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Oxycodone
Kinds of Oxycodone Selected AbstractsCONTROLLED-RELEASE OXYCODONE RELIEVES MODERATE TO SEVERE PAIN IN A 3-MONTH STUDY OF PERSISTENT MODERATE TO SEVERE BACK PAINPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Patricia Richards, MD, PhD; Pinggao Zhang, PhD; Michael Friedman, PhD; Rahul Dhanda, PhD. (Purdue Pharma L.P.) Introduction: Opioids are frequently prescribed for management of persistent low back pain, however, efficacy has not been well documented, and concerns are that opioids may impair physical functioning. Objective: To compare controlled-release oxycodone (CRO) with placebo in controlling pain and to observe the effect of CRO on quality of life and functionality. Methods: A double-blind, randomized, placebo-controlled, parallel-group study of 3 months duration was conducted in 110 subjects (49 males, 61 females), mean age 48 years (19,80 years). Subjects had a 3- to 12-month history of moderate to severe persistent low back pain and were previously unresponsive to therapeutic doses of NSAIDs, and/or low dose combination opioid analgesics. At baseline 4% of subjects were on opioids, 39% on NSAIDs, and 57% both NSAIDs and opioids. Subjects were treated with 10 mg CRO tablet or 10 mg oral placebo q12h, titrated to stable pain control. Existing treatment regimens of acetaminophen, NSAIDs, or oral steroids were allowed to continue. The Brief Pain Inventory (BPI), the Roland Morris Functionality Questionnaire, and the MOS 36-Item Short-Form Health Survey (SF-36) were the measures of pain intensity, functionality, and quality of life. Treatments were compared using repeated measures ANCOVA with baseline value as covariate. Results: CRO treatment was significantly superior to placebo on the BPI average pain intensity and average percent pain relief scores overall (4.6 vs 5.4, P = .03, and 47.2 vs 36.3, P = .05, respectively). Fewer CRO subjects discontinued because of inadequate pain control (P < .001). No significant differences between treatments were observed in either Roland Morris or SF-36 scores. Common adverse events for CRO were nausea, constipation, somnolence, headache, and pruritus, consistent with opioid use. Conclusions: Three-month treatment with CRO provides significant pain relief for subjects with persistent moderate to severe back pain, without significantly impairing functionality and quality of life. The support of Purdue Pharma L.P. for this research project is gratefully acknowledged. [source] Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010S. T. ZWISLER Background: Oxycodone is a semi-synthetic opioid with a ,-receptor agonist-mediated effect in several pain conditions, including post-operative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O -demethylation via the polymorphic CYP2D6. The aim of this study was to investigate whether CYP2D6 poor metabolizers (PMs) yield the same analgesia post-operatively from intravenous oxycodone as extensive metabolizers (EMs). Methods: Two hundred and seventy patients undergoing primarily thyroid surgery or hysterectomy were included and followed for 24 h post-operatively. The CYP2D6 genotype was blinded until study procedures had been completed for all patients. All patients received intravenous oxycodone as pain treatment for 24 h post-operatively and morphine 5 mg was used as escape medication. A responder was characterized as a patient without the need for escape medication and a positive evaluation in a questionnaire 24 h post-operatively. Results: Twenty-four patients were PM (8.9%) and 246 were EM (91.1%). One PM (4.17%, CI=0.1,21.1) was a non-responder and 42 EM (17.07%, CI=12.6,22.4) were non-responders. The non-responder rate did not differ between the two genotypes (P=0.14). There was no difference in the total consumption of oxycodone between the two genotypes (EM=14.7 mg, CI=13.0,16.4 and PM=13.0 mg, CI=8.9,17.0, P=0.42). The mean oxymorphone/oxycodone ratios were 0.0031 and 0.00081 in the EMs and PMs, respectively (P<0.0001). Conclusion: This study showed for the first time in patients that the oxymorphone formation depends on CYP2D6, but we found no difference in the post-operative analgesic effect of intravenous oxycodone between the two CYP2D6 genotypes. [source] Cerebral kinetics of oxycodone in conscious sheepJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2006Hanne H. Villesen Abstract Oxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebral kinetics of oxycodone was quantified using a conscious chronically instrumented sheep preparation. Five sheep were administered oxycodone as intravenous infusions (30 mg over 4 min). Using hybrid physiologically based kinetic models, cerebral kinetics was estimated from arterio-sagittal sinus concentration gradients and cerebral blood flow (CBF). A two-compartment membrane-limited model best described the data. The volume of the first brain compartment was 35.4 mL with a half-life of equilibrium of 0.6 min. The brain:blood equilibration of oxycodone was relatively slow (half-life of 7.2 min), with a large deep cerebral distribution volume (222.8 mL) for the second compartment and a moderate membrane permeability of 54.8 mL/min, which exceeded the nominal CBF (40 mL/min). Drug retention in the brain was 1.3% after 45 min. In conclusion, pharmacokinetic modelling of oxycodone showed a delayed equilibration between brain and blood of a nature that would be affected by changes in both CBF and blood brain barrier permeability. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1666,1676, 2006 [source] Toward Evidence-Based Prescribing at End of Life: A Comparative Analysis of Sustained-Release Morphine, Oxycodone, and Transdermal Fentanyl, with Pain, Constipation, and Caregiver Interaction Outcomes in Hospice PatientsPAIN MEDICINE, Issue 4 2006BCPS, Douglas J. Weschules PharmD ABSTRACT Objective., The primary goal of this investigation was to examine selected outcomes in hospice patients who are prescribed one of three sustained-release opioid preparations. The outcomes examined include: pain score, constipation severity, and ability of the patient to communicate with caregivers. Patients and Settings., This study included 12,000 terminally ill patients consecutively admitted to hospices and receiving pharmaceutical care services between the period of July 1 and December 31, 2002. Design., We retrospectively examined prescribing patterns of sustained-release morphine, oxycodone, and transdermal fentanyl. We compared individual opioids on the aforementioned outcome markers, as well as patient gender, terminal diagnosis, and median length of stay. Results., Patients prescribed a sustained-release opioid had similar average ratings of pain and constipation severity, regardless of the agent chosen. Patients prescribed transdermal fentanyl were reported to have more difficulty communicating with friends and family when compared with patients prescribed either morphine or oxycodone. On average, patients prescribed transdermal fentanyl had a shorter length of stay on hospice as compared with those receiving morphine or oxycodone. Conclusion., There was no difference in observed pain or constipation severity among patients prescribed sustained-release opioid preparations. Patients receiving fentanyl were likely to have been prescribed the medication due to advanced illness and associated dysphagia. Diminished ability to communicate with caregivers and a shorter hospice course would be consistent with this profile. Further investigation is warranted to examine the correlation between a patient's ability to interact with caregivers and pain control achieved. [source] 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)PAIN PRACTICE, Issue 4 2008Joseph Pergolizzi MD ,,Abstract 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.,, [source] Grapefruit Juice Enhances the Exposure to Oral OxycodoneBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2010Tuija H. Nieminen The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration,time curve (AUC0,,) by 1.7-fold (p < 0.001), the peak plasma concentration by 1.5-fold (p < 0.001) and the half-life of oxycodone by 1.2-fold (p < 0.001) as compared to the water. The metabolite-to-parent AUC0,, ratios (AUCm/AUCp) of noroxycodone and noroxymorphone decreased by 44% (p < 0.001) and 45% (p < 0.001), respectively. Oxymorphone AUC0,, increased by 1.6-fold (p < 0.01) after grapefruit juice, but the AUCm/AUCp remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use. [source] Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 aloneBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Juha Grönlund WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Oxycodone is an opioid analgesic that is metabolized mainly in the liver by cytochrome P450 (CYP) 2D6 and 3A4 enzymes. , So far, the effects of CYP2D6 or CYP3A4 inhibitors on the pharmacokinetics of oxycodone in humans have not been systematically studied. WHAT THIS STUDY ADDS , Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone. , When both of CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. AIM The aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone. METHODS A randomized placebo-controlled cross-over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre-treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated. RESULTS Paroxetine alone reduced the area under concentration,time curve (AUC(0,0,48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,,) of oxycodone increased by 2.9-fold (P < 0.001), and its Cmax by 1.8-fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre-treatment when compared with placebo. CONCLUSIONS Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. [source] Critical review of oral drug treatments for diabetic neuropathic pain,clinical outcomes based on efficacy and safety data from placebo-controlled and direct comparative studiesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2005Hugo Adriaensen Abstract The present review aims to evaluate the efficacy and safety of a selection of oral treatments for the management of painful diabetic neuropathy. A literature review was conducted retrieving placebo-controlled and direct comparative studies with a selection of oral treatments for painful diabetic neuropathy. All studies were analyzed with regard to efficacy and tolerability. Efficacy was evaluated as the percentage improvement in pain intensity between baseline and endpoint. Tolerability was evaluated by means of study discontinuations due to adverse events and by incidence of drug-related adverse events. The analyzed trials enrolled different patient populations with mostly small numbers of patients. The great variability in dosages and dose titration schemes, cross-over designs with variable wash-out periods, and other design schemes made comparison between the different studies difficult. Gabapentin, lamotrigine, tramadol, oxycodone, mexiletine, and acetyl-L-carnitine were the only treatments studied in large (at least 100 patients), placebo-controlled parallel group trials. It is concluded that standardization in design and reporting for comparison of treatments is needed. Validated questionnaires for evaluation of the efficacy and safety should be further developed. Based on the reviewed randomised controlled trials, gabapentin shows good efficacy, a favourable side-effect profile with lack of drug interactions and therefore it may be a first choice treatment in painful diabetic neuropathy, especially in the elderly. However, head to head trials of current treatments are lacking and therefore randomized controlled trials are required to address this issue. Copyright © 2005 John Wiley & Sons, Ltd. [source] A comparison of drug overdose deaths involving methadone and other opioid analgesics in West VirginiaADDICTION, Issue 9 2009Leonard J. Paulozzi ABSTRACT Aims To describe all people dying from unintentional overdoses of methadone or other opioid analgesics (OOA) in West Virginia in 2006. Design We analyzed medical examiner data supplemented by data from the state prescription drug monitoring program. We compared people whose deaths involved methadone with those whose deaths involved OOA. Findings The methadone group included 87 decedents, and the OOA group included 163 decedents. Most were male. Decedents in the methadone group were significantly younger than those in the OOA group: more than a quarter were 18,24 years of age. For both groups, approximately 50% had a history of pain, and 80% had a history of substance abuse. There was no intergroup difference in the prevalence of benzodiazepines at post-mortem. Methadone was significantly less likely to have ever been prescribed than OOA. Among those with prescriptions, the proportion prescribed within 30 days of death was significantly greater for methadone than for hydrocodone, but not for oxycodone. Ten (11.5%) of the methadone decedents were enrolled in an opiate treatment program (OTP) at the time of death. Conclusions The high prevalence of a substance abuse history and lack of prescriptions suggest that most of the deaths in both groups are related to substance abuse. There was no indication of a harmful effect from methadone's metabolic interaction with benzodiazepines, but provider or patient unfamiliarity with methadone may have been a risk factor. Prescribing methadone, especially to young males, requires extra care. Providers, OTPs and coroners/medical examiners should use state prescription drug monitoring programs to monitor the use of controlled substances by their patients. [source] Analysis of oxycodol and noroxycodol stereoisomers in biological samples by capillary electrophoresisELECTROPHORESIS, Issue 10 2005Andrea Baldacci Abstract A capillary electrophoresis (CE) method for the separation of the diastereoisomers of 6-oxycodol (6OCOL) and nor-6-oxycodol (N6OCOL), the 6-keto-reduced metabolites of oxycodone (OCOD) and noroxycodone (NOCOD), respectively, is reported and employed to assess the stereoselectivity of these metabolic steps in vivo, in vitro, and in chemical synthesis. CE in an untreated fused-silica capillary with acidic buffers containing 2-hydroxypropyl-,-cyclodextrin, randomly sulfated ,-cyclodextrin, or single isomer heptakis(2,3-diacetyl-6-sulfato)-,-cyclodextrin (HDAS-,-CD) is shown to permit the simultaneous separation of the stereoisomers of 6OCOL and N6OCOL. A 100 mM phosphate buffer of pH 2.0 containing 2.05% w/v HDAS-,-CD provides a medium for rapid analysis and unambiguous identification of these stereoisomers in solid-phase extracts of (i) urines stemming from patients under pharmacotherapy with OCOD, (ii) incubations of OCOD and NOCOD with human liver cytosol and the human liver S9 fraction, and (iii) after chemical synthesis from OCOD and NOCOD using NaBH4. In all cases, ,-N6OCOL is shown to be the predominant stereoisomer of N6OCOL. For 6OCOL, the same is true for in vitro formation and for chemical synthesis. In urine, however, ,-6OCOL is observed to be excreted in a higher amount than ,-6OCOL. For the urinary ,-/,-isomer ratio of 6OCOL and N6OCOL, there are no differences between the data obtained for nonhydrolyzed and enzymatically hydrolyzed urines. The data document the stereoselectivity of the 6-keto-reduction of OCOD and NOCOD in man. [source] Dexamethasone decreases oxycodone consumption following osteotomy of the first metatarsal bone: a randomized controlled trial in day surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010K. MATTILA Background: Dexamethasone may improve multimodal pain management following painful orthopedic day surgery procedures, and decrease the need for post-operative opioids. We hypothesized that dexamethasone would reduce the need for oxycodone after surgical correction of hallux valgus. Methods: Sixty patients planned to undergo unilateral osteotomy of the first metatarsal as a day surgery procedure were randomized to receive pre-operatively and 24 h afterwards, orally either dexamethasone 9 mg or placebo. For pain medication, paracetamol and oxycodone capsules for rescue medication were given. The study ended on the evening of the third post-operative day (POD). The primary endpoint was the cumulative oxycodone consumption. Secondary endpoints were maximal pain scores before oxycodone intake and daily oxycodone doses. In addition, adverse effects were documented. Results: Twenty-five patients in both groups completed the study. The total median (range) oxycodone consumption during the study period was 45 (0,165) mg in the dexamethasone group and 78 (15,175) mg in the placebo group (P=0.049). The major differences in oxycodone consumption were seen on PODs 0,1. In the dexamethasone group, patients reported significantly lower pain scores on PODs 0,1, and significantly less nausea on POD 1. On PODs 2,3 no differences were seen. However, at 2 weeks post-operatively, patient satisfaction to drug therapy did not differ , in both groups 81% would have chosen the same medication again. Conclusion: Oral dexamethasone combined with paracetamol significantly reduced total oxycodone consumption following surgical correction of hallux valgus. [source] Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010S. T. ZWISLER Background: Oxycodone is a semi-synthetic opioid with a ,-receptor agonist-mediated effect in several pain conditions, including post-operative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O -demethylation via the polymorphic CYP2D6. The aim of this study was to investigate whether CYP2D6 poor metabolizers (PMs) yield the same analgesia post-operatively from intravenous oxycodone as extensive metabolizers (EMs). Methods: Two hundred and seventy patients undergoing primarily thyroid surgery or hysterectomy were included and followed for 24 h post-operatively. The CYP2D6 genotype was blinded until study procedures had been completed for all patients. All patients received intravenous oxycodone as pain treatment for 24 h post-operatively and morphine 5 mg was used as escape medication. A responder was characterized as a patient without the need for escape medication and a positive evaluation in a questionnaire 24 h post-operatively. Results: Twenty-four patients were PM (8.9%) and 246 were EM (91.1%). One PM (4.17%, CI=0.1,21.1) was a non-responder and 42 EM (17.07%, CI=12.6,22.4) were non-responders. The non-responder rate did not differ between the two genotypes (P=0.14). There was no difference in the total consumption of oxycodone between the two genotypes (EM=14.7 mg, CI=13.0,16.4 and PM=13.0 mg, CI=8.9,17.0, P=0.42). The mean oxymorphone/oxycodone ratios were 0.0031 and 0.00081 in the EMs and PMs, respectively (P<0.0001). Conclusion: This study showed for the first time in patients that the oxymorphone formation depends on CYP2D6, but we found no difference in the post-operative analgesic effect of intravenous oxycodone between the two CYP2D6 genotypes. [source] Does 1 or 2 g paracetamol added to ketoprofen enhance analgesia in adult tonsillectomy patients?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009A. SALONEN Background: We have evaluated whether co-administration of intravenous (i.v.) paracetamol could enhance the analgesic efficacy of ketoprofen (a non-steroidal anti-inflammatory drug or NSAID) in patients undergoing a tonsillectomy. Methods: This prospective, randomized, double-blinded and placebo-controlled add-on study with three parallel groups included 114 patients, aged 16,50 years, and scheduled for elective tonsillectomy. All patients were given ketoprofen 1 mg/kg i.v. after surgery, followed 5 min later by paracetamol 1 or 2 g i.v., or normal saline as a placebo. The primary outcome measure was the proportion of patients requiring oxycodone for rescue analgesia over the first 6 h (pain score >30/100 mm at rest or >50/100 mm during swallowing) after surgery. Results: No difference was detected in the proportion of patients receiving oxycodone (31/37 in the paracetamol 1 g group, 29/39 in the paracetamol 2 g group and 30/38 in the ketoprofen-alone group) between the three groups. However, significantly less doses of rescue analgesia were provided in the paracetamol groups than in the ketoprofen-alone group (P=0.005); among those who required rescue analgesia, 27% less oxycodone was required in the paracetamol 1 g group (80 doses, P=0.023) and 38% less in the paracetamol 2 g group (64 doses, P=0.002) than in the ketoprofen-alone group (106 doses). Conclusion: Combining paracetamol i.v. with ketoprofen at the end of tonsillectomy did not reduce the proportion of the patients requiring rescue analgesia, but the number of opioid doses was less in the add-on groups. [source] Fracture risk associated with the use of morphine and opiatesJOURNAL OF INTERNAL MEDICINE, Issue 1 2006P. VESTERGAARD Abstract. Objectives., To study the effect of morphine and opiates on fracture risk. Design., Case,control study. Setting., Nationwide register-based study. Subjects., Cases were all subjects with any fracture sustained during the year 2000 (n = 124 655). For each case, three controls (n = 373 962) matched on age and gender were randomly drawn from the background population. The primary exposure variables were use of morphine and opiates. Morphine and other opiates had been used by 10 015 (8.0%) of the case subjects and 12 108 (3.2%) of the controls. Adjustments were made for several confounders including prior fracture, and use of weak analgesics [nonsteroidal anti-inflammatory drugs, acetylsalicylic acid (ASA) and acetaminophene]. The effect of dose was examined by stratifying for cumulated dose (defined daily dose). Main outcome measure., Fracture. Results., Morphine (1.47, 95% CI 1.37,1.58), fentanyl (2.23, 95% CI 1.89,2.64), methadone (1.39, 95% CI 1.05,1.83), oxycodone (1.36, 95% CI 1.08,1.69), nicomorphine (1.57, 95% CI 1.38,1.78), ketobemidone (1.07, 95% CI 1.02,1.13), tramadol (1.54, 95% CI 1.49,1.58) and codeine (1.16, 95% CI 1.12,1.20) were all associated with an increase in overall fracture risk. No increase was present for buprenorphine (0.86, 95% CI 0.79,0.95), pethidine (0.98, 95% CI 0.89,1.08), dextropropoxiphene (1.02, 95% CI 0.90,1.16), and combinations of ASA and codeine (0.94, 95% CI 0.88,1.01). Conclusions., An increased fracture risk is seen in users of morphine and opiates. The reason for this may be related to the risk of falls due to central nervous system effects such as dizziness. [source] GC-MS analysis of multiply derivatized opioids in urineJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2007Bud-Gen Chen Abstract Opiates such as hydrocodone, hydromorphone, oxycodone, noroxycodone, and oxymorphone reportedly may interfere with the analysis of morphine and codeine. The analysis of these compounds themselves also is an important issue. Thus, double derivatization approaches utilizing methoxyamine and hydroxylamine to first form oxime products with keto-opiates, followed by the derivatization with trimethylsilyl (TMS) or propionyl groups, have been developed for the simultaneous analysis of these compounds. However, these studies have not included all compounds of interest and resulted in inadequate chromatographic resolution or significant intensity cross-contribution between the ions designating the analyte and its deuterated internal standard for certain compounds. By exploring three-step derivatization approaches with the combination of various derivatization groups and orders, this study concluded that application of methoxyimino/propionyl/TMS groups, in the order listed, facilitated the simultaneous analysis of eight opiates (morphine, 6-acetylmorphine, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone and noroxycodone) in urine samples, achieving satisfactory limits of quantitation and detection. In addition, the adapted approach resulted in two usable products for morphine and codeine providing alternatives, should interferences render any of these products non-usable. Copyright © 2007 John Wiley & Sons, Ltd. [source] Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009A. PESONEN Background: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients. Methods: Thirty (,75 years, gender M9/F21) and 20 (,60 years, gender M20/F0) patients scheduled to undergo cardiac surgery. A standard anesthesia with fentanyl as an opioid was used. Fentanyl plasma concentrations were measured at the end of surgery and 2 h later. After tracheal extubation, when the pain intensity was at least moderate, blood samples for fentanyl and oxycodone plasma concentration measurements were taken. Thereafter, oxycodone hydrochloride 0.05 mg/kg i.v. was administered. After 15 and 45 min, pain intensity, sedation and oxycodone plasma concentration were determined. This test protocol was repeated twice. Results: The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients (5.7±2.2 vs. 3.8±1.2 ng/ml, P=0.001). The plasma concentrations of oxycodone were comparable between the groups. The interval between the second and the third oxycodone dose was longer in the elderly patients (P=0.036). Pain intensity on the verbal rating scale was lower at the 45-min assessment point after all three oxycodone test doses (P=0.008) and sedation scores were significantly higher after the third dose in the elderly patients (P=0.035). Conclusions: In elderly patients, the plasma concentration of fentanyl was higher but plasma levels of oxycodone were at a similar level compared with middle-aged patients. However, the elderly patients had less pain and were more sedated after doses of oxycodone. [source] Cerebral kinetics of oxycodone in conscious sheepJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2006Hanne H. Villesen Abstract Oxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebral kinetics of oxycodone was quantified using a conscious chronically instrumented sheep preparation. Five sheep were administered oxycodone as intravenous infusions (30 mg over 4 min). Using hybrid physiologically based kinetic models, cerebral kinetics was estimated from arterio-sagittal sinus concentration gradients and cerebral blood flow (CBF). A two-compartment membrane-limited model best described the data. The volume of the first brain compartment was 35.4 mL with a half-life of equilibrium of 0.6 min. The brain:blood equilibration of oxycodone was relatively slow (half-life of 7.2 min), with a large deep cerebral distribution volume (222.8 mL) for the second compartment and a moderate membrane permeability of 54.8 mL/min, which exceeded the nominal CBF (40 mL/min). Drug retention in the brain was 1.3% after 45 min. In conclusion, pharmacokinetic modelling of oxycodone showed a delayed equilibration between brain and blood of a nature that would be affected by changes in both CBF and blood brain barrier permeability. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1666,1676, 2006 [source] Prediction of post-operative pain by an electrical pain stimulusACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2007P. R. Nielsen Background:, Treatment of post-operative pain is still a significant problem. Recently, interest has focused on pre-operative identification of patients who may experience severe post-operative pain in order to offer a more aggressive analgesic treatment. The nociceptive stimulation methods have included heat injury and pressure algometry. A simple method, Pain Matcher® (PM), using electrical stimulation, is validated for pain assessment, but has not been evaluated as a tool for prediction of post-operative pain. Our aim was to assess the predictive value of pre-caesarean section pain threshold on intensity of post-caesarean section pain using the PM. Patients and methods:, Thirty-nine healthy women scheduled for elective caesarean section were studied. The anaesthetic/analgesic procedures included spinal anaesthesia, paracetamol, diclofenac, controlled-release (CR) oxycodone and morphine on request. Pre-operatively, the sensory and pain thresholds were measured using the PM. Post-operatively, a midwife, blinded for pre-caesarean pain threshold assessments, assessed the pain at rest and during mobilization every 12 h for 2 days. Consumption of analgesics was also recorded. Results:, Pre-operative pain threshold correlated significantly with post-caesarean pain score (VAS) at rest and mobilization: [Spearman's rho =,0.65 (,0.30 to ,0.75), P < 0.01] and [Spearman's rho =,0.52 (,0.23 to ,0.72), P < 0.01], respectively. There was no significant correlation between pre-operative PM assessment of sensory threshold and post-operative pain. Conclusion:, Electrical pain threshold before caesarean section seems to predict the intensity of post-operative pain. This method may be used as a screening tool to identify patients at high risk of post-operative pain. [source] The electrocardiographic and hemodynamic effect of metohexital and propofol with and without esmololACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2006R. Korpinen Background:, Metohexital and propofol are short-acting induction agents, which have a tendency to prolong the QTc interval of the ECG. We studied whether this increase could be prevented by combining a beta-blocking agent, esmolol, with these drugs. Simultaneously, we studied the hemodynamic effects of these combinations. Methods:, In a randomized, double-blind study, 80 ASA I,II young adults were premedicated with oxycodone and atropin and allocated to one of four groups: propofol (P), propofol + esmolol (P + E), metohexital (E) or metohexital + esmolol (M + E). The doses were 2 mg/kg propofol/metohexital and 1 mg/kg esmolol. Alfentanil 15 µg/kg was used in all groups. The hemodynamic parameters were measured non-invasively and the electrocardiographic parameters using the signal processing method. Result:, The highest QTc values, which often exceeded the normal upper limit of 440 ms, were recorded at the baseline or immediately after the administration of the induction drugs. The intervals were significantly shorter if esmolol was co-administered with either propofol or metohexital. The heart rate increased in the group M and decreased in the group P + E but remained unchanged in the groups P and M + E. Systolic and diastolic arterial pressures decreased during the study in all groups, most prominently in group P + E. Conclusions:, During the anesthesia induction, the QTc interval was significantly shorter when esmolol was co-administered with either propofol or metohexital. The hemodynamic responses were properly controlled with the combination of metohexital and esmolol as well as with propofol alone, but the combination of propofol and esmolol tended to cause hemodynamic depression. [source] Treatment of restless legs syndrome: An evidence-based review and implications for clinical practice,,MOVEMENT DISORDERS, Issue 16 2008Claudia Trenkwalder MD Abstract Only in the last three decades, the restless legs syndrome (RLS) has been examined in randomized controlled trials. The Movement Disorder Society (MDS) commissioned a task force to perform an evidence-based review of the medical literature on treatment modalities used to manage patients with RLS. The task force performed a search of the published literature using electronic databases. The therapeutic efficacy of each drug was classified as being either efficacious, likely efficacious, investigational, nonefficacious, or lacking sufficient evidence to classify. Implications for clinical practice were generated based on the levels of evidence and particular features of each modality, such as adverse events. All studies were classed according to three levels of evidence. All Level-I trials were included in the efficacy tables; if no Level-I trials were available then Level-II trials were included or, in the absence of Level-II trials, Level-III studies or case series were included. Only studies published in print or online before December 31, 2006 were included. All studies published after 1996, which attempted to assess RLS augmentation, were reviewed in a separate section. The following drugs are considered efficacious for the treatment of RLS: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Drugs considered likely efficacious are rotigotine, bromocriptine, oxycodone, carbamazepine, valproic acid, and clonidine. Drugs that are considered investigational are dihydroergocriptine, lisuride, methadone, tramadol, clonazepam, zolpidem, amantadine, and topiramate. Magnesium, folic acid, and exercise are also considered to be investigational. Sumanirole is nonefficacious. Intravenous iron dextran is likely efficacious for the treatment of RLS secondary to end-stage renal disease and investigational in RLS subjects with normal renal function. The efficacy of oral iron is considered investigational; however, its efficacy appears to depend on the iron status of subjects. Cabergoline and pergolide (and possibly lisuride) require special monitoring due to fibrotic complications including cardiac valvulopathy. Special monitoring is required for several other medications based on clinical concerns: opioids (including, but not limited to, oxycodone, methadone and tramadol), due to possible addiction and respiratory depression, and some anticonvulsants (particularly, carbamazepine and valproic acid), due to systemic toxicities. © 2008 Movement Disorder Society [source] Toward Evidence-Based Prescribing at End of Life: A Comparative Analysis of Sustained-Release Morphine, Oxycodone, and Transdermal Fentanyl, with Pain, Constipation, and Caregiver Interaction Outcomes in Hospice PatientsPAIN MEDICINE, Issue 4 2006BCPS, Douglas J. Weschules PharmD ABSTRACT Objective., The primary goal of this investigation was to examine selected outcomes in hospice patients who are prescribed one of three sustained-release opioid preparations. The outcomes examined include: pain score, constipation severity, and ability of the patient to communicate with caregivers. Patients and Settings., This study included 12,000 terminally ill patients consecutively admitted to hospices and receiving pharmaceutical care services between the period of July 1 and December 31, 2002. Design., We retrospectively examined prescribing patterns of sustained-release morphine, oxycodone, and transdermal fentanyl. We compared individual opioids on the aforementioned outcome markers, as well as patient gender, terminal diagnosis, and median length of stay. Results., Patients prescribed a sustained-release opioid had similar average ratings of pain and constipation severity, regardless of the agent chosen. Patients prescribed transdermal fentanyl were reported to have more difficulty communicating with friends and family when compared with patients prescribed either morphine or oxycodone. On average, patients prescribed transdermal fentanyl had a shorter length of stay on hospice as compared with those receiving morphine or oxycodone. Conclusion., There was no difference in observed pain or constipation severity among patients prescribed sustained-release opioid preparations. Patients receiving fentanyl were likely to have been prescribed the medication due to advanced illness and associated dysphagia. Diminished ability to communicate with caregivers and a shorter hospice course would be consistent with this profile. Further investigation is warranted to examine the correlation between a patient's ability to interact with caregivers and pain control achieved. [source] CONTROLLED-RELEASE OXYCODONE RELIEVES MODERATE TO SEVERE PAIN IN A 3-MONTH STUDY OF PERSISTENT MODERATE TO SEVERE BACK PAINPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Patricia Richards, MD, PhD; Pinggao Zhang, PhD; Michael Friedman, PhD; Rahul Dhanda, PhD. (Purdue Pharma L.P.) Introduction: Opioids are frequently prescribed for management of persistent low back pain, however, efficacy has not been well documented, and concerns are that opioids may impair physical functioning. Objective: To compare controlled-release oxycodone (CRO) with placebo in controlling pain and to observe the effect of CRO on quality of life and functionality. Methods: A double-blind, randomized, placebo-controlled, parallel-group study of 3 months duration was conducted in 110 subjects (49 males, 61 females), mean age 48 years (19,80 years). Subjects had a 3- to 12-month history of moderate to severe persistent low back pain and were previously unresponsive to therapeutic doses of NSAIDs, and/or low dose combination opioid analgesics. At baseline 4% of subjects were on opioids, 39% on NSAIDs, and 57% both NSAIDs and opioids. Subjects were treated with 10 mg CRO tablet or 10 mg oral placebo q12h, titrated to stable pain control. Existing treatment regimens of acetaminophen, NSAIDs, or oral steroids were allowed to continue. The Brief Pain Inventory (BPI), the Roland Morris Functionality Questionnaire, and the MOS 36-Item Short-Form Health Survey (SF-36) were the measures of pain intensity, functionality, and quality of life. Treatments were compared using repeated measures ANCOVA with baseline value as covariate. Results: CRO treatment was significantly superior to placebo on the BPI average pain intensity and average percent pain relief scores overall (4.6 vs 5.4, P = .03, and 47.2 vs 36.3, P = .05, respectively). Fewer CRO subjects discontinued because of inadequate pain control (P < .001). No significant differences between treatments were observed in either Roland Morris or SF-36 scores. Common adverse events for CRO were nausea, constipation, somnolence, headache, and pruritus, consistent with opioid use. Conclusions: Three-month treatment with CRO provides significant pain relief for subjects with persistent moderate to severe back pain, without significantly impairing functionality and quality of life. The support of Purdue Pharma L.P. for this research project is gratefully acknowledged. [source] PHYSIOLOGIC ABNORMALITIES AS BIOLOGIC MARKERS IN SEVERE, INTRACTABLE PAINPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Forest Tennant, MD, Dr PH; Laura Herman RN BSN FNP Veract Intractable Pain Centers, 338 S. Glendora Ave., West Covina, CA 91790 It is recognized that biologic markers of severe, intractable pain (SIP) can help distinguish degrees of pain and assist in monitoring treatment effectiveness. Fifty (50.0%) adult ambulatory SIP patients, at the time of referral described their pain as constant, excruciating, produced a bed or house-bound state, and was uncontrolled by non-opioid medications and low dosages of the weak opioids, hydrocodone or codeine. Patients were treated with a long-acting opioid preparation consisting of methadone, oxycodone, morphine, or transdermal fentanyl in addition to a short-acting opioid for breakthrough pain. These patients were screened before treatment and after three months of opioid treatment by: (1) blood pressure; (2) pulse rate; (3) morning cortisol and pregnenolone serum concentrations; and (4) erythrocyte sedimentation rate (ESR). The percentage of patients with physiologic abnormalities before and after three months of treatment were as follows: (1) hypertension above 140/90 mm/Hg; 28 (56.0%) vrs 14 (28.0%); (2) tachycardia above 84/minute; 21 (42.0%) vrs 9 (18.0%); (3) elevated serum cortisol concentration; 12 (24.0%) vrs 2 (4.0%); (4) low serum cortisol serum concentration; 7 (14.0% vrs 1 (2.0%); (5) low pregnenolone serum concentration; 18 (36.0%) vrs 3 (6.0%); and (6) elevated ESR; 10 (20.0%) vrs 3 (6.0%) (p<.05). Mean blood pressure, pulse rate, ESR, and serum concentrations of cortisol and pregnenolone in patients who demonstrated a physiologic abnormality all positively and significantly (p<.05) altered these markers toward normal. This study indicates that some physiologic abnormalities, particularly those related to pituitary-adrenal over-stimulation with excess output of catecholamines and glucocorticoids, may serve as biologic markers which can help to identify SIP and monitor treatment effectiveness. [source] (229) Serum Cortisol Concentrations and Adrenal Reserve May Be Altered by Severe Chronic PainPAIN MEDICINE, Issue 3 2001Forest Tennant It has been postulated that chronic pain over-stimulates the hypothalamus-pituitary-adrenal axis to produce an extended stress response. If this assumption is true, patients with severe, chronic pain should demonstrate abnormalities of the pituitary-adrenal axis. To evaluate this premise, we screened 40 adult, chronic pain patients in the first week of treatment with serum cortisol concentrations taken between 8:00 and 10:00 AM. Criteria for inclusion in this study required that pain be present for at least one year and be constant, incurable, interfere with sleep, and cause the patient to be bed or house-bound without opioid treatment. Sixteen (16) of the subjects were challenged with cosyntropin, 0.25mg, given intramuscularly immediately after blood was drawn for determination of baseline serum cortisol concentration. Normal serum cortisol concentrations was considered to range from 5.0 to 25.0 ug/dl at baseline, and normal cortisol reserve was considered to be at least a doubling of the baseline concentration determined one hour after cosyntropin administration. Ten (25%) of the patients had evaluated serum cortisol concentrations above 25ug/dl with the highest being 54.4 ug/dl. Nine (20%) demonstrated low serum cortisol concentrations under 5 ug/dl, and 5 of 16 (31.25%) given cosyntropin challenge demonstrated inadequate adrenal reserve by failing to double their baseline cortisol concentration. All patients with high or low serum cortisol concentration demonstrated a normal cortisol concentration following pain control with a long-acting opioid including methadone, extended-length morphine or oxycodone, or transdermal fentanyl. This study suggests that severe, chronic pain may produce profound abnormalities of serum cortisol and cortisol reserve, and normalization of these alterations may require pain treatment with long-acting opioids. [source] Patterns in nursing home medication errors: disproportionality analysis as a novel method to identify quality improvement opportunitiesPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2010Richard A. Hansen Abstract Purpose To explore the use of disproportionality analysis of medication error data as a novel method to identify relationships that might not be obvious through traditional analyses. This approach can supplement descriptive data and target quality improvement efforts. Methods Data came from the Medication Error Quality Initiative (MEQI) individual event reporting system. Participants were North Carolina nursing homes who submitted incident reports to the Web-based MEQI data repository during the 2006 and 2007 reporting years. Data from 206 nursing homes were summarized descriptively and then disproportionality analysis was applied. Associations between medication type and possible causes at the state level were explored. A single nursing home was selected to illustrate how the method might inform quality improvement at the facility level. Disproportionality analysis of drug errors in this home was compared with benchmarking. Results Statewide, 59 drug-cause pairs met the disproportionality signal and 11 occurred in 10 or more reports. Among these, warfarin was co-reported with communication errors; esomeprazole, risperidone, and nitrofurantoin were disproportionately associated with transcription error; and oxycodone and morphine were disproportionately reported with name confusion. Facility-level analyses illustrate how descriptive frequencies and disproportionality analysis are complementary, but also identify different safety targets. Conclusions Exploratory analysis tools can help identify medication error types that occur at disproportionate rates. Candidate associations might be used to target patient safety work, although further evaluation is needed to determine the value of this information. Copyright © 2010 John Wiley & Sons, Ltd. [source] Usefulness of prescription monitoring programs for surveillance,analysis of Schedule II opioid prescription data in Massachusetts, 1996,2006,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2010Nathaniel Katz Abstract Purpose Electronic prescription monitoring programs (PMPs) have been developed in many states as a public health surveillance tool. We analyze herein 11 years of Massachusetts PMP data to evaluate trends in opioid prescribing, dispensing, and usage. Methods Prescription records from the Massachusetts PMP for Schedule II opioids from fiscal year 1996 to 2006 were analyzed. ,Questionable activity' (potential ,doctor shopping') estimates were based on individual use of multiple prescribers and pharmacies, and early refills. Results The number of prescriptions, doses prescribed, and individuals receiving Schedule II prescription opioids steadily increased from 1996 to 2006. Most individuals (87.5%) used 1,2 prescribers, 1,2 pharmacies, and had no early refills (2006). The greater the number of prescribers used, the greater the number of pharmacies used. When defined as the use of ,4 prescribers and ,4 pharmacies, questionable activity accounted for 2748 individuals, 47,953 prescriptions, and 2,966,056 doses (2006). The Schedule II opioid most highly associated with questionable activity was short-acting oxycodone. Conclusions PMPs can become a useful public health surveillance tool to monitor the medical and non-medical use of prescription opioids and to inform public health and safety policy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Integrating nine prescription opioid analgesics and/or four signal detection systems to summarize statewide prescription drug abuse in the United States in 2007,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 9 2009Michael F. Schneider MS Abstract Purpose Integrate statewide rankings of abuse across different drugs and/or signal detection systems to summarize prescription drug abuse in each state in 2007. Methods Four signal detection systems (Opioid Treatment Programs, Key Informants, Drug Diversion, and Poison Centers) that covered heterogeneous populations collected data on the abuse of nine opioids: hydrocodone, immediate-release oxycodone, tramadol, extended-release [ER] oxycodone, fentanyl, morphine, methadone, hydromorphone, and buprenorphine). We introduce here linearized maps which integrate nine drugs within each system; four systems for each drug; or all drugs and systems. Results When rankings were integrated across drugs, Rhode Island, New Hampshire, Maine, West Virginia, and Michigan were in the highest tertile of abuse in three systems. When rankings were integrated across signal detection systems, there was a geographic clustering of states with the highest rates for ER oxycodone (in Tennessee, Mississippi, Kentucky, Ohio, Indiana, Michigan, and in Massachusetts, New Hampshire, Maine, and Vermont) and methadone (Massachusetts, Rhode Island, New Hampshire, Maine, Vermont, Connecticut, and New Jersey). When rankings were integrated across both drugs and signal detection systems, states with 3-digit ZIP codes below 269 (i.e., from Massachusetts to West Virginia): Massachusetts, New Hampshire, Maine, Vermont, Washington DC, Virginia, and West Virginia were in the highest tertile and only Delaware was in the lowest tertile. Conclusions We have presented methods to integrate data on prescription opioid abuse collected by signal detection systems covering different populations. Linearized maps are effective graphical summaries that depict differences in the level of prescription opioid abuse at the state level. Copyright © 2009 John Wiley & Sons, Ltd. [source] Relationship between therapeutic use and abuse of opioid analgesics in rural, suburban, and urban locations in the United States,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2007Theodore J. Cicero PhD Abstract Purpose The goal of these studies was to determine the relationship between prescribed use of opioid analgesics and their non-medically related use (abuse) at a regional level across the country. Methods To gather information about prescription drug abuse, we asked 233 drug abuse treatment specialists to provide us Quarterly reports on the number of cases of prescription opioid analgesic abusers who used opioid analgesics to get high in the past 30 days. Results and Conclusions We found that there was a very strong correlation between therapeutic exposure to opioid analgesics, as measured by prescriptions filled, and their abuse. There were, however, geographical loci that represented outliers in which abuse was disproportionately high relative to therapeutic use (>95th percentile), most of which were in very small urban, suburban, and rural areas. The rank order of abuse shows that buprenorphine products, extended release (ER) oxycodone and methadone are the most intensely abused prescription opioid analgesics, with hydrocodone the least abused, when the data are corrected for degree of exposure, i.e., cases/1000 persons filling a prescription. If, on the other hand, one uses the number of cases/100,000 population, hydrocodone ranked as high as ER oxycodone and all other drugs grouped together at very low levels of abuse. Since the latter conclusion ignores therapeutic exposure, we conclude that the rate of abuse of highly efficacious opioid analgesics is best expressed as cases of abuse/1000 persons filling a prescription, which yields the best possible estimate of the risk-benefit ratio of these drugs. Copyright © 2007 John Wiley & Sons, Ltd. [source] Analgesic efficacy of local anaesthetic wound administration in knee arthroplasty: volume vs concentrationANAESTHESIA, Issue 10 2010L. Ø. Andersen Summary 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 was reduced in both groups with ropivacaine administration 24 h postoperatively (p < 0.02), but with no difference in analgesia between groups at all time intervals. No reduction in pain scores was observed with ropivacaine injection 6 h postoperatively. The median (IQR [range]) dose of oxycodone administered was 12.5 (10,19 [0,35]) mg in the high volume/low concentration group, and 20 mg (16,40 [0,65]) mg in the low volume/high concentration group (p = 0.005). In conclusion, intracapsular administration of local anaesthetic may have limited analgesic efficacy with no volume vs concentration relationship after total knee arthroplasty. [source] A comparison of the respiratory effects of oxycodone versus morphine: a randomised, double-blind, placebo-controlled investigation,ANAESTHESIA, Issue 10 2010S. H. Chang Summary Oxycodone's respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri-operative period. We randomly assigned ASA 1-2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg,1, or oxycodone 0.05 mg.kg,1, 0.1 mg.kg,1, or 0.2 mg.kg,1. Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg,1, oxycodone 0.05 mg.kg,1 and 0.1 mg.kg,1, and from 10 patients who received oxycodone 0.2 mg.kg,1. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p < 0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine. [source] | |||||||||||||||||||||||||||||||