Increasing availability of illicit and prescription opioids among people who inject drugs in a Canadian setting, 2010-2014.

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Ho, Joel; DeBeck, Kora; Milloy, M-J; Dong, Huiru; Wood, Evan; Kerr, Thomas; Hayashi, Kanna

2018-01-01

Nonmedical use of prescription opioid and illicit opioid has been increasing at an alarming rate in North America over the past decade. We sought to examine the temporal trends and correlates of the availability of illicit and prescription opioids among people who inject drugs (PWID) in Vancouver, Canada. Data were derived from three prospective cohort studies of PWID in Vancouver between 2010 and 2014. In semiannual interviews, participants reported the availability of five sets of illicit and prescription opioids: (1) heroin; (2) Percocet (oxycodone/acetaminophen), Vicodin (hydrocodone/acetaminophen), or Demerol (meperidine); (3) Dilaudid (hydromorphone); (4) Morphine; (5) oxycontin/OxyNEO (controlled-release oxycodone). We defined perceived availability as immediate (e.g., available within 10 minutes) versus no availability/available after 10 minutes. The trend and correlation of immediate availability were identified by multivariable generalized estimating equations logistic regression. Among 1584 participants, of which 564 (35.6%) were female, the immediate availability of all illicit and prescribed opioids (except for oxycontin/OxyNEO) increased over time, independent of potential confounders. The Adjusted Odds Ratios of immediate availability associated with every calendar year increase were between 1.09 (95% confidence interval 1.05-1.12) (morphine and Dilaudid) and 1.13 (95% confidence interval 1.09-1.17) (Percocet/Vicodin/Demerol) (all p-values illicit and prescription opioid use among PWID that could potentially increase the risk of overdose.

Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing.

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Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie L; Boston, Raymond C

2015-12-01

(1) To quantify hydrocodone (HC) and hydromorphone (HM) metabolite pharmacokinetics with pharmacogenetics in CYP2D6 ultra-rapid metabolizer (UM), extensive metabolizer (EM), and poor metabolizer (PM) metabolizer phenotypes. (2) To develop an HC phenotype-specific dosing strategy for HC that accounts for HM production using clinical pharmacokinetics integrated with pharmacogenetics for patient safety. In silico clinical trial simulation. Healthy white men and women without comorbidities or history of opioid, or any other drug or nutraceutical use, age 26.3±5.7 years (mean±SD; range, 19 to 36 y) and weight 71.9±16.8 kg (range, 50 to 108 kg). CYP2D6 phenotype-specific HC clinical pharmacokinetic parameter estimates and phenotype-specific percentages of HM formed from HC. PMs had lower indices of HC disposition compared with UMs and EMs. Clearance was reduced by nearly 60% and the t1/2 was increased by about 68% compared with EMs. The canonical order for HC clearance was UM>EM>PM. HC elimination mainly by the liver, represented by ke, was reduced about 70% in PM. However, HC's apparent Vd was not significantly different among UMs, EMs, and PM. The canonical order of predicted plasma HM concentrations was UM>EM>PM. For each of the CYP2D6 phenotypes, the mean predicted HM levels were within HM's therapeutic range, which indicates HC has significant phenotype-dependent pro-drug effects. Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body.

76 FR 62450 - Manufacturer of Controlled Substances; Notice of Application

Science.gov (United States)

2011-10-07

... Hydromorphone (9150) II Hydrocodone (9193) II Morphine (9300) II Oripavine (9330) II Thebaine (9333) II Opium extracts (9610) II Opium fluid extract (9620) II Opium tincture (9630) II Opium, powdered (9639) II Opium...

Comparative Analysis of Opioid Queries on Erowid.org: An Opportunity to Advance Harm Reduction.

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Wightman, Rachel S; Perrone, Jeanmarie; Erowid, Fire; Erowid, Earth; Meisel, Zachary F; Nelson, Lewis S

2017-08-24

Many individuals who use opioids turn to online resources to gather information on effects, availability, and safety. Describe opioid index page views on Erowid.org to assess trends in public interest in particular opioids. Retrospective analysis of Erowid.org site traffic was performed to identify unique average daily visits to opioid pages. All data was normalized to that of visits to the heroin index page. Average daily visits to the index pages of each of 6 commonly abused opioids were assessed during the period of 2009 to 2015. Similarly, visits to 15 distinct opioid index pages at 5 time points (July, October 2014 and Jan, April, and July 2015) were described. From 2009 to 2015 a decrease in the number of page visits versus heroin (1.00) occurred for hydrocodone (0.87 to 0.59, -32%), oxycodone (1.38 to 0.99, -28%), and morphine (0.26 to 0.25, -6%). Increases in page visits compared to heroin occurred for fentanyl (0.18 to 0.47, +157%), tramadol (0.43 to 0.88, +106%), hydromorphone (0.19 to 0.24, +29%), and oxymorphone (0.11 to 0.13, +18%). Indexed to heroin (1.00) average opioid page visit frequencies from July 2014 to July 2015 were highest for oxycodone (1.02) and tramadol (0.81). Conclusion/Importance: Oxycodone and tramadol represent the greatest number of Erowid.org opioid page visits compared to heroin. The largest increase in visits over the study periods was for fentanyl and tramadol. The relationship of page visits on Erowid.org creates a unique opportunity for real-time evaluation of emerging drug trends and epidemiological study.

Increasing deaths involving oxycodone, Victoria, Australia, 2000-09.

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Rintoul, Angela C; Dobbin, Malcolm D H; Drummer, Olaf H; Ozanne-Smith, Joan

2011-08-01

In light of an emerging epidemic identified in the United States and Canada, to identify trends in fatal drug toxicity involving oxycodone and the demographic characteristics and indicators of socioeconomic disadvantage of the deceased. Population-based observational study in Victoria, Australia. Decedents whose death was reported to the Victorian Coroner between 2000 and 2009 and where oxycodone was detected. Association between supply of oxycodone and deaths. Demographic characteristics of decedents. Rate ratios of the rural or metropolitan location and socioeconomic indicators of disadvantage of the deceased. Supply to Victoria has increased nine-fold from 7.5 mg per capita in 2000 to 67.5 mg per capita in 2009. Detection of oxycodone in deaths reported to the Victorian Coroner has increased from 4 (0.08/100,000 population) in 2000 to 97 (1.78/100,000 population) in 2009-a 21-fold increase in deaths. Of the 320 cases described, 53.8% (172) were the result of drug toxicity. Of these, 52.3% were unintentional and 19.8% intentional self-harm; the remaining 27.9% are either still under investigation by the coroner or intent is unknown. Drug toxicity deaths were overrepresented in both rural areas and areas indexed with high levels of disadvantage. The substantial increase in the number of deaths involving oxycodone is strongly and significantly associated with the increase in supply. Most drug toxicity deaths involving oxycodone were unintentional. This newly identified trend in fatalities in Victoria supports concerns that a pattern of increasing deaths involving oxycodone is emerging globally.

Morphine and oxycodone in the management of cancer pain

International Nuclear Information System (INIS)

Kalso, E.; Vainio, A.; Rosenberg, P.H.; Mattila, M.J.; Seppaelae, T.

1990-01-01

Morphine and oxycodone were administered to ten patients suffering from severe cancer pain in a double-blind cross-over study. The patients titrated themselves pain-free, first intravenously, using a patient-controlled analgesia device, and then orally. Each titration phase lasted for 48 hours. Blood samples were drawn after 36 hr of each administration phase. The plasma levels of morphine, morphine-6- and morphine-3 glucuronides were determined with high performance liquid chromatography (HPLC), whereas the oxycodone samples were assayed with gas chromatography (GC). Twin samples were analyzed for plasma opioid activity with a radioreceptor assay (RRA) using 3 H-dihydromorphien and 3 H-naloxone as radioligands. Adequate analgesia was achieved with both morphine and oxycodone. About 30% more oxycodone was needed intravenously, whereas 25% less oxycodone than morphine was consumed orally. There was a good linear correlation between the morphine concentrations measured with HPLC and RRA. The mean morphine-6-glucuronide to morphine concentration ratio was 2.3 after intravenous and 4.6 after oral administration. Results from RRA indicate that oxycodone in vivo is a potent μ-agonist and that a least part of its analgesic action is mediated by active metabolites. In vitro morphine glucuronides enhanced morphine in displacing radioligands from the opioid receptors, thus suggesting their complex interactions in vivo. (author)

Synthesis of N-[methyl-11C]hydromorphone by using multivariate strategies for optimization of radiochemical yields

International Nuclear Information System (INIS)

Rimland, Annika; Bergson, Goeran; Obenius, Ulf; Sjoeberg, Stefan; Langstroem, Bengt

1987-01-01

The synthesis of N-[methyl- 11 C]hydromorphone has been performed by using [ 11 C]methyl iodide and desmethyl hydromorphone in a mixture of dimethylsulphoxide and dimethylformamide as solvent. Optimization of the radiochemical yield by varying the reaction conditions was performed by using multivariate strategies. The labelled hydromorphone was obtained in 72% radiochemical yield in the alkylation reaction with [ 11 C]-methyl iodide, counted from the end of the [ 11 C]methyl iodide synthesis. N-[Methyl- 11 C]hydromorphone was obtained as a ready injectable pharmaceutical solution with a total synthesis time of 40 min and in a 10% total radiochemical yield, with a radiochemical purity > 99.5%, according to HPLC analysis. (author)

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

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

2015-12-01

In April 2014, a tamper-resistant controlled-release oxycodone formulation was introduced into the Australian market. This study aimed to identify the level and methods of tampering with reformulated oxycodone, demographic and clinical characteristics of those who reported tampering with reformulated oxycodone, and perceived attractiveness of original and reformulated oxycodone for misuse (via tampering). A prospective cohort of 522 people who regularly tampered with pharmaceutical opioids and had tampered with the original oxycodone product in their lifetime completed two interviews before (January-March 2014: Wave 1) and after (May-August 2014: Wave 2) introduction of reformulated oxycodone. Four-fifths (81%) had tampered with the original oxycodone formulation in the month prior to Wave 1; use and attempted tampering with reformulated oxycodone amongst the sample was comparatively low at Wave 2 (29% and 19%, respectively). Reformulated oxycodone was primarily swallowed (15%), with low levels of recent successful injection (6%), chewing (2%), drinking/dissolving (1%), and smoking (word-of-mouth or the internet). Participants rated reformulated oxycodone as more difficult to prepare and inject and less pleasant to use compared to the original formulation. Current findings suggest that the introduction of the tamper-resistant product has been successful at reducing, although not necessarily eliminating, tampering with the controlled-release oxycodone formulation, with lower attractiveness for misuse. Appropriate, effective treatment options must be available with increasing availability of abuse-deterrent products, given the reduction of oxycodone tampering and use amongst a group with high rates of pharmaceutical opioid dependence. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice.

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Yang, Pao-Pao; Yeh, Geng-Chang; Huang, Eagle Yi-Kung; Law, Ping-Yee; Loh, Horace H; Tao, Pao-Luh

2015-09-22

Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α). Co-administration of DM10 potentiated these effects of oxycodone. The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.

CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.

Science.gov (United States)

Stamer, Ulrike M; Zhang, Lan; Book, Malte; Lehmann, Lutz E; Stuber, Frank; Musshoff, Frank

2013-01-01

The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12(th) hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes. In this postoperative setting, the number of functionally active CYP2D6 alleles had an impact

CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.

Directory of Open Access Journals (Sweden)

Ulrike M Stamer

Full Text Available BACKGROUND: The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. METHODS: Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele, HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity, EM (extensive metabolizers, normal CYP2D6 activity and UM (ultrarapid metabolizers, increased CYP2D6 activity. Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. RESULTS: Metabolism differed between CYP2D6 genotypes. Mean (95%-CI oxymophone/oxycodone ratios were 0.10 (0.02/0.19, 0.13 (0.11/0.16, 0.18 (0.16/0.20 and 0.28 (0.07/0.49 in PM, HZ/IM, EM and UM, respectively (p = 0.005. Oxycodone consumption up to the 12(th hour was highest in PM (p = 0.005, resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8; EM and UM 2.2 (2.1/2.3; p<0.001. Pain scores did not differ between genotypes. CONCLUSIONS: In this postoperative setting, the number of

Impact of the Hydrocodone Schedule Change on Opioid Prescription Patterns in South Dakota.

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Kuschel, Lauren M; Mort, Jane M

2017-10-01

Prescription opioid use is becoming increasingly common; consequently, opioid overdose deaths are increasing at an alarming rate. Hydrocodone, one of the most commonly abused opioids, was changed from a schedule III controlled substance to the more stringent schedule II to decrease abuse and diversion, effective Oct. 6, 2014. The objective of this study was to examine the impact of the hydrocodone schedule change on opioid prescribing in South Dakota. Opioid prescription patterns were examined in the following six-month phases: the baseline phase before the change, the transition phase when existing hydrocodone prescriptions could still be refilled, and the final phase. The South Dakota Board of Pharmacy Prescription Drug Monitoring Program provided aggregate monthly data for South Dakota opioid prescriptions (i.e., total number of prescriptions and days supplied), including urban and rural stratification. T-tests were performed on the monthly values for each phase to determine the significance of differences in prescription features between phases. The number of hydrocodone prescriptions significantly decreased 14 percent from baseline to final phase, while the days supplied per prescription significantly increased 7.4 percent. These changes were greater in rural areas than in urban areas. Conversely, the number of other opioid prescriptions significantly increased by 6.5 percent over this timeframe. The number of hydrocodone prescriptions decreased, while the days supplied per prescription increased. These changes were greater in rural areas than in urban areas. In addition, the number of other opioid prescriptions increased. These trends may reflect some unintended effects of the schedule change.

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.

Choice between delayed food and immediate oxycodone in rats.

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Secci, Maria E; Factor, Julie A; Schindler, Charles W; Panlilio, Leigh V

2016-12-01

The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.

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.

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.

Fatal overdoses involving hydromorphone and morphine among inpatients: a case series.

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Lowe, Amanda; Hamilton, Michael; Greenall BScPhm MHSc, Julie; Ma, Jessica; Dhalla, Irfan; Persaud, Nav

2017-01-01

Opioids have narrow therapeutic windows, and errors in ordering or administration can be fatal. The purpose of this study was to describe deaths involving hydromorphone and morphine, which have similar-sounding names, but different potencies. In this case series, we describe deaths of patients admitted to hospital or residents of long-term care facilities that involved hydromorphone and morphine. We searched for deaths referred to the Patient Safety Review Committee of the Office of the Chief Coroner for Ontario between 2007 and 2012, and subsequently reviewed by 2014. We reviewed each case to identify intervention points where errors could have been prevented. We identified 8 cases involving decedents aged 19 to 91 years. The cases involved errors in prescribing, order processing and transcription, dispensing, administration and monitoring. For 7 of the 8 cases, there were multiple (2 or more) possible intervention points. Six cases may have been prevented by additional patient monitoring, and 5 cases involved dispensing errors. Opioid toxicity deaths in patients living in institutions can be prevented at multiple points in the prescribing and dispensing processes. Interventions aimed at preventing errors in hydromorphone and morphine prescribing, administration and patient monitoring should be implemented and rigorously evaluated.

Evaluation of the Relative Abuse of an OROS® Extended-release Hydromorphone HCI Product: Results from three Post-market Surveillance Studies.

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Butler, Stephen F; McNaughton, Emily C; Black, Ryan A; Cassidy, Theresa A

2018-01-02

Formulating prescription opioids to limit abuse remains a priority. OROS® extended-release (ER) hydromorphone HCl (EXALGO®) may have low abuse potential. Three post-marketing studies of the relative abuse liability of OROS hydromorphone ER were conducted. Estimates of abuse, unadjusted and adjusted for prescription volume, were generated for OROS hydromorphone ER and comparators from Q2 2010 through Q2 2014 for a high-risk, substance abuse treatment population and the general population using poison control center data. Comparators were selected for compound, market penetration, and route of administration (ROA) profile. ROA comparisons were made among the substance abuse treatment population. Internet discussion was examined to determine abusers' interest in and desire for the OROS formulation. Examination of abuse prevalence among adults within substance abuse treatment, intentional poison exposures and Internet discussion levels generally support the hypothesis that OROS hydromorphone ER may have lower abuse potential than many other opioid products. OROS hydromorphone ER also appears to be abused less often by alternate ROAs (e.g., snorting and injection). Lower levels of online discussion were observed along with relatively low endorsement for abuse. Abuse of OROS hydromorphone ER was observed in high-risk substance abuse and general population samples but at a very low relative prevalence. Evidence suggests it may be less often abused by alternate ROAs than some comparators. Online data did not find evidence of high levels of desire for OROS hydromorphone ER by recreational abusers. Continued monitoring of this product's abuse liability is warranted.

Stability of Hydromorphone-Ketamine Solutions in Glass Bottles, Plastic Syringes, and IV Bags for Pediatric Use.

Science.gov (United States)

Ensom, Mary H H; Decarie, Diane; Leung, Karen; Montgomery, Carolyne

2009-03-01

To evaluate the stability of mixtures of hydromorphone and ketamine in 0.9% sodium chloride (normal saline [NS]) after storage for up to 7 days at room temperature (25°C). The stability of 3 standard mixtures of hydromorphone and ketamine (hydromorphone 0.2 mg/mL + ketamine 0.2 mg/mL, hydromorphone 0.2 mg/mL + ketamine 0.6 mg/mL, and hydromorphone 0.2 mg/mL + ketamine 1.0 mg/mL) in NS was studied. Portions of each mixture were transferred to 3 brown glass bottles (100 mL), 3 plastic syringes (50 mL), and 3 IV bags (50 mL), which were then stored at room temperature (25°C). Physical characteristics, including pH, colour, and precipitation, were evaluated daily. Three 1.5-mL samples were collected from each bottle, syringe, and IV bag at baseline, at 24, 48, and 72 hours, and on day 7. Samples were analyzed in triplicate by a stability-indicating high-performance liquid chromatography method. Solutions were considered stable if they maintained 90% of the initial concentration of each drug. Samples from syringes and IV bags were subjected to standard sterility testing by incubation for 5 days in an enriched culture media. No notable changes in pH or colour were observed, and no precipitation occurred in any of the solutions. All formulations maintained more than 90% of the initial concentration of each drug on day 7. No bacterial growth was observed in any of the samples tested. Mixtures of hydromorphone and ketamine were stable for up 7 days at 25°C, and the sterility of the preparations was maintained. Because stability alone does not guarantee efficacy, it is recommended that clinical studies be conducted to evaluate the pharmacokinetics and pharmacodynamics of these formulations.

Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone.

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Maddocks, I; Somogyi, A; Abbott, F; Hayball, P; Parker, D

1996-09-01

We have observed among patients of the Southern Community Hospice Programme that up to 25% experience acute delirium when treated with morphine and improve when the opioid is changed to oxycodone or fentanyl. This study aimed to confirm by a prospective trial that oxycodone produces less delirium than morphine in such patients. Oxycodone was administered by a continuous subcutaneous infusion, as this allowed more flexible and reliable dosing, and patients were monitored for any adverse reactions to the drug. Thirteen patients completed the study. Statistically significant improvements in mental state and nausea and vomiting occurred following a change from morphine to oxycodone. Pain scores improved but did not reach a level of statistical significance. The phenotype status of the patients was tested to establish their capacity to metabolize oxycodone. One patient who did not achieve adequate pain control proved to be a poor metabolizer. These results show that oxycodone administered by the subcutaneous route can provide effective analgesia without significant side effects in patients with morphine-induced delirium. This treatment allows patients to remain more comfortable and lucid in their final days. A small proportion of patients who do not metabolize oxycodone effectively may not receive this benefit.

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

DEFF Research Database (Denmark)

Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie

2017-01-01

/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...

Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability.

Science.gov (United States)

Cooper, Ziva D; Bedi, Gillinder; Ramesh, Divya; Balter, Rebecca; Comer, Sandra D; Haney, Margaret

2018-02-05

Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5, and 5.0 mg, PO) with smoked cannabis (0.0, 5.6% Δ 9 tetrahydrocannabinol [THC]) and analgesia was assessed using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4 °C); times to report pain (pain threshold) and withdraw the hand from the water (pain tolerance) were recorded. Abuse-related effects were measured and effects of oxycodone on cannabis self-administration were determined. Alone, 5.0 mg oxycodone increased pain threshold and tolerance (p ≤ 0.05). Although active cannabis and 2.5 mg oxycodone alone failed to elicit analgesia, combined they increased pain threshold and tolerance (p ≤ 0.05). Oxycodone did not increase subjective ratings associated with cannabis abuse, nor did it increase cannabis self-administration. However, the combination of 2.5 mg oxycodone and active cannabis produced small, yet significant, increases in oxycodone abuse liability (p ≤ 0.05). Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis's abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.

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

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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.

Antinociceptive efficacy of buprenorphine and hydromorphone in red-eared slider turtles (Trachemys scripta elegans).

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Mans, Christoph; Lahner, Lesanna L; Baker, Bridget B; Johnson, Stephen M; Sladky, Kurt K

2012-09-01

Despite the frequent clinical use of buprenorphine in reptiles, its antinociceptive efficacy is not known. In a randomized, complete cross-over study, the antinociceptive efficacy of buprenorphine (0.2 mg/kg s.c.) was compared with hydromorphone (0.5 mg/kg s.c.), and saline (0.9% s.c. equivalent volume) in 11 healthy red-eared slider turtles (Trachemys scripta elegans). Additionally, buprenorphine at 0.1 and 1 mg/kg was compared with saline in six turtles. Hindlimb withdrawal latencies were measured after exposure to a focal, thermal noxious stimulus before and between 3 hr and up to 96 hr after drug administration. Buprenorphine did not significantly increase hindlimb withdrawal latencies at any time point compared with saline. In contrast, hydromorphone administration at 0.5 mg/kg significantly increased hindlimb withdrawal latencies for up to 24 hr. These results show that hydromorphone, but not buprenorphine, provides thermal antinociception in red-eared slider turtles.

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

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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. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolism of oxycodone in human hepatocytes from different age groups and prediction of hepatic plasma clearance

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Timo eKorjamo

2012-01-01

Full Text Available 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 hours, 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. In general, this in vitro to in vivo extrapolation method provides valuable information on the maturation of oxycodone metabolism that can be utilized in the design of clinical pharmacokinetic studies in infants and young children.

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

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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

Randomized clinical trial of an intravenous hydromorphone titration protocol versus usual care for management of acute pain in older emergency department patients.

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Chang, Andrew K; Bijur, Polly E; Davitt, Michelle; Gallagher, E John

2013-09-01

Opioid titration is an effective strategy for treating pain; however, titration is generally impractical in the busy emergency department (ED) setting. Our objective was to test a rapid, two-step, hydromorphone titration protocol against usual care in older patients presenting to the ED with acute severe pain. This was a prospective, randomized clinical trial of patients 65 years of age and older presenting to an adult, urban, academic ED with acute severe pain. The study was registered at http://www.clinicaltrials.gov (NCT01429285). Patients randomized to the hydromorphone titration protocol initially received 0.5 mg intravenous hydromorphone. Patients randomized to usual care received any dose of any intravenous opioid. At 15 min, patients in both groups were asked, 'Do you want more pain medication?' Patients in the hydromorphone titration group who answered 'yes' received a second dose of 0.5 mg intravenous hydromorphone. Patients in the usual care group who answered 'yes' had their ED attending physician notified, who then could administer any (or no) additional medication. The primary efficacy outcome was satisfactory analgesia defined a priori as the patient declining additional analgesia at least once when asked at 15 or 60 min after administration of the initial opioid. Dose was calculated in morphine equivalent units (MEU: 1 mg hydromorphone = 7 mg morphine). The need for naloxone to reverse adverse opioid effects was the primary safety outcome. 83.0 % of 153 patients in the hydromorphone titration group achieved satisfactory analgesia compared with 82.5 % of 166 patients in the usual care group (p = 0.91). Patients in the hydromorphone titration group received lower mean initial doses of opioids at baseline than patients in the usual care group (3.5 MEU vs. 4.7 MEU, respectively; p ≤ 0.001) and lower total opioids through 60 min (5.3 MEU vs. 6.0 MEU; p = 0.03). No patient needed naloxone. Low-dose titration of intravenous hydromorphone in increments of

Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.

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Chai, Peter R; Carreiro, Stephanie; Innes, Brendan J; Chapman, Brittany; Schreiber, Kristin L; Edwards, Robert R; Carrico, Adam W; Boyer, Edward W

2017-12-01

Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction. We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion. In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3-9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest

Analgesic efficacy and safety of epidural oxycodone in patients undergoing total hip arthroplasty: a pilot study

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Olczak B

2017-09-01

Full Text Available Bogumił Olczak,1 Grzegorz Kowalski,1,2 Wojciech Leppert,2 Agnieszka Bienert,3 Artur Teżyk,4 Michał Adamski,1 Stanisław Rzymski,1 Katarzyna Wieczorowska-Tobis2 1Department of Anaesthesiology, Józef Struś Multiprofile Municipal Hospital, Poznań, 2Department of Palliative Medicine, 3Department of Clinical Pharmacy and Biopharmacy, 4Department of Forensic Medicine, Poznan University of Medical Sciences, Poznań, Poland Background and objectives: Oxycodone is poorly studied as an adjuvant to central blockades. The aim of this pilot study was to assess the efficacy and safety of oxycodone hydrochloride in epidural blockade among patients undergoing total hip arthroplasty (THA.Patients and methods: In 11 patients (American Society of Anesthesiologists physical status classification system II/III, age range: 59–82 years, THA was conducted with an epidural blockade using 15 mL 0.25% bupivacaine (37.5 mg with 5 mg oxycodone hydrochloride and sedation with propofol infusion at a dose of 3–5 mg/kg/h. After the surgery, patients received ketoprofen at a dose of 100 mg twice daily. In the first 24 hours postoperative period, pain was assessed by numerical rating scale at rest and on movement; adverse effects (AEs were recorded; and plasma concentrations of oxycodone, noroxycodone, and bupivacaine were measured.Results: The administration of epidural oxycodone at a dose of 5 mg in patients undergoing THA provided analgesia for a mean time of 10.3±4.89 h. In one patient, mild pruritus was observed. Oxycodone did not evoke other AEs. Plasma concentrations of oxycodone while preserving analgesia were >2.9 ng/mL. Noroxycodone concentrations in plasma did not guarantee analgesic effect.Conclusion: The administration of epidural oxycodone at a dose of 5 mg prolongs the analgesia period to ~10 hours in patients after THA. Oxycodone may evoke pruritus. A 5 mg dose of oxycodone hydrochloride used in an epidural blockade seems to be a safe drug in patients

Profile of extended-release oxycodone/acetaminophen for acute pain

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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 

Use of continuous ambulatory infusions of concentrated subcutaneous (s.q.) hydromorphone versus intravenous (i.v.) morphine: cost implications for palliative care.

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Fudin, J; Smith, H S; Toledo-Binette, C S; Kenney, E; Yu, A B; Boutin, R

2000-01-01

Health care practitioners are increasingly under pressure to curtail spending while trying to deliver excellent patient care. These issues are also affecting palliative care, particularly now that palliative care programs are expanding. A comparison of cost-effectiveness and feasibility of using continuous subcutaneous (s.q.) ambulatory infusion of hydromorphone versus intravenous (i.v.) ambulatory morphine is illustrated in this study. With the high doses of morphine required in chronic cancer pain, the use of subcutaneous morphine is not feasible due to the volume of solution required to be delivered. Hydromorphone can be prepared in concentrated solutions enabling it to be delivered by the subcutaneous route. Morphine stability data are available. However, hydromorphone stability has only been verified for seven days; thus, stability data were needed post-seven days. Concentrations of 10 mg/ml, 20 mg/ml, 50 mg/ml, and 100 mg/ml, in 0.9 percent normal saline or dextrose 5 percent water, were analyzed via high-performance liquid chromatography (HPLC) at seven and 28 days. Cost comparisons of supplies and associated costs with subcutaneous versus intravenous solutions were obtained. Hydromorphone was found to be stable for 28 days in both dilutants. Cost analysis of a hydromorphone 28-day supply resulted in substantial savings over the equivalent costs of morphine infusions.

Impact of pharmacists assisting with prescribing and undertaking medication review on oxycodone prescribing and supply for patients discharged from surgical wards.

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Tran, T; Taylor, S E; Hardidge, A; Findakly, D; Aminian, P; Elliott, R A

2017-10-01

Overprescribing of oxycodone is a contributor to the epidemic of prescription opioid misuse and deaths. Practice models to optimize oxycodone prescribing and supply need to be evaluated. We explored the impact of pharmacist-assisted discharge prescribing and medication review on oxycodone prescribing and supply for patients discharged from surgical wards. A retrospective audit was conducted on two surgical inpatient wards following a 16-week prospective pre- and post-intervention study. During the pre-intervention period, discharge prescriptions were prepared by hospital doctors and then reviewed by a ward pharmacist (WP) before being dispensed. Post-intervention, prescriptions were prepared by a project pharmacist in consultation with hospital doctors and then reviewed by a WP and dispensed. Proportion of patients who were prescribed, and proportion supplied, oxycodone on discharge; Median amount (milligrams) of oxycodone prescribed and supplied, for patients who were prescribed and supplied at least one oxycodone-containing preparation, respectively. A total of 320 and 341 patients were evaluated pre- and post-intervention, respectively. Pre-intervention, 75.6% of patients were prescribed oxycodone; after WP review, 60.3% were supplied oxycodone (Psupplied was 100 milligrams/patient. Post-intervention, 68.6% of patients were prescribed oxycodone; after WP review, 57.8% were supplied oxycodone (Psupplied was 50 milligrams/patient (difference in amount prescribed and supplied: 50 milligrams, Psupplied oxycodone but not the amount supplied/patient. Having a pharmacist assist with prescribing reduced the amount of oxycodone supplied. © 2017 John Wiley & Sons Ltd.

Potentiation of oxycodone antinociception in mice by agmatine and BMS182874 via an imidazoline I2 receptor-mediated mechanism.

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Bhalla, Shaifali; Ali, Izna; Lee, Hyaera; Andurkar, Shridhar V; Gulati, Anil

2013-01-01

The potentiation of oxycodone antinociception by BMS182874 (endothelin-A (ET(A)) receptor antagonist) and agmatine (imidazoline receptor/α(2)-adrenoceptor agonist) is well-documented. It is also known that imidazoline receptors but not α(2)-adrenoceptors are involved in potentiation of oxycodone antinociception by agmatine and BMS182874 in mice. However, the involvement of specific imidazoline receptor subtypes (I(1), I(2), or both) in this interaction is not clearly understood. The present study was conducted to determine the involvement of imidazoline I(1) and I(2) receptors in agmatine- and BMS182874-induced potentiation of oxycodone antinociception in mice. Antinociceptive (tail flick and hot-plate) latencies were determined in male Swiss Webster mice treated with oxycodone, agmatine, BMS182874, and combined administration of oxycodone with agmatine or BMS182874. Efaroxan (imidazoline I(1) receptor antagonist) and BU224 (imidazoline I(2) receptor antagonist) were used to determine the involvement of I(1) and I(2) imidazoline receptors, respectively. Oxycodone produced significant antinociceptive response in mice which was not affected by efaroxan but was blocked by BU224. Agmatine-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. Similarly, BMS182874-induced potentiation of oxycodone antinociception was blocked by BU224 but not by efaroxan. This is the first report demonstrating that BMS182874- or agmatine-induced enhancement of oxycodone antinociception is blocked by BU224 but not by efaroxan. We conclude that imidazoline I(2) receptors but not imidazoline I(1) receptors are involved in BMS182874- and agmatine-induced potentiation of oxycodone antinociception in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats.

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Pypendop, Bruno H; Shilo-Benjamini, Yael; Ilkiw, Jan E

2016-11-01

To determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Randomized crossover study. Six healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. Morphine sulfate (0.2 mg kg -1 IV or 0.5 mg kg -1 buccal), methadone hydrochloride (0.3 mg kg -1 IV or 0.75 mg kg -1 buccal), hydromorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) or oxymorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. Administration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. At the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Effect size comparison of ketorolac nasal spray and commonly prescribed oral combination opioids for pain relief after third molar extraction surgery.

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Niebler, Gwendolyn; Dayno, Jeffrey

2016-01-01

Opioids are frequently used for treatment of moderate to severe short-term pain, but concerns exist about this treatment approach. Ketorolac tromethamine nasal spray, a nonsteroidal anti-inflammatory, is indicated for the short-term management of moderate to moderately severe pain requiring analgesia at the opioid level. However, there are no direct comparison studies between ketorolac nasal spray and opioids. The objective of this study was to use an effect size analysis to compare the effectiveness of ketorolac nasal spray with oral combination opioid formulations in treating moderate to severe short-term pain. An effect size analysis of three randomized, double-blind, placebo-controlled studies of third molar extraction surgery compared pain relief with ketorolac nasal spray and commonly prescribed combination opioids including hydrocodone/acetaminophen (APAP), oxycodone/APAP, oxycodone/ibuprofen and tramadol HCl/APAP. Effect size comparisons were made using total pain relief scores (TOTPAR6 or TOTPAR8; the weighted sum of pain relief scores through 6 or 8 h). Pain relief was measured using a five-point categorical rating scale (0 = none; 4 = complete). The effect size equivalent correlation, r, was determined using an online effect size calculator. The treatment effect size r compared with placebo was classified using established criteria (small = 0.20-0.49, moderate = 0.50-0.79 and large = ≥ 0.80). TOTPAR6 data indicated a moderate effect size for ketorolac nasal spray 31.5 mg (0.51) and oxycodone/ibuprofen 5/400 mg (0.64) and a small effect size for hydrocodone/APAP 7.5/500 mg (0.24) and oxycodone/APAP 5/325 mg (0.32). TOTPAR8 data indicated small effect sizes for ketorolac nasal spray (0.48), hydrocodone/APAP 10/650 mg (0.43), tramadol HCl/APAP 75/650 mg (0.35) and tramadol HCl/APAP 37.5/325 mg (0.17). The treatment effect sizes of ketorolac nasal spray were similar to or higher than the opioid comparators after third molar surgery, a well-accepted pain

Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials.

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Wang, Li; Johnston, Bradley; Kaushal, Alka; Cheng, Davy; Zhu, Fang; Martin, Janet

2016-03-01

To determine whether ketamine added to morphine or hydromorphone patient-controlled analgesia (PCA) provides clinically relevant reductions in postoperative pain, opioid requirements, and adverse events when compared with morphine or hydromorphone PCA in adults undergoing surgery. We systematically searched six databases up to June 2, 2015 for randomized controlled trials (RCTs) comparing ketamine plus morphine/hydromorphone PCA vs morphine/hydromorphone PCA for postoperative pain in adults. Thirty-six RCTs including 2,502 patients proved eligible, and 22 of these were at low risk of bias. The addition of ketamine to morphine/hydromorphone PCA decreased postoperative pain intensity at six to 72 hr when measured at rest (weighted mean difference [WMD] on a 10-cm visual analogue scale ranged from -0.4 to -1.3 cm) and during mobilization (WMD ranged from -0.4 to -0.5 cm). Adjunctive ketamine also significantly reduced cumulative morphine consumption at 24-72 hr by approximately 5-20 mg. Predefined subgroup analyses and meta-regression did not detect significant differences across subgroups, including a dose-response relationship. There was no significant difference in patient satisfaction scores at 24 and 48 hr. Nevertheless, the addition of ketamine to morphine/hydromorphone PCA significantly reduced postoperative nausea and vomiting (relative risk, 0.71; 95% confidence interval [CI], 0.60 to 0.85; absolute risk reduction, 8.9%; 95% CI, 4.6 to 12.2). Significant effects on other adverse events (e.g., hallucinations, vivid dreams) were not detected, though only a few studies reported on them. Adding ketamine to morphine/hydromorphone PCA provides a small improvement in postoperative analgesia while reducing opioid requirements. Adjunctive ketamine also reduces postoperative nausea and vomiting without a detected increase in other adverse effects; however, adverse events were probably underreported.

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

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M D Raleigh

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

Venlafaxine and Oxycodone Effects on Human Spinal and Supraspinal Pain Processing

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Lelic, D; Fischer, I W D; Olesen, Anne Estrup

2016-01-01

affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole......Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine...

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

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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...... for genetic covariates. Model simulations were used to predict how population and effect-size impact the power to detect clinical significant SNPs. METHOD: The population pharmacokinetic-pharmacodynamic (PKPD) model of oral single-dosed oxycodone was based on pooled data from three published studies...... 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...

Bioavailability of morphine, methadone, hydromorphone, and oxymorphone following buccal administration in cats.

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Pypendop, B H; Ilkiw, J E; Shilo-Benjamini, Y

2014-06-01

Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time-concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7-49.5), 44.2 ± 7.9 (18.7-70.5), 22.4 ± 6.9 (6.4-43.4), and 18.8 ± 2.0 (12.9-23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone. © 2013 John Wiley & Sons Ltd.

Opioid-Induced "Likeability" and "Feeling Good" Are Not Associated With Return Visits to an ED Among Migraine Patients Administered IV Hydromorphone.

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Friedman, Benjamin W; Latev, Alexander; Campbell, Caron; White, Deborah

2018-05-01

Parenteral opioids are used in more than 50% of emergency department (ED) visits for migraine. Use of opioids for migraine has been associated with subsequent ED visits, perhaps because of opioid-induced euphoria. In this study, we quantify the extent to which nontherapeutic effects of opioids influence migraine outcomes. We hypothesized that "feeling good" and medication likeability would in fact be associated with receipt of opioids (rather than relief of migraine pain) and that receipt of opioids (rather than relief of migraine pain) would be associated with return visits to the ED. During an ED-based clinical trial, migraine patients were randomized to receive hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg IV. Thirty minutes after medication administration, we asked, (1) How much did you like the medication you received? and (2) How good did the medication make you feel? Participants were asked to provide answers on a 0-10 scale. We also determined 0-10 pain scores at baseline and 1 hour and number of return visits for headache during the subsequent month. Sixty-three patients received prochlorperazine and 64 hydromorphone. Prochlorperazine pain scores improved by 6.8 (SD: 2.6), hydromorphone by 4.7 (SD: 3.3) (95%CI for difference of 2.1: 1.0, 3.2). On the 0-10 likeability scale, prochlorperazine patients reported a mean of 7.2 (SD: 2.8), hydromorphone 6.9 (SD: 2.9) (95% CI for difference of 0.3: -0.7, 1.3). On the 0-10 feeling good scale, prochlorperazine patients reported a mean of 7.5 (SD: 2.3), hydromorphone 6.8 (SD: 2.8) (95%CI: for difference of 0.7: -0.2, 1.6). In the hydromorphone group, 8/57 (14%, 95%CI: 7, 26%) returned to the ED vs 5/63 (8%, 95%CI: 3,18%) in the prochlorperazine group. In regression modeling, feeling good was independently associated with pain relief (P relief (P relief was associated with medication likeability and feeling good. © 2018 American Headache Society.

Involvement of α₂-adrenoceptors, imidazoline, and endothelin-A receptors in the effect of agmatine on morphine and oxycodone-induced hypothermia in mice.

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

2013-10-01

Potentiation of opioid analgesia by endothelin-A (ET(A)) receptor antagonist, BMS182874, and imidazoline receptor/α₂-adrenoceptor agonists such as clonidine and agmatine are well known. It is also known that agmatine blocks morphine hyperthermia in rats. However, the effect of agmatine on morphine or oxycodone hypothermia in mice is unknown. The present study was carried out to study the role of α₂-adrenoceptors, imidazoline, and ET(A) receptors in morphine and oxycodone hypothermia in mice. Body temperature was determined over 6 h in male Swiss Webster mice treated with morphine, oxycodone, agmatine, and combination of agmatine with morphine or oxycodone. Yohimbine, idazoxan, and BMS182874 were used to determine involvement of α₂-adrenoceptors, imidazoline, and ET(A) receptors, respectively. Morphine and oxycodone produced significant hypothermia that was not affected by α₂-adrenoceptor antagonist yohimbine, imidazoline receptor/α₂ adrenoceptor antagonist idazoxan, or ET(A) receptor antagonist, BMS182874. Agmatine did not produce hypothermia; however, it blocked oxycodone but not morphine-induced hypothermia. Agmatine-induced blockade of oxycodone hypothermia was inhibited by idazoxan and yohimbine. The blockade by idazoxan was more pronounced compared with yohimbine. Combined administration of BMS182874 and agmatine did not produce changes in body temperature in mice. However, when BMS182874 was administered along with agmatine and oxycodone, it blocked agmatine-induced reversal of oxycodone hypothermia. This is the first report demonstrating that agmatine does not affect morphine hypothermia in mice, but reverses oxycodone hypothermia. Imidazoline receptors and α₂-adrenoceptors are involved in agmatine-induced reversal of oxycodone hypothermia. Our findings also suggest that ET(A) receptors may be involved in blockade of oxycodone hypothermia by agmatine. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de

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

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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.

An Unusual Case of Serotonin Syndrome with Oxycodone and Citalopram

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Clare Walter

2012-01-01

Full Text Available A 77-year-old female with recurrent non-small-cell lung cancer presented to a hospital outpatient clinic with tremor, weakness, inability to coordinate motor movements, and confusion. It was suspected that the symptoms were due to possible central nervous system metastases; however, a CT scan of her head was unremarkable. The lung clinic liaison pharmacist took a medication history from the patient, complimented by extra information from the patient’s community pharmacy. The pharmacist suspected the rare side effect of serotonin syndrome was responsible for the patient’s presenting symptoms caused by the combination of oxycodone and citalopram. The patient’s symptoms resolved soon after oxycodone was changed to morphine.

Automated solid-phase extraction-liquid chromatography-tandem mass spectrometry analysis of 6-acetylmorphine in human urine specimens: application for a high-throughput urine analysis laboratory.

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Robandt, P V; Bui, H M; Scancella, J M; Klette, K L

2010-10-01

An automated solid-phase extraction-liquid chromatography- tandem mass spectrometry (SPE-LC-MS-MS) method using the Spark Holland Symbiosis Pharma SPE-LC coupled to a Waters Quattro Micro MS-MS was developed for the analysis of 6-acetylmorphine (6-AM) in human urine specimens. The method was linear (R² = 0.9983) to 100 ng/mL, with no carryover at 200 ng/mL. Limits of quantification and detection were found to be 2 ng/mL. Interrun precision calculated as percent coefficient of variation (%CV) and evaluated by analyzing five specimens at 10 ng/mL over nine batches (n = 45) was 3.6%. Intrarun precision evaluated from 0 to 100 ng/mL ranged from 1.0 to 4.4%CV. Other opioids (codeine, morphine, oxycodone, oxymorphone, hydromorphone, hydrocodone, and norcodeine) did not interfere in the detection, quantification, or chromatography of 6-AM or the deuterated internal standard. The quantified values for 41 authentic human urine specimens previously found to contain 6-AM by a validated gas chromatography (GC)-MS method were compared to those obtained by the SPE-LC-MS-MS method. The SPE-LC-MS-MS procedure eliminates the human factors of specimen handling, extraction, and derivatization, thereby reducing labor costs and rework resulting from human error or technique issues. The time required for extraction and analysis was reduced by approximately 50% when compared to a validated 6-AM procedure using manual SPE and GC-MS analysis.

Analgesic efficacy, adverse effects, and safety of oxycodone administered as continuous intravenous infusion in patients after total hip arthroplasty

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Olczak B

2017-05-01

Full Text Available Bogumił Olczak,1 Grzegorz Kowalski,1,2 Wojciech Leppert,2 Iwona Zaporowska-Stachowiak,3 Katarzyna Wieczorowska-Tobis2 1Department of Anesthesiology, Józef Struś Multiprofile Municipal Hospital, 2Department of Palliative Medicine, Poznan University of Medical Sciences, 3Department of Pharmacology, Poznan University of Medical Sciences, Poland Background: Total hip arthroplasty (THA causes extensive tissue damage and severe pain. This study aimed to assess the analgesic efficacy, adverse effects (AEs, and safety of continuous intravenous (iv oxycodone infusion with ketoprofen (injected into the iv line in patients after THA, and to assay serum oxycodone levels.Patients and methods: Fourteen patients, aged 59‒82 years with American Society of Anesthesiologists (ASA classification I or III, underwent THA with intrathecal analgesia and sedation induced by iv propofol. After the surgery, oxycodone (continuous iv infusion at a dose of 1 mg/h (five patients or 2 mg/h (nine patients with 100 mg ketoprofen (injected into the iv line was administered to each patient every 12 h. Pain was assessed using a numerical rating scale (NRS: 0 – no pain, 10 – the most severe pain at rest and during movement. AEs, including hemodynamic unsteadiness, nausea, vomiting, pruritus, cognitive impairment, and respiratory depression, were registered during the first 24 h after surgery.Results: Oxycodone (continuous iv infusion at a dose of 2 mg/h with ketoprofen (100 mg administered every 12 h provided satisfactory analgesia in all nine patients without the need of rescue analgesics within the first 24 h after THA. In three out of five patients, oxycodone at 1 mg/h was effective. Oxycodone did not induce drowsiness, vomiting, pruritus, respiratory depression, or changes in blood pressure. Bradycardia appeared in two patients, and nausea was observed in one patient.Conclusion: Oxycodone infusion with ketoprofen administered by iv is effective in patients after THA

Does acetaminophen/hydrocodone affect cold pulpal testing in patients with symptomatic irreversible pulpitis? A prospective, randomized, double-blind, placebo-controlled study.

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Fowler, Sara; Fullmer, Spencer; Drum, Melissa; Reader, Al

2014-12-01

The purpose of this prospective randomized, double-blind, placebo-controlled study was to determine the effects of a combination dose of 1000 mg acetaminophen/10 mg hydrocodone on cold pulpal testing in patients experiencing symptomatic irreversible pulpitis. One hundred emergency patients in moderate to severe pain diagnosed with symptomatic irreversible pulpitis of a mandibular posterior tooth randomly received, in a double-blind manner, identical capsules of either a combination of 1000 mg acetaminophen/10 hydrocodone or placebo. Cold testing with Endo-Ice (1,1,1,2 tetrafluoroethane; Hygenic Corp, Akron, OH) was performed at baseline and every 10 minutes for 60 minutes. Pain to cold testing was recorded by the patient using a Heft-Parker visual analog scale. Patients' reaction to the cold application was also rated. Cold testing at baseline and at 10 minutes resulted in severe pain for both the acetaminophen/hydrocodone and placebo groups. Although pain ratings decreased from 20-60 minutes, the ratings still resulted in moderate pain. Patient reaction to cold testing showed that 56%-62% had a severe reaction. Although the reactions decreased in severity over the 60 minutes, 20%-34% still had severe reactions at 60 minutes. Regarding pain and patients' reactions to cold testing, there were no significant differences between the combination acetaminophen/hydrocodone and placebo groups at any time period. A combination dose of 1000 mg of acetaminophen/10 mg of hydrocodone did not statistically affect cold pulpal testing in patients presenting with symptomatic irreversible pulpitis. Patients experienced moderate to severe pain and reactions to cold testing. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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

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2010-10-05

... marketing for reasons other than safety or effectiveness. ANDAs that refer to AZDONE (hydrocodone bitartrate... Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... or effectiveness. This determination will allow FDA to approve abbreviated new drug applications...

Recrudescence of Focal Stroke Symptoms During Pain Management with Hydromorphone

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Joshua D. Bernstock

2016-03-01

Full Text Available Abstract: Patients who have recovered from a prior stroke may experience a reemergence of their original stroke syndrome secondary to metabolic derangements, sedation, infection, and/or fatigue. Critically, the molecular/cellular mechanisms mediating symptom recurrence after exposure to analgesic agents remain unknown. Accordingly, herein we report a unique case of a patient with hydromorphone-induced recrudescence 30 years after her initial stroke event(s, and in so doing propose a putative mechanism related to post-infarction functional neuroplasticity.

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

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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

Do Diuretics have Antinociceptive Actions: Studies of Spironolactone, Eplerenone, Furosemide and Chlorothiazide, Individually and with Oxycodone and Morphine.

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Jokinen, Viljami; Lilius, Tuomas; Laitila, Jouko; Niemi, Mikko; Kambur, Oleg; Kalso, Eija; Rauhala, Pekka

2017-01-01

Spironolactone, eplerenone, chlorothiazide and furosemide are diuretics that have been suggested to have antinociceptive properties, for example via mineralocorticoid receptor antagonism. In co-administration, diuretics might enhance the antinociceptive effect of opioids via pharmacodynamic and pharmacokinetic mechanisms. Effects of spironolactone (100 mg/kg, i.p.), eplerenone (100 mg/kg, i.p.), chlorothiazide (50 mg/kg, i.p.) and furosemide (100 mg/kg, i.p.) were studied on acute oxycodone (0.75 mg/kg, s.c.)- and morphine (3 mg/kg, s.c.)-induced antinociception using tail-flick and hot plate tests in male Sprague Dawley rats. The diuretics were administered 30 min. before the opioids, and behavioural tests were performed 30 and 90 min. after the opioids. Concentrations of oxycodone, morphine and their major metabolites in plasma and brain were quantified by mass spectrometry. In the hot plate test at 30 and 90 min., spironolactone significantly enhanced the antinociceptive effect (% of maximum possible effect) of oxycodone from 10% to 78% and from 0% to 50%, respectively, and that of morphine from 12% to 73% and from 4% to 83%, respectively. The brain oxycodone and morphine concentrations were significantly increased at 30 min. (oxycodone, 46%) and at 90 min. (morphine, 190%). We did not detect any independent antinociceptive effects with the diuretics. Eplerenone and chlorothiazide did not enhance the antinociceptive effect of either opioid. The results suggest that spironolactone enhances the antinociceptive effect of both oxycodone and morphine by increasing their concentrations in the central nervous system. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Continuous subcutaneous infusion of compound oxycodone for the relief of dyspnea in patients with terminally ill cancer: a retrospective study.

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Kawabata, Masahiro; Kaneishi, Keisuke

2013-05-01

Pain and dyspnea are the most prevalent and distressing symptoms in patients with terminally ill cancer. Evidences have accumulated for the effects of morphine on dyspnea, whereas little is known about the effects of oxycodone on dyspnea. We investigated the effectiveness of oxycodone for dyspnea in patients with terminally ill cancer. The injectable form of compound oxycodone (iOC) containing hydrocotarnine was administered continuously via subcutaneous route. We administered iOC to 136 patients. The effect on dyspnea was less conspicuous than pain, yet iOC was effective for dyspnea with varying degrees. None of the adverse effects observed were serious. These results suggest that continuous subcutaneous administration of oxycodone could be one of the reasonable alternatives in the management of dyspnea in patients with terminally ill cancer.

Hapten-specific naïve B cells are biomarkers of vaccine efficacy against drugs of abuse.

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Taylor, J J; Laudenbach, M; Tucker, A M; Jenkins, M K; Pravetoni, M

2014-03-01

Vaccination against drugs of abuse shows efficacy in animal models, yet few subjects achieve effective serum antibody titers in clinical studies. A barrier to translation is the lack of pre-vaccination screening assays that predict the most effective conjugate vaccines or subjects amenable to vaccination. To address this obstacle, we developed a fluorescent antigen-based enrichment method paired with flow cytometry to characterize hapten-specific B cells. Using this approach, we studied naïve and activated B cells specific for structurally-related model haptens based on derivatization of the morphinan structure at the C6 position on oxycodone or at the C8 position on hydrocodone, and showing different pre-clinical efficacy against the prescription opioid oxycodone. Prior to vaccination, naïve B cells exhibited relatively higher affinity for the more effective C6-derivatized oxycodone-based hapten (6OXY) and the 6OXY-specific naïve B cell population contained a higher number of B cells with greater affinity for free oxycodone. Higher affinity of naïve B cells for hapten or oxycodone reflected greater efficacy of vaccination in blocking oxycodone distribution to brain in mice. Shortly after immunization, activated hapten-specific B cells were detected prior to oxycodone-specific serum antibodies and provided earlier evidence of vaccine failure or success. Analysis of hapten-specific naïve and activated B cells may aid rational vaccine design and provide screening tools to predict vaccine clinical efficacy against drugs of abuse or other small molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

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Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2013-09-01

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Validation of an automated solid-phase extraction method for the analysis of 23 opioids, cocaine, and metabolites in urine with ultra-performance liquid chromatography-tandem mass spectrometry.

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Ramírez Fernández, María del Mar; Van Durme, Filip; Wille, Sarah M R; di Fazio, Vincent; Kummer, Natalie; Samyn, Nele

2014-06-01

The aim of this work was to automate a sample preparation procedure extracting morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-monoacetyl-morphine, hydrocodone, ethylmorphine, benzoylecgonine, cocaine, cocaethylene, tramadol, meperidine, pentazocine, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine from urine samples. Samples were extracted by solid-phase extraction (SPE) with cation exchange cartridges using a TECAN Freedom Evo 100 base robotic system, including a hydrolysis step previous extraction when required. Block modules were carefully selected in order to use the same consumable material as in manual procedures to reduce cost and/or manual sample transfers. Moreover, the present configuration included pressure monitoring pipetting increasing pipetting accuracy and detecting sampling errors. The compounds were then separated in a chromatographic run of 9 min using a BEH Phenyl analytical column on a ultra-performance liquid chromatography-tandem mass spectrometry system. Optimization of the SPE was performed with different wash conditions and elution solvents. Intra- and inter-day relative standard deviations (RSDs) were within ±15% and bias was within ±15% for most of the compounds. Recovery was >69% (RSD automated SPE system was observed. The extracted samples were stable for 72 h in the autosampler (4°C). This method was applied to authentic samples (from forensic and toxicology cases) and to proficiency testing schemes containing cocaine, heroin, buprenorphine and methadone, offering fast and reliable results. Automation resulted in improved precision and accuracy, and a minimum operator intervention, leading to safer sample handling and less time-consuming procedures.

National All Schedules Prescription Electronic Reporting Act (NASPER): balancing substance abuse and medical necessity.

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Manchikanti, Laxmaiah; Brown, Keith R; Singh, Vijay

2002-07-01

The National All Schedules Prescription Electronic Reporting Act, or NASPER, is a bill proposed by the American Society of Interventional Pain Physicians to provide and improve patient access with quality care, and protect patients and physicians from deleterious effects of controlled substance misuse, abuse and trafficking. Controlled prescription drugs, including narcotic analgesics, anxiolytics, anti-depressants, stimulants, and sedative-hypnotics play a significant and legitimate role in interventional pain management practices in managing chronic pain and related disorders. Based on the 1997 household survey on drug abuse it is estimated that 76.9 million Americans had used an illicit drug at least once in their life. In 1997, 4.2 million people used analgesics, 2.1 million used tranquillizers, and an additional 2.3 million people used various other drugs, including sedatives, tranquillizers, etc. The non-medical use of prescription drugs exceeds that of all illicit substances except for marijuana and hashish. The report on epidemiology trends in drug abuse, based on community epidemiology work group analysis showed continued increase of abuse of prescription drugs in urban, suburban, and rural areas. The most commonly abused drugs include oxycodone, hydrocodone, hydromorphone, morphine, codeine, clonazepam, alprazolam, lorazepam, diazepam and carisoprodol. The diversion of prescription controlled substances to illicit channels is a public health and safety issue. This review describes the role of controlled substances in chronic pain management, prevalence and economic impact of controlled substance abuse, prescription accountability, effectiveness of prescription monitoring programs, and rationale for national controlled substance electronic reporting system.

Buprenorphine/naloxone as a promising therapeutic option for opioid abusing patients with chronic pain: reduction of pain, opioid withdrawal symptoms, and abuse liability of oral oxycodone.

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Roux, Perrine; Sullivan, Maria A; Cohen, Julien; Fugon, Lionel; Jones, Jermaine D; Vosburg, Suzanne K; Cooper, Ziva D; Manubay, Jeanne M; Mogali, Shanthi; Comer, Sandra D

2013-08-01

Few studies have examined abuse of prescription opioids among individuals with chronic pain under buprenorphine/naloxone (Bup/Nx) maintenance. The current 7-week inpatient study assessed oral oxycodone self-administration by patients with chronic pain who had a history of opioid abuse. Participants (n=25) were transitioned from their preadmission prescribed opioid to Bup/Nx. All of the participants were tested under each of the sublingual Bup/Nx maintenance doses (2/0.5, 8/2 or 16/4 mg) in random order. During each maintenance period, participants could self-administer oxycodone orally (0, 10, 20, 40 or 60 mg prescription opioids) or receive money during laboratory sessions. Drug choice (percentage) was the primary dependent variable. Subjective ratings of clinical pain and withdrawal symptoms also were measured. Mann-Whitney tests compared percentage of drug choice for each active oxycodone dose to placebo. Logistic regression analyses identified correlates of oxycodone preference, defined as 60% or greater choice of oxycodone compared to money. Pain was significantly reduced while participants were maintained on Bup/Nx compared to preadmission ratings. No differences in percentage drug choice were observed between the active oxycodone doses and placebo under each Bup/Nx maintenance dose. However, factors associated with oxycodone preference were lower Bup/Nx maintenance dose, more withdrawal symptoms and more pain. These data suggest that Bup/Nx was effective in reducing pain and supplemental oxycodone use. Importantly, adequate management of pain and withdrawal symptoms by Bup/Nx may reduce oxycodone preference in this population. Published by Elsevier B.V.

The Decline in Hydrocodone/Acetaminophen Prescriptions in Emergency Departments in the Veterans Health Administration Between 2009 to 2015

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Michael A. Grasso

2016-06-01

Full Text Available Introduction: The purpose of the study was to measure national prescribing patterns for hydrocodone/acetaminophen among veterans seeking emergency medical care, and to see if patterns have changed since this medication became a Schedule II controlled substance. Methods: We conducted a retrospective cohort study of emergency department (ED visits within the Veterans Health Administration (VA between January 2009 and June 2015. We looked at demographics, comorbidities, utilization measures, diagnoses, and prescriptions. Results: During the study period, 1,709,545 individuals participated in 6,270,742 ED visits and received 471,221 prescriptions for hydrocodone/acetaminophen (7.5% of all visits. The most common diagnosis associated with a prescription was back pain. Prescriptions peaked at 80,776 in 2011 (8.7% of visits, and declined to 35,031 (5.6% during the first half of 2015 (r=‒0.99, p<0.001. The percentage of hydrocodone/acetaminophen prescriptions limited to 12 pills increased from 22% (13,949 in 2009 to 31% (11,026 in the first half of 2015. A prescription was more likely written for patients with a pain score≥7 (OR 3.199, CI [3.192‒3.205], a musculoskeletal (OR 1.622, CI [1.615‒1.630] or soft tissue (OR 1.656, CI [1.649‒1.664] diagnosis, and those below the first quartile for total ED visits (OR 1.282, CI [1.271‒1.293] and total outpatient ICD 9 codes (OR 1.843, CI [1.833‒1.853]. Conclusion: Hydrocodone/acetaminophen is the most frequently prescribed ED medication in the VA. The rate of prescribing has decreased since 2011, with the rate of decline remaining unchanged after it was classified as a Schedule II controlled substance. The proportion of prescriptions falling within designated guidelines has increased but is not at goal. [West J Emerg Med. 2016;17(4:396-403.

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.

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

2017-10-01

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®.

Opioid withdrawal presenting only nausea during tapering of oxycodone after celiac plexus block: a case report.

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Sakamoto, Akiyuki; Takayama, Hiroto; Mamiya, Keiko; Koizumi, Tomonobu

2016-01-01

Celiac plexus block (CPB) is an effective treatment for patients suffering pain. CPB may allow for a reduction in opioid dosage, and may alleviate some of the unwanted side effects of these drugs. However, there is a substantial risk of withdrawal symptoms after reduction of opioid dose. We describe a case of pancreatic cancer developing opioid withdrawal after CPB, who presented only nausea. A 70-year-old man was referred to our hospital due to severe pancreatic cancer pain. He was administered oxycodone (oxycontin®) at 240 mg per day, and presented nausea and anorexia as side effects. CPB was performed due to insufficient pain relief. His pain disappeared on the same day as treatment. Oxycodone was reduced to 160 mg/day, and further reduced two days later to 80 mg/day. However, he complained of more severe nausea and loss of appetite even after tapering of oxycodone. Physical examination, blood chemistry examination, and brain computed tomography (CT) showed no abnormalities. Administration of fast-release oxycodone (Oxinome®) at a dose of 10 mg immediately improved his nausea. There have been no previous reports of nausea as the sole symptom of opioid withdrawal. The present case indicates that unless opioid side effects improve after dosage reduction, the possibility that they may be withdrawal symptoms should also be considered.

Managing cancer pain and symptoms of outpatients by rotation to sustained-release hydromorphone: a prospective clinical trial

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Wirz, Stefan; Wartenberg, Hans Christian; Elsen, Christian; Wittmann, Maria; Diederichs, Marta; Nadstawek, Joachim

2006-01-01

PURPOSE: In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. METHODS: Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical

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

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Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael

2013-01-01

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 than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of

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

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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

A Prospective Multicentre Study to Evaluate the Efficacy and Tolerability of Osmotic Release Oral System (Oros® Hydromorphone in Opioid-Naive Cancer Patients: Results of the Korean South West Oncology Group Study

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Eun-Kee Song

2015-01-01

Full Text Available BACKGROUND: Osmotic release oral system (OROS® hydromorphone is a potent, long-acting opioid analgesic, effective and safe for controlling cancer pain in patients who have received other strong opioids. To date, few studies have examined the efficacy of hydromorphone for pain relief in opioid-naive cancer patients.

Effect of hydromorphone hydrochloride combined with ropivacaine for PCEA after transurethral resection of prostate on pain mediators and stress response

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Yu-Lin Ma

2017-08-01

Full Text Available Objective: To study the effect of hydromorphone hydrochloride combined with ropivacaine for patient-controlled epidural analgesia (PCEA after transurethral resection of prostate on pain mediators and stress response. Methods: A total of 138 patients who received transurethral resection of prostate in Ankang Central Hospital between May 2014 and October 2016 were selected and randomly divided into group A and group B, group A received postoperative hydromorphone hydrochloride combined with ropivacaine for PCEA, and group B received postoperative morphine hydrochloride combined with ropivacaine for PCEA. The serum contents of pain mediators, inflammatory response cytokines and stress hormones of the two groups were detected before surgery as well as 12 h, 24 h and 48 h after surgery. Results: 12 h, 24 h and 48 h after surgery, serum SP, BK, HIS, CX3CL1, CCL2, IL-1β, TNF-α, IL-10, ACTH, CORT, TSH, FT3, FT4 and GH levels of both groups of patients were significantly higher than those before surgery, and serum SP, BK, HIS, CX3CL1, CCL2, IL-1β, TNF-α, IL-10, ACTH, CORT, TSH, FT3, FT4 and GH levels of group A were significantly lower than those of group B. Conclusion: Hydromorphone hydrochloride combined with ropivacaine for PCEA can effectively reduce the pain and stress after transurethral resection of prostate.

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

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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

Oxycodone Self-Administration Induces Alterations in Expression of Integrin, Semaphorin and Ephrin Genes in the Mouse Striatum

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Vadim Yuferov

2018-06-01

Full Text Available Oxycodone is one a commonly used medication for pain, and is also a widely abused prescription opioid, like other short-acting MOPr agonists. Neurochemical and structural adaptations in brain following chronic MOPr-agonist administration are thought to underlie pathogenesis and persistence of opiate addiction. Many axon guidance molecules, such as integrins, semaphorins, and ephrins may contribute to oxycodone-induced neuroadaptations through alterations in axon-target connections and synaptogenesis, that may be implicated in the behaviors associated with opiate addiction. However, little is known about this important area. The aim of this study is to investigate alterations in expression of selected integrin, semaphorin, ephrins, netrin, and slit genes in the nucleus accumbens (NAc and caudate putamen (CPu of mice following extended 14-day oxycodone self-administration (SA, using RNAseq.Methods: Total RNA from the NAc and CPu were isolated from adult male C57BL/6J mice within 1 h after the last session of oxycodone in a 14-day self-administration paradigm (4h/day, 0.25 mg/kg/infusion, FR1 or from yoked saline controls. Gene expressions were examined using RNA sequencing (RNA-Seq technology. RNA-Seq libraries were prepared using Illumina's TruSeq® Stranded Total RNA LT kit. The reads were aligned to the mouse reference genome (version mm10 using STAR. DESeq2 was applied to the counts of protein coding genes to estimate the fold change between the treatment groups. False Discovery Rate (FDR q < 0.1 were used to select genes that have a significant expression change. For selection of a subset of genes related to axon guidance pathway, REACTOME was used.Results: Among 38 known genes of the integrin, semaphorin, and ephrin gene families, RNA-seq data revealed up-regulation of six genes in the NAc: heterodimer receptor, integrins Itgal, Itgb2, and Itgam, and its ligand semaphorin Sema7a, two semaphorin receptors, plexins Plxnd1 and Plxdc1. There was

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

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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

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

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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

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.

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Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar

2015-01-01

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. 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. 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. Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.

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.

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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. Copyright © 2015 Elsevier B.V. All

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

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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…

Effect of preoperative acetaminophen/hydrocodone on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind, placebo-controlled study.

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Fullmer, Spencer; Drum, Melissa; Reader, Al; Nusstein, John; Beck, Mike

2014-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of the administration of the combination acetaminophen/hydrocodone on the anesthetic success of mandibular posterior teeth in patients experiencing symptomatic irreversible pulpitis. One hundred emergency patients in moderate to severe pain diagnosed with symptomatic irreversible pulpitis of a mandibular posterior tooth randomly received, in a double-blind manner, identical capsules of either a combination dose of 1000 mg acetaminophen/10 mg hydrocodone or placebo 60 minutes before the administration of a conventional inferior alveolar nerve (IAN) block. Endodontic access was begun 15 minutes after completion of the block, and all patients used for data analysis had profound lip numbness. Success was defined as no or mild pain (visual analog scale recordings) on pulpal access or instrumentation. The success rate for the IAN block was 32% for the combination dose of 1000 mg acetaminophen/10 hydrocodone and 28% for the placebo dose, with no statistically significant difference between the 2 groups (P = .662). A combination dose of 1000 mg acetaminophen/10 mg hydrocodone given 60 minutes before the administration of the IAN block did not result in a statistically significant increase in anesthetic success for mandibular posterior teeth in patients experiencing symptomatic irreversible pulpitis. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

A Dose-Finding Study of Dexketoprofen in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Clinical Trial on Effects on the Analgesic Concentration of Oxycodone.

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Piirainen, Annika; Kokki, Hannu; Immonen, Satu; Eskelinen, Matti; Häkkinen, Merja R; Hautajärvi, Heidi; Kokki, Merja

2015-12-01

Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC). Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was dexketoprofen. At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration. In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC.

The genetic influences on oxycodone response characteristics in human experimental pain

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

2015-01-01

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 respon......; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone....

U.S. Pharmacist Opinions Regarding the Rescheduling of Hydrocodone Combination Products: A Pilot Study

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Jordan R. Covvey

2015-08-01

Full Text Available In October 2014, the Drug Enforcement Administration in the U.S. reclassified hydrocodone combination products (HCPs from Schedule III to Schedule II, initiating one of the most significant and controversial regulatory changes for opioids in recent national history. The aim of the present study was to determine community pharmacist opinions on the effect of the rescheduling of HCPs on their personal practice. A web-based pilot survey was emailed to a convenience sample through online newsletters of professional pharmacy organizations in Pennsylvania, Kentucky and West Virginia in April/May 2015. A total of 62 surveys were initiated, yielding 56 complete responses. More than 75% of respondents noted increases in their workload as a result of the rescheduling of HCPs. Opinions regarding the intended outcomes of rescheduling were only weakly positive, with only 37.5% of respondents believing it has increased safety and 44.6% of respondents believing it has lessened abuse/diversion. For overall attitudes regarding the rescheduling, respondents were split between positive (26.8%, neutral (26.8% and negative (46.4%. These initial data suggest that pharmacists have encountered barriers in practice resulting from the rescheduling. Further expanded work is necessary to verify these results from the small sample, and to assess the intended effects of the rescheduling upon the safe and effective use of hydrocodone.

Open-label study on the long-term efficacy, safety, and impact on quality of life of OROS hydromorphone ER in patients with chronic low back pain.

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Wallace, Mark; Thipphawong, John

2010-10-01

To investigate the efficacy, safety, and impact on quality of life of long-term administration of OROS hydromorphone ER (8-128mg) in patients with chronic low back pain. A total of 113 adults with chronic low back pain who completed a 6-week open-label study were enrolled in this 6-month extension study. The primary end point was the daily pain relief rating obtained during monthly study visits. Secondary end points included Investigator and Patient Global Evaluations, Brief Pain Inventory scores obtained at monthly study visits, and quality-of-life measures (Medical Outcomes Study Questionnaire and 36-Item Short-Form Health Survey score) obtained at monthly intervals. Mean±SD change from baseline in pain relief with OROS hydromorphone ER for the Month 6 visit was 0.9±2.55 (P=0.0007) and for the last assessment of the extension study was 0.9±2.53 (P=0.0002). At the Month 6 visit, 81.3% of investigators and 71.0% of patients rated their satisfaction of pain relief with OROS hydromorphone ER treatment as good, very good, or excellent. Changes on the 36-item Short Form Health Survey, a quality-of-life measure, were statistically significant for the physical composite scores for all extension phase time points, including Month 6 (2.1±5.34; Psleep disturbances. Adverse events included gastrointestinal and central nervous system symptoms. The results support the long-term use of OROS hydromorphone ER in managing chronic moderate to severe low back pain. Wiley Periodicals, Inc.

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

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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...... including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold...... pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P...

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

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Anderson, Collin; MacKay, Mark

2015-12-16

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. Four 5 mL samples of each drug and concentration were prepared in 10 mL polypropylene syringes. The samples were stored at ambient room temperature in a locked cabinet. Triplicate determinations of drug concentration for each sample were performed initially, on day 50 or 51, and on day 100 using high-performance liquid chromatography with diode-array detection. With the exception of the hydromorphone 100 mcg/mL dilution, all compounds were found to contain greater than 95% of their initial concentration remaining at 100 days. Each sample remained clear and colorless when visually inspected.

Comparison of the effects of oxycodone versus fentanyl on airway reflex to tracheal extubation and postoperative pain during anesthesia recovery after laparoscopic cholecystectomy: A double-blind, randomized clinical consort study.

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Choi, Eun Kyung; Kwon, Nyeongkeon; Park, Sang-Jin

2018-03-01

Fentanyl has been suggested to be effective for controlling airway and hemodynamic responses to tracheal extubation. This study was performed to compare the effects of oxycodone and fentanyl on airway and hemodynamic responses and postoperative pain during the recovery period in patients undergoing laparoscopic cholecystectomy. Ninety patients aged 18 to 65 years were randomly allocated to 1 of 3 groups: fentanyl, oxycodone, and control. Coughing responses (incidence and severity), hemodynamic responses during the recovery period, and acute postoperative pain were assessed. The incidence of cough was decreased in the fentanyl and oxycodone groups compared with that in the control group at the points of awareness and extubation, and no significant difference was observed between the 2 treatment groups. Severe cough response was decreased in the fentanyl and oxycodone groups compared with that in the control group at the point of extubation, and no significant change was observed in cough severity between the 2 treatment groups. Postoperative pain scores were lower in the fentanyl and oxycodone groups than those in the control group at 5 and 30 minutes postoperatively, and no significant difference was observed between the 2 treatment groups. Hemodynamic responses did not differ among the 3 groups during the recovery period. Oxycodone treatment before tracheal extubation reduced cough response and was as effective as fentanyl treatment for improving extubation quality. Furthermore, single boluses of fentanyl and oxycodone showed equal effectiveness in attenuating acute postoperative pain in patients undergoing laparoscopic cholecystectomy.

Effect of hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia on serum pain mediators and placental hypoxia molecules after cesarean section

Institute of Scientific and Technical Information of China (English)

Xiao-Hui Yuan; Jian-Guo Xia; Xiao-Yang Jiang

2017-01-01

Objective:To study the effect of hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia on serum pain mediators and placental hypoxia molecules after cesarean section.Methods: 126 women accepting cesarean section in our hospital between May 2013 and December 2015 were selected as the research subjects and randomly divided into two groups, observation group of subjects received hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia and control group of subjects accepted bupivacaine combined spinal-epidural anesthesia. 1, 3 and 5 d after delivery, serum was collected to determine the levels of pain mediators; the placenta tissue was collected to detect the levels of oxidative stress molecules and endoplasmic reticulum stress molecules.Results: 1, 3 and 5 d after delivery, serum substance P (SP),β-endorphin (β-EP), 5-hydroxytryptamine (5-HT), nitric oxide (NO) and norepinephrine (NE) levels of observation group were significantly lower than those of control group whileβ-EP levels were significantly higher than those of control group (P<0.05); reactive oxide species (ROS), reactive nitrogen species (RNS), GRP78, ERdj1, CHOP and ASK1 levels in placenta tissue of observation group were significantly lower than those of control group while glutathione peroxidase (GPx), catalase (CAT) and vitamin C (VitC) levels were significantly higher than those of control group (P<0.05).Conclusions: Hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia can adjust the pain mediator secretion, relieve postoperative pain and inhibit oxidative stress and endoplasmic reticulum stress.

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...... and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain...... 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...

Venlafaxine and oxycodone have different effects on spinal and supra-spinal activity in Man

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Lelic, Dina; Valeriani, Massimiliano; Fischer, Iben W D

2017-01-01

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 (SNRI......) modulate spinal and supraspinal sensory processing. METHODS: Twenty volunteers were included in this randomized, double blinded, three-way (placebo, oxycodone, venlafaxine), cross-over study. Spinal and full scalp cortical evoked potentials (EPs) to median nerve stimulation were recorded before and after...... sources underlying early cortical EPs and 5) brain networks underlying the late cortical EPs. RESULTS: In the venlafaxine arm, the spinal P11 and the late cortical N60-80 latencies were reduced by 1.8%(95%CI:1.7,1.9%) and 5.7%(95%CI:5.3,6.1%), whereas the early cortical P25 amplitude was decreased by 7...

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

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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.

Quantitative study of controlled substance bedside wasting, disposal and evaluation of potential ecologic effects.

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Mankes, Russell F; Silver, Charles D

2013-02-01

Drugs in wastewater arise from many sources. For health care, these include excretion and direct disposal (bedside wasting). The present study reports on the dispensing and wasting of 15 controlled substances (CS) at two health care facilities in Albany, NY over a nearly two year period. The study considered measures of ecotoxicity, drug metabolism, excretion and disposal of these CS. Potential alternatives to flushing of CS into wastewaters from healthcare facilities are discussed. Drug medication and waste collection records (12,345) included: numbers of drugs dispensed, returned and wasted. Overall, 8528 g of 15 CS were wasted. Three (midazolam, acetaminophen-codeine and fentanyl) accounted for 87.5% of the total wasted. Wasting varied by hospital, 14 CS at the academic medical center hospital and 8 at the surgical care center were wasted. Liquids were more frequently wasted than tablets or pills. Some combination drugs (acetaminophen (APAP)-codeine) were frequently (50% of drug dispensed) wasted while others were less wasted (APAP-hydrocodone-6.3%; APAP-oxycodone-1.3%). The 8 CS judged more hazardous to aquatic life were: APAP-codeine, APAP-hydrocodone, APAP-oxycodone, alprazolam, diazepam, fentanyl, midazolam, and testosterone. Ketamine, morphine, oxycodone and zolpidem were of lesser acute toxicity based on available LC50 values. These CS might provide a therapeutically equivalent alternative to the more environmentally harmful drugs. In health care facilities, professionals dispose of CS by bedside wasting into water or other receptacles. This can be avoided by returning CS to the hospital's pharmacy department, thence to a licensed distributor. Study of this process of drug wasting can identify opportunities for process improvements. We found 3 CS (APAP-codeine, midazolam and testosterone) where ½ to 1/3 of the drug was wasted and 5 others with 30 to 13% wasted. Knowledge of the adverse impacts from the release of highly toxic drugs into the environment

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

% for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild......-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone...

Effect of hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia on serum pain mediators and placental hypoxia molecules after cesarean section

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Xiao-Hui Yuan

2017-05-01

Full Text Available Objective: To study the effect of hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia on serum pain mediators and placental hypoxia molecules after cesarean section. Methods: 126 women accepting cesarean section in our hospital between May 2013 and December 2015 were selected as the research subjects and randomly divided into two groups, observation group of subjects received hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia and control group of subjects accepted bupivacaine combined spinal-epidural anesthesia. 1, 3 and 5 d after delivery, serum was collected to determine the levels of pain mediators; the placenta tissue was collected to detect the levels of oxidative stress molecules and endoplasmic reticulum stress molecules. Results: 1, 3 and 5 d after delivery, serum substance P (SP, β-endorphin (β-EP, 5-hydroxytryptamine (5-HT, nitric oxide (NO and norepinephrine (NE levels of observation group were significantly lower than those of control group while β-EP levels were significantly higher than those of control group (P<0.05; reactive oxide species (ROS, reactive nitrogen species (RNS, GRP78, ERdj1, CHOP and ASK1 levels in placenta tissue of observation group were significantly lower than those of control group while glutathione peroxidase (GPx, catalase (CAT and vitamin C (VitC levels were significantly higher than those of control group (P<0.05. Conclusions: Hydromorphone hydrochloride combined with bupivacaine combined spinal-epidural anesthesia can adjust the pain mediator secretion, relieve postoperative pain and inhibit oxidative stress and endoplasmic reticulum stress.

Assessment of the use of oral fluid as a matrix for drug monitoring in patients undergoing treatment for opioid addiction.

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Kunkel, Frank; Fey, Elizabeth; Borg, Damon; Stripp, Richard; Getto, Christine

2015-01-01

Drug testing is an important clinical tool that is available to physicians who are assessing the effectiveness of drug treatment as well as patient compliance to the administered program. While urine has traditionally been the matrix of choice for drug monitoring, oral fluid, a filtrate of the blood, has shown great promise as an alternative matrix for such applications. Oral fluid collection can be accomplished without the need for highly trained medical staff through the use of a simple, noninvasive oral fluid collection device, which obtains an adequate sample in only a few minutes. There has been a significant amount of research performed on the use of oral fluid for forensic toxicology application; however, more studies assessing the use of oral fluid drug testing are required to validate its ability to achieve clinical drug monitoring goals. Testing for various drugs in oral fluid may yield a different result when compared to the same drugs in urine, requiring an assessment of the utility of oral fluid for such practices. The purpose of this study was to examine the application of oral fluid drug testing in patients undergoing buprenorphine treatment for opioid dependence. A retrospective analysis of drug testing results obtained from 6,928 patients (4,560 unobserved urine collections and 2,368 observed oral fluid collections) monitored for heroin metabolite, amphetamine, benzodiazepines, buprenorphine, tetrahydrocannabinol, cocaine, codeine, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and oxymorphone was completed. Results of this statistical exercise indicated that patients undergoing observed oral fluid collection tested positive more frequently than those unobserved urine collections for several illicit drugs and prescription medications targeted. Oral fluid was shown to detect illicit drug use as well as noncompliance in this patient population under the studied conditions more often than the urine specimens.

Assessment of Tapentadol API Abuse Liability With the Researched Abuse, Diversion and Addiction-Related Surveillance System.

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Vosburg, Suzanne K; Severtson, S Geoffrey; Dart, Richard C; Cicero, Theodore J; Kurtz, Steven P; Parrino, Mark W; Green, Jody L

2018-04-01

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted. This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol. Copyright © 2018. Published by Elsevier Inc.

Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

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Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

2017-11-01

To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

Effect of oxycodone hydrochloride combined with flurbiprofen axetil for intravenous patient-controlled analgesia in lower abdominal patients: A randomized trial.

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Xiang, Xiaobing; Yuan, Xiaohong; Lian, Yanhong; Fang, Jun; Wu, Yingli

2018-02-01

Problems like postoperative pain are still common phenomena after general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid with a safe and excellent therapeutic effect on visceral pain. Flurbiprofen axetil has the efficacy of targeted analgesia. We hypothesize that different doses of oxycodone hydrochloride combined with flurbiprofen axetil would generate great results on postoperative intravenous analgesia in lower abdominal patients. In the clinical trial, 90 American Society of Anesthesiologists I or II patients scheduled for elective general anesthesia were randomly divided into 3 groups, 30 cases in each group. Group I: oxycodone hydrochloride 0.5 mg/kg + flurbiprofen axetil 150 mg, group II: oxycodone hydrochloride 0.75 mg/kg + flurbiprofen axetil 150 mg, group III: oxycodone hydrochloride 1.0 mg/kg + flurbiprofen axetil 150 mg. Dilute them with 0.9% saline to 150 mL, respectively, with the background dose of 2 mL/h, patient-controlled analgesia 2 mL per time, with an interval of 10 min, and the loading dose of 0.1 mL/kg. Record the preoperative situation, 24 h (T0) before surgery, postoperative situation, 1 h (T1), 4 h (T2), 8 h (T3), 12 h (T4), 24 h (T5), 48 h (T6), 72 h (T7) after the surgery, including the mean arterial pressure, heart rate, saturation of pulse oximetry, static and dynamic pain rating (NRS) and Ramsay sedation score, effective pressing and total pressing ratio (referred to as the pressing ratio), patient satisfaction, and occurrence of adverse reactions. There was no significant statistic difference in mean arterial blood pressure, heart rate, arterial oxygen saturation, and adverse reactions among the 2 groups at each time point (P > .05). Compared with group I, the static NRS rating in group II and group III were significantly lower than that in group I (P  .05). Compared with group III, the Ramsay sedation scores of group I and group II were significantly lower from T1 to T4 (P�

In vitro evaluation of extemporaneously compounded slow-release capsules containing morphine sulfate or oxycodone hydrochloride.

Science.gov (United States)

Glowiak, Dana L; Green, Julie L; Bowman, Bill J

2005-01-01

The in vitro performance of extemporaneously compounded morphine sulfate and oxycodone hydrochloride slow-release capsules was evaluated. Capsules containing varying amoutns of morphine sulfate (15, 60, 200 mg) or oxycodone hydrochloride (10, 80, 200 mg) were prepared and provided by a Phoenix, Arizona, pharmacy. The capsules also contained 40% Methocel E4M Premium to slow the release of their active ingredient and sufficient lactose to fill the capsules. Three batches of each capsule strength were prepared, and replicates from each batch were evlauated using United Stated Pharmacopeia dissolution apparatus II. Samples were taken at regular time intervals over 24 hours. After 1 hour the pH of the dissolution medium was adjusted form 1.2 to 4.0, and after 2 hours the pH was adjusted to 6.8. The amount of drug released at each time point was determined spectrophotometrically. The compounded capsules released 14% to 23%, 67% to 85% and 93% to 98% of their active ingredient after 0.5, 4 and 12 hours, respectively. The relative standard deviations between the replicates from each batch were less than 10% for most time points. The percent of drug released over the first 4 hours was linear (r squared = 0.9409-0.9999) when plotted versus time 1/2, indicating adherence to the simplified Higuchi model. Statistical analysis of the Higuchi dissolution constants indicated a significant difference (P less than 0.05) between batch No.3 and the other two batches of 200-mg oxycodone hydrochloride capsules. There was also a statistical difference between most of the Higuchi dissolution constants for the different-strength slow-release capsules and most slow-release capsules and equivalent strength controlled-release manufactured tablets (P less than 0.05). Using 40% Methocel E4M Premium slowed the release of morphine sulfate and oxycodone hydrochloride from extemporaneously compounded capsules. The in vitro performance of the slow-release capsules showed little intrabatch variation

Effect of hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery on the synthesis of pain mediators, inflammatory mediator and oxygen free radicals

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Liang-Ying Luo

2017-08-01

Full Text Available Objective: To explore the effect of hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery on the synthesis of pain mediators, inflammatory mediator and oxygen free radicals. Methods: A total of 120 patients with fracture who underwent operation in the hospital between July 2014 and December 2016 were collected and divided into control group and observation group according to the random number table method, 60 cases in each group. Control group received morphine hydrochloride combined with ropivacaine for analgesia, observation group received hydromorphone hydrochloride combined with ropivacaine for analgesia, and the postoperative analgesia lasted for 48 h. The differences in serum levels of pain mediators, inflammatory mediators and oxidative stress indexes were compared between the two groups. Results: Immediately after operation, the differences in serum levels of pain mediators, inflammatory mediators and oxidative stress indexes were not statistically significant between the two groups. 48 h after operation, serum PGE2, SP, β-EP, IL-6, MCP-1, HMGB-1 and MDA levels of both groups of patients were significantly lower than those immediately after operation while Cu-Zn SOD and GSH-Px levels were significantly higher than those immediately after operation, and serum PGE2, SP, β-EP, IL-6, MCP-1, HMGB-1 and MDA levels of observation group were significantly lower than those of control group while Cu-Zn SOD and GSH-Px levels were significantly higher than those of control group. Conclusion: Hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery is effective in alleviating pain and inhibiting systemic inflammatory response.

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

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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

Reformulation of controlled-release oxycodone and pharmacy dispensing patterns near the US-Canada border.

Science.gov (United States)

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

2012-01-01

In August 2010, a tamper-resistant formulation of controlled-release oxycodone (OxyContin-OP) was introduced in the United States but not in Canada. Our objective was to determine whether introduction of OxyContin-OP in the United States influenced prescription volumes for the original controlled-release oxycodone formulation (OxyContin) at Canadian pharmacies near the international border. We conducted a population-based, serial, cross-sectional study of prescriptions dispensed from pharmacies in the 3 cities with the highest volume of US-Canada border crossings in Ontario: Niagara Falls, Windsor and Sarnia. We analyzed data on all outpatient prescriptions for OxyContin dispensed by Canadian pharmacies near each border crossing between 2010 Apr. 1 and 2012 Feb. 29. We calculated and compared monthly prescription rates, adjusted per 1000 population and stratified by tablet strength. The number of tablets dispensed near 4 border crossings in the 3 Canadian cities remained stable over the study period. However, the rate of dispensing at pharmacies near the Detroit-Windsor Tunnel increased roughly 4-fold between August 2010 and February 2011, from 505 to 1969 tablets per 1000 population. By April 2011, following warnings to prescribers and pharmacies regarding drug-seeking behaviour, the dispensing rate declined to 1683 tablets per 1000 population in this area. By November 2011, the rate had returned to levels observed in early 2010. Our analyses suggest that 242 075 excess OxyContin tablets were dispensed near the Detroit-Windsor Tunnel between August 2010 and October 2011. Prescribing of the original formulation of controlled-release oxycodone rose substantially near a major international border crossing following the introduction of a tamper-resistant formulation in the United States. It is possible that the restriction of this finding to the area surrounding the Detroit-Windsor Tunnel reflects specific characteristics of this border crossing, including its high

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

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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.

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

OpenAIRE

Anderson, Collin; MacKay, Mark

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...

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.

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

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Feng XQ

2017-05-01

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

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

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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.

Consumption of three strong opioids (morphine, oxycodone and fentanyl) in seven European countries during seven years (2003-2009).

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Hudec, R; Tisonova, J; Foltan, V; Kristova, V

2013-01-01

The aim was to analyse the consumption of selected strong opioid analgesics during a seven-year period of 2003-2009 in order to compare Slovak consumption with that in six other European countries and to determine our position. Drug consumption data from the State Institute for Drug Control in Slovak Republic were used. As to the data from other countries, annual health statistics published on websites were used in comparison. Obviously the consumption of one of studied opioid drugs with transdermal aplication route, particularly fentanyl, tended to increase in all countries during the observed period. Oxycodone tends to yield a rapid increase in consumption as well. As opposed to the latter drugs, the consumption of morphine was decreasing throughout the observed period. The consumption of these drugs in Slovakia remains low (except for that of fentanyl). Our analysis confirmed a clear shift from oral to transdermal therapy as well as usage of newer drugs. Drug consumption data are a relatively new source of information for health research. Our analysis showed increasing trends in fentanyl (patch opioid) consumption in all compared countries as well as an increasing consumption of oxycodone and decreasing consumption of morphine (Fig. 3, Ref. 17).

A preclinical physiological assay to test modulation of knee joint pain in the spinal cord: effects of oxycodone and naproxen.

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Miranda, Jason A; Stanley, Phil; Gore, Katrina; Turner, Jamie; Dias, Rebecca; Rees, Huw

2014-01-01

Sensory processing in the spinal cord during disease states can reveal mechanisms for novel treatments, yet very little is known about pain processing at this level in the most commonly used animal models of articular pain. Here we report a test of the prediction that two clinically effective compounds, naproxen (an NSAID) and oxycodone (an opiate), are efficacious in reducing the response of spinal dorsal horn neurons to noxious knee joint rotation in the monosodium iodoacetate (MIA) sensitized rat. The overall objective for these experiments was to develop a high quality in vivo electrophysiology assay to confidently test novel compounds for efficacy against pain. Given the recent calls for improved preclinical experimental quality we also developed and implemented an Assay Capability Tool to determine the quality of our assay and ensure the quality of our results. Spinal dorsal horn neurons receiving input from the hind limb knee joint were recorded in anesthetized rats 14 days after they were sensitized with 1 mg of MIA. Intravenous administered oxycodone and naproxen were each tested separately for their effects on phasic, tonic, ongoing and afterdischarge action potential counts in response to innocuous and noxious knee joint rotation. Oxycodone reduced tonic spike counts more than the other measures, doing so by up to 85%. Tonic counts were therefore designated the primary endpoint when testing naproxen which reduced counts by up to 81%. Both reductions occurred at doses consistent with clinically effective doses for osteoarthritis. These results demonstrate that clinically effective doses of standard treatments for osteoarthritis reduce pain processing measured at the level of the spinal cord for two different mechanisms. The Assay Capability Tool helped to guide experimental design leading to a high quality and robust preclinical assay to use in discovering novel treatments for pain.

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

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Ughi N

2016-03-01

Full Text Available Nicola Ughi, Chiara Crotti, Francesca Ingegnoli Division of Rheumatology, Department of Clinical Sciences and Community Health, Gaetano Pini Institute, The University of Milan, Milan, Italy Abstract: 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. Keywords: oxycodone, naloxone, systemic sclerosis, pain, digital ulcer, scleroderma, analgaesia, wound healing, opioids, calcinosis, UCLA-SCTC GIT 2.0

Monitoring of internet forums to evaluate reactions to the introduction of reformulated OxyContin to deter abuse.

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McNaughton, Emily C; Coplan, Paul M; Black, Ryan A; Weber, Sarah E; Chilcoat, Howard D; Butler, Stephen F

2014-05-02

Reformulating opioid analgesics to deter abuse is one approach toward improving their benefit-risk balance. To assess sentiment and attempts to defeat these products among difficult-to-reach populations of prescription drug abusers, evaluation of posts on Internet forums regarding reformulated products may be useful. A reformulated version of OxyContin (extended-release oxycodone) with physicochemical properties to deter abuse presented an opportunity to evaluate posts about the reformulation in online discussions. The objective of this study was to use messages on Internet forums to evaluate reactions to the introduction of reformulated OxyContin and to identify methods aimed to defeat the abuse-deterrent properties of the product. Posts collected from 7 forums between January 1, 2008 and September 30, 2013 were evaluated before and after the introduction of reformulated OxyContin on August 9, 2010. A quantitative evaluation of discussion levels across the study period and a qualitative coding of post content for OxyContin and 2 comparators for the 26 month period before and after OxyContin reformulation were conducted. Product endorsement was estimated for each product before and after reformulation as the ratio of endorsing-to-discouraging posts (ERo). Post-to-preintroduction period changes in ERos (ie, ratio of ERos) for each product were also calculated. Additionally, post content related to recipes for defeating reformulated OxyContin were evaluated from August 9, 2010 through September 2013. Over the study period, 45,936 posts related to OxyContin, 18,685 to Vicodin (hydrocodone), and 23,863 to Dilaudid (hydromorphone) were identified. The proportion of OxyContin-related posts fluctuated between 6.35 and 8.25 posts per 1000 posts before the reformulation, increased to 10.76 in Q3 2010 when reformulated OxyContin was introduced, and decreased from 9.14 in Q4 2010 to 3.46 in Q3 2013 in the period following the reformulation. The sentiment profile for Oxy

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

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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

The Effect of Opioid Prescribing Guidelines on Prescriptions by Emergency Physicians in Ohio.

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Weiner, Scott G; Baker, Olesya; Poon, Sabrina J; Rodgers, Ann F; Garner, Chad; Nelson, Lewis S; Schuur, Jeremiah D

2017-12-01

The objective of our study is to evaluate the association between Ohio's April 2012 emergency physician guidelines aimed at reducing inappropriate opioid prescribing and the number and type of opioid prescriptions dispensed by emergency physicians. We used Ohio's prescription drug monitoring program data from January 1, 2010, to December 31, 2014, and included the 5 most commonly prescribed opioids (hydrocodone, oxycodone, tramadol, codeine, and hydromorphone). The primary outcome was the monthly statewide prescription total of opioids written by emergency physicians in Ohio. We used an interrupted time series analysis to compare pre- and postguideline level and trend in number of opioid prescriptions dispensed by emergency physicians per month, number of prescriptions stratified by 5 commonly prescribed opioids, and number of prescriptions for greater than 3 days' supply of opioids. Beginning in January 2010, the number of prescriptions dispensed by all emergency physicians in Ohio decreased by 0.3% per month (95% confidence interval [CI] -0.49% to -0.15%). The implementation of the guidelines in April 2012 was associated with a 12% reduction (95% CI -17.7% to -6.3%) in the level of statewide total prescriptions per month and an additional decline of 0.9% (95% CI -1.1% to -0.7%) in trend relative to the preguideline trend. The estimated effect of the guidelines on total monthly prescriptions greater than a 3-day supply was an 11.2% reduction in level (95% CI -18.8% to -3.6%) and an additional 0.9% (95% CI -1.3% to -0.5%) decline in trend per month after the guidelines. Guidelines were also associated with a reduction in prescribing for each of the 5 individual opioids, with various effect. In Ohio, emergency physician opioid prescribing guidelines were associated with a decrease in the quantity of opioid prescriptions written by emergency physicians. Although introduction of the guidelines occurred in parallel with other opioid-related interventions, our

Determination of oxycodone and its major metabolites noroxycodone and oxymorphone by ultra-high-performance liquid chromatography tandem mass spectrometry in plasma and urine: application to real cases.

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Pantano, Flaminia; Brauneis, Stefano; Forneris, Alexandre; Pacifici, Roberta; Marinelli, Enrico; Kyriakou, Chrystalla; Pichini, Simona; Busardò, Francesco Paolo

2017-08-28

Oxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma concentrations of parent drug and its active metabolite, oxymorphone. To evaluate patient compliance and to set up therapeutic drug monitoring (TDM), an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay was developed and validated for the parent drug and its major metabolites noroxycodone and oxymorphone. Extraction of analytes from plasma and urine samples was obtained by simple liquid-liquid extraction. The chromatographic separation was achieved with a reversed phase column using a linear gradient elution with two solvents: acetic acid 1% in water and methanol. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI). Separation of analytes was obtained in less than 5 min. Linear calibration curves for all the analytes under investigation in urine and plasma samples showed determination coefficients (r2) equal or higher than 0.990. Mean absolute analytical recoveries were always above 86%. Intra- and inter-assay precision (measured as coefficient of variation, CV%) and accuracy (measured as % error) values were always better than 13%. Limit of detection at 0.06 and 0.15 ng/mL and limit of quantification at 0.2 and 0.5 ng/mL for plasma and urine samples, respectively, were adequate for the purpose of the present study. Rapid extraction, identification and quantification of oxycodone and its metabolites both in urine and plasma by UHPLC-MS/MS assay was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in patients under oxycodone treatment.

Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial.

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Walsh, Sharon L; Comer, Sandra D; Lofwall, Michelle R; Vince, Bradley; Levy-Cooperman, Naama; Kelsh, Debra; Coe, Marion A; Jones, Jermaine D; Nuzzo, Paul A; Tiberg, Fredrik; Sheldon, Behshad; Kim, Sonnie

2017-09-01

Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation. To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD. This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit). A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18 mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24 mg (n = 22) or 32 mg (n = 25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13). The primary end point was maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes. A total of 46 of 47 randomized participants (mean [SD] age, 35.5 [9] years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24 mg: effect size, 0.617; P opioid blockade and withdrawal suppression. The results support the use of this depot formulation for treatment initiation and stabilization of patients with OUD, with

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

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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

Food and Drug Administration upscheduling of hydrocodone and the effects on nurse practitioner pain management practices.

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Mack, Rachel

2018-06-01

In 2013, the Advisory Committee of the Food and Drug Administration determined hydrocodone combination medications (HCMs) needed tighter regulation due to high abuse potential; they recommended upscheduling HCMs from Schedule III to II. The purpose of this study was to examine the effect of upscheduling of HCMs on pain management practices of advanced practiced registered nurses (APRNs) in Oklahoma. In this qualitative study, 25 participants described their primary care experiences after the upscheduling. A thematic analysis was used to understand the effects on APRN pain management practices. The upscheduling of HCMs has greatly affected the pain management practices of APRNs in a state where Schedule II narcotic prescribing is forbidden. Findings will assist APRNs with improving patient access to care, implementing practice regulations, and exploring options for alternative pain therapies in primary care. Upscheduling of HCMs has had a severe impact on APRNs, affecting their prescribing practices and leading to increased referrals. They noted limited treatment options, increased health care costs, and decreased access to care. The APRNs understand the problem of prescription opioid abuse, diversion, and misuse. A consensus model could standardize the regulatory process for APRNs, increase interstate mobility for practice, and increase access to APRN care nationwide.

Effects of oxycodone on brain responses to emotional images.

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Wardle, Margaret C; Fitzgerald, Daniel A; Angstadt, Michael; Rabinak, Christine A; de Wit, Harriet; Phan, K Luan

2014-11-01

Evidence from animal and human studies suggests that opiate drugs decrease emotional responses to negative stimuli and increase responses to positive stimuli. Such emotional effects may motivate misuse of oxycodone (OXY), a widely abused opiate. Yet, we know little about how OXY affects neural circuits underlying emotional processing in humans. We examined effects of OXY on brain activity during presentation of positive and negative visual emotional stimuli. We predicted that OXY would decrease amygdala activity to negative stimuli and increase ventral striatum (VS) activity to positive stimuli. Secondarily, we examined the effects of OXY on other emotional network regions on an exploratory basis. In a three-session study, healthy adults (N = 17) received placebo, 10 and 20 mg OXY under counterbalanced, double-blind conditions. At each session, participants completed subjective and cardiovascular measures and underwent functional MRI (fMRI) scanning while completing two emotional response tasks. Our emotional tasks reliably activated emotional network areas. OXY produced subjective effects but did not alter either behavioral responses to emotional stimuli or activity in our primary areas of interest. OXY did decrease right medial orbitofrontal cortex (MOFC) responses to happy faces. Contrary to our expectations, OXY did not affect behavioral or neural responses to emotional stimuli in our primary areas of interest. Further, the effects of OXY in the MOFC would be more consistent with a decrease in value for happy faces. This may indicate that healthy adults do not receive emotional benefits from opiates, or the pharmacological actions of OXY differ from other opiates.

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

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Pergolizzi, J

2018-02-01

Full Text Available Joseph V Pergolizzi, Jr,1 Robert Taylor Jr,1 Jo Ann LeQuang,1 Robert B Raffa2,3 On behalf of the NEMA Research Group 1NEMA Research Inc., Naples, FL, USA; 2University of Arizona College of Pharmacy, Tucson, AZ, USA; 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF. ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations. Keywords: oxycodone/naltrexone, abuse-deterrent formulation, abuse-deterrent opioid, oxycodone, abuse liability

Most drug overdose deaths from nonprescription opioids

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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 …

Drug take back in Hawai'i: partnership between the University of Hawai'i Hilo College of Pharmacy and the Narcotics Enforcement Division.

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Ma, Carolyn S; 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.

Pain management of musculoskeletal injuries in children: current state and future directions.

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Ali, Samina; Drendel, Amy L; Kircher, Janeva; Beno, Suzanne

2010-07-01

Pain is the most common reason for seeking health care in the Western world and is a contributing factor in up to 80% of all emergency department (ED) visits. In the pediatric emergency setting, musculoskeletal injuries are one of the most common painful presentations. Inadequate pain management during medical care, especially among very young children, can have numerous detrimental effects. No standard of care exists for the management of acute musculoskeletal injury-related pain in children. Within the ED setting, pain from such injuries has been repeatedly shown to be undertreated. Upon completion of this CME article, the reader should be better able to (1) distinguish multiple nonpharmacological techniques for minimizing and treating pain and anxiety in children with musculoskeletal injuries, (2) apply recent medical literature in deciding pharmacological strategies for the treatment of children with musculoskeletal injuries, and (3) interpret the basic principles of pharmacogenomics and how they relate to analgesic efficacy. Pediatric musculoskeletal injuries are both common and painful. There is growing evidence that, in addition to pharmacological therapy, nonpharmacological methods can be introduced to improve analgesia in the ED and after discharge. Traditionally, acetaminophen with codeine has been used to treat moderate orthopedic injury-related pain in children. Other oral opioids (hydrocodone, oxycodone) are gaining popularity, as well. Current data suggest that ibuprofen is at least as effective as acetaminophen-codeine and codeine alone. Medication compliance might be improved if adverse effects were minimized, and ibuprofen has been shown to have a similar or better adverse effect profile than the oral opioids to which it has been compared. Pharmacogenomic data show that nearly 50% of individuals have at least 1 reduced functioning allele resulting in suboptimal conversion of codeine to active analgesic, so it is not surprising that codeine

Contamination profiles, mass loadings, and sewage epidemiology of neuropsychiatric and illicit drugs in wastewater and river waters from a community in the Midwestern United States.

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Skees, Allie J; Foppe, Katelyn S; Loganathan, Bommanna; Subedi, Bikram

2018-08-01

In this study, residues of the neuropsychiatric and illicit drugs including stimulants, opioids, hallucinogens, antischizophrenics, sedatives, and antidepressants were determined in influent and effluent samples from a small wastewater treatment plant, a receiving creek, and river waters in the Four Rivers region of the Midwestern United States. Nineteen neuropsychiatric drugs, eight illicit drugs, and three metabolites of illicit drugs were detected and quantitated in the water samples using HPLC-MS/MS. Residual concentrations of the drugs varied from below the detection limit to sub-μg/L levels. The source of residual cocaine and benzoylecgonine in wastewater is primarily from human consumption of cocaine rather than direct disposal. Wastewater based epidemiology is utilized to estimate the community usage of drugs based on the concentration of drug residues in wastewater, wastewater inflow, and the population served by the centralized wastewater treatment plant. The per-capita consumption rate of methamphetamine (1740 mg/d/1000 people) and amphetamine (970 mg/d/1000 people) found in this study were the highest reported per-capita consumption rates in the USA. Antidepressant venlafaxine found to have the highest environmental emission from the WWTP (333 ± 160 mg/d/1000 people) followed by citalopram (132 ± 60.2 mg/d/1000 people), methamphetamine (111 ± 43.6 mg/d/1000 people), and hydrocodone (108 ± 90.1 mg/d/1000 people). Bee Creek, an immediate receiving water body, is found to be a source of several neuropsychiatric and illicit drugs including methamphetamine, methadone, alprazolam, oxazepam, temazepam, carbamazepine, venlafaxine, citalopram, sertraline, oxycodone, and hydrocodone (p < 0.036) in the Clarks River. Copyright © 2018 Elsevier B.V. All rights reserved.

Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

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Larochelle, Marc R; Zhang, Fang; Ross-Degnan, Dennis; Wharam, J Frank

2015-06-01

In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown. To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates. Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012). Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010. Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions. Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, -32.2 mg morphine-equivalent dose per member per quarter [95% CI, -38.1 to -26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was -11.3 (95% CI, -12.4 to -10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, -8.19 (95% CI, -9.30 to -7.08) for propoxyphene, and -16.2 (95% CI, -18.8 to -13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, -1.10 per 100,000 members per quarter [95% CI, -1.47 to -0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100

Twitter-Based Detection of Illegal Online Sale of Prescription Opioid.

Science.gov (United States)

Mackey, Tim K; Kalyanam, Janani; Katsuki, Takeo; Lanckriet, Gert

2017-12-01

To deploy a methodology accurately identifying tweets marketing the illegal online sale of controlled substances. We first collected tweets from the Twitter public application program interface stream filtered for prescription opioid keywords. We then used unsupervised machine learning (specifically, topic modeling) to identify topics associated with illegal online marketing and sales. Finally, we conducted Web forensic analyses to characterize different types of online vendors. We analyzed 619 937 tweets containing the keywords codeine, Percocet, fentanyl, Vicodin, Oxycontin, oxycodone, and hydrocodone over a 5-month period from June to November 2015. A total of 1778 tweets (marketing the sale of controlled substances online; 90% had imbedded hyperlinks, but only 46 were "live" at the time of the evaluation. Seven distinct URLs linked to Web sites marketing or illegally selling controlled substances online. Our methodology can identify illegal online sale of prescription opioids from large volumes of tweets. Our results indicate that controlled substances are trafficked online via different strategies and vendors. Public Health Implications. Our methodology can be used to identify illegal online sellers in criminal violation of the Ryan Haight Online Pharmacy Consumer Protection Act.

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

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

Employment and paid work among participants in a randomized controlled trial comparing diacetylmorphine and hydromorphone.

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Nikoo, Mohammadali; Vogel, Marc; Choi, Fiona; Song, Michael J; Burghardt, Jensen; Zafari, Zafar; Tabi, Katarina; Frank, Anastasia; Barbic, Skye; Schütz, Christian; Jang, Kerry; Krausz, Michael

2018-04-12

Employment is one of the less studied but a significant outcome of medication-assisted treatment. Thus, we aimed to explore employment outcomes of medication-assisted treatment with hydromorphone (HDM) or diacetylmorphine (DAM). The secondary aim was to estimate characteristics of this population as well as treatment-related factors associated with these outcomes. This was a secondary analysis of a randomized, double blind controlled trial. A total of 102 and 100 participants were randomized to receive injectable DAM or HDM for 6 months respectively. In stage 2, 144 participants were randomized again to receive either oral or injectable forms of the medication they received for another 6 months. Participants were interviewed at 5 timepoints: before and 3, 6, 9 and 12 months after treatment assignment. Generalized estimating equations (GEE) with a logit link was fitted to determine factors related to paid work in the past 30 days. Mean age of participants was 44.3 (SD = 9.6) and 59 (29.2%) participants were men. At each timepoint, 6-8 (3.6%-4.1%) participants reported employment in the past 30 days and 40 to 52 (19.7%-26.7%) reported minimum 1 day of paid work. University or college education [OR = 2.12: 95% CI = (1.25, 3.62), P = 0.01] was significantly associated with paid work after adjustment for age, gender, treatment arms, timepoints, days receiving study treatment, physical health, psychological health and crack cocaine use in the past 30 days. The rate of employment was lower among participants of this study compared to similar studies on heroin-assisted treatment. Higher education was associated with increased odds of paid work. A large gap exists between employment rate and the proportion of participants who reported paid work. Supported employment and occupational therapy could optimize the employment outcomes of this population. Copyright © 2018 Elsevier B.V. All rights reserved.

氢吗啡酮对硬膜外阻滞分娩镇痛时布比卡因最低有效浓度的影响%The minimum local analgesic concentration of epidural bupivacaine with hydromorphone for labour

Institute of Scientific and Technical Information of China (English)

林雷; 陈春; 柯齐斌; 汤和青; 方为; 侯俊

2015-01-01

目的：通过建立临床模型研究氢吗啡酮对硬膜外分娩镇痛时布比卡因最低有效镇痛浓度（MLAC）的影响，以探讨第一产程硬膜外镇痛过程中与氢吗啡酮配伍的布比卡因的浓度和剂量。方法选择单胎足月临产妇64例，ASAⅠ～Ⅱ级，均进入第一产程活跃期，分为两组：布比卡因对照组和布比卡因-氢吗啡酮组，每组30例。所有患者于 L3～4间隙行硬膜外穿刺置管，以10 mL／min 的速度分别给予15 mL 布比卡因注射液和含有200μg 氢吗啡酮注射液的布比卡因注射液。根据双盲、序贯的方法，以 VAPS 作为镇痛标准进行布比卡因适宜浓度的研究。结果 4例临产妇退出研究，余每组30例进入分析。两组布比卡因的MLAC 值分别为布比卡因对照组0．103％（95％ CI ：0．094％～0．113％）；布比卡因-氢吗啡酮组0．044％（95％CI ：0．034％～0．053％），差异有统计学意义（P ＜0．05）。两组间 Bromage 评分，患者心率（HR）、血压（BP）、胎心（FHR）、宫缩强度、不良反应的发生情况差异均无统计学意义（P ＞0．05）。结论该研究显示硬膜外腔复合使用氢吗啡酮能显著降低布比卡因的 MLAC，氢吗啡酮能安全地应用于硬膜外分娩镇痛。%Objective To investigate the minimum local analgesic concentration(MLAC)of epidural hydromorphone combined with bupivacaine for analgesia during the first stage of labor by establishing clinical model.Methods Sixty four labouring parturi-ents at 3-7 cm cervical dilation who requested epidural analgesia were allocated to one of two groups.After a lumbar epidural cath-eter was placed,study participants received 15 mL bupivacaine(n=30),bupivacaine with hydromorphone 200 μg(n=30).The con-centration of bupivacaine was determined by the response of the previous patient using 0 - 100 mm visual analog pain scores, with≤30 mm within 30 min defined as effective

Case report: efficacy and tolerability of ketamine in opioid-refractory cancer pain.

Science.gov (United States)

Amin, Priya; Roeland, Eric; Atayee, Rabia

2014-09-01

A 36-year-old female with metastatic breast cancer involving bones, liver, lung, and pleura/chest wall with worsening back pain received weight-based intravenous (IV) ketamine and was transitioned to oral ketamine for cancer-related neuropathic pain. She had responded poorly to outpatient pain regimen of oxycodone sustained and immediate release, hydromorphone, gabapentin, and duloxetine (approximate 480 mg total oral morphine equivalents [OME]), reporting an initial pain score of 10/10. She was started on hydromorphone parenteral patient-controlled analgesia (PCA) bolus dose in addition to her outpatient regimen. Despite escalating doses of opioids and the addition of a lidocaine 5% patch, the patient's pain remained uncontrolled 6 days after admission. On hospital day 7, utilizing a hospital weight-based ketamine protocol, the patient was started on subanesthetic doses of ketamine at 0.2 mg/kg/h (288 mg/24 h) and titrated over 2 days to 0.4 mg/kg/h (576 mg/24 h). Then, a 3-day rotation from intravenous to oral ketamine was initiated, and the patient was discharged on ketamine oral solution, 75 mg every 8 hours. When the patient's dose was increased to 0.4 mg/kg/h, adequate pain relief was charted by the nurse within 120 minutes, "patient pain free and resting comfortably." Her pain continued to be well managed, with an average pain score of 5/10 with the ketamine continuous infusion and sustained with conversion to oral ketamine without any report of side effects. This was a 37% reduction in pain scores. With the patient's stabilized dose of ketamine, opioid requirements decreased by 61.4% (1017.5 mg reduction in total OME). The use of weight-based dosing of IV continuous infusion and transition to oral ketamine was effective and tolerable in the management of opioid-refractory, neuropathic cancer pain. It is hoped that this case report promotes a discussion regarding ketamine dosing in refractory neuropathic cancer pain.

Point-of-care detection and real-time monitoring of intravenously delivered drugs via tubing with an integrated SERS sensor.

Science.gov (United States)

Wu, Hsin-Yu; Cunningham, Brian T

2014-05-21

We demonstrate an approach for detection, identification, and kinetic monitoring of drugs flowing within tubing, through the use of a plasmonic nanodome array (PNA) surface. The PNA structures are fabricated using a low-cost nanoreplica molding process upon a flexible plastic substrate that is subsequently integrated with a flow cell that connects in series with ordinary intravenous (IV) drug delivery tubing. To investigate the potential clinical applications for point-of-care detection and real-time monitoring, we perform SERS detection of ten pharmaceutical compounds (hydrocodone, levorphanol, morphine, oxycodone, methadone, phenobarbital, dopamine, diltiazem, promethazine, and mitoxantrone). We demonstrate dose-dependent SERS signal magnitude, resulting in detection limits (ng ml(-1)) well below typical administered dosages (mg ml(-1)). Further, we show that the detected drugs are not permanently attached to the PNA surface, and thus our approach is capable of performing continuous monitoring of drug delivery as materials flow through IV tubing that is connected in series with the sensor. Finally, we demonstrate the potential co-detection of multiple drugs when they are mixed together, and show excellent reproducibility and stability of SERS measurements for periods extending at least five days. The capabilities reported here demonstrate the potential to use PNA SERS surfaces for enhancing the safety of IV drug delivery.

Assessment and Comparison of Vitreous Humor as an Alternative Matrix for Forensic Toxicology Screening by GC-MS.

Science.gov (United States)

Metushi, Imir G; Fitzgerald, Robert L; McIntyre, Iain M

2016-05-01

Alternative specimens have been occasionally considered as substitutes for whole blood for postmortem toxicology testing. We studied the applicability of vitreous humor, and evaluated whether it would be suitable to replace (or augment) whole blood for routine drug screening. Results showed that from 51 autopsy cases, we were able to identify an aggregate of 209 findings in whole blood compared with 169 in vitreous. The total number of compounds identified was 71 for whole blood and 60 for vitreous humor. Quantitative analysis showed that whole-blood concentrations of trazodone were several fold higher than vitreous humor concentrations (1.42 ± 0.57 vs. 0.15 ± 0.05 mg/L, respectively) and similar results were also obtained for diazepam (0.37 ± 0.06 vs. 0.13 ± 0.01, respectively). For other drugs such as oxycodone, hydrocodone and doxylamine, a trend suggesting higher concentrations in vitreous humor vs. whole blood was observed; however, this was not significant. Our results are consistent with the limited work of other investigators, and suggest that vitreous humor could be an appropriate matrix for drug screening in postmortem toxicology. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Physicians' intention to prescribe hydrocodone combination products after rescheduling: A theory of reasoned action approach.

Science.gov (United States)

Fleming, Marc L; Driver, Larry; Sansgiry, Sujit S; Abughosh, Susan M; Wanat, Matthew; Sawant, Ruta V; Ferries, Erin; Reeve, Kathleen; Todd, Knox H

The U.S. Drug Enforcement Administration (DEA) rescheduled hydrocodone combination products (HCPs) in an attempt to mitigate the prescription opioid epidemic. Many in the medical and pharmacy community expressed concerns of unintended consequences as a result of rescheduling. This study examined physicians' intentions to prescribe HCPs after rescheduling using the framework of the theory of reasoned action (TRA). A cover letter containing a link to the online questionnaire was sent to physicians of the Texas Medical Association who were likely to prescribe opioids. The questionnaire assessed physicians' intentions to prescribe HCPs after rescheduling. Predictor variables included attitude toward rescheduling, subjective norm toward HCP prescribing, and past prescribing behavior of schedule II prescriptions. All variables were measured on a 7-point, Likert-type scale. Intention to prescribe as a dependent variable was regressed over TRA variables and respondent characteristics. A total of 1176 usable responses were obtained, yielding a response rate of 13.3%. Mean (M) age was 53.07 ± 11 and most respondents were male (70%) and Caucasian (75%). Physicians held a moderately positive intention to prescribe HCPs (M = 4.36 ± 2.08), held a moderately negative attitude towards rescheduling, M = 4.68 ± 1.51 (reverse coded). Subjective norm was moderately low, M = 3.06 ± 1.78, and past prescribing behavior M = 2.43 ± 1.21. The linear regression analysis indicated that attitude (β = 0.10; P = 0.006), subjective norm (β = 0.35; P < 0.0001) and past prescribing behavior (β = 0.59; P < 0.0001) were significant predictors of intention to prescribe HCPs after rescheduling. TRA was shown to be a predictive model of physicians' intentions to prescribe HCPs after rescheduling. Overall, physicians held a moderately positive intention to prescribe HCPs. Past behavior concerning schedule II prescribing was found to be the most significant predictor

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

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

2014-09-01

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

Drug: D02154 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available D02154 Mixture ... Drug Aspirin - oxycodone hydrochloride - oxycodone terephthalate ...mixt; Percodan (TN) Oxycodone hydrochloride [DR:D00847], Oxycodone terephthalate [DR:D03783], Aspirin [DR:D00109] ... ATC code: N02AJ18 ... PubChem: 7849215 ...

Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I.

Science.gov (United States)

Armstrong, Scott C; Cozza, Kelly L

2003-01-01

Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column. Morphine is a naturally occurring opiate that is metabolized chiefly through glucuronidation by uridine diphosphate glucuronosyl transferase (UGT) enzymes in the liver. These enzymes produce an active analgesic metabolite and a potentially toxic metabolite. In vivo drug-drug interaction studies with morphine are few, but they do suggest that inhibition or induction of UGT enzymes could alter morphine and its metabolite levels. These interactions could change analgesic efficacy. Hydromorphone and oxymorphone, close synthetic derivatives of morphine, are also metabolized primarily by UGT enzymes. Hydromorphone may have a toxic metabolite similar to morphine. In vivo drug-drug interaction studies with hydromorphone and oxymorphone have not been done, so it is difficult to make conclusions with these drugs.

Adverse events associated with opioid-containing cough and cold medications in children.

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Paul, Ian M; Reynolds, Kate M; Green, Jody L

2018-04-10

Until recently most of the scrutiny of opioid-containing cough and cold medications (CCMs) by the US Food and Drug Administration (FDA) was focused on codeine, only recently shifting equal focus to those containing hydrocodone. We characterized adverse events (AEs) in children Dictionary for Regulatory Activities with preferred terms reported. One hundred and fourteen of the 7035 (2%) cases reviewed involved an opioid-containing product. Ninety-eight cases involved an AE at least potentially related to the opioid ingredient (38 (39%) codeine; 60 (61%) hydrocodone). All three fatality cases involved hydrocodone with an antihistamine. Among non-fatalities, somnolence, lethargy, and/or respiratory depression were more commonly reported among hydrocodone cases than codeine cases (86% vs. 61%; p = .005). These safety surveillance data support the FDA's expanded label changes limiting opioid CCMs for children.

The association between nicotine dependence and physical health among people receiving injectable diacetylmorphine or hydromorphone for the treatment of chronic opioid use disorder

Directory of Open Access Journals (Sweden)

Heather Palis

2018-06-01

Full Text Available Introduction: People with chronic opioid use disorder often present to treatment with individual and structural vulnerabilities and remain at risk of reporting adverse health outcomes. This risk is greatly compounded by tobacco smoking, which is highly prevalent among people with chronic opioid use disorder. Despite the known burden of tobacco smoking on health, the relationship between nicotine dependence and health has not been studied among those receiving injectable opioid agonist treatment. As such, the present study aims to explore the association between nicotine dependence and physical health among participants of the Study to Assess Longer-Term Opioid Medication Effectiveness (SALOME at baseline and six-months. Methods: SALOME was a double-blind phase III clinical trial testing the non-inferiority of injectable hydromorphone to injectable diacetylmorphine for chronic opioid use disorder. Participants reporting tobacco smoking were included in a linear regression analysis of physical health at baseline (before receiving treatment and at six-months. Results: At baseline, nicotine dependence score, lifetime history of emotional, physical, or sexual abuse and prior month safe injection site access were independently and significantly associated with physical health. At six-months nicotine dependence score was the only variable that maintained this significant and independent association with physical health. Conclusions: Findings indicate that after six-months, the injectable treatment effectively brought equity to patients' physical health status, yet the association with nicotine dependence remained. Findings could inform whether the provision of treatment for nicotine dependence should be made a priority in settings where injectable opioid agonist treatment is delivered to achieve improvements in overall physical health in this population.

Hydromorphone Rectal

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... the thyroid gland produces less hormone than normal); Addison's disease (condition in which the adrenal gland produces less hormone than normal); any condition that causes difficulty urinating such as an enlarged prostate (a ...

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

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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.

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

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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. © 2015 Wiley Periodicals, Inc.

A comparison between the administration of oral prolonged-release oxycodone-naloxone and transdermal fentanyl in patients with moderate-to-severe cancer pain: a propensity score analysis

Directory of Open Access Journals (Sweden)

Roberto A

2017-09-01

Full Text Available A Roberto,1 MT Greco,2 L Legramandi,3 F Galli,3 M Galli,4 O Corli1 1Pain and Palliative Care Research Unit, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 2Department of Clinical Sciences and Community, University of Milan, Milan, Italy, 3Methodology for Clinical Research Laboratory, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 4Scientific Medical Communication srl, Novara, Italy Background: Opioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF and oral prolonged-release oxycodone-naloxone (OXN-PR are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared.Patients and methods: Cancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days. The primary endpoint was 28-day analgesic response rate (average pain intensity decrease ≥30% from baseline. Other outcome measures included opioid daily dose changes over time; need for adjuvant analgesics; number of switches; premature discontinuation; presence and severity of constipation; and other adverse drug reactions. To compare the efficacy and the safety of TDF and OXN-PR, we used the propensity score analysis to adjust for heterogeneity between the two patient groups.Results: Three hundred ten out of 336 patients originally treated (119 TDF and 191 OXN-PR were included in the comparative analysis. The amount of responders was comparable after TDF (75.3% and OXN-PR administration (82.9%, not significant [NS]. The final opioid daily dose expressed as morphine equivalent was 113.6 mg for TDF and 44.5 mg for OXN-PR (p<0.0001. A daily opioid dose escalation >5% was less common after

Urine specimen detection of zolpidem use in patients with pain.

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Mann, Lindsey M; Atayee, Rabia S; Best, Brookie M; Morello, Candis M; Ma, Joseph D

2014-01-01

This study examined zolpidem and concurrent opioid, benzodiazepine, other central nervous system (CNS) depressants, and alcohol use. Urine specimens were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Specimens were tested for zolpidem (n = 71,919) and separated into a provider-reported medication list documenting (n = 5,257) or not documenting zolpidem use (n = 66,662). Zolpidem-positive specimens were further separated into reported and unreported use cohorts. The total number of zolpidem-positive specimens in the reported and unreported use cohorts was 3,391 and 3,190, respectively. Non-informed prescribers were 4.4% (3,190/71,919) among the general population and 48.5% (3,190/6,581) when only zolpidem users were considered. In the zolpidem user population, the most common concurrent opioids in both cohorts were hydrocodone and oxycodone. Alprazolam and clonazepam were higher in the unreported use cohort (P ≤ 0.05). The unreported use cohort also had a higher detection of zolpidem plus a benzodiazepine (49.7 vs. 46%; P ≤ 0.05), zolpidem plus an opioid and a benzodiazepine (40.8% vs. 37.4%; P ≤ 0.05) and zolpidem plus an opioid, a benzodiazepine, and an other CNS depressant (12.9 vs. 10.9%; P ≤ 0.05). Concurrent use of zolpidem, an opioid, a benzodiazepine and an other CNS depressant is prevalent in a pain patient population. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Novel polymeric bioerodable microparticles for prolonged-release intrathecal delivery of analgesic agents for relief of intractable cancer-related pain.

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Han, Felicity Y; Thurecht, Kristofer J; Lam, Ai-Leen; Whittaker, Andrew K; Smith, Maree T

2015-07-01

Intractable cancer-related pain complicated by a neuropathic component due to nerve impingement is poorly alleviated even by escalating doses of a strong opioid analgesic. To address this unmet medical need, we developed sustained-release, bioerodable, hydromorphone (potent strong opioid)- and ketamine (analgesic adjuvant)-loaded microparticles for intrathecal (i.t.) coadministration. Drug-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared using a water-in-oil-in-water method with evaporation. Encapsulation efficiency of hydromorphone and ketamine in PLGA (50:50) microparticles was 26% and 56%, respectively. Microparticles had the desired size range (20-60 μm) and in vitro release was prolonged at ≥28 days. Microparticles were stable for ≥6 months when stored refrigerated protected from light in a desiccator. Desirably, i.t. injected fluorescent dye-labeled PLGA microparticles in rats remained in the lumbar region for ≥7 days. In a rat model of neuropathic pain, i.t. coinjection of hydromorphone- and ketamine-loaded microparticles (each 1 mg) produced analgesia for 8 h only. Possible explanations include inadequate release of ketamine and/or hydromorphone into the spinal fluid, and/or insufficient ketamine loading to prevent development of analgesic tolerance to the released hydromorphone. As sub-analgesic doses of i.t. ketamine at 24-48 h intervals restored analgesia on each occasion, insufficient ketamine loading appears problematic. We will investigate these issues in future work. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

76 FR 51417 - Surinder Dang, M.D.; Revocation of Registration

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2011-08-18

... and handed him a business card listing her name as R.K. and her position as ``president.'' Id. R.K... the latter's report.\\7\\ Id. at 6. \\7\\ More specifically, there were 14 bottles of 500 count of hydrocodone/apap 7.5/500 mg, 10 bottles of 500 count hydrocodone/ apap 10/500 mg, 36 bottles of 500 count...

Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl.

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Lloyd, Renae A; Hotham, Elizabeth; Hall, Catherine; Williams, Marie; Suppiah, Vijayaprakash

2017-12-01

Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl. A literature search of databases Medline and Embase was carried out, and studies up to April 2016 were included in this review. Studies were included based on a combination of key words: chronic pain and related terms, pharmacogenetics and related terms, and opioids and related terms. Among the 1,408 individual papers retrieved from the search in Medline and Embase, 32 original articles were included in this review, with none related to codeine. The 32 papers reported various study designs, opioids, and polymorphisms being studied for associations with treatment outcomes. This literature review reveals that variants in ABCB1, OPRM1, and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects. Currently, there are few validated studies to form a strong evidence base to support pharmacogenomics testing when initiating opioid therapy. However, the field of pharmacogenomics in chronic pain is likely to expand over the coming years, with the increasing number of treatment options available and larger cohorts being assembled in order to identify true associations. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Ketamine Use for Successful Resolution of Post-ERCP Acute Pancreatitis Abdominal Pain

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Agerwala, Suneel M.; Sundarapandiyan, Divya; Weber, Garret

2017-01-01

We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and post...

Oxycodone

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... used to the effects of the medication) to opioid medications because they have taken this type of ... stop taking this medication suddenly, you may experience withdrawal symptoms such as restlessness, watery eyes, runny nose, ...

Using Pill Identification Calls to Poison Centers as a Marker of Drug Abuse at Three Texas Military Bases.

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Ng, Patrick C; Maddry, Joseph K; Sessions, Daniel; Borys, Douglas J; Bebarta, Vikhyat S

2017-11-01

Opioid abuse is a growing problem in civilian communities, and it has developed in the military as well. Telephone calls to poison centers requesting pill identification (ID) is a marker of drug abuse. This study identifies the number of pill ID calls made to the poison centers from areas containing and surrounding three Texas military bases during an 8-year period. We performed a retrospective observational study identifying calls to certified poison centers in Texas from 2002 to 2009 that identified hydrocodone tablets and other pain medications. We noted the calls made from ZIP codes containing and surrounding the three largest military bases in Texas. We reviewed 75,537 drug ID calls for any drug from the ZIP codes of interest. Total drug ID calls increased 105% and the number of calls for hydrocodone increased 463%. In our study most of the drug ID calls from military communities in Texas were for hydrocodone. The rate of calls for hydrocodone increased more than the rate of calls for other analgesics from 2002 to 2009. Using drug ID calls as a surrogate of drug abuse, our results suggest that hydrocodone abuse has increased within military communities and that poison center data can be a reliable surrogate for prescription drug abuse near military bases. Future studies are needed to further understand the extent of this problem in military and civilian communities. We can use this information to heighten awareness, influence prescription practices, establish practice guidelines, and develop educational programs to mitigate the increasing rate of prescription analgesic abuse in the United States.

Lumbar neuropathic pain of lower limbs treated by spinal infusion of ziconotide a case – report

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Luca Quadrino

2008-09-01

Full Text Available The Author reports the case of a patient with severe lumbar pain unresponsive to NSAIDs. Initial treatment with tramadol gave poor results and a new protocol with hydromorphone – pregabalin was started. The analgesic response was observed only following high hydromorphone doses, associated with unacceptable side effects. A spinal device for continuous intrathecal infusion was then implanted, in order to administer ziconotide, a new opioid drug. Associated therapy included hydromorphone – pregabalin. At the 4 mcg/die dose ziconotide resulted highly effective (with a VAS reduction pain 6-7 to 2-3 even at 1st day after implantation; in addition at day 10, opioid dose was strongly reduced and pregabalin withdrawn. The treatment was associated with a good tolerability. The encouraging results prompted the Author to test ziconotide in further cases of severe chronic pain.

Effects of Modification of Pain Protocol on Incidence of Post Operative Nausea and Vomiting.

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Schwarzkopf, Ran; Snir, Nimrod; Sharfman, Zachary T; Rinehart, Joseph B; Calderon, Michael-David; Bahn, Esther; Harrington, Brian; Ahn, Kyle

2016-01-01

A Perioperative Surgical Home (PSH) care model applies a standardized multidisciplinary approach to patient care using evidence-based medicine to modify and improve protocols. Analysis of patient outcome measures, such as postoperative nausea and vomiting (PONV), allows for refinement of existing protocols to improve patient care. We aim to compare the incidence of PONV in patients who underwent primary total joint arthroplasty before and after modification of our PSH pain protocol. All total joint replacement PSH (TJR-PSH) patients who underwent primary THA (n=149) or TKA (n=212) in the study period were included. The modified protocol added a single dose of intravenous (IV) ketorolac given in the operating room and oxycodone immediate release orally instead of IV Hydromorphone in the Post Anesthesia Care Unit (PACU). The outcomes were (1) incidence of PONV and (2) average pain score in the PACU. We also examined the effect of primary anesthetic (spinal vs . GA) on these outcomes. The groups were compared using chi-square tests of proportions. The incidence of post-operative nausea in the PACU decreased significantly with the modified protocol (27.4% vs . 38.1%, p=0.0442). There was no difference in PONV based on choice of anesthetic or procedure. Average PACU pain scores did not differ significantly between the two protocols. Simple modifications to TJR-PSH multimodal pain management protocol, with decrease in IV narcotic use, resulted in a lower incidence of postoperative nausea, without compromising average PACU pain scores. This report demonstrates the need for continuous monitoring of PSH pathways and implementation of revisions as needed.

Complex mixtures, complex responses: Assessing pharmaceutical mixtures using field and laboratory approaches

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Schoenfuss, Heiko L.; Furlong, Edward T.; Phillips, Patrick J.; Scott, Tia-Marie; Kolpin, Dana W.; Cetkovic-Cvrlje, Marina; Lesteberg, Kelsey E.; Rearick, Daniel C.

2016-01-01

Pharmaceuticals are present in low concentrations (pharmaceutical formulation facilities. Using existing concentration data, the authors assessed pharmaceuticals in laboratory exposures of fathead minnows (Pimephales promelas) and added environmental complexity through effluent exposures. In the laboratory, larval and mature minnows were exposed to a simple opioid mixture (hydrocodone, methadone, and oxycodone), an opioid agonist (tramadol), a muscle relaxant (methocarbamol), a simple antidepressant mixture (fluoxetine, paroxetine, venlafaxine), a sleep aid (temazepam), or a complex mixture of all compounds. Larval minnow response to effluent exposure was not consistent. The 2010 exposures resulted in shorter exposed minnow larvae, whereas the larvae exposed in 2012 exhibited altered escape behavior. Mature minnows exhibited altered hepatosomatic indices, with the strongest effects in females and in mixture exposures. In addition, laboratory-exposed, mature male minnows exposed to all pharmaceuticals (except the selective serotonin reuptake inhibitor mixture) defended nest sites less rigorously than fish in the control group. Tramadol or antidepressant mixture exposure resulted in increased splenic T lymphocytes. Only male minnows exposed to whole effluent responded with increased plasma vitellogenin concentrations. Female minnows exposed to pharmaceuticals (except the opioid mixture) had larger livers, likely as a compensatory result of greater prominence of vacuoles in liver hepatocytes. The observed alteration of apical endpoints central to sustaining fish populations confirms that effluents containing waste streams from pharmaceutical formulation facilities can adversely impact fish populations but that the effects may not be temporally consistent. The present study highlights the importance of including diverse biological endpoints spanning levels of biological organization and life stages when assessing contaminant interactions.

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

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

2015-06-01

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

Identifying Drugs

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... Morphine Opium Oxycodone PCP (Phencyclidine) Peyote and Mescaline Psilocybin Rohypnol Salvia Divinorum Spice/ K2, Synthetic Marijuana Steroids ... Morphine Opium Oxycodone PCP (Phencyclidine) Peyote and Mescaline Psilocybin Rohypnol Salvia Divinorum Spice/ K2, Synthetic Marijuana Steroids ...

Overprescription of postoperative narcotics: a look at postoperative pain medication delivery, consumption and disposal in urological practice.

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Bates, Cory; Laciak, Robert; Southwick, Andrew; Bishoff, Jay

2011-02-01

Prescription narcotic abuse is a significant social problem. Surplus medication following surgery is 1 source of prescription diversion. We assessed prescribing practices, consumption and disposal of prescribed narcotics after urological surgery. Surveys were administered to a 3-month consecutive sample of adult patients who underwent surgery performed by full and adjunct University of Utah Urology faculty. Surveys were performed 2 to 4 weeks postoperatively. With the exception of the investigators, prescribing physicians had no prior knowledge of the study. Data collected included perception of pain control, type and quantity of medication prescribed, quantity of leftover medication, refills needed, disposal instructions and surplus medication disposition. Overall 47% of 586 patients participated in the study. Hydrocodone was prescribed most commonly (63%), followed by oxycodone (35%), and 86% of the patients were satisfied with pain control. Of the dispensed narcotics 58% was consumed and 12% of patients requested refills. A total of 67% of patients had surplus medication from the initial prescription and 92% received no disposal instructions for surplus medication. Of those patients with leftover medication 91% kept the medication at home while 6% threw it in the trash, 2% flushed it down the toilet and less than 1% returned it to a pharmacy. Overprescription of narcotics is common and retained surplus medication presents a readily available source of opioid diversion. It appears that no entity on the prescribing or dispensing ends of prescription opioid delivery is fulfilling the responsibility to accurately educate patients on proper surplus medication disposal. Surgeons should analyze prescribing practices and consider decreasing the quantity of postoperative narcotics prescribed. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Factors Associated With the Prophylactic Prescription of a Bowel Regimen to Prevent Opioid-Induced Constipation.

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Chen, Nancy Y; Nguyen, Eugene; Schrager, Sheree M; Russell, Christopher J

2016-11-01

Identify factors associated with the prophylactic prescription of a bowel regimen with an inpatient opioid prescription. This was a retrospective cohort study from June 1, 2013, to October 31, 2014 of pediatric inpatients prescribed an oral or intravenous opioid on the general medical/surgical floors. We identified patients with or without a prophylactic prescription of a bowel regimen. We obtained patient demographics, prescriber training level and service and used multivariate logistic regression to analyze the factors associated with prophylactic bowel regimen and opioid prescription. Of the 6682 encounters that met study criteria, only 966 (14.5%) encounters had prophylactic prescriptions. Patient factors associated with prophylactic prescription include increasing age (per year; odds ratio [OR] = 1.06, 95% confidence interval [CI] 1.05-1.07) and sickle cell diagnosis (OR = 3.19, 95% CI 2.08-4.91). Medication factors associated with prophylactic prescription include a scheduled opioid prescription (OR = 1.75, 95% CI 1.46-2.1) and a prescription for oxycodone (OR = 3.59, 95% CI 2.57-5.00) or morphine (OR = 1.84, 95% CI 1.39-2.44), compared with acetaminophen-hydrocodone. Compared with medical providers, surgeons were less likely (OR = 0.43, 95% CI 0.35-0.53) and pain service providers were more likely to prescribe a prophylactic bowel regimen (OR = 4.12, 95% CI 3.13-5.43). More than 85% of inpatient opioid prescriptions did not receive a prophylactic bowel regimen. Future research should examine factors (eg, clinical decision support tools) to increase prophylactic prescription of bowel regimens with opioids for populations found to have lower rates. Copyright © 2016 by the American Academy of Pediatrics.

Hydrocodone and acetaminophen overdose

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... of Drugs . 16th ed. Waltham, MA: Elsevier; 2016:474-493. Bardsley CH. Opioids. In: Marx JA, Hockberger ... RSS Follow us Disclaimers Copyright Privacy Accessibility Quality Guidelines Viewers & Players MedlinePlus Connect for EHRs For Developers ...

Effectiveness of injection of local anesthetic into the retrobulbar space for postoperative analgesia following eye enucleation in dogs.

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Myrna, Kathern E; Bentley, Ellison; Smith, Lesley J

2010-07-15

To assess the efficacy of a retrobulbar bupivacaine nerve block for postoperative analgesia following eye enucleation in dogs. Randomized controlled trial. 22 dogs. Client-owned dogs admitted to the hospital for routine eye enucleation were enrolled with owner consent and randomly assigned to a treatment (bupivacaine hydrochloride) or control (saline [0.9% NaCl] solution) group. Baseline subjective pain scores were recorded. Anesthesia consisted of hydromorphone and midazolam preoperatively, thiopental or propofol for induction, and isoflurane in oxygen for maintenance. An inferior-temporal palpebral retrobulbar injection of either saline solution or bupivacaine was administered. Transpalpebral eye enucleation was performed. Pain scores were recorded at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours after extubation (time 0) by observers masked to treatment groups. Dogs were given hydromorphone (0.2 mg/kg [0.09 mg/lb], IM or IV) as a rescue analgesic if the subjective pain score totaled >or= 9 (out of a maximum total score of 18) or >or= 3 in any 1 category. 9 of 11 control dogs required a rescue dose of hydromorphone, but only 2 of 11 dogs in the bupivacaine treatment group required rescue analgesia. Mean time to treatment failure (ie, administration of rescue analgesia following extubation) was 0.56 hours (95% confidence interval, 0.029 to 1.095 hours) for the 11 dogs that received hydromorphone. Retrobulbar administration of bupivacaine in dogs in conjunction with traditional premedication prior to eye enucleation was an effective form of adjunctive analgesia and reduced the need for additional postoperative analgesics.

77 FR 57133 - T.J. Mcnichol, M.D.; Decision and Order

Science.gov (United States)

2012-09-17

... the latter's MRI and physical exam, he would give him 180 tablets of oxycodone 30mg but not the 15s... on July 28, 2011, Respondent ``distributed'' 180 tablets of oxycodone 30mg and 60 tablets of... MRI, and although ``UC1 provided no history or illness that warranted the distribution of a controlled...

Incidence of Delirium Among Patients Having Cancer Injected With Different Opioids for the First Time.

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Tanaka, Rei; Ishikawa, Hiroshi; Sato, Tetsu; Shino, Michihiro; Matsumoto, Teruaki; Mori, Keita; Omae, Katsuhiro; Osaka, Iwao

2017-07-01

Despite the risk of drug-induced delirium, it is difficult to avoid the use of opioids in palliative care. However, no previous study has carefully investigated how the development of delirium varies among patients injected with different opioids for the first time. To reveal the difference in the incidence of delirium between different opioids. The incidence of delirium was compared among 114 patients who had started morphine, oxycodone, or fentanyl injection at Shizuoka Cancer Center between June 2012 and September 2014. The incidence of delirium was 28.9% in the morphine group (n = 38), 19.5% in the oxycodone group (n = 41), and 8.6% in the fentanyl group (n = 35). There was a significant difference between the morphine and fentanyl groups (Fisher's exact test, P = 0.04) but not between the morphine and oxycodone groups (P = 0.43) nor between the oxycodone and fentanyl groups (P = 0.21). The incidence of delirium after the commencement of fentanyl injection was significantly lower, suggesting that fentanyl is a useful opioid injection drug from the perspective of delirium risk.

Influence of intravenous opioid dose on postoperative ileus.

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Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

2011-07-01

Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

Ketamine Use for Successful Resolution of Post-ERCP Acute Pancreatitis Abdominal Pain

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Suneel M. Agerwala

2017-01-01

Full Text Available We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and postprocedure anxiolytics. Pain management was consulted and a ketamine infusion was trialed, leading to a dramatic reduction in pain. This case suggests that ketamine may be a promising option in treating intractable pain associated with ERCP acute pancreatitis.

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

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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

An internet survey of 2,596 people with fibromyalgia

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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

Pharmacologic management of non-cancer pain among nursing home residents.

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Lapane, Kate L; Quilliam, Brian J; Chow, Wing; Kim, Myoung S

2013-01-01

Pain is common in nursing home settings. To describe scheduled analgesic use among nursing home (NH) residents experiencing non-cancer pain and evaluate factors associated with scheduled analgesic use. We identified 2508 residents living in one of 185 NHs predominantly from one for-profit chain, with pain recorded on two consecutive Minimum Data Set assessments. Pharmacy transaction files provided detailed medication information. Logistic regression models adjusted for clustering of residents in NHs identified factors related to scheduled prescription analgesics. Twenty-three percent had no scheduled analgesics prescribed. Those with scheduled analgesics were more likely to have excruciating pain (5.5% vs. 1.2%) and moderate pain documented (64.7% vs. 47.5%) than residents without scheduled analgesics. Hydrocodone (41.7%), short-acting oxycodone (16.6%), and long-acting fentanyl (9.4%) were common, and 13.8% reported any nonsteroidal anti-inflammatory agent use. Factors associated with decreased odds of scheduled analgesics included severe cognitive impairment (adjusted odds ratio [AOR] 0.56; 95% confidence interval [CI] 0.36 to 0.88), age more than 85 years (AOR 0.57; 95% CI 0.41 to 0.80), and Parkinson's disease (AOR 0.55; 95% CI 0.30 to 0.99). Factors associated with increased odds of scheduled analgesic use included history of fracture (AOR 1.79; 95% CI 1.16 to 2.76), diabetes (AOR 1.30; 95% CI 1.02 to 1.66), and higher Minimum Data Set mood scores (AOR 1.11; 95% CI 1.04 to 1.19). Some improvements in pharmacologic management of pain in NHs have been realized. Yet, presence of pain without scheduled analgesics prescribed was still common. Evidence-based procedures to assure adherence to clinical practice guidelines for pain management in this setting are warranted. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

Science.gov (United States)

Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

2016-01-01

To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of

Opioid Concentrations in Oral Fluid and Plasma in Cancer Patients With Pain.

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Heiskanen, Tarja; Langel, Kaarina; Gunnar, Teemu; Lillsunde, Pirjo; Kalso, Eija A

2015-10-01

Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R(2) = 0.628 and 0.700, respectively), but not morphine (R(2) = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing*

Science.gov (United States)

Antoine, Denis G.; Strain, Eric C.; Tompkins, D. Andrew; Bigelow, George E.

2013-01-01

Background Abuse liability assessments influence drug development, federal regulation, and clinical care. One suggested procedure to reduce variability of assessments is a qualification phase, which assesses whether study applicants adequately distinguish active drug from placebo; applicants failing to make this distinction are disqualified. The present analyses assessed differences between qualification phase qualifiers and non-qualifiers. Methods Data were collected from 23 completers of the qualification phase of an abuse liability study. Opioid abusing participants received 30 mg oxycodone and placebo orally on separate days, and were characterized as qualifiers (vs. non-qualifiers) if their peak visual analog scale liking rating for oxycodone was at least 20 points higher than placebo’s peak rating. Groups were compared on demographic characteristics, drug history, and physiologic, subject and observer ratings. Results 61% of participants were qualifiers and 39% were non-qualifiers. Groups had similar demographic characteristics, drug use histories, and pupillary constriction responses. However, unlike qualifiers, non-qualifiers had an exaggerated placebo response for the liking score (p=0.03) and an attenuated oxycodone response for the liking score (p<.0001). Non-qualifiers’ failure to differentiate oxycodone versus placebo was evident for subject and observer ratings. Conclusion Different subjective responses to identical stimuli support the use of a qualification phase in abuse liability assessments. Further research should explore objective measures that may better account for these differences, determine optimal qualification criteria, and explore the developmental course of drug use. This study also documents certain opioid abusers fail to differentiate 30 mg of oxycodone from placebo, a phenomenon deserving further study. PMID:23369645

Fatal Fentanyl: One Pill Can Kill.

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Sutter, Mark E; Gerona, Roy R; Davis, M Thais; Roche, Bailey M; Colby, Daniel K; Chenoweth, James A; Adams, Axel J; Owen, Kelly P; Ford, Jonathan B; Black, Hugh B; Albertson, Timothy E

2017-01-01

The current national opioid epidemic is a public health emergency. We have identified an outbreak of exaggerated opioid toxicity caused by fentanyl adulterated tablets purchased on the street as hydrocodone/acetaminophen. Over an 8-day period in late March 2016, a total of 18 patients presented to our institution with exaggerated opioid toxicity. The patients provided a similar history: ingesting their "normal dose" of hydrocodone/acetaminophen tablets but with more pronounced symptoms. Toxicology testing and analysis was performed on serum, urine, and surrendered pills. One of the 18 patients died in hospital. Five patients underwent cardiopulmonary resuscitation, one required extracorporeal life support, three required intubation, and two received bag-valve-mask ventilation. One patient had recurrence of toxicity after 8 hours after naloxone discontinuation. Seventeen of 18 patients required boluses of naloxone, and four required prolonged naloxone infusions (26-39 hours). All 18 patients tested positive for fentanyl in the serum. Quantitative assays conducted in 13 of the sera revealed fentanyl concentrations of 7.9 to 162 ng/mL (mean = 52.9 ng/mL). Pill analysis revealed fentanyl amounts of 600-6,900 μg/pill. The pills are virtually indistinguishable from authentic hydrocodone/acetaminophen tablets and are similar in weight. To date, our county has reported 56 cases of fentanyl opioid toxicity, with 15 fatalities. In our institution, the outbreak has stressed the capabilities and resources of the emergency department and intensive care units. A serious outbreak of exaggerated opioid toxicity caused by fentanyl-adulterated tablets purchased on the street as hydrocodone/acetaminophen is under way in California. These patients required higher dosing and prolonged infusions of naloxone. Additionally, observation periods off naloxone were extended due to delayed, recurrent toxicity. The outbreak has serious ramifications for public health and safety, law

A Novel Chronic Opioid Monitoring Tool to Assess Prescription Drug Steady State Levels in Oral Fluid.

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Shaparin, Naum; Mehta, Neel; Kunkel, Frank; Stripp, Richard; Borg, Damon; Kolb, Elizabeth

2017-11-01

Interpretation limitations of urine drug testing and the invasiveness of blood toxicology have motivated the desire for the development of simpler methods to assess biologically active drug levels on an individualized patient basis. Oral fluid is a matrix well-suited for the challenge because collections are based on simple noninvasive procedures and drug concentrations better correlate to blood drug levels as oral fluid is a filtrate of the blood. Well-established pharmacokinetic models were utilized to generate oral fluid steady state concentration ranges to assess the interpretive value of the alternative matrix to monitor steady state plasma oxycodone levels. Paired oral fluid and plasma samples were collected from patients chronically prescribed oxycodone and quantitatively analyzed by liquid chromatography tandem mass spectrometry. Steady state plasma concentration ranges were calculated for each donor and converted to an equivalent range in oral fluid. Measured plasma and oral fluid oxycodone concentrations were compared with respective matrix-matched steady state ranges, using each plasma steady state classification as the control. A high degree of correlation was observed between matrices when classifying donors according to expected steady state oxycodone concentration. Agreement between plasma and oral fluid steady state classifications was observed in 75.6% of paired samples. This study supports novel application of basic pharmacokinetic knowledge to the pain management industry, simplifying and improving individualized drug monitoring and risk assessment through the use of oral fluid drug testing. Many benefits of established therapeutic drug monitoring in plasma can be realized in oral fluid for patients chronically prescribed oxycodone at steady state. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Opiate and opioid withdrawal

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... opiate withdrawal; Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are severe. ...

Improving postoperative tonsillectomy pain management in children--a double blinded randomised control trial of a patient analgesia information sheet.

Science.gov (United States)

Bailey, Lucas; Sun, Jing; Courtney, Mark; Murphy, Paul

2015-05-01

To evaluate paediatric post-tonsillectomy pain management using oxycodone when a specific analgesia information sheet is included with standard postoperative information. Oxycodone information sheets were randomly allocated to half the study children's post-tonsillectomy information pack. The trial was double-blinded to the surgeon, anaesthetist, nursing and administrative staff. Parents and children completed the pain assessment on day 3, 5 and 7. On day 10 the parents completed a questionnaire. A postoperative analgesia information sheet provides for higher satisfaction and knowledge for parents using oxycodone (psheet, most significantly at day 3 and 7 post operatively (psheets are useful in education and use of postoperative analgesia. The primary objective to explore the efficacy of the information sheet has proved to be successful in this setting. Given risks of opioid analgesia, it is recommended that postoperative information sheets be given to all parents, to provide for improved analgesia control and safe management of children in the postoperative period. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

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Tenore, Peter L

2012-01-01

In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

77 FR 64143 - Manufacturer of Controlled Substances; Notice of Application; Noramco, Inc.

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2012-10-18

... Hydrocodone (9193) II Morphine (9300) II Oripavine (9330) II Thebaine (9333) II Opium extracts (9610) II Opium fluid extract (9620) II Opium tincture (9630) II Opium, powdered (9639) II Opium, granulated (9640) II...

77 FR 7603 - Manufacturer of Controlled Substances; Notice of Registration

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2012-02-13

... Hydrocodone (9193) II Morphine (9300) II Oripavine (9330) II Thebaine (9333) II Opium extracts (9610) II Opium fluid extract (9620) II Opium tincture (9630) II Opium, powdered (9639) II Opium, granulated (9640) II...

Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery?

DEFF Research Database (Denmark)

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

2015-01-01

were undergoing cardiac surgery for the first time, were randomly allocated either to a regimen of slow-release oxycodone (10 mg twice daily) or slow-release ibuprofen (800 mg twice daily) combined with lansoprazole. Data relating to blood-tests, angiographies, surgical details and administered...... 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....

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.

Zohydro approval by food and drug administration: controversial or frightening?

Science.gov (United States)

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

The actions and regulations of the Food and Drug Administration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health

Opioid-induced bowel dysfunction in healthy volunteers assessed with questionnaires and MRI

DEFF Research Database (Denmark)

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

2016-01-01

Twenty-five healthy men were assigned randomly to oxycodone or placebo for 5 days in a cross-over design. The analgesic effect was assessed with muscle pressure algometry and adverse effects were measured using questionnaires including the bowel function index, gastrointestinal symptom rating scale....../ascending colon by 41% (P =0.005) and in the transverse colon by 20% (P= 0.005). No associations were detected between questionnaire scores and colorectal volumes. Conclusion Experimental OIBD in healthy volunteers was induced during oxycodone treatment. This model has potential for future interventional studies...

Acute opioid withdrawal precipitated by ingestion of crushed embeda (morphine extended release with sequestered naltrexone): case report and the focused review of the literature.

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Ruan, Xiulu; Chen, Tao; Gudin, Jeff; Couch, John Patrick; Chiravuri, Srinivas

2010-01-01

The introduction of newly formulated extended release (ER) morphine with sequestered naltrexone (Embeda) has provided another treatment option for moderate to severe persistent pain. Embeda was designed to be an abuse-deterrent opioid formulation. Naltrexone is a centrally acting opioid receptor antagonist that blocks the action of opioid. When taken as directed, insignificant amount of sequestered naltrexone would reach systemic circulation, but upon tampering, the released naltrexone may blunt the euphoria of opioids, and possibly precipitate opioid withdrawal in opioid-dependent patient. To describe a case report ofa 50-year-old opioid-dependent male who developed acute opioid withdrawal after taking crushed Embeda. A 50-year-old male with severe, chronic low back pain due to degenerative disc disease was referred to our clinic for pain management. He was taking ER oxycodone 80 mg tid and Roxicodone 30 mg qid prn, with inadequate pain relief A trial of ER oxymorphone was decided, at 40 mg 1-2 doses bid. The patient returned to the clinic 1 week early, out of his ER oxymorphone. At this time, the decision to switch him to Embeda was made, at 80 mg/3.2 mg, 1-2 doses bid. The patient and his family members were counseled about risk involved with tampering with Embeda. A few hours later, our clinic was informed that the patient was brought to emergency room by ambulance, in severe opioid withdrawal. He was treated with IV fluid, antiemetics, clonidine, and IV hydromorphone. His condition improved and he was discharged home the next morning. Later on, the patient admitted that he took two prescribed Embeda within half an hour, the 1st one whole and the 2nd one crushed. He further admitted that he did so against our medical advice. CONCLUSION. Taking tampered Embeda may precipitate opioid withdrawal in opioid-tolerant patient. To the best of our knowledge, this is the first report of induced opioid withdrawal following consumption of crushed Embeda.

77 FR 55500 - Controlled Substances: Final Adjusted Aggregate Production Quotas for 2012

Science.gov (United States)

2012-09-10

... (for conversion), amphetamine (for sale), codeine (for conversion), codeine (for sale), desomorphine...), desomorphine, diethyltryptamine, dihydromorphine, gamma hydroxybutyric acid, hydrocodone (for sale... g Codeine-N-oxide 602 g Desomorphine 10 g Diethyltryptamine 18 g Difenoxin 50 g Dihydromorphine 3...

Preoperative opioid strength may not affect outcomes of anterior cervical procedures: a post hoc analysis of 2 prospective, randomized trials

Science.gov (United States)

Kelly, Michael P.; Anderson, Paul A.; Sasso, Rick C.; Riew, K. Daniel

2015-01-01

Object The aim of this study is to evaluate the relationship between preoperative opioid strength and outcomes of anterior cervical decompressive surgery. Methods A retrospective cohort of 1004 patients enrolled in 1 of 2 investigational device exemption studies comparing cervical total disc arthroplasty (TDA) and anterior cervical discectomy and fusion (ACDF) for single-level cervical disease causing radiculopathy or myelopathy was selected. At a preoperative visit, opioid use data, Neck Disability Index (NDI) scores, 36-ltem Short-Form Health Survey (SF-36) scores, and numeric rating scale scores for neck and arm pain were collected. Patients were divided into strong (oxycodone/morphine/meperidine), weak (codeine/propoxyphene/ hydrocodone), and opioid-naïve groups. Preoperative and postoperative (24 months) outcomes scores were compared within and between groups using the paired t-test and ANCOVA, respectively. Results Patients were categorized as follows: 226 strong, 762 weak, and 16 opioid naïve. The strong and weak groups were similar with respect to age, sex, race, marital status, education level, Worker's Compensation status, litigation status, and alcohol use. At 24-month follow-up, no differences in change in arm or neck pain scores (arm: strong –52.3, weak –50.6, naïve –54.0, p = 0.244; neck: strong –52.7, weak –50.8, naïve –44.6, p = 0.355); NDI scores (strong –36.0, weak –33.3, naïve –32.3, p = 0.181); or SF-36 Physical Component Summary scores (strong: 14.1, weak 13.3, naïve 21.7, p = 0.317) were present. Using a 15-point improvement in NDI to determine success, the authors found no between-groups difference in success rates (strong 80.6%, weak 82.7%, naïve 73.3%, p = 0.134). No difference existed between treatment arms (TDA vs ACDF) for any outcome at any time point. Conclusions Preoperative opioid strength did not adversely affect outcomes in this analysis. Careful patient selection can yield good results in this patient

Variability in prescription opioid intake and reinforcement amongst 129 substrains.

Science.gov (United States)

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

2017-09-01

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

76 FR 39128 - Manufacturer of Controlled Substances; Notice of Registration

Science.gov (United States)

2011-07-05

... February 23, 2011, 76 FR 10068, Johnson Matthey Pharmaceutical Materials Inc., Pharmaceutical Service, 25...) II Sufentanil (9740) 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...

75 FR 76756 - Manufacturer of Controlled Substances; Notice of Registration

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2010-12-09

... Johnson Matthey Pharmaceutical Materials, Inc. to ensure that the company's registration is consistent..., 2010, (75 FR 44285), Johnson Matthey Pharmaceutical Materials, Inc., Pharmaceuticals Service, 25 Patton... (9740) II Remifentanil (9739) II Hydrocodone (9193) II The company plans to utilize this facility to...

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

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

2016-07-01

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

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

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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.

76 FR 77257 - Manufacturer of Controlled Substances; Notice of Application

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2011-12-12

...), this is notice that on September 15, 2011, Johnson Matthey Pharma Services, 70 Flagship Drive, North... Schedule Amphetamine (1100) II Methylphenidate (1724) II Hydrocodone (9193) II The company plans to utilize... conduct analytical testing in support of the company's primary manufacturing facility in West Deptford...

76 FR 25376 - Manufacturer of Controlled Substances; Notice of Application

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2011-05-04

...), this is notice that on January 5, 2011, Johnson Matthey Pharma Services, 70 Flagship Drive, North... Schedule Amphetamine (1100) II Methylphenidate (1724) II Hydrocodone (9193) II The company plans to utilize... conduct analytical testing in support of the company's primary manufacturing facility in West Deptford...

75 FR 47029 - Manufacturer of Controlled Substances; Notice of Application

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2010-08-04

...), this is notice that on January 27, 2009, Johnson Matthey Pharma Services, 70 Flagship Drive, North... Schedule Amphetamine (1100) II Hydrocodone (9193) II Methylphenidate (1724) II The company plans to utilize... conduct analytical testing in support of the company's primary manufacturing facility in West Deptford...

Targinact--opioid pain relief without constipation?

Science.gov (United States)

2010-12-01

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

Changing patterns in opioid addiction

Science.gov (United States)

Sproule, Beth; Brands, Bruna; Li, Selina; Catz-Biro, Laura

2009-01-01

ABSTRACT OBJECTIVE To evaluate the clinical observation that the number of individuals seeking opioid detoxification from oxycodone was increasing at the Centre for Addiction and Mental Health (CAMH) in Toronto, Ont; and to identify the characteristics of individuals seeking opioid detoxification at CAMH. DESIGN Retrospective analysis of patient health records. SETTING Medical Withdrawal Management Service at CAMH. PARTICIPANTS All patients admitted for opioid detoxification between January 2000 and December 2004. MAIN OUTCOME MEASURES Number of opioid detoxification admissions each year; type, dose, and source of opioids; comorbid problems and symptoms. RESULTS There were 571 opioid detoxification admissions during the 5-year study period. The number of admissions increased steadily over the 5 years; in particular, the number of admissions related to controlled-release oxycodone increased substantially (3.8%, 8.3%, 20.8%, 30.6%, and 55.4% of the total opioid admissions in 2000 to 2004, respectively; χ42= 105.5, P < .001). The rates of admissions involving heroin remained low and stable. Use of controlled-release oxycodone was associated with considerably higher doses than use of other prescription opioids was. Physician prescriptions were the source of the prescription opioids for a large percentage of patients, particularly for older patients. Prescription opioid users reported considerable comorbid substance use problems, pain, and psychiatric symptoms. CONCLUSION This study has demonstrated a significant rise in the number of individuals seeking treatment at CAMH for controlled-release oxycodone addiction. The substantial comorbid pain, psychiatric symptoms, and other psychoactive substance use problems in these patients, coupled with the finding that prescriptions were an important source of opioids, highlight the clinical complexities encountered in the treatment of these individuals. Further research examining these complexities and the many possible

76 FR 25376 - Manufacturer of Controlled Substances; Notice of Registration

Science.gov (United States)

2011-05-04

... the public interest at this time. DEA has investigated Johnson Matthey Inc. to ensure that the company... February 3, 2011, 76 FR 6159, Johnson Matthey Inc., Pharmaceuticals Materials, 900 River Road, Conshohocken...) II Hydrocodone (9193) II Morphine (9300) II Thebaine (9333) II The company plans to manufacture the...

Effectiveness of Liposomal Bupivacaine in Colorectal Surgery: A Pragmatic Nonsponsored Prospective Randomized Double Blinded Trial in a Community Hospital.

Science.gov (United States)

Knudson, Rachel A; Dunlavy, Paul W; Franko, Jan; Raman, Shankar R; Kraemer, Soren R

2016-09-01

Prior industry conducted studies have shown that long acting liposomal bupivacaine injection improves pain control postoperatively. To evaluate whether liposomal bupivacaine reduced the use of postoperative opioid (http://links.lww.com/DCR/A253) pain medication as compared to standard bupivacaine following colorectal surgery. A double blinded, prospective, randomized controlled trial comparing liposomal bupivacaine versus standard bupivacaine in patients undergoing elective colon resection. Community hospital with general surgery residency program with all cases performed by colorectal surgeons. Fifty-seven patients were randomized and reported as intention-to-treat analysis with 6 protocol violations. Sensitivity analysis excluding these 6 patients demonstrated no change in study results or conclusion. Mean age was 67 ± 2 years and 56% were male. There were 36 patients who underwent minimally invasive surgery, and 21 patients had an open colon resection. Experimental arm received liposomal bupivacaine while control arm received standard bupivacaine. Primary outcome measure was intravenous hydromorphone equivalent used via PCA during first 48 hours after operation. There was no significant difference between the two groups in the amount of opioid used orally or intravenously in the postoperative period. The primary outcome measure was PCA hydromorphone consumption during first two postoperative days after operation (hydromorphone equivalent use in standard bupivacaine group 11.3 ± 8.9 mg versus 13.3 ± 11.9 mg in liposomal bupivacaine group, p = 0.58 Mann-Whitney test). Small pragmatic trials typically remain underpowered for secondary analyses. A larger study could help to further delineate other outcomes that are impacted by postoperative pain. Liposomal bupivacaine did not change the amount of opioid used postoperatively. Based on our study, liposomal bupivacaine does not provide any added benefit over conventional bupivacaine after colon

75 FR 49995 - Robert F. Hunt, D.O. Revocation of Registration

Science.gov (United States)

2010-08-16

... patient had in his possession 150 tablets of a controlled substance containing hydrocodone, which he had... thought ``anything is bad like you're going to need x-rays or an MRI scan or anything like that?'' Id. The... controlled substances. Specifically, Respondent wrote for: 100 tablets of Vicodin ES, with three refills; \\18...

Muscle pain

African Journals Online (AJOL)

damage or inflammation, like fibromyalgia, tension headaches .... This group includes the following examples: codeine, morphine, oxycodone ... insufficient evidence to support a preference of one opioid ..... [Homepage on internet]. Available ...

Outpatient unicompartment knee arthroplasty with indwelling femoral nerve catheter.

Science.gov (United States)

Dervin, Geoffrey F; Madden, Susan M; Crawford-Newton, Barbara A; Lane, Alan T; Evans, Holly C

2012-06-01

Contemporary multimodal anesthesia regimens allow the performance of unicompartment knee arthroplasty (UKA) on an outpatient basis. Our initial pilot experience is presented using a continuous femoral nerve block as an adjunct for 24 patients classified as American Society of Anesthesiology class 1 (14 men, 10 women; median age, 56 years; range, 46-72 years). After minimally invasive UKA, patients documented their pain and oral medication use while at home for the first 5 days. Adverse events, medication adverse effects, and the amount of infused ropivacaine were recorded. Median pain scores for the first 3 days were 1, 2, and 2 (at rest) and 4, 5, and 3 (during physical therapy). Eighteen patients (75%) required less than 4 mg oral hydromorphone/d. Of the 18, 10 (42%) did not require supplemental oral opioids. The median catheter use was 3 days. Our results suggest that with careful patient selection and adequate teaching, continuous femoral nerve blocks may be used as part of a multimodal pain regimen to assist the delivery of outpatient UKA with high patient satisfaction. Copyright © 2012 Elsevier Inc. All rights reserved.

76 FR 66968 - Abelardo E. Lecompte-Torres, M.D. Decision and Order

Science.gov (United States)

2011-10-28

.... Finally, the Show Cause Order alleged that on January 10, 2008, Respondent pled guilty to one count of... evidenced by the signed returned receipt card. See id. at 2 (citing 21 CFR 1301.43(a)); see also GX 10... to one count of Conspiracy to Possess with Intent to Distribute Hydrocodone, in violation of 21 U.S.C...

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

Diet and substance abuse recovery

Science.gov (United States)

... of different drugs on nutrition is described below. OPIATES Opiates (including codeine, oxycodone, heroin, and morphine) affect the ... High blood pressure Permanent liver damage (or cirrhosis ) Seizures Severe malnutrition Shortened life expectancy Laboratory tests for ...

75 FR 49979 - Tony T. Bui, M.D.; Revocation of Registration

Science.gov (United States)

2010-08-16

... where either a TENS unit or a stimulator had been placed in his back. Id. at 504, 506, 508. D.M. also... testified that he had prescribed fifteen tablets of hydrocodone to D.C. for acute back pain caused by a disk... hair testing is not ``sensitive enough to see low doses of cocaine'' and probably would not pick up...

A case report of dexmedetomidine used to treat intractable pain and delirium in a tertiary palliative care unit.

Science.gov (United States)

Hilliard, Neil; Brown, Stuart; Mitchinson, Steve

2015-03-01

This case report describes an end-stage cancer patient with intractable neuropathic pain and delirium who was successfully managed during the last 3 weeks of her life with a continuous subcutaneous infusion of dexmedetomidine. A 55-year-old woman with locally advanced cervical cancer and uncontrolled pelvic pain was admitted to a tertiary palliative care unit for pain management. As her disease progressed, the patient's pelvic pain intensified despite treatment with methadone, gabapentin, ketamine, and hydromorphone administered by continuous subcutaneous infusion plus frequent breakthrough doses of hydromorphone and sufentanil. A continuous subcutaneous infusion of dexmedetomidine was started and titrated to achieve pain relief. The patient's pain and delirium cleared. The treatment was successful in fulfilling the patient's goal of care: not to be deeply and continuously sedated, but to be rousable and of clear mind while still having good pain control. Dexmedetomidine is a potentially useful medication for the targeted treatment of intractable pain and delirium in the tertiary palliative care environment. Future research is required to compare dexmedetomidine infusion to standard treatment with midazolam infusion for treatment of intractable symptoms in the palliative care environment. © The Author(s) 2014.

Desomorphine Screening Using Commercial Enzyme-Linked Immunosorbent Assays.

Science.gov (United States)

Winborn, Jessica; Kerrigan, Sarah

2017-06-01

Desomorphine ("Krokodil") is a semi-synthetic opioid that has drawn attention as a recreational drug, particularly in Russia, neighboring former Soviet Republics, Eastern and Central Europe. It has no accepted medicinal uses and is currently a schedule I drug in the United States. In clandestine environments, desomorphine is synthesized from codeine using red phosphorous, hydroiodic acid and gasoline. Residual starting materials in illicit preparations have been associated with severe dermatological effects and extensive tissue necrosis. Desomorphine is not well studied, and there are limited reports concerning its pharmacology or detection in biological matrices. Immunoassays are widely relied upon for both antemortem and postmortem toxicology screening. Although desomorphine is an opioid of the phenanthrene-type, its ability to bind to conventional opioid antibodies has not been described. In this report we describe the cross-reactivity of desomorphine using six commercially available enzyme-linked immunosorbent assays (Immunalysis Opiates Direct ELISA, Immunalysis Oxycodone/Oxymorphone Direct ELISA, Randox Opiate ELISA, OraSure Technologies OTI Opiate Micro-plate EIA, Neogen Opiate Group ELISA and Neogen Oxycodone/Oxymorphone ELISA). Cross-reactivites were highly variable between assays, ranging from 77 to desomorphine than those directed towards oxycodone. The Immunalysis Opiates Direct ELISA produced the greatest cross-reactivity, although several of the assays evaluated produced cross-reactivity of a sufficient magnitude to be effective for desomorphine screening. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Impact of Opioid Treatment on Regional Gastrointestinal Transit.

Science.gov (United States)

Poulsen, Jakob L; Nilsson, Matias; Brock, Christina; Sandberg, Thomas H; Krogh, Klaus; Drewes, Asbjørn M

2016-04-30

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-dimensional (3D)-Transit system. 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 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. GI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P= 0.001). No associations between questionnaire scores and segmental transit times were detected. Self-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation.

Dental therapeutic practice patterns in the U.S. II. Analgesics, corticosteroids, and antibiotics.

Science.gov (United States)

Moore, Paul A; Nahouraii, Helen S; Zovko, Jayme G; Wisniewski, Stephen R

2006-01-01

This article examines the prescribing practices for peripherally acting and centrally acting analgesics, corticosteroids, and antibiotics following third molar extraction. A nationwide survey involving the prescribing patterns of a random national sample of 850 practicing oral surgeons was performed in 2004. Ibuprofen was the peripherally acting analgesic respondents used most frequently in the previous month, selected by 73.5% of the respondents. The ibuprofen dose prescribed most frequently was 800 mg, followed by doses of 600 mg and 400 mg. The centrally acting analgesic prescribed most frequently was the combination formulation of hydrocodone with acetaminophen, selected by 64.0% of the respondents. Recommendations for oral analgesics to manage postoperative pain relied on the peripherally acting analgesic ibuprofen or the centrally acting analgesic combination formulation hydrocodone with acetaminophen. Routine instructions to use centrally acting analgesics "as needed for pain" suggest that centrally acting analgesics are offered to manage pain that postoperative peripherally acting analgesics and intraoperative long-acting local anesthetics do not control adequately. The frequency with which oral and maxillofacial surgeons administered antibiotics and corticosteroids varied widely based on perceived patient need and dentist expectations.

Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers.

Science.gov (United States)

Polepally, Akshanth R; King, Jennifer R; Ding, Bifeng; Shuster, Diana L; Dumas, Emily O; Khatri, Amit; Chiu, Yi-Lin; Podsadecki, Thomas J; Menon, Rajeev M

2016-08-01

The three direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D regimen) is approved for treatment of hepatitis C virus (HCV) genotype 1 infection. Drug-drug interaction (DDI) studies of the 3D regimen and commonly used medications were conducted in healthy volunteers to provide information on coadministering these medications with or without dose adjustments. Three phase I studies evaluated DDIs between the 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily + dasabuvir 250 mg twice daily) and hydrocodone bitartrate/acetaminophen (5/300 mg), metformin hydrochloride (500 mg), diazepam (2 mg), cyclobenzaprine hydrochloride (5 mg), carisoprodol (250 mg), or sulfamethoxazole/trimethoprim (SMZ/TMP) (800/160 mg twice daily), all administered orally. DDI magnitude was determined using geometric mean ratios and 90 % confidence intervals for the maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC). Changes in exposures (C max and AUC geometric mean ratios) of acetaminophen, metformin, sulfamethoxazole, trimethoprim, and diazepam were ≤25 % upon coadministration with the 3D regimen. The C max and AUC of nordiazepam, an active metabolite of diazepam, increased by 10 % and decreased by 44 %, respectively. Exposures of cyclobenzaprine and carisoprodol decreased by ≤40 and ≤46 %, respectively, whereas exposures of hydrocodone increased up to 90 %. Ombitasvir, paritaprevir, ritonavir, and dasabuvir exposures changed by ≤25 %, except for a 37 % decrease in paritaprevir C max with metformin and a 33 % increase in dasabuvir AUC with SMZ/TMP. Acetaminophen, metformin, sulfamethoxazole, and trimethoprim can be coadministered with the 3D regimen without dose adjustment. Higher doses may be needed for diazepam, cyclobenzaprine, and carisoprodol based on clinical monitoring. A 50 % lower dose and/or clinical monitoring should be considered for hydrocodone. No dose

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

to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI). Methods Twenty healthy males were included in this randomized, cross-over, double-blinded study. 61-channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release......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...... b.i.d) or venlafaxine (37.5 mg extended release b.i.d) at rest and during tonic pain (hand immersed in 2 °C water for 80 s). Subjective pain and unpleasantness scores of tonic pain were recorded. Spectral analysis and sLORETA source localization were done in delta (1–4 Hz), theta (4–8 Hz), alpha (8...

77 FR 62316 - Holiday CVS, L.L.C., d/b/a CVS/Pharmacy Nos. 219 and 5195; Decision and Order

Science.gov (United States)

2012-10-12

... testimony centered on certain prescriptions that presented a collection of red flags that no reasonable and... Warrants at both Respondents and interviewed various employees of each store's pharmacy departments.... Merrill stated that ``once the limit [wa]s reached,'' customers who then presented oxycodone prescriptions...

Pharmacological and clinical aspects of immediate release fentanyl preparations: Criteria for selection

NARCIS (Netherlands)

D.A. van der Kuip (Deirdre); C.Th. Zandvliet; A.H.J. Mathijssen (Ron); C.C.D. van der Rijt (Carin)

2012-01-01

textabstractIn palliative care, pain management is often hampered by episodes of breakthrough pain, characterised by a rapid onset and, on average, duration less than 1 h. Until recently, only immediate release morphine and oxycodon preparations were available for the treatment of these episodes but

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...

76 FR 5827 - Importer of Controlled Substances; Notice of Registration

Science.gov (United States)

2011-02-02

... (9300) II Nabilone (7379) II Opium, raw (9600) II Opium extracts (9610) II Opium fluid extract (9620) II Opium tincture (9630) II Opium, granulated (9640) II Oxycodone (9143) II Oxymorphone (9652) II... (8501) II Piminodine (9730) II Powdered opium (9639) II Racemethorphan (9732) II Racemorphan (9733) II...

Fully automated drug screening of dried blood spots using online LC-MS/MS analysis

Directory of Open Access Journals (Sweden)

Stefan Gaugler

2018-01-01

Full Text Available A new and fully automated workflow for the cost effective drug screening of large populations based on the dried blood spot (DBS technology was introduced in this study. DBS were prepared by spotting 15 μL of whole blood, previously spiked with alprazolam, amphetamine, cocaine, codeine, diazepam, fentanyl, lysergic acid diethylamide (LSD, 3,4-methylenedioxymethamphet-amine (MDMA, methadone, methamphetamine, morphine and oxycodone onto filter paper cards. The dried spots were scanned, spiked with deuterated standards and directly extracted. The extract was transferred online to an analytical LC column and then to the electrospray ionization tandem mass spectrometry system. All drugs were quantified at their cut-off level and good precision and correlation within the calibration range was obtained. The method was finally applied to DBS samples from two patients with back pain and codeine and oxycodone could be identified and quantified accurately below the level of misuse of 89.6 ng/mL and 39.6 ng/mL respectively.

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.

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.

Enhanced bioavailability of opiates after intratracheal administration

International Nuclear Information System (INIS)

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

1986-01-01

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

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

By Default: The Effect of Prepopulated Prescription Quantities on Opioid Prescribing in the Emergency Department.

Science.gov (United States)

Santistevan, Jamie R; Sharp, Brian R; Hamedani, Azita G; Fruhan, Scott; Lee, Andrew W; Patterson, Brian W

2018-03-01

Opioid prescribing patterns have come under increasing scrutiny with the recent rise in opioid prescriptions, opioid misuse and abuse, and opioid-related adverse events. To date, there have been limited studies on the effect of default tablet quantities as part of emergency department (ED) electronic order entry. Our goal was to evaluate opioid prescribing patterns before and after the removal of a default quantity of 20 tablets from ED electronic order entry. We performed a retrospective observational study at a single academic, urban ED with 58,000 annual visits. We identified all adult patients (18 years or older) seen in the ED and discharged home with prescriptions for tablet forms of hydrocodone and oxycodone (including mixed formulations with acetaminophen). We compared the quantity of tablets prescribed per opioid prescription 12 months before and 10 months after the electronic order-entry prescription default quantity of 20 tablets was removed and replaced with no default quantity. No specific messaging was given to providers, to avoid influencing prescribing patterns. We used two-sample Wilcoxon rank-sum test, two-sample test of proportions, and Pearson's chi-squared tests where appropriate for statistical analysis. A total of 4,104 adult patients received discharge prescriptions for opioids in the pre-intervention period (151.6 prescriptions per 1,000 discharged adult patients), and 2,464 post-intervention (106.69 prescriptions per 1,000 discharged adult patients). The median quantity of opioid tablets prescribed decreased from 20 (interquartile ration [IQR] 10-20) to 15 (IQR 10-20) (pdefault quantity. While the most frequent quantity of tablets received in both groups was 20 tablets, the proportion of patients who received prescriptions on discharge that contained 20 tablets decreased from 0.5 (95% confidence interval [CI] [0.48-0.52]) to 0.23 (95% CI [0.21-0.24]) (pdefault quantity removal. Although the median number of tablets differed significantly

DOD and VA Health Care: Actions Needed to Help Ensure Appropriate Medication Continuation and Prescribing Practices

Science.gov (United States)

2016-01-01

Hydrocodone ibuprofen 0.1 Oxymorphone 0.1 Meperidinee 0.1 Methadone √ 0.1 Codeine √ 0.1 Tapentadol < 0.1 Oxaprozin < 0.1 Diclofenac misoprostopolf...formulation (e.g., extended or immediate release), salt form (e.g., hydrochloride or sulfate), or strength of the medication. bThis represents the most...form (e.g., liquid or tablet), modified release formulation (e.g., extended or immediate release), salt form (e.g., hydrochloride or sulfate

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

78 FR 62676 - Anthony E. Wicks, M.D. Decision and Order

Science.gov (United States)

2013-10-22

... registration BW7987184, while listing his address as Pain Management of Winter Springs, 165 W. SR 434, Winter... practice address. Id. at 2, ] 5. \\2\\ Documentary evidence, which the Government acquired through... prescriptions for oxycodone,\\4\\ diazepam, and lorazepam.\\5\\ GX 15, at 2, ] 7; GX 13. \\3\\ The documentary...

Det legale opioidforbrug i Danmark

DEFF Research Database (Denmark)

Jarlbaek, Lene; Kehlet, Henrik; Sjøgren, Per

2010-01-01

To identify users and use of opioids in Denmark three databases were combined. The latest fifteen years an increase in users has been noted, and the costs of opioids have increased from 175 million DKK (1994) to 540 million DKK (2008). Oxycodone and transdermal fentanyl constitute 60% of the total...

Det legale opioidforbrug i Danmark

DEFF Research Database (Denmark)

Jarlbaek, Lene; Kehlet, Henrik; Sjøgren, Per

2010-01-01

To identify users and use of opioids in Denmark three databases were combined. The latest fifteen years an increase in users has been noted, and the costs of opioids have increased from 175 million DKK (1994) to 540 million DKK (2008). Oxycodone and transdermal fentanyl constitute 60% of the tota...

76 FR 19401 - Beau Boshers, M.D.; Decision and Order

Science.gov (United States)

2011-04-07

... of a Boston-based drug trafficking organization, who had been arrested with 3,000 oxycodone tablets... MRI. If not, the receptionist would issue that individual an MRI prescription in exchange for a $50 cash payment, and the patient ``would be directed to a place to obtain an MRI.'' Id. at 822. Burt...

Stable Biodegradable Polymers for Delivery of Both Polar and Non-Polar Drugs. Phase I

Science.gov (United States)

1996-10-01

containing hydromorphone hydrochloride (HMh). In two, containing HMh at 25 and 50% (w/w), the lactide to glycolide ratio of the polymer was 85:15...semisynthetic opioid analgesic which meets these criteria. It is sold as the hydrochloride under the trade name Dilaudid. A dose of 1.5 mg can achieve a 50...Numorphan) 1.0-1.1 Slightly shorter Levorphanol tartrate (Levo-Dromoran) 2.0-2.3 Same Butorphanol tartrate (Stadol) 1.5-2.5 Same Methadone HC1 (Dolophine

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

The Misuse of Prescription Opioids: A Threat for Europe?

NARCIS (Netherlands)

van Amsterdam, Jan; van den Brink, Wim

2015-01-01

In the the past two decades the medical use of prescription opioids (POs), in particular oxycodone, increased up to 14-fold in the U.S. and Canada. The high consumption of these pain relievers also led to non-medical use and abuse of these substances which in turn resulted in a dramatic increase in

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

Science.gov (United States)

2011-09-30

... physical examination was Respondent's discussion of UC2's MRI. More specifically, the ALJ found that... MRI might well show that a person has a bulging disc but that the condition is asymptomatic. Yet as... prescribed 180 tablets of Oxycodone 15 mg to UC1, with the dosing instruction to take one tablet every 6...

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 groups and also a significantly longer (P communication, which can serve as an effective means to minimize narcotic analgesia after surgery.

78 FR 57656 - S & S Pharmacy, Inc., d/b/a Platinum Pharmacy & Compounding; Decision and Order

Science.gov (United States)

2013-09-19

... documentation for the sale of the oxycodone to the CS; Barsoum also explained that the phone number would be... to Barsoum had not been returned. Id. That day, the CS placed a phone call to Barsoum, which was... under the supervision of a doctor so as to prevent addiction and recreational abuse. As a corollary, the...

Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation.

Science.gov (United States)

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

2014-12-15

To compare analgesia provided by carprofen and tramadol in dogs after enucleation. Randomized, masked clinical trial. 43 dogs. 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 signs of pain at baseline (ie, before carprofen or tramadol administration) and 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 (maximum possible score of 20), there was a score ≥ 3 in any of 5 behavioral categories (highest score possible per category was 3 or 4), or the visual analog scale (VAS) score was ≥ 35 (maximum possible score of 100) combined with a palpation score > 0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded. No differences were found in age, sex, or baseline pain scores between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21), compared with dogs receiving carprofen (1/22). Pain and VAS scores decreased linearly over time. No significant differences were found in pain or VAS scores between groups at any time point (dogs were excluded from analysis after rescue). Results of this study suggested that carprofen, with opioid premedication, may provide more effective postoperative analgesia than tramadol in dogs undergoing enucleation.

Impact of an emergency department pain management protocol on the pattern of visits by patients with sickle cell disease.

Science.gov (United States)

Givens, Melissa; Rutherford, Cynthia; Joshi, Girish; Delaney, Kathleen

2007-04-01

This study explores how implementation of pain management guidelines in concert with clinic case management affected emergency department (ED) utilization, clinic visits, and hospital admissions for patients with sickle cell disease. A pain management guideline that eliminated meperidine and encouraged timely use of morphine or hydromorphone for pain control in sickle cell crisis was introduced as a quality improvement project. This study is a retrospective review of ED visits, clinic visits, and admissions from 1 year before and 3 years after the guideline implementation. Working with the ED, the Hematology Clinic began to proactively seek the return of their patients for clinic follow-up. A formal case management program for sickle cell patients was initiated in June 2003. A total of 1584 visits by 223 patients were collected, 1097 to the ED and 487 to the Hematology Clinic. Total hospital visits did not change significantly in any of the 4 years, p > 0.10 for each comparison. Total ED visits decreased significantly over the 4-year study period (p study period, p = 0.001. Although total admissions per hospital visit did not change, the proportion of ED visits that resulted in admission in year 1 (29%) was significantly lower than the proportion admitted in year 2 (43%), p = 0.04. A pain protocol using morphine or hydromorphone coupled with increased access to outpatient clinics decreased ED visits, hospitalizations, and increased utilization of a more stable primary care clinic setting by patients with sickle cell disease.

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.

Long-Term Intravenous Ketamine for Analgesia in a Child with Severe Chronic Intestinal Graft versus Host Disease

Directory of Open Access Journals (Sweden)

Jennifer Busse

2015-01-01

Full Text Available Ketamine is reported to be an effective adjuvant to opioids in the treatment of refractory cancer pain; however, the use of high doses of ketamine for extended periods in pediatric patients has not been described. We present a five-year-old male with grade IV intestinal GVHD whose abdominal pain required both hydromorphone and ketamine for a period of over four months. There was no evidence of hepatotoxicity, hemorrhagic cystitis, or other adverse effects. Possible withdrawal symptoms were mild and were readily mitigated by gradually weaning ketamine.

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.

Lignes directrices canadiennes sur l’utilisation sécuritaire et efficace des opioïdes pour la douleur chronique non cancéreuse

Science.gov (United States)

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

2011-01-01

Résumé Objectif Présenter aux médecins de famille un résumé clinique pratique des lignes directrices canadiennes sur l’utilisation sécuritaire et efficace des opioïdes pour la douleur chronique non cancéreuse, produites par le National Opioid Use Guideline Group. Qualité des données Pour produire les lignes directrices, les chercheurs ont effectué une synthèse critique de la littérature médicale sur l’efficacité et l’innocuité des opioïdes pour la douleur chronique non cancéreuse et ont rédigé une série de recommandations. Un panel de 49 cliniciens experts de toutes les régions du Canada ont passé en revue l’ébauche et ont atteint un consensus sur 24 recommandations. Message principal Il est recommandé de faire un dépistage du risque de dépendance avant de prescrire des opioïdes. On recommande des opioïdes faibles (codéine et tramadol) pour une douleur de légère à modérée qui n’a pas répondu aux traitements de première intention. On peut essayer l’oxycodone, l’hydromorphone et la morphine chez les patients qui n’ont pas eu de soulagement avec des opioïdes plus faibles. Une faible dose initiale et une lente hausse du titrage sont recommandées, ainsi qu’une étroite surveillance du patient qu’on a d’abord renseigné. Les médecins doivent surveiller l’apparition de complications comme l’apnée du sommeil. La dose optimale est celle qui améliore le fonctionnement ou atténue les cotes d’évaluation de la douleur d’au moins 30 %. Pour la grande majorité des patients, la dose optimale sera bien en deçà de l’équivalent de 200 mg de morphine par jour. On recommande le sevrage progressif pour les patients qui n’ont pas répondu à un essai d’opioïdes adéquat. Conclusion Les opioïdes jouent un rôle important dans la prise en charge de la douleur chronique non cancéreuse, mais il faut en prescrire avec prudence pour limiter les dommages potentiels. Les nouvelles lignes directrices

Solution to Detect, Classify, and Report Illicit Online Marketing and Sales of Controlled Substances via Twitter: Using Machine Learning and Web Forensics to Combat Digital Opioid Access

Science.gov (United States)

Klugman, Josh; Kuzmenko, Ella; Gupta, Rashmi

2018-01-01

Background On December 6 and 7, 2017, the US Department of Health and Human Services (HHS) hosted its first Code-a-Thon event aimed at leveraging technology and data-driven solutions to help combat the opioid epidemic. The authors—an interdisciplinary team from academia, the private sector, and the US Centers for Disease Control and Prevention—participated in the Code-a-Thon as part of the prevention track. Objective The aim of this study was to develop and deploy a methodology using machine learning to accurately detect the marketing and sale of opioids by illicit online sellers via Twitter as part of participation at the HHS Opioid Code-a-Thon event. Methods Tweets were collected from the Twitter public application programming interface stream filtered for common prescription opioid keywords in conjunction with participation in the Code-a-Thon from November 15, 2017 to December 5, 2017. An unsupervised machine learning–based approach was developed and used during the Code-a-Thon competition (24 hours) to obtain a summary of the content of the tweets to isolate those clusters associated with illegal online marketing and sale using a biterm topic model (BTM). After isolating relevant tweets, hyperlinks associated with these tweets were reviewed to assess the characteristics of illegal online sellers. Results We collected and analyzed 213,041 tweets over the course of the Code-a-Thon containing keywords codeine, percocet, vicodin, oxycontin, oxycodone, fentanyl, and hydrocodone. Using BTM, 0.32% (692/213,041) tweets were identified as being associated with illegal online marketing and sale of prescription opioids. After removing duplicates and dead links, we identified 34 unique “live” tweets, with 44% (15/34) directing consumers to illicit online pharmacies, 32% (11/34) linked to individual drug sellers, and 21% (7/34) used by marketing affiliates. In addition to offering the “no prescription” sale of opioids, many of these vendors also sold other

Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic low back pain with a neuropathic component: a blinded end point analysis of randomly selected routine data from 12-week prospective open-label observations.

Science.gov (United States)

Ueberall, Michael A; Mueller-Schwefe, Gerhard H H

2016-01-01

To evaluate the benefit-risk profile (BRP) of oxycodone/naloxone (OXN) and tapentadol (TAP) in patients with chronic low back pain (cLBP) with a neuropathic component (NC) in routine clinical practice. This was a blinded end point analysis of randomly selected 12-week routine/open-label data of the German Pain Registry on adult patients with cLBP-NC who initiated an index treatment in compliance with the current German prescribing information between 1st January and 31st October 2015 (OXN/TAP, n=128/133). Primary end point was defined as a composite of three efficacy components (≥30% improvement of pain, pain-related disability, and quality of life each at the end of observation vs baseline) and three tolerability components (normal bowel function, absence of either central nervous system side effects, and treatment-emergent adverse event [TEAE]-related treatment discontinuation during the observation period) adopted to reflect BRP assessments under real-life conditions. Demographic as well as baseline and pretreatment characteristics were comparable for the randomly selected data sets of both index groups without any indicators for critical selection biases. Treatment with OXN resulted formally in a BRP noninferior to that of TAP and showed a significantly higher primary end point response vs TAP (39.8% vs 25.6%, odds ratio: 1.93; P =0.014), due to superior analgesic effects. Between-group differences increased with stricter response definitions for all three efficacy components in favor of OXN: ≥30%/≥50%/≥70% response rates for OXN vs TAP were seen for pain intensity in 85.2%/67.2%/39.1% vs 83.5%/54.1%/15.8% ( P = ns/0.031/<0.001), for pain-related disability in 78.1%/64.8%/43.8% vs 66.9%/50.4%/24.8% ( P =0.043/0.018/0.001), and for quality of life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% ( P =0.026/0.022/0.017). Overall, OXN vs TAP treatments were well tolerated, and proportions of patients who either maintained a normal bowel function (68.0% vs 72

Opioid Abuse After Traumatic Brain Injury: Evaluation Using Rodet Models

Science.gov (United States)

2014-07-01

pressing behavior was less likely to occur in brain-injured subjects following both exposure to oxycodone-associated cues as well as priming with a...pain medications. There is significant overlap in anatomical brain regions involved in reward pathways associated with addiction and the brain regions...commonly damaged in TBI which suggests that TBI could alter the reward circuitry, thereby increasing the likelihood of opioid abuse and addiction

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

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

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

Science.gov (United States)

2014-05-01

Bjork, S.J. Grant , Does traumatic brain injury increase risk for substance abuse?, J Neurotrauma (2009). [13] D.P. Graham, A.L. Cardon , An update on...Preliminary Study” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-2-0126 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Lt Col Vikhyat Bebarta, MD 5d. PROJECT

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

Science.gov (United States)

2010-01-01

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

Analgesic efficacy of local anaesthetic wound administration in knee arthroplasty: volume vs concentration

DEFF Research Database (Denmark)

Andersen, L Ø; Gaarn-Larsen, L; Kristensen, B B

2010-01-01

arthroplasty were randomly assigned to receive either a high volume/low concentration solution of ropivacaine (20 ml, 0.5%) or a low volume/high concentration solution of ropivacaine (10 ml, 1%), 6 and 24 h postoperatively through an intracapsular catheter. Pain was assessed for 2 h after administration. Pain...... was reduced in both groups with ropivacaine administration 24 h postoperatively (p ropivacaine injection 6 h postoperatively. The median (IQR [range]) dose of oxycodone administered...

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.

Pain Analysis in Patients with Hepatocellular Carcinoma: Irreversible Electroporation versus Radiofrequency Ablation—Initial Observations

International Nuclear Information System (INIS)

Narayanan, Govindarajan; Froud, Tatiana; Lo, Kaming; Barbery, Katuska J.; Perez-Rojas, Evelyn; Yrizarry, Jose

2013-01-01

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.

Ketamine as an adjunct to postoperative pain management in opioid tolerant patients after spinal fusions: a prospective randomized trial.

Science.gov (United States)

Urban, Michael K; Ya Deau, Jacques T; Wukovits, Barbara; Lipnitsky, Jane Y

2008-02-01

Management of acute postoperative pain is challenging, particularly in patients with preexisting narcotic dependency. Ketamine has been used at subanesthetic doses as a N-methyl D-aspartate (NMDA) receptor antagonist to block the processing of nociceptive input in chronic pain syndromes. This prospective randomized study was designed to assess the use of ketamine as an adjunct to acute pain management in narcotic tolerant patients after spinal fusions. Twenty-six patients for 1-2 level posterior lumbar fusions with segmental instrumentation were randomly assigned to receive ketamine or act as a control. Patients in the ketamine group received 0.2 mg/kg on induction of general anesthesia and then 2 mcg kg(-1) hour(-1) for the next 24 hours. Patients were extubated in the operating room and within 15 minutes of arriving in the Post Anesthesia Care Unit (PACU) were started on intravenous patient-controlled analgesia (PCA) hydromorphone without a basal infusion. Patients were assessed for pain (numerical rating scale [NRS]), narcotic use, level of sedation, delirium, and physical therapy milestones until discharge. The ketamine group had significantly less pain during their first postoperative hour in the PACU (NRS 4.8 vs 8.7) and continued to have less pain during the first postoperative day at rest (3.6 vs 5.5) and with physical therapy (5.6 vs 8.0). Three patients in the control group failed PCA pain management and were converted to intravenous ketamine infusions when their pain scores improved. Patients in the ketamine group required less hydromorphone than the control group, but the differences were not significant. Subanesthetic doses of ketamine reduced postoperative pain in narcotic tolerant patients undergoing posterior spine fusions.

Clearing the smoke around medical marijuana.

Science.gov (United States)

Ware, M A

2011-12-01

The hazy world of "medical marijuana" continues to cry out for clear data on which to base medical decision making and rational policy design. In this issue of Clinical Pharmacology & Therapeutics, Abrams and colleagues report that vaporized cannabis does not meaningfully affect opioid plasma levels and may even augment the efficacy of oxycodone and morphine in patients with chronic non-cancer pain. This Commentary considers the implications of this work for clinical practice and further research initiatives.

Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

Science.gov (United States)

2015-09-01

craniotomy was cut with a trephine by hand over the right motor cortex . An injury cannula was fashioned from the hub of a female leur-lock 20g needle...ABSTRACT This project evaluated the effect of a moderate-level brain injury on risk for opioid abuse using preclinical models in rats . We assessed the...effect of brain injury on the rewarding effects of oxycodone in three rat self-administration procedures and found significant differences in the

Solution to Detect, Classify, and Report Illicit Online Marketing and Sales of Controlled Substances via Twitter: Using Machine Learning and Web Forensics to Combat Digital Opioid Access.

Science.gov (United States)

Mackey, Tim; Kalyanam, Janani; Klugman, Josh; Kuzmenko, Ella; Gupta, Rashmi

2018-04-27

On December 6 and 7, 2017, the US Department of Health and Human Services (HHS) hosted its first Code-a-Thon event aimed at leveraging technology and data-driven solutions to help combat the opioid epidemic. The authors—an interdisciplinary team from academia, the private sector, and the US Centers for Disease Control and Prevention—participated in the Code-a-Thon as part of the prevention track. The aim of this study was to develop and deploy a methodology using machine learning to accurately detect the marketing and sale of opioids by illicit online sellers via Twitter as part of participation at the HHS Opioid Code-a-Thon event. Tweets were collected from the Twitter public application programming interface stream filtered for common prescription opioid keywords in conjunction with participation in the Code-a-Thon from November 15, 2017 to December 5, 2017. An unsupervised machine learning–based approach was developed and used during the Code-a-Thon competition (24 hours) to obtain a summary of the content of the tweets to isolate those clusters associated with illegal online marketing and sale using a biterm topic model (BTM). After isolating relevant tweets, hyperlinks associated with these tweets were reviewed to assess the characteristics of illegal online sellers. We collected and analyzed 213,041 tweets over the course of the Code-a-Thon containing keywords codeine, percocet, vicodin, oxycontin, oxycodone, fentanyl, and hydrocodone. Using BTM, 0.32% (692/213,041) tweets were identified as being associated with illegal online marketing and sale of prescription opioids. After removing duplicates and dead links, we identified 34 unique “live” tweets, with 44% (15/34) directing consumers to illicit online pharmacies, 32% (11/34) linked to individual drug sellers, and 21% (7/34) used by marketing affiliates. In addition to offering the “no prescription” sale of opioids, many of these vendors also sold other controlled substances and illicit drugs

CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications

Directory of Open Access Journals (Sweden)

St Sauver JL

2017-07-01

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–drug interactions could be substantial. Keywords: CYP2D6, opioid, phenotype, adverse effects

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, ppain (p=0.915) or VAS scores (p=0.372) between groups at any time point (dogs were excluded from analysis after rescue). Conclusions and Clinical Relevance This study suggests that carprofen, with opioid premedication, provides more effective post-operative analgesia than tramadol in dogs undergoing enucleation. PMID:25459482

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Palatoplasty.

Science.gov (United States)

Day, Kristopher M; Nair, Narayanan M; Sargent, Larry A

2018-05-14

Liposomal bupivacaine (LB) is a long-acting local anesthetic reported to decrease postoperative pain in adults. The authors demonstrate the safe use of LB in pediatric patients with improved pain control following palatoplasty. Retrospective patient series of all single-surgeon palatoplasty patients treated at a tertiary craniofacial center from August 2014 to December 2015 were included. All patients received 1.3% LB intraoperatively as greater palatal nerve and surgical field blocks in 2-flap V-Y pushback palatoplasty. Postoperative oral intake, opioids administered, duration of hospitalization, and FLACC (face, legs, activity, cry, consolability) pain scores were measured. Twenty-seven patients (16 males and 11 females, average age of 10.8 months, weight 8.8 kg) received 2.9 ± 0.9 mL (2.6 ± 1.9 mg/kg) 1.3% LB. Average FLACC scores were 2.4 ± 2.2/10 in the postanesthesia care unit and 3.8 ± 1.8/10 while inpatients. Oral intake was first tolerated 10.3 ± 11.5 hours postoperatively and tolerated 496.4 ± 354.2 mL orally in the first 24 hours postoperatively. Patients received 8.5 ± 8.4 mg hydrocodone equivalents (0.46 ± 0.45 mg/kg per d hydrocodone equivalents) and were discharged 2.1 ± 1.3 days postoperatively. Opioid-related adverse events included emesis in 7.4% and pruritis in 3.7% of patients. The LB may be used safely in pediatric patients. Intraoperative injection of LB during palatoplasty can yield low postoperative opioid use and an early and adequate volume of oral intake over an average hospital stay. Further cost-efficacy studies of LB are needed to assess its value in pediatric plastic surgery.

Emergency Department Patient Perspectives on the Risk of Addiction to Prescription Opioids.

Science.gov (United States)

Conrardy, Michael; Lank, Patrick; Cameron, Kenzie A; McConnell, Ryan; Chevrier, Alison; Sears, Jill; Ahlstrom, Eric; Wolf, Michael S; Courtney, D Mark; McCarthy, Danielle M

2016-01-01

To characterize emergency department (ED) patients' knowledge and beliefs about the addictive potential of opioids. Mixed methods analysis of data from a randomized controlled trial. Urban academic ED (>88,000 visits). One hundred and seventy four discharged ED patients prescribed hydrocodone-acetaminophen for acute pain. The study analyzed data collected from a randomized controlled trial investigating patients' knowledge of opioids. ED patients discharged with hydrocodone-acetaminophen completed an audio-recorded phone interview 4–7 days later. This analysis focuses on responses about addiction. Responses were categorized using content analysis; thematic analysis identified broad themes common across different categories. Participants' mean age was 45.5 years (SD, 14.8), 58.6% female, 50.6% white, and the majority had an orthopedic diagnosis (24.1% back pain, 52.3% other injuries). Responses were categorized first based on whether the patient believed that opioids could be addictive (categorized as: yes, 58.7%; no, 19.5%; depends, 17.2%; or do not know, 4.6%), and second based on whether or not the patient discussed his/her own experience with the medication (categorized as: personalized, 35.6%; or not personalized, 64.4%). Cohen's Kappa was 0.84 for all categories. Three themes emerged in the thematic analysis: theme 1) patients expect to “feel” addicted if they are addicted, theme 2) patients fear addiction, and theme 3) side effects affected patient views of addiction. In this sample, patients had misconceptions about opioid addiction. Some patients did not know opioids could be addictive, others underestimated their personal risk of addiction, and others overtly feared addiction and, therefore, risked inadequate pain management. Despite limited data, we recommend providers discuss opioid addiction with their patients. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government

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

Science.gov (United States)

2011-12-30

... discontinued from marketing for reasons other than safety or effectiveness. ANDAs that refer to HYCODAN... Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for...

Analysis of Drugs of Abuse in Anonymously Collected Urine and Soil samples from a Music Festival in Scandinavia

DEFF Research Database (Denmark)

Mardal, Marie; Ramin, Pedram; Plósz, Benedek G.

Aim: Pooled human urine and soil from urinating spots were collected anonymously at a Scandinavian music festival. Samples should be screened for drugs of abuse, particularly novel psychoactive substances (NPS), but also therapeutic drugs and ethanol. Methods: Twenty-one urine samples were...... be detected besides several therapeutic drugs: cocaine (9), MDMA (7), sildenafil (2), ketamine (1), amphetamine (1), and oxycodone (1). Conclusions: NPS were detected neither in urine nor in soil samples. This might be due to low concentrations based on their negligible consumption at the studied festival...

Renal function and symptoms/adverse effects in opioid-treated patients with cancer

DEFF Research Database (Denmark)

Kurita, G P; Lundström, S; Sjøgren, P

2015-01-01

BACKGROUND: Renal impairment and the risk of toxicity caused by accumulation of opioids and/or active metabolites is an under-investigated issue. This study aimed at analysing if symptoms/adverse effects in opioid-treated patients with cancer were associated with renal function. METHODS: Cross...... loss of appetite (P = 0.04). No other significant associations were found. CONCLUSION: Only severe constipation and loss of appetite were associated with low GFR in patients treated with morphine. Oxycodone and fentanyl, in relation to the symptoms studied, seem to be safe as used and titrated...

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

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

2017-11-01

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-HT 2C 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.

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

Science.gov (United States)

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

2017-07-01

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

Safety of oral dronabinol during opioid withdrawal in humans.

Science.gov (United States)

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

2015-12-01

Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30 mg qid. Double-blind placebo substitutions occurred for 21 h before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60 mg, dronabinol 5, 10, 20, and 30 mg [decreased from 40 mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. Dronabinol 40 mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30 mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30 mg produced significant increases in heart rate beginning 1h after drug administration that lasted approximately 2h (popioid agonist effects (e.g., miosis). Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Science.gov (United States)

Holzer, Peter

2012-01-01

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

Changing Trends in Opioid Use Among Patients With Rheumatoid Arthritis in the United States.

Science.gov (United States)

Curtis, Jeffrey R; Xie, Fenglong; Smith, Christian; Saag, Kenneth G; Chen, Lang; Beukelman, Timothy; Mannion, Melissa; Yun, Huifeng; Kertesz, Stefan

2017-09-01

Opioid prescribing recently has come under intense scrutiny. However, longitudinal patterns of prescription opioid receipt in a population-based cohort of patients with chronic pain, such as those with rheumatoid arthritis (RA), have not been well characterized. The aim of this study was to examine both trends over time and variability in individual physician prescribing of short-term and long-term use of opioids. We identified a cohort of RA patients based on 2006-2014 Medicare data and evaluated longitudinal time trends in "regular" use of opioids. A separate analysis conducted in 2014 assessed rheumatologist-specific variability in regular use of opioid prescriptions in patients with RA. We identified 97,859 RA patients meeting the eligibility criteria. The mean age of the patients was 67 years, 80% were female, 82% were white, and 12% were African American. The most commonly used opioids were those that combined acetaminophen with hydrocodone or propoxyphene. Regular opioid prescribing increased slowly but peaked in 2010 before propoxyphene was withdrawn from the market. Following the withdrawal of propoxyphene, receipt of hydrocodone and tramadol increased commensurately, and overall opioid use declined only slightly. Factors associated with regular use of opioids included younger age, female sex, African American race, back pain, fibromyalgia, anxiety, and depression. Variability between US rheumatologists (n = 4,024) in prescribing the regular use of opioids for their RA patients was high; in the average rheumatologist's practice, 40% of RA patients used prescription opioids regularly. In almost half of the patients, at least some opioid prescriptions were written by a rheumatologist, and 14% received opioids that were co-prescribed concurrently by more than 1 physician. In the US, opioid use in older patients with RA peaked in 2010 and is now declining slightly. Withdrawal of propoxyphene from the US market in 2010 had minimal effect on overall opioid

Opioid-induced hyponatremia in a patient with central diabetes insipidus: independence from ADH.

Science.gov (United States)

Bhat, Nandini; Balliu, Erjola; Osipoff, Jennifer; Lane, Andrew; Wilson, Thomas

2017-05-24

Hyponatremia can be a complication of opioid therapy, which has been postulated to occur secondary to inappropriate antidiuretic hormone secretion (syndrome of inappropriate antidiuretic hormone secretion [SIADH]). We report severe hyponatremia following wisdom teeth extraction with opioid analgesia in a 19-year-old female with diabetes insipidus (DI) and acquired panhypopituitarism that challenges this theory. As this patient has DI, we believe opioid treatment caused severe hyponatremia by the following mechanisms: (1) Opioids have a direct antidiuretic effect independent of changes in ADH, as demonstrated in Brattleboro rats with central DI. (2) Hydrocodone may have stimulated this patient's thirst center contributing to hyponatremia, as demonstrated in animal studies. Opioid use can cause hyponatremia in patients independent of ADH. It is important for clinicians to be aware of this so that patients can be appropriately counseled.

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.

Administration of a co-crystal of tramadol and celecoxib in a 1:1 molecular ratio produces synergistic antinociceptive effects in a postoperative pain model in rats.

Science.gov (United States)

Merlos, Manuel; Portillo-Salido, Enrique; Brenchat, Alex; Aubel, Bertrand; Buxens, Jordi; Fisas, Angels; Codony, Xavier; Romero, Luz; Zamanillo, Daniel; Vela, José Miguel

2018-06-19

Drug combination for the treatment of pain is common clinical practice. Co-crystal of Tramadol-Celecoxib (CTC) consists of two active pharmaceutical ingredients (APIs), namely the atypical opioid tramadol and the preferential cyclooxygenase-2 inhibitor celecoxib, at a 1:1 molecular ratio. In this study, a non-formulated 'raw' form of CTC administered in suspension (referred to as ctc susp ) was compared with both tramadol and celecoxib alone in a rat plantar incision postoperative pain model. For comparison, the strong opioids morphine and oxycodone, and a tramadol plus acetaminophen combination at a molecular ratio of 1:17 were also tested. Isobolographic analyses showed that ctc susp exerted synergistic mechanical antiallodynic (experimental ED 50 =2.0±0.5mg/kg, i.p.; theoretical ED 50 =3.8±0.4mg/kg, i.p.) and thermal (experimental ED 50 =2.3±0.5mg/kg, i.p.; theoretical ED 50 =9.8±0.8mg/kg, i.p.) antihyperalgesic effects in the postoperative pain model. In contrast, the tramadol and acetaminophen combination showed antagonistic effects on both mechanical allodynia and thermal hyperalgesia. No synergies between tramadol and celecoxib on locomotor activity, motor coordination, ulceration potential and gastrointestinal transit were observed after the administration of ctc susp . Overall, rat efficacy and safety data revealed that ctc susp provided synergistic analgesic effects compared with each API alone, without enhancing adverse effects. Moreover, ctc susp showed similar efficacy but improved safety ratio (80, measured as gastrointestinal transit vs postoperative pain ED 50 ratios) compared with the strong opioids morphine (2.5) and oxycodone (5.8). The overall in vivo profile of ctc susp supports the further investigation of CTC in the clinical management of moderate-to-severe acute pain as an alternative to strong opioids. Copyright © 2018. Published by Elsevier B.V.

Behavioral architecture of opioid reward and aversion in C57BL/6 substrains

Directory of Open Access Journals (Sweden)

Stacey L Kirkpatrick

2015-01-01

Full Text Available Drug liking versus drug disliking is a subjective motivational measure in humans that assesses the addiction liability of drugs. Variation in this trait is hypothesized to influence vulnerability versus resilience toward substance abuse disorders and likely contains a genetic component. In rodents and humans, conditioned place preference (CPP / aversion (CPA is a Pavlovian conditioning paradigm whereby a learned preference for the drug-paired environment is used to infer drug liking whereas a learned avoidance or aversion is used to infer drug disliking. C57BL/6 inbred mouse substrains are nearly genetically identical, yet demonstrate robust differences in addiction-relevant behaviors, including locomotor sensitization to cocaine and consumption of ethanol. Here, we tested the hypothesis that B6 substrains would demonstrate differences in the rewarding properties of the mu opioid receptor agonist oxycodone (5 mg/kg, i.p. and the aversive properties of the opioid receptor antagonist naloxone (4 mg/kg, i.p.. Both substrains showed similar degrees of oxycodone-induced CPP; however, there was a three-fold enhancement of naloxone-induced CPA in agonist-naïve C57BL/6J relative to C57Bl/6NJ mice. Exploratory factor analysis of CPP and CPA identified unique factors that explain variance in behavioral expression of reward versus aversion. Conditioned Opioid-Like Behavior was a reward-based factor whereby drug-free locomotor variables resembling opioid treatment co-varied with the degree of CPP. Avoidance and Freezing was an aversion-based factor, whereby the increase in the number of freezing bouts co-varied with the degree of aversion. These results provide new insight into the behavioral architecture of the motivational properties of opioids. Future studies will use quantitative trait locus mapping in B6 substrains to identify novel genetic factors that contribute to the marked strain difference in NAL-CPA.

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

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

Science.gov (United States)

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

2016-12-01

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

Prescription opioid use: Patient characteristics and misuse in community pharmacy.

Science.gov (United States)

Cochran, Gerald; Bacci, Jennifer L; Ylioja, Thomas; Hruschak, Valerie; Miller, Sharon; Seybert, Amy L; Tarter, Ralph

2016-01-01

Opioid pain medication misuse is a major concern for US public health. The purpose of this article is to: 1) describe the demographic and physical, behavioral, and mental health characteristics of patients who fill opioid medications in community pharmacy settings; and 2) describe the extent of opioid medication misuse behaviors among these patients. We recruited and screened a convenience sample of patients with the use of a tablet computer-based assessment protocol that examined behavioral, mental, and physical health. Descriptive and inferential statistics were calculated to describe respondents and their opioid medication misuse and health characteristics. Patients were screened in 2 urban and 2 rural community pharmacies in southwestern Pennsylvania. Survey participants were adult patients filling opioid pain medications who were not currently receiving treatment for a cancer diagnosis. None. Validated screening measures included the Prescription Opioid Misuse Index, Alcohol Use Disorders Identification Test C, Short Form 12, Drug Abuse Screening Test 10, Primary Care Post-traumatic Stress Disorder (PTSD) screen, and the Patient Health Questionnaire 2. A total of 333 patients were screened (71.2% response rate). Nearly the entire population reported pain above and general health below national norms. Hydrocodone (19.2%) and morphine (20.8%) were found to be the medications with the highest rates of misuse-with hydrocodone having more than 4 times higher odds of misuse compared with other medications (adjusted odds ratio [AOR] 4.48, 95% confidence interval [CI] 1.1-17.4). Patients with positive screens for illicit drug use (AOR 8.07, 95% CI 2.7-24.0), PTSD (AOR 5.88, 95% CI 2.3-14.7), and depression (AOR 2.44, 95% CI 1.0-5.9) also had significantly higher odds for misuse compared with those with negative screening results. These findings provide important foundational data that suggest implementation of regular opioid misuse screening protocols within

The effects of preoperative oral administration of carprofen or tramadol on postoperative analgesia in dogs undergoing cutaneous tumor removal.

Science.gov (United States)

Karrasch, Nicole M; Lerche, Phillip; Aarnes, Turi K; Gardner, Heather L; London, Cheryl A

2015-08-01

This prospective, blinded, controlled clinical study compared the effects of pre-emptive oral administration of carprofen or tramadol on pain scores and analgesic requirement in dogs undergoing cutaneous tumor removal. Thirty-six client-owned dogs presenting for cutaneous tumor removal were randomly assigned to receive carprofen, tramadol, or no treatment prior to surgery. Pain was assessed using a visual analog scale (VAS), the Modified Glasgow Composite Measure Pain Score (MGCMPS), and algometry at enrollment, prior to premedication, at extubation, then hourly for the first 4 h, and every 4 h for 24 h. Dogs scoring ≥ 7 (MGCMPS), or having a VAS measurement ≥ 40 mm were given rescue analgesia. There were no significant differences in pain VAS, MGCMPS, or algometry. There were no differences in rescue analgesia requirement, or time to rescue analgesia among groups. Carprofen, tramadol, or no pre-emptive analgesia, combined with pre-operative hydromorphone and rescue analgesia, resulted in satisfactory analgesia in the 24-hour postoperative period.

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.

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period

DEFF Research Database (Denmark)

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose

2018-01-01

analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology......Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug......-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid...

Analgesic efficacy of local anaesthetic wound administration in knee arthroplasty: volume vs concentration

DEFF Research Database (Denmark)

Andersen, L Ø; Gaarn-Larsen, L; Kristensen, B B

2010-01-01

was reduced in both groups with ropivacaine administration 24 h postoperatively (p time intervals. No reduction in pain scores was observed with ropivacaine injection 6 h postoperatively. The median (IQR [range]) dose of oxycodone administered......Wound administration of local anaesthetic may be effective for postoperative pain management in knee arthroplasty, but the analgesic efficacy of local anaesthetic in relation to volume vs concentration has not been determined. In a double-blinded trial, 48 patients scheduled for total knee...... arthroplasty were randomly assigned to receive either a high volume/low concentration solution of ropivacaine (20 ml, 0.5%) or a low volume/high concentration solution of ropivacaine (10 ml, 1%), 6 and 24 h postoperatively through an intracapsular catheter. Pain was assessed for 2 h after administration. Pain...

To prescribe codeine or not to prescribe codeine?

Science.gov (United States)

Fleming, Marc L; Wanat, Matthew A

2014-09-01

A recently published study in Pediatrics by Kaiser et al. (2014; Epub April 21, DOI: 10.1542/peds.2013-3171) reported that on average, over the past decade, children aged 3 to 17 were prescribed approximately 700,000 prescriptions for codeine-containing products each year in association with emergency department (ED) visits. Although, guidelines from the American Academy of Pediatrics issued warnings in 1997 and reaffirmed their concerns regarding the safety and effectiveness of codeine in 2006, it is still often prescribed for pain and cough associated with upper respiratory infection. With the impending rescheduling of hydrocodone combination products to Schedule II, physicians and mid-level prescribers may be compelled to prescribe codeine-containing products (e.g., with acetaminophen) due to reduced administrative burden and limits on Schedule II prescriptive authority for nurse practitioners and physician assistants in some states. This commentary expounds on the safety and effectiveness concerns of codeine, with a primary focus on patients in the ED setting.

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

Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?

Science.gov (United States)

Currow, David C; Quinn, Stephen; Ekstrom, Magnus; Kaasa, Stein; Johnson, Miriam J; Somogyi, Andrew A; Klepstad, Päl

2015-01-01

Objectives Opioids modulate the perception of breathlessness with a considerable variation in response, with poor correlation between the required opioid dose and symptom severity. The objective of this hypothesis-generating, secondary analysis was to identify candidate single nucleotide polymorphisms (SNP) from those associated with opioid receptors, signalling or pain modulation to identify any related to intensity of breathlessness while on opioids. This can help to inform prospective studies and potentially lead to better tailoring of opioid therapy for refractory breathlessness. Setting 17 hospice/palliative care services (tertiary services) in 11 European countries. Participants 2294 people over 18 years of age on regular opioids for pain related to cancer or its treatment. Primary outcome measures The relationship between morphine dose, breathlessness intensity (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs from 25 genes (n=588). Secondary outcome measures The same measures for people on oxycodone (n=402) or fentanyl (n=429). Results SNPs not in Hardy-Weinberg equilibrium or with allele frequencies (<5%) were removed. Univariate associations between each SNP and breathlessness intensity were determined with Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal logistic regression, clustering over country and adjusting for available confounders, was conducted with remaining SNPs. For univariate morphine associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on the β-2-arrestin gene (ARRB2) were associated with more intense breathlessness. 1 SNP remained significant in the multivariable model: people with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to 5.62; p=0.002). No associations were seen with fentanyl nor with

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

Science.gov (United States)

2012-07-06

... being manufactured and distributed. In 2009, the Agency sent warning letters to companies manufacturing... opportunity to assess the adequacy of their chemistry, manufacturing, and controls specifications before...), have the potential to be highly addictive, and are extremely popular drugs of abuse. The particular...

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

International Nuclear Information System (INIS)

Krizsan, D.; Varga, E.; Benyhe, S.; Szucs, M.; Borsodi, A.; Hosztafi, S.

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 ( 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 + -index of compounds indicating their mixed agonist-antagonist character. The dihydromorphinone derivatives are all capable to block irreversibly the high affinity binding site of ( 3 H)naloxone, whereas the dihydrocodeinone derivatives block irreversibly the low affinity site. A possible mechanism for the inhibition is suggested

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......Painful Diabetic peripheral neuropathy (painful DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors are proven to contribute to the aetiology...... of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been proven to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements...

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

Directory of Open Access Journals (Sweden)

Terrien BD

2017-01-01

Full Text Available Brian D Terrien,1 David Espinoza,2 Charles C Stehman,3 Gabriel A Rodriguez,1 Nicholas C Connolly1 1Department of Anesthesiology, Naval Medical Center San Diego, 2Surface Warfare Medical Institute, San Diego, 3Department of Anesthesiology, Robert E. Bush Naval Hospital, Twenty Nine Palms, CA, USA Abstract: 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. Keywords: liposome bupivacaine (bupivacaine liposome injectable suspension, plasma bupivacaine levels, transversus abdominis plane (TAP nerve block, thoracic epidural

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.

Forskelle på ordinationsmønstret af analgetika ved behandling af cancersmerter på seks danske smertebehandlingsenheder

DEFF Research Database (Denmark)

Olesen, Anne Estrup; Jarvig, Line; Hansen, Ole Bo

2007-01-01

. For the treatment of background pain opioids were prescribed for the majority of the cancer patients. Morphine and oxycodone were prescribed most frequently. Secondary analgesics and paracetamol and/or NSAID were also prescribed for background pain. The strong opioids were prescribed for the treatment......30-40% of cancer patients suffer from pain at diagnosis while 70-80% of patients at progressed stages of the disease suffer from pain. Background pain is treated with long-acting opioids. Breakthrough pain can be treated with shorter acting non-opioid analgesics or opioids. The aim of this study...... was to describe the medical treatment of pain in cancer patients in connection with six Danish hospital units with special expertise in pain treatment. Differences in the prescription of analgesics were studied. The study was performed as a cross section study of prescribed analgesics. Data was collected...

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

Science.gov (United States)

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

2015-03-01

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

Multi-centre European study of breakthrough cancer pain: pain characteristics and patient perceptions of current and potential management strategies

DEFF Research Database (Denmark)

Davies, Andrew; Zeppetella, Giovambattista; Andersen, Steen

2011-01-01

This study involved 320 cancer patients from four Northern European countries. Patients with breakthrough pain were questioned about the characteristics of their pain, the current management of their pain, and the acceptability/utility of alternative routes of administration. The median number...... of episodes was 3/day. Forty-four percent patients reported incident-type pain, 39% spontaneous-type pain, and 17% a combination of these pains. The median duration was 60 min, and the median time to peak intensity was 15 min. Three percent patients reported "mild" pain, 37% "moderate" pain, and 60% "severe......" pain. Ninety percent patients stated that the pain interfered with their daily activities. All patients were using opioids as rescue medication (mainly oral morphine/oxycodone), whilst 28% patients were using non-opioids, and 50% patients were using non-pharmacological interventions. Only 55% patients...

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...

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

DEFF Research Database (Denmark)

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

2017-01-01

: The literature search was conducted in Pub Med (http://www.ncbi.nlm.nih.gov/pubmed) from November 2014 to June 2016, using free-text terms: "opioid", "morphine" and "oxycodone" combined with the terms "pupillometry," "magnetic resonance spectroscopy," "fMRI," "BOLD," "PET," "pharmaco-EEG", "electroencephalogram...... imaging (fMRI), positron emission tomography (PET), spontaneous electroencephalogram (EEG) and evoked potentials (EPs). Pupillometry is a non-invasive tool used in research as well as in the clinical setting. Proton magnetic resonance spectroscopy has been used for the last decades and it is a non......-invasive technique for measurement of in vivo brain metabolite concentrations. fMRI has been a widely used non-invasive method to estimate brain activity, where typically from the blood oxygen level-dependent (BOLD) signal. PET is a nuclear imaging technique based on tracing radio labeled molecules injected...

Fracture of an endoluminal nitinol stent used in the treatment of tracheal collapse in a dog.

Science.gov (United States)

Mittleman, Elise; Weisse, Chick; Mehler, Stephen J; Lee, Justine A

2004-10-15

A 5-year-old castrated male Pomeranian was evaluated because of severe dyspnea and coughing, and a diagnosis of complete, static collapse of the trachea at the thoracic inlet was made. After failure to improve with medical management alone, an endoluminal tracheal stent was placed, which resulted in resolution of signs. Ten weeks after stent placement, the dog underwent tracheal resection and anastomosis because the stent had fractured at the level of the thoracic inlet. One year after surgery, the dog was doing well and required treatment with hydrocodone infrequently. Compared with other surgical treatment options, placement of an endoluminal tracheal stent is a relatively noninvasive intervention that can provide effective relief from the clinical signs associated with tracheal collapse in dogs. Implantation of endoluminal tracheal stents may be associated with complications; therefore, the procedure may best be regarded as a salvage procedure for dogs with end-stage disease that are refractory to appropriate medical management, have extensive collapse of the intrathoracic portion of the trachea, or are poor candidates for surgery.

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

Science.gov (United States)

2013-04-18

... mitigation strategy (REMS) http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor... Blueprint for Prescriber Education for Extended- Release and Long-Acting Opioid Analgesics'' ( http://www...

Adult emergency department patients with sickle cell pain crisis: results from a quality improvement learning collaborative model to improve analgesic management.

Science.gov (United States)

Tanabe, Paula; Hafner, John W; Martinovich, Zoran; Artz, Nicole

2012-04-01

period than during the preintervention period (-4.1 vs. -3.6, t = 2.6, p 19 visits). There was an overall decrease in the use of morphine sulfate (MS) and increase in the use of hydromorphone (χ(2) = 105.67, p manage pain in the ED between study periods (p = 0.54). While the use of a learning collaborative and implementation of nurse-initiated analgesic protocols was not associated with improvement in time to administration of the initial analgesic, improvements in the decrease in the arrival to discharge pain score and increased use of hydromorphone and the SC route were noted in adults with SCD in the ED. © 2012 by the Society for Academic Emergency Medicine.

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

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

Characterization of [³H] oxymorphone binding sites in mouse brain

DEFF Research Database (Denmark)

Yoo, Ji Hoon; Borsodi, Anna; Tóth, Géza

2017-01-01

Oxymorphone, one of oxycodone's metabolic products, is a potent opioid receptor agonist which is thought to contribute to the analgesic effect of its parent compound and may have high potential abuse liability. Nonetheless, the in vivo pharmacological binding profile of this drug is still unclear....... This study uses mice lacking mu (MOP), kappa (KOP) or delta (DOP) opioid receptors as well as mice lacking all three opioid receptors to provide full characterisation of oxymorphone binding sites in the brain. Saturation binding studies using [3H]oxymorphone revealed high affinity binding sites in mouse......]Oxymorphone binding was completely abolished across the majority of the brain regions in mice lacking MOP as well as in mice lacking all three opioid receptors. DOP and KOP knockout mice retained [3H]oxymorphone binding sites suggesting oxymorphone may not target DOP or KOP. These results confirm that the MOP...

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

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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

Structural Determinants for the Binding of Morphinan Agonists to the μ-Opioid Receptor.

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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.

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.

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

International Nuclear Information System (INIS)

Alburges, M.E.

1988-01-01

The assay is based on the competition of these drugs with [ 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 [ 3 H]fentanyl for the opioid receptor, but other morphine-like compounds were relatively weak displacers of [ 3 H]fentanyl. Many other commonly abused drugs do not compete with [ 3 H]fentanyl for the opioid receptors. Urine samples from animals injected with fentanyl, (±)-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

Neurobiology of opioid withdrawal: Role of the endothelin system.

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

2016-08-15

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

The impact of pharmacy services on opioid prescribing in dental practice.

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Stewart, Autumn; Zborovancik, Kelsey J; Stiely, Kara L

To compare rates of dental opioid prescribing between periods of full and partial integration of pharmacy services and periods of no integration. This observational study used a retrospective chart review of opioid prescriptions written by dental providers practicing in a free dental clinic for the medically underserved over a period of 74 months. Pharmacy services were fully integrated into the practice model for 48 of the 74 months under study. During this time frame, all dental opioid orders required review by the pharmacy department before prescribing. Outcomes related to prescribing rates and errors were compared between groups, which were defined by the level of integrated pharmacy services. Demographic and prescription-specific data (drug name, dose, quantity, directions, professional designation of individual entering order) and clinic appointment data were collected and analyzed with the use of descriptive and inferential statistics. A total of 102 opioids were prescribed to 89 patients; hydrocodone-acetaminophen combination products were the most frequently used. Opioid prescribing rates were 5 times greater when pharmacy services were not integrated (P dental practice. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Quantitative sensory testing measures individual pain responses in emergency department patients

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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

Evaluation of abalone β-glucuronidase substitution in current urine hydrolysis procedures.

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Malik-Wolf, Brittany; Vorce, Shawn; Holler, Justin; Bosy, Thomas

2014-04-01

This study examined the potential of abalone β-glucuronidase as a viable and cost effective alternative to current hydrolysis procedures using acid, Helix pomatia β-glucuronidase and Escherichia coli β-glucuronidase. Abalone β-glucuronidase successfully hydrolyzed oxazepam-glucuronide and lorazepam-glucuronide within 5% of the spiked control concentration. Benzodiazepines present in authentic urine specimens were within 20% of the concentrations obtained with the current hydrolysis procedure using H. pomatia β-glucuronidase. JWH 018 N-(5-hydroxypentyl) β-d-glucuronide was hydrolyzed within 10% of the control concentration. Authentic urine specimens showed improved glucuronide cleavage using abalone β-glucuronidase with up to an 85% increase of drug concentration, compared with the results obtained using E. coli β-glucuronidase. The JWH 018 and JWH 073 carboxylic acid metabolites also showed increased drug concentrations of up to 24%. Abalone β-glucuronidase was able to completely hydrolyze a morphine-3-glucuronide control, but only 82% of total morphine was hydrolyzed in authentic urine specimens compared with acid hydrolysis results. Hydrolysis of codeine and hydromorphone varied between specimens, suggesting that abalone β-glucuronidase may not be as efficient in hydrolyzing the glucuronide linkages in opioid compounds compared with acid hydrolysis. Abalone β-glucuronidase demonstrates effectiveness as a low cost option for enzyme hydrolysis of benzodiazepines and synthetic cannabinoids.

Trends in Substance Use Across the Nation and South Dakota.

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Daniel, Jeremy; Owen, Amanda

2016-01-01

With the discovery of morphine in the early 1800s, substance abuse quickly followed. Next came the production of heroin and other synthetic opioids, along with increases in nonmedical use of prescription medications. In the 21st century, drug abuse and addiction continues to rise nationwide with the three most common drugs abused in adolescents being marijuana, synthetic marijuana, and hallucinogens. Among adolescents and adults nationwide, rates of alcohol, opioids, and amphetamine use have increased over the last decade. In South Dakota, the most prevalent drugs consist of alcohol, methamphetamine, heroin, and prescription opioids. Through the implementation and use of the Prescription Drug Monitoring Program (PDMP) by the South Dakota Board of Pharmacy (SDBOP), hydrocodone/acetaminophen has been identified as the most dispensed controlled substance in the state with roughly 21,000 prescriptions dispensed last November alone. While the PDMP does not necessarily encompass all controlled substances used by the patient (e.g., those purchased from illicit sources), the generation of PDMP reports by physicians and pharmacists is still beneficial. With increased use of the PDMP along with urine drug screens and patient interviews, health care professionals can continue to work collaboratively to help curb the growing epidemic of substance use. Copyright© South Dakota State Medical Association.

Psychosocial and pharmacological management of pain in pediatric sickle cell disease.

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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.

Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

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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.

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period.

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Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian

2018-04-01

Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results. Copyright © 2018 Elsevier B.V. All rights reserved.

Body pushing, prescription drugs and hospital admission.

Science.gov (United States)

Byard, Roger W; Kenneally, Michaela

2017-09-01

A 39-year-old man died of multi-organ failure complicating mixed drug toxicity that included methadone, oxazepam, oxycodone and nitrazepam. His past medical history involved alcohol and poly-substance abuse with chronic self-harm and suicidal ideation. There had been multiple hospital admissions for drug overdoses. At autopsy the most unusual finding was of two packages of 10 tablets each, wrapped in thin plastic film within the rectum. The insertion of drugs into body orifices and cavities has been termed body pushing to distinguish it from body packing where illicit drugs are wrapped and swallowed for transport and smuggling, and body stuffing where small amounts of loosely wrapped or unwrapped drugs are swallowed to conceal evidence from police. This case demonstrates that body pushing may not always involve illicit drugs or attempted concealment from police or customs officials. It appears that the drugs had been hidden to ensure an additional supply during the time of residence in hospital. The extent to which body pushing is currently being used by patients to smuggle drugs into secure medical facilities is yet to be determined.

Characteristics of Suicides Caused by Drug Overdose in the State of Maryland

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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

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

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

2017-03-01

oxycodone in RLS, opioids have been considered an efficacious off-label therapy in patients with severe RLS. A recent trial has proved the efficacy of a combination of prolonged release oxycodone/naloxone in patients with severe RLS as second-line therapy, with a mean dosage of 10/5 mg twice daily (mean difference of International Restless Legs Syndrome Study Group Rating Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been licensed as the first opioid therapy in Europe. The current results from both short- and long-term trials and studies with opioids encourage optimism in alleviating RLS symptoms in patients with severe RLS, or possibly during or after augmentation. Copyright © 2016 Elsevier B.V. All rights reserved.

PCA-derived factors that may be predictive of postoperative pain in pediatric patients: a possible role for the PCA ratio.

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McDonnell, Conor; Pehora, Carolyne; Crawford, Mark W

2012-01-01

No method exists to reliably predict which patients will develop severe postoperative pain. The authors hypothesized that data derived from patient-controlled analgesia (PCA) pumps (specifically the ratio of patient demands to pump deliveries) may predict which patients would develop severe pain after scoliosis repair. Quaternary, university-affiliated, pediatric hospital. Forty American Society of Anesthesiologists I-Il pediatric patients who had undergone elective scoliosis repair and had consented to recruitment to a randomized clinical trial investigating the effects of early morphine administration on remifentanil-induced hyperalgesia. To test the hypothesis of the current study, the authors calculated the PCA ratio of demand to delivery at every 4 hours throughout the first 24 hours after surgery for all the patients recruited to the original study. The authors compared calculated PCA ratios, numeric rating scale pain scores, and cumulative morphine consumption for those patients who developed severe postoperative pain and met the criteria for opioid rotation versus those patients who did not. Seven patients required opioid rotation from PCA morphine to PCA hydromorphone. Eight hours after surgery, the median PCA ratio for those seven patients (2.5[range, 1.8-4.3]) was significantly greater than that for all other recruited patients (1.3 [range, 0-2.7]; p PCA ratios of demand to delivery as early as 8 hours after surgery.

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. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of cold compress application on tissue temperature in healthy dogs.

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Millard, Ralph P; Towle-Millard, Heather A; Rankin, David C; Roush, James K

2013-03-01

To measure the effect of cold compress application on tissue temperature in healthy dogs. 10 healthy mixed-breed dogs. Dogs were sedated with hydromorphone (0.1 mg/kg, IV) and diazepam (0.25 mg/kg, IV). Three 24-gauge thermocouple needles were inserted to a depth of 0.5 (superficial), 1.0 (middle), and 1.5 (deep) cm into a shaved, lumbar, epaxial region to measure tissue temperature. Cold (-16.8°C) compresses were applied with gravity dependence for periods of 5, 10, and 20 minutes. Tissue temperature was recorded before compress application and at intervals for up to 80 minutes after application. Control data were collected while dogs received identical sedation but with no cold compress. Mean temperature associated with 5 minutes of application at the superficial depth was significantly decreased, compared with control temperatures. Application for 10 and 20 minutes significantly reduced the temperature at all depths, compared with controls and 5 minutes of application. Twenty minutes of application significantly decreased temperature at only the middle depth, compared with 10 minutes of application. With this method of cold treatment, increasing application time from 10 to 20 minutes caused a further significant temperature change at only the middle tissue depth; however, for maximal cooling, the minimum time of application should be 20 minutes. Possible changes in tissue temperature and adverse effects of application > 20 minutes require further evaluation.

The efficacy of a lidocaine-infused pain pump for postoperative analgesia following elective augmentation mammaplasty or abdominoplasty.

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Chavez-Abraham, Victor; Barr, Jason S; Zwiebel, Paul C

2011-08-01

Postoperative pain management following aesthetic plastic surgery traditionally has been achieved by systemic administration of several narcotic pain medications. Because this method can lead to undesirable side effects such as sedation, nausea, vomiting, and respiratory depression, a more efficacious method of postoperative analgesia with fewer side effects needs to be implemented in outpatient cosmetic surgery. From March of 2003 until December of 2008, 690 patients underwent augmentation mammaplasty and 215 patients underwent abdominoplasty. All of these patients were equipped with an elastomeric continuous infusion pump postoperatively and were prescribed oral narcotics. Prior to 2003, patients were prescribed only oral narcotics postoperatively. A retrospective chart review of patients before and after implementation of the pain pump was undertaken to review the perceived pain patients experienced postoperatively with and without the pump. The self-administration of oral narcotics was also assessed. Patients equipped with the pain pump experienced a statistically significant decrease in perceived pain compared to those without the pump (augmentation mammaplasty: 2.27 vs. 3.68, p use of the oral narcotic Vicodin™ at 72 h postoperatively (5 mg hydrocodone/500 mg acetaminophen, Abbott Laboratories, Abbott Park, IL) (augmentation mammaplasty: 26.5 mg/2650 mg vs. 49 mg/4900 mg, p reduce both the amount of pain patients experience and the quantity of narcotics used postoperatively.

Direct detection of illicit drugs from biological fluids by desorption/ionization mass spectrometry with nanoporous silicon microparticles.

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Guinan, T M; Kirkbride, P; Della Vedova, C B; Kershaw, S G; Kobus, H; Voelcker, N H

2015-12-07

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is a high throughput analytical technique capable of detecting low molecular weight analytes, including illicit drugs, and with potential applications in forensic toxicology as well as athlete and workplace testing, particularly for biological fluids (oral fluids, urine and blood). However, successful detection of illicit drugs using SALDI-MS often requires extraction steps to reduce the inherent complexity of biological fluids. Here, we demonstrate an all-in-one extraction and analytical system consisting of hydrophobically functionalized porous silicon microparticles (pSi-MPs) for affinity SALDI-MS of prescription and illicit drugs. This novel approach allows for the analysis of drugs from multiple biological fluids without sample preparation protocols. The effect of pSi-MP size, pore diameter, pore depth and functionalization on analytical performance is investigated. pSi-MPs were optimized for the rapid and high sensitivity detection of methadone, cocaine and 3,4-methylenedioxymethamphetamine (MDMA). This optimized system allowed extraction and detection of methadone from spiked saliva and clinical urine samples. Furthermore, by detecting oxycodone in additional clinical saliva and plasma samples, we were able to demonstrate the versatility of the pSi-MP SALDI-MS technique.

The older orthopaedic patient: general considerations.

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Potter, Jane F

2004-08-01

People older than 65 years are more likely to need elective and emergent orthopaedic surgery compared with younger persons. They also experience significant benefits. Although age-related changes increase the risk of perioperative complications, understanding those changes allows prevention or at least early recognition and treatment when problems arise. Because of comorbidities, older persons take more medications that need to be managed in the perioperative period. Care could be simplified if patients were to bring their medications to the preoperative evaluation. Central nervous system sensitivity to certain pain medications (meperidine and propoxyphene) means that these drugs are best avoided as good alternatives exist (morphine and oxycodone). Adverse reactions to drugs are an important cause of acute confusion (delirium) that often complicates orthopaedic care. Early mobilization after surgery, avoiding certain drugs, avoiding restraints (including Foley catheters), attending to hydration, promoting normal sleep, compensating for sensory disorders, and stimulating daytime activities can prevent delirium. Patients with dementia are more likely to have delirium develop and, like many older people, will present special challenges in communication and decision making. Including family members in discussions may be helpful in ensuring truly informed consent.

Pain Management of Malignant Psoas Syndrome Under Epidural Analgesia During Palliative Radiotherapy.

Science.gov (United States)

Ota, Takayo; Makihara, Masaru; Tsukuda, Hiroshi; Kajikawa, Ryuji; Inamori, Masayuki; Miyatake, Nozomi; Tanaka, Noriko; Tokunaga, Masahiro; Hasegawa, Yoshikazu; Tada, Takuhito; Fukuoka, Masahiro

2017-06-01

Malignant psoas syndrome is a rare malignant condition presenting as lumbosacral plexopathy and painful fixed flexion of the hip. Metastasis to the psoas muscle is observed, which damages the nerve bundles in the lumbosacral plexuses. The syndrome presents as refractory lower back pain with several other neurological symptoms. The pain is difficult to control because it is a mixture of nociceptive and neuropathic pain, which indicates that treatment requires a versatile approach. The authors report a case of severe back pain caused by metastasis to the psoas muscle of advanced gastric cancer in a patient who underwent palliative radiotherapy under epidural analgesia. Despite conventional analgesics and subcutaneous oxycodone, he had difficulties in maintaining supine position because of the back pain and had a problem to receive radiotherapy, which required him to stay still in the same position during the treatment. By epidural analgesia, he could remain in supine position and complete radiotherapy without increasing opioid administration. His back pain was improved after the radiotherapy. Epidural analgesia is an effective treatment choice for a patient who is unable to keep the position during palliative radiotherapy.

Benzylisoquinoline alkaloid biosynthesis in opium poppy.

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Beaudoin, Guillaume A W; Facchini, Peter J

2014-07-01

Opium poppy (Papaver somniferum) is one of the world's oldest medicinal plants and remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The plant also produces several other benzylisoquinoline alkaloids with potent pharmacological properties including the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine and the antimicrobial agent sanguinarine. Opium poppy has served as a model system to investigate the biosynthesis of benzylisoquinoline alkaloids in plants. The application of biochemical and functional genomics has resulted in a recent surge in the discovery of biosynthetic genes involved in the formation of major benzylisoquinoline alkaloids in opium poppy. The availability of extensive biochemical genetic tools and information pertaining to benzylisoquinoline alkaloid metabolism is facilitating the study of a wide range of phenomena including the structural biology of novel catalysts, the genomic organization of biosynthetic genes, the cellular and sub-cellular localization of biosynthetic enzymes and a variety of biotechnological applications. In this review, we highlight recent developments and summarize the frontiers of knowledge regarding the biochemistry, cellular biology and biotechnology of benzylisoquinoline alkaloid biosynthesis in opium poppy.

Continuous subcutaneous infusion of opiates at end-of-life.

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Anderson, Stacey L; Shreve, Scott T

2004-06-01

To review pertinent controlled trials using the continuous subcutaneous infusion of opioids (CSIO) at end-of-life and offer insight to pharmacists and clinicians into the appropriate use of this route of administration. A MEDLINE search for information regarding the subcutaneous administration of opioids in terminally ill patients (1975-December 2002) was conducted using the key words subcutaneous, narcotics, morphine, hydromorphone, fentanyl, pain, hospices, and palliative care. Additional references were located through review of bibliographies of the articles cited. Case reports and postsurgical studies were excluded. Searches were limited to English-language studies using humans. Experimental and observational studies were evaluated, using prospective trials as the evidence base for conclusions and including pertinent retrospective trials as they relate to the subcutaneous infusion of opioids at end-of-life. CSIO is effective and safe for use in terminal illness. Appropriate situations for consideration of CSIO are when difficulties arise in using the oral route, standard oral opiate therapy has failed adequate trials, the patient has limited intravenous access, adequate supervision of the CSIO is present, and CSIO will not unduly limit the functional activity of the patient. CSIO has a proven role in the management of pain at end-of-life. CSIO should not be considered the first route for administration of opiates, but does offer distinct advantages in the appropriate setting. CSIO continues to be a choice for end-of-life patients and is gradually becoming a standard practice in palliative medicine.

Sodium channel blockade with QRS widening after an escitalopram overdose.

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Schreffler, Susan M; Marraffa, Jeanna M; Stork, Christine M; Mackey, Jennifer

2013-09-01

Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose. A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen. Laboratory results were significant for 4-hour acetaminophen 21.1 μg/mL. Serum electrolytes including potassium, magnesium, and calcium were all normal. Initial electrocardiogram (ECG) revealed a widened QRS with an incomplete right bundle branch pattern. After administration of 100-mEq sodium bicarbonate, a repeat ECG revealed narrowing of the QRS complex and a prolonged QTc interval. Magnesium sulfate 2 g intravenous and sodium bicarbonate drip were initiated. A repeat ECG, 1 hour after the second, revealed normalization of the QRS complex and QTc interval. Prolongation of the QTc interval is an expected effect of escitalopram. Both escitalopram and citalopram are metabolized to the cardiotoxic metabolite S-didesmethylcitalopram and didesmethylcitalopram, respectively, which have been implicated in numerous cardiac abnormalities including widening of the QRS complex. Although never previously described with escitalopram, this mechanism provides a reasonable explanation for the QRS complex widening and incomplete right bundle branch block that occurred in our patient. Both QRS complex widening and QTc interval prolongation should be monitored in cases of escitalopram and citalopram overdoses.

Fast quantitation of opioid isomers in human plasma by differential mobility spectrometry/mass spectrometry via SPME/open-port probe sampling interface.

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Liu, Chang; Gómez-Ríos, Germán Augusto; Schneider, Bradley B; Le Blanc, J C Yves; Reyes-Garcés, Nathaly; Arnold, Don W; Covey, Thomas R; Pawliszyn, Janusz

2017-10-23

Mass spectrometry (MS) based quantitative approaches typically require a thorough sample clean-up and a decent chromatographic step in order to achieve needed figures of merit. However, in most cases, such processes are not optimal for urgent assessments and high-throughput determinations. The direct coupling of solid phase microextraction (SPME) to MS has shown great potential to shorten the total sample analysis time of complex matrices, as well as to diminish potential matrix effects and instrument contamination. In this study, we demonstrate the use of the open-port probe (OPP) as a direct and robust sampling interface to couple biocompatible-SPME (Bio-SPME) fibres to MS for the rapid quantitation of opioid isomers (i.e. codeine and hydrocodone) in human plasma. In place of chromatography, a differential mobility spectrometry (DMS) device was implemented to provide the essential selectivity required to quantify these constitutional isomers. Taking advantage of the simplified sample preparation process based on Bio-SPME and the fast separation with DMS-MS coupling via OPP, a high-throughput assay (10-15 s per sample) with limits of detection in the sub-ng/mL range was developed. Succinctly, we demonstrated that by tuning adequate ion mobility separation conditions, SPME-OPP-MS can be employed to quantify non-resolved compounds or those otherwise hindered by co-extracted isobaric interferences without further need of coupling to other separation platforms. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterizing fentanyl use in methadone-maintained clients.

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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 (pFentanyl-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.

Is magnesium sulfate effective for pain in chronic postherpetic neuralgia patients comparing with ketamine infusion therapy?

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Kim, Yang Hyun; Lee, Pyung Bok; Oh, Tak Kyu

2015-06-01

Postherpetic neuralgia (PHN) is a frequent debilitating complication and one of the most intractable pain disorders, particularly in elderly patients. Although tricyclic antidepressants, topical capsaicin, gabapentin, and oxycodone are effective for alleviating PHN, many patients remain refractory to current therapies. Here, the analgesic effects of ketamine or magnesium for PHN were assessed in an open prospective study. Thirty patients with severe, intractable PHN who were unresponsive to conservative therapy participated. The effects of ketamine hydrochloride (Ketara, Parke Davis) 1 mg/kg and magnesium sulfate (Magnesin) 30 mg/kg were investigated. The patients were randomly divided into 2 groups of 15 patients each, and ketamine 1 mg/kg or magnesium 30 mg/kg was administered intravenously for 1 hour after midazolam sedation. Pain was rated on a visual analog scale (VAS) during a 2-week follow-up. All patients also completed the Doleur Neuropathique 4 questionnaire at baseline and final visits. Response to treatment, defined as a 50% reduction in VAS score 2 weeks after, was recorded in 10 of 15 patients in the ketamine group and 7 of 15 patients in the magnesium group. The difference in VAS reduction was not significant between the 2 groups. Ketamine and magnesium showed significant analgesic effects in patients with PHN. Copyright © 2015 Elsevier Inc. All rights reserved.

Palliative Care Development in Mongolia.

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Davaasuren, Odontuya; Ferris, Frank D

2018-02-01

Since the year 2000, Mongolia has established the foundation measures for a national palliative care program and has made several significant achievements. Systematic reviews and observational studies on palliative care development in Mongolia have taken place over the past 16 years. Mongolia began palliative care development in 2000 with the creation of the Mongolian Palliative Care Society and the Palliative Care Department. Palliative care is included in the Mongolia's Health Law, Health Insurance Law, Social Welfare Law, National Cancer Control Program, and the National Program for Non-Communicable Diseases, and has approved Palliative Care Standards and Pain Management Guidelines. Palliative care education is included in the undergraduate and postgraduate curriculum in all medical universities. Six hospice units in Ulaanbaatar have 50 beds; each of the nine districts and all 21 provinces have up to four to five palliative beds, and there are 36 palliative care units, for a total 190 beds for three million people. In 2014, a pediatric palliative care inpatient unit was established with five beds. Essential drugs for palliative care have been available in Mongolia since 2015. The pharmaceutical company IVCO produces morphine, codeine, pethidine, and oxycodone in Ulaanbaatar. Mongolia has made real progress in integrating palliative care into the health system. Copyright © 2017. Published by Elsevier Inc.

Retrospective analyses versus RCTs: comparing like with like?

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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.

Digital Pills to Measure Opioid Ingestion Patterns in Emergency Department Patients With Acute Fracture Pain: A Pilot Study.

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Chai, Peter R; Carreiro, Stephanie; Innes, Brendan J; Rosen, Rochelle K; O'Cleirigh, Conall; Mayer, Kenneth H; Boyer, Edward W

2017-01-13

Nonadherence to prescribed regimens for opioid analgesic agents contributes to increasing opioid abuse and overdose death. Opioids are frequently prescribed on an as-needed basis, placing the responsibility to determine opioid dose and frequency with the patient. There is wide variability in physician prescribing patterns because of the lack of data describing how patients actually use as-needed opioid analgesics. Digital pill systems have a radiofrequency emitter that directly measures medication ingestion events, and they provide an opportunity to discover the dose, timing, and duration of opioid therapy. The purpose of this study was to determine the feasibility of a novel digital pill system to measure as-needed opioid ingestion patterns in patients discharged from the emergency department (ED) after an acute bony fracture. We used a digital pill with individuals who presented to a teaching hospital ED with an acute extremity fracture. The digital pill consisted of a digital radiofrequency emitter within a standard gelatin capsule that encapsulated an oxycodone tablet. When ingested, the gastric chloride ion gradient activated the digital pill, transmitting a radiofrequency signal that was received by a hip-worn receiver, which then transmitted the ingestion data to a cloud-based server. After a brief, hands-on training session in the ED, study participants were discharged home and used the digital pill system to ingest oxycodone prescribed as needed for pain for one week. We conducted pill counts to verify digital pill data and open-ended interviews with participants at their follow-up appointment with orthopedics or at one week after enrollment in the study to determine the knowledge, attitudes, beliefs, and practices regarding digital pills. We analyzed open-ended interviews using applied thematic analysis. We recruited 10 study participants and recorded 96 ingestion events (87.3%, 96/110 accuracy). Study participants reported being able to operate all

Prescription opioid related misuse, harms, diversion and interventions in Canada: a review.

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Fischer, Benedikt; Argento, Elena

2012-07-01

The non-medical use of and harms related to prescription opioid (PO) analgesics - key medications to treat severe and chronic pain - are an emerging public health concern globally. PO use is proportionally highest in North America, where, consequently, nonmedical PO use (NMPOU) and morbidity/mortality are high and well documented for the United States. Canada is the country with the second highest PO consumption rate in the world - with steeper recent increases in PO use than the US - mainly driven by substantial increases in the use of strong opioids (e.g., oxycodone). Indications and select data of NMPOU and PO-related morbidity and mortality have emerged in recent years, yet a systematic and comprehensive collection of relevant data to characterize the phenomenon in Canada does not exist. This paper comprehensively reviews the available data in Canada regarding NMPOU, and PO-related harms, diversion, and interventions, and discusses implications for interventions and policy. Narrative literature/data review. Canada. Publicly available data and information - either from journal publications, "grey literature" (e.g., government/technical reports) or Web sites reporting relevant data on Canada - were searched and narratively reviewed. Indicators on NMPOU and PO-related harms in Canada are highly fragmented, and not nearly as systematic and comprehensive as they are in the US; virtually no national statistics/data are collected. Available -largely provincial/local - data indicate that PO misuse is increasingly common in key populations, including general adult and student populations, street-drug users, First Nations/Aboriginal Peoples, and correctional populations. Co-morbidities - e.g., pain, mental health problems, polysubstance use - among people reporting NMPOU appear to be high. Substance use treatment admissions for those with problematic PO use have risen substantially where reported. Opioid-related mortality (and oxycodone-related mortality, specifically

Intubation following high-dose rocuronium in a cat with protracted laryngospasm

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Graeme M Doodnaught

2017-10-01

Full Text Available Case summary An 11-year-old spayed female domestic shorthair cat with a history of laryngospasm at induction of general anesthesia presented for dental evaluation and treatment. The cat was premedicated with hydromorphone (0.05 mg/kg and alfaxalone (0.5 mg/kg intravenously, pre-oxygenated for 5 mins (3 l/min, face mask and anesthesia was induced with alfaxalone (to effect intravenously. Lidocaine (0.1 ml, 2% was applied topically to the arytenoid cartilages following loss of jaw tone. Laryngospasm was not noted during or immediately following lidocaine application. However, after waiting 60 s for the onset of effect of the topical lidocaine, laryngospasm was apparent. Orotracheal intubation by direct visualization was unsuccessful after four attempts by three anesthetists (with increasing levels of experience. At this point, a failed intubation was declared and the non-depolarising neuromuscular blocking agent rocuronium (1 mg/kg IV given, resulting in arytenoid abduction and appropriate conditions for intubation. Successful intubation occurred 9 mins after induction of anesthesia. Oxygen was continuously supplemented throughout and arterial hemoglobin saturation with oxygen was never <94%. Relevance and novel information To the authors’ knowledge, this is the first report of the use of high-dose rocuronium to successfully resolve prolonged laryngospasm at induction of general anesthesia in a cat. Despite laryngospasm and a delay in achieving orotracheal intubation, low values for arterial hemoglobin saturation with oxygen (indicative of hypoxemia were not observed, highlighting the benefits of pre-oxygenation and apneic oxygenation. The principles of the Difficult Airway Society 2015 guidelines were followed in managing this difficult intubation.

Anesthetic Overdose Leading to Cardiac Arrest Diagnosed by End-Tidal Inhalant Concentration Analysis in a Dog

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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.

Effect of warm compress application on tissue temperature in healthy dogs.

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Millard, Ralph P; Towle-Millard, Heather A; Rankin, David C; Roush, James K

2013-03-01

To measure the effect of warm compress application on tissue temperature in healthy dogs. 10 healthy mixed-breed dogs. Dogs were sedated with hydromorphone (0.1 mg/kg, IV) and diazepam (0.25 mg/kg, IV). Three 24-gauge thermocouple needles were inserted to a depth of 0.5 cm (superficial), 1.0 cm (middle), and 1.5 cm (deep) into a shaved, lumbar, epaxial region to measure tissue temperature. Warm (47°C) compresses were applied with gravity dependence for periods of 5, 10, and 20 minutes. Tissue temperature was recorded before compress application and at intervals for up to 80 minutes after application. Control data were collected while dogs received identical sedation but with no warm compress. Mean temperature associated with 5 minutes of heat application at the superficial, middle, and deep depths was significantly increased, compared with the control temperature. Application for 10 minutes significantly increased the temperature at all depths, compared with 5 minutes of application. Mean temperature associated with 20 minutes of application was not different at the superficial or middle depths, compared with 10 minutes of application. Temperature at the deep depth associated with 10 minutes of application was significantly higher, compared with 20 minutes of application, but all temperature increases at this depth were minimal. Results suggested that application of a warm compress should be performed for 10 minutes. Changes in temperature at a tissue depth of 1.5 cm were minimal or not detected. The optimal compress temperature to achieve therapeutic benefits was not determined.

Methadone conversion in infants and children: Retrospective cohort study of 199 pediatric inpatients.

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Fife, Alexandra; Postier, Andrea; Flood, Andrew; Friedrichsdorf, Stefan J

2016-01-01

Methadone administration has increased in pediatric clinical settings. This review is an attempt to ascertain an equianalgesic dose ratio for methadone in the pediatric population using standard adult dose conversion guidelines. US tertiary children's hospital. Hospitalized pediatric patients, 0-18 years of age. A retrospective chart review was conducted for patients who were converted from their initial opioid therapy regimen (morphine, hydromorphone, and/or fentanyl) to methadone. The primary endpoint was whether or not a dose correction was needed for methadone in the 6 days following conversion using standard dose conversion charts for adults. Documented clinical signs of withdrawal, unrelieved pain, or oversedation were examined. The majority (53.7 percent) of the 199 children were converted to methadone on intensive care units prior extubation or postextubation. The mean conversion ratio was 23.7 mg of oral morphine to 1 mg of oral methadone (median, 18.8 mg:1 mg, SD=25.7). Most patients experienced an adequate conversion (n=115, 57.8 percent), while 83 (41.7 percent) appeared undermedicated, and one child was oversedated. There were no associations found with conversion ratios for initial morphine dose, days to conversion, or effect of withdrawal of concomitant agents with potential for withdrawal. Opioid conversion to methadone is commonly practiced at our institution; however, dosing was significantly lower compared to adult conversion ratios, and more than 40 percent of children were undermedicated. The majority of children in this study received opioids for sedation while intubated and ventilated; therefore, safe and efficacious pediatric methadone conversion rates remain unclear. Prospective studies are needed.

Emerging analgesic drugs for Parkinson's disease.

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Perez-Lloret, Santiago; Rey, María Verónica; Dellapina, Estelle; Pellaprat, Jean; Brefel-Courbon, Christine; Rascol, Olivier

2012-06-01

Pain affects between 40 and 85% of Parkinson's disease (PD) patients. It is a frequently disabling and overlooked feature, which can significantly reduce health-related quality of life. Unfortunately, there are no universally recommended treatments for this condition. Evidence about the efficacy and safety of available analgesic treatments is summarized in this review. Potential targets for upcoming therapies are then discussed in light of what is currently known about the physiopathology of pain in PD. Protocols for efficacy and safety assessment of novel analgesic therapies are discussed. Finally, critical aspects of study protocol design such as patient selection or outcomes to be evaluated are discussed. Preliminary results indicate that duloxetine, cranial electrotherapy stimulation, rotigotine, subthalamic or pallidum nuclei stimulation or lesion or levodopa could be effective for treating pain in PD. Similarly, some case reports indicate that repetitive transcranial magnetic stimulation (rTMS) or apomorphine could be effective for relieving painful off-period dystonia. Clinical trials with rTMS or oxycodone/naloxone prolonged-release tablets for neuropathic pain or botulinum toxin for off-period dystonia are underway. Success of clinical trials about analgesic strategies in PD will depend on the selection of the right PD population to be treated, according to the type of pain, and the proper selection of study outcomes and follow-up of international recommendations.

Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children

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Ida Aka

2017-11-01

Full Text Available Cytochrome P450 (CYP enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug–CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC data and surveyed 10 years of electronic health records (EHR data for the number of children exposed to CYP-associated drugs. Subsequently, we performed a focused literature review for drugs commonly used in pediatrics, defined as more than 5000 pediatric patients exposed in the decade-long EHR cohort. There were 48 drug–CYP interactions with a high level of evidence in the CPIC database. Of those, only 10 drugs were commonly used in children (ondansetron, oxycodone, codeine, omeprazole, lansoprazole, sertraline, amitriptyline, citalopram, escitalopram, and risperidone. For these drugs, reports of the drug–CYP interaction in cohorts including children were sparse. There are adequate data for implementation of genotype-guided therapy for children for three of the 10 commonly used drugs (codeine, omeprazole and lansoprazole. For the majority of commonly used drugs with known CYP interactions, more data are required to support pharmacogenomic implementation in children.

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant.

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Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine ® , which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed.

Tunable detection sensitivity of opiates in urine via a label-free porous silicon competitive inhibition immunosensor.

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Bonanno, Lisa M; Delouise, Lisa A

2010-01-15

Currently, there is need for laboratory-based high-throughput and reliable point-of-care drug screening methodologies. We demonstrate here a chip-based label-free porous silicon (PSi) photonic sensor for detecting opiates in urine. This technique provides a cost-effective alternative to conventional labeled drug screening immunoassays with potential for translation to multiplexed analysis. Important effects of surface chemistry and competitive binding assay protocol on the sensitivity of opiate detection are revealed. Capability to tune sensitivity and detection range over approximately 3 orders of magnitude (18.0 nM to 10.8 muM) was achieved by varying the applied urine specimen volume (100-5 muL), which results in systematic shifts in the competitive binding response curve. A detection range (0.36-4.02 muM) of morphine in urine (15 muL) was designed to span the current positive cutoff value (1.05 muM morphine) in medical opiate urine screening. Desirable high cross-reactivity to oxycodone, in addition to other common opiates, morphine, morphine-3-glucuronide, 6-acetyl morphine, demonstrates an advantage over current commercial screening assays, while low interference with cocaine metabolite was maintained. This study uniquely displays PSi sensor technology as an inexpensive, rapid, and reliable drug screening technology. Furthermore, the versatile surface chemistry developed can be implemented on a range of solid-supported sensors to conduct competitive inhibition assays.

Evaluation of Intraosseous Fluid as an Alternative Biological Specimen in Postmortem Toxicology.

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Rodda, Luke N; Volk, Justin A; Moffat, Ellen; Williams, Chinyere M; Lynch, Kara L; Wu, Alan H B

2018-04-01

The postmortem redistribution phenomenon is an important factor in the interpretation of blood drug concentrations as a cause or factor in death. Intraosseous fluid (IOF) may serve as an alternative matrix for drug testing. Intraosseous fluid was collected from the left and right tibias and humerus of 29 decedents using the Arrow EZ-IO Intraosseous Vascular Access System. Standard autopsy specimens including blood were also collected at the same time during autopsy. Blood and IOF specimens were screened by immunoassay for opioids, fentanyl analogs, oxycodone, methadone, cocaine, methamphetamine, amphetamines, phencyclidine, tricyclic antidepressants, benzodiazepines and cannabinoids, using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Correlation between cardiac/central blood ELISA and IOF ELISA results was mostly 100% for drug targets. Further blood confirmation analysis was performed by gas chromatography mass spectrometry also showed comparable correlation to IOF screen results. There was no significant difference between the IOF sites or sides of the body. This novel study supports the use of IOF as an alternative postmortem specimen for toxicological investigations as a potentially less-compromised tissue in decomposed or traumatized bodies. Preliminary data is provided for the screening of common drugs of abuse in IOF that may show to be subject to alternative rates of postmortem redistribution than to that of other biological specimens in future studies that quantitate IOF drug concentrations.

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

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

2017-09-01

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

Transversus abdominis plane block reduces morphine consumption in the early postoperative period following microsurgical abdominal tissue breast reconstruction: a double-blind, placebo-controlled, randomized trial.

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Zhong, Toni; Ojha, M; Bagher, Shaghayegh; Butler, Kate; Srinivas, Coimbatore; McCluskey, Stuart A; Clarke, Hance; O'Neill, Anne C; Novak, Christine B; Hofer, Stefan O P

2014-11-01

The analgesic efficacy of the transversus abdominis plane peripheral nerve block following abdominal tissue breast reconstruction has not been studied in a randomized controlled trial. The authors conducted a double-blind, placebo-controlled, 1:1 allocation, two-arm parallel group, superiority design, randomized controlled trial in patients undergoing microsurgical abdominally based breast reconstruction. Intraoperatively, epidural catheters were inserted under direct vision through the triangle of Petit on both sides of the abdomen into the transversus abdominis plane just before rectus fascial closure. Patients received either bupivacaine (study group) or saline (placebo group) through the catheters for 2 postoperative days. All patients received hydromorphone by means of a patient-controlled analgesic pump. The primary outcome was the difference in the parenteral opioid consumption on each postoperative day between the groups. The secondary outcome measures included the following: total in-hospital opioid; antinausea medication; pain, nausea, and sedation scores; Quality of Recovery Score; time to ambulation; and hospital stay duration. Between September of 2011 and June of 2013, 93 patients were enrolled: 49 received bupivacaine and 44 received saline. There were 11 postoperative complications (13 percent); none were related to the catheter. Primary outcomes were completed by 85 of 93 patients (91.3 percent); the mean parenteral morphine consumption was significantly reduced on postoperative day 1 in the bupivacaine group (20.7±20.1 mg) compared with 30.0±19.1 mg in the control group (p=0.02). There were no significant differences in secondary outcomes. Following abdominally based breast reconstruction, transversus abdominis plane peripheral nerve block is safe and significantly reduces morphine consumption in the early postoperative period. Therapeutic, II.

Effects of ketamine and alfaxalone on application of a feline pain assessment scale.

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Buisman, Mandy; Wagner, Marika C; Hasiuk, Michelle Mm; Prebble, Melanie; Law, Laura; Pang, Daniel Sj

2016-08-01

The objective of this study was to compare the effects of ketamine and alfaxalone on the application of a validated feline-specific multidimensional composite pain scale (UNESP-Botucatu MCPS). In a prospective, randomized, blinded, crossover trial, 11 adult cats (weight 4.4 ± 0.6 kg) were given dexmedetomidine (15 μg/kg) and hydromorphone (0.05 mg/kg) with either alfaxalone (2 mg/kg) or ketamine (5 mg/kg) as a single intramuscular injection for the induction of general anesthesia. After orotracheal intubation, general anesthesia (without surgery) was maintained for 32 mins with isoflurane, followed by atipamezole. The following parameters were recorded at baseline, 1-8 h and 24 h post-extubation: pain (pain expression and psychomotor subscales) and sedation scale scores. Alfaxalone treatment injection sites were examined for inflammation at baseline, postinjection, and 8 h and 24 h post-extubation. Psychomotor scores were higher with ketamine at hours 1 (3.5 [0-5.0], P ketamine group crossed the analgesic intervention threshold. In contrast, pain expression scores did not differ significantly between treatments at any time (P >0.05); one cat from each group crossed the analgesic intervention threshold. Sedation was greater with ketamine (1 [0-3], P = 0.02) than alfaxalone (0 [0-1]) 1 h post-extubation. No cats had visible inflammation at the injection sites at any time. Ketamine has a confounding effect on the psychomotor subscale of the pain scale studied, which may lead to erroneous administration of rescue analgesia. In contrast, alfaxalone was not associated with significant increases in either pain subscale. These effects of ketamine should be considered when evaluating acute postoperative pain in cats. © The Author(s) 2015.

Pharmacist's impact on acute pain management during trauma resuscitation.

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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.

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment.

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Marchand, Kirsten; Oviedo-Joekes, Eugenia; Guh, Daphne; Marsh, David C; Brissette, Suzanne; Schechter, Martin T

2012-01-25

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. 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 to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months). A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. NCT00175357.

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment

Directory of Open Access Journals (Sweden)

Marchand Kirsten

2012-01-01

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. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. 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 to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months. Results A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. Conclusions After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. Trial Registration NCT00175357.

Electronic medication complete communication strategy for opioid prescriptions in the emergency department: Rationale and design for a three-arm provider randomized trial.

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McCarthy, Danielle M; Courtney, D Mark; Lank, Patrick M; Cameron, Kenzie A; Russell, Andrea M; Curtis, Laura M; Kim, Kwang-Youn A; Walton, Surrey M; Montague, Enid; Lyden, Abbie L; Gravenor, Stephanie J; Wolf, Michael S

2017-08-01

Thousands of people die annually from prescription opioid overdoses; however there are few strategies to ensure patients receive medication risk information at the time of prescribing. To compare the effectiveness of the Emergency Department (ED) Electronic Medication Complete Communication (EMC 2 ) Opioid Strategy (with and without text messaging) to promote safe medication use and improved patient knowledge as compared to usual care. The ED EMC 2 Opioid Strategy consists of 5 automated components to promote safe medication use: 1) physician reminder to counsel, 2) inbox message sent on to the patient's primary care physician, 3) pharmacist message on the prescription to counsel, 4) MedSheet supporting prescription information, and 5) patient-centered Take-Wait-Stop wording of prescription instructions. This strategy will be assessed both with and without the addition of text messages via a three-arm randomized trial. The study will take place at an urban academic ED (annual volume>85,000) in Chicago, IL. Patients being discharged with a new prescription for hydrocodone-acetaminophen will be enrolled and randomized (based on their prescribing physician). The primary outcome of the study is medication safe use as measured by a demonstrated dosing task. Additionally actual safe use, patient knowledge and provider counseling will be measured. Implementation fidelity as well as costs will be reported. The ED EMC 2 Opioid Strategy embeds a risk communication strategy into the electronic health record and promotes medication counseling with minimal workflow disruption. This trial will evaluate the strategy's effectiveness and implementation fidelity as compared to usual care. This trial is registered on clinicaltrials.gov with identifier NCT02431793. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of preemptive intra-articular morphine and ketamine on pain after arthroscopic rotator cuff repair: a prospective, double-blind, randomized controlled study.

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Khashan, M; Dolkart, O; Amar, E; Chechik, O; Sharfman, Z; Mozes, G; Maman, E; Weinbroum, A A

2016-02-01

Rotator cuff tear is a leading etiology of shoulder pain and disability. Surgical treatment is indicated in patients with persistent pain who fail a trial of non-surgical treatment. Pain reduction following rotator cuff repair, particularly within the first 24-48 h, is a major concern to both doctors and patients. This study aimed to compare the postoperative antinociceptive additive effects of pre-incisional intra-articular (IA) ketamine when combined with morphine with two times the dose of morphine or saline. In this prospective, randomized, double blind, controlled trial patients undergoing arthroscopic rotator cuff tear repair (ARCR) under general anesthesia were enrolled. Patients were randomly assigned to one of the three intervention groups. Twenty minutes prior to incision, morphine (20 mg/10 ml), ketamine (50 mg + morphine 10 mg/10 ml), or saline (0.9 % 10 ml) (n = 15/group), were administered to all patients. First 24 h postoperative analgesia consisted of intravenous patient controlled analgesia (IV-PCA) morphine and oral rescue paracetamol 1000 mg or oxycodone 5 mg. 24-h, 2-week and 3-month patient rated pain numeric rating scale (NRS) and analgesics consumption were documented. Patients' demographic and perioperative data were similar among all groups. The 24-h and the 2-week NRSs were significantly (p pain in the first 2 weeks after arthroscopic rotator cuff repair. Further research is warranted to elucidate the optimal timing and dosing of IA ketamine and morphine for postoperative analgesic effects.

Increases in self-reported fentanyl use among a population entering drug treatment: The need for systematic surveillance of illicitly manufactured opioids.

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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 (Pfentanyl 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.

A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study.

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Lucenteforte, Ersilia; Vagnoli, Laura; Pugi, Alessandra; Crescioli, Giada; Lombardi, Niccolò; Bonaiuti, Roberto; Aricò, Maurizio; Giglio, Sabrina; Messeri, Andrea; Mugelli, Alessandro; Vannacci, Alfredo; Maggini, Valentina

2018-05-18

Inter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients. We conducted a systematic literature search in EMBASE and PubMed up to the 24th of November 2016 following Cochrane Handbook and PRISMA guidelines. Two independent reviewers screened titles and abstracts along with full-text papers; disagreements were resolved by discussion with two other independent reviewers. We used a data extraction form to provide details of the included studies, and conducted quality assessment using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Young age, lung or gastrointestinal cancer, neuropathic or breakthrough pain and anxiety or sleep disturbance were associated to a worse response to opioid analgesia. No clear association was identified in literature regarding gender, ethnicity, weight, presence of metastases, biochemical or hematological factors. Studies in children were lacking. Between June 2011 and April 2014, the Italian STOP Pain project enrolled 87 paediatric cancer patients under treatment with opioids (morphine, codeine, oxycodone, fentanyl and tramadol). Future studies on cancer pain should be designed with consideration for the highlighted factors to enhance our understanding of opioid non-response and safety. Studies in children are mandatory. CRD42017057740 .

Fatal poisonings involving propoxyphene before and after voluntary withdrawal from the United States' market: An analysis from the state of Florida.

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Delcher, Chris; Chen, Guanming; Wang, Yanning; Slavova, Svetla; Goldberger, Bruce A

2017-11-01

The synthetic opioid propoxyphene was a schedule IV controlled substance with multiple reported health risks before the US Food and Drug Administration issued a request for voluntary market withdrawal in November 2010. The purpose of this study is to investigate the characteristics and occurrences of propoxyphene-related deaths in Florida before and after voluntary market removal. Decedent-level toxicology data from Florida's Medical Examiners Commission was used to compare the temporal, polysubstance use, sociodemographic, and geographic profiles associated with propoxyphene-involved deaths for a pre-withdrawal (November 2008-November 2010) and post-withdrawal (December 2010-December 2012) period. Sensitivity analyses using multiple data sources, including Florida's Prescription Drug Monitoring Program and other states' data, were conducted to examine potential reporting bias. Results showed that the number of propoxyphene-involved deaths declined by 84% from 580 deaths to 92 deaths after market withdrawal. The co-occurrence of other prevalent drugs, such as oxycodone (17.2% to 26.1%, p=0.0422) increased significantly in the post-withdrawal study period. A larger proportion of the propoxyphene-related deaths were reported from South Florida after the withdrawal (28.4% to 56.5%, pmarket withdrawal, as recently as 2016. Our findings are consistent with previous studies that propoxyphene was still available after removal from the US market. Continued surveillance is recommended after highly abused opioids are withdrawn from the market due to on-going safety risks. Copyright © 2017 Elsevier B.V. All rights reserved.

Reimbursement of analgesics for chronic pain.

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Pedersen, Line; Hansen, Anneli Borge; Svendsen, Kristian; Skurtveit, Svetlana; Borchgrevink, Petter C; Fredheim, Olav Magnus S

2012-11-27

The prevalence of chronic non-malignant pain in Norway is between 24% and 30%. The proportion of the population using opioids for non-malignant pain on a long-term basis is around 1%. The purpose of our study was to investigate how many were prescribed analgesics on reimbursable prescription under reimbursement code -71 (chronic non-malignant pain) in 2009 and 2010, which analgesics were prescribed and whether prescribing practices were in accordance with national guidelines. We retrieved pseudonymised data from the National Prescription Database on all those who received drugs with reimbursement code -71 in 2009 and 2010. The data contain information on drug, dosage, formulation, reimbursement code and date of issue. 90,731 patients received reimbursement for drugs indicated for chronic non-malignant pain in 2010. Of these, 6,875 were given opioids, 33,242 received paracetamol, 25,865 non-steroid inflammatory drugs (NSAIDs), 20,654 amitryptiline and 16,507 gabapentin. Oxycodone was the most frequently prescribed opioid, followed by buprenorphine, tramadol and codeine/paracetamol. Of those who were prescribed opioids, 4,047 (59%) received mainly slow-release opioids, 2,631 (38%) also received benzodiazepines and 2,418 (35%) received benzodiazepine-like sleep medications. The number of patients who received analgesics and opioids on reimbursable prescriptions was low compared to the proportion of the population with chronic pain and the proportion using opioids long-term. 38% of those reimbursed for opioids also used benzodiazepines, which is contrary to official Norwegian guidelines.

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

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

2010-01-01

Background The leading cause of injury death among adults in Connecticut (CT), USA is drug poisonings. We analyzed the epidemiology and geographic distribution of opioid-involved accidental drug-involved intoxication deaths (“overdoses”) in CT over an 11-year period. Methods We reviewed data from 1997 to 2007 on all adult accidental/undetermined drug intoxication deaths in CT that were referred to the Office of the Chief Medical Examiner (OCME). Regression analyses were conducted to uncover risk factors for fatal opioid-involved intoxications and to compare heroin- to prescription opioid- and methadone-involved deaths. Death locations were mapped to visualize differences in the geographic patterns of overdose by opioid type. Results Of the 2900 qualifying deaths, 2231 (77%) involved opioids. Trends over time revealed increases in total opioid-related deaths although heroin-related deaths remained constant. Methadone, oxycodone and fentanyl, the most frequently cited prescription opioids, exhibited significant increases in opioid deaths. Prescription opioid-only deaths were more likely to involve other medications (e.g., benzodiazepines) and to have occurred among residents of a suburban or small town location, compared to heroin-involved or methadone-involved deaths. Heroin-only deaths tended to occur among non-Whites, were more likely to involve alcohol or cocaine and to occur in public locations and large cities. Conclusions The epidemiology of fatal opioid overdose in CT exhibits distinct longitudinal, risk factor, and geographic differences by opioid type. Each of these trends has implications for public health and prevention efforts. PMID:21131140

Opioid analgesic use in Australia and The Netherlands: a cross-country comparison.

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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.

Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report.

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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.

Motor/Prefrontal Transcranial Direct Current Stimulation (tDCS) Following Lumbar Surgery Reduces Postoperative Analgesia Use.

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Glaser, John; Reeves, Scott T; Stoll, William David; Epperson, Thomas I; Hilbert, Megan; Madan, Alok; George, Mark S; Borckardt, Jeffrey J

2016-05-01

Randomized, controlled pilot trial. The present study is the first randomized, double-blind, sham-controlled pilot clinical trial of transcranial direct current stimulation (tDCS) for pain and patient-controlled analgesia (PCA) opioid usage among patients receiving spine surgery. Lumbar spinal surgeries are common, and while pain is often a complaint that precedes surgical intervention, the procedures themselves are associated with considerable postoperative pain lasting days to weeks. Adequate postoperative pain control is an important factor in determining recovery and new analgesic strategies are needed that can be used adjunctively to existing strategies potentially to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including tDCS are beginning to demonstrate promise as treatments for a variety of pain conditions. Twenty-seven patients undergoing lumbar spine procedures at Medical University of South Carolina were randomly assigned to receive four 20-minute sessions of real or sham tDCS during their postsurgical hospital stay. Patient-administered hydromorphone usage was tracked along with numeric rating scale pain ratings. The effect of tDCS on the slope of the cumulative PCA curve was significant (P tDCS was associated with a 23% reduction in PCA usage. In the real tDCS group a 31% reduction was observed in pain-at-its-least ratings from admission to discharge (P = 0.027), but no other changes in numeric rating scale pain ratings were significant in either group. The present pilot trial is the first study to demonstrate an opioid sparing effect of tDCS after spine surgical procedures. Although this was a small pilot trial in a heterogeneous sample of spinal surgery patients, a moderate effect-size was observed for tDCS, suggesting that future work in this area is warranted. 2.

Bar Code Medication Administration Technology: Characterization of High-Alert Medication Triggers and Clinician Workarounds.

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Miller, Daniel F; Fortier, Christopher R; Garrison, Kelli L

2011-02-01

Bar code medication administration (BCMA) technology is gaining acceptance for its ability to prevent medication administration errors. However, studies suggest that improper use of BCMA technology can yield unsatisfactory error prevention and introduction of new potential medication errors. To evaluate the incidence of high-alert medication BCMA triggers and alert types and discuss the type of nursing and pharmacy workarounds occurring with the use of BCMA technology and the electronic medication administration record (eMAR). Medication scanning and override reports from January 1, 2008, through November 30, 2008, for all adult medical/surgical units were retrospectively evaluated for high-alert medication system triggers, alert types, and override reason documentation. An observational study of nursing workarounds on an adult medicine step-down unit was performed and an analysis of potential pharmacy workarounds affecting BCMA and the eMAR was also conducted. Seventeen percent of scanned medications triggered an error alert of which 55% were for high-alert medications. Insulin aspart, NPH insulin, hydromorphone, potassium chloride, and morphine were the top 5 high-alert medications that generated alert messages. Clinician override reasons for alerts were documented in only 23% of administrations. Observational studies assessing for nursing workarounds revealed a median of 3 clinician workarounds per administration. Specific nursing workarounds included a failure to scan medications/patient armband and scanning the bar code once the dosage has been removed from the unit-dose packaging. Analysis of pharmacy order entry process workarounds revealed the potential for missed doses, duplicate doses, and doses being scheduled at the wrong time. BCMA has the potential to prevent high-alert medication errors by alerting clinicians through alert messages. Nursing and pharmacy workarounds can limit the recognition of optimal safety outcomes and therefore workflow processes

Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.

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Witkop, M; Neff, A; Buckner, T W; Wang, M; Batt, K; Kessler, C M; Quon, D; Boggio, L; Recht, M; Baumann, K; Gut, R Z; Cooper, D L; Kempton, C L

2017-07-01

Haemophilia is characterized by frequent haemarthrosis, leading to acute/chronic joint pain. To assess self-reported prevalence, description and management of pain in adult males with mild-to-severe haemophilia and history of joint pain/bleeding. Participants completed a pain survey and five patient-reported outcome instruments assessing pain, functional impairment and health-related quality of life (HRQoL). Of 381 participants enrolled, median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65% were overweight/obese. Many (56%) were not receiving routine infusions; 30% never received routine infusions. During the prior 6 months, 20% experienced acute pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed (30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti-inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice (65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common opioid for both acute/chronic pain (30%); other long-acting opioids were infrequently used specifically for chronic but not acute pain (morphine, 7%; methadone, 6%; fentanyl patch, 2%). Patients with chronic pain, particularly those with both acute/chronic pain, frequently experience psychological issues, functional disability and reduced HRQoL. Treatment strategies for acute pain (e.g. routine infusions to prevent bleeding) and for chronic pain (e.g. long-acting opioids) may be underused. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

A case of moderate liver enzyme elevation after acute acetaminophen overdose despite undetectable acetaminophen level and normal initial liver enzymes.

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Bebarta, Vikhyat S; Shiner, Drew C; Varney, Shawn M

2014-01-01

Liver function test (LFT) increase is an early sign of acetaminophen (APAP) toxicity. Typically, when an acute overdose patient is evaluated and has an initial undetectable APAP level and normal liver enzymes, the patient is not treated with N-acetylcysteine, and liver enzymes are not expected to increase later. We report a case of moderate LFT increase despite normal LFTs and an undetectable APAP level after delayed presentation of an APAP ingestion. A 22-year-old male with no medical history ingested 15-25 hydrocodone/APAP tablets (5 mg/500 mg). His suicide note and his bunkmate corroborated the overdose time. He arrived at the emergency department 16 hours after ingestion. At that time, his APAP level was enzymes were normal [aspartate transaminase (AST) 31 U/L and alanine transaminase (ALT) 34 U/L]. Twenty-nine hours after ingestion, the psychiatry team obtained LFTs (AST 45, ALT 61). He had persistent nausea and diffuse abdominal pain. On repeat analysis, the APAP level at 36 hours was found to be <10 μg/mL, AST 150, and ALT 204. After 2 more days of increasing LFTs and persistent abdominal pain and nausea, the toxicology department was consulted, the patient was transferred to the medicine department, and intravenous N-acetylcysteine was started 66 hours after ingestion. He was treated for 16 hours and had a significant decline in LFTs and symptom resolution. His prothrombin time, bilirubin, lactate, creatinine, and mental status were normal throughout the admission. Other cases of LFT increase were excluded. Our case report illustrates that a moderate increase in liver transaminase may occur despite an initial undetectable APAP level and normal transaminases after a delayed presentation. In our case, no serious clinical effects were reported.

Tamsulosin does not increase 1-week passage rate of ureteral stones in ED patients.

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Berger, David A; Ross, Michael A; Hollander, Jay B; Ziadeh, James; Chen, Charity; Jackson, Raymond E; Swor, Robert A

2015-12-01

The objective of the study is to determine if tamsulosin initiated in the emergency department (ED) decreases the time to ureteral stone passage at 1 week or time to pain resolution, compared to placebo. We performed a prospective, randomized, double-blinded, placebo-controlled trial of tamsulosin vs placebo in ED patients with ureterolithiasis on computed tomography. Patients were identified and enrolled between April 2007 and February 2009 and were randomized to either 0.4 mg of tamsulosin or placebo for 1 week. We contacted participants using a telephone survey on post-ED visit days 1, 2, 3, and 7. The primary outcome was time to stone passage, with secondary outcomes being maximum pain score and amount of pain medication required. Of the 127 patients enrolled during this study, 15 were lost to follow-up, and 12 required surgical interventions before the 7-day mark, leaving 100 patients for analysis. Of the 100 patients, 53 received tamsulosin and 47 received placebo. There was no difference between groups in percentage of male, mean age, initial serum creatinine, average stone size, stone location, and history of prior stone. The probability that the patient did not pass a stone at 7 days was not different between tamsulosin and placebo, 62.1% (95% confidence interval, 49.1%-75.1%) vs 54.4% (95% confidence interval, 40.3%-68.6%; P = .58). There was no significant difference in the high pain score (P = .12) or hydrocodone/acetaminophen intake (P = .76) between treatment groups at any of the time points. This study reveals no difference in the proportion of stone passage or high pain score and pain medication utilization at 7 days between tamsulosin and placebo. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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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.

A retrospective study on the influence of nutritional status on pain management in cancer patients using the transdermal fentanyl patch.

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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.

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant

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Itzoe M

2017-05-01

Full Text Available MariaLisa Itzoe, Michael Guarnieri Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT. For decades, oral or intravenous (IV MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone, antagonists (naltrexone, naloxone, and combinations of the two (buprenorphine/naloxone. While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016 is Probuphine®, which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed. Keywords: addiction, opioids, medication-assisted therapy, long-acting implant, buprenorphine, Probuphine®

[Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network].

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Frauger, Elisabeth; Pochard, Liselotte; Boucherie, Quentin; Giocanti, Adeline; Chevallier, Cécile; Daveluy, Amélie; Gibaja, Valérie; Caous, Anne-Sylvie; Eiden, Céline; Authier, Nicolas; Le Boisselier, Reynald; Guerlais, Marylène; Jouanjus, Émilie; Lepelley, Marion; Pizzoglio, Véronique; Pain, Stéphanie; Richard, Nathalie; Micallef, Joëlle

2017-09-01

It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs. Among them, 77% received an opiate maintenance treatment: 68% methadone (half of them consumed capsule form) and 27% buprenorphine (39% consumed generic form). Brand-name buprenorphine is more often injected than generic buprenorphine (10% vs. 2%) and among methadone consumers 7% of methadone capsule consumers have illegally obtained methadone (vs. 9% for syrup form). The proportion of medications among psychoactive drugs injected is important (42%), with morphine representing 21% of the total psychoactive drugs injected and buprenorphine, 16%. OPPIDUM highlighted emergent behaviors of abuse with some analgesic opioids (like tramadol, oxycodone or fentanyl), pregabalin, or quetiapine. OPPIDUM highlighted variations of drugs use regarding geographic approaches or by drug dependence care centers (like in harm reduction centers). OPPIDUM clearly demonstrated that collection of valid and useful data on drug abuse is possible, these data have an interest at regional, national and international levels. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

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

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

2011-06-01

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

The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

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Gonçalves, Leonor; Friend, Lauren V.; Dickenson, Anthony H.

2015-01-01

Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain. PMID:25576174

Misuse of prescription and illicit drugs among high-risk young adults in Los Angeles and New York

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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.

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

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

2009-02-01

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

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

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Parvaz Madadi

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

TRV0109101, a G Protein-Biased Agonist of the µ-Opioid Receptor, Does Not Promote Opioid-Induced Mechanical Allodynia following Chronic Administration.

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Koblish, Michael; Carr, Richard; Siuda, Edward R; Rominger, David H; Gowen-MacDonald, William; Cowan, Conrad L; Crombie, Aimee L; Violin, Jonathan D; Lark, Michael W

2017-08-01

Prescription opioids are a mainstay in the treatment of acute moderate to severe pain. However, chronic use leads to a host of adverse consequences including tolerance and opioid-induced hyperalgesia (OIH), leading to more complex treatment regimens and diminished patient compliance. Patients with OIH paradoxically experience exaggerated nociceptive responses instead of pain reduction after chronic opioid usage. The development of OIH and tolerance tend to occur simultaneously and, thus, present a challenge when studying the molecular mechanisms driving each phenomenon. We tested the hypothesis that a G protein-biased µ -opioid peptide receptor (MOPR) agonist would not induce symptoms of OIH, such as mechanical allodynia, following chronic administration. We observed that the development of opioid-induced mechanical allodynia (OIMA), a model of OIH, was absent in β -arrestin1 -/- and β -arrestin2 -/- mice in response to chronic administration of conventional opioids such as morphine, oxycodone and fentanyl, whereas tolerance developed independent of OIMA. In agreement with the β -arrestin knockout mouse studies, chronic administration of TRV0109101, a G protein-biased MOPR ligand and structural analog of oliceridine, did not promote the development of OIMA but did result in drug tolerance. Interestingly, following induction of OIMA by morphine or fentanyl, TRV0109101 was able to rapidly reverse allodynia. These observations establish a role for β -arrestins in the development of OIH, independent of tolerance, and suggest that the use of G protein-biased MOPR ligands, such as oliceridine and TRV0109101, may be an effective therapeutic avenue for managing chronic pain with reduced propensity for opioid-induced hyperalgesia. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

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Winchester, Wendy J; Gore, Katrina; Glatt, Sophie; Petit, Wendy; Gardiner, Jennifer C; Conlon, Kelly; Postlethwaite, Michael; Saintot, Pierre-Philippe; Roberts, Sonia; Gosset, James R; Matsuura, Tomomi; Andrews, Mark D; Glossop, Paul A; Palmer, Michael J; Clear, Nicola; Collins, Susie; Beaumont, Kevin; Reynolds, David S

2014-11-01

The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia.

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Montilla-García, Ángeles; Tejada, Miguel Á; Perazzoli, Gloria; Entrena, José M; Portillo-Salido, Enrique; Fernández-Segura, Eduardo; Cañizares, Francisco J; Cobos, Enrique J

2017-10-01

Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80 mg/kg) induced a better recovery of grip strength than acetaminophen (40-320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or celecoxib (40-160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Postoperative Pain Management After Primary Total Knee Arthroplasty: The Value of Liposomal Bupivacaine.

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Sporer, Scott M; Rogers, Thea

2016-11-01

Multimodal pain protocols have been proposed to achieve improved long-acting postoperative analgesia. Controlling postoperative pain after joint arthroplasty is especially important as it relates to patient satisfaction and outcomes. The purpose of this study was to compare the postoperative pain, time to ambulation, and overall narcotic usage between patients who received either a femoral nerve block with a periarticular bupivacaine injection or a periarticular bupivacaine and extended-release liposomal bupivacaine injection after primary total knee arthroplasty. A total of 597 consecutive primary total knee arthroplasties performed between September 1, 2012 and August 31, 2014 received preoperative celecoxib, oxycodone, and transdermal scopolamine. Intraoperatively, patients either received a single-dose bupivacaine femoral nerve block along with 30-mL 0.25% bupivacaine periarticular injection (group A) or a 60-mL periarticular injection alone (20-mL liposomal bupivacaine, 30-mL 0.25% bupivacaine, and 10-mL saline; group B). The postoperative pain scores, narcotic usage, and time to ambulation were retrospectively collected from the electronic medical record. These outcomes were compared between treatment groups. There were 325 patients in group A compared with 272 in group B during the time frame. There was no difference among age, gender, race, and body mass index between the groups. Group B demonstrated a decreased need for breakthrough pain medication (16.9% vs 36.3% P bupivacaine resulted in a decrease need for breakthrough pain medication, improved pain scores at 12 hours, and an earlier time to ambulation compared to a combined femoral nerve block and periarticular bupivacaine injection. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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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.

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

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Veal, Felicity C; Peterson, Gregory M

2015-06-01

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

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

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

2014-09-01

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

Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma

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Radi, Zaher; Bartholomew, Phillip; Elwell, Michael; Vogel, W. Mark

2013-01-01

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

Management of pediatric tonsillectomy pain: a review of the literature

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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

Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma

Energy Technology Data Exchange (ETDEWEB)

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

DRUG INTERACTIONS WITH DIAZEPAM

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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

Safety and efficacy of nurse-controlled analgesia in patients less than 1 year of age

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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

A precision medicine approach to a patient with unresolved pain following orthopedic surgery: a case report.

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Gazzaniga, David; Brenton, Ashley; Meshkin, Brian

2017-02-24

Precision medicine is a promising technology in patient care that combines genetic analysis with clinical data, such as health, behavioral, functional, environment, and lifestyle information. Here we present the case of a 54-year old woman who, following an accident, had uncontrolled chronic pain and was subsequently labeled a drug seeker. A 54-year-old white woman who was experiencing severe calf pain was referred for treatment. Her pain was insufficiently controlled immediately following knee arthroplasty with multiple opioid medications, as well as non-opioids. Precision medicine testing was ordered for her so that we could assess her pain sensitivity objectively to determine if the pill seeker designation was correct and to determine the best medications for her. Based on the Proove profiles, we determined that she had moderately low pain sensitivity, which means that clinically she may underreport pain and may have decreased medication needs. This result suggested that her continued reporting of unresolved pain was probably due to a condition unresolved by her right knee arthroplasty. In addition, she was found to be at low risk of opioid addiction, based on the Proove Opioid Risk Profile. Taken together, along with the high levels of pain she described, we determined that her pain was not properly controlled and that the designation of pill seeker was incorrect. The next step was to determine which medications and which doses would result in the most favorable outcomes for our patient. To determine this, we used the results of the Proove Opioid Response, Proove Drug Metabolism, and Proove Non-Opioid Profiles to guide her treatment. We reduced her pain medications to a single opioid, Vicodin (acetaminophen and hydrocodone), which also eliminated the adverse side effects she experienced. Precision medicine offers an important health care decision tool which can reduce emotional and physical costs to patients and may reduce the economic health care burden of

Toxicology findings in cases of hanging in the City and County of San Francisco over the 3-year period from 2011 to 2013.

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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

Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy.

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Talamo, Giampaolo; Liao, Jason; Bayerl, Michael G; Claxton, David F; Zangari, Maurizio

2010-03-01

Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.

A practical and ethical solution to the opioid scheduling conundrum

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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

Functional expression of a proton-coupled organic cation (H+/OC antiporter in human brain capillary endothelial cell line hCMEC/D3, a human blood–brain barrier model

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Shimomura Keita

2013-01-01

Full Text Available Abstract Background Knowledge of the molecular basis and transport function of the human blood–brain barrier (BBB is important for not only understanding human cerebral physiology, but also development of new central nervous system (CNS-acting drugs. However, few studies have been done using human brain capillary endothelial cells, because human brain materials are difficult to obtain. The purpose of this study is to clarify the functional expression of a proton-coupled organic cation (H+/OC antiporter in human brain capillary endothelial cell line hCMEC/D3, which has been recently developed as an in vitro human BBB model. Methods Diphenhydramine, [3H]pyrilamine and oxycodone were used as cationic drugs that proved to be H+/OC antiporter substrates. The in vitro uptake experiments by hCMEC/D3 cells were carried out under several conditions. Results Diphenhydramine and [3H]pyrilamine were both transported into hCMEC/D3 cells in a time- and concentration-dependent manner with Km values of 59 μM and 19 μM, respectively. Each inhibited uptake of the other in a competitive manner, suggesting that a common mechanism is involved in their transport. The diphenhydramine uptake was significantly inhibited by amantadine and quinidine, but not tetraethylammonium and 1-methyl-4-phenylpyridinium (substrates for well-known organic cation transporters. The uptake was inhibited by metabolic inhibitors, but was insensitive to extracellular sodium and membrane potential. Further, the uptake was increased by extracellular alkalization and intracellular acidification. These transport properties are completely consistent with those of previously characterized H+/OC antiporter in rat BBB. Conclusions The present results suggest that H+/OC antiporter is functionally expressed in hCMEC/D3 cells.

Adjuvants for vaccines to drugs of abuse and addiction.

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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 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, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. Copyright © 2014. Published by Elsevier Ltd.

Internet pseudoscience: Testing opioid containing formulations with tampering potential.

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

2018-05-10

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

Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature.

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Uprety, Dipesh; Baber, Aurangzeb; Foy, Maria

2014-05-01

This article reports a rare case of the use of low-dose ketamine infusion as an adjuvant to opioids to treat pain in sickle cell disease. A 31-year-old African-American male with history of sickle cell disease presented to the emergency department with complaints of chest tightness, multiple joint pain, and headache for 1 week. His vital signs and physical examination were unremarkable. His admission lab included hemoglobin of 8.4 g/dl, reticulocyte count of 16.3%, bilirubin of 1.7 mg/dl, and LDH of 1,267 U/l. Chest X-ray showed middle and lower lobe opacity and interstitial thickening. He was treated for acute pain crisis and community-acquired pneumonia with intravenous fluids, supplemental oxygen, and intravenous levofloxacin. He was placed on fentanyl patient-controlled analgesia (PCA), oxycodone, ketorolac, and methadone with co-analgesic gabapentin and venlafaxine. Over the course of his hospitalization, his chest pain resolved, but the joint pains continued. He was then transferred to the ICU and was discharged a day later after 7 days of ketamine infusion. Ketamine is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. This property has been shown to modulate opioid tolerance and opioid-induced hyperalgesia. There have been a very few published reports on the use of low-dose ketamine in sickle cell pain management. A PubMed search revealed four published articles (Table 1). Fourteen out of the 17 cases (82.35%) who received ketamine infusion showed improvement in self-reported pain intensity and significant reduction in opioid dosage. Only one patient (5.9%) developed serious side effect leading to discontinuation of the drug. A low-dose ketamine can be an option for pain control in sickle cell disease. Randomized trial is required to establish this benefit of ketamine over currently available therapies.

Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note.

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Blum, Kenneth; Oscar-Berman, Marlene; Femino, John; Waite, Roger L; Benya, Lisa; Giordano, John; Borsten, Joan; Downs, William B; Braverman, Eric R; Loehmann, Raquel; Dushaj, Kristina; Han, David; Simpatico, Thomas; Hauser, Mary; Barh, Debmalya; McLaughlin, Thomas

2013-04-23

While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage. We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12-14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1-2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3. At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized -placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct.

Comparison of ultrasonic shears and traditional suture ligature for vaginal hysterectomy: randomized controlled trial.

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Fitz-Gerald, Alison Louise; Tan, Jason; Chan, Kok-Weng; Polyakov, Alex; Edwards, Geoff N; Najjar, Haider; Tsaltas, Jim; Vollenhoven, Beverley

2013-01-01

To compare operating time, intraoperative blood loss, postoperative analgesia, and length of hospital stay using ultrasonic shears vs traditional suture ligature in vaginal hysterectomy. Randomized controlled trial (Canadian Task Force classification I). Gynecology units within a single health network, university hospital. Forty women requiring vaginal hysterectomy because of benign disease. Vaginal hysterectomy performed using either ultrasonically activated shears (USS) or traditional suture ligatures. Twenty-one patients were randomized to the USS arm, and 19 patients to the traditional suture ligature arm. Patient characteristics were comparable. Mean (SD) hysterectomy time and was similar in both the USS and traditional arms, 28.66 (4.0) minutes vs 32.37 (3.18) minutes (p = .47), as was total operating time, 97.38 (8.9) minutes vs 91.63 (7.69) minutes (p = .63). Operative blood loss was significantly decreased in the USS group: 62.63 (12.46) mL vs 136.05 (21.54) mL (p = .006). There was, however, no significant change in hemoglobin concentration between the 2 groups: 19.53 (1.79) g/L vs -16.72 (2.5) g/L. There was no significant difference in mean oxycodone use: 9.29 (2.66) mg vs 8.06 (3.19) mg (p = .77). Length of hospital stay was similar in both groups: 58.98 (3.27) hours vs 60.05 (6.48) hours (p = .88). There was no significant difference in overall complication rates between the groups. Although the Harmonic scalpel system, compared with the traditional suture ligation method, seems to be a safe alternative for securing the pedicles in vaginal hysterectomy, it offers no benefit insofar as operative time, reduction in clinically significant blood loss, and analgesic requirements. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

Predicting opioid use disorder in patients with chronic pain who present to the emergency department.

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Gardner, Robert Andrew; Brewer, Kori L; Langston, Dennis B

2018-04-06

Emergency department (ED) patients with chronic pain challenge providers to make quick and accurate assessments without an in-depth pain management consultation. Emergency physicians need reliable means to determine which patients may receive opioid therapy without exacerbating opioid use disorder (OUD). Eighty-nine ED patients with a chief complaint of chronic pain were enrolled. Researchers administered questionnaires and reviewed medical and state prescription monitoring database information. Participants were classified as either OUD or non-OUD. Statistical analysis included a bivariate analysis comparing differences between groups and multivariate logistic regression evaluating ORs. The 45 participants categorised as OUD had a higher proportion of documented or reported psychiatric diagnoses (p=0.049), preference of opioid treatment (p = 0.005), current oxycodone prescription (p = 0.043), borrowed pain medicine (p=0.004) and non-authorised dose increase (pOUD group to have an increased number of opioid prescriptions (p=0.005) and pills (p=0.010). Participants who borrowed pain medicine and engaged in non-authorised dose increase were 5.2 (p=0.025, 95% CI 1.24 to 21.9) and 6.1 times (p=0.001, 95% CI 1.55 to 24.1) more likely to have OUD, respectively. Major limitations of our study include a small sample size, self-reported measures and convenience sample which may introduce selection bias. Patients with chronic pain with OUD have distinguishable characteristics. Emergency physicians should consider such evidence-based variables prior to opioid therapy to ameliorate the opioid crisis and limit implicit bias. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Continuous chloroprocaine infusion for thoracic and caudal epidurals as a postoperative analgesia modality in neonates, infants, and children.

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Veneziano, Giorgio; Iliev, Peter; Tripi, Jennifer; Martin, David; Aldrink, Jennifer; Bhalla, Tarun; Tobias, Joseph

2016-01-01

Neonates and infants have decreased metabolic capacity for amide local anesthetics and increased risk of local anesthetic toxicity compared to the general population. Chloroprocaine is an ester local anesthetic that has an extremely short plasma half-life in infants as well as adults. Existing reports support the safety and efficacy of continuous chloroprocaine epidural infusions in neonates and young infants during the intraoperative period. Despite this, continuous chloroprocaine epidural infusion may be an under-utilized method of postoperative analgesia for this patient population. In particular, it may improve pain control in neonates and infants with incisions stretching many dermatomes or those with hepatic impairment. We retrospectively reviewed our experience over 4 years with continuous chloroprocaine epidural infusions in neonates, infants, and children with a focus on the postoperative management of pain. Twenty-one pediatric patients received continuous 2-chloroprocaine epidural infusions for postoperative pain management from January 2010 to April 2014 for thoracic, abdominal, and limb procedures. The epidural infusion consisted of 1.5% chloroprocaine or 1.5% chloroprocaine with fentanyl. Tabulating the morphine and hydromorphone used for rescue analgesia, the median (interquartile range) opioid consumption (mg·kg(-1) ·day(-1) of intravenous morphine equivalents) for the first, second, and third 24-h postoperative periods were 0.02 (0-0.48), 0.30 (0-0.44), and 0.14 (0-0.29), respectively. Examining the total fentanyl usage, the median (interquartile range) fentanyl consumption (μg·kg(-1) ·day(-1)) for first, second, and third 24-h postoperative periods were 3.89 (0.41-7.24), 0 (0.00-4.06), and 0 (0.00-0.51), respectively. The median N-PASS score assessed every 6 h from 0 to 72 h postoperatively was 0, 1, 2, 0, 0, 1, 0, 0, 0, 0, 1, 0, and 0, respectively. The median FLACC score assessed every 6 h from 0 to 72 h postoperatively was 0, 0, 2, 0, 0, 0

Kratom alkaloids and O-desmethyltramadol in urine of a "Krypton" herbal mixture consumer.

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Arndt, Torsten; Claussen, Ulrich; Güssregen, Brunhilde; Schröfel, Stefanie; Stürzer, Birgit; Werle, Annika; Wolf, Gerald

2011-05-20

A drug and alcohol withdrawal rehabilitation centre requested an analysis for "Krypton" in urine of a former opiate-addictive woman. She showed an altered clinical picture and behaviour with miosis, itchiness, agitation, and moderate euphoria after 3 months of until than successful treatment. Literature search revealed that "Krypton" is said to contain "Kratom" (leaves of Mitragyna speciosa), but could also contain O-desmethyltramadol (European Monitoring Centre for Drugs and Drug Addiction thematic paper "Spice"). Immunological drug screenings were done with test strips (nal von minden, Regensburg, Germany) and with cloned enzyme donor immunoassay (Microgenics, Passau, Germany). "Kratom" alkaloids and tramadol (metabolites) were analyzed by LC-MS/MS (ThermoFisher Scientific Quantum Ultra Triple Quadrupole mass spectrometer). Immunoassays were negative for amphetamines, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, ethylglucuronide, methadone (metabolite), opiates, oxycodone, and THC-COOH, and test strips were negative for tramadol and its metabolites (cut-off 10 mg/L for O-desmethyltramadol). LC-MS/MS detected the "Kratom" alkaloids mitragynine, speciociliatine, speciogynine, mitraciliatine, and paynantheine and approximately 9mg/L O-desmethyltramadol, but no tramadol and N-desmethyltramadol. The detection of M. speciosa alkaloids is a proof of "Kratom" abuse. Confronted with the analysis data, the patient admitted to have consumed 3-4 infusions of "Krypton". The origin of the O-desmethyltramadol is unclear. Tramadol abuse is unlikely since tramadol and N-desmethyltramadol (physiologically occurring in urine after tramadol intake) were not detectable. Consumption of a "Krypton" product spiked with O-desmethyltramadol could explain our findings and the patient's clinical picture. This would be in agreement with a most recent report about spiking apparently natural herbal mixtures with the synthetic opioid O-desmethyltramadol. Analysis of "Kratom

Severe, childhood-onset, idiopathic, life-long insomnia responding selectively to opiate therapy: case report with 19 year follow-up.

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Schenck, C H; Mahowald, M W

2001-11-01

Idiopathic (primary) insomnia can be difficult to treat; only two prior cases responsive to opiate therapy have been reported. A case is now presented of severe, idiopathic, childhood-onset, familial insomnia, with increased libido, absence of psychopathology, tardive emergence of restless legs syndrome (RLS), and selective response to opiate therapy. A 39-year-old woman was referred in 1981 by her physician who had discovered 3 years earlier that propoxyphene treatment of migraines also controlled her chronic insomnia. She had experienced severe insomnia since childhood, and during early adulthood the insomnia intensified, as she would sleep 0-3 h nightly and never napped. Daily generalized motor restlessness resulted in her frequently walking around the house while feeling exhausted. The quality of her life was considerably compromised by her insomnia, motor restlessness, and by an increased libido that was present since puberty and that was only partially relieved by having sex repeatedly with her husband. Nightly opiate therapy for 19 years has controlled the insomnia, motor restlessness, and excessive libido without affecting her normal libido. The insomnia had not responded to treatment with >25 agents covering >10 pharmacologic categories. During her first (unmedicated) polysomnographic (PSG) study in 1981, she slept 0 min while spending 436 min in bed. In 1984, four consecutive PSG studies were conducted in a design that confirmed the efficacy of propoxyphene therapy of her insomnia. In 1990, an ambulatory PSG revealed two runs of EEG rhythmic paroxysmal activity arising from sleep and wakefulness, without clinical correlate. Neurologic history was negative for seizures, but positive for complete right carotid artery occlusion and three transient ischemic attacks. At age 55 years, typical RLS emerged that was controlled with levodopa therapy, and a concurrent relapse of insomnia was controlled with oxycodone replacing propoxyphene. Nightly opiate therapy of

Non-medical use of psychoactive prescription drugs is associated with fatal poisoning.

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Haukka, Jari; Kriikku, Pirkko; Mariottini, Claudia; Partonen, Timo; Ojanperä, Ilkka

2018-03-01

The aims of this study were to estimate the prevalence and predictors of non-medical substance use, and to assess the association between non-medical substance use and fatal poisoning or history of drug abuse in Finland. Retrospective cohort study of all medico-legally investigated death cases in Finland. The postmortem toxicology database was linked together with the register on reimbursed prescription medicines. All postmortem cases between 2011 and 2013 positive for one or more of the following drugs: oxycodone, fentanyl, tramadol, clonazepam, gabapentin, pregabalin, tizanidine, olanzapine, quetiapine, risperidone, alprazolam, zolpidem, mirtazapine and bupropion, n = 2974. Non-medical use of substance was the outcome variable. Predictors were the following: gender, residence at the time of death, place of death, blood alcohol concentration, age, drug abuse, number of prescriptions of any psychoactive drugs in last year and proportion of prescriptions issued by psychiatrist in last year. In 50.4% of the studied cases, at least one drug was detected without a prescription. Clonazepam, alprazolam and tramadol were the most prevalent non-medical findings in these cases (6.6, 6.1 and 5.6%, respectively). The risk of non-medical use of prescription drugs was especially high in cases with history of drug abuse (88.5%) and in fatal poisonings (71.0%). The proportion of non-medical use of the studied substances varied between 5.9% [95% confidence interval (CI) = 3.1-10.1%)] for risperidone and 55.7% for fentanyl (95% CI = 44.1-66.9%). Valid prescription for one or more of any psychoactive drug was associated with lower odds for non-medical use of the studied substances. Additionally, the higher the proportion of psychoactive drugs prescribed by a psychiatrist, the lower the probability of non-medical use. Non-prescribed psychoactive drugs are found commonly at postmortem in drug poisoning deaths in Finland, with history of drug abuse being a major contributing

Physician assessments of drug seeking behavior: A mixed methods study.

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Michael A Fischer

Full Text Available Pain complaints are common, but clinicians are increasingly concerned about overuse of opioid pain medications. This may lead patients with actual pain to be stigmatized as "drug-seeking," or attempting to obtain medications they do not require medically. We assessed whether patient requests for specific opioid pain medication would lead physicians to classify them as drug-seeking and change management decisions.Mixed-methods analysis of interviews with 192 office-based primary care physicians after viewing video vignettes depicting patients presenting with back pain. For each presentation physicians were randomly assigned to see either an active request for a specific medication or a more general request for help with pain. The main outcome was assignment by the physician of "drug-seeking" as a potential diagnosis among patients presenting with back pain. Additional outcomes included other actions the physician would take and whether the physician would prescribe the medication requested. A potential diagnosis of drug-seeking behavior was included by 21% of physicians seeing a specific request for oxycodone vs. 3% for a general request for help with back pain(p<0.001. In multivariable models an active request was most strongly associated with a physician-assigned diagnosis of drug-seeking behavior(OR 8.10; 95% CI 2.11-31.15;p = 0.002; other major patient and physician characteristics, including gender and race, did not have strong associations with drug-seeking diagnosis. Physicians described short courses of opioid medications as a strategy for managing patients with pain while avoiding opioid overuse.When patients make a specific request for opioid pain medication, physicians are far more likely to suspect that they are drug-seeking. Physician suspicion of drug-seeking behavior did not vary by patient characteristics, including gender and race. The strategies used to assess patients further varied widely. These findings indicate a need for

Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

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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

Clinical potential of naloxegol in the management of opioid-induced bowel dysfunction

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Poulsen JL

2014-09-01

Full Text Available Jakob Lykke Poulsen,1 Christina Brock,1,2 Anne Estrup Olesen,1,2 Matias Nilsson,1 Asbjørn Mohr Drewes1,3 1Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkAbstract: Opioid-induced bowel dysfunction (OIBD is a burdensome condition which limits the therapeutic benefit of analgesia. It affects the entire gastrointestinal tract, predominantly by activating opioid receptors in the enteric nervous system, resulting in a wide range of symptoms, such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation. The majority of studies evaluating OIBD focus on constipation experienced in approximately 60% of patients. Nevertheless, other presentations of OIBD seem to be equally frequent. Furthermore, laxative treatment is often insufficient, which in many patients results in decreased quality of life and discontinuation of opioid treatment. Novel mechanism-based pharmacological approaches targeting the gastrointestinal opioid receptors have been marketed recently and even more are in the pipeline. One strategy is prolonged release formulation of the opioid antagonist naloxone (which has limited systemic absorption and oxycodone in a combined tablet. Another approach is peripherally acting, µ-opioid receptor antagonists (PAMORAs that selectively target µ-opioid receptors in the gastrointestinal tract. However, in Europe the only PAMORA approved for OIBD is the subcutaneously administered methylnaltrexone. Alvimopan is an oral PAMORA, but only approved in the US for postoperative ileus in hospitalized patients. Finally, naloxegol is a novel, oral PAMORA expected to be approved soon. In this review, the prevalence and pathophysiology of OIBD is presented. As PAMORAs seem to be a promising approach, their potential

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

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Kimberly Fernandes

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

The use of self-gripping (Progrip™) mesh during laparoscopic total extraperitoneal (TEP) inguinal hernia repair: a prospective feasibility and long-term outcomes study.

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Bresnahan, Erin; Bates, Andrew; Wu, Andrew; Reiner, Mark; Jacob, Brian

2015-09-01

The use of self-gripping mesh during laparoscopic TEP inguinal hernia repairs may eliminate the need for any additional fixation, and thus reduce post-operative pain without the added concern for mesh migration. Long-term outcomes are not yet prospectively studied in a controlled fashion. Under IRB approval, from January 2011-April 2013, 91 hernias were repaired laparoscopically with self-gripping mesh without additional fixation. Patients were followed for at least 1 year. Demographics and intraoperative data (defect location, size, and mesh deployment time) are recorded. VAS is used in the recovery room (RR) to score pain, and the Carolinas Comfort Scale ™ (CCS), a validated 0-5 pain/quality of life (QoL) score where a mean score of >1.0 means symptomatic pain, is employed at 2 weeks and at 1 year. Morbidities, narcotic usage, days to full activity and return to work, and CCS scores are reported. Sixty two patients, with 91 hernias repaired with self-gripping mesh, completed follow-up at a mean time period of 14.8 months. Seventeen hernias were direct defects (average size 3.0 cm). Mesh deployment time was 193.7 s. RR pain was 1.1/10 using a VAS. Total average oxycodone/acetaminophen (5 mg/325 mg) usage = 5.0 tablets, days to full activity was 1.6, and return to work was 4.2 days. Thirteen small asymptomatic seromas were palpated without any recurrences or groin tenderness, and all seromas resolved by the 6 month visit. Transient testis discomfort was reported in five patients. Urinary retention was 3.2%. Mean CCS™ scores at the first visit for groin pain laying, bending, sitting, walking, and step-climbing were 0.2, 0.5, 0.4, 0.3, and 0.3, respectively. At the first post op visit, 4.8% had symptomatic pain (CCS > 1). At 14.8 months, no patients reported symptomatic pain with CCS scores for all 62 patients averaging 0.02, (range 0-0.43). There are no recurrences thus far. Self-gripping mesh can be safely used during laparoscopic TEP inguinal hernia repairs

Adult emergency department patients with sickle cell pain crisis: a learning collaborative model to improve analgesic management.

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Tanabe, Paula; Artz, Nicole; Mark Courtney, D; Martinovich, Zoran; Weiss, Kevin B; Zvirbulis, Elena; Hafner, John W

2010-04-01

between 10 and 67 visits. Fifty-nine percent of patients were discharged home. The median time to initial analgesic for the cohort was 74 minutes (IQR = 48-135 minutes). Differences between choice of analgesic agent and route selected were evident between sites. For the cohort, 680 initial analgesic doses were given (morphine sulfate, 42%; hydromorphone, 46%; meperidine, 4%; morphine sulfate and ibuprofen or ketorolac, 7%) using the following routes: oral (2%), intravenous (67%), subcutaneous (3%), and intramuscular (28%). Patients reported a significantly lower targeted discharge pain score (mean +/- SD = 4.19 +/- 1.18) compared to the actual documented discharge pain score within 45 minutes of discharge (mean +/- SD = 5.77 +/- 2.45; mean difference = 1.58, 95% confidence interval = .723 to 2.44, n = 43). While half of the patients had one to three ED visits during the study period, many patients had more frequent visits. Delays to receiving an initial analgesic were common, and post-ED interviews reveal that sickle cell pain patients are discharged from the ED with higher pain scores than what they perceive as desirable.

Contribution of positron emission tomography for the study of response variability to opioid drugs

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Auvity, Sylvain

2017-01-01

investigate the neuro-pharmacokinetic component of opioid pharmacology. "1"1C-diphenhydramine was developed in rats as a specific probe to estimate the H"+/antiporter function at the blood-brain barrier. This newly identified carrier transport System was shown to control the brain exposure of many CNS drugs, including oxycodone. Then, we used "1"1C-buprenorphine PET imaging and validated a co-injection strategy to quantify the parameters that describe the brain kinetics of buprenorphine in nonhuman primates. Throughout this project, several methods have been evaluated or developed in order to address original hypothesis regarding the pharmacology of opioid drugs. The choice for noninvasive and quantitative methods such as PET imaging allows for clinical translation. These tools may thus be useful to investigate the neuro-immune and neuro-pharmacokinetic component of the variability of response to opioid drugs in humans. (author) [fr

Tapentadol in the management of chronic low back pain: a novel approach to a complex condition?

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Pergolizzi J

2011-07-01

pharmacological therapy, but clinical evidence for this approach is currently lacking. Tapentadol combines µ-opioid agonism with noradrenaline reuptake inhibition in a single molecule. There is strong evidence of synergistic antinociception between these two mechanisms of action. In preclinical and clinical testing, tapentadol has shown efficacy against both nociceptive and neuropathic pain. Preclinical data indicate that tapentadol’s µ-opioid agonism makes a greater contribution to analgesia in acute pain, while noradrenaline reuptake inhibition makes a greater contribution in chronic neuropathic pain models. Tapentadol also produces fewer adverse events than oxycodone at equianalgesic doses, and thus may have a ‘µ-sparing effect’. Current evidence indicates that tapentadol’s efficacy/tolerability ratio may be better than those of classical opioids. However, further research is needed to establish its role in pain management.Keywords: chronic low back pain, neurophysiological changes, neuropathic component, multimechanistic approach, efficacy/side effect ratio, tapentadol

Análise clínica e terapêutica dos pacientes oncológicos atendidos no programa de dor e cuidados paliativos do Hospital Universitário Clementino Fraga Filho no ano de 2003 Análisis clínico y terapéutico de los pacientes oncológicos atendidos en el programa de dolor y cuidados paliativos del Hospital Universitario Clementino Fraga Filho en el año 2003 Clinical and therapeutic analysis of oncology patients treated at the pain and palliative care program of the Hospital Universitário Clementino Fraga Filho in 2003

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Giselane Lacerda Figueredo Salamonde

2006-12-01

los pacientes y la humanización en el término de la vida.BACKGROUND AND METHODS: The main goal of palliative care is the control of pain and other symptoms in patients with chronic diseases without possibility of cure, especially advanced cancer. About 75% of patients with advanced cancer experience severe pain, which interferes with quality of life and, according to the WHO, it is considered a worldwide medical emergency. This study evaluated the profile of oncology patients enrolled in the Chronic Pain Treatment and Palliative Care Program of the HUCFF/FM/UFRJ, focusing on the role of the anesthesiologist, medications used, humanization of the treatment, and improvement in patient's quality of life. METHODS: The 2003-oncology patients' charts were analyzed retrospectively. Several parameters were compared: age, race, gender, preexisting conditions organ the cancer originated from, type of pain and other symptoms, medications, hospital routine, and end of treatment. RESULTS: The types of pain included nociceptive, neuropathic, and incidental, which were evaluated using the unidimensional faces pain rating scale. In the first week, patients were treated with home-based patient controlled analgesia (PCA with oral methadone. After this period, the patient returned to the clinic to calculate the regular dose of methadone. Other opioids used included codeine, tramadol, morphine, and oxycodone. Besides pain, patients experienced: constipation, vomiting, delirium, sleep disturbances, and dyspnea. Neuroleptics, corticosteroids, and laxatives were also used as adjuvant therapy. CONCLUSIONS: Patient controlled analgesia with methadone is safe and effective, since there were no significant side effects. The clinical and pharmacological knowledge of the anesthesiologist in the multidisciplinary team provided for better patient care, relief of symptoms, and humanization of the final stages of life.