (Hungary)); Hosztafi, S. (Alkaloida Chemical Works, Tiszavasvari (Hungary))

    1991-01-01

    C-6 derivatives-hydrazones, phenylhydrazones, dinitrophenylhydrazones, oximes and semicarbazones - of morphinane-6-ones were synthesized and their binding characteristics were studied on rat brain membranes. The dihydromorphinone and oxymorphone derivatives compete for the ({sup 3}H)naloxone binding sites with high affinity, while the dihydrocodeinone and oxycodone derivatives are less potent. The affinity of the new compounds is decreased for the delta sites as compared to the parent ligands. The ligands bearing bulky substituents also bind with low affinity to the kappa sites. The modification decreased the Na{sup +}-index of compounds indicating their mixed agonist-antagonist character. The dihydromorphinone derivatives are all capable to block irreversibly the high affinity binding site of ({sup 3}H)naloxone, whereas the dihydrocodeinone derivatives block irreversibly the low affinity site. A possible mechanism for the inhibition is suggested.

  8. A poor metabolizer of both CYP2C19 and CYP2D6 identified by mechanistic pharmacokinetic simulation in a fatal drug poisoning case involving venlafaxine

    DEFF Research Database (Denmark)

    Jornil, J; Nielsen, T S; Rosendal, I

    2013-01-01

    Abstract We present a fatal drug poisoning case involving venlafaxine (VEN). The deceased took his medication regularly (including 150 mg VEN twice daily), and nothing in the case or autopsy findings pointed towards suicide. The toxicological assessment concluded that the cause of death was most...... likely due to a poisoning with a combination of VEN, oxycodone and ethanol, and the manner of death was considered to be an accident. The blood concentration of VEN was high (4.5 mg/kg), and the ratio of the VEN metabolite O-desmethylvenlafaxine (ODV) to VEN was exceptionally low (0.006). Mechanistic...... would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations...

  9. Effects of amphetamine, morphine, and CP 55, 940 on Go/No-Go task performance in rhesus monkeys.

    Science.gov (United States)

    Koek, Wouter; Gerak, Lisa R; France, Charles P

    2015-08-01

    In humans, impulsivity measured as false alarms in a Go/No-Go task is reportedly decreased by amphetamine and is not affected by oxycodone and delta(9)-tetrahydrocannabinol. To model these findings in animals, three rhesus monkeys were trained to perform a food-reinforced Go/No-Go task. In this task, amphetamine was found to decrease false alarms (i.e. responding during No-Go trials), but only at doses that also decreased hits (i.e. responding during Go trials). Morphine generally decreased hits but not false alarms. The cannabinoid receptor agonist CP 55, 940 decreased both false alarms and hits, but only at doses that also decreased the number of trials completed. Additional studies in animals and humans are necessary to delineate the conditions under which amphetamine and other psychoactive drugs affect impulsivity in Go/No-Go tasks.

  10. Long-term, high-dose benzodiazepine prescriptions in veteran patients with PTSD: influence of preexisting alcoholism and drug-abuse diagnoses.

    Science.gov (United States)

    Hermos, John A; Young, Melissa M; Lawler, Elizabeth V; Rosenbloom, David; Fiore, Louis D

    2007-10-01

    Databases from the New England Veterans Integrated Service Network were analyzed to determine factors associated with long-term, high-dose anxiolytic benzodiazepine prescriptions dispensed to patients with posttraumatic stress disorder (PTSD) and existing alcoholism and/or drug abuse diagnoses. Among 2,183 PTSD patients, 234 received the highest 10% average daily doses for alprazolam, clonazepam, diazepam, or lorazepam, doses above those typically recommended. Highest doses were more commonly prescribed to patients with existing drug abuse diagnoses. Among patients with PTSD and alcoholism, younger age, drug abuse, and concurrent prescriptions for another benzodiazepine and oxycodone/acetaminophen independently predicted high doses. Results indicate that for veteran patients with PTSD, alcoholism alone is not associated with high-dose benzodiazepines, but existing drug abuse diagnoses do increase that risk.

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

    Science.gov (United States)

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

    2015-02-01

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

  12. Candidate metrics for evaluating the impact of prescriber education on the safe use of extended-release/long-acting (ER/LA) opioid analgesics.

    Science.gov (United States)

    Willy, Mary E; Graham, David J; Racoosin, Judith A; Gill, Rajdeep; Kropp, Garner F; Young, Jessica; Yang, Jeff; Choi, Joyce; MaCurdy, Thomas E; Worrall, Chris; Kelman, Jeffrey A

    2014-09-01

    The objective of this study was to develop metrics to assess opioid prescribing behavior as part of the evaluation of the Extended-Release/Long-Acting (ER/LA) Opioid Analgesic Risk Evaluation and Mitigation Strategies (REMS). Candidate metrics were selected using published guidelines, examined using sensitivity analyses, and applied to cross-sectional rolling cohorts of Medicare patients prescribed with extended-release oxycodone (ERO) between July 2, 2006 and July 1, 2011. Potential metrics included prescribing opioid-tolerant-only ER/LA opioid analgesics to non-opioid-tolerant patients, prescribing early fills to patients, and ordering drug screens. Proposed definitions for opioid tolerance were seven continuous days of opioid usage of at least 30 mg oxycodone equivalents, within the 7 days (primary) or 30 days (secondary) prior to first opioid-tolerant-only ERO prescription. Forty-four percent of opioid-tolerant-only ERO episodes met the primary opioid tolerance definition; 56% met the secondary definition. Fills were deemed "early" if a prescription was filled before 70% (primary) or 50% (secondary) of the prior prescription's days' supply was to be consumed. Five percent (primary) and 2% (secondary) of episodes had more than or equal to two early fills during treatment. At least one drug screen was billed in 14% of episodes. Stratified analyses indicated that older patients were less likely to be opioid tolerant at the time of the first opioid-tolerant-only ERO prescription. Investigators propose three metrics to monitor changes in prescribing behaviors for opioid analgesics that might be used to evaluate the ER/LA Opioid Analgesics REMS. Low frequencies of patients, particularly those >85 years, were likely to be opioid tolerant prior to receiving prescriptions for opioid-tolerant-only ERO. Wiley Periodicals, Inc.

  13. Choice between delayed food and immediate opioids in rats: treatment effects and individual differences.

    Science.gov (United States)

    Panlilio, Leigh V; Secci, Maria E; Schindler, Charles W; Bradberry, Charles W

    2017-09-04

    Addiction involves maladaptive choice behavior in which immediate drug effects are valued more than delayed nondrug rewards. To model this behavior and extend our earlier work with the prescription opioid oxycodone, we allowed rats to choose between immediate intravenous delivery of the short-acting opioid remifentanil and delayed delivery of highly palatable food pellets. Treatment drugs were tested on a baseline where remifentanil was preferred over food. Treatment with a high dose of the opioid antagonist naltrexone decreased but did not reverse the preference for remifentanil. Treatment with the serotonin 5-HT2C agonist lorcaserin decreased remifentanil and food self-administration nonselectively. Across conditions in which the alternative to delayed food was either a moderate dose of oxycodone, a moderate or high dose of remifentanil, a smaller more immediate delivery of food, or timeout with no primary reinforcement, choice was determined by both the length of the delay and the nature of the alternative option. Delayed food was discounted most steeply when the alternative was a high dose of remifentanil, which was preferred over food when food was delayed by 30 s or more. Within-subject comparisons showed no evidence for trait-like impulsivity or sensitivity to delay across these conditions. Choice was determined more by the current contingencies of reinforcement than by innate individual differences. This finding suggests that people might develop steep delay-discounting functions because of the contingencies in their environment, and it supports the use of contingency management to enhance the relative value of delayed nondrug reinforcers.

  14. Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.

    Science.gov (United States)

    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.

  15. The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Alvin Ho Yeung Au

    Full Text Available To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question "which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?".A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review.Fourteen studies with 3521 subjects, with 10 groups (17 dosages of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6 and total pain relief at 6 hours (TOTPAR6. The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 - 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31. Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects.This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study.

  16. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics.

    Science.gov (United States)

    Raehal, Kirsten M; Bohn, Laura M

    2011-01-01

    Ligands acting at the same receptor can differentially activate distinct signal transduction pathways, which in turn, can have diverse functional consequences. Further, receptors expressed in different tissues may utilize intracellular signaling proteins in response to a ligand differently as well. The mu opioid receptor (MOR), which mediates many of the pharmacological actions of opiate therapeutics, is also subject to differential signaling in response to diverse agonists. To study the effect of diverse agonists on MOR signaling, we examined the effects of chronic opiate treatment on two distinct physiological endpoints, antinociceptive tolerance and physical dependence, in mice lacking the intracellular regulatory molecule, βarrestin2. While βarrestin2 knockout (βarr2-KO) mice do not become tolerant to the antinociceptive effects of chronic morphine in a hot plate test, tolerance develops to the same degree in both wild type and βarr2-KO mice following chronic infusion with methadone, fentanyl, and oxycodone. Studies here also assess the severity of withdrawal signs precipitated by naloxone following chronic infusions at three different doses of each opiate agonist. While there are no differences in withdrawal responses between genotypes at the highest dose of morphine tested (48 mg/kg/day), the βarr2-KO mice display several less severe withdrawal responses when the infusion dose is lowered (12 or 24 mg/kg/day). Chronic infusion of methadone, fentanyl, and oxycodone all lead to equivalent naloxone-precipitated withdrawal responses in both genotypes at all doses tested. These results lend further evidence that distinct agonists can differentially impact on opioid-mediated responses in vivo in a βarrestin2-dependent manner.

  17. The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan

    2015-01-01

    Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953

  18. Pharmacist and Physician Interpretation of Abbreviations for Acetaminophen Intended for Use in a Consumer Icon

    Directory of Open Access Journals (Sweden)

    Saul Shiffman

    2015-10-01

    Full Text Available Concomitant use of multiple acetaminophen medications is associated with overdose. To help patients identify acetaminophen medications and thus avoid concomitant use, an icon with an abbreviation for “acetaminophen” has been proposed for all acetaminophen medications. This study assessed pharmacists’ and physicians’ use and interpretation of abbreviations for “acetaminophen”, to identify abbreviations with other meanings that might cause confusion. Physicians (n = 150 reported use and interpretation of candidate abbreviations Ac and Acm. Pharmacists (n = 150 interpretations of prescription orders using the candidate abbreviations APAP, Ac, Ace and Acm in typed, handwritten or spoken form, were judged for critical confusions likely to cause patient harm. Critical confusion was rare, except for omission by pharmacists of the acetaminophen dose for Hydrocodone/APAP prescriptions (10%. Ac was in common use to indicate “before meals”, and was interpreted as such, but some physicians (8% said they use Ac to indicate anticoagulant drugs. Most pharmacists (54% interpreted Ace as acetaminophen, and none interpreted it as referring to ACE-inhibitors. Acm was rarely used in prescriptions, had no common interfering meanings, and was often (63% interpreted as acetaminophen, especially when prescribed in combination with an opiate (85%. The data validated concerns about abbreviations in prescribing: all abbreviations resulted in some misinterpretations. However, Acm was rarely misinterpreted, was readily associated with “acetaminophen”, and seemed appropriate for use in a graphic icon to help consumers/patients identify acetaminophen medications.

  19. Removal of emerging contaminants from municipal wastewater with an integrated membrane system, MBR-RO.

    Science.gov (United States)

    Dolar, Davor; Gros, Meritxell; Rodriguez-Mozaz, Sara; Moreno, Jordi; Comas, Joaquim; Rodriguez-Roda, Ignasi; Barceló, Damià

    2012-11-15

    The presence of emerging contaminants in the aquatic environment and their potential effects on living organisms has become an issue of growing concern. Among emerging contaminants, pharmaceuticals may enter the aquatic environment due to their high consumption and their incomplete removal in conventional municipal wastewater treatment plants (WWTPs). The main goal of this study was the assessment of the removal efficiency of pharmaceuticals found in municipal wastewater of a coastal WWTP (Castell-Platja d'Aro, Spain) using an integrated pilot scale membrane system (MBR-RO). Twenty multiple-class pharmaceuticals (including psychiatric drugs, macrolide antibiotics, β-blockers, sulfonamide and fluoroquinolone antibiotics, histamine H2 receptor antagonists, anti-inflammatories, nitroimidazole, β-agonist and antiplatelet agent) were measured in real influent with the lowest average concentration for psychiatric drugs (0.017 μg L(-1)) to the highest for macrolide antibiotics (2.02 μg L(-1)). Although some contaminants were in relatively high concentrations (even up to 2.90 μg L(-1) in the case of ofloxacin). The combination of MBR and RO treatment showed excellent overall removal of target emerging contaminants with removal rates above 99% for all of them. For some compounds (metronidazole, hydrocodone, codein, ranitidine) MBR provided high removal efficiency (up to 95%). Additionally RO membrane showed removal rates always higher than 99%.

  20. Receptor Reserve Moderates Mesolimbic Responses to Opioids in a Humanized Mouse Model of the OPRM1 A118G Polymorphism

    Science.gov (United States)

    Robinson, J Elliott; Vardy, Eyal; DiBerto, Jeffrey F; Chefer, Vladimir I; White, Kate L; Fish, Eric W; Chen, Meng; Gigante, Eduardo; Krouse, Michael C; Sun, Hui; Thorsell, Annika; Roth, Bryan L; Heilig, Markus; Malanga, C J

    2015-01-01

    The OPRM1 A118G polymorphism is the most widely studied μ-opioid receptor (MOR) variant. Although its involvement in acute alcohol effects is well characterized, less is known about the extent to which it alters responses to opioids. Prior work has shown that both electrophysiological and analgesic responses to morphine but not to fentanyl are moderated by OPRM1 A118G variation, but the mechanism behind this dissociation is not known. Here we found that humanized mice carrying the 118GG allele (h/mOPRM1-118GG) were less sensitive than h/mOPRM1-118AA littermates to the rewarding effects of morphine and hydrocodone but not those of other opioids measured with intracranial self-stimulation. Reduced morphine reward in 118GG mice was associated with decreased dopamine release in the nucleus accumbens and reduced effects on GABA release in the ventral tegmental area that were not due to changes in drug potency or efficacy in vitro or receptor-binding affinity. Fewer MOR-binding sites were observed in h/mOPRM1-118GG mice, and pharmacological reduction of MOR availability unmasked genotypic differences in fentanyl sensitivity. These findings suggest that the OPRM1 A118G polymorphism decreases sensitivity to low-potency agonists by decreasing receptor reserve without significantly altering receptor function. PMID:25881115

  1. Substance use disorders in the U.S. Armed Forces, 2000-2011.

    Science.gov (United States)

    Servies, Tammy; Hu, Zheng; Eick-Cost, Angelia; Otto, Jean Lin

    2012-11-01

    Drug misuse is associated with serious health consequences and has detrimental effects on military readiness. During 2000 to 2011, 70,104 service members received an incident diagnosis of a substance use disorder (SUD) (excluding alcohol and tobacco-related disorders). Incidence rates declined with increasing age, time in service, rank, and number of combat deployments. Service members in a combat occupation had 1.2 times the rate of individuals in a health care or administation/supply occupation. The median time to discharge after an SUD diagnosis was longest in the Air Force (327 days) and shortest in the Navy (133 days). The substances with the highest incidence rates were cannabis (160 per 100,000 person-years [p-yrs]), "mixed/unspecified/other" (125 per 100,000 p-yrs), and cocaine (61 per 100,000 p-yrs). Incidence rates of cannabis and cocaine use diagnoses generally declined while rates of mixed/unspecified/other and opioid use increased over the surveillance period. The increasing trend in opioid-related diagnoses since 2002 may reflect an increase in prescription drug misuse. The Department of Defense recently expanded its drug testing program to screen for hydrocodone and benzodiazepines.

  2. A comparison of crushed ice and continuous flow cold therapy.

    Science.gov (United States)

    Barber, F A

    2000-01-01

    Crushed ice was compared to continuous flow cold therapy for control of postoperative pain after arthroscopic patellar tendon autograft anterior cruciate ligament (ACL) reconstruction. With all other variables held constant, cold was administered by either continuous flow (group 1) or crushed ice (group 2). The cold therapy was constant for 3 days, then as needed in days 4 through 7. Data were collected by investigator evaluations and patient diaries. Pain was assessed by visual analog scale (VAS) and categorical pain scale (Likert). Eighty-seven patients were included (52 continuous flow and 35 crushed ice). Continuous passive motion averaged 54 hours for group 1 and 43 hours for group 2 (Pcold therapy lowered VAS and Likert pain scores more, reduced hydrocodone bitartrate with acetaminophen use, was used more often, increased continuous passive motion, increased 1-week knee flexion, and was given significantly higher performance ratings by patients. Continuous flow cold is superior to crushed ice for outpatient ACL reconstruction pain and should not be considered an equivalent modality.

  3. Structural Determinants for the Binding of Morphinan Agonists to the μ-Opioid Receptor.

    Directory of Open Access Journals (Sweden)

    Xiaojing Cong

    Full Text Available Atomistic descriptions of the μ-opioid receptor (μOR noncovalently binding with two of its prototypical morphinan agonists, morphine (MOP and hydromorphone (HMP, are investigated using molecular dynamics (MD simulations. Subtle differences between the binding modes and hydration properties of MOP and HMP emerge from the calculations. Alchemical free energy perturbation calculations show qualitative agreement with in vitro experiments performed in this work: indeed, the binding free energy difference between MOP and HMP computed by forward and backward alchemical transformation is 1.2±1.1 and 0.8±0.8 kcal/mol, respectively, to be compared with 0.4±0.3 kcal/mol from experiment. Comparison with an MD simulation of μOR covalently bound with the antagonist β-funaltrexamine hints to agonist-induced conformational changes associated with an early event of the receptor's activation: a shift of the transmembrane helix 6 relative to the transmembrane helix 3 and a consequent loss of the key R165-T279 interhelical hydrogen bond. This finding is consistent with a previous proposal suggesting that the R165-T279 hydrogen bond between these two helices indicates an inactive receptor conformation.

  4. Ethanol-resistant polymeric film coatings for controlled drug delivery.

    Science.gov (United States)

    Rosiaux, Y; Muschert, S; Chokshi, R; Leclercq, B; Siepmann, F; Siepmann, J

    2013-07-10

    The sensitivity of controlled release dosage forms to the presence of ethanol in the gastro intestinal tract is critical, if the incorporated drug is potent and exhibits severe side effects. This is for instance the case for most opioid drugs. The co-ingestion of alcoholic beverages can lead to dose dumping and potentially fatal consequences. For these reasons the marketing of hydromorphone HCl extended release capsules (Palladone) was suspended. The aim of this study was to develop a novel type of controlled release film coatings, which are ethanol-resistant: even the presence of high ethanol concentrations in the surrounding bulk fluid (e.g., up to 40%) should not affect the resulting drug release kinetics. Interestingly, blends of ethylcellulose and medium or high viscosity guar gums provide such ethanol resistance. Theophylline release from pellets coated with the aqueous ethylcellulose dispersion Aquacoat® ECD 30 containing 10 or 15% medium and high viscosity guar gum was virtually unaffected by the addition of 40% ethanol to the release medium. Furthermore, drug release was shown to be long term stable from this type of dosage forms under ambient and stress conditions (without packaging material), upon appropriate curing.

  5. April 2015 critical care case of the month: half-sided light house

    Directory of Open Access Journals (Sweden)

    Loftsgard T

    2015-04-01

    Full Text Available No abstract available. Article truncated after 150 words. History of Present Illness: A 55 year old woman was transferred to the ICU from the general medicine ward for tachycardia and acute hypoxic respiratory distress. She has multiple myeloma and had received cycle one of bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide and etoposide (VDT-PACE and radiotherapy to T7 for a pathologic compression. She was admitted for pain control from mucositis.Past Medical History: In addition to the multiple myeloma she has a past medical history of asthma, ovarian cysts, diverticulitis, eczema, pneumonia, laparoscopic cholecystectomy, total abdominal hysterectomy with bilateral salpingo-oophorectomy, appendectomy, ectopic pregnancy in the past, and left Bell's palsy. Current Medications: Acyclovir 400 mg BID, Albuterol 90 HFA prn, Allopurinol 300 mg daily, Fluconazole 200 mg BID, Gabapentin 300 mg BID, Hydromorphone , Levofloxacin 500 daily, Morphine, Omeprazole, Bactrim 400-80 mg daily for PCP prophylaxis, Thalomid 200 mg capsule daily, Ativan 0.5 mg just prior to transfer. Physical Examination ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Alburges, M.E.

    1988-01-01

    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 radioreceptor 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.

  7. Evaluation of concomitant methylphenidate and opioid use in patients with pain.

    Science.gov (United States)

    Jiang, Joy Y; Best, Brookie M; Morello, Candis M; Atayee, Rabia S; Ma, Joseph D

    2014-09-01

    Methylphenidate is a central nervous system simulant that is used for management of opioid-induced sedation. Sparse data exist regarding use patterns of methylphenidate and opioids in patients with pain. This retrospective data analysis evaluated concomitant methylphenidate and opioid use from physician-reported medication lists and in urine specimens of patients with pain. All specimens were analyzed and quantified with LC-MS-MS. Concomitant methylphenidate and opioid use (e.g., sample population) were compared with a baseline population of patients taking opioids. There were 3,326 patients with physician-reported use of methylphenidate. Of these, 1,089 patients were tested for the presence of methylphenidate in urine. Methylphenidate was positive in urine for 551 patients (detection rate of 50.6%). Ritalinic acid was positive in 776 patients (detection rate of 71.3%). The current study observed differences in the use pattern of methylphenidate based on opioid type. Physician-reported use revealed methadone had the highest percent difference between the sample and baseline populations (77%, P ≤ 0.05). Fentanyl, morphine and hydromorphone also had higher percent differences of 19.6, 25.3 and 32.3%, respectively. Further studies need to examine the apparent discrepancies between the physician-reported medication lists and urine drug testing of concomitant methylphenidate and opioid use in patients with pain.

  8. June 2012 pulmonary case of the month: what's a millet seed look like?

    Directory of Open Access Journals (Sweden)

    Wesselius LJ

    2012-06-01

    Full Text Available No abstract available. Article truncated at 145 words. History of Present IllnessA 32 year old woman presents with a week long history of dyspnea, cough, fatigue, tiredness and pruritis. She has a past medical history (PMH of Stage IIB, nodular sclerosing Hodgkin’s disease diagnosed in January, 2011. She underwent several cycles of chemotherapy and eventually an autologous stem cell transplant in January, 2012. Her current medications include:■Acyclovir 800mg bid■Ativan 0.5mg q4h/ prn■Hydromorphone 8mg q4h/ prn■Atarax 100mg q6h/ prn■Compazine 10mg q6h/ prnShe had just finished a course of levofloxacin.PMH, SH and FHAs above. She is a life-long nonsmoker and has no history of lung disease.Physical ExaminationHer physical examination was normal.Chest X-rayHer chest x-ray was interpreted as unchanged from previous examinations. Which of the following are indicated?1.Thoracic CT scanning 2.PET scanning 3.Empiric treatment with broad spectrum antibiotics4.All of the above ...

  9. The cardiovascular effects of sevoflurane and isoflurane after premedication of healthy dogs undergoing elective surgery.

    Science.gov (United States)

    Abed, Janan M; Pike, Fred S; Clare, Monica C; Brainard, Benjamin M

    2014-01-01

    Sevoflurane and isoflurane are commonly used in veterinary anesthesia. The objective of this prospective, randomized, open-label clinical study was to compare the cardiovascular effects of sevoflurane and isoflurane via direct arterial blood pressure measurements and the lithium dilution cardiac output (LDCO) on premedicated healthy dogs undergoing elective tibial plateau leveling osteotomy (TPLO). Nineteen client-owned dogs were included. All dogs were premedicated with hydromorphone (0.05 mg/kg IV and glycopyrrolate 0.01 mg/kg subcutaneously). Ten dogs were anesthetized with sevoflurane and nine dogs were anesthetized with isoflurane. Eighteen dogs were instrumented with a dorsal pedal arterial catheter, and one dog had a femoral arterial catheter. All dogs had continuous, direct systolic (SAP), diastolic (DAP), and mean arterial (MAP) blood pressure readings as well as heart rate (HR), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), stroke volume variation (SVV), and pulse pressure variation (PPV) recorded q 5 min during the surgical procedure. There was no significant statistical difference in all parameters between the sevoflurane and isoflurane treatment groups. Both sevoflurane and isoflurane inhalant anesthetics appear to have similar hemodynamic effects when used as part of a multimodal anesthetic protocol in premedicated healthy dogs undergoing an elective surgical procedure.

  10. Pathophysiology and principles of management of the many faces of the acute vaso-occlusive crisis in patients with sickle cell disease.

    Science.gov (United States)

    Ballas, Samir K

    2015-08-01

    Effective management of sickle cell pain entails a thorough understanding of its pathophysiology and the pharmacogenomics of the opioids used to manage it. In recent years, there has been significant progress along these two lines. At the pathophysiologic level, there is evidence that the severity and frequency of painful stimuli modulate their transmission at the level of the dorsal horn of the spinal cord. This modulation is achieved via two channels: the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors. Initially, the AMPA channel controls the transmission of stimuli of mild-moderate severity. Once the AMPA channel reaches its limit of membrane depolarization, the NMDA channel is activated and facilitates the transmission of painful stimuli in a progressive fashion leading to central sensitization and glial activation. At the level of pharmacogenomics, the metabolism of each opioid is patient-specific. Glucuronidation is unique for the metabolism of morphine, hydromorphone, and oxymorphone. The metabolism of all other opioids requires specific Cytochrome P450 (CYP) isoenzymes. The activity of each isoenzyme and the activity of the metabolites of each opioid vary among patients depending on their genetic makeup and coexistent environmental factors such as the use of other medications that may enhance or inhibit the CYP isoenzyme activity.

  11. Impact of capillary flow hydrodynamics on carrier-mediated transport of opioid derivatives at the blood-brain barrier, based on pH-dependent Michaelis-Menten and Crone-Renkin analyses.

    Science.gov (United States)

    Yusof, Siti R; Abbott, N Joan; Avdeef, Alex

    2017-08-30

    Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10(-6)cm·s(-1). The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (p

  12. Clinical Observation in the Treatment of Pain in Bone Metastatic Cancer with Yishengukang Formula and Thermal Therapy%益肾骨康方联合热疗治疗骨转移癌疼痛的临床观察

    Institute of Scientific and Technical Information of China (English)

    高音; 冯利; 王芳; 勾涛

    2014-01-01

    Objective ToobservetheclinicalefficacyofYishenggukangFormulaandthermalthera-pyinthepatientsofpainofbonemetastaticcancer.Methods Fortycaseswererandomizedintoatreatment group and a control group.In the control group,20 cases were treated with Acetaminiphen Oxycodone Tablets to suppress pain of bone metastatic cancer.In the treatment group,20 cases were treated with Yishenggukang Formula and local thermal therapy beside the medication as the control group.In 2 weeks of treatment,pain relief,drug dose of Acetaminiphen Oxycodone Tablets and physical condition were observed and analyzed in thetwogroups.Results Aftertreatment,inthetreatmentgroup,theresultofpainreliefwasremarkablysu-perior to the control group(P<0.05).The reducing rate of the drug dose of Acetaminiphen Oxycodone Tab-lets was quite higher than that in the control group(P<0.05).The improvement rate of physical condition in thetreatmentgroupwashigherthanthatinthecontrolgroup(P<0.05).Conclusion TheallianceofYish-enggukang Formula and local thermal therapy remarkably suppresses pain of bone metastatic cancer,reduces the dose of strong opioids and improves physical condition.It plays the significant role in the improvement of survival quality of patients.%目的:观察骨转移癌疼痛患者应用益肾骨康方联合热疗镇痛的临床疗效。方法将40例伴有不同程度骨转移癌疼痛的患者随机分为治疗组和对照组。对照组20例,单纯应用氨酚羟考酮片(泰勒宁)控制骨转移癌疼痛。治疗组20例,在对照组治疗基础上内服益肾骨康方联合骨转移部位局部热疗。治疗2周后对两组患者治疗前后疼痛缓解情况、氨酚羟考酮片(泰勒宁)用药剂量、体力状况进行观察和分析。结果治疗后治疗组疼痛缓解情况明显优于对照组(P<0.05);治疗组氨酚羟考酮片使用量减少率远高于对照组(P<0.05);两组治疗后体力状况评分提高率比较,治疗组高于

  13. Effects of μ-opioid receptor agonists in assays of acute pain-stimulated and pain-depressed behavior in male rats: role of μ-agonist efficacy and noxious stimulus intensity.

    Science.gov (United States)

    Altarifi, Ahmad A; Rice, Kenner C; Negus, S Stevens

    2015-02-01

    Pain is associated with stimulation of some behaviors and depression of others, and μ-opioid receptor agonists are among the most widely used analgesics. This study used parallel assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats to compare antinociception profiles for six μ-agonists that varied in efficacy at μ-opioid receptors (from highest to lowest: methadone, fentanyl, morphine, hydrocodone, buprenorphine, and nalbuphine). Intraperitoneal injection of diluted lactic acid served as an acute noxious stimulus to either stimulate stretching or depress operant responding maintained by electrical stimulation in an intracranial self-stimulation (ICSS). All μ-agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy agonists methadone and fentanyl were more potent at blocking acid-induced depression of ICSS than acid-stimulated stretching, whereas lower-efficacy agonists displayed similar potency across assays. All μ-agonists except morphine also facilitated ICSS in the absence of the noxious stimulus at doses similar to those that blocked acid-induced depression of ICSS. The potency of the low-efficacy μ-agonist nalbuphine, but not the high-efficacy μ-agonist methadone, to block acid-induced depression of ICSS was significantly reduced by increasing the intensity of the noxious stimulus to 5.6% acid. These results demonstrate sensitivity of acid-induced depression of ICSS to a range of clinically effective μ-opioid analgesics and reveal distinctions between opioids based on efficacy at the μ-receptor. These results also support the use of parallel assays of pain-stimulated and -depressed behaviors to evaluate analgesic efficacy of candidate drugs.

  14. Renal infarction during the use of rizatriptan and zolmitriptan: two case reports.

    Science.gov (United States)

    Fulton, Jessica A; Kahn, Jason; Nelson, Lewis S; Hoffman, Robert S

    2006-01-01

    Rizatriptan and zolmitriptan are both used to relieve acute migraine and cluster headaches. The mechanism of action is similar to the other triptans, in that they reverse abnormal cerebral vasodilation through their activity as 5-HT1B receptor agonists. Triptan-induced vasoconstriction is attributed to its activity on peripheral 5-HT1B receptors and has rarely been reported to result in stroke, myocardial infarction and ischemic colitis. We present two cases of renal infarction associated with therapeutic triptan use. The first patient is a 57-year-old man with a history of hypertension that was well controlled on valsartan and hydrochlorothiazide. He was recently diagnosed with cluster headaches and was treated with indomethacin, prednisone, butalbital-acetaminophen-caffeine and hydrocodone without relief. He then received two therapeutic doses of rizatriptan on each of the two days prior to presentation. Subsequently, he presented to the emergency department complaining of nausea, vomiting and right-sided abdominal pain. A computerized tomography (CT) scan of the abdomen and pelvis with intravenous contrast revealed a very large wedge shaped infarction of the right kidney. The second patient is a 34-year-old man with a past medical history significant only for life-long migraine headaches successfully treated for the past six years with zolmitriptan. Shortly after taking one therapeutic dose of zolmitriptan, he presented to the emergency department complaining of nausea and left-sided abdominal pain. A CT scan of the abdomen and pelvis with intravenous contrast revealed multiple wedge-shaped infarctions of the left kidney. Renal infarction was confirmed in both patients by arteriogram of the renal arteries. Although both rizatriptan and zolmitriptan are effective in the treatment of migraine and cluster headaches, they may induce peripheral vasospasm leading to renal infarction.

  15. Characterizing fentanyl use in methadone-maintained clients.

    Science.gov (United States)

    Arfken, Cynthia L; Suchanek, Jessica; Greenwald, Mark K

    2017-04-01

    Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl. A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan. Urine drug screens (UDS) including fentanyl (and its metabolite norfentanyl) were conducted clinically. To obtain additional data, 113 clients in this clinic subsequently completed an anonymous survey. Of 368 unique clients with UDS, 38.0% had at least one and 26.1% had ≥2 fentanyl-positive UDS results. None had a fentanyl prescription. Clients ever testing positive for fentanyl were significantly (p<0.05) more likely to use cocaine, have multiple treatment admissions to the clinic, and leave treatment sooner. Fentanyl-positive UDS results coincided most commonly with metabolites of cocaine- and heroin-positive UDS results. Of the anonymously surveyed clients, most (67.3%) reported they did not know anyone seeking fentanyl, a proportion significantly higher than for heroin, cocaine, alprazolam, hydrocodone and morphine. Fentanyl was commonly detected during this period with some clients having multiple fentanyl-positive UDS. Most clients did not know anyone seeking to obtain fentanyl. Regardless, the high exposure underscores that naloxone training and distribution is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress

    Directory of Open Access Journals (Sweden)

    Sanoara Mazid

    2016-12-01

    Full Text Available Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs. Immediately after acute immobilization stress (AIS or one-day after chronic immobilization stress (CIS, the brains of adult female and male rats were perfusion-fixed with aldehydes. The CA3b region and the dentate hilus of the dorsal hippocampus were quantitatively analyzed by light microscopy using DOR immunoperoxidase or dual label electron microscopy for DOR using silver intensified immunogold particles (SIG and GABA using immunoperoxidase. At baseline, females compared to males had more DORs near the plasmalemma of pyramidal cell dendrites and about 3 times more DOR-labeled CA3 dendritic spines contacted by mossy fibers. In AIS females, near-plasmalemmal DOR-SIGs decreased in GABAergic hilar dendrites. However, in AIS males, near-plasmalemmal DOR-SIGs increased in CA3 pyramidal cell and hilar GABAergic dendrites and the percentage of CA3 dendritic spines contacted by mossy fibers increased to about half that seen in unstressed females. Conversely, after CIS, near-plasmalemmal DOR-SIGs increased in hilar GABA-labeled dendrites of females whereas in males plasmalemmal DOR-SIGs decreased in CA3 pyramidal cell dendrites and near-plasmalemmal DOR-SIGs decreased hilar GABA-labeled dendrites. As CIS in females, but not males, redistributed DOR-SIGs near the plasmalemmal of hilar GABAergic dendrites, a subsequent experiment examined the acute affect of oxycodone on the redistribution of DOR-SIGs in a separate cohort of CIS females. Plasmalemmal DOR-SIGs were significantly elevated on hilar

  17. Six-year follow-up of impact of co-proxamol withdrawal in England and Wales on prescribing and deaths: time-series study.

    Directory of Open Access Journals (Sweden)

    Keith Hawton

    Full Text Available BACKGROUND: The analgesic co-proxamol (paracetamol/dextropropoxyphene combination has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005-2010 compared with 1998-2004, including estimation of possible substitution effects by other analgesics. METHODS AND FINDINGS: We obtained prescribing data from the NHS Health and Social Care Information Centre (England and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales, and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine during 2005-2010 compared with 1998-2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of -21 deaths (95% CI -34 to -8 per quarter, equating to approximately 500 fewer suicide deaths (-61% over the 6 years 2005-2010, and -25 deaths (95% CI -38 to -12 per quarter, equating to 600 fewer deaths (-62% when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed. CONCLUSIONS

  18. 我院肿瘤Ⅰ科癌痛治疗药物使用情况分析%Analysis of the utilization of pain-relief drugs of cancer in the 1st tumor department in our hospital

    Institute of Scientific and Technical Information of China (English)

    毛伟; 袁孔现

    2016-01-01

    Objective To analyze and evaluate the pain-relief drugs of cancer used in the 1st tumor department in our hospital .Meth-ods Varieties of the pain-relief drugs of cancer ,the amount of drug scheduling and medication frequency(DDDs) sort ratio and daily expense (DDC) in 2014 were used as the evaluation index .Results 15 pain-relief drugs of cancer were used in the 1st tumor department .The top four in DDDs were Oxycodone Hydrochloride Prolonged-Release Tablets(10 mg) ,Oxycodone Hydrochloride Prolonged-release Tablets(40 mg) ,Acetaminophen Tablets(5 mg/325 mg) and Morphine Hydrochloride Tablets(10 mg) .Con-clusion With the establishment of the Good Pain Management Ward(GPD-Ward) ,the application of pain-relief drugs of cancer was tending to be reasonable .%目的:调查分析我院肿瘤Ⅰ科癌痛治疗药物使用情况。方法对我院肿瘤Ⅰ科2014年癌痛治疗用药的品种、数量、用药金额、用药频度(DDDs)和日均费用(DDC)进行统计分析。结果我院肿瘤Ⅰ科治疗癌痛的药物有15个品规,DDDs居前4位的依次是:盐酸羟考酮缓释片(10 mg)、盐酸羟考酮缓释片(40 mg)、氨酚羟考酮片(5 mg/325 mg)和盐酸吗啡片(10 mg)。结论随着癌痛规范化治疗病房的建立和运行,我院肿瘤Ⅰ科癌痛治疗用药情况趋于合理,遵循口服给药、按阶梯用药、按时服药、个体化给药及注意具体细节的方案给药。

  19. Pharmacokinetic-pharmacodynamic modelling of opioids in healthy human volunteers. a minireview.

    Science.gov (United States)

    Ing Lorenzini, Kuntheavy; Daali, Youssef; Dayer, Pierre; Desmeules, Jules

    2012-03-01

    Pain is characterized by its multi-dimensional nature, explaining in part why the pharmacokinetic/pharmacodynamic (PK/PD) relationships are not straightforward for analgesics. The first part of this MiniReview gives an overview of PK, PD and PK/PD models, as well as of population approach used in analgesic studies. The second part updates the state-of-the-art in the PK/PD relationship of opioids, focusing on data obtained on experimental human pain models, a useful tool to characterize the PD of analgesics. For the so-called weak opioids such as codeine, experimental human studies showed that analgesia relies mainly upon biotransformation into morphine. However, the time-course of plasma concentrations of morphine did not always reflect the time-course of effects, the major site of action being the central nervous system. For tramadol, a correlation has been observed between the analgesic response and the PK of the (+)R-O-demethyl-tramadol metabolite. For 'stronger' opioids such as oxycodone, studies assessing the PK/PD of oxycodone suggested that active metabolite oxymorphone also strongly contributes to the analgesia and that analgesia may also be partially related through an action to peripherally located κ-opioid receptors. Different models have been proposed to describe the time-course of buprenorphine. An effect-compartment model was adopted to describe the PK/PD of morphine and its active metabolite, morphine-6-glucuronide (M6G). A longer blood-effect site equilibration half-life t(1/2) k(e0) was observed for M6G, suggesting a longer onset of action. The studies assessing the PK/PD of fentanyl and its derivatives showed a short t(1/2) k(e0) for analgesia, between 0.2 and 9 min., reflecting a short onset of effect. In conclusion, depending on the speed of transfer between the plasma and the effect site as well as the participation of active metabolites, the time-course of the analgesic effects can be close to the plasma concentrations (alfentanil and

  20. Síndrome das pernas inquietas: diagnóstico e tratamento. Opinião de especialistas brasileiros Restless legs syndrome: diagnosis and treatment. Opinion of Brazilian experts

    Directory of Open Access Journals (Sweden)

    2007-09-01

    Full Text Available Este artigo contém as conclusões de reunião de 17-18 de novembro de 2006 do Grupo Brasileiro de Estudo em Síndrome das Pernas Inquietas (GBE-SPI sobre diagnóstico e tratamento de SPI. Reiterou-se que se trata de condição de diagnóstico exclusivamente clínico, caracterizada por sensação anormal localizada, sobretudo, mas não exclusivamente, em membros inferiores, com piora noturna e alívio por movimentação da parte envolvida. Agentes terapêuticos com eficácia comprovada por estudos classe I são agonistas dopaminérgicos, levodopa e gabapentina enquanto que ácido valpróico de liberação lenta, clonazepam, oxicodona e reposição de ferro têm eficácia sugerida por estudos classe II. As recomendações do GBE-SPI para manejo de SPI primária são medidas de higiene do sono, suspensão de agentes agravantes de SPI, tratamento de comorbidades e agentes farmacológicos. Para estes as drogas de primeira escolha são agentes dopaminérgicos; segunda escolha são gabapentina ou oxicodona; e terceira escolha são clonazepam ou ácido valpróico de liberação lenta.This article contains the conclusions of the November 17-18, 2006 meeting of the Brazilian Study Group of Restless Legs Syndrome (GBE-SPI about diagnosis and management of restless legs syndrome (RLS. RLS is characterized by abnormal sensations mostly but not exclusively in the legs which worsen in the evening and are improved by motion of the affected body part. Its diagnosis is solely based on clinical findings. Therapeutic agents with efficacy supported by Class I studies are dopamine agonists, levodopa and gabapentine. Class II studies support the use of slow release valproic acid, clonazepan and oxycodone. The GBE-SPI recommendations for management of SPI are sleep hygiene, withdrawal of medications capable of worsening the condition, treatment of comorbidities and pharmacological agents. The first choice agents are dopaminergic drugs, second choice are gabapentine or

  1. Quantitative sensory testing measures individual pain responses in emergency department patients

    Directory of Open Access Journals (Sweden)

    Duffy KJ

    2017-05-01

    Full Text Available Kevin J Duffy, Katharyn L Flickinger, Jeffrey T Kristan, Melissa J Repine, Alexandro Gianforcaro, Rebecca B Hasley, Saad Feroz, Jessica M Rupp, Jumana Al-Baghli, Maria L Pacella, Brian P Suffoletto, Clifton W Callaway Department of Emergency Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Background: Refining and individualizing treatment of acute pain in the emergency department (ED is a high priority, given that painful complaints are the most common reasons for ED visits. Few tools exist to objectively measure pain perception in the ED setting. We speculated that variation in perception of fixed painful stimuli would explain individual variation in reported pain and response to treatment among ED patients. Materials and methods: In three studies, we 1 describe performance characteristics of brief quantitative sensory testing (QST in 50 healthy volunteers, 2 test effects of 10 mg oxycodone versus placebo on QST measures in 18 healthy volunteers, and 3 measure interindividual differences in nociception and treatment responses in 198 ED patients with a painful complaint during ED treatment. QST measures adapted for use in the ED included pressure sensation threshold, pressure pain threshold (PPT, pressure pain response (PPR, and cold pain tolerance (CPT tests. Results: First, all QST measures had high inter-rater reliability and test–retest reproducibility. Second, 10 mg oxycodone reduced PPR, increased PPT, and prolonged CPT. Third, baseline PPT and PPR revealed hyperalgesia in 31 (16% ED subjects relative to healthy volunteers. In 173 (88% ED subjects who completed repeat testing 30 minutes after pain treatment, PPT increased and PPR decreased (Cohen’s dz 0.10–0.19. Verbal pain scores (0–10 for the ED complaint decreased by 2.2 (95% confidence intervals [CI]: 1.9, 2.6 (Cohen’s dz 0.97 but did not covary with the changes in PPT and PPR (r=0.05–0.13. Treatment effects were greatest in ED subjects

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

    Science.gov (United States)

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

    2011-01-01

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

  3. Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress.

    Science.gov (United States)

    Mazid, Sanoara; Hall, Baila S; Odell, Shannon C; Stafford, Khalifa; Dyer, Andreina D; Van Kempen, Tracey A; Selegean, Jane; McEwen, Bruce S; Waters, Elizabeth M; Milner, Teresa A

    2016-12-01

    Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs). Immediately after acute immobilization stress (AIS) or one-day after chronic immobilization stress (CIS), the brains of adult female and male rats were perfusion-fixed with aldehydes. The CA3b region and the dentate hilus of the dorsal hippocampus were quantitatively analyzed by light microscopy using DOR immunoperoxidase or dual label electron microscopy for DOR using silver intensified immunogold particles (SIG) and GABA using immunoperoxidase. At baseline, females compared to males had more DORs near the plasmalemma of pyramidal cell dendrites and about 3 times more DOR-labeled CA3 dendritic spines contacted by mossy fibers. In AIS females, near-plasmalemmal DOR-SIGs decreased in GABAergic hilar dendrites. However, in AIS males, near-plasmalemmal DOR-SIGs increased in CA3 pyramidal cell and hilar GABAergic dendrites and the percentage of CA3 dendritic spines contacted by mossy fibers increased to about half that seen in unstressed females. Conversely, after CIS, near-plasmalemmal DOR-SIGs increased in hilar GABA-labeled dendrites of females whereas in males plasmalemmal DOR-SIGs decreased in CA3 pyramidal cell dendrites and near-plasmalemmal DOR-SIGs decreased hilar GABA-labeled dendrites. As CIS in females, but not males, redistributed DOR-SIGs near the plasmalemmal of hilar GABAergic dendrites, a subsequent experiment examined the acute affect of oxycodone on the redistribution of DOR-SIGs in a separate cohort of CIS females. Plasmalemmal DOR-SIGs were significantly elevated on hilar interneuron

  4. Characteristics of Suicides Caused by Drug Overdose in the State of Maryland

    Directory of Open Access Journals (Sweden)

    Ling Li

    2015-01-01

    Full Text Available Suicidal drug overdose is a major public health issue. In the United States, every year more than 33,000 people commit suicides. Our study focused on the characteristics of suicide victims in the state of Maryland. Material and methods: This study was a retrospective review of autopsy cases of all suicide deaths caused by drug (s or drug (s with alcohol intoxication investigated by the OCME in Maryland over a 7-year period from January 2004 to December 2011. All deaths investigated by the OCME that require autopsy examination are subject to comprehensive toxicology testing for drugs and alcohol. The screen tests were performed using gas chromatography (GC and radioimmunoassay techniques. All detected drugs and/or metabolites were confirmed using GC-mass spectrometry (GC-MS. Results: From 2004 to 2011, 434 deaths were certified as suicide. Of the 434 suicidal overdose deaths, 84% were white, 11% were African-American, and about 5% were either Hispanic or Asian. The male and female ratio was almost equal. Their ages ranged 15-82 years. Of the 434 suicidal drug overdose deaths, 277 victims (63.8% consumed a single drug type and 157 (36.2% consumed more than one type of drug. Of the 277 single-drug overdose cases, 71.1% suicides were due to prescription drugs, 23.5% due to over-the-counter drugs, and 5.4% due to street/recreational drugs. Among single-type prescription drugs, analgesic (N = 76, antidepressant (N = 45, and neuroleptic (N = 35 classes were the three leading type of drugs used in suicidal deaths. Oxycodone, morphine, quetiapine, and amitriptyline were the most common prescription drugs in suicidal overdose. Diphenhydramine was the leading over-the-counter drug. Of the 157 victims who consumed more than one drug, combined prescription drugs were present in 54.1%, mixed prescription and over-the-counter drugs in 29.3%, and prescription drugs/over-the-counter drugs and street drugs in 16.6% of cases. Of the multiple-drug overdose suicides

  5. A prospective evaluation of the incidence of adverse events in nurse-administered moderate sedation guided by sedation scores or Bispectral Index.

    Science.gov (United States)

    Yang, Katie S; Habib, Ashraf S; Lu, Minyi; Branch, M S; Muir, Holly; Manberg, Paul; Sigl, Jeffrey C; Gan, Tong J

    2014-07-01

    Moderate sedation is routinely performed in patients undergoing minor therapeutic and diagnostic procedures outside the operating room. The level of sedation is often monitored by sedation nurses using clinical criteria, such as sedation scores. The Bispectral Index (BIS) is derived from changes in the electroencephalograph profile that may provide an objective measure of the level of sedation. In this prospective observational study, we investigated whether using BIS values to guide sedative drug administration influences the level of sedation and the incidence of adverse events compared with using Ramsay sedation scale (RSS) only in nurse-administered moderate sedation. We hypothesized that both depth of sedation and the incidence of adverse events related to oversedation would decrease when sedation nurses used BIS values to help guide sedative drug administration. Sedation care was provided by trained sedation nurses under the supervision of a physician performing the procedure. The sedation regimen was initiated with IV midazolam 1 to 2 mg and fentanyl 50 mcg or hydromorphone 0.2 mg. Additional small boluses of midazolam, fentanyl, or hydromorphone were administered to maintain an RSS of 2 to 3 (cooperative, oriented, and responding to verbal command). Propofol was not used. Information including patient demographics, type of procedure, medication administered, RSS, and rates of adverse events was recorded by the sedation nurses for each patient on a computer-readable form. The study was divided into 3 phases. In phase 1 (baseline, 6 months' duration), baseline data on sedation practice were prospectively collected. There was no change from standard of care for all patients except that each patient had a BIS sensor attached, but the monitor was covered and nurses were blinded to the BIS values. In phase 2 (training, 3 months), the sedation nurses received comprehensive education on the use of BIS to guide sedative drug administration, pharmacology of commonly

  6. Postoperative epidural analgesia for patients undergoing pectus excavatum corrective surgery: a 10-year retrospective analysis

    Directory of Open Access Journals (Sweden)

    Siddiqui A

    2016-05-01

    Full Text Available Asad Siddiqui,1 Andrew Tse,2 James E Paul,3 Peter Fitzgerald,4 Bernice Teh,51Department of Anesthesia, University of Toronto, Toronto, 2Department of Anesthesia, University of Ottawa, Ottawa, 3Department of Anesthesia, 4Department of Surgery, McMaster University, Hamilton, Ontario, Canada; 5Canterbury Anesthetic Services, Victoria, Australia Introduction: Managing postoperative pain in patients undergoing minimally invasive pectus excavatum repair (Nuss procedure is challenging but essential in facilitating ambulation and minimizing the length of stay. Although multiple epidural regimens with varying opioids are presently used for pain management, there is currently no clinical consensus regarding which epidural regimen provides the best analgesia outcomes with the fewest side effects. This 10-year retrospective cohort study was performed to compare the quality of analgesia and the incidence of side effects associated with the three most common epidural regimens used at a tertiary care children's hospital, in patients undergoing the Nuss procedure. Methods: Seventy-two pediatric patients were identified as having been treated with one of three epidural regimens for postoperative pain management following the Nuss procedure: Group A (n=12 received 0.125% bupivacaine and 5 µg/mL fentanyl, Group B (n=21 received 0.125% bupivacaine and 10 µg/mL hydromorphone, and Group C (n=39 received 0.1% ropivacaine and 20 µg/mL hydromorphone. Our primary outcome was maximal daily pain scores (numerical rating scale 0–10, with an analytical focus on postoperative day 1 scores. The primary outcome was analyzed using linear regression. The secondary outcomes included the length of stay, side-effect profiles as reflected by the number of treatments for nausea and pruritus, pain scores according to epidural site insertion, occurrence of breakthrough pain, and presence of severe pain throughout their hospital stay. Secondary outcomes were analyzed using linear or

  7. Postoperative epidural analgesia for patients undergoing pectus excavatum corrective surgery: a 10-year retrospective analysis

    Science.gov (United States)

    Siddiqui, Asad; Tse, Andrew; Paul, James E; Fitzgerald, Peter; Teh, Bernice

    2016-01-01

    Introduction Managing postoperative pain in patients undergoing minimally invasive pectus excavatum repair (Nuss procedure) is challenging but essential in facilitating ambulation and minimizing the length of stay. Although multiple epidural regimens with varying opioids are presently used for pain management, there is currently no clinical consensus regarding which epidural regimen provides the best analgesia outcomes with the fewest side effects. This 10-year retrospective cohort study was performed to compare the quality of analgesia and the incidence of side effects associated with the three most common epidural regimens used at a tertiary care children’s hospital, in patients undergoing the Nuss procedure. Methods Seventy-two pediatric patients were identified as having been treated with one of three epidural regimens for postoperative pain management following the Nuss procedure: Group A (n=12) received 0.125% bupivacaine and 5 µg/mL fentanyl, Group B (n=21) received 0.125% bupivacaine and 10 µg/mL hydromorphone, and Group C (n=39) received 0.1% ropivacaine and 20 µg/mL hydromorphone. Our primary outcome was maximal daily pain scores (numerical rating scale 0–10), with an analytical focus on postoperative day 1 scores. The primary outcome was analyzed using linear regression. The secondary outcomes included the length of stay, side-effect profiles as reflected by the number of treatments for nausea and pruritus, pain scores according to epidural site insertion, occurrence of breakthrough pain, and presence of severe pain throughout their hospital stay. Secondary outcomes were analyzed using linear or logistic regression adjusted for pain scores at baseline. The criterion for statistical significance was set a priori at alpha =0.05. Results Group A had significantly higher day-1 pain scores (score 5.42/10) than Group B (4.52/10; P=0.030) and Group C (4.49/10; P=0.015) after adjusting for baseline pain and age. No significant difference in maximum daily

  8. Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma

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    Radi, Zaher, E-mail: zaher.radi@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States); Bartholomew, Phillip, E-mail: phillip.m.bartholomew@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, Eastern Point Road, Groton, CT 06340 (United States); Elwell, Michael, E-mail: michael.elwell@covance.com [Covance Laboratories, Chantilly, VA 20151 (United States); Vogel, W. Mark, E-mail: w.mark.vogel@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States)

    2013-12-15

    In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernoma in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages. - Highlights: • Highly variable incidence of spontaneous hibernoma in carcinogenicity studies • Recent increase in the spontaneous incidence of hibernomas

  9. Do fentanyl and morphine influence body temperature after severe burn injury?

    Science.gov (United States)

    Kahn, Steven Alexander; Beers, Ryan J; Lentz, Christopher W

    2011-01-01

    Fentanyl lacks the antiinflammatory properties of morphine. Morphine attenuates the inflammatory response through differential stimulation of μ-receptor subtypes. Patients who receive morphine during coronary artery bypass graft have been shown to experience less postoperative fever than those who receive fentanyl. Patients who receive continuous fentanyl infusions in increased room temperatures after thermal injury may be at increased risk to experience higher body temperature than those who receive morphine. The records of 28 patients with >20%TBSA burn in 30 intensive care unit rooms (13 received fentanyl and 15 received morphine or hydromorphone) and 12 trauma patients who received fentanyl in 22°C intensive care unit rooms were reviewed. Mean maximum core temperature and percentage of temperature recordings > 39°C in the first 48 hours of admission were compared between burn patients who received fentanyl, those who did not, and with trauma patients. Burn patients exposed to fentanyl experienced significantly higher temperatures (40.1 ± 0.9°C) compared with those given morphine (38.7 ± 0.8°C) and compared with trauma patients (37.5 ± 2.4°C), P Burn patients on fentanyl had temperatures > 39°C for a higher percentage of time (33 ± 27%) than those without fentanyl (7.2 ± 13%) and trauma patients (1 ± 2.8%), P Burn patients who receive fentanyl in 30°C rooms experience higher body temperatures and are febrile for a higher percentage of time than those receiving morphine only. Morphine has well-established antiinflammatory properties and likely attenuates the postburn inflammatory response more than fentanyl, resulting in lower body temperatures. This phenomenon needs to be further investigated in additional studies.

  10. Cost considerations in headache treatment. Part 2: Acute migraine treatment.

    Science.gov (United States)

    Von Seggern, R L; Adelman, J U

    1996-09-01

    Today's physician has many useful medication options available for acute migraine treatment. There is a wide cost range among these drugs and today's health care environment demands that cost be factored into the decision process. Effective migraine abortive treatment decreases the costs of repeat dosing and disability. Early use of migraine abortive medication can increase its rapidity of action and effectiveness. Adjunctive medication such as metoclopramide ($0.10) is inexpensive and may improve the effectiveness of the primary abortive medication. Over-the-counter medications such as aspirin ($0.02/325 mg), Excedrin ($0.09/tablet), ibuprofen ($0.04/200 mg), or naproxen sodium ($0.09/220 mg) are inexpensive and effective. "Triple therapy" combining metoclopramide, a nonsteroidal anti-inflammatory agent, and an ergotamine preparation may improve tolerance and effectiveness of the ergot. Locally compounded dihydroergotamine nasal spray is inexpensive ($0.78/1 mg spray). The cost of using oral sumatriptan can be almost halved by prescribing half of a 50-mg tablet. Emergency department services are expensive. Huge cost savings occur through self-controlled administration of oral, rectal, or even intramuscular narcotic medications. Oral narcotic agents such as hydromorphone ($0.42/4 mg) and meperidine ($0.92/200 mg) are generally used in inadequate doses to be effective for severe migraine. Guidelines are give for more effective use of these agents. Sophisticated comparative studies are needed to evaluate, not only the direct costs of medications, but all costs of treatment of an acute migraine attack, as well as indirect costs to the patient, family, and society.

  11. Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS).

    Science.gov (United States)

    Poklis, Justin L; Mohs, Amanda J; Wolf, Carl E; Poklis, Alphonse; Peace, Michelle R

    2016-10-01

    In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOF(TM) time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Adjuvants to local anesthetics: Current understanding and future trends

    Science.gov (United States)

    Swain, Amlan; Nag, Deb Sanjay; Sahu, Seelora; Samaddar, Devi Prasad

    2017-01-01

    Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal

  13. Abuse liability of intravenous buprenorphine vs. buprenorphine/naloxone: Importance of absolute naloxone amount.

    Science.gov (United States)

    Jones, Jermaine D; Manubay, Jeanne M; Mogali, Shanthi; Metz, Verena E; Madera, Gabriela; Martinez, Suky; Mumtaz, Mudassir; Comer, Sandra D

    2017-10-01

    This study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects. Heroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing and subjective effects of intravenous (IV) doses of Bup (1.51, 2.16, 6.15, and 8.64mg) and Bup/Nx (1.51/0.44, 2.16/0.61, 6.15/1.71, and 8.64/2.44mg). Placebo (Pbo), heroin (25mg) and Nx (0.3mg) were tested as neutral, positive, and negative controls, respectively. IV Bup alone was self-administered substantially less than IV heroin, though the two largest doses of Bup produced positive subjective effects, drug "Liking" (0-100mm), which were comparable to heroin (mean difference: Heroin vs Bup 6.15mg: -3.4mm, Heroin vs Bup 8.64mg: -11.3mm). All indicators of abuse potential seen with IV Bup alone were substantially decreased with the addition of Nx. All Bup/Nx combinations produced ratings of aversive effects, "Bad", which were comparable to, or greater than IV, Nx. On three of the four measures of aversive effects, the largest difference is seen with the 8.64 vs 8.64/2.44 condition. This study further demonstrates the ability of the Bup/Nx combination to deter IV use. Although none of the Bup/Nx combinations showed indications of abuse potential, formulations with larger absolute Nx, may be less abusable as they precipitate a greater degree of withdrawal. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Randomized Prospective Trial Comparing the Use of Intravenous versus Oral Acetaminophen in Total Joint Arthroplasty.

    Science.gov (United States)

    Politi, Joel R; Davis, Richard L; Matrka, Alexis K

    2017-04-01

    Multimodal pain management has had a significant effect on improving total joint arthroplasty recovery and patient satisfaction. There is literature supporting that intravenous (IV) acetaminophen reduces postoperative pain and narcotic use in the total joint population. However, there are no studies comparing the effectiveness of IV vs oral (PO) acetaminophen as part of a standard multimodal perioperative pain regimen. One hundred twenty patients undergoing hip and knee arthroplasty surgeries performed by one joint arthroplasty surgeon were prospectively randomized into 2 groups. Group 1 (63 patients) received IV and group 2 (57 patients) received PO acetaminophen in addition to a standard multimodal perioperative pain regimen. Each group received 1 gram of acetaminophen preoperatively and then every 6 hours for 24 hours. Total narcotic use and visual analog scale (VAS) scores were collected every 4 hours postoperatively. The 24-hour average hydromorphone equivalents given were not different between groups (3.71 vs 3.48) at 24 hours (P = .76), or at any of the individual 4-hour intervals. The 24-hour average visual analog scale scores in group 1 (IV) was 3.00 and in group 2 (PO) was 3.40 (P = .06). None of the 4-hour intervals were significantly different except the first interval (0-4 hour postoperatively), which favored the IV group (P = .03). The use of IV acetaminophen may have a role when given intraoperatively to reduce the immediate pain after surgery. Following that, it does not provide a significant benefit in reducing pain or narcotic use when compared with the much less expensive PO form. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Pharmacist's impact on acute pain management during trauma resuscitation.

    Science.gov (United States)

    Montgomery, Kayla; Hall, A Brad; Keriazes, Georgia

    2015-01-01

    The timely administration of analgesics is crucial to the comprehensive management of trauma patients. When an emergency department (ED) pharmacist participates in trauma resuscitation, the pharmacist acts as a medication resource for trauma team members and facilitates the timely administration of analgesics. This study measured the impact of a pharmacist on time to first analgesic dose administered during trauma resuscitation. All adult (>18 years) patients who presented to this level II trauma center via activation of the trauma response system between January 1, 2009, and May 31, 2013, were screened for eligibility. For inclusion, patients must have received intravenous fentanyl, morphine, or hydromorphone in the trauma bay. The time to medication administration was defined as the elapsed time from ED arrival to administration of first analgesic. There were 1328 trauma response system activations during the study period; of which 340 patients were included. The most common analgesic administered was fentanyl (62% in both groups). When a pharmacist was participating, the mean time to first analgesic administered was decreased (17 vs 21 minutes; P = .03). Among the 78% of patients with documented pain scores, the overall mean reduction in pain scores from ED arrival to ED discharge was similar between the 2 groups. There was a 2.4 point reduction with a pharmacist versus 2.7 without a pharmacist, using a 0 to 10 numeric pain rating scale. The participation of a clinical pharmacist during trauma resuscitation significantly decreased the time to first analgesic administration in trauma patients. The results of this study supplement the literature supporting the integration of clinical ED pharmacists on trauma teams.

  16. Safety and efficacy of nurse-controlled analgesia in patients less than 1 year of age

    Directory of Open Access Journals (Sweden)

    Walia H

    2016-06-01

    Full Text Available Hina Walia,1 Dmitry Tumin,1 Sharon Wrona,1 David Martin,1,2 Tarun Bhalla,1,2 Joseph D Tobias,1-3 1Department of Anesthesiology and Pain Medicine, Nationwide Children’s Hospital, 2Department of Anesthesiology and Pain Medicine, 3Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA Background: The management of acute pain presents unique challenges in the younger pediatric population. Although patient-controlled devices are frequently used in patients ≥6 years of age, alternative modes of analgesic delivery are needed in infants.Objective: To examine the safety and efficacy of nurse-controlled analgesia (NCA in neonates less than 1 year of age.Methods: Data from patients <1 year of age receiving NCA as ordered by the Acute Pain Service at our institution were collected over a 5-year period and reviewed retrospectively. The primary outcomes were activation of the institution’s Rapid Response Team (RRT or Code Blue, signifying severe adverse events. Pain score after NCA initiation was a secondary outcome.Results: Among 338 girls and 431 boys, the most common opioid used for NCA was fentanyl, followed by morphine and hydromorphone. There were 39 (5% cases involving RRT or Code Blue activation, of which only one (Code Blue was activated due to a complication of NCA (apnea. Multivariable logistic regression demonstrated morphine NCA to be associated with greater odds of RRT activation (OR=3.29, 95% CI=1.35, 8.03, P=0.009 compared to fentanyl NCA. There were no statistically significant differences in pain scores after NCA initiation across NCA agents.Conclusion: NCA is safe in neonates and infants, with comparable efficacy demonstrated for the three agents used. The elevated incidence of RRT activation in patients receiving morphine suggests caution in its use and consideration of alternative agents in this population. Keywords: nurse-controlled analgesia, pain medicine, Rapid Response Team

  17. Management of pediatric tonsillectomy pain: a review of the literature

    Directory of Open Access Journals (Sweden)

    Hansen J

    2016-05-01

    Full Text Available Jennifer Hansen, Ravi D Shah, Hubert A Benzon Department of Pediatric Anesthesiology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Abstract: Tonsillectomy is associated with significant pain and postoperative pain control is often unsatisfactory. We discuss the various strategies that have been investigated to control pain following tonsillectomy. Codeine is a weak analgesic frequently used in children for the treatment of mild-to-moderate pain, however, due to adverse events related to its metabolism, it has been contraindicated for postoperative pain in children since 2013. Intravenous morphine is frequently used for moderate-to-severe pain in children, however, its active metabolite can lead to respiratory depressant and other undesirable side effects. Hydromorphone is a commonly used alternative that has been studied infrequently. Alternatives to narcotic pain strategies have also been studied. Nonsteroidal anti-inflammatory drugs (NSAIDs are effective as analgesics, yet many practitioners avoid their use given the concern for postoperative bleeding. Intraoperative acetaminophen has been shown to improve postoperative pain and decrease recovery room time. Dexamethasone has been shown to improve postoperative pain, vomiting, and decrease airway swelling, and seems to be effective for use during tonsillectomy surgery. Ketamine has been shown to decrease analgesic requirements without adverse affects of hallucinations. Direct injection of local anesthetic into the tonsillar bed has been shown to be effective in improving pain control, however, there is concern that local anesthetic could be erroneously injected into the carotid artery and lead to devastating consequences. Optimal pain control regimens following pediatric tonsillectomy continue to be a challenge for both anesthesiologists and otorhinolaryngologists. Opioids are the most commonly used but are

  18. Anesthetic Overdose Leading to Cardiac Arrest Diagnosed by End-Tidal Inhalant Concentration Analysis in a Dog

    Directory of Open Access Journals (Sweden)

    Erik Hofmeister

    2013-01-01

    Full Text Available A 5-year-old male-castrated Cocker Spaniel presented to the Veterinary Teaching Hospital of the University of Georgia for a total ear canal ablation. Premedication was with carprofen 2.2 mg/kg SQ, hydromorphone 0.1 mg/kg IM, diazepam 0.2 mg/kg IM, and glycopyrrolate 0.01 mg/kg IM. The patient was induced with lidocaine 2 mg/kg IV and etomidate 1 mg/kg IV and maintained with sevoflurane and a constant rate infusion consisting of lidocaine 0.05 mg/kg/min. Before surgery start, the patient’s systolic arterial blood pressure was 110 mmHg, heart rate (HR was 85 beats/min, respiratory rate was 8 breaths/min, end-tidal sevoflurane concentration was 3.2%, and end-tidal CO2 (ETCO2 was 23 mmHg. As a scrub was being performed, the patient’s HR abruptly dropped to 20 beats/min over the course of 2 minutes. His ETCO2 simultaneously decreased to 16 mmHg. At this time, cardiopulmonary arrest was diagnosed. After two minutes of resuscitation, a spontaneous heart beat was obtained and the patient was successfully recovered and discharged without further incident. The cardiac arrest in this case is most likely attributable to an overdose of inhalant anesthesia, which was diagnosed by an anesthetic inhalant concentration monitor. A gas analyzer may be a helpful contribution to the small animal practitioner, particularly those performing more lengthy or complex procedures.

  19. Randomised, double-blind, parallel group, placebo-controlled study to evaluate the analgesic efficacy and safety of VVZ-149 injections for postoperative pain following laparoscopic colorectal surgery

    Science.gov (United States)

    Nedeljkovic, Srdjan S; Correll, Darin J; Bao, Xiaodong; Zamor, Natacha; Zeballos, Jose L; Zhang, Yi; Young, Mark J; Ledley, Johanna; Sorace, Jessica; Eng, Kristen; Hamsher, Carlyle P; Maniam, Rajivan; Chin, Jonathan W; Tsui, Becky; Cho, Sunyoung; Lee, Doo H

    2017-01-01

    Introduction In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery. Methods and analysis Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships. Ethics and dissemination Ethical approval of the study protocol has been obtained from

  20. Intrathecal Analgesic Drug Delivery is Effective for Analgesia in a Patient with Post-Poliomyelitis Syndrome: A Case Report

    Science.gov (United States)

    van Tilburg, Cornelis W.J.

    2016-01-01

    Patient: Female, 45 Final Diagnosis: Post-poliomyelitis syndrome Symptoms: Chronic pain Medication: Fentanyl • Oxycodone • Gabapentin • Naproxen • Paracetamol Clinical Procedure: Intrathecal analgesic drug delivery Specialty: Anesthesiology Objective: Unusual setting of medical care Background: Post-poliomyelitis syndrome (PPS) is a progressive neuromuscular syndrome, with chronic pain being one of the most prevalent symptoms. We present a case report on intrathecal analgesic drug delivery to diminish chronic, refractory pain in a patient with PPS. Case Report: In a wheelchair-bound 45-year-old female patient (Caucasian, body mass index [BMI] 20.5) with severe chronic, refractory pain, a Synchromed® II pump (Medtronic, Minneapolis, Minnesota, USA) was implanted after multi-disciplinary consultation and a successful trial period. After 8 months, relocation of the pump due to regional pressure problems with surrounding erythema had to occur. A second pump relocation due to pressure problems and skin erosion was needed 18 months after the first relocation, moving from the abdominal wall to the sheath of the rectus abdominis muscle, resulting in resolution of the problems. Conclusions: In patients with PPS, intrathecal analgesic drug delivery can be an option to treat chronic, refractory pain. Multidisciplinary consultation is necessary to deal with the wide variety of problems in these patients. Skin problems at the site of the pump reservoir can be challenging and time-consuming and, ultimately, can necessitate relocation (or removal) of the device. PMID:27980323

  1. [Emergent drugs (II): the Pharming phenomenon].

    Science.gov (United States)

    Burillo-Putze, G; Aldea-Perona, A; Rodríguez-Jiménez, C; García-Sáiz, M M; Climent, B; Dueñas, A; Munné, P; Nogué, S; Hoffman, R S

    2013-01-01

    The use of medicines, with or without medical prescription, for recreational ends by the young population has received little attention from doctors. In the USA, one in five adolescents has used medicines for recreational purposes, and consultations in Emergency Departments for medicine abuse have exceeded those for illegal drugs. Although few data are available in Spain, such consumption is situated between 3.1 and 8.6% according to surveys. The medicines most used are dextromethorphan and methylphenidate. The former, on sale without prescription, presents a varied symptomatology, dosage and dependent metabolic action, ranging from euphoria to hallucinations. Methylphenidate, taken orally, nasally or intravenously, is used as a stimulant in substitution for cocaine and is one of the medicines most diverted onto the illicit market at the world level. In principle, other substances like modafinil and propofol present a limited incidence of non-medical use, but they have a probable abuse potential that should be borne in mind, above all in the health context. Finally, opiates like fentanyl, oxycodone and buprenorphine, with new pharmaceutical presentations, have recently become generalized in the therapeutic arsenal of many medical specialities; they are giving rise to phenomena of abuse, dependence and diversion towards the illicit market. Demands for detoxification treatment, their mixture with illegal substances, and cases of death should alert us to the abuse of these medicines.

  2. Trends in opioid analgesics sales to community pharmacies and hospitals in Italy (2000-2010).

    Science.gov (United States)

    Caraceni, A T; Brunelli, C; Rocco, P; Minghetti, P

    2013-08-01

    Opioid consumption data in Italy have been widely studied. However, only aggregate data can be found in the published literature, and differences are expected by distribution setting (community pharmacies and hospitals). The aim of our paper is to analyse opioids sales trends in Italy in the decade 2000-2010, in an effort to explore such differences. Quarterly sales data of opioid medicinal products sold by wholesalers to both community pharmacies (retail) and to hospitals (non-retail) during the time period 2000-2010 were supplied by IMS Italy. Data were standardized using the Defined Daily Doses per day per 1000 inhabitants (DDDd/1000). Opioid sales have steadily increased during the time period considered going from 1.04 DDDd/1000 in 2000 to 4.9 in 2010 (+292%). Nonetheless relevant differences can be found both by distribution setting and drug type. In particular retail sales have increased by 286 % for WHO Step II opioids and by 575% for WHO Step III drugs, while non-retail sales have increased by 48% and 263%, respectively. In 2010, fentanyl and buprenorphine transdermal patches and oxycodone are more widely prescribed than morphine, in the retail setting, with fentanyl at large in the first position. In hospitals morphine and fentanyl almost equally share the 75% of the market. Data suggest that morphine is no more the opioid of first choice for severe pain in Italy, at least for outpatients. This is contradicting most international guidelines available in the 2000-2010 decade.

  3. Simultaneous screening and quantification of 25 opioid drugs in post-mortem blood and urine by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Gergov, M; Nokua, P; Vuori, E; Ojanperä, I

    2009-04-15

    A method for simultaneous screening and quantification was developed for the fentanyls alfentanil, fentanyl, p-fluorofentanyl, cis-3-methylfentanyl, trans-3-methylfentanyl, alpha-methylfentanyl, norfentanyl, remifentanil, sufentanil, and the other opioid drugs 6-acetylmorphine, buprenorphine, codeine, dextropropoxyphene, ethylmorphine, heroin, methadone, morphine, naloxone, naltrexone, norbuprenorphine, normethadone, oxycodone, pentazocine, pethidine, and tramadol in post-mortem blood and urine samples by LC-MS/MS. Samples were extracted with butyl acetate at pH 7. The drugs were separated by LC on a Genesis C(18) reversed-phase column, with a gradient consisting of acetonitrile and ammonium acetate at pH 3.2. The mass spectrometric analysis was performed with a quadrupole-linear ion-trap mass spectrometer equipped with a turbo ion spray interface in positive mode using multiple reaction monitoring (MRM). Quantification was performed based on five isotope-labelled internal standards. Validation included assessment of linearity, limit of quantification, inaccuracy, precision, and matrix effects. The limits of quantification were adequate for screening and quantification of opioid drugs at low therapeutic or abuse concentration levels, with inaccuracy less than 23% and precision better than 24% both in blood and urine samples. When this method was applied to autopsy cases, its results were in agreement with those of reference methods.

  4. Prescription opioid related deaths in New York City: a 2 year retrospective analysis prior to the introduction of the New York State I-STOP law.

    Science.gov (United States)

    Sgarlato, Anthony; deRoux, Stephen J

    2015-09-01

    The United States is in the midst of an unprecedented drug epidemic. Illicit use of prescription medicine, predominantly opioids, has become one of the nation's fastest-growing drug problems. We have conducted a retrospective review of prescription opioid fatalities in New York City (NYC) prior to the introduction of a 2013 law intended to curtail prescription drug abuse. Over the 2 years of our study, there were 1286 chemical intoxication fatalities in NYC. Of these, 547 (42.5%) were associated with prescription opioids (6.5/100,000 population). Methadone was most frequently encountered followed by oxycodone. Only 36.7% of decedents had a valid opioid prescription. Of non-opioid medications associated with the prescription opiate deaths, benzodiazepines were the most frequently encountered (68.4%), and alprazolam (35.1%) was most common. Though prescribers have no control over drug diversion they should be cognizant of the urgent public health concern regarding prescription opioid abuse and associated fatalities and attempt to identify doctor shoppers and limit prescription of these potent drugs to those with a legitimate need for pain control. They also need to be aware of the high incidence of fatalities due to combined opioid and benzodiazepine use/abuse and refrain from prescribing them in tandem.

  5. Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Carlo Luca Romanò

    2012-01-01

    Full Text Available Purpose. Chronic low back pain (LBP is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy, with similar side effects.

  6. A prospective analysis of the preventability of adverse drug reactions reported in Sweden.

    Science.gov (United States)

    Lövborg, Henrik; Eriksson, Linda Ring; Jönsson, Anna K; Bradley, Thomas; Hägg, Staffan

    2012-08-01

    Adverse drug reactions (ADRs) are a major patient safety issue, and a substantial proportion of ADRs are, in fact, preventable. The aim of this study was to describe the proportion and pattern of preventable ADRs in spontaneously reported suspected ADRs and to study the feasibility of using data from an ADR reporting system for this purpose. All reports of ADRs, except those in which a vaccine was the suspected drug, submitted to the regional pharmacovigilance center of southeastern Sweden between 2008 and 2009 were analyzed. Causality between the suspected ADR and the medication was assessed using the World Health Organization (WHO) criteria, and preventability was assessed using Hallas criteria. During the study period, 1,290 ADRs were received and 1,255 were classified as having at least a possible causality between a reaction and a drug. Of these, 172 (14%) ADRs were considered preventable, 35 (20%) were classified as definitely preventable, and 137 (80%) as possibly preventable. Of all preventable ADRs, 96 (56%) were related to prescribing, 35 (20%) to administration, and 41 (24%) to clinical and laboratory monitoring of treatment. Warfarin, oxycodone, and ioversol were the most common drugs with preventable ADRs. This study found that a substantial part of reported ADRs are preventable. Most of these are related to drug prescription, suggesting that interventions aiming to reduce preventable ADRs should focus on this process. Moreover, systems for ADR reporting may be useful in the mission of reducing the unsafe use of drugs.

  7. 鼻咽癌IMRT同期化疗的疼痛管理%Pain management of nasopharyngeal carcinoma with IMRT concurrent chemotherapy

    Institute of Scientific and Technical Information of China (English)

    黄中; 邵汛帆; 郑乃莹

    2014-01-01

    Objective Through the analysis of oxycodone pain treatment opportunity to investigate how to improve the analgesic effect of radioactive oral mucositis of NPC patients with IMRT concurrent chemotherapy. Methods 102 cases of patients with nasopharyngeal carcinoma from January 2012 to March 2014 treated in our hospital were selected,received the same IMRT concurrent chemoradiotherapy,nutrition interventions and oral care,chemotherapy injury pain in oral mucositis were scored according to the visual analog scale(VAS),were randomly divided into the first,second and third group,the first group of patients began to oral oxycodone zyban with mild pain(1 to 3 points);The second group of patients began to oral oxycodone zyban with moderate pain(4-6 points);The third group of patients started to oral oxycodone zyban with moderate to severe pain(7 to 9 points);The changes in pain scores,improved quality of life,nutritional status,the average amount of pain medication and adverse drug reactions,etc between three groups of patients were observed and compared. Results After the first seven weeks long radiotherapy,the differences of VAS score and QOL scores of the first group compared with the second or third group were significant(P<0.05),the incidence of malnutrition,nausea,vomiting,constipation,drowsiness,dizziness,headache and other drugs reactions of the first group were significantly less than the second group and the third group,the difference was statistically significant(P<0.05),patients of three groups had no serious adverse effects such as respiratory depression as opioid analgesic drug used ,analgesic drug average usage amount of the first group was significantly less than the second or third group,with statistically significant difference(P < 0.05). Conclusion Patients with pain of nasopharyngeal IMRT concurrent chemoradiotherapy-induced oral mucosal injury, are given early analgesic treatment,the analgesic effect is obvious,less adverse drug reactions,patients with

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

    Science.gov (United States)

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

    2017-01-01

    Prescription opioid related abuse, suicide and death are significant public health problems. This study compares rates of poison center calls categorized as intentional abuse, suspected suicidal intent or fatality for the 7-day buprenorphine transdermal system/patch (BTDS) with other extended-release and long-acting (ER/LA) opioids indicated for chronic pain. Retrospective 24-month cohort study using National Poison Data System data from July 2012 through June 2014. BTDS was introduced in the United States in January 2011. Numbers and rates of calls of intentional abuse, suspected suicidal intent and fatalities were evaluated for BTDS, ER morphine, ER oxycodone, fentanyl patch, ER oxymorphone and methadone tablets/capsules, using prescription adjustment to account for community availability. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. Absolute numbers and prescription-adjusted rates of intentional abuse and suspected suicidal intent with BTDS were significantly lower (p opioid analgesics examined. No fatalities associated with BTDS exposure were reported. This post-marketing evaluation of BTDS indicates infrequent poison center calls for intentional abuse and suspected suicidal intent events, suggesting lower rates of these risks with BTDS compared to other ER/LA opioids.

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

    Science.gov (United States)

    Mercer, Susan L; Coop, Andrew

    2011-01-01

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

  10. Pocket-size near-infrared spectrometer for narcotic materials identification

    Science.gov (United States)

    Pederson, Christopher G.; Friedrich, Donald M.; Hsiung, Chang; von Gunten, Marc; O'Brien, Nada A.; Ramaker, Henk-Jan; van Sprang, Eric; Dreischor, Menno

    2014-05-01

    While significant progress has been made towards the miniaturization of Raman, mid-infrared (IR), and near-infrared (NIR) spectrometers for homeland security and law enforcement applications, there remains continued interest in pushing the technology envelope for smaller, lower cost, and easier to use analyzers. In this paper, we report on the use of the MicroNIR Spectrometer, an ultra-compact, handheld near infrared (NIR) spectrometer, the, that weighs less than 60 grams and measures heroin, oxycodone, diazepam), as well as synthetic cathinones (also known as bath salts), and synthetic cannabinoids. A library of the materials was created from a master MicroNIR spectrometer. A set of 25 unknown samples were then identified with three other MicroNIRs showing: 1) the ability to correctly identify the unknown with a very low rate of misidentification, and 2) the ability to use the same library with multiple instruments. In addition, we have shown that through the use of innovative chemometric algorithms, we were able to identify the individual compounds that make up an unknown mixture based on the spectral library of the individual compounds only. The small size of the spectrometer is enabled through the use of high-performance linear variable filter (LVF) technology.

  11. Synergy between mu opioid ligands: evidence for functional interactions among mu opioid receptor subtypes.

    Science.gov (United States)

    Bolan, Elizabeth A; Tallarida, Ronald J; Pasternak, Gavril W

    2002-11-01

    Pharmacological differences among mu opioid drugs have been observed in in vitro and in vivo preclinical models, as well as clinically, implying that all mu opioids may not be working through the same mechanism of action. Here we demonstrate analgesic synergy between L-methadone and several mu opioid ligands. Of the compounds examined, L-methadone selectively synergizes with morphine, morphine-6beta-glucuronide, codeine, and the active metabolite of heroin, 6-acetylmorphine. Morphine synergizes only with L-methadone. In analgesic assays, D-methadone was inactive alone and did not enhance morphine analgesia when the two were given together, confirming that L-methadone was not acting through N-methyl-D-aspartate mechanisms. Both L-methadone and morphine displayed only additive effects when paired with oxymorphone, oxycodone, fentanyl, alfentanyl, or meperidine. Although it displays synergy in analgesic assays, the L-methadone/morphine combination does not exhibit synergy in the gastrointestinal transit assay. This analgesic synergy of L-methadone with selective mu opioid drugs and the differences in opioid-mediated actions suggest that these drugs may be acting via different mechanisms. These findings provide further evidence for the complexity of the pharmacology of mu opioids.

  12. Psychosocial and pharmacological management of pain in pediatric sickle cell disease.

    Science.gov (United States)

    Hildenbrand, Aimee K; Nicholls, Elizabeth G; Daly, Brian P; Marsac, Meghan L; Tarazi, Reem; Deepti, Raybagkar

    2014-03-01

    For children with sickle cell disease (SCD), pain is associated with significant current and future morbidity and mortality. Unfortunately, few evidence-based guidelines exist for the management of pain episodes in children with SCD. To inform empirically based treatment strategies for pain management in pediatric SCD, this review integrates and evaluates the extant literature on psychosocial and pharmacological approaches to the management of pain. Findings reveal a paucity of rigorous investigations of psychosocial and pharmacological pain management interventions in children with SCD. Psychosocial interventions included were primarily cognitive-behavioral in nature, whereas pharmacological approaches targeted non-opioid analgesics (ie, nonsteroidal anti-inflammatory drugs and corticosteroids) and opioid medications (ie, morphine and oxycodone). However, to date there is not a "gold standard" for pain management among children with SCD. Because psychosocial and physiological processes each play a role in the etiology and experience of pain, effective pain management requires multidimensional, comprehensive treatment approaches. Considering the significant impact of pain on functional outcomes and quality of life among children with SCD, additional clinical trials are warranted to ensure that interventions are safe and efficacious.

  13. Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

    Science.gov (United States)

    Romanò, Carlo Luca; Romanò, Delia; Lacerenza, Marco

    2012-01-01

    Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy, with similar side effects. PMID:22619711

  14. Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic-Cationic Drugs to the Brain.

    Science.gov (United States)

    Kitamura, Atsushi; Okura, Takashi; Higuchi, Kei; Deguchi, Yoshiharu

    2016-02-01

    Brain microdialysis is a powerful tool to estimate brain-to-plasma unbound concentration ratio at the steady state (Kp,uu) of compounds by direct measurement of the unbound concentration in brain interstitial fluid. Here, we evaluated a method to estimate Kp,uu values of multiple organic-cationic drugs simultaneously, by means of brain microdialysis combined with cocktail dosing. Five cationic drugs (diphenhydramine, memantine, oxycodone, pyrilamine, and tramadol), substrates of the proton-coupled organic cation antiport system, were selected as model drugs, and compared under single-dosing and cocktail-dosing conditions. We selected doses of the drugs at which no significant drug-drug interaction occurs at the proton-coupled organic cation antiport system in the blood-brain barrier (BBB). This was confirmed by uptake studies in hCMEC/D3 cells, an in vitro BBB model. The Kp,uu values after cocktail administration were in the range of 1.8-5.2, and were in good agreement with those after single administration. These results suggest that the microdialysis method with cocktail dosing is suitable to estimate Kp,uu values of several cationic drugs simultaneously, if there is no drug-drug interaction during BBB transport. The method could be useful for evaluating drug candidates with high Kp,uu values at an early stage in the development of central nervous system-acting drugs.

  15. [NON-ONCOLOGIC CHRONIC PAIN TREATMENT WITH OPIATES].

    Science.gov (United States)

    Molas Ferrer, Glòria; Castellà Kastner, Montse; Lombraña Mencia, María

    2014-09-01

    Non-oncologic chronic pain is a very common symptom. It causes great impact on daily activities of people who suffer it. The incidence of this type of pain is rising due to the increase in life expectancy. The most affected population is geriatric population. Back pain, osteoarthritic pain and neuropathic pain are the most prevalent types of non-oncologic chronic pain. Opiates, among other analgesic drugs, are used to alleviate this type of pain. Opiates are divided into minor opiates (tramadol, codeine) and major opiates (morphine, fentanyl, oxycodone, methadone). Opiates are very effective to treat pain, but they also have important adverse effects that we must know and try to prevent. One of these adverse effects is the opiates ability to cause dependence, tolerance, addiction and other aberrant behaviors. Terminology of these concepts is sometimes confusing. It is necessary to be careful and control the patient periodically in order to avoid these aberrant behaviors. However, if health professionals take precautions to prevent these behaviors, the risk is considerably reduced. Controlling patients on opiate treatment is essential to achieve a correct use if these drugs.

  16. [Opioids in chronic neuropathic pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration].

    Science.gov (United States)

    Sommer, C; Welsch, P; Klose, P; Schaefert, R; Petzke, F; Häuser, W

    2015-02-01

    The efficacy and safety of opioid therapy in chronic neuropathic pain (CNP) is under debate. We updated a recent Cochrane systematic review on the efficacy, tolerability and safety of opioids in CNP. We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CNP. We included double-blind randomized placebo-controlled studies of at least 4 weeks duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. We included 12 RCTs with 1192 participants. The included diagnostic entities were painful diabetic neuropathy (four studies), postherpetic neuralgia (three studies), mixed polyneuropathic pain (two studies), and lumbar root, spinal cord injury and postamputation pain (one study each). Mean study duration was 6 (4-12) weeks. Four studies tested morphine, three studies tramadol, two studies oxycodone and one study tapentadol. These are the pooled results of studies with a parallel or cross-over design: opioids were superior to placebo in reducing pain intensity (SMD - 0.64 [95 % confidence interval, CI - 0.81, - 0.46], p SpringerLink (under "Supplementary Material").

  17. The histopathology of drugs of abuse.

    Science.gov (United States)

    Milroy, Christopher Mark; Parai, Jacqueline Louise

    2011-10-01

    The use of drugs for recreational purposes is widespread. The drugs used can be divided into groups including stimulants (cocaine, amphetamines, etc.), opiates and opioids (heroin, oxycodone, methadone, fentanyl, etc.), sedatives (benzodiazepines and related substances) and miscellaneous drugs, including ketamine and cannabis (marijuana). These drugs can have profound effects on all organ systems in the body. The method of administration, whether by injection or inhalation, can cause localized and systemic effects, including the transmission of infection and granulomata at the site of injection and in the lungs. Suppurative abscesses from injection can result in systemic amyloidosis. Stimulants have profound effects on the cardiovascular and cerebrovascular systems, with enlarged hearts with fibrosis seen microscopically and cerebral infarction and haemorrhage. Crack cocaine use is also associated with changes in the pulmonary system, including carbon pigmented intra-alveolar macrophages, emphysema and pulmonary arterial changes. Cannabis use is associated with brown pigmented macrophages in the lung as well as changes in the respiratory tract epithelium. Opiates/opioids are associated with inhalational pneumonitis and hypoxic brain damage due to their respiratory depressant effects. Heroin use has been associated with focal segmental glomerulonephritis (heroin-associated nephropathy: HAN). 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) use is associated with changes in the cardiovascular system. Its use can lead to hyperpyrexia, which results in systemic changes. Ketamine abuse has been associated with cystitis. Drugs of abuse may affect testicular function. In analysing the effects of drugs at autopsy a systematic approach to sampling of histology is required.

  18. Retrospective analyses versus RCTs: comparing like with like?

    Directory of Open Access Journals (Sweden)

    Baron R

    2017-03-01

    Full Text Available Ralf Baron,1 Lieven Nils Kennes,2 Christian Elling31Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital of Schleswig-Holstein, Kiel Campus, Kiel, 2Department of Economics and Business Administration, University of Applied Sciences Stralsund, Stralsund, 3Grünenthal GmbH, Medical Affairs Europe and North America, Aachen, GermanyIn their recent retrospective analysis assessing oxycodone/naloxone (OXN vs. tapentadol (TAP treatment for chronic low-back pain with a neuropathic component, Ueberall and Mueller-Schwefe1 compare their results to the findings of an earlier phase 3b/4 study.2 In our opinion, a proper comparison to the prospective, randomized, controlled, open-label study by Baron and colleagues is scientifically not appropriate. Although Ueberall and Mueller-Schwefe use the terms “prospective,” “randomly,” and “blinded” and refer to the PROBE design (prospective, randomized, open-label, blinded endpoint,3 their database study is retrospective, nonrandomized, and nonblinded with the treatment choice left to the discretion of the physicians. In this context, the use of the term “intention-to-treat (ITT population” is inappropriate because ITT is unambiguously defined as including all randomized subjects and thus inseparable from true randomization (ICH E9.4View original paper by Ueberall and Mueller-Schwefe.

  19. Label-free porous silicon immunosensor for broad detection of opiates in a blind clinical study and results comparison to commercial analytical chemistry techniques.

    Science.gov (United States)

    Bonanno, Lisa M; Kwong, Tai C; DeLouise, Lisa A

    2010-12-01

    In this work, we evaluate for the first time the performance of a label-free porous silicon (PSi) immunosensor assay in a blind clinical study designed to screen authentic patient urine specimens for a broad range of opiates. The PSi opiate immunosensor achieved 96% concordance with liquid chromatography-mass spectrometry/tandem mass spectrometry (LC-MS/MS) results on samples that underwent standard opiate testing (n = 50). In addition, successful detection of a commonly abused opiate, oxycodone, resulted in 100% qualitative agreement between the PSi opiate sensor and LC-MS/MS. In contrast, a commercial broad opiate immunoassay technique (CEDIA) achieved 65% qualitative concordance with LC-MS/MS. Evaluation of important performance attributes including precision, accuracy, and recovery was completed on blank urine specimens spiked with test analytes. Variability of morphine detection as a model opiate target was <9% both within-run and between-day at and above the cutoff limit of 300 ng mL(-1). This study validates the analytical screening capability of label-free PSi opiate immunosensors in authentic patient samples and is the first semiquantitative demonstration of the technology's successful clinical use. These results motivate future development of label-free PSi technology to reduce complexity and cost of diagnostic testing particularly in a point-of-care setting.

  20. Removal of pharmaceuticals and personal care products in a membrane bioreactor wastewater treatment plant.

    Science.gov (United States)

    Kim, M; Guerra, P; Shah, A; Parsa, M; Alaee, M; Smyth, S A

    2014-01-01

    Ninety-nine pharmaceuticals and personal care products (PPCPs) were analyzed in influent, final effluent, and biosolids samples from a wastewater treatment plant employing a membrane bioreactor (MBR). High concentrations in influent were found for acetaminophen, caffeine, metformin, 2-hydroxy-ibuprofen, paraxanthine, ibuprofen, and naproxen (10(4)-10(5) ng/L). Final effluents contained clarithromycin, metformin, atenolol, carbamazepine, and trimethoprim (>500 ng/L) at the highest concentrations, while triclosan, ciprofloxacin, norfloxacin, triclocarban, metformin, caffeine, ofloxacin, and paraxanthine were found at high concentrations in biosolids (>10(3) ng/g dry weight). PPCP removals varied from -34% to >99% and 23 PPCPs had ≥90% removal. Of the studied PPCPs, 26 compounds have been rarely or never studied in previous membrane bioreactor (MBR) investigations. The removal pathway showed that acetaminophen, 2-hydroxy-ibuprofen, naproxen, ibuprofen, codeine, metformin, enalapril, atorvastatin, caffeine, paraxanthine, and cotinine exhibited high degradation/transformation. PPCPs showing strong sorption to solids included triclocarban, triclosan, miconazole, tetracycline, 4-epitetracycline, norfloxacin, ciprofloxacin, doxycycline, paroxetine, and ofloxacin. Trimethoprim, oxycodone, clarithromycin, thiabendazole, hydrochlorothiazide, erythromycin-H2O, carbamazepine, meprobamate, and propranolol were not removed during treatment, and clarithromycin was even formed during treatment. This investigation extended our understanding of the occurrence and fate of PPCPs in an MBR process through the analysis of the largest number of compounds in an MBR study to date.

  1. Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report.

    Science.gov (United States)

    Lalanne, Laurence; Nicot, Chloe; Lang, Jean-Philippe; Bertschy, Gilles; Salvat, Eric

    2016-11-10

    Opioids are good painkillers, but many patients treated with opioids as painkillers developed a secondary addiction. These patients need to stop misusing opioids, but the mild-to-severe clinical symptoms associated with opioid withdrawal risk increasing their existing pain. In such cases, ketamine, which is used by anaesthetists and pain physicians to reduce opioid medication, may be an effective agent for managing opioid withdrawal. We describe the case of a woman who developed a severe secondary addiction to opioids in the context of lombo-sciatic pain. She presented a severe opioid addiction, and her physicians refused to prescribe such high doses of opioid treatment (oxycontin® extended-release 120 mg daily, oxycodone 60 mg daily, and acetaminophen/codeine 300 mg/25 mg 6 times per day). To assist her with her opioid withdrawal which risked increasing her existing pain, she received 1 mg/kg ketamine oral solution, and two days after ketamine initiation her opioid treatment was gradually reduced. The patient dramatically reduced the dosage of opioid painkillers and ketamine was withdrawn without any withdrawal symptoms. Ketamine displays many interesting qualities for dealing with all symptoms relating to opioid withdrawal. Accordingly, it could be used instead of many psychotropic treatments, which interact with each other, to help with opioid withdrawal. However, the literature describes addiction to ketamine. All in all, although potentially addictive, ketamine could be a good candidate for the pharmacological management of opioid withdrawal.

  2. Opioid use for chronic pain management in Italy: results from the Orthopedic Instant Pain survey project

    Directory of Open Access Journals (Sweden)

    Guido Fanelli

    2014-06-01

    Full Text Available Pain is a common symptom in orthopedic patients, but is managed sub-optimally, partly due to scarce opioid use in severe cases. The aim of the Orthopedic Instant Pain Survey (POIS was to evaluate changes in pain management in Italian orthopedic practice 2 years after a legislative change (Law 38/2010 simplifying opioid access for pain control. A web-based survey on the knowledge of this law and trends observed in clinical practice for severe pain treatment was administered to 143 Italian orthopedic specialists. In total, 101 (70% respondents showed a high level of knowledge. Nevertheless, 54.5% stated that they do not use opioids for severe osteo-articular pain management. Main barriers to opioid use are fear of adverse events (61.4%, especially nausea/vomiting and constipation, and patient resistance (29.7%. A modest knowledge of pain classification was also demonstrated. Opioid use remains very limited in Italian orthopedic practice. Physicians’ fear of side effects showed poor knowledge of strategies for effective management of opioid-related adverse events, such as combined oral prolonged-release oxycodone/naloxone. Continuing educational programs could improve delivery of evidence-based pain management.

  3. Opioid analgesic use in Australia and The Netherlands: a cross-country comparison.

    Science.gov (United States)

    Wagemaakers, Francisca N; Hollingworth, Samantha A; Kreijkamp-Kaspers, Sanne; Tee, Ernest H L; Leendertse, Anne J; van Driel, Mieke L

    2017-08-01

    Background Increasing use of opioid analgesics (OA) has been reported worldwide. Objective To compare the use of OA in two countries in order to better understand these trends. Setting Outpatient settings in Australia and The Netherlands. Method We analysed publicly available government data on outpatient OA dispensing over 15 years (2000-2014). We compared dispensing trends for specific OA and explored medical (national clinical guidelines), contextual and policy-related factors to explain differences in use between the two countries. Main outcome measure OA prescribing in Australia and The Netherlands, absolute volume of use, preferred types of opioids and changes over time. Results The average annual increase in OA prescribing was 10% in Australia and 8% in The Netherlands between 2000 and 2014. In 2014, the total use of OA was 10.0 daily defined doses (DDD)/1000 population/day in Australia and 9.4 DDD/1000 population/day in The Netherlands. In Australia, the most commonly prescribed opioids were oxycodone and tramadol, compared to fentanyl and tramadol in The Netherlands. We found differences in prescribing guidelines, culture of prescribing and regulatory frameworks that could explain some of the observed differences. Conclusion OA prescribing has increased remarkably in both countries between 2000 and 2014 but the types of prescribed OA vary. Differences in national evidence-based guidelines influenced the types of OA used. Prescribing culture as well as regulatory policies and costs, may also contribute to the different patterns of OA use.

  4. DSA引导下背根节脉冲射频治疗带状疱疹后神经痛的疗效及安全性%Dosal root ganglion pulsed radiofrequency guided by DSA for postherpetic neuralgia

    Institute of Scientific and Technical Information of China (English)

    黄乔东; 宫庆娟; 薄存菊; 刘晓明; 陈金生; 卢振和; 高崇荣

    2012-01-01

    目的:观察DSA引导下背根节脉冲射频治疗带状疱疹后神经痛的疗效及其安全性.方法:60例带状疱疹后神经痛患者(VAS≥4.0),随机分为A、B两组,每组30例:A组使用加巴喷丁、阿米替林、奥施康定等药物治疗;B组在上述药物治疗的基础上.联合DSA引导下背根节脉冲射频进行治疗.观察患者射频治疗前,治疗后1、7、30、90、180 d的疼痛视觉模拟评分(VAS)、奥施康定使用量、药物副作用、治疗并发症等情况.结果:A组患者射频治疗前,治疗后1、7、30、90、180 d VAS分别为:(8.2±1.7)、(6.3±1.8)、(4.1±1.4)、(3.2 ±1.5)、(3.1 ±1.2)和(2.6 ±1.1)分.奥施康定使用量分别为:(28.8±5.5)、(35.6±8.5)、(42.3±8.9)、(18.6 ±4.3)、(10.7 ±2.4)和(8.1 ±1.6)mg.B组患者治疗前,治疗后1、7、30、90、180 d VAS分别为:(8.1 ±1.6)、(4.5 ±1.6)、(3.0 ±1.2)、(2.1±1.1)、(1.8±0.9)和(1.5±0.9)分.奥施康定使用量分别为:(29.1±5.8)、(17.6 ±5.4)、(12.4 ±3.8)、(5.1 ±1.6)、(6.0 ±1.3)和(4.2±0.9)mg,组间比较有显著差异(P<0.05),B组药物副作用减轻,无严重并发症.结论:DSA引导下背根节脉冲射频术能迅速减轻疼痛,降低镇痛药使用量并减少其相关副作用.是带状疱疹后神经痛的一种安全、有效的治疗方法.%Objective To observe the efficacy and safety of dosal root ganglion (DRG) pulsed radiofrequency for treating postherpetic neuralgia (PHN) guided by digital subtraction angiography (DSA). Methods 60 patients with PHN were randomly divided into two groups (each n= 30). Patients in Group A were treated with gabapentin, amitriptyline, and oxycodone, and patients in Group B were treated with DRG pulsed radiofrequency guided by DSA along with the same medicines used in Group A. VAS and oxycodone dosage before and 1d, 7 d, 30 d, 90 d, and 180 d after treatment, and side effects and complications during the treatment in the two groups were recorded. Results The VAS of patients in

  5. Compartment syndrome of the deltoid: a case report of a common presentation in a rare location.

    Science.gov (United States)

    Harrison, Andrew; Sumner, Michael; Sobecki, Jeffrey; Christiansen, Gregory

    2016-10-01

    Compartment syndrome presents with a slow onset of pain. Anything that causes an increased intra-compartmental pressure can lead to surgical emergency. A 45-year-old male presents to the emergency department with prolonged syncope. The patient is unable to recall the previous night except for using oxycodone. Patient medical history is significant for ischemic cardiomyopathy and myocardial infarction. Physical exam showed left arm pain and swelling, decreased sensation to light touch, and decreased range of motion. The left forearm was cool to touch with decreased pulses. Blood urea nitrogen/creatinine ratio was 47/4.0, white blood cell was 15.1, troponin was 34.2, and creatine kinase was immeasurable. Electrocardiogram showed non-specific T-wave abnormalities. Computed tomography showed left hemithoracic musculature enlargement. The patient's symptoms continued to worsen. The patient underwent emergency fasciotomy to relieve intra-compartmental pressure. Compartment syndrome of the deltoid is rare and yielded less than ten cases in our literature review. Although compartment syndrome usually affects the forearm, one must consider its possibility in any anatomical location.

  6. Synthesis of 14-Alkoxymorphinan Derivatives and Their Pharmacological Actions

    Science.gov (United States)

    Schmidhammer, Helmut; Spetea, Mariana

    Among opioids, morphinans play an important role as therapeutically valuable drugs. They include pain relieving agents such as naturally occurring alkaloids (e.g. morphine, codeine), semisynthetic derivatives (e.g. oxycodone, oxymorphone, buprenorphine), and synthetic analogs (e.g. levorphanol). Currently used opioid analgesics also share a number of severe side effects, limiting their clinical usefulness. The antagonist morphinans, naloxone and naltrexone are used to treat opioid overdose, opioid dependence, and alcoholism. All these opioid drugs produce their biological actions through three receptor types, µ, δ, and κ, belonging to the G-protein-coupled receptor family. Considerable effort has been put forward to understand the appropriate use of opioid analgesics, while medicinal chemistry and opioid pharmacology have been continuously engaged in the search for safer, more efficacious and nonaddicting opioid compounds, with the final goal to reduce complications and to improve patient compliance. Toward this goal, recent advances in chemistry, ligand-based structure activity relationships and pharmacology of 14-alkoxymorphinans are reviewed in this chapter. Current developments of different structural patterns of 14-alkoxymorphinans as research tools and their potential therapeutic opportunities are also summarized.

  7. Non-analgesic effects of opioids: interactions between opioids and other drugs.

    Science.gov (United States)

    Heiskanen, Tarja; Kalso, Eija

    2012-01-01

    Opioids are increasingly used to manage not only acute but also chronic pain and heroine addiction. These patients usually receive many other medications that can interfere with the effects of opioids and vice versa. Patients often need combinations of drugs for their pain management, for treating opioid-related adverse effects or for other indications including depression and anxiety. Several antibiotics can also have interactions with opioids. It is important to understand what potential interactions exist between opioids and other drugs. Drug interactions can occur due to pharmacokinetic interactions including effects of absorption, metabolic pathways, drug transport through membranes and protein binding. Our knowledge of the metabolism of opioids has significantly increased over the last years and it is now possible to appreciate the role CYP enzymes, mainly CYP 2D6 and 3A4/5, in the metabolism of many commonly used opioids like codeine and oxycodone. Our knowledge regarding the role of the transporter proteins in drug interactions related to opioids is unfortunately meagre. Opioids inhibit the gastrointestinal system and can thus change the absorption of other drugs. Opioids can have synergistic or additive interactions with other drugs that have analgesic or sedative effects. Endogenous opioids control many physiological functions and exogenous opioids can have effects on all important transmitter systems (cholinergic, GABAergic, dopaminergic and serotonergic). The literature in this field is mainly based on case reports. Interindividual differences play an important role. Other potential interactions include prolongation of the QT-interval and lowering of the threshold for convulsions.

  8. ADMET considerations when prescribing novel therapeutics to treat restless legs syndrome.

    Science.gov (United States)

    de Biase, Stefano; Merlino, Giovanni; Lorenzut, Simone; Valente, Mariarosaria; Gigli, Gian Luigi

    2014-10-01

    Restless legs syndrome (RLS) is a commonly occurring sensory motor disorder that might impair nocturnal rest causing decreased alertness, depression, reduced job performance and poor quality of life. In patients affected by severe RLS, a pharmacological treatment is mandatory. The present review is based on a search using PubMed from 1994 to 2014. It is focused on the Absorption, Distribution, Metabolism, Elimination and Toxicology (ADMET) characteristics of drugs currently used and under development for the treatment of RLS. The drugs currently available for RLS treatment do not always provide an optimal control of symptoms. There is still need for effective and well-tolerated new drugs. Long-acting dopamine agonists showed better efficacy than short-acting compounds in the treatment of severe RLS. There seems to be an inverse relationship between the half-life of the compound and the development of augmentation. Monoamine oxidase B inhibitors could be good candidates for initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS insufficiently treated with first-line drugs and could be used as a long-term treatment in severe RLS when alternative satisfactory drug regimens are unavailable.

  9. Investigational approaches to therapies for restless legs syndrome.

    Science.gov (United States)

    de Biase, Stefano; Merlino, Giovanni; Lorenzut, Simone; Valente, Mariarosaria; Gigli, Gian Luigi

    2014-06-01

    Restless Legs Syndrome (RLS) is a common neurological disorder that impairs nocturnal rest, causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by severe RLS, pharmacological treatment is mandatory. The present review is based on an extensive Internet and PubMed search from 1994 - 2014. It focuses on drugs currently in development for the treatment of RLS. The drugs currently available for treating RLS do not always allow the patient to obtain a dose capable of controlling the symptoms, particularly in the long term. There is still the need for effective and well-tolerated new drugs. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone has demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled with first-line drugs; it could be used as a long-term treatment option in severe cases of RLS for which alternative satisfactory drug regimens are unavailable. There is a paucity of data comparing medications in head-to-head trials to determine their relative effectiveness and adverse event profiles. Furthermore, there is also a need for further studies that evaluate nondopaminergic agonists and combination therapies for treating RLS.

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

    Science.gov (United States)

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

    2014-02-01

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

  11. Toxicology findings in cases of hanging in the City and County of San Francisco over the 3-year period from 2011 to 2013.

    Science.gov (United States)

    San Nicolas, A C; Lemos, N P

    2015-10-01

    In postmortem cases where the cause of death is hanging, toxicological analyses may be considered unnecessary by some medical examiners, toxicologists, and other persons involved in medico-legal investigations because the cause of death seems "obvious." To ascertain if toxicological analyses are necessary when the cause of death is hanging, all 102 hanging cases (25 females; 77 males) from 2011 to 2013 that came under the jurisdiction of the San Francisco Office of the Chief Medical Examiner were examined from a total of 3912 sudden, unexpected, or violent death cases in the same period. Suicide was the manner of death in 99 of these cases, with two accidental and one undetermined death. The average age of decedents was 43.9 years (median 41), the youngest was an 11-year old male and the oldest was an 86-year old female. Of the 102 cases, 33 had negative toxicology while 69 cases had at least one positive toxicology result. Females were equally likely to have negative or positive results (12 and 13 cases respectively), but males were 37.5% more likely to have positive toxicology (n=56) rather than negative toxicology (n=21). For females, alcohol, mirtazapine, venlafaxine, and trazodone were the top psychoactive substances in peripheral blood while THC, cocaine, hydrocodone, bupropion, olanzapine, doxylamine, quetiapine and dextromethorphan were also reported. For males, alcohol, THC, cocaine, amphetamine, methamphetamine, bupropion, and diphenhydramine were the top psychoactive substances in blood, but several other drugs were also found in individual cases. Our study of hanging cases over a 3-year period support the idea that complete postmortem toxicology investigation of hangings should be performed, even when the "obvious" cause of death is asphyxia due to hanging. Many of these cases involved psychoactive substances (most often alcohol and cannabis), and having such knowledge provides a better understanding of the circumstances surrounding the decedent's death

  12. Trastornos del sueño e incidencia de ansiedad y depresión en pacientes con dolor crónico no maligno tratados con opioides potentes Sleep disorders and incidence of anxiety and depresion in patients with chronic nonmalignant pain treated with strong opioids

    Directory of Open Access Journals (Sweden)

    I. Velázquez

    2012-04-01

    were patients younger than 18 years, those who would not cooperate, diagnosed with fibromyalgia and those who were in psychiatric treatment. As an assessment tool of sleep we used the Oviedo Sleep Questionnaire (COS and in measuring the degree of anxiety-depression we used the Test Hospital Anxiety and Depression (HAD on its overall assessment. Statistical analysis for qualitative variables was performed using the Pearson χ2. Quantitative variables were compared with a Student test. Values with a p-value less than 0.05 were accepted as significant (95% confidence interval. We used the statistical package for Windows SPSS.15. Results: in the assessment of sleep disorders there were significant differences according to the type of opioid consumed, being the group treated with Hydromorphone the one with the best results made in the three subscales tested: COS's subjective assessment, objective subscale of insomnia and those who consumed fewer drugs to sleep. We also found differences in the incidence of anxiety / depression, statistically significant, depending on the type of opioid, again being the group treated with Hydromorphone the one with lower incidence of psychological impact. No significant differences were found in sleep disorders and in the prevalence of anxiety-depression in terms of the other variables: type of pain, or sex. Conclusions: in our study, patients who consumed Hydromorphone showed better sleep quality, less use of hypnotics and a lower rate of developing an anxiety-depressive picture. It is true, perhaps, that to corroborate these results and avoid elements that distort them, there will in future works be necessary to assess the presence of other variables.

  13. Pediatric palliative care: use of opioids for the management of pain.

    Science.gov (United States)

    Zernikow, Boris; Michel, Erik; Craig, Finella; Anderson, Brian J

    2009-01-01

    Pediatric palliative care (PPC) is provided to children experiencing life-limiting diseases (LLD) or life-threatening diseases (LTD). Sixty to 90% of children with LLD/LTD undergoing PPC receive opioids at the end of life. Analgesia is often insufficient. Reasons include a lack of knowledge concerning opioid prescribing and adjustment of opioid dose to changing requirements. The choice of first-line opioid is based on scientific evidence, pain pathophysiology, and available administration modes. Doses are calculated on a bodyweight basis up to a maximum absolute starting dose. Morphine remains the gold standard starting opioid in PPC. Long-term opioid choice and dose administration is determined by the pathology, analgesic effectiveness, and adverse effect profile. Slow-release oral morphine remains the dominant formulation for long-term use in PPC with hydromorphone slow-release preparations being the first rotation opioid when morphine shows severe adverse effects. The recently introduced fentanyl transdermal therapeutic system with a drug-release rate of 12.5 microg/hour matches the lower dose requirements of pediatric cancer pain control. Its use may be associated with less constipation compared with morphine use. Though oral transmucosal fentanyl citrate has reduced bioavailability (25%), it inherits potential for breakthrough pain management. However, the gold standard breakthrough opioid remains immediate-release morphine. Buprenorphine is of special clinical interest as a result of its different administration routes, long duration of action, and metabolism largely independent of renal function. Antihyperalgesic effects, induced through antagonism at the kappa-receptor, may contribute to its effectiveness in neuropathic pain. Methadone also has a long elimination half-life (19 [SD 14] hours) and NMDA receptor activity although dose administration is complicated by highly variable morphine equianalgesic equivalence (1 : 2.5-20). Opioid rotation to methadone

  14. Intravenous vs Oral Acetaminophen as an Adjunct to Multimodal Analgesia After Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind Clinical Trial.

    Science.gov (United States)

    O'Neal, Jason B; Freiberg, Andrew A; Yelle, Marc D; Jiang, Yandong; Zhang, Chengwei; Gu, Yin; Kong, Xiangyi; Jian, Wenling; O'Neal, Wesley T; Wang, Jingping

    2017-05-18

    The efficacy of intravenous (IV) acetaminophen compared with its oral formulation for postoperative analgesia is unknown. We hypothesized that the addition of acetaminophen to a multimodal analgesia regimen would provide improved pain management in patients after total knee arthroplasty (TKA) and that the effect of acetaminophen would be variable based on the route of delivery. The study was a single-center, randomized, double-blinded, placebo-controlled clinical trial on the efficacy of IV vs oral acetaminophen in patients undergoing unilateral TKA. One hundred seventy-four subjects were randomized to one of the 3 groups: IV acetaminophen group (IV group, n = 57) received 1 g IV acetaminophen and oral placebo before postanesthesia care unit (PACU) admission; oral acetaminophen group (PO group, n = 58) received 1 g oral acetaminophen and volume-matched IV normal saline; placebo group (Placebo group, n = 59) received oral placebo and volume-matched IV normal saline. Pain scores were obtained every 15 minutes during PACU stay. Average pain scores, maximum pain score, and pain scores before physical therapy were compared among the 3 groups. Secondary outcomes included total opiate consumption, time to PACU discharge, time to rescue analgesia, and time to breakthrough pain. The average PACU pain score was similar in the IV group (0.56 ± 0.99 [mean ± standard deviation]) compared with the PO group (0.67 ± 1.20; P = .84) and Placebo group (0.58 ± 0.99; P = .71). Total opiate consumption at 6 hours (0.47 mg hydromorphone equivalents ± 0.56 vs 0.54 ± 0.53 vs 0.54 ± 0.61; P = .69) and at 24 hours (1.25 ± 1.30 vs 1.49 ± 1.34 vs 1.36 ± 1.31; P = .46) were also similar between the IV, PO, and Placebo groups. No significant differences were found between all groups for any other outcome. Neither IV nor oral acetaminophen provides additional analgesia in the immediate postoperative period when administered as an adjunct to multimodal analgesia in patients

  15. Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

    Science.gov (United States)

    Lennernäs, Hans

    2009-01-01

    Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is

  16. DRUG INTERACTIONS WITH DIAZEPAM

    Directory of Open Access Journals (Sweden)

    Zoran Bojanić

    2011-06-01

    Full Text Available Diazepam is a benzodiazepine derivative with anxyolitic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, antitremor, and amnestic activity. It is metabolized in the liver by the cytochrome P (CYP 450 enzyme system. Diazepam is N-demethylated by CYP3A4 and CYP2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-desmethyl-diazepam and temazepam are both further metabolized to oxazepam. Concomitant intake of inhibitors or inducers of the CYP isozymes involved in the biotransformation of diazepam may alter plasma concentrations of this drug, although this effect is unlikely to be associated with clinically relevant interactions.The goal of this article was to review the current literature on clinically relevant pharmacokinetic drug interactions with diazepam.A search of MEDLINE and EMBASE was conducted for original research and review articles published in English between January 1971. and May 2011. Among the search terms were drug interactions, diazepam, pharmacokinetics, drug metabolism, and cytochrome P450. Only articles published in peer-reviewed journals were included, and meeting abstracts were excluded. The reference lists of relevant articles were hand-searched for additional publications.Diazepam is substantially sorbed by the plastics in flexible containers, volume control set chambers, and tubings of intravenous administration sets. Manufacturers recommend not mixing with any other drug or solution in syringe or solution, although diazepam is compatible in syringe with cimetidine and ranitidine, and in Y-site with cisatracurium, dobutamine, fentanyl, hydromorphone, methadone, morphine, nafcillin, quinidine gluconate, remifentanil, and sufentanil. Diazepam is compatible with: dextrose 5% in water, Ringers injection, Ringers injection lactated and sodium chloride 0.9%. Emulsified diazepam is compatible with Intralipid and Nutralipid.Diazepam has low potential

  17. Long-term efficacy and safety of oxycodone–naloxone prolonged release in geriatric patients with moderate-to-severe chronic noncancer pain: a 52-week open-label extension phase study

    Directory of Open Access Journals (Sweden)

    Guerriero F

    2016-04-01

    Full Text Available Fabio Guerriero,1,2 Anna Roberto,3 Maria Teresa Greco,4 Carmelo Sgarlata,1 Marco Rollone,2 Oscar Corli3 1Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, 2Department of Geriatrics, Agency for Elderly People of Pavia, Santa Margherita Institute, Pavia, 3Department of Oncology, Pain and Palliative Care Research Unit, IRCCS-Mario Negri Institute for Pharmacological Research, 4Unit of Medical Statistics, Biometry and Epidemiology GA Maccacaro, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Background: Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone–naloxone (OXN-PR in patients aged ≥70 (mean 81.7 years.Methods: In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0, after 4 weeks (T4, and after 52 weeks (T52.Results: Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P<0.0001. Pain intensity, measured on a 0–10 numerical rating scale, decreased from 6.0 at T0 to 2.8 at T4 and to 1.7 at T52 (P<0.0001. Mean daily dose of oxycodone increased from 10 to 14.4 mg (T4 and finally to 17.4 mg (T52. Bowel Function Index from 35.1 to 28.7 at T52. No changes were observed in cognitive functions (Mini-Mental State Examination evaluation, while daily functioning improved (Barthel Index from 53.1 to 61.0, P<0.0001. The Screener and Opioid Assessment for Patients with Pain-Revised score at 52 weeks was 2.6 (standard deviation 1.6, indicating a low risk of aberrant medication

  18. Modulation of peripheral μ-opioid analgesia by σ1 receptors.

    Science.gov (United States)

    Sánchez-Fernández, Cristina; Montilla-García, Ángeles; González-Cano, Rafael; Nieto, Francisco Rafael; Romero, Lucía; Artacho-Cordón, Antonia; Montes, Rosa; Fernández-Pastor, Begoña; Merlos, Manuel; Baeyens, José Manuel; Entrena, José Manuel; Cobos, Enrique José

    2014-01-01

    We evaluated the effects of σ1-receptor inhibition on μ-opioid-induced mechanical antinociception and constipation. σ1-Knockout mice exhibited marked mechanical antinociception in response to several μ-opioid analgesics (fentanyl, oxycodone, morphine, buprenorphine, and tramadol) at systemic (subcutaneous) doses that were inactive in wild-type mice and even unmasked the antinociceptive effects of the peripheral μ-opioid agonist loperamide. Likewise, systemic (subcutaneous) or local (intraplantar) treatment of wild-type mice with the selective σ1 antagonists BD-1063 [1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine dihydrochloride] or S1RA [4-[2-[[5-methyl-1-(2-naphthalenyl)1H-pyrazol-3-yl]oxy]ethyl] morpholine hydrochloride] potentiated μ-opioid antinociception; these effects were fully reversed by the σ1 agonist PRE-084 [2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate) hydrochloride], showing the selectivity of the pharmacological approach. The μ-opioid antinociception potentiated by σ1 inhibition (by σ1-receptor knockout or σ1-pharmacological antagonism) was more sensitive to the peripherally restricted opioid antagonist naloxone methiodide than opioid antinociception under normal conditions, indicating a key role for peripheral opioid receptors in the enhanced antinociception. Direct interaction between the opioid drugs and σ1 receptor cannot account for our results, since the former lacked affinity for σ1 receptors (labeled with [(3)H](+)-pentazocine). A peripheral role for σ1 receptors was also supported by their higher density (Western blot results) in peripheral nervous tissue (dorsal root ganglia) than in several central areas involved in opioid antinociception (dorsal spinal cord, basolateral amygdala, periaqueductal gray, and rostroventral medulla). In contrast to its effects on nociception, σ1-receptor inhibition did not alter fentanyl- or loperamide-induced constipation, a peripherally mediated nonanalgesic opioid effect. Therefore

  19. Changes in drug use patterns reported on the web after the introduction of ADF OxyContin: findings from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Web Monitoring Program.

    Science.gov (United States)

    Vosburg, Suzanne K; Haynes, Colleen; Besharat, Andrea; Green, Jody L

    2017-09-01

    This qualitative study summarizes information that individuals shared online about use of OxyContin following the August 2010 introduction of the abuse deterrent formulation (ADF). The primary objective was to study online posts that endorsed continued use of OxyContin or a switch from OxyContin to another formulation of oxycodone or another substance altogether following the introduction of the ADF. A secondary objective was to determine whether posts revealed that the ADF led to cessation of OxyContin use. Data were collected with the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program, an online surveillance system that collects and organizes posts about prescription drugs from social media websites, blogs, and forums from 3Q2009 to 4Q2014 using a commercially available web platform. Posts were categorized by whether they conveyed a switch to drugs other than reformulated OxyContin or a continuation of reformulated OxyContin abuse. "Switch posts" primarily discussed switching to immediate-release opioids. "Continue abusing" posts identified tampering strategies for alternate routes of administration, oral use, and continued use although post authors were generally unhappy with the experience. No reference to OxyContin cessation as a function of the introduction of the ADF was found; however, discontinued use was discussed. Web Monitoring data are useful for capturing cross sections of Internet conversation reflecting reactions to new drug formulations. These data support the notion that users will gravitate to non-ADFs generally, and to immediate-release non-ADF opioid formulations, specifically, as long as these options remain on the market. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Misuse of prescription and illicit drugs among high-risk young adults in Los Angeles and New York

    Directory of Open Access Journals (Sweden)

    Stephen E. Lankenau

    2012-02-01

    Full Text Available Background. Prescription drug misuse among young adults is increasingly viewed as a public health concern, yet most research has focused on student populations and excluded high-risk groups. Furthermore, research on populations who report recent prescription drug misuse is limited. This study examined patterns of prescription drug misuse among high-risk young adults in Los Angeles (LA and New York (NY, which represent different local markets for illicit and prescription drugs. Design and Methods. Between 2009 and 2011, 596 young adults (16 to 25 years old who had misused prescription drugs within the past 90 days were interviewed in Los Angeles and New York. Sampling was stratified to enroll three groups of high-risk young adults: injection drug users (IDUs; homeless persons; and polydrug users. Results. In both sites, lifetime history of receiving a prescription for an opioid, tranquilizer, or stimulant was high and commonly preceded misuse. Moreover, initiation of opioids occurred before heroin and initiation of prescription stimulants happened prior to illicit stimulants. NY participants more frequently misused oxycodone, heroin, and cocaine, and LA participants more frequently misused codeine, marijuana, and methamphetamine. Combining prescription and illicit drugs during drug using events was commonly reported in both sites. Opioids and tranquilizers were used as substitutes for other drugs, e.g., heroin, when these drugs were not available. Conclusion. Patterns of drug use among high-risk young adults in Los Angeles and New York appear to be linked to differences in local markets in each city for illicit drugs and diverted prescription drugs.

  1. Current considerations for the treatment of severe chronic pain: the potential for tapentadol.

    Science.gov (United States)

    Pergolizzi, Joseph; Alegre, Cayetano; Blake, David; Alén, Jaime Calvo; Caporali, Roberto; Casser, Hans-Raimund; Correa-Illanes, Gerardo; Fernandes, Pedro; Galilea, Eugenio; Jany, Richard; Jones, Anthony; Mejjad, Othmane; Morovic-Vergles, Jadranka; Oteo-Álvaro, Ángel; Álvaro, Ángel Oteo; Radrigán Araya, Francisco J; Simões, Maria Eugénia C; Uomo, Generoso

    2012-04-01

    Studies suggest that around 20% of adults in Europe experience chronic pain, which not only has a considerable impact on their quality of life but also imposes a substantial economic burden on society. More than one-third of these people feel that their pain is inadequately managed. A range of analgesic drugs is currently available, but recent guidelines recommend that NSAIDs and COX-2 inhibitors should be prescribed cautiously. Although the short-term efficacy of opioids is good, adverse events are common and doses are frequently limited by tolerability problems. There is a perceived need for improved pharmacological treatment options. Currently, many treatment decisions are based solely on pain intensity. However, chronic pain is multifactorial and this apaproach ignores the fact that different causative mechanisms may be involved. The presence of more than one causative mechanism means that chronic pain can seldom be controlled by a single agent. Therefore, combining drugs with different analgesic actions increases the probability of interrupting the pain signal, but is often associated with an increased risk of drug/drug interactions, low compliance and increased side effects. Tapentadol combines μ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule, with both mechanisms contributing to its analgesic effects. Preclinical testing has shown that μ-opioid agonism is primarily responsible for analgesia in acute pain, whereas noradrenaline reuptake inhibition is more important in chronic pain. In clinical trials in patients with chronic pain, the efficacy of tapentadol was similar to that of oxycodone, but it produced significantly fewer gastrointestinal side-effects and treatment discontinuations. Pain relief remained stable throughout a 1-year safety study. Thus, tapentadol could possibly overcome some of the limitations of currently available analgesics for the treatment of chronic pain.

  2. Drug overdose deaths--Florida, 2003-2009.

    Science.gov (United States)

    2011-07-08

    In the United States in 2007, unintentional poisonings were the second leading cause of injury death (after motor-vehicle crashes); approximately 93% of all unintentional poisoning deaths were caused by drug poisoning, also known as drug overdose. From 1990 to 2001 in Florida, the nonsuicidal poisoning death rate increased 325%. To characterize recent trends in drug overdose death rates in Florida, CDC analyzed data from the Florida Medical Examiners Commission. This report summarizes the results of that analysis, which found that, from 2003 to 2009, the number of annual deaths in which medical examiner testing showed lethal concentrations of one or more drugs increased 61.0%, from 1,804 to 2,905, and the death rate increased 47.5%, from 10.6 to 15.7 per 100,000 population. During 2003-2009, death rates increased for all substances except cocaine and heroin. The death rate for prescription drugs increased 84.2%, from 7.3 to 13.4 per 100,000 population. The greatest increase was observed in the death rate from oxycodone (264.6%), followed by alprazolam (233.8%) and methadone (79.2%). By 2009, the number of deaths involving prescription drugs was four times the number involving illicit drugs. These findings indicate the need to strengthen interventions aimed at reducing overdose deaths from prescription drugs in Florida. Medical examiner records are a timely, population-based source for data regarding overdose deaths from specific drugs. The data in this report and subsequent analyses can be used to design and measure the effectiveness of interventions.

  3. Can differences in the type, nature or amount of polysubstance use explain the increased risk of non-fatal overdose among psychologically distressed people who inject drugs?

    Science.gov (United States)

    Betts, Kim S; McIlwraith, Fairlie; Dietze, Paul; Whittaker, Elizabeth; Burns, Lucy; Cogger, Shelley; Alati, Rosa

    2015-09-01

    This study investigates whether the type, nature or amount of polysubstance use can explain the increased risk of non-fatal overdose among people who inject drugs with severe psychological distress. Data came from three years (2011-2013) of the Illicit Drug Reporting System (IDRS), an annual sentinel sample of injecting drug users across Australia (n=2673). Structural Equation Modelling (SEM) was used on 14 drug types to construct five latent factors, each representing a type of polysubstance use. Tests of measurement invariance were carried out to determine if polysubstance use profiles differed between those with and without severe psychological distress. Next, we regressed non-fatal overdose on the polysubstance use factors with differences in the relationships tested between groups. Among those with severe psychological distress a polysubstance use profile characterised by heroin, oxycodone, crystal methamphetamine and cocaine use was associated with greater risk of non-fatal overdose. Among those without severe psychological distress, two polysubstance use profiles, largely characterised by opioid substitution therapies and prescription drugs, were protective against non-fatal overdose. The types of polysubstance use profiles did not differ between people who inject drugs with and without severe psychological distress. However, the nature of use of one particular polysubstance profile placed the former group at a strongly increased risk of non-fatal overdose, while the nature of polysubstance use involving opioid substitution therapies was protective only among the latter group. The findings identify polysubstance use profiles of importance to drug-related harms among individuals with psychological problems. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Analysis of drugs of abuse in wastewater from two Canadian cities.

    Science.gov (United States)

    Yargeau, Viviane; Taylor, Bryanne; Li, Hongxia; Rodayan, Angela; Metcalfe, Chris D

    2014-07-15

    Several drugs of abuse, including amphetamines, cocaine and its metabolite, benzoylecgonine and several opioid prescription drugs were detected in wastewater from two Canadian cities, a small community (75,000 population) and a large urban center (1.6 million population). The objective of this study was to evaluate community use of these drugs in two cities with large differences in population size and demographics. In addition, we evaluated the use of the Polar Organic Chemical Integrative Sampler (POCIS) as a monitoring tool for drugs of abuse. Heroin was not detected at either location, probably because this illicit drug is metabolized to morphine prior to excretion. Acetylcodeine and acetylmorphine were also not detected. Estimates of community consumption from wastewater analysis indicated that the most widely used drug was cocaine at a median level of consumption in the larger city of approximately 38 doses per day per 1000 people. Consumption of the substituted amphetamine, ephedrine, as well as methamphetamine was also higher in the larger city, at 21 and 1.8 doses per day per 1000 people, respectively. Use of amphetamine, MDMA and tramadol were similar in both centers, but use of oxycodone was greater in the smaller city. Use of MDMA (ecstasy) peaked on weekends. Ketamine was detected in wastewater from the larger city; the first report of abuse of this veterinary anesthetic in a North American city. POCIS sampling rates were determined for the first time for 7 of the target compounds. Comparing the time weighted average concentrations estimated from POCIS data to the concentrations obtained from 24-h composite samples, the data were generally comparable, except for some compounds which were not detected in POCIS deployed in the untreated wastewater, probably because of biofouling or accumulation of debris on the cages containing the POCIS. This study indicates that the size and demographics of population centers can influence the patterns of abuse of

  5. Selective Opioid Usage for Cancer Pain in Patients with Hepatic or Renal Dysfunction%阿片类药物在肝肾功能不全癌痛患者中的选择应用

    Institute of Scientific and Technical Information of China (English)

    程熠; 于世英

    2011-01-01

    Opioid is essential drug for cancer pain. It should be very careful to choose opioid drugs for patients with hepatic or renal dysfunction. Dose and dosing interval of the sustained-released formulation of morphine should be adjusted, while the immediate-released formulation could be prescribed temporarily. Codeine should be forbidden. Oxycodone is safe for patients with mild or moderate hepatic or renal dysfunction, but should not be used in ones with severe renal dysfunction. Transdermal fentanyl is the first choice for patients with severe hepatic or renal dysfunction, and for dialytic patients. However, in some cases buprenorphine could replace it for dialytic patients.%阿片类药物是控制癌痛的必备药物.对于癌症合并有肝肾功能不全的患者,阿片类药物的选择应慎重.吗啡的缓释剂型应注意调整剂量和给药的间隔时间,即释剂型可临时应用.应禁用可待因.轻中度的肝肾功能不全患者,羟考酮的应用是安全的;但重度肾功能不全者禁用羟考酮.芬太尼透皮贴剂是重度肝肾功能不全患者和透析患者的首选.丁丙诺啡在某些情况下可代替芬太尼应用于透析患者.

  6. Antidepressant treatment with MAO-inhibitors during general and regional anesthesia: a review and case report of spinal anesthesia for lower extremity surgery without discontinuation of tranylcypromine.

    Science.gov (United States)

    Krings-Ernst, Ilana; Ulrich, Sven; Adli, Mazda

    2013-10-01

    Monoamine oxidase-(MAO)-inhibitors are a treatment of last resort in treatment resistant depression, which is regarded as a condition of increased psychiatric risk. General and regional anesthesia for elective surgery during use of long-term MAO-inhibitors remains a matter of debate because of an increased risk of drug interactions and decreased sympathetic stability. A series of case reports and new comparative studies reveal the safety of anesthesia/analgesia in non-cardiac surgery without discontinuation of the MAO-inhibitor if best effort is made for maintenance of sympathetic homeostasis and if known drug interactions are avoided. Very few reports with severe adverse incidents have been noted. Severe cardiovascular morbidity, a contraindication of MAO-inhibitors, probably contributed to peri- and postoperative complications. According to new studies, the risk of pharmacokinetic drug interactions is lower for tranylcypromine than for phenelzine. In the present case, a 66-year-old psychiatric patient on permanent treatment with 20 mg/day tranylcypromine was admitted for forefoot surgery. Anesthetic premedication consisted of 7.5 mg oral midazolam. Intravenous midazolam (0.5 mg) was dispensed for intraoperative sedation. After local anesthesia of the puncture site with 30 mg isobar prilocaine, spinal anesthesia was achieved by a single shot of 13.5 mg hyperbar bupivacaine (0.5%) intrathecally. Postoperative regional and general analgesia were accomplished by a peripheral nerve block with 50 mg isobar bupivacaine as well as oral etoricoxib and oxycodone. No peri- or postoperative complications were encountered. It is concluded that general or regional anesthesia for noncardiac surgery without discontinuation of MAO-inhibitor treatment may be a safe intervention after careful evaluation of an individual's perioperative and psychiatric risk. The increased psychiatric risk in patients treated with MAO-inhibitors outweighs the increased, however manageable

  7. Low-back pain at the emergency department: still not being managed?

    Science.gov (United States)

    Rizzardo, Alessandro; Miceli, Luca; Bednarova, Rym; Guadagnin, Giovanni Maria; Sbrojavacca, Rodolfo; Della Rocca, Giorgio

    2016-01-01

    Low-back pain (LBP) affects about 40% of people at some point in their lives. In the presence of "red flags", further tests must be done to rule out underlying problems; however, biomedical imaging is currently overused. LBP involves large in-hospital and out-of-hospital economic costs, and it is also the most common musculoskeletal disorder seen in emergency departments (EDs). This retrospective observational study enrolled 1,298 patients admitted to the ED, including all International Classification of Diseases 10 diagnosis codes for sciatica, lumbosciatica, and lumbago. We collected patients' demographic data, medical history, lab workup and imaging performed at the ED, drugs administered at the ED, ED length of stay (LOS), numeric rating scale pain score, admission to ward, and ward LOS data. Thereafter, we performed a cost analysis. Mean numeric rating scale scores were higher than 7/10. Home medication consisted of no drug consumption in up to 90% of patients. Oxycodone-naloxone was the strong opioid most frequently prescribed for the home. Once at the ED, nonsteroidal anti-inflammatory drugs and opiates were administered to up to 72% and 42% of patients, respectively. Imaging was performed in up to 56% of patients. Mean ED LOS was 4 hours, 14 minutes. A total of 43 patients were admitted to a ward. The expense for each non-ward-admitted patient was approximately €200 in the ED, while the mean expense for ward-admitted patients was €9,500, with a mean LOS of 15 days. There is not yet a defined therapeutic care process for the patient with LBP with clear criteria for an ED visit. It is to this end that we need a clinical pathway for the prehospital management of LBP syndrome and consequently for an in-hospital time-saving therapeutic approach to the patient.

  8. A retrospective study on the influence of nutritional status on pain management in cancer patients using the transdermal fentanyl patch.

    Science.gov (United States)

    Takahashi, Hiroaki; Chiba, Takeshi; Tairabune, Tomohiko; Kimura, Yusuke; Wakabayashi, Go; Takahashi, Katsuo; Kudo, Kenzo

    2014-01-01

    It is unknown whether nutritional status influences pain intensity in cancer patients receiving a transdermal fentanyl patch (FP). This study aimed to determine whether nutritional status is associated with pain intensity and to evaluate the influence of changes in nutritional status on pain intensity in cancer patients receiving transdermal FP treatment. We included 92 patients receiving transdermal FP treatment for the first time with switching from oxycodone. The patients were classified into low- and normal-nutrition groups based on their nutritional status, which was assessed according to the Nutrition Risk Screening 2002 (NRS 2002) parameters. The pain intensity of each patient was evaluated by a numeric rating scale (11-point scale from 0 to 10). NRS 2002 score and pain intensity were obtained on day 3 after the FP was applied to the skin. Pain intensities were significantly higher among patients in the low-nutrition group than among patients in the normal-nutrition group. NRS 2002 scores showed a significant positive correlation with the pain intensities. In 52 of 92 patients, who were evaluated using the NRS 2002 score and pain intensity on day 30 after FP application, the changes in NRS 2002 scores were significantly related to changes in pain intensities (odds ratio, 30.0; 95% confidence interval, 4.48-200.97; p=0.0005). These results suggest that an increase in the NRS 2002 score is a risk factor for an increase in pain intensity in cancer patients receiving FP treatment. Malnutrition may lead to poor pain management in cancer patients receiving FP treatment.

  9. Analysis of the usage of sustained and controlled-release opioids in elderly patients with cancer%缓控释强阿片类药物在老年癌痛患者中的应用分析

    Institute of Scientific and Technical Information of China (English)

    张丽莹

    2011-01-01

    目的 了解缓控释强阿片类药物在老年癌痛患者中的应用情况及用药趋势.方法 对2008年1月至2010年12月在镇痛科就诊的776例年龄≥65岁的老年癌症患者使用缓控释强阿片类药物的情况进行统计和分析.结果 缓控释强阿片类药物在老年癌痛患者的用量逐年增加,在硫酸吗啡缓释片、芬太尼透皮贴剂以及盐酸羟考酮控释片这三类缓控释强阿片类药物中,芬太尼透皮贴剂的用药频度位居第一,盐酸羟考酮控释片的用量增长迅速.结论 本院老年癌症止痛治疗中用药是合理的.%Objective To observe the status and to find out the trend of the use of sustained and controlled-release strong opioids in elderly patients with cancer. Methods 776 cases of cancer patients over 65 years old receiving opioids treatment from January 2008 to December 2010 were retrospectively studied. Results The consumption of sustained and controlled-release strong opioids increased year by year. Among 3 commonly used painkillers, fentanyl transdermal patehes, morphine sulfate sustained-release tablets and oxycodone hydrochloride controlled-release tablets, the DDDs of the former one ranked in the first place. Conclusions The results demonstrate that painkillers are appropriately used in aged patients in our hospital.

  10. Important statistical considerations in the evaluation of post-market studies to assess whether opioids with abuse-deterrent properties result in reduced abuse in the community.

    Science.gov (United States)

    By, Kunthel; McAninch, Jana K; Keeton, Stephine L; Secora, Alex; Kornegay, Cynthia J; Hwang, Catherine S; Ly, Thomas; Levenson, Mark S

    2017-08-23

    Abuse, misuse, addiction, overdose, and death associated with non-medical use of prescription opioids have become a serious public health concern. Reformulation of these products with abuse-deterrent properties is one approach for addressing this problem. FDA has approved several extended-release opioid analgesics with abuse-deterrent labeling, the bases of which come from pre-market studies. As all opioid analgesics must be capable of delivering the opioid in order to reduce pain, abuse-deterrent properties do not prevent abuse, nor do pre-market evaluations ensure that there will be reduced abuse in the community. Utilizing data from various surveillance systems, some recent post-market studies suggest a decline in abuse of extended-release oxycodone after reformulation with abuse-deterrent properties. We discuss challenges stemming from the use of such data. We quantify the relationship between the sample, the population, and the underlying sampling mechanism and identify the necessary conditions if valid statements about the population are to be made. The presence of other interventions in the community necessitates the use of comparators. We discuss the principles under which the use of comparators can be meaningful. Results based on surveillance data need to be interpreted with caution as the underlying sampling mechanisms can bias the results in unpredictable ways. The use of comparators has the potential to disentangle the effect due to the abuse-deterrence properties from those due to other interventions. However, identifying a comparator that is meaningful can be very difficult. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  11. Real-time 2D separation by LC × differential ion mobility hyphenated to mass spectrometry.

    Science.gov (United States)

    Varesio, Emmanuel; Le Blanc, J C Yves; Hopfgartner, Gérard

    2012-03-01

    The liquid chromatography-mass spectrometry (LC-MS) analysis of complex samples such as biological fluid extracts is widespread when searching for new biomarkers as in metabolomics. The success of this hyphenation resides in the orthogonality of both separation techniques. However, there are frequent cases where compounds are co-eluting and the resolving power of mass spectrometry (MS) is not sufficient (e.g., isobaric compounds and interfering isotopic clusters). Different strategies are discussed to solve these cases and a mixture of eight compounds (i.e., bromazepam, chlorprothixene, clonapzepam, fendiline, flusilazol, oxfendazole, oxycodone, and pamaquine) with identical nominal mass (i.e., m/z 316) is taken to illustrate them. Among the different approaches, high-resolution mass spectrometry or liquid chromatography (i.e., UHPLC) can easily separate these compounds. Another technique, mostly used with low resolving power MS analyzers, is differential ion mobility spectrometry (DMS), where analytes are gas-phase separated according to their size-to-charge ratio. Detailed investigations of the addition of different polar modifiers (i.e., methanol, ethanol, and isopropanol) into the transport gas (nitrogen) to enhance the peak capacity of the technique were carried out. Finally, a complex urine sample fortified with 36 compounds of various chemical properties was analyzed by real-time 2D separation LC×DMS-MS(/MS). The addition of this orthogonal gas-phase separation technique in the LC-MS(/MS) hyphenation greatly improved data quality by resolving composite MS/MS spectra, which is mandatory in metabolomics when performing database generation and search.

  12. Warfarin and royal jelly interaction.

    Science.gov (United States)

    Lee, Nancy J; Fermo, Joli D

    2006-04-01

    An 87-year-old African-American man came to the internal medicine clinic for a routine anticoagulation management visit. He had no complaints. His medical history was significant for stage IV-A follicular non-Hodgkin's lymphoma, atrial fibrillation, and hypertension. His long-term drug therapy consisted of warfarin, felodopine, lisinopril-hydrochlorothiazide, controlled-release diltiazem, potassium chloride, and oxycodone. He reported adherence with his prescribed drugs and denied taking any over-the-counter or herbal products. Overall, the patient's drug therapy had been consistent during the preceding 3 months, no significant changes had occurred in his clinical status, and no significant changes had been noted in his diet; his international normalized ratio (INR) had ranged from 1.9-2.4 (therapeutic range 2-3). He denied tobacco use, alcohol consumption, and recent travel. Four weeks later, the patient came to the emergency department with hematuria. He denied dysuria, taking more than the prescribed amount of warfarin, any changes in his diet, taking any over-the-counter or herbal products, and any other bleeding. On admission to the hospital, his INR was 6.88, which increased to 7.29 during his hospital stay. On further investigation, the patient admitted that he had started taking an herbal supplement, royal jelly, 1 week earlier. When asked specifically about the ingredients in the supplement, he stated that royal jelly was the only component. Relative to the patient's denial of any other changes in his condition or drug regimen, the most probable explanation for his elevated INR and subsequent bleeding is a possible interaction between royal jelly and warfarin. To our knowledge, no case reports concerning royal jelly and warfarin taken concomitantly have been reported. Clinicians should be proactive and repeatedly provide education regarding the potential dangers of dietary supplements taken with conventional drugs.

  13. A Nationwide Retrospective Study of Opioid Management Patterns in 2,468 Patients with Spinal Pain in Korea

    Science.gov (United States)

    Chung, Sung-Soo; Cho, Kyu-Jung; Choi, Kyoung Hyo; Kim, Jin-Hyok; Kim, Sung-Bum; Kuh, Sung-Uk; Lee, Jae Chul; Lee, Jae Hyup; Lee, Kyu-Yeol; Lee, Sun-Ho; Moon, Seong-Hwan; Park, Si-Young; Shim, Jae Hang; Son, Byung-Chul; Yoon, Myung Ha; Park, Hye-Jeong

    2016-01-01

    Study Design Retrospective patient data collection and investigator survey. Purpose To investigate patterns of opioid treatment for pain caused by spinal disorders in Korea. Overview of Literature Opioid analgesic prescription and adequacy of consumption measures in Korea have markedly increased in the past decade, suggesting changing patterns in pain management practice; however, there is lack of integrated data specific to Korean population. Methods Patient data were collected from medical records at 34 university hospitals in Korea. Outpatients receiving opioids for pain caused by spinal disorders were included in the study. Treatment patterns, including opioid types, doses, treatment duration, outcomes, and adverse drug reactions (ADRs), were evaluated. Investigators were interviewed on their perceptions of opioid use for spinal disorders. Results Among 2,468 analyzed cases, spinal stenosis (42.8%) was the most common presentation, followed by disc herniation (24.2%) and vertebral fracture (17.5%). In addition, a greater proportion of patients experienced severe pain (73.9%) rather than moderate (19.9%) or mild (0.7%) pain. Oxycodone (51.9%) and fentanyl (50.8%) were the most frequently prescribed opioids; most patients were prescribed relatively low doses. The median duration of opioid treatment was 84 days. Pain relief was superior in patients with longer treatment duration (≥2 months) or with nociceptive pain than in those with shorter treatment duration or with neuropathic or mixed-type pain. ADRs were observed in 8.6% of cases. According to the investigators' survey, "excellent analgesic effect" was a perceived advantage of opioids, while safety concerns were a disadvantage. Conclusions Opioid usage patterns in patients with spinal disorders are in alignment with international guidelines for spinal pain management. Future prospective studies may address the suitability of opioids for spinal pain treatment by using appropriate objective measurement tools

  14. Tapentadol immediate release: a new treatment option for acute pain management

    Directory of Open Access Journals (Sweden)

    Marc Afilalo

    2010-02-01

    Full Text Available Marc Afilalo1, Jens-Ulrich Stegmann2, David Upmalis31Sir Mortimer B. Davis Jewish General Hospital, Montréal, Canada; 2Global Drug Safety, Grünenthal GmbH, Aachen, Germany; 3Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, New Jersey, USAAbstract: The undertreatment of acute pain is common in many health care settings. Insufficient management of acute pain may lead to poor patient outcomes and potentially life-threatening complications. Opioids provide relief of moderate to severe acute pain; however, therapy with pure µ-opioid agonists is often limited by the prevalence of side effects, particularly opioid-induced nausea and vomiting. Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action, µ-opioid receptor agonism and norepinephrine reuptake inhibition. The analgesic effects of tapentadol are independent of metabolic activation and tapentadol has no active metabolites; therefore, in theory, tapentadol may be associated with a low potential for interindividual efficacy variations and drug–drug interactions. Previous phase 3 trials in patients with various types of moderate to severe acute pain have shown that tapentadol immediate release (IR; 50 to 100 mg every 4 to 6 hours provides analgesia comparable to that provided by the pure µ-opioid agonist comparator, oxycodone HCl IR (10 or 15 mg every 4 to 6 hours, with a lower incidence of nausea, vomiting, and constipation. Findings suggest tapentadol may represent an improved treatment option for acute pain.Keywords: tapentadol IR, acute pain, opioid, gastrointestinal tolerability

  15. Cause of death conundrum with methadone use: a case report.

    Science.gov (United States)

    Letsky, Michael C; Zumwalt, Ross E; Seifert, Steven A; Benson, Blaine E

    2011-06-01

    Deaths caused by a methadone intoxication or overdose are becoming more frequent. We report a case involving a patient who had extremely high methadone blood concentrations but whose cause of death may have been unrelated to the drug. A 51-year-old woman was found deceased in bed by her daughter. At the scene were numerous bottles of methadone, with the chronic dosage of 240 mg 3 times a day. There was no history of prior suicide attempts, there were no reports of suicidal ideation having been voiced and there was no suicide note. At autopsy, there were no pills found in the stomach. Microscopic tissue examination revealed lobar pneumonia of the right lower lobe. Postmortem lung cultures grew out Streptococcus pneumoniae. Femoral blood contained methadone, 5.7 mg/L; EDDP, 2.1 mg/L; oxycodone, 0.017 mg/L; doxylamine, 0.022 mg/L; and ethanol, 13.0 mg/dL. The postmortem methadone concentration was consistent with her known dose, plausible pharmacokinetics and conditions of discovery. Various causes of death, such as a methadone-related arrhythmia from QTc prolongation or the contribution of methadone to the development of the pneumonia, cannot be ruled out and may well have caused or contributed to death, but the pneumonia was felt to be a competent cause of death. Ultimately, the most likely cause(s) of death, is a decision left to the individual medical examiner. This case is illustrative of the growing number of similar cases facing forensic pathologists. The cause of death cannot be solely based on drug concentrations and it may not be possible to come to a conclusion as to "the" cause of death and the forensic pathologist must be content with "a" cause of death.

  16. Towards safer and more predictable drug treatment--reflections from studies of the First BCPT Prize awardee.

    Science.gov (United States)

    Neuvonen, Pertti J

    2012-03-01

    This MiniReview is a personal recollection of selected research topics, which the author in collaboration with colleagues has studied, aiming to improve the predictability of drug therapy. In early studies, we found bi- and trivalent cations to reduce the absorption of various tetracyclines and fluoroquinolones. Certain antacids elevated the bioavailability of some non-steroidal anti-inflammatory drugs and sulphonylureas. Various brands of phenytoin tablets revealed great differences in their bioavailability, causing clinical consequences. Numerous factors affecting the antidotal effect of activated charcoal were also studied, with charcoal compared to other gastrointestinal decontamination methods, including ipecac and gastric lavage. Effect of age and diseases on the pharmacokinetics of drugs was a research topic. Acute sotalol intoxications revealed its QT-prolonging properties, and even small mixed overdoses of moclobemide with serotonergic drugs proved fatal. Itraconazole and other potent inhibitors of CYP3A4 could drastically increase exposure to drugs like midazolam, triazolam, buspirone, lovastatin, simvastatin and oxycodone, whereas rifampicin greatly reduced their plasma concentrations. A change from potent inhibition to induction caused a 400-fold change in the exposure to oral midazolam. CYP2C8 was revealed to be crucial in the metabolism and interactions of several drugs. Many interactions affecting statins are CYP3A4-mediated, but transporters are important in certain interactions. Tizanidine is very susceptible to CYP1A2 inhibition. Fruit juices such as grapefruit juice can raise or lower exposure to different drugs. Both drug interactions and pharmacogenetics can modify the activity of cell membrane transporters and cause variability in the pharmacokinetics of and response to their substrate drugs.

  17. Co-prescription of opioids with benzodiazepine and other co-medications among opioid users: differential in opioid doses

    Science.gov (United States)

    Zin, Che Suraya; Ismail, Fadhilah

    2017-01-01

    Purpose This study investigated the patterns of opioid co-prescription with benzodiazepine and other concomitant medications among opioid users. Opioid dose in each type of co-prescription was also examined. Patients and methods This cross-sectional study was conducted among opioid users receiving concomitant medications at an outpatient tertiary hospital setting in Malaysia. Opioid prescriptions (morphine, fentanyl, oxycodone, dihydrocodeine and tramadol) that were co-prescribed with other medications (opioid + benzodiazepines, opioid + antidepressants, opioid + anticonvulsants, opioid + antipsychotics and opioid + hypnotics) dispensed from January 2013 to December 2014 were identified. The number of patients, number of co-prescriptions and the individual mean opioid daily dose in each type of co-prescription were calculated. Results A total of 276 patients receiving 1059 co-prescription opioids with benzodiazepine and other co-medications were identified during the study period. Of these, 12.3% of patients received co-prescriptions of opioid + benzodiazepine, 19.3% received opioid + anticonvulsant, 6.3% received opioid + antidepressant and 10.9% received other co-prescriptions, including antipsychotics and hypnotics. The individual mean opioid dose was <100 mg/d of morphine equivalents in all types of co-prescriptions, and the dose ranged from 31 to 66 mg/d in the co-prescriptions of opioid + benzodiazepine. Conclusion Among the opioid users receiving concomitant medications, the co-prescriptions of opioid with benzodiazepine were prescribed to 12.3% of patients, and the individual opioid dose in this co-prescription was moderate. Other co-medications were also commonly used, and their opioid doses were within the recommended dose. Future studies are warranted to evaluate the adverse effect and clinical outcomes of the co-medications particularly in long-term opioid users with chronic non-cancer pain. PMID:28182128

  18. Evaluating a switch from meconium to umbilical cord tissue for newborn drug testing: A retrospective study at an academic medical center.

    Science.gov (United States)

    Palmer, Kendra L; Wood, Kelly E; Krasowski, Matthew D

    2017-04-01

    The objective of this study was to compare detection rates of newborn drug exposure at an academic medical center transitioning from meconium to umbilical cord tissue toxicology testing. We performed an Institutional Review Board-approved retrospective chart review on all newborns (n=2072) for whom newborn drug testing was ordered at our academic medical center between June 2012 and August 2015 (in August 2013, umbilical cord tissue became the preferred specimen). Meconium toxicology testing was positive for at least one compound in 221 cases (21.3% of 1037 total specimens), with non-medical drug use identified in 85 cases (8.2%). Umbilical cord tissue toxicology testing was positive for at least one compound in 302 cases (29.2%), with non-medical drug use identified in 107 cases (10.3%). Of the cases involving non-medical drug use, the most common compounds detected were tetrahydrocannabinol and amphetamines. Non-medical drug use did not differ significantly between meconium and umbilical cord tissue, either as a total or for classes of drugs such as amphetamines, cannabinoids, and opiates. Maternal non-medical use of tramadol (not tested for in meconium) was identified in 5 cases (0.4%). There were significant differences in rate of detection of iatrogenic medications. Specifically, morphine, lorazepam, phenobarbital, and codeine were more commonly detected in meconium, while oxycodone was more commonly detected in umbilical cord tissue. Umbilical cord tissue toxicology testing yielded a similar detection rate compared to meconium testing. The use of umbilical cord tissue avoids detection of medications given to the neonate prior to meconium collection. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  19. Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids.

    Science.gov (United States)

    Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

    2017-08-01

    Recent reports indicate a sharp increase in fentanyl-related overdose deaths across the United States, much of which is likely related to the introduction of cheap, illicitly manufactured fentanyl derivatives. In this study, we sought to estimate the magnitude of illicit fentanyl use from 2012 to 2016 using a national opioid abuse surveillance system. The study program surveyed 10,900 individuals entering substance abuse treatment for opioid use disorder, with participants asked to endorse past month 'use to get high' of fentanyl drugs, stratified by identifiable (i.e., branded) fentanyl formulations or a 'type unknown' drug alleged to contain fentanyl. Total past-month fentanyl-use rose modestly from 2012 to 2016. While use of known fentanyl products remained relatively stable (mean=10.9%; P=0.25), endorsements of 'unknown' fentanyl products nearly doubled from 9% in 2013 to 15.1% by 2016 (P<0.001). Data show no discernable indication that this increase is diminishing or stabilizing. This first attempt to assess the prevalence of illicit fentanyl use shows that recent increases in fentanyl use seem to be due almost entirely to 'unknown' fentanyl presumed to be illicitly manufactured. Given that it is difficult to assess the extent to which fentanyl may have been substituted for another drug (i.e., oxycodone, alprazolam, etc.) or was used as a heroin admixture, our data likely represent an underestimation of the full magnitude of illicit fentanyl abuse. As such, this growing public health problem requires immediate attention and more systematic efforts to identify and track its abuse. Copyright © 2017. Published by Elsevier B.V.

  20. Fentanyl Pharmacokinetics in Pregnant Sheep after Intravenous and Transdermal Administration to the Ewe.

    Science.gov (United States)

    Heikkinen, Emma M; Voipio, Hanna-Marja; Laaksonen, Sakari; Haapala, Linnea; Räsänen, Juha; Acharya, Ganesh; Erkinaro, Tiina; Haapsamo, Mervi; Hautajärvi, Heidi; Kokki, Hannu; Kokki, Merja; Heikkinen, Aki T

    2015-09-01

    Fentanyl is used for pain treatment during pregnancy in human beings and animals. However, fentanyl pharmacokinetics during pregnancy has not been fully established. The aim of this study was to characterize fentanyl pharmacokinetics in pregnant sheep after intravenous and transdermal dosing during surgical procedure performed to ewe and foetus. Pharmacokinetic parameters reported for non-pregnant sheep and nominal transdermal dose rate were utilized for a priori calculation to achieve analgesic fentanyl concentration (0.5-2 ng/ml) in maternal plasma. A total of 20 Aland landrace ewes at 118-127 gestational days were used. In the first protocol, 1 week before surgery, 10 animals received 2 μg/kg fentanyl intravenous bolus, and on the operation day, transdermal fentanyl patches at nominal dose rate of 2 μg/kg/hr were applied to antebrachium, and ewes were then given a 2 μg/kg intravenous bolus followed by an intra-operative 2.5 μg/kg/hr infusion. In the second protocol, 10 animals received fentanyl only as transdermal patches on the operation day and oxycodone for rescue analgesia. The data were analysed with population pharmacokinetic modelling. Intra- and post-operative fentanyl concentrations were similar and slightly lower than the a priori predictions, and elimination and distribution clearances appeared slower during than before or after the surgery. Transdermal patches provided sustained fentanyl absorption for up to 5 days, but the absorption rate was slower than the nominal dose rate and showed a high interindividual variability. Further research is warranted to evaluate the clinical relevance of the observations made in sheep.

  1. Removal of micropollutants through a biological wastewater treatment plant in a subtropical climate, Queensland-Australia.

    Science.gov (United States)

    Cardenas, Miguel Antonio Reyes; Ali, Imtiaj; Lai, Foon Yin; Dawes, Les; Thier, Ricarda; Rajapakse, Jay

    2016-01-01

    Municipal wastewaters contain a multitude of organic compounds derived from domestic and industrial sources including active components of pharmaceutical and personal care products and compounds used in agriculture, such as pesticides, or food processing such as artificial sweeteners often referred to as micropollutants. Some of these compounds or their degradation products may have detrimental effects on the environment, wildlife and humans. Acesuflame is one of the most popular artificial sweeteners to date used in foodstuffs. The main objectives of this descriptive study were to evaluate the presence of micropollutants in both the influent and effluent of a large-scale conventional biological wastewater treatment plant (WWTP) in South-East Queensland receiving wastewater from households, hospitals and various industries. Based on USEPA Method 1694: Filtered samples were spiked with mass-labelled chemical standards and then analysed for the micropollutants using liquid chromatography coupled with tandem mass spectrometry. The presence of thirty-eight compounds were detected in the wastewater influent to the treatment plant while nine of the compounds in the categories of analgesic, anti-inflammatory, alkaloid and lipid/cholesterol lowering drugs were undetectable (100 % removed) in the effluent. They were: Analgesic: Paracetamol, Salicylic acid, Oxycodone; Anti-inflammatory: Naproxen + ve, Atorvastatin, Indomethacin, Naproxen; Alkaloid: Caffeine; Lipid/cholesterol lowering: Gemfibrozol. The study results revealed that the micropollutants removal through this biological treatment process was similar to previous research reported from other countries including Europe the Americas and Asia, except for acesulfame, a highly persistent artificial sweetener. Surprisingly, acesulfame was diminished to a much greater extent (>90 %) than previously reported research for this type of WWTPs (45-65 %) that only include physical removal of objects and solids and a

  2. A practical and ethical solution to the opioid scheduling conundrum

    Directory of Open Access Journals (Sweden)

    Schatman ME

    2013-12-01

    Full Text Available Michael E Schatman,1 Beth D Darnall21Foundation for Ethics in Pain Care, Bellevue, WA, USA; 2Stanford University School of Medicine, Division of Pain Medicine, Palo Alto, CA, USAAbuse-deterrent formulations (ADFs of opioids have been in existence since the 1970s,1 with abuse-deterrent mechanisms including physical barriers (eg, barriers to crushing, chemical additives such as opioid antagonists or irritants, and prodrugs that require conversion of the medication into their active forms in the gastrointestinal tract.2 A recent systematic review and meta-analysis3 found no difference between ADFs and non-ADFs in terms of efficacy or adverse events including nausea, vomiting, dizziness, headache, somnolence, constipation, and pruritus. Notably, the efficacy of ADFs in preventing abuse is not yet established, and therefore the authors could only comment on their "potential … to deter or resist some of the common forms of tampering associated with opioid misuse and abuse". While Turk et al2 have elucidated the complexity of producing high-quality research on the efficacy of ADFs to reduce opioid abuse, recent data are encouraging. For example, since Purdue Pharma’s (Stamford, CT, USA voluntary reformulation of OxyContin® to an ADF in 2010, abuse of the medication has decreased significantly.4–6 As a specific example, National Poison Data System statistics indicated a 36% reduction in abuse exposure for OxyContin following ADF reformulation. Meanwhile, researchers for Purdue Pharma found an increase in abuse exposure for other single-entity oxycodone products and a 42% increase in abuse exposure for heroin during the same time frame.7 Although OxyContin has been the most investigated abuse deterrent formulation, ADFs of other opioids have demonstrated promise in preliminary investigations.8,9

  3. Limited Knowledge of Acetaminophen in Patients with Liver Disease.

    Science.gov (United States)

    Saab, Sammy; Konyn, Peter G; Viramontes, Matthew R; Jimenez, Melissa A; Grotts, Jonathan F; Hamidzadah, Wally; Dang, Veronica P; Esmailzadeh, Negin L; Choi, Gina; Durazo, Francisco A; El-Kabany, Mohamed M; Han, Steven-Huy B; Tong, Myron J

    2016-12-28

    Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease. Methods: We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California, Los Angeles between June 2015 and August 2016. Patients completed a demographic questionnaire and an acetaminophen knowledge survey. Additional information was obtained from the medical record. Results: Of 401 patients with liver disease, 30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of acetaminophen. The majority of patients (79.9%-86.8%) did not know that Norco® (hydrocone/acetaminophen), Vicodin® (hydrocone/acetaminophen) and Percocet® (oxycodone/acetaminophen) contained acetaminophen. Only 45.3% of the patients knew that Tylenol® #3 contained acetaminophen. Conclusions: We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen, putting them at risk both of acetaminophen overdose, as well as undermedication, and inadequate management of chronic pain. We recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver disease. Increasing education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management.

  4. Thoracic Intercostal Nerve Blocks Reduce Opioid Consumption and Length of Stay in Patients Undergoing Implant-Based Breast Reconstruction.

    Science.gov (United States)

    Shah, Ajul; Rowlands, Megan; Krishnan, Naveen; Patel, Anup; Ott-Young, Anke

    2015-11-01

    Traditionally, narcotics have been used for analgesia after breast surgery. However, these agents have unpleasant side effects. Intercostal nerve blockade is an alternative technique to improve postoperative pain. In this study, the authors investigate outcomes in patients who receive thoracic intercostal nerve blocks for implant-based breast reconstruction. A retrospective chart review was performed. The operative technique for breast reconstruction and administration of nerve blocks is detailed. Demographic factors, length of stay, and complications were recorded. The consumption of morphine, Valium, Zofran, and oxycodone was recorded. Data sets for patients receiving thoracic intercostal nerve blocks were compared against those that did not. One hundred thirty-two patients were included. For patients undergoing bilateral reconstruction with nerve blocks, there was a significant reduction in length of stay (1.87 days versus 2.32 days; p = 0.001), consumption of intravenous morphine (5.15 mg versus 12.68 mg; p = 0.041) and Valium (22.24 mg versus 31.13 mg; p = 0.026). For patients undergoing unilateral reconstruction with nerve blocks, there was a significant reduction in consumption of intravenous morphine (2.80 mg versus 8.17 mg; p = 0.007). For bilateral reconstruction with intercostal nerve block, cost savings equaled $2873.14 per patient. For unilateral reconstruction with intercostal nerve block, cost savings equaled $1532.34 per patient. The authors' data demonstrate a reduction in the consumption of pain medication, in the hospital length of stay, and in hospital costs for patients receiving intercostal nerve blocks at the time of pectoralis elevation for implant-based breast reconstruction. Therapeutic, III.

  5. Diversion and abuse of buprenorphine: findings from national surveys of treatment patients and physicians.

    Science.gov (United States)

    Johanson, Chris-Ellyn; Arfken, Cynthia L; di Menza, Salvatore; Schuster, Charles Roberts

    2012-01-01

    Since 2003, buprenorphine has been approved for the treatment of opioid dependence in office-based practice. Diversion and abuse can be a threat to its continued approval under these conditions. As part of a national postmarketing surveillance program, applicants to substance abuse treatment and physicians certified to prescribe buprenorphine were surveyed about their perceptions of buprenorphine/naloxone diversion and abuse. These surveys were supplemented by information from national databases. Availability of buprenorphine/naloxone was measured by number of tablets dispensed. Measures of diversion and abuse of buprenorphine/naloxone increased from 2005 to 2009. The results from the applicant survey showed that the perceptions of the extent of diversion and abuse were lower than positive controls, methadone, oxycodone and heroin, but higher than the negative control, amitriptyline. By 2009, 46% of the physicians believed that buprenorphine/naloxone was diverted but 44% believed illegal use was for self-management of withdrawal and 53% believed the source of the medication was substance abuse patients. Other measures from national databases showed similar results. When adjusted for millions of tablets sold per year, slopes for measures of diversion and abuse were reduced. The increases in diversion and abuse measures indicate the need to take active attempts to curb diversion and abuse as well as continuous monitoring and surveillance of all buprenorphine products. However, these increases parallel the increased number of tablets sold. Finding a balance of risk/benefit (i.e. diversion and abuse versus expanded treatment) remains a challenge. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Treatment Options in Intractable Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED).

    Science.gov (United States)

    Rinaldi, Fabrizio; Galbiati, Andrea; Marelli, Sara; Ferini Strambi, Luigi; Zucconi, Marco

    2016-02-01

    Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a common condition characterized by an irresistible urge to move the legs, concomitant with an unpleasant sensation in the lower limbs, which is typically relieved by movement. Symptoms occur predominantly at rest and prevail in the afternoon or evening. Treatment of patients with RLS/WED is indicated for those patients who suffer from clinically relevant symptoms. The management of mild forms of RLS/WED is mainly based on dopamine agonists (DA) therapy (including pramipexole and ropinirole) and α-2-δ calcium-channel ligand. Nevertheless, with passing of time, symptoms tend to become more severe and the patient can eventually develop pharmacoresistance. Furthermore, long-term treatment with dopaminergic agents may be complicated by the development of augmentation, which is defined by an increase in the severity and frequency of RLS/WED symptoms despite adequate treatment. Here, we discuss which are the best therapeutic options when RLS/WED becomes intractable, with a focus on advantages and side effects of the available medications. Prevention strategies include managing lifestyle changes and a good sleep hygiene. Different drug options are available. Switching to longer-acting dopaminergic agents may be a possibility if the patient is well-tolerating DA treatment. An association with α-2-δ calcium-channel ligand is another first-line approach. In refractory RLS/WED, opioids such as oxycodone-naloxone have demonstrated good efficacy. Other pharmacological approaches include IV iron, benzodiazepines such as clonazepam, and antiepileptic drugs, with different level of evidence of efficacy. Therefore, the final decision regarding the agent to use in treating severe RLS/WED symptoms should be tailored to the patient, taking into account the symptomatology, comorbidities, the availability of treatment and the history of the disease.

  7. Adjuvants for vaccines to drugs of abuse and addiction.

    Science.gov (United States)

    Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-09-22

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the