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Sample records for buprenorphine

  1. Buprenorphine and Buprenorphine/Naloxone Diversion, Misuse, and Illicit Use: An International Review

    OpenAIRE

    Yokell, Michael A.; Zaller, Nickolas D.; Green, Traci C.; Rich, Josiah D

    2011-01-01

    The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world.

  2. [Breast feeding during methadon- and buprenorphin therapy].

    Science.gov (United States)

    Müller, M J; Lange, M; Paul, T; Seeliger, S

    2011-12-01

    The number of opiate addicted patients treated with opioid replacement therapy is continuously increasing. In Germany, 57.7% of these patients are treated with methadone and 18.6% with buprenorphine. This maintenance therapy provides several advantages while addicted pregnant women and their foetus have a high benefit from appropriate replacement therapy. However, the recommendations concerning breast feeding during an opioid replacement therapy are discussed controversially, because methadone as well as buprenorphine accumulate in breast milk. This accumulation might cause damages to the newborn's health; so, child benefits of breast feeding have to be balanced with possible health risks.This review provides an overview of a selective literature search based on the PubMed-database and german consensus recommendations. Used search terms included: (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk), (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human milk).According to the available literature, addicted women, substinated with methadone or buprenorphine are allowed to breast feed their newborns. The advantages of breast feeding prevail the risks of an infant opiate intoxication caused by methadone or buprenorphine. PMID:21969026

  3. Comparison of Buprenorphine Treatment for Opioid Dependence in Three Settings

    OpenAIRE

    Miotto, Karen; Hillhouse, Maureen; Donovick, Roger; Cunningham-Rathner, Jerry; Charuvastra, Charlie; Torrington, Matthew; Esagoff, Asher E.; Ling, Walter

    2012-01-01

    Although use of buprenorphine in the treatment of opioid dependence is expected to continue to increase, little is known about the optimal setting for providing the medical and psychosocial care required with buprenorphine pharmacotherapy.

  4. Epidural Naloxone to Prevent Buprenorphine Induced PONV

    Directory of Open Access Journals (Sweden)

    Ashok Jadon

    2008-01-01

    Full Text Available Epidural infusion of local analgesic and opioid are commonly used for postoperative pain relief. This combina-tion gives excellent anlgesia but nausea and vomiting remains a major concern. Low dose epidural naloxone prevents PONV induced by spinal opioids like morphine, fentanyl and sufentanil. However, it is not known that epidural naloxone administration prevents PONV induced by epidural buprenorphine. We have reported three cases of major abdominal operation in which lowdose epidural infusion of naloxone releived the symptom of buprenorphine induced severe PONV and improved the quality of analgesia.

  5. Quantitation of Buprenorphine, Norbuprenorphine, Buprenorphine Glucuronide, Norbuprenorphine Glucuronide, and Naloxone in Urine by LC-MS/MS.

    Science.gov (United States)

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Some formulations of buprenorphine also contain naloxone to discourage misuse. The major metabolite of buprenorphine is norbuprenorphine. Both compounds are pharmacologically active and both are extensively metabolized to their glucuronide conjugates, which are also active metabolites. Direct quantitation of the glucuronide conjugates in conjunction with free buprenorphine, norbuprenorphine, and naloxone in urine can distinguish compliance with prescribed therapy from specimen adulteration intended to mimic compliance with prescribed buprenorphine. This chapter quantitates buprenorphine, norbuprenorphine, their glucuronide conjugates and naloxone directly in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine is pretreated with formic acid and undergoes solid phase extraction (SPE) prior to analysis by LC-MS/MS. PMID:26660175

  6. Epidural Naloxone to Prevent Buprenorphine Induced PONV

    OpenAIRE

    Ashok Jadon; S S Parida; Swastika Chakroborty; Amrita Panda

    2008-01-01

    Epidural infusion of local analgesic and opioid are commonly used for postoperative pain relief. This combina-tion gives excellent anlgesia but nausea and vomiting remains a major concern. Low dose epidural naloxone prevents PONV induced by spinal opioids like morphine, fentanyl and sufentanil. However, it is not known that epidural naloxone administration prevents PONV induced by epidural buprenorphine. We have reported three cases of major abdominal operation in which lowdose epidural infus...

  7. The animal pharmacology of buprenorphine, an oripavine analgesic agent.

    Science.gov (United States)

    Cowan, A; Doxey, J C; Harry, E J

    1977-08-01

    1. The general pharmacology of buprenorphine, a potent analgesic agent derived from oripavine, is described. 2. After cute administration of buprenorphine, the spontaneous locomotor activity of mice was increased; rats displayed stereotyped licking and biting movements; behavioural depression was marked in guinea-pigs but mild in rhesus monkeys. The behaviour of cats was unchanged. 3. In general, buprenorphine reduced heart rate but had no significant effect on arterial blood pressure in conscious rats and dogs. 4. In anaesthetized, open-chest cats buprenorphine (0.10 and 1.0 mg/kg, i.v.) caused no major haemodynamic changes. 5. Buprenorphine (0.01-10 mg/kg i.a.) and morphine (0.30-30 mg/kg, i.a.) increased arterial PCO2 values and reduced PO2 values in conscious rats. With doses of buprenorphine greater than 0.10 mg/kg (a) the duration of respiratory depression became less, (b) ceiling effects occurred such that the maximum effects produced were less than those obtained with morphine. 6. Buprenorphine was a potent and long-lasting antagonist of citric acid-induced coughing in guinea-pigs. 7. At a dose level 20 times greater than the ED50 for antinociception (tail pressure), morphine suppressed urine output to a greater extent than the corresponding dose of buprenorphine in rats. 8. Over the range 0.01-1.0 mg/kg (s.c.), buprenorphine slowed the passage of a charcoal meal along the gastrointestinal tract in rats. After doses in excess of 1 mg/kg, the meal travelled increasingly further such that the distances measured at 10 and 30 mg/kg did not differ significantly from control values. In contrast, the morphine dose-response relationship was linear. PMID:409449

  8. Comparison of Buprenorphine Treatment for Opioid Dependence in Three Settings

    Science.gov (United States)

    Hillhouse, Maureen; Donovick, Roger; Cunningham-Rathner, Jerry; Charuvastra, Charlie; Torrington, Matthew; Esagoff, Asher E.; Ling, Walter

    2011-01-01

    Although use of buprenorphine in the treatment of opioid dependence is expected to continue to increase, little is known about the optimal setting for providing the medical and psychosocial care required with buprenorphine pharmacotherapy. OBJECTIVE This study compared buprenorphine therapy delivered in three distinct treatment settings: an opioid-treatment program (OTP) offering individual counseling; a group counseling program utilizing the manualized Matrix Model (MMM) of cognitive-behavioral treatment; and a private clinic setting mirroring standard medical management for buprenorphine treatment provided specifically at a psychiatrist’s private practice (PCS). METHOD Participants were inducted on buprenorphine and provided with treatment over a 52-week study duration. All participants were scheduled for weekly treatment visits for the first 6 study weeks, and two sites reduced treatment to monthly visits for dispensing of medication and psychosocial counseling. Outcomes include opioid use, participant retention in treatment, and treatment participation. RESULTS Participants presenting for treatment at the sites differed only by race/ethnicity, and opioid use did not differ by site. Retention differed by treatment site, with the number of participants who stayed in the study until the end of 20 weeks significantly associated with treatment site. The mean number of minutes spent in each individual counseling session also differed by site. Although no difference in opioid use by treatment site was found, results document a significant association between opioid use and buprenorphine dose. DISCUSSION These results show some differences by treatment site, although the similarity and relative ease in which the sites were able to recruit participants for treatment with buprenorphine, and minor implementation problems reported suggests the feasibility of treatment with buprenorphine across various treatment settings. CONCLUSION Similar rates of continued opioid use

  9. A Urinalysis-based Comparative Study of Treatment Adherence on Buprenorphine and Buprenorphine/Naloxone Combination Used as Opioid Substitution Therapy

    OpenAIRE

    Pal Singh Balhara, Yatan; Jain, Raka

    2012-01-01

    Objective: The objective of the current study was to explore the difference in treatment adherence to directly supervised buprenorphine and take-home buprenorphine/ naloxone combination for opioid substitution therapy. Urinalysis findings have been used to check treatment adherence on opioid substitution therapy agent. Additionally the study aimed to explore the misuse rate of buprenorphine/naloxone combination based on urinalysis findings.

  10. Facts about Buprenorphine for Treatment of Opioid Addiction

    Science.gov (United States)

    the facts about BUPRENORPHINE for Treatment of Opioid Addiction U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance ... escape from the misery and risks of drug addiction? Most people cannot do it on their own. ...

  11. A review of the studies using buprenorphine in cats.

    Science.gov (United States)

    Steagall, P V M; Monteiro-Steagall, B P; Taylor, P M

    2014-01-01

    Pain management is a crucial component of feline medicine and surgery. This review critically evaluates studies using buprenorphine in cats and highlights the clinical application of the opioid in this species. The pharmacokinetic-pharmacodynamic (PK-PD) modeling of IV buprenorphine has been best described by a combined effect compartmental/receptor association-dissociation model with negative hysteresis. Therefore, plasma concentrations of the drug are not correlated with analgesia, and clinicians should not expect to observe pain relief immediately after drug administration. In addition, a ceiling effect has not been demonstrated after administration of clinical doses of buprenorphine in cats; dosages of up to 0.04 mg/kg have been reported. The route of administration influences the onset, duration, and magnitude of antinociception and analgesia when using this drug in cats. At clinical dosages, the SC route of administration does not appear to provide adequate antinociception and analgesia whereas the buccal route has produced inconsistent results. Intravenous or IM administration at a dosage of 0.02-0.04 mg/kg is the preferred for treatment of pain in the acute setting. A literature search found 14 clinical trials evaluating buprenorphine sedation, analgesia, or both in cats. There were 22 original research studies reporting the antinociceptive effects of buprenorphine by means of thermal threshold, mechanical threshold, or both, minimal alveolar concentration, or PK-PD. Individual variability in response to buprenorphine administration has been reported, indicating that buprenorphine may not provide sufficient analgesia in some cats. Pain assessment is important when evaluating the efficacy of buprenorphine and determining whether additional analgesic treatment is needed. PMID:24655078

  12. Buprenorphine and Methadone Maintenance in Jail and Post-Release: A Randomized Clinical Trial

    OpenAIRE

    Magura, Stephen; Lee, Joshua D.; Hershberger, Jason; Joseph, Herman; Marsch, Lisa; Shropshire, Carol; Rosenblum, Andrew

    2008-01-01

    Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting. This study introduced buprenorphine maintenance in a large urban jail, Rikers Island in New York City. Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10-90 days in jail (N=116) were voluntarily randomly assigned either to buprenorphine or methadone maintenance, the latter being the standard of care for eligible inmates at Rikers. Buprenorphine and...

  13. The effect of voluntarily ingested buprenorphine on rats subjected to surgically induced global cerebral ischaemia

    DEFF Research Database (Denmark)

    Kalliokoski, Otto Henrik; Abelson, Klas; Koch, Janne; Boschian, Anna; Thormose, Sarah F; Fauerby, Natasha; Rasmussen, Rune Skovgaard; Johansen, Flemming Fryd; Hau, Jann

    2010-01-01

    The effect of perioperatively administered buprenorphine analgesia on rats subjected to surgically induced global ischaemia was assessed. Rats supplied with buprenorphine, mixed in nut paste for voluntary ingestion, displayed significant reductions in postoperative excretions of faecal corticoste......The effect of perioperatively administered buprenorphine analgesia on rats subjected to surgically induced global ischaemia was assessed. Rats supplied with buprenorphine, mixed in nut paste for voluntary ingestion, displayed significant reductions in postoperative excretions of faecal...

  14. Population pharmacokinetics of buprenorphine following a two-stage intravenous infusion in healthy volunteers

    DEFF Research Database (Denmark)

    Jensen, Mette Lykke; Foster, David J.R.; Upton, Richard N.;

    2007-01-01

    The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only.......The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only....

  15. Comparison of two formulations of buprenorphine in cats administered by the oral transmucosal route.

    Science.gov (United States)

    Bortolami, Elisa; Slingsby, Louisa; Love, Emma J

    2012-08-01

    This randomised, blinded, cross-over study investigated the ease of oral transmucosal administration of two formulations of buprenorphine using glucose as a control in 12 cats. The cats received three treatments: buprenorphine multi-dose, buprenorphine and the equivalent volume of glucose 5%. Ease of treatment administration, observation of swallowing, changes in pupil size, sedation, salivation, vomiting, behaviour and food intake were assessed. The data were analysed using MLwiN and multi-level modelling. Ease of administration of buprenorphine multi-dose was statistically different from glucose (P 0.05). Mydriasis was evident after the administration of both formulations of buprenorphine. Sedation, salivation, vomiting, behavioural changes or in-appetence were not observed after any treatment. Cats tolerated oral transmucosal administration of glucose better than buprenorphine multi-dose, while buprenorphine administration was tolerated as well as glucose. PMID:22403414

  16. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    International Nuclear Information System (INIS)

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process

  17. Effects of various combinations of benzodiazepines with buprenorphine on arterial blood gases in rats.

    Science.gov (United States)

    Pirnay, Stéphane O; Mégarbane, Bruno; Borron, Stephen W; Risède, Patricia; Monier, Claire; Ricordel, Ivan; Baud, Frédéric J

    2008-09-01

    Fatalities have been attributed to combinations of high-dose buprenorphine with benzodiazepines. In rats, high-dose buprenorphine combined with midazolam was shown to induce sustained respiratory acidosis, while buprenorphine alone did not. However, the effects of buprenorphine combined with pharmacological doses of benzodiazepines remain unknown. Our objective was to compare the acute effects of four selected benzodiazepines used intravenously at equi-efficacious doses in rats, alone and in combination with buprenorphine on sedation, respiratory rate and arterial blood gases. Buprenorphine (30 mg/kg) did not significantly modify sedation level or respiratory rate, but induced mild and transient effects on pH and PaCO(2) (P < 0.05). Similarly, despite having no effects on respiratory rate, nordiazepam (10 mg/kg), bromazepam (1 mg/kg) and oxazepam (12 mg/kg) mildly and transiently altered pH and PaCO(2) (P < 0.05), whereas clonazepam (5 mg/kg) did not. Buprenorphine combined with each benzodiazepine induced no significant effects on respiratory rate or blood gases, in comparison with buprenorphine alone. However, combinations of oxazepam or nordiazepam with buprenorphine significantly deepened sedation. While both combinations reduced respiratory rate, buprenorphine + 30 mg/kg clonazepam significantly increased PaCO(2) and buprenorphine + 30 mg/kg nordiazepam decreased PaO(2). In conclusion, not all benzodiazepines induce significant respiratory depression at therapeutic doses. We were unable to demonstrate significant effects on rat ventilatory parameters of buprenorphine combined with equi-efficacious pharmacological doses of benzodiazepines in comparison with buprenorphine alone. Our results may suggest that effects of these combinations are rather mild. Respiratory failure may, however, result from the association of buprenorphine with elevated doses of benzodiazepines. PMID:18684226

  18. Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering

    Science.gov (United States)

    Greenwald, Mark K.

    2008-01-01

    A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

  19. The Implementation of Buprenorphine/Naloxone in College Health Practice

    Science.gov (United States)

    DeMaria, Peter A., Jr.; Patkar, Ashwin A.

    2008-01-01

    Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their healthcare providers. The…

  20. [Transdermal buprenorphine: a current overview of pharmacological and clinical data].

    Science.gov (United States)

    Faymonville, M E; Libbrecht, D

    2008-11-01

    Our understanding of the pathophysiologic mechanisms of chronic pain progresses; the complexity of the problem justifies our need for new molecules and new ways of administration that will help to further optimise and better individualize our pharmacologic therapies. Whereas acute pain can be considered an alarm signal, chronic pain constitutes, per se, a syndrome that requires a meticulous selection of the analgesic drug(s). Since pain is permanent, the continuous administration of the analgesic is recommended rather than an on demand administration. Transdermic modes of administration are of value for the treatment of chronic pain because they allow a progressive delivery of the active compound together with the maintenance of stable plasma levels of the drug. Buprenorphine is a semi-synthetic opioid that is available in the sublingual, injectable, or transdermic forms. The matrix patch of buprenorphine represents a major asset for the treatment of chronic pain, whether it be cancerous in origin, or not. Its efficacy and safety have been clearly demonstrated in randomised double blind trials as well as in post-marketing surveillance observations. Buprenorphine, administered as a transdermal therapeutic system, induces a dose-related pain relief, whatever the nature of the pain and the age of the patient. Buprenorphine also exerts an analgesic action on neuropathic pain. It differs from other opioids by its affinity as a partial agonist on mu and kappa receptors, and as a complete agonist of ORL-1 receptors. Therefore, transdermal buprenorphine will be useful to all physicians having to control severe pain by powerful opioids. PMID:19112993

  1. Plasma concentrations of corticosterone and buprenorphine in rats subjected to jugular vein catheterization

    DEFF Research Database (Denmark)

    Goldkuhl, Renée; Jacobsen, Kirsten Rosenmaj; Kalliokoski, Otto Henrik;

    2010-01-01

    The present study investigated the postoperative plasma concentrations of corticosterone and buprenorphine in male Wistar and Sprague-Dawley rats, treated with buprenorphine administered either through subcutaneous (SC) injection or through voluntary ingestion (VI). The animals were treated with...... buprenorphine for pre-emptive analgesia prior to surgical placement of a jugular catheter, followed by automated blood sampling during 96 h. Buprenorphine was administered on a regular basis throughout the experiment, and blood was collected on selected time points. Body weight was measured before and 96 h......-treated animals than in the VI-treated animals during the first 18 h of the study, while plasma buprenorphine concentration was at least as high and more even over time after VI treatment. The present study shows that buprenorphine administration through VI is suitable for both Wistar and Sprague-Dawley rats...

  2. Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin overdose

    OpenAIRE

    Yokell, Michael A.; Zaller, Nickolas D.; Green, Traci C.; McKenzie, Michelle; Rich, Josiah D.

    2012-01-01

    A case of heroin overdose reversed through the intravenous (IV) administration of a crushed sublingual tablet of buprenorphine/naloxone (Suboxone®) by a lay responder is described. Although the sublingual administration of buprenorphine/naloxone to reverse an overdose has been reported elsewhere, this is the first report of IV administration. Healthcare professionals should be aware that injection drug users may respond to an opioid overdose by injecting buprenorphine/naloxone and should cons...

  3. Buprenorphine Treatment for Opioid Addiction in the Primary Care Setting: Predictors of Treatment Success and Failure

    OpenAIRE

    Drago, Joshua

    2015-01-01

    Buprenorphine is a partial mu-opioid agonist with well-demonstrated efficacy in the medical treatment of opioid addiction. Little is known about which patients respond successfully to treatment with buprenorphine. To help answer this question, we performed a retrospective cohort analysis of 160 patients who received outpatient buprenorphine therapy for opioid addiction at MGH Charlestown HealthCare Center. We gathered information on 36 observable patient characteristics, and searched for vari...

  4. Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Jacobsen, Kirsten R; Sundbom, Renée;

    2012-01-01

    An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously validated a method for administering buprenorphine in a nut paste......, adequate concentrations and amounts of buprenorphine/nut paste, and dosage of buprenorphine to rats and mice....

  5. The Reinforcing and Subjective Effects of Intravenous and Intranasal Buprenorphine in Heroin Users

    OpenAIRE

    Jones, Jermaine D.; Madera, Gabriela; Comer, Sandra D.

    2014-01-01

    Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphi...

  6. Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

    International Nuclear Information System (INIS)

    In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg-1 was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg-1 buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P -1 buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts

  7. Depression-like effect of prenatal buprenorphine exposure in rats.

    Directory of Open Access Journals (Sweden)

    Chih-Jen Hung

    Full Text Available Studies indicate that perinatal opioid exposure produces a variety of short- and long-term neurobehavioral consequences. However, the precise modes of action are incompletely understood. Buprenorphine, a mixed agonist/antagonist at the opioid receptors, is currently being used in clinical trials for managing pregnant opioid addicts. This study provides evidence of depression-like consequence following prenatal exposure to supra-therapeutic dose of buprenorphine and sheds light on potential mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days. Results showed that pups at postnatal day 21 but not the dams had worse parameters of depression-like neurobehaviors using a forced swimming test and tail suspension test, independent of gender. Neurobehavioral changes were accompanied by elevation of oxidative stress, reduction of plasma levels of brain-derived neurotrophic factor (BDNF and serotonin, and attenuation of tropomyosin-related kinase receptor type B (TrkB phosphorylation, extracellular signal-regulated kinase (ERK phosphorylation, protein kinase A activity, cAMP response element-binding protein (CREB phosphorylation, and CREB DNA-binding activity. Since BDNF/serotonin and CREB signaling could orchestrate a positive feedback loop, our findings suggest that the induction of oxidative stress, reduction of BDNF and serotonin expression, and attenuation of CREB signaling induced by prenatal exposure to supra-therapeutic dose of buprenorphine provide evidence of potential mechanism for the development of depression-like neurobehavior.

  8. SUBLINGUAL BUPRENORPHINE VS MIDAZOLAM FOR PREMEDICATION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V.A HASANI

    2000-03-01

    Full Text Available Background. Preanesthetic medication may reduce the risks of adverse psychological and physiological sequel of induction in children. Administration of premedication by sublingual route may provide the best compromise because of relatively rapid absorption without causing pain. In this study sedative and anxitolytic effects of sublingual midazolam and buprenorphine in children were compared. Methods. In a randomized, controlled, double blind clinical trial, one hundred and fifty children aged between 4 to 10 years in first or second class of ASA scheduled for adenotonsillectomy were divided in three equal groups. These groups recieved sublingual bupronorphine 3 µg/kg, midazolam 0.2 mg/kg and no premedication respectively. Cardiorespiratory variables were recorded from the time of premedication to awakening from anesthesia. Anxiety and sedation scores and patients acceptance of mask at induction were recorded using four point rating scales. Time of spontaneous eye opening and postoperative emesis occurrence were also recorded. Findings. Children recieving sublingual midazolam or buprenorphine had similar sedation, anxiety and mask acceptance scores, but different from no premedication group (P < 0.0001. None of the children experienced respiratory depression or oxygen desaturation after drug administration and during postoperative period. Time of spontaneous eye opening was longer in the midazolam group (P < 0.0001.Emetic episodes were similar in all groups. Conclusion. Midazolam is extensively studied and demonstrated that the drug is highly effective in alleviating anxiety and increasing cooperation. We concluded that sublingual buprenorphine is as effective as sublingual midazolam in providing sedation and anxitolysis for pediatric premedication.

  9. Evaluation of a Combined Online and in Person Training in the Use of Buprenorphine

    Science.gov (United States)

    Gunderson, Erik W.; Levin, Frances R.; Kleber, Herbert D.; Fiellin, David A.; Sullivan, Lynn E.

    2006-01-01

    To evaluate buprenorphine training methodology, we surveyed physicians who had completed a combined online and in person buprenorphine curriculum. Of 53/70 (76%) survey respondents, 57% were psychiatrists and 40% generalists. On a scale of 1 (very poor) to 7 (superlative), the overall training rated a mean of 5.8. The online course (5.0) rated…

  10. Treating Opioid Addiction With Buprenorphine-Naloxone in Community-Based Primary Care Settings

    OpenAIRE

    Mintzer, Ira L.; Eisenberg, Mark; Terra, Maria; MacVane, Casey; Himmelstein, David U.; Woolhandler, Steffie

    2007-01-01

    PURPOSE Office-based treatment of opioid addiction with a combination of buprenorphine and naloxone was approved in 2002. Efficacy of this treatment in nonresearch clinical settings has not been studied. We examined the efficacy and practicality of buprenorphine-naloxone treatment in primary care settings.

  11. 78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

    Science.gov (United States)

    2013-06-06

    ... Naloxone Hydrochloride) Sublingual Tablets, 2 Milligrams/0.5 Milligrams and 8 Milligrams/2 Milligrams, Were... (buprenorphine hydrochloride (HCl) and naloxone HCl) sublingual tablets, 2 milligrams (mg)/0.5 mg and 8 mg/2 mg... to approve abbreviated new drug applications (ANDAs) for buprenorphine HCl and naloxone...

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

    Science.gov (United States)

    Wiegand, Timothy J

    2016-03-01

    Buprenorphine represents a safe and effective therapy for treating opioid dependence, alleviating craving and withdrawal symptoms in opioid-dependent patients. Buprenorphine has a "blocking" effect against the action of other opioids at the mu-receptor, preventing not only opioid-induced euphoria, but CNS and respiratory depressant effects as well. Buprenorphine was approved for the treatment of opioid dependence in 2002 after the passage of Drug Abuse Treatment Act 2000 (DATA 2000) which allowed clinicians to treat opioid-dependent patients with specifically named opioid agonist therapies in an office setting. Buprenorphine programs reduce the prevalence of HIV and hepatitis C and reduce criminal behaviors associated with illicit drug use. Patients stabilized on buprenorphine have increased employment, enhanced engagement with social services, and better overall health and well-being. PMID:26574020

  13. A Question About the Safety of Buprenorphine/Naloxone and Benzodiazepine Drugs.

    Science.gov (United States)

    Howland, Robert H

    2015-12-01

    Drug overdose is the leading cause of injury death in the United States, and most deaths are related to prescription drugs. A substantial proportion of these deaths involve opioid or benzodiazepine drugs, and many overdoses include a combination of both drug classes. Buprenorphine/naloxone has an unusual pharmacology that distinguishes it from other opioid drugs. Animal and human studies have found that buprenorphine is associated with a ceiling to its cardio-respiratory depressant effect at higher doses, such that it may have a wider safety margin compared to other opioid drugs. Compared to buprenorphine alone, buprenorphine/naloxone is associated with less cardiorespiratory depression. Drug safety data from the National Poison Data System, Drug Abuse Warning Network, and other sources suggest that the safety of buprenorphine/naloxone is favorable compared to the morbidity and mortality associated with other opioid drugs and other classes of psychotropic drugs. PMID:26653090

  14. Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants.

    Science.gov (United States)

    Grinnell, Steven G; Ansonoff, Michael; Marrone, Gina F; Lu, Zhigang; Narayan, Ankita; Xu, Jin; Rossi, Grace; Majumdar, Susruta; Pan, Ying-Xian; Bassoni, Daniel L; Pintar, John; Pasternak, Gavril W

    2016-10-01

    Buprenorphine has long been classified as a mu analgesic, although its high affinity for other opioid receptor classes and the orphanin FQ/nociceptin ORL1 receptor may contribute to its other actions. The current studies confirmed a mu mechanism for buprenorphine analgesia, implicating several subsets of mu receptor splice variants. Buprenorphine analgesia depended on the expression of both exon 1-associated traditional full length 7 transmembrane (7TM) and exon 11-associated truncated 6 transmembrane (6TM) MOR-1 variants. In genetic models, disruption of delta, kappa1 or ORL1 receptors had no impact on buprenorphine analgesia, while loss of the traditional 7TM MOR-1 variants in an exon 1 knockout (KO) mouse markedly lowered buprenorphine analgesia. Loss of the truncated 6TM variants in an exon 11 KO mouse totally eliminated buprenorphine analgesia. In distinction to analgesia, the inhibition of gastrointestinal transit and stimulation of locomotor activity were independent of truncated 6TM variants. Restoring expression of a 6TM variant with a lentivirus rescued buprenorphine analgesia in an exon 11 KO mouse that still expressed the 7TM variants. Despite a potent and robust stimulation of (35) S-GTPγS binding in MOR-1 expressing CHO cells, buprenorphine failed to recruit β-arrestin-2 binding at doses as high as 10 µM. Buprenorphine was an antagonist in DOR-1 expressing cells and an inverse agonist in KOR-1 cells. Buprenorphine analgesia is complex and requires multiple mu receptor splice variant classes but other actions may involve alternative receptors. PMID:27223691

  15. Umbilical cord monitoring of in utero drug exposure to buprenorphine and correlation with maternal dose and neonatal outcomes.

    Science.gov (United States)

    Concheiro, Marta; Jones, Hendreé E; Johnson, Rolley E; Choo, Robin; Shakleya, Diaa M; Huestis, Marilyn A

    2010-10-01

    Buprenorphine is under investigation in the U.S. as pharmacotherapy for opioid-dependent pregnant women. Buprenorphine and metabolites were quantified in umbilical cord specimens from women receiving daily buprenorphine doses. Correlations between maternal buprenorphine dose, buprenorphine and metabolite umbilical cord concentrations, and neonatal outcomes were investigated, as well as the ability to identify heroin and cocaine relapse during pregnancy. Umbilical cord concentrations were compared to those of matched umbilical cord plasma and meconium. Buprenorphine metabolites were detected in all cords, but buprenorphine itself was absent. Concentration ranges were 1.2-5.1 ng/g norbuprenorphine, 1.7-4.2 ng/g buprenorphine-glucuronide, and 8.3-23 ng/g norbuprenorphine-glucuronide. Cord concentrations were similar to those in plasma, and lower (16-210-fold), although statistically correlated, than those in meconium. Significant positive correlations were observed for buprenorphine-glucuronide concentrations in umbilical cord and mean maternal BUP daily dose throughout pregnancy and third trimester, but buprenorphine biomarker concentrations did not predict neonatal outcomes. Opiate concentrations were lower (200-fold) in umbilical cord than in meconium, and when cocaine was present in meconium, it was not identified in cord. Umbilical cord can serve as an alternative matrix for identifying prenatal drug-exposure, but is much less sensitive than meconium. Buprenorphine provided a controlled drug administration model for evaluating drug disposition in the maternal-fetal dyad. PMID:21819795

  16. A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes

    OpenAIRE

    Lund, Ingunn O.; Gabriele Fischer; Gabrielle K. Welle-Strand; O’Grady, Kevin E.; Kimber Debelak; William R. Morrone; Jones, Hendrée E

    2013-01-01

    Given that buprenorphine + naloxone is prescribed for opioid-dependent pregnant women, it is important to examine the extent to which it differs from buprenorphine alone, methadone, or methadone-assisted withdrawal on neonatal and maternal outcomes. Summary statistics on maternal and neonatal outcomes were collected from 7 previously published studies examining treatment for opioid-dependent pregnant women that represented a range of research methodologies. Outcomes from these studies were co...

  17. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Khanna IK

    2015-12-01

    Full Text Available Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed µ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other µ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.Keywords: buprenorphine, opioids, opioid dependence, partial agonist, hyperalgesia, neuropathic pain

  18. Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds

    Science.gov (United States)

    Whelan, Paul J; Remski, Kimberly

    2012-01-01

    Heroin dependence is a major health and social problem associated with increased morbidity and mortality that adversely affects social circumstances, productivity, and healthcare and law enforcement costs. In the UK and many other Western countries, both methadone and buprenorphine are recommended by the relevant agencies for detoxification from heroin and for opioid maintenance therapy. However, despite obvious benefits due to its unique pharmacotherapy (eg, greatly reduced risk of overdose), buprenorphine has largely failed to overtake methadone in managing opioid addiction. The experience from the developing world (based on data from India) is similar. In this article we compare the advantages and disadvantages of the use methadone and buprenorphine for the treatment of opioid addiction from both a developed and developing world perspective; and explore some of the reasons why buprenorphine has not fulfilled the expectations predicted by many in the addictions field. PMID:22346191

  19. Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Foster, David J R; Upton, Richard N;

    2014-01-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine in a...... cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed-effects...... modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both...

  20. Text message content preferences to improve buprenorphine maintenance treatment in primary care.

    Science.gov (United States)

    Tofighi, Babak; Grossman, Ellie; Bereket, Sewit; D Lee, Joshua

    2016-01-01

    Few studies have evaluated text message content preferences to support evidence-based treatment approaches for opioid use disorders, and none in primary care office-based buprenorphine treatment settings. This study assessed the acceptability and preferences for a tailored text message intervention in support of core office-based buprenorphine treatment medical management components (e.g., treatment adherence, encouraging abstinence, 12-step group participation, motivational interviewing, and patient-provider communication as needed). There were 97 patients enrolled in a safety net office-based buprenorphine treatment program who completed a 24-item survey instrument that consisted of multiple-choice responses, 7-point Likert-type scales, binomial "Yes/No" questions, and open-ended responses. The sample was predominately male (81%), had an average age of 46 years, and was diverse (64% ethnic/racial minorities); 56% lacked stable employment. Respondents were interested in receiving text message appointment reminders (90%), information pertaining to their buprenorphine treatment (76%), supportive content (70%), and messages to reduce the risk of relapse (88%). Participants preferred to receive relapse prevention text messages during all phases of treatment: immediately after induction into buprenorphine treatment (81%), a "few months" into treatment (57%), and after discontinuing buprenorphine treatment (72%). Respondents also expressed interest in text message content enhancing self-efficacy, social support, and frequent provider communication to facilitate unobserved "home" induction with buprenorphine. Older participants were significantly less receptive to receiving text message appointment reminders; however, they were as interested in receiving supportive, informational, and relapse prevention components compared to younger respondents. Implications for integrating a text message support system in office-based buprenorphine treatment are discussed. PMID

  1. Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation

    International Nuclear Information System (INIS)

    High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD5) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD5 was 10 mg kg-1. Norbuprenorphine 3 mg kg-1 produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO2 (8.4 ± 0.9 versus 5.7 ± 0.1 kPa), decrease in arterial pH (7.25 ± 0.06 versus 7.44 ± 0.01), and hypoxia (8.3 ± 0.6 versus 11.1 ± 0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg-1 norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for mu- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use

  2. Sublingual buprenorphine for acute renal colic pain management: a double-blind, randomized controlled trial

    OpenAIRE

    Payandemehr, Pooya; Jalili, Mohammad; Mostafazadeh Davani, Babak; Dehpour, Ahmad Reza

    2014-01-01

    Background The aim of this study was to compare the efficacy and safety of sublingual buprenorphine with intravenous morphine sulfate for acute renal colic in the emergency department. Methods In this double-dummy, randomized controlled trial, we enrolled patients aged 18 to 55 years who had a clinical diagnosis of acute renal colic. Patients received either 2 mg sublingual buprenorphine with an IV placebo, or 0.1 mg/kg IV morphine sulfate with a sublingual placebo. Subjects graded their pain...

  3. Course and Treatment of Buprenorphine/naloxone Withdrawal: An Analysis of Case Reports

    OpenAIRE

    Westermeyer, Joseph; McCance-Katz, Elinore F.

    2012-01-01

    Currently published information on buprenorphine-naloxone withdrawal recommends a gradually decreasing dosage over weeks to months. In this case report, abrupt cessation of buprenorphine/naloxone at various doses, and after variable durations of treatment, resulted in mild opiate withdrawal lasting over approximately 1–2 days that did not require additional opioid medication or only specific symptom-relieving, non-opioid, medications. Lengthy withdrawal regimens might prolong withdrawal sympt...

  4. Bringing Buprenorphine-Naloxone Detoxification to Community Treatment Providers: The NIDA Clinical Trials Network Field Experience

    OpenAIRE

    Amass, Leslie; Ling, Walter; Freese, Thomas E.; Reiber, Chris; Annon, Jeffrey J.; Cohen, Allan J.; M.F.T.; McCarty, Dennis; Reid, Malcolm S.; Brown, Lawrence S.; Clark, Cynthia; Ziedonis, Douglas M.; Krejci, Jonathan; Stine, Susan; Winhusen, Theresa

    2004-01-01

    In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone®) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opi...

  5. Budgetary impact analysis of buprenorphine-naloxone combination (Suboxone®) in Spain

    OpenAIRE

    Martinez-Raga, Jose; Gonzalez-Saiz, Francisco; Oñate, Julian; Oyagüez, Itziar; Sabater, Eliazar; A. Casado, Miguel

    2012-01-01

    Background: Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial kappa-opiod agonist and a my-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. Methods: A budgetary impact model was developed to estimate healthcare cost...

  6. Development of a radioimmunoassay for the determination of buprenorphine in biological samples

    International Nuclear Information System (INIS)

    The development of a specific and sensitive radioimmunoassay for the detection of buprenorphine in urine samples is described. With minor adjustments, the assay was also applied to the analysis for buprenorphine in plasma samples. The 2-diazobenzoic acid derivative of buprenorphine has been prepared as a hapten. The immunization of rabbits with the hapten-bovine serum albumin conjugate resulted in the production of antibodies, which cross-reacted with N-dealkylbuprenophine up to about the 90% level. The antibodies showed very low cross-reactivities with the 3-O-glucuronides and with the structural analogue etorphine. The assay was mainly used to prescreen for buprenorphine in urine samples of persons suspected of Temgesic misuse and to determine buprenorphine in plasma samples. A linear calibration graph for buprenorphine was obtained after logit-log regression. The spiking recovery study showed a linear regression. Intra-and inter-assay relative standard deviations were -1 (Student's t-distribution, p 0.01, degrees of freedom = 8). (Author)

  7. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.

    Science.gov (United States)

    KuKanich, B; Allen, P

    2014-12-01

    The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. PMID:24684621

  8. Buprenorphine detection in hair samples by immunometric screening test: preliminary experience.

    Science.gov (United States)

    Svaizer, Fiorenza; Lotti, Andrea; Gottardi, Massimo; Miozzo, Maria Pia

    2010-03-20

    The recent introduction of buprenorphine use by the Drug Addiction Services has induced toxicology laboratories to develop new qualitative or semiquantitative screening assay for its determination in hair samples. The aim of this preliminary study was to verify the correlation between the buprenorphine intake and the immunometric screening test results (VMA-T Comedical and buprenorphine CEDIA/Thermo-Fisher/Microgenics reagents) and therefore their comparison with the liquid chromatography coupled with mass spectrometry (LC/MS) results. Hair samples were obtained from 32 subjects without buprenorphine-therapy reported and 17 in treatment. In glass test tube with hermetic cap were weighed 33 mg of 49 finely cut hair samples, washed with 1 mL of SLV-VMA-T washing solution, which is then completely sucked and eliminated. The samples were extracted with 400 microL of VMA-T reagent for an hour at 100 degrees C. The extracts were analysed by immunometric screening test on ILab 650 chemistry analyser, using buprenorphine CEDIA reagent assay. From the 32 non-takers of drug, 30 semiquantitative results were less than 10 pg/mg and 2 were over 10 pg/mg; from the 17 subjects with therapy, all were over 10 pg/mg (range 13-50 pg/mg); no samples were false-negative. Results suggest that exist a good relationship between the administration of buprenorphine and its concentration in hair, detectable through this method and reagents line. PMID:20080369

  9. Pharmacokinetics of morphine and its surrogates. X: Analyses and pharmacokinetics of buprenorphine in dogs.

    Science.gov (United States)

    Garrett, E R; Chandran, V R

    1990-01-01

    Specific and sensitive reverse-phase HPLC assays of buprenorphine and its metabolite in biological fluids were developed with sensitivities of 2-6 ng ml-1 using fluorimetric detection. Pharmacokinetics were monitored on acute bolus administration of buprenorphine in 6 dogs within the 0.7-2.6 mg kg-1 dose range. Toxicity was circumvented when terminal plasma concentrations were increased by infusing 3.7-4.8 mg kg-1 doses of buprenorphine over 3 h in six studies in 6 dogs. The terminal rate constants of the IV infusion studies from the triexponential fits of plasma concentration-time data averaged 41.6 +/- 7.5 h with an averaged total body clearance of 191 +/- 19 ml min-1. This terminal rate constant was in contrast to the less than 100 min half-life of the second exponential fitting of the less lipophilic morphine, naloxone, and naltrexone. The apparent volumes of distribution of buprenorphine, referenced to the total plasma concentration, were 33 +/- 61 (Vc, central compartment volume) and 663 +/- 891 (Vd, total body volume), indicative of a highly bound, sequestered or lipophilic drug. Unchanged buprenorphine was insignificantly renally (less than 0.2 per cent of the dose) and biliary (less than 0.6 per cent) excreted. The major route of buprenorphine disposition was by hepatic conjugation to glucuronide which was eliminated into the bile (about 92 per cent) with only small amounts appearing in urine (less than 1 per cent as metabolite). Minor metabolites excreted in the bile accounted for about 3 per cent of the administered dose. Direct IV administration of the metabolite, buprenorphine glucuronide, gave a terminal half-life of 6 h and more than 90 per cent of the systemically circulating metabolite was excreted in bile; only 10 per cent in urine. The oral bioavailability, estimated from the areas under the buprenorphine plasma concentration-time curve following IV and oral administration of buprenorphine in the dogs, was 3-6 per cent. There were no apparent

  10. Evaluation of medetomidine, ketamine and buprenorphine for neutering feral cats.

    Science.gov (United States)

    Harrison, Kelly A; Robertson, Sheilah A; Levy, Julie K; Isaza, Natalie M

    2011-12-01

    A combination of medetomidine (M, 100 μg/kg), ketamine (K, 10 mg/kg) and buprenorphine (B, 10 μg/kg), administered by intramuscular injection, was evaluated for spaying and castration (neutering) of feral cats (n = 101). Eleven animals (11%) required supplemental anesthesia (isoflurane by mask) to maintain an adequate plane of surgical anesthesia. Atipamezole (A, 125 μg/kg) was administered subcutaneously at the completion of surgery. All cats recovered from surgery and were released the following day. A hemoglobin saturation (SpO(2)) value of < 95% was recorded at least once during anesthesia in all cats. This MKB combination can be used in a feral cat sterilization clinic, but isoflurane supplementation may be necessary. Further research is indicated to determine the clinical significance of the low SpO(2) values associated with this anesthetic regimen. PMID:21885310

  11. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Unal, Cemal; Finn, Andrew

    2015-01-01

    In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN) sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV) naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15) of placebo-treated subjects and 47% (7/15) of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS) score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (Pnaloxone-containing treatments was significantly greater than for buprenorphine alone (PNaloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. PMID:26604818

  12. Effects of voluntarily-ingested buprenorphine on plasma corticosterone levels, body weight, water intake, and behaviour in permanently catheterised rats

    DEFF Research Database (Denmark)

    Goldkuhl, Renée; Hau, Jann; Abelson, Klas

    2010-01-01

    corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference...

  13. Buprenorphine-naloxone use in pregnancy for treatment of opioid dependence

    Science.gov (United States)

    Dooley, Joe; Gerber-Finn, Lianne; Antone, Irwin; Guilfoyle, John; Blakelock, Brittany; Balfour-Boehm, Jazmyn; Hopman, Wilma M.; Jumah, Naana; Kelly, Len

    2016-01-01

    Abstract Objective To examine the maternal course and neonatal outcomes for women using buprenorphine-naloxone for opioid dependence in pregnancy. Design Retrospective cohort study comparing outcomes for the group of pregnant patients exposed to buprenorphine-naloxone with outcomes for those exposed to other narcotics and those not exposed to narcotics. Setting Northwestern Ontario obstetric program. Participants A total of 640 births in an 18-month period from July 1, 2013, to January 1, 2015. Main outcome measures Maternal outcomes included route and time of delivery, medical and surgical complications, out-of hospital deliveries, change in illicit drug use, and length of stay. Neonatal outcomes included stillbirths, incidence and severity of neonatal abstinence syndrome, birth weight, gestational age, Apgar scores, and incidence of congenital abnormalities. Results Thirty pregnant women used buprenorphine-naloxone for a mean (SD) of 18.8 (11.2) weeks; an additional 134 patients were exposed to other opioids; 476 pregnant women were not exposed to opioids. Maternal and neonatal outcomes were similar among the 3 groups, other than the expected clinically insignificant lower birth weights among those exposed to opioids other than buprenorphine-naloxone. Conclusion Buprenorphine-naloxone appears to be safe for use in pregnancy for opioid-dependence substitution therapy. Transferring a pregnant patient to another opioid agonist that has greater abuse potential might not be necessary.

  14. Clinical Efficacy of Sustained-Release Buprenorphine with Meloxicam for Postoperative Analgesia in Beagle Dogs Undergoing Ovariohysterectomy

    Science.gov (United States)

    Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

    2014-01-01

    The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a predetermined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey–Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

  15. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model

    DEFF Research Database (Denmark)

    Ravn, Pernille; Secher, EL; Skram, U;

    2013-01-01

    Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than μ-opioid receptor agonists. The primary outcome of this study was therefore to...... investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending...... pain modulation....

  16. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

    Directory of Open Access Journals (Sweden)

    Webster LR

    2015-11-01

    Full Text Available Lynn R Webster,1 Michael D Smith,1 Cemal Unal,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, USA; 2Biometrical Solutions LLC, Raleigh, NC, USA; 3BioDelivery Sciences International, Inc., Raleigh, NC, USA Abstract: In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15 of placebo-treated subjects and 47% (7/15 of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001, and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001. Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. Keywords: opioid dependence, withdrawal symptoms, abuse-deterrent, buprenorphine

  17. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    Directory of Open Access Journals (Sweden)

    Chen HH

    2015-03-01

    Full Text Available Hwei-Hsien Chen,1,2,* Yao-Chang Chiang,3,4,* Zung Fan Yuan,5,6 Chung-Chih Kuo,5,6 Mei-Dan Lai,2 Tsai-Wei Hung,1 Ing-kang Ho,1,3,4 Shao-Tsu Chen2,7 1Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan; 2Master and PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan; 3Center for Drug Abuse and Addiction, China Medical University Hospital, 4Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 5Master Program in Physiological and Anatomical Medicine, 6Department of Physiology, School of Medicine, Tzu Chi University, 7Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualien, Taiwan *These authors contributed equally to this work Abstract: Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female

  18. Management of chronic pain in the elderly: focus on transdermal buprenorphine

    Directory of Open Access Journals (Sweden)

    Nalini Vadivelu

    2008-09-01

    Full Text Available Nalini Vadivelu, Roberta L HinesDepartment of Anesthesiology, Yale University School of Medicine, New Haven, USAAbstract: Chronic pain in the elderly is a significant problem. Pharmacokinetic and metabolic changes associated with increased age makes the elderly vulnerable to side effects and overdosing associated with analgesic agents. Therefore the management of chronic cancer pain and chronic nonmalignant pain in this growing population is an ongoing challenge. New routes of administration have opened up new treatment options to meet this challenge. The transdermal buprenorphine matrix allows for slow release of buprenorphine and damage does not produce dose dumping. In addition the long-acting analgesic property and relative safety profile makes it a suitable choice for the treatment of chronic pain in the elderly. Its safe use in the presence of renal failure makes it an attractive choice for older individuals. Recent scientific studies have shown no evidence of a ceiling dose of analgesia in man but only a ceiling effect for respiratory depression, increasing its safety profile. It appears that transdermal buprenorphine can be used in clinical practice safely and efficaciously for treating chronic pain in the elderly.Keywords: transdermal buprenorphine, chronic pain, elderly

  19. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Adams Clive E

    2007-01-01

    Full Text Available Abstract Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices, Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065. A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028. People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52 and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49. Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.

  20. Oral self-administration of buprenorphine in the diet for analgesia in mice.

    Science.gov (United States)

    Molina-Cimadevila, M J; Segura, S; Merino, C; Ruiz-Reig, N; Andrés, B; de Madaria, E

    2014-04-23

    Postsurgical oral self-administration of analgesics in rodents is an interesting technique of providing analgesia, avoiding the negative effects of manipulation. Several strategies, using gelatin or nutella, have already been described. However, rodents require some habituation period to reach a good intake because of their neophobic behavior. The current study aimed to explore whether buprenorphine when mixed with an extruded diet offers a potential treatment option in the pain management of mice using a triple approach: by measuring the spontaneous intake in healthy animals; by using the hot-plate test; and finally by assessing the drug's ability to provide postoperative analgesia in a surgical intervention of moderate severity (intra-utero electroporation). Mice consumed during 20 hours, similar amounts of extruded diet alone, mixed with glucosaline, and mixed with buprenorphine (0.03 mg per pellet) or meloxicam (0.25 mg per pellet) both of which were diluted in glucosaline, showing that no neophobia was associated with these administrations. Relative increase from baseline latency (% maximal possible effect) in the hot-plate test at 20 h of administration was significantly higher for oral buprenorphine in diet 0.03 mg/pellet, and diet 0.15 mg/pellet, compared with placebo and no differences were found between those oral administrations and subcutaneous buprenorphine 0.1 mg/kg measured 3 h later. The treatment was also effective in attenuating the reductions in food consumption and body weight that occur after surgery. These data suggest that providing buprenorphine with the diet is a feasible and effective way of self-administration of analgesia in mice and does not cause neophobia and may easily contribute to the refinement of surgical procedures. PMID:24759572

  1. Cost-effectiveness of buprenorphine and naltrexone treatments for heroin dependence in Malaysia.

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    Jennifer Prah Ruger

    Full Text Available AIMS: To aid public health policymaking, we studied the cost-effectiveness of buprenorphine, naltrexone, and placebo interventions for heroin dependence in Malaysia. DESIGN: We estimated the cost-effectiveness ratios of three treatments for heroin dependence. We used a microcosting methodology to determine fixed, variable, and societal costs of each intervention. Cost data were collected from investigators, staff, and project records on the number and type of resources used and unit costs; societal costs for participants' time were estimated using Malaysia's minimum wage. Costs were estimated from a provider and societal perspective and reported in 2004 US dollars. SETTING: Muar, Malaysia. PARTICIPANTS: 126 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial in Malaysia (2003-2005 receiving counseling and buprenorphine, naltrexone, or placebo for treatment of heroin dependence. MEASUREMENTS: Primary outcome measures included days in treatment, maximum consecutive days of heroin abstinence, days to first heroin use, and days to heroin relapse. Secondary outcome measures included treatment retention, injection drug use, illicit opiate use, AIDS Risk Inventory total score, and drug risk and sex risk subscores. FINDINGS: Buprenorphine was more effective and more costly than naltrexone for all primary and most secondary outcomes. Incremental cost-effectiveness ratios were below $50 for primary outcomes, mostly below $350 for secondary outcomes. Naltrexone was dominated by placebo for all secondary outcomes at almost all endpoints. Incremental treatment costs were driven mainly by medication costs, especially the price of buprenorphine. CONCLUSIONS: Buprenorphine appears to be a cost-effective alternative to naltrexone that might enhance economic productivity and reduce drug use over a longer term.

  2. Effects of buprenorphine and meloxicam analgesia on induced cerebral ischemia in C57BL/6 male mice

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy;

    2013-01-01

    Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we...... investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects...... were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam...

  3. Patient Perspectives on Buprenorphine/Naloxone: A Qualitative Study of Retention During the Starting Treatment with Agonist Replacement Therapies (START) Study

    OpenAIRE

    Teruya, Cheryl; Schwartz, Robert P.; Mitchell, Shannon Gwin; Hasson, Albert L.; Thomas, Christie; Buoncristiani, Samantha H.; Hser, Yih-Ing; Wiest, Katharina; Cohen, Allan J.; Glick, Naomi; Jacobs, Petra; McLaughlin, Paul; Ling, Walter

    2014-01-01

    This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n=105) were recruited up to three-and-a-half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had ter...

  4. Disposition in the rat of buprenorphine administered parenterally and as a subcutaneous implant.

    Science.gov (United States)

    Pontani, R B; Vadlamani, N L; Misra, A L

    1985-04-01

    Disposition of [15, 16(n)-3H]buprenorphine in the rat has been investigated after a single 0.2 mg/kg i.v. bolus dose and continuous administration via a s.c. implantable long-acting delivery system. After the i.v. injection, the tri-exponential decay of drug from brain occurred with t1/2 values of 0.6, 2.3 and 7.2 h, respectively (plasma t1/2 0.5, 1.4 h, third phase not estimated due to sustained concn.) Decay of drug from another high-affinity binding site in brain occurred with t1/2 values of 1.1 and 68.7 h, respectively. Fat and lung had higher concn. than other tissues and plasma. No metabolites of drug were detected in brain. Unmetabolized drug excreted in urine and faeces one week after i.v. injection were 1.9 and 22.4% of dose, respectively, and 92% of the dose was accounted for in one week. Urinary metabolites (%) were: conjugated buprenorphine 0.9; norbuprenorphine (free 9.4, conjugated 5.2); tentative 6-O-desmethylnorbuprenorphine (free 5.4, conjugated 15.9). Peak plasma concn. of buprenorphine occurred four weeks after s.c. implantation of a long-acting 10 mg 3H-buprenorphine pellet, and apparent dissociation half-lives of drug from low- and high-affinity binding sites in brain were 4.6 and 6.8 weeks, respectively. Fat, spleen and skeletal muscle had higher concn. than other tissues and plasma. No significant difference in brain morphine concn. was observed in placebo and nonlabelled buprenorphine-pelleted animals after a 2 mg/kg i.v. challenge dose of 3H-morphine. This study emphasizes the importance of high-affinity binding of buprenorphine in brain and subsequent slow dissociation as a prime factor in its prolonged agonist/antagonist effects and higher potency than other narcotic agonists. PMID:4024663

  5. Buprenorphine 5, 10 and 20 μg/h transdermal patch: a review of its use in the management of chronic non-malignant pain.

    Science.gov (United States)

    Plosker, Greg L

    2011-12-24

    This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20 μg/h) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes. In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and

  6. A COMPARATIVE STUDY BETWEEN INTRATHECAL MORPHINE AND INTRATHECAL BUPRENORPHINE FOR POST - OPERATIVE ANALGESIA FOLLOWING CAESARIAN SECTION UNDER SUB ARACHNOID BLOCK

    Directory of Open Access Journals (Sweden)

    Anish M

    2015-05-01

    Full Text Available BACKGROUND: Good pain relief following caesarian section is of great importance and intrathecal opioids provide good quality postoperative analgesia for longer duration. So the following study describes a comparative study between intrathecal morphine and intrathecal buprenorphine for postoperative pain relief following caesarian section (CS under subarachnoid blockade. AIMS: The study was conducted to compare intrathecal morphine and buprenorphine for post of analgesia following CS, to achieve analgesia without seda tion for better maternal child bondage and to popularize intrathecal opioids . MATERIALS AND METHODS: 60 patients posted for CS under SAB were randomly allocated into group A and group B of 30 each, the group A received morphine 0.1 mg and buprenorphine 0 . 0 3 mg was given for group B patients along with the local anaesthetic. Subjective assessment of post - operative analgesia was done by direct questioning of the patient and by a five point pain scores. Duration of analgesia was taken as the time interval betw een the time of injection of intrathecal opiate and the time at which the patient felt pain and requested for additional analgesics. Data’s were analyzed using SPSS 16th version. OBSERVATION AND RESU LTS: The mean duration of post - operative analgesia with i ntrathecal morphine was 24.19+4 . 8 hours and that with buprenorphine was only 11.7+3.28 hours. Over weight patients reported a lower mean duration of analgesia. None of the patients in the study showed any bradycardia, hypotension, desaturation or respirato ry depression. Intrathecal opiates decreased the parenteral opiate requirements. The main side effects noticed were nausea in about 43% of patients in morphine group and 33% of patients in buprenorphine group. CONCLUSIONS: Intrathecal morphine 0 . 1 mg gives good post - operative analgesia of longer duration than buprenorphine 0 . 03mg. The quality of analgesia provided by intrathecal morphine was superior to

  7. Criminal charges prior to and after initiation of office-based buprenorphine treatment

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    Harris Elizabeth E

    2012-03-01

    Full Text Available Abstract Background There is little data on the impact of office-based buprenorphine therapy on criminal activity. The goal of this study was to determine the impact of primary care clinic-based buprenorphine maintenance therapy on rates of criminal charges and the factors associated with criminal charges in the 2 years after initiation of treatment. Methods We collected demographic and outcome data on 252 patients who were given at least one prescription for buprenorphine. We searched a public database of criminal charges and recorded criminal charges prior to and after enrollment. We compared the total number of criminal cases and drug cases 2 years before versus 2 years after initiation of treatment. Results There was at least one criminal charge made against 38% of the subjects in the 2 years after initiation of treatment; these subjects were more likely to have used heroin, to have injected drugs, to have had any prior criminal charges, and recent criminal charges. There was no significant difference in the number of subjects with any criminal charge or a drug charge before and after initiation of treatment. Likewise, the mean number of all cases and drug cases was not significantly different between the two periods. However, among those who were opioid-negative for 6 or more months in the first year of treatment, there was a significant decline in criminal cases. On multivariable analysis, having recent criminal charges was significantly associated with criminal charges after initiation of treatment (adjusted odds ratio 3.92; subjects who were on opioid maintenance treatment prior to enrollment were significantly less likely to have subsequent criminal charges (adjusted odds ratio 0.52. Conclusions Among subjects with prior criminal charges, initiation of office-based buprenorphine treatment did not appear to have a significant impact on subsequent criminal charges.

  8. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

    OpenAIRE

    Adams Clive E; Tompkins Charlotte NE; Sheard Laura; Wright Nat MJ; Allgar Victoria L; Oldham Nicola S

    2007-01-01

    Abstract Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual b...

  9. Comparison of the analgesic effects of robenacoxib, buprenorphine and their combination in cats after ovariohysterectomy.

    Science.gov (United States)

    Staffieri, F; Centonze, P; Gigante, G; De Pietro, L; Crovace, A

    2013-08-01

    The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ≥ 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone. PMID:23434263

  10. Effect of fentanyl versus buprenorphine on the pupil size in phacoemulsification cataract surgery

    OpenAIRE

    Abdolreza Najafi Anaraki; Abbas Akrami; Niloofar Motamed; Elham Seydali

    2012-01-01

    Background: Despite several recent innovations in phacoemulsification surgery, importance of pupil diameter in this surgery is becoming more evident. Purpose : To compare the effect of opioid agonist (fentanyl) versus opioid agonist-antagonist (buprenorphine) on pupil diameter in cataract surgery and to choose the best opioid in high-risk phacoemulsification surgery. Methods: In this randomized double-blinded clinical trial, 60 patients who were candidates for elective phacoemulsification sur...

  11. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy Greyhound dogs

    OpenAIRE

    KuKanich, Butch; Allen, Philip

    2014-01-01

    The purpose of this study was to compare the pharmacokinetics of two highly protein bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy Greyhound dogs (3 males and 3 females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry and noncompartmental pharmacokinetics were estimated with computer software. The v...

  12. Two Models of Integrating Buprenorphine Treatment and Medical Staff within Formerly "Drug-Free" Outpatient Programs.

    Science.gov (United States)

    Monico, Laura; Schwartz, Robert P; Gryczynski, Jan; O'Grady, Kevin E; Mitchell, Shannon Gwin

    2016-01-01

    "Drug-free" outpatient programs deliver treatment to the largest number of patients of all treatment modalities in the U.S., providing a significant opportunity to expand access to medication treatments for substance use disorders. This analysis examined staff perceptions of organizational dynamics associated with the delivery of buprenorphine maintenance within three formerly "drug-free" outpatient treatment programs. Semi-structured interviews (N = 15) were conducted with counseling and medical staff, and respondents were predominantly African American (n = 11) and female (n = 12). Themes and concepts related to medical staff integration emerged through an inductive and iterative coding process using Atlas.ti qualitative analysis software. Two treatment clinics incorporated buprenorphine maintenance into their programs using a co-located model of care. Their staff generally reported greater intra-organizational discord regarding the best ways to combine medication and counseling compared to the clinic using an integrated model of care. Co-located program staff reported less communication between medical and clinical staff, which contributed to some uncertainty about proper dosing and concerns about the potential for medication diversion. Clinics that shift from "drug-free" to incorporating buprenorphine maintenance should consider which model of care they wish to adapt and how to train staff and structure staff communication. PMID:26940870

  13. Effects of voluntarily-ingested buprenorphine on plasma corticosterone levels, body weight, water intake, and behaviour in permanently catheterised rats.

    Science.gov (United States)

    Goldkuhl, Renée; Hau, Jann; Abelson, Klas S P

    2010-01-01

    This study investigated the peri- and postoperative effect of pre-emptive analgesia through voluntary ingestion of buprenorphine in Nutella, in male Sprague-Dawley rats. An arterial catheter was inserted and the rats were connected to an automated blood sampling device (AccuSampler). Blood samples were drawn up to 18 h after surgery and the plasma concentrations of corticosterone were quantified. Postoperative changes in water intake and body weight were recorded, and the behaviour of the rats was analysed during two 30-min periods. Pre-emptive oral buprenorphine treatment reduced the plasma corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference in the operated rats. The present study strengthens the hypothesis that pre-emptive oral buprenorphine in Nutella is suitable for treatment of postoperative pain in rats. PMID:20363983

  14. A prospective multi-centre clinical trial to compare buprenorphine and butorphanol for postoperative analgesia in cats.

    Science.gov (United States)

    Taylor, Polly M; Kirby, Jonathan J; Robinson, Clare; Watkins, Elizabeth A; Clarke, David D; Ford, Marion A; Church, Karen E

    2010-04-01

    One hundred and fifty-three cats undergoing surgery in seven veterinary practices in Great Britain were studied. They were randomly allocated to receive either 10-20 microg/kg buprenorphine or 0.4 mg/kg butorphanol with acepromazine before anaesthesia with propofol, Saffan or thiopentone and isoflurane or halothane. Routine monitoring was undertaken. Pain and sedation were assessed blind using a four point (0-3) simple descriptive scale (SDS) at 1, 2, 4, 8 and 24h. Pain and sedation data were compared using non-parametric statistical tests and continuous data using t tests or analysis of variance (ANOVA). Anaesthesia and surgery were uneventful, and cardiorespiratory data were within normal limits. After surgery, overall, more cats had pain score 0 after buprenorphine and more had pain score 3 after butorphanol (P=0.0465). At individual time points, more cats had lower pain scores after buprenorphine at 2 (P=0.040) and 24 (P=0.036)h. At 24h 83% after buprenorphine and 63% after butorphanol had pain score 0 (P<0.04). Buprenorphine provided better and longer lasting postoperative analgesia than butorphanol. PMID:19836984

  15. Subarachnoidally administered hyperbaric morphine, buprenorphine, methadone, and 10% dextrose on cardiopulmonary function and behavior in horses Administração subaraquenóide de morfina, buprenorfina, metadona hiperbáricos e dextrose 10% sobre as funções cardiopulmonar e comportamental em cavalos

    OpenAIRE

    Cláudio Corrêa Natalini; Renata Lehn Linardi; Alexandre da Silva Polydoro

    2006-01-01

    The study was done to compare the heart rate, arterial blood pressure, arterial blood gases, respiratory rate, body temperature, and behavior after subarachnoid administration of hyperbaric morphine (MorphineD10), buprenorphine (BuprenorphineD10), methadone (Methadone D10), and 10% dextrose (D10) in conscious horses. Six adult horses were studied. Treatments were administered into the lombo-sacral subarachnoid space through an epidural catheter, MorphineD10 at 0.01mg kg-1, BuprenorphineD10 at...

  16. Switching from high doses of pure u-opioid agonists to transdermal buprenorphine in patients with cancer

    DEFF Research Database (Denmark)

    Lundorff, Lena; Sjøgren, Per; Hansen, Ole Bo;

    2013-01-01

    BACKGROUND: Several myths on buprenorphine's pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain...... relief after switching to transdermal (TD) buprenorphine and 2) whether the numbers of breakthrough pain episodes after switching increased and whether they could be treated with the same doses of pure agonist as before switching. DESIGN: The prospective open multicenter study included outpatients with...... moderate-to-severe cancer pain satisfactorily controlled. SETTING: Patients were switched from the usual pure agonist to TD buprenorphine and were titrated to a stable dose. The assessments were: 1) daily self-assessment of pain intensity, numbers of rescue medications, and pain interference with sleep; 2...

  17. Messages about methadone and buprenorphine in reality television: a content analysis of celebrity rehab with Dr. Drew.

    Science.gov (United States)

    Roose, Robert; Fuentes, Liza; Cheema, Mandeep

    2012-08-01

    Medication-assisted treatment for opioid dependence is safe and effective, yet negative perceptions about methadone and buprenorphine may discourage patients from entering treatment. One source of information that may influence viewers' perceptions is television. We performed a content analysis of a popular reality television program on addiction treatment. Although many patients had histories of opioid use, there were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information. PMID:22587811

  18. Post operative analgesia after incisional infiltration of bupivacaine v/s bupivacaine with buprenorphine

    Directory of Open Access Journals (Sweden)

    Tanu R Mehta

    2011-01-01

    Full Text Available Introduction: Opioid receptors have been demonstrated in the peripheral nerve endings of afferent neurons. Blockade of these receptors with peripherally administered opioid is believed to result in analgesia. Aim: To evaluate whether buprenorphine added to bupivacaine for wound infiltration can enhance post-operative analgesia via peripheral mechanisms. Materials and Methods: Forty ASA I and II adult patients scheduled for open donor nephrectomy were enrolled in this randomized double blind prospective study. In group A ( n=20 patients, the wound was infiltrated with bupivacaine 0.5% (2 mg/kg and in group B ( n=20 with bupivacaine 0.5% (2 mg/kg and buprenorphine (2 μg/kg. All patients were given diclofenac 75 mg IM at 8 h interval. Post-operative quality of analgesia was assessed by VAS (0-10 for 24 h and when VAS > 4 rescue analgesic was administered. Total dose of rescue analgesic and side effects were noted. Results: The time of administration of first rescue analgesic was significantly higher in group B (10.52±5.54 h as compared to group A (3.275±1.8 h. Mean VAS was significantly lower in group B as compared to group A. The total dosage of rescue analgesic was more in group A as compared to group B patients. Conclusion: Addition of buprenorphine to the local anesthetic significantly prolonged the time to first rescue analgesic requirement and the total consumption of rescue analgesic in 24 h, thus providing evidence in support of the existence of peripheral opioid receptors.

  19. Psychological barriers to tobacco cessation in Indian buprenorphine-naloxone maintained patients: A pilot study

    Directory of Open Access Journals (Sweden)

    Piyali Mandal

    2015-01-01

    Full Text Available Context: The prevalence of smoking in opioid agonist treatment programmes remains high, leading to significant tobacco related health hazards and mortality. This is the first study from India addressing tobacco cessation and related barriers among recipients of buprenorphine-naloxone maintenance treatment. Aims: The purpose of the study was to investigate Indian buprenorphine-naloxone maintained patients′ willingness to quit tobacco use, to determine its possible association with demographic, agonist maintenance treatment, tobacco use related variables and personal health and risk perceptions related to health hazards associated with tobacco use. Settings and Design: The study was cross-sectional, observational. It was conducted in the out-patient department of a national level de-addiction centre in India. Materials and Methods: Fifty-five males on buprenorphine-naloxone treatment were assessed using Tobacco Use Characteristics, Fagerstrom Test for Nicotine Dependence (FTND and FTND-ST, Readiness to Change questionnaire (RCQ, Smoker′s Perceived Health Risk Evaluation (SPHERE, Importance of Intervention scale and a semi-structured questionnaire. Statistical Analysis: Descriptive statistics, Kruskal-Wallis Chi-square test, Spearman rank order correlation, paired-t test, ANOVA (STATA 9.2 statistical package. Results: Around 65.4% of the subjects were smokers, 9% were using smokeless tobacco only whereas 25.6% were using both. Mean duration of tobacco use was 20 ± 1.5 years. Only 20% had past quit attempts. Only 24% were in action phase of change. Personal health and risk perceptions were poor and only 61.62% considered intervention tobacco smoking cessation important. Conclusions: Higher severity of nicotine dependence, low perception of harm from tobacco warrant immediate attention and need for on-site treatment opportunity.

  20. High dose of buprenorphine in terminally ill patient with liver failure: efficacy and tolerability.

    Science.gov (United States)

    Ciccozzi, Alessandra; Angeletti, Chiara; Baldascino, Giada; Petrucci, Emiliano; Bonetti, Cristina; De Santis, Stefania; Paladini, Antonella; Varrassi, Giustino; Marinangeli, Franco

    2012-01-01

    Pain in terminally ill patients with cancer can be often hard to manage, due to the unpredictable kinetics of drugs caused by progressive kidney and liver dysfunction. Plasma concentrations of active metabolites-also a cause of dangerous side effects--could be difficult to estimate. This case report holds the idea that buprenorphine, a partial agonist of m-receptors, even at high dosage, may be effective and safe to use in terminally ill patients with significant liver and kidney impairment. PMID:22941853

  1. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

    OpenAIRE

    Webster LR; Smith MD; Unal C; Finn A

    2015-01-01

    Lynn R Webster,1 Michael D Smith,1 Cemal Unal,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, USA; 2Biometrical Solutions LLC, Raleigh, NC, USA; 3BioDelivery Sciences International, Inc., Raleigh, NC, USA Abstract: In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN) sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This w...

  2. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40

    Science.gov (United States)

    Boone, Margaret; Brown, Nancy J.; Moon, Mary A.; Schuman, Deborah J.; Thomas, Josephine; Wright, Denise L.

    2004-01-01

    This Treatment Improvement Protocol (TIP) addresses the clinical use of buprenorphine in the treatment of opioid addiction. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts…

  3. Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth

    Science.gov (United States)

    Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

    2011-01-01

    Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

  4. Management of opioid addiction with buprenorphine: French history and current management

    Directory of Open Access Journals (Sweden)

    Poloméni P

    2014-03-01

    Full Text Available Pierre Poloméni,1 Raymund Schwan2,3 1Department of Addictology, Paris Seine Saint Denis University Hospital, AP-HP, Site René Muret Sevran, France; 2Care Center for the Treatment and Prevention of Addictions (CSAPA, Nancy University Hospital, 3General Psychiatric Division for the Greater Nancy Urban Community, Psychotherapeutic Center of Nancy, Laxou, France Abstract: The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000–360,000 "problem drug users" being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the

  5. Rifampin reduces oral morphine absorption: a case of transdermal buprenorphine selection based on morphine pharmacokinetics.

    Science.gov (United States)

    Fudin, Jeffrey; Fontenelle, Dania Vanesta; Payne, Annette

    2012-12-01

    A 51-year-old male was referred to the Stratton Veterans Affairs Medical Center Pain Service after hospital admission for endocarditis with a history of heroin use and chronic low back pain. During his hospital stay he experienced a reduction in his serum morphine level ostensibly as a result of concomitant rifampin administration. We hypothesize that diminished absorption was from rifampin-mediated intestinal P-glycoprotein induction, ultimately decreasing serum free morphine and metabolites. The case became more complex in an attempt to balance managed pain, history of substance abuse, completion of antibiotic therapy, and a reasonable pain regimen upon discharge. Ultimately, the patient was titrated onto a buprenorphine transdermal patch, the initiation of which was based on serum free morphine and an extrapolated oral morphine dose by calculation. PMID:23216174

  6. Evaluation on drug dependence of buprenorphine%丁丙诺啡药物依赖性评价

    Institute of Scientific and Technical Information of China (English)

    刘志民; 吕宪祥; 连智; 穆悦; 郭平; 安欣

    2003-01-01

    AIM: To survey and assess the drug dependence and abuse potential liability of buprenorphine among opiate abusers. METHODS: Subjects of opiate dependence with history of buprenorphine use for 3 d at least were surveyed by interview. Physical dependence of buprenorphine was assessed using 30 items opiate withdrawal scale (OWS), which composed of 30 symptoms/signs. A 4-point scale was used to rate each symptoms/signs: zero (0), mild (1), moderate (2), and severe (3). Subjects were asked to rate their symptoms according to severity of previous experienced buprenorphine withdrawal. The estimate of the degree of subjective euphoria for buprenorphine was assessed using visual analogue scale (VAS). RESULTS: Subjects 1235 who met the research criteria cases completed this survey in multi-detoxification treatment centers. The main initial purposes of buprenorphine use were detoxification (77.4 %) and protracted abstinence treated (26.6 %) respectively. The scores of OWS of buprenorphine were between 0.2 to 1.3; The mean scores of OWS in 3 different categories of frequency of buprenorphine use on "continuous use", "un-continuous use", and "sometimes continuous, sometimes un-continuous" were 0.9±0.9, 0.4±0.5, and 0.7±0.4, respectively (F=70.846, P<0.05). The degree of subjective euphoria for buprenorphine was slight to sub-moderate (mean score of VAS was 27 mm ±24 mm). The mean scores of VAS in different routes of buprenorphine administration of sublingual and injection were (24±23) mm and (27 ±24) mm, respectively. No significant difference was found between sublingual and injection use of buprenorphine (u=1.516, P>0.05). CONCLUSION: Both physical and psychic dependence of buprenorphine were low.%目的:调查评价阿片滥用人群中丁丙诺啡(buprenorphine,Bup)的药物依赖性及滥用潜力.方法:采用询问调查方法,对戒毒机构收治的阿片依赖者进行Bup使用情况、药物依赖性及滥用潜力的调查.被调查对象为使用Bup 3天

  7. Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the Cape ground squirrel (Xerus inauris

    Directory of Open Access Journals (Sweden)

    K. E. Joubert

    2011-04-01

    Full Text Available The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6±9.2 μg/kg, ketamine 13.6±1.9 mg/kg and buprenorphine 0.5±0.06 μg/kg. Induction time was 3.1 ± 1.4 min. This produced surgical anaesthesia for 21± 4.2 min. Atipamezole 232±92 μg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 ± 2.2 min.

  8. Simultaneous quantification of buprenorphine, naloxone and phase I and II metabolites in plasma and breastmilk by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Swortwood, Madeleine J; Scheidweiler, Karl B; Barnes, Allan J; Jansson, Lauren M; Huestis, Marilyn A

    2016-05-13

    Opioid abuse during pregnancy is associated with fetal growth restriction, placental abruption, preterm labor, fetal death, and Neonatal Abstinence Syndrome. Current guidelines for medication-assisted opioid addiction treatment during pregnancy are methadone or buprenorphine monotherapy. Buprenorphine/naloxone combination therapy (Suboxone(®)) has not been thoroughly evaluated during pregnancy and insufficient naloxone safety data exist. While methadone- and buprenorphine-treated mothers are encouraged to breastfeed, no studies to date investigated naloxone concentrations during breastfeeding following Suboxone administration. For this reason, we developed and fully validated a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of buprenorphine, buprenorphine-glucuronide, norbuprenorphine, norbuprenorphine-glucuronide, naloxone, naloxone-glucuronide and naloxone-N-oxide in 100μL human plasma and breastmilk in a single injection following protein precipitation and solid-phase extraction. Lowest limits of quantification were 0.1-2μg/L with 20-100μg/L upper limits of linearity. Bias and imprecision were <±16%. Matrix effects ranged from -57.9 to 11.2 and -84.6 to 29.3% in plasma and breastmilk, respectively. All analytes were stable (within ±20% change from baseline) under all tested conditions (24h room temperature, 72h at 4°C, 3 freeze/thaw cycles at -20°C, and in the autosampler for 72h at 4°C). For proof of concept, buprenorphine and its metabolites were successfully quantified in authentic positive maternal and infant plasma and paired breastmilk specimens. This comprehensive, highly sensitive and specific method detects multiple buprenorphine markers in a small specimen volume. PMID:27083254

  9. Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry

    OpenAIRE

    Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2010-01-01

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3′-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strat...

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

    Science.gov (United States)

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

    2011-01-01

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

  11. Comparison of the effects of buprenorphine, oxymorphone hydrochloride, and ketoprofen for postoperative analgesia after onychectomy or onychectomy and sterilization in cats.

    Science.gov (United States)

    Dobbins, Stephanie; Brown, Nancy O; Shofer, Frances S

    2002-01-01

    In this prospective, randomized, blinded study, 68 clinically healthy cats that had onychectomy (n = 20), onychectomy and castration (n = 20), or onychectomy and ovariohysterectomy (n = 28) were randomly assigned to one of four postoperative analgesic treatment groups: buprenorphine (0.01 mg/kg body weight, intramuscularly [IM]), oxymorphone hydrochloride (0.05 mg/kg body weight, IM), ketoprofen (2 mg/kg body weight, IM), and placebo (physiological saline). Sedation scores, visual analog pain scores, cumulative pain scores, serum cortisol concentration, and appetite were used to assess postoperative analgesic effect. Buprenorphine demonstrated the highest efficacy with the lowest cumulative pain scores and serum cortisol levels. PMID:12428880

  12. [Is the availability of buprenorphine/naloxone therapy for opioid-dependent inmates a necessity? ].

    Science.gov (United States)

    Marco, A; López-Burgos, A; García-Marcos, L; Gallego, C; Antón, J J; Errasti, A

    2013-02-01

    Agonist therapy (OAT) programs in combination with a psychosocial approach are the most effective way to prevent relapse in opioid-dependent patients. These programs reduce morbidity and risk behaviours for HIV transmission and other infections, improve quality of life and retention in treatment, and have a positive impact on antisocial behaviour. They are therefore very useful for prisoners with a history of opiate use. OATs based on buprenorphine/naloxone (B/N), along with others using methadone, are currently available in Spain. Diversified treatment offers an alternative treatment for opioid dependence that is more personalized and tailored to the patient's characteristics. As regards effectiveness, both drugs are very similar, but B/N shows a better safety profile and fewer drug-drug interactions and can be dispensed in pharmacies once the patient is released, which can assist with the patient' social reintegration. B/N treatment is more expensive than methadone. It is advisable to have different modes of OAT. These should be prescribed according to the characteristics and needs of each case, without incarceration impeding the right to drug treatment, which should be similar to that performed outside prison. PMID:24270319

  13. Stability of buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9% sodium chloride solution.

    Science.gov (United States)

    Jäppinen, A; Kokki, H; Naaranlahti, T J; Rasi, A S

    1999-12-01

    Combinations of opioids and adjuvant drug solutions are often used in clinical practice while little information is available on their microbiological or chemical stability. Currently there are no commercially available, prepacked, ready-to-use epidural or subcutaneous mixtures. Thus, epidural and subcutaneous analgesic mixtures must be prepared in the pharmacy on an as-needed basis. Such mixtures are typically used for the treatment of severe pain in cancer patients. The aim of this study was to investigate the microbiological and chemical stability of a buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9% sodium chloride solution. A high performance liquid chromatographic (HPLC) method and pH-meter were used to conduct the analyses. Antimicrobial activity of each component was studied by an agar dilution method. According to the results from the chemical and microbiological stability studies, this mixture can be stored in polypropylene (PP) syringes and polyvinyl chloride (PVC) medication cassettes for at least 30 days at either 21 degrees C or 4 degrees C, and for 16 days in PP syringes at 36 degrees C, and for 9 days in PVC medication cassettes at 36 degrees C. PMID:10658237

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

    Science.gov (United States)

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

    2016-08-01

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

  15. Issues pertaining to the analysis of buprenorphine and its metabolites by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Wang, Yu-Shan; Lin, Dong-Liang; Yang, Shu-Ching; Wu, Meng-Yan; Liu, Ray H; Su, Lien-Wen; Cheng, Pai-Sheng; Liu, Chiareiy; Fuh, Ming-Ren

    2010-03-01

    "Substitution therapy" and the use of buprenorphine (B) as an agent for treating heroin addiction continue to gain acceptance and have recently been implemented in Taiwan. Mature and widely utilized gas chromatography-mass spectrometry (GC-MS) technology can complement the low cost and highly sensitive immunoassay (IA) approach to facilitate the implementation of analytical tasks supporting compliance monitoring and pharmacokinetic/pharmacogenetic studies. Issues critical to GC-MS analysis of B and norbuprenorphine (NB) (free and as glucuronides), including extraction, hydrolysis, derivatization, and quantitation approaches were studied, followed by comparing the resulting data against those derived from IA and two types of liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Commercial solid-phase extraction devices, highly effective for recovering all metabolites, may not be suitable for the analysis of free B and NB; acetyl-derivatization products exhibit the most favorable chromatographic, ion intensity, and cross-contribution characteristics for GC-MS analysis. Evaluation of IA, GC-MS, and LC-MS/MS data obtained in three laboratories has proven the 2-aliquot GC-MS protocol effective for the determination of free B and NB and their glucuronides. PMID:20122691

  16. COMPARATIVE STUDY BETWEEN EPIDURAL BUPIVACAINE WITH BUPRENORPHINE AND EPIDURAL BUPIVACAINE FOR POST - OPERATIVE ANALGESIA IN ABDOMINAL AND LOWER LIMB SURGERY

    Directory of Open Access Journals (Sweden)

    Nagesh

    2015-02-01

    Full Text Available Epidural administration of various analgesics gained increasing popularity following the discovery of opioid receptors in the spinal cord capable of producing potent analgesia. This effect seems to be greatest when epidural anaesthesia in continued in the post - operative period as epidural analgesia . It is now clear that epidural administration of opioids. Ours was a comparative study between epidural bupivacaine with buprenorphine and epidural bupivacaine for post - operative analgesia in abdominal and lower limb surgery. METHODS: 60 patients undergoing lower abdominal and lower limb surgeries of either sex with ASA grade 1 and 2 a ged between 20 and 60 years for divided into two groups. After completion of the surgery and when the effect of local anaesthetic wears of and the patients complains of pain the intended study drugs were given when visual analogue pain score touched 5 cm m ark. Group – A: Patients received 8ml of 0.25% bupivacaine + 0.15mg of buprenorphine. Group – B: patients received 0.25% of bupivacaine alone. In the post - operative period the following parameters were studied , 1. Onset of analgesia , 2. Duration of analges ia , 3. Vital parameters such as heart beat , blood pressure , respiratory rate , sedation score and visual analogue score were recorded , 4. Side effects like nausea , vomiting , hypotension , respiratory depression , and pruritus allergic reaction were looked for . RESULTS: It is observed that onset of analgesia in Group A (0.25% bupivacaine + 0.15mg buprenorphine was 7.35 min. When compared to Group B which 15.5 min , which is statically significant (P<0.05. Duration of analgesia in Group A is 17.23 hrs compared to Group B , which is 5.2 hrs , this is statically significant (P<0.05. Visual analogue scale was reduced in Group A compared to Group B CONCLUSIONS: Addition of buprenorphine to bupivacaine by epidural injection for post - operative analgesia improves the on set , The duration and the

  17. Improved HIV and Substance Abuse Treatment Outcomes for Released HIV-Infected Prisoners: The Impact of Buprenorphine Treatment

    OpenAIRE

    Springer, Sandra Ann; Chen, Shu; Altice, Frederick L.

    2010-01-01

    HIV-infected prisoners fare poorly after release. Though rarely available, opioid agonist therapy (OAT) may be one way to improve HIV and substance abuse treatment outcomes after release. Of the 69 HIV-infected prisoners enrolled in a randomized controlled trial of directly administered antiretroviral therapy, 48 (70%) met DSM-IV criteria for opioid dependence. Of these, 30 (62.5%) selected OAT, either as methadone (N = 7, 14.5%) or buprenorphine/naloxone (BPN/NLX; N = 23, 48.0%). Twelve-week...

  18. Poly-substance use and antisocial personality traits at admission predict cumulative retention in a buprenorphine programme with mandatory work and high compliance profile

    DEFF Research Database (Denmark)

    Öhlin, Leif; Hesse, Morten; Fridell, Mats;

    2011-01-01

    . In this study the structure was reinforced by the addition of supervised urine samples three times a week and mandatory daily work/structured education activities as a prerequisite of inclusion in the program. Methods Of 128 patients consecutively admitted to buprenorphine maintenance treatment five...

  19. Antidepressant-like Effects of Buprenorphine are Mediated by Kappa Opioid Receptors.

    Science.gov (United States)

    Falcon, Edgardo; Browne, Caroline A; Leon, Rosa M; Fleites, Vanessa C; Sweeney, Rachel; Kirby, Lynn G; Lucki, Irwin

    2016-08-01

    Previous studies have identified potential antidepressant effects of buprenorphine (BPN), a drug with high affinity for mu opioid receptor (MORs) and kappa opioid receptors (KORs) and some affinity at delta opioid receptor (DOR) and opioid receptor-like 1 (ORL-1) receptors. Therefore, these studies examined which opioid receptors were involved in BPN's effects on animal behavior tests sensitive to antidepressant drugs. The acute effects of BPN were tested in the forced swim test (FST) using mice with genetic deletion of individual opioid receptors or after pharmacological blockade of receptors. For evaluating the effects of BPN on chronic stress, separate groups of mice were exposed to unpredictable chronic mild stress (UCMS) for 3 weeks and treated with BPN for at least 7 days before behavioral assessment and subsequent measurement of Oprk1, Oprm1, and Pdyn mRNA expression in multiple brain regions. BPN did not reduce immobility in mice with KOR deletion or after pretreatment with norbinaltorphimine, even though desipramine remained effective. In contrast, BPN reduced immobility in MOR and DOR knockout mice and in mice pretreated with the ORL-1 antagonist JTC-801. UCMS reduced sucrose preference, decreased time in the light side of the light/dark box, increased immobility in the FST and induced region-specific alterations in Oprk1, Oprm1, and PDYN mRNA expression in the frontal cortex and striatum. All of these changes were normalized following BPN treatment. The KOR was identified as a key player mediating the effects of BPN in tests sensitive to antidepressant drugs in mice. These studies support further development of BPN as a novel antidepressant. PMID:26979295

  20. Antidepressant-like Effects of Buprenorphine in Rats Are Strain Dependent

    Science.gov (United States)

    Browne, Caroline A.; van Nest, Duncan; Lucki, Irwin

    2014-01-01

    The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains. PMID:25453747

  1. Long-term administration of high doses of transdermal buprenorphine in cancer patients with severe neuropathic pain

    Science.gov (United States)

    Leppert, Wojciech; Kowalski, Grzegorz

    2015-01-01

    Background Buprenorphine is often administered by the transdermal route (transdermal buprenorphine [TB]) in cancer patients with severe neuropathic pain. However, high doses of TB of 140 µg/h are rarely used. Patients and methods Three cancer patients with severe neuropathic Numeric Rating Scale (NRS) pain scores of 8–10 who were successfully treated with high doses of TB up to 140 µg/h along with other opioids and adjuvant analgesics. Results TB was administered for a long period of follow-up (9 months to 4 years, including 34–261 days of treatment with the dose of 140 µg/h), which allowed achievement of satisfactory analgesia (NRS 3–5) and good treatment tolerance. In all three patients, TB dose was gradually titrated from 35 to 140 µg/h, and all patients used morphine at least for some time for breakthrough and background pain management along with adjuvant analgesics. Two patients continued the treatment with TB until the end of life, and one patient is still receiving the treatment. Conclusion TB at doses of up to 140 µg/h in cancer patients with severe neuropathic pain seems to be effective and safe in combination with other opioids and with adjuvant analgesics, and may significantly improve patients’ quality of life. Clinical studies may explore higher than maximal 140 µg/h TB doses recommended by a manufacturer, and also in combination with other opioids and adjuvant analgesics. PMID:26675083

  2. Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Concheiro, Marta; Shakleya, Diaa M; Huestis, Marilyn A

    2011-04-01

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3'-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1-1,000 ng/patch, except EME 5-1,000 ng/patch. Intra-, inter-day and total imprecision were metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

  3. Simultaneous determination of opiates, methadone, buprenorphine and metabolites in human urine by superficially porous liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lin, Huei-Ru; Chen, Chin-Lun; Huang, Chieh-Liang; Chen, Shao-Tsu; Lua, Ahai-Chuang

    2013-04-15

    For monitoring compliance of methadone or buprenorphine maintenance patient, a method for the simultaneous determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, opiates (morphine, codeine, 6-monoacetylmorphine) in urine by superficially porous liquid chromatography tandem mass spectrometry was developed and validated. After enzyme digestion and liquid-liquid extraction, reverse-phase separation was achieved in 5.2 min and quantification was performed by multiple reaction monitoring. Chromatographic separation was performed at 40 °C on a reversed phase Poroshell column with gradient elution. The mobile phase consisted of water and methanol, each containing 0.1% formic acid, at a flow rate of 0.32 mL/min. Intra-day and inter-day precision were less than 12.1% and accuracy was between -9.8% and 13.7%. Extraction efficiencies were more than 68%. Although ion suppression was detected, deuterated internal standards compensated for these effects. Carryover was minimal, less than 0.20%. All analytes were stable at room temperature for 16 h, 4 °C for 72 h, and after three freeze-thaw cycles. The assay also fulfilled compound identification criteria in accordance with the European Commission Decision 2002/657/EC. We analyzed 62 urine samples from patients received maintenance therapy and found that 54.8% of the patient samples tested were detected for morphine, codeine, or 6-monoacetylmorphine. This method provides a reliable and simultaneous quantification of opiates, maintenance drugs, and their metabolites in urine samples. It facilitates the routine monitoring in individuals prescribed the drug to ensure compliance and help therapeutic process. PMID:23507455

  4. Opioid receptor imaging and displacement studies with [6-O-[11C]methyl]buprenorphine in baboon brain

    International Nuclear Information System (INIS)

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[11C]methyl]buprenorphine ([11C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% ± 2.2% and 43% ± 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [11C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (11C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi

  5. Opioid receptor imaging and displacement studies with [6-O-[11C] methyl]buprenorphine in baboon brain.

    Science.gov (United States)

    Galynker, I; Schlyer, D J; Dewey, S L; Fowler, J S; Logan, J; Gatley, S J; MacGregor, R R; Ferrieri, R A; Holland, M J; Brodie, J; Simon, E; Wolf, A P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[11C]methyl]buprenorphine ([11C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% +/- 2.2% and 43% +/- 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [11C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [11C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi. PMID:8782244

  6. Opioid receptor imaging and displacement studies with [6-O-[{sup 11}C]methyl]buprenorphine in baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Galynker, Igor; Schlyer, David J.; Dewey, Stephen L.; Fowler, Joanna S.; Logan, Jean; Gatley, S. John; MacGregor, Robert R.; Ferrieri, Richard A.; Holland, M. J.; Brodie, Jonathan; Simon, Eric; Wolf, Alfred P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[{sup 11}C]methyl]buprenorphine ([{sup 11}C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% {+-} 2.2% and 43% {+-} 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [{sup 11}C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [{sup 11}C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi.

  7. Satisfaction, adherence and health-related quality of life with transdermal buprenorphine compared with oral opioid medications in the usual care of osteoarthritis pain

    OpenAIRE

    Conaghan, Philip G; Serpell, Michael; McSkimming, Paula; Junor, Rod; Dickerson, Sara

    2016-01-01

    Background: Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. Methods: Patients in the UK with self-repor...

  8. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    Science.gov (United States)

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. PMID:27473985

  9. Cross-reactivity of the CEDIA buprenorphine assay in drugs-of-abuse screening: influence of dose and metabolites of opioids

    OpenAIRE

    Berg, Jon

    2015-01-01

    Jon Andsnes Berg,1 Jan Schjøtt,1,2 Kjell O Fossan,1 Bettina Riedel1,21Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, 2Faculty of Medicine and Dentistry, Department of Clinical Science, University of Bergen, Bergen, NorwayPurpose: The cloned enzyme donor immunoassay (CEDIA) for buprenorphine is applied for both urine drugs-of-abuse screening and compliance monitoring. Sensitivity, specificity, and optimal cutoff of this assay ha...

  10. Cross-reactivity of the CEDIA buprenorphine assay in drugs-of-abuse screening: influence of dose and metabolites of opioids

    OpenAIRE

    Berg JA; Schjøtt J; Fossan KO; Riedel B

    2015-01-01

    Jon Andsnes Berg,1 Jan Schjøtt,1,2 Kjell O Fossan,1 Bettina Riedel1,21Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, 2Faculty of Medicine and Dentistry, Department of Clinical Science, University of Bergen, Bergen, NorwayPurpose: The cloned enzyme donor immunoassay (CEDIA) for buprenorphine is applied for both urine drugs-of-abuse screening and compliance monitoring. Sensitivity, specificity, and optimal cutoff of this assay have d...

  11. Satisfaction, adherence and health-related quality of life with transdermal buprenorphine compared with oral opioid medications in the usual care of osteoarthritis pain

    OpenAIRE

    Conaghan, Philip G.; Serpell, Michael; McSkimming, Paula; Junor, Rod; Dickerson, Sara

    2016-01-01

    Background Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. Methods Patients in the UK with self-reported knee and/o...

  12. Comparative study of bupivacaine alone and bupivacaine along with buprenorphine in axillary brachial plexus block: a prospective, randomized, single blind study

    OpenAIRE

    Kinjal S. Sanghvi; Vibhuti A. Shah; Kirti D. Patel

    2013-01-01

    Background: Different additives have been used to prolong brachial plexus block. We performed a prospective, randomized single-blind study to compare Bupivacaine alone and Bupivacaine along with Buprenorphine for onset, quality, and duration of block as well as post-operative analgesia and any complication in axillary brachial- plexus block. Methods: Randomized controlled study was carried out among 60 patients of either sex, aged 20-60 years. ASA grade I or II undergoing elective hand, forea...

  13. 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.

    OpenAIRE

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

    2013-01-01

    International audience 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/...

  14. High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry

    OpenAIRE

    Concheiro, Marta; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

    2010-01-01

    A method for simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), morphine, codeine, 6-acetylmorphine (6AM), heroin, 6-acetylcodeine (6AC), nicotine, cotinine, and trans-3′-hydroxycotinine (OH-cotinine) by liquid chromatography tandem mass spectrometry in oral fluid (OF) was developed and extensively valida...

  15. Azole antifungal inhibition of buprenorphine, methadone and oxycodone in vitro metabolism.

    Science.gov (United States)

    Moody, David E; Liu, Fenyun; Fang, Wenfang B

    2015-06-01

    Opioid-related mortality rates have escalated. Drug interactions may increase blood concentrations of the opioid. We therefore used human liver microsomes (HLMs) and cDNA-expressed human cytochrome P450s (rCYPs) to study in vitro inhibition of buprenorphine metabolism to norbuprenorphine (CYP3A4 and 2C8), oxycodone metabolism to noroxycodone (CYP3A4 and 2C18) and oxymorphone (CYP2D6), and methadone metabolism to R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP; CYP3A4 and 2B6). In this study, we have examined the inhibitory effect of 12 (mostly antifungal) azoles. These compounds have a wide range of solubility; to keep organic solvent ≤1%, there was an equally wide range of highest concentration tested (e.g., itraconazole 5 µM to fluconazole 1000 µM). Inhibitors were first incubated with HLMs at three concentrations with or without preincubation of inhibitor with reducing equivalents to also screen for time-dependent inhibition (TDI). Posaconazole displayed evidence of TDI; metronidazole and albendazole had no significant effect. Azoles were next screened at the highest achievable concentration for non-CYP3A4 pathways. IC50 values (µM) were determined for most CYP3A4 pathways (ranges) and other pathways as dictated by screen results: clotrimazole (0.30 - 0.35; others >30 µM); econazole (2.2 - 4.9; 2B6 R-EDDP - 9.5, S-EDDP - 6.8; 2C8 - 6.0; 2C18 - 1.0; 2D6 - 1.2); fluconazole (7.7 - 66; 2B6 - 313, 361; 2C8 - 1240; 2C18 - 17; 2D6 - 1000); itraconazole (2.5 to >5; others >5); ketoconazole (0.032 - 0.094; 2B6 - 12, 31; 2C8 - 78; 2C18 - 0.98; 2D6 - 182); miconazole (2.3 - 7.6; 2B6 - 2.8, 2.8; 2C8 - 5.3; 2C18 - 3.1; 2D6 - 5.9); posaconazole (3.4 - 20; 2C18 - 3.8; others >30); terconazole (0.48 to >10; 2C18 - 8.1; others >10) and voriconazole (0.40 - 15; 2B6 - 2.4, 2.5; 2C8 - 170; 2C18 - 13; 2D6 >300). Modeling based on estimated Ki values and plasma concentrations from the literature suggest that the orally administered azoles, particularly

  16. Development and validation of a HPLC method for the determination of buprenorphine hydrochloride, naloxone hydrochloride and noroxymorphone in a tablet formulation.

    Science.gov (United States)

    Mostafavi, Ali; Abedi, Ghazaleh; Jamshidi, Ahmad; Afzali, Daryoush; Talebi, Mohammad

    2009-02-15

    A simple isocratic reversed-phase high-performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous determination of buprenorphine hydrochloride, naloxone hydrochloride dihydrate and its major impurity, noroxymorphone, in pharmaceutical tablets. The chromatographic separation was achieved with 10 mmol L(-1) potassium phosphate buffer adjusted to pH 6.0 with orthophosphoric acid and acetonitrile (17:83, v/v) as mobile phase, a C-18 column, Perfectsil Target ODS3 (150 mm x 4.6mm i.d., 5 microm) kept at 35 degrees C and UV detection at 210 nm. The compounds were eluted isocratically at a flow rate of 1.0 mL min(-1). The average retention times for naloxone, noroxymorphone and buprenorphine were 2.4, 3.8 and 8.1 min, respectively. The method was validated according to the ICH guidelines. The validation characteristics included accuracy, precision, linearity, range, specificity, limit of quantitation and robustness. The calibration curves were linear (r>0.996) over the concentration range 0.22-220 microg mL(-1) for buprenorphine hydrochloride and 0.1-100 microg mL(-1) for naloxone hydrochloride dihydrate and noroxymorphone. The recoveries for all three compounds were above 96%. No spectral or chromatographic interferences from the tablet excipients were found. This method is rapid and simple, does not require any sample preparation and is suitable for routine quality control analyses. PMID:19084658

  17. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals

    Directory of Open Access Journals (Sweden)

    Rapeli Pekka

    2009-04-01

    Full Text Available Abstract Background Opioid-substitution treatment (OST for opioid dependence (OD has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST. Methods Within the first two months (T1 and between 6–9 months (T2 after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone- and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions. Results Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine-only patients leaving 12 patients to

  18. Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence

    Directory of Open Access Journals (Sweden)

    Santosh Ramdurg

    2015-01-01

    Full Text Available Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30 and naltrexone (n = 30 maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05 there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

  19. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

    Directory of Open Access Journals (Sweden)

    Sandra A Springer

    Full Text Available INTRODUCTION: HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD. METHODS: From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups. RESULTS: The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS. CONCLUSIONS: In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

  20. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification

    Directory of Open Access Journals (Sweden)

    Dalton Richard

    2007-01-01

    Full Text Available Abstract Background In the United Kingdom (UK, there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons. Methods/Design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.

  1. Opioid substitution treatment with sublingual buprenorphine in Manipur and Nagaland in Northeast India: what has been established needs to be continued and expanded

    Directory of Open Access Journals (Sweden)

    Sharma Charan

    2009-02-01

    Full Text Available Abstract Manipur and Nagaland in northeast India report an antenatal HIV prevalence of > 1% and the current HIV prevalence among injecting drug users is 24% and 4.5% respectively. Through support from DFID's Challenge Fund, Emmanuel Hospital Association (EHA established thirteen drop-in-centres across the two states to deliver opioid substitution treatment with sublingual buprenorphine for 1200 injecting drug users. Within a short span of time the treatment has been found to be attractive to the clients and currently 1248 injecting opioid users are receiving opioid substitution treatment. The project is acceptable to the drug users, the families, the communities, religious as well as the militant groups. The treatment centres operate all days of the week, have trained staff members, utilize standardized protocols and ensure a strict supervised delivery system to prevent illicit diversion of buprenorphine. The drug users receiving the substitution treatment are referred to HIV voluntary counselling and testing. As this treatment has the potential to change HIV related risk behaviours, what has been established in the two states needs to be continued and expanded with the support from the Government of India.

  2. Buprenorphine and norbuprenorphine quantification in human plasma by simple protein precipitation and ultra-high performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lüthi, Guillaume; Blangy, Valeria; Eap, Chin B; Ansermot, Nicolas

    2013-04-15

    A highly sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantification of buprenorphine and its major metabolite norbuprenorphine in human plasma. In order to speed up the process and decrease costs, sample preparation was performed by simple protein precipitation with acetonitrile. To the best of our knowledge, this is the first application of this extraction technique for the quantification of buprenorphine in plasma. Matrix effects were strongly reduced and selectivity increased by using an efficient chromatographic separation on a sub-2 μm column (Acquity UPLC BEH C18 1.7 μm, 2.1×50 mm) in 5 min with a gradient of ammonium formate 20 mM pH 3.05 and acetonitrile as mobile phase at a flow rate of 0.4 ml/min. Detection was made using a tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring. The procedure was fully validated according to the latest Food and Drug Administration guidelines and the Société Française des Sciences et Techniques Pharmaceutiques. Very good results were obtained by using a stable isotope-labeled internal standard for each analyte, to compensate for the variability due to the extraction and ionization steps. The method was very sensitive with lower limits of quantification of 0.1 ng/ml for buprenorphine and 0.25 ng/ml for norbuprenorphine. The upper limit of quantification was 250 ng/ml for both drugs. Trueness (98.4-113.7%), repeatability (1.9-7.7%), intermediate precision (2.6-7.9%) and internal standard-normalized matrix effects (94-101%) were in accordance with international recommendations. The procedure was successfully used to quantify plasma samples from patients included in a clinical pharmacogenetic study and can be transferred for routine therapeutic drug monitoring in clinical laboratories without further development. PMID:23357637

  3. Buprenorphine Transdermal Patch

    Science.gov (United States)

    ... other condition that caused high pressure inside your skull; biliary tract disease; slowed heartbeat; low blood pressure; ... overdose may include the following: small, pinpoint pupils (black circles in the center of the eye) extreme ...

  4. Efeitos cardiorrespiratórios da buprenorfina em cães anestesiados pelo desfluorano Cardiorespiratory effects of buprenorphine in dogs anesthetized with desflurane

    Directory of Open Access Journals (Sweden)

    Almir Pereira de Souza

    2005-12-01

    Full Text Available Objetivou-se, com este estudo, avaliar os efeitos da buprenorfina sobre variáveis cardiovasculares e respiratórias em cães durante anestesia com desfluorano. Para tanto, foram utilizados 20 cães adultos, distribuídos em dois grupos (GB e GC. A anestesia foi induzida com propofol (8mg kg-1 IV e em seguida os animais foram intubados com sonda de Magill, a qual foi conectada ao aparelho de anestesia para administração de desfluorano (1,5 CAM. Após 30 minutos, foi aplicado no GB buprenorfina (0,02mg kg-1 e no GC solução de NaCl à 0,9% (0,05ml kg-1. Avaliaram-se: freqüências cardíaca e respiratória (FC e ¦; pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM; débito cardíaco (DC; pressão venosa central (PVC; e as variáveis hemogasométricas pH, PaCO2, PaO2, HCO3, SatO2 e DB. As colheitas dos dados foram feitas aos 30 minutos após o início da administração do desfluorano (MO, 15 minutos após a administração do opióide ou placebo (M15, e a cada 15 minutos após Ml5 (M30, M45, M60 e M75. A avaliação estatística dos dados foi efetuada por meio de Análise de Perfil (P¦ e o pH tiveram reduções no GB, enquanto a PaCO2 esteve aumentada. Concluiu-se que a inclusão da buprenorfina durante anestesia inalatória pelo desfluorano determina discretas alterações cardiovasculares, bem-como potencializa a hipoventilação promovida pelo desfluorano, com a manifestação de hipercapnia, o que não contra-indica o seu uso em pacientes estáveis.The aim of this study was to evaluate the effects of buprenorphine on cardiovascular and respiratory variables in dogs anesthetized with desflurane. Twenty adult healthy male and female mongrel dogs were randomly distributed in two groups of ten animals each (GB and GC. The anesthetic induction was done using propofol (8mg kg-1, IV, and immediately, the dogs were intubated and submited to desflurane anesthesia administrated at 1.5 MAC. After 30 minutes of induction, animals

  5. Analgesia after feline ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia with buprenorphine or butorphanol, and carprofen or meloxicam: a prospective, randomised clinical trial.

    Science.gov (United States)

    Polson, Sally; Taylor, Polly M; Yates, David

    2012-08-01

    One hundred female cats undergoing routine ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia were included in a blinded, randomised, prospective clinical study to compare postoperative analgesia produced by four analgesic drug combinations given preoperatively (n = 25 per group). A secondary aim was to assess the effects in kittens and pregnant animals. Buprenorphine 180 µg/m(2) or butorphanol 6 mg/m(2) were given with either carprofen 4 mg/kg (groups BUPC and BUTC, respectively) or meloxicam 0.3 mg/kg (groups BUPM or BUTM, respectively). Medetomidine was not antagonised. A simple, descriptive scale (SDS; 0-4), a dynamic and interactive visual analogue scale (DIVAS; 0-100 mm) and mechanical nociceptive thresholds (MT; 2.5-mm diameter probe) were used to evaluate postoperative pain. All pain scores were low (DIVAS 10 N) and there were no significant differences between the groups. It was concluded that all protocols provided adequate analgesia and when used with midazolam-medetomidine-ketamine are effective for routine feline ovariohysterectomy. PMID:22505603

  6. Efeitos antinociceptivos e sedativos da buprenorfina, da acepromazina ou da associação buprenorfina e acepromazina em gatos Antinociceptive and sedative effects of buprenorphine, acepromazine, or combination of both, in conscious cats

    Directory of Open Access Journals (Sweden)

    Luciana Alvarez Santana

    2010-10-01

    Full Text Available O efeito antinociceptivo da buprenorfina tem sido relatado em cães e gatos. No presente estudo, avaliou-se o limiar nociceptivo mecânico em felinos tratados com buprenorfina, acepromazina ou ambas associadas e foram comparados os efeitos antinociceptivos e sedativos da associação em relação ao uso isolado desses fármacos determinados pelo mesmo observador, por meio de analgesiômetro e da escala analógica visual dinâmica interativa (DIVAS, respectivamente. Os oito animais empregados no estudo foram previamente familiarizados com os procedimentos utilizados. Após quatro mensurações basais, foram administrados, por via intramuscular, 0,02mg kg-1 de buprenorfina, 0,06mg kg-1 de acepromazina ou 0,01mg kg-1 de buprenorfina associada a 0,03mg kg-1 de acepromazina, em um estudo cego, com delineamento em quadrado latino e tratamento semanal. Os efeitos antinociceptivos e sedativos foram avaliados aos 15, 30, 45 minutos e uma, duas, três, quatro, seis, oito e 12 horas após a administração do tratamento. O limiar nociceptivo mecânico se elevou significativamente apenas no grupo tratado com a associação buprenorfina-acepromazina (entre 45 minutos e uma hora. Em relação à sedação, nos grupos tratados com acepromazina e com a associação, os valores da DIVAS foram significativamente maiores, respectivamente, de 15 minutos até quatro horas e de 15 minutos até três horas pós-tratamento, não apresentando elevação desses valores com a buprenorfina. Concluiu-se que não foi possível verificar a superioridade da neuroleptoanalgesia em relação ao uso dos fármacos isoladamente.The antinociceptive effects of buprenorphine have been reported in dogs and cats. This study evaluated changes in the mechanical nociceptive threshold and the sedative effects of buprenorphine, acepromazine and its combination in cats, determined by the same observer using a nociceptive threshold testing device and DIVAS, respectively. Eight animals were

  7. Clinical observation of preventive effect of buprenorphine on shivering following Spinal anesthesia%布托啡诺预防脊髓麻醉后寒战反应的临床观察

    Institute of Scientific and Technical Information of China (English)

    郭瑶; 李妍; 黄威; 孟凌新

    2012-01-01

    目的 观察布托啡诺对脊髓麻醉后寒战反应发生的预防作用.方法 选择ASA I~Ⅱ级择期行子宫全切或次全切除患者90例,随机分为3组,每组30例.分别在脊髓麻醉后,切皮前静脉滴注2 mL布托啡诺0.5 mg(B1组)、布托啡诺0.3 mg(B2组)和生理盐水(C组).观察3组寒战反应及恶心、呕吐、嗜睡等不良反应的发生率.结果 B1、B2组和C组寒战例数分别为1、3、10例.B1组与其他两组相比,差异有统计学意义.结论 布托啡诺0.5 mg单次静脉注射,可以有效预防脊髓麻醉后的寒战反应.%Objective To observe the preventive effects of different doses of buprenorphine on shivering fol lowing spinal anesthesia. Methods 90 ASA Ⅰ ~ Ⅱ patients undergoing selective hysterectomy were allocated into 3 groups randomly,30 patients in each group. 2 mL of buprenorphine 0. 5 mg,buprenorphine 0. 3 mg and neutral saline were administered intravenously in the 3 groups after spinal anesthesia respectively. The incidence of shivering and side effects including nausea,vomiting and drowsiness were observed and recorded. Results There were 1 ,3,10 cases of shivering in group Bl, group B2 and group C respectively, with significant difference between group Bl and the other two groups. Conclusion Buprenorphine 0. 5 mg is effective to prevent shivering after spinal anesthesia.

  8. Patients' Beliefs About Medications are Associated with Stated Preference for Methadone, Buprenorphine, Naltrexone, or no Medication-Assisted Therapy Following Inpatient Opioid Detoxification.

    Science.gov (United States)

    Uebelacker, Lisa A; Bailey, Genie; Herman, Debra; Anderson, Bradley; Stein, Michael

    2016-07-01

    Subsequent to initial opioid detoxification, people with opioid use disorder are typically advised to engage in follow-up treatment to prevent relapse. Medication-assisted treatments (MATs) - i.e., the opioid agonist methadone (MMT) or partial agonist/antagonist, buprenorphine/naltrexone (BUP) -- are the maintenance treatment options with the best research support for positive outcomes. A third MAT, injectable extended-release naltrexone (XR-NTX), was approved by the FDA for opioid dependence in 2010 and shows promise. However, relatively few eligible patients choose to initiate one of these MATs following initial detoxification treatment. Consistent with the health belief model, we hypothesized that beliefs about 1) efficacy of each MAT; 2) safety of each MAT; and 3) perceived consistency with being drug-free would predict stated patient preferences for a particular MAT or for no MAT. We also hypothesized that perceived structural barriers (e.g., time, transportation) would decrease the likelihood of stating a preference for a given MAT. To assess these hypotheses, we surveyed 372 people undergoing inpatient opioid detoxification treatment. Results supported hypotheses for all 3 sets of patient beliefs, with the patient group stating that they preferred a particular MAT having significantly more positive beliefs about that MAT relative to other groups (p<.001). The group that preferred "no MAT" had the most negative beliefs about all MATs. Perceived structural barriers were not related to stated preferences, except that people who preferred BUP were more likely to endorse barriers to MMT than any of the other 3 groups. Notably, a relatively high proportion (32%) of participants were most interested in XR-NTX despite a lack of prior experience with this medication. These results suggest that efforts to increase MAT enrollment following detoxification might benefit from including patient beliefs as one set of factors to assess and target for change. PMID:27211996

  9. Poly-substance use and antisocial personality traits at admission predict cumulative retention in a buprenorphine programme with mandatory work and high compliance profile

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    Fridell Mats

    2011-05-01

    Full Text Available Abstract Background Continuous abstinence and retention in treatment for alcohol and drug use disorders are central challenges for the treatment providers. The literature has failed to show consistent, strong predictors of retention. Predictors and treatment structure may differ across treatment modalities. In this study the structure was reinforced by the addition of supervised urine samples three times a week and mandatory daily work/structured education activities as a prerequisite of inclusion in the program. Methods Of 128 patients consecutively admitted to buprenorphine maintenance treatment five patients dropped out within the first week. Of the remaining 123 demographic data and psychiatric assessment were used to predict involuntary discharge from treatment and corresponding cumulative abstinence probability. All subjects were administered the Structured Clinical Interview for DSM-IV-TR, and the Symptom Checklist 90 (SCL-90, the Alcohol Use Disorder Identification Test (AUDIT, the Swedish universities Scales of Personality (SSP and the Sense of Coherence Scale (SOC, all self-report measures. Some measures were repeated every third month in addition to interviews. Results Of 123 patients admitted, 86 (70% remained in treatment after six months and 61 (50% remained in treatment after 12 months. Of those discharged involuntarily, 34/62 individuals were readmitted after a suspension period of three months. Younger age at intake, poly-substance abuse at intake (number of drugs in urine, and number of conduct disorder criteria on the SCID Screen were independently associated with an increased risk of involuntary discharge. There were no significant differences between dropouts and completers on SCL-90, SSP, SOC or AUDIT. Conclusion Of the patients admitted to the programme 50% stayed for the first 12 months with continuous abstinence and daily work. Poly-substance use before intake into treatment, high levels of conduct disorder on SCID

  10. INTRATHECAL BUPRENORPHINE, CLONIDINE AND FENTANYL AS ADJUVANTS TO 0.5% HYPERBARIC BUPIVACAINE IN LOWER ABDOMINAL AND LOWER LIMB SURGERIES: A PROSPECTIVE, RANDOMIZED AND COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Rashmi

    2015-06-01

    Full Text Available BACKGROUND: Among all the spinal adjuvants, clonidine, an alpha - 2 agonist has the ability to alleviate both the somatic and visceral pain and is more potent at spinal site, favoring its neuraxial administration. OBJECTIVE: This study was done to compare the onset and duration of sensory and motor blocks, duration of analgesia, haemodynamic and adverse effects of Clonidine, buprenorhine and fentanyl used intrathecally with hyperbaric 0.5% bupuvacaine. SETTINGS & DESIGN: This prospective, randomized and comparative study included 90 ASA class 1 & 2 patients undergoing lower abdominal and lower limb surgeries under spinal anesthesia after approval from hospital ethics committee with written i nformed consent of patients. MATERIALS AND METHOD S: Patients were randomly allocated into three groups (n=30 and received 50μg of clonidine, 25μg of fentanyl and 75μg of buprenorphine respectively in group BC,BF and BB as adjuvants to 15mg of 0.5% hyperba ric bupivacaine (3.0ml. The onset time and duration of sensory and motor block, duration of analgesia, haemodynamic changes and side effects were recorded. RESULTS: The onset time of motor block and durations of sensory, motor blockade and analgesia were prolonged in - group BC as compared to group BF and BB (P.05. Group BC had lower heart rate and mean blood pressure and higher sedation score. CONCLUSION: Intr athecal Clonidine in a dose of 50μg is an effective adjuvant to local anesthetics in neuraxial blocks despite mild sedation and haemodynamic variations.

  11. Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine Infusão continua em cães fêmeas submetidas à ovariohisterectomia com midazolam/cetamina/xilazina e/ou medetomidina pré-tratadas com levomepromazina e buprenorfina

    OpenAIRE

    Fernando do Carmo Silva; Eduardo Hatschbach; Alfredo Feio da Maia Lima; Yuri Karaccas de Carvalho; Flavio Massone

    2007-01-01

    PURPOSE: To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis, myorelaxation, anesthetic quality and surgical feasibility through evaluation of possible parametric alterations and recovery quality. METHODS: 20 healthy adult females dogs, aged 3 to 5 years, body weight between 7 and 15 kg, were assigned randomly and homogenously to 2 groups of 10 animals each (n=10), group 1 (G1) and group...

  12. High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry

    Science.gov (United States)

    Concheiro, Marta; Gray, Teresa R.; Shakleya, Diaa M.

    2011-01-01

    A method for simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), morphine, codeine, 6-acetylmorphine (6AM), heroin, 6-acetylcodeine (6AC), nicotine, cotinine, and trans-3′-hydroxycotinine (OH-cotinine) by liquid chromatography tandem mass spectrometry in oral fluid (OF) was developed and extensively validated. Acetonitrile (800 μL) and OF (250 μL) were added to a 96-well Isolute-PPT+protein precipitation plate. Reverse-phase separation was achieved in 16 min and quantification was performed by multiple reaction monitoring. The assay was linear from 0.5 or 1 to 500 μg/L. Intraday, interday, and total imprecision were less than 13% (n=20), analytical recovery was 92–114% (n= 20), extraction efficiencies were more than 77% (n=5), and process efficiencies were more than 45% (n=5). Although ion suppression was detected for EME, cocaine, morphine, 6AC, and heroin (less than 56%) and enhancement was detected for BE and nicotine (less than 316%), deuterated internal standards compensated for these effects. The method was sensitive (limit of detection 0.2–0.8 μg/L) and specific (no interferences) except that 3-hydroxy-4-methoxyamphetamine interfered with AEME. No carryover was detected, and all analytes were stable for 24 h at 22 °C, for 72 h at 4 °C, and after three freeze–thaw cycles, except cocaine, 6AC, and heroin (22–97% loss). The method was applied to 41 OF specimens collected throughout pregnancy with a Salivette® OF collection device from an opioid-dependent BUP-maintained pregnant woman. BUP ranged from 0 to 7,400 μg/L, NBUP from 0 to 71 μg/L, methadone from 0 to 3 μg/L, nicotine from 32 to 5,020 μg/L, cotinine from 125 to 508 μg/L, OH-cotinine from 11 to 51 μg/L, cocaine from 0 to 419 μg/L, BE from 0 to 351 μg/L, EME from 0 to 286 μg/L, AEME from 0 to

  13. High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Concheiro, Marta; Gray, Teresa R; Shakleya, Diaa M; Huestis, Marilyn A

    2010-09-01

    A method for simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), morphine, codeine, 6-acetylmorphine (6AM), heroin, 6-acetylcodeine (6AC), nicotine, cotinine, and trans-3'-hydroxycotinine (OH-cotinine) by liquid chromatography tandem mass spectrometry in oral fluid (OF) was developed and extensively validated. Acetonitrile (800 μL) and OF (250 μL) were added to a 96-well Isolute-PPT+protein precipitation plate. Reverse-phase separation was achieved in 16 min and quantification was performed by multiple reaction monitoring. The assay was linear from 0.5 or 1 to 500 μg/L. Intraday, interday, and total imprecision were less than 13% (n = 20), analytical recovery was 92-114% (n = 20), extraction efficiencies were more than 77% (n = 5), and process efficiencies were more than 45% (n = 5). Although ion suppression was detected for EME, cocaine, morphine, 6AC, and heroin (less than 56%) and enhancement was detected for BE and nicotine (less than 316%), deuterated internal standards compensated for these effects. The method was sensitive (limit of detection 0.2-0.8 μg/L) and specific (no interferences) except that 3-hydroxy-4-methoxyamphetamine interfered with AEME. No carryover was detected, and all analytes were stable for 24 h at 22 °C, for 72 h at 4 °C, and after three freeze-thaw cycles, except cocaine, 6AC, and heroin (22-97% loss). The method was applied to 41 OF specimens collected throughout pregnancy with a Salivette® OF collection device from an opioid-dependent BUP-maintained pregnant woman. BUP ranged from 0 to 7,400 μg/L, NBUP from 0 to 71 μg/L, methadone from 0 to 3 μg/L, nicotine from 32 to 5,020 μg/L, cotinine from 125 to 508 μg/L, OH-cotinine from 11 to 51 μg/L, cocaine from 0 to 419 μg/L, BE from 0 to 351 μg/L, EME from 0 to 286

  14. Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand*

    Science.gov (United States)

    Lucas, Gregory M.; Young, Alicia; Donnell, Deborah; Richardson, Paul; Aramrattana, Apinun; Shao, Yiming; Ruan, Yuhua; Liu, Wei; Fu, Liping; Ma, Jun; Celentano, David D.; Metzger, David; Jackson, J. Brooks; Burns, David

    2014-01-01

    Background Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX. Methods We compared rates of alanine aminotransferase (ALT) elevation ≥ grade 3 (ALT ≥ 5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants. Results Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation ≥ grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations ≥ grade 2 occurred in 2% of subjects, with no significant difference between arms. Conclusions Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors. PMID:24999060

  15. Management of opioid-dependent patients: comparison of the cost associated with use of buprenorphine/naloxone or methadone, and their interactions with concomitant treatments for infectious or psychiatric comorbidities.

    Science.gov (United States)

    Roncero, Carlos; Domínguez-Hernández, Raquel; Díaz, Tomás; Fernández, José Manuel; Forcada, Rafael; Martínez, José Manuel; Seijo, Pedro; Terán, Antonio; Oyagüez, Itziar

    2015-01-01

    The objective was to estimate the annual interaction management cost of agonist opioid treatment (AOT) for opioid-dependent (OD) patients with buprenorphine-naloxone (Suboxone®) (B/N) or methadone associated with concomitant treatments for infectious (HIV) or psychiatric comorbidities. A costs analysis model was developed to calculate the associated cost of AOT and interaction management. The AOT cost included pharmaceutical costs, drug preparation, distribution and dispensing, based on intake regimen (healthcare center or take-home) and type and frequency of dispensing (healthcare center or pharmacy), and medical visits. The cost of methadone also included single-dose bottles, monthly costs of custody at pharmacy, urine toxicology drug screenings and nursing visits. Potential interactions between AOT and concomitant treatments (antivirals, antibacterials/antifungals, antipsychotics, anxiolytics, antidepressant and anticonvulsants), were identified to determine the additional use of healthcare resources for each interaction management. The annual cost per patient of AOT was €1,525.97 for B/N and €1,467.29 for methadone. The average annual cost per patient of interaction management was €257.07 (infectious comorbidities), €114.03 (psychiatric comorbidities) and €185.55 (double comorbidity) with methadone and €7.90 with B/N in psychiatric comorbidities. Total annual costs of B/N were €1,525.97, €1,533.87 and €1,533.87 compared to €1,724.35, €1,581.32 and €1,652.84 for methadone per patient with infectious, psychiatric or double comorbidity respectively.Compared to methadone, the total cost per patient with OD was lower with B/N (€47.45-€198.38 per year). This is due to the differences in interaction management costs associated with the concomitant treatment of infectious and/or psychiatric comorbidities. PMID:26437312

  16. Buprenorphine During Pregnancy Reduces Neonate Distress

    Science.gov (United States)

    ... maternal outcomes of these two medications for pregnant women who also abuse alcohol and benzodiazepines,” Dr. Jones says. “The field also ... Prevention Research Training Treatment Research Trends and Statistics Women and Drugs Drugs of Abuse ... Salts Club Drugs Cocaine Emerging Drugs ...

  17. Buprenorphine Sublingual and Buccal (opioid dependence)

    Science.gov (United States)

    ... flushes, restlessness, teary eyes, runny nose, sweating, chills, muscle pain, vomiting, or diarrhea. ... gland produces less hormone than normal); benign prostatic hypertrophy (BPH, enlargement of the prostate gland); difficulty urinating; ...

  18. Longitudinal Observation on Brain Structure in Patients with Dependence on Sublingual Buprenorphine, Scopolamine and Promethazine in Different Stages of Abstinence%丁丙诺啡舌下片合并东莨菪碱、异丙嗪药物依赖者脑灰质密度的研究

    Institute of Scientific and Technical Information of China (English)

    周旭辉; 王绪轶; 刘军; 郝伟

    2011-01-01

    目的:观察盐酸丁丙诺啡舌下片(sublingual buprenorphine)合并东莨菪碱(scopolamine)、异丙嗪(promethazine)药物依赖者(简称BSP依赖者)脑灰质密度的变化,并比较其与海洛因依赖者脑结构损害的异同.方法:采用基于像素的形态学测量(voxel-based morphometry,VBM)方法对16例BSP依赖者、20例海洛因依赖者停药第3天、第2个月的脑灰质密度进行了组间以及组内自身前后对比研究,并设立18例正常对照者.结果:与正常对照组相比,BSP滥用可导致成瘾者大脑广泛性脑结构损害,表现为灰质密度下降,涉及额叶、顶叶、颞叶、枕叶、岛叶、纹状体等脑区;与海洛因依赖组相比,停药3天BSP依赖组脑区灰质受损程度重于海洛因依赖组,且随着停药时间的延长,BSP依赖者灰质恢复进程慢于海洛因依赖者.结论:BSP滥用可造成依赖者广泛性、严重的脑皮质结构异常,主要集中在额叶等与成瘾关系密切的脑区.BSP滥用较海洛因更易损伤大脑皮质神经元,且大脑灰质恢复进程慢于海洛因依赖组,这提示BSP滥用对大脑皮质神经元的损害在短时间难以恢复.%Objective: Recently, an intravenous abuse of buprenorphine tablets, scopolamine and promethazine solution (BSP) has been emerging among heroin-dependent individuals in some areas of Southern China. The aim of this study was to explore the brain structural pathological changes in the patients with BSP dependence, by three dimensional MRI(3D)and compare their impairment of the brain with that of the heroin addicts. Methods: BSP-dependent patients(n=16), heroin-dependent individuals (n=20) and age/eduction-matched healthy control subjects (n=18) were assessed by 3D during resting state. Patients with BSP and heroin dependence were examined by MRI scanning after 3 days and 2 months of abstinence, while control subjects were tested only once. Results: Compared with health controls, GMD was significantly lower in

  19. Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine Infusão continua em cães fêmeas submetidas à ovariohisterectomia com midazolam/cetamina/xilazina e/ou medetomidina pré-tratadas com levomepromazina e buprenorfina

    Directory of Open Access Journals (Sweden)

    Fernando do Carmo Silva

    2007-08-01

    Full Text Available PURPOSE: To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis, myorelaxation, anesthetic quality and surgical feasibility through evaluation of possible parametric alterations and recovery quality. METHODS: 20 healthy adult females dogs, aged 3 to 5 years, body weight between 7 and 15 kg, were assigned randomly and homogenously to 2 groups of 10 animals each (n=10, group 1 (G1 and group 2 (G2, respectively. Animals of G1 were subjected to a pre-treatment with intravenous 1.0 mg/kg methotrimeprazine and or 3ì/kg. After 15 minutes, a 5.0 mg/kg ketamine and 0.2 mg/kg midazolam were intravenously injected. Immediately after induction, an anesthetic combination of 0.4 mg/kg/h midazolam, 20 mg/kg/h ketamine and 1.0 mg/kg/h xylazine, was continuously and intravenously administered for 30 minutes. The same techniques were used in G2 except for the substitution of xylazine for 30ìg/kg/h medetomidine. RESULTS: In G1 there was a 1st and 2nd degree atrioventricular heart block, a longer recovery period and lower quality. In G2 a 1st degree atrioventricular heart block occurred but isolated and ephemeral. CONCLUSIONS: The continuous infusion method, besides reducing drugs utilization, prevented collateral effects allowing a more tranquil recovery with no excitations, both protocols permitted the surgical procedure (ovary-hysterectomy bringing about a reduction in hypnosis and an accentuated myorelaxation. Xylazine and medetomidine showed a similar pharmacodynamic behavior but with different clinical aspects. The electrocardiographic alterations observed in G2 and in a lower degree in G1 must be well studied. Describers: dogs, ketamine, methotrimeprazine, medetomidine, midazolam and xylazine.OBJETIVO: Comparar através de infusão contínua de xilazina ou medetomidina associada à metotrimeprazina e buprenorfina, cetamina e midazolam, o grau de hipnose

  20. Avaliação algimétrica por estímulo nociceptivo térmico e pressórico em cães pré-tratados com levomepromazina, midazolam e quetamina associados ou não ao butorfanol ou buprenorfina The algimetry evaluation for thermic and pressoric nociceptive stimulus in pre treated dogs with methotrimeprazine, midazolam and ketamine associated or not with butorphanol or buprenorphine

    Directory of Open Access Journals (Sweden)

    André Leguthe Rosa

    2005-02-01

    methotrimeprazine and midazolam put on the same syringe with ketamine. The animals of GII received the same treatment of GI but associated with butorphanol and finally the animals of GIII received the same treatment of GI but associated with buprenorphine. The routine parametric evaluations has been proceeded, although using the thermo algimetry measured in °C with the average of 52°C and the pressoric algimetry in Kg. RESULTS: In the thermo algimetry, there has been significant difference in GI at the moments M0, M1, M4 and M5; in GII it was found at M0, M1, M5 and M6 and in GIII it was observed the significant at M0 and M1. It has also been shown in pressoric algimetry significant difference in GI at the moments M0, M2 and M3. Among GII it has observed significant difference at all moments and it has found at M0, M9 in GIII. Thus, it has observed significant differences between all groups; for such the M2 of GII smaller than the others; and M4, M5 of GIII bigger than GI and GII. In the assessment of all periods it was observed significant latent period bigger in GI, however, with reasonable period and short recovery in GII and GIII. In the order hand, the postural tonus recovery it was longer in GIII, followed by GII and finally GI. CONCLUSION: The used method for the measurement of algic stimulus was efficient, noticing a reasonable analgesic period of 3 hours for butorphanol and 6 hours for buprenorphine.

  1. Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans

    OpenAIRE

    Bershad, Anya K.; Jaffe, Jerome H.; Childs, Emma; de Wit, Harriet

    2014-01-01

    Preclinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the ...

  2. The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

    DEFF Research Database (Denmark)

    Jessen, L; Bjerrum, Ole Jannik; Christensen, Sten

    2007-01-01

    Postoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as...... drinking water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes....

  3. Management of opioid addiction with buprenorphine: French history and current management

    OpenAIRE

    Poloméni P; Schwan R

    2014-01-01

    Pierre Poloméni,1 Raymund Schwan2,3 1Department of Addictology, Paris Seine Saint Denis University Hospital, AP-HP, Site René Muret Sevran, France; 2Care Center for the Treatment and Prevention of Addictions (CSAPA), Nancy University Hospital, 3General Psychiatric Division for the Greater Nancy Urban Community, Psychotherapeutic Center of Nancy, Laxou, France Abstract: The way in which opioid addiction is managed in France is unique, as it is based on the prescription o...

  4. Management of chronic pain in the elderly: focus on transdermal buprenorphine

    OpenAIRE

    Vadivelu, Nalini

    2008-01-01

    Nalini Vadivelu, Roberta L HinesDepartment of Anesthesiology, Yale University School of Medicine, New Haven, USAAbstract: Chronic pain in the elderly is a significant problem. Pharmacokinetic and metabolic changes associated with increased age makes the elderly vulnerable to side effects and overdosing associated with analgesic agents. Therefore the management of chronic cancer pain and chronic nonmalignant pain in this growing population is an ongoing challenge. New routes of administration ...

  5. A new buprenorphine analogy, thenorphine,inhibits morphine-induced behavioral sensitization in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-liZHAO; Ze-huiGONG; Jian-huiLIANG

    2004-01-01

    AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the locomotor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01). Co-administration of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the development,transfer, and expression of behavioral sensitization to morphine in mice (P<0.05 or P<0.01). CONCLUSION:Thenorphine inhibited morphine-induced behavioral sensitization in mice, suggesting that thenorphine may be effective against the addiction of opioids.

  6. A new buprenorphine analogy,thenorphine,inhibits morphine-induced behavioral sensitization in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-li ZHAO; Ze-hui GONG; Jian-hui LIANG

    2004-01-01

    AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the locomotor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01).Co-administration of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the development,transfer, and expression of behavioral sensitization to morphine in mice (P<0.05 or P<0.01). CONCLUSION:Thenorphine inhibited morphine-induced behavioral sensitization in mice, suggesting that thenorphine may be effective against the addiction of opioids.

  7. The applicability of a gel delivery system for self-administration of buprenorphine to laboratory mice

    DEFF Research Database (Denmark)

    Hovard, A. M. B.; Teilmann, A. C.; Hau, J.;

    2015-01-01

    Oral administration of perioperative analgesia to laboratory mice is beneficial compared with administration by injection. The mice become less stressed when allowed to voluntarily ingest the drug in a palatable feed item and it results in high and long-lasting serum concentrations of the drug. We...... have previously demonstrated sticky nut and chocolate paste to be well-liked by mice and readily ingested in most cases. However, a disadvantage with nut and chocolate paste is its high content of fat and sugar, which may have undesirable effects in some experimental models. Alternatively, a delivery...... system using an aqueous gel may serve as a supplementary source of fluid post-operatively and as a vehicle for analgesic drugs. In the present study, we investigated the willingness of the mice to ingest a commercially available gel, by measuring the duration from introduction of the gel to first...

  8. Maternal stress and behavioral adaptation in methadone- or buprenorphine-exposed toddlers.

    Science.gov (United States)

    Sarfi, Monica; Sundet, Jon Martin; Waal, Helge

    2013-12-01

    The current study examined the relationship between early interaction, parenting stress, maternal psychological distress symptoms, and behavior problems and health-related quality of life among children born to mothers in opioid maintenance treatment (OMT) in Norway during the period 2005-2007 (N = 36). This group was compared with a normative sample of mothers without substance abuse problems and their children (N = 36). There were significant group differences (p maternal psychological well-being for child development, and underscore the need to address opioid-maintained women's personal maladjustment and the constellation of stress experienced by mothers in recovery. PMID:23999378

  9. Drug: D10250 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10250 Mixture, Drug Buprenorphine - naloxone ... mixt; Suboxone (TN) (Buprenorphine hydrochloride [ ... DR:D00836] | Buprenorphine [DR:D07132]), (Naloxone ... hydrochloride [DR:D01340] | Naloxone ... [DR:D08249]) ... Buprenorphine, combinations D10250 Buprenorphine - naloxone ... mixt USP drug classification [BR:br08302] Anti-Add ...

  10. Prescription Pain Medicines - An Addictive Path?

    Science.gov (United States)

    ... The study will test the effectiveness of buprenorphine/naloxone tablets, marketed as Suboxone, along with different models ... high or dangerous side effects. When combined with naloxone, buprenorphine's abuse potential is further limited, since those ...

  11. Manejo de buprenorfina transdérmica en pacientes que no han usado previamente opioides Transdermal buprenorphine in opioid naive patients

    Directory of Open Access Journals (Sweden)

    M. Rull

    2006-03-01

    Full Text Available Tras una breve revisión de las características de la buprenorfina transdérmica y de sus efectos secundarios, se describe el inicio del tratamiento en el paciente que previamente no ha recibido opioides.After a brief survey of the characteristics and side effects of transdermal fentanyl, its use in an opioid naive patient is described.

  12. C7β-Methyl Analogues of the Orvinols: The Discovery of Kappa Opioid Antagonists with Nociceptin/Orphanin FQ Peptide (NOP) Receptor Partial Agonism and Low, or Zero, Efficacy at Mu Opioid Receptors

    OpenAIRE

    Cueva, Juan Pablo; Roche, Christopher; Ostovar, Mehrnoosh; Kumar, Vinod; Clark, Mary J.; Hillhouse, Todd M.; Lewis, John W.; Traynor, John R.; Husbands, Stephen. M.

    2015-01-01

    Buprenorphine is a successful analgesic and treatment for opioid abuse, with both activities relying on its partial agonist activity at mu opioid receptors. However, there is substantial interest in its activities at the kappa opioid and nociceptin/orphanin FQ peptide receptors. This has led to an interest in developing compounds with a buprenorphine-like pharmacological profile but with lower efficacy at mu opioid receptors. The present article describes aryl ring analogues of buprenorphine ...

  13. Efeitos antinociceptivos e sedativos da buprenorfina, da acepromazina ou da associação buprenorfina e acepromazina em gatos Antinociceptive and sedative effects of buprenorphine, acepromazine, or combination of both, in conscious cats

    OpenAIRE

    Luciana Alvarez Santana; Stelio Pacca Loureiro Luna; Paulo Vinicius Mortensen Steagall; Tatiana Henriques Ferreira; Polly Taylor; Mike Dixon

    2010-01-01

    O efeito antinociceptivo da buprenorfina tem sido relatado em cães e gatos. No presente estudo, avaliou-se o limiar nociceptivo mecânico em felinos tratados com buprenorfina, acepromazina ou ambas associadas e foram comparados os efeitos antinociceptivos e sedativos da associação em relação ao uso isolado desses fármacos determinados pelo mesmo observador, por meio de analgesiômetro e da escala analógica visual dinâmica interativa (DIVAS), respectivamente. Os oito animais empregados no estudo...

  14. Fatal poisoning in drug addicts in the Nordic countries in 2012

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Edvardsen, Hilde Marie Erøy; Thelander, Gunilla;

    2015-01-01

    the main cause of death, but medicinal opioids like methadone, buprenorphine, fentanyl and tramadol mainly replaced heroin. Methadone was the main intoxicant in Denmark and Sweden, whereas heroin/morphine caused the most deaths in Norway. Finland differed from the other Nordic countries in that...... buprenorphine was the main intoxicant with only a few heroin/morphine and methadone deaths. Deaths from methadone, buprenorphine and fentanyl increased immensely in Sweden compared to 2007. Poly-drug use was widespread in all countries. The median number of drugs per case varied from 4 to 5. Heroin...

  15. Partnership at Drugfree.org

    Science.gov (United States)

    ... to Improve Buprenorphine Treatment in Young Adults When addiction treatment specialist Zev Schuman-Olivier, MD, found that young ... Would Place Fee on Opioid Drugs to Fund Addiction Treatment May 25, 2016 Senators: Allow Doctors to Treat ...

  16. Substance Abuse in Rural Areas

    Science.gov (United States)

    ... availability of illicit drugs, the weakening of the traditional family unit, the diminishing rural economy, and the ... that is proven to be successful in treating addiction such as the drug, buprenorphine, which is used ...

  17. Akut smertebehandling af stofbrugere i substitutionsbehandling med metadon eller buprenorfin

    DEFF Research Database (Denmark)

    Zinck, Louise; Sonne, Nan M; Madsen, Sidsel Lægdsgaard; Nikolajsen, Lone

    2015-01-01

    In Denmark, approximately 7,600 patients receive maintenance therapy with methadone or buprenorphine because of opioid addiction. These patients have an increased risk of inadequate pain treatment during hospitalization, among others because of tolerance to opioids and poor communication with the...... staff. The present article describes four common misconceptions among health-care providers that underlie inadequate pain treatment and provides practical recommendations for the analgesic management of acute pain in patients receiving methadone or buprenorphine....

  18. Do We Really Need to Continue Pharmacotherapy for Opioid Use Disorder (OUD Indefinitely?

    Directory of Open Access Journals (Sweden)

    Rajendra D. Badgaiyan

    2015-02-01

    Full Text Available It is unclear whether pharmacotherapy for opioid use disorder (OUD should be continued for short or long-term. Before introduction of buprenorphine, methadone was the primary pharmacotherapy for OUD in the United States. Because of its specific pharmacokinetic properties methadone was recommended for long-term use with some justification. Introduction of buprenorphine however has altered the treatment protocol because of milder adverse effects and withdrawal symptoms. The adverse effects of buprenorphine are milder but not negligible. Therefore, indefinite prescription is justified only if there is a significant benefit. Studies that have compared short and long-term treatment of buprenorphine protocols do not show a significant benefit of long-term treatment over relatively short-term (few months treatment protocols. Obviously, the ultra short-term treatment lasting a few days has very little or no benefit on long-term treatment of buprenorphine protocols that use buprenorphine for 3 to 9 months is comparable to that of the long-term (years to lifetime treatment without financial and medical consequences of the long-term treatment.

  19. Fatal poisoning in drug addicts in the Nordic countries in 2007

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Normann, P.T.; Ceder, G.;

    2011-01-01

    Norway and Sweden, heroin/ morphine was still the main intoxicant with a frequency of 68% and 48%, respectively. In Iceland, 3 deaths each were due to heroin/morphine and methadone, respectively. Finland differs from other Nordic countries in having a high number of poisonings caused by buprenorphine and...... very few caused by heroin/morphine. The total number of buprenorphine deaths in Finland doubled from 16 in 2002 to 32 in 2007, where it constituted 25% of deaths. The general toxicological screening program showed widespread multi-drug use in all countries. The median number of drugs per case varied...... from 3 to 5. The most frequently detected substances were heroin/morphine, methadone, buprenorphine, tramadol, amphetamine, cocaine, tetrahydrocannabinol, benzodiazepines and ethanol....

  20. Selective review and commentary on emerging pharmacotherapies for opioid addiction

    Directory of Open Access Journals (Sweden)

    Miotto K

    2011-10-01

    Full Text Available Walter Ling1, Larissa Mooney1, Min Zhao2, Suzanne Nielsen1, Matthew Torrington1, Karen Miotto1 1Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA; 2Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China Abstract: Pharmacotherapies for opioid addiction under active development in the US include lofexidine (primarily for managing withdrawal symptoms and Probuphine®, a distinctive mode of delivering buprenorphine for six months, thus relieving patients, clinicians, and regulatory personnel from most concerns about diversion, misuse, and unintended exposure in children. In addition, two recently approved formulations of previously proven medications are in early phases of implementation. The sublingual film form of buprenorphine + naloxone (Suboxone® provides a less divertible, more quickly administered, more child-proof version than the buprenorphine + naloxone sublingual tablet. The injectable depot form of naltrexone (Vivitrol® ensures consistent opioid receptor blockade for one month between administrations, removing concerns about medication compliance. The clinical implications of these developments have attracted increasing attention from clinicians and policymakers in the US and around the world, especially given that human immunodeficiency virus/acquired immunodeficiency syndrome and other infectious diseases are recognized as companions to opioid addiction, commanding more efforts to reduce opioid addiction. While research and practice improvement efforts continue, reluctance to adopt new medications and procedures can be expected, especially considerations in the regulatory process and in the course of implementation. Best practices and improved outcomes will ultimately emerge from continued development efforts that reflect input from many quarters. Keywords: buprenorphine, naltrexone, probuphine, lofexidine, implant buprenorphine, buprenorphine film

  1. Colon anastomotic leakage

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Achiam, Michael Patrick; Rosenberg, Jacob

    2014-01-01

    final successful experiment (B), eight and four absorbable sutures were used in the control and intervention anastomoses, respectively, and buprenorphine in chocolate spread was used for pain treatment. RESULTS: In the final model (experiment B), significantly more animals in the intervention group had...

  2. Easy-Access Services in Low-Threshold Opiate Agonist Maintenance

    Science.gov (United States)

    Hesse, Morten; Pedersen, Mads U.

    2008-01-01

    Background: There is currently evidence that methadone and buprenorphine maintenance is effective in reducing substance abuse. However, it is not known whether psychosocial support improves the outcome of methadone maintenance in the absence of control measures, such as regular urine testing. Materials and Methods: In a prospective observational…

  3. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS project: An open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728

    Directory of Open Access Journals (Sweden)

    Sheard Laura

    2004-04-01

    Full Text Available Abstract Background Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. Methods/design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

  4. Mechanism-based pharmacokinetic-pharmacodynamic modeling of the efficacy and safety of (semi-)synthetic opioids

    NARCIS (Netherlands)

    Yassen, Ashraf

    2007-01-01

    The objective of the investigations described in this thesis was to characterize the in vivo pharmacological and PK-PD properties of buprenorphine relative to fentanyl with respect to: 1) kinetics of onset and offset of the pharmacological effects at the mu-opioid receptor, 2) selectivity of action

  5. A Collection of NIDA NOTES. Articles That Address Research on Heroin.

    Science.gov (United States)

    National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

    Included in this document are selections of topic-specific articles on heroin research reprinted from the National Institute on Drug Abuses (NIDA) research newsletter, NIDA Notes. Titles include: Buprenorphine Taken Three Times Per Week Is as Effective as Daily Doses in Treating Heroin Addiction; 33-Year Study Finds Lifelong, Lethal Consequences…

  6. Frequent use of opioids in patients with dementia and nursing home residents

    DEFF Research Database (Denmark)

    Jensen-Dahm, Christina; Gasse, Christiane; Astrup, Aske; Mortensen, Preben Bo; Waldemar, Gunhild

    2015-01-01

    (41%), followed by home-living patients with dementia (27.5%) and home-living patients without dementia (16.9%). Buprenorphine and fentanyl (primarily patches) were commonly used among NHRs (18.7%) and home-living patients with dementia (10.7%) but less often by home-living patients without dementia...

  7. Medication-assisted therapy for opioid addiction

    OpenAIRE

    Tai, Betty; Saxon, Andrew J.; Ling, Walter

    2013-01-01

    The “Medication-Assisted Therapy for Opioid Addiction” session was chaired by Dr. Betty Tai and had three presenters. The presenters (and their topics) were: Dr. Andrew J. Saxon (Methadone and Buprenorphine for Treatment of Opioid Addiction and HIV Risk Reduction), Dr. Walter Ling (Opioid Antagonist Treatment for Opioid Addiction), and Dr. Betty Tai (Chronic Care Model for Substance Use Disorder).

  8. Managing Opioid Abuse in Older Adults: Clinical Considerations and Challenges.

    Science.gov (United States)

    Loreck, David; Brandt, Nicole J; DiPaula, Bethany

    2016-04-01

    Opioid use disorder is a public health epidemic. There is increasing attention being given to opioid abuse and overdose in the United States. The overall use of illicit substances by older adults is on the rise and in part can be attributed to the aging of Baby Boomers. Furthermore, much attention is being given to prescription opioid drug overdose, but it is important to note that heroin-related deaths have also increased sharply. Heroin use is part of a larger substance abuse problem, with more than nine in 10 individuals who use heroin also using at least one other drug (e.g., cocaine, prescription opioid medication). The current article highlights treatment approaches, namely buprenorphine, buprenorphine/naloxone, and naltrexone; insurance considerations; and resources to aid in understanding and managing this public health crisis. PMID:27027362

  9. Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healing-associated genes

    Institute of Scientific and Technical Information of China (English)

    Matt C Danzi; Dario Motti; Donna L Avison; John L Bixby; Vance P Lemmon

    2016-01-01

    Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regen-eration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientiifc goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion (DRG) sensory neurons of a panel of genes associated with wound healing. These ifndings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

  10. It’s MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system

    OpenAIRE

    Chartoff, Elena H.; Connery, Hilary S.

    2014-01-01

    Opioids selective for the G protein-coupled mu opioid receptor (MOR) produce potent analgesia and euphoria. Heroin, a synthetic opioid, is considered one of the most addictive substances, and the recent exponential rise in opioid addiction and overdose deaths has made treatment development a national public health priority. Existing medications (methadone, buprenorphine, and naltrexone), when combined with psychosocial therapies, have proven efficacy in reducing aspects of opioid addiction. U...

  11. Client and Counselor Attitudes Toward the Use of Medications for Treatment of Opioid Dependence

    OpenAIRE

    Rieckmann, Traci; Daley, Marilyn; Fuller, Bret E.; Thomas, Cindy P.; McCarty, Dennis

    2006-01-01

    Attitudes, perceived social norms and intentions were assessed for 376 counselors and 1083 clients from outpatient, methadone and residential drug treatment programs regarding four medications used to treat opiate dependence: methadone, buprenorphine, clonidine, and ibogaine. Attitudes, social norms and intentions to use varied by treatment modality. Methadone clients and counselors had more positive attitudes toward the use of methadone, while their counterparts in residential and outpatient...

  12. Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2).

    Science.gov (United States)

    Tournier, Nicolas; Chevillard, Lucie; Megarbane, Bruno; Pirnay, Stéphane; Scherrmann, Jean-Michel; Declèves, Xavier

    2010-08-01

    Drug interaction with P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may influence its tissue disposition including blood-brain barrier transport and result in potent drug-drug interactions. The limited data obtained using in-vitro models indicate that methadone, buprenorphine, and cannabinoids may interact with human P-gp; but almost nothing is known about drugs of abuse and BCRP. We used in vitro P-gp and BCRP inhibition flow cytometric assays with hMDR1- and hBCRP-transfected HEK293 cells to test 14 compounds or metabolites frequently involved in addiction, including buprenorphine, norbuprenorphine, methadone, ibogaine, cocaine, cocaethylene, amphetamine, N-methyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, nicotine, ketamine, Delta9-tetrahydrocannabinol (THC), naloxone, and morphine. Drugs that in vitro inhibited P-gp or BCRP were tested in hMDR1- and hBCRP-MDCKII bidirectional transport studies. Human P-gp was significantly inhibited in a concentration-dependent manner by norbuprenorphine>buprenorphine>methadone>ibogaine and THC. Similarly, BCRP was inhibited by buprenorphine>norbuprenorphine>ibogaine and THC. None of the other tested compounds inhibited either transporter, even at high concentration (100 microm). Norbuprenorphine (transport efflux ratio approoximately 11) and methadone (transport efflux ratio approoximately 1.9) transport was P-gp-mediated; however, with no significant stereo-selectivity regarding methadone enantiomers. BCRP did not transport any of the tested compounds. However, the clinical significance of the interaction of norbuprenorphine with P-gp remains to be evaluated. PMID:19887017

  13. Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’-diphospho-glucuronosyltransferase isoforms

    OpenAIRE

    Munirah Haron; Sabariah Ismail

    2015-01-01

    Background: Glucuronidation catalyzed by uridine 5′- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbellifero...

  14. Engagement and Substance Dependence in a Primary Care-Based Addiction Treatment Program for People Infected with HIV and People at High-Risk for HIV Infection.

    Science.gov (United States)

    Walley, Alexander Y; Palmisano, Joseph; Sorensen-Alawad, Amy; Chaisson, Christine; Raj, Anita; Samet, Jeffrey H; Drainoni, Mari-Lynn

    2015-12-01

    To improve outcomes for people with substance dependence and HIV infection or at risk for HIV infection, patients were enrolled in a primary care-based addiction treatment program from 2008-2012 that included a comprehensive substance use assessment, individual and group counseling, addiction pharmacotherapy and case management. We examined whether predisposing characteristics (depression, housing status, polysubstance use) and an enabling resource (buprenorphine treatment) were associated with engagement in the program and persistent substance dependence at 6 months. At program enrollment 61% were HIV-infected, 53% reported heroin use, 46% reported alcohol use, 37% reported cocaine use, and 28% reported marijuana use in the past 30 days, 72% reported depression, 19% were homeless, and 53% had polysubstance use. Within 6-months 60% had been treated with buprenorphine. Engagement (defined as 2 visits in first 14 days and 2 additional visits in next 30 days) occurred in 64%; 49% had substance dependence at 6-months. Receipt of buprenorphine treatment was associated with engagement (Adjusted Odds Ratio (AOR) 8.32 95% CI: 4.13-16.77). Self-reported depression at baseline was associated with substance dependence at 6-months (AOR 3.30 95% CI: 1.65-6.61). Neither housing status nor polysubstance use was associated with engagement or substance dependence. The FAST PATH program successfully engaged and treated patients in a primary care-based addiction treatment program. Buprenorphine, a partial opioid agonist, was a major driver of addiction treatment engagement. Given depression's association with adverse outcomes in this clinical population, including mental health treatment as part of integrated care holds potential to improve addiction treatment outcomes. PMID:26298399

  15. Opioids Switching with Transdermal Systems in Chronic Cancer Pain

    OpenAIRE

    Barbarisi M; Sansone P; Pota V; Pace MC; Aurilio C; Grella E; Passavanti MB

    2009-01-01

    Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switche...

  16. Violence and diversion of prescribed opioids among individuals in opioid maintenance treatment. A complementary methods study of violent crime convictions in a national cohort and qualitative interviews among prisoners

    OpenAIRE

    2015-01-01

    Background: Opioid dependence is linked to crime, morbidity and mortality, directly through drug overdoses and indirectly via drug-related mortality, accidents, suicides and violence. Violence in general is a major health concern worldwide. Opioid maintenance treatment, OMT, is found to reduce mortality, morbidity and criminal behaviour, but less is known about the effect of OMT on violent crime. A possible negative consequence of OMT is diversion of methadone and buprenorphine and rising ove...

  17. Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5′-diphospho-glucuronosyltransferase isoforms

    Directory of Open Access Journals (Sweden)

    Munirah Haron

    2015-01-01

    Full Text Available Background: Glucuronidation catalyzed by uridine 5′- diphospho-glucuronosyltransferase (UGT is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms. Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC 50 value of 6.21 ± 1.51 mM followed by buprenorphine with an IC 50 value of 73.22 ± 1.63 mM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC 50 value of 6.32 ± 1.39 mM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC 50 value of 7.13 ± 1.16 mM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC 50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 mM. Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug

  18. Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5’-diphospho-glucuronosyltransferase isoforms

    Science.gov (United States)

    Haron, Munirah; Ismail, Sabariah

    2015-01-01

    Background: Glucuronidation catalyzed by uridine 5’- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation. Objective: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms. Materials and Methods: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection. Results: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM. Conclusions: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur. PMID

  19. Pharmacotherapy for opioid dependence in jails and prisons: research review update and future directions

    Science.gov (United States)

    Sharma, Anjalee; O’Grady, Kevin E; Kelly, Sharon M; Gryczynski, Jan; Mitchell, Shannon Gwin; Schwartz, Robert P

    2016-01-01

    Purpose The World Health Organization recommends the initiation of opioid agonists prior to release from incarceration to prevent relapse or overdose. Many countries in the world employ these strategies. This paper considers the evidence to support these recommendations and the factors that have slowed their adoption in the US. Methods We reviewed randomized controlled trials (RCTs) and longitudinal/observational studies that examine participant outcomes associated with the initiation or continuation of opioid agonists (methadone, buprenorphine) or antagonists (naltrexone) during incarceration. Papers were identified through a literature search of PubMed with an examination of their references and were included if they reported outcomes for methadone, buprenorphine, or naltrexone continued during incarceration or initiated prior to release in a correctional institution. Results Fourteen studies were identified, including eight RCTs and six observational studies. One RCT found that patients treated with methadone who were continued on versus tapered off methadone during brief incarceration were more likely to return to treatment upon release. A second RCT found that the group starting methadone treatment in prison versus a waiting list was less likely to report using heroin and sharing syringes during incarceration. A third RCT found no differences in postrelease heroin use or reincarceration between individuals initiating treatment with methadone versus those initiating treatment with buprenorphine during relatively brief incarcerations. Findings from four additional RCTs indicate that starting opioid agonist treatment during incarceration versus after release was associated with higher rates of entry into community treatment and reduced heroin use. Finally, one pilot RCT showed that providing extended-release naltrexone prior to discharge resulted in significantly lower rates of opioid relapse compared to no medication. Conclusion Reasons why uptake of these

  20. Antinociceptive Interactions between the Imidazoline I2 Receptor Agonist 2-BFI and Opioids in Rats: Role of Efficacy at the μ-Opioid Receptor.

    Science.gov (United States)

    Siemian, Justin N; Obeng, Samuel; Zhang, Yan; Zhang, Yanan; Li, Jun-Xu

    2016-06-01

    Although μ-opioids have been reported to interact favorably with imidazoline I2 receptor (I2R) ligands in animal models of chronic pain, the dependence on the μ-opioid receptor ligand efficacy on these interactions had not been previously investigated. This study systematically examined the interactions between the selective I2 receptor ligand 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI) and three μ-opioid receptor ligands of varying efficacies: fentanyl (high efficacy), buprenorphine (medium-low efficacy), and 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[(3'-isoquinolyl) acetamido] morphine (NAQ; very low efficacy). The von Frey test of mechanical nociception and Hargreaves test of thermal nociception were used to examine the antihyperalgesic effects of drug combinations in complete Freund's adjuvant-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to examine the rate-suppressing effects of each drug combination. Dose-addition and isobolographical analyses were used to characterize the nature of drug-drug interactions in each assay. 2-BFI and fentanyl fully reversed both mechanical and thermal nociception, whereas buprenorphine significantly reversed thermal but only slightly reversed mechanical nociception. NAQ was ineffective in both nociception assays. When studied in combination with fentanyl, NAQ acted as a competitive antagonist (apparent pA2 value: 6.19). 2-BFI/fentanyl mixtures produced additive to infra-additive analgesic interactions, 2-BFI/buprenorphine mixtures produced supra-additive to infra-additive interactions, and 2-BFI/NAQ mixtures produced supra-additive to additive interactions in the nociception assays. The effects of all combinations on schedule-controlled responding were generally additive. Results consistent with these were found in experiments using female rats. These findings indicate that lower-efficacy μ-opioid receptor agonists may interact more favorably with I2R

  1. Effects of lidocaine constant rate infusion on sevoflurane requirement, autonomic responses, and postoperative analgesia in dogs undergoing ovariectomy under opioid-based balanced anesthesia.

    Science.gov (United States)

    Columbano, Nicolò; Secci, Fabio; Careddu, Giovanni M; Sotgiu, Giovanni; Rossi, Gabriele; Driessen, Bernd

    2012-08-01

    The effects of constant rate infusion (CRI) of lidocaine on sevoflurane (SEVO) requirements, autonomic responses to noxious stimulation, and postoperative pain relief were evaluated in dogs undergoing opioid-based balanced anesthesia. Twenty-four dogs scheduled for elective ovariectomy were randomly assigned to one of four groups: BC, receiving buprenorphine without lidocaine; FC, receiving fentanyl without lidocaine; BL, receiving buprenorphine and lidocaine; FL, receiving fentanyl and lidocaine. Dogs were anesthetized with intravenous (IV) diazepam and ketamine and anesthesia maintained with SEVO in oxygen/air. Lidocaine (2mg/kg plus 50 μg/kg/min) or saline were infused in groups BL/FL and BC/FC, respectively. After initiation of lidocaine or saline CRI IV buprenorphine (0.02 mg/kg) or fentanyl (4 μg/kg plus 8 μg/kg/h CRI) were administered IV in BC/BL and FC/FL, respectively. Respiratory and hemodynamic variables, drug plasma concentrations, and end-tidal SEVO concentrations (E'SEVO) were measured. Behaviors and pain scores were subjectively assessed 1 and 2h post-extubation. Lidocaine CRI produced median drug plasma concentrations <0.4 μg/mL during peak surgical stimulation. Lidocaine produced a 14% decrease in E'SEVO in the BL (P<0.01) but none in the FL group and no change in cardio-pulmonary responses to surgery or postoperative behaviors and pain scores in any group. Thus, depending on the opioid used, supplementing opioid-based balanced anesthesia with lidocaine (50 μg/kg/min) may not have any or only a minor impact on anesthetic outcome in terms of total anesthetic dose, autonomic responses to visceral nociception, and postoperative analgesia. PMID:22261004

  2. Pharmacotherapy for opioid dependence in jails and prisons: research review update and future directions

    Directory of Open Access Journals (Sweden)

    Sharma A

    2016-04-01

    Full Text Available Anjalee Sharma,1 Kevin E O'Grady,1,2 Sharon M Kelly,1 Jan Gryczynski,1 Shannon Gwin Mitchell,1 Robert P Schwartz1 1Friends Research Institute, Baltimore, 2Department of Psychology, University of Maryland, College Park, MD, USA Purpose: The World Health Organization recommends the initiation of opioid agonists prior to release from incarceration to prevent relapse or overdose. Many countries in the world employ these strategies. This paper considers the evidence to support these recommendations and the factors that have slowed their adoption in the US. Methods: We reviewed randomized controlled trials (RCTs and longitudinal/observational studies that examine participant outcomes associated with the initiation or continuation of opioid agonists (methadone, buprenorphine or antagonists (naltrexone during incarceration. Papers were identified through a literature search of PubMed with an examination of their references and were included if they reported outcomes for methadone, buprenorphine, or naltrexone continued during incarceration or initiated prior to release in a correctional institution. Results: Fourteen studies were identified, including eight RCTs and six observational studies. One RCT found that patients treated with methadone who were continued on versus tapered off methadone during brief incarceration were more likely to return to treatment upon release. A second RCT found that the group starting methadone treatment in prison versus a waiting list was less likely to report using heroin and sharing syringes during incarceration. A third RCT found no differences in postrelease heroin use or reincarceration between individuals initiating treatment with methadone versus those initiating treatment with buprenorphine during relatively brief incarcerations. Findings from four additional RCTs indicate that starting opioid agonist treatment during incarceration versus after release was associated with higher rates of entry into community

  3. The use of analgesic drugs by South African veterinarians : continuing education

    OpenAIRE

    K.E. Joubert

    2001-01-01

    According to a survey, non-steroidal anti-inflammatory agents were the most popular analgesic used in South Africa for management of peri-operative pain, acute post-operative pain and chronic pain. The most popular non-steroidal anti-inflammatory agents are flunixin meglumine and phenylbutazone. The most popular opioid type drug is buprenorphine, followed by morphine. In the peri-operative setting, analgesic agents were not actively administered to 86.3 % of cats and 80.7 % of dogs. Analgesic...

  4. Hemodynamics and bispectral index (BIS) of dogs anesthetized with midazolam and ketamine associated with medetomidine or dexmedetomidine and submitted to ovariohysterectomy Avaliação hemodinâmica e do índice bispectral (BIS) de cadelas anestesiadas com midazolam e cetamina associados à medetomidina ou dexmedetomidina e submetidas a ovário-salpingo-histerectomia

    OpenAIRE

    Fernando do Carmo Silva; Eduardo Hatschbach; Yuri Karaccas de Carvalho; Bruno Watanabe Minto; Flávio Massone; Paulo do Nascimento Junior

    2010-01-01

    PURPOSE: To evaluate hemodynamics and bispectral index (BIS) in bitches anesthetized with ketamine and midazolam in combination with dexmedetomidine or medetomidine and submitted to ovariohysterectomy. METHODS: Twenty bitches pretreated with levomedetomidine and buprenorphine were anesthetized with 5 mg.kg-1 ketamine and 0.2 mg.kg-1 midazolam i.v. Continuous infusion of 0.4 mg.kg-1.h-1 midazolam and 20 mg.kg-1.h-1 ketamine was initiated in combination with DEX (n=10): 20 µg.kg-1.h-1 dexmedeto...

  5. Non-medical use of opioids among HIV-infected opioid dependent individuals on opioid maintenance treatment: the need for a more comprehensive approach

    Directory of Open Access Journals (Sweden)

    Roux Perrine

    2011-11-01

    Full Text Available Abstract Background Opioid maintenance treatment (OMT has a positive impact on substance use and health outcomes among HIV-infected opioid dependent patients. The present study investigates non-medical use of opioids by HIV-infected opioid-dependent individuals treated with buprenorphine or methadone. Methods The MANIF 2000 study is a longitudinal study that enrolled a cohort of 476 HIV-infected opioid-dependent individuals. Data were collected in outpatient hospital services delivering HIV care in France. The sample comprised all patients receiving OMT (either methadone or buprenorphine who attended at least one follow-up visit with data on adherence to OMT (N = 235 patients, 1056 visits. Non-medical use of opioids during OMT was defined as having reported use of opioids in a non-medical context, and/or the misuse of the prescribed oral OMT by an inappropriate route of administration (injection or sniffing. After adjusting for the non-random assignment of OMT type, a model based on GEE was then used to identify predictors of non-medical use of opioids. Results Among the 235 patients, 144 (61.3% and 91 (38.9% patients were receiving buprenorphine and methadone, respectively, at baseline. Non-medical use of opioids was found in 41.6% of visits for 83% of individual patients. In the multivariate analysis, predictors of non-medical use of opioids were: cocaine, daily cannabis, and benzodiazepine use, experience of opioid withdrawal symptoms, and less time since OMT initiation. Conclusions Non-medical use of opioids was found to be comparable in OMT patients receiving methadone or buprenorphine. The presence of opioid withdrawal symptoms was a determinant of non-medical use of opioids and may serve as a clinical indicator of inadequate dosage, medication, or type of follow-up. Sustainability and continuity of care with adequate monitoring of withdrawal symptoms and polydrug use may contribute to reduced harms from ongoing non-medical use of opioids.

  6. Screening for illicit and medicinal drugs in whole blood using fully automated SPE and UHPLC-TOF-MS with data-independent acquisition

    DEFF Research Database (Denmark)

    Pedersen, Anders Just; Dalsgaard, Petur Weihe; Rode, Andrej Jaroslav;

    2013-01-01

    . Of these, 992 cases (74%) were positive for one or more traffic relevant drugs above the Danish legal limits. Commonly abused drugs such as amphetamine, cocaine, and frequent types of benzodiazepines were the major findings. Nineteen less frequently encountered drugs were detected e.g., buprenorphine......, butylone, cathine, fentanyl, LSD, mCPP, MDPV, mephedrone, 4-methylamphetamine, p-fluoroamphetamine, and PMMA. In conclusion, using UHPLC-TOF-MS screening with data-independent acquisition resulted in detection of common drugs of abuse as well as new designer-drugs and more rarely occurring drugs. Thus, TOF...

  7. Effects of multimodal analgesia on the success of mouse embryo transfer surgery.

    Science.gov (United States)

    Parker, John M; Austin, Jamie; Wilkerson, James; Carbone, Larry

    2011-07-01

    Multimodal analgesia is promoted as the best practice pain management for invasive animal research procedures. Universal acceptance and incorporation of multimodal analgesia requires assessing potential effects on study outcome. The focus of this study was to assess effects on embryo survival after multimodal analgesia comprising an opioid and nonsteroidal antiinflammatory drug (NSAID) compared with opioid-only analgesia during embryo transfer procedures in transgenic mouse production. Mice were assigned to receive either carprofen (5 mg/kg) with buprenorphine (0.1 mg/kg; CB) or vehicle with buprenorphine (0.1 mg/kg; VB) in a prospective, double-blinded placebo controlled clinical trial. Data were analyzed in surgical sets of 1 to 3 female mice receiving embryos chimeric for a shared targeted embryonic stem-cell clone and host blastocyst cells. A total of 99 surgical sets were analyzed, comprising 199 Crl:CD1 female mice and their 996 offspring. Neither yield (pups weaned per embryo implanted in the surgical set) nor birth rate (average number of pups weaned per dam in the set) differed significantly between the CB and VB conditions. Multimodal opioid-NSAID analgesia appears to have no significant positive or negative effect on the success of producing novel lines of transgenic mice by blastocyst transfer. PMID:21838973

  8. Opioids Switching with Transdermal Systems in Chronic Cancer Pain

    Directory of Open Access Journals (Sweden)

    Barbarisi M

    2009-05-01

    Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

  9. 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.

    Science.gov (United States)

    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 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. PMID:24790061

  10. Prepubertal gonadectomy in cats: different injectable anaesthetic combinations and comparison with gonadectomy at traditional age.

    Science.gov (United States)

    Porters, Nathalie; de Rooster, Hilde; Moons, Christel P H; Duchateau, Luc; Goethals, Klara; Bosmans, Tim; Polis, Ingeborgh

    2015-06-01

    Anaesthetic and analgesic effects of three different injectable anaesthetic combinations for prepubertal gonadectomy (PPG) in cats were studied. One anaesthetic protocol was compared with a similar one for gonadectomy at traditional age (TAG). Kittens were randomly assigned to PPG or TAG. For PPG, three different protocols were compared: (1) intramuscular (IM) administration of 60 μg/kg dexmedetomidine plus 20 μg/kg buprenorphine followed by an IM injection of the anaesthetic agent (20 mg/kg ketamine) (DB-IM protocol); (2) oral transmucosal (OTM) administration of 80 μg/kg dexmedetomidine plus 20 μg/kg buprenorphine followed by an IM injection of 20 mg/kg ketamine combined with 20 µg/kg dexmedetomidine (DB-OTM protocol); (3) IM injection of a 40 μg/kg medetomidine-20 μg/kg buprenorphine-20 mg/kg ketamine combination (MBK-IM protocol). For TAG, a DB-IM protocol was used, but with different doses for dexmedetomidine (40 μg/kg) and ketamine (5 mg/kg). All cats (PPG and TAG) received a non-steroidal anti-inflammatory before surgery. Anaesthetic and analgesic effects were assessed pre- and postoperatively (until 6 h). Cumulative logit, linear and logistic regression models were used for statistical analysis. Compared with the DB-OTM protocol, the DB-IM and MBK-IM protocols provided better anaesthesia with fewer adverse effects in PPG cats. Postoperative pain was not significantly different between anaesthetic protocols. PPG and TAG cats anaesthetised with the two DB-IM protocols differed significantly only for sedation and pain scores, but sedation and pain scores were generally low. Although there were no anaesthesia-related mortalities in the present study and all anaesthetic protocols for PPG in cats provided a surgical plane of anaesthesia and analgesia up to 6 h postoperatively, our findings were in favour of the intramuscular (DB-IM and MBK-IM) protocols. PMID:25170033

  11. Biochemical genomics for gene discovery in benzylisoquinoline alkaloid biosynthesis in opium poppy and related species.

    Science.gov (United States)

    Dang, Thu Thuy T; Onoyovwi, Akpevwe; Farrow, Scott C; Facchini, Peter J

    2012-01-01

    Benzylisoquinoline alkaloids (BIAs) are a large, diverse group of ∼2500 specialized plant metabolites. Many BIAs display potent pharmacological activities, including the narcotic analgesics codeine and morphine, the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine, the antimicrobial agents sanguinarine and berberine, and the muscle relaxant (+)-tubocurarine. Opium poppy remains the sole commercial source for codeine, morphine, and a variety of semisynthetic drugs, including oxycodone and buprenorphine, derived primarily from the biosynthetic pathway intermediate thebaine. Recent advances in transcriptomics, proteomics, and metabolomics have created unprecedented opportunities for isolating and characterizing novel BIA biosynthetic genes. Here, we describe the application of next-generation sequencing and cDNA microarrays for selecting gene candidates based on comparative transcriptome analysis. We outline the basic mass spectrometric techniques to perform deep proteome and targeted metabolite analyses on BIA-producing plant tissues and provide methodologies for functionally characterizing biosynthetic gene candidates through in vitro enzyme assays and transient gene silencing in planta. PMID:22999177

  12. The unsolved case of "bone-impairing analgesics": the endocrine effects of opioids on bone metabolism.

    Science.gov (United States)

    Coluzzi, Flaminia; Pergolizzi, Joseph; Raffa, Robert B; Mattia, Consalvo

    2015-01-01

    The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density. PMID:25848298

  13. Stereospecific potentiation of opiate analgesia by cocaine: predominant role of noradrenaline.

    Science.gov (United States)

    Misra, A L; Pontani, R B; Vadlamani, N L

    1987-01-01

    Cocaine hydrochloride (50 mg) pellets implanted subcutaneously in male Wistar rats potentiated the analgesia of morphine, levorphanol, methadone and buprenorphine as measured by the tail-withdrawal test. Potentiated opiate analgesia was abolished by naloxone and further enhanced by desipramine and phenoxybenzamine. Yohimbine, alpha-methyl p-tyrosine, haloperidol, zimelidine, methysergide, p-chlorophenylalanine produced no significant effect on potentiated opiate analgesia. Pseudo-cocaine (dextro-cocaine), which is several-fold less potent than cocaine as an inhibitor of noradrenaline and dopamine reuptake in the CNS, had no significant effect on opiate analgesia. Analgesia produced by low doses of baclofen, a GABA agonist, was also not potentiated by cocaine. This study suggests a predominant role for noradrenaline in the stereospecific potentiation of opiate analgesia by cocaine. PMID:3822492

  14. Perception and knowledge about narcotics among nurses

    Directory of Open Access Journals (Sweden)

    Desai Geetha

    2003-01-01

    Full Text Available Aim: To determine the extent to which nurses are able to correctly identify drugs as narcotics and to ascertain their perception of the addiction potential of opiates when used for pain management. Methods: A questionnaire was administered to 86 nurses who attended palliative care workshops in India. Findings: Only morphine (95%, heroin (71% and codeine (75% were correctly identified as narcotics by the majority of participants. Imipramine (34%, diazepam (20% and phenobarbitone (39% were wrongly classified as narcotics by many nurses. Dextropropoxyphene (11%, pentazocine (21%, buprenorphine (15% were correctly classified as narcotics by fewer than half the participants. Only 14% knew that that the frequency of psychological dependence due to use of morphine for cancer pain was less than 1%.

  15. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen

    DEFF Research Database (Denmark)

    Fanoe, Søren; Hvidt, C; Ege, P;

    2007-01-01

    Background: Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too...... were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 ( 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed...... odds for syncope. Conclusions: Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts. Abbreviations: HERG, human ether-a-go-go related gene; LQT2, type 2 of the long QT syndrome; TdP, torsade de pointes....

  16. Determination of illicit drugs and related substances by high-performance liquid chromatography with an electrochemical coulometric-array detector.

    Science.gov (United States)

    Achilli, G; Cellerino, G P; Melzi d'Eril, G V; Tagliaro, F

    1996-04-01

    A general method for the simultaneous determination of fifteen common drugs (6-acetylmorphine, 3,4-methylenedioxymetamphetamine, buprenorphin, cocaine, codeine, dihydrocodeine, ethylmorphine, heroin, hydrocodone, lidocaine, methadone, morphine, naloxone, procaine and thebaine) was developed using reversed-phase HPLC and electrochemical detection. The separation of the drugs was achieved by using as the mobile phase 20 mM monobasic sodium phosphate-acetonitrile (90:10) with a gradient to 50% of the organic modifier, on a silica based C18 column (150 x 4.6 mm I.D.) of 3 microns particle size and by the selectivity supplied by an array of eight coulometric electrodes at increasing potential. It was possible to identify and to determine fifteen different drugs in the same chromatographic run in 50 min. The method was tentatively applied to the determination of drugs in extracts of human hair. PMID:9004949

  17. [Palliative pain therapy, cannabinoids].

    Science.gov (United States)

    Radbruch, L; Elsner, F

    2005-10-01

    Cancer pain treatment should follow the recommendations of the World Health Organisation. Treatment should be with oral application, regular application times and following the analgesic step-ladder. Non-opioids such as dipyrone or non-steroids are used for slight to moderate pain, step-2 opioids such as tramadol or tilidine/naloxone for moderate pain and step-3 opioids such as morphine, oxycodone or hydromorphone for severe pain. Transdermal application of fentanyl or buprenorphine offer a non-invasive parenteral alternative for patients with stable pain syndromes. Cannabinoids such as tetrahydrocannabinol offer a valuable add-on option for cancer patients with refractory pain, spasticity, nausea or appetite loss. PMID:15965665

  18. Effects of an Organizational Linkage Intervention on Inter-Organizational Service Coordination Between Probation/Parole Agencies and Community Treatment Providers.

    Science.gov (United States)

    Welsh, Wayne N; Knudsen, Hannah K; Knight, Kevin; Ducharme, Lori; Pankow, Jennifer; Urbine, Terry; Lindsey, Adrienne; Abdel-Salam, Sami; Wood, Jennifer; Monico, Laura; Link, Nathan; Albizu-Garcia, Carmen; Friedmann, Peter D

    2016-01-01

    Weak coordination between community correctional agencies and community-based treatment providers is a major barrier to diffusion of medication-assisted treatment (MAT)--the inclusion of medications (e.g., methadone and buprenorphine) in combination with traditional counseling and behavioral therapies to treat substance use disorders. In a multisite cluster randomized trial, experimental sites (j = 10) received a 3-h MAT training plus a 12-month linkage intervention; control sites (j = 10) received the 3-h training alone. Hierarchical linear models showed that the intervention resulted in significant improvements in perceptions of interagency coordination among treatment providers, but not probation/parole agents. Implications for policy and practice are discussed. PMID:25559124

  19. Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Irfanali R. Kugasia

    2014-01-01

    Full Text Available Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

  20. Newer approaches to opioid detoxification

    Directory of Open Access Journals (Sweden)

    Siddharth Sarkar

    2012-01-01

    Full Text Available Opioid use disorders present with distressing withdrawal symptoms at the time of detoxification. The pharmacological agents and methods currently in use for detoxification mainly include buprenorphine, methadone, and clonidine. Many other pharmacological agents have been tried for opioid detoxification. This review takes a look at the newer pharmacological options, both opioid agonists and non-agonist medications that have been utilized for detoxification. Peer reviewed articles were identified using PubMed and PsychInfo databases. The keywords included for the search were a combination of ′opioid′ and ′detoxification′ and their synonyms. All the articles published in the last 10 years were screened for. Relevant data was extracted from identified studies. Many newer pharmacological agents have been tried in detoxification of opioids. However, the quest for a safe, efficacious, cost-effective pharmacological option which requires minimal monitoring still continues. The role of non-pharmacological measures and alternative medicine needs further evaluation.

  1. Opium Syrup Distribution, Limitation and Challenges

    Directory of Open Access Journals (Sweden)

    Mostafa Dahmardehei

    2012-06-01

    Full Text Available Addiction is one of dilemmas in the current society. Formal statistics report of 2 million addict people in the country. Among important activities for addiction prevention and therapy is implementation of protecting treatment. Protecting treatments are done through Methadone, Buprenorphine and tincture-opium. Tincture-opium is a solution of 10 g morphine in one litter liquid containing 20% alcohol. The first report about using this medicine has been in 1994, in French in connection with successful therapy of 18 patients. A study in Australia, in 2004, proposed detoxification with tincture-opium in 15 migrated Vietnamese, in high dosage for therapy. In Iran, since 1384 many researches were done, which 34% responded the therapy appropriately; and in 1387, 130 people reached final treatment.

  2. Effects of a standardized anesthetic protocol on hematologic variables in healthy cats.

    Science.gov (United States)

    Dhumeaux, Marc P; Snead, Elisabeth C R; Epp, Tasha Y; Taylor, Susan M; Carr, Anthony P; Dickinson, Ryan M; Leis, Marina L

    2012-10-01

    This study evaluated the effects of an anesthetic protocol using intravenous ketamine and midazolam, and intramuscular buprenorphine on hematologic variables in cats. Twelve healthy adult cats had blood collected for a complete blood count before and after the induction of anesthesia. There were significant decreases in red blood cell counts, hemoglobin concentrations and hematocrits after the induction of anesthesia. On average, red blood cell counts and hematocrits decreased by 25%, and hemoglobin concentrations decreased by 24%. Based on hematocrit, 3/12 samples (25%) taken while the cats were anesthetized would have been interpreted as belonging to anemic patients while none of the cats would have been considered anemic before anesthesia. This study suggests that a complete blood count performed on blood taken under anesthesia with this anesthetic protocol should be interpreted cautiously in order to not make a false diagnosis of anemia. PMID:22577050

  3. The use of analgesic drugs by South African veterinarians : continuing education

    Directory of Open Access Journals (Sweden)

    K.E. Joubert

    2001-07-01

    Full Text Available According to a survey, non-steroidal anti-inflammatory agents were the most popular analgesic used in South Africa for management of peri-operative pain, acute post-operative pain and chronic pain. The most popular non-steroidal anti-inflammatory agents are flunixin meglumine and phenylbutazone. The most popular opioid type drug is buprenorphine, followed by morphine. In the peri-operative setting, analgesic agents were not actively administered to 86.3 % of cats and 80.7 % of dogs. Analgesic premedications were frequently administered, e.g. xylazine or ketamine, but no specific drug was administered for post-operative pain. Veterinarians need to critically review their anaesthetic and analgesic practices in order to achieve balanced anaesthesia.

  4. Preconditioning cortical lesions reduce the incidence of peri-infarct depolarizations during focal ischemia in the Spontaneously Hypertensive Rat: interaction with prior anesthesia and the impact of hyperglycemia.

    Science.gov (United States)

    Zhao, Liang; Nowak, Thaddeus S

    2015-07-01

    The relationship between peri-infarct depolarizations (PIDs) and infarction was investigated in a model of preconditioning by cortical freeze lesions (cryogenic lesions, CL) in the Spontaneously Hypertensive Rat. Small (chloralose during perfusion imaging. As an additional methodological concern, blood glucose was frequently elevated at the time of the second surgery, reflecting buprenorphine-induced pica and other undefined mechanisms. Even modest hyperglycemia (>10 mmol/L) reduced PID incidence. In normoglycemic animals CL preconditioning reduced PID number by 50%, demonstrating associated effects on PID incidence, penumbral perfusion, and infarct progression. Hyperglycemia suppressed PIDs without affecting the relationship between CBF and infarction. This suggests that the primary effect of preconditioning is to improve penumbral perfusion, which in turn impacts PID incidence and infarct size. PMID:25757750

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

    Science.gov (United States)

    Todadze, Kh; Mosia, S

    2016-05-01

    Injecting drug user size estimation studies carried out in 2009, 2012 and 2015 revealed growing trends of drug abuse in Georgia:estimated number of people who inject drugs (PWID) have been increased from 40000 and 45000 to 50000. Since Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine ("Krokodile") replacing each other on the black market. Self-made desomorphine typically contains big amounts of different toxic substances and causes significant somatic disorders, especially skin, bone, blood infections, liver and kidney failure; is highly addictive, associates with frequent injections that enhance injecting-related harm, including the risk of HIV transmission, in comparison with typical opioids. The aim of the study was to determine the effectiveness of opioid substitution treatment (OST) on depression and anxiety in opioid dependent clients with history of different opioid substance use. 104 opioid drug users undergoing OST with intensive psychological counseling have been divided in 5 groups according to the principal opioid drug that was abused during past 6 months before starting treatment: heroine, desomorphine, illicit methadone injectors, illicit buprenorphine injectors, and multiple drug abusers consuming opioids as primary drugs. Level of depression (Beck Depression Inventory), anxiety (Spielberger Anxiety Inventory) as well as clinical symptoms, risky behavior, quality of life (WHO), and other data were measured before starting and after 3, 9, 15, 21 months of treatment. The illegal use of psychotropic-narcotics was checked through random urine-testing 1-2 times per patient per month. In all five groups remarkable decrease of depression and anxiety was observed in comparison with the starting data. Before inclusion desomorphine and poly-drug users had the highest scores of depression and anxiety while buprenorphine users manifested the lowest rate. Improvement of

  6. Transdermal delivery: product and patent update.

    Science.gov (United States)

    Gupta, Himanshu; Babu, R J

    2013-12-01

    Transdermal drug delivery is an attractive alternative to the oral and parenteral drug delivery. Drugs which are prone to first-pass metabolism can be delivered easily in small doses with sustained blood levels through this method. An update to available products along with a review of clinical trials and patents are discussed in this study. In this review, we have compiled 16 drugs, i.e. Buprenorphine, Clonidine, Estradiol, Fentanyl, Granisetron, Lidocaine, Methylphenidate, Nicotine, Nitroglycerin, Oxybutynin, Rivastigmine, Rotigotine, Scopolamine, Selegiline, Testosterone, Influenza virus vaccine (Microneedle) and covering about 22 marketed products on the transdermal system. We present instrumental information on them along with the compilation of current clinical trials on transdermal systems. We summarize the contents of patents granted in last 5 years under different pharmacological categories. This article serves, accordingly as a source of available information focused on transdermal drug delivery research. PMID:24025130

  7. Primary care for opioid use disorder

    Directory of Open Access Journals (Sweden)

    Mannelli P

    2016-08-01

    Full Text Available Paolo Mannelli,1 Li-Tzy Wu1–41Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University Medical Center, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, USARecent reports on prescription opioid misuse and abuse have described unprecedented peaks of a national crisis and the only answer is to expand prevention and treatment, including different levels of care.1 Nonetheless, concerns remain about the ability of busy primary care settings to manage problem opioid users along with other patients. In particular, proposed extensions of buprenorphine treatment, a critically effective intervention for opioid use disorder (OUD, are cautiously considered due to the potential risk of misuse or abuse.2 General practitioners are already facing this burden daily in the treatment of chronic pain, and expert supervision and treatment model adjustment are needed to help improve outcomes. Approximately 20% of patients in primary care have noncancer pain symptoms, with most of them receiving opioid prescriptions by their physicians, and their number is increasing.3 Pain diagnoses are comparable in severity to those of tertiary centers and are complicated by significant psychiatric comorbidity, with a measurable lifetime risk of developing OUD.4,5 Some primary care physicians report frustration about opioid abuse and diversion by their patients; support from pain specialists would improve their competence, the quality f their performance, and the ability to identify patients at risk of opioid misuse.6 Thus, buprenorphine treatment should not be adding to a complex clinical scenario. To this end, the promising models of care emphasize the integration of medical with psychological and pharmacological expertise for the management of OUD. 

  8. Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine

    Science.gov (United States)

    Hill, Rob; Lyndon, Abi; Withey, Sarah; Roberts, Joanne; Kershaw, Yvonne; MacLachlan, John; Lingford-Hughes, Anne; Kelly, Eamonn; Bailey, Chris; Hickman, Matthew; Henderson, Graeme

    2016-01-01

    Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths. PMID:26171718

  9. Prenatal drug exposure: infant and toddler outcomes.

    Science.gov (United States)

    Bandstra, Emmalee S; Morrow, Connie E; Mansoor, Elana; Accornero, Veronica H

    2010-04-01

    This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may

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

    Science.gov (United States)

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

    2016-08-01

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

  11. Metabolism and Disposition of Prescription Opioids: A Review.

    Science.gov (United States)

    DePriest, A Z; Puet, B L; Holt, A C; Roberts, A; Cone, E J

    2015-07-01

    Opioid analgesics are commonly prescribed for acute and chronic pain, but are subject to abuse. Consequently, toxicology testing programs are frequently implemented for both forensic and clinical applications. Understanding opioid metabolism and disposition is essential for assessing risk of toxicity and, in some cases, providing additional information regarding risk of therapeutic failure. Opioids significantly metabolized by the cytochromeP450 (CYP450) enzyme system maybe subjectto drug-drug interactions, including codeine, hydrocodone, oxycodone, fentanyl, meperidine, methadone, buprenorphine, and tramadol. CYP2D6 metabolism is polymorphic, and pharmacogenetic testing has been investigated for codeine, tramadol, oxycodone, and hydrocodone. CYP2B6 pharmacogenetic testing of methadone may reduce the risk of cardiac toxicity associated with the S-enantiomer. Opioids metabolized primarily by uridine 5'-diphospho-glucuronsyltransferase (UGT) enzymes include morphine, hydromorphone, dihydrocodeine, oxymorphone, levorphanol, and tapentadol. Parent and metabolite disposition is described for blood, oral fluid, and urine. Parent drug is most commonly detected in blood and oral fluid, whereas metabolites typically predominate in urine. Oral fluid/blood ratios exceed 1 for most opioids, making this an excellent alternative matrix for testing of this drug class. Metabolites of codeine, hydrocodone, and oxycodone are commercially available, and knowledge of metabolism is necessary for correct interpretation. PMID:26227254

  12. Sexual dysfunction in patients with alcohol and opioid dependence

    Directory of Open Access Journals (Sweden)

    Sandeep Grover

    2014-01-01

    Full Text Available There are limited numbers of studies which have evaluated the sexual dysfunction (SD in patients with alcohol and opioids dependence. This article reviews the existing literature. Electronic searches were carried out using the PubMed, Google Scholar, and ScienceDirect to locate the relevant literature. Subjects addicted to heroin or on methadone maintenance treatment (MMT or buprenorphine maintenance treatment (BMT show higher rates of SD in comparison to the general population. SD rates have ranged 34-85% for heroin addicts, 14-81% for MMT, 36-83% for BMT, and 90% for naltrexone maintenance. The rates of SD in alcohol-dependent population have ranged 40-95.2%, with rates being consistently much higher in alcohol-dependent population than in the healthy controls or social drinkers. The common SDs reported have been erectile dysfunction followed by premature ejaculation, retarded ejaculation and decreased sexual desire among men, and dyspareunia and vaginal dryness among women. This review suggests that long-term use of alcohol and opioids are associated with SD in almost all domains of sexual functioning. There is a need to increase the awareness of clinicians about this association as many times SD in patients with substance abuse lead to poor treatment compliance and relapse. Further, there is a need to carry out more number of studies to understand the relationship in a better way.

  13. Outcome of heroin-dependent adolescents presenting for opiate substitution treatment.

    LENUS (Irish Health Repository)

    Smyth, Bobby P

    2012-01-01

    Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants\\' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame.

  14. Are Pharmacotherapies Ineffective in Opioid-Dependent Smokers? Reflections on the Scientific Literature and Future Directions.

    Science.gov (United States)

    Miller, Mollie E; Sigmon, Stacey C

    2015-08-01

    While rates of smoking in the general population have decreased in recent years, dramatic disparities remain among disadvantaged subgroups of smokers, particularly those with concurrent substance abuse. Prevalence rates of smoking among opioid-dependent patients, for example, are fourfold those of the general population. While pharmacotherapies are recommended as a first-line treatment for nicotine dependence, the few studies that have investigated their effectiveness in this population have shown dramatically poorer outcomes compared to the general population. Indeed, these findings have led some researchers to suggest that pharmacotherapies may simply be ineffective in opioid-maintained smokers. In this commentary, we briefly summarize the extant literature on pharmacotherapies in opioid-maintained smokers and contribute new data investigating the contribution of bupropion on smoking outcomes in 81 methadone- and buprenorphine-maintained participants from two randomized trials of financial incentives for smoking cessation. We also discuss several important parameters (ie, timing of the quit attempt, medication adherence, nicotine withdrawal) that may be leveraged to strengthen smoking pharmacotherapy outcomes in opioid-dependent patients. Taken together, an improved understanding of these issues will aid efforts to reduce tobacco-related health disparities in this group of challenging smokers. PMID:26180219

  15. Injecting drug users and their health seeking behavior: a cross-sectional study in dhaka, bangladesh.

    Science.gov (United States)

    Shariful Islam, Sheikh Mohammed; Biswas, Tuhin; Bhuiyan, Faiz Ahmed; Islam, Md Serajul; Rahman, Mohammad Mizanur; Nessa, Hurun

    2015-01-01

    Introduction and Aim. Injecting drug users (IDUs) are amongst the most vulnerable people to acquisition of HIV/AIDS. This study aims to collect information on IDUs and their health seeking behavior in Bangladesh. Design and Methods. A cross-sectional study was conducted among 120 IDUs attending a drug rehabilitation center in Dhaka, Bangladesh. Data were collected on sociodemographics, drug use, health seeking behavior, knowledge of injecting drugs, and sexual behavior. Results. The mean ± SD and median (IQR) age of the participants were 32.5 ± 21.3 and 33 (27-38) years, respectively, with only 9.2% females. Injection buprenorphine was the drug of choice for 40% of participants, and 58% of the participants first started drug use with smoking cannabis. 73.3% of participants shared needles sometimes and 57.5% were willing to use the needle exchange programs. 60% of the participants had no knowledge about the diseases spread by injection. Condom use during the last intercourse with regular partners was 11.7% and with any partners 15.8%. Conclusion. IDUs in Bangladesh are a high-risk group for HIV/AIDS due to lack of knowledge and risky behaviors. Education and interventions specifically aimed at IDUs are needed, because traditional education may not reach IDUs or influence their behavior. PMID:25692067

  16. High rates of sustained virological response in hepatitis C virus-infected injection drug users receiving directly observed therapy with peginterferon alpha-2a (40KD) (PEGASYS) and once-daily ribavirin.

    Science.gov (United States)

    Waizmann, Michael; Ackermann, Grit

    2010-06-01

    This retrospective study evaluated the efficacy and tolerability of directly observed therapy with peginterferon alfa-2a and once-daily ribavirin (RBV) for chronic hepatitis C in 49 opioid-addicted injection drug users (IDUs) participating in a drug treatment program at a specialized outpatient center. Patients also received prophylactic citalopram to minimize the risk of interferon-induced depression. Patients had daily access to and support from specialist physicians, nurses and counseling services at the center, and a 24-hour helpline. Sustained virological response was achieved by 48 of 49 patients (98%) overall, including 20 of 21 (95%) hepatitis C virus (HCV) Genotype 1/4-infected patients and 28 of 28 (100%) Genotype 2/3-infected patients. Treatment was well tolerated, and no unexpected side effects of peginterferon treatment were seen. The safety profile of once-daily RBV was not different from twice-daily dosing. Decline in hemoglobin levels was similar to those reported in clinical trials including once-daily RBV and did not lead to dose reduction or treatment withdrawal. Our data demonstrate that HCV-infected IDUs on stable L-polamidone (methadone) or buprenorphine maintenance can be successfully and safely treated with peginterferon alfa-2a and RBV in an optimal substitution setting. PMID:20362408

  17. Affective preclinical modeling of psychiatric disorders: taking imbalanced primal emotional feelings of animals seriously in our search for novel antidepressants.

    Science.gov (United States)

    Panksepp, Jaak

    2015-12-01

    Preclinical animal models of psychiatric disorders are of critical importance for advances in development of new psychiatric medicine. Regrettably, behavior-only models have yielded no novel targeted treatments during the past half-century of vigorous deployment. This may reflect the general neglect of experiential aspects of animal emotions, since affective mental states of animals supposedly cannot be empirically monitored. This supposition is wrong-to the extent that the rewarding and punishing aspects of emotion circuit arousals reflect positive and negative affective states. During the past decade, the use of such affective neuroscience-based animal modeling has yielded three novel antidepressants (i) via the alleviation of psychic pain with low doses of buprenorphine; (ii) via the amplification of enthusiasm by direct stimulation of the medial forebrain bundle); and (iii) via the facilitation of the capacity for social joy with play facilitators such as rapastinel (GLYX13). All have progressed to successful human testing. For optimal progress, it may be useful for preclinical investigators to focus on the evolved affective foundations of psychiatrically relevant brain emotional disorders for optimal animal modeling. PMID:26869838

  18. Generic on-line solid phase extraction sample preparation strategies for the analysis of drugs in biological matrices by LC-MS/MS.

    Science.gov (United States)

    Bourgogne, Emmanuel; Grivet, Chantal; Varesio, Emmanuel; Hopfgartner, Gérard

    2015-01-01

    In the present work we investigate the integration of a single hardware platform (Prospekt-2) allowing on-line SPE with pre-/post-trapping dilution and direct injection of plasma extracts, and also compare the benefits and challenges of the different approaches for pharmaceutical drugs with heterogeneous physicochemical properties. In the first part, the generic use of on-line SPE with direct plasma injection or after protein precipitation was investigated for the quantitative analysis of talinolol. In the second part, pre-trapping and post-trapping dilution for on-line SPE is discussed for generic method development on an oxadiazole and its major metabolite. Finally, the difference of performance between direct plasma injection vs. off-line liquid-liquid extraction is also described for the quantification of buprenorphine and naltrexone down to 50 and 100 pg/ml using a 0.25 ml plasma aliquot. All assays were in human plasma and detection was performed by mass spectrometry detection either on simple or triple stage quadrupoles. Regardless of the tested strategy, assays were found linear, with precision and accuracy with <15% for all quality controls samples and <20% for lower limit of quantitation. PMID:25459926

  19. Upper extremity nerve block: how can benefit, duration, and safety be improved? An update

    Science.gov (United States)

    Brattwall, Metha; Jildenstål, Pether; Warrén Stomberg, Margareta; Jakobsson, Jan G.

    2016-01-01

    Upper extremity blocks are useful as both sole anaesthesia and/or a supplement to general anaesthesia and they further provide effective postoperative analgesia, reducing the need for opioid analgesics. There is without doubt a renewed interest among anaesthesiologists in the interscalene, supraclavicular, infraclavicular, and axillary plexus blocks with the increasing use of ultrasound guidance. The ultrasound-guided technique visualising the needle tip and solution injected reduces the risk of side effects, accidental intravascular injection, and possibly also trauma to surrounding tissues. The ultrasound technique has also reduced the volume needed in order to gain effective block. Still, single-shot plexus block, although it produces effective anaesthesia, has a limited duration of postoperative analgesia and a number of adjuncts have been tested in order to prolong analgesia duration. The addition of steroids, midazolam, clonidine, dexmedetomidine, and buprenorphine has been studied, all being off-label when administered by perineural injection, and the potential neurotoxicity needs further study. The use of perineural catheters is an effective option to improve and prolong the postoperative analgesic effect. Upper extremity plexus blocks have an obvious place as a sole anaesthetic technique or as a powerful complement to general anaesthesia, reducing the need for analgesics and hypnotics intraoperatively, and provide effective early postoperative pain relief. Continuous perineural infusion is an effective option to prolong the effects and improve postoperative quality.

  20. A pilot survey of attitudes and knowledge about opioid substitution therapy for HIV-infected prisoners.

    Science.gov (United States)

    Springer, Sandra A; Bruce, Robert D

    2008-01-01

    A majority of inmates in the state of Connecticut Department of Corrections use opioids or are opioid dependent before incarceration. None of the state's prisons offer opioid substitution therapy other than for detoxification or maintenance therapy for women during pregnancy. On release to the community, most prisoners relapse to drug use and this has been associated with higher recidivism rates, and less adherence to antiretroviral medications for HIV-infected persons. Nationally and internationally, methadone (METH) and buprenorphine (BUP) have been found to decrease relapse to drug use, decrease recidivism rates, improve adherence to antiretroviral medications, decrease HIV-risk taking behaviors, and improve mortality. However, the general knowledge about opioid substitution therapy among correctionalfacility staff has been reported as substandard. This pilot study compiled results of answers to anonymous surveys from 27 individuals who work directly with inmates in a patient-care capacity for the Connecticut Department of Corrections (CT DOC) and CT DOC case-management referral program (Project TLC) in the year 2006. The surveys included questions regarding current attitudes and knowledge about opioid substitution therapy for prisoners. A minority of respondents refer released prisoners with a history of opioid dependency to METH or BUP treatment. The majority of correctional workers and case-management referral workers did not have knowledge about BUP or METH's ability to improve health and decrease HIV risk taking behaviors. This study found that more education of individuals treating and caring for HIV-infected opioid dependent prisoners is needed. PMID:18557164

  1. Drug-related HIV epidemic in Pakistan: a review of current situation and response and the way forward beyond 2015.

    Science.gov (United States)

    Bergenstrom, Anne; Achakzai, Baseer; Furqan, Sofia; ul Haq, Manzoor; Khan, Rajwal; Saba, Marc

    2015-01-01

    Pakistan is among four countries in Asia where the estimated number of new HIV infections has been increasing year by year ever since 1990. The Asian Epidemic Modelling (AEM), conducted in 2015, reconfirmed that the use of contaminated injection equipment among people who inject drugs (PWID) remains the main mode of HIV transmission in the country. The estimated number of PWID ranges from 104,804 to 420,000 PWID. HIV prevalence in this population is above 40 % in several cities, including Faisalabad (52.5 %), D.G. Khan (49.6 %), Gujrat (46.2 %), Karachi (42.2 %) and Sargodha (40.6 %), respectively. Harm reduction service delivery is being implemented through a public-private partnership led by the National and Provincial AIDS Control Programmes and Nai Zindagi with funding support from the Global Fund. Current programmatic coverage of the needle and syringe programme, HIV testing and counselling and antiretroviral treatment among PWID remain insufficient to control ongoing transmission of HIV in the country. While opioid substitution therapy (OST) is yet to be introduced, significant progress and coordination among various ministries have taken place recently to register buprenorphine in the dosage required for treatment of opioid dependence, and possible introduction of OST will greatly facilitate adherence to antiretroviral treatment among PWID living with HIV. PMID:26471874

  2. Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

    Science.gov (United States)

    Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures. PMID:22710371

  3. Workplace drug testing in Italy: findings about second-stage testing.

    Science.gov (United States)

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; San Bartolomeo, Paolo; Groppi, Angelo

    2015-03-01

    Workplace Drug Testing (WDT) in Italy includes two levels of monitoring: a first stage concerning drug testing on urine samples and a second involving both urine and hair analysis. The second stage is performed only on workers who tested positive at the first level. We analyzed urine and hair specimens from 120 workers undergoing second-level testing between 2009 and 2012. Eighty percent of them had tested positive for cannabinoids during the first level analysis, and 15.8% for cocaine. Both urine and hair samples were analyzed in order to find the following drugs of abuse: amphetamines, buprenorphine, cannabinoids, cocaine, ecstasy, methadone, and opiates. Urine analyses were performed by immunological screening (EMIT); urine confirmatory tests and hair analyses were performed by gas chromatography-mass spectrometry (GC-MS). As regards second-stage testing on urine samples, 71.2% of workers were always negative, whereas 23.9% tested positive at least once for cannabinoids and 2.5% for cocaine. Hair analyses produced surprising results: 61.9% of hair samples tested negative, only 6.2% tested positive for cannabinoids, whereas 28.8% tested positive for cocaine. These findings confirm that second-level surveillance of WDT, which includes hair analysis, is very effective because it highlights drug intake - sometimes heavy - that cannot be revealed only through urine analyses. The employees for whom drug addiction is proved can begin rehabilitation, while keeping their job. Eventually, our results confirmed the widespread and undeclared use of cocaine in Italy. PMID:24652693

  4. Screening of several drugs of abuse in Italian workplace drug testing: performance comparisons of on-site screening tests and a fluorescence polarization immunoassay-based device.

    Science.gov (United States)

    Basilicata, Pascale; Pieri, Maria; Settembre, Veronica; Galdiero, Alessandra; Della Casa, Elvira; Acampora, Antonio; Miraglia, Nadia

    2011-11-15

    According to the Italian laws, some categories of workers entrusted with duties possibly constituting a threat to security, physical safety, and health of third parties have to be screened to exclude the use/abuse of the following drugs of abuse: opiates, cocaine, cannabinoids, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methadone, and buprenorphine. Toxicological tests can be performed with urinary on-site rapid screening devices, provided that sensitivities up to specified cutoffs are ensured. The present study reports performances, in terms of sensitivity, specificity, and accuracy, of an automatic on-site test and of an FPIA-based device, using gas chromatography/mass spectrometry (GC/MS) as a reference methodology. Three levels of concentration were tested, corresponding to the cutoff and to 2 and 3 times the limits, respectively. In terms of sensitivities, neither the on-site nor the benchtop instrumentations gave positive results, since values of zero percentage were obtained for concentrations up to 2-fold the limits. Even if good results were obtained in terms of specificity and accuracy by both devices, none of them seem to be adequate for the current application to the toxicological screening at workplaces. In fact, a rapid screening device can be used for drug tests provided that it ensures sensitivity at the prescribed cutoffs. Data showed that such is completely rejected and a more sensitive instrumentation should be preferred. PMID:21992470

  5. Feasibility of radial and circumferential strain analysis using 2D speckle tracking echocardiography in cats.

    Science.gov (United States)

    Takano, Hiroshi; Isogai, Tomomi; Aoki, Takuma; Wakao, Yoshito; Fujii, Yoko

    2015-02-01

    The purpose of the present study is to investigate the feasibility of strain analysis using speckle tracking echocardiography (STE) in cats and to evaluate STE variables in cats with hypertrophic cardiomyopathy (HCM). Sixteen clinically healthy cats and 17 cats with HCM were used. Radial and circumferential strain and strain rate variables in healthy cats were measured using STE to assess the feasibility. Comparisons of global strain and strain variables between healthy cats and cats with HCM were performed. Segmental assessments of left ventricle (LV) wall for strain and strain rate variables in cats with HCM were also performed. As a result, technically adequate images were obtained in 97.6% of the segments for STE analysis. Sedation using buprenorphine and acepromazine did not affect any global strain nor strain rate variable. In LV segments of cats with HCM, reduced segmental radial strain and strain rate variables had significantly related with segmental LV hypertrophy. It is concluded that STE analysis using short axis images of LV appeared to be clinically feasible in cats, having the possibility to be useful for detecting myocardial dysfunctions in cats with diseased heart. PMID:25373881

  6. Practice guidelines for transdermal opioids in malignant pain.

    Science.gov (United States)

    Skaer, Tracy L

    2004-01-01

    Patients with moderate-to-severe malignancy-related pain require opioid pharmacotherapy. Many cancer patients continue to be prescribed subtherapeutic doses of pain medications resulting in undue suffering and diminished quality of life. Pain associated with malignancy and its treatment may exacerbate other symptoms associated with cancer, including nausea, fatigue, weakness, dyspnoea, constipation and impaired cognition. The choice of analgesic pharmacotherapy should be individualised and based on the intensity of pain reported by the patient, rather than its specific aetiology. When selecting pain management pharmacotherapy, the healthcare provider should consider the patient's pain level, activity level and any comorbid illness. Intolerable adverse effects, ineffective pain relief or a change in the patient's clinical status can dictate the need for a new pain management regimen. Healthcare providers must be able to readily quantify the relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal formulations of fentanyl and buprenorphine are effective pharmacotherapy that can be safely used for cancer patients with pain. However, clinicians need to be cognisant that the US/UK manufacturer's recommendations for equianalgesic dose administration of transdermal fentanyl may result in initial doses that produce subtherapeutic concentrations and unrelieved pain in some patients. A less conservative dose administration algorithm for transdermal fentanyl using a 2:1 (mg/day of oral morphine : microg/h of transdermal fentanyl) conversion ratio that considers both a review of the literature and clinical experience should help clinicians individualise cancer pain pharmacotherapy. PMID:15537367

  7. Pharmacopsychosocial Treatment of Opioid Dependence Harm Reduction Palliation or Simply Good Medical Practice

    Directory of Open Access Journals (Sweden)

    A.J. Reid Finlayson

    2011-01-01

    symptoms that accompany cessation of drug use. Withdrawal from chronic opioid self-administration consists of: 1 specific signs and symptoms which mirror the pharmacological actions of opioids (e.g., intoxication with opioids causes severe constipation, while withdrawal causes the opposite, diarrhea; and 2 generalized autonomic hyperactivity due to a “stress response” to overcome the homeostatic disequilibrium that emerges as chronic opioid use is discontinued. This withdrawal syndrome is very uncomfortable (like a bad case of the flu with sweating, muscle aches, cramps, nausea, diarrhea, vomiting, lachrymation, rhinorrhea, and can be associated with extreme feelings of anxiousness. However, opioid withdrawal is not life threatening unless the patient has medical problems that are adversely affected by the autonomic instability (e.g., coronary artery disease or pregnancy. A commonly employed strategy for alleviating opioid withdrawal has been administration or tapering of the long-acting opioid, methadone. Recently, the partial mu-opioid agonist buprenorphine has become the preferred medication for opioid withdrawal treatment; however, care must be taken to ensure that the patient is actually in withdrawal prior to starting buprenorphine, because administration of this partial agonist can precipitate or worsen withdrawal if mu-opioid receptors are still occupied by the opioid of abuse. Detoxification can also be accomplished by using an alpha2-noradrenergic agonist (e.g., clonidine and lofexidine which partially blocks autonomic opioid withdrawal symptoms by inhibiting noradrenergic outflow from neurons in the brain to the periphery and modulates the activity of cells in the gut responsible for fluid absorption and intestinal motility. Although detoxification may be achieved technically within a few days, it is increasingly recognized that detoxification alone does not affect the long-term course of opioid dependence. Protracted (post-acute withdrawal symptoms such as

  8. A designated centre for people with disabilities operated by Health Service Executive, Sligo

    LENUS (Irish Health Repository)

    Smyth, Bobby P

    2012-01-01

    Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants\\' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame.

  9. Prevalence and seroincidence of hepatitis B and hepatitis C infection in high risk people who inject drugs in china and Thailand.

    Science.gov (United States)

    Jackson, J Brooks; Wei, Liu; Liping, Fu; Aramrattana, Apinun; Celentano, David D; Walshe, Louise; Xing, Yi; Richardson, Paul; Jun, Ma; Beauchamp, Geetha; Donnell, Deborah; Ruan, Yuhua; Ma, Liying; Metzger, David; Shao, Yiming

    2014-01-01

    We determined the prevalence and incidence of HBV and HCV infection in people who inject drugs (PWIDs) at high risk for HIV in China and Thailand and determined the association of HBV and HCV incidence with urine opiate test results and with short-term versus long-term buprenorphine-naloxone (B-N) treatment use in a randomized clinical trial (HPTN 058). 13.8% of 1049 PWIDs in China and 13.9% of 201 PWIDs in Thailand were HBsAg positive at baseline. Among HBsAg negative participants, the HBsAg incidence rate was 2.7/100 person years in China and 0/100 person years in Thailand. 81.9% of 1049 PWIDs in China and 59.7% of 201 in Thailand were HCV antibody positive at baseline. The HCV confirmed seroincidence rate among HCV antibody negative PWIDs was 22/100 person years in China and 4.6/100 person years in Thailand. Incident HBsAg was not significantly different in the short-term versus long-term B-N arm in China or Thailand. Participants with positive opiate results in at least 75% of their urines during the time period were at increased risk of incident HBsAg (HR = 5.22; 95% CI, 1.08 to 25.22; P = 0.04) in China, but not incident HCV conversion in China or Thailand. PMID:24860664

  10. Drug screening of whole blood by ultra-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Oiestad, Elisabeth Leere; Johansen, Unni; Oiestad, Ase Marit Leere; Christophersen, Asbjørg Solberg

    2011-06-01

    An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for screening of drugs in whole blood has been developed and validated. Samples were prepared by supported liquid-liquid extraction on ChemElute(®) columns with ethyl acetate/heptane (4:1). LC separation was achieved with an Acquity HSS T3-column (2.1 100 mm, 1.8-μm particle). Mass detection was performed by positive ion mode electrospray MS-MS and included the following drugs/metabolites: morphine, codeine, ethyl morphine, oxycodone, buprenorphine, methadone, cocaine, methylphenidate, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), Δ(9)-tetrahydrocannabinol (THC), fentanyl, alprazolam, bromazepam, clonazepam, diazepam, nordiazepam, 3-OH-diazepam, fenazepam, flunitrazepam, lorazepam, nitrazepam, oxazepam, zopiclone, zolpidem, carisoprodol, and meprobamate. The cycle time was 9 min, and within- and between-day relative coefficients of variation varied from 1% to 33% and 2% to 58%, respectively. Extraction recoveries from whole blood were > 50% except for morphine and THC. The limit of quantitation was 0.1 to 521 ng/mL, depending on the drug. PMID:21619723

  11. Quantitative analysis of 26 opioids, cocaine, and their metabolites in human blood by ultra performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Fernández, María del Mar Ramírez; Wille, Sarah M R; Kummer, Nathalie; Di Fazio, Vincent; Ruyssinckx, Evi; Samyn, Nele

    2013-08-01

    A sensitive and selective ultra performance liquid chromatographic-tandem mass spectrometric method was developed and fully validated for the simultaneous determination of (in order of chromatographic elution) methylecgonine, pholcodine, morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-Monoacetylmorphine (6-MAM), hydrocodone, ethylmorphine, norfentanyl, benzoylecgonine, tramadol, normeperidine, meperidine, cocaine, pentazocine, cocaethylene, fentanyl, norbuprenorphine, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, propoxyphene, and methadone in blood. The matrixes analyzed during the validation experiments were as follows: citrated blank plasma for calibrators, fluoride blank plasma for internal quality control (QC), lyophilized serum for external QC, fluoride plasma and whole blood for authentic samples, and lyophilized serum and whole blood for proficiency testing schemes. Samples were extracted with cation exchange solid-phase extraction cartridges. The target drugs were separated and quantified in a chromatographic run of 8.1 minutes using 0.1% formic acid in water and methanol (with 0.1% formic acid) as mobile phase. The limit of quantification ranged from 0.5 to 2.5 ng/mL depending on the compound and the therapeutic concentration. The intra- and interassay precision was less than 15% for all the compounds (except for pentazocine and EDDP, which was heroin, cocaine, tramadol, and methadone, and to proficiency testing schemes. PMID:23783166

  12. In vivo receptor binding of opioid drugs at the mu site

    International Nuclear Information System (INIS)

    The in vivo receptor binding of a series of opioid drugs was investigated in intact rats after s.c. administration of [3H]etorphine tracer, which selectively binds to mu sites in vivo. Receptor binding was determined by a membrane filtration assay immediately after sacrifice of the animals and brain homogenization. Coadministration of unlabeled opioid drugs together with tracer led to a dose-dependent decrease of in vivo tracer binding. Estimates of the doses required to occupy 50% of the mu sites in vivo established the following potency rank order: diprenorphine, naloxone, buprenorphine, etorphine, levallorphan, cyclazocine, sufentanil, nalorphine, ethylketocyclazocine, ketocyclazocine, pentazocine, morphine. In vivo-in vitro differences among the relative receptor binding potencies were only partially accounted for by differences in their access to the brain and the regulatory effects of Na+ and GTP, which are expected to reduce agonist affinities in vivo. The relationship among mu receptor occupancy in vivo and pharmacological effects of the opioid drugs is described

  13. Pharmacotherapy of Pain in the Older Population: The Place of Opioids.

    Science.gov (United States)

    Prostran, Milica; Vujović, Katarina Savić; Vučković, Sonja; Medić, Branislava; Srebro, Dragana; Divac, Nevena; Stojanović, Radan; Vujović, Aleksandar; Jovanović, Lepa; Jotić, Ana; Cerovac, Nataša

    2016-01-01

    Pain is a common symptom in older people. It is possible that pain is underreported in older persons due to an incorrect belief that it is an inevitable part of aging. Opioid analgesics are potent medications, with confirmed efficacy for the treatment of moderate to severe pain. These drugs are commonly used in older persons. However, there is insufficient evidence regarding safety of opioids in older patients. One of the reasons for this is the lack of randomized, controlled clinical trials. People of advanced age often have comorbidites and use other prescription drugs, as well as over-the-counter (OTC) compounds, thus making them more suceptible to the risk of interactions with opioids. Significant pharmacokinetic and pharmacodynamic changes that occur with advancing age increase the risk of adverse effects of opioids. There are also some discrepancies between guidelines, which recommend the use of lower doses of opioids in older patients, and the findings in the literature which suggest that pain is often undertreated in this age group. It seems that there are significant variations in the tolerability of different opioid analgesics in older people. Morphine, fentanyl, oxycodone, and buprenorphine are still the preferred evidence-based choices for add-on opioid therapy for these patients. However, the safety and efficacy of other opioids in older patients, especially if comorbidities and polypharmacy are present, is still questionable. This review addresses the most important aspects of the use of opioids in older persons, focusing on pharmacokinetics, pharmacodynamics, adverse effects, and interactions. PMID:27378916

  14. A tentative component analysis of Norjizak: A new abused drug in Iran.

    Science.gov (United States)

    Sadeghi, Mandana; Farhoudian, Ali; Vishteh, Hamid Reza Khoddami; Rahimzadeh, Shadi; Fekri, Monir; Movaghar, Afarin Rahimi; Sefatian, Saeed

    2015-09-01

    Norjizak is a new drug abused in the past few years in Iran with symptoms and complications distinct from other common forms of drug and characterized by higher rate of mortality. The present study aims to analyze the chemical components of this substance. Five samples were obtained from abusers referring from different areas of Tehran to a treatment clinic. All samples were 2 ml vials with yellowish fluid. Thin Layer Chromatography (TLC) was performed first to analyze the samples semi-quantitatively and the quantitative levels of components were then explored using high-performance liquid chromatography (HPLC). TLC revealed steroid (in form of betamethasone), heroin, codeine, morphine and thebaine in all five samples. Four samples contained acetaminophen and two samples contained caffeine. None of them contained amphetamine, benzodiazepine, tricyclic antidepressant, aspirin, barbiturates, tramadol and buprenorphine. HPLC revealed that heroin, codeine, morphine and thebaine constituted the narcotic foundation in all samples. In addition, the heroin to acetylcodeine ratio was significantly lower in three samples, which indicates their higher toxicity. The results of the present study on the chemical components of Norjizak showed that this substance is an opiate one similar to heroin and the heroin-based crack prevalent in Iran which contains betamethasone. PMID:26408883

  15. [Guidelines for substitution treatments in prison populations].

    Science.gov (United States)

    Michel, L; Maguet, O

    2005-01-01

    Care access for the drug addict patients in prison (in particular for the treatments of substitution) in France is very unequal from one establishment to another. This reflects the great variability of the practices of substitution and especially the absence of consensus on the methods of adaptation of these practices to the prison environment. Because of difficulties expressed by prisoners and medical staff on this subject and of stakes (let us recall that approximately 30% of the prisoners are dependent or abusers of one or more psychoactive substances), the formulation of recommendations or of a good practices guide of substitution in prison appeared necessary. Work that we detail here answers a ordering of the Advisory Commission of the Treatments of Substitution (September 2001) whose authors are members. It was presented at the session April 2003. It results from the confrontation of a review of the literature (including legal texts and official reports concerning substitution, the organization of the care in prison environment and the lawful framework), with a vast investigation. The latter was carried out near medical staff (22 prisons), penitentiary staff (3 prisons, 27 people met including directors of these establishments) and prisoners (7 establishments, 28 prisoners met) in the form of individual talks (semi-directing interviews with evaluation of the type of existing device and its knowledge by the penitentiary staff and the prisoners; statement of the suggestions, needs and requests of the medical, penitentiary staffs and of the prisoners). In the whole visited prisons, 7.8% (870) of the prisoners received substitution treatments (6.35% by buprenorphine, 1.44% by methadone), representing a proportion of substituted drug addicts (870 substituted for an evaluation of 3,350 prisoners drug addicts among the 11,168 prisoners of the 22 visited prisons) notably lower than that in free environment (56%, ie 96,000 substituted for an evaluated population of

  16. Confecção de um modelo experimental in vitro do espaço subaracnóide eqüino para teste de opióides hiperbáricos Making of an in vitro experimental model of equine subarachnoid space to test hyperbaric opioids

    Directory of Open Access Journals (Sweden)

    Alexandre da Silva Polydoro

    2008-04-01

    Full Text Available Com o objetivo de avaliar as características de distribuição de agentes hiperbáricos no líquido cérebro-espinhal (LCE eqüino, é apresentado um modelo in vitro do espaço subaracnóide confeccionado em policloreto de vinila (PVC transparente, no qual se adaptou um cateter para a infusão contínua de glicose a 10%, morfina hiperbárica, buprenorfina hiperbárica e metadona hiperbárica marcadas com azul de metileno para permitir a visualização da distribuição destas substâncias no LCE. Avaliaram-se a distância alcançada pelos diferentes agentes minuto a minuto e a forma de distribuição dos mesmos. Todas as substâncias testadas mostraram comportamento de distribuição vertical a partir da extremidade do cateter, quando se deu o início da migração cranial no LCE, sendo que o avanço máximo registrado foi aos 15 minutos após o término da infusão, com migração de 15cm para glicose a 10%, 13cm para a morfina hiperbárica, 18cm para a buprenorfina hiperbárica e 17cm para a metadona hiperbárica. O modelo proposto mostrou-se eficiente para a avaliação do comportamento físico dos agentes hiperbáricos no interior do espaço subaracnóide, oferecendo a possibilidade de teste de substâncias a serem utilizadas pela via subaracnóide de cavalos.The aim of this study was to evaluate the distribution characteristics of hyperbaric solutions in equine cerebrospinal fluid (CSF, in an in vitro model of the subarachnoid space. The model was made with transparent PVC in which a catheter was adapted to infuse 10% glucose, 10% hyperbaric morphine, hyperbaric buprenorphine, and hyperbaric methadone, dyed with methilene blue in order to visualize the solutions distribution in the CSF. The distance in cm reached by the different agents every minute as well as the pattern of distribution were evaluated. All tested solutions distributed itself in a forward and vertically pattern from the tip of the catheter. Maximum distance reached after

  17. Neurobiology of opioid dependence in creating addiction vulnerability.

    Science.gov (United States)

    Evans, Christopher J; Cahill, Catherine M

    2016-01-01

    Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality - the "drug-dependent" state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadone or buprenorphine, is generally indistinguishable from the drug-naïve state for most overt behaviors. The consequences of the allostatic changes (cellular, circuit, and system adaptations) that accompany the drug-dependent state are revealed during drug withdrawal. Drug cessation triggers a temporally orchestrated allostatic re-establishment of neuronal systems, which is manifested as opposing physiological and psychological effects to those exhibited by acute drug intoxication. Some withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea) resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can linger for months, and some adaptations, such as learned associations, may be established for life. We will briefly discuss the cellular mechanisms and neural circuitry that contribute to the opioid drug-dependent state, inferring an emerging role for neuroinflammation. We will argue that opioid addictive behaviors result from a learned relationship between opioids and relief from an existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a future stressful life event can recall the memory that opioid drugs alleviate negative affect (despair, sadness, and anxiety) and thereby precipitate craving, resulting in relapse. A learned association of relief of aversive states would fuel drug craving in vulnerable people living in an increasingly stressful society. We suggest that this route to addiction is contributive to

  18. Treatment-refractory substance use disorder: Focus on alcohol, opioids, and cocaine.

    Science.gov (United States)

    Soyka, Michael; Mutschler, Jochen

    2016-10-01

    Substance use disorders are common, but only a small minority of patients receive adequate treatment. Although psychosocial therapies are effective, relapse is common. This review focusses on novel pharmacological and other treatments for patients with alcohol, opioid, or cocaine use disorders who do not respond to conventional treatments. Disulfiram, acamprosate, and the opioid antagonist naltrexone have been approved for the treatment of alcoholism. A novel, "as needed" approach is the use of the mu-opioid antagonist and partial kappa agonist nalmefene to reduce alcohol consumption. Other novel pharmacological approaches include the GABA-B receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the partial nicotine receptor agonist varenicline, and other drugs. For opioid dependence, opioid agonist therapy with methadone or buprenorphine is the first-line treatment option. Other options include oral or depot naltrexone, morphine sulfate, depot or implant formulations, and heroin (diacetylmorphine) in treatment-refractory patients. To date, no pharmacological treatment has been approved for cocaine addiction; however, 3 potential pharmacological treatments are being studied, disulfiram, methylphenidate, and modafinil. Pharmacogenetic approaches may help to optimize treatment response in otherwise treatment-refractory patients and to identify which patients are more likely to respond to treatment, and neuromodulation techniques such as repeated transcranial magnetic stimulation and deep brain stimulation also may play a role in the treatment of substance use disorders. Although no magic bullet is in sight for treatment-refractory patients, some novel medications and brain stimulation techniques have the potential to enrich treatment options at least for some patients. PMID:26577297

  19. Use of anti-inflammatory and analgesic drugs in dogs and cats.

    Science.gov (United States)

    Watson, A D; Nicholson, A; Church, D B; Pearson, M R

    1996-09-01

    Responses (486) were collared from a survey of 5054 Australian veterinarians on their use of anti-inflammatory and analgesic drugs in dogs and cats. Almost all respondents used glucocorticoids (usually prednisolone) to treat allergic, pruritic dermatoses in dogs, while two-thirds also gave fatty acid supplements and one-half used antihistamines. Almost 60% of respondents initially injected a glucocorticoid (frequently a long-acting preparation) when treating inflammatory skin diseases in dogs. More than 90% of respondents used glucocorticoids to treat immune-mediated haemolytic anaemia or thrombocytopenia, and about one-third also gave cytotoxic drugs. Administration of prednisolone on alternate days was generally favoured for long-term enteral steroid therapy. Phenylbutazone was the most preferred treatment for painful or inflammatory musculoskeletal disorders of dogs, but aspirin and pentosan polysulphate were also used widely. Regarding the use of analgesics drugs generally, both narcotic analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) were used more widely in dogs than in cats, but alpha-2 agonists were used similarly in both species. The most commonly used narcotic analgesics were pethidine and buprenorphine in both species, while the NSAIDs used most often were flunixin and dipyrone in dogs and ketoprofen in cats. More than 80% of respondents generally used analgesic drugs with potentially painful surgical procedures, with doses given usually before anaesthetic recovery. Analgesic use rates varied with the condition, ranging from 94% for patients with acute severe trauma, through 60% for cruciate ligament repair and 29% for perineal herniorrahphy, to about 5% for ovariohysterectomy and dog castration. The three clinical signs most frequently nominated as indicators of pain in dogs and cats were (in descending order) vocalisation, response to handling or palpating the affected area, and mental depression. Other items mentioned frequently were

  20. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism

    Directory of Open Access Journals (Sweden)

    Coluzzi F

    2015-03-01

    Full Text Available Flaminia Coluzzi,1,2 Joseph Pergolizzi,3,4 Robert B Raffa,5 Consalvo Mattia1,2 1Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesiology, Intensive Care Medicine and Pain Therapy, Faculty of Pharmacy and Medicine – Polo Pontino, Sapienza University of Rome, Latina, Italy; 2SIAARTI Study Group on Acute and Chronic Pain, Rome, Italy; 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 4Naples Anesthesia and Pain Associates, Naples, FL, 5Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1 the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2 reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3 chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine. Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily should be monitored for the early detection of hormonal impairment and low bone mass density. Keywords: opioids side effects, bone metabolism, fractures, OPIAD, endocrine system, chronic pain

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

    Science.gov (United States)

    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. PMID:26025117

  2. Assessment of an Orofacial Operant Pain Assay as a Preclinical Tool for Evaluating Analgesic Efficacy in Rodents.

    Science.gov (United States)

    Ramirez, Harvey E; Queeney, Timothy J; Dunbar, Misha L; Eichner, Michael C; Del Castillo, Dania I; Battles, August H; Neubert, John K

    2015-07-01

    A model system capable of providing clinically relevant analgesic doses with minimal trauma has been elusive in laboratory animal medicine. Our laboratory has developed an orofacial operant pain system that effectively discriminates between non-noxious and noxious thermal stimuli in rats and mice. Male and female rats (Crl:SD) and mice (Crl:SKR-HR(hr)) were trained to perform a task (placing their face through an opening and having their cheeks stay in contact with thermodes) to receive a reward (a solution of sweetened condensed milk). Currently accepted doses of buprenorphine were tested by using a crossover design. Pain was induced in both species by sensitizing the depilated skin over both cheeks with capsaicin cream or by creating a surgical incision (rats only) and then allowing the animals to contact a temperature-regulated thermode while obtaining a reward. Optimal antinociceptive doses included 0.05 and 0.1 mg/kg in male mice but only 0.05 mg/kg in female mice. In rats, optimal antinociceptive doses included 0.03 and 0.05 mg/kg for male rats but only 0.03 mg/kg for female rats. The 2 pain-induction models in rats (capsaicin cream and surgical incision) did not differ. Our orofacial operant pain assay can determine clinically relevant analgesic doses for rodents in a preclinical assay. The automated, investigator-independent nature of the assay, in conjunction with its high sensitivity, makes this method an improvement over traditional noninvasive methods, providing better data for developing optimal analgesic recommendations for rats and mice. PMID:26224444

  3. Pharmacokinetics of bupivacaine after intraperitoneal administration to cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Benito, Javier; Monteiro, Beatriz P; Beaudry, Francis; Lavoie, Anne-Marie; Lascelles, B Duncan X; Steagall, Paulo V

    2016-06-01

    OBJECTIVE To evaluate pharmacokinetics of bupivacaine after IP administration to cats undergoing ovariohysterectomy. ANIMALS 8 healthy cats. PROCEDURES Anesthesia was induced with propofol and maintained with isoflurane. Buprenorphine (0.02 mg/kg, IV) and meloxicam (0.2 mg/kg, SC) were administered. A 20-gauge catheter was inserted into a jugular vein for blood sample collection. A ventral midline incision was made, and a solution of 0.5% bupivacaine (2 mg/kg) diluted with an equal volume of saline (0.9% NaCl) solution (final concentration, 0.25% bupivacaine) was injected into the peritoneal space over the right and left ovarian pedicles and caudal aspect of the uterus before ovariohysterectomy. Cats were monitored for signs of bupivacaine toxicosis. Venous blood samples (2 mL) were collected before (time 0) and 2, 5, 10, 15, 20, 30, 60, 120, and 240 minutes after bupivacaine administration. Plasma bupivacaine concentrations were determined with a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined by data plotting followed by analysis with a noncompartmental model. RESULTS No signs of bupivacaine toxicosis were observed. Maximum bupivacaine plasma concentration was 1,030 ± 497.5 ng/mL at a mean ± SD value of 30 ± 24 minutes after administration. Mean elimination half-life was 4.79 ± 2.7 hours. Mean clearance indexed by bioavailability and volume of distribution indexed by bioavailability were 0.35 ± 0.18 L•h/kg and 2.10 ± 0.84 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Intraperitoneal administration of bupivacaine resulted in concentrations that did not cause observable toxicosis. Studies to investigate analgesic effects for this technique in cats are warranted. PMID:27227503

  4. Suppression of Locomotor Activity in Female C57Bl/6J Mice Treated with Interleukin-1β: Investigating a Method for the Study of Fatigue in Laboratory Animals.

    Directory of Open Access Journals (Sweden)

    David R Bonsall

    Full Text Available Fatigue is a disabling symptom in patients with multiple sclerosis and Parkinson's Disease, and is also common in patients with traumatic brain injury, cancer, and inflammatory disorders. Little is known about the neurobiology of fatigue, in part due to the lack of an approach to induce fatigue in laboratory animals. Fatigue is a common response to systemic challenge by pathogens, a response in part mediated through action of the pro-inflammatory cytokine interleukin-1 beta (IL-1β. We investigated the behavioral responses of mice to IL-1β. Female C57Bl/6J mice of 3 ages were administered IL-1β at various doses i.p. Interleukin-1β reduced locomotor activity, and sensitivity increased with age. Further experiments were conducted with middle-aged females. Centrally administered IL-1β dose-dependently reduced locomotor activity. Using doses of IL-1β that caused suppression of locomotor activity, we measured minimal signs of sickness, such as hyperthermia, pain or anhedonia (as measured with abdominal temperature probes, pre-treatment with the analgesic buprenorphine and through sucrose preference, respectively, all of which are responses commonly reported with higher doses. We found that middle-aged orexin-/- mice showed equivalent effects of IL-1β on locomotor activity as seen in wild-type controls, suggesting that orexins are not necessary for IL-1β -induced reductions in wheel-running. Given that the availability and success of therapeutic treatments for fatigue is currently limited, we examined the effectiveness of two potential clinical treatments, modafinil and methylphenidate. We found that these treatments were variably successful in restoring locomotor activity after IL-1β administration. This provides one step toward development of a satisfactory animal model of the multidimensional experience of fatigue, a model that could allow us to determine possible pathways through which inflammation induces fatigue, and could lead to novel

  5. A model of integrated primary care for HIV-positive patients with underlying substance use and mental illness.

    Science.gov (United States)

    Zaller, N; Gillani, F S; Rich, J D

    2007-10-01

    There is a high burden of underlying substance use and mental illness in HIV-infected populations. HIV-care settings provide an important opportunity to assess substance and mental health needs among HIV-positive patients and to provide or make referrals for appropriate treatment services. In 2003, with funding from the Center for Substance Abuse Treatment (CSAT), we developed a model of integrated substance-use counselling and referral for treatment within a primary care HIV-care setting at The Miriam Hospital in Providence, Rhode Island. The project uses a multidisciplinary approach to provide linkage to treatment services for substance use and mental illness as well as to help participants with social service needs, such as housing and medical coverage, to ensure continuity of care and optimal HIV treatment adherence. Twelve percent of the 965 HIV-infected patients in care at our center have been enrolled in the project. Of these, all have a current substance-use disorder and 79.3% have been diagnosed with a mental illness. In addition, most participants are hepatitis C-positive (HCV) (65.5%). The majority of participants are on antiretroviral therapy (76.7%). Participants have been referred for the following treatment modalities: intensive outpatient services, methadone, buprenorphine, outpatient services and residential as well as individual and group counselling. Our model has been successful in assessing the substance-use and mental health needs of HIV-infected individuals with numerous co-morbidities and referring them for ancillary medical and social services. PMID:18058396

  6. Dihydrocodeine / Agonists for Alcohol Dependents

    Directory of Open Access Journals (Sweden)

    Albrecht eUlmer

    2012-03-01

    Full Text Available Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients.Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC to 102 heavily alcohol addict-ed patients, later, also Buprenorphine, Clomethiazole (>6 weeks, Baclofen and in one case Amphetamine, each on individual indication. This paper focuses on the data with DH, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC-treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-step scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details.Conclusions: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around ¼ of the patients already. Many further

  7. Pain in cancer. An outcome research project to evaluate the epidemiology, the quality and the effects of pain treatment in cancer patients

    Directory of Open Access Journals (Sweden)

    Nicora Mariaflavia

    2006-02-01

    Full Text Available Abstract Background Management of pain related to advanced or metastatic cancer, although the availability of several pharmacological and non-pharmacological interventions and the existence of well-known guidelines and protocols, is often difficult and inadequate. Evidence of the relative effectiveness of current options for treating cancer pain from comparative randomized studies is scanty. Methods In the context of a wider project, a multicenter, open label, prospective Outcome Research study will be launched in Italy in 2006 to investigate the epidemiology of cancer pain and of its treatments, the quality of analgesic-drug therapy and the effectiveness of alternative analgesic strategies in a large, prospective, unselected cohort of cancer patients using the state-of-the art of patient-reported-outcomes. About 100 Italian centers will recruit 2500 patients with advanced/progressive/metastatic cancer with pain (related to the cancer disease requiring analgesic treatments. Each center is expected to recruit 25 consecutive and eligible patients during the study inception period. Approximately two months will be allowed for subject recruitment and enrollment. Subject evaluation and follow-up will be for 3 months. The effect on outcomes of various therapeutic analgesic options administered by physicians, given the observational approach where patients are not assigned at random to different treatments, will be compared using the propensity score approach, allowing the adjustment for treatment selection bias. Later, after the launch of the observational study and on the basis of results, in specific subsamples of patients and in select centers of the network, a Randomized Controlled Trial will be carried out to formally compare the efficacy of alternative analgesic strategies, with particular emphasis on oral morphine (as comparator and buprenorphine patch (as experimental arm. Results from the outcome (cohort and experimental (Randomized

  8. Long-term course of opioid addiction.

    Science.gov (United States)

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

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed. PMID:25747921

  9. It’s MORe exciting than mu: Crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system

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    ElenaHChartoff

    2014-05-01

    Full Text Available Opioids selective for the G-protein coupled mu opioid receptor (MOR produce potent analgesia and euphoria. Heroin, a synthetic opioid, is considered one of the most addictive substances, and the recent exponential rise in opioid addiction and overdose deaths has made treatment development a national public health priority. Existing medications (methadone, buprenorphine, and naltrexone, when combined with psychosocial therapies, have proven efficacy in reducing aspects of opioid addiction. Unfortunately, these medications have critical limitations including those associated with opioid agonist therapies (e.g., sustained physiological dependence and opioid withdrawal leading to high relapse rates upon discontinuation, nonadherence to daily dosing, and non-renewal of monthly injection with extended-release naltrexone. Furthermore, current medications fail to ameliorate key aspects of addiction such as powerful conditioned associations that trigger relapse (e.g., cues, stress, the drug itself. Thus, there is a need for developing novel treatments that target neural processes corrupted with chronic opioid use. This requires a basic understanding of molecular and cellular mechanisms underlying effects of opioids on synaptic transmission and plasticity within reward-related neural circuits. The focus of this review is to discuss how crosstalk between MOR-associated G-protein signaling and glutamatergic neurotransmission leads to immediate and long-term effects on emotional states (e.g., euphoria, depression and motivated behavior (e.g., drug-seeking, relapse. Our goal is to integrate findings on how opioids modulate synaptic release of glutamate and postsynaptic transmission via AMPA and NMDA receptors in the nucleus accumbens (NAc and ventral tegmental area (VTA with the clinical (neurobehavioral progression of opioid dependence, as well as to identify gaps in knowledge that can be addressed in future studies.

  10. Investigating expectation and reward in human opioid addiction with [11C]raclopride PET

    Science.gov (United States)

    Watson, Ben J; Taylor, Lindsay G; Reid, Alastair G; Wilson, Sue J; Stokes, Paul R; Brooks, David J; Myers, James F; Turkheimer, Federico E; Nutt, David J; Lingford-Hughes, Anne R

    2014-01-01

    The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [11C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals. PMID:23829344

  11. Five-factor model personality traits in opioid dependence

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    Nordvik Hilmar

    2007-08-01

    Full Text Available Abstract Background Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence. Methods We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R, a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores. Results The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores. Conclusion We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers.

  12. Neurobiology of opioid dependence in creating addiction vulnerability [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Christopher J. Evans

    2016-07-01

    Full Text Available Opioid drugs are potent modulators of many physiological and psychological processes. When given acutely, they can elicit the signature responses of euphoria and analgesia that societies have coveted for centuries. Repeated, or chronic, use of opioids induces adaptive or allostatic changes that modify neuronal circuitry and create an altered normality — the “drug-dependent” state. This state, at least that exhibited by those maintained continuously on long-acting opioid drugs such as methadone or buprenorphine, is generally indistinguishable from the drug-naïve state for most overt behaviors. The consequences of the allostatic changes (cellular, circuit, and system adaptations that accompany the drug-dependent state are revealed during drug withdrawal. Drug cessation triggers a temporally orchestrated allostatic re-establishment of neuronal systems, which is manifested as opposing physiological and psychological effects to those exhibited by acute drug intoxication. Some withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can linger for months, and some adaptations, such as learned associations, may be established for life. We will briefly discuss the cellular mechanisms and neural circuitry that contribute to the opioid drug-dependent state, inferring an emerging role for neuroinflammation. We will argue that opioid addictive behaviors result from a learned relationship between opioids and relief from an existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a future stressful life event can recall the memory that opioid drugs alleviate negative affect (despair, sadness, and anxiety and thereby precipitate craving, resulting in relapse. A learned association of relief of aversive states would fuel drug craving in vulnerable people living in an increasingly stressful society. We suggest that this route to

  13. Management of poor grade subarachnoid hemorrhage. Unsolved problems in the ultra-acute phase

    International Nuclear Information System (INIS)

    We evaluated the management of patients with subarachnoid hemorrhage (SAH) after arrival for surgical intervention in the ultra-acute stage. Immediately after brief neurological and systemic examination, patients were deeply sedated to prevent aneurysmal rerupture. Principally they were intubated with intensive control of systolic blood pressure below 120 mmHg by radial arterial monitoring. Buprenorphine, midazolam, and vecuronium were routinely intravenously administered; and propofol, barbiturate, nicardipine, or prostaglandin was added to lower blood pressure if necessary. A total of 163 consecutive patients with SAH (59 men and 104 women, mean age of 61.1 years) arrived between 2003 and 2005 were enrolled. The majority of patients were in poor grade: 26 with Grade IV, 54 with Grade V by grading scale of the World Federation of Neurological Society, and 32 with cardiopulmonary arrest. Eighty-seven patients (53%) arrived within 1 hour after onset of SAH and 127 patients (78%) arrived within 3 hours. Most of the poor-grade patients were intubated before initial brain CT scan. Mean systolic blood pressure was around 170 mmHg at the time of arrival, which was controlled around 120 mmHg or less during resuscitation and angiography. A total of 117 patients had DSA, 111 of them (68%) within 3 hours, and 111 patients underwent surgery, 81 of them (85%) within 6 hours. Despite intensive resuscitation, 36 episodes of rebleeding were detected in 32 patients, 24 before and 12 after arrival. Extravasation of contrast media was seen in 6 patients during cerebral angiography. Favorable outcome (good recovery and moderate disability) was obtained in 69% of Grade IV and 24% of the Grade V patients. The risk of ultra-early rebleeding is highest for patients with poor grades. Deep sedation and strict blood pressure control followed by urgent obliteration of the ruptured aneurysm have a strong rationale to prevent rerupture and to achieve better overall outcome. (author)

  14. Exhaled breath for drugs of abuse testing - evaluation in criminal justice settings.

    Science.gov (United States)

    Beck, Olof

    2014-01-01

    Exhaled breath is being developed as a possible specimen for drug testing based on the collection of aerosol particles originating from the lung fluid. The present study was aimed to evaluate the applicability of exhaled breath for drugs of abuse testing in criminal justice settings. Particles in exhaled breath were collected with a new device in parallel with routine urine testing in two Swedish prisons, comprising both genders. Urine screening was performed according to established routines either by dipstick or by immunochemical methods at the Forensic Chemistry Laboratory and confirmations were with mass spectrometry methods. A total of 247 parallel samples were studied. Analysis of exhaled breath samples was done with a sensitive mass spectrometric method and identifications were made according to forensic standards. In addition tested subjects and personnel were asked to fill in a questionnaire concerning their views about drug testing. In 212 cases both the urine and breath testing were negative, and in 22 cases both urine and breath were positive. Out of 6 cases where breath was negative and urine positive 4 concerned THC. Out of 7 cases where, breath was positive and urine negative 6 concerned amphetamine. Detected substances in breath comprised: amphetamine, methamphetamine, THC, methylphenidate, buprenorphine, 6-acetylmorphine, cocaine, benzoylecgonine, diazepam and tramadol. Both the prison inmates and staff members reported breath testing to be preferable due to practical considerations. The results of this study documented that drug testing using exhaled breath provided as many positives as urine testing despite an expected shorter detection window, and that the breath sampling procedure was well accepted and provided practical benefits reported both by the prison inmates and testing personnel. PMID:24438778

  15. The current status of opioid maintenance treatment in France: a survey of physicians, patients, and out-of-treatment opioid users

    Directory of Open Access Journals (Sweden)

    Benyamina A

    2014-09-01

    Full Text Available Amine Benyamina National Institute for Medical Research (INSERM U-669, Hôpital Universitaire Paul Brousse, 94804 Villejuif, France Aim: Project Access France was a national survey designed to provide real-world observations on the status of opioid dependence treatment in France. Methods: The views of physicians (n=100, patients (n=130, and out-of-treatment opioid users (n=33 were collected via interviews and questionnaires. Results: Physicians reported being moderately satisfied with treatment programs in their area (rating 6.9 out of 10. Most physicians (82% reported being concerned about misuse and diversion of medication-assisted treatment (MAT medications and 50% identified psychosocial/behavioral counseling as the key change that would most improve patient care. Among patients, the mean number of previous MAT episodes was low (1.5; 78% reported that it was easy to access a doctor to undergo MAT; 14% reported regularly or sometimes using heroin; misuse and diversion were reported in 15% and 39% of patients, respectively; and 57% of patients were not receiving psychosocial help. Out-of-treatment opioid users reported using drugs on a regular basis (42% regularly used heroin and cited 'not wanting to give up drugs completely' as the most frequent reason for staying out of MAT. Conclusion: This survey highlights a number of positive features of the open-access, GP-based treatment model for opioid dependence in France. Challenges remain with regard to continued misuse/diversion of MAT medications and limited patient access to psychosocial support. Keywords: opioid maintenance treatment, medication-assisted treatment, buprenorphine, methadone, buprenorphine–naloxone, France

  16. Effect of Acupuncture on Detoxification of Heroin Addicts at Late Stage

    Institute of Scientific and Technical Information of China (English)

    WU Jun-mei; LUO Yong-fen; WEI Dong-yan

    2005-01-01

    Objective: To study the action of acupuncture on the morbid psychology of the heroine addicts at late stage of detoxification. Methods: Four methods including acupuncture, combination of opium and acupuncture, combination of opium and buprenorphine, and combination of opium and Han's drug withdrawal instrument were adopted to study the effect of acupuncture on each factor in 90 listing symptoms of heroin addicts at late stage of detoxification by the self-evaluation scales. Result: Acupuncture had more advantages in improving obsessive symptoms, anxiety, psychogenic symptoms and No 10 factor (P< 0.01). Conclusion: Acupuncture can correct the morbid psychology of the addicts and help them enter the recovery stage smoothly.%目的:研究针刺对海洛因依赖者脱毒末期病态心理的改善作用.方法:选用针刺疗法、阿片加针刺疗法与阿片加丁丙诺啡及阿片加韩氏戒毒仪四种脱毒方法,应用症状自评量表,研究针刺对海洛因依赖者脱毒末期90项症状清单各因子的影响.结果:针刺能改善患者的病态心理,对强迫症状、焦虑、精神病性和因子十的调节更具优势(P<0.01).结论:针刺能改善患者病态心理,有希望帮助患者平稳地进入康复期.

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

    Science.gov (United States)

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

    2015-09-15

    A liquid chromatography-tandem mass spectrometry method using electrospray ionization in positive ionization mode was developed for the simultaneous detection of multiple opioid-type drugs in plasma. The presented assay allows the quantitative determination of alfentanil, buprenorphine, codeine, desomorphine, dextromethorphan, dextrorphan, dihydrocodeine, dihydromorphine, ethylmorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, naloxone, naltrexone, oxycodone, oxymorphone, pentazocine, pethidine, pholcodine, piritramide, remifentanil, sufentanil, and tramadol as well as the metabolites 6-monoacetylmorphine, bisnortilidine, morphine-3-glucuronide, morphine-6-glucuronide, naltrexol, norbuprenorphine, norfentanyl, norpethidine, nortilidine, and O-desmethyltramadol. Serum and blood samples were purified by solid-phase extraction. The analytes were separated on a phenyl-hexyl (100mm) column by formic acid/acetonitrile gradient elution using an UPLC 1290 Infinity coupled with a 6490 Triple Quadrupole mass spectrometer. The limits of detection ranged from 0.02 to 0.6ng/mL and the lower limits of quantification ranged from 0.1 to 2.0ng/mL. The calibration curves were linear between Calibration Levels 1-6 for all 35 substances. Recovery rates ranged between 51 and 88% for all compounds except alfentanil, bisnortilidine, pethidine, and morphine-3-glucuronide. The matrix effect ranged from 86% for ethylmorphine to 105% for desomorphine. Using the validation procedure proposed by the German Society of Toxicological and Forensic Chemistry, acceptable precision and accuracy data for almost all analytes were obtained. The method was successfully applied to 206 authentic serum samples provided by the palliative and intensive care units of the University Medical Center and the police authorities. Furthermore, a suspected fatal intoxication is demonstrated by an analysis of the sufentanil in post mortem body fluids and tissues. PMID:26241181

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

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    Havens Jennifer R

    2010-10-01

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

  19. Anaesthesia and analgesia for dogs and cats in South Africa undergoing sterilisation and with osteoarthritis - an update from 2000 : report

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    K.E. Joubert

    2006-06-01

    Full Text Available A survey was conducted in 2000 into the use of analgesic drugs by veterinarians in South Africa. This survey was repeated in 2005 to establish whether the use of analgesic drugs has increased and which analgesic drugs are being used for acute pain and osteoarthritis. The number of sterilisations performed and the number of new cases of osteoarthritis in dogs and cats was estimated. It is estimated that approximately 260 000 cats are operated on each year in South Africa and that 150 000 cats are sterilised. Five hundred thousand dogs undergo surgery, of which 242 000 are sterilised. It appears that the number of surgical procedures performed in South Africa has decreased. The estimated death rate following anaesthesia has remained unchanged at 1:1004. Overall, the use of analgesics by South African veterinarians has increased significantly. Fifty-six per cent of cats and 74% of dogs were given peri-operative analgesics but this increased to 94 % and 84 % after including pre-anaesthetic medications with analgesic properties. The use of opioids (morphine and buprenorphine and propofol has increased significantly. Approximately 253 000 dogs and 33 000 cats with osteoarthritis are seen by veterinarians in South Africa annually. The recognition by veterinarians of osteoarthritis in cats appears to be poor and is in need of attention. Carprofen and glucosamine / chondroitin are the most commonly used agents for the treatment of osteoarthritis. Details of the drugs used by veterinarians are given. Knowledge of analgesic drugs has increased significantly over the last 5 years. Continuing education is thought to have played an important role in the changes reported in this study.

  20. Beneficial properties of maraviroc on neuropathic pain development and opioid effectiveness in rats.

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    Kwiatkowski, Klaudia; Piotrowska, Anna; Rojewska, Ewelina; Makuch, Wioletta; Jurga, Agnieszka; Slusarczyk, Joanna; Trojan, Ewa; Basta-Kaim, Agnieszka; Mika, Joanna

    2016-01-01

    Targeting chemokine signaling pathways is crucial in neuropathy development. In this study, we investigated the influence of chronic administration of maraviroc (CCR5 antagonist) on nociception and opioid effectiveness during neuropathy, which develops as a result of chronic constriction injury (CCI) of the sciatic nerve. To investigate the mechanism of action of maraviroc, we measured the expression of glial cell markers, CCR5 and certain CCR5 ligands (CCL3, CCL4, CCL5, CCL7, CCL11), in the spinal cord and dorsal root ganglia (DRG) of vehicle- and maraviroc-treated, CCI-exposed rats. Our results demonstrate that chronic intrathecal administration of maraviroc diminished neuropathic pain symptoms on day 7 post-CCI. Western blot analysis showed that maraviroc diminished protein level of Iba-1 and GFAP and reversed the up-regulated CCR5 expression observed in spinal cord and DRG after CCI. Additionally, using qRT-PCR, we demonstrated that CCR5 and some of its pronociceptive ligands (CCL3, CCL4, CCL5) increased in the spinal cord after nerve injury, and maraviroc effectively diminished those changes. However, CCL11 spinal expression was undetectable, even after injury. In vitro primary culture studies showed that CCL3, CCL4, CCL5 and CCL7 (but not CCL11) were of microglial and astroglial origin and were up-regulated after LPS stimulation. Our results indicate that maraviroc not only attenuated the development of neuropathic pain symptoms due to significant modulation of neuroimmune interactions but also intensified the analgesic properties of morphine and buprenorphine. In sum, our results suggest the pharmacological modulation of CCR5 by maraviroc as a novel therapeutic approach for co-treatment of patients receiving opioid therapy for neuropathy. PMID:26190414

  1. Sprcial discussion: Future Roles for Tincture of Opium in Medical Intervention for Opioid Dependence Treads and Hopes

    Directory of Open Access Journals (Sweden)

    2009-02-01

    Full Text Available Opium tincture or tincture of opium (TOP, also known as Laudanum, is an alcoholic herbal preparation of opium. It is made by combining ethanol with opium latex or powder. After works of Paracelsus, the 16th century Swiss-German alchemist, who discovered that the alkaloids in opium are far more soluble in alcohol compared to water and named Opium tincture as Laudanum, this drug has been found a broad range of applications as the drug of choice for practically every ailment through 17th to 19th centuries. The early 20th century brought increased regulation of all manner of narcotics, including laudanum, as the addictive properties of opium became more widely understood. By the late 20th century, TOP's use was almost exclusively confined to treating severe diarrhea. During these thirty years, The efficacy and cost-effectiveness of opioid substitution therapy for the treatment of opioid addiction has been well documented by methadone and buprenorphine. Based on the idea of substitution therapy, TOP and slow releasing oral morphine (SROM have been proposed as the new alternatives. TOP could be used in three different ways in interventions for opioid dependency, first, as a supportive drug to reduce withdrawal syndrome during detoxification programs, second, as a substitution drug in long term maintenance, third, as a legal form of opioid drugs for harm reduction purposes. A little but growing evidences are supporting effectiveness of TOP for detoxification programs, in Iran, some preliminary open label studies showed effectiveness of TOP as a detoxifying drug in three to six month program, Now another open label study is evaluating TOP in a specific detoxification program with monthly evaluation and providing long term follow up after reaching to abstinence. There are a strong debate among the policy makers and clinicians on implementation of TOP in Iranian National Substance Abuse Treatment Facilities. In this article, We reviewed the proposed

  2. Initial evaluation of a canine stifle arthrotomy post-operative pain model.

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    Tomas, A; Bledsoe, D; Wall, S; Davidson, G; Lascelles, B D X

    2015-06-01

    Most models of acute post-operative orthopedic pain involve the injection of a clinically irrelevant pro-inflammatory agent. The ideal model should, however, be clinically relevant and allow full functional recovery of enrolled animals after research is completed. This study explored the validity of a model employing arthrotomy and objectively measured limb use. Six purpose-bred Beagles underwent arthrotomies on each stifle with a washout period in between. Using a randomized crossover design, each dog received placebo and an extended-release buprenorphine (ER-Bup) preparation. Static and dynamic ground reaction forces (GRFs) were measured prior to and for 72 h following surgery using a pressure sensitive walkway (PSW). GRFs for each hind limb were compared using difference (delta), and symmetry indices (SI). The effects of surgery and of treatment were analyzed using repeated measures ANCOVA. The results indicated significantly decreased limb use compared to baseline for placebo, and significantly increased limb use in the ER-Bup group over placebo at all times for % bodyweight distribution (%BWdistrib), peak vertical force (PVF) and vertical impulse (VI). There was a significant treatment by time interaction for velocity (P = 0.03) and %BWdistrib (P = 0.01, 0.003). Overall, the data show that reduced limb use was present for at least 72 h following arthrotomy. In addition, the use of the ER-Bup analgesic decreased lameness, confirming the validity of this approach as a model of post-operative pain. Subjective assessments did not detect the pain-inducing effects of arthrotomy or pain-alleviating effects of treatment, and subjective measures of procedural pain in research dogs need to be developed. PMID:25910516

  3. Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

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    Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

    2015-12-01

    The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

  4. Breastfeeding among Mothers on Opioid Maintenance Treatment: A Literature Review.

    Science.gov (United States)

    Tsai, Lillian C; Doan, Therese Jung

    2016-08-01

    Although there is an abundance of interventional studies to increase breastfeeding rates, little is known about how to support and promote breastfeeding among mothers on opioid maintenance treatment (OMT). The studies on maternal OMT mainly focus on medication excreted in breast milk and breastfeeding benefits for infants with neonatal abstinence syndrome (NAS). We aim to review interventions to improve breastfeeding outcomes among mothers on OMT to make recommendations for practice and future research. We searched CINAHL, PubMed, PsycINFO, and the Cochrane Database of Systematic Reviews for articles, preferably experimental/quasi-experimental studies published within the past 10 years, that examined interventions to increase rates of breastfeeding initiation and duration among mothers on OMT. Nine studies met our inclusion criteria, comprising 5 categories: 4 combined obstetric and addiction care, 1 rooming-in, 1 Baby-Friendly hospital, 2 inpatient/outpatient NAS treatment, and 1 divided methadone dose. Breastfeeding rates were relatively higher for divided methadone dose (81% initiated any breastfeeding) and rooming-in (62% initiated any breastfeeding); lower in Baby-Friendly hospital (24%) and inpatient/outpatient NAS treatment (45% and 24%, respectively); and mixed in combined obstetric and addiction care programs (2 studies reported 70% and 76%; 2 studies reported 17% and 28%). Studies that included both methadone and buprenorphine did not specify breastfeeding results by medication. We recommend future research to differentiate breastfeeding types and duration by OMT medication. Qualitative studies are needed to explore maternal view on breastfeeding regarding need, barrier, and motivating factors in order to develop effective interventions to promote breastfeeding among mothers on OMT. PMID:27053175

  5. Efficacy of flurbiprofen axetil in patient-controlled intravenous analgesia for preeclampsia patients after cesarean section%氟比洛芬酯对子痫前期患者剖宫产术后静脉自控镇痛疗效观察

    Institute of Scientific and Technical Information of China (English)

    邵志强; 陈新忠; 宋晓峰; 王志刚; 陆丽华; 周利鹏; 徐韡

    2015-01-01

    Objective To evaluate the efficacy of flurbiprofen axetil in patient- control ed intravenous analgesia (PCIA) for preeclampsia patients after cesarean section. Methods Ninety preeclampsia patients undergoing caesarean section were randomly assigned to one of the three groups (n=30 in each):group A (flurbiprofen axetil i.v and PCIA with buprenorphine), group B (PCIA with flurbiprofen axetil and buprenorphine) and group C (PCIA with buprenorphine). The VAS scores and Ramsay seda-tion scores at 1h, 2h, 4h, 12h and 24h after operation were assessed, mean artery pressure, HR , adverse reaction were recorded, the serum level of adrenaline(E), noradrenaline(NE), dopamine(DA) and ET- 1 level was detected, Results VAS scores of group A and group B at 1h, 2h, 4h, 12h and 24h after operation were significantly lower than those in groups C (P<0.05), Ramsay se-dation scores of group A and group B at 1h, 2h, 4h, 12h and 24h after operation were significantly higher than those in groups C (P<0.05);24h PCIA pressing times of group A and group B were significantly lower than that in groups C(P<0.05); serum E, NE, DA and ET- 1 levels of group A and group B were lower than those of group C (al P<0.05). ET- 1 level at 4h after operation of group A were lower than that of group B (P<0.05). The incidence of dizziness, drowsiness, nausea and vomiting in group A and groups B were significantly lower than that in group C al P<0.05). Conclusion Intravenous infusion of flurbiprofen axetil during the delivery can effectively inhibit postoperative stress with good analgesia effect and few adverse reactions, which is suitable for postoperative analgesia in preeclampsia patients undergoing cesarean section.%目的:观察氟比洛芬酯复合丁丙诺啡和单用丁丙诺啡对子痫前期患者剖宫产术后静脉自控镇痛(PCIA)的临床效果和应用价值。方法选择90例ASAⅠ~Ⅱ级在腰硬联合麻醉下行子痫前期剖宫产术患者,按随机数字表法分为A组(

  6. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  7. Naltrexone extended-release injection: an option for the management of opioid abuse

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    Taylor Jr R

    2011-12-01

    Full Text Available Robert Taylor Jr1, Robert B Raffa2, Joseph V Pergolizzi Jr3,41NEMA Research Inc, Naples, FL, 2Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, 3Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 4Department of Anesthesiology, Georgetown University School of Medicine, Washington, DC, USAAbstract: The United States Food and Drug Administration (FDA approved naltrexone, a synthetic competitive antagonist at opioid receptors, in oral form in 1984 for use in the management of opioid abuse and addiction. Because naltrexone and its major metabolite, 6-ß-naltrexone, are both competitive antagonists at opioid receptors – and thereby inhibit opioid agonist-induced effects including those desired by abusers – it was hypothesized that once maintained on naltrexone, opioid-induced desirable effects would be diminished to the point that relapse to illicit use would decline because it was no longer rewarding. However, good medication compliance is a requisite for such a strategy to be effective and a systematic review of oral naltrexone concluded that this method of treatment was not superior for any outcomes measured (ie, retention, abstinence, or side effects to placebo, psychotherapy, benzodiazepines, or buprenorphine treatment. In addition, the retention rate on oral naltrexone was very low (less than 30%. Recently, the FDA approved an extended-release formulation (intramuscular depot injection of naltrexone for prevention of relapse to opioid dependence following opioid detoxification and to be used along with counseling and social support. Since it needs to be administered only monthly, as opposed to the daily administration required for the oral formulation, naltrexone injection has the potential for increasing adherence and retention rates. Concerns include liver damage at high doses (oral formulation and possible opioid overdose if an attempt is made to surmount

  8. Gender and racial/ethnic differences in addiction severity, HIV risk, and quality of life among adults in opioid detoxification: results from the National Drug Abuse Treatment Clinical Trials Network

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    Bruce Burchett

    2010-12-01

    more likely than whites to use heroin and cocaine and to have more severe alcohol and employment problems.Conclusions: Women and whites show more psychopathology than men and African Americans. These results highlight the need to monitor an increased trend of opioid addiction among women and whites and to develop effective combined psychosocial and pharmacologic treatments to meet the diverse needs of the expanding opioid-abusing population. Elevated levels of HIV risk behaviors among Hispanics and whites also warrant more research to delineate mechanisms and to reduce their risky behaviors.Keywords: buprenorphine, clinical trials network, gender differences, heath disparity, HIV risk behavior, methadone, opioid dependence, rehabilitation

  9. Opioid substitution therapy in manipur and nagaland, north-east india: operational research in action

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    Langkham Biangtung

    2010-12-01

    Full Text Available Abstract Background There is good evidence for the effectiveness of opioid substitution therapy (OST for injecting drug users (IDUs in middle and high-income countries but little evidence regarding the provision of OST by non-government organisations (NGOs in resource-poor settings. This paper reports on outcomes of an NGO-based OST program providing sub-lingual buprenorphine to opiate dependent IDUs in two north-east Indian states (Manipur and Nagaland, a region where conflict, under-development and injecting of heroin and Spasmoproxyvon (SP are ongoing problems. The objectives of the study were: 1 to calculate OST treatment retention, 2 to assess the impact on HIV risk behaviours and quality of life, and 3 to identify client characteristics associated with cessation of treatment due to relapse. Methods This study involves analysis of data that were routinely and prospectively collected from all clients enrolled in an OST program in Manipur and Nagaland between May 2006 and December 2007 (n = 2569, 1853 in Manipur and 716 in Nagaland using standardised questionnaires, and is best classified as operational research. The data were recorded at intake into the program, after three months, and at cessation. Outcome measures included HIV risk behaviours and quality of life indicators. Predictors of relapse were modelled using binary logistic regression. Results Of all clients enrolled in OST during the month of May 2006 (n = 713, 72.8% remained on treatment after three months, and 63.3% after six months. Statistically significant (p = 0.05 improvements were observed in relation to needle sharing, unsafe sex, incidents of detention, and a range of quality of life measures. Greater spending on drugs at intake (OR 1.20, frequently missing doses (OR 8.82, and having heroin rather than SP as the most problematic drug (OR 1.95 were factors that increased the likelihood of relapse, and longer duration in treatment (OR 0.76 and regular family involvement in

  10. [Prevention and treatment of hepatitis C in illicit drug users].

    Science.gov (United States)

    Sakoman, Slavko

    2009-12-01

    Drug use is a complex behavior with multidimensional determinants, including social, psychological, cultural, economic, and biological factors. Blood borne viral infections including hepatitis C virus are transmitted when an uninfected intravenous drug user (IVDU) uses injection equipment, especially syringes, that have previously been used by an infected person. The transmission can also result from sharing other injection equipment such as 'cookers' and 'cottons'. Recent studies have shown that the prevalence and incidence of drug abuse have declined substantially since the introduction of needle exchange. Infection with hepatitis C may spontaneously resolve during the acute stage and never progress to chronic infection, or the infection may become chronic without medical complications, or the infection may become chronic with progressive medical complications. Regular testing for infection is an important strategy for secondary prevention of chronic hepatitis C infection. Care for hepatitis C is a vital component of a comprehensive health program for persons using illicit drugs. Such care includes screening for transmission risk behavior, prevention counseling and education, testing for HCV antibody and RNA. IDUs found to have chronic HCV infection should be assessed for the presence and degree of liver disease and evaluated for treatment for HCV Hepatitis C care also requires providing access to treatment for substance use and abuse. Therapy with opioid agonists, including methadone maintenance treatment, has been shown to diminish and often eliminate opioid use and reduce transmission of infection. Approval of buprenorphine makes office-based pharmacotherapy for opioid addiction possible. When considering treatment for hepatitis C, particular attention must be paid to mental health conditions. As a group, IDUs exhibit higher rates of comorbid psychiatric disorders than the general population. IFN-based regimens for hepatitis C are often complicated by

  11. Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl.

    Science.gov (United States)

    Grond, S; Radbruch, L; Lehmann, K A

    2000-01-01

    adverse effects as other opioids, mainly sedation, nausea, vomiting and constipation. In comparison with oral morphine, TTS fentanyl causes fewer gastrointestinal adverse events. The risk of hypoventilation is comparatively low in cancer patients. Sufentanil and buprenorphine may also be suitable for transdermal delivery, but clinical results are not yet available. Transdermal morphine is only useful if applied to de-epithelialised skin. However, iontophoresis may allow transdermal administration of opioids, including morphine, with a rapid achievement of steady state concentrations and the ability to adjust delivery rates. This would be beneficial for acute and/or breakthrough pain, and initial clinical trials are in progress. PMID:10668859

  12. CR4056, a new analgesic I2 ligand, is highly effective against bortezomib-induced painful neuropathy in rats

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    Meregalli C

    2012-06-01

    Full Text Available Cristina Meregalli,1 Cecilia Ceresa,1 Annalisa Canta,1 Valentina Alda Carozzi,1 Alessia Chiorazzi,1 Barbara Sala,1 Norberto Oggioni,1 Marco Lanza,2 Ornella Letar,i2 Flora Ferrari,2 Federica Avezza,1 Paola Marmiroli,1 GianFranco Caselli,2 Guido Cavaletti11Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 2Pharmacology and Toxicology Department, Rottapharm | Madaus Research Center, Monza, ItalyAbstract: Although bortezomib (BTZ is the frontline treatment for multiple myeloma, its clinical use is limited by the occurrence of painful peripheral neuropathy, whose treatment is still an unmet clinical need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week for 8 weeks to female Wistar rats induced a peripheral neuropathy similar to that observed in humans. In this animal model of BTZ-induced neurotoxicity, the present authors evaluated the efficacy of CR4056, a novel I2 ligand endowed with a remarkable efficacy in several animal pain models. CR4056 was administered in a wide range of doses (0.6–60 mg/kg by gavage every day for 2–3 weeks in comparison with buprenorphine (Bupre (28.8 µg/kg subcutaneously every day for 2 weeks and gabapentin (Gaba (100 mg/kg by gavage every day for 3 weeks. Chronic administration of BTZ reduced nerve conduction velocity and induced allodynia. CR4056, Bupre, or Gaba did not affect the impaired nerve conduction velocity. Conversely, CR4056 dose-dependently reversed BTZ-induced allodynia (minimum effective dose 0.6 mg/kg. The optimal dose found, 6 mg/kg, provided a constant pain relief throughout the treatment period and without rebound after suspension, being effective when coadministered with BTZ, starting before or after allodynia was established, or when administered alone after BTZ cessation. A certain degree of tolerance was seen after 7 days of administration, but only at the highest doses (20 and 60 mg/kg. Bupre was effective

  13. Patients in long-term maintenance therapy for drug use in Italy: analysis of some parameters of social integration and serological status for infectious diseases in a cohort of 1091 patients

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    Montanari Linda

    2006-08-01

    Full Text Available Abstract Background Heroin addiction often severely disrupts normal social functioning. The aims of this multi-centre study of heroin users in long-term replacement treatment were: i to provide information on aspects of social condition such as employment, educational background, living status, partner status and any history of drug addiction for partners, comparing these data with that of the general population; ii to assess the prevalence of hepatitis, syphilis and HIV, because serological status could be a reflection of the social conditions of patients undergoing replacement treatment for drug addiction; iii to analyse possible relationships between social conditions and serological status. Methods A cross-sectional study was carried out in sixteen National Health Service Drug Addiction Units in northern Italy. The data were collected from February 1, 2002 to August 31, 2002. Recruitment eligibility was: maintenance treatment with methadone or buprenorphine, treatment for the previous six months, and at least 18 years of age. In the centres involved in the study no specific criteria or regulations were established concerning the duration of replacement therapy. Participants underwent a face-to-face interview. Results The conditions of 1091 drug treatment patients were evaluated. The mean duration of drug use was 14.5 years. Duration was shorter in females, in subjects with a higher educational background, and in stable relationships. Most (68% had completed middle school (11–14 years of age. Seventy-nine percent were employed and 16% were unemployed. Fifty percent lived with their parents, 34% with a partner and 14% alone. Males lived more frequently with their parents (55%, and females more frequently with a partner (60%. Sixty-seven percent of male patients with a stable relationship had a partner who had never used heroin. HCV prevalence was 72%, HBV antibodies were detected in 42% of patients, while 30% had been vaccinated; 12.5% of

  14. Hemodynamics and bispectral index (BIS of dogs anesthetized with midazolam and ketamine associated with medetomidine or dexmedetomidine and submitted to ovariohysterectomy Avaliação hemodinâmica e do índice bispectral (BIS de cadelas anestesiadas com midazolam e cetamina associados à medetomidina ou dexmedetomidina e submetidas a ovário-salpingo-histerectomia

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    Fernando do Carmo Silva

    2010-04-01

    Full Text Available PURPOSE: To evaluate hemodynamics and bispectral index (BIS in bitches anesthetized with ketamine and midazolam in combination with dexmedetomidine or medetomidine and submitted to ovariohysterectomy. METHODS: Twenty bitches pretreated with levomedetomidine and buprenorphine were anesthetized with 5 mg.kg-1 ketamine and 0.2 mg.kg-1 midazolam i.v. Continuous infusion of 0.4 mg.kg-1.h-1 midazolam and 20 mg.kg-1.h-1 ketamine was initiated in combination with DEX (n=10: 20 µg.kg-1.h-1 dexmedetomidine or MED (n=10: 30 µg.kg-1.h-1 medetomidine over 30 minutes. A pharmacokinetic study provided dexmedetomidine plasma concentration, set to be 3.0 ng.mL-1. RESULTS: BIS decreased in both groups (P0.05, but heart rate decreased in both groups, as compared to control values (POBJETIVO: Verificar o comportamento hemodinâmico e o índice bispectral de cadelas anestesiadas com cetamina e midazolam associados à dexmedetomidina ou medetomidina. MÉTODOS: Vinte cadelas receberam pré-tratamento com levomepromazina e buprenorfina e foram anestesiadas com cetamina, 5 mg.kg-1 i.v., e midazolam, 0,2 mg.kg-1 i.v., seguidos da administração contínua de midazolam, 0,4 mg.kg-1.h-1, e cetamina, 20 mg.kg-1.h-1, associados, conforme o grupo, à: DEX (n=10: dexmedetomidina 20 µg.kg-1.h-1 ou MED (n=10: medetomidina 30 µg.kg-1.h-1, mantidos por 30 minutos. A dose de dexmedetomidina foi obtida por meio de estudo farmacocinético planejando-se concentração plasmática de 3,0 ng.mL-1. RESULTADOS: Os valores do BIS diminuíram em ambos os grupos (P0,05, sem a presença de efeitos adversos. CONCLUSÃO: A administração contínua de dexmedetomidina em concentração plasmática calculada de 3 ng.mL-1, em combinação com midazolam e cetamina, resulta em plano anestésico adequado para castração de cadelas, estabilidade hemodinâmica e despertar tranquilo, sem efeitos adversos.

  15. Simultaneous determination in hair of multiclass drugs of abuse (including THC) by ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Di Corcia, D; D'Urso, F; Gerace, E; Salomone, A; Vincenti, M

    2012-06-15

    A simple procedure for the quantitative determination in hair samples of 13 common drugs of abuse or metabolites (morphine, 6-acetylmorphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, benzoylecgonine, cocaine, buprenorphine, methadone and Δ(9)-tetrahydrocannabinol) has been developed and fully validated. The analytes were extracted from the matrix by a simple overnight incubation with methanol at 55 °C. An aliquot of the extract was directly injected into an ultra-high performance liquid chromatography system equipped with Waters Acquity UHPLC BEH C18 column (100 mm × 2.1mm, 1.7 μm). The mobile phase eluted with a linear gradient (water/formic acid 5 mM:acetonitrile; v:v) from 98:2 to 0:100 in 4.5 min, followed by isocratic elution at 100% B for 1.0 min. The flow rate was 0.6 mL/min and the total run time was 8.0 min including re-equilibration at the initial conditions. The compounds were revealed by a triple quadrupole mass spectrometer operating in the selected reaction monitoring mode. The absence of matrix interferents, together with excellent repeatability of both retention times and relative abundances of diagnostic transitions, allowed the correct identification of all analytes tested. The method proved linear in the interval from the limit of quantification to 5.0 ng/mg (1.0 ng/mg for Δ⁹-tetrahydrocannabinol) with correlation coefficient values ranging from 0.9970 to 0.9997. Quantitation limits were below the cut-off values recommended by the Society of Hair Testing and ranged from 0.02 to 0.08 ng/mg. Application of the present UHPLC-MS/MS procedure and instrumentation to hair analysis allows high sample-throughput, together with excellent sensitivity and selectivity, in workplace drug-screening controls and forensic investigations. These qualities, combined with minimal sample workup, make the cost of this screening affordable for most private and

  16. Obsessive-compulsive disorder, impulse control disorders and drug addiction: common features and potential treatments.

    Science.gov (United States)

    Fontenelle, Leonardo F; Oostermeijer, Sanne; Harrison, Ben J; Pantelis, Christos; Yücel, Murat

    2011-05-01

    The basic concepts underlying compulsive, impulsive and addictive behaviours overlap, which may help explain why laymen use these expressions interchangeably. Although there has been a large research effort to better characterize and disentangle these behaviours, clinicians and scientists are still unable to clearly differentiate them. Accordingly, obsessive-compulsive disorder (OCD), impulse control disorders (ICD) and substance-related disorders (SUD) overlap on different levels, including phenomenology, co-morbidity, neurocircuitry, neurocognition, neurochemistry and family history. In this review we summarize these issues with particular emphasis on the role of the opioid system in the pathophysiology and treatment of OCD, ICD and SUD. We postulate that with progression and chronicity of OCD, the proportion of the OCD-related behaviours (e.g. checking, washing, ordering and hoarding, among others) that are driven by impulsive 'rash' processes increase as involvement of more ventral striatal circuits becomes prominent. In contrast, as SUD and ICD progress, the proportion of the SUD- and ICD-related behaviours that are driven by compulsive 'habitual' processes increase as involvement of more dorsal striatal circuits become prominent. We are not arguing that, with time, ICD becomes OCD or vice versa. Instead, we are proposing that these disorders may acquire qualities of the other with time. In other words, while patients with ICD/SUD may develop 'compulsive impulsions', patients with OCD may exhibit 'impulsive compulsions'. There are many potential implications of our model. Theoretically, OCD patients exhibiting impulsive or addictive features could be managed with drugs that address the quality of the underlying drives and the involvement of neural systems. For example, agents for the reduction or prevention of relapse of addiction (e.g. heavy drinking), which modulate the cortico-mesolimbic dopamine system through the opioid (e.g. buprenorphine and naltrexone

  17. A COMPARATIVE STUDY OF BUPIVACAINE AND BUPIVACAINE WITH CLONIDINE UNDER SPINAL ANESTHESIA IN PATIENT FOR TOTAL ABDOMINAL HYSTERECTOMY

    Directory of Open Access Journals (Sweden)

    Manuraj

    2015-02-01

    Full Text Available BACKGROUND: Bupivacaine is the most commonly used drug for spinal anesthesia . To improve upon the quality of analgesia and prolong the duration of its action, many adjuvants have been tried. Intrathecal clonidine an α2 adrenoreceptor agonist with analgesic effect at spinal level mediated by postsynaptically situated adrenoreceptor in dorsal horn of spinal cord. Low doses of clonidine and buprenorphine have shown effectiveness in i ntensifying spinal anesthesia. AIM: This study is designed to evaluate the effectiveness of spinal blockade by adding 50μgm clonidine to bupivacaine. SET TINGS AND DESIGN: This a prospective, randomized , comparative clinical study involved 60 ASA grade Ι/ΙΙ patients aged 18 - 55 years undergoing elective hysterectomy under spinal anesthesia after approval from hospital ethics committee with written an d inform ed consent of patients. MATERIALS AND METHODS: 60 ASA grade Ι/ΙΙ patients aged 18 - 55 years selected for the study are divided in two groups of 30 each. Group B (Bupivacaine group patients will receive intrathecally 0.5% hyperbaric bupivacaine 4 ml (Total 4 ml whereas Group C (Clonidine group patient will receive intrathecally 0.5% hyperbaric bupivacaine 3. 5 ml + 50μg (Total 4 ml. The onset time to reach peak sensory and motor level, post - operative analgesia , hem odynamic changes, and side effects were recorded. RESULTS: The onset of sensory and motor blockade was faster in the group C compared to group B [137.60 seconds and 112.22 seconds] (p<0.001, [231.80 seconds and 165.1 seconds] (p<0.001. Duration of sensor y block, motor block and postoperative analgesia [221.4 minutes in group B vs. 362.84 minutes in group C] (P<0.001, was significantly prolonged in group C. There were no significant hemodynamic changes in both the groups. CONCLUSION: Clonidine potentiates bupivacaine spinal anesthesia by increasing the duration and improving the quality of analgesia without significant hemodynamic side

  18. 美沙酮维持治疗门诊服药人员的不安全性行为及其相关因素%Unsafe sexual behaviors and associated factors among clients attending methadone maintenance treatment clinics

    Institute of Scientific and Technical Information of China (English)

    张欢; 陈涛; 庞琳; 刘恩武; 柔克明; 张洪波; 吴尊友

    2013-01-01

    目的 了解目前美沙酮维持治疗(MMT)门诊服药人员的不安全性行为状况及相关因素.方法 在重庆、广东、江苏三省(直辖市)6个MMT门诊,选取符合条件的服药人员进行问卷调查及尿液检测,收集研究对象的一般情况、性行为状况、美沙酮服药情况及多药滥用信息.结果 共调查1 202人,平均年龄(39.7±6.8)岁;其中男性占75.7%(910人),平均吸食海洛因年限(15.6±4.8)年.758人(63.1%)过去6个月有过性行为,其中10.2%(77/758)存在不安全性行为.男性、未婚单身/离异丧偶、与家人关系差、存在药物滥用、HIV阳性与不安全性行为的发生存在正向的统计学关联(P<0.05).结论 不安全性行为普遍存在于所调查的MMT门诊服药人员中,针对服药人员不安全性行为的健康教育和行为干预需要进一步加强.%Objective To understand the unsafe sexual behaviors among heroin addicts attending methadone maintenance treatment (MMT) clinics and to analyze the associated factors. Methods A total of 1 202 clients from 6 MMT clinics from Chongqing, Guangdong and Jiangsu were included in the study. The information of social demographics, sexual behaviors, multi drug use-related behaviors was collected by a questionnaire survey and urine samples were tested to identify if heroin or methamphetamine or ecstasy or benzodiazepine or buprenorphine had been used. Results The average age of the 1 202 clients was (39.7 ± 6.8) years. Among them, 75.7% were males, the average year of using heroin was (15. 6 ± 4. 8)years. Among all the participants, 758(63. 1%) had sexual behavior in the last 6 months, and 10. 2%(77/758) had unsafe sexual behavior. In males, who were unmarried, divorced or widowed, or had a bad relationship with their families, or used multi drugs, HIV positive status was positively correlated with unsafe sexual behavior (P<0. 05). Conclusion The clients of MMT also have a high percentage of unsafe sexual

  19. Substitution treatment for opioid addicts in Germany

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    Gerlach Ralf

    2007-02-01

    Full Text Available Abstract Background After a long and controversial debate methadone maintenance treatment (MMT was first introduced in Germany in 1987. The number of patients in MMT – first low because of strict admission criteria – increased considerably since the 1990s up to some 65,000 at the end of 2006. In Germany each general practitioner (GP, who has completed an additional training in addiction medicine, is allowed to prescribe substitution drugs to opioid dependent patients. Currently 2,700 GPs prescribe substitution drugs. Psychosocial care should be made available to all MMT patients. Results The results of research studies and practical experiences clearly indicate that patients benefit substantially from MMT with improvements in physical and psychological health. MMT proves successful in attaining high retention rates (65 % to 85 % in the first years, up to 50 % after more than seven years and plays a major role in accessing and maintaining ongoing medical treatment for HIV and hepatitis. MMT is also seen as a vital factor in the process of social re-integration and it contributes to the reduction of drug related harms such as mortality and morbidity and to the prevention of infectious diseases. Some 10 % of MMT patients become drug-free in the long run. Methadone is the most commonly prescribed substitution medication in Germany, although buprenorphine is attaining rising importance. Access to MMT in rural areas is very patchy and still constitutes a problem. There are only few employment opportunities for patients participating in MMT, although regular employment is considered unanimously as a positive factor of treatment success. Substitution treatment in German prisons is heterogeneous in access and treatment modalities. Access is very patchy and the number of inmates in treatment is limited. Nevertheless, substitution treatment plays a substantial part in the health care system provided to drug users in Germany. Conclusion In Germany, a

  20. [Review of current pharmacologic treatment of pain].

    Science.gov (United States)

    Brasseur, L

    1997-01-01

    drugs known to have a central mechanism of action can also have peripheral activity. As a result, several therapeutic classes have been identified. Firstly NSAIDs, which act by inhibiting the enzymes that synthesise prostaglandins, cyclooxygenases (COX-1, COX-2), but which also act upon lipo-oxygenases: Their efficacy is interesting, although somewhat limited by both their ceiling effect and the frequent adverse gastrointestinal reactions they produce. Specific inhibitors of COX-2 could well reduce the risk of adverse effects. Opioids constitute the first-line treatment for pain, particularly severe pain. There are several classifications for these drugs. Firstly, weak opioids (such as codeine) and strong opioids (such as morphine) are differentiated. Secondly, a distinction is made between pure agonists (such as morphine), partial agonists (such as buprenorphine), agonist-antagonists (such as nalbuphine) and antagonists (such as naloxone). Finally, agents are distinguished on the basis of their chemical structure (synthetic, semi-synthetic or natural derivatives). These molecules act upon different receptors (mu, delta, kappa, sigma) and, although peripheral mechanisms have been described, their activity occurs mainly at spinal and supraspinal levels. They provide a potent analgesic effect but are also responsible for various adverse effects-nausea, vomiting, sedation, constipation and respiratory depression-which seriously limit their use. As long as the indication is appropriate, these drugs should not be withheld because of fear of dependence or abuse. It has been observed that other adjuvant therapeutic approaches, generally used to treat conditions other than pain, provide pain relief in certain situations. These include corticosteroids, which are-widely used in rheumatology and oncology, and antidepressants, which are frequently used to treat chronic pain, especially that with a neuropathic component. Anti-epileptics are also used, particularly for excrutiating

  1. New disposition for pain therapy in Italy, center for headache should be integrated in the network.

    Science.gov (United States)

    Gensini, Gian Franco

    2011-05-01

    -territory without pain". The Ministry of Health has established a deadline within which this law must be implemented at the regional level, and further establishes a specific National Observatory, an annual report on the use of drugs in the treatment of pain, and other provisions. The levels of spending by region will also be monitored in compliance with this law; university courses and masters are required to update professionals involved in pain treatment. In July 2010, in Florence, during the interdisciplinary IMPACT 2010 summit, Institutions and Scientific Societies met to define the concrete implementation of Law No. 38, in terms of the arrangements to ensure access to palliative care and pain management. Subsequently, last November, a new meeting was held bringing together medical directors from public hospitals; further meetings are planned with Regional Health Authorities to reaffirm the importance of this law and to implement it. The most important molecules in the opioids are traditionally divided into two groups: weak and strong. Among the strong analgesics are morphine, methadone, buprenorphine, fentanyl, oxycodone, hydromorphone. Among the weak are codeine and tramadol, or opiates administered at low doses, such as oxycodone combined with acetaminophen. IMPACT's aim is also to stimulate scientific association to consider with attention and continuous medical education on the appropriates of diagnosis and administration of these medications according to data flow sheets approved in Italy. Regarding the headaches, it should be noted that the law 38 cited above includes all forms of pain, and headaches should be integrated into the care networks. In this context, several multi-disciplinary professionals within the centers (hub and spoke) or territory (GPs, specialists from neurologists and other professionals involved) should be integrated to offer the best response to the needs of the citizen. The diagnosis and treatment of various forms of headache have to be integrated

  2. 神经生长因子联合西酞普兰对海洛因依赖者脱毒期抑郁及心理渴求症状的疗效观察%Therapeutic effects of nerve growth factor combined with citalopram for depressive and psychological desire of heroin addicts

    Institute of Scientific and Technical Information of China (English)

    王强; 汪青松; 吴庆; 张园园

    2013-01-01

    Objective To evaluate the therapeutic effects of nerve growth factor combined with citalopram for depressive and psychological desire of heroin. Methods 93 male patients were randomly assigned into two groups,including citalopram treatment group(41) and nerve growth factor(NGF) combined with citalopram treatment group(42) . There was no significant differences in offenders age,length of sentence and BDI-13 rating between the two groups before the treatment. In addition to drug medication methadone and buprenorphine , joint application of nerve growth factors for treatment was conducted for six weeks. Beck Depression self-assessment questionnaire(BDI-13) and the craving were used to evaluate the efficacy of self-rating scale. Results In nerve growth factor combined with citalopram group BDI-13 score and the reduction rates at the end of 2,4,6 week after treatment were statistically different from those in citalopram group(r =3.25,6.12,7.15;r =3. 56,4. 59,6.21,P<0. 05 ) ;craving score at 14,28 ,35,42 day significantly reduced,which was significantly different from citalopram group(r =2. 24,3. 12,3. 21,2. 56 ,P <0. 05 ). Conclusion Nerve growth factor combined with citalopram may be effective alleviating heroin addicts in during and after detoxification of coke depression and psychological desire symptoms.%目的 评价神经生长因子联合西酞普兰对海洛因依赖者的抑郁及心理渴求症状的治疗效果.方法 将93例男性患者随机分为两组,其中西酞普兰治疗组41例;神经生长因子(NGF)联合西酞普兰治疗组42例,治疗前两组罪犯的年龄、刑期及BDI-13评分比较均无统计学差异.除戒毒用药美沙酮及丁丙诺啡外,两组分别应用神经生长因子联合西酞普兰和西酞普兰进行治疗,疗程为6周.采用Beck抑郁自评问卷(BDI-13)及及心理渴求自评量表进行评定疗效.结果 神经生长因子联合西酞普兰组治疗后2、4、6周末BDI-13评分及减分率较西酞普兰

  3. [Pharmacotherapy of cancer pain : 2. Use of opioids.].

    Science.gov (United States)

    Cherny, N I; Portenoy, R K; Raber, M; Zenz, M

    1995-01-01

    The adequate use of opioids in the treatment of chronic cancer pain requires sound knowledge of selection criteria for the various opioids, the routes of administration, dosages, dosing schemes and possible side effects. Drug selection depends on the intensity of pain rather than on the specific pathophysiology. Mild to moderate pain can often be treated effectively by so-called "weak" opioids. These include codeine, dihydrocodeine and dextropropoxyphene. Non-opioid analgesics, like acetylsalicylic acid or paracetamol can be added according to the "analgesic ladder" proposed by the World Health Organization (WHO). If adequate pain relief is not achieved "strong" opioids are required. The route of administration that is the safest and the least invasive for the patient should be chosen. Non-invasive (oral, rectal, sublingual, transdermal and intranasal) and invasive routes (intravenous, subcutaneous, spinal and epidural) are available (Table 8). Noninvasive routes are preferred, and most patients can be maintained on oral opioids. Alternatively, in some patients pain can be managed by the sublingual (buprenorphine) route. A transdermal preparation exists for fentanyl, but has not yet been approved for the German market. If the oral route cannot be used or if large doses are required, it will be necessary to change to an invasive route. Intravenous bolus injections provide the fastest onset of analgesic action. They are mostly used in very severe pain. Repeated injections can be avoided by using intravenous or subcutaneous infusions. Various types of pumps delivering analgesics at constant basal infusion rates with the option of rescue doses in case of breakthrough pain are available (patient-controlled analgesia=PCA). Opioids frequently used for s. c. infusion are morphine and hydromorphone. Adjuvant drugs (antiemetics, anxiolytics) can be added. Epidural or intrathecal administration of opioids should only be used in intractable pain or if severe side effects, such

  4. 长沙市甲基苯丙胺使用情况"应答者驱动抽样"流行病学调查%EPIDEMIOLOGICAL RESEARCH OF METHAMPHETAMINE USE AND ITS DETERMINANTS AND CONSEQUENCES IN CHANGSHA CITY

    Institute of Scientific and Technical Information of China (English)

    张官柏; 刘铁桥; 郝伟; Brian C Kelly; 王济川; 胡红星; 曾敏; 柳红

    2011-01-01

    participated in the investigation. Most of them were male, Han nationality, employed, having a partner (including spouse, girlfriend/boyfriend or cohabitant), received junior or high middle school education and higher level of income. The average age was 29.0 a ±s 7.8 a (ranging from 18 a to 48 a) ,none of the 102 participants who accepted HIV antibody test was HIV positive. Most of them (94/129,72.9% ) had ever used other illicit addictive drugs including katemine, Ecstasy, heroin, marijuana,buprenorphine, tramadol,methadone,and diazepam. No one reported ever having used cocaine or crack.Meth was commonly found in two swbstances. One is ice, which is pure meth, and the other is called Magu made of meth, caffeine, and perfume, etc. All the users smoked meth with a special instrument ' ice pot' in private locations including home,rented apartment and hotel. The mean days of meth use within last 3 months were 21.4 d ± s 31.3 d (median 10 d), and the mean doses used for ice and Magu were 0.3 gram and 3.8 tablets, respectively for each time. Meth was highly available, and more than 2/3 of the participants(87/129, 67. 4% )reported "they can easily or very easily" get this drug. The main determinants of meth use were: peer influence, sensory - seeking, promotion of sexual pleasure, and escaping from bad mood. Only a few people used meth for weight reduction. The adverse consequences of meth use included bad appetite, weigh loss, bad health, loss of money, bad emotion, and harm to the family. Conclusion:Meth has brought great harm to the users. High level of meth availability and peer influence may result in more and more meth users. Measures should be taken specifically to reduce drug availability and propaganda carried out to reduce meth use.

  5. 低强度氦氖激光血管内照射治疗对海洛因戒断症状抑制效应的定量评估%Quantitative efficacy evaluation of intravascular low-level He-Ne laser irradiation for heroin withdrawal syndrome

    Institute of Scientific and Technical Information of China (English)

    贾文英; 田红召; 杨婷婷; 海国军

    2005-01-01

    BACKGROUND: Intravascular low-level laser irradiation (ILLLI) therapy with He-Ne laser can effectively inhibit the occurrence of heroin withdrawal syndrome, but the therapeutic effect should be evaluated by quantitative standards.OBJECTIVE: To evaluate the effect of intravascular low-level He-Ne laser irradiation against withdrawal syndrome with intravenous according to the criteria proposed by the authors.DESIGN: Randomized controlled trial in heroin-addicted patients.SETTING: Analysis and Testing Laboratory of Xinxiang Medical College and Center of Laser Medical Research of Zhenzhou University Medical CollegePARTICIPANTS: The study was completed in Center of Laser Medical Research in Zhengzhou University in January 2003. Thirty heroin addicts from the Detoxification Center of Zhengzhou including 25 male and 5 female patients aged 19- 45 years were divided randomly into experimental group and control group with 15 cases in each. The patients' history of drug abuse ranged from 0. 5 to 5 years and the daily doses they took was 1.0-4.0 g.INTERVENTIONS: Patients in the experimental group were treated by ILLLI therapy after hospitalization. The therapy was administered once daily for 60 minutes in each session, for a total of 10 days for a treatment course. The irradiating power of the laser was 2.0-3.0 mW with a power density of 7.07-10.6 mW/mm2. Patients in the control group were treated with conventional therapy with algidon combined with buprenorphine hydrochloride. The 12 main symptoms(vomiting, goose pimples, sweating, agitation, shaking, lacrimation, nasal congestion, insomnia, abdominal pain,body temperature changes, muscular pain, and heart rate changes) were scored for 0, 1, 2, and 3 corresponding to absent, mild, moderate, and severe symptoms, with the total score of 36.MAIN OUTCOME MEASURES: Comparison of the scores for the withdrawal symptoms between the two groups.RESULTS: The 30 cases were all available for result analysis. The scores of vomiting

  6. Gabapentina en el tratamiento de la fibromialgia Gabapentin for the management of fibromyalgia

    Directory of Open Access Journals (Sweden)

    M. P. Acín

    2005-05-01

    ,16% (1 se suspende el tratamiento por efectos secundarios. La dosis diaria media inicial de gabapentina es de 300 mg.día-1 y la final 762,5 ± 409,46 mg.día-1. El tiempo medio de tratamiento es de 9,04 ± 6,7 meses. Los efectos secundarios aparecen en 9 pacientes (37,5%, que presentan mareo 6 (25%, inestabilidad 2 (8,33% y 1 hay que suspenderlo por excesiva somnolencia. En el momento de finalizar el estudio siguen en tratamiento 23 pacientes, 4 de ellas, con dosis bajas (300 mg/día por manifestar efectos secundarios. Conclusiones: Frecuentemente, los pacientes de fibromialgia son tratados con diferentes terapias y con resultados modestos, y aunque en nuestra serie hay casos con un control analgésico bueno a baja dosificación, serán necesarios nuevos estudios comparativos que nos aporten más datos para valorar mejor dichos resultados.Objectives: Fibromyalgia is one of the most common causes of local or widespread chronic musculoskeletal pain that is characterized by the presence of painful anatomical points, morning rigidity, easy fatigue, sleep disorders and other related symptoms. Some authors claim that fibromyalgia is due to an abnormal processing of pain at the central nervous system and has a neuropathic component. A deficit in the release of serotonin and other substances involved in the regulation of nociceptive processes has also been shown. In this study we determined the effectiveness of gabapentin in patients diagnosed of fibromyalgia. Material and method: We studied 24 patients, all of them women with a mean age of 42.54 ± 13.08 (33-60. Fifty per cent (12 had cervical pain and 50% (12, cervical and lumbar pain as the main painful symptoms. Fifteen patients were being treated with NSAIDs, 12 with tramadol, 2 with fentanyl TTS, 9 with sedatives, 9 with antidepressants, 1 with buprenorphin TDS, 14 with physiotherapy, 13 with injection of local anesthetic at the trigger points and 1 with iontophoresis. These therapies had somewhat improved their condition