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Sample records for buprenorphine

  1. Buprenorphine

    Science.gov (United States)

    Kahan, Meldon; Srivastava, Anita; Ordean, Alice; Cirone, Sharon

    2011-01-01

    Abstract Objective To review the use of buprenorphine for opioid-addicted patients in primary care. Quality of evidence The MEDLINE database was searched for literature on buprenorphine from 1980 to 2009. Controlled trials, meta-analyses, and large observational studies were reviewed. Main message Buprenorphine is a partial opioid agonist that relieves opioid withdrawal symptoms and cravings for 24 hours or longer. Buprenorphine has a much lower risk of overdose than methadone and is preferred for patients at high risk of methadone toxicity, those who might need shorter-term maintenance therapy, and those with limited access to methadone treatment. The initial dose should be given only after the patient is in withdrawal. The therapeutic dose range for most patients is 8 to 16 mg daily. It should be dispensed daily by the pharmacist with gradual introduction of take-home doses. Take-home doses should be introduced more slowly for patients at higher risk of abuse and diversion (eg, injection drug users). Patients who fail buprenorphine treatment should be referred for methadone- or abstinence-based treatment. Conclusion Buprenorphine is an effective treatment of opioid addiction and can be safely prescribed by primary care physicians. PMID:21402963

  2. Buprenorphine

    Directory of Open Access Journals (Sweden)

    Jaroslaw Mazurek

    2014-06-01

    Full Text Available In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S-2-[(5R,6R,7R,14S-9α-cyclopropylmethyl-3-hydroxy-6-methoxy-4,5-epoxy-6,14-ethanomorphinan-7-yl]-3,3-dimethylbutan-2-ol}, the cyclopropylmethyl group is disordered over two sites with an occupancy factor of 0.611 (3 for the major component. One of the hydroxy groups is involved in intramolecular O—H...O hydrogen bond. The other hydroxy group acts as a proton donor in an intermolecular O—H...O interaction that connects molecules into a zigzag chain along the b axis.

  3. Buprenorphine.

    Science.gov (United States)

    Mazurek, Jaroslaw; Hoffmann, Marcel; Fernandez Casares, Anna; Cox, Phillip D; Minardi, Mathew D

    2014-06-01

    In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S)-2-[(5R,6R,7R,14S)-9α-cyclo-propyl-methyl-3-hy-droxy-6-meth-oxy-4,5-ep-oxy-6,14-ethano-morphinan-7-yl]-3,3-di-methyl-butan-2-ol}, the cyclo-propyl-methyl group is disordered over two sites with an occupancy factor of 0.611 (3) for the major component. One of the hy-droxy groups is involved in intra-molecular O-H⋯O hydrogen bond. The other hy-droxy group acts as a proton donor in an inter-molecular O-H⋯O inter-action that connects mol-ecules into a zigzag chain along the b axis.

  4. Buprenorphine kinetics.

    Science.gov (United States)

    Bullingham, R E; McQuay, H J; Moore, A; Bennett, M R

    1980-11-01

    Buprenorphine kinetics was determined in surgical patients using radioimmunoassay. Buprenorphine was measured in the plasma of 24 patients who had received 0.3 mg buprenorphine intraoperatively. After 3 hr 10 of these patients then received a further 0.3 mg buprenorphine intravenously for postoperative pain relief, and 11 patients were given 0.3 mg intramuscularly; again, plasma levels were measured for 3 hr. The data fitted closely to a triexponential decay curve. There was a very fast initial phase, with a half-life (t1/2) of 2 min. The terminal t1/2 was slow, approximately 3 hr. Comparison of the kinetics of the same patient, awake and anesthetized, showed that the clearance was significantly lower in the anesthetized state. A notable feature of the drug given intramuscularly is rapid systemic availability, so that peaks are obtained in 2 to 5 min, and in 10 min the resulting levels are the same as for the intravenous and intramuscular routes.

  5. Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.

    Science.gov (United States)

    Jones, Jermaine D; Sullivan, Maria A; Vosburg, Suzanne K; Manubay, Jeanne M; Mogali, Shanthi; Metz, Verena; Comer, Sandra D

    2015-07-01

    In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.

  6. Radioimmunoassay of buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, A.J.; Lloyd-Jones, J.G.; Rance, M.J.; Flockhart, I.R.; Dockray, G.J.; Bennett, M.R.D.

    1980-01-01

    Antisera to buprenorphine were obtained in rabbits immunised with 3-0-carboxymethylbuprenorphine and N-hemisuccinyl-norbuprenorphine conjugated to bovine serum albumin. Using the latter antiserum and tritium labelled buprenorphine a radioimmunoassay having good accuracy and precision was developed for concentrations as low as 50 picograms in 1 ml of plasma. The N-hemisuccinyl antiserum crossreacted with norbuprenorphine, and the 3-0-glucuronide conjugate with the 3-0-carboxy-methyl antiserum. Cross-reactivity of both antisera to other pharmacologically related compounds was negligible. The assay was employed to determine plasma buprenorphine concentration following its parenteral administration to dog and man.

  7. [Modified neuroleptanalgesia with buprenorphine].

    Science.gov (United States)

    Weidler, B; von Bormann, B; Seim, M; Sturm, G; Schwanen, N; Hempelmann, G

    1982-12-01

    A modification of neuroleptanalgesia by substituting fentanyl with buprenorphine is presented. Both anaesthesia techniques could be applied alternatively. We did not recognize any significant difference between the two groups concerning haemodynamics, the secretion of the so called stress hormones (antidiuretic hormone, cortisol) as well as the postoperative respiratory depression. The long lasting analgesia, which could be achieved by buprenorphine, can be advantageous in certain surgical interventions. The lack of a potent antagonist for buprenorphine in addition to its longer half-life for--not being of advantage in any anaesthesia--is discussed.

  8. Abuse Potential of Intranasal Buprenorphine versus Buprenorphine/Naloxone in Buprenorphine-Maintained Heroin Users

    OpenAIRE

    2014-01-01

    In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital ...

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

    OpenAIRE

    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.

  10. Illicit buprenorphine use, interest in and access to buprenorphine treatment among syringe exchange participants.

    Science.gov (United States)

    Fox, Aaron D; Chamberlain, Adam; Sohler, Nancy L; Frost, Taeko; Cunningham, Chinazo O

    2015-01-01

    Poor access to buprenorphine maintenance treatment (BMT) may contribute to illicit buprenorphine use. This study investigated illicit buprenorphine use and barriers to BMT among syringe exchange participants. Computer-based interviews conducted at a New York City harm reduction agency determined: prior buprenorphine use; barriers to BMT; and interest in BMT. Of 102 opioid users, 57 had used illicit buprenorphine and 32 had used prescribed buprenorphine. When illicit buprenorphine users were compared to non-users: barriers to BMT ("did not know where to get treatment") were more common (64 vs. 36%, pbuprenorphine users were interested in BMT but did not know where to go for treatment. Addressing barriers to BMT could reduce illicit buprenorphine use.

  11. Supply of buprenorphine waivered physicians: the influence of state policies.

    Science.gov (United States)

    Stein, Bradley D; Gordon, Adam J; Dick, Andrew W; Burns, Rachel M; Pacula, Rosalie Liccardo; Farmer, Carrie M; Leslie, Douglas L; Sorbero, Mark

    2015-01-01

    Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008-11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine.

  12. Pharmacokinetics of intravenous buprenorphine in children.

    OpenAIRE

    1989-01-01

    Buprenorphine (3 micrograms kg-1) was given intravenously as premedication to small children (age 4-7 years) undergoing minor surgery. Because of the rapid decline of the plasma buprenorphine concentrations, the terminal elimination half-life could not be estimated reliably. Given this constraint, values of clearance appeared to be higher than those in adults but values of Vss were similar.

  13. Pharmacokinetics of intravenous buprenorphine in children.

    Science.gov (United States)

    Olkkola, K T; Maunuksela, E L; Korpela, R

    1989-08-01

    Buprenorphine (3 micrograms kg-1) was given intravenously as premedication to small children (age 4-7 years) undergoing minor surgery. Because of the rapid decline of the plasma buprenorphine concentrations, the terminal elimination half-life could not be estimated reliably. Given this constraint, values of clearance appeared to be higher than those in adults but values of Vss were similar.

  14. Clinical experience with fortnightly buprenorphine/naloxone versus buprenorphine in Italy: preliminary observational data in an office-based setting.

    Science.gov (United States)

    Amato, Patrizia

    2010-01-01

    Buprenorphine/naloxone is a new option for the management of opioid dependence. It has a reduced potential for abuse or misuse compared with methadone and buprenorphine alone, and has a long half-life allowing less frequent dosing. Buprenorphine/naloxone appears to be well suited for the management of opioid dependence in an office-based setting. The aim of this study was to evaluate the efficacy and safety of a buprenorphine/naloxone combination treatment in an office-based setting. Therefore, we evaluated the effect on misuse/diversion, quality of care, quality of life and service delivery. Seventy-eight patients were switched to buprenorphine/naloxone from either methadone or buprenorphine alone; the median duration of previous buprenorphine or methadone treatment was 10 years. Patients received buprenorphine/naloxone and were evaluated throughout a 1-year follow-up period. Treatment was self-administered by the patients every 2 weeks and the mean buprenorphine dosage at 1 year was 8 mg/day. Comparisons were made before and after the switch for patients who switched from buprenorphine alone to buprenorphine/naloxone. Switching to buprenorphine/naloxone was not associated with clinically relevant problems in 50% of patients studied. Buprenorphine/naloxone provided satisfactory coverage of withdrawal symptoms in 78.1% of patients, and 50% of patients were satisfied with buprenorphine/naloxone therapy. Seventy-eight per cent of patients reported improved psychosocial functioning. The majority of patients (approximately 85%) were negative for opioids during toxicological testing. A significantly higher proportion of treatment recipients were highly satisfied during buprenorphine/naloxone administration (p buprenorphine given before the switch). Other outcomes were similar during buprenorphine and buprenorphine/naloxone administration. Fortnightly self-administration of buprenorphine/naloxone appeared to be cost saving for the clinic. Buprenorphine/naloxone is an

  15. Buprenorphine Sublingual and Buccal (opioid dependence)

    Science.gov (United States)

    ... buprenorphine and naloxone are used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic ... as ketoconazole (Nizoral); medications for anxiety such as benzodiazepines; cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; ...

  16. 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.

  17. Pharmacokinetics of the combination tablet of buprenorphine and naloxone.

    Science.gov (United States)

    Chiang, C Nora; Hawks, Richard L

    2003-05-21

    The sublingual combination tablet formulation of buprenorphine and naloxone at a fixed dose ratio of 4:1 has been shown to be as effective as the tablet formulation containing only buprenorphine in treating opiate addiction. The addition of naloxone does not affect the efficacy of buprenorphine for two reasons: (1) naloxone is poorly absorbed sublingually relative to buprenorphine and (2) the half-life for buprenorphine is much longer than for naloxone (32 vs. 1 h for naloxone). The sublingual absorption of buprenorphine is rapid and the peak plasma concentration occurs 1 h after dosing. The plasma levels for naloxone are much lower and decline much more rapidly than those for buprenorphine. Increasing dose results in increasing plasma levels of buprenorphine, although this increase is not directly dose-proportional. There is a large inter-subject variability in plasma buprenorphine levels. Due to the large individual variability in opiate dependence level and the large variability in the pharmacokinetics (PK) of buprenorphine, the effective dose or effective plasma concentration is also quite variable. Doses must be titrated to a clinically effective level for individual patients.

  18. 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.

  19. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence.

    Science.gov (United States)

    Elkader, Alexander; Sproule, Beth

    2005-01-01

    Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine is unique in that it is a partial agonist at the opioid mu receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore has very low oral bioavailability; however, its bioavailability sublingually is extensive enough to make this a feasible route of administration for the treatment of opioid dependence. The mean time to maximum plasma concentration following sublingual administration is variable, ranging from 40 minutes to 3.5 hours. Buprenorphine has a large volume of distribution and is highly protein bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is eliminated in the faeces, with approximately 10-30% excreted in urine. Naloxone has been added to a sublingual formulation of buprenorphine to reduce the abuse liability of the product. The presence of naloxone does not appear to influence the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk. Buprenorphine dosage does not need to be significantly adjusted in patients with renal impairment; however, since CYP3A activity may be decreased in patients with severe chronic liver disease, it is possible that the metabolism of buprenorphine will be altered in these patients. Although there is limited evidence in the literature to date, drugs that are known to inhibit or induce CYP3A4 have the potential to diminish or enhance buprenorphine N-dealkylation. It appears that the interaction between buprenorphine and benzodiazepines is more likely to be a pharmacodynamic (additive or synergistic) than a

  20. Human pharmacokinetics of intravenous, sublingual, and buccal buprenorphine.

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    Kuhlman, J J; Lalani, S; Magluilo, J; Levine, B; Darwin, W D

    1996-10-01

    Buprenorphine is a potent opioid analgesic used in the treatment of moderate to severe pain. At higher doses, it has demonstrated potential for treating heroin dependence. This study was undertaken to investigate buprenorphine pharmacokinetics by different routes of administration at dosages approximating those used in opioid-dependence studies. Six healthy men who were nondependent but who had a history of heroin use were administered buprenorphine in a crossover design study by intravenous (1.2 mg), sublingual (4.0 mg), and buccal (4.0 mg) routes of administration. Plasma samples were collected up to 96 h and assayed for buprenorphine and norbuprenorphine by negative chemical ionization tandem mass spectrometry. Plasma concentrations of buprenorphine and norbuprenorphine were analyzed by nonlinear regression analysis with standard noncompartmental methods. Buprenorphine biovailability by the sublingual and buccal routes was estimated as 51.4% and 27.8%, respectively, although there was considerable interindividual variability by both routes of administration. The terminal elimination half-lives were longer for the sublingual and buccal routes than for the intravenous route. The extended elimination half-lives may be due to a shallow depot effect involving sequestration of buprenorphine in the oral mucosa. Norbuprenorphine mean peak plasma concentrations were less than 1 ng/mL and were highly variable among different routes of administration and individuals. The terminal elimination half-life of norbuprenorphine was longer than buprenorphine.

  1. A urinalysis-based study of buprenorphine and non-prescription opioid use among patients on buprenorphine maintenance

    Directory of Open Access Journals (Sweden)

    Yatan Pal Singh Balhara

    2012-01-01

    Full Text Available Objectives: To understand the pattern of use of opioid-substitution therapy (OST and opioid abuse among patients on buprenorphine maintenance using urinalysis. Materials and Methods: The study was conducted at a tertiary care de-addiction center. We reviewed the laboratory record of all consecutive urine samples sent for drug analysis over a period of 1 year. In all, 179 consecutive urine samples were included in the analysis. The chi-square test was used to compare opioid abuse among those testing positive and negative for buprenorphine on urinalysis. Additionally, in order to assess the potential impact of the prescribed induction and maximum dose of buprenorphine on the findings, we carried out the independent-samples t test. Level of statistical significance was kept at P<0.05 for all the tests. Results: Urinalysis failed to detect buprenorphine in 44.7% of the samples. Rate of detection of dextropropoxyphene was significantly higher among buprenorphine-negative samples (P<0.005. The prescribed induction dose of buprenorphine was significantly lower among those testing positive for heroin. This was found for both buprenorphine-positive (P<0.005 as well as buprenorphine-negative samples (P<0.005. Conclusions: These findings support the routine use of urine drug screening among individuals on OST.

  2. French Experience with Buprenorphine : Do Physicians Follow the Guidelines?

    Directory of Open Access Journals (Sweden)

    Morgane Guillou Landreat

    Full Text Available Opiate dependence affects about 15,479,000 people worldwide. The effectiveness of opiate substitution treatments (OST has been widely demonstrated. Buprenorphine plays a particular role in opiate dependence care provision in France. It is widely prescribed by physicians and national opiate substitution treatment guidelines have been available since 2004. In order to study the prescribing of buprenorphine, we used a questionnaire sent by email, to a large sample of physicians. These physicians were either in practice, or belonged to an addiction treatment network or a hospital. The main objective of this work was to measure the extent to which the theoretical, clinical attitude of physicians towards prescribing buprenorphine (BHD complied with the statutory guidelines. We showed that the physicians we interviewed rarely took into account the guidelines regarding buprenorphine prescription. The actual prescribing of Buprenorphine differed from the guidelines. Only 42% of independent Family Physicians (FPs, working outside the national health care system, had prescribed buprenorphine as a first-time prescription and 40% of FPs do not follow up patients on buprenorphine. In terms of compliance with the guidelines, 55% of FPs gave theoretical answers that only partially complied with the guidelines. The variations in compliance with the guidelines was noted according to different variables and took into particular account whether the physician were affiliated to a network or in training.

  3. French Experience with Buprenorphine : Do Physicians Follow the Guidelines?

    Science.gov (United States)

    Guillou Landreat, Morgane; Rozaire, Charles; Guillet, Jean Yves; Victorri Vigneau, Caroline; Le Reste, Jean Yves; Grall Bronnec, Marie

    2015-01-01

    Opiate dependence affects about 15,479,000 people worldwide. The effectiveness of opiate substitution treatments (OST) has been widely demonstrated. Buprenorphine plays a particular role in opiate dependence care provision in France. It is widely prescribed by physicians and national opiate substitution treatment guidelines have been available since 2004. In order to study the prescribing of buprenorphine, we used a questionnaire sent by email, to a large sample of physicians. These physicians were either in practice, or belonged to an addiction treatment network or a hospital. The main objective of this work was to measure the extent to which the theoretical, clinical attitude of physicians towards prescribing buprenorphine (BHD) complied with the statutory guidelines. We showed that the physicians we interviewed rarely took into account the guidelines regarding buprenorphine prescription. The actual prescribing of Buprenorphine differed from the guidelines. Only 42% of independent Family Physicians (FPs), working outside the national health care system, had prescribed buprenorphine as a first-time prescription and 40% of FPs do not follow up patients on buprenorphine. In terms of compliance with the guidelines, 55% of FPs gave theoretical answers that only partially complied with the guidelines. The variations in compliance with the guidelines was noted according to different variables and took into particular account whether the physician were affiliated to a network or in training.

  4. Buprenorphine for cancer pain: is it ready for prime time?

    Science.gov (United States)

    Prommer, Eric

    2015-12-01

    Buprenorphine (BUP) is a semisynthetic derivative of the opium alkaloid thebaine found in the poppy Papaver somniferum. Its chemical structure contains the morphine structure but differs by having a cyclopropylmethyl group. Buprenorphine is a potent µ opioid agonist. Buprenorphine undergoes extensive first-pass metabolism in the liver and gut. The development of a transdermal BUP formulation in 2001 led to its evaluation in cancer pain. This article provides the practitioner with an update on the current role of BUP in cancer care. It highlights data suggesting effectiveness in various types of cancer pain. The article reviews pharmacology, routes of administration, adverse effects, drug interactions, and cost considerations.

  5. The pharmacokinetics and physiological effects of buprenorphine infusion in premature neonates.

    OpenAIRE

    1993-01-01

    1. The pharmacokinetics and physiological effects of buprenorphine were studied in 12 newborn premature neonates (27 to 32 weeks gestational age) who were given a loading dose of 3.0 micrograms kg-1 of buprenorphine followed by an intravenous infusion of 0.72 micrograms kg-1 h-1 of buprenorphine. Plasma concentrations of buprenorphine were measured during the infusion, at steady-state and for 24 h after the cessation of the buprenorphine infusion. 2. The mean steady-state plasma buprenorphine...

  6. Sublingual buprenorphine used postoperatively: clinical observations and preliminary pharmacokinetic analysis.

    OpenAIRE

    Bullingham, R E; McQuay, H. J.; Dwyer, D.; Allen, M C; Moore, R A

    1981-01-01

    1 Buprenorphine is a long-acting opiate analgesic. This study was designed to investigate the pharmacokinetics of this drug when given by the sublingual route to ten postoperative patients. Plasma levels of buprenorphine were measured by a specific radioimmunoassay. 2 Plasma levels of the drug following sublingual administration of 0.4 mg showed an apparent delay in absorption and then rose slowly to reach low but significant levels by 3 h. There was considerable variation in the time at whic...

  7. Substance misuse problems during pregnancy with special emphasis on buprenorphine

    OpenAIRE

    2011-01-01

    Maternal drug abuse during pregnancy endangers the future health and wellbeing of the infant and growing child. On the other hand, via maternal abstinence, these problems would never occur; so the problems would be totally preventable. Buprenorphine is widely used in opioid maintenance treatment as a substitute medication. In Finland, during 2000 s buprenorphine misuse has steadily increased. In 2009 almost one third of clientele of substance treatment units were in treatment because of bupre...

  8. Effect of telaprevir on the pharmacokinetics of buprenorphine in volunteers on stable buprenorphine/naloxone maintenance therapy.

    Science.gov (United States)

    Luo, Xia; Trevejo, Jose; van Heeswijk, Rolf P G; Smith, Frances; Garg, Varun

    2012-07-01

    This was an open-label, single-sequence trial in hepatitis C virus-negative volunteers on stable, individualized, buprenorphine maintenance therapy. Telaprevir at 750 mg every 8 h was coadministered with buprenorphine/naloxone (4:1 ratio as sublingual tablets) for 7 days with food. Pharmacokinetic profiles of buprenorphine, norbuprenorphine, and naloxone were measured over the 24-hour dosing interval on day -1 (buprenorphine/naloxone alone, reference) and day 7 of telaprevir coadministration (test). Geometric least-squares mean ratios and associated 90% confidence intervals of treatment ratios (test/reference) were calculated using log-transformed pharmacokinetic parameters. Opioid withdrawal symptoms were evaluated throughout the study (via questionnaires and pupillometry). Pharmacokinetic data were available for 14 and 13 volunteers on day -1 and day 7, respectively. The area under the concentration-time curve (AUC) for buprenorphine was unchanged and the maximum concentration of drug in serum (C(max)) for buprenorphine, C(max) and AUC for norbuprenorphine, and C(max) naxolone were modestly decreased during coadministration with telaprevir. Geometric least-squares mean ratios (90% confidence intervals) for buprenorphine were 0.80 (0.69, 0.93) for the C(max) and 0.96 (0.84, 1.10) for the AUC from 0 to 24 h (AUC(0-24)); for norbuprenorphine, values were 0.85 (0.66, 1.09) for C(max) and 0.91 (0.71, 1.16) for AUC(0-24); for naloxone, the C(max) was 0.84 (0.62, 1.13). Coadministration of telaprevir did not increase withdrawal symptom frequency, and there were no serious adverse events reported during or after completion of telaprevir coadministration. Results suggest dose adjustment may not be necessary when telaprevir and buprenorphine/naloxone are coadministered.

  9. 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....

  10. 78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

    Science.gov (United States)

    2013-06-06

    ... HUMAN SERVICES Food and Drug Administration Determination That SUBOXONE (Buprenorphine Hydrochloride and... (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...

  11. Serum concentrations of buprenorphine after oral and parenteral administration in male mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten R; Hau, Jann

    2011-01-01

    Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post......-administration serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T. [Dept. of Obstetrics and Gynecology, Dept. of Pediatrics, and Helsinki Medical Imaging Center, Helsinki Univ. Central Hospital (Finland)

    2007-02-15

    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.

  13. Voluntary ingestion of buprenorphine as a refined analgesic strategy

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten Rosenmaj; Kalliokoski, Otto Henrik; Hau, Jann;

    2011-01-01

    Buprenorphine is a widely used analgesic for laboratory rodents. Administration of the drug in an attractive food item for voluntary ingestion is a desirable way to administer the drug noninvasively. The method refi nes the standard analgesic procedure and has the potential to improve the welfare...... of laboratory mice and rats. However, many aspects of the voluntary ingestion method still need to be investigated. This paper examines the concept of voluntary ingestion of analgesia and reports new findings about voluntary ingestion of buprenorphine in mice....

  14. A novel approach in the detoxification of intravenous buprenorphine dependence

    Science.gov (United States)

    Sarkar, Sukanto; Subramaniam, Eswaran; Konthoujam, Janet

    2016-01-01

    Background: Opioid dependence remains a significant problem in India, and of late intravenous (IV) buprenorphine use has increased in India, especially in combination with antihistamines and benzodiazepines. Its usage has many serious consequences in the form of needle-transmitted hepatitis and HIV, which is showing an increasing trend. Buprenorphine is a partial agonist at μ-opioid receptors. In tablet form (and rarely as IV), it is widely used in the treatment of opioid detoxification. We assessed the safety and efficacy of transdermal patch of buprenorphine with week long duration of action in the treatment of detoxification of IV buprenorphine dependence in view of its many advantages. Materials and Methods: Six consecutive patients with International Classification of Diseases diagnosis of Opioid Dependence Syndrome (IV buprenorphine) were given a buprenorphine patch for treatment of withdrawal symptoms after receiving consent. Severity of opioid dependence was assessed by using Severity of Opioid Dependence Questionnaire on the day of presentation. Subjective and objective rating for opioid withdrawal was done by subjective opiate withdrawal scale (SOWS) and objective opiate withdrawal scale (OOWS) prepatch and postpatch 3rd and 7th day. Buprenorphine side effect checklist was applied on a daily basis. Results: The patients had a mean age of 30 years, of whom 83.3% are males. All were educated and 50% were currently employed. All of them had additional comorbid substance use as well as a comorbid psychiatric diagnosis. Each of them received a patch of varying dosage. The patch dose used initially was based on clinical considerations alone and was fairly adequate in controlling acute withdrawal symptoms. There is a significant improvement in SOWS and OOWS while comparing the baseline (prepatch) with 3rd and 7th day (postpatch) (P ≤ 0.05). None of the patients reported any side effect with the patch. Conclusion: This study shows that transdermal

  15. The pharmacokinetics and physiological effects of buprenorphine infusion in premature neonates.

    Science.gov (United States)

    Barrett, D A; Simpson, J; Rutter, N; Kurihara-Bergstrom, T; Shaw, P N; Davis, S S

    1993-09-01

    1. The pharmacokinetics and physiological effects of buprenorphine were studied in 12 newborn premature neonates (27 to 32 weeks gestational age) who were given a loading dose of 3.0 micrograms kg-1 of buprenorphine followed by an intravenous infusion of 0.72 micrograms kg-1 h-1 of buprenorphine. Plasma concentrations of buprenorphine were measured during the infusion, at steady-state and for 24 h after the cessation of the buprenorphine infusion. 2. The mean steady-state plasma buprenorphine concentration (+/- s.d.) for an infusion rate of 0.72 micrograms kg-1 h-1 was 4.3 +/- 2.6 ng ml-1. 3. Buprenorphine clearance was 0.23 +/- 0.07 l h-1 kg-1, the elimination half-life was 20 +/- 8 h and the volume of distribution was 6.2 +/- 2.11 l kg-1. 4. Small but significant falls were noted in systolic blood pressure at 6 h and heart rate at 1, 6 and 12 h after the administration of buprenorphine, but these did not appear to cause any clinical deterioration. 5. Four of the 12 subjects studied required an increase in the infusion rate of buprenorphine to achieve adequate sedation. 6. The results suggest that this dosing regimen of buprenorphine is safe but may not be as effective as other opioids in producing sedation and analgesia in premature newborns.

  16. Flunitrazepam does not alter cerebral distribution of buprenorphine in the rat.

    Science.gov (United States)

    Megarbane, Bruno; Pirnay, Stéphane; Borron, Stephen W; Trout, Hervé; Monier, Claire; Risède, Patricia; Boschi, Gabrielle; Baud, Frédéric J

    2005-07-04

    Deaths have been reported among heroin addicts related to combined buprenorphine and flunitrazepam use. The aim of this study was to determine the existence of a drug-drug interaction during the distribution phase of buprenorphine. Arterial blood gases were measured after intravenous administration of buprenorphine alone (30 mg/kg), flunitrazepam alone (40 mg/kg) or both drugs in rats. Buprenorphine kinetics was studied in plasma and in striatum using cerebral microdialysis, both alone and after rat pretreatment with flunitrazepam. In contrast to buprenorphine or flunitrazepam alone, buprenorphine in combination with flunitrazepam induced a significant, rapid and sustained respiratory depression. Arterial PCO2 was increased at 1.5 min (6.7+/-0.2 versus 5.4+/-0.3 and 5.5+/-0.3 kPa, respectively, P=0.04) (mean+/-S.E.M.), and arterial pH decreased (7.37+/-0.02 versus 7.45+/-0.02 and 7.45+/-0.01, respectively, P=0.03). Plasma buprenorphine kinetics was well described by a three-compartment linear model, with a distribution half-life of 7.4+/-2.7 min and an elimination half-life of 463.9+/-152.3 min. However, neither plasma nor striatal buprenorphine kinetics were significantly altered by pre-administration of flunitrazepam. The adverse interaction between flunitrazepam and buprenorphine cannot be explained by a pharmacokinetic drug-drug interaction during the distribution phase of buprenorphine.

  17. 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…

  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. Systemic uptake of buprenorphine by cats after oral mucosal administration.

    Science.gov (United States)

    Robertson, S A; Taylor, P M; Sear, J W

    2003-05-31

    The plasma concentration of buprenorphine was measured by radioimmunoassay in six female cats after the administration of 0.01 mg/kg (0.033 ml/kg) buprenorphine hydrochloride solution into the side of the cat's mouth. Blood samples were taken through a preplaced jugular catheter before and one, two, four, six, 10, 15, 30, 45 and 60 minutes, and two, four, six, 12 and 24 hours after the dose was administered. The buprenorphine was accepted well by all the cats and did not cause salivation or vomiting. Its median peak plasma concentration was 7.5 ng/ml and was reached after 15 minutes. The pharmacokinetic data were similar to the pharmacokinetic data obtained after the intramuscular and intravenous administration of buprenorphine to cats from the same colony, suggesting that the mucosal route of administration should be as effective as intravenous and intramuscular injections. In addition, the pH of the oral cavity of 26 cats was measured with pH paper, and 100 cat owners were asked their preferred method of administering drugs to cats. The pH of the cats' mouths was between 8 and 9, and the technique preferred by the cat owners was the use of drops placed in the mouth.

  20. Clinical pharmacology of buprenorphine in healthy, lactating goats.

    Science.gov (United States)

    Ingvast-Larsson, C; Svartberg, K; Hydbring-Sandberg, E; Bondesson, U; Olsson, K

    2007-06-01

    The pharmacokinetics and the effects of the opioid buprenorphine on behavior, cardiovascular parameters, plasma concentrations of cortisol and vasopressin were studied in the goat. After intravenous injection at a dosage of 0.02 mg/kg bw, the terminal half-life was 73.8+/-19.9 min (mean+/-SD), the apparent volume of distribution 5.22+/-1.01 L/kg, and total body clearance 79.1+/-18.5 mL/min/kg. After intramuscular administration of buprenorphine at the same dosage, bioavailability was complete and clearance was 54.7+/-16.6 mL/min/kg. Heart rate, blood pressure and concentrations of cortisol and vasopressin in plasma increased after drug administration. The goats became agitated and stopped ruminating. The effects were more pronounced the first time the animals received the drug, especially the influence on the hormone levels. The concentrations of cortisol and vasopressin in plasma remained unaffected after the second dose despite a wash-out period of 3-6 weeks. Buprenorphine may be an unsuitable drug in goats because of the profound inhibition of rumination and the agitation it causes. The short half-life of buprenorphine may limit its use if long-term analgesia is required but be advantageous if a short acting drug is desirable.

  1. Plasma concentrations of buprenorphine after epidural administration in conscious cats.

    Science.gov (United States)

    Duke-Novakovski, Tanya; Clark, Christopher R; Ambros, Barbara; Gilbert, Peter; Steagall, Paulo V M

    2011-06-01

    Buprenorphine plasma concentrations were measured after administering buprenorphine (20 μg/kg) into the lumbosacral epidural space of conscious cats chronically instrumented with an epidural catheter. Blood was collected from a jugular vein before injection and 15, 30, 45 and 60 min and 2, 3, 4, 5, 6, 8, 12 and 24 h after administration. Plasma buprenorphine concentrations were measured using ELISA. Background concentration (before injection) was 1.27 ± 0.27 ng/mL (mean ± SD). Including background concentration, the mean peak plasma concentration was obtained 15 min after injection (5.82 ± 3.75 ng/mL), and ranged from 3.79 to 2.20 ng/mL (30 min-3 h), remaining between 1.93 and 1.77 ng/mL (4-12 h), and declined to 1.40 ± 0.62 ng/mL at 24h. Elimination half-life was 58.8 ± 40.2 min and clearance 56.7 ± 21.5 mL/min. Results indicate early rapid systemic uptake of buprenorphine from epidural administration with plasma concentrations similar to using buccal or IM routes by 15 min postinjection.

  2. Morphine, pethidine and buprenorphine disposition in the cat.

    Science.gov (United States)

    Taylor, P M; Robertson, S A; Dixon, M J; Ruprah, M; Sear, J W; Lascelles, B D; Waters, C; Bloomfield, M

    2001-12-01

    Pharmacokinetics of morphine, buprenorphine and pethidine were determined in 10 cats. Six cats received morphine (0.2 mg/kg) intravenously and four intramuscularly. Five received buprenorphine (0.01 mg/kg) intravenously and six intramuscularly. Six received pethidine (5 mg/kg) intramuscularly. Jugular venous blood samples were collected at time points to 24 h, and plasma morphine concentrations were measured by high performance liquid chromatograpy (HPLC), buprenorphine by radioimmunoassay (RIA) and pethidine by gas chromatography. Our data for morphine show elimination half-life (t1/2el) 76.3 min intravenous (i.v.) and 93.6 min intramuscular (i.m.); mean residence time (MRT) 105.0 and 120.5 min; clearance (Clp) 24.1 and 13.9 mL/kg/min; and volume of distribution (V(dss)) 2.6 and 1.7 L/kg, respectively. Comparable data for buprenorphine are t1/2el 416.8 and 380.2 min; MRT 417.6 and 409.8 min; Clp 16.7 and 23.7 mL/kg/min; and V(dss) 7.1 and 8.9 L/kg. For i.m. pethidine, t1/2el 216.4 min; MRT 307.5 min; Clp 20.8 mL/kg/min and V(dss) 5.2 L/kg. For i.m. dosing, the tmax for morphine, buprenorphine and pethidine were 15, 3 and 10 min, respectively. The pharmacokinetics of the three opioids in cats are broadly comparable with those of the dog, although there is a suggestion that the cat may clear morphine more slowly.

  3. Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS.

    Science.gov (United States)

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine (Suboxone, Zubsolv, Buprenex, Butrans, etc.) 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. Pregnant women may be prescribed buprenorphine as part of a treatment plan for opioid addiction. This chapter quantitates buprenorphine and norbuprenorphine in meconium by liquid chromatography tandem mass spectrometry (LC-MS/MS).

  4. Prior criminal charges and outcomes among individuals initiating office-based buprenorphine treatment

    OpenAIRE

    Harris, Elizabeth E; Jacapraro, Janet S; Rastegar, Darius A

    2013-01-01

    Background There is little data on the impact of prior criminal activity on the treatment of opioid dependence with office-based buprenorphine. The goal of this study was to investigate the association between prior criminal charges and treatment outcomes in a cohort of patients initiating buprenorphine treatment in a primary care practice. Methods This was a retrospective study of 252 consecutive patients with opioid dependence who were given at least one prescription for buprenorphine in a ...

  5. Pharmacokinetics of 2 formulations of buprenorphine in macaques (Macaca mulatta and Macaca fascicularis).

    Science.gov (United States)

    Nunamaker, Elizabeth A; Halliday, Lisa C; Moody, David E; Fang, Wenfang B; Lindeblad, Matthew; Fortman, Jeffrey D

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tested doses. The low and high doses of buprenorphine had elimination half-lives of 2.6 ± 0.7 and 5.3 ± 2.0 h, respectively, but the low-dose data were constrained by the sensitivity of the analytical method. Sustained-release buprenorphine had an elimination half-life of 42.6 ± 26.2 h. The AUC0-Tlast of buprenorphine were 9.1 ± 4.3 and 39.0 ± 25.1 ng × h/mL for the low and high doses, respectively, and sustained-release buprenorphine had an AUC0-Tlast of 177 ± 74 ng × h/mL. Assuming a hypothesized therapeutic buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h. These results further demonstrate that a single 0.2-mg/kg SC injection of sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL for 5 d in macaques. These findings support a new dosing strategy using sustained-release buprenorphine to improve pain management, decrease animal stress, improve animal welfare, and simplify the postoperative management of nonhuman primates in laboratory animal and zoological settings.

  6. 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......-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...

  7. Pharmacokinetics of 2 Formulations of Buprenorphine in Macaques (Macaca mulatta and Macaca fascicularis)

    OpenAIRE

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the ...

  8. 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.

  9. 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.

  10. Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.

    Science.gov (United States)

    Davis, J L; Messenger, K M; LaFevers, D H; Barlow, B M; Posner, L P

    2012-02-01

    The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra-performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97±5.16 mL/kg/min, and half-life (T(1/2)) was 3.58 h (harmonic mean). Volume of distribution was 3.01±1.69 L/kg. Following i.m. administration, maximum concentration (C(max)) was 1.74±0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34±1.22 ng/mL) after i.v. administration (PBuprenorphine has a moderate T(1/2) in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted.

  11. Fulminant hepatic failure after intravenous injection of sublingual buprenorphine in a patient with hepatitis C.

    Science.gov (United States)

    French, Janine; Mujumdar, Avik; Angus, Peter; Gow, Paul

    2015-08-01

    A 20-year-old indigenous Australian male was admitted to the intensive care unit with fulminant hepatic failure secondary to intravenous use of buprenorphine, which had been prescribed sublingually for opioid dependence. Intravenous buprenorphine-induced hepatitis is well recognized, however, life-threatening fulminant hepatic failure has not previously been reported.

  12. 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;

    2010-01-01

    in buprenorphine-treated and untreated animals. A part from a slightly higher hyperthermia immediately after surgery and typical opiate-associated behaviour, the buprenorphine treatment had no apparent adverse effects on the experimental model. In contrast, the analgesic treatment improved the model by minimizing...

  13. Buprenorphine-containing treatments: place in the management of opioid addiction.

    Science.gov (United States)

    Robinson, Susan E

    2006-01-01

    Although the synthetic opioid buprenorphine has been available clinically for almost 30 years, its use has only recently become much more widespread for the treatment of opioid addiction. The pharmacodynamic and pharmacokinetic profiles of buprenorphine make it unique in the armamentarium of drugs for the treatment of opioid addiction. Buprenorphine has partial mu-opioid receptor agonist activity and is a kappa-opioid receptor antagonist; hence, it can substitute for other micro-opioid receptor agonists, yet is less apt to produce overdose reactions or dysphoria. On the other hand, buprenorphine can block the effects of opioids such as heroin (diamorphine) and morphine, and can even precipitate withdrawal in individuals physically dependent upon these drugs. Buprenorphine has significant sublingual bioavailability and a long half-life, making administration on a less than daily basis possible. Furthermore, its discontinuation is associated with only a mild withdrawal syndrome. Clinical trials have demonstrated that sublingual buprenorphine is effective in both maintenance therapy and detoxification of individuals addicted to opioids. The introduction of a sublingual formulation combining naloxone with buprenorphine further reduces the risk of diversion to illicit intravenous use. Because of its relative safety and lower risk of illegal diversion, buprenorphine has been made available in several countries for treating opioid addiction in the private office setting, greatly enhancing treatment options for this condition.

  14. 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...... after surgery. It was found that the two rat stocks responded in a similar manner to both buprenorphine treatments, with the exception of body weight change in Wistar rats, in which body weight was reduced after SC treatment. The plasma concentration of corticosterone was significantly higher in the SC...

  15. Buprenorphine: an analgesic with an expanding role in the treatment of opioid addiction.

    Science.gov (United States)

    Robinson, Susan E

    2002-01-01

    Buprenorphine, a long-acting opioid with both agonist and antagonist properties, binds to mu-opioid (OP(3)), kappa-opioid (OP(2)), delta-opioid (OP(1)), and nociceptin (ORL-1) receptors. Its actions at these receptors have not been completely characterized, although buprenorphine is generally regarded as a mu-opioid receptor partial agonist and a kappa-opioid receptor antagonist. Its pharmacology is further complicated by an active metabolite, norbuprenorphine. Although buprenorphine can be used as an analgesic agent, it is of greater importance in the treatment of opioid abuse. Because of its partial agonist activity at mu-opioid receptors and its long half-life, buprenorphine has proven to be an excellent alternative to methadone for either maintenance therapy or detoxification of the opioid addict. Although buprenorphine may ultimately prove to be superior to methadone in the maintenance of the pregnant addict, its effects on the developing fetus must be carefully evaluated.

  16. 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.

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

    Science.gov (United States)

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-Kang; Chen, Shao-Tsu

    2015-01-01

    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 offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders.

  18. Crushed and injected buprenorphine tablets: characteristics of princeps and generic solutions.

    Science.gov (United States)

    Bouquié, Régis; Wainstein, Laura; Pilet, Paul; Mussini, Jean-Marie; Deslandes, Guillaume; Clouet, Johann; Dailly, Eric; Jolliet, Pascale; Victorri-Vigneau, Caroline

    2014-01-01

    Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened.

  19. 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

  20. Radioimmunoassay of buprenorphine in urine: Studies in patients and in a drug clinic

    Energy Technology Data Exchange (ETDEWEB)

    Hand, C.W.; Ryan, K.E.; Dutt, S.K.; Moore, R.A. (DPC European Research Institute, Witney (England)); O' Connor, J.; Talbot, D. (Jervis Street Hospital, Dublin (Ireland)); McQuay, H.J. (Abingdon Hospital, Oxford (England))

    A radioimmunoassay kit (DPC buprenorphine double antibody) was evaluated with clinical samples and samples from a drug clinic. Urine samples were collected over a 2-day period from 5 hospital in-patients receiving sublingual buprenorphine, 400 to 2000 {mu}g/day, for the relief of chronic pain. Samples were measured before and after enzymatic hydrolysis. Urine buprenorphine concentrations were measurable at all doses studied (minimum value 5.6 ng/mL) and were greater with larger doses. The increase in concentration after hydrolysis averaged 49% and was similar for all doses studied. The authors conclude that the method has extensive cross-reactivity with glucuronides of buprenorphine and its metabolites and that samples may be analyzed without prior hydrolysis. The prevalence of buprenorphine use in 97 patients attending a drug clinic was also studied. Sixty (62%) had measurable urinary buprenorphine concentrations of 1 ng/mL or more by direct assay. The buprenorphine users were significantly younger and reported significantly greater use of opiates than nonusers.

  1. False-positive buprenorphine by CEDIA in patients prescribed amisulpride or sulpiride.

    Science.gov (United States)

    Birch, M A; Couchman, L; Pietromartire, S; Karna, T; Paton, C; McAllister, R; Marsh, A; Flanagan, R J

    2013-05-01

    Buprenorphine is a potent partial opioid agonist that is analyzed in urine to (i) monitor adherence to maintenance or detoxification therapy and (ii) detect illicit use. Buprenorphine analysis is commonly conducted on urine by immunoassay, but is subject to cross-reactivity from other drugs/drug metabolites, including morphine, codeine and dihydrocodeine. This study reports false-positive buprenorphine analysis [Thermo Fisher Scientific cloned enzyme donor immunoassay (CEDIA)] in patients who denied unauthorized buprenorphine use prior to sampling, but who had been prescribed amisulpride. In two cases, confirmatory analysis by liquid chromatography-tandem mass spectrometry was negative (sulpiride in the CEDIA buprenorphine assay is low (estimated at 0.003 and 0.002%, respectively), it remains a significant consideration given the likely high concentrations of these compounds in urine relative to the low cutoff of the buprenorphine assay. Neither amisulpride nor sulpiride was listed as potential sources of interference on the CEDIA data sheet when this work was performed. These findings highlight the importance of confirming immunoassay-positive buprenorphine results using a more selective analytical technique.

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

    Science.gov (United States)

    Abelson, Klas S P; Jacobsen, Kirsten R; Sundbom, Renée; Kalliokoski, Otto; Hau, Jann

    2012-10-01

    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 for voluntary ingestion. This method has many advantages over parenteral administration. To use the method in a successful way, however, it is important to prepare and administer the mix correctly. The present paper describes in detail how to implement the method, by means of habituation, presentation, adequate concentrations and amounts of buprenorphine/nut paste, and dosage of buprenorphine to rats and mice.

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

    Science.gov (United States)

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

    2009-01-01

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

  4. Integrating buprenorphine treatment into a public healthcare system: the San Francisco Department of Public Health's office-based Buprenorphine Pilot Program.

    Science.gov (United States)

    Hersh, David; Little, Sherri L; Gleghorn, Alice

    2011-01-01

    Despite well-documented efficacy, US physicians have been relatively slow to embrace the use of buprenorphine for the treatment of opioid dependence. In order to introduce and support the use of buprenorphine across the San Francisco Department of Public Health system of care, the Buprenorphine Pilot Program was initiated in 2003. Program treatment sites included a centralized buprenorphine induction clinic and program pharmacy, and three community-based treatment sites; two primary care clinics and a private dual diagnosis group practice. The target patient population consisted of opioid-dependent patients typically seen in an urban, public health setting, including individuals experiencing extreme poverty, homelessness/unstable housing, unemployment, polysubstance abuse/dependence, coexisting mental health disorders, and/or little psychosocial support. This program evaluation reviews patient characteristics, treatment retention, substance use over time, patient impressions, and provider practices for the 57 patients admitted between 9/1/03 and 8/31/05. At baseline, over 80% of patients were injecting heroin, over 40% were homeless, and over one-third were using cocaine. Outcomes included an overall one-year retention rate of 61%, a rapid and dramatic decline in opioid use, very positive patient impressions of the program and of buprenorphine, and significant shifts in provider practices over time.

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

    Directory of Open Access Journals (Sweden)

    Paul J Whelan

    2012-01-01

    Full Text Available 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.

  6. To Be Free and Normal: Addiction, Governance, and the Therapeutics of Buprenorphine.

    Science.gov (United States)

    Harris, Shana

    2015-12-01

    Methadone maintenance has dominated opiate addiction treatment in the United States for decades. Since 2002, opiate addiction has also been treated in general medical settings with a substance called buprenorphine. Based on interviews and participant observation conducted in northern California, this article analyzes how discourses of freedom and normalcy in patient and provider narratives reflect and affect experiences with this treatment modality. I discuss how buprenorphine treatment, in contrast to methadone maintenance, offers patients and providers a greater sense of autonomy and flexibility in how they receive and deliver treatment. It presents them with new obligations, responsibilities, and choices around care and conduct. It simultaneously perpetuates and shapes a desire to be "free" and "normal." I argue that the therapeutics of buprenorphine govern patients and providers through this desire for freedom and normalcy. Buprenorphine is thus a technology of governmentality that extends neoliberal discourses and values and produces self-governing subjects.

  7. In vitro dissolution method for evaluation of buprenorphine in situ gel formulation: A technical note

    OpenAIRE

    Graves, Richard A.; Freeman, Thomas; Tarun K. Mandal

    2007-01-01

    The in situ gel formulation of buprenorphine showed sustained drug release for a prolonged period of time. The drug release from RG 502 followed a linear pattern throughout the dissolution without any significant burst release. The amount of buprenorphine released during the first 30 minutes, irrespective of the type of Resomer or dissolution medium, was less than 3%. Drug release continued over 55 days in phosphate buffer and 35 days in Tween 80. The in vitro dissolution method developed dur...

  8. Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model.

    Science.gov (United States)

    Koppert, Wolfgang; Ihmsen, Harald; Körber, Nicole; Wehrfritz, Andreas; Sittl, Reinhard; Schmelz, Martin; Schüttler, Jürgen

    2005-11-01

    Different mechanisms were proposed for opioid-induced analgesia and antihyperalgesia, which might result in different pharmacodynamics. To address this issue, the time course of analgesic and antihyperalgesic effects of intravenous (i.v.) and sublingual (s.l.) buprenorphine was assessed in an experimental human pain model. Fifteen volunteers were enrolled in this randomized, double-blind, and placebo controlled cross-over study. The magnitude of pain and the area of secondary hyperalgesia following transcutaneous stimulation were repetitively assessed before and up to 150 min after administration of (1) 0.15 mg buprenorphine i.v. and placebo pill s.l., (2) 0.2 mg buprenorphine s.l. and saline 0.9% i.v. or (3) saline 0.9% i.v. and placebo pill s.l. as a control. The sessions were separated by 2 week wash-out periods. For both applications of buprenorphine the antihyperalgesic effects were more pronounced as compared to the analgesic effects (66+/-9 vs. 26+/-5% and 43+/-10 vs. 10+/-6%, for i.v. and s.l. application, respectively). This contrasts the pattern for the intravenous administration of pure mu-receptor agonists in the same model in which the antihyperalgesic effects are weaker. The apparent bioavailability of buprenorphine s.l. as compared to buprenorphine i.v. was 58% with a 15.8 min later onset of antinociceptive effects. The half-life of buprenorphine-induced analgesic and antihyperalgesic effects were 171 and 288 min, respectively. In contrast to pure mu-receptor agonists, buprenorphine exerts a lasting antihyperalgesic effect in our model. It will be of major clinical interest whether this difference will translate into improved treatment of pain states dominated by central sensitization.

  9. Successful transition to buprenorphine in a patient with methadone-induced torsades de pointes.

    Science.gov (United States)

    Esses, Jason Levi; Rosman, Jonathan; Do, Lien Thanh; Schweitzer, Paul; Hanon, Sam

    2008-11-01

    A 56-year-old-man presented with syncope and torsades de pointes secondary to methadone-induced QT prolongation. After transition from methadone to buprenorphine, a partial mu-opiate-receptor agonist and a kappa-opiate-receptor antagonist, the QT normalized and ventricular arrhythmias resolved. Buprenorphine should be used for opiate dependence and chronic pain in patients with methadone-induced QT prolongation and as first line therapy in patients with risk factors for torsades de pointes.

  10. Randomized, Placebo-Controlled Pilot Trial of Gabapentin During an Outpatient, Buprenorphine-Assisted Detoxification Procedure1

    OpenAIRE

    Sanders, Nichole C.; Mancino, Michael J.; Gentry, W Brooks; Guise, J. Benjamin; Bickel, Warren K.; Thostenson, Jeff; Oliveto, Alison H.

    2013-01-01

    This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-wk, double blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during week 1, were randomized and inducted onto gabapen...

  11. Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure.

    Science.gov (United States)

    Sanders, Nichole C; Mancino, Michael J; Gentry, W Brooks; Guise, J Benjamin; Bickel, Warren K; Thostenson, Jeff; Oliveto, Alison H

    2013-08-01

    This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-week, double-blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during Week 1, were randomized and inducted onto gabapentin or placebo during Week 2, underwent a 10-day buprenorphine taper during Weeks 3 and 4, and then were tapered off gabapentin/placebo during Week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male; 17 Caucasian, 3 African American, 4 Latino; mean age 29.7 years) participated in the detoxification portion of the study (gabapentin, n = 11; placebo, n = 13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a Drug × Time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure.

  12. Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats.

    Science.gov (United States)

    Porters, N; de Rooster, H; Bosmans, T; Baert, K; Cherlet, M; Croubels, S; De Backer, P; Polis, I

    2015-04-01

    Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.

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

    Energy Technology Data Exchange (ETDEWEB)

    Debrabandere, L.; Boven, M. Van; Daenens, P. (Louvain Univ. (Belgium))

    1993-02-01

    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 < 4.35 and < 6.36%, respectively. A comparison study of the high-performance liquid chromatographic determination (X) to the radioimmunoassay (Y) resulted in the following regression equation for the urine samples: Y = 1.44 + 1.64 X (n = 32; r 0.910) and Y = 0.007 + 1.58 X (n = 10; r = 0.930) for plasma specimens. The minimum detectable dose of the immunoassay was calculated to be 10 pg ml[sup -1] (Student's t-distribution, p 0.01, degrees of freedom = 8). (Author).

  14. 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.

  15. Buprenorphine in the treatment of opiate dependence: its pharmacology and social context of use in the U.S.

    Science.gov (United States)

    Wesson, Donald R

    2004-05-01

    Buprenorphine's physiological effects are produced when it attaches to specific opiate receptors that are designated mu, kappa, or delta. Buprenorphine, a partial agonist at the mu receptor and an antagonist at the kappa receptor, produces typical morphine-like effects at low doses. At higher doses, it produces opiate effects that are less than those of full opiate agonists. Knowledge of the physiological effects of opiate receptors and the way they interact with opiate agonists, partial opiate agonists, and opiate antagonists is fundamental to understanding the safety and efficacy of buprenorphine in treatment of pain and opiate addiction. Knowledge of the historical and social context of opiate agonist treatment of opiate dependence is fundamental to understanding how nonpharmacological factors may limit the clinical adoption and utility of a safe and effective medication in treatment of opiate dependence. This article reviews the pharmacology of sublingual buprenorphine and the historical context of opiate agonist therapy; delineates classes of opiate receptors and their interaction with opiate agonists, partial agonists, and antagonists; and describes the commercially available pharmaceutical formulations of buprenorphine. It focuses on sublingual buprenorphine tablets, Subutex and Suboxone, the FDA-approved formulations of buprenorphine for treatment of opiate dependence. Sublingual buprenorphine, and the combination of sublingual buprenorphine/naloxone, have unique pharmacological properties that make them a logical first-line intervention in the treatment of opioid dependence.

  16. 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

    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...

  17. Plasma buprenorphine concentrations after the application of a 70 microg/h transdermal patch in dogs. Preliminary report.

    Science.gov (United States)

    Andaluz, A; Moll, X; Ventura, R; Abellán, R; Fresno, L; García, F

    2009-10-01

    The objective of the present study was to evaluate the plasma concentrations and pharmacokinetics of buprenorphine after transdermal application in dogs (n = 4). A 70 microg/h transdermal buprenorphine patch was applied to the ventral abdomen of four healthy beagles. Blood samples were collected through a preplaced jugular catheter before and at 1, 2, 4, 8, 12, 24, 36, 48 and every 6 h until 108 h after the patch application. Plasma buprenorphine concentrations were measured using a (125)I-labelled radioimmunoassay (RIA) assay. No adverse effects were observed in any of the dogs. Concentrations of buprenorphine were detected in plasma after the application of the transdermal buprenorphine patch on the four experimental animals. Buprenorphine plasma concentrations increased during the first 36 h and then remained in the 0.7-1.0 ng/mL range during the study period. A decrease in plasma buprenorphine concentration was not observed during the study. Although analgesia could not be demonstrated the present study shows the ability of buprenorphine transdermal delivery systems developed for human use to deliver measurable concetrations of buprenorphine in dogs.

  18. 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

  19. [Transdermal buprenorphine for treatment of chronic tumor and non-tumor pain].

    Science.gov (United States)

    Likar, Rudolf; Griessinger, Norbert; Sadjak, Anton; Sittl, Reinhard

    2003-01-01

    Patients with moderate to severe pain were treated with buprenorphine patches in one of 3 concentrations: 35 micrograms/h, 52.5 micrograms/h and 70 micrograms/h (= 0.8 mg/d, 1.2 mg/d and 1.6 mg/d respectively). The aim of this review was to assess the efficacy and tolerability of this transdermal system (TDS) in patients with chronic pain. A total of 445 patients were included in 3 double-blinded studies. The dosage titration with buprenorphine patches followed pretreatment with buprenorphine sublingual tablets, higher doses of weak opioids (level 2 substances), low dose morphine (level 3) or other analgesics. Patients with chronic tumour or non-tumour pain were recruited for these studies and treated with buprenorphine patches or placebo for 6 to 15 days. All patients were offered, in addition, buprenorphine sublingual tablets to be taken as required for supplementary pain relief. Pain intensity, analgesia, consumption of buprenorphine sublingual tablets and sleep duration were all assessed. All patients in the double-blinded studies were between the ages of 22 and 88. 249 patients suffered from tumour pain and 196 patients suffered from non-tumour pain. To examine long-term efficacy and tolerability of the transdermal system, treatment was expanded, if the patients were interested in participating in an open-label-study. In all 3 studies, the number of patients with moderate, severe and very severe pain increased in the placebo-patch treated group, while the patients in the buprenorphine transdermal system treated group had a greater incidence of mild or no pain. A further benefit in the buprenorphine transdermal system treated group was evidenced by a great number of patients with a daily sleep duration of more than 6 hours compared to the placebo group--an indicator of greater well-being. The systemic side-effects were typically opioid in nature and rare and usually only mild. Of particular note was the very low incidence of constipation in only 5.3% of cases

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

    Science.gov (United States)

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

    2015-02-01

    Pre-clinical 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 effects of buprenorphine, a μ-opioid partial agonist used to treat opioid dependence and pain, on subjective and physiological responses to a stressful public speaking task in healthy adults. We hypothesized that buprenorphine would reduce subjective and physiological stress responses. Healthy adult volunteers (N=48) were randomly assigned to receive placebo, 0.2mg sublingual buprenorphine, or 0.4mg sublingual buprenorphine in a two-session study with a stressful speaking task (Trier Social Stress Test; TSST) and a non-stressful control task. During the sessions, the participants reported on their mood states, provided subjective appraisals of the task, and measures of salivary cortisol, heart rate, and blood pressure at regular intervals. Stress produced its expected effects, increasing heart rate, blood pressure, salivary cortisol, and subjective ratings of anxiety and negative mood. In line with our hypothesis, both doses of buprenorphine significantly dampened salivary cortisol responses to stress. On self-report ratings, buprenorphine reduced how threatening participants found the tasks. These results suggest that enhanced opioid signaling dampens responses to social stress in humans, as it does in laboratory animals. This stress-dampening effect of buprenorphine may contribute to the non-medical use of opioid drugs.

  1. Opioid-induced constipation: rationale for the role of norbuprenorphine in buprenorphine-treated individuals

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    Webster LR

    2016-06-01

    Full Text Available Lynn R Webster,1 Michael Camilleri,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, 2Mayo Clinic Rochester, MN, 3BioDelivery Sciences, Inc., Raleigh, NC, USA Abstract: Buprenorphine and buprenorphine–naloxone fixed combinations are effective for managing patients with opioid dependence, but constipation is one of the most common side effects. Evidence indicates that the rate of constipation is lower when patients are switched from sublingual buprenorphine–naloxone tablets or films to a bilayered bioerodible mucoadhesive buccal film formulation, and while the bilayered buccal film promotes unidirectional drug flow across the buccal mucosa, the mechanism for the reduced constipation is unclear. Pharmacokinetic simulations indicate that chronic dosing of sublingually administered buprenorphine may expose patients to higher concentrations of norbuprenorphine than buprenorphine, while chronic dosing of the buccal formulation results in higher buprenorphine concentrations than norbuprenorphine. Because norbuprenorphine is a potent full agonist at mu-opioid receptors, the differences in norbuprenorphine exposure may explain the observed differences in treatment-emergent constipation between the sublingual formulation and the buccal film formulation of buprenorphine–naloxone. To facilitate the understanding and management of opioid-dependent patients at risk of developing opioid-induced constipation, the clinical profiles of these formulations of buprenorphine and buprenorphine-naloxone are summarized, and the incidence of treatment-emergent constipation in clinical trials is reviewed. These data are used to propose a potential role for exposure to norbuprenorphine, an active metabolite of buprenorphine, in the pathophysiology of opioid-induced constipation. Keywords: opioid, safety, buccal, sublingual, dependence, maintenance

  2. Effect of buprenorphine on total intravenous anesthetic requirements during spine surgery.

    Science.gov (United States)

    Khelemsky, Yury; Schauer, Jacob; Loo, Nathaniel

    2015-01-01

    Buprenorphine is a partial mu receptor agonist and kappa/delta antagonist commonly used for the treatment of opioid dependence or as an analgesic. It has a long plasma half-life and a high binding affinity for opioid receptors. This affinity is so high, that the effects are not easily antagonized by competitive antagonists, such as naloxone. The high affinity also prevents binding of other opioids, at commonly used clinical doses, to receptor sites - preventing their analgesic and likely minimum alveolar concentration (MAC) reducing benefits. This case report contrasts the anesthetic requirements of a patient undergoing emergency cervical spine surgery while taking buprenorphine with anesthetic requirements of the same patient undergoing a similar procedure after weaning of buprenorphine. Use of intraoperative neurophysiological monitoring prevented use of paralytics and inhalational anesthetics during both cases, therefore total intravenous anesthesia (TIVA) was maintained with propofol and remifentanil infusions. During the initial surgery, intraoperative patient movement could not be controlled with very high doses of propofol and remifentanil. The patient stopped moving in response to surgical stimulation only after the addition of a ketamine. Buprenorphine-naloxone was discontinued postoperatively. Five days later the patient underwent a similar cervical spine surgery. She had drastically reduced anesthetic requirements during this case, suggesting buprenorphine's profound effect on anesthetic dosing. This case report elegantly illustrates that discontinuation of buprenorphine is likely warranted for patients who present for major spine surgery, which necessitates the avoidance of volatile anesthetic and paralytic agents. The addition of ketamine may be necessary in patients maintained on buprenorphine in order to ensure a motionless surgical field.

  3. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).

    Science.gov (United States)

    Taylor, Bryan F; Ramirez, Harvey E; Battles, August H; Andrutis, Karl A; Neubert, John K

    2016-01-01

    Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period.

  4. Post-operative pain relief in children following caudal bupivacaine and buprenorphine--a comparative study.

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    Anilkumar T

    1994-04-01

    Full Text Available Eighty-five paediatric patients (age range: 6 mths-12yrs undergoing lower abdominal surgery were studied for post-operative pain relief following either caudal bupivacaine (GpI: n = 43 or buprenorphine (GpII: n = 42. Bupivacaine was administered as 0.5ml/kg body weight of 0.25% solution and buprenorphine as 4 micrograms/ml and volume of 0.5 ml/Kg body weight in normal saline. Post-operatively pain was graded on a 4-point scale and behaviour on a 5-point scale. Any post-operative complications and need for additional analgesia were also noted. Bupivacaine provided good pain relief in the early post-operative hours but buprenorphine provided pain relief lasting for 24 hrs or more post-operatively. Post-operative behaviour of 10 patients receiving buprenorphine was graded as cheerful as compared to 2 from bupivacaine group. Till the end of observation period (i.e. 8 hr post-operatively, majority of patients receiving buprenorphine remained cheerful.

  5. State policy influence on the early diffusion of buprenorphine in community treatment programs

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    Abraham Amanda J

    2008-06-01

    Full Text Available Abstract Background Buprenorphine was approved for use in the treatment of opioid dependence in 2002, but its diffusion into everyday clinical practice in community-based treatment programs has been slow. This study examines the net impact of efforts by state agencies, including provision of Medicaid coverage, on program-level adoption of buprenorphine as of 2006. Methods Interviews were conducted with key informants in 49 of the 50 state agencies with oversight responsibility for addiction treatment services. Information from these interviews was integrated with organizational data from the 2006 National Survey of Substance Abuse Treatment Services. A multivariate logistic regression model was estimated to identify the effects of state efforts to promote the use of this medication, net of a host of organizational characteristics. Results The availability of Medicaid coverage for buprenorphine was a significant predictor of its adoption by treatment organizations. Conclusion Inclusion of buprenorphine on state Medicaid formularies appears to be a key element in ensuring that patients have access to this state-of-the-art treatment option. Other potential barriers to the diffusion of buprenorphine require identification, and the value of additional state-level policies to promote its use should be evaluated.

  6. Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

    Science.gov (United States)

    Holbrook, Amber M

    2015-01-01

    The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States.

  7. Buprenorphine pharmacotherapy and behavioral treatment: comparison of outcomes among prescription opioid users, heroin users and combination users.

    Science.gov (United States)

    Nielsen, Suzanne; Hillhouse, Maureen; Mooney, Larissa; Ang, Alfonso; Ling, Walter

    2015-01-01

    Most research examining buprenorphine has been conducted with heroin users. Few studies have examined buprenorphine pharmacotherapy for prescription opioid users. Data were from a randomized controlled trial of behavioral treatment provided for 16weeks on a platform of buprenorphine pharmacotherapy and medication management. We compared heroin (H, n=54), prescription opioid (PO, n=54) and combination heroin+prescription opioid (POH, n=71) users to test the hypothesis that PO users will have better treatment outcomes compared with heroin users. The PO group provided more opioid-negative urine drug screens over the combined treatment period (PO:70%, POH:40%, H:38%, pbuprenorphine dose between the groups. PO users appear to have better outcomes in buprenorphine pharmacotherapy compared to those reporting any heroin use, confirming that buprenorphine pharmacotherapy is effective in PO users.

  8. Expanding treatment capacity for opioid dependence with office-based treatment with buprenorphine: National surveys of physicians.

    Science.gov (United States)

    Arfken, Cynthia L; Johanson, Chris-Ellyn; di Menza, Salvatore; Schuster, Charles Roberts

    2010-09-01

    Office-based treatment of opioid dependence with buprenorphine has the potential to expand treatment capacity in the United States. However, nationally, little is known about the number, characteristics, and experiences of physicians certified to prescribe buprenorphine. Moreover, little is known about the impact of easing federal regulations on the number of patients a physician is allowed to treat concurrently. To address these questions, surveys of national samples of physicians certified to prescribe buprenorphine (2004-2008) were analyzed (N = 6,892). There has been a continual increase in the number of physicians certified to prescribe buprenorphine, increase in the mean number of patients treated by physicians, and decrease in patients turned away, coinciding temporally with easing of federal regulations. In addition, most physicians prescribed buprenorphine outside of traditional treatment settings. The U.S. experiment in expanding Schedule III-V medications for opioid dependence to physicians outside of formal substance abuse treatment facilities appears to have resulted in expanded capacity.

  9. Use of an Acetyl Derivative to Improve GC-MS Determination of Norbuprenorphine in the Presence of High Concentrations of Buprenorphine in Urine.

    Science.gov (United States)

    Gervais, Joel R; Hobbs, Gregory A

    2016-04-01

    Certain patients being treated with Suboxone™ or Subutex™ can exhibit very high buprenorphine and low norbuprenorphine concentrations in urine. Very high buprenorphine can interfere with buprenorphine-D4 used as an internal standard, causing errors in norbuprenorphine determination by gas chromatography-mass spectrometry (GC-MS). We used a modified method of Wu et al. to introduce norbuprenorphine-D3 as a separate internal standard for norbuprenorphine. This allowed us to accurately measure norbuprenorphine in neat urine specimens when buprenorphine is present in extremely high concentrations. Laboratories measuring buprenorphine and metabolite by GC-MS may face this problem if their clientele includes patients being treated with other medications that interfere with the cytochrome p450 CYP 3A4-mediated conversion of buprenorphine to norbuprenorphine.

  10. Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats.

    Science.gov (United States)

    Hestehave, Sara; Munro, Gordon; Pedersen, Tina Brønnum; Abelson, Klas S P

    2016-09-27

    Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in laboratory rats and mice. In addition, it is desirable to provide post-operative analgesia using methods that are minimally invasive and stressful. This study investigated the antinociceptive effects of orally administered buprenorphine ingested in Nutella® in comparison with subcutaneous buprenorphine administration. By exposing the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella® were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration (P Nutella® in a 10-fold higher dose, as well as approximately 60 min earlier, than with the more commonly employed subcutaneous route of administration.

  11. Pharmacokinetic Profiles of Meloxicam and Sustained-release Buprenorphine in Prairie Dogs (Cynomys ludovicianus).

    Science.gov (United States)

    Cary, Cynthia D; Lukovsky-Akhsanov, Nicole L; Gallardo-Romero, Nadia F; Tansey, Cassandram M; Ostergaard, Sharon D; Taylor, Willie D; Morgan, Clint N; Powell, Nathaniel; Lathrop, George W; Hutson, Christina L

    2017-03-01

    In this study, we evaluated the pharmacokinetic profiles of meloxicam and sustained-release (SR) buprenorphine in prairie dogs. The 4 treatment groups were: low-dose meloxicam (0.2 mg/kg SC), high-dose meloxicam (4 mg/kg SC), low-dose buprenorphine SR (0.9 mg/kg SC), and high-dose buprenorphine SR (1.2 mg/kg SC). The highest plasma concentrations occurred within 4 h of administration for both meloxicam treatment groups. The therapeutic range of meloxicam in prairie dogs is currently unknown. However, as compared with the therapeutic range documented in other species (0.39 - 0.91 μg/mL), the mean plasma concentration of meloxicam fell below the minimal therapeutic range prior to 24 h in the low-dose group but remained above therapeutic levels for more than 72 h in the high-dose group. These findings suggest that the current meloxicam dosing guidelines may be subtherapeutic for prairie dogs. The highest mean plasma concentration for buprenorphine SR occurred at the 24-h time point (0.0098 μg/mL) in the low-dose group and at the 8-h time point (0.015 μg/mL) for the high-dose group. Both dosages of buprenorphine SR maintained likely plasma therapeutic levels (0.001 μg/mL, based on previous rodent studies) beyond 72 h. Given the small scale of the study and sample size, statistical analysis was not performed. The only adverse reactions in this study were mild erythematous reactions at injection sites for buprenorphine SR.

  12. Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

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    L. DeTolla

    2014-01-01

    Full Text Available Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine.

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

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    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

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

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    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

  15. Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery.

    Science.gov (United States)

    Amani, A; Joseph, T; Balasaraswathi, K

    1997-10-01

    The pharmacokinetic parameters of buprenorphine (BN) after a single bolus dose of 10 microg/kg i.v. was investigated in 6 male patients whose age averaged 59+/-9.8 years and body weight of 65.8+/-5.7 kg undergoing coronary artery bypass graft surgery (CABG). The unbound BN plasma concentrations were detected using ultrafiltration and high performance liquid chromatography/electro-chemical detection (HPLC/ECD) method. During cardiopulmonary bypass (CPB) there was a fall in BN plasma concentrations, observations similar to reports on fentanyl, sufentanil and alfentanil. This is probably due to haemodilution, hypothermia and hydrophobic sequestration of drug on to the CPB tubing. After CPB the concentrations rose to values higher than during CPB, though it did not attain pre CPB concentrations. These variations were not statistically significant indicating that plasma levels were adequately stable during CPB. The plasma concentration time curves were biexponential and the pharmacokinetic parameters obtained were : distribution half-life 37.24+/-6.57 min, elimination half-life 482.69+/-79 min, clearance 1221.97+/-209.42 ml/min, and volume of distribution 736.46+/-71.25 L. BN in the dose used follows the pharmacokinetic pattern of other commonly used narcotics during CABG. The mean +/- SEM plasma BN concentration during CPB was 0.51+/-0.03 ng/ml which was adequate for the maintenance of analgesia and anaesthesia, as none of our patients expressed the signs and symptoms of awareness during surgery. Further, unlike the other narcotics muscle rigidity was absent. Thus BN is a safe and good alternative to other narcotics for patients undergoing CABG.

  16. 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...

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

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    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

  18. Synthesis of high-specific activity [15,16-{sup 3}H{sub 2}]buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Oetvoes, F.; Toth, G. [Hungarian Academy of Sciences, Szeged (Hungary). Isotope Lab.; Hosztafi, S.; Simon, C. [Alkaloida Chemical Factory Ltd., Tiszavasvari (Hungary)

    1995-01-01

    Tritium labelling of buprenorphine, a mixed agonist-antagonist opioid ligand, was performed with a specific activity of 2.35 TBq/mmol (63.6 Ci/mmol) starting with 15,16-didehydrobuprenorphine. Labels at positions 15 and 16 of the morphine skeleton proved to be sufficiently stable under strong acidic or basic conditions. (Author).

  19. Developing and Implementing a New Prison-Based Buprenorphine Treatment Program

    Science.gov (United States)

    Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

    2010-01-01

    Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of…

  20. Pharmacokinetic-pharmacodynamic relationships of cognitive and psychomotor effects of intravenous buprenorphine infusion in human volunteers.

    Science.gov (United States)

    Jensen, Mette L; Sjøgren, Per; Upton, Richard N; Foster, David J R; Bonde, Peter; Graae, Christian; Skram, Ulrik; Stevner, Lene; Christrup, Lona L

    2008-07-01

    The main objective of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of the effects of buprenorphine on cognitive functioning in healthy volunteers. Twenty-three male volunteers received 0.6 mg buprenorphine as an intravenous infusion over 150 min. The cognitive and psychomotor performance was evaluated before and at various times after drug administration by a test battery consisting of trail-making test for visual information processing, finger-tapping test for psychomotor speed, and continuous reaction time for attention. Non-linear mixed effect modelling was used in the analysis of the PK/PD relationships. Buprenorphine caused significant deficits in cognitive and psychomotor functioning. The time course of cognitive and psychomotor impairment was found to have a slow distribution to the biophase from plasma with PK/PD models involving an effect compartment providing the best descriptions of the time course of the data. The values for half-life of biophase equilibration were consistent between the neuropsychological tests in the range of 66.6-84.9 min. The time to onset and duration of the cognitive and psychomotor impairment of buprenorphine was determined by a slow distribution to the biophase.

  1. Effects of regulation on methadone and buprenorphine provision in the wake of Hurricane Sandy.

    Science.gov (United States)

    McClure, Bridget; Mendoza, Sonia; Duncan, Laura; Rotrosen, John; Hansen, Helena

    2014-10-01

    Hurricane Sandy led to the closing of many major New York City public hospitals including their substance abuse clinics and methadone programs, and the displacement or relocation of thousands of opioid-dependent patients from treatment. The disaster provided a natural experiment that revealed the relative strengths and weaknesses of methadone treatment in comparison to physician office-based buprenorphine treatment for opioid dependence, two modalities of opioid maintenance with markedly different regulatory requirements and institutional procedures. To assess these two modalities of treatment under emergency conditions, semi-structured interviews about barriers to and facilitators of continuity of care for methadone and buprenorphine patients were conducted with 50 providers of opioid maintenance treatment. Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing. Buprenorphine treatment presented fewer regulatory barriers, but buprenorphine providers had little to no cross-coverage options compared to methadone providers, who could refer to alternate methadone programs. The findings point to the need for well-defined emergency procedures with flexibility around regulations, the need for a central registry with patient dose information, as well as stronger professional networks and cross-coverage procedures. These interventions would improve day-to-day services for opioid-maintained patients as well as services under emergency conditions.

  2. 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.

  3. 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

    2014-07-01

    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.

  4. Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold.

    Science.gov (United States)

    Hedges, A R; Pypendop, B H; Shilo-Benjamini, Y; Stanley, S D; Ilkiw, J E

    2014-06-01

    This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal).

  5. Pharmacokinetics and Paw Withdrawal Pressure in Female Guinea Pigs (Cavia porcellus) Treated with Sustained-Release Buprenorphine and Buprenorphine Hydrochloride.

    Science.gov (United States)

    Smith, Brian J; Wegenast, Daniel J; Hansen, Ryan J; Hess, Ann M; Kendall, Lon V

    2016-11-01

    Providing appropriate analgesia is essential in minimizing pain and maintaining optimal animal care and welfare in laboratory animals. Guinea pigs are common animal models in biomedical research, often requiring analgesic support. Here we evaluated the pharmacokinetics and efficacy of a sustained-release formulation of buprenorphine (Bup-SR) in this species. Guinea pigs (n = 7 each group) received either Bup-HCl (0.05 mg/kg BID for 3 d) or Bup-SR (0.3 mg/kg once). Plasma collection and measurement of paw-withdrawal pressure (PWP) was conducted at 0, 1, 3, 6, 12, 26, 48, and 72 h after treatment. Plasma levels of Bup-HCl peaked at 2331 pg/mL at 1 h after administration and declined to 165 pg/mL by 12 h. Plasma concentrations of Bup-SR peaked at 1344 pg/mL at 26 h after administration and declined to 429 pg/mL by 48 h. The PWP of the Bup-HCltreated guinea pigs peaked at 674 g at 1 h and declined to 402 g at 6 h, whereas that of Bup-SRtreated guinea pigs at 1 h was 361 g, 555 g at 6 h (significantly higher than that after Bup-HCl), and peaked at 680 g at 12 h. The PWP of both treatments was similar from 24 to 72 h and ranged from 348 to 450 g. The plasma concentration and PWP showed good correlation. These results suggest that Bup-SR provides consistent analgesia equivalent to that of Bup-HCl for a prolonged period of time and that Bup-SR is an alternative method of analgesia in guinea pigs.

  6. An unusual case of death probably triggered by the association of buprenorphine at therapeutic dose with ethanol and benzodiazepines and with very low norbuprenorphine level.

    Science.gov (United States)

    Bardy, Guillaume; Cathala, Philippe; Eiden, Céline; Baccino, Eric; Petit, Pierre; Mathieu, Olivier

    2015-01-01

    Buprenorphine is largely prescribed for maintenance treatment in opioid dependence due to its safety profile. Nevertheless, fatalities at therapeutic dose have been described when associated with other central nervous system depressants, such as ethanol or benzodiazepines. Here, we report a case of death due to association of buprenorphine at therapeutic dose with benzodiazepines and ethanol. Although toxicity has been often attributed to its metabolite norbuprenorphine rather than to buprenorphine itself, in our case, norbuprenorphine was not detected in urine and bile and only in traces in blood. Moreover, the presence in blood of free buprenorphine but not of glucuronide metabolites argues for an unusual early death, at the beginning of buprenorphine metabolism. We propose that in the context of prior toxic impregnation, buprenorphine directly (and not via its metabolite norbuprenorphine) acted as a triggering factor by blocking the ventilatory response, rapidly leading to fatal respiratory depression.

  7. Effect of buprenorphine on genotoxicity evaluation of chemicals by the rat liver micronucleus test with partial hepatectomy.

    Science.gov (United States)

    Itoh, Satoru; Nagata, Mayumi; Hattori, Chiharu; Takasaki, Wataru

    2015-02-01

    In the view of animal welfare considerations, we investigated the suitability of modifying the rat liver micronucleus test with partial hepatectomy to include administration of an analgesic drug to minimize pain and distress as much as possible. The effects of the analgesic, buprenorphine, on the genotoxicity evaluation of structural chromosome aberration inducers (cyclophosphamide, diethylnitrosamine and 1,2-dimethylhydrazine) and numerical chromosome aberration inducers (colchicine and carbendazim) were examined. The genotoxicants were given orally to 8-week-old male F344 rats a day before or after partial hepatectomy and hepatocytes were isolated 4 days after the partial hepatectomy. Buprenorphine was injected subcutaneously twice a day with at least a 6-hr interval for 2 days from just after partial hepatectomy. As results, buprenorphine caused neither change in clinical signs (except for one animal death) nor increase in the incidence of micronucleated hepatocytes of vehicle treated animals. In the case of concomitant treatment of buprenorphine and a genotoxicant, one out of 8 animals died in each group given buprenorphine with cyclophosphamide, carbendazim or colchicine (lower dose level only). Slight changes in clinical signs were noted in the group given buprenorphine with cyclophosphamide or carbendazim. A statistically significant increase in the incidence of micronucleated hepatocytes was obtained in concomitant treatment of buprenorphine and genotoxicant compared with genotoxicant alone for 1,2-dimethylhydrazine, colchicine and carbendazim. It is concluded that use of buprenorphine as an analgesic drug to minimize pain and distress for rats that are given partial hepatectomy is not appropriate under the present experimental conditions, because it could enhance the general toxicity and genotoxicity of the test chemical.

  8. 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

    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...... 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....

  9. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method

    Science.gov (United States)

    Hämmig, Robert; Kemter, Antje; Strasser, Johannes; von Bardeleben, Ulrich; Gugger, Barbara; Walter, Marc; Dürsteler, Kenneth M; Vogel, Marc

    2016-01-01

    Background Buprenorphine is a partial µ-opioid receptor agonist used for maintenance treatment of opioid dependence. Because of the partial agonism and high receptor affinity, it may precipitate withdrawal symptoms during induction in persons on full µ-opioid receptor agonists. Therefore, current guidelines and drug labels recommend leaving a sufficient time period since the last full agonist use, waiting for clear and objective withdrawal symptoms, and reducing pre-existing full agonist therapies before administering buprenorphine. However, even with these precautions, for many patients the induction of buprenorphine is a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the full agonist bears the risk of relapse to illicit opioid use. Cases We present two cases of successful initiation of buprenorphine treatment with the Bernese method, ie, gradual induction overlapping with full agonist use. The first patient began buprenorphine with overlapping street heroin use after repeatedly experiencing relapse, withdrawal, and trauma reactivation symptoms during conventional induction. The second patient was maintained on high doses of diacetylmorphine (ie, pharmaceutical heroin) and methadone during induction. Both patients tolerated the induction procedure well and reported only mild withdrawal symptoms. Discussion Overlapping induction of buprenorphine maintenance treatment with full µ-opioid receptor agonist use is feasible and may be associated with better tolerability and acceptability in some patients compared to the conventional method of induction. PMID:27499655

  10. French general practitioners' prescribing high-dosage buprenorphine maintenance treatment: is the existing training (good) enough?

    Science.gov (United States)

    Feroni, Isabelle; Peretti-Watel, Patrick; Masut, Alain; Coudert, Christine; Paraponaris, Alain; Obadia, Yolande

    2005-01-01

    In France, since 1996, any general practitioner (GP) can prescribe high-dosage buprenorphine maintenance treatment (BMT) for opioid-dependent patients. The health authorities initially provided mandatory specific training, but since 1998, such training is only delivered by specialized networks and the pharmaceutical industry. Among a random sample of GPs from southeastern France (N=345), we found that many untrained GPs, as well as a significant minority of trained GPs, were likely to prescribe an ineffective dosage of buprenorphine or a potentially dangerous treatment (BMT+a short half-life benzodiazepine). These results highlight the necessity to edit clear guidelines, especially concerning situations of polyaddiction and psychiatric comorbidity, and to extend and improve BMT training in France with a renewed involvement of health authorities for quality control of such training. They even suggest that GPs' participation to specialized training sessions should become a mandatory prerequisite for prescribing BMT.

  11. 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

  12. Sublingual Buprenorphine and Methadone Maintenance Treatment: A Three-Year Follow-Up of Quality of Life Assessment

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    Salvatore M. Giacomuzzi

    2005-01-01

    Full Text Available This study was conducted to compare long-term outcome effects on the quality of life (QOL of oral methadone with sublingual buprenorphine maintenance treatment. The QOL status of opioid-dependent patients was assessed using the German version (“Berlin Quality of Life Profile” of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opiate Withdrawal Scale (OWS. Urine tests were carried out randomly to detect additional consumption. In the first study period, 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years. The retention rate was 50% for methadone and 45% for buprenorphine (p = 0.786. Baseline values of the total sample (completers and noncompleters QOL and somatic complaints did not show significant differences between the two treatment groups. QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job (p = 0.013, family, and total score of physical symptoms (p = 0.002, in which the completer group showed the more favorable values. Concerning physical symptoms at 36 months, logistic regression revealed significantly less stomach cramps (p = 0.037 and fatigue and tiredness (p = 0.034 in buprenorphine compared to the methadone. Moreover, the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines (p = 0.015 compared with methadone participants. It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine. In summary, regarding QOL and health status, the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients.

  13. Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation.

    Science.gov (United States)

    Jirkof, P; Tourvieille, A; Cinelli, P; Arras, M

    2015-07-01

    Sustained-release formulations of analgesic drugs are promising alternatives to repeated drug injections. Here, we compared a sustained-release formulation of buprenorphine (SB, 2.2 mg/kg) with a standard protocol of three injections of buprenorphine (Temgesic, 0.1 mg/kg/8 h) in mice. Buprenorphine serum concentration and analgesic action (thermal sensitivity) were determined in healthy mice. Additionally, the pain relief properties of both protocols were assessed after laparotomy using physiological and ethological measures of pain and recovery. Serum concentrations and thermal sensitivity tests indicated duration of action of at least 4 h (but less than 8 h) with the Temgesic protocol, and 24-48 h with SB. Behavioural and clinical parameters indicated at least partial pain relief after surgery for both protocols. Observed side-effects of buprenorphine independent of the protocol were increased activity, disturbed circadian rhythm and several abnormal behaviours. A tendency for decreased food and water intake as well as body weight reduction was also seen. Body weight decreased significantly in animals that received three injections of Temgesic, regardless of whether surgery was performed or not (P = 0.015; P = 0.023), hinting at a stress response towards this repeated intervention. In conclusion, an application interval of 8 h (Temgesic) appears too long and might lead to repeated periods with insufficient analgesia in animals undergoing lasting and/or substantial pain after surgery. In comparison to the standard protocol, SB provided a long-lasting, assured analgesia without possible stressful repeated injections in a standard surgical model, with only limited and acceptable behavioural side-effects.

  14. 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.

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

    OpenAIRE

    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...

  16. COMPARISON OF ANALGESIC EFFECT OF INTRA-ARTICULAR BUPRENORPHINE AND MORPHINE FOLLOWING ARTHROSCOPIC SURGERY OF KNEE

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    Shashidhar Gowdra Sugandarajappa

    2016-07-01

    Full Text Available BACKGROUND AND AIMS Pain after orthopaedic surgery depends on the site and extent of surgery and the preoperative use of analgesics by the patient. Arthroscopic procedures are routinely performed on outpatient basis and have spared patients large incisions and decreased morbidity compared with open incisions, but has not eliminated pain. At present several techniques are available to treat pain following arthroscopic surgeries; these include the use of opioids, local anaesthetics, NSAIDs, corticosteroids, clonidine and cryotherapy. Here, we compared the analgesic effect of intra-articular administration of morphine, buprenorphine and placebo following arthroscopic surgery of knee. METHODS A prospective, randomised, placebo-controlled double-blind comparative study conducted in 60 patients of either sex who underwent arthroscopic surgery of knee; between the age group of 18 and 65 years and of ASA class I and II physical status were included in the study. Patients were randomly assigned equally to one of the 3 groups of 20 each by a sealed envelope method. The groups were Group A - Patients receiving IA Buprenorphine 100 mcg in 20 mL normal saline. Group B - Patients receiving IA Morphine 3 mg in 20 mL normal saline. Group C - Patients receiving IA 20 mL normal saline as placebo. Parameters monitored were degree of analgesia along with haemodynamic parameters and side effects. Data were analysed using student’s t-test for continuous variables and Chi-Square test. RESULTS We found that 100 mcg buprenorphine when injected intra-articularly produced good and comparable postoperative pain control and reduced supplementary analgesic requirement when compared to other groups. CONCLUSION In summary, this study demonstrated that for eight hours postoperatively 100 mcg buprenorphine provided superior postoperative analgesia to that of 3 mg morphine

  17. Effects of buprenorphine, meloxicam, and flunixin meglumine as postoperative analgesia in mice.

    Science.gov (United States)

    Tubbs, Jacquelyn T; Kissling, Grace E; Travlos, Greg S; Goulding, David R; Clark, James A; King-Herbert, Angela P; Blankenship-Paris, Terry L

    2011-03-01

    C57BL/6NCrl male mice (n = 60; age, 6 to 7 wk) underwent partial hepatectomy or no surgery and were given 1 of 3 analgesics pre- and postoperatively. Food and water consumption, body weight, running wheel activity, locomotor activity, and serum corticosterone concentrations were measured before and after surgery. Mice that were surgically manipulated weighed significantly less on days 1 through 3 after surgery than did mice not manipulated surgically. On the day of surgery, the surgery groups consumed significantly less feed (-1.5±0.35 g) than did nonsurgery groups. There were no differences in water consumption on any day between surgery and nonsurgery groups or among the 3 analgesic groups. For running wheel activity, significant decreases in the surgery groups were seen at day 1 after surgery compared with baseline. Surgery groups that received buprenorphine and meloxicam returned to baseline activity levels on day 2 after surgery. Open-field testing revealed no significant differences in locomotor activity in any groups; however, posttreatment locomotor activity in the buprenorphine nonsurgery group was increased compared with baseline, and posttreatment locomotor activity in the flunixin meglumine surgery group was decreased compared with baseline. Serum corticosterone concentrations were within normal limits regardless of treatment in all groups. Comparison of the overall results indicated that meloxicam and buprenorphine, at the dose given, appear to be suitable postoperative analgesics for partial hepatectomy in mice. Flunixin meglumine at the given dosage (2.5 mg/kg) may not provide adequate analgesia for partial hepatectomy.

  18. Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS.

    Science.gov (United States)

    Berg, Thomas; Jørgenrud, Benedicte; Strand, Dag Helge

    2013-04-01

    A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed and validated for the quantification of buprenorphine, fentanyl and lysergic acid diethylamide (LSD) in whole blood. Sample preparation was performed by liquid-liquid extraction (LLE) with methyl tert-butyl ether. UPLC-MS-MS analysis was performed with a mobile phase consisting of ammonium formate (pH 10.2) and methanol. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each of the analytes and the deuterium labeled internal standards. Limit of detection values of buprenorphine, fentanyl and LSD were 0.28, 0.044 and 0.0097 ng/mL and limit of quantification values were 0.94, 0.14 and 0.036 ng/mL, respectively. Most phospholipids were removed during LLE. No or only minor matrix effects were observed. The method has been routinely used at the Norwegian Institute of Public Health since September 2011 for qualitative and quantitative detections of buprenorphine, fentanyl and/or LSD in more than 400 whole blood samples with two replicates per sample.

  19. Tobacco Addiction and Smoking Status in Heroin Addicts under Methadone vs. Buprenorphine Therapy

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    Rebecca Casari

    2012-03-01

    Full Text Available Aims of the present investigation were: (i to assess the prevalence of current smokers and relative smoking status among a large number of heroin addicts attending opioid-substitution therapy prevalence; (ii to evaluate the relationship between the type (methadone, buprenorphine and dosage of opioid substitution therapy and nicotine dependence. Three hundred and five (305 heroin addicts under opioid-substitution therapy were recruited at five Addiction Units. All participants completed a questionnaire assessing sociodemographic information, type and dose of opioid-substitution therapy, smoking history and status, Fagerström Test for Nicotine Dependence (FTND, and the Zung Self-Rating Depression scale (SDS. 298 subjects, out of 305 (97.2% were smokers, with an average of 20.5 cigarette/day and a median FTND of 6. Our data confirmed the high prevalence of smokers among heroin addicts, the highest described in the literature to date among heroin addicts under substitution therapies, without any significant difference between methadone vs. buprenorphine therapy groups. There was no correlation between dose of methadone or buprenorphine and average number of cigarettes/day. Patients in substance abuse treatment very frequently smoke cigarettes and often die of tobacco-related diseases. Substance abuse treatment programs too often ignore tobacco use. We hope that these findings will help to incorporate smoking cessation in substance abuse treatments.

  20. Characteristics of U.S. substance abuse treatment facilities adopting buprenorphine in its initial stage of availability.

    Science.gov (United States)

    Koch, Alison L; Arfken, Cynthia L; Schuster, Charles R

    2006-07-27

    This study examined the adoption of buprenorphine for the treatment of opiate dependence among U.S. substance abuse treatment facilities and their characteristics at the time of the initial availability of the medication. Data come from a 2003 national survey of all substance abuse treatment facilities in the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they offered buprenorphine. Not unexpectedly, the prevalence was higher in certified opioid treatment programs (11.3%) compared to other facilities (4.6%). For opioid treatment programs, offering Naltrexone (OR=8.34, 95% CI=5.53, 12.58) and offering medically supervised withdrawal (OR=2.76, 95% CI=1.38, 5.52) were independent and robust predictors of offering buprenorphine. These same variables were independent predictors for the non-opioid treatment programs as well (Naltrexone, OR=14.32, 95% CI=7.85, 26.10; and medically supervised withdrawal services, OR=4.42, 95% CI=3.01, 6.49). Our results suggest that the adoption of buprenorphine soon after the Food and Drug Administration approved its use for treatment of opioid dependence and the shipping of the medication commenced was associated with facilities already offering pharmacotherapies such as Naltrexone and medically assisted withdrawal. These findings provide baseline data to track the adoption of buprenorphine by substance abuse treatment programs in future years.

  1. 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.

  2. Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the “Bernese method”

    Directory of Open Access Journals (Sweden)

    Hämmig R

    2016-07-01

    Full Text Available Robert Hämmig,1 Antje Kemter,2 Johannes Strasser,2 Ulrich von Bardeleben,1 Barbara Gugger,1 Marc Walter,2 Kenneth M Dürsteler,2 Marc Vogel2 1Division of Addiction, University Psychiatric Services Bern, Bern, Switzerland; 2Division of Substance Use and Addictive Disorders, University of Basel Psychiatric Hospital, Basel, Switzerland Background: Buprenorphine is a partial µ-opioid receptor agonist used for maintenance treatment of opioid dependence. Because of the partial agonism and high receptor affinity, it may precipitate withdrawal symptoms during induction in persons on full µ-opioid receptor agonists. Therefore, current guidelines and drug labels recommend leaving a sufficient time period since the last full agonist use, waiting for clear and objective withdrawal symptoms, and reducing pre-existing full agonist therapies before administering buprenorphine. However, even with these precautions, for many patients the induction of buprenorphine is a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the full agonist bears the risk of relapse to illicit opioid use.Cases: We present two cases of successful initiation of buprenorphine treatment with the ­Bernese method, ie, gradual induction overlapping with full agonist use. The first patient began buprenorphine with overlapping street heroin use after repeatedly experiencing relapse, withdrawal, and trauma reactivation symptoms during conventional induction. The second patient was maintained on high doses of diacetylmorphine (ie, pharmaceutical heroin and methadone during induction. Both patients tolerated the induction procedure well and reported only mild withdrawal symptoms.Discussion: Overlapping induction of buprenorphine maintenance treatment with full µ-opioid receptor agonist use is feasible and may be associated with better tolerability and acceptability in some patients compared to the conventional method of induction. Keywords: subutex, suboxone, heroin

  3. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    Science.gov (United States)

    Wurst, Keele E.; Zedler, Barbara K.; Joyce, Andrew R.; Sasinowski, Maciek; Murrelle, E. Lenn

    2016-01-01

    BACKGROUND Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. OBJECTIVE The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. METHODS Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher’s exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. RESULTS A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby’s father. CONCLUSIONS An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment

  4. Pharmacokinetics of high-dose buprenorphine following single administration of sublingual tablet formulations in opioid naïve healthy male volunteers under a naltrexone block.

    Science.gov (United States)

    McAleer, Sarah D; Mills, Richard J; Polack, Torsten; Hussain, Tanweer; Rolan, Paul E; Gibbs, Alan D; Mullins, Frank G P; Hussein, Ziad

    2003-10-24

    Sublingual buprenorphine formulations have been developed as treatments for opioid dependence. In three studies, opioid naïve healthy male subjects received Subutex tablets (buprenorphine 2 and 8 mg [N=27] or 12 and 16 mg [N=27]) or Suboxone (two formulations) tablets (buprenorphine 8 mg/naloxone 2 mg [N=36]) sublingually, under a naltrexone block for assessment of buprenorphine pharmacokinetics and tablet disintegration times. Plasma buprenorphine was quantified up to 72 h post-dose using a sensitive LC-MS/MS assay. Mean Cmax values ranged from 1.6 to 6.4 ng/ml and tmax from 0.5 to 3 h. Concentrations declined bi-exponentially and fluctuations after a meal suggested enterohepatic recirculation of buprenorphine. The terminal half-life was approximately 26 h (range 9-69). Cmax and AUC appeared to increase in proportion to Subutex dose over 8-16 mg. The Suboxone formulations were bioequivalent. The least squares mean (90% CI) treatment ratio for Cmax was 1.00 (0.92-1.10) and AUC was 1.00 (0.95-1.06). Median times of disintegration were similar for all doses and formulations (range 6-12 min). Sublingual buprenorphine, up to 40 times the 400 microg analgesic dose, was well tolerated in these opioid naïve subjects, as administration of naltrexone 50-150 mg was sufficient to attenuate anticipated adverse effects in this population of subjects.

  5. Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment.

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    Anne Yee

    Full Text Available Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT and methadone maintenance treatment (MMT. The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients.Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15, and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders.The study population consisted of 171 patients (71.8% on MMT and 67 (28.2% on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012 and overall satisfaction (p = 0.043 domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008 compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026 and overall satisfaction (p = 0.039 were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables.Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus, clinicians may consider the former when

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

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    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.

  7. COMPARISON OF DEXMEDETOMIDINE, BUPRENORPHINE AND FENTANYL AS AN ADJUVANT TO BUPIVACAINE DURING SPINAL ANAESTHESIA FOR HEMIARTHROPLASTY

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    Pradeep R

    2016-10-01

    Full Text Available BACKGROUND Opioids such as fentanyl or buprenorphine are being added as adjuvant to local anaesthetic for spinal anaesthesia. Dexmedetomidine, a new α2 agonist is being tried as an adjuvant in the recent times. MATERIALS AND METHODS The patients were randomised into three Groups (n=30 each by closed envelope technique. Patients in Group 1 received 10 µg fentanyl with 15 mg of 0.5% hyperbaric bupivacaine, Group 2 received 15 mg of 0.5% hyperbaric bupivacaine supplemented with 30 µg of buprenorphine and Group 3 received 15 mg of 0.5% hyperbaric bupivacaine plus 5 µg dexmedetomidine intrathecally. The time to reach maximum sensory and motor level, the regression time of the same, any adverse effects were recorded. Data were analysed using chi-square test or Fisher’s exact test for categorical data and analysis of variance for continuous data. A value of P<0.05 was accepted as statistically significant. Settings and Design- The study was conducted in a prospective, randomised and double-blind manner. It included ninety American Society of Anaesthesiologists class I and II patients undergoing hemiarthroplasty under spinal anaesthesia. RESULTS In this study, the patients in dexmedetomidine group showed significantly longer duration of motor block (240±20 mins. and sensory blockade (180±22.2 mins. compared to other groups, which is statistically significant (P=0.0001 and P=0.006, respectively. The time to first request of analgesic postoperatively was also longer (260±30.2 in dexmedetomidine group when compared with other groups (P=0.0001. Haemodynamic parameters were stable and there were no complications in any group. CONCLUSIONS We concluded that intrathecal dexmedetomidine (5 µg with bupivacaine provides significantly longer duration of sensory and motor blockade and longer duration for first request of analgesia in the recovery than intrathecal buprenorphine (30 µg or fentanyl (10 µg with bupivacaine for spinal anaesthesia for

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

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    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.

  9. Simultaneous Quantification of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide and Norbuprenorphine-Glucuronide in Human Umbilical Cord by Liquid Chromatography Tandem Mass Spectrometry

    Science.gov (United States)

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

    2009-01-01

    A LCMS method was developed and validated for the simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc) and norbuprenorphine glucuronide (NBUP-Gluc) in human umbilical cord. Quantification was achieved by selected ion monitoring of precursor ions m/z 468.4 for BUP; 414.3 for NBUP; 644.4 for BUP-Gluc and 590 for NBUP-Gluc. BUP and NBUP were identified by MS2, with m/z 396, 414 and 426 for BUP, and m/z 340, 364 and 382 for NBUP. Glucuronide conjugates were identified by MS3 with m/z 396 and 414 for BUP-Gluc and m/z 340 and 382 for NBUP-Gluc. The assay was linear 1–50 ng/g. Intra, inter-day and total assay imprecision (%RSD) were 66.3%, and process efficiency >73.4%. Matrix effect ranged, in absolute value, from 3.7% to 27.4% (CV<21.8%, n=8). The method was selective with no endogenous or exogenous interferences from 41 compounds evaluated. Sensitivity was high with limits of detection of 0.8 ng/g. In order to prove method applicability, an authentic umbilical cord obtained from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. Interestingly, BUP was not detected but concentrations of the other metabolites were NBUP-Gluc 13.4 ng/g, BUP-Gluc 3.5 ng/g and NBUP 1.2 ng/g. PMID:19406593

  10. 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...... for voluntary ingestion. This method has many advantages over parenteral administration. To use the method in a successful way, however, it is important to prepare and administer the mix correctly. The present paper describes in detail how to implement the method, by means of habituation, presentation, adequate...

  11. Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats

    DEFF Research Database (Denmark)

    Kristensen, Sara Hestehave; Munro, Gordon; Pedersen, Tina Brønnum

    2017-01-01

    Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in laboratory rats and mice...... the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella® were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration (P 

  12. EFFECT OF BUPRENORPHINE ON POST OPERATIVE ANALGESI A IN SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK USING PERIPHE RAL NERVE LOCATOR

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    Ritesh

    2013-01-01

    Full Text Available ABSTRACT : Supraclavicular brachial plexus block is known for its simplicity, effectiveness, safety, reliability and being economical for day ca re and emergency surgery, circumventing problems of full stomach. In our randomized prospective, double blind study, t otal 60 adult ASA class I and II patients undergoing upper limb surgeri es were given supraclavicular brachial plexus block with peripheral nerve locator and studied for effect of addition of buprenorphine on post operative analgesia. 30 Patients received 0.2 5% bupivacaine 40 ml in group Bupivacaine (B and added buprenorphine 3 μgm/kg in th e other group Bupivacaine + Buprenorphine (BB. All the patients were monitored fo r onset of effect, post op analgesia, time of first analgesic drug and number of analgesic dru g require in first 24 hrs. Onset and duration of motor and sensory block were same in both groups. Post operative analgesia was significantly better in BB. Consequently, number of doses of analgesic required in first 24 hours was less in buprenorphine group (BB.

  13. [Modification of the analgetic effects (buprenorphine, pentazocine, pethidine) on respiration and haemodynamics by epidural, halothane- or neuroleptanaesthesia (author's transl)].

    Science.gov (United States)

    Wüst, H J; Moritz, K G; Sandmann, W; Richter, O

    1980-04-01

    In 38 patients buprenorphine, meperidine and pentazocine were given in a single dose for postoperative pain relief 20 hours after the end of anaesthesia. Measuring the parameters of the high- and low-pressure system as well as the metabolism the authors found that the effects of these analgetic medicaments, intravenously injected were significantly influenced by fentanyl, halothane or diazepam, given under the course of operation. Especially buprenorphine, injected after epidural anaesthesia in combination with diazepam sedation, proved to have a rather negative effect, because it caused a strong depression of respiration and circulation. On the other hand buprenorphine had, given after neuroleptanaesthesia, a neutralizing - and pentazocine and pethidine in combination with neuroleptanaesthesia a stimulating influence on the circulation. After halothane-anaesthesia the effect of the analegtics on the cardiovascular system was, when buprenorphine was given, depressing and when pentazocine was given indifferent. Similar reactions, but more pronounced, could be seen in the epidural group. With certain reservations, caused by the preliminary character of this study, the following conclusions can be drawn for the anaesthetic practice: 1 Choosing analgetic drugs for postoperative pain relief, the anaesthesist has to be aware of the interactions, possibly resulting from the medicaments, given during anaesthesia. 2. The number of medicaments, given during anaesthesia, should be kept small, considering the eventual interactions and the unintentional secondary effects.

  14. 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…

  15. 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…

  16. Switching from high doses of pure μ-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...

  17. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

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    Ghasem Soltani

    2015-09-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  18. Psychiatric comorbidity, red flag behaviors, and associated outcomes among office-based buprenorphine patients following Hurricane Sandy.

    Science.gov (United States)

    Williams, Arthur R; Tofighi, Babak; Rotrosen, John; Lee, Joshua D; Grossman, Ellie

    2014-04-01

    In October 2012, Bellevue Hospital Center (Bellevue) in New York City was temporarily closed as a result of Hurricane Sandy, the largest hurricane in US history. Bellevue's primary care office-based buprenorphine program was temporarily closed and later relocated to an affiliate public hospital. Previous research indicates that the relationships between disaster exposure, substance use patterns, psychiatric symptoms, and mental health services utilization is complex, with often conflicting findings regarding post-event outcomes (on the individual and community level) and antecedent risk factors. In general, increased use of tobacco, alcohol, and illicit drugs is associated with both greater disaster exposure and the development or exacerbation of other psychiatric symptoms and need for treatment. To date, there is limited published information regarding post-disaster outcomes among patients enrolled in office-based buprenorphine treatment, as the treatment modality has only been relatively approved recently. Patients enrolled in the buprenorphine program at the time of the storm were surveyed for self-reported buprenorphine adherence and illicit substance and alcohol use, as well as disaster-related personal consequences and psychiatric sequelae post-storm. Baseline demographic characteristics and insurance status were available from the medical record. Analysis was descriptive (counts and proportions) and qualitative, coding open-ended responses for emergent themes. There were 132 patients enrolled in the program at the time of the storm; of those, 91 were contacted and 89 completed the survey. Almost half of respondents reported disruption of their buprenorphine supply. Unexpectedly, patients with psychiatric comorbidity were no more likely to report increased use/relapse as a result. Rather, major risk factors associated with increased use or relapse post-storm were: (1) shorter length of time in treatment, (2) exposure to storm losses such as buprenorphine

  19. Urine analysis of buprenorphine/norbuprenorphine/ naloxone in drugs and driving cases

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    Albert A. Elian

    2015-07-01

    Full Text Available Buprenorphine is now being detected as a drug of abuse in drugs/driving cases alongside side naloxone. Being a semi synthetic opiate, it has the potential to impair motorists in a similar fashion to morphine. Many laboratories have observed that buprenorphine does not produce a positive response with typical opiate immunoassays or routine basic GC-MS drug screens. In this study, samples of urine were enzymatically hydrolyzed after which they were extracted on mixed mode solid phase (SPE columns, after which the extracted samples were analyzed by LC-MS/MS analysis in positive multiple reaction monitoring mode. The LOD/LOQ were determined to be 0.5 and 1.0 ng/mL, respectively for the analytes; linearity (10 to 1000 ng/mL and (r2>0.999. The recovery of the analytes was found to be greater than 90%. Interday/intraday analysis was found to <8% and <10%, respectively. Matrix effects were determined to be <6%.

  20. Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine.

    Science.gov (United States)

    Pilat, Dominika; Piotrowska, Anna; Rojewska, Ewelina; Jurga, Agnieszka; Ślusarczyk, Joanna; Makuch, Wioletta; Basta-Kaim, Agnieszka; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Currently, the low efficacy of antinociceptive drugs for the treatment of neuropathic pain is a major therapeutic problem. Here, we show the potential role of interleukin (IL)-18 signaling in this phenomenon. IL-18 is an important molecule that performs various crucial functions, including the alteration of nociceptive transmission in response to neuropathic pain. We have studied the changes in the mRNA and protein levels (qRT-PCR and Western blot analysis, respectively) of IL-18, IL-18-binding protein (IL-18BP) and the IL-18 receptor (IL-18R) over time in rats following chronic constriction injury (CCI) of the sciatic nerve. Our study demonstrated that the spinal levels of IL-18BP were slightly downregulated at days 7 and 14 in the rats subjected to CCI. In contrast, the IL-18 and IL-18R mRNA expression and protein levels were elevated in the ipsilateral spinal cord on days 2, 7 and 14. Moreover, in rats exposed to a single intrathecal administration of IL-18BP (50 and 100 ng) 7 or 14 days following CCI, symptoms of neuropathic pain were attenuated, and the analgesia pursuant to morphine and buprenorphine (0.5 and 2.5 μg) was enhanced. In summary, the restoration of the analgesic activity of morphine and buprenorphine via the blockade of IL-18 signaling suggests that increased IL-18 pathway may account for the decreased analgesic efficacy of opioids for neuropathic pain.

  1. The barriers to smoking cessation in Swiss methadone and buprenorphine-maintained patients

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    Stohler Rudolf

    2008-03-01

    Full Text Available Abstract Background Smoking rates in methadone-maintained patients are almost three times higher than in the general population and remain elevated and stable. Due to the various negative health effects of smoking, nicotine dependence contributes to the high mortality in this patient group. The purpose of the current study was to investigate Swiss methadone and buprenorphine-maintained patients' willingness to stop smoking and to clarify further smoking cessation procedures. Methods Substance abuse history, nicotine dependence, and readiness to stop smoking were assessed in a sample of 103 opiate-dependent patients in the metropolitan area of Zurich, Switzerland. Patients were asked to document their smoking patterns and readiness to quit. Results Only a small number of patients were willing to quit smoking cigarettes (10.7% and, even though bupropione or nicotine replacement therapy was included in the fixed daily treatment care, only one patient received nicotine replacement therapy for smoking cessation. A diagnosis of depression in patients' clinical records was associated with readiness to stop smoking. No significant associations were found between readiness to quit smoking and age, methadone treatment characteristics, and presence of co-dependencies. Conclusion The current prescription level of best medicine for nicotine dependence in Swiss methadone and buprenorphine-maintained patients is far from adequate. Possible explanations and treatment-relevant implications are discussed.

  2. [Effectiveness and tolerance of tramadol in cancer pain. A comparative study with respect to buprenorphine].

    Science.gov (United States)

    Bono, A V; Cuffari, S

    1997-01-01

    Opioid analgesics represent one of the most important tools in a sequential pharmacological approach to oncological pain relief. They are recommended by the WHO when nonsteroidal anti-inflammatory drugs (NSAIDs) no longer provide adequate analgesia. However, the use of opioids is limited because of their numerous and often severe adverse effects. This aspect of opioids has motivated continuous research projects aimed at discovering drugs that can provide maximum pain relief but with improved tolerability. Tramadol is a new, centrally acting analgesic with a dual mechanism of action. It shows a selective interaction with mu receptors, which are responsible for nociception, and has weak pharmacodynamic activity on other opioid receptors. At the same time, it acts synergistically on neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine) reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT) release. From a pharmacokinetic standpoint, tramadol offers high bioavailability, with similar patterns after oral or parenteral administration (half-life 5 to 7 hours, time to peak plasma concentration 3.1 hours, and approximately 20% plasma protein binding). Although the efficacy of tramadol is comparable to that of other drugs with similar modes of action, the incidence of side effects such as constipation and respiratory depression is lower. The frequency of euphoria and dysphoria is negligible, resulting in little risk of abuse or dependence. It therefore seemed appropriate to further investigate the efficacy and tolerability of tramadol, defined as having only weak potency, in comparison with a widely used opioid, in oncological pain. Buprenorphine was selected as an opioid with a potency equivalent to half that of morphine, but with tolerability that is partially limited by the fact that it frequently gives rise to adverse reactions considered typical of stronger opioids. To compare the analgesic effect and tolerability of tramadol

  3. Effects of multimodal analgesia with LowDose buprenorphine and meloxicam on fecal glucocorticoid metabolites after surgery in New Zealand white rabbits (Oryctolagus cuniculus).

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    Goldschlager, Gregg B; Gillespie, Virginia L; Palme, Rupert; Baxter, Mark G

    2013-09-01

    Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine-meloxicam (0.01 mg/kg-0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine-meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine-meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses.

  4. A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm.

    Science.gov (United States)

    Cordery, Sarah F; Taverner, Alistair; Ridzwan, Irna E; Guy, Richard H; Delgado-Charro, M Begoña; Husbands, Stephen M; Bailey, Christopher P

    2014-07-01

    Concurrent use of cocaine and heroin is a major public health issue with no effective relapse prevention treatment currently available. To this purpose, a combination of buprenorphine and naltrexone, a mixed very-low efficacy mu-opioid receptor agonist/kappa-opioid receptor antagonist/nociceptin receptor agonist, was investigated. The tail-withdrawal and the conditioned place preference (CPP) assays in adult Sprague Dawley rats were used to show that naltrexone dose-dependently blocked the mu-opioid receptor agonism of buprenorphine. Furthermore, in the CPP assay, a combination of 0.3 mg/kg buprenorphine and 3.0 mg/kg naltrexone was aversive. A combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone was neither rewarding nor aversive, but still possessed mu-opioid receptor antagonist properties. In the CPP extinction and reinstatement method, a combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone completely blocked drug-primed reinstatement in cocaine-conditioned rats (conditioned with 3 mg/kg cocaine, drug prime was 3 mg/kg cocaine) and attenuated drug-primed reinstatement in morphine-conditioned rats (conditioned with 5 mg/kg morphine, drug prime was 1.25 mg/kg morphine). These data add to the growing evidence that a buprenorphine/naltrexone combination may be protective against relapse in a polydrug abuse situation.

  5. Patient perspectives on buprenorphine/naloxone: a qualitative study of retention during the starting treatment with agonist replacement therapies (START) study.

    Science.gov (United States)

    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 terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial; (2) negative medication or treatment experience; and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication; (2) personal determination and commitment to complete; and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients' prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential.

  6. 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

  7. 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 administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats...... 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....

  8. Development, Implementation, and Evaluation of a Pilot Parenting Educational Intervention in a Pregnancy Buprenorphine Clinic.

    Science.gov (United States)

    Giles, Averie C; Ren, Dianxu; Founds, Sandra

    2016-01-01

    We developed a pilot evidence-based prenatal educational intervention to increase knowledge of neonatal abstinence syndrome (NAS) and early parenting skills for women with opiate dependency who enrolled in a pregnancy buprenorphine clinic. We developed, implemented, and tested modules regarding expectations during newborn hospitalization for observation or treatment of NAS and regarding evidence-based parenting skills in response to NAS behaviors. Testing evaluated baseline knowledge of early parenting skills with newborns at risk for NAS and change from baseline after the educational intervention. No statistically significant difference in composite knowledge scores was observed. A brief survey completed by the participants postpartum affirmed the perception of women that the educational intervention effectively prepared them for the early postpartum period while their newborns were hospitalized.

  9. Facile synthesis of ( sup 11 C)buprenorphine for positron emission tomographic studies of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lever, J.R.; Dannals, R.F.; Wagner, H.N. Jr. (Johns Hopkins Univ., Baltimore, MD (USA). School of Hygiene and Public Health Johns Hopkins Univ., Baltimore, MD (USA). Dept. of Radiology); Mazza, S.M. (Johns Hopkins Univ., Baltimore, MD (USA). School of Hygiene and Public Health); Ravert, H.T.; Wilson, A.A. (Johns Hopkins Univ., Baltimore, MD (USA). Dept. of Radiology)

    1990-01-01

    We have developed a simple and rapid method for the production of buprenorphine (BPN), a potent opioid partial agonist, labelled with carbon-11 at the 6-methoxy position. The procedure uses a precursor synthesized in high yield (89%) from BPN in two steps and employs ({sup 11}C)iodomethane as the radiolabelling reagent. ({sup 11}C)BPN of 97% radiochemical purity can be prepared in high specific activity (41 GBq/{mu}mol; 1120 mCi/{mu}mol) in a radiochemical yield of 10% at end-of-synthesis (not decay corrected). The ({sup 11}C)BPN is available for use in studies of cerebral opioid receptors by positron emission tomography within 24 min from end-of-bombardment, including radiosynthesis, purification, formulation for i.v. injection and determination of specific activity. (author).

  10. 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

  11. Efficacy of Sustained-Release Buprenorphine in an Experimental Laparotomy Model in Female Mice.

    Science.gov (United States)

    Kendall, Lon V; Wegenast, Daniel J; Smith, Brian J; Dorsey, Kathryn M; Kang, Sooah; Lee, Na Young; Hess, Ann M

    2016-01-01

    Mice purportedly require dosing with the opioid buprenorphine (Bup-HCl) at least every 8 to 12 h to maintain an adequate plane of analgesia. Here we used an experimental laparotomy model to determine the clinical efficacy of sustained-release formulations of buprenorphine (Bup-SR) after surgery in mice. Female CD1 mice underwent laparotomy and received either Bup-SR (0.6 mg/kg), Bup-HCl (0.1 mg/kg every 12 h), or saline (every 12 h). Pain was assessed at 1, 3, 6, 12, 24, 48, and 72 h according to the frequency of several behaviors (general activity, wheel-running activity, rearing, grooming, wound licking, orbital tightening, and percentage of integrated nest material) and daily body weight. Over time, wheel running was increased and wound licking was decreased in Bup-SR-treated mice compared with Bup-HCl- and saline-treated mice. Compared with Bup-HCl- and saline-treated mice, Bup-SR-treated mice had increased general activity and percentage of integrated nest material and decreased orbital tightening for 1 to 6 h after surgery. The Bup-HCl- and saline-treated mice had similar general activity, orbital tightening scores, and wheel running activity. Rearing activity and body weight did not differ throughout the study, and none of the observed behaviors differed between groups at 24, 48, and 72 h after surgery. These results suggest that Bup-SR at 0.6 mg/kg provides adequate analgesia after laparotomy in mice and can be used as an alternative analgesic in this context. Furthermore, Bup-HCl at 0.1 mg/kg every 12 h may be inadequate in providing analgesia for abdominal procedures in mice.

  12. Comparison of Interpleural and Thoracic Epidural Bupivacaine with Buprenorphine for Post-Thoracotomy Analgesia

    Directory of Open Access Journals (Sweden)

    S K Mathur

    2008-01-01

    Full Text Available The study was designed to compare the efficacy of interpleural and thoracic epidural analgesia after thorac-otomy with regard to quality of analgesia and complications. Sixty patients undergoing elective thoracotomy were randomly and equally placed into either interpleural (IP or thoracic epidural (TE group. In IP group an interpleural catheter was placed in paravertebral space under direct vision during surgery and received 0.25% bupivacaine 20 ml with buprenorphine 150 mcg. In TE group an epidural catheter was inserted in the T6-7 / T7-8 interspace and received 0.25% bupivacaine 10 ml with buprenorphine 150 mcg. Dosage were repeated in both the groups to keep a VAS score < 40 for 48 hours post-operatively. Spirometry was done preoperatively and 12, 24 and 36 hours post-opera-tively. Vital parameters were monitored for 48 hours. The mean analgesia time was 331.73±94.03 min and 567.33±127.33 min in IP and TE groups respectively. The VAS score was significantly reduced within the first 30 minutes of injection in both the groups. Post injection VAS was significantly better in TE group. Mean time taken for interpleural and epidural catheter placement was 5.0±0.0 min and 33.83±3.39 min respectively. Postoperative forced expiratory volume in 1 second(FEV1, forced vital capacity (FVC and forced expiratory ratio (FER were similar in both the groups while peak expiratory flow rate (PEFR, maximal expiratory flow (MEF and F50 were slightly better in TE group. Vital parameters showed similar changes in both the groups. The TE group had more complications. Interpleural analgesia, though of shorter duration, is a safe and effective alternative technique for post-thoracotomy analgesia and has a low complication rate.

  13. IL-1 receptor antagonist improves morphine and buprenorphine efficacy in a rat neuropathic pain model.

    Science.gov (United States)

    Pilat, Dominika; Rojewska, Ewelina; Jurga, Agnieszka M; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2015-10-05

    An interesting research and therapeutic problem is the reduced beneficial efficacy of opioids in the treatment of neuropathic pain. The present study sought to investigate the potential role of IL-1 family members in this phenomenon. We studied the time course of changes in IL-1alpha, IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist mRNA and protein levels experienced by rats after chronic constriction injury (CCI) of the sciatic nerve using qRT-PCR and Western blot analysis. In CCI-exposed rats, spinal levels of IL-1alpha mRNA were slightly downregulated on the 7th day, and protein levels were not changed on the 7th and 14th days. Levels of IL-1 receptor antagonist and IL-1 receptor type I were slightly upregulated in the ipsilateral part of the spinal cord on the 7th and 14th days; however, protein levels were not changed at those time points. Interestingly, we observed that IL-1beta mRNA and protein levels were strongly elevated in the ipsilateral part of the dorsal spinal cord on the 7th and 14th days following CCI. Moreover, in rats exposed to a single intrathecal administration of an IL-1 receptor antagonist (100 ng i.t.) on the 7th and 14th day following CCI, symptoms of neuropathic pain were attenuated, and the analgesic effects of morphine (2.5 µg i.t.) and buprenorphine (2.5 µg i.t.) were enhanced. In summary, restoration of the analgesic activity of morphine and buprenorphine by blockade of IL-1 signaling suggests that increased IL-1beta responses may account for the decreased analgesic efficacy of opioids observed in the treatment of neuropathy.

  14. 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.

  15. Preparation of (/sup 11/C)buprenorphine - a potential radioligand for the study of the opiate receptor system in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Luthra, S.K.; Pike, V.W.; Brady, F.; Horlock, P.L.; Prenant, C.; Crouzel, C.

    1987-01-01

    A method is described for the preparation of (/sup 11/C)buprenorphine in high specific activity, based on the reaction of N-(de-cyclopropylmethyl)buprenorphine with ''no carrier added'' (1-/sup 11/C)cyclopropanecarbonyl chloride followed by reduction with lithium aluminium hydride. The (1-/sup 11/C)cyclopropanecarbonyl chloride is itself prepared from cyclotron-produced (/sup 11/C)carbon dioxide. The overall preparation time is 57 min from the end of radionuclide production, and the radiochemical yield is ca 20%, (decay-corrected from (/sup 11/C)-carbon dioxide). (/sup 11/C)Buprenophine has potential as a radio-ligand for the study of the opiate receptor system in vivo by means of position emission tomography.

  16. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    Science.gov (United States)

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps.

  17. On deriving the dose–effect relation of an unknown second component: An example using buprenorphine preclinical data

    OpenAIRE

    Tallarida, Ronald J.; Cowan, Alan; Raffa, Robert B.

    2010-01-01

    Buprenorphine, like many other drugs, displays a biphasic dose–response relation (‘hormesis’), viz., its antinociceptive effect in some preclinical models increases up to some dose level (often achieving 100% effect) and decreases at high-doses. A decreasing component was evident in the tail-flick tests described here, occurring in both the mouse and the rat. While the mechanism of dose-related decline in antinociceptive effect, when observed, might be related to nociceptin/orphanin-FQ, the p...

  18. Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad.

    Science.gov (United States)

    Adamson, Trinka W; Kendall, Lon V; Goss, Sherri; Grayson, Kevin; Touma, Chadi; Palme, Rupert; Chen, Jane Q; Borowsky, Alexander D

    2010-09-01

    The purpose of this study was to determine the level of pain elicited by mammary fat pad removal surgery and the effects of postoperative analgesics on recovery. Female FVB mice were anesthetized, and mammary fat pad removal was performed. After surgery, mice received carprofen, buprenorphine, a combination of carprofen and buprenorphine, or saline treatment. Additional mice received anesthesia but no surgery or treatment. Food and water intake, body weight, wheel running activity, and a visual assessment score were recorded daily for 4 d after surgery and compared with presurgical findings. Corticosterone metabolites in fecal samples were analyzed at 12 and 24 h postsurgically and compared with baseline values. All surgical groups had significantly decreased food intake at 24 h, with a return to baseline by 48 h. The combination treatment resulted in a significantly decreased water intake and body weight at 24 h. All surgical groups had significantly decreased wheel running activity at 24 h only. The visual assessment scores indicated mild pain for all surgical groups, with the buprenorphine treated mice showing the highest pain index scores, as compared with nonsurgical controls. Fecal corticosterone metabolite levels did not differ significantly between any of the groups or across time. The parameters used in this study did not indicate that administration of these analgesic regimens improved recovery as compared with that of saline-treated mice. Care should be taken when using visual assessment scores to evaluate pain in mice, given that analgesics may have side effects that inadvertently elevate the score.

  19. In vitro release of clomipramine HCl and buprenorphine HCl from poly adipic anhydride (PAA) and poly trimethylene carbonate (PTMC) blends.

    Science.gov (United States)

    Dinarvand, Rassoul; Alimorad, Mohammed Massoud; Amanlou, Massoud; Akbari, Hamid

    2005-10-01

    Controlled drug-delivery technology is concerned with the systematic release of a pharmaceutical agent to maintain a therapeutic level of the drug in the body for modulated and/or prolonged periods of time. This may be achieved by incorporating the therapeutic agent into a degradable polymer vehicle, which releases the agent continuously as the matrix erodes. In this study, poly trimethylene carbonate (PTMC), an aliphatic polycarbonate, and poly adipic anhydride (PAA), an aliphatic polyanhydride, were synthesized via melt condensation and ring-opening polymerization of trimethylene carbonate and adipic acid, respectively. The release of clomipramine HCl and buprenorphine HCl from discs prepared with the use of PTMC-PAA blends in phosphate buffer (pH 7.4) are also described. Clomipramine HCl and buprenorphine HCl were both used as hydrophilic drug models. Theoretical treatment of the data with the Peppas model revealed that release of clomipramine HCl (5%) in devices containing 70% PTMC or more followed a Fickian diffusion model. However, the releases of buprenorphine HCl (5%) in the same devices were anomalous. For devices containing 50% and more PAA, surface erosion may play a significant role in the release of both molecules.

  20. Primary tumour growth in an orthotopic osteosarcoma mouse model is not influenced by analgesic treatment with buprenorphine and meloxicam.

    Science.gov (United States)

    Husmann, K; Arlt, M J E; Jirkof, P; Arras, M; Born, W; Fuchs, B

    2015-10-01

    Little is known about the treatment of bone pain in animal models of bone cancer. In the present study, the orthotopic 143-B human osteosarcoma xenotransplantation model was used to address the following questions: (1) Can repetitive analgesic treatment extend the experimental period by prolonging the time to reach humane endpoints and (2) Does repetitive analgesic treatment affect bone tumour development and metastasis? The analgesics, buprenorphine and meloxicam, were either applied individually or in combination at 12 h intervals as soon as the animals began to avoid using the tumour cell injected leg. While control mice treated with NaCl showed continuous body weight loss, the major criterion previously for terminating the experiments, animals treated with analgesic substances did not. The control mice had to be sacrificed 26 days after tumour cell injection, whereas the groups of animals with the different pain treatments were euthanized after an additional eight days. Importantly, primary intratibial tumour growth was not affected in any of the experimental groups by any of the pain treatment procedures. Between days 26 and 34 after tumour cell injection an increase of about 100% of the number of lung metastases was found for the groups treated with buprenorphine alone or together with meloxicam, but not for the group treated with meloxicam alone. In summary, the results indicated that both buprenorphine and meloxicam are suitable analgesics for prolonging the experimental periods in an experimental intratibial osteosarcoma mouse model.

  1. 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

  2. Simultaneous determination of buprenorphine, norbuprenorphine and naloxone in human plasma by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Liu, Yongzhen; Li, Xiaohua; Xu, Allan; Nasser, Azmi F; Heidbreder, Christian

    2016-02-20

    A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for simultaneous quantification of naloxone, buprenorphine and its metabolite norbuprenorphine in human plasma. Human plasma samples were extracted using a single step liquid-liquid extraction, and then separated on an Imtakt Unison UK-C18 column (2.1×50mm, 3μm) using alkaline mobile phases with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation, precision, accuracy, recoveries and stability were determined. The linear range was 20-10000pg/mL for buprenorphine and norbuprenorphine; and 1-500pg/mL for naloxone. The correlation coefficient (R(2)) values for all three analytes were ≥0.995. The precision and accuracy for intra-day and inter-day were 63% and matrix effects were tracked by the deuterated internal standards (IS) with the IS-normalized matrix factor ranging from 0.96 to 1.33 for all three analytes. The validated method was successfully applied in a clinical pharmacokinetic study with low dose administration of sublingual buprenorphine and naloxone.

  3. Correlates of Nine-Month Retention following Interim Buprenorphine-Naloxone Treatment in Opioid Dependence: A Pilot Study

    Directory of Open Access Journals (Sweden)

    A. Håkansson

    2016-01-01

    Full Text Available Interim medication-only treatment has been suggested for the initiation of opioid maintenance treatment (OMT in opioid-dependent subjects, but this rarely has been studied using buprenorphine instead of methadone. Following a pilot trial assessing interim buprenorphine-naloxone treatment in order to facilitate transfer into OMT, we here aimed to study retention, and potential correlates of retention, in full-scale treatment. Thirty-six patients successfully referred from a waiting list through an interim treatment phase were followed for nine months in OMT. Baseline characteristics, as well as urine analyses during the interim phase and during full-scale OMT, were studied as potential correlates of retention. The nine-month retention in OMT was 83 percent (n=30. While interim-phase urine samples positive for benzodiazepines did not significantly predict dropout from full-scale OMT (p=0.09, urine samples positive for benzodiazepines within full-scale OMT were significantly associated with dropout (p<0.01, in contrast to other substances and baseline characteristics. Retention remained high through nine months in this pilot study sample of patients referred through buprenorphine-naloxone interim treatment, but use of benzodiazepines is problematic, and the present data suggest that it may be associated with treatment dropout.

  4. Comparison of prescriber evaluations and patient-directed self-reports in office-based practice for buprenorphine treatment of opiate-dependent individuals in France, 2002

    Directory of Open Access Journals (Sweden)

    Estelle Lavie

    2008-11-01

    Full Text Available Estelle Lavie1, Mélina Fatséas1, Jean-Pierre Daulouède1,2, Cécile Denis1, Jacques Dubernet1, Laurent Cattan3, Marc Auriacombe11Laboratoire de psychiatrie/EA4139, INSERM IFR-99 and Faculté de médecine Victor Pachon, University Victor Segalen Bordeaux 2, Bordeaux, France; 2Bizia, Centre de soins d’addictologie, Centre Hospitalier de la Côte Basque, Bayonne, France; 3Centre médical, Noisy-le-sec, FranceAbstract: The objective of this cross-sectional evaluation study was to compare data generated through prescriber assessments, and data generated from independent direct contact with opiate-dependent patients in office-based practice to evaluate buprenorphine treatment for modality of buprenorphine absorption, benzodiazepine use, and depressive symptoms. A group of buprenorphine office-based practice prescribers was selected to participate in this study. They were asked to screen for inclusion all their patients coming for a visit from February to August 2002. Once included by their prescribing physician, patients were given a series of self-administered questionnaires to be returned directly to the research staff, independently of their prescriber. Each prescriber was given a questionnaire to complete based on their knowledge and interview of the patient. Items assessed were history of current treatment, current substance use, buprenorphine treatment related behavior (daily frequency of intake, route of administration, benzodiazepine use and existence of a major depressive episode. Prescribers and patients’ questionnaires were compared. Concordance of both assessments was assessed by kappa statistics. The sensitivity and specificity as well as the positive and negative predictive values of prescriber collected information were compared to that of their patients’. There was an overall good correlation between both data sources on the procedures for buprenorphine use especially for intravenous use of buprenorphine. There were important

  5. Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids

    Directory of Open Access Journals (Sweden)

    Hale M

    2017-01-01

    Full Text Available Martin Hale,1 Veronica Urdaneta,2 M Todd Kirby,3 Qinfang Xiang,4 Richard Rauck5 1Gold Coast Research, LLC, Plantation, FL, USA; 2Pharmacovigilance and Risk Management, 3Clinical Development, 4Biometrics, Endo Pharmaceuticals Inc., Malvern, PA, USA; 5Carolinas Pain Institute, Wake Forest Baptist Health, Winston Salem, NC, USA Background: This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids.Methods: The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients or were recruited de novo for this study (n=61 were enrolled in this study. All patients underwent a dose titration period of ≤6 weeks, during which doses of buprenorphine buccal film were adjusted to a maximum 900 µg every 12 hours, depending on tolerability and the need for rescue medication. An optimal dose was defined as the dose that the patient found satisfactory for both pain relief and tolerability, without the need for rescue medication or with ≤2 tablets of rescue medication per day. Once the optimal dose was reached, treatment was continued for ≤48 weeks. Pain intensity was measured throughout the study using a 0–10 numerical rating scale.Results: Of 435 patients achieving an optimal dose of buprenorphine buccal film who commenced long-term treatment, 158 (36.3% completed 48 weeks of treatment. Treatment-related adverse events occurred in 116 patients (22.9% during the titration phase and 61 patients (14.0% during the long-term treatment phase, and adverse events leading to discontinuation of treatment occurred in 14 (2.8% and 14 (3.2% patients, respectively. The most common adverse events were those typically

  6. Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.

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    Ma, Lin-Lin; Freret, Thomas; Lange, Mathilde; Bourgine, Joanna; Coquerel, Antoine; Lelong-Boulouard, Véronique

    2014-12-01

    Buprenorphine (BPN) is widely used as a substitution treatment for opioid addiction. Some cases of abuse and misuse, especially associated with various benzodiazepines (BZDs), have been described, and a previous study has shown that BZDs increase the sedative effect of BPN and decrease its anxiogenic properties. To investigate the reward effect that may lead to the abusive combination of BPN and BZD, we studied the influence of different doses of three BZDs extensively used with BPN by drug addicts on conditioned place preference behavior in mice. BPN (0.3, 1, 3 mg/kg) was injected subcutaneously into male mice alone or in combination with a BZD administered intraperitoneally: dipotassium clorazepate (CRZ; 1, 4, 16 mg/kg), diazepam (DAZ; 0.5, 1, 5 mg/kg), or bromazepam (BMZ; 0.5, 1, 3 mg/kg). Amphetamine (8 mg/kg) was used as a reference drug. Reward effects of BPN alone or in combination were measured in a conditioned place preference paradigm using an unbiased procedure. Our results showed that groups treated with BPN associated with different doses of diazepam and clorazepate, but not bromazepam, spent significantly more time in the drug-paired compartment compared to the group treated with BPN alone. Our study shows that joint consumption of diazepam and clorazepate, but not bromazepam, can increase the reward properties of BPN alone in mice. These results could help to explain the use of this type of drug combination in the drug addict population.

  7. A role for the mu opioid receptor in the antidepressant effects of buprenorphine.

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    Robinson, Shivon A; Erickson, Rebecca L; Browne, Caroline A; Lucki, Irwin

    2017-02-15

    Buprenorphine (BPN), a mixed opioid drug with high affinity for mu (MOR) and kappa (KOR) opioid receptors, has been shown to produce behavioral responses in rodents that are similar to those of antidepressant and anxiolytic drugs. Although recent studies have identified KORs as a primary mediator of BPN's effects in rodent models of depressive-like behavior, the role of MORs in BPN's behavioral effects has not been as well explored. The current studies investigated the role of MORs in mediating conditioned approach behavior in the novelty-induced hypophagia (NIH) test, a behavioral measure previously shown to be sensitive to chronic treatment with antidepressant drugs. The effects of BPN were evaluated in the NIH test 24h post-administration in mice with genetic deletion of the MOR (Oprm1(-/-)) or KOR (Oprk1(-/-)), or after pharmacological blockade with the non-selective opioid receptor antagonist naltrexone and selective MOR antagonist cyprodime. We found that behavioral responses to BPN in the NIH test were blocked in Oprm1(-/-) mice, but not in Oprk1(-/-) mice. Both cyprodime and naltrexone significantly reduced approach latency at doses experimentally proven to antagonize the MOR. In contrast the selective MOR agonist morphine and the selective KOR antagonist nor-BNI were both ineffective. Moreover, antinociceptive studies revealed persistence of the MOR antagonist properties of BPN at 24h post-administration, the period of behavioral reactivity. These data support modulation of MOR activity as a key component of BPN's antidepressant-like effects in the NIH paradigm.

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

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    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.

  9. Comparison of cerebral pharmacokinetics of buprenorphine and norbuprenorphine in an in vivo sheep model.

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    Jensen, M L; Foster, D; Upton, R; Grant, C; Martinez, A; Somogyi, A

    2007-04-01

    The pharmacokinetics and time course of blood-brain equilibration of buprenorphine (BUP) and norbuprenorphine (norBUP) in sheep were characterized. Sheep were administered 0.04 mg kg(-1) BUP or 0.6 mg kg(-1) norBUP as 4-min i.v. infusions. The cerebral kinetics were inferred from arterio-sagittal sinus concentration gradients and changes in cerebral blood flow. These data were fitted to physiologically based pharmacokinetic models. BUP cerebral kinetics were best described by a membrane-limited model with a large equilibration delay (half-life of 20 min) between brain and blood due to intermediate permeability (47 ml min(-1)) and a large cerebral distribution volume (595 ml). Significant limitation in permeability (6 ml min(-1)) characterized the cerebral kinetics of norBUP with a cerebral distribution volume (157 ml) giving a blood-brain equilibration half-life (21 min) similar to that for BUP. The logD of BUP and norBUP were 3.93 +/- 0.08 and 1.18 +/- 0.04 (mean +/- SD), respectively. Both compounds revealed slow cerebral equilibration with variations in degree of permeability and distribution volume reflecting the difference in lipophilicity. It is possible that norBUP contributes to the central effects seen after chronic BUP administration as this study demonstrated its entry into the brain.

  10. Clinical effects of buprenorphine on open field behaviour and gait symmetry in healthy and lame weaned piglets.

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    Meijer, Ellen; van Nes, Arie; Back, Willem; van der Staay, Franz Josef

    2015-12-01

    Lameness in pigs decreases animal welfare and economic profit for the farmer. An important reason for impaired welfare in lame animals is pain due to lameness. No direct measurement of pain is possible in animals, and methods to indirectly detect and quantify the amount of pain an animal is experiencing are urgently needed. In this study, two methods to assess pain associated with lameness in pigs were evaluated to determine if they were sensitive enough to detect a lameness reduction as an effect of an experimental analgesic medication. Asymmetry associated with lameness was objectively quantified using pressure mat kinetic parameters: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Locomotor activity was assessed in an open field test. A dose of 0.04 mg/kg buprenorphine, a strong analgesic, was used to treat 10 lame pigs, while eight other lame pigs, treated with physiological saline solution, served as controls. Buprenorphine decreased lameness-associated asymmetry for pressure mat LR (P = 0.002), VI (P = 0.003) and PVP (P = 0.001) and increased activity of the lame pigs in the open field (P = 0.023), while saline-treated animals did not show any changes in asymmetry and became less active in the open field (P open field test are both sensitive enough to detect the analgesic effects of buprenorphine when used to treat moderate to severe clinical pain in a relatively small group of affected pigs. The methods used in this study may also provide promising additional tools for future research into early pain recognition and lameness treatment in pigs.

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

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    Leppert W

    2015-12-01

    Full Text Available Wojciech Leppert, Grzegorz Kowalski Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland 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. Keywords: adverse effects, analgesia, cancer, neuropathic pain, transdermal buprenorphine, treatment

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

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    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

  13. Buprenorphine for postoperative analgesia: Axillary brachial plexus block versus intramuscular administration in a placebo-controlled trial

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    Deepali Thakur

    2015-01-01

    Full Text Available Background and Aims: Peripheral administration of opioids has been suggested for prolongation of regional analgesia. This prospective, randomized, double-blind placebo-controlled study was undertaken to compare the effect of regional (axillary brachial plexus block [ABPB] versus intramuscular (IM buprenorphine (2 μg/kg in adults. Material and Methods: Seventy-five adults undergoing upper limb surgery received ABPB with local anaesthetic (15 ml 0.5% bupivacaine, 15 ml 2% lignocaine with adrenaline 1:200,000, 9 ml normal saline [NS]. In addition, regional group RB (n = 25 received buprenorphine 2 μg/kg in ABPB and 1 ml NS IM. Systemic Group SB (n = 25 received 1 ml NS in ABPB and buprenorphine 2 μg/kg IM. Group C (n = 25 received 1 ml NS in ABPB and IM. Onset, duration of sensory and motor block, hemodynamic parameters, sedation score, pain scores using visual analog scale, duration of postoperative analgesia, rescue analgesic (RA requirement, adverse events, and patient satisfaction were noted. Results: Demographics, onset and duration of sensory, motor block were similar. RB group had longest duration of analgesia (20.61 ± 1.33 h compared to SB (10.91 ± 0.90 h and control group (5.86 ± 0.57 h (P < 0.05 RB vs. SB/C and SB vs. C. RA requirement was highest in the control group and least in RB group (P = 0.000 RB vs. SB/C and SB vs. C. SB group had a maximum number of side effects (P = 0.041, SB vs. RB/C. Patient satisfaction was highest with group RB (P < 0.05 RB vs. SB/C, and P = 0.06 SB vs. C. Conclusion: Buprenorphine 2 μg/kg in axillary plexus block provides significantly prolonged analgesia with less RA requirement and greater patient satisfaction compared to IM administration. This is highly suggestive of action on peripheral opioid receptors.

  14. Investigation of cross-species translatability of pharmacological MRI in awake nonhuman primate - a buprenorphine challenge study.

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    Stephanie Seah

    Full Text Available BACKGROUND: Pharmacological MRI (phMRI is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP. Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored. METHODOLOGY: We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v., a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC values from brain areas with high density of µ-opioid receptors. PRINCIPAL FINDINGS: In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, p<0.05, n = 4. This observation is strikingly consistent with µ-opioid receptor distribution depicted by [6-O-[(11C]methyl]buprenorphine ([(11C]BPN positron emission tomography imaging study in baboons. Furthermore, our findings are consistent with previous buprenorphine phMRI studies in humans and conscious rats which collectively

  15. Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis.

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    Brogly, Susan B; Saia, Kelley A; Walley, Alexander Y; Du, Haomo M; Sebastiani, Paola

    2014-10-01

    Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.

  16. Pharmacokinetic analysis of enterohepatic circulation of buprenorphine and its active metabolite, norbuprenorphine, in rats.

    Science.gov (United States)

    Ohtani, M; Kotaki, H; Uchino, K; Sawada, Y; Iga, T

    1994-01-01

    The pharmacokinetic characteristics of buprenorphine (BN) and its active metabolite, norbuprenorphine (NBN), was investigated using rats. The elimination half-life (t1/2), total body clearance (CLtot), and steady-state volume of distribution (Vdss) of BN (0.6 mg/kg iv dose) in the intact rat were 2.8 hr, 23.3 ml/min/kg, and 4.2 liters/kg, respectively, and those of NBN (0.6 mg/kg iv dose) were 0.9 hr, 35.0 ml/min/kg, and 2.0 liters/kg. Within 24 hr after administration of BN (0.6 mg/kg dose) to the bile-fistula rat, 74.1% of dose was excreted in the bile as BN glucuronide (BN-Glu) and 18.5% as NBN glucuronide (NBN-Glu), and in urine < 3.2% as BN-Glu. After administration of NBN to the bile-fistula rat, 85.1% and 9.1% of the dose were excreted as NGN-Glu in bile and urine, respectively. The existence of the enterohepatic circulation (EHC) of BN and NBN was confirmed by using paired rats: the donor and recipient rats. Within 24 hr after administration of BN (0.6 mg/kg dose) to the donor rat, 58.8% of the dose was reexcreted as NBN-Glu in bile of the recipient and 25.1% as BN-Glu. Based on the results of in vitro metabolism, it was suggested that this increase in the proportion of NBN-Glu in bile observed after one enterohepatic cycling of BN may be due to the first-pass metabolism in the liver. BN was detected in the plasma of the recipient rat after administration of BN, to the donor rat.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. On deriving the dose–effect relation of an unknown second component: An example using buprenorphine preclinical data

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    Tallarida, Ronald J.; Cowan, Alan; Raffa, Robert B.

    2014-01-01

    Buprenorphine, like many other drugs, displays a biphasic dose–response relation (‘hormesis’), viz., its antinociceptive effect in some preclinical models increases up to some dose level (often achieving 100% effect) and decreases at high-doses. A decreasing component was evident in the tail-flick tests described here, occurring in both the mouse and the rat. While the mechanism of dose-related decline in antinociceptive effect, when observed, might be related to nociceptin/orphanin-FQ, the precise mechanism remains unknown. Regardless of the mechanism, the values of this dose-related decline yield data that can be used to calculate the dose–effect relation of the decreasing (unknown second) component. The calculation, which uses the same concept of dose equivalence that underlies additivity in isobolographic analysis, was employed here from tail-flick data obtained in mouse and rat. The derived dose–effect curves of the second component, though differing in efficacy between mouse and rat, displayed a very notable similarity. This novel technique offers possible insight into the dual low-dose (analgesic), high-dose (addiction medication) uses of buprenorphine. PMID:20061095

  18. On deriving the dose-effect relation of an unknown second component: an example using buprenorphine preclinical data.

    Science.gov (United States)

    Tallarida, Ronald J; Cowan, Alan; Raffa, Robert B

    2010-06-01

    Buprenorphine, like many other drugs, displays a biphasic dose-response relation ('hormesis'), viz., its antinociceptive effect in some preclinical models increases up to some dose level (often achieving 100% effect) and decreases at high-doses. A decreasing component was evident in the tail-flick tests described here, occurring in both the mouse and the rat. While the mechanism of dose-related decline in antinociceptive effect, when observed, might be related to nociceptin/orphanin-FQ, the precise mechanism remains unknown. Regardless of the mechanism, the values of this dose-related decline yield data that can be used to calculate the dose-effect relation of the decreasing (unknown second) component. The calculation, which uses the same concept of dose equivalence that underlies additivity in isobolographic analysis, was employed here from tail-flick data obtained in mouse and rat. The derived dose-effect curves of the second component, though differing in efficacy between mouse and rat, displayed a very notable similarity. This novel technique offers possible insight into the dual low-dose (analgesic), high-dose (addiction medication) uses of buprenorphine.

  19. 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.

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

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    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.

  1. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study

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    Ravn P

    2013-01-01

    Full Text Available Pernille Ravn,1 Erik L Secher,2 Ulrik Skram,3 Trine Therkildsen,1 Lona L Christrup,1 Mads U Werner41Department of Drug Design and Pharmacology, University of Copenhagen, 2Department of Anesthesiology, Juliane Marie Center, Rigshospitalet, Copenhagen University Hospitals, 3Department of Intensive Care, Gentofte Hospital, Copenhagen University Hospitals, 4Multidisciplinary Pain Center, Neuroscience Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, DenmarkPurpose: 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.Subjects and methods: Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg, buprenorphine (0.3/0.6 mg, or placebo (normal saline were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm2, and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist.Results: For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia

  2. COMPARISON OF BUTORPHANOL AND BUPRENORPHINE AS AN ADJUVANT TO LOCAL ANAESTHESIA IN SUPRACLAVICULAR BRACHIAL PLEXUS BLOCK FOR POST-OPERATIVE ANALGESIA

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    Vinod

    2014-04-01

    Full Text Available BACKGROUND: Supraclavicular brachial plexus block provides anesthesia for surgeries around elbow, forearm and hand. With advent of opioid receptors, variety of opioid agents is used for postoperative analgesia via brachial plexus block. Butorphanol and Buprenorphine can be used along with local anesthetics to provide post op analgesia. AIMS: 1 To study the onset and extent of sensory and motor blockade. 2 To compare the duration of postoperative analgesia in two groups. METHODOLOGY: A study was carried out in 30 patients aged 18-60yr of ASA grade I & II of either sex in each group undergoing orthopedic upper limb surgeries via supraclavicular brachial plexus block. Injection Butorphanol 1mg (Group-I and Buprenorphine150µg (Group-II were added to local anesthetic mixture. Onset of sensory and motor blockade, extent of blockade and occurrence of any complications were studied in both the groups. All patients were observed for analgesia hourly until patient demanded analgesia post-operatively by VAS pain score. RESULTS: In Group II (Buprenorphine onset of sensory, motor blockade and complete blockade was delayed as compared to Group I (Butorphanol. In Group I patients, VAS score was 39.44  16.66 at the end of 5 hours while in Group II patients 50.35  25.65 VAS score at the end of 8 hours. So the duration of analgesia was upto 5-6 hours in Group I, where it was upto 8-9 hours in Group II. CONCLUSION: Both drugs are potent analgesic in brachial plexus block, but Buprenorphine is more potent and produces longer duration of postoperative analgesia than Butorphanol.

  3. Clinical application of buprenorphine and its in vitor determination%丁丙诺啡的临床应用及其体外检测

    Institute of Scientific and Technical Information of China (English)

    陈永对; 刘丽华

    2006-01-01

    丁丙诺啡(buprenorphine,Bup)是蒂巴因的衍生物,是阿片受体激动-拮抗剂.其最早是20世纪60年代由英国药物学家合成,注射液用于镇痛.80年代,丁丙诺啡作为临床手术镇痛药物,在许多国家登记注册.

  4. Effect of buprenorphine as an adjunct with plain local anesthetic solution in supraclavicular brachial plexus block on quality and duration of postoperative analgesia

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    Surekha Patil

    2015-01-01

    Full Text Available Background and Aims: Supraclavicular brachial plexus block is ideal for upper limb surgical procedures. Buprenorphine, an agonist antagonist opioid has been used as an adjunct to prolong analgesia. We aimed to evaluate the quality and duration of postoperative analgesia by addition of buprenorphine to local anesthetic solution. Material and Methods: A prospective, randomized, double-blind control study was conducted on 50 healthy patients of ASA Grade I/II of age group 20-70 years scheduled for orthopedic and reconstructive surgery of upper limb under supraclavicular brachial plexus block. Patients were allocated into two groups, 25 in each group viz.: Group B (buprenorphine group received 20 ml 0.5% bupivacaine + 15 ml 2% lignocaine with adrenaline (1:200,000 + 4 ml normal saline + 1500 units hyaluronidase + 3 μg/kg buprenorphine diluted to 1 ml normal saline. Group C (control group received 20 ml 0.5% bupivacaine + 15 ml 2% lignocaine with adrenaline (1:200,000 + 4 ml normal saline + 1500 units hyaluronidase + 1 ml normal saline. The parameters observed were onset and duration of sensory and motor block, quality and duration of analgesia and side-effects. Results: The mean duration of postoperative analgesia was significantly longer in Group B (16.04 ± 3.19 h than in Group C (6.20 ± 0.74 h. There was no difference between two groups on mean onset of sensory block. The mean duration motor block was significantly longer in Group B (4.93 ± 0.94 h than in Group C (2.25 ± 0.62 h [P < 0.05]. The mean duration of sensory block was also significantly longer in Group B (5.71 ± 0.94 h than in Group C (4.94 ± 0.70 h with P < 0.05. Conclusion: Addition of 3 μg/kg buprenorphine to 0.5% bupivacaine for supraclavicular brachial plexus block prolonged duration of postoperative analgesia and sensory blockade without an increase in side effects.

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

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    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

  6. 美沙酮与丁丙诺啡联用治疗海洛因依赖的临床效果%Effect of Methadone Plus Buprenorphine on the Alleviation of Heroin Withdrawal Symptoms

    Institute of Scientific and Technical Information of China (English)

    家有荣

    2001-01-01

    Objective:To explore the effectiveness of methadone combined with buprenorphine on the alleviation of heroin withdrawal symptoms. Methods: One hundred and twenty patients with heroin dependence were randomly divided into two groups , namely the methadone combined buprenorphine treatment group (n=60)and the methadone alone treatment group (n=60). Rating scales were employed to assess the treatment outcomes. Results: Compared with patients in the methadone alone treatment group, patients in the combined treatment group reported fewer withdrawal symptoms, especially in first four days. They also subjectively considered the combined treatment as more acceptable. This effect was more pronounced in patients with relatively high levels of initial withdrawal symptoms. Conclusion: Methadone with buprenorphine was proved to be a favourable combination treatment in terms of reducing withdrawal symptoms, as well as improving the short-term detoxification success rate, especially in patients with severe heroin withdrawal symptoms.

  7. Determination of buprenorphine by differential pulse voltammetry on carbon paste electrode using SDS as an enhancement factor.

    Science.gov (United States)

    Behpour, Mohsen; Valipour, Akram; Keshavarz, Mahin

    2014-09-01

    In the present study, a facile electrochemical approach is proposed for the determination of buprenorphine (BPR) in the presence of sodium dodecyl sulfate (SDS). SDS was applied for amplification of oxidation signal. Carbon paste electrode (CPE) used as working electrode and cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) were carried out in phosphate buffer solution (pH3.0). Under optimal experimental conditions, the oxidation current increased with the addition of BPR in the sample and two dynamic ranges obtained from 4.00 nM to 0.126 μM and from 0.126 to 0.317 μM by DPV and exhibited a low detection limit (LOD) of 1.33 nM (S/N=3). This offered method has been used for the determination of BPR in the real samples and has validated with the recovery test for BPR spiked urine samples. The result demonstrated that this method is a simple, sensitive, rapid, low-cost, and stable method for BPR detection.

  8. Evaluation of buprenorphine LUCIO immunoassay versus GC-MS using urines from a workplace drug testing program.

    Science.gov (United States)

    Alves, Marcela Nogueira Rabelo; Piccinotti, Alberto; Tameni, Silvia; Polettini, Aldo

    2013-04-01

    The buprenorphine (BUP) LUCIO Nal Von Minden screening assay was evaluated. Urine samples from subjects enrolled in a workplace drug testing program were screened according to the manufacturer's instruction using a Roche COBAS Integra 800 analyser. For gas chromatography-mass spectrometry (GC-MS) confirmatory analysis, samples were submitted to enzymatic hydrolysis with β-glucuronidase and mixed-mode solid-phase extraction. Imprecision (coefficient of variation) for 3.0, 7.0, and 13.0 ng/mL calibrators varied within 2.8-8.7 intra-day (n = 20) and 7.7-8.6 inter-day (n = 19). Inaccuracy (bias) was between -5.6-30.5 intra-day and -13.2-4.2 inter-day. At the 5 ng/mL cut-off, the immunoassay showed 100% sensitivity and 88% specificity, with an overall agreement of 94% between immunoassay and GC-MS. Raising the cut-off to 10 ng/mL provided an identical overall agreement between immunoassay and GC-MS (94%), despite the decrease in sensitivity (90%) and the increase in specificity (100%). According to these results, the BUP LUCIO Nal Von Minden screening assay provides adequate sensitivity and specificity for BUP screening in urine samples using a cut-off concentration of 5 ng/mL.

  9. P-glycoprotein mediates brain-to-blood efflux transport of buprenorphine across the blood-brain barrier.

    Science.gov (United States)

    Suzuki, Toyofumi; Zaima, Chika; Moriki, Yoshiaki; Fukami, Toshiro; Tomono, Kazuo

    2007-01-01

    The involvement of P-glycoprotein (P-gp) in buprenorphine (BNP) transport at the blood-brain barrier (BBB) in rats was investigated in vivo by means of both the brain uptake index technique and the brain efflux index technique. P-gp inhibitors, such as cyclosporin A, quinidine and verapamil, enhanced the apparent brain uptake of [3H]BNP by 1.5-fold. The increment of the BNP uptake by the brain suggests the involvement of a P-gp efflux mechanism of BNP transport at the BBB. [3H]BNP was eliminated with an apparent elimination half-life of 27.5 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [3H]BNP across the BBB was 0.154 ml/min/g brain, which was calculated from the elimination rate constant (2.52 x 10- 2 min- 1) and the distribution volume in the brain (6.11 ml/g brain). The efflux transport of [3H]BNP was inhibited by range from 32 to 64% in the presence of P-gp inhibitors. The present results suggest that BNP is transported from the brain across the BBB via a P-gp-mediated efflux transport system, at least in part.

  10. Longitudinal missing data strategies for substance use clinical trials using generalized estimating equations: an example with a buprenorphine trial

    Science.gov (United States)

    McPherson, Sterling; Barbosa-Leiker, Celestina; McDonell, Michael; Howell, Donelle; Roll, John

    2013-01-01

    Objective A review of substance use clinical trials indicates that sub-optimal methods are the most commonly used procedures to deal with longitudinal missing information. Methods Listwise deletion (i.e., using complete cases only), positive urine analysis (UA) imputation, and multiple imputation (MI) were used to evaluate the effect of baseline substance use and buprenorphine/naloxone tapering schedule (7 or 28 days) on the probability of a positive UA (UA+) across the 4-week treatment period. Results The listwise deletion generalized estimating equations (GEE) model demonstrated that those in the 28-day taper group were less likely to submit a UA+ for opioids during the treatment period (odds ratios (OR) = 0.57, 95% confidence interval (CI): 0.39–0.83), as did the positive UA imputation model (OR = 0.43, CI: 0.34–0.55). The MI model also demonstrated a similar effect of taper group (OR = 0.57, CI: 0.42–0.77), but the effect size was more similar to that of the listwise deletion model. Conclusions Future researchers may find utilization of the MI procedure in conjunction with the common method of GEE analysis as a helpful analytic approach when the missing at random assumption is justifiable. PMID:24014144

  11. A comparative study of extradural anesthesia using 0.75% ropivacaine, 0.75% ropivacaine with fentanyl, and 0.75% ropivacaine with buprenorphine for cesarean section from a rural teaching hospital in India

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    Grace Maria George

    2014-01-01

    Full Text Available Context: The study was to compare the analgesic efficacy of three different epidural solutions - ropivacaine, ropivacaine fentanyl mixture, and ropivacaine buprenorphine mixture - for cesarean section. Materials and Methods: This was a prospective, randomized, controlled, double blind study carried out in primi parturients undergoing elective cesarean section with singleton fetus. A total of 102 parturients in the age group of 20-35 years, American Society of Anesthesiologists (ASA I or II scheduled for elective cesarean under continuous epidural anesthesia were divided into three groups using a computer-generated random number list. The test dose (3 ml 2% lignocaine with 15 μg adrenaline and 0.75% ropivacaine 12 ml were given to all parturients. In addition, normal saline 1 ml, fentanyl 50 μg, and buprenorphine 300 μg were given to Group I, II, and III respectively. Sensory block, motor block, analgesia, maternal effects, fetal outcome, and surgeons′ and parturients′ satisfaction were evaluated. Results: Onset of sensory block was faster in the fentanyl and buprenorphine groups compared to ropivacaine group (9.94 ± 0.48, 10.72 ± 0.26 versus 14.59 ± 0.34. Duration of sensory block was prolonged in buprenorphine group as compared to fentanyl and ropivacaine groups (120.41 ± 4.31 versus (95.68 ± 3.28, 98.28 ± 3.42. Duration of analgesia was prolonged in buprenorphine group compared to fentanyl and ropivacaine groups (516.38 ± 29.14 versus 327.06 ± 12.41, 285.78 ± 10.10. It proved to be safe for mother and fetus. The surgeon and the parturients were satisfied with the mode of anesthesia. Conclusion: Ropivacaine 0.75%, ropivacaine 0.75% with fentanyl 50 mg, or buprenorphine 300 mg provided safe anesthesia when given extradurally for cesarean section. Addition of both fentanyl and buprenorphine to ropivacaine hastened the onset of sensory block, while addition of buprenorphine provided prolonged excellent postoperative analgesia.

  12. Automated radiosyntheses of [6-0-methyl-[sup 11]C]diprenorphine and [6-0-methyl-[sup 11]C]buprenorphine from 3-0-trityl protected precursors

    Energy Technology Data Exchange (ETDEWEB)

    Luthra, S.K.; Brady, F.; Turton, D.R.; Brown, D.J.; Dowsett, K.; Waters, S.L.; Jones, A.K.P. (Hammersmith Hospital, London (United Kingdom). M.R.C. Cyclotron Unit); Matthews, R.W.; Crowder, J.C. (North London Univ., London (United Kingdom). School of Applied Chemistry)

    1994-08-01

    The antagonist [6-0-methyl-[sup 11]C]diprenorphine and the mixed agonist/antagonist [6-0-methyl-[sup 11]C]buprenorphine, radioligands for studying the opioid receptor system in vivo with positron emission tomography, were preapred by 0-methylation of (3-0-trityl, 6-desmethyl)diprenorphine and [3-0-trityl,6-desmethyl]buprenorphine, respectively, with [[sup 11]C]iodomethane. The use of the base-stable, acid labile trityl protecting group minimizes the formation of byproducts and allows reproducible radiosyntheses. (author).

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

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    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.

  14. 氯诺昔康与丁丙诺啡术后镇痛效果比较%Comparison of postoperative analgesia between lornoxicam and buprenorphine

    Institute of Scientific and Technical Information of China (English)

    王秀峰

    2010-01-01

    Objective To study the efficacy arid side effects of postoperative analgesia between Lornoxicam and Buprenorphine. Methods Sixty ASA I-II patients were randomly divided into Lomoxicam group(group A) and Buprenorphine group(group B). Analgesiae were subcutaneously injected via an electronic patients controlled analgesic pump post surgeries. The visual analgesiae sacle( VAS) was used to evaluate the postoperative pain relief,and analgesic response was recorded. Result There were no significant differences between Lomoxicam and Buprenorphine about the analgesic response(P>0. 05),moreover,no stastical differences in the patients demography,analgesic and anesthetic type were associated with the analgestic outcomes. Conclusion Lomoxicam without respiratory distuber-ance was a good alternative to Buprenorphine in PCSA.%目的 比较氯诺昔康和丁丙诺啡的术后镇痛效果及不良反应.方法 60例ASA Ⅰ-Ⅱ级患者,随机分为两组:氯诺昔康A组(n=30)和丁丙诺啡B组(n=30),两组均通过电子泵经皮下给药.采用视觉模拟评分法(VAS)测定患者的术后镇痛效果,记录不良反应.结果 两组患者的性别、年龄、身高、手术类型和麻醉方法等一般情况差异无统计学意义(P>0.05).两组的术后镇痛效果和不良反应的指标均差异无统计学意义(P>0.05).结论 在术后患者自控镇痛中,氯诺昔康因其与丁丙诺啡相似的镇痛效果且无呼吸抑制的优点可以作为丁丙诺啡的替代用药.

  15. Comparing methadone and buprenorphine maintenance with methadone-assisted withdrawal for the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes

    Directory of Open Access Journals (Sweden)

    Lund IO

    2012-02-01

    Full Text Available Ingunn O Lund1, Heather Fitzsimons2, Michelle Tuten2, Margaret S Chisolm2, Kevin E O’Grady3, Hendrée E Jones2,41SERAF-Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway; 2Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; 3Department of Psychology, University of Maryland, College Park, MD; 4Substance Abuse Treatment Evaluations and Interventions Research Program, RTI International, Research Triangle Park, NC, USAAbstract: Pregnancy can motivate opioid-dependent women to seek substance abuse treatment. Research has demonstrated that although prenatal exposure to buprenorphine results in less severe neonatal abstinence syndrome (NAS relative to prenatal methadone exposure, the maternal and other neonatal outcomes are similar for the two medications. Maternal and neonatal outcomes for opioid-dependent pregnant women receiving these medications have not been systematically compared with methadone-assisted withdrawal. The present study provides an initial assessment of the relative efficacy of both methadone and buprenorphine maintenance versus methadone-assisted withdrawal in terms of neonatal and maternal delivery outcomes. Data were derived from (1 the MOTHER (Maternal Opioid Treatment: Human Experimental Research study at the Johns Hopkins University Bayview Medical Center (JHBMC, or (2 retrospective records review of women who underwent methadone-assisted withdrawal at the JHBMC during the time period in which participants were enrolled in the MOTHER study. Compared with the methadone maintenance group, the methadone-assisted withdrawal group had a significantly lower mean NAS peak score (Means = 13.7 vs 7.0; P = 0.002, required a significantly lower mean amount of morphine to treat NAS (Means = 82.8 vs 0.2; P < 0.001, had significantly fewer days medicated for NAS (Means = 31.5 vs 3.9; P < 0.001, and remained in the hospital for a significantly fewer number of

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

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    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.

  17. Predisposing, enabling and need factors of heroin addicts’ using prescribed methadone or buprenorphine for a year or longer: An exploratory study of drug treatment for heroin addicts in the Swedish welfare system

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    Nilsson Marcus Blom

    2014-04-01

    Full Text Available AIM - This exploratory study draws on national register data for 2,638 opioid users from 2004- 2008 to examine whether or not certain predisposing, enabling and need factors are associated with taking methadone or buprenorphine continuously on doctor’s orders for one year or more. DESIGN - Chi-square analysis, one-way Anova and logistic regression methods were used to explore the association between self-reported demographic characteristics, alcohol/drug use severity, substance use disorder treatment history, criminal justice history, level of mental health symptomatology, mental health treatment history, and whether or not adult opioid users had taken methadone or buprenorphine continuously on doctor’s orders for one year or longer. RESULTS - Having a job and having had more voluntary treatment episodes were significantly associated with using methadone or buprenorphine. Those opioid users who had a job were 19 times more likely to be on methadone or buprenorphine than opiate users who did not have a job. CONCLUSIONS - In our study, individuals who were working were significantly more likely to medicate against their opioid abuse. This suggests that they may be more socially integrated than their non-medicating counterparts

  18. 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

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    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.

  19. Validated Method for the Quantification of Buprenorphine in Postmortem Blood Using Solid-Phase Extraction and Two-Dimensional Gas Chromatography-Mass Spectrometry.

    Science.gov (United States)

    Nahar, Limon Khatun; Andrews, Rebecca; Paterson, Sue

    2015-09-01

    A highly sensitive and fully validated method was developed for the quantification of buprenorphine in postmortem blood. After a two-step protein precipitation process using acetonitrile, buprenorphine was purified using mixed-mode (C8/cation exchange) solid-phase extraction cartridges. Endogenous water-soluble compounds and lipids were removed from the cartridges before the samples were eluted, concentrated and derivatized using N-methyl-N-trimethylsilyltrifluoroacetamide. The samples were analyzed using two-dimensional gas chromatography-mass spectrometry (2D GC-MS) in selective ion-monitoring mode. A low polarity Rxi(®)-5MS (30 m × 0.25 mm I.D. × 0.25 µm) was used as the primary column and the secondary column was a mid-polarity Rxi(®) -17Sil MS (15 m × 0.32 mm I.D. × 0.25 µm). The assay was linear from 1.0 to 50.0 ng/mL (r(2) > 0.99; n = 6). Intraday (n = 6) and interday (n = 9) imprecisions (percentage relative standard deviation, % RSD) were selective with no interference from endogenous compounds or from 62 commonly encountered drugs. To prove method applicability to forensic postmortem cases, 14 authentic postmortem blood samples were analyzed.

  20. Blockade of Toll-Like Receptors (TLR2, TLR4) Attenuates Pain and Potentiates Buprenorphine Analgesia in a Rat Neuropathic Pain Model.

    Science.gov (United States)

    Jurga, Agnieszka M; Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Pilat, Dominika; Przewlocka, Barbara; Mika, Joanna

    2016-01-01

    Accumulating evidence indicates that microglial TLR2 and TLR4 play a significant role in nociception. Experiments were conducted to evaluate the contribution of TLR2 and TLR4 and their adaptor molecules to neuropathy and their ability to amplify opioid effectiveness. Behavioral tests (von Frey's and cold plate) and biochemical (Western blot and qRT-PCR) analysis of spinal cord and DRG tissue were conducted after chronic constriction injury (CCI) to the sciatic nerve. Repeated intrathecal administration of LPS-RS (TLR2 and TLR4 antagonist) and LPS-RS Ultrapure (TLR4 antagonist) attenuated allodynia and hyperalgesia. Biochemical analysis revealed time-dependent upregulation of mRNA and/or protein levels of TLR2 and TLR4 and MyD88 and TRIF adaptor molecules, which was paralleled by an increase in IBA-1/CD40-positive cells under neuropathy. LPS-RS and LPS-RS Ultrapure similarly influenced opioid analgesia by enhancing the effectiveness of buprenorphine but not morphine. Summing up, in light of their upregulation over the course of pain, both TLR2 and TLR4 may indeed play a significant role in neuropathy, which could be linked to the observed activation of IBA-1/CD40-positive cells. Blockade of TLR2 and TLR4 produced analgesia and enhanced buprenorphine's effectiveness, which suggests that they may be a putative target for future pharmacological pain relief tools, especially for opioid rotation, when the effect of morphine is tolerated.

  1. Blockade of Toll-Like Receptors (TLR2, TLR4) Attenuates Pain and Potentiates Buprenorphine Analgesia in a Rat Neuropathic Pain Model

    Science.gov (United States)

    Jurga, Agnieszka M.; Rojewska, Ewelina; Makuch, Wioletta; Pilat, Dominika; Przewlocka, Barbara

    2016-01-01

    Accumulating evidence indicates that microglial TLR2 and TLR4 play a significant role in nociception. Experiments were conducted to evaluate the contribution of TLR2 and TLR4 and their adaptor molecules to neuropathy and their ability to amplify opioid effectiveness. Behavioral tests (von Frey's and cold plate) and biochemical (Western blot and qRT-PCR) analysis of spinal cord and DRG tissue were conducted after chronic constriction injury (CCI) to the sciatic nerve. Repeated intrathecal administration of LPS-RS (TLR2 and TLR4 antagonist) and LPS-RS Ultrapure (TLR4 antagonist) attenuated allodynia and hyperalgesia. Biochemical analysis revealed time-dependent upregulation of mRNA and/or protein levels of TLR2 and TLR4 and MyD88 and TRIF adaptor molecules, which was paralleled by an increase in IBA-1/CD40-positive cells under neuropathy. LPS-RS and LPS-RS Ultrapure similarly influenced opioid analgesia by enhancing the effectiveness of buprenorphine but not morphine. Summing up, in light of their upregulation over the course of pain, both TLR2 and TLR4 may indeed play a significant role in neuropathy, which could be linked to the observed activation of IBA-1/CD40-positive cells. Blockade of TLR2 and TLR4 produced analgesia and enhanced buprenorphine's effectiveness, which suggests that they may be a putative target for future pharmacological pain relief tools, especially for opioid rotation, when the effect of morphine is tolerated. PMID:26962463

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

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    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.

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

    Science.gov (United States)

    Kumar, M Suresh; Natale, Richard D; Langkham, B; Sharma, Charan; Kabi, Rachel; Mortimore, Gordon

    2009-02-26

    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.

  4. The analgesic effect of plexus anesthesia with buprenorphine in patients%丁丙诺啡在臂丛麻醉患者中的镇痛作用

    Institute of Scientific and Technical Information of China (English)

    李斌; 陈学丽; 孙翠翠; 吕国义

    2011-01-01

    目的 研究对行臂神经丛阻滞的患者丁丙诺啡加入局麻药中与肌肉注射两种镇痛方式对麻醉效果、麻醉维持时间、术后镇痛等方面的作用.方法 选择2009年9月至2009年12月天津市天津医院60例拟行上肢、手部手术的患者,数字随机法分为3组.A组(局麻药中无丁丙诺啡组,n=20);B组(局麻药中加丁丙诺啡2μg/kg组,n=20);C组(麻醉前肌肉注射丁丙诺啡2 μg/kg组,n=20).用B/BRAMN-STIMMPLEX-DIG神经刺激仪引导定位行腋路臂神经丛阻滞.3组患者记录(1)麻醉起效时间;(2)麻醉维持时间;(3)手术时间;(4)术后4、8、12、24、36、48、72 h各时间点的疼痛评分;(5)恶心、呕吐的发生率;(6)观察其他副作用.结果 3组患者年龄、体重、性别、手术时间之间比较,差异无统计学意义(P>0.05);麻醉起效时间3组之间比较差异无统计学意义(P>0.05).麻醉维持时间:A、C组明显短于B组(P<0.01);疼痛评分4 h时A与B、C组之间差异无统计学意义(P>0.05);8、12、24 h时A组极显著高于B、C组(P<0.01),36、48、72 h时A组与B、C组之间差异无统计学意义(P>0.05);恶心发生率A组为10%,B组20%,C组20%.呕吐发生率A、B组为0,C组30%.结论 丁丙诺啡加入局麻药中进行臂神经丛阻滞或阻滞前肌肉注射丁丙诺啡都可以取得满意的术后镇痛效果,丁丙诺啡加入局麻药中进行臂神经丛阻滞麻醉可延长麻醉维持时间、对术后镇痛有明显疗效,且不良反应较少.%Objective To study the anesthetic effect of brachial plexus block by adding buprenorphine in local anesthetics and patients with intramuscular injection , and observe the anesthesia effects, the anesthesia maintenance time, postoperative analgesia effects. Methods 60 cases of upper limb to line, hand surgery patients from Sep. 2009 to Dec. 2009 in Tianjin Hospital were randomly divided into 3groups. A (local anesthetics without buprenorphine, n = 20); B group (plus 2

  5. Development of a Rapid and Simultaneous Detection Method for Buprenorphine, Norbuprenorphine and Naloxone in Human Plasma Using Ultra-high Performance Liquid Chromatography- tandem Mass Spectrometer with Solid-phase Extraction%Development of a Rapid and Simultaneous Detection Method for Buprenorphine, Norbuprenorphine and Naloxone in Human Plasma Using Ultra-high Performance Liquid Chromatography- tandem Mass Spectrometer with Solid-phase Extraction

    Institute of Scientific and Technical Information of China (English)

    Guo, Qiaozhen; Du, Zhenxia

    2011-01-01

    A simultaneous method was successfully established and validated for the separation and determination of bu- prenorphine (BP), its primary metabolite, nor-buprenorphine (NBP) and a proposed co-formulate, naloxone (NLX) in human plasma. The method used buprenorphine-d4 (BP-D4), nor-buprenorphine-d3 (NBP-D3), naltrexone (NTX) as internal standards (ISs). 100 μL of plasma sample fortified with the ISs was cleaned up by solid-phase extraction (SPE), and was then separated on a Waters AcquityTM BEH C18 column with gradient elution using methanol and water (containing 0.2% formic) at a flow rate of 0.25 mL·min^-1. The mass spectrometer was used for detection and was operated in the positive electrospray ionization with multiple reaction monitoring (MRM) mode. The three compounds were effectively separated in 5 min. The linear ranges of the compounds were 0.1--25, 0.25--25 and 0.05--25 ng·mL^-1 for BP, NBP and NLX, respectively, with r≥0.9935. The method had high sensitivity (the lim- its of detection were 0.02, 0.1 and 0.01 ng.mL-1 for BP, NBP and NLX, respectively) and high recoveries (≥97.6%). The result was shown to be linear and satisfactorily met current acceptance criteria for validation of bio- analytical method: intra and inter assay precisions within the required limits of ≤25% RSD. The LOQs fulfilled the LOQ requirements: precision≤25% RSD, and was fully validated according to the State Food and Drug Administration (SFDA) regulations. The results demonstrated that ultra-high performance liquid chromatography- tandem mass spectrometer (UPLC-MS/MS) with SPE was a powerful detection tool and contributed to pharmaceutical analysis in biological matrices.

  6. 超高效液相色谱法同时测定盐酸丁丙诺啡舌下含片中丁丙诺啡和纳洛酮的含量%Simultaneous determination of buprenorphine and naloxone in buprenorphine sublingual tablets by ultrahigh performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    郭巧珍; 杜振霞

    2011-01-01

    A simultaneous method was established for the separation and determination of buprenorphine and naloxone in buprenorphine sublingual tablets by ultra-high performance liquid chromatography. The samples were separated on a Waters Acquity BEH C18 column with gradient elution using methanol and water (containing 0. 2% formic), the two compounds were effectively separated in 3 min, and the detection was performed with an UV dector at the wavelength of 280 nm. The linear ranges of the compounds were from l to 25 μ/mL for naloxone and 2 to 50 μ/mL for buprenorphine, the correlation coefficients were 0. 9992 and 0. 9995, respectively, and the limits of detection (LOI)) of the method for the two compounds were 0. 2 μg/mL. A comparative study of two mobile phase systems methanol and acetonitrile were performed, and the response of methanol is higher than that for acetonitrile. Under optimum conditions, the actual buprenorphine sublingual tablets and spiked samples were determined. The average recoveries were 91.3% ~ 100. 1%, and RSD less than 5%.%建立了同时检测丁丙诺啡和纳洛酮的超高效液相色谱的分析方法.分析柱为Waters Acquity BEH C18超高效液相色谱柱,紫外检测波长为280 nm,流动相为甲醇-甲酸(0.2%)水,梯度洗脱,两种分析物在3 min内即可达到良好分离.纳洛酮和丁丙诺啡的线性范围分别为1~25 μg/mL,2~50 μg/mL,线性相关系数分别为0.9992,0.9995.检出限为0.2μg/mL.考察了甲醇和乙腈两种流动相体系对样品的分离效果,发现甲醇流动相体系的响应高于乙腈流动相体系.在优化条件下,对丁丙诺啡舌下含片以及加标后样品进行测定,且对其方法学进行考察,加标平均回收率在91.3%~100.1%之间,RSD小于5%.

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

    Directory of Open Access Journals (Sweden)

    Li Ryan

    2009-02-01

    Full Text Available Abstract Background Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares dihydrocodeine with buprenorphine. Methods Open label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data. Results 64% of those approached took part in the study. 63 men (70% gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent compared with those who received dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02–2.56. At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community. Conclusion These findings would suggest that dihydrocodeine should not be routinely

  8. A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone

    Science.gov (United States)

    Weinrib, Aliza Z; Burns, Lindsay C; Mu, Alex; Azam, Muhammad Abid; Ladak, Salima SJ; McRae, Karen; Katznelson, Rita; Azargive, Saam; Tran, Cieran; Katz, Joel; Clarke, Hance

    2017-01-01

    In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS). A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery. After surgery, the TPS provided integrated pharmacological and behavioral treatment, including buprenorphine combined with naloxone and acceptance and commitment therapy (ACT) using the ACT Matrix. The result was dramatic pain reduction and improved functioning and quality of life after 40+ years of chronic pain, thus changing the pain trajectory of a chronic, complex, opioid-dependent patient.

  9. Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study.

    Science.gov (United States)

    Whitham, Justine N; Spurrier, Nicola J; Baghurst, Peter A; Weston, Paul; Sawyer, Michael G

    2015-01-01

    This study compared the latency of pattern reversal visual evoked potentials (VEP) of 36-month old children exposed to opioid pharmacotherapy in utero to that of a group of non-exposed children. Pregnant women were enrolled as part of an open-label non-randomised flexible dosing longitudinal study. Participants were 21 children whose mothers were treated with buprenorphine- (n=11) or methadone-pharmacotherapy (n=10) during pregnancy, and 15 children not exposed to opioids in pregnancy. One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Standard multiple regression analyses were conducted to determine whether there was a significant relationship between group status and VEP latencies after adjusting for the effect of covariates. VEP latencies ranged from 98 to 112 milliseconds (ms) for checks of 48' arc, and from 95 to 113ms for checks of 69' arc. Latencies were comparable across groups. After adjusting for covariates children prenatally exposed to methadone or buprenorphine did not differ significantly from non-opioid exposed children in their responses to either check size. Nor were there any significant differences in VEP latencies between children prenatally exposed to methadone and children prenatally exposed to buprenorphine. Head circumference (HC) was significantly associated with P100 latencies for both check sizes. Data from this controlled, non-randomised study suggest that neither buprenorphine nor methadone appear to have any long-term effects on visual maturity assessed at 36months of age.

  10. Buprenorphine Transdermal Patch

    Science.gov (United States)

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

  11. Buprenorphine Buccal (chronic pain)

    Science.gov (United States)

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

  12. 吗啡与丁丙诺啡的蛛网膜下腔与皮下联合给药的相互作用%Interaction of combined administration of intrathecal morphine with subcutaneous morphine or buprenorphine

    Institute of Scientific and Technical Information of China (English)

    陈莲华; Alexander NEMIROVSKy; 贡沁燕

    2000-01-01

    AIM: To analyze the mode of interaction of combined administration of intrathecal morphine with subcutaneous morphine or buprenorphine. METHODS: Different groups of rats were scheduled to undergo administration of intrathecal (ith) morphine, subcutaneous (sc) morphine,sc buprenorphine, and the combinations of ith morphine with sc morphine or buprenorphine in a series of dose rarios. Nociceptive responses of hind paws of each animal were measured by means of "plantar stimulation" test.The test latency was converted to the percent of maximal possible effect ( % MPE). RESULT: Morphine ith,morphine sc, buprenorphine sc, as well as combinations in all dose ratios increased the % MPE in a dose-depen-dent manner. Isobolograms showed that the EDs0 points determined for the combinations were plotted significantly left to the theoretical additive line. CONCLUSION:The combination of morphine ith with either morphine sc or buprenorphine sc resulted in a synergistic effect. This interaction might be due to the activation of the synergistic antinociceptive mechanisms between supraspinal and spinal levels.%目的:观察大鼠吗啡与丁丙诺啡(或吗啡)的蛛网膜下腔与皮下联合给药的相互作用.方法:SD大鼠,置人蛛网膜下腔导管.辐射热诱发鼠腿撤退试验测痛阈.分别蛛网膜下腔给予吗啡、皮下注射丁丙诺啡(或吗啡)、蛛网膜下腔给予吗啡与皮下注射丁丙诺啡(或吗啡)的联合给药.结果:单独和联合给药均剂量依赖性地提高鼠痛阈.联合给药的量效曲线的斜率均显著大于吗啡单独给药的曲线斜率.等效线图显示联合给药的ED50均位于理论推测的叠加效应线的左侧.结论:吗啡与丁丙诺啡(或吗啡)的蛛网膜下腔与皮下联合给药呈协同效应.

  13. 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

  14. Blockade of Toll-Like Receptors (TLR2, TLR4 Attenuates Pain and Potentiates Buprenorphine Analgesia in a Rat Neuropathic Pain Model

    Directory of Open Access Journals (Sweden)

    Agnieszka M. Jurga

    2016-01-01

    Full Text Available Accumulating evidence indicates that microglial TLR2 and TLR4 play a significant role in nociception. Experiments were conducted to evaluate the contribution of TLR2 and TLR4 and their adaptor molecules to neuropathy and their ability to amplify opioid effectiveness. Behavioral tests (von Frey’s and cold plate and biochemical (Western blot and qRT-PCR analysis of spinal cord and DRG tissue were conducted after chronic constriction injury (CCI to the sciatic nerve. Repeated intrathecal administration of LPS-RS (TLR2 and TLR4 antagonist and LPS-RS Ultrapure (TLR4 antagonist attenuated allodynia and hyperalgesia. Biochemical analysis revealed time-dependent upregulation of mRNA and/or protein levels of TLR2 and TLR4 and MyD88 and TRIF adaptor molecules, which was paralleled by an increase in IBA-1/CD40-positive cells under neuropathy. LPS-RS and LPS-RS Ultrapure similarly influenced opioid analgesia by enhancing the effectiveness of buprenorphine but not morphine. Summing up, in light of their upregulation over the course of pain, both TLR2 and TLR4 may indeed play a significant role in neuropathy, which could be linked to the observed activation of IBA-1/CD40-positive cells. Blockade of TLR2 and TLR4 produced analgesia and enhanced buprenorphine’s effectiveness, which suggests that they may be a putative target for future pharmacological pain relief tools, especially for opioid rotation, when the effect of morphine is tolerated.

  15. 舒芬太尼与丁丙诺啡在术后自控镇痛中的疗效与安全性评价%Sulfentanyl versus buprenorphine for controlled intravenous analgesia on patients undergoing maxillofacial operation

    Institute of Scientific and Technical Information of China (English)

    闫俊杰; 刘伟东; 江银华; 陈慧敏

    2015-01-01

    目的:评价舒芬太尼( SF)对比丁丙诺啡( BP)在口腔颌面部手术( OMS)后自控镇静脉痛( PCIA)的临床疗效及安全性。方法79例OMS患者随机分为舒芬太尼组(41例)和丁丙诺非组(38例),舒芬太尼组术后予以舒芬太尼50μg;丁丙诺非组术后给予丁丙诺非0.6 mg,分别于术后2,8,24,48 h用视觉模拟评份量表和镇静评分量表对患者术后疼痛及镇静情况进行评定,同时记录2组患者术后48 h内生命体征及不良反应。结果舒芬太尼组与丁丙诺非组患者镇痛、镇静评分及生命体征指标差异均无统计学意义(P>0.05),但舒芬太尼组患者药物相关不良反应发生率显著低于丁丙诺非组( P<0.05)。结论舒芬太尼与丁丙诺非用于OMS术后自控镇痛、镇静效果无差异,但舒芬太尼药品不良反应低于丁丙诺非。%Objective To assess the clinical efficacy and safety of sulfentanyl versus buprenorphine for controlled intravenous analgesia on patients undergoing oral and maxillofacial surgery ( OMS) , as the patient controlled intravenous analgesia ( PCIA) way.Methods A total of 79 patients who received OMS were randomly divided into sulfentanyl group ( n=41 ) and buprenorphine group ( n =38 ).Patients in sulfentanyl group were given sulfentanyl 50 μg and patients in BP group were given buprenorphine 0.6 mg.Visual analogue scale ( VAS) and sedation scale were used to evaluate the pain control and sedation effects at the time points of 2, 8, 24 and 48 hours after operation.The vital signs and adverse events of the patients in two groups were recorded in 48 hours after operation.Results No difference was found between the two groups in the aspects of pain control, sedation effects and vital signs ( P>0.05).Adverse drug reactions were much more in buprenorphine group than those in sulfentanyl group ( P<0.05 ).Conclusion There were no differences in pain control and sedation effects

  16. 丁丙诺啡治疗海洛因依赖戒断综合征临床疗效分析%The efficacy of buprenorphine in heroin dependence withdraw-al syndrome

    Institute of Scientific and Technical Information of China (English)

    刘海波; 商田歌

    2014-01-01

    Objective To explore the efficacy of buprenorphine in heroin depend-ence withdrawal syndrome (HDWS) .Methods A total of 521 HDWS patients were randomly assigned to two groups ,research group was treated with sublingually buccal buprenorphine and intravenous drip of haloperidol+scopolamine ,and control group took orally methadone for 2 weeks .Efficacies of two groups were contrastively analyzed .Results Effective rate was respectively 95 .1% in research and 75 .1% in con-trol group ,the former significantly higher than the latter (χ2 =41 .99 ,P<0 .01) .Conclusion Sublingually buccal buprenorphine and intravenous drip of haloperidol + scopolamine have an evident effect compared with methadone replacement therapy in HAWS .%目的:探讨丁丙诺啡治疗海洛因依赖戒断综合征的临床疗效。方法将521例海洛因依赖戒断综合征患者随机分为两组,研究组舌下含服丁丙诺啡,静脉滴注氟哌啶醇+东莨菪碱治疗,对照组口服美沙酮治疗,观察2周。对两组临床疗效进行对比分析。结果研究组有效率为95.1%,对照组为75.1%,研究组有效率显著高于对照组(χ2=41.99,P<0.01)。结论舌下含服丁丙诺啡、静脉滴注氟哌啶醇+东莨菪碱治疗海洛因依赖戒断综合征疗效显著,优于美沙酮替代治疗。

  17. RP-HPLC法测定丁丙诺啡贴剂中药物的含量%Determining of Medicine Content in Buprenorphine Patches Using the RP-HPLC Method

    Institute of Scientific and Technical Information of China (English)

    曹建中

    2015-01-01

    Objective To explore significance of the RP - HPLC method for determination e medicine content of buprenorphine patches. Methods Chromatographic column and mobile phase were respectively 5 um Waters Symmetry C18 column and methanol- 0.02 mol · L-1 buf er salt solution, detection wavelength and velocity were respectively 286 nm and 1.0 ml min -1. Results 070919, 070920, 070921 batches of buprenorphine patch content levels were 0.156 mg·cm -2, 0.150 mg·cm-2, 0.149 mg·cm-2, RSD was 1.1%, 0.83%and 1.7%respectively. Conclusion RP -HPLC method for determining the content of medicine of buprenorphine patch was accurate, reliable and has high sensitivity, which is worthy of promoting.%目的:探讨RP-HPLC法测定丁丙诺啡贴剂中药物含量的意义。方法色谱柱和流动相分别为5 um的Waters Symmetry C18柱和甲醇-0.02mol•L-1的缓冲盐溶液,检测波长和流速分别为286nm和1.0ml•min-1。结果070919,070920,070921批号的丁丙诺啡贴剂的含量分别为0.156 mg•cm-2、0.150 mg•cm-2、0.149 mg•cm-2,RSD分别为1.1%、0.83%、1.7%。结论 RP-HPLC法测定丁丙诺啡贴剂中药物的含量准确可靠,具有较高的灵敏度,值得推广。

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  1. A ‘Missing Not at Random’ (MNAR) and ‘Missing at Random’ (MAR) Growth Model Comparison with a Buprenorphine/Naloxone Clinical Trial

    Science.gov (United States)

    McPherson, Sterling; Barbosa-Leiker, Celestina; Mamey, Mary Rose; McDonell, Michael; Enders, Craig K.; Roll, John

    2014-01-01

    Aims To compare three missing data strategies: 1) Latent growth model that assumes the data are missing at random (MAR) model, 2) Diggle-Kenward missing not at random (MNAR) model where dropout is a function of previous/concurrent urinalysis (UA) submissions, and 3) Wu-Carroll MNAR model where dropout is a function of the growth factors. Design Secondary data analysis of a National Drug Abuse Treatment Clinical Trials Network trial that examined a 7-day versus 28-day taper (i.e., stepwise decrease in buprenorphine/naloxone) on the likelihood of submitting an opioid-positive UA during treatment. Setting 11 outpatient treatment settings in 10 US cities. Participants 516 opioid dependent participants. Measurements Opioid UAs provided across the 4-week treatment period. Findings The MAR model showed a significant effect (B=−0.45, p <0.05) of trial arm on the opioid-positive UA slope (i.e., 28-day taper participants were less likely to submit a positive UA over time) with a small effect size (d=0.20). The MNAR Diggle-Kenward model demonstrated a significant (B=−0.64, p<0.01) effect of trial arm on the slope with a large effect size (d=0.82). The MNAR Wu-Carroll model evidenced a significant (B=−0.41, p<0.05) effect of trial arm on the UA slope that was relatively small (d=0.31). Conclusions This performance comparison of three missing data strategies (latent growth model, Diggle-Kenward selection model, Wu-Carrol selection model) on sample data indicates a need for increased use of sensitivity analyses in clinical trial research. Given the potential sensitivity of the trial arm effect to missing data assumptions, it is critical for researchers to consider whether the assumptions associated with each model are defensible. PMID:25170740

  2. The effectiveness of buprenorphine in combination with scopolamine and promethazine on conditioned place preference in SD rats%丁丙诺啡、东莨菪碱与异丙嗪联合使用对大鼠位置偏爱的影响

    Institute of Scientific and Technical Information of China (English)

    黄劲松; 王育红; 周旭辉; 王全升; 谌红献; 王绪轶; 向小军; 郝伟

    2008-01-01

    Objective To study the potentiality of psychological dependence of the so-called "1+1" compound (the elements are buprenorphine, scopolamine and promethazine). Methods One hundred and sixty-one male Sprague-Dawley rats were randomly assigned to 9 groups: buprenorphine, scopolamine, promethazine, buprenorphine plus scopolamine, buprenorphine plus promethazine, buprenorphine plus scopolamine and promethazine, scopolamine plus promethazine, morphine and saline groups respectively. All the 9 groups were trained by using the conditioned place preference(CPP) paradigm for 10 days. Results The rats in the five groups treated with buprenorphine alone or in combination with scopolamine/promethazine and morphine developed CPP. The time change spent by the rats in the buprenorphine plus scopolamine and promethazine group are (378.6±120.8)s , apparently longer than that by the rats in the buprenorphine group (302.2±133.9)s,but compared with that by rats in the morpine group(419.8±146.4)s, there is no significant difference(F=14.3,P=0.63). Conclusion The combination use of buprenorphine plus scopolamine and promethazine may act synergistically, and scopolamine and promethazine may enhance psychological dependence of buprenorphine.%目的 通过观察丁丙诺啡、东莨菪碱与异丙嗪三药联合使用(俗称"1+1")对大鼠位置偏爱的影响,探索"1+1"对实验大鼠的精神依赖性潜力.方法 161只雄性SD大鼠随机分成9组,分别采用丁丙诺啡、丁丙诺啡+东莨菪碱、丁丙诺啡+异丙嗪、丁丙诺啡+东莨菪碱+异丙嗪、东莨菪碱、异丙嗪、东莨菪碱+异丙嗪、吗啡、以及生理盐水等进行腹腔内注射,同时进行药物匹配CPP训练,共10d,比较各组大鼠训练前后以及训练后各组大鼠之间在药物训练侧(简称伴药侧)停留时间的差异,探索各处理因素的精神依赖性潜力及其差异.结果 注射吗啡、丁丙诺啡、丁丙诺啡+东莨菪碱、丁丙诺啡+异丙嗪、丁丙

  3. 舒芬太尼与丁丙诺啡在口腔外科术后镇痛的比较%Comparison of the postoperative analgesic efficacy between sufentanil and buprenorphine in patients undergoing oral surgeries

    Institute of Scientific and Technical Information of China (English)

    单东海; 黄旭平; 陈光娥; 王润莉; 李友安; 陶静; 方园; 郭翠

    2011-01-01

    目的 比较等效剂量丁丙诺啡与舒芬太尼在口腔外科术后镇痛的效果.方法 60例ASAⅠ或Ⅱ级口腔外科术病人依病历号奇偶数分为舒芬太尼组(S)与丁丙诺啡组(B),每组30例.两组均采用静脉自控镇痛(PCIA)给药,S组舒芬太尼50μg,B组丁丙诺啡0.6 mg,总量100 ml,首次负荷剂量4 ml.术后5、10、20及40 h行VAS疼痛与Ramsay运动评分,记录PCA有效按压次数及不良反应发生率.结果 两组VAS疼痛评分、Ramsay运动评分及PCA有效按压次数差异均无统计学意义,而不良反应发生率B组显著高于S组(P<0.05或P<0.01).结论 等效剂量舒芬太尼与丁丙诺啡用于口腔外科术后镇痛效果相当,但舒芬太尼不良反应发生率较低,更适合口腔外科术后镇痛使用.%Objective To compare the analgesic efficacy of equivalent buprenorphine and sufentanil in patients undergoing oral surgeries. Methods Sixty patients with ASA Ⅰ or Ⅱ scheduled for oral surgeries were divided into sufentanil group (S) and buprenorphine group (B) with 30 cases each according to the odd-even property of their enrollment IDs. Both groups received patient-controlled intravenous analgesia (PCIA), drugs in the group S was sufentanil 50 μg and buprenorphine 0.6 mg in the group B, total volume was 100 ml, loading bolus was 4 ml. The pain intensity was scored with visual analog scale (VAS), and motor was assessed with Ramsay scale at 5,10, 20 and 40 h after operation, and the effective PCA boluses and rate of side effects were recorded.Results No significant difference was observed between the two groups in the VAS and Ramsay scales and PCA boluses, but side effects in the group B were more than that of the group S (P<0. 05 or P<0. 01). Conclusion Equivalent sufentanil and buprenorphine produce similar analgesic efficacy,but the incidence of side effect of sufentanil is lower. So sufentanil is more suitable than buprenorphine for postoperative analgesia in oral surgeries.

  4. Outcomes of subcutaneous patient-controlled analgesia with buprenorphine combined with dezocine%丁丙诺啡复合地佐辛皮下患者自控镇痛的术后镇痛效果

    Institute of Scientific and Technical Information of China (English)

    刘玮玲; 陈海涛; 郁燕; 曹汉忠

    2016-01-01

    目的:探讨丁丙诺啡联合地佐辛皮下患者自控镇痛(PCA )的术后镇痛效果。方法择期手术患者643例实施皮下 PCA。镇痛药:S组(153例)为丁丙诺啡(0.034~0.036) mg/kg+0.75%左旋布比卡因20 m l+雷莫司琼0.6 m g ,用0.9%氯化钠稀释至150 m l;P组(490例)在上述配方中增加地佐辛10 mg。于术后1、24、48和72 h采用痛觉数字评价量表(NRS)评分和镇静程度(LOS )评分评估镇痛、镇静效果,记录相关不良反应发生情况。结果两组患者静息和活动状态下的NRS评分相仿,镇痛效果满意(P>0.05)。P组术后24 h的LOS评分低于S组(P<0.01)。P组丁丙诺啡用量少于S组[(0.027±0.007) mg/kg vs .(0.034±0.013) mg/kg](P<0.01)。S组镇痛泵夹管、恶心、呕吐、皮肤瘙痒及嗜睡发生率高于P组(P<0.05)。结论丁丙诺啡联合地佐辛皮下PCA镇痛效果满意,加用地佐辛可减少丁丙诺啡用量及其相关不良反应。%Objective To observe the efficacy of subcutaneous patient-controlled analgesia (PCA) with buprenorphine combined with dezocine .Methods Subcutaneous PCA was performed in 643 patients after elective surgeries .The analgesic solution in group S (153 cases ) consisted of buprenorphine 0.034~0.036 mg/kg ,0.75% levobupivacaine 20 ml and ramosetron 0.6 mg ,which was diluted with normal saline up to 150 ml .Dezocine 10 mg in group P(490 cases) was added into the analgesic solution of group S .The outcomes of analgesia and sedation were evaluated with numeric rating scale (NRS) and level of sedation (LOS) scoring at 1 ,24 ,48 and 72 hours during PCA .The analgesia-related adverse effects were recorded .Results The analgesia of both groups was all satisfactory and there was no significant difference in NRS scores at rest and active status between groups of P and S(P>0 .05) .The LOS score at 24 hours was significantly lower in group P than that in

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

    Science.gov (United States)

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

    2008-01-01

    SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional

  6. Determination of Related Substances and Content of Buprenorphine Hydrochloride Sublingual Tablet by HPLC%HPLC法测定盐酸丁丙诺啡舌下片的含量和有关物质

    Institute of Scientific and Technical Information of China (English)

    刘胜春; 赵学刚; 冯雅慧; 康海霞; 滑千里; 王乃浩

    2013-01-01

    OBJECTIVE:To establish a method for the determination of content and related substances in Buprenorphine hydrochloride sublingual tablets.METHODS:HPLC method was adopted.The determination was performed on Agilent Eclipse XDB C18 column with mobile phase consisted of 1% ammonium acetate (containing 0.1% acetic acid)-methanol (15∶85) at the flow rate of 1.0 ml/min.The column temperature was 40 ℃,and detection wavelength was 288 nm.RESULTS:Buprenorphine hydrochloride was separated with its impurities thoroughly,and its linear range were 0.004 04-0.040 4 mg/ml (r=0.999 9) with average recovery of 100.1% (RSD=0.33 %,n=9).The detection limit was 0.5 ng.CONCLUSIONS:The method is simple,sensitive and accurate.It could be applied for the determination of content and related substance in Buprenorphine hydrochloride sublingual tablets.%目的:建立同时测定盐酸丁丙诺啡舌下片含量和有关物质的方法.方法:采用高效液相色谱法.色谱柱为Agilent Eclipse XDB C18,流动相为1%醋酸铵溶液(含0.1%冰醋酸)-甲醇(15∶85),流速为1.0 ml/min,柱温为40℃,检测波长为288nm.结果:有关物质与主成分有较好的分离,盐酸丁丙诺啡检测质量浓度线性范围为0.004 04~0.040 4 mg/ml(r=0.999 9),检测限为0.5 ng,平均回收率为100.1%,RSD为0.33%(n=9).结论:本方法简便、灵敏度高、结果准确,可用于盐酸丁丙诺啡舌下片含量和有关物质测定.

  7. 右美托咪啶复合丁丙诺啡用于术后静脉自控镇痛的临床研究%Clinical study of buprenorphine be used for postoperative patient-control ed venous analgesia

    Institute of Scientific and Technical Information of China (English)

    王警卫; 张蓬勃; 蒋敢

    2013-01-01

    目的:探讨右美托咪啶复合丁丙诺啡用于术后静脉P C A的安全性及效果。方法60例择期大手术后患者随机分为右美托咪啶组和丁丙诺啡组两组(n=30),术后右美托咪啶组以右美托咪啶2μg/kg和丁丙诺啡6μg/kg加盐水至100ml行术后静脉PCA,丁丙诺啡组以丁丙诺啡12μg/kg加盐水至100ml行术后静脉PCA。观察并记录两组的镇痛效果及副作用并进行统计学分析。结果右美托咪啶组较单纯丁丙诺啡组镇痛效果更好,副作用少。结论右美托咪啶组复合丁丙诺啡用于术后静脉PCA效果确切,可减少丁丙诺啡用量和并发症。%Objective To study the security and efficacy of postoperative patient-control ed venous analgesia with dexmedetomidine al ying buprenorphine. Methods 60 patients undergoing a elective capital operation were randomly divided into tow groups: dexmedetomidine group (Group D) and buprenorphine group (Group B ) (n=30). Al the patients received either dexmedetomidine2μg/kg and buprenorphine 6μg/kg (Group D)or buprenorphine 12μg/kg (Group B) adding sodium chloride injection to 100ml used to postoperative patient-control ed venous analgesia. The effects on the pain and the side-effects were recorded to make a statistical analysis of. Results The analgesia effect in dexmedetomidine group was significant better than in buprenorphine group and the incidence of side-effects lower. Conclusion Dexmedetomidine al yingbuprenorphine can be used effectively and safely to postoperative patient-control ed venous analgesia. And it could decrease the dose of buprenorphine.

  8. Effects of Postoperative Analgesia with Buprenorphine on Cell Immunity in Patients with Gastric Cancer%丁丙诺啡术后镇痛对胃癌患者细胞免疫的影响

    Institute of Scientific and Technical Information of China (English)

    杨少勇; 张广华; 李锦成

    2011-01-01

    Objective: Surgical stress, including pain, may induce cell immunodepression and can even affect postoperative recurrence of cancer. The influence of the postoperative analgesic buprenorphine and fentanyl on the perioperative cell immunity of gastric cancer patients was compared. Methods: A total of 40 patients umdergoing surgery for gastric cancer were randomly divided into group B ( n = 20 ) with postoperative buprenorphine 0.3 μg·kg-1·h-1 as the experiment group and group F ( n = 20 ) with fentanyl 0.3 μg·kg-1·h-1 as the controls. Blood samples were collected before the surgery and at one day and three days after the surgery. T-cell subgroups CD3+, CD4+, CD8+, CD4+/CD8+, and NK cell were analyzed by flow cytometry, and the levels of cytokines INF-γ and IL-10 were determined using ELISA. Results: The surgical procedure and analgesic effects were similar between the two groups. There were reductions in the number of T cells and NK cells, and increased immunologic derangement, such as inflammatory cytokines, after the surgery. Compared with fentany 1, buprenorphine was beneficial to the recovery of inmnume indices. Conclusion: Surgical stress can induce changes in T lymphocyte subsets, NK cells, and cytokines. Buprenorphine is more beneficial to immune recovery than fentanyl when used as a postoperative analgesic.%目的:外科手术应激(包括疼痛)可抑制细胞免疫甚至促进恶性肿瘤术后转移复发.本研究比较丁丙诺啡与芬太尼术后镇痛对胃癌手术患者围术期细胞介导免疫功能的影响.方法:选取天津医科大学附属肿瘤医院2009年3月至2010年5月间40例胃癌切除术患者,随机分为丁丙诺啡组(A组20例)和芬太尼组(B组20例).A组使用丁丙诺啡背景输注剂量为0.3μg/(kg·h)行术后镇痛,追加剂量为0.3 μg/kg;B组使用芬太尼0.3 μg/(kg·h)行术后镇痛,追加剂量0.3 μg/kg.分别在术前、术后24 h、术后72 h取血进行T细胞亚群、NK细胞

  9. 丁丙诺啡超前镇痛对围术期应激反应和术后自控镇痛的影响%Preemptive analgesia effects of buprenorphine on stress responses and postoperative pain management

    Institute of Scientific and Technical Information of China (English)

    粱琪; 金梅生

    2012-01-01

    Objective: To study the preemptive analgesia effects of buprenorphine on postoperative pain management and stress responses. Methods: 60 patients underwent spinal surgery were randomly divided into two groups with 30 cases each, patients in group P were administrated with 0. 15mg buprenorphine intravenously 30 min before operation. In group C, patients were administrated with 0. 15mg buprenorphine at the end of operation. All patients received postoperative analgesia with patient controlled intravenously analgesia(PCIA). The analgesic effect was evaluated by VAS score at 2,6,12,24 and 48 h after operation. The concentration of Cor and CRP in serum a-head of anesthesia induction (TO) and at 6h (Tl) , 12h (T2) after operation was measured. Results: VAS scores of group P were significantly lower than those in group C at the different time point (P<0. 05). The concentrations of Cor and CRP in two groups were significantly increased at Tl, T2, respectively, as compared with values at TO. Compared to group C, the concentrations of Cor and CRP were significantly lower at Tl and T2 than those in group P (P<0. 05). Conclusion;Preemptive analgesia with buprenorphine can more effectively inhibit perioperatively stress responses and have effective postoperative analgesia.%目的:观察丁丙诺啡超前镇痛对围术期患者应激反应及自控镇痛的影响.方法:60例于全身麻醉下行脊柱内固定术患者,随机分为超前镇痛(P)组,于手术开始前30min静脉缓慢注射丁丙诺啡0.15mg;术后镇痛(C)组,于手术结束时静脉缓慢注射丁丙诺啡0.15mg.两组患者术后均行静脉自控镇痛.术后不同时间点观察视觉模拟评分(VAS).并于麻醉前(T0)、术后6h(T1)、术后12h(T2)分别测定皮质醇(Cor)、C反应蛋白(CRP).结果:P组与C组均能在术后产生良好的镇痛效果,P组在术后2、6、12、24、48h VAS评分显著低于C组(P<0.05),24h内各时点PCIA有效按压次数P组明显少于C组(P<0.05),与T0

  10. 关节腔内注射丁丙诺啡对膝关节镜术后疼痛的影响%ANALGESIC EFFECT OF LOW DOSE BUPRENORPHINE INJECTED INTRA-ARTICULARLY AFTER KNEE ARTHROSCOPY

    Institute of Scientific and Technical Information of China (English)

    刘凤梅; 张忠; 谢金瑞

    2004-01-01

    目的:观察关节腔内注射丁丙诺啡(Buprenorphine)对膝关节镜术后的镇痛效果,并与注射小剂量吗啡(Morphine)进行对比分析.方法:48例腰麻下行膝关节镜手术病人,双盲法随机均分为关节腔内注射Buprenorphine(B)、Morphine(M)与生理盐水对照组(C)3组,给药后记录术后2h、4h、8h、12h与24h患者屈膝关节90°状态下的视觉模拟评分(VAS)、对镇痛效果的满意度及术后8h按需注射哌替啶的量.结果: B、M组术后8h哌替啶平均使用量分别为9.4mg与28.1mg,较C组(51.6mg)明显减少;术后4h、8h、12h、24h 患者屈膝90° VAS评分B、M组均显著低于C组,B组亦较M组低,比较统计学差异均非常显著(P<0.001);术后镇痛满意度,B、M组较C组高,组间差异非常显著(P<0.001).结论: 关节腔内注射Buprenorphine可有效缓解膝关节镜术后疼痛,效果优于吗啡.

  11. 丁丙诺啡透皮贴剂的缓释镇痛作用%Buprenorphine transdermal patches as preemptive analgesia

    Institute of Scientific and Technical Information of China (English)

    任晓凤; 任娜娜; 张爱文; 哈承志; 郑颂浩; 刘宁; 徐建

    2015-01-01

    背景:丁丙诺啡透皮贴剂具有血药浓度稳定、镇痛时间长、呼吸抑制和其他不良反应较小的特点,被广泛应用于治疗中度到重度慢性疼痛.目的:观察丁丙诺啡透皮贴剂超前镇痛对腰椎后路椎弓根螺钉内固定治疗后疼痛的抑制效果.方法:选择拟行全麻下腰椎后路减压椎间植骨融合椎弓根螺钉内固定患者80例,其中男45例,女35例,年龄42-71岁,随机均分为两组,试验组于内固定治疗前2 d使用丁丙诺啡透皮贴剂,治疗后使用帕瑞昔布钠镇痛;对照组内固定治疗前给予与丁丙诺啡透皮贴剂相似的空白贴剂,治疗后使用静脉自控镇痛泵及帕瑞昔布钠镇痛.记录患者治疗后 6,12,24,48 h的目测类比评分、术后追加盐酸曲马多及盐酸哌替啶用量和不良反应,治疗后48 h患者满意度、引流量及血常规、血沉、C-反应蛋白水平.结果与结论:两组目测类比评分、术后追加盐酸曲马多及盐酸哌替啶用量、术后引流量、白细胞总数、血沉、C-反应蛋白水平比较差异无显著性意义(P > 0.05),试验组恶心呕吐及术后谵妄的发生率低于对照组(P 0.05). Postoperative incidence of nausea, vomiting and delirium was lower in the experimental group than the control group (P < 0.05), but the patient's satisfaction in the experimental group was better than that in the control group (P< 0.05). These findings indicate that buprenorphine transdermal patches have better preemptive analgesia for posterior lumbar surgery, with less adverse effects and better patient's satisfaction.

  12. The preemptive analgesia observation of buprenorphine hydrochloride for the lower uterine segment cesarean section%盐酸丁丙诺啡用于子宫下段剖宫产术的超前镇痛效果观察

    Institute of Scientific and Technical Information of China (English)

    刘晓燕

    2013-01-01

    Objective To observe the effect of preemptive analgesia with epidural buprenorphine on the postoperative pain for patients who were undergoing cesarean section.Methods Eighty ASA Ⅰ-Ⅱ patients underwent selective cesarean section under combined spinal epidural analgesia were randomly divided into two groups:preemptive analgesia group (group A,n =40) and control group (group B,n =40).Ten minutes before operation,the patients in group A received epidural injection of buprenorphine 0.15 mg and group B received normal saline 4 ml.The analgesia effect was assessed by visual analogue scale (VAS) at 4,8,12,24,48 hours after operation,side effects and effective pressing times of PCEA were also recorded.Results The VAS scores of group A were significantly lower than those of group B at 4,8 and 12 hours after operation(P <0.05).The incidence of side effects in the two groups was not significant(P >0.05).Conclusions Preemptive analgesia with epidural buprenorphine can provide satisfactory pain relief with no obvious side effects after lower uterine segment cesarean section.%目的 观察硬膜外腔注入盐酸丁丙诺啡用于子宫下段剖宫产术进行超前镇痛的效果.方法 将80例ASAⅠ~Ⅱ级择期子宫下段剖宫产术患者于硬-腰联合麻醉后随机分为两组:超前镇痛组(A组)40例,于手术切皮前10 min经硬膜外导管注入含盐酸丁丙诺啡0.15 mg的生理盐水4ml;对照组(B组)40例,于手术切皮前10 min经硬膜外导管注入生理盐水4ml,观察术后4、8、12、24、48h两组患者的视觉模拟评分(VAS),各时段自控硬膜外镇痛(PCEA)有效按压次数和不良反应.结果 术后4、8、12 h VAS评分A组明显低于B组(P<0.05),两组不良反应的发生率比较差异无统计学意义(P>0.05).结论 盐酸丁丙诺啡硬膜外超前镇痛能有效减轻子宫下段剖宫产术的术后疼痛.

  13. 布托啡诺复合小剂量氯氨酮用于剖宫产术后镇痛%Postoperative analgesia of cesarean section by buprenorphine hydrochloride combined with low ketamine

    Institute of Scientific and Technical Information of China (English)

    张勇; 邓燕

    2010-01-01

    目的 观察术后硬膜外持续泵入布托啡诺复合小剂量氯胺酮用于剖宫产术后镇痛的效果和对初乳及不良反应的影响. 方法选择40例Ⅰ~Ⅱ级择期或急症孕足月行剖宫产手术后的产妇,年龄23~35岁,随机分为两组.A组为观察组(n=20),用布托啡诺0.1 mg/kg+氯胺酮1 mg/kg+生理盐水至 100 ml持续泵入;B组为对照组(n=20),用0.15%罗哌卡因+0.004%芬太尼+0.1%地塞米松+生理盐水总量100 ml持续泵入.观察产妇术后各时间段的视觉模拟镇痛评分(VAS)、镇静评分、泌乳时间,并对术后产妇的总体感觉满意度进行评分.结果 A、B两组在泵药后4、12、24、48 h的VAS评分、镇静评分差异无统计学意义(P>0.05).A组产妇的总体感觉满意度高于B组(P0.05).结论 布托啡诺复合小剂量氯胺酮硬膜外持续泵入用于剖宫产术后镇痛可以提供满意的镇痛效果,而且也有利于术后产妇的恢复,并且不影响泌乳.%Objective To observe the analgesia effects of buprenorphine hydrochloride combined with low ketamine that continued to pump into epidural space,which were used to treat postoperative analgesia of cesarean section and to study their on colostrums and side reactions. Methods Forty patients were at age of 23-35 years and term pregnancy, who were 1-2 grade or emergency.These cases were randomly divided into two groups: group A(study group,n=20) and group B(control group,n=20),group A were treated with buprenorphine hydrochloride(0.1 mg/kg)+ ketamine(1 mg/kg)+NS(coming to 100 ml),which continued to pump into epidural space. Group B were treated with ropivacaine(0.15%)+febtanyl citrate(0.004%)+dexame thasone(0.1%)(coming to 100 ml), which continued to pump into epidural space.We observe postoperative parturients mimic analgesia VAS of visual sense,sedation VAS,lactigenous time and the total degree of satisfaction. Results There were no significant difference between group A and group B about mimic analgesia

  14. 舒芬太尼与丁丙诺啡对老年骨科患者术后镇痛效果比较%Comparison of postoperative analgesia effect between sufentanil and buprenorphine on elderly orthopedic patients

    Institute of Scientific and Technical Information of China (English)

    孟海; 王宁

    2014-01-01

    Objective To Compare effect of postoperative analgesia between equivalent dose of sufentanil and buprenor -phine on elderly orthopedic patients .Methods 60 cases of ASA Ⅱ-Ⅲ patients, aged 65~78 and ready for open reduction and internal fixation,were randomly divided into a sufentanil group (S) and a buprenorphine group (D),30 cases in each one.Both were treated with intravenous patient-controlled intravenous analgesia ( PCIA) administration ( group S sufentanil 100 μg;group D buprenorphine 1.2mg, total 100ml).After 5,10,20 and 40 hs respectively,VAS pain and Ramsay scores were graded .The number of effective PCA pressing and incidence of adverse reaction were accordingly recorded .Results The two groups had no significant statistic difference in terms of VAS pain score ,Ramsay score and PCA effective pressing number , but the incidence of adverse reactions in group D was significantly higher than that in group S (P<0.01).Conclusion Sufentanil and buprenorphine of equivalent dose ,if used after operation in elderly orthopedic patients ,have nearly equal analge-sia effect.But the adverse reaction rate of sufentanil is relatively lower .Thus it is more suitable for postoperative analgesia for elderly orthopedic patients .%目的:比较等效剂量舒芬太尼与丁丙诺啡对骨科老年病人患者术后镇痛的效果。方法选择60例ASAⅠ~Ⅱ级65~78岁的下肢骨折需行切开复位内固定术的患者,随机分为舒芬太尼组(S)和丁丙诺啡组(D),每组30例。2组均采用静脉自控镇痛(PCIA)给药,S组:舒芬太尼100μg,D组:丁丙诺啡1.2 mg,总量100 ml,术后5、10、20及40 h行VAS疼痛与Ramsay评分,记录PCA有效按压次数及不良反应发生率。结果2组VAS疼痛评分、Ramsay评分及PCA有效按压次数差异均无统计学意义,而不良反应发生率D组显著高于S组(P<0.01)。结论等效剂量舒芬太尼与丁丙诺啡用于骨科老年病人术后镇痛效

  15. 丁丙诺啡、曲马多用于雷米芬太尼全麻苏醒过渡期镇痛%Analgesic effect of buprenorphine comparied with tramadol on emergence after remifentanil-based general anesthesia

    Institute of Scientific and Technical Information of China (English)

    杨金凤; 常业恬; 周志国

    2005-01-01

    目的对照观察丁丙诺啡、曲马多用于雷米芬太尼全麻苏醒过渡期镇痛的安全性和有效性.方法120例全麻开胸手术患者分为三组,术毕关胸时停静脉麻醉,同时A组静脉给予丁丙诺啡3μg/Kg,B组曲马多2 mg/Kg,C组注射用水2 mL.观察三组患者用药前(t1)、用药后10′(t2)、30′(t3)、拔管时(t4)、拔管后5′(t5)、10′(t6)各时点血流动力学、血氧饱和度、呼末CO2分压、躁动评分(RS)、Ramsay镇静评分、术后身体舒适评分(BCS)、苏醒时间、PCA按压次数、剂量及不良反应.结果A、B两组较C组在苏醒期血流动力学更稳定;给药后10′开始A、B两组RS明显低于C组(P<0.01).给药后30′开始RSS A、B两组明显高于C组(P<0.01),且拔管时开始A组明显高于B组(P<0.01);BCS A、B两组明显高于C组(P<0.01);B组出汗明显多于A组或C组(p<0.05);PCA按压次数及用药量C组>B组>A组(P<0.01,P<0.05).结论丁丙诺啡、曲马多均可安全有效应用于雷米芬太尼全麻苏醒过渡期镇痛,其中丁丙诺啡效果更好,副作用更少.%[Objective] To observe the analgesic effect of buprenorphine comparied with tramadol on emergence.after remifentanil-based general anesthesia. [Methods] 120 patients undergoing elective thoracotomy under general anesthesia were randomly divided into 3 equal groups(group A, B, C), stoped general anesthesia when starting to shut off thorax and injected buprenorphine 3 μg/kg at group A, tramadol 2 mg/kg at group B, 0.9%NS 2 mL at group C.At three groups the HR, MAP, SPO2, PETCO2, RS, RSS at every time point(t1~t6) and BCS, the waken time, PCA bolus times, PCA dosage, side reactions were observed. [Results] There were more steadily hemodynamics at group A、B than group C; Since 10' after drugs given RS of group A、B were apparently lower than group C (P <0.01).Since 30' after drugs given RSS of group A、B were obviously higher than group C (P <0.01), and there were

  16. Efficacy of adjuvant analgesia with buprenorphine transdermal patch in early rehabilitation after total hip replacement%丁丙诺啡透皮贴剂辅助镇痛在全髋关节置换术后早期康复锻炼中的疗效

    Institute of Scientific and Technical Information of China (English)

    孙钰; 李小磊; 颜连启; 王静成; 王强; 陈岗; 熊传芝; 胡翰生

    2015-01-01

    目的 探讨使用丁丙诺啡透皮贴剂辅助镇痛在全髋关节置换(T HR)术后早期康复锻炼中的临床疗效.方法 51例T H R患者随机分为丁丙诺啡透皮贴剂辅助镇痛组(A组 ,25例)和对照组(B组 ,26例) ,比较两组术后镇痛效果和关节功能相关指标.结果 术后A组VAS疼痛评分低于B组 ,关节活动度、直腿抬高能力和髋关节功能评分的改善均优于B组( P0 .05).结论 T HR术后使用丁丙诺啡透皮贴剂辅助镇痛能有效减少术后早期康复锻炼时的疼痛 ,保证术后康复计划的顺利进行.%Objective To investigate the clinical efficacy of adjuvant analgesia with buprenorphine transdermal patch in the early rehabilitation after total hip replacement (THR) . Methods A total of 51 patients underwent THR was randomly divided into two groups of A (treated with buprenorphine transdermal patch ,25 cases) and B(blank control ,26 cases) .Postopera-tive VAS pain score and joint function-related indicators were compared between two groups .Results Postoperative VAS pain scores were lower in group A than those in group B(P0 .05) .Conclusion Use of buprenorphine transdermal patch can effectively alleviate pain in the early rehabilitation and assure the outcomes of rehabilitation exercise in the patients after THR .

  17. 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

    2015-09-15

    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.

  18. Efeitos cardiovasculares e neuroendócrinos do butorfanol e da buprenorfina em cães anestesiados pelo desfluorano Cardiovascular and neuroendocrine effects of butorphanol and buprenorphine in dogs anesthetized with desflurane

    Directory of Open Access Journals (Sweden)

    A.P. Souza

    2007-04-01

    Full Text Available Avaliaram-se os efeitos do butorfanol e da buprenorfina sobre variáveis cardiovasculares e neuroendócrinas em cães anestesiados com desfluorano, utilizando-se 30 cães adultos, machos e fêmeas, distribuídos em três grupos denominados grupo butorfanol (GBT, grupo buprenorfina (GBP e grupo-controle (GCO. A anestesia foi induzida com propofol (8mg/kgIV e nos animais intubados administrou-se desfluorano (1,5CAM. Após 30 minutos, nos cães do GBT, aplicou-se butorfanol (0,4mg/kgIM; nos do GBP, buprenorfina (0,02mg/kgIM; e nos do GCO, solução de NaCl a 0,9% (0,05ml/kgIM. Avaliaram-se: freqüência cardíaca; pressões arteriais sistólica, diastólica e média; débito cardíaco; pressão venosa central; cortisol; hormônio adrenocorticotrópico; noradrenalina; e glicose. As colheitas dos dados foram feitas aos 30 minutos após o início da administração do desfluorano (M0, 15 minutos após a administração do opióide ou placebo (M15, e a cada 15 minutos após M15 (M30, M45, M60 e M75. Para a avaliação neuroendócrina utilizaram-se os momentos M-30 (antes da administração dos fármacos, M0, M15 e M45. Na freqüência cardíaca houve diferença entre M0 e M15 (129 e 111bat/min em GBT, e entre M0 e M30 (131 e 112bat/min em GBP. Na pressão arterial média, a diferença foi entre M0 (86mmHg e todos os momentos que se seguiram (todos os valores foram menores que 72mmHg, em GBT. A pressão arterial diastólica foi menor em todos os momentos (The effects of butorphanol and buprenorphine on cardiovascular and neuroendocrine variables in dogs anesthetized with desflurane were studied. Thirty adult healthy, males and females, mongrel dogs were distributed in three groups denominated butorphanol group (BTG, buprenorphine group (BPG and control group (COG. The anesthetic induction was done using propofol (8mg/kg, IV, and immediately, the dogs were intubated and submited to desflurane anaesthesia (1.5 MAC. After 30 minutes, the BTG animals

  19. 丁丙诺啡透皮贴剂在释放度测定中桨碟法与转筒法的差异%Difference between methods of cylinder and paddle over disk used in the release test of buprenorphine transdermal patches

    Institute of Scientific and Technical Information of China (English)

    陈华; 毛睿; 李永庆; 南楠

    2011-01-01

    Objective : To compare the difference between the methods of cylinder and paddle over disk used in the release test of transdermal drug deliver system. Method:The cylinder and paddle over disk method were used respectively to test buprenorphine transdermal patches with the release media of 900 mL of 0. 9% sodium chloride solution. Agilent column which packed TC - C18 as solid phase (250 mm ×4. 6 mm,5 μm) and the mixture of acetonitrile and 0. 05 mol · L-1 potassium dihydrogen phosphate solution( 1: 1. 3) as mobile phase were adoptd. The flow rate was 1.0 mL · min-1. The column temperature was kept at 30 ℃ and the detective wave length was 220 nm.Result : The linear correlation of buprenorphine was observed from the concentrations of 0. 4 - 24 μg · mL-1 ( r =0. 9999) . The recovery of buprenorphine was 102. 1% . There were not difference between the methods of cylinder and paddle over disk used in the release test of transdermal drug deliver system in testing 20 mg of buprenorphine transdermal patches , while there existed difference in testing 5 mg and 10 mg of buprenorphine transdermal patches.Conclusion : There will be error when testing large area patch with paddle over disk method.%目的:对透皮贴剂释放度测定中转筒法装置与中国药典桨碟法装置进行比较.方法:分别使用转筒法装置与中国药典桨碟法装置对丁丙诺啡透皮贴剂的释放曲线进行测定,释放介质为0.9%的氯化钠溶液900 mL;以TC-C18为固定相的Agilent色谱柱(250mmx4.6 mm,5μm),0.05 mol·L-1的磷酸二氢钾溶液与乙腈的混合溶液(1.3:1)为流动相,流速为1.0 mL·min-1,柱温为30℃,检测波长为220 nm.结果:丁丙诺啡在0.4~24μg·mL-1范围内线性关系良好(r=0.9999),回收率为102.1%.对于20 mg规格的透皮贴剂采用不同方法所得的丁丙诺啡释放曲线不存在差异,而对于5 mg规格和10 mg规格则存在差异.结论:中国药典桨碟法装置在测量透皮贴剂的释放度时不

  20. 盐酸曲马多与丁丙诺啡抑制气管拔管期应激反应比较%Comparison on the effects of tramadoi and buprenorphine on reducing stress response from tracheal extubation

    Institute of Scientific and Technical Information of China (English)

    吴青华; 唐时荣; 王玲; 张中利; 胡百奇; 李澜; 马丹

    2008-01-01

    目的 观察并比较盐酸曲马多与盐酸丁丙诺啡对全身麻醉苏醒拔管期机体应激反应的影响.方法 90例ASA Ⅰ~Ⅱ级择期全麻下开腹手术患者,随机分为三组,每组30例.对照组(C组)缝皮前注射生理盐水5ml;盐酸曲马多组(T100)缝皮前静脉注射盐酸曲马多100mg;盐酸丁丙诺啡(buprenorphine)(B0.15)缝皮前静脉注射盐酸丁丙诺啡0.15mg.所有患者均给予异丙酚、维库溴胺、芬太尼作为全麻诱导用药,气管捅管后及手术中微泵持续静脉注射异丙酚,间断静脉注射维库溴胺维持全麻及肌松.分别于术前、拔管时和拔管后5min测量血压、心率和呼吸及血氧饱和度:并对患者清醒程度、血压、呼吸、肢体运动进行评估.记录拔管时躁动的发生率及清醒时间拔管时间.结果 C组血液动力学受影响较大,拔管时SBP和HR与术前比较有非常显著升高(P0.05),应激反应较小.拔管后5min各组各项指标基本恢复到术前水平.结论 盐酸曲马多和盐酸丁丙诺啡都能减轻全身麻醉苏醒拔管期机体应激反应,而且不良反应小.

  1. Study on Gradient Treatment of Heroin Addiction Withdrawal Syndrome by Methadone,buprenorphine and Lofexidine%美沙酮、丁丙诺啡、洛非西定梯度治疗海洛因依赖戒断症状的研究

    Institute of Scientific and Technical Information of China (English)

    谌益华; 郭田生; 阎翰; 何伯玲; 陈列

    2001-01-01

    目的探索美沙酮与丁丙诺啡加洛非西定梯度治疗海洛因依赖戒断症状的疗效。方法将150例海洛因依赖者分为三组,每组50例,进行为期12 d的戒毒治疗,研究组采用美沙酮(总量80~110 mg),丁丙诺啡(总量0.6~1.5 mg)。洛非西定(总量1.6 mg)治疗。美沙酮组(对照A组)采用美沙酮(总量139~175 mg)口服治疗;美沙酮加丁丙诺啡组(对照B组),采用美沙酮(总量90~120 mg),丁丙诺啡(总量0.9~2.3 mg)治疗。用统一的评定量表评定治疗结果。结果研究组在控制戒断症状、停药后无反跳现象、脱试率低、成瘾风险性小等方面均优于两个对照组。结论美沙酮加丁丙诺啡加洛非西定梯度治疗海洛因依赖戒断症状效果满意,是一种较好的戒毒方法。%ObjectiveTo study the therapeutic effects of gradient treatment in heroin addiction withdrawal syndrome (HAWS) blocked by methadone, buprenorphine plus lofexidine. Method150 heroin addicts were divided into 3 groups and detoxification treatment was carried out for 12 days in each group (50 addicts). Group 1(Therapy study): total P.O. doses of 80~110 mg methadone plus 0.6~1.5 mg buprenorphine (im) and 1.6 mg lofexidine (P.O.)were administered; Group 2(Control A):a total P.O. dose of 139~175 mg methadone was given; Group 3(Control B): a combined therapy of 90~120 mg methadone (P.O.) plus 0.9~2.3 mg buprenorphine (im) was designed. The effects of treatment were scored according to the uniform scale tables. Results The therapeutic effects of Group 1 were more effective than those of both control groups in controlling the withdrawal syndrome, and no rebound phenomenon was found after withdrawal. Conclusion The effects of methadone combined with buprenorphine and lofexidine is satisfactory in blocking HAWS.

  2. Effect of expression of P-glycoprotein in tumor tissue on analgesic efficacy of morphine and buprenorphine in advanced cancer patients with pain%P-糖蛋白表达对晚期癌痛病人吗啡或丁丙诺啡镇痛效果的影响

    Institute of Scientific and Technical Information of China (English)

    王军; 胡毅平; 李筱; 杨树东; 过林

    2010-01-01

    Objective To evaluate the effect of the expression of P-glycoprotein (P-gp) in tumor tissue on analgesic efficacy of morphine and buprenorphine in advanced cancer patients with pain. Methods One hundred and fifty advanced cancer patients with pain aged 51-64 yr weighing 54-65 kg were included in this study. The expression of P-gp was negative in the tumor tissue in 50 patients (group M1 and B1, n = 25 each) and positive in 100 patients (group M2 ,M3 ,and B2 ,B3, n =25 each). The PCA regimen for the 6 groups were listed in the table .Pain was assessed with VAS scores (0 = no pain, 10 = worst pain) and venous blood samples were taken for determination of blood morphine/buprenorphine concentrations at 4, 12, 24 and 48 h of PCIA. Results The six groups were comparable with respect to age, body weight, M/F sex ratio, types of cancer, baseline pain level and education. The analgesic efficacy of morphine and buprenorphine was better ( VAS scores were significantly lower)in P-gp expression negative patients (group M1 and B1 ) than in P-gp expression positive patients (group M2 and B2 ). Higher doses of morphine and buprenorphine provided better analgesic efficacy in P-gp expression positive patients in group M3 and B3 than in group M2 and B2. Plasma morphine and buprenorphine concentrations were comparable between group M1 , B1 and M2, B2 and were significantly higher in group M3 and B3 at each time point. Conclusion Positive P-gp expression in the tumor tissue can decrease the analgesic efficacy of morphine and buprenorphine in advanced cancer patients with pain.%目的 评价P-糖蛋白(P-gp)表达对晚期癌痛病人吗啡或丁丙诺啡镇痛效果的影响.方法 晚期癌痛病人150例,其中50例肿瘤组织P-gp表达阴性病人随机分为2组(n=25):M1组和B1组,100例肿瘤组织P-gp表达阳性病人随机分为4组(n=25):M2组、M3组、B2组和B3组.各组静脉注射负荷量后进行PCIA,M1组、M2组和M3组负荷量为吗啡2.5 mg,B1组、B2组和B3

  3. Buprenorphine During Pregnancy Reduces Neonate Distress

    Science.gov (United States)

    ... percentage of abnormal fetal presentations or need for Cesarean section, need for analgesia during delivery, or serious medical ... Adults Comorbidity Criminal Justice Drug Testing Drugged Driving Evidence-Based Practices Genetics HIV or AIDS Medical Consequences Mental ...

  4. Bupivacaína-buprenorfina vs. bupivacaína por vía caudal para analgesia postoperatoria en el paciente pediátrico en cirugía ortopédica Bupivacaine-buprenorphine vs. caudal bupivacaine as postoperative analgesia for pediatric patients undergoing orthopedic surgery

    Directory of Open Access Journals (Sweden)

    M. E. Flores Arana

    2011-04-01

    Full Text Available Introducción: el dolor postoperatorio en el niño constituye una entidad especial ya que en el influyen varios factores, por tanto es una experiencia no esperada por el niño y más difícil de tratar. Objetivos: evaluar y comparar la duración y calidad de la analgesia postoperatoria caudal así como la estabilidad hemodinámica y los efectos adversos entre bupivacaína-buprenorfina contra bupivacaína. Material y método: ensayo clínico controlado, prospectivo, longitudinal y comparativo; se estudian 40 pacientes de 1 a 7 años, para cirugía ortopédica bajo bloqueo caudal en el HTO No 21 de Monterrey, Nuevo León, de mayo 2009 a enero 2010. Se asignan en forma aleatoria a dos grupos: grupo A bupivacaína 0,25% 1,4 ml/kg y grupo B se le administrará bupivacaína al 0,25% 1,4 ml/kg adicionada de 1 μg/kg de buprenorfina. La intensidad del dolor postoperatorio se medirá a través del EVA, NIPS Y CRIES a las 2, 4, 6, 12 y 24 horas posteriores. Análisis estadístico: T de Student, U de Mann-Whitney; y prueba de Chi cuadrado. Resultados: el tiempo de administración del primer analgésico posterior a cirugía fue más corto en el grupo A (5,33 vs. 8,46 horas, con una diferencia a favor del grupo B (p Background: postoperative pain in children is a special entity and that the influence various factors, therefore it is an unexpected experience for the child and more difficult to treat. Objective: to evaluate and compare the length and quality of post-operative caudal analgesia and hemodynamic stability and adverse effects between bupivacaine-buprenorphine against bupivacaine. Material and methods: a controlled clinical trial, prospective, longitudinal, comparative study included 40 patients 1-7 years for orthopedic surgery under caudal block in the HTO No 21, of Monterrey, Nuevo Leon, from May 2009 to January 2010. Are assigned at random to two groups: group A 0.25% bupivacaine 1.4 ml/kg, and group B bupivacaine mL/kg 0.25% 1.4 mg/kg of

  5. Clinical Effects of Combined Buprenorphine Transdermal Patch and Pregabalin on Gerontic Postherpetic Neuralgia%丁丙诺菲透皮贴联合普瑞巴林治疗老年带状疱疹后神经痛的临床观察

    Institute of Scientific and Technical Information of China (English)

    何颖; 万成福; 宋涛

    2015-01-01

    目的:观察丁丙诺菲透皮贴联合普瑞巴林治疗老年带状疱疹后神经痛的临床效果。方法60例老年带状疱疹后神经痛患者随机分为试验组和对照组。试验组:丁丙诺菲透皮贴联合普瑞巴林;对照组:单独应用口服普瑞巴林。治疗8周后记录两组患者用药前、用药后2周、4周、8周的疼痛评分(visual analogue scale,VAS)、睡眠评分、普瑞巴林日剂量及不良反应发生率。结果两组患者治疗后VAS评分明显低于治疗前(P<0.01),治疗后4周及8周试验组VAS评分明显低于对照组(P<0.05);用药治疗后两组患者睡眠质量明显改善(P<0.05);联合应用丁丙诺菲透皮贴后可明显减少试验组普瑞巴林的用量(P<0.05);联合应用丁丙诺菲透皮贴可以显著减少普瑞巴林相关不良反应头晕、嗜睡的发生率(P<0.05)。结论丁丙诺菲透皮贴联合普瑞巴林对老年带状疱疹后神经痛患者的临床效果优于单独应用普瑞巴林,不良反应较小。%ObjectiveTo observed the effect of buprenorphine transdermal patches combined with pregabalin in gerontic patients with PHN.Methods60 patients were divided into experimental group and control group randomly. Patients of experimental group were treated with buprenorphine transdermal patches combined with pregabalin. The control group were orally administered pregabalin simply. The pain scores (VAS scores), sleep scores, doses of pregabalin and adverse reactions at each time point were recorded.ResultsThere were a signiifcant decline in VAS scores and sleep scores after treatment in 2 groups(P<0.01). Compared with the control group, the VAS scores and the dose of pregabalin were signiifcantly lower at 4, 8 weeks after treatment(P<0.05). The incidence of dizzy and drowsiness were higher in control group(P<0.05), but there were no signiifcant difference in the incidence of other side effects.ConclusionThe combination of buprenorphine transdermal

  6. Buprenorphine Transdermal Patch for Clinical Effect in the Treatment of Pain Associated with Spinal Degeneration%丁丙诺啡透皮贴用于脊柱退变相关疼痛治疗中的临床效果分析

    Institute of Scientific and Technical Information of China (English)

    代浩平; 应吕方; 李文平; 冯大雄

    2016-01-01

    Objective To observe the therapeutic effect of buprenorphine transdermal patch in the degenerative spine relat-ed pain in.Methods Randomly selected in January 2015 to December 2015 to our hospital was performed in 100 cases of patients with degenerative disease of the spine for the treatment of pain associated, were randomly divided into observation group and control group, each of 50 cases, the control group received tramadol hydrochloride for treatment, the observation group given buprenorphine transdermal treatment, the treatment in the two groups were observed before and after treatment, 24 h, 72 h, 7 d and 14 d resting state and activity state changes in pain and treatment of adverse reactions occurred. Re-sults After treatment 72 h, 7 d, 14 d, observe group in the resting state and active state of VAS score respectively (1.94 ± 0.78) scores, (2.52 ± 0.84 scores); (1.14 ± 0.54) scores, (1.85 ±0.77) scores; (0.81 ± 0.30) scores, (1.52 ±0.64) scores were significantly lower than those of the control group, and the difference is statistically significant. There was no significant dif-ference in the incidence of adverse reactions between the two groups. Conclusion Buprenorphine transdermal patch has good therapeutic effect on spinal degeneration related pain, and high safety.%目的:探讨丁丙诺啡透皮贴在脊柱退变相关疼痛中的治疗作用。方法随机选择2015年1—12月该院进行脊柱退变相关疼痛治疗的患者100例,随机分为观察组和对照组各50例,对照组给予盐酸曲马多进行治疗,观察组给予丁丙诺啡透皮贴进行治疗,观察两组患者治疗前、治疗后24 h、72 h、7 d以及14 d静息状态和活动状态下疼痛变化情况以及治疗中不良反应发生情况。结果治疗后72 h、7 d、14 d,观察组在静息状态和活动状态下的VAS评分分别为(1.94±0.78)分、(2.52±0.84)分;(1.14±0.54)分、(1.85±0.77)分;(0.81±0.30)分、(1.52±0.64)分均明显低于对照组,

  7. Clinical observation on combined buprenorphine transdermal patch and gabapentin in the treatment of diabetic peripheral neuralgia%加巴喷丁联合小剂量丁丙诺菲透皮贴治疗糖尿病周围神经痛的临床观察

    Institute of Scientific and Technical Information of China (English)

    何颖; 万成福; 宋涛

    2015-01-01

    Objective To observe the effect of buprenorphine transdermal patch combined with gabapentin in patients with diabetic peripheral neuralgia (DPN).Methods Sixty patients were divided randomly into experimental (A) and control (B) groups.Patients in group A were treated with buprenorphine transdermal patch combined gabapentin.Patients in group B were orally administered pregabalin only.The period of treatment was 8 weeks.The analgesic effect [visual analogue scale (VAS) scores] , sleep scores, daily doses of gabapentin, and adverse reactions were evaluated before treatment, and the 2nd weeks, 4th weeks and 8th weeks after treatment.Results The VAS scores of group A were significantly lower than group B at 4th weeks and 8th weeks after treatment [(2.8 ± 1.6) points vs (3.8 ± 1.5) points,(2.6 ± 0.5) points vs (3.5 ± 1.6) points, P < 0.05].The sleep scores of group A were significantly higher than group B (P < 0.01).The daily doses of gabapentin were significantly lower [(853.0 ± 349.8) mg vs (1575.8 ± 351.0) mg, (845.1 ± 342.7) mg vs (1434.2 ± 440.8) mg, (826.9 ± 298.5) mg vs (1389.8 ±356.6)mg, P < 0.05].The incidence of adverse reactions was significantly lower in group A (10.7% vs 25.9% , 10.7% vs 29.6% , P < 0.05).Conclusions The combination of buprenorphine transdermal patch and gabapentin is effective and safe for the patients with DPN.%目的 观察加巴喷丁联合小剂量丁丙诺菲透皮贴治疗糖尿病周围神经痛的临床效果.方法 60例糖尿病周围神经痛患者随机分为两组,对照组单独应用加巴喷丁,观察组加巴喷丁联合应用丁丙诺菲透皮贴.治疗8周后记录两组患者用药前、用药后2、4、8周的疼痛视觉模拟评分(VAS)、睡眠评分、加巴喷丁日剂量及不良反应发生率.结果 两组患者治疗后各时间点VAS评分明显低于治疗前(P<0.05);用药治疗后两组患者睡眠质量明显改善(P<0.01);观察组加巴喷丁的日剂量明显减少(P<0

  8. EPIDEMIOLOGICAL SURVEY ON BUPRENORPHINE ABUSE/USE IN 4 PROVINCES%四省市吸毒人群中丁丙诺啡药物滥用/使用的现况调查

    Institute of Scientific and Technical Information of China (English)

    连智; 孙桂宽; 刘锐克; 刘志民

    2010-01-01

    目的:调查丁丙诺啡(buprenorphine, Bup)在吸毒人群中滥用/使用的一般情况,评价其药物滥用与药物依赖性潜力.方法:自拟调查表,采取回顾性调查方法,于2006年1月-2006年7月在北京、云南、湖北和广东四地区的六所公安、司法强制戒毒机构,以戒毒所为单位,对符合调查对象条件的全体戒毒人员进行整群调查.结果:(1)使用率:在3254例被调查者中,27.4% (892例)不同程度、不同目的使用过Bup.使用率以云南个旧最高,北京地区次之.(2)使用目的及场所:用于"戒毒或临时替代"及"治疗戒毒后稽延性症状"分别占55.8%和40.6%;82例(9.2%)为"体验特殊精神效应(如欣快、飘等)".使用场所:主要是在"自己家中"(74.4%)和"戒毒所"(32.1%).(3)使用方式:47.7%的人有多药使用的经历.在有多药使用者中,采用Bup加镇静催眠药(三唑仑、安定)、氯丙嗪、东莨菪碱和异丙嗪分别占47.6%、5.8%、1.2%和10.1%.(4)使用频率:连续3 d以上使用经历者占36.1%,偶尔使用/间断使用占34.3%,有时连续、有时间断使用占29.5%.(5)主要来源:"医院或诊所"、 "戒毒机构"(或在戒毒机构中使用)、"药店"、"非正常渠道"(黑市)、"亲朋"分别占24.7%、38.7%、29.0%、18.4%,4.9%.(6)获得的难易程度:34.0%表示很容易得到,23.4%表示比较容易得到,12.5%表示比较困难得到,7.2%表示非常困难得到,22.8%表示不知道或不便回答.(7)使用后的感觉:46.0%应答者主诉使用后"有感觉",其中"快感"占33.8%,"幻觉"占26.6%,"飘感"占34.8%.这种特殊感觉"同海洛因不一样"占67.6%;"同海洛因一样,但比海洛因作用小"占25.8%;"同海洛因一样,但比海洛因作用强"占4.5%.以上主观效应是单一使用丁丙诺啡产生的占63.8%,合并用药产生的占36.2%.结论:本次调查有近30%的人不同程度和不同目的使用过丁丙诺啡;大多数Bup使用者属于医疗目的使用,但也有少数为"体验Bup特殊

  9. 中重度疼痛治疗药丁丙诺啡透皮贴剂的药理作用及临床评价%Pharmacology and clinical evaluation of transdermal patch of buprenorphine for relieving moderate to severe pain

    Institute of Scientific and Technical Information of China (English)

    徐建国; 王楠

    2013-01-01

    丁丙诺啡(buprenorphine)是阿片μ受体部分激动剂,对K,δ受体有弱的拮抗作用,具有高效镇痛而呼吸抑制、戒断症状、成瘾性等不良反应轻的特点.其皮肤渗透力强,血浆蛋白结合力高等药理学特性适于经皮给药.丁丙诺啡透皮贴剂具有丁丙诺啡的一般药理性能,且疗效稳定、作用持久,广泛应用于中重度疼痛治疗.美国FDA2010年7月1日批准其上市,本文就其药理作用、药动学、临床应用及不良反应进行综述.

  10. 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

  11. 丁丙诺啡舌下含片与美沙酮用于海洛因依赖门诊稽延期治疗的对照研究%Control study of buprenorphine sublingual tablets and methadone for heroin addicts on out patients treatment during recovery period

    Institute of Scientific and Technical Information of China (English)

    牛光胜; 杜万君; 王玉明; 郑杰

    2011-01-01

    目的 观察丁丙诺啡舌下含片与美沙酮用于海洛因依赖者稽延期治疗的价值。方法 对完成脱毒治疗患者,依先后次序交叉纳入观察组与对照组,分别给予丁丙诺啡舌下含片和美沙酮治疗6个月,观察操守时间,并于入组前后做焦虑量表评分。结果 丁丙诺啡舌下含片组比美沙酮组的操守时间长(P<0.01),焦虑评分低(P<0.05)。结论 丁丙诺啡舌下含片于海洛因依赖门诊稽延期治疗能更好地缓解焦虑情绪并延长操守时间。%Objective To observe the effect of buprenorphine sublingual tablets (Bup) and methadone for heroin addicts on out patients treatment during recovery period. Methods Heroin addicts who completed acute drug detoxification treatment were assigned in the order of cross to the observation group and control group. The observation group and the control group were treated with Bup and methadone, respectively for six months. Both groups were observed on the time of keeping heroin abstinence during the treatment and were assessed with Anxiety Scale before and after Bup or methadone treatment. Results Bup group kept abstinence from heroin longer than methadone group ( P <0.01 ) ,and had lower anxiety scores( P <0.05). Conclusion Bupernorphine sublingual tablets used for out patients at recovery period could better alleviate heroin addicts' anxiety and prolong their abstinence time.

  12. 丁丙诺啡透皮贴剂治疗膝关节骨性关节炎的效果和安全性评价%Evaluation of the efficacy and safety of buprenorphine transdermal patches in patients with knee osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    尹一然; 鲁晓波; 陈歌

    2016-01-01

    目的:观察丁丙诺啡透皮贴剂治疗骨性关节炎的临床疗效和安全性。方法:将90例膝关节关节骨性关节炎患者随机分为2组:试验组45例,使用5 mg药物含量丁丙诺啡透皮贴剂贴于上臂外侧,1贴/7 d;对照组45例,采用口服塞来昔布20 mg,2次/d。两组疗程均为2周。判断指标为用药前后患者自我评价、医生对患者情况评价、患者关节压痛情况以及骨关节炎指数(WOMAC)评分,同时观察患者可能发生的不良反应。结果:药物使用两周后,试验组患者自评视觉模拟评分(VAS)试验前为(68±14),试验后为(39±12),差异有统计学意义(P 0.05). Conclusion: Buprenorphine transdermal patches is at least as effective as celecoxib in treating knee osteoarthritis.

  13. Clinical effects of buprenorphine transdermal patch combined with gabapentin on gerontic postherpetic neuralgia%加巴喷丁联合小剂量丁丙诺菲透皮贴治疗老年带状疱疹后神经痛的临床观察

    Institute of Scientific and Technical Information of China (English)

    何颖; 刘妍; 万成福; 宋涛

    2015-01-01

    目的 观察加巴喷丁联合小剂量丁丙诺菲透皮贴治疗老年带状疱疹后神经痛( PHN)的临床效果. 方法 60例PHN患者随机分为对照组和试验组. 对照组:单独应用加巴喷丁;试验组:加巴喷丁联合应用丁丙诺菲透皮贴5 mg,每7天贴敷1次. 根据患者疼痛情况逐渐调整加巴喷丁剂量,直至患者疼痛评分4 ) gradually. The maximum dose of gabapentin was 1 800 mg/d in both groups. The VAS scores,sleep scores,doses of gabapentin and adverse reactions at each time point were recorded. Results There was a significant decline in VAS scores and sleep scores after treatment in the two groups ( P<0. 01). Compared with control group,the VAS scores and the doses of gabapentin were significantly lower at 4,8 weeks after treatment (P<0. 05). The incidence of dizzy and drowsiness were higher in control group (P<0. 05),but there was no significant difference in the incidence of other side effects. Conclusion The combination of buprenor-phine transdermal patches with gabapentin is effective and safe for the gerontic patients with PHN.

  14. 硫酸吗啡控释片联合丁丙诺啡舌下含片用于中重度癌痛患者的疗效观察%Efficacy of combination of morphine sulfate controlled-release tablet and buprenorphine sublingual tablet in moderate to severe cancer pain patient

    Institute of Scientific and Technical Information of China (English)

    周亮; 孙亮; 王海燕; 董彦鹏; 武林鑫; 孙莉

    2015-01-01

    目的 观察硫酸吗啡控释片联合丁丙诺啡治疗中重度癌痛的临床疗效,探讨临床合理治疗晚期癌痛的有效方法. 方法 选择止痛门诊的癌症晚期疼痛患者,视觉模拟评分(visual analog scale,VAS)>3分,用单一吗啡控释片治疗后,VAS评分仍>3分,止痛效果欠佳的150例患者,采用随机数字表法分为两组,每组75例:吗啡控释片组(M组),使用单一硫酸吗啡控释片;吗啡控释片联合丁丙诺啡组(MB组),采用硫酸吗啡控释片+丁丙诺啡.通过对两组止痛效果、副作用、生活质量及患者对镇痛治疗满意度的比较,探讨联合用药治疗晚期癌痛的优点和可行性. 结果 联合用药较单一用药镇痛效果显著,中重度VAS评分例数明显减少(M组/MB组:中度26/10,重度4/0)(P<0.05);恶心、呕吐等副作用的发生例数明显减少(M组/MB组:恶性呕吐12/2,嗜睡4/2,呼吸抑制9/4,排尿困难8/3,便秘8/4)(P<0.05);患者对镇痛效果的满意度明显提高(M组/MB组:很满意10/14,满意36/47)(P<0.05);生活质量明显改善[M组/MB组:睡眠(5.5±1.2)/(4.6±0.7),情绪(5.4±0.5)/(4.6±1.2),日常活动(5.1±0.4)/(4.9±0.5),社交活动(5.5±0.4)/(4.8±1.6)](P<0.05).结论 硫酸吗啡控释片联合丁丙诺啡治疗晚期癌痛可以提高镇痛效果,降低副作用的发生率,提高患者的生活质量.%Objective To investigate the efficacy of combination of morphine sulfate controlled-release tablet and buprenorphine sublingual tablet in patients with moderate to severe cancer pain,and explore effective analgesic therapies for advanced cancer pain patients.Methods One hundred and fifty patients with advanced cancer pain whose visual analog scale (VAS) scores were greater than 3 points and VAS scores were still greater than 3 points after treated with controlled-release tablet of morphine alone were randomly divided into two groups (n=75):controlled-release morphine tablet alone group (M group) and conbination use

  15. Therapeutic Effect of Transdermal Patch of Buprenorphine Combined with Gabapentin on Pain from Spinal Degenerative Disease%丁丙诺啡透皮贴联合加巴喷丁用于脊柱退变相关疼痛的临床观察

    Institute of Scientific and Technical Information of China (English)

    邓伟; 邓晖; 王磊; 邢伟

    2015-01-01

    目的:观察丁丙诺啡透皮贴联合加巴喷丁胶囊对老年脊柱退行性病变相关疼痛,尤其神经病理性痛的疗效。方法将河南省安阳市人民医院在2013年12月~2014年12月期间明确诊断为脊柱退变引起的疼痛患者54例随机分成两组:A组(n=27)采用丁丙诺啡透皮贴联合加巴喷丁胶囊进行药物治疗,B组(n=27)采用经典非甾体消炎镇痛药(NSAIDs)进行治疗;同时对两组患者进行健康宣教和康复训练。用简化麦吉尔疼痛问卷(SF‐MPQ)评价两组患者14 d内疼痛评估指数(PRI);记录静息和运动时的疼痛强度评分(VAS),监测用药前、用药后7 d患者的血浆炎症因子(血浆P物质、C反应蛋白、IL‐6)浓度,并观察用药后出现的恶心、呕吐、头晕、呼吸抑制等不良反应。结果用药24 h后两组PRI、VAS出现差异(均 P<0.05),血浆炎性因子在用药7 d后出现差异(均 P<0.05),两组患者均无呼吸抑制。A组曾出现5例头晕、嗜睡,与加巴喷丁有关;B组出现13例恶心、呕吐,21例盘源性神经病理性痛症状无法缓解。结论丁丙诺啡透皮贴联合加巴喷丁胶囊在镇痛效果、不良反应和依从性方面占优势,对脊柱退变相关神经病理性痛症状控制针对性强。%Objective To evaluate the therapeutic effect of transdermal patch of buprenorphine combined with gabapentin on pain ,especially ,neuropathic pain related to spinal degenerative disease.Methods Totally ,54 patients who were diagnosed as spinal degenerative disease in our hospital from December 2013 to December 2014 for treating pain were enrolled in our study and randomly divided into two groups :group A(n=27) ,patients were treated with transdermal patch of buprenorphine com‐bined with gabapentin ;group B(n=27) ,patients were treated with conventional NSAIDs.At the same time ,patients in the two groups received training of health

  16. The pharmacological preconditioning of nitroglycerin and buprenorphine used in combination against myocardial ischemia in rats%硝酸甘油与丁丙诺啡合用抗大鼠心肌缺血的药理性预适应研究

    Institute of Scientific and Technical Information of China (English)

    孔雁军; 刘艳霞; 娄建石

    2003-01-01

    目的研究硝酸甘油(nitroglycerin, NG)和丁丙诺啡(buprenorphine, BU)两药单用及合用抗心肌缺血的药理性预适应的延迟相保护作用.方法♂大鼠分为5组,Sham组静注等容积NS,DIP组行肠系膜上动脉结扎10 min处理,BU组静注盐酸丁丙诺啡1.0 mg*kg-1,NG组静注NG 0.3 mg*kg-1,B+N组分别给上述剂量BU和NG.24 h后各组行30 min冠脉结扎缺血/2 h再灌.各组均于术后15 min、缺血期和再灌期连续监测心率、血压、ST-段和心律失常情况;测定缺血30 min和再灌2 h血浆LDH、CK;再灌2 h后行HE染色与TTC染色定性和定量测定心肌坏死情况.结果与Sham组比较,DIP组可降低心脏缺血期ST段抬高幅度(P<0.01),推迟VPC出现时间,缩短持续时间(P<0.05),降低二联律发生率,降低缺血期血浆LDH水平(P<0.05),缩小心肌坏死面积(P<0.05).BU组可降低心脏缺血期ST段抬高幅度(P<0.01),推迟VPC出现时间,缩短持续时间(P<0.05),降低二联律和室颤的发生率(P<0.05),降低缺血期血浆LDH水平,缩小心肌坏死面积(P<0.05).NG组可降低ST段抬高幅度(P<0.01),缩短VPC持续时间(P<0.01),降低二联律、室速和室颤的发生率(P<0.01),明显缩小心肌坏死面积(P<0.01),减轻心肌坏死程度.B+N组可明显降低ST-段抬高幅度(P<0.01),推迟VPC出现时间,缩短持续时间(P<0.01),降低二联律、室速、室颤的发生率,缩小心肌坏死面积(P<0.01),降低血浆LDH水平(P<0.01).B+N组与BU组或NG组比较,在推迟室早出现时间、持续时间和发生率方面差异有显著性(P<0.05).结论两药具有明显的抗大鼠心肌缺血的药理性预适应延迟相心脏保护作用,合用优于单用.

  17. The pharmacological preconditioning of nitroglycerin and buprenorphine used in combination against myocardial ischemia in rats: early cardioprotection%硝酸甘油与丁丙诺啡合用抗大鼠心肌缺血的药理性预适应研究:早期心脏保护作用

    Institute of Scientific and Technical Information of China (English)

    娄建石; 梁会旭; 刘艳霞

    2003-01-01

    目的研究硝酸甘油(nitroglycerin, NG)和丁丙诺啡(buprenorphine, BU)两药单用及合用抗心肌缺血的药理性预适应的早期保护作用.方法♂ Wistar大鼠分为5组,行30 min冠脉结扎缺血/2 h再灌.各组手术之前行不同处理,Sham组静注等容积NS,早期预适应(EIP)组行3个循环5 min缺血/5 min再灌预处理,BU组静注盐酸丁丙诺啡1.0 mg*kg-1,NG组静注NG 0.3 mg*kg-1,B+N组分别给上述剂量BU和NG.各组均于给药前、后及缺血和再灌期连续监测心率、血压、ST-段和心律失常情况;测定缺血30 min和再灌2 h血浆LDH、CK;再灌2 h后行心肌HE染色与TTC染色定性和定量测定心肌坏死情况.结果与Sham组比较,BU组明显推迟缺血期心律失常出现时间,缩短室早持续时间(P<0.01),降低二联律和室速发生率;降低缺血期血LDH(P<0.05)水平,缩小心肌坏死面积(P<0.01),但未降低血CK水平和缺血期ST-段抬高.与Sham组比较,NG组明显降低缺血和再灌期ST段(P<0.01)、降低缺血期血LDH(P<0.01)和CK(P<0.05)水平,缩小心肌坏死面积(P<0.01),减轻HE染色心肌坏死程度,缩短心律失常持续时间.药物合用后与Sham组比较,不仅明显降低缺血和再灌期ST段、血LDH和CK水平,缩小心肌坏死面积(P<0.01),减轻HE染色心肌坏死程度,还推迟了心律失常出现时间(P<0.01),缩短持续时间(P<0.01),降低发生率,各项指标达到EIP组水平.B+N组与BU组或NG组比较,在推迟室早出现时间、持续时间、发生率和IS/AAR有显著差异(P<0.05).结论两药具有明显的抗大鼠心肌缺血的药理性预适应早期心脏保护作用,合用优于单用.

  18. Facts about Buprenorphine for Treatment of Opioid Addiction

    Science.gov (United States)

    ... Treatment may include medication. Medication-assisted treatment is treatment for addiction that includes the use of medication along with ... Counseling can help. Medication is one part of treatment for opioid addiction. For many people, another important part is counseling : ...

  19. 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.

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

    Lifescience Database Archive (English)

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

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

    OpenAIRE

    Chen HH; Chiang YC; Yuan ZF; Kuo CC; Lai MD; Hung TW; Ho IK; Chen ST

    2015-01-01

    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,...

  2. 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

    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...

  3. 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.

  4. 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.

  5. ANALGELSIC EFFECT OF BUPRENORPHINE IN AN EXPERIMENTAL MODEL OF PAINFUL DIABETIC PERIPHERAL NEUROPATHY

    OpenAIRE

    Chiorazzi, A; Carozzi, V; Canta, A; Meregalli, C.; Oggioni, N; Bianchi, R; Lombardi, R.; Camozzi, F; Lauria, G.; Cavaletti, G

    2008-01-01

    AIM: Diabetic peripheral neuropathy (DPN) is a complication of inadequately treated diabetes mellitus leading to sensory loss and neuropathic pain. DPN of different severity is present during in the majority of diabetic patients. Although most patients with DPN do not have pain, a clinically-relevant proportion of them complain of chronic painful symptoms that affect their quality of life, disrupt sleep, and can lead to depression. Recent advances in understanding DPN-associated pain are like...

  6. Improved memory for reward cues following acute buprenorphine administration in humans

    NARCIS (Netherlands)

    Syal, Supriya; Ipser, Jonathan; Terburg, David; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Bos, Peter A.; Montoya, Estrella R.; Stein, Dan J.; van Honk, Jack

    2015-01-01

    In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are d

  7. Advance in research of buprenorphine%丁丙诺啡的研究进展

    Institute of Scientific and Technical Information of China (English)

    焦艳; 翟光喜

    2015-01-01

    丁丙诺啡是半合成的阿片生物碱蒂巴因的衍生物,具有阿片受体激动剂和拮抗剂活性,临床上用于镇痛和阿片类依赖的维持治疗.本文就近年来丁丙诺啡的药理学研究、制剂学及体内分析方法方面的研究进行介绍.

  8. HPLC determination of buprenorphine in buprenorphine patches and its skin permeation behavior in vitro%HPLC法测定丁丙诺啡贴剂中药物的含量及其体外透皮释放量

    Institute of Scientific and Technical Information of China (English)

    许丽丽; 杜洪光; 王刚; 陆玉成; 谢昀; 张恩宏

    2009-01-01

    目的:建立丁丙诺啡贴剂中丁丙诺啡含量和体外透皮释放量的HPLC分析方法.方法:采用Waters Symmetry(R)C18(150mm×4.6 mm,5μm)色谱柱,流动相:甲醇-0.02 mol·L-1缓冲盐溶液(20 mmol·L-1醋酸铵溶液,氨水调节pH=4.5)(50:50),流速1.0 mL·min-1,检测波长286 nm.结果:在2.0~10.0μg·mL-1的浓度范围内旱良好的线性关系,r=0.9999.方法的平均回收率在99.9%~100.3%;日内和日间RSD分别小于0.38%和0.98%.最小检测浓度为0.2μg·mL-1.结论:该方法准确、可靠、灵敏度高,适用于丁丙诺啡贴剂的定量榆测.

  9. Behavioural Outcomes of Four-Year-Old Children Prenatally Exposed to Methadone or Buprenorphine: A Test of Three Risk Models

    Science.gov (United States)

    Konijnenberg, Carolien; Lund, Ingunn Olea; Melinder, Annika

    2015-01-01

    It is still under debate whether the reported effects of opioid maintenance therapy (OMT) on child behaviour are a direct effect of prenatal exposure, or whether other factors are involved. This prospective cohort study investigated three models: the teratogenic risk model, the maternal risk model, and a combined risk model in a group of 35…

  10. Determination of buprenorphine by thin layer chromatography%薄层色谱法检测丁丙诺啡

    Institute of Scientific and Technical Information of China (English)

    刘冬娴; 贺江南

    2007-01-01

    目的 建立丁丙诺啡薄层色谱分析方法.方法 血浆先用乙醇除蛋白,尿、水剂样品则直接加pH10.8Na2CO3/NaHCO3缓冲溶液后用氯仿提取,提取液经净化浓缩后进行薄层色谱分析.结果 选定碘化铋钾作显色剂,丁丙诺啡薄层色谱分析展开效果较好,检测灵敏度为0.5μg,血浆、尿液和水剂中检出限分别为0.7、0.7和0.6μg/ml.结论 该方法适用于涉毒案件中丁丙诺啡的日常检验.

  11. Research Progress of Buprenorphin Hydrochloride%盐酸丁丙诺啡的研究进展

    Institute of Scientific and Technical Information of China (English)

    储靖; 陈宁

    2009-01-01

    盐酸丁丙诺啡为部分阿片激动剂.它对μ受体有很大亲和力,并缓慢释放,镇痛作用强且持久.它能有效减轻术中及术后疼痛与各种急慢性疼痛,成瘾性很低,同时对阿片成瘾治疗有效.用药后,血浆药物峰值浓度在静脉注射后30 min出现,半衰期约3 h,血浆蛋白结合率约为96%.经静脉注射常用剂量为0.15~0.3 mg.不良反应少,主要表现有嗜睡、头晕、恶心和(或)呕吐.

  12. 丁丙诺啡的药理学研究进展%Pharmacological feature of buprenorphine: research advances

    Institute of Scientific and Technical Information of China (English)

    张开镐

    2010-01-01

    丁丙诺啡是半合成的阿片生物碱蒂巴因的衍生物,对阿片受体家族的4个成员μ、κ、δ和ORL-1都有一定的亲和力,但内在活性不同;同时,与这些受体具有缓慢结合与分离的动力学特征,决定了它有一些不同于其他μ阿片受体激动剂的药理特性.本文介绍近期对丁丙诺啡药理特性进一步研究的资料,以期对丁丙诺啡临床应用的有效性和安全性有新的认识.

  13. Analysis of buprenorphine by using TLC and GC/MS%丁丙诺啡的检验

    Institute of Scientific and Technical Information of China (English)

    李常明; 匡荣凡; 陈文斌

    2005-01-01

    目的建立检验丁丙诺啡的方法.方法用气质联用仪与高效TLC法进行定性分析.结果丁丙诺啡在展开剂苯:正己烷:二乙胺=40:10:10时,Rf值为0.55;环己烷:丙酮=1:1时,Rf值为0.35;质谱图保留时间为19.617min.结论本方法操作简便、准确,适合办案.

  14. 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

    ), 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......-IV-TR, and the Symptoms 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...

  15. 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.

  16. 血浆中丁丙诺啡提取方法研究%A Study on Extraction Method of Buprenorphine in Plasma

    Institute of Scientific and Technical Information of China (English)

    刘冬娴; 贺江南

    2007-01-01

    报道了液相萃取法、固相萃取法提取血浆中丁丙诺啡的方法.血浆中添加丁丙诺啡,液相萃取时调pH至7用三氯甲烷提取、固相萃取时调pH至10.8用401有机担体作吸附剂、用三氯甲烷作洗脱剂,GC/NPD法进行检测.液相萃取血浆中丁丙诺啡萃取率可达85.8%以上,固相萃取血浆中丁丙诺啡萃取率可达87.7%以上.该提取方法萃取率高,可用于血浆中丁丙诺啡的提取.

  17. Clinical observation of domestic Buprenorphine in treatment of cancer ache%国产丁丙诺啡用于癌痛的临床观察

    Institute of Scientific and Technical Information of China (English)

    潘霞云; 朱明瑶; 潘道波; 马明祥; 陈安基

    2003-01-01

    目的观察国产丁丙诺啡用于癌症的止痛效果.方法对42例中晚期癌症患者舌下含服丁丙诺啡每日4次,连续服药7d,观察用药前后疼痛评分(VAS),疼痛缓解程度及镇静效果,生活质量评价等.结果疼痛明显缓解32(42)例,镇静评分3分以上者为31(42)例,副作用总发生率为55.1%.结论国产丁丙喏啡舌下含片对晚期癌症具有较好的镇痛效果.

  18. 新型滥用药物丁丙诺啡分析方法研究进展%The development of research on determination methods of buprenorphine

    Institute of Scientific and Technical Information of China (English)

    张忠辉; 王瑞花; 于忠山

    2010-01-01

    本文介绍了丁丙诺啡的提取及检测现状,比较了液-液提取、固相萃取、酶消化、衍生化等前处理方法的优劣和TLC、GC、GC/MS以及LC、LC/MS等不同分析方法的应用情况.

  19. 盐酸丁丙诺啡术后镇痛的临床观察%Clinical Observation on Postoperative Analgesia of Buprenorphine

    Institute of Scientific and Technical Information of China (English)

    苏永军; 方惠; 秦波; 曹美芬

    2006-01-01

    目的探讨盐酸丁丙诺啡含片用于术后疼痛的镇痛效果.方法40例四肢、下腹部手术的病人随机分为2组,术后分别给予盐酸丁丙诺啡含片0.4 mg舌下含化或哌替啶片100 mg口服,给药后6 h内,记录各观察点疼痛程度差值、疼痛缓解度及药物不良反应.结果盐酸丁丙诺啡含片0.4 mg与哌替啶100 mg有相同的镇痛效果,中等度以上疼痛缓解率达90%以上,镇痛时间平均为7.5 h.结论盐酸丁丙诺啡含片有较好镇痛效果,可作为术后镇痛的选择.对呼吸、血压、血氧饱和度无明显的影响,不良反应主要是头晕、恶心、呕吐.

  20. Determination of Buprenorphine by Gas Chromatography with Microwave Derivation%微波照射衍生化气相色谱法检测丁丙诺啡

    Institute of Scientific and Technical Information of China (English)

    刘冬娴; 贺江南

    2007-01-01

    报道了微波照射衍生化气相色谱法检测丁丙诺啡的最佳条件和方法.丁丙诺啡,加入N,O-双(三甲基硅烷基)三氟乙酰胺试剂,于微波炉560W衍生化3min,GC/NPD检测,线性范围为0.2-80 μg/mL,检出限10ng/mL.该方法灵敏度高,稳定性好,操作简单,可用于涉毒案件中丁丙诺啡的检验.

  1. A Study in Extraction Method of Buprenorphine in Urine%尿液中丁丙诺啡的提取方法

    Institute of Scientific and Technical Information of China (English)

    刘冬娴; 贺江南

    2007-01-01

    目的 建立尿液中丁丙诺啡提取方法.方法 尿液加pH 7.0缓冲液后,用三氯甲烷进行液相萃取或加pH 10.8缓冲液后,用401有机担体作吸附剂、三氯甲烷作洗脱剂进行固相萃取,GC/NPD法检测.结果 尿液中丁丙诺啡液相萃取萃取率可达86.6%以上,固相萃取可达83.0%以上.结论 两种提取方法萃取率高,可用于尿液中丁丙诺啡的提取.

  2. 国产丁丙诺啡PICA术后镇痛的临床应用%Clinical Application of PICA with Homemade Buprenorphine on Postoperative Analgesia

    Institute of Scientific and Technical Information of China (English)

    李锦成; 张凤文

    2003-01-01

    目的:观察国产丁丙诺啡静脉病人自控镇痛(PICA)术后镇痛的疗效.方法:30例肿瘤患者术后应用伟氏PICA泵,每次0.5ml,含丁丙诺啡0.03~0.06mg,并观察镇痛效果、时间和不良反应.结果:30例患者采用丁丙诺啡PICA镇痛均取得满意疗效.平均镇痛时间1.5~2小时.所有病例均未出现眩晕、嗜睡等严重不良反应,2例出现呕吐,1例出现恶心.结论:国产丁丙诺啡PICA术后镇痛方法简单、疗效满意.

  3. Clinical study of methadone hydrochloride combined with buprenorphine hydrochloride in the treatment with gradually reducing dosage of heroin addicts, compared with ordinary dosage of buprenorphine hydrochloride%美沙酮与丁丙诺啡联合梯度递减治疗海洛因依赖者疗效观察

    Institute of Scientific and Technical Information of China (English)

    肖国椿; 肖李莉; 赖朝东; 黎力勋

    2001-01-01

    目的对比研究美沙酮和丁丙诺啡联合梯度递减疗法与单纯丁丙诺啡梯度递减疗法治疗海洛因依赖的临床效果.方法对1444例海洛因依赖者采用10 d递减疗法进行戒毒治疗,随机分为两组,A组:1 028例,联合应用美沙酮与丁丙诺啡治疗;B组:416例,应用丁丙诺啡治疗.结果治疗后两组轻、中、重度积分均明显降低,治疗前5 d A组比B组戒断症状积分要低得多,A组治疗期间戒断症状控制平稳,效果确切,总体临床脱瘾率为96.89%,与单用丁丙诺啡治疗脱瘾率94.71%比,差异显著(P<0.05).结论美沙酮与丁丙诺啡联合梯度治疗海洛因依赖的替代递减疗法联用合理安全,效果好,递减迅速,副作用轻微,值得临床推荐应用.

  4. Study on Colloidal Gold Labeled Anti-Buprenorphine Monoclonal Antibody for Rapid Test Kit to Detect Buprenorphine%检测丁丙诺啡的胶体金标记单克隆抗体免疫试剂盒研制

    Institute of Scientific and Technical Information of China (English)

    曾立波; 陈连康; 胡小龙; 陈亮; 王学生; 张玉荣

    2006-01-01

    目的采用免疫竞争法原理,建立一种简便快速检测丁丙诺啡的方法.方法将20nm胶体金颗粒标记的抗丁丙诺啡单克隆抗体,均匀浸在吸水玻璃纤维上,将丁丙诺啡-BSA和纯化后的羊抗鼠IgG多克隆抗体在硝酸纤维薄膜分别划1 mm宽的检测线(T线)和质控线(C线),制成丁丙诺啡胶体金标记单克隆抗体免疫层析检测条,并组装成检测板.结果以GC/MS为标准对照,100例样品检测结果显示,本检测板的准确率为99.0%.丁丙诺啡胶体金标记单克隆抗体免疫层析检测板在对45种药(毒)物的测试中,仅识别丁丙诺啡及其主要代谢产物.结论丁丙诺啡胶体金标记单克隆抗体免疫层析检测板在5min内可检出样品中的丁丙诺啡及其代谢物,检测丁丙诺啡的阈值为100ng/mL.

  5. Use of Operant Performance to Guide and Evaluate Medical Treatment in an Adult Male Cynomolgus Macaque (Macaca fascicularis)

    Science.gov (United States)

    2011-11-01

    treatment. The affected monkey received ketoprofen , buprenorphine, or their combination but continued to perform poorly during daily operant behavioral...evening administration of buprenorphine (0.01 mg/kg IM) was added to the treatment regimen of ketoprofen (2.0 mg/kg IM) ad- ministration in the...well below the reinforced band. Treatment with ketoprofen or the ketoprofen -buprenorphine combination failed to increase mean response duration

  6. Genetic Influences on Survival Time After Severe Hemorrhage in Inbred Rat Strains

    Science.gov (United States)

    2011-04-12

    were conducted 24 h postsurgery to minimize confounding influences of isoflurane and buprenorphine on survival time. The half - life for isoflurane (30...detail previously (25). At the end of surgery, rats were injected with buprenorphine (25 g/kg body wt sc) and with 10 ml of 0.9% saline (sc)/400 g body...min, Ref. 22) and buprenorphine (2.1–3 h, Ref. 33) would suggest a clearance from the blood compatible with our assumption. However, one cannot

  7. 77 FR 72752 - Opioid Drugs in Maintenance and Detoxification Treatment of Opiate Addiction; Proposed...

    Science.gov (United States)

    2012-12-06

    ... responsibility and stability to receive opioid addiction treatment medication. Opioid treatment programs that use... permits OTPs to dispense buprenorphine addiction treatment products to patients without requiring the... flexibility in treatment and is justified by the experience to date with buprenorphine addiction...

  8. New developments in the management of opioid dependence: focus on sublingual buprenorphine–naloxone

    Directory of Open Access Journals (Sweden)

    Soyka M

    2015-01-01

    Full Text Available Michael Soyka1,21Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany; 2Private Hospital Meiringen, Meiringen, SwitzerlandAbstract: Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine–naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed.Keywords: buprenorphine, methadone, naloxone, opioids, opioid dependence, therapy

  9. 新的透皮疼痛治疗剂丁丙诺啡不久将以贴剂面市%Neue Transdermale Schmerztherapie Buprenorphin bald als Pflaster erhaltlich

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    丁丙诺啡是强效类鸦片,尤其适用于慢性疼痛的治疗.因为丁丙诺啡口服生物利用度低,不久将作为透皮治疗剂面世.新剂型的疗效,已在三项双盲研究中得到证实.

  10. A Multicentric Study on Analgesic Effect of Buprenorphine Hydrochloride Sublingual Tablets in Treatment of Cancer Pain%盐酸丁丙诺啡舌下片用于癌症镇痛的多中心临床观察

    Institute of Scientific and Technical Information of China (English)

    王杰军; 李睿

    2006-01-01

    目的:观察盐酸丁丙诺啡舌下片治疗癌症疼痛的临床镇痛效果和不良反应.方法:采用多中心开放试验,对120例癌痛患者用盐酸丁丙诺啡舌下片进行治疗,观察镇痛效果、生活质量和不良反应.结果:盐酸丁丙诺啡舌下片适用于用于癌痛患者,镇痛效果确切,不良反应与其他阿片类药物类似.结论:盐酸丁丙诺啡舌下片可用于治疗癌痛.

  11. 丁丙诺啡复方制剂治疗阿片类依赖研究进展%Recent advances in the treatment of opiate addiction with buprenorphine-naloxone combination tablet

    Institute of Scientific and Technical Information of China (English)

    张晓军; 韩学文

    2006-01-01

    阿片类依赖问题是伴随着阿片类药物医疗使用和非法使用(药物滥用)而出现的。我国目前阿片类药物非法使用和蔓延的形势较为严峻,海洛因仍是在我国滥用流行的主要毒品。全国现有海洛因滥用者70万,占吸毒人员总数的78.3%。其中,35a以下的青少年近70%。截至2005年9月底,我国累计报告的135630例艾滋病病毒(HIV)感染者中,有40.8%因静脉注射毒品而感染,居艾滋病传播途径的首位。全国登记在册吸毒人员中,80%患有各种传染性疾病。阿片类药物依赖及与此相关的艾滋病等传染病的广泛传播已成为我国乃至全球严重的健康和社会问题。

  12. 昂丹司琼复合丁丙诺啡预防阑尾牵拉反应的临床观察%Clinical Observation on Prevention of Appemdix Drag Reaction with Ondansetron and Buprenorphine

    Institute of Scientific and Technical Information of China (English)

    曹艳; 杨红飞

    2010-01-01

    目的 比较阑尾切除手术过程中,运用昂丹司琼复合布托啡诺和氟芬合剂对阑尾牵拉反应的抑制效果.方法 选择连续硬膜外麻醉下行阑尾切除手术的患者80例,随机分为布托啡诺组(n=40)、氟芬合剂组(n=40).两组均在切皮时静脉给药,观察并记录各组阑尾牵拉时的不良反应及镇静评分,并进行组间比较分析.结果 昂丹司琼复合布托啡诺组抑制阑尾牵拉反应的有效性明显优于氟芬合剂组(P<0.05).结论 阑尾切除术中运用昂丹司琼复合布托啡诺,可以明显减轻手术中牵拉反应.

  13. HPLC法测定盐酸丁丙诺啡注射液中5-羟甲基糠醛%Determination of 5-Hydroxymethyl Furfuraldehyde in Buprenorphine Hydrochloride Injection by HPLC

    Institute of Scientific and Technical Information of China (English)

    杨杨; 刘永成; 姜连阁; 白政忠

    2009-01-01

    目的:建立高效液相色谱法检查盐酸丁丙诺啡注射液中5-羟甲基糠醛.方法:采用Diamonsil C18(4.6mm×250mm,5μ),甲醇-乙腈-2%醋酸铵溶液-冰醋酸(60:10:40:5)为流动相,流速为1.0ml/min,检测波长为284nm,柱温为30℃.结果:5-羟甲基糠醛色谱峰与主峰能够达到有效分离,检测限为0.752ng/ml,定量限为4.512ng/ml,平均回收率为99.9%(RSD=1.2%).结论:本法简便,灵敏、准确、专属性强,可用于盐酸丁丙诺啡注射液中5-羟甲基糠醛的检查.

  14. A Comparison of Analgesic Effect of Buprenorphine and Morphine after Operation%丁丙诺啡、吗啡用于硬膜外术后镇痛的比较观察

    Institute of Scientific and Technical Information of China (English)

    刘炜; 邹志伟; 刘剑锋; 吴春峰

    2005-01-01

    目的:探讨丁丙诺啡用于硬膜外术后镇痛的价值.方法:选择ASA(Ⅰ~Ⅱ)级病人160例,以随机、双盲的方式将病人分为两组,以吗啡为对照组.结果:丁丙诺啡用于硬膜外术后镇痛组,其镇痛效果及并发症均与吗啡组类同.结论:丁丙诺啡可用于硬膜外术后镇痛,但优势不明显.

  15. Application of Patient Controlled Subcutaneous Analgesia with Buprenorphine After Thoracotomy%丁丙诺啡在开胸术后皮下自控镇痛中的应用

    Institute of Scientific and Technical Information of China (English)

    沈蓓

    2007-01-01

    目的 观察丁丙诺啡皮下自控镇痛用于开胸手术术后镇痛的镇痛效果及不良反应.方法 将40例择期行开胸手术患者随机分为皮下镇痛组和硬膜外镇痛组,观察术后镇痛效果及不良反应.结果 两组患者术后的MAP、HR、RR、SpO2、镇痛评分(VAS)、镇痛评分(Ramsay scale)、镇痛泵按压次数及不良反应等差异均无显著性.结论 丁丙诺啡皮下自控镇痛能安全有效地用于开胸手术术后镇痛.

  16. The resear of buprenorphine used in Cure-psin with General anaesthesia%丁丙诺非在硬膜外中用于恶性疼痛的研究

    Institute of Scientific and Technical Information of China (English)

    李冰

    2006-01-01

    目的:探讨丁丙诺非在硬膜外中用于恶性疼痛的安全性和可行性.方法:选择ASA2~3级的癌症患者,共35例.随机分为2组,一组为静脉自控镇痛(PCIA),以15μg/ml芬太尼+格拉司凉8mg为镇痛液;一组为选用丁丙诺非0.1~0.3mg为镇痛液用于硬膜外镇痛.在4,8,12,24,48h进行镇痛评分并观察其不良反应.结果:在4,8,12,24,48h静息状态下,丁丙诺非在镇痛及镇痛时间方面与一组相比无显著差异,(P>0.05),而不良反应则明显少于一组.(P<0.05).结论:丁丙诺非在硬膜外中用于恶心疼痛的镇痛,不仅简单可行,而且也是非常安全可靠的.

  17. Molecular simulations of the loading of methadone and buprenorphine into carbon nanotubes%美沙酮、丁丙诺啡纳米碳管封装的分子模拟

    Institute of Scientific and Technical Information of China (English)

    沈海军

    2006-01-01

    目的 模拟纳米碳管对美沙酮、丁丙诺啡有效成分C21H27NO和C29H41NO4的吸入与俘获,探讨美沙酮、丁丙诺啡纳米碳管封装及其缓释、长效药物开发的可能性.方法 基于MM+力场的传统分子动力学方法.结果 对于直径分别大于1或1.25 nm的开口碳管,C21H27NO或C29H41NO4分子在管口处的势能高于管中央,分子可主动进入碳管内;目前制备的单壁纳米碳管非常适合于封装美沙酮及丁丙诺啡.结论 以纳米碳管为载体有望研发新的美沙酮与丁丙诺啡的缓释、长效戒毒药物.

  18. Comparison of effects of patient-controlled intravenous analgesia with nefopam or buprenorphine after lower abdominal or lower limb surgery%奈福泮与丁丙诺啡术后自控镇痛的效果比较

    Institute of Scientific and Technical Information of China (English)

    李秀泽; 孙德友

    2006-01-01

    目的 比较奈福泮和丁丙诺啡静脉自控镇痛(PCIA)对下腹部及下肢手术患者的镇痛效果.方法 40例择期手术患者随机分为奈福泮组(N组)及丁丙诺啡组(B组),术后4、8、12、24、48h分别观察疼痛评分(VAS)、镇静评分(SS)及恶心、呕吐、呼吸抑制、皮肤瘙痒、尿潴留等不良反应.结果 两组患者镇痛效果相似.N组镇静评分明显低于B组.术后24h B组恶心、呕吐等不良反应发生率明显高于N组.结论 PCIA奈福泮对下腹部及下肢手术患者可以提供满意的镇痛效果,而且其不良反应发生率低.

  19. Buprenorphine Buccal-Analgesic Effects in Advanced Cancer%丁丙诺啡含片对晚期癌症患者镇痛效果的临床研究

    Institute of Scientific and Technical Information of China (English)

    江勃年; 胡炳强; 王平辉; 罗容喜; 符红普

    2003-01-01

    目的研究丁丙诺啡含片的临床镇痛效果.方法与丁丙诺啡针剂比较,将60例晚期癌症病人随机分为两组,对两组各30例进行双模拟双盲试验.结果该药两种剂型的镇痛强度和疼痛缓解度均无统计学差异(P>0.05);不良反应中恶心呕吐片剂小于针剂(P<0.05),恶心、头晕、出汗和嗜睡无统计学差异(P>0.05);片剂与针剂对心率、呼吸频率、血压均无明显影响.结论丁丙诺啡含片为良好的强效镇痛药,服用携带方便,值得临床推广使用,但应注意监测可能出现的依赖性倾向.

  20. EFFICACY OF BUPRENORPHINE HYDROCHLORIDE ON RELAPSE-PREVENTION AMONG HERION DEPENDENT PATIENTS AFTER DETOXIFICATION——248 CASES ON BUPRENORPHINE MAINTENANCE TREATMENT%盐酸丁丙诺啡对海洛因依赖者脱毒后预防复吸的研究——248例盐酸丁丙诺啡维持治疗临床研究

    Institute of Scientific and Technical Information of China (English)

    黄威巍; 徐荣海

    2006-01-01

    目的:研究盐酸丁丙诺啡对海洛因依赖者脱毒后预防复吸的效能.方法:248例海洛因依赖者完成脱毒后给予盐酸丁丙诺啡舌下含片维持治疗,药物剂量从第1月4 mg·d-1,2 mg·d-1到第2月后一直以1.5 mg·d-1维持;维持者每次来所取药时做尿液吗啡检测,填写相关量表.结果:丁丙诺啡舌下含片维持治疗第1,3,6,12,18,24月时的保持率分别为61.69%,29.84%,12.10%,2.65%,1.61%和0.81%.尿液吗啡检测阴性率在前2个月占应检人数的75%以上;渴求强度"非常想"和"不想"因子在第1,6,12月时差异有显著性(P<0.01);稽延性戒断症状总平均分第1月和第3,6,12月比较差异有显著性(P<0.01);不良反应以思睡、便秘为主,后者随维持治疗时间延长而加重.结论:盐酸丁丙诺啡舌下含片维持治疗对海洛因依赖者脱毒后预防复吸有肯定的作用.

  1. Anti-Addiction Meds Given in ER Can Help Battle Abuse

    Science.gov (United States)

    ... received one of three treatments: a referral to addiction treatment services; a short interview including discussion of treatment; ... buprenorphine were more likely to be in formal addiction treatment and to report reduced opioid use than those ...

  2. Innovative Programs Help Addicts Get Off Opioids

    Science.gov (United States)

    ... trying to kick addiction to heroin or prescription painkillers often wait weeks or months before they can ... a treatment program. Buprenorphine acts on the same brain receptors targeted by heroin and morphine, reducing drug ...

  3. Drug: D10250 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 249]) treatment of opioid dependence ATC code: N07BC51 Anatomical Therapeutic Chemical (ATC) classification ...DDICTIVE DISORDERS N07BC Drugs used in opioid dependence N07BC51 Buprenorphine, combinations D10250 Buprenor

  4. American College of Medical Toxicology

    Science.gov (United States)

    ... FAQ Methadone FAQ Buprenorphine FAQ Dextromethorphan Ethylene Glycol Pesticides AnabolicSteroids HomeNaloxone Button Batteries Cocaine Carbon Monoxide Designer Amphetamines NSAID_FAQ Killer Bees Energy Drinks Heat Illness Nicotine Magnets Synthetic Cannabinoids ...

  5. Pesticides

    Science.gov (United States)

    ... FAQ Methadone FAQ Buprenorphine FAQ Dextromethorphan Ethylene Glycol Pesticides AnabolicSteroids HomeNaloxone Button Batteries Cocaine Carbon Monoxide Designer Amphetamines NSAID_FAQ Killer Bees Energy Drinks Heat Illness Nicotine Magnets Synthetic Cannabinoids ...

  6. Impact of surgical severity and analgesic treatment on plasma corticosterone in rats during surgery

    DEFF Research Database (Denmark)

    Goldkuhl, Renée; Klockars, Anica; Hau, Jann;

    2010-01-01

    of the present investigation was to study the effect of surgical severity and analgesic treatment on circulating corticosterone in male Sprague-Dawley rats. Male rats were treated with either lidocaine infiltrated during surgery, buprenorphine (0.05 or 0.1 mg/kg subcutaneously) or saline subcutaneously. Each...... to saline treatment after catheterisation but not after laparotomy. Buprenorphine treatment reduced the corticosterone levels during the first hour after surgery after both catheterisation and laparotomy. The higher buprenorphine dose led to an earlier and more pronounced reduction, especially after...... laparotomy. In the present study, the corticosterone response during surgery in laboratory rats is correlated with the severity of the procedure, and buprenorphine reduces the surgical stress response more effectively than lidocaine treatment....

  7. Primary care management of opioid use disorders

    Science.gov (United States)

    Srivastava, Anita; Kahan, Meldon; Nader, Maya

    2017-01-01

    Abstract Objective To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance. Sources of information PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included. Main message Both methadone and buprenorphine-naloxone are substantially more effective than abstinence-based treatment. Methadone has higher treatment retention rates than buprenorphine-naloxone does, while buprenorphine-naloxone has a lower risk of overdose. For all patient groups, physicians should recommend methadone or buprenorphine-naloxone treatment over abstinence-based treatment (level I evidence). Methadone is preferred over buprenorphine-naloxone for patients at higher risk of treatment dropout, such as injection opioid users (level I evidence). Youth and pregnant women who inject opioids should also receive methadone first (level III evidence). If buprenorphine-naloxone is prescribed first, the patient should be promptly switched to methadone if withdrawal symptoms, cravings, or opioid use persist despite an optimal buprenorphine-naloxone dose (level II evidence). Buprenorphine-naloxone is recommended for socially stable prescription oral opioid users, particularly if their work or family commitments make it difficult for them to attend the pharmacy daily, if they have a medical or psychiatric condition requiring regular primary care (level IV evidence), or if their jobs require higher levels of cognitive functioning or psychomotor performance (level III evidence). Buprenorphine-naloxone is also recommended for patients at high risk of methadone toxicity, such as the elderly, those taking high doses of benzodiazepines or other sedating drugs, heavy drinkers, those with a lower

  8. Synthesis of iodobuprenorphine for use in radioimmunoassay. [Analgesic

    Energy Technology Data Exchange (ETDEWEB)

    Debrabandere, L.; Boven, M. van; Daenens, P. (Leuven Univ. (Belgium). Lab. of Toxicology)

    1992-08-01

    The synthesis of [[sup 125]I]iodobuprenorphine is described. This compound has been used as a tracer molecule in the development of a new radioimmunoassay for buprenorphine. The parameters that effect the direct iodination of buprenorphine using sodium [[sup 127]I]iodide, in the presence of either chloramine-T or Iodo-Beads, were studied. The structure of iodobuprenorphine was confirmed by mass spectrometry. (author).

  9. 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.

  10. Opiate addiction therapies and HIV-1 Tat: interactive effects on glial [Ca²⁺]i, oxyradical and neuroinflammatory chemokine production and correlative neurotoxicity.

    Science.gov (United States)

    Fitting, Sylvia; Zou, Shiping; El-Hage, Nazira; Suzuki, Masami; Paris, Jason J; Schier, Christina J; Rodríguez, José W; Rodriguez, Myosotys; Knapp, Pamela E; Hauser, Kurt F

    2014-01-01

    Few preclinical studies have compared the relative therapeutic efficacy of medications used to treat opiate addiction in relation to neuroAIDS. Here we compare the ability of methadone and buprenorphine, and the prototypic opiate morphine, to potentiate the neurotoxic and proinflammatory ([Ca²⁺]i, ROS, H₂O₂, chemokines) effects of HIV-1 Tat in neuronal and/or mixed-glial co-cultures. Repeated observations of neurons during 48 h exposure to combinations of Tat, equimolar concentrations (500 nM) of morphine, methadone, or buprenorphine exacerbated neurotoxicity significantly above levels seen with Tat alone. Buprenorphine alone displayed marked neurotoxicity at 500 nM, prompting additional studies of its neurotoxic effects at 5 nM and 50 nM concentrations ± Tat. In combination with Tat, buprenorphine displayed paradoxical, concentration-dependent, neurotoxic and neuroprotective actions. Buprenorphine neurotoxicity coincided with marked elevations in [Ca²⁺]i, but not increases in glial ROS or chemokine release. Tat by itself elevated the production of CCL5/RANTES, CCL4/MIP-1β, and CCL2/MCP-1. Methadone and buprenorphine alone had no effect, but methadone interacted with Tat to further increase production of CCL5/RANTES. In combination with Tat, all drugs significantly increased glial [Ca²⁺]i, but ROS was only significantly increased by co-exposure with morphine. Taken together, the increases in glial [Ca²⁺]i, ROS, and neuroinflammatory chemokines were not especially accurate predictors of neurotoxicity. Despite similarities, opiates displayed differences in their neurotoxic and neuroinflammatory interactions with Tat. Buprenorphine, in particular, was partially neuroprotective at a low concentration, which may result from its unique pharmacological profile at multiple opioid receptors. Overall, the results reveal differences among addiction medications that may impact neuroAIDS.

  11. 静脉注射丁丙诺啡舌下片合并东莨菪碱、异丙嗪注射液成瘾一例%A case report on addiction to intravenous injection of buprenorphine,scopolamine and promethazine

    Institute of Scientific and Technical Information of China (English)

    周旭辉; 黄劲松; 张登科; 张雪辉; 邱进平; 郝伟

    2007-01-01

    患者,男,32a,未婚,初中文化,因静脉注射丁丙诺啡舌下片(沙菲片)合并东莨菪碱、异丙嗪成瘾3a,于2006年3月29日入戒毒所。患者系海洛因成瘾者,自2003年3月在毒友的推荐下开始静脉注射沙菲片加东莨菪碱、异丙嗪注射液(俗称“1+1”)。刚开始使用的日剂量为,沙菲片0.8mg·d-1,东莨菪碱注射液0.6mg·d-1,

  12. Reducing Drug Harms to Heroin Dependents by Combining Low Dosage of Buprenorphine with Multi-dimension Family-based Therapy%小剂量丁丙诺啡联合多维度家庭治疗降低毒品危害的运用

    Institute of Scientific and Technical Information of China (English)

    童芳; 龚昌海; 李沛亨; 黄国平

    2004-01-01

    目的:寻找能有效降低毒品危害的方法.方法:配合治疗的海洛因依赖者83例,脱毒治疗后以小剂量丁丙诺啡(0.8 mg·d-1)联合多维度家庭治疗半年,观察评定疗效.结果:半年操守率42.17%,留治率43.37%,静脉使用海洛因量、次数、方式均有明显降低和改变,且不良反应少.结论:小剂量丁丙诺啡联合多维度家庭治疗在降低毒品危害方面效果显著.

  13. 吗啡依赖、戒断及丁丙诺啡的替代治疗对大鼠垂体 POMC基因表达的影响%BEHAVIOR PITUITARY POMC GENE EXPRESSION OF MORPHINE DEPENDENT AND WITHDRAWAL RATS AND SUBSTITUTIVE EFFICACY OF BUPRENORPHINE

    Institute of Scientific and Technical Information of China (English)

    阎晓凯; 洪敏; 李光虎; 刘畅

    2001-01-01

    目的 :结合戒断体征的观察从分子水平研究吗啡依赖和戒断机理及丁丙诺啡对吗啡戒断的影响。方法 :观察吗啡戒断及经丁丙诺啡治疗大鼠的戒断体征;利用核酸分子杂交技术研究其垂体阿黑皮源 (POMC)基因表达的变化。结果 :丁丙诺啡能有效减轻或消除戒断体征 ,吗啡依赖及戒断时大鼠垂体 POMC-mRNA含量下降 ,丁丙诺啡对其影响不大。结论 : 吗啡依赖和戒断抑制大鼠垂体 POMC基因表达 ,丁丙诺啡能纠正吗啡躯体依赖 ,但从基因水平看丁丙诺啡可能也具有依赖潜能。

  14. Evaluation of common anesthetic and analgesic techniques for tail biopsy in mice.

    Science.gov (United States)

    Jones, Carissa P; Carver, Scott; Kendall, Lon V

    2012-11-01

    Tail biopsy in mice is a common procedure in genetically modified mouse colonies. We evaluated the anesthetic and analgesic effects of various agents commonly used to mitigate pain after tail biopsy. We used a hot-water immersion assay to evaluate the analgesic effects of isoflurane, ice-cold ethanol, ethyl chloride, buprenorphine, and 2-point local nerve blocks before studying their effects on mice receiving tail biopsies. Mice treated with ethyl chloride spray, isoflurane and buprenorphine, and 2-point local nerve blocks demonstrated increased tail-flick latency compared with that of untreated mice. When we evaluated the behavior of adult and preweanling mice after tail biopsy, untreated mice demonstrated behavioral changes immediately after tail biopsy that lasted 30 to 60 min before returning to normal. The use of isoflurane, isoflurane and buprenorphine, buprenorphine, 2-point nerve block, or ethyl chloride spray in adult mice did not significantly improve their behavioral response to tail biopsy. Similarly, the use of buprenorphine and ethyl chloride spray in preweanling mice did not improve their behavioral response to tail biopsy compared with that of the untreated group. However, immersion in bupivacaine for 30 s after tail biopsy decreased tail grooming behavior during the first 30 min after tail biopsy. The anesthetic and analgesic regimens tested provide little benefit in adult and preweanling mice. Given that tail biopsy results in pain that lasts 30 to 60 min, investigators should carefully consider the appropriate anesthetic or analgesic regimen to incorporate into tail-biopsy procedures for mice.

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

    DEFF Research Database (Denmark)

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

    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......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....

  16. Evaluation of a direct high-capacity target screening approach for urine drug testing using liquid chromatography-time-of-flight mass spectrometry.

    Science.gov (United States)

    Saleh, Aljona; Stephanson, Niclas Nikolai; Granelli, Ingrid; Villén, Tomas; Beck, Olof

    2012-11-15

    In this study a rapid liquid chromatography-time-of-flight mass spectrometry method was developed, validated and applied in order to evaluate the potential of this technique for routine urine drug testing. Approximately 800 authentic patient samples were analyzed for amphetamines (amphetamine and methamphetamine), opiates (morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine and codeine-6-glucuronide) and buprenorphines (buprenorphine and buprenorphine-glucuronide) using immunochemical screening assays and mass spectrometry confirmation methods for comparison. The chromatographic application utilized a rapid gradient with high flow and a reversed phase column with 1.8 μm particles. Total analysis time was 4 min. The mass spectrometer operated with an electrospray interface in positive mode with a resolution power of >10,000 at m/z 956. The applied reporting limits were 100 ng/mL for amphetamines and opiates, and 5 ng/mL for buprenorphines, with lower limits of quantification were 2.8-41 ng/mL. Calibration curves showed a linear response with coefficients of correlation of 0.97-0.99. The intra- and interday imprecision in quantification at the reporting limits were amphetamines and opiates; 3.2% for buprenorphines) and negatives (1.8% for amphetamines; 0.6% for opiates; 0% for buprenorphines). The overall agreement between the two screening methods was between 94.2 and 97.4%. Comparison of data with the confirmation (LC-MS) results for all individual 9 analytes showed that most deviating results were produced in samples with low levels of analytes. False negatives were mainly related to failure of detected peak to meet mass accuracy criteria (±20 mDa). False positives was related to presence of interfering peaks meeting mass accuracy and retention time criteria and occurred mainly at low levels. It is concluded that liquid chromatography-time-of-flight mass spectrometry has potential both as a complement and as replacement of immunochemical screening

  17. Telemedical Advice to Long Distance Passenger Ferries

    DEFF Research Database (Denmark)

    Jensen, Olaf Chresten; Bøggild, Niels Bo; Kristensen, Søren

    with morphine. The NSAID drugs were supplied from the other passengers. Among the patients with visceral pain 1 was treated with NSAID and 22 with opioids. Of the 23 patients treated with opioids, 19 had sublingual Buprenorphine, 3 morphine injections and 1 used his personal codeine tablets. No problems were...... reported from resorption of the Buprenorphine resoriblets, which therefore seemed to work well. At least 77 patients would have benefited from use of non-steroid anti-inflammatory drugs. Conclusions: The paramedical assistance and the medicine chest content were considered insufficient in The paramedical...

  18. Conversation with Walter Ling.

    Science.gov (United States)

    Ling, Walter

    2015-01-01

    In this occasional series, we record the views and personal experiences of people who have especially contributed to the evolution of ideas in the journal's field of interest. Dr Walter Ling is a neurologist and psychiatrist, and is Director of the Integrated Substance Abuse Programs (ISAP) at the University of California, Los Angeles (UCLA), one of the foremost substance abuse research groups in the world. Dr Ling led pivotal clinical trials in the United States for all three of the only US Food and Drug Administration-approved opiate pharmacotherapies, levo-acetylmethadol (LAAM), buprenorphine and naltrexone, and is leading ongoing efforts for approval for sustained-release buprenorphine.

  19. 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…

  20. Pain (PDQ)

    Science.gov (United States)

    ... opioids: Buprenorphine . Codeine . Diamorphine . Fentanyl . Hydrocodone . Hydromorphone . Methadone . Morphine (the most commonly used opioid for cancer pain). ... may also help by offering spiritual care and social support . For more ... the risk of drug interactions . Drugs taken together can change how they work ...

  1. 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.

  2. Colon anastomotic leakage

    DEFF Research Database (Denmark)

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

    2014-01-01

    /experiments. In the 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...

  3. Opioid receptor agonists may favorably affect bone mechanical properties in rats with estrogen deficiency-induced osteoporosis.

    Science.gov (United States)

    Janas, Aleksandra; Folwarczna, Joanna

    2017-02-01

    The results of epidemiological, clinical, and in vivo and in vitro experimental studies on the effect of opioid analgesics on bone are inconsistent. The aim of the present study was to investigate the effect of morphine (an agonist of opioid receptors), buprenorphine (a partial μ opioid receptor agonist and κ opioid receptor antagonist), and naloxone (an antagonist of opioid receptors) on the skeletal system of female rats in vivo. The experiments were carried out on 3-month-old Wistar rats, divided into two groups: nonovariectomized (intact; NOVX) rats and ovariectomized (OVX) rats. The bilateral ovariectomy was performed 7 days before the start of drug administration. Morphine hydrochloride (20 mg/kg/day s.c.), buprenorphine (0.05 mg/kg/day s.c.), or naloxone hydrochloride dihydrate (2 mg/kg/day s.c.) were administered for 4 weeks to NOVX and OVX rats. In OVX rats, the use of morphine and buprenorphine counteracted the development of osteoporotic changes in the skeletal system induced by estrogen deficiency. Morphine and buprenorphine beneficially affected also the skeletal system of NOVX rats, but the effects were much weaker than those in OVX rats. Naloxone generally did not affect the rat skeletal system. The results confirmed the role of opioid receptors in the regulation of bone remodeling processes and demonstrated, in experimental conditions, that the use of opioid analgesics at moderate doses may exert beneficial effects on the skeletal system, especially in estrogen deficiency.

  4. Drug: D07132 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07132 Drug Buprenorphine (JAN/INN); Temgesic (TN) C29H41NO4 467.3036 467.6401 D07132.gif Opioid analgesic...(4986+4988) Neuroactive ligand-receptor interaction map07039 Opioid analgesics ma...ecting nervous system and sensory organs 11 Agents affecting central nervous system 114 Antipyretics and analgesic

  5. Livedoid Dermatitis Treated With Nifedipine

    Directory of Open Access Journals (Sweden)

    Lee Wheless MD, PhD

    2016-02-01

    Full Text Available Intravenous injection of buprenorphine as a cause of livedoid dermatitis is a recently described phenomenon. This report reviews the brief literature of this finding, and presents a case of livedoid dermatitis of both heels following injection more than one day prior, and thesuccessful treatment with nifedipine monotherapy.

  6. Reversal of drug-affected breathing

    NARCIS (Netherlands)

    Bijl, Johan Haiko Leonard

    2006-01-01

    Opioid analgesics are frequently used for pain relief. However, they may cause respiratory depression which is life-threatening. Animal studies suggest an apparent maximum in respiratory depression by buprenorphine regardless of drug-dose (ceiling phenomenon). In the first part of this thesis, ceili

  7. 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

  8. Perioperative Pain Relief by a COX-2 Inhibitor Affects Ileal Repair and Provides a Model for Anastomotic Leakage in the Intestine

    NARCIS (Netherlands)

    Vijver, R.J. van der; Laarhoven, C.J. van; Man, B.M. de; Lomme, R.M.L.M.; Hendriks, T.

    2013-01-01

    The authors examined the potential of the cyclooxygenase 2 (COX-2) inhibitor carprofen to reproducibly induce anastomotic leakage. In experiment 1, an anastomosis was constructed in both ileum and colon of 20 rats, and they were given carprofen (5 mg/kg subcutaneously every 24 hours) or buprenorphin

  9. Det legale opioidforbrug i Danmark

    DEFF Research Database (Denmark)

    Jarlbaek, Lene; Kehlet, Henrik; Sjøgren, Per

    2010-01-01

    annual costs, and together with the increasing costs of buprenorphine, the three opioids constitute 70% of the total costs in the primary health care sector. The largest group of users is individuals with acute pain, however, the highest consumption is generated by individuals with chronic non...

  10. 单独使用氯氮平、氯羟安定与氯氮平、氯羟安定联用丁丙诺啡用于海洛因依赖者的临床脱毒疗效对照研究%Comparative Research of Curative Effact for Heroinism's Withdrawal treat by Clozapine,Lorazepam only or combined with Buprenorphine

    Institute of Scientific and Technical Information of China (English)

    梁伟德; 陶林; 余常红; 周欣萍

    2002-01-01

    目的以往人们对各种临床脱毒治疗方法的总体疗效较为关注,对具体症状不够重视,什么方法主要能缓解那些戒断症状,仍不够清楚,为了回答这一具体问题,我们采用自行设计的海洛因戒断症状和药物副作用观察量表,对连续入院进入海洛因依赖脱毒治疗的病人首先单独使用氯氮平、氯羟安定治疗30例之后用氯氮平、氯羟安定联用丁丙诺啡治疗60例,评价有无丁丙诺啡在戒断症状药物副作用方面的差异.两组病人基本情况相似,经统计学处理两组具有可比性.结果表明两种治疗方案均对海洛因脱毒治疗有效,流泪、躯体虚弱、呕吐三种戒断症状两组间有显著性差异,四肢酸痛、哈欠、易怒、睡眠不安、烦躁不安,两组间有极显著性差异,意识障碍为氯氮平的药物副作用,在组间有极显著性差异,联合用药组对戒断症状的控制优于单独使用氯氮平和氯羟安定组,治疗安全性更大,病人也相对容易管理.

  11. Analisi dei costi di buprenorfina vs metadone nella terapia dei soggetti con dipendenza da oppiacei

    Directory of Open Access Journals (Sweden)

    Giorgio L. Colombo

    2003-12-01

    Full Text Available In the last decades, methadone has virtually represented the only available option for the treatment of opioid addicts in Italy. Early in the year 2000 buprenorphine has been introduced on the market as a possible alternative to methadone. While most of the research conducted so far in our country has focused on possible differences in clinical outcomes, depending on the pharmacological differences among the two molecules, the economical aspects of the choice between the two drugs have barely been addressed. In this paper we present a pharmacoeconomical comparison between buprenorphine and methadone in the treatment of heroin dependence by the Italian health service, adopting the perspective of the Society. For this purpose, we constructed a decision analysis model comprising the possible clinical pathways a patient can go through following the inclusion in the therapeutic programs of the SerT. Two types of incremental costs have been considered in the model: direct health costs, i.e. drug acquisition and medical staff costs, and indirect cost, due to loss of working hours for the administration of the drug. The analysis was conducted with a cost-minimization approach, mandatory in the absence of reliable data on clinical differences, and with a time perspective of 12 months. Our results indicate that buprenorphine, despite its higher pharmaceutical cost, is the more convenient option for the treatment of opioid dependence in Italy, as it permits a significant saving of productivity losses. The difference in indirect costs relies on the shorter mean treatment time with buprenorphine and on the possibility of reducing dosing frequency, which allows many patients to attend health services only thrice in week, instead of the daily visits to the SerT necessary for most methadone-treated patients. The results were challenged in a series of sensibility analysis conducted on all relevant and uncertain paramenters, and in no case the option methadone

  12. Comparison of spinal block after intrathecal clonidine–bupivacaine, buprenorphine–bupivacaine and bupivacaine alone in lower limb surgeries

    Science.gov (United States)

    Arora, Major Vishal; Khan, Mohammad Zafeer; Choubey, Major Sanjay; Rasheed, Mohammad Asim; Sarkar, Arindam

    2016-01-01

    Context: Various adjuvants are being used with local anesthetics for prolongation of intraoperative and postoperative analgesia. The α2-adrenergic agonist clonidine and potent opioid buprenorphine have the ability to potentiate the effects of local anesthetics. Aims: The purpose of this prospective, double-blind study was to compare onset, duration of sensory and motor block, effect on hemodynamics, level of sedation, duration of postoperative analgesia, and any adverse effects of clonidine and buprenorphine. Settings and Design: Seventy-five American Society of Anesthesiologists Class I and II patients undergoing lower limb surgery under spinal anesthesia were randomly allocated into three Groups A, B, and C. Subjects and Methods: Control Group A received injection bupivacaine 0.5% (heavy) 2.5 ml + saline 0.5 ml whereas Group B received injection bupivacaine 0.5% (heavy) 2.5 ml + injection buprenorphine 50 μg and Group C received injection bupivacaine 0.5% (heavy) 2.5 ml + preservative free injection clonidine 50 μg intrathecally. Statistical Analysis Used: Unpaired Student's t-test and Z-test were used for comparing data. Results: Statistically highly significant differences in mean time of sensory regression to L1, mean time to attain the Bromage Score of 1, and mean time of first rescue analgesic request were observed between the three groups. The patients did not suffer any serious side effects. Conclusion: Administration of buprenorphine and clonidine intrathecally does potentiate the duration of analgesia, sensory and motor block, with buprenorphine having a long-lasting effect. PMID:27746532

  13. Evaluation and Management of Opioid Dependence in Pregnancy

    Science.gov (United States)

    Park, Eliza M; Meltzer-Brody, Samantha; Suzuki, Joji

    2017-01-01

    Background Opioid use disorders are a growing public health problem in the United States. Most women who are opioid dependent are of childbearing age and management of opioid dependence during pregnancy poses unique challenges. Assessment includes evaluation for addiction, withdrawal syndromes, and co-morbid psychiatric diagnoses. Consultation-liaison psychiatrists may also be involved in acute pain management, perinatal medication management, buprenorphine induction and stabilization. For the past four decades, the standard of care has included methadone maintenance, but the increasing use of buprenorphine creates new treatment issues and opportunities. Objective To educate consultation-liaison psychiatrists in emergency and obstetrical settings about the appropriate approach toward the evaluation and basic management of women with opioid dependence in pregnancy. Method The authors reviewed the consensus literature and all new treatment options on opioid dependence during pregnancy. Discussion In this review, the authors summarize known and emerging management strategies for opioid dependence in pregnancy pertinent to consultation-liaison psychiatrists. PMID:22902085

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

    Science.gov (United States)

    Armstrong, Scott C; Cozza, Kelly L

    2003-01-01

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Matt C Danzi

    2016-01-01

    Full Text Available Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific 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 findings 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.

  17. FDA十月份最新批准药物

    Institute of Scientific and Technical Information of China (English)

    李行

    2002-01-01

    双“SUB”剑斩断鸦片依赖 美国食品药物管理局(FDA)2002年10月8日宣布批准Subutex (buprenorphine hydrochloride,盐酸丁丙诺啡)和Suboxone(buprenorphine hydrochloride and naloxone hydrochloride,盐酸丁丙诺啡和盐酸纳洛酮)这两种片剂作为治疗鸦片依赖的药物上市,这两种药品主要通过治疗海洛因和其它阿片类制品的戒断症状达到疗效。

  18. Expansion of opiate agonist treatment: an historical perspective

    Directory of Open Access Journals (Sweden)

    Newman Robert G

    2006-07-01

    Full Text Available Abstract Untreated opiate addiction remains a major health care crisis in New York and in most other urban centers in America. Optimism for closing the gap between need and demand for treatment and its availability has greeted the recent approval of a new opiate medication for addiction, buprenorphine – which unlike methadone may be prescribed by independent, office-based practitioners. The likelihood of buprenorphine fulfilling its potential is assessed in the light of the massive expansion of methadone treatment more than 30 years earlier. It is concluded that the key, indispensable ingredient of success will be true commitment on the part of Government to provide care to all those who need it.

  19. Role of ATP-sensitive potassium channels in the piracetam induced blockade of opioid effects.

    Science.gov (United States)

    Rehni, Ashish K; Singh, Nirmal; Jindal, Seema

    2007-12-01

    The present study has been designed to investigate the effect of piracetam on morphine/ buprenorphine-induced antinociception in rats and effect of piracetam on morphine or minoxidil induced relaxation in KCl-precontracted isolated rat aortic ring preparation. Nociceptive threshold was measured by the tail flick test in rats. The cumulative dose responses of morphine or minoxidil were recorded in KCl-precontracted isolated rat aortic ring preparation. Piracetam attenuated buprenorphine-induced antinociception in rats. Piracetam significantly reduced the morphine and minoxidil induced relaxation in KCl precontracted isolated rat aortic ring preparation suggesting that piracetam interferes with opioid receptor and ATP-sensitive potassium channel (KATP) opener mediated responses in vitro. Thus, it may be suggested that piracetam attenuates opioid effects by an opioid receptor-KATP channel linked mechanism.

  20. Implementation of a Functional Observation Battery for the Assessment of Postoperative Well-being in Rats Subjected to Fimbria-Fornix Transection

    DEFF Research Database (Denmark)

    Marschner, Linda; Wogensen, Elise; Mogensen, Jesper;

    2016-01-01

    -fornix transected animals (FF), sham-operated animals (Sham), and two non-operated control groups with and without administration of buprenorphine (+BUP and -BUP, respectively) were observed twice daily for seven days after surgery. Buprenorphine (0.4 mg/kg) mixed in a nut paste for voluntary ingestion was supplied...... twice daily for 84 h to all groups except the -BUP control group starting on the day of surgery. Body weight was slightly decreased postoperatively in both surgical groups (FF and Sham) compared to control groups. The +BUP control group lost weight starting at day four after discontinuation......, the FOB implemented in the present study appears to be a sensitive and accurate protocol for assessing animal well-being in the experimental setup applied. It is apparent that the FF transection is an invasive procedure that causes mildly adverse postoperative effects on the rats' well-being. We therefore...

  1. 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.

  2. Biotic - Abiotic Interface Between they Body and the Artificial Limb

    Science.gov (United States)

    2008-09-29

    stability, and biocompatibility, titanium is a commonly used material in dental and orthopedic applications (Pohler 2000). Its excellent biocompatibility...administrated inhaled anethesia using isofluorane. Pre-emptive analgesia was given 30 minutes before the procedure as a subcutaneous injection of buprenorphine...155–170. Bränemark PI, Breine U, Adell R, and Breine U. Intra-osseous anchorage of dental prostheses. Scand J Plast Recon Surg 1969;3:81-100

  3. Translational Advances in Pain and Anesthesia for Cancer Patients

    Science.gov (United States)

    2012-01-01

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

  4. Post-surgical analgesia in rainbow trout: is reduced cardioventilatory activity a sign of improved animal welfare or the adverse effects of an opioid drug?

    Science.gov (United States)

    Gräns, Albin; Sandblom, Erik; Kiessling, Anders; Axelsson, Michael

    2014-01-01

    The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM), on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss) at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4-7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation.

  5. Post-surgical analgesia in rainbow trout: is reduced cardioventilatory activity a sign of improved animal welfare or the adverse effects of an opioid drug?

    Directory of Open Access Journals (Sweden)

    Albin Gräns

    Full Text Available The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM, on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4-7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation.

  6. Enhanced Healing of Segmental Bone Defects by Modulation of the Mechanical Environment

    Science.gov (United States)

    2013-10-01

    Male, Sprague-Dawley rats (325-400g) were anesthetized with isoflurane and given prophylactic antibiotics and analgesics. The diaphysis of the femur... INFUSE (Medtronic) and OP-1 (osteogenic protein; Stryker), respectively4. There is also interest in using osteoprogenitor cells5, induced membranes6, and...2% with 2 L/min O2 by air mask). Before sur- gery, each rat was given an antibiotic (20 mg/kg of cefazolin) and the analgesic buprenorphine (0.08 mg

  7. Long Term Suboxone™ Emotional Reactivity As Measured by Automatic Detection in Speech

    OpenAIRE

    2013-01-01

    Addictions to illicit drugs are among the nation’s most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX) as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states (“true ground emotionality”) in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of “true” emotionality in 36 ...

  8. Evaluation of Carbohydrate-Derived Fulvic Acid (CHD-FA) as a Topical Broad-Spectrum Antimicrobial for Drug-Resistant Wound Infections

    Science.gov (United States)

    2013-10-01

    0.5 0.5 Aspergillus flavus 12 0.5 0.5 0.5 0.5 Aspergillus terreus 5 0.125 0.125 0.5 0.5 Aspergillus niger 10 0.5 0.5 0.5 0.5 Candida albicans...with saline administered via subcutaneous injection. The analgesic buprenorphine (0.05mg/kg) was administered twice daily for two days to minimize pain

  9. Prevalence of psychoactive substances in truck drivers in the Nord-Pas-de-Calais region (France).

    Science.gov (United States)

    Labat, Laurence; Fontaine, Bernard; Delzenne, Chantal; Doublet, Anne; Marek, Marie Christine; Tellier, Dominique; Tonneau, Murielle; Lhermitte, Michel; Frimat, Paul

    2008-01-30

    A previous study conducted in 1995 showed that psychoactive drug use by workers was higher in safety/security workstations than in the rest of the labour force. In order to verify this finding, we conducted a new study in 2003-2004 in the Nord-Pas-de-Calais region, restricted to truck drivers. The aim of this study was to allow harmonizing the professional practice of the occupational physicians, proposing drug prevention and drug testing policies, validating the analytical methods and the guidelines in case of positive testing results. One thousand truck drivers were studied. Urines were tested for amphetamines, cannabinoids, cocaine, opiates, benzodiazepines, buprenorphine and methadone by immunoassay. Urine ethanol determinations were performed by an ADH method. Positive urines for drugs of abuse, methadone or buprenorphine were then tested by gas chromatography or liquid chromatography coupled to mass spectrometry. Out of the 1000 drivers, cannabinoids were detected in 85 cases, opiates in 41 cases, amphetamines in 3 cases and cocaine in only one case. Buprenorphine was detected in 18 cases, methadone in 5 cases and benzodiazepines in 4 cases. Urine ethanol was positive in 50 cases. We found only one case with 6-monoacetylmorphine. Other positive opiates were metabolites of antitussives. The relatively low number of benzodiazepine positive urines could be explained by the lack of sensitivity of the test we used. All these results confirm those of the previous study for cannabinoids and ethanol in safety/security workstations. Positive results for methadone and buprenorphine are eight times higher than in the general population. In conclusion, the authors think that it will be of a great interest to test urine of truck drivers for other classes of psychoactive drugs, using a liquid chromatography-mass spectrometry method.

  10. The Noninvasive Carbon Dioxide Gradient (NICO2G) during Hemorrhagic Shock

    Science.gov (United States)

    2014-07-01

    temperature (in degrees Celsius); HR, heart rate; MAP, mean arterial pressure (in millimeters mercury); CVP, central venous pressure (in millimeters...Telazol (tiletamine/zolazepam 4 Y 6 mg/kg) by i.m. injection. Analgesia was provided using buprenorphine hydrochloride i.m. (0.25 mg/kg). Venous access was...Capnostream 20 device with a FilterLine H Set CO2 sidestream sampling line and an airway adapter (Oridion Medical, Jerusalem, Israel) were used for

  11. 自愿戒毒者停用丁丙诺啡后出现精神障碍1例

    Institute of Scientific and Technical Information of China (English)

    黎雪松; 陈志锐; 曾宪韶; 陈顺英; 曾霭良

    1998-01-01

    @@ 患者男性,31岁.吸食海洛因2年,因停吸时出现躯体和心理依赖症状于1996年9月18日入院.入院前曾住某"戒毒中心"自愿戒毒,以"递减法"使用丁丙诺啡(buprenorphine)7天.

  12. 丁丙诺啡用于开胸术后硬膜外患者自控镇痛

    Institute of Scientific and Technical Information of China (English)

    卞振东

    2004-01-01

    丁丙诺啡(buprenorphine)是一种新型强效镇痛药,具有镇痛作用强、持续时间长,对呼吸、循环影响轻微等优点。本文对开胸手术后患者行丁丙诺啡硬膜外自控镇痛,现报道如下。

  13. Hemostatic Efficacy of Two Advanced Dressings in an Aortic Hemorrhage Model in Swine

    Science.gov (United States)

    2005-07-01

    wounds accounts for more than half of the potentially preventable deaths in combat.1,5 Thus, hemostasis research and the development of an effective...by twice- daily intramuscular injections of buprenorphine (0.05 mg/kg) for 4 days. Midazolam (0.4 mg/kg) was also prepared for immediate intravenous...durable; long shelf life (2–3 years); functional in extreme temperatures (from 10° to 50°C); biodegradable and fully reabsorbable; and inexpen- sive

  14. Use of Ultra Rapid Opioid Detoxification in the Treatment of US Military Burn Casualties

    Science.gov (United States)

    2011-07-01

    military burn patients had a much greater reduction in their opioid usage as calculated by daily MEUs, decreasing the opioid burden by as much as half ... life while minimizing many of the negative consequences of chronic opioid prescription. Future studies may validate decreases in sedation...116. 12. Collins ED, Kleber HD, Whittington RA, Heitler NE. Anesthesia- assisted vs buprenorphine - or clonidine-assisted heroin detoxification and

  15. Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-Abdominal Adhesions, and Arterial Injuries

    Science.gov (United States)

    2006-02-01

    stimulators from the blood.’’ (VEGF has a half - life of ¨3.5 min in the circulation.) Folkman formulated this hypothesis after reading Noel Bouck’s first...day) compared to 60% for endostatin alone [65]. This is another example that increasing the half - life of circulating endostatin increases its efficacy...were pre- medicated with glycopyrrolate and buprenorphine , induced with 3-4% isoflurane and placed under general endotracheal anesthesia. A 5 cm

  16. Comparison of Experimental Models for Predicting Laser Tissue Interaction from 3.8-Micron Lasers

    Science.gov (United States)

    2007-11-02

    Corning Life Sciences, Kennebunk, Maine) polycarbonate tissue culture insert contained within a 12 well tissue culture plate. Type I collagen (BD 8 9...10.0ml/lb/min) for all exposures. Analgesia was administered ( Buprenorphine 0.005 to 0.01 mg/kg IM) prior to recovery, post recovery and as needed...slight discoloration on the tissue edge. The histopathology showed that the stratum corneum and the upper half of the stratum spinosum were absent

  17. Low-Level Cyclo-Sarin (GF) Vapor Exposure in the Gottingen Minipig: Effect of Exposure Concentration and Duration on Pupil Size

    Science.gov (United States)

    2007-05-01

    Animal Resources, Commission of Life Sciences, National Research Council, Washington, D.C. These investigations were also performed in accordance with...almost half as potent as GB. Potency comparisons between GB and GF at low-level vapor concentrations cannot be successfully drawn because of a lack of... buprenorphine 0.01 - 0.05mg/kg, BD) for at least 24 hr and subsequently, if needed. The pigs were allowed at least three days for recovery from the

  18. Hyperalgesia in Heroin Dependent Patients and the Effects of Opioid Substitution Therapy

    OpenAIRE

    2012-01-01

    Evidence suggests that patients on opiate maintenance therapy for the treatment of addiction present with opioid-induced hyperalgesia (OIH). This study compared the experimental (cold-pressor, electrical stimulation) pain responses of 82 treatment-seeking heroin-dependent adults randomized to methadone (METH, n = 11) or buprenorphine (BUP, n = 64) therapy, with matched drug free controls (n = 21). Heroin-dependent participants were evaluated at baseline (treatment entry), medication (METH or ...

  19. A case of topical opioid-induced delirium mistaken as behavioural and psychological symptoms of dementia in demented state.

    Science.gov (United States)

    Ito, Go; Kanemoto, Kousuke

    2013-06-01

    In Japan, indications for opioid analgesics, once exclusively used as pain killers for patients suffering from malignant cancer, have been expanded for a wide range of pain. Herein we report a patient with opioid-induced delirium associated with the administration of buprenorphine patches that was well below the indicated therapeutic range limit. An 82-year-old woman was referred to us from an orthopaedic practitioner for uncontrollable behavioural problems apparently caused by the beginning of dementia; the patient had gradually developed disorientation, visual hallucinations, and delusions. Laboratory and imaging findings excluded common causes of delirium including Alzheimer's disease and diffuse Lewy body disease. Detailed questioning revealed that the patient's confused state appeared following a buprenorphine patch dose increase and subsequently disappeared after administration was stopped. Delirium has not been reported as a side-effect in clinical trials of buprenorphine patches. However, our findings in this case show that even topical opioids can precipitate the development of a delirious state in elderly patients.

  20. National and State Treatment Need and Capacity for Opioid Agonist Medication-Assisted Treatment

    Science.gov (United States)

    Campopiano, Melinda; Baldwin, Grant; McCance-Katz, Elinore

    2015-01-01

    Objectives. We estimated national and state trends in opioid agonist medication-assisted treatment (OA-MAT) need and capacity to identify gaps and inform policy decisions. Methods. We generated national and state rates of past-year opioid abuse or dependence, maximum potential buprenorphine treatment capacity, number of patients receiving methadone from opioid treatment programs (OTPs), and the percentage of OTPs operating at 80% capacity or more using Substance Abuse and Mental Health Services Administration data. Results. Nationally, in 2012, the rate of opioid abuse or dependence was 891.8 per 100 000 people aged 12 years or older compared with national rates of maximum potential buprenorphine treatment capacity and patients receiving methadone in OTPs of, respectively, 420.3 and 119.9. Among states and the District of Columbia, 96% had opioid abuse or dependence rates higher than their buprenorphine treatment capacity rates; 37% had a gap of at least 5 per 1000 people. Thirty-eight states (77.6%) reported at least 75% of their OTPs were operating at 80% capacity or more. Conclusions. Significant gaps between treatment need and capacity exist at the state and national levels. Strategies to increase the number of OA-MAT providers are needed. PMID:26066931

  1. Random Forest Segregation of Drug Responses May define Regions of Biological Significance

    Directory of Open Access Journals (Sweden)

    Qasim eBukhari

    2016-03-01

    Full Text Available The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF method to detect differences in the pharmacological MRI (phMRI response in rats to treatment with an analgesic drug (buprenorphine as compared to control (saline. Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD and high dose (HD, and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow an unsupervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

  2. Random Forest Segregation of Drug Responses May Define Regions of Biological Significance.

    Science.gov (United States)

    Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

    2016-01-01

    The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus, and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow a supervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

  3. Novelty seeking as a predictor of treatment retention for heroin dependent cocaine users.

    Science.gov (United States)

    Helmus, T C; Downey, K K; Arfken, C L; Henderson, M J; Schuster, C R

    2001-02-01

    This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant relationships with overall retention were entered into a logistic regression analysis. In addition, using a survival analysis, all variables with significant relationships with time to drop-out were entered into a multivariate proportional hazards regression with time dependent covariates. Results demonstrated that although high novelty seekers, in comparison to low novelty seekers, were more likely to drop-out by the end of treatment, they had higher retention rates during the early phases of treatment. It is suggested that buprenorphine and contingency management were viewed by participants as novel treatment components and thus facilitated high novelty seekers' success early in treatment. If replicated, results suggest that inclusion of novel treatment components might facilitate retention among this at-risk group.

  4. Treating opioid dependence. Growing implications for primary care.

    Science.gov (United States)

    Krantz, Mori J; Mehler, Philip S

    2004-02-01

    Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

  5. 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

  6. An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.

    Science.gov (United States)

    Crist, Richard C; Clarke, Toni-Kim; Ang, Alfonso; Ambrose-Lanci, Lisa M; Lohoff, Falk W; Saxon, Andrew J; Ling, Walter; Hillhouse, Maureen P; Bruce, R Douglas; Woody, George; Berrettini, Wade H

    2013-09-01

    Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44-0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95-2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population.

  7. Post-operative corticosterone levels in plasma and feces of mice subjected to permanent catheterization and automated blood sampling.

    Science.gov (United States)

    Sundbom, Renée; Jacobsen, Kirsten R; Kalliokoski, Otto; Hau, Jann; Abelson, Klas S P

    2011-01-01

    This study investigated the effects of surgical placement of permanent arterial catheters on plasma corticosterone levels, fecal corticosterone excretion and body weight in male BALB/c/Sca mice. In addition, the effects of voluntarily ingested buprenorphine in doses of 0.5 and 1.0 mg/kg body weight on these parameters were studied. A catheter was placed in the carotid artery during isoflurane anesthesia. Immediately after surgery, the mice were connected to an AccuSampler® μ and blood samples for plasma corticosterone quantification were collected automatically during the first 24 h postoperatively. All fecal boli produced 24 h before and 24 h after surgery were collected for fecal corticosterone excretion measures and the pre- and post-operative body weights were registered. Plasma corticosterone levels were in the range of 150-300 ng/ml after the surgical procedure and the body weight was significantly lower 24 h after surgery compared to its pre-operative value. Contrary to what was expected, the total fecal corticosterone excretion was significantly reduced 24 h after surgery, as was the defecation. Buprenorphine treatment significantly lowered the plasma corticosterone levels, but had no effect on fecal corticosterone excretion or body weight change. It was concluded that surgical placement of an arterial catheter induces a significant stress response, as judged by its effect on plasma corticosterone and body weight. Voluntary ingestion of buprenorphine improved postoperative recovery by lowering plasma corticosterone concentrations. Neither fecal corticosterone excretion nor body weight change seems suitable for postoperative stress assessment in mice in the present experimental setup.

  8. The effects of repeated opioid administration on locomotor activity: II. Unidirectional cross-sensitization to cocaine.

    Science.gov (United States)

    Smith, Mark A; Greene-Naples, Jennifer L; Felder, Jennifer N; Iordanou, Jordan C; Lyle, Megan A; Walker, Katherine L

    2009-08-01

    Sensitization refers to an increase in sensitivity to the effects of a drug and is believed to play a role in the etiology of substance use disorders. Cross-sensitization has been observed between drugs from different pharmacological classes and may play a role in the escalation of drug use in polydrug-abusing populations. The purpose of this study was to examine cross-sensitization between opioids and cocaine and to determine the extent to which cross-sensitization is mediated by an opioid's selectivity for mu, kappa, and delta receptors. Separate groups of rats were treated with opioid receptor agonists and antagonists every other day for 10 days, and the locomotor effects of cocaine were tested 8 days later. The mu agonists, morphine and buprenorphine, and the delta agonist, BW373U86 [(+/-)-4-[(R(*))-[(2S(*),5R(*))-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide hydrochloride], produced cross-sensitization to cocaine, such that repeated administration of these drugs over a 10-day period significantly enhanced cocaine's locomotor effects when tested later. Coadministration of the opioid antagonist naltrexone prevented morphine and buprenorphine from producing cross-sensitization. Coadministration of naltrexone, but not the delta antagonist naltrindole, also prevented BW373U86 from producing cross-sensitization. The kappa agonist spiradoline failed to produce cross-sensitization, but coadministration of spiradoline prevented morphine and buprenorphine from producing cross-sensitization. The ability of spiradoline to block cross-sensitization was itself blocked by the kappa antagonist nor-binaltorphimine. The mixed mu/kappa opioids butorphanol, nalbuphine, and nalorphine did not produce cross-sensitization under any condition examined. These data indicate that agonist activity at mu receptors positively modulates cross-sensitization between opioids and cocaine, whereas agonist activity at kappa receptors negatively modulates

  9. Impaired Auditory and Contextual Fear Conditioning in Soman-Exposed Rats

    Science.gov (United States)

    2011-01-01

    around the electrodes and secured in place using dental acrylic. The incision sites were sutured and the rats were administered buprenorphine (10.5...and sarin induce a long-lasting naloxone-reversible analgesia in mice. Life Sci 1984;34:1415–22. Clement JG, Rosario S, Bessette E, Erhardt N. Soman and...Shih TM, Romano JA. The effects of choline on soman-induced analgesia and toxicity. Neurotoxicol Teratol 1988;10:287–94. Shih TM, Duniho SM, McDonough JH

  10. 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...

  11. Stroke from Vasospasm due to Marijuana Use: Can Cannabis Synergistically with Other Medications Trigger Cerebral Vasospasm?

    Directory of Open Access Journals (Sweden)

    Marium Jamil

    2016-01-01

    Full Text Available We present a case of imaging proven cerebral vasospasm causing ischemic stroke in a young patient chronically on buprenorphine-naloxone for heroin remission who started smoking cannabis on a daily basis. With cannabis legalization spreading across the states in the USA, it is important for physicians not only to be aware of cannabis reported association with cerebral vasospasm in some patients but also to be on the lookout for possible interacting medications that can synergistically affect cerebral vessels causing debilitating strokes.

  12. 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

  13. Challenges and Opportunities for the Use of Medications to Treat Opioid Addiction in the United States and Other Nations of the World.

    Science.gov (United States)

    Parrino, Mark W; Maremmani, Angelo Giovanni Icro; Samuels, Paul N; Maremmani, Icro

    2015-01-01

    There has been a well documented increase in the use and abuse of prescription opioids and heroin in the United States and other parts of the world. There has also been an increasing focus to increase access to the use of medications (methadone, buprenorphine, Naltrexone/Vivitrol) for opioid addicted individuals under legal supervision. As policymakers engage in strategic initiatives to better prevent and effectively treat chronic opioid addiction, both in the United States and other countries, there are a number of unintended consequences, complicating how best to increase access to effective treatment.

  14. Comparison of pain models to detect opioid-induced hyperalgesia

    Directory of Open Access Journals (Sweden)

    Krishnan S

    2012-04-01

    Full Text Available Sumithra Krishnan1, Amy Salter2, Thomas Sullivan2, Melanie Gentgall3, Jason White4, Paul Rolan11Discipline of Pharmacology, School of Medical Sciences, The University of Adelaide, 2Discipline of Public Health, The University of Adelaide, 3Pain and Anesthesia Research Clinic, Royal Adelaide Hospital, 4Pharmacy School, University of South Australia, Adelaide, South Australia, AustraliaObjective: Chronic opioid therapy may be associated with hyperalgesia. Our objective was to determine if opioid-induced hyperalgesia detection sensitivity is dependent on the stimulus used to detect it.Methods: This open design study compared the detection of hyperalgesia in opioid-dependent subjects (n = 16 and healthy control subjects (n = 16 using the following pain stimuli: cold pain, electrical stimulation, mechanical pressure, and ischemic pain. The opioid-dependent subjects were maintained on either methadone (n = 8 or buprenorphine (n = 8 for at least 3 months. None of the controls was dependent on opioids or other drugs of abuse.Results: The opioid-dependent subjects were markedly more sensitive than controls to the cold pain test. Compared with the control group, the hazard ratio for ceasing the test due to intolerable pain was 7.7 (95% confidence interval [CI] 2.6–23.3 in the buprenorphine group and 4.5 (95% CI 1.7–15.6 in the methadone group, with similar data for the cold pain threshold. Of the remaining tests, there were differences only for the electrical pain threshold between treatment groups, with the geometric mean threshold in the buprenorphine group being 1.5 (95% CI 1.1–1.9-fold higher (ie, less sensitive than that of the controls; the geometric mean for the methadone group was 1.3 (95% CI 1.04–1.7-fold higher than that of the controls. There were no significant differences between buprenorphine and methadone patients in test responses. Women were more sensitive to the cold pain (hazard ratio for tolerance, 3.1 [95% CI 1.4–7.3] and

  15. 丁丙诺啡治疗阿片依赖性的研究进展

    Institute of Scientific and Technical Information of China (English)

    郑继旺; 张开镐

    1992-01-01

    丁丙诺啡(buprenorphine)是60年代末合成的舆列巴文(oripavine)类衍生物.它的药理作用和临床研究已于70年代陆续报道,并相继在西欧和美国作为新型强效镇痛药用于临床;60年代后开始在美国等地用于阿片类成瘾者的替代治疗。

  16. Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice

    Science.gov (United States)

    2009-06-29

    PerkinElmer Life and Analytical Sciences Inc., Wellesley, MA). Introduction of bioluminescence genes into the clinical isolate of A. bauman- nii. The...the National Institutes of Health. The mice received buprenorphine (0.03 mg/kg of body weight subcutaneously twice a day) for 3 days after the burn for...log units higher than that of the treated mouse burn (2.73 104 RLU). The burned areas of the two mice were then excised. Half of each excised burn

  17. Pathogenesis of Acute and Delayed Corneal Lesions After Ocular Exposure to Sulfur Mustard Vapor

    Science.gov (United States)

    2012-03-01

    0.98) and cleared with a half - life of 130 ± 21 hours (Fig. 7B; R2 . 0.98), similar to the half - life of rabbit albumin.24,25 Applying this analysis to...The half - life of the different serum protein fractions in the circulating blood. Bull Exp Biol Med. 1957;43:172–175. 25. Dixon FJ, Maurer PH...injection of ketamine HCl (15 mg/kg) and xylazine (7 mg/kg), and a loading dose of buprenorphine HCl (0.05 mg/mL) was administered subcutaneously. Osmotic

  18. Testing of Intravenous Hemostatic Agents in a Novel Swine Model of Bleeding: Preliminary Results With FXa-PCPs

    Science.gov (United States)

    2005-08-01

    final cumulative dose of 700 pmoles VIIa using a half - life of 147 min for factor Vl~a. Drug administered every 20 min. "a•bHigh dose given first...take into account the extremely short half - life of FXa (᝿ sec). In two of these pigs (#102 and #103), the low dose of drug (2.5 pmoles FXa/4.0 nmoles...using glycopyrrolate and TelazolR. Buprenorphine (0.9 mg, i.m.) was administered for analgesia. They were then and anesthetized (1-4% isoflurane in

  19. 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.

  20. Opioid substitution treatment in New Zealand: a 40 year perspective.

    Science.gov (United States)

    Deering, Daryle; Sellman, J Douglas; Adamson, Simon

    2014-07-04

    We provide an overview of the history and philosophy of the treatment for opioid dependence, which has been dominated by methadone substitution treatment for the past 40 years in New Zealand. Although changes in approach have occurred over this time, influenced by various sociopolitical events and changing ideologies, opioid substitution treatment has still "not come of age". It remains undermined by stigma and risk concerns associated with methadone and has struggled to be accessible and attractive to illicit opioid drug users, comprehensive and integrated into mainstream health care. However, the introduction in 2012 of Pharmac-subsidised buprenorphine combined with naloxone (Suboxone) in the context of an emerging trend towards a broader recovery and well-being orientation could signal a new era in treatment. The availability of buprenorphine-naloxone may also facilitate a further shift in treatment from primarily siloed specialist addiction services to integrated primary care services. This shift will help reduce stigma, promote patient self-management and community integration and align opioid substitution treatment with treatment for other chronic health conditions such as diabetes and asthma.

  1. Advances in the treatment of opioid use disorders

    Science.gov (United States)

    Woody, George E.

    2017-01-01

    The development of medications for treating persons with opioid use disorders has expanded the number of evidence-based treatment options, particularly for persons with the most severe disorders. It has also improved outcomes compared to psychosocial treatment alone and expanded treatment availability by increasing the number of physicians involved in treatment and the settings where patients can be treated. The medications include methadone, buprenorphine, buprenorphine/naloxone, and extended-release injectable naltrexone. Studies have shown that they are most effective when used over an extended, but as-yet-unspecified, period of time and with counseling and other services, particularly for the many with psychosocial problems. Though controversial in some cultures, well-designed studies in Switzerland, the Netherlands, Germany, and Canada have demonstrated the efficacy of supervised heroin injecting for persons who responded poorly to other treatments, and this treatment option has been approved by Switzerland and a few other E.U. countries. The degree to which medication-assisted therapies are available is dependent on many variables, including national and local regulations, preferences of individual providers and their geographical location, treatment costs, and insurance policies. Greater availability of medication-assisted therapies has become a major focus in the U.S. and Canada, where there has been a marked increase in deaths associated with heroin and prescription opioid use. This paper provides a brief summary of these developments. PMID:28184294

  2. Do drug treatment variables predict cognitive performance in multidrug-treated opioid-dependent patients? A regression analysis study

    Directory of Open Access Journals (Sweden)

    Rapeli Pekka

    2012-11-01

    Full Text Available Abstract Background Cognitive deficits and multiple psychoactive drug regimens are both common in patients treated for opioid-dependence. Therefore, we examined whether the cognitive performance of patients in opioid-substitution treatment (OST is associated with their drug treatment variables. Methods Opioid-dependent patients (N = 104 who were treated either with buprenorphine or methadone (n = 52 in both groups were given attention, working memory, verbal, and visual memory tests after they had been a minimum of six months in treatment. Group-wise results were analysed by analysis of variance. Predictors of cognitive performance were examined by hierarchical regression analysis. Results Buprenorphine-treated patients performed statistically significantly better in a simple reaction time test than methadone-treated ones. No other significant differences between groups in cognitive performance were found. In each OST drug group, approximately 10% of the attention performance could be predicted by drug treatment variables. Use of benzodiazepine medication predicted about 10% of performance variance in working memory. Treatment with more than one other psychoactive drug (than opioid or BZD and frequent substance abuse during the past month predicted about 20% of verbal memory performance. Conclusions Although this study does not prove a causal relationship between multiple prescription drug use and poor cognitive functioning, the results are relevant for psychosocial recovery, vocational rehabilitation, and psychological treatment of OST patients. Especially for patients with BZD treatment, other treatment options should be actively sought.

  3. Long term Suboxone™ emotional reactivity as measured by automatic detection in speech.

    Science.gov (United States)

    Hill, Edward; Han, David; Dumouchel, Pierre; Dehak, Najim; Quatieri, Thomas; Moehs, Charles; Oscar-Berman, Marlene; Giordano, John; Simpatico, Thomas; Barh, Debmalya; Blum, Kenneth

    2013-01-01

    Addictions to illicit drugs are among the nation's most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX) as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states ("true ground emotionality") in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of "true" emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP) and 33 members of Alcoholics Anonymous (AA). Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate "true ground" emotionality in long-term buprenorphine/naloxone combination (Suboxone™). We found in long-term SUBX patients a significantly flat affect (p<0.01), and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction.

  4. Long term Suboxone™ emotional reactivity as measured by automatic detection in speech.

    Directory of Open Access Journals (Sweden)

    Edward Hill

    Full Text Available Addictions to illicit drugs are among the nation's most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states ("true ground emotionality" in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of "true" emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP and 33 members of Alcoholics Anonymous (AA. Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate "true ground" emotionality in long-term buprenorphine/naloxone combination (Suboxone™. We found in long-term SUBX patients a significantly flat affect (p<0.01, and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction.

  5. October 2016 critical care case of the month

    Directory of Open Access Journals (Sweden)

    Fountain S

    2016-09-01

    Full Text Available No abstract available. Article truncated after first 150 words. A 27-year-old Caucasian man with past medical history of opioid abuse (reportedly sober for 10 years on buprenorphine, post traumatic stress disorder, depression and anxiety presented to the emergency department complaining of dysarthria after taking diphenhydramine and meclizine in addition to his prescribed trazodone and buprenorphine to try to sleep. He was discharged to home after his symptoms appeared to improve with intravenous fluid. He returned to the emergency department the following afternoon with worsening dysarthria, dysphagia, and subjective weakness. The patient was non toxic appearing, afebrile, vital signs were stable and his strength was reported as 5/5. Computed tomography of his head did not show any evidence of acute intracranial abnormality. Given his ongoing complaints, he was admitted for observation to the general medicine wards. That night a rapid response was initiated when the nurse found the patient to be unresponsive, but spontaneously breathing. The patient’s clinical status did ...

  6. Thermal latency studies in opiate-treated mice

    Directory of Open Access Journals (Sweden)

    Noam Schildhaus

    2014-01-01

    Full Text Available Background: The change in the reaction time of a tail or paw exposed to a thermal stimulus is a measure of nociceptive activity in laboratory animals. Tail-flick and plantar thermal sensitivity (Hargreaves tests are non-invasive, minimize stress, and can be used to screen animals for phenotype and drug activity. Objective: Hargreaves testing has been widely used in rats. We investigated its use to measure the activity of opiate analgesia in mice. Methods: Mice were used in thermal stimulus studies at 1-5 hours and 1-5 days to test acute and extended release preparations of buprenorphine. Results: Hargreaves testing had limited value at 1-5 hours because mice can have an obtunded response to opiate therapy. Tail-flick studies with restrained mice are not affected by the initial locomotor stimulation. Discussion: The present report describes a simple restraint system for mice. The utility of the system is demonstrated by examining the efficacy of acute and extended release buprenorphine injections in Balb/c and Swiss mice. Conclusion: Standardized tail-flick testing provides a sensitive robust method to monitor opiate activity in mice.

  7. Psychotherapeutic benefits of opioid agonist therapy.

    Science.gov (United States)

    Tenore, Peter L

    2008-01-01

    Opioids have been used for centuries to treat a variety of psychiatric conditions with much success. The so-called "opium cure" lost popularity in the early 1950s with the development of non-addictive tricyclic antidepressants and monoamine oxidase inhibitors. Nonetheless, recent literature supports the potent role of methadone, buprenorphine, tramadol, morphine, and other opioids as effective, durable, and rapid therapeutic agents for anxiety and depression. This article reviews the medical literature on the treatment of psychiatric disorders with opioids (notably, methadone and buprenorphine) in both the non-opioid-dependent population and in the opioid-dependent methadone maintenance population. The most recent neurotransmitter theories on the origin of depression and anxiety will be reviewed, including current information on the role of serotonin, N-Methyl d-Aspartate, glutamate, cortisol, catecholamine, and dopamine in psychiatric disorders. The observation that methadone maintenance patients with co-existing psychiatric morbidity (so called dual diagnosis patients) require substantially higher methadone dosages by between 20% and 50% will be explored and qualified. The role of methadone and other opioids as beneficial psychiatric medications that are independent of their drug abuse mitigating properties will be discussed. The mechanisms by which methadone and other opioids can favorably modulate the neurotransmitter systems controlling mood will also be discussed.

  8. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

    Science.gov (United States)

    Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

    2014-02-01

    The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence.

  9. No-carrier-added (NCA) N-(3-( sup 18 F)fluoropropyl)-N-norbuprenorphine and N-(3-( sup 18 F)fluoropropyl)-N-nordiprenorphine -synthesis, anatomical distribution in mice and rats, and tomographic studies in a baboon

    Energy Technology Data Exchange (ETDEWEB)

    Lanqin Bai; Renrui Teng; Chyngyann Shiue; Wolf, A.P.; Dewey, S.L. (Brookhaven National Lab., Upton, NY (USA)); Holland, M.J.; Simon, E.J. (New York Univ., NY (USA). Medical Center)

    1990-01-01

    N-(3-Fluoropropyl)-N-norbuprenorphine (3a) and N-(3-fluoropropyl)-N-nordiprenorphine (4a) were synthesized by N-alkylation of norbuprenorphine (1) and nordiprenorphine (2) with 1-bromo-3-fluoropropane. The corresponding no-carrier-added (NCA) N-(3-({sup 18}F)fluoropropyl)-N-norbuprenorphine (3b) and N-(3-({sup 18}F)fluoropropyl)-N-nordiprenorphine (4b) were synthesized by N-alkylation of 1 and 2 with NCA 1-({sup 18}F)fluoro-3-iodopropane. In vitro studies indicate that in the absence of sodium chloride, compounds 3a, 4a, N-propyl-N-norbuprenorphine (5), buprenorphine and diprenorphine are reasonably comparable in binding affinity for opioid receptors. In the presence of 100 mM sodium chloride, however, compounds 3a, 4a and 5, are clearly less potent than buprenorphine and diprenorphine. The anatomical distribution study of compound 3b in mice shows radioactivity accumulating in bone. Rat studies of both compounds 3b and 4b indicate the specific distribution of these two radioligands within certain cortical and subcortical regions of rat brain. However, the absolute uptake of compound 4b in rat brain was only half that of compound 3b. PET studies of 3b in a baboon revealed specific binding of compound 3b in striatum and cerebellum. At 1 h after injection, ratios of specific/non-specific binding of 3b in striatum and cerebellum of a baboon were 1.9 and 1.7 respectively. (author).

  10. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    Directory of Open Access Journals (Sweden)

    Michael Guarnieri

    2014-01-01

    Full Text Available Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs.

  11. 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.

  12. 舒芬太尼用于剖宫产术后静脉自控镇痛35例%Sufentanil Used for Patient Controlled Intravenous Analgesia after Cesarean Section in 35 Cases

    Institute of Scientific and Technical Information of China (English)

    蒋永春; 张健; 成勤

    2016-01-01

    目的:观察比较舒芬太尼与丁丙诺啡用于剖宫产术后静脉自控镇痛(PCIA)的效果及不良反应。方法将择期剖宫产术产妇70例随机分为舒芬太尼组和丁丙诺啡组,各35例。术后使用患者静脉自控镇痛( PCIA ),于4,8,24,48 h进行视觉模拟评分(VAS)和Ramsay镇静评分,记录镇痛泵的有效按压次数,观察比较不良反应发生情况,回访镇痛效果。结果两组间VAS评分无显著差异, Ramsay评分和有效按压次数有显著差异,舒芬太尼组的主观满意度高于丁丙诺啡组( P<0.05),丁丙诺啡组的不良反应发生率高于舒芬太尼组( P<0.05)。结论舒芬太尼用于剖宫产术后PCIA具有与丁丙诺啡相当的镇痛效果,但不良反应的发生率低于后者,值得临床推广。%Objective To compare the analgesic effect and adverse reaction of PCIA using sufentanil and buprenorphine in cesarean sec-tion. Methods 70 lying-in women of elective caesarean birth operation were randomly divided into 2 groups, including the sufentanil group of 35 cases and the buprenorphine group of 35 cases. And after the postoperative use of PCIA, score VAS and Ramsay at 4, 8, 24, 48 h respectively to record analgesic pump′s effective pressing number of times and to observe and compare and the adverse reac-tions, paying the return visit to the patients about the analgesic effect. Results There were no significant differences between the VAS scores of 2 groups, while there were significant differences in Ramsay scores and effective pressing number of time ( P < 0. 05 ) . The subjective satisfaction degree of the sufentanil group was higher than that of the buprenorphine group ( P < 0. 05 ) . And the adverse re-actions of buprenorphine group occurred more than those of sufentanil group ( P < 0. 05 ) . Conclusion The analgesic effect of sufentanil applied in cesarean section postoperative PCIA is almost same with buprenorphine, but the adverse

  13. Opioid dependence and pregnancy: minimizing stress on the fetal brain.

    Science.gov (United States)

    McCarthy, John J; Leamon, Martin H; Finnegan, Loretta P; Fassbender, Catherine

    2017-03-01

    Increase in the number of opioid-dependent pregnant women delivering babies at risk for neonatal abstinence syndrome prompted a US Government Accountability Office report documenting deficits in research and provider knowledge about care of the maternal/fetal unit and the neonate. There are 3 general sources of dependence: untreated opioid use disorder, pain management, and medication-assisted treatment with methadone or buprenorphine. A survey of methadone patients' experiences when telling a physician of their pregnancy and opioid dependence demonstrated physician confusion about proper care, frequent negative interactions with the mother, and failures to provide appropriate referral. Patients in pain management were discharged without referral when the physician was told of the pregnancy. Methadone and buprenorphine were frequently seen negatively because they "caused" neonatal abstinence syndrome. Most mothers surveyed had to find opioid treatment on their own. How dependence is managed medically is a critical determinant of the level of stress on both mother and fetus, and therefore another determinant of neonatal health. The effects of both opioid withdrawal stress and maternal emotional stress on neonatal and developmental outcomes are reviewed. Currently, there have been efforts to criminalize maternal opioid dependence and to encourage or coerce pregnant women to undergo withdrawal. This practice poses both acute risks of fetal hypoxia and long-term risks of adverse epigenetic programming related to catecholamine and corticosteroid surges during withdrawal. Contemporary studies of the effects of withdrawal stress on the developing fetal brain are urgently needed to elucidate and quantify the risks of such practices. At birth, inconsistencies in the hospital management of neonates at risk for neonatal abstinence syndrome have been observed. Neglect of the critical role of maternal comforting in neonatal abstinence syndrome management is an iatrogenic and

  14. On drug treatment and social control: Russian narcology's great leap backwards

    Directory of Open Access Journals (Sweden)

    Drucker Ernest

    2008-06-01

    Full Text Available Abstract The medical discipline of narcology in Russia is a subspecialty of psychiatry from the Soviet era and it is given warrant to define the scope of health activities with regard to alcohol and other drug use, drug users, and related problems. Narcological practice is in turn constrained by the State. The emergence of widespread injection opiate use and associated HIV morbidities and mortalities during the first decade following the collapse of the Soviet Union has brought the contradictions in Russian narcological discourse into high relief. Narcology officials in the Russian Federation have consistently opposed substitution treatment for opiate dependence – the replacement of a short-acting illegal substance with a longer acting prescribed drug with similar pharmacological action but lower degree of risk. Thus, despite the addition of methadone and buprenorphine to WHO's list of essential medicines in 2005 and multiple position papers by international experts calling for substitution treatment as a critical element in the response to HIV (IOM, 2006; UNODC, UNAIDS, and WHO, 2005, methadone or buprenorphine remain prohibited by law in Russia. The authors detail Russian opposition to the prescription of methadone and buprenorphine, describing four phenomena: (1 the dominance of law enforcement and drug control policy over public health and medical ethics ; (2 the conflation of Soviet era alcoholism treatment with treatment for opiate dependence; (3 the near universal representation of detoxification from drugs as treatment for dependence; and (4 a framework for judging treatment efficacy that is restricted to "cure" versus "failure to cure," and does not admit its poor outcomes or recognize alternative frameworks for gauging treatment of opiate dependence. In keeping with this position, Russian narcology officials have taken an implacable ideological stance toward illicit drug use, the people who use drugs, and their treatment. By adopting

  15. Which potent opioid? Important criteria for selection.

    Science.gov (United States)

    Bovill, J G

    1987-05-01

    Opioids remain the drugs of choice for the treatment of severe pain. In recent years several new potent opioids have become available for clinical use. These newer drugs are generally safer than the older morphine-like compounds and their differing pharmacological and pharmacokinetic properties allow the physician to choose an appropriate drug according to the clinical situation and need of an individual patient. These drugs are classified according to their activity at the opioid receptors. The opioid agonists produce their pharmacological effect by an almost exclusive action at mu-receptors. The agonist-antagonist group are kappa-receptor agonists and either competitive antagonists at the mu-receptor or weak mu-agonists. The use of the potent opioid agonists, because of their potential for causing respiratory depression, is restricted to hospitals. Fentanyl, the oldest drug of this class, is extensively used as a supplement to general anaesthesia, or in high doses as a 'complete' anaesthetic for patients undergoing cardiac surgery. Alfentanil and sufentanil are newer fentanyl derivatives. Alfentanil is unique in having a very short elimination half-life. This is a particular advantage during short operations and for day-case surgery. For longer operations alfentanil can be given as a continuous infusion to supplement nitrous oxide anaesthesia. Sufentanil is about 10 times more potent than fentanyl and is more rapidly eliminated. Initial reports suggest that it may be more effective than fentanyl as an anaesthetic supplement and that recovery may be more rapid. Both sufentanil and alfentanil are also used in cardiac anaesthesia. The newer agonist-antagonist opioids, butorphanol, nalbuphine and buprenorphine, have largely replaced pentazocine in clinical practice. Unlike pentazocine, they cause a low incidence of dysphoric side effects. Like the pure agonists, they cause respiratory depression; however, in contrast to the pure agonists this is not dose related

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

    Science.gov (United States)

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

    2012-08-01

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

  17. 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

    The frequency of medico-legally examined fatal poisonings in 2007 among drug addictswas investigated in five Nordic countries; Denmark, Finland, Iceland, Norway, and Sweden. The number of deaths, age, sex, place of death, main intoxicant, and other drugs present in blood samples were recorded...... to obtain national and comparable Nordic data, as well as data to compare with earlier studies in 2002, 1997, and 1991. Norway had the highest incidence of drug addict deaths by poisoning followed by Denmark, with 8.24 and 6.92 per 100,000 inhabitants, respectively. The death rates in Finland (4...... 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...

  18. 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....

  19. 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

  20. Fate of psychoactive compounds in wastewater treatment plant and the possibility of their degradation using aquatic plants.

    Science.gov (United States)

    Mackuľak, Tomáš; Mosný, Michal; Škubák, Jaroslav; Grabic, Roman; Birošová, Lucia

    2015-03-01

    In this study we analyzed and characterized 29 psychoactive remedies, illicit drugs and their metabolites in single stages of wastewater treatment plants in the capital city of Slovakia. Psychoactive compounds were present within all stages, and tramadol was detected at a very high concentration (706 ng/L). Significant decreases of codeine, THC-COOH, cocaine and buprenorphine concentration were observed in the biological stage. Consequently, we were interested in the possibility of alternative tertiary post-treatment of effluent water with the following aquatic plants: Cabomba caroliniana, Limnophila sessiliflora, Egeria najas and Iris pseudacorus. The most effective plant for tertiary cleansing was I. pseudacorus which demonstrated the best pharmaceutical removal capacity. After 48 h codeine and citalopram was removed with 87% efficiency. After 96 h were all analyzed compounds were eliminated with efficiencies above 58%.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Refractometry for quality control of anesthetic drug mixtures.

    Science.gov (United States)

    Stabenow, Jennifer M; Maske, Mindy L; Vogler, George A

    2006-07-01

    Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

  7. Dual isolation technique for paediatric lung surgery.

    Directory of Open Access Journals (Sweden)

    Pantvaidya S

    1994-04-01

    Full Text Available This report describes a dual isolation technique adopted to isolate the lungs from one another at the time of right pneumonectomy in a child (age: 5 yrs, 10 kg weight with evidence of infective lung disease associated with copious purulent secretion and compromised respiratory function. The isolation of right lung from left was achieved by placing Fogarty embolectomy catheter in right main bronchus and a plain polyvinylchloride endotracheal tube (which was aseptically preshaped to have a distal 45 degrees angulation towards left in left main bronchus. No soiling of left lung occurred during surgery and patient remained hemodynamically stable. In the same child, post-thoracotomy pain was relieved for five days with buprenorphine, administered through a lumbar epidural catheter. The child had an uneventful post-operative course and cooperated for physiotherapy.

  8. 丁丙诺啡在癌性疼痛应用上的临床观察

    Institute of Scientific and Technical Information of China (English)

    刘刚; 蒋顺

    2015-01-01

    Objective: To Investigate the efficacy and safety of buprenorphine hydrochloride injection in treatment of cancer pain. Methods:70 advanced malignant tumor patients with moderate or severe cancer pain were enrolled in our hospital. They were divided into two groups:observation group ( 35 cases) and control group ( 35 cases). Patients in the control group were treated with morphine hydrochloride injection, and the observation group was treated with buprenorphine hydrochloride injection. The course of treatment was 1 week. The analgesic effect and adverse drug reaction were compared between two groups. Results: The analgesic effect of the observation group was better than the control group (P<0.05). The number of patients in observation group with adverse reactions were significantly less than that of the control group (P<0.05). Conclusion:It has obvious effect of buprenorphine and morphine in treatment of cancer pain. The analgesic effect of buprenorphine is better than that of morphine, and it has less adverse reactions. It is worth to be popularized in treatment of cancer pain.%目的:本研究旨在探讨盐酸丁丙诺啡注射液控制癌性疼痛的有效性和安全性。方法:选取2013年12月~2014年12月于我院就诊的70例伴有中重度癌痛的晚期恶性肿瘤患者,根据随机分组原则将患者分成观察组(35例)和对照组(35例)。对照组患者癌痛发作时给予盐酸吗啡注射液治疗,观察组患者给予盐酸丁丙诺啡注射液治疗。连续用药1周为一疗程,对比两组患者疼痛控制效果及用药不良反应。结果:两组患者用药后临床疗效均较好,但观察组镇痛疗效好于对照组(P<0.05)。观察组发生不良反应发生率显著少于对照组(P<0.05)。结论:丁丙诺啡及吗啡用于控制中晚期恶性肿瘤患者癌痛均有明显效果,丁丙诺啡镇痛效果优于吗啡,且不良反应较少,用法简便,值得在癌性疼痛治疗工作中加以推广。

  9. 丁丙诺啡临床应用研究进展

    Institute of Scientific and Technical Information of China (English)

    肖国椿; 肖李莉

    2002-01-01

    @@ 丁丙诺啡(Buprenorphine,Bup)是蒂巴因衍生物,化学名称为N-环丙基甲基-7 α[I-(s)-1-羟基-1,2,3三甲基]-6,14桥Z烷-6,7,8,14-四氢化降东罂粟碱,是阿片受体激动-拮抗剂,镇痛作用强,持续时间长,是目前临床上用于治疗疼痛和对阿片类依赖患者戒毒治疗的有效、安全的药物之一.

  10. 盐酸丁丙诺啡的镇痛作用

    Institute of Scientific and Technical Information of China (English)

    丁长玲; 周肖龙

    2002-01-01

    @@ 盐酸丁丙诺啡(Buprenorphine,Temgesic)是人工合成的菲类阿片生物碱蒂巴茵的衍生物[1].属吗啡受体的混合型激动拮抗镇痛药,1990年卫生部正式批准丁丙诺啡作为镇痛药用于临床.随着临床的应用,有关该药的研究不断深入,为了给临床提供该药的最新研究成果,现将有关本药镇痛方面的研究进展情况简述如下.

  11. Torsades de pointes with methadone.

    Science.gov (United States)

    2005-04-01

    (1) Methadone is an opiate used for replacement therapy of opiate addiction that causes dose-dependent QT prolongation. (2) Severe ventricular arrhythmias such as torsades de pointes have been reported, usually in patients on high doses (100 mg to 400 mg/day). (3) Methadone has a long plasma elimination half-life, and this poses a risk of accumulation. Accumulation is especially problematic when the dose is increased too rapidly. Combining methadone with a CYP 3A4 inhibitor increases the risk of torsades de pointes, as methadone is metabolised by this enzyme system. (4) Factors potentially predisposing patients to torsades de pointes must be analysed in each case; these include preexisting bradycardia, congenital QT prolongation, hypokalemia, and concomitant use of other drugs inducing QT prolongation. (5) This adverse effect has also been reported with levacetylmethadol (another opiate) and with heroin. It does not seem to occur with buprenorphine.

  12. [Taking care of drug addict in odontology].

    Science.gov (United States)

    Pirnay, Philippe; Pirnay, Stéphane

    2010-01-01

    In the dental surgery practice, a drug addicted patient declares suffering from high pain and asks with insistence to be examined in emergency. The clinical examination shows a pity overall dental status: an important dental deterioration, a periodontal disease. At the end of the examination, the patient suffering withdrawal syndrome, asks with a high demand up to physical threat, to get a prescription of psychotropic medicines, and especially opiates (high dose buprenorphine). In front of this situation, the dental surgeon will face two aspects: first of all, clinical issues, as taking care of the odontological pathologies, management of the pain and of the withdrawal syndrome and second of all, the legislation issues related to its responsibility of prescription writer and the specific attitude to adjust in front of a patient with withdrawal syndrome at the dental surgery practice.

  13. The Opioid Epidemic: What Does it Mean for Nurses?

    Science.gov (United States)

    Leahy, Laura G

    2017-01-01

    The United States is facing a major crisis with the current opioid epidemic. Tens of thousands of individuals are dying each year due to abuse and misuse of heroin and prescription opiate drugs. Nurses play an integral role in these aspects of health care and offer solutions by providing education; preventive measures; treatments, including medication-assisted treatments (MATs); and ongoing recovery options for individuals with opioid use disorders. Nurses provide education, issue prescriptions and dispense medications, and provide overall physical and mental health care to patients struggling with this "disease of the brain," and with the signing of the Comprehensive Addiction and Recovery Act, advanced practice RNs will soon be able to include MATs related to buprenorphine as part of their treatment plan. The current article explores the anatomy, physiology, and genetics of addiction and how they relate to the pharmacological MATs used to treat opioid use disorders. [Journal of Psychosocial Nursing and Mental Health Services, 55(1), 18-23.].

  14. Opiate addiction - current trends and treatment options

    Directory of Open Access Journals (Sweden)

    Achal Bhatt

    2016-07-01

    Full Text Available Opioids are widely used drugs for treatment of pain and related disorders. Opiate addiction is a major public health concern in the United States causing significant increase in healthcare expenditure. They produce euphoria and sense of well-being which makes them addictive to some people. Used in higher doses they can lead to cardiac or respiratory compromise. They also impair cognition leading to impaired decision making. Opioids exert their effects by acting on three different types of receptors mu, delta, and kappa located on neuronal cell membranes causing inhibition of neurotransmitter release. Prolonged use of these drugs can lead to physical dependence causing withdrawal symptoms if a person stops using them. Commonly used medications to treat opiate addiction are methadone, LAAM (longer acting derivative of methadone, buprenorphine, and naltrexone. [Int J Res Med Sci 2016; 4(7.000: 2503-2507

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

    Science.gov (United States)

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

    2016-08-05

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

  16. Psychometric assessment of the Rat Grimace Scale and development of an analgesic intervention score.

    Directory of Open Access Journals (Sweden)

    Vanessa Oliver

    Full Text Available Our limited ability to assess spontaneous pain in rodent models of painful human conditions may be associated with a translational failure of promising analgesic compounds in to clinical use. If measurement of spontaneous pain behaviours can be used to generate an analgesic intervention score their use could expand to guide the use of analgesics, as mandated by regulatory bodies and ethical and welfare obligations. One such measure of spontaneous pain, the Rat Grimace Scale (RGS, has recently been described and shown to exhibit reliability. However, reliability of measurement scores is context and content specific, and further testing required to assess translation to a heterogenous setting (different model, raters, environment. The objectives of this study were to perform reliability testing with the Rat Grimace Scale in a heterogenous setting and generate an analgesic intervention score for its use. In a randomised, blinded study, sixteen adult female rats received one of three analgesia treatments (0.05 mg/kg buprenorphine subcutaneously, 1 mg/kg meloxicam subcutaneously, 0.2 mg/kg oral buprenorphine in jelly peri-operatively (telemetry unit implantation surgery. Rats were video-recorded (before, 1-6 and 12 hours post-operatively and images collected for independent scoring by three blinded raters using the RGS, and five experts based on "pain/no pain" assessment. Scores were used to calculate inter- and intra-rater reliability with an intraclass correlation coefficient and generate an analgesic intervention score with receiver operating characteristic curve analysis. The RGS scores showed very good inter- and intra-rater reliability (0.85 [0.78-0.90 95% CI] and 0.83 [0.76-0.89], respectively. An analgesic intervention threshold of greater than 0.67 was determined. These data demonstrate that the RGS is a useful tool which can be successfully employed in a heterogenous setting, and has the potential to guide analgesic intervention.

  17. Impact of efficacy at the μ-opioid receptor on antinociceptive effects of combinations of μ-opioid receptor agonists and cannabinoid receptor agonists.

    Science.gov (United States)

    Maguire, David R; France, Charles P

    2014-11-01

    Cannabinoid receptor agonists, such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC), enhance the antinociceptive effects of μ-opioid receptor agonists, which suggests that combining cannabinoids with opioids would improve pain treatment. Combinations with lower efficacy agonists might be preferred and could avoid adverse effects associated with large doses; however, it is unclear whether interactions between opioids and cannabinoids vary across drugs with different efficacy. The antinociceptive effects of μ-opioid receptor agonists alone and in combination with cannabinoid receptor agonists were studied in rhesus monkeys (n = 4) using a warm water tail withdrawal procedure. Etorphine, fentanyl, morphine, buprenorphine, nalbuphine, Δ(9)-THC, and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol) each increased tail withdrawal latency. Pretreatment with doses of Δ(9)-THC (1.0 mg/kg) or CP 55,940 (0.032 mg/kg) that were ineffective alone shifted the fentanyl dose-effect curve leftward 20.6- and 52.9-fold, respectively, and the etorphine dose-effect curve leftward 12.4- and 19.6-fold, respectively. Δ(9)-THC and CP 55,940 shifted the morphine dose-effect curve leftward only 3.4- and 7.9-fold, respectively, and the buprenorphine curve only 5.4- and 4.1-fold, respectively. Neither Δ(9)-THC nor CP 55,940 significantly altered the effects of nalbuphine. Cannabinoid receptor agonists increase the antinociceptive potency of higher efficacy opioid receptor agonists more than lower efficacy agonists; however, because much smaller doses of each drug can be administered in combinations while achieving adequate pain relief and that other (e.g., abuse-related) effects of opioids do not appear to be enhanced by cannabinoids, these results provide additional support for combining opioids with cannabinoids to treat pain.

  18. 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. 

  19. Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

    Directory of Open Access Journals (Sweden)

    Alexandra L Whittaker

    Full Text Available Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8. Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg and NSAID (carprofen; 15mg/kg in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg. Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001. Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

  20. Patterns of drug abuse among drug users with regular and irregular attendance for treatment as detected by comprehensive UHPLC-HR-TOF-MS.

    Science.gov (United States)

    Sundström, Mira; Pelander, Anna; Simojoki, Kaarlo; Ojanperä, Ilkka

    2016-01-01

    The most severe consequences of drug abuse include infectious diseases, overdoses, and drug-related deaths. As the range of toxicologically relevant compounds is continually changing due to the emergence of new psychoactive substances (NPS), laboratories are encountering analytical challenges. Current immunoassays are insufficient for determining the whole range of the drugs abused, and a broad-spectrum screening method is therefore needed. Here, the patterns of drug abuse in two groups of drug users were studied from urine samples using a comprehensive screening method based on high-resolution time-of-flight mass spectrometry. The two groups comprised drug abusers undergoing opioid maintenance treatment (OMT) or drug withdrawal therapy and routinely visiting a rehabilitation clinic, and drug abusers with irregular attendance at a harm reduction unit (HRU) and suspected of potential NPS abuse. Polydrug abuse was observed in both groups, but was more pronounced among the HRU subjects with a mean number of concurrent drugs per sample of 3.9, whereas among the regularly treated subjects the corresponding number was 2.1. NPS and pregabalin were more frequent among HRU subjects, and their abuse was always related to drug co-use. The most common drug combination for an HRU subject included amphetamine, cannabis, buprenorphine, benzodiazepine, and alpha-pyrrolidinovalerophenone. A typical set of drugs for treated subjects was buprenorphine, benzodiazepine, and occasionally amphetamine. Abuse of several concurrent drugs poses a higher risk of drug intoxication and a threat of premature termination of OMT. Since the subjects attending treatment used fewer concurrent drugs, this treatment could be valuable in reducing polydrug abuse.

  1. Non-analgesic effects of opioids: opioid-induced respiratory depression.

    Science.gov (United States)

    Boom, Merel; Niesters, Marieke; Sarton, Elise; Aarts, Leon; Smith, Terry W; Dahan, Albert

    2012-01-01

    Opioids induce respiratory depression via activation of μ-opioid receptors at specific sites in the central nervous system including the pre-Bötzinger complex, a respiratory rhythm generating area in the pons. Full opioid agonists like morphine and fentanyl affect breathing with onset and offset profiles that are primarily determined by opioid transfer to the receptor site, while the effects of partial opioid agonists such as buprenorphine are governed by transfer to the receptor site together with receptor kinetics, in particular dissociation kinetics. Opioid-induced respiratory depression is potentially fatal but may be reversed by the opioid receptor antagonist naloxone, an agent with a short elimination half-life (30 min). The rate-limiting factor in naloxone-reversal of opioid effect is the receptor kinetics of the opioid agonists that requires reversal. Agents with slow dissociation kinetics (buprenorphine) require a continuous naloxone infusion while agents with rapid kinetics (fentanyl) will show complete reversal upon a single naloxone dose. Since naloxone is non-selective and will reverse analgesia as well, efforts are focused on the development of compounds that reverse opioid-induced respiratory depression without affecting analgesic efficacy. Such agents include ampakines and serotonin agonists which are aimed at selectively enhancing central respiratory drive. A novel approach is aimed at the reduction of respiratory depression from opioid-activation of (micro-)glia cells in the pons and brainstem using micro-glia cell stabilizers. Since this approach simultaneously enhances opioid analgesic efficacy it seems an attractive alternative to the classical reversal strategies with naloxone.

  2. 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

    2016-02-01

    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.

  3. The perfect storm: incarceration and the high-risk environment perpetuating transmission of HIV, hepatitis C virus, and tuberculosis in Eastern Europe and Central Asia.

    Science.gov (United States)

    Altice, Frederick L; Azbel, Lyuba; Stone, Jack; Brooks-Pollock, Ellen; Smyrnov, Pavlo; Dvoriak, Sergii; Taxman, Faye S; El-Bassel, Nabila; Martin, Natasha K; Booth, Robert; Stöver, Heino; Dolan, Kate; Vickerman, Peter

    2016-09-17

    Despite global reductions in HIV incidence and mortality, the 15 UNAIDS-designated countries of Eastern Europe and Central Asia (EECA) that gained independence from the Soviet Union in 1991 constitute the only region where both continue to rise. HIV transmission in EECA is fuelled primarily by injection of opioids, with harsh criminalisation of drug use that has resulted in extraordinarily high levels of incarceration. Consequently, people who inject drugs, including those with HIV, hepatitis C virus, and tuberculosis, are concentrated within prisons. Evidence-based primary and secondary prevention of HIV using opioid agonist therapies such as methadone and buprenorphine is available in prisons in only a handful of EECA countries (methadone or buprenorphine in five countries and needle and syringe programmes in three countries), with none of them meeting recommended coverage levels. Similarly, antiretroviral therapy coverage, especially among people who inject drugs, is markedly under-scaled. Russia completely bans opioid agonist therapies and does not support needle and syringe programmes-with neither available in prisons-despite the country's high incarceration rate and having the largest burden of people with HIV who inject drugs in the region. Mathematical modelling for Ukraine suggests that high levels of incarceration in EECA countries facilitate HIV transmission among people who inject drugs, with 28-55% of all new HIV infections over the next 15 years predicted to be attributable to heightened HIV transmission risk among currently or previously incarcerated people who inject drugs. Scaling up of opioid agonist therapies within prisons and maintaining treatment after release would yield the greatest HIV transmission reduction in people who inject drugs. Additional analyses also suggest that at least 6% of all incident tuberculosis cases, and 75% of incident tuberculosis cases in people who inject drugs are due to incarceration. Interventions that reduce

  4. Effect of gabapentin on patient controlled intravenous analgesia after modified radical mastectomy%加巴喷丁对乳腺癌术后患者自控静脉镇痛的影响

    Institute of Scientific and Technical Information of China (English)

    崔修德; 刘峰; 刘鹏; 荆凤娥; 刘有才; 马驰骋; 张利军

    2010-01-01

    Objective To evaluate the effects of a single preoperative dose of gabapentin on buprenorphine patient controlled intravenous analgesia after modified radical mastectorny. Methods Sixty female patients,ASA physical starus Ⅰ and Ⅱ undergoing modified radical mastectomy under general anesthesia were divided into two groups of 30 each group by random digits table to receive either gabapentin 1200 mg (gabapentin group) or a matching placebo (control group), administered orally 2 h before the induction of anesthesia. Subjects received patient controlled intravenous buprenorphi(n)e analgesia during thepostoperative period. Fifty-three patients finished this study, 28 cases in control group,25 cases in gabapentin group. Postoperative pain (static and dynamic),postoperative nausea and vomiting,anxiety,sedation were assessed by pain visual analogue scale(VAS), four-point ordinal scale, anxiety visual analogue scale, Ramsay sedation scale respectively. Postoperative buprenorphine consumption and time to first patient controlled analgesia were observed. Results Postoperative VAS (static and dynamic) was lower in gabapentin group than that in control group (P <0.05). Postoperative buprenorphine consumption was (506.1 ±37.9)μg , time to first patient controlled analgesia was (21.1 ±2.3)min,incidence rate of postoperative nausea and vomiting was 40.0% (10/25), antemetic rate was 12.0% (3/25), grade of anxiety was (28.5 ± 12.1) scores in gabapentin group, (699.8 ± 87.8)μ g, (4.3 ±0.8) min,64.3% (18/28),32.1%(9/28) and (66.3±15.7) scores in control group respectively. There were significant differences between two groups (P < 0.05). Conclusion A single preoperative oral dose of gabapentin 1200 mg can effectively attenuate postoperative pain,reduce the consumption of buprenorphine,decrease the incidence rate of postoperative nausea and vomiting,improve patients' anxiety in patients undergoing modified radical mastectomy under general anesthesia.%目的 评价乳腺

  5. P-gp/ABCB1 exerts differential impacts on brain and fetal exposure to norbuprenorphine.

    Science.gov (United States)

    Liao, Michael Z; Gao, Chunying; Shireman, Laura M; Phillips, Brian; Risler, Linda J; Neradugomma, Naveen K; Choudhari, Prachi; Prasad, Bhagwat; Shen, Danny D; Mao, Qingcheng

    2017-01-19

    Norbuprenorphine is the major active metabolite of buprenorphine which is commonly used to treat opiate addiction during pregnancy. Norbuprenorphine produces marked respiratory depression and was 10 times more potent than buprenorphine. Therefore, it is important to understand the mechanism that controls fetal exposure to norbuprenorphine, as exposure to this compound may pose a significant risk to the developing fetus. P-gp/ABCB1 and BCRP/ABCG2 are two major efflux transporters regulating tissue distribution of drugs. Previous studies have shown that norbuprenorphine, but not buprenorphine, is a P-gp substrate. In this study, we systematically examined and compared the roles of P-gp and BCRP in determining maternal brain and fetal distribution of norbuprenorphine using transporter knockout mouse models. We administered 1mg/kg norbuprenorphine by retro-orbital injection to pregnant FVB wild-type, Abcb1a(-/-)/1b(-/-), and Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice on gestation day 15. The fetal AUC of norbuprenorphine was ∼64% of the maternal plasma AUC in wild-type mice, suggesting substantial fetal exposure to norbuprenorphine. The maternal plasma AUCs of norbuprenorphine in Abcb1a(-/-)/1b(-/-) and Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice were ∼2 times greater than that in wild-type mice. Fetal AUCs in Abcb1a(-/-)/1b(-/-) and Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice were also increased compared to wild-type mice; however, the fetal-to-maternal plasma AUC ratio remained relatively unchanged by the knockout of Abcb1a/1b or Abcb1a/1b/Abcg2. In contrast, the maternal brain-to-maternal plasma AUC ratio in Abcb1a(-/-)/1b(-/-) or Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice was increased ∼30-fold compared to wild-type mice. Protein quantification by LC-MS/MS proteomics revealed significantly higher amounts of P-gp protein in the wild-type mice brain than that in the placenta. These results indicate that fetal exposure to norbuprenorphine is substantial and that P-gp has a minor impact on

  6. "Weak" opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine.

    Science.gov (United States)

    2016-02-01

    So-called weak opioid analgesics are often used to treat severe pain, or when paracetamol or a nonsteroidal anti-inflammatory drug (NSAID) proves inadequate. But are weak opioids any more effective than paracetamol or NSAIDs on nociceptive pain, and are they better tolerated than morphine? To answer these questions, we conducted a review of literature using the standard Prescrire methodology. The potency of codeine and tramadol is strongly influenced by the cytochrome P450 isoenzyme CYP2D6 genotype, which varies widely from one person to another. This explains reports of overdosing or underdosing after administration of standard doses of the two drugs. The potency of morphine and that of buprenorphine, an opioid receptor agonist-antagonist, appears to be independent of CYP2D6 activity. All "weak" opioids can have the same dose-dependent adverse effects as morphine. There is no evidence that, at equivalent analgesic efficacy, weak opioids carry a lower risk of addiction than low-dose morphine. Respiratory depression can occur in ultrarapid metabolisers after brief exposure to standard doses of codeine or tramadol. Similar cases have been reported with dihydrocodeine in patients with renal failure. In addition, tramadol can cause a serotonin syndrome, hypoglycaemia, hyponatraemia and seizures. Several trials have compared different weak opioids in patients with post-operative pain. A single dose of a weak opioid, possibly combined with paracetamol, has greater analgesic efficacy than paracetamol alone but is not more effective than an NSAID alone. There is a dearth of evidence on weak opioids in patients with chronic pain. Available trials fail to show that a weak opioid has markedly superior analgesic efficacy to paracetamol or an NSAID. Sublingual buprenorphine at analgesic doses appears less likely to cause respiratory depression, but it seems to have weak analgesic efficacy. In practice, when opioid therapy is needed, there is no evidence that codeine

  7. Refinement of analgesia following thoracotomy and experimental myocardial infarction using the Mouse Grimace Scale

    Science.gov (United States)

    Faller, Kiterie M. E.; McAndrew, Debra J.; Schneider, Jurgen E.

    2015-01-01

    New Findings What is the central question of this study? There is an ethical imperative to optimize analgesia protocols for laboratory animals, but this is impeded by our inability to recognize pain reliably. We examined whether the Mouse Grimace Scale (MGS) provides benefits over a standard welfare scoring system for identifying a low level of pain in the frequently used murine surgical model of myocardial infarction. What is the main finding and its importance? Low‐level pain, responsive to analgesia, was detected by MGS but not standard methods. In this model, most of the pain is attributable to the thoracotomy, excepted in mice with very large infarcts. This approach represents a model for assessing postsurgical analgesia in rodents. The Mouse Grimace Scale (MGS) was developed for assessing pain severity, but the general applicability to complex postsurgical pain has not been established. We sought to determine whether the MGS provides benefits over and above a standard welfare scoring system for identifying pain in mice following experimental myocardial infarction. Female C57BL/6J mice (n = 60), anaesthetized with isoflurane, were subjected to thoracotomy with ligation of a coronary artery or sham procedure. A single s.c. dose of buprenorphine (1.1 mg kg−1) was given at the time of surgery and pain assessed at 24 h by MGS and a procedure‐specific welfare scoring system. In some animals, a second dose of 0.6 mg kg−1 buprenorphine was given and pain assessment repeated after 30 min. The MGS was scored from multiple photographs by two independent blinded observers with good correlation (r = 0.98). Using the average MGS score of both observers, we identified a subset of mice with low scores that were not considered to be in pain by the welfare scoring system or by single observer MGS. These mice showed a significant improvement with additional analgesia, suggesting that this low‐level pain is real. Pain attributable to the myocardial injury, as

  8. INVESTIGATION ON NON-OPIOID ABUSE AMONG OUTPATIENTS RECEIVING METHADONE MAINTENANCE TREATMENT IN BAOAN DISTRICT OF SHENZHEN%深圳市宝安区美沙酮维持治疗者滥用甲基苯丙胺等非阿片类成瘾物质的情况调查

    Institute of Scientific and Technical Information of China (English)

    张泉水; 夏莉; 黎超雄; 蔡翠兰; 刘文红; 杨梅; 麦梅英

    2011-01-01

    目的:调查深圳市宝安区美沙酮维持治疗者使用非阿片类成瘾物质情况,为维持治疗策略提供科学依据.方法:对参加美沙酮维持治疗的符合条件的海洛因依赖者进行尿吗啡检测的同时,进行常见非阿片类成瘾物质尿检,包括甲基苯丙胺、亚甲基二氧基苯丙胺、氯胺酮、丁丙诺啡等,共完成160例.结果:美沙酮维持治疗者尿吗啡阳性率为36.2%.非阿片类成瘾物质甲基苯丙胺、亚甲基二氧基苯丙胺、氯胺酮、丁丙诺啡的阳性率分别为5.0%、1.2%、0.62%和0%.甲基苯丙胺阳性与吗啡阳性无相关性(χ2=1.458,P>0.05).结论:美沙酮维持治疗者中存在多种成瘾物质滥用现象,非阿片类物质中最常用的是甲基苯丙胺,但与其是否仍在使用海洛因无相关性.%Objective:To investigate non- opioid abuse among out-patients receiving methadone maintenance treatment (MMT) in Baoan District Shenzhen City and provide scientific basis for the management of MMT.Methods: Urine tests were conducted for morphine and non - opioid drugs such as methamphetamine, methylenedioxy amphetamine, ketamine, buprenorphine among 160 heroin addicts receiving MMT.Results: The positive rates of morphine, methamphetamine, methylenedioxy amphetamine,ketamine and buprenorphine were 36.2%, 5.0%, 1.2%, 0.6% and 0%, respectively.There was no correlation between positive rates of methamphetamine and morphine.Conclusion: Polydrug abuse,especially, methamphetamine abuse commonly exists in MMT clinic,which needs public attention.

  9. [Therapy with opioids in liver or renal failure].

    Science.gov (United States)

    Tegeder, I; Geisslinger, G; Lötsch, J

    1999-06-11

    In patients with renal or hepatic failure, the pharmacokinetics of opioids may be affected in several ways, leading to the necessity to correct the dose. The liver is the major site for biotransformation of most opioids. The major metabolic pathway is oxidation. Exceptions to this are morphine and buprenorphine, which undergo primarily glucuronidation, and remifentanil which is cleared by esther hydrolysis. The hydrophilic metabolites are predominantly excreted by the kidneys and may accumulate in patients with renal insufficiency. Some metabolites such as morphine-6-glucuronide (M6G) or normeperidine are active opioid agonists. With high concentrations they may cause narcotic effects or respiratory depression. In addition, special risks are known for normepridine that has been shown to exert neurotoxic effects with the risk of seizures. Few cases of respiratory depression following the administration of codeine, dihydrocodeine and tramdol have been reported. The elimination half-life of these drugs was prolonged. Lastly, the disposition of methadone, buprenorphine, fentanyl, sufentanyl and remifentanil appears to be unaffected in renal failure. In patients with hepatic cirrhosis it has been shown that oxidation of opioids is reduced, resulting in a decreased drug clearance (meperidine, propoxyphene, pentazocine, tramadol and alfentanil) and increased oral bioavailability due to reduced first-pass metabolism (meperidine, propoxyphene, pentazocine, dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, the clearance of morphine was found to be decreased and its oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administrations. As for patients with renal failure, special risks are known for meperidine with potential accumulation of normeperidine, which can cause seizures, and for propoxyphene for which several cases of hepatotoxicity have

  10. Pharmacokinetic-pharmacodynamic modelling of opioids in healthy human volunteers. a minireview.

    Science.gov (United States)

    Ing Lorenzini, Kuntheavy; Daali, Youssef; Dayer, Pierre; Desmeules, Jules

    2012-03-01

    Pain is characterized by its multi-dimensional nature, explaining in part why the pharmacokinetic/pharmacodynamic (PK/PD) relationships are not straightforward for analgesics. The first part of this MiniReview gives an overview of PK, PD and PK/PD models, as well as of population approach used in analgesic studies. The second part updates the state-of-the-art in the PK/PD relationship of opioids, focusing on data obtained on experimental human pain models, a useful tool to characterize the PD of analgesics. For the so-called weak opioids such as codeine, experimental human studies showed that analgesia relies mainly upon biotransformation into morphine. However, the time-course of plasma concentrations of morphine did not always reflect the time-course of effects, the major site of action being the central nervous system. For tramadol, a correlation has been observed between the analgesic response and the PK of the (+)R-O-demethyl-tramadol metabolite. For 'stronger' opioids such as oxycodone, studies assessing the PK/PD of oxycodone suggested that active metabolite oxymorphone also strongly contributes to the analgesia and that analgesia may also be partially related through an action to peripherally located κ-opioid receptors. Different models have been proposed to describe the time-course of buprenorphine. An effect-compartment model was adopted to describe the PK/PD of morphine and its active metabolite, morphine-6-glucuronide (M6G). A longer blood-effect site equilibration half-life t(1/2) k(e0) was observed for M6G, suggesting a longer onset of action. The studies assessing the PK/PD of fentanyl and its derivatives showed a short t(1/2) k(e0) for analgesia, between 0.2 and 9 min., reflecting a short onset of effect. In conclusion, depending on the speed of transfer between the plasma and the effect site as well as the participation of active metabolites, the time-course of the analgesic effects can be close to the plasma concentrations (alfentanil and

  11. Prescription of antidepressants to patients on opioid maintenance therapy – a pharmacoepidemiological study

    Directory of Open Access Journals (Sweden)

    Ingeborg Hartz

    2011-12-01

    Full Text Available Background and aims: Depression and anxiety are commonly reported among patients in opioid maintenance treatment (OMT. The aim of the present study was to describe aspects of prescription of antidepresant drug therapy among patients on OMT. Our research questions were: 1 What is the prevalence of antidepressant use according to age and gender? 2 Which antidepressants are used? 3 How are antidepressants used in terms of reimbursement codes, dispensed dose and duration of therapy?Methods: Pharmacoepidemiological data were retrieved from the complete national Norwegian Prescription Database which contains information on all prescription drugs (such as Anatomical Theraputical Chemical (ATC-code, Defined Daily Dose (DDDs, dispensed at pharmacies to individual patients. Norwegian OMT-patients (N=4374, 3035 men and 1339 women who received methadone mixture, buprenorphine capsules or combined buprenorphine-naloxone capsules for at least 6 months in 2009 were included. Prevalence of antidepressant use in the studied patients was measured in terms of retrieval of prescriptions.Results: During 2009 21.7% of the studied patients filled at least one prescription for an antidepressant drugs (men: 21.2%; women: 22.9%. The subgroup of antidepressants most frequently dispensed was selective serotonin reuptake inhibitors (SSRIs (33%, followed by the sedative antidepressants mianserin and mirtazapin (22% and tricyclic antidepressants (TCAs (20%. Except for TCAs, prescriptions of all antidepressant subgroups were reimbursed for either anxiety or depression in 90% of the cases. Overall, 46.9% of the antidepressant users were prescribed antidepressants in the category < 1 DDD per day and/or treatment < 3 months, with no gender difference.Conclusions: About one out of five OMT-patients filled a prescription for an antidepressant drug in 2009. Above 90% had their prescriptions reimbursed for either depression or anxiety. Use at low doses and/or sporadic use among half

  12. Nonnatural deaths among users of illicit drugs: pathological findings and illicit drug abuse stigmata.

    Science.gov (United States)

    Delaveris, Gerd Jorunn Møller; Hoff-Olsen, Per; Rogde, Sidsel

    2015-03-01

    The aim of the study was to provide information on illicit drug abuse stigmata and general pathological findings among an adult narcotic drug-using population aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin, amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP (phencyclidine), and high levels of GHB (γ-hydroxybutyric acid) in addition to methadone and buprenorphine were investigated. Reported findings of hepatitis, portal lymphadenopathy, recent injection marks, drug user's equipment, and numbers of significant pathological conditions were registered and analyzed according to cases positive for opiates, opioids (OPs), and central nervous system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305 were positive for one or more opiate or OP. Cases positive for OPs had significantly more findings of noninfectious pathological conditions. Hepatitis, portal lymphadenopathy, recent injections marks findings of drug user's equipment were all findings found more frequently among the opiate OP-positive individuals. Portal lymphadenopathy was significantly more often found in cases with hepatitis than in cases with other or no infection. In the population positive for CNS stimulants, hepatitis recent injection marks were more frequent findings than in the CNS stimulant-negative group, irrespective of whether they were opiate OP positive or negative.

  13. Deficit of circulating stem – progenitor cells in opiate addiction: a pilot study

    Directory of Open Access Journals (Sweden)

    Davidson Peter

    2007-07-01

    Full Text Available Abstract A substantial literature describes the capacity of all addictive drugs to slow cell growth and potentiate apoptosis. Flow cytometry was used as a means to compare two lineages of circulating progenitor cells in addicted patients. Buprenorphine treated opiate addicts were compared with medical patients. Peripheral venous blood CD34+ CD45+ double positive cells were counted as haemopoietic stem cells (HSC's, and CD34+ KDR+ (VEGFR2+ cells were taken as endothelial progenitor cells (EPC's. 10 opiate dependent patients with substance use disorder (SUD and 11 non-addicted (N-SUD were studied. The ages were (mean + S.D. 36.2 + 8.6 and 56.4 + 18.6 respectively (P 0.15, OR = 0.09, 95% C.I. 0.01–0.97, a finding of some interest given the substantially older age of the N-SUD group. These laboratory data are thus consistent with clinical data suggesting accelerated ageing in addicted humans and implicate the important stem cell pool in both addiction toxicology and ageing. They carry important policy implications for understanding the fundamental toxicology of addiction, and suggest that the toxicity both of addiction itself and of indefinite agonist maintenance therapies may have been seriously underestimated.

  14. Neurofeedback training for opiate addiction: improvement of mental health and craving.

    Science.gov (United States)

    Dehghani-Arani, Fateme; Rostami, Reza; Nadali, Hosein

    2013-06-01

    Psychological improvements in patients with substance use disorders have been reported after neurofeedback treatment. However, neurofeedback has not been commonly accepted as a treatment for substance dependence. This study was carried out to examine the effectiveness of this therapeutic method for opiate dependence disorder. The specific aim was to investigate whether treatment leads to any changes in mental health and substance craving. In this experimental study with a pre-post test design, 20 opiate dependent patients undergoing Methadone or Buprenorphine maintenance treatment were examined and matched and randomized into two groups. While both experimental and control groups received their usual maintenance treatment, the experimental group received 30 sessions of neurofeedback treatment in addition. The neurofeedback treatment consisted of sensory motor rhythm training on Cz, followed by an alpha-theta protocol on Pz. Data from the general health questionnaire and a heroin craving questionnaire were collected before and after treatment. Multivariate analysis of covariance showed that the experimental group achieved improvement in somatic symptoms, depression, and total score in general mental health; and in anticipation of positive outcome, desire to use opioid, and relief from withdrawal of craving in comparison with the control group. The study supports the effectiveness of neurofeedback training as a therapeutic method in opiate dependence disorder, in supplement to pharmacotherapy.

  15. New challenges and opportunities in managing substance abuse in Malaysia.

    Science.gov (United States)

    Mazlan, Mahmud; Schottenfeld, Richard S; Chawarski, Marek C

    2006-09-01

    Until recently, Malaysia has lagged behind in the treatment of drug addiction and related disorders, despite experiencing severe drug problems. By the end of 2004, 234,000 heroin users or heroin-dependent individuals had been registered in the official government registry, but other estimates exceed 500,000 for heroin abusers in the country. Amphetamine-type stimulant abuse is also increasing and of considerable public and government concern. Among the population of drug users, HIV and other infectious diseases rates are very high. In the Western Pacific regions, Malaysia has the second highest HIV prevalence (after Vietnam) among adult populations (0.62%) and the highest proportion of HIV cases resulting from injection drug use (76.3%). Drug use and related disorders exert a heavy burden on the country's health care and legal systems. Historically, drug abusers were rehabilitated involuntarily in correctional, rather than health-care, facilities. This primarily criminal treatment approach had limited effectiveness which led to widespread public dissatisfaction and the recent introduction of medical treatments for addiction. Naltrexone was introduced in 1999; buprenorphine was introduced in 2001 and methadone in 2003. Agonist maintenance programmes were embraced rapidly by the medical community in Malaysia. Currently, over 30,000 opiate-dependent patients are treated with agonist maintenance treatments by more than 500 medical practitioners in Malaysia. Despite these recent advances, treatments for amphetamine-type stimulant abuse or dependence are underdeveloped, and diversion of agonist medications is an emerging concern.

  16. Methadone for the treatment of Prescription Opioids Dependence. A retrospective chart review.

    Science.gov (United States)

    Barrio, Pablo; Ezzeldin, Mohamed; Bruguera, Pol; Pérez, Ana; Mansilla, Sara; Fàbrega, Marina; Lligoña, Anna; Mondón, Sílvia; Balcells, Mercè

    2016-06-14

    Prescription opioids (PO) addiction is increasing to an epidemic level. Few studies exist regarding its treatment. Although buprenorphine has been the mainstay so far, other treatment options might be considered, such as methadone. We conducted a retrospective assessment of all patients admitted to a psychiatry ward for PO detoxification using methadone between 2010 and 2013. The assessment and description was carried out during a 3-month follow-up period after their discharge. Although this is a retrospective chart review, our exploration included sociodemographic and treatment variables in addition to the abstinence rates for the whole sample. Eleven patients were included, mostly women (81.8%), with a median age of 50 years. The median duration of dependence was 8 years. Dependence on other substances and psychiatric comorbidities were high. Eight patients were monitored during three months. Of these, 7 (87.5%) were abstinent after that period. The results suggest that methadone deserves further exploration as a potentially efficacious treatment option for PO dependence.

  17. OPPIDUM surveillance program: 20 years of information on drug abuse in France.

    Science.gov (United States)

    Frauger, Elisabeth; Moracchini, Christophe; Le Boisselier, Reynald; Braunstein, David; Thirion, Xavier; Micallef, Joëlle

    2013-12-01

    It is important to assess drug abuse liability in 'real life' using different surveillance systems. Some are based on specific population surveys, such as individuals with drug abuse or dependence, or under opiate maintenance treatment, because this population is very familiar with drugs and is more likely to divert or abuse them. In France, an original surveillance system based on this specific population and called 'Observation of illegal drugs and misuse of psychotropic medications (OPPIDUM) survey' was set up in 1990 as the first of its kind. The aim of this article is to describe this precursor of French drug abuse surveillance using different examples, to demonstrate its ability to effectively give health authorities and physicians interesting data on drug abuse. OPPIDUM is an annual, cross-sectional survey that anonymously collects information on abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. From 1990 to 2010, a total of 50,734 patients were included with descriptions of 102,631 psychoactive substance consumptions. These data have outlined emergent behaviors such as the misuse of buprenorphine by intravenous or nasal administration. It has contributed to assess abuse liability of emergent drugs such as clonazepam or methylphenidate. This surveillance system was also able to detect the decrease of flunitrazepam abuse following implementation of regulatory measures. OPPIDUM's twenty years of experience clearly demonstrate that collection of valid and useful data on drug abuse is possible and can provide helpful information for physicians and health authorities.

  18. Pain management in total knee arthroplasty: efficacy of a multimodal opiate-free protocol

    Science.gov (United States)

    CANATA, GIAN LUIGI; CASALE, VALENTINA; CHIEY, ALFREDO

    2016-01-01

    Purpose this study was conducted to identify the most effective method of postoperative pain management, comparing the intravenous opiate infusion protocol with the use of a single periarticular local anesthetic infiltration (LAI) in patients undergoing total knee arthroplasty (TKA) surgery. Methods 50 patients submitted to TKA surgery between 2013 and 2015 were divided into two groups. Buprenorphine was administered intravenously to the patients in Group A, while the Group B patients received a single periarticular LAI (ropivacaine and ketorolac) during surgery. Pain was assessed using a visual analog scale (VAS) and the knee injury and osteoarthritis outcome score. Hemoglobin and hematocrit were measured in the early postoperative period and at 40 days post-surgery. Range of motion and inflammatory markers were also assessed. Statistical analysis was performed using Student’s t-test. Results student’s t-test showed no significant difference between the groups in functional outcomes or blood values, but a difference in VAS score on the day of surgery was found (p < 0.0001), in favor of Group B. Conclusions LAI considerably reduces postoperative pain, allowing rapid mobilization and accelerating functional recovery. Level of evidence Level I, prospective single-blind randomized trial. PMID:28217658

  19. [Emergent drugs (II): the Pharming phenomenon].

    Science.gov (United States)

    Burillo-Putze, G; Aldea-Perona, A; Rodríguez-Jiménez, C; García-Sáiz, M M; Climent, B; Dueñas, A; Munné, P; Nogué, S; Hoffman, R S

    2013-01-01

    The use of medicines, with or without medical prescription, for recreational ends by the young population has received little attention from doctors. In the USA, one in five adolescents has used medicines for recreational purposes, and consultations in Emergency Departments for medicine abuse have exceeded those for illegal drugs. Although few data are available in Spain, such consumption is situated between 3.1 and 8.6% according to surveys. The medicines most used are dextromethorphan and methylphenidate. The former, on sale without prescription, presents a varied symptomatology, dosage and dependent metabolic action, ranging from euphoria to hallucinations. Methylphenidate, taken orally, nasally or intravenously, is used as a stimulant in substitution for cocaine and is one of the medicines most diverted onto the illicit market at the world level. In principle, other substances like modafinil and propofol present a limited incidence of non-medical use, but they have a probable abuse potential that should be borne in mind, above all in the health context. Finally, opiates like fentanyl, oxycodone and buprenorphine, with new pharmaceutical presentations, have recently become generalized in the therapeutic arsenal of many medical specialities; they are giving rise to phenomena of abuse, dependence and diversion towards the illicit market. Demands for detoxification treatment, their mixture with illegal substances, and cases of death should alert us to the abuse of these medicines.

  20. 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

    2014-01-01

    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

  1. Maintenance Treatment with Opium Tincture: A Preliminary Qualitative Study of the Factors Related to Treatment entry.

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    Reza Daneshmand

    2014-08-01

    Full Text Available The current preliminary study aimed to explore the reasons that a group of opiate-dependent patients reported for entry into opium tincture treatment (OTT.Through examinations of 52 qualitative focus group interviews with patients from six OTT centers and 10 health providers (in key informant interviews in Tehran, this study highlights the factors that participants reported as the reasons associated with entry into OTT. Quantitative data including demographic data and details of drug use were analyzed by using SPSS.v.18.0. Qualitative data was analyzed by using Atlas-ti software.86.5% of patients were male and 13.5% were female. The median age of patients was 39 yr. The most frequently reasons associated with entry into OTT included methadone misconceptions including dissatisfaction with taking methadone as a chemical medication, methadone dependence, and long duration of MMT. The other reasons included the recommendation of other people in treatment and OT-related characteristics and expectations including the herbal compound of OT, treating opiate craving and withdrawal symptoms, and improving general health.The study findings preliminarily showed the reasons associated with entry into OTT in a sample of treatment seekers. Longitudinal studies with more representative samples and follow-up stages are required to evaluate the clinical effectiveness of OTT as a maintenance treatment in comparison with methadone and buprenorphine. Patient-centered program and policy implications are discussed.

  2. Sexual dysfunction in patients with alcohol and opioid dependence

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    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.

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

    Science.gov (United States)

    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 treatment outcome (odds ratio = 0.55, p 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.

  4. Workplace drug testing in Italy - critical considerations.

    Science.gov (United States)

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; Pozzi, Fulvia; Collo, Giancarlo; Groppi, Angelo

    2013-04-01

    Workplace drug testing (WDT) was established in Italy on 30 October 2007. Two tiers of survey are required: the first tier concerns drug testing on urine samples, the second involves both urine and hair analysis. Between July 2008 and December 2011, 10 598 workers' urine samples and 72 hair samples for opiates, cocaine, cannabinoids, amphetamines, methylenedioxyamphetamines, methadone, and buprenorphine were tested in our laboratory. Urine analyses were performed by immunological screening (EMIT); hair analysis and confirmation tests in urine were performed by gas chromatography-mass spectrometry (GC-MS). Employees tested positive in urine for drugs of abuse numbered 2.8% in 2008, 2.03% in 2009, 1.62% in 2010, and 1.43% in 2011. As regards the second level of analysis, we observed that only one-third of the workers who had been tested positive for drugs of abuse were referred to an Addiction Treatment Unit in order to verify drug addiction. Our experience shows that, four years after approval of the law on WDT, the percentage of workers positive for drugs of abuse in urine has reduced in comparison to the first year. Moreover, our data show that most of the times employees who tested positive are tardily referred or not referred at all to a Public Addiction Treatment Unit to verify drug addiction. This makes us believe that the legal provisions are widely disregarded not paying the right tribute to the fact that Italy is one of few European countries with legislation on WDT.

  5. Suicidal ideation and HIV risk behaviors among a cohort of injecting drug users in New Delhi, India

    Directory of Open Access Journals (Sweden)

    Sarin Enisha

    2013-01-01

    Full Text Available Abstract Background Data on mental health among injecting drug users in South Asia is scarce yet poor mental health among users has significant implications for the success of HIV prevention and treatment programmes. A cohort of 449 injecting drug users in Delhi was examined on the following issues (1 examine trends in suicidal ideation, suicide plan and suicidal attempts over a 12-month period, (2 examine association between injecting practices (receive and give used syringes and suicidal ideation over a 12 month study period. Methods An observational study was conducted providing phased interventions with follow up interviews every 3 months to 449 injecting drug users (IDUs, from August 2004 to November 2005. The study was conducted in Yamuna Bazaar, a known hub of drug peddling in Delhi. Interventions included nutrition, basic medical services, needle exchange, health education, HIV voluntary counseling and testing, STI diagnosis and treatment, oral buprenorphine substitution, and detoxification, each introduced sequentially. Results Suicidal ideation and suicide attempts, did not significantly change over 12 months of observation, while suicide plans actually increased over the time period. Keeping other factors constant, IDUs with suicidal ideation reported more giving and receiving of used syringes in the recent past. Conclusions: Mental health services are warranted within harm reduction programmes. Special attention must be paid to suicidal IDUs given their higher risk behaviours for acquiring HIV and other blood borne infections. IDU intervention programmes should assess and address suicide risk through brief screening and enhanced counseling.

  6. 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.

  7. Pain control in horses: what do we really know?

    Science.gov (United States)

    Sanchez, L C; Robertson, S A

    2014-07-01

    Currently, approaches to pain control in horses are a mixture of art and science. Recognition of overt pain behaviours, such as rolling, kicking at the abdomen, flank watching, lameness or blepharospasm, may be obvious; subtle signs of pain can include changes in facial expression or head position, location in the stall and response to palpation or human interaction. Nonsteroidal anti-inflammatory drugs (i.e. phenylbutazone, flunixin meglumine and firocoxib), opioids (i.e. butorphanol, morphine and buprenorphine) and α2 -adrenergic agonists (i.e. xylazine, detomidine, romifidine and medetomidine) are the most commonly used therapeutic options. Multimodal therapy using constant-rate infusions of lidocaine, ketamine and/or butorphanol has gained popularity for severe pain in hospitalised cases. Drugs targeting neuropathic pain, such as gabapentin, are increasingly used for conditions such as laminitis. Optimal strategies for management of pain are based upon severity and chronicity, including special considerations for use of intra-articular or epidural delivery and therapy in foals. Strategies that aim to mitigate adverse effects associated with use of various analgesic agents are briefly discussed.

  8. Agonist substitution--a treatment alternative for high-dose benzodiazepine-dependent patients?

    Science.gov (United States)

    Liebrenz, Michael; Boesch, Lukas; Stohler, Rudolf; Caflisch, Carlo

    2010-11-01

    There is vast evidence for the superiority of agonist treatments (methadone, buprenorphine) over a withdrawal approach in opioid-dependent populations. Little research, however, has been conducted on the same approach for the treatment of high-dose benzodiazepine (BZD) dependence. Even large-scale reviews and meta-analyses discussing treatment strategies for benzodiazepine-dependent patients focus solely upon approaches that aim at achieving abstinence, namely on complete BZD withdrawal. While the types of interventions differ (e.g. gradual benzodiazepine taper with a long or a short half-life benzodiazepine, switching to non-benzodiazepine anxiolytics or prescribing adjunctive medications such as antidepressants or anticonvulsants on an in- or out-patient basis), the common aim of treatment still is total abstinence from benzodiazepines. However, the majority of patients suffering from high-dose BZD dependence do not succeed with long-term abstinence, irrespective of the procedure, and clinicians have been using BZD 'substitution' treatment in such cases for decades. Therefore, we suggest the evaluation of a substitution approach in this group, consisting of maintenance treatment with a slow-onset, long-acting BZD. Advantages of such a procedure may be improved health, less craving, fewer withdrawal complications, reduced anxiety, increased treatment retention, improvements in social functioning and less illegal activity. Cognitive impairments, the most problematic side effects of substitution treatment with benzodiazepines, could possibly be minimized by using an optimal agonist.

  9. Synthesis of 14-Alkoxymorphinan Derivatives and Their Pharmacological Actions

    Science.gov (United States)

    Schmidhammer, Helmut; Spetea, Mariana

    Among opioids, morphinans play an important role as therapeutically valuable drugs. They include pain relieving agents such as naturally occurring alkaloids (e.g. morphine, codeine), semisynthetic derivatives (e.g. oxycodone, oxymorphone, buprenorphine), and synthetic analogs (e.g. levorphanol). Currently used opioid analgesics also share a number of severe side effects, limiting their clinical usefulness. The antagonist morphinans, naloxone and naltrexone are used to treat opioid overdose, opioid dependence, and alcoholism. All these opioid drugs produce their biological actions through three receptor types, µ, δ, and κ, belonging to the G-protein-coupled receptor family. Considerable effort has been put forward to understand the appropriate use of opioid analgesics, while medicinal chemistry and opioid pharmacology have been continuously engaged in the search for safer, more efficacious and nonaddicting opioid compounds, with the final goal to reduce complications and to improve patient compliance. Toward this goal, recent advances in chemistry, ligand-based structure activity relationships and pharmacology of 14-alkoxymorphinans are reviewed in this chapter. Current developments of different structural patterns of 14-alkoxymorphinans as research tools and their potential therapeutic opportunities are also summarized.

  10. A Systematic Review on the Use of Psychosocial Interventions in Conjunction With Medications for the Treatment of Opioid Addiction.

    Science.gov (United States)

    Dugosh, Karen; Abraham, Amanda; Seymour, Brittany; McLoyd, Keli; Chalk, Mady; Festinger, David

    2016-01-01

    Opioid use and overdose rates have risen to epidemic levels in the United States during the past decade. Fortunately, there are effective medications (ie, methadone, buprenorphine, and oral and injectable naltrexone) available for the treatment of opioid addiction. Each of these medications is approved for use in conjunction with psychosocial treatment; however, there is a dearth of empirical research on the optimal psychosocial interventions to use with these medications. In this systematic review, we outline and discuss the findings of 3 prominent prior reviews and 27 recent publications of empirical studies on this topic. The most widely studied psychosocial interventions examined in conjunction with medications for opioid addiction were contingency management and cognitive behavioral therapy, with the majority focusing on methadone treatment. The results generally support the efficacy of providing psychosocial interventions in combination with medications to treat opioid addictions, although the incremental utility varied across studies, outcomes, medications, and interventions. The review highlights significant gaps in the literature and provides areas for future research. Given the enormity of the current opioid problem in the United States, it is critical to gain a better understanding of the most effective ways to deliver psychosocial treatments in conjunction with these medications to improve the health and well-being of individuals suffering from opioid addiction.

  11. [Guideline 'Medicinal care for drug addicts in penal institutions'].

    Science.gov (United States)

    Westra, Michel; de Haan, Hein A; Arends, Marleen T; van Everdingen, Jannes J E; Klazinga, Niek S

    2009-01-01

    In the Netherlands, the policy on care for prisoners who are addicted to opiates is still heterogeneous. The recent guidelines entitled 'Medicinal care for drug addicts in penal institutions' should contribute towards unambiguous and more evidence-based treatment for this group. In addition, it should improve and bring the care pathways within judicial institutions and mainstream healthcare more into line with one another. Each rational course of medicinal treatment will initially be continued in the penal institution. In penal institutions the help on offer is mainly focused on abstinence from illegal drugs while at the same time limiting the damage caused to the health of the individual user. Methadone is regarded at the first choice for maintenance therapy. For patient safety, this is best given in liquid form in sealed cups of 5 mg/ml once daily in the morning. Recently a combination preparation containing buprenorphine and naloxone - a complete opiate antagonist - has become available. On discontinuation of opiate maintenance treatment intensive follow-up care is necessary. During this period there is considerable risk of a potentially lethal overdose. Detoxification should be coupled with psychosocial or medicinal intervention aimed at preventing relapse. Naltrexone is currently the only available opiate antagonist for preventing relapse. In those addicted to opiates, who also take benzodiazepines without any indication, it is strongly recommended that these be reduced and discontinued. This can be achieved by converting the regular dosage into the equivalent in diazepam and then reducing this dosage by a maximum of 25% a week.

  12. A designated centre for people with disabilities operated by SOS Kilkenny Ltd, Kilkenny

    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.

  13. Concurrent and simultaneous polydrug use: latent class analysis of an Australian nationally representative sample of young adults.

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    Lake-Hui eQuek

    2013-11-01

    Full Text Available Background: Alcohol use and illicit drug use peak during young adulthood (around 18-29 years of age, but comparatively little is known about polydrug use in nationally representative samples of young adults. Drawing on a nationally representative cross-sectional survey (Australian National Drug Strategy Household Survey, this study examines polydrug use patterns and associated psychosocial risk factors among young adults (n = 3,333; age 19-29. Method: The use of a broad range of licit and illicit drugs were examined, including alcohol, tobacco, cannabis, cocaine, hallucinogens, ecstasy, ketamine, GHB, inhalants, steroids, barbiturates, meth/amphetamines, heroin, methadone/buprenorphine, other opiates, painkillers and tranquillizers/sleeping pills. Latent class analysis was employed to identify patterns of polydrug use. Results: Polydrug use in this sample was best described using a 5-class solution. The majority of young adults predominantly used alcohol only (52.3%, alcohol and tobacco (34.18%. The other classes were cannabis, ecstasy, and licit drug use (9.4%, cannabis, amphetamine derivative, and licit drug use (2.8%, and sedative and alcohol use (1.3%. Young adult males with low education and/or high income were most at risk of polydrug use. Conclusion: Almost half of young adults reported polydrug use, highlighting the importance of post-high school screening for key risk factors and polydrug use profiles, and the delivery of early intervention strategies targeting illicit drugs.

  14. Cigarette smoking and short-term addiction treatment outcome.

    Science.gov (United States)

    Harrell, P T; Montoya, I D; Preston, K L; Juliano, L M; Gorelick, D A

    2011-06-01

    Cigarette smoking is common among patients in cocaine and opioid dependence treatment, and may influence treatment outcome. We addressed this issue in a secondary analysis of data from an outpatient clinical trial of buprenorphine treatment for concurrent cocaine and opioid dependence (13 weeks, N=200). The association between cigarette smoking (lifetime cigarette smoking status, number of cigarettes smoked per day prior to study entry) and short-term treatment outcome (% of urine samples positive for cocaine or opioids, treatment retention) was evaluated with analysis of covariance, bivariate correlations, and multivariate linear regression. Nicotine-dependent smokers (66% of participants) had a significantly higher percentage of cocaine-positive urine samples than non-smokers (12% of participants) (76% vs. 62%), but did not differ in percentage of opioid-positive urine samples or treatment retention. Number of cigarettes smoked per day at baseline was positively associated with percentage of cocaine-positive urine samples, even after controlling for baseline sociodemographic and drug use characteristics, but was not significantly associated with percentage of opioid-positive urine samples or treatment retention. These results suggest that cigarette smoking is associated with poorer short-term outcome of outpatient treatment for cocaine dependence, but perhaps not of concurrent opioid dependence, and support the importance of offering smoking cessation treatment to cocaine-dependent patients.

  15. Studies on the adrenomedullary dependence of kappa-opioid agonist-induced diuresis in conscious rats.

    Science.gov (United States)

    Borkowski, K. R.

    1989-01-01

    1. The dependence of kappa-opioid agonist-induced diuresis, upon an intact and functional adrenal medulla in conscious rats, was investigated in order to test the hypothesis that the diuresis is mediated by a blood-borne 'diuretic factor', of adrenomedullary origin, released by kappa-opioid receptor stimulation. 2. Confirming previous observations, adrenal demedullation significantly attenuated diuretic responses to the kappa-opioid agonists U50488H, ethylketocyclazocine (EKC) and tifluadom, but did not affect basal urine output, furosemide-induced diuresis or the antidiuretic response to the mu-opioid agonist, buprenorphine. Naloxone abolished U50488H-induced diuresis, confirming an involvement of opioid receptors. 3. Transfusion studies established that blood, from intact rats treated with U50488H, induced diuresis in intact and demedullated recipient rats, whether or not the recipients had been pretreated with naloxone. However, blood from demedullated rats treated with U50448H was unable to induce diuresis when administered to intact or demedullated recipients. 4. It is concluded that kappa-opioid agonist-induced diuresis is dependent upon an intact and functional adrenal medulla and appears to be mediated by a blood-borne 'diuretic factor' of adrenomedullary origin. PMID:2558758

  16. On the mechanisms of kappa-opioid-induced diuresis.

    Science.gov (United States)

    Blackburn, T. P.; Borkowski, K. R.; Friend, J.; Rance, M. J.

    1986-01-01

    In conscious saline loaded rats, the kappa-opioid agonists tifluadom, U50488, and ethylketocyclazocine, given subcutaneously, induced a characteristic diuresis which could be antagonized by naloxone. Bilateral adrenal demedullation significantly reduced adrenal gland catecholamine content and plasma adrenaline levels, but did not significantly affect plasma corticosterone levels, indicating that the adrenal cortex remained both intact and functional. Seven days following bilateral adrenal demedullation, the subcutaneous administration of the kappa-agonists no longer induced diuresis. However, demedullation did not affect the diuretic response to frusemide or clonidine, nor did it affect the antidiuretic response induced by the mu-opioid agonists morphine and buprenorphine. Adrenal catecholamines do not appear to be involved in kappa-opioid-induced diuresis, since pretreatment with propranolol, prazosin and idazoxan did not affect the diuretic response in intact animals. The results indicate a link between the adrenal medulla and kappa-opioid-induced diuresis and suggest that a peripheral mechanism may also be involved in mediating this effect. PMID:3542107

  17. [Sedation and anesthesia in dogs and cats with cardiovascular diseases. III. Ventilation, respiratory monitoring, treatment for postoperative pain].

    Science.gov (United States)

    Skarda, R T; Hubbell, J A; Muir, W W; Bednarski, R M; Mason, D E

    1996-01-01

    The purpose of this study was to review ventilation and postoperative analgesic technics in 137 dogs and 13 cats with congenital or acquired heart disease. The animals were referred to the Department of Veterinary Clinical Sciences at The Ohio State University, U.S.A, for the following surgical interventions: correction of patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch ring anomaly (3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). Controlled ventilation was used in all animals during thoracotomy. Anesthesia was maintained over 2.3 +/- 1.3 hours by using either isoflurane, halothane, propofol, or diazepam-ketamine in 64%, 32%, 2%, and 0.7% of animals, respectively. Postoperative analgesia was necessary in 20% of animals and was provided by using different technics over several hours. The technics and respective percentages of animals in which they were used, were: intravenous buprenorphine (3.3%), intercostal nerve blocks (8.7%), epidural morphine (4%), and interpleural regional analgesia (4%).

  18. 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.

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

    Science.gov (United States)

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

    2009-08-01

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

  20. Pharmacological treatment of opioid-induced hyperalgesia: a review of the evidence.

    Science.gov (United States)

    Ramasubbu, Chitra; Gupta, Anita

    2011-01-01

    Opioids are commonly used to treat moderate to severe pain. Opioid-induced hyperalgesia is a paradoxical response to opioid agonists resulting in an increased perception of pain rather than an antinociceptive effect. Even though there is a debate regarding its clinical relevance, it is becoming a challenge in both acute and chronic pain settings. The study of opioid-induced hyperalgesia is an emerging field with multiple challenges faced by investigators with regard to defining the diagnosis and characterizing the findings. The objective of this study was to review the preliminary evidence related to the treatment and management of opioid-induced hyperalgesia. Lack of data, small patient numbers, short-term follow-up, and variations in study design limited the review. With the literature on this subject being sparse, this study attempts to provide a preliminary look at the available data and to set the stage for an eventual meta-analysis. Case reports in the literature have shown success with various pharmacological interventions. Possible treatment regimens include ketamine, dextromethorphan, and nonsteroidal anti-inflammatory drugs (NSAIDs), opioid switching, amantadine, buprenorphine, α(2) agonists, and methadone. These agents are briefly discussed in this paper. Further well-designed, placebo-controlled trials are needed to assess the effectiveness of the interventions investigated in this review.

  1. Pain-Suppressed Behaviors in the Red-tailed Hawk 1 (Buteo jamaicensis).

    Science.gov (United States)

    Mazor-Thomas, Jana E; Mann, Phyllis E; Karas, Alicia Z; Tseng, Flo

    2014-03-01

    Our ability to provide analgesia in wild and exotic patients is hampered by a lack of species-specific information on effective drugs and protocols. One contributing factor is the difficulty of applying data from traditional laboratory tests of nociception to clinical conditions frequently involving combinations of inflammatory, mechanical, and neuropathic pain. Pain-suppressed behaviors have become a valuable predictor of clinical utility in other species; in this study we extend this framework to red -tailed hawks in a wildlife hospital, in an attempt to develop a new, humane testing method for birds of prey. We scored six behaviors in hawks hospitalized either for orthopedic trauma or for non-painful conditions. These behaviors included: movement about the cage, grooming, head motions, foot shifts, beak clacks, and rouse. Movement, head motions, and beak clacks were all significantly reduced in hawks with recent orthopedic injury, but not in hawks with healed or minor injuries (Pred -tailed hawks with recent orthopedic trauma show consistent and marked red uctions in several normal maintenance behaviors. Head movements, reported for the first time in this study as a potential marker of pain in birds, in particular seem to be insensitive to sedative side effects of buprenorphine, while being a sensitive measu re of affective state in hawks with painful injuries. These behaviors can be scored humanely and with minimal expense, and should be considered for further research on pain and analgesia in avian species.

  2. Partnerships and Pathways of Dissemination: The NIDA-SAMHSA Blending Initiative in the Clinical Trials Network

    Science.gov (United States)

    Martino, Steve; Brigham, Gregory S.; Higgins, Christine; Gallon, Steve; Freese, Thomas E.; Albright, Lonnetta M.; Hulsey, Eric G.; Krom, Laurie; Storti, Susan A.; Perl, Harold; Nugent, Cathrine D.; Pintello, Denise; Condon, Timothy P.

    2010-01-01

    Since 2001, the National Drug Abuse Treatment Clinical Trials Network (CTN) has worked to put the results of its trials into the hands of community treatment programs, in large part through its participation in the National Institute on Drug Abuse - Substance Abuse and Mental Health Services Administration Blending Initiative and its close involvement with the Center for Substance Abuse Treatment’s Addiction Technology Transfer Centers. This article describes 1) the CTN’s integral role in the Blending Initiative, 2) key partnerships and dissemination pathways through which the results of CTN trials are developed into blending products and then transferred to community treatment programs, and 3) three blending initiatives involving buprenorphine, motivational incentives, and motivational interviewing. The Blending Initiative has resulted in high utilization of its products, preparation of over 200 regional trainers, widespread training of service providers in most U.S. States, Puerto Rico, and the U.S. Virgin Islands, and movement toward the development of web-based implementation supports and technical assistance. Implications for future directions of the Blending Initiative and opportunities for research are discussed. PMID:20307793

  3. Meconium drug testing reveals maternal misuse of medicinal opioids among addicted mothers.

    Science.gov (United States)

    Launiainen, Terhi; Nupponen, Irmeli; Halmesmäki, Erja; Ojanperä, Ilkka

    2013-07-01

    Meconium drug testing is a non-invasive method to detect prenatal drug exposure, which can cause severe problems for the infant, indicating the need for follow-up measures to ensure the welfare of the child. Meconium samples for drug testing were collected from 143 infants as part of routine clinical work among addicted mothers. The drug testing findings were combined with medical records including clinical background and follow-up data. The substances screened for included medicinal opioids, 6-monoacetylmorphine (a metabolite of heroin), amphetamines and tetrahydrocannabinolic acid. At least one of the 13 target drugs was detected in 57 (40%) meconium samples. In 21 cases, the findings were unexpected on the basis of clinical data or denied by the mother. Medicinal opioids, especially the opioid substitution treatment drugs buprenorphine and methadone, comprised the majority of the findings of both admitted and unexpected drug misuse. Meconium drug testing methods should target not just traditional illicit drugs but also prescription drugs with misuse potential.

  4. 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

    2012-06-07

    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.

  5. Investigating expectation and reward in human opioid addiction with [(11) C]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

    2014-11-01

    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 [(11) C]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.

  6. INDUCTION AND MAINTENANCE OF ANAESTHESIA BY TWO DIFFERENT INTRAVENOUS ANALGESIC AND SEDATIVE COMBINATION WITHOUT USE OF VOLATILE AGENTS- A CONTROLLED COMPARATIVE CLINICAL STUDY IN DIABETIC AND HYPERTENSIVE PATIENTS

    Directory of Open Access Journals (Sweden)

    Ajay

    2016-01-01

    Full Text Available BACKGROUND In developing country like India with limited resources we need to find ways and means of cutting the anaesthetic cost without compromising safety of patient. With the availability of various intravenous analgesics and sedatives drugs safe anaesthesia can be delivered without the use of costly volatile agents and vaporisers. METHODS 90 Adult diabetic and/or hypertensive patients were divided into three groups of 30 each. Group I patients received inj. Morphine followed by Midazolam. Group II patients received inj. Diazepam followed by Buprenorphine. Group III patients were induced with inj. Fentanyl followed by Thiopentone sodium while maintenance of anaesthesia was achieved using halothane. Hemodynamic parameters, induction and awakening time, postoperative analgesia, and cost were statistically analyzed. RESULTS Hemodynamic parameters showed no significant fluctuations and stayed within the acceptable sinus range in all three groups. Induction time was short but awakening time was longer in group III as compared to other two groups. Postoperative analgesia was longest in group II and this group was cost effective too.

  7. 浅述中医戒毒常用治疗方法

    Institute of Scientific and Technical Information of China (English)

    白晓菊; 宋树立; 高学敏

    2001-01-01

    @@近年来我国阿片类物质滥用人群有不断扩增的趋势,目前对脱毒和康复尚无理想的治疗方法.西药如美沙酮(methabone)、丁丙诺啡(buprenorphine,BPN)等阿片类激动剂替代治疗;纳洛酮(naloxone)和纳屈酮(naltrexone)等阿片拮抗剂戒断治疗和预防复发.前者实际上是用一种具有成瘾性的药物替代另一种具有成瘾性的药物,往往导致新的依赖和复发;后者由于人为的阻断了阿片受体,使成瘾者不可避免的出现不同程度的戒断症状,不易被成瘾者接受.

  8. Activated Carbon-Based System for the Disposal of Psychoactive Medications

    Directory of Open Access Journals (Sweden)

    Yang Song

    2016-11-01

    Full Text Available The misuse and improper disposal of psychoactive medications is a major safety and environmental concern. Hence, the proper disposal of these medications is critically important. A drug deactivation system which contains activated carbon offers a unique disposal method. In the present study, deactivation efficiency of this system was tested by using three model psychoactive drugs. HPLC validation was performed for each drug to ensure that the analytical method employed was suitable for its intended use. The method was found to be specific, accurate and precise for analyzing the drugs. The extent and rate of deactivation of the drugs was determined at several time points. After 28 days in the presence of activated carbon, the extent of leaching out of the drugs was evaluated. Deactivation started immediately after addition of the medications into the disposal pouches. Within 8 h, around 47%, 70% and 97% of diazepam, lorazepam and buprenorphine were adsorbed by the activated carbon, respectively. By the end of 28 days, over 99% of all drugs were deactivated. The desorption/leaching study showed that less than 1% of the active ingredients leached out from the activated carbon. Thus, this deactivation system can be successfully used for the disposal of psychoactive medications.

  9. @@%药物贴剂治疗骨科疼痛

    Institute of Scientific and Technical Information of China (English)

    沈龙祥; 曾炳芳

    2014-01-01

    肌肉骨骼疼痛牵涉部位多、持续时间长、影响劳动力,成为患者个人和社会的沉重负担,其治疗事关民生.药物治疗是处理肌肉骨骼疼痛的重要手段,而药物外用是首选方法,它具有使用方便、机体不良反应小的优点.研究表明,半合成的阿片类止痛剂丁丙诺啡(buprenorphine)克服了阿片类药物的不良反应,且戒断症状轻,脂溶性高,有利于皮肤渗透及制成透皮贴剂(BTDS)局部外用治疗慢性中度至重度腰背痛、骨关节炎痛等骨科疼痛及慢性非癌性疼痛.一系列随机对照临床研究证实BTDS的有效性和安全性,且疗效持久,耐受性好,用于老年患者不需要调整剂量,值得推崇和临床应用.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rosenbaum, J.S.; Holford, N.H.; Sadee, W.

    1985-06-01

    The in vivo receptor binding of a series of opioid drugs was investigated in intact rats after s.c. administration of (/sup 3/H)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.

  11. [Practice, problems and perspectives of opioid substitution treatment (OST) in Germany].

    Science.gov (United States)

    Michels, I I; Sander, G; Stöver, H

    2009-01-01

    Opioid dependency is a complex and chronically relapsing disease with high risks of morbidity and mortality. Frequent relapses and in most of the cases a long process of maturing out characterize this disease. Opioid substitution programs with methadone, buprenorphine and other opioids are a suitable intervention and form the first choice in the treatment of this disease. In Germany, compared to its neighboring countries, this treatment was introduced relatively late. However, in the last five years, the number of patients in substitution treatment has increased significantly to more than 70,000 patients, which marks an increase of 50%, meaning that one third to one half of the estimated opiate users are being reached. Despite the widely acknowledged success with respect to the improvement of the quality of life, survival rates, and accessibility of the target groups for ongoing treatments of drug-related diseases (such as HIV/HCV infections), opioid substitution treatment is still discussed controversially. In this contribution, problems in the areas of service provision, juristic, social, health and research policies are discussed and possibilities of increasing the access and quality of this treatment are introduced.

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

    Science.gov (United States)

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

    2010-06-01

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

  13. Development of enhanced sensitivity to naloxone.

    Science.gov (United States)

    Dykstra, L A

    1983-11-21

    The effects of naloxone were examined over a period of three and a half years in squirrel monkeys responding under a mult FR, FI schedule of food presentation. During the initial observation of naloxone's effects, monkeys were drug naive. At that time, doses of naloxone up to 3.0 mg/kg had very little effect on rates of responding under the multiple schedule. The effects of naloxone were then examined in combination with meperidine. Doses of naloxone between 0.3 and 3.0 mg/kg produced a dose-dependent antagonism of meperidine's effects. Monkeys were then exposed to ketocyclazocine and phencyclidine, alone and in combination with naloxone. When the naloxone dose-effect curve was redetermined subsequently, it had shifted to the left. Monkeys were then exposed to buprenorphine and diprenorphine, alone and in combination with naloxone. Redetermination of the naloxone dose-effect curve following this exposure revealed a further shift to the left. The effects of naloxone were then reexamined in combination with meperidine, and it was found that the leftward shift in the naloxone dose-effect curve was not accompanied by a decrease in the doses of naloxone which would reverse the effects of meperidine. Naloxone's effects were then examined in combination with either acute or chronic diazepam. The naloxone dose-effect curve determined during the chronic diazepam regimen was shifted to the right of that obtained prior to chronic diazepam.

  14. Simultaneous screening and quantification of 25 opioid drugs in post-mortem blood and urine by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Gergov, M; Nokua, P; Vuori, E; Ojanperä, I

    2009-04-15

    A method for simultaneous screening and quantification was developed for the fentanyls alfentanil, fentanyl, p-fluorofentanyl, cis-3-methylfentanyl, trans-3-methylfentanyl, alpha-methylfentanyl, norfentanyl, remifentanil, sufentanil, and the other opioid drugs 6-acetylmorphine, buprenorphine, codeine, dextropropoxyphene, ethylmorphine, heroin, methadone, morphine, naloxone, naltrexone, norbuprenorphine, normethadone, oxycodone, pentazocine, pethidine, and tramadol in post-mortem blood and urine samples by LC-MS/MS. Samples were extracted with butyl acetate at pH 7. The drugs were separated by LC on a Genesis C(18) reversed-phase column, with a gradient consisting of acetonitrile and ammonium acetate at pH 3.2. The mass spectrometric analysis was performed with a quadrupole-linear ion-trap mass spectrometer equipped with a turbo ion spray interface in positive mode using multiple reaction monitoring (MRM). Quantification was performed based on five isotope-labelled internal standards. Validation included assessment of linearity, limit of quantification, inaccuracy, precision, and matrix effects. The limits of quantification were adequate for screening and quantification of opioid drugs at low therapeutic or abuse concentration levels, with inaccuracy less than 23% and precision better than 24% both in blood and urine samples. When this method was applied to autopsy cases, its results were in agreement with those of reference methods.

  15. Missing Data in Substance Abuse Treatment Research: Current Methods and Modern Approaches

    Science.gov (United States)

    McPherson, Sterling; Barbosa-Leiker, Celestina; Burns, G. Leonard; Howell, Donelle; Roll, John

    2013-01-01

    Two common procedures for the treatment of missing information, listwise deletion and positive urine analysis (UA) imputation (e.g., if the participant fails to provide urine for analysis, then score the UA positive), may result in significant biases during the interpretation of treatment effects. To compare these approaches and to offer a possible alternative, these two procedures were compared to the multiple imputation (MI) procedure with publicly available data from a recent clinical trial. Listwise deletion, single imputation (i.e., positive UA imputation), and MI missing data procedures were used to comparatively examine the effect of two different buprenorphine/naloxone tapering schedules (7- or 28-days) for opioid addiction on the likelihood of a positive UA (Clinical Trial Network 0003; Ling et al., 2009). The listwise deletion of missing data resulted in a nonsignificant effect for the taper while the positive UA imputation procedure resulted in a significant effect, replicating the original findings by Ling et al. (2009). Although the MI procedure also resulted in a significant effect, the effect size was meaningfully smaller and the standard errors meaningfully larger when compared to the positive UA procedure. This study demonstrates that the researcher can obtain markedly different results depending on how the missing data are handled. Missing data theory suggests that listwise deletion and single imputation procedures should not be used to account for missing information, and that MI has advantages with respect to internal and external validity when the assumption of missing at random can be reasonably supported. PMID:22329556

  16. Detection and quantification of benzodiazepines in hair by ToF-SIMS: preliminary results

    Science.gov (United States)

    Audinot, J.-N.; Yegles, M.; Labarthe, A.; Ruch, D.; Wennig, R.; Migeon, H.-N.

    2003-01-01

    Successful results have been obtained in detection and quantification of buprenorphine in urine and hemolysed blood by time of flight-secondary ion mass spectrometry (ToF-SIMS). The present work is focused on four molecules of the benzodiazepine's family: nordiazepam, aminoflunitrozepam, diazepam and oxazepam. These drugs remain difficult to analyse in routine clinical and forensic toxicology because of their thermal instability and low therapeutic range (0.5-5 ng/ml). Internal standards are prepared by means of deuterated molecules. The benzadiazepine and their deuterated form (nordiazepam-D5, amino-flunitrazepam-D3, diazepam-D5 and oxazepam-D5) were added, in known concentration, in urine. These molecules were then extracted with several methods (pH, solvent, etc.) and, after adsorption on a noble metal, analysed by ToF-SIMS. The paper will focus for the different molecules on the comparison of the different preparation procedures, the optimisation of the SIMS conditions, the limits of detection and the limits of quantification.

  17. 植入型长效纳曲酮缓释剂治疗海洛因依赖者心理渴求的临床价值%Study of the curative effect on heroin craving among heroin dependence treated with long-term sustained release naltrexone(LSRNTX)implants

    Institute of Scientific and Technical Information of China (English)

    胡疏; 尹述贵; 贾少微; 侯海峰; 刘克菊; 孙志俊; 孙涛涛; 樊蓉

    2010-01-01

    目的 研究植入型长效纳曲酮缓释剂(Long-term sustained release naltrexone,LSRNTX)对海洛因依赖者心理渴求的疗效.方法 对接受植入型LSRNTX治疗的108例海洛因依赖患者,进行治疗前后的海洛因渴求量表分析,同步进行治疗后尿液吗啡、美沙酮和丁丙诺啡突击性定性检测.结果 (1)108例患者接受植入型LSRNTX治疗后海洛因渴求量表总分及用药意向、用药渴望、效果期待、自我控制4个因子得分均显著低于治疗前得分,差异具有统计学意义.(2)治疗后的108例患者中,95例(87.96%)尿吗啡、美沙酮、丁丙诺啡检测结果为全阴性,阳性结果者13例(12.04%).(3)治疗后尿液检测阴性结果者海洛因渴求量表得分较治疗前得分减低幅度高于阳性结果者得分减低幅度.结论 植入型LSRNTX对海洛因依赖患者具有降低心理渴求的良好疗效,有利于防治海洛因依赖患者复吸.%Objective To investigate heroin craving changes among heroin dependence treated with longterm sustained release naltrexone(LSRNTX)implants.Methods Before and after the treatment of LSRNTX implants,the levels of heroin craving were evaluated with Rating Scale for Heroin Craving among 108 heroin addicts,and urine analysis for morphine,methadone,and buprenorphine were performed among them without prior notification.Results(1)After the treatment of LSRNTX implants,the total scores of Rating Scale for Heroin Craving and the scores of the four factors of abusing intent,abusing spiration,expect effect,and self-control among the 108 heroin addicts were much less lower than those before the treatment,and the differences are statistically significant.(2)After the treatment,the outcomes of urine analysis for morphine,methadone,and buprenorphine were completely negative among 95 subjects(87.96%),the positive outcomes were found in 13(12.04%)subjects.(3)After the treatment,the scores of Rating Scale for Heroin Craving among the subjects with

  18. Co-occurring amphetamine use and associated medical and psychiatric comorbidity among opioid-dependent adults: results from the Clinical Trials Network

    Directory of Open Access Journals (Sweden)

    Blazer DG

    2011-07-01

    Full Text Available Daniel J Pilowsky1, Li-Tzy Wu2, Bruce Burchett2, Dan G Blazer2, George E Woody3, Walter Ling41Departments of Epidemiology and Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York City, NY; 2Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University Medical Center, Durham, NC; 3Department of Psychiatry, School of Medicine, University of Pennsylvania and Treatment Research Institute, Philadelphia, PA; 4David Geffen School of Medicine, NPI/Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USABackground: In response to the rising rate of treatment admissions related to illicit use of amphetamines (eg, methamphetamine, we examined the prevalence of amphetamine use among treatment-seeking, opioid-dependent adults, explored whether amphetamine users were as likely as nonamphetamine users to enroll in opioid-dependence treatment trials, and determined whether amphetamine users manifested greater levels of medical and psychiatric comorbidity than nonusers.Methods: The sample included 1257 opioid-dependent adults screened for participation in threemultisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-003, which studied the effectiveness of buprenorphine for opioid detoxification under varying treatment conditions. Patients were recruited from 23 addiction treatment programs across the US. Medical and psychiatric comorbidity were examined by past-month amphetamine use (current vs former and route of administration. Five mutually exclusive groups were examined, ie, nonusers, current amphetamine injectors, current amphetamine noninjectors, former amphetamine injectors, and former amphetamine noninjectors.Results: Of the sample (n = 1257, 22.3% had a history of regular amphetamine use. Of the 280 amphetamine users, 30.3% reported injection as their primary route. Amphetamine users were more likely than nonusers to be white and use more

  19. 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

  20. Clinical Effects of Patient-controlled Epidural Analgesia in Children%小儿术后硬膜外自控镇痛的临床效果

    Institute of Scientific and Technical Information of China (English)

    刘继云; 佘守章; 谢晓青

    2000-01-01

    Objective: To evaluate the feasibility and safety of postoperative patient-controlled epidural analgesia (PCEA)in children. Methods: Forty postoperative pediatric patients(5-11 years old)were divided into two groups. A and B. Both wereinstituted with postoperative PCEA with LCP model (loading dose 2.05 + 0.13ml), continuos infusion rate 0.82 + 0.15mi/h, PCA dose 0.81 + 0.16ml)by Graseby-9300 PCA pump. The PCEA solution of group A was 0.075% bupivacaine plus0.0012 % buprenorphine, that of group B was same while 0. 005% droperidol was added as an adjuvant. Results:The volumeof PCEA sdution consumption in group B was significantly less than that in group A on the first and second postoperative day (P< 0.01-0.05). Good analgesic efficiency with little side effects was obtained, as evaluated by the VASF emasay or D/D score and complications in two groups, but the analgesic effect of group B was better than that of group A. Conclusion: Thepediatric PCEA with low concentration of bupivaeaine plus buprenorphine is feasible and safe. Droperidol may enhance theanalgesic effects of PCEA.%目的:探讨小儿术后硬膜外自控镇痛(PCEA)的可行性和安全性。方法:术后5~11岁的小儿40例,分成A、B两组。A组镇痛液配方为0.075%布比卡因+0.0012%丁丙诺啡(12μg/ml),B组配方与A组相同并加入小剂量氟哌啶(50μg/ml)。以LCP模式(负荷量2.05±0.13ml,持续量0.82±0.15ml,PCA量0.81±0.16m1)实施PCEA。结果:B组2天用量均少于A组(P<0.01~0.05)。从三种评分指标(VASF、ramsay、D/D)和并发症综合比较分析,提示两组均能达到满意的镇痛效果,但B组优于A组。结论:小儿术后用0.075%布比卡因+丁丙诺啡行PCEA是安全有效的,辅助少量氟哌啶可进一步增强PCA效果。

  1. Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation

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    Murray, Donna E; Durazzo, Timothy C; Schmidt, Thomas P; Abé, Christoph; Guydish, Joseph; Meyerhoff, Dieter J

    2016-01-01

    Objective Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence. Methods Single-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions. Results Compared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits. Conclusion The anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment. PMID:27695638

  2. Pharmacological maintenance treatments of opiate addiction.

    Science.gov (United States)

    Bell, James

    2014-02-01

    For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some 'nonresponders' and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy.

  3. Pyrrolidine dithiocarbamate attenuates surgery-induced neuroinflammation and cognitive dysfunction possibly via inhibition of nuclear factor κB.

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    Zhang, J; Jiang, W; Zuo, Z

    2014-03-07

    Surgery induces learning and memory impairment. Neuroinflammation may contribute to this impairment. Nuclear factor κB (NF-κB) is an important transcription factor to regulate the expression of inflammatory cytokines. We hypothesize that inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC) reduces neuroinflammation and the impairment of learning and memory. To test this hypothesis, four-month-old male Fischer 344 rats were subjected to right carotid exploration under propofol and buprenorphine anesthesia. Some rats received two doses of 50mg/kg PDTC given intraperitoneally 30min before and 6h after the surgery. Rats were tested in the Barnes maze and fear conditioning paradigm begun 6days after the surgery. Expression of various proteins related to inflammation was examined in the hippocampus at 24h or 21days after the surgery. Here, surgery, but not anesthesia alone, had a significant effect on prolonging the time needed to identify the target hole during the training sessions of the Barnes maze. Surgery also increased the time for identifying the target hole in the long-term memory test and decreased context-related learning and memory in fear conditioning test. Also, surgery increased nuclear expression of p65, a NF-κB component, decreased cytoplasmic amount of inhibitor of NF-κB, and increased the expression of interleukin-1β, interleukin-6, ionized calcium binding adaptor molecule 1 and active matrix metalloproteinase 9 (MMP-9). Finally, surgery enhanced IgG extravasation in the hippocampus. These surgical effects were attenuated by PDTC. These results suggest that surgery, but not propofol-based anesthesia, induces neuroinflammation and impairment of learning and memory. PDTC attenuates these effects possibly by inhibiting NF-κB activation and the downstream MMP-9 activity.

  4. 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

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

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    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

  6. Position of immunological techniques in screening in clinical toxicology.

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    George, Steve

    2004-01-01

    There is a continuing increase in the use of immunological techniques in the field of clinical toxicology. This is primarily due to the rapidity by which analytical results are now required, and can be obtained, following the testing of individuals for drug use. There has recently been an increase in the repertoire of assays now available to testing laboratories (e.g., buprenorphine and heroin metabolite assays), with the techniques themselves becoming increasingly more specific for the drugs and/or metabolites being monitored (e.g., methadone metabolite assays). The near patient testing (NPT), or point-of-care testing (POCT), devices are now several generations forward from their inception, with some tests now approaching the sensitivity and specificity of automated laboratory-based methods. This review has been collated from the literature to illustrate some of the possible reasons for the move towards the increasing use of immunological techniques, and to highlight some of the advantages and disadvantages associated with such drug screening methods. In particular, it has been shown that it is important to determine, monitor and review the knowledge and training of the individual using the technique. In addition, quality control and quality assessment are paramount to ensure the validity of any drug testing being performed. It has also been shown that it is vital to maintain and develop the relationships between the staff performing the testing, the laboratory (if the testing is performed using NPT devices), and the clinicians utilising the results obtained from drug testing. Without these links, interpretive errors could arise which could adversely affect the diagnosis and management of patients.

  7. 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.

  8. Examining the factor structure of the Clinical Opiate Withdrawal Scale: A secondary data analysis from the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003

    Science.gov (United States)

    Barbosa-Leiker, Celestina; McPherson, Sterling; Mamey, Mary Rose; Burns, G. Leonard; Layton, Matthew E.; Roll, John; Ling, Walter

    2015-01-01

    Background The Clinical Opiate Withdrawal Scale (COWS) is used to assess withdrawal in clinical trials and practice. The aims of this study were to examine the inter-item correlations and factor structure of the COWS in opioid-dependent men and women. Methods This is a secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network 0003, a randomized clinical trial that compared buprenorphine/naloxone tapering strategies. The trial included 11 sites in 10 US cities. Participants were opioid-dependent individuals (n=516) that had data on the COWS. The COWS at study baseline was analyzed in this study. Results Inter-item correlations showed weak to moderate relationships among the items. A 1-factor model did not fit the data for men (comparative fit index (CFI)=.801, root mean square error of approximation (RMSEA)=.073, weighted root mean square residual (WRMR)=1.132) or women (CFI=.694, RMSEA=.071, WRMR=.933), where resting pulse rate was not related to withdrawal for men, and yawning and gooseflesh skin was not related to withdrawal for women. A reduced model comprised of only the 8 items that were significantly related to the construct of withdrawal in both men and women, and an exploratory 2-factor model, were also assessed but not retained due to inconsistencies across gender. Conclusions When traditional psychometric models are applied to the COWS, it appears that the scale may not relate to a single underlying construct of withdrawal. Further research testing the hypothesized factor structure in other opioid-dependent samples is needed. PMID:25908321

  9. Impact of Illicit Drug Use on Health-Related Quality of Life in Opioid Dependent Patients Undergoing HIV Treatment

    Science.gov (United States)

    Aden, Brandon; Dunning, Allison; Nosyk, Bohdan; Wittenberg, Eve; Bray, Jeremy W.; Schackman, Bruce R.

    2015-01-01

    Objective To assess the impact of illicit drug use on health-related quality of life (health utility) among opioid-dependent, HIV-infected patients. Design Secondary analyses of data from the Buprenorphine-HIV Evaluation and Support (BHIVES) cohort of HIV-infected patients with opioid dependence in 9 U.S. HIV clinics between 2004 and 2009. Health status (Short Form-12 (SF-12)), combination antiretroviral treatment (ART) status, CD4 cell count, HCV antibody status, current drug use, and demographics were assessed at an initial visit and quarterly follow-up visits for up to one year. Short Form-6D health utility scores were derived from the SF-12. Multivariate mixed effects regression models were used to assess the impact of illicit drug use on health utility controlling for demographic, clinical and social characteristics. Results Health utility was assessed among 307 participants, 67% male, with median age 46 at 1089 quarterly assessments. In multivariate analyses, illicit opioid use, non-opioid illicit drug use, not being on ART and being on ART with poor adherence were associated with lower health utility. The observed decrement in health utility associated with illicit opioid use was larger for those on ART with good adherence (beta = −0.067; popioid drug use are negatively associated with health utility in patients with HIV, however the relative effect of illicit opioid use is smaller than that of not being on ART. Postponing ART until initiation of opioid substitution therapy or abstinence may have limited benefits from the perspective of maximizing health utility. PMID:26218410

  10. Neurobiology of opioid dependence in creating addiction vulnerability.

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    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

  11. 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.

  12. Should psychosocial intervention be added to pharmacological treatment for opiate abuse/dependence? An overview of systematic reviews of the literature

    Directory of Open Access Journals (Sweden)

    Laura Amato

    2006-06-01

    Full Text Available

    Background: Opioid abuse and dependence are major health and social issues in most societies. Different interventions are available, but the majority of heroin patients relapse and these relapses are a substantial problem to their rehabilitation. Psychosocial interventions for drug addicts have been suggested as possible instruments to overcome the difficulty of maintaining a drug-free state. The aim of this paper is to provide a summary of the available evidence of effectiveness.

    Methods: We summarised the results from two systematic reviews on psychosocial interventions combined with Methadone Maintenance Treatment and Methadone or Buprenorphine Detoxification Treatment.

    Results: For detoxification treatments, the results show that benefits can be gained from adding any psychosocial treatment to any substitution detoxification treatment in terms of completion of treatment: relative risk (RR 1.68 (95% CI 1.11-2.55, and compliance (proportion of clinical absences: RR 0.48 (95% CI 0.38-0.59; for the use of heroin during treatment, the differences were not statistically significant. For maintenance treatments, there is an additional benefit to be gained in adding any psychosocial treatment to methadone maintenance treatment in relation to the use of heroin during treatment: RR 0.69(95% CI 0.53-0.91; no statistically significant additional benefit was shown in terms of treatment retention and results at follow-up.

    Conclusions: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment and compliance, while adding any psychosocial support to methadone maintenance significantly improves the non-use of heroin during treatment but does not improve the other outcomes considered.

  13. Development and validation of two LC-MS/MS methods for the detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine using turbulent flow chromatography.

    Science.gov (United States)

    Schaefer, Nadine; Peters, Benjamin; Schmidt, Peter; Ewald, Andreas H

    2013-01-01

    In the context of driving ability diagnostics in Germany, administrative cutoffs for various drugs and pharmaceuticals in urine have been established. Two liquid chromatography-tandem mass spectrometry methods for simultaneous detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine were developed and validated. A 500-μL aliquot of urine was diluted and fortified with an internal standard solution. After enzymatic cleavage, online extraction was performed by an ion-exchange/reversed-phase turbulent flow column. Separation was achieved by using a reversed-phase column and gradient elution. For detection, a Thermo Fisher TSQ Quantum Ultra Accurate Mass tandem mass spectrometer with positive electrospray ionization was used, and the analytes were measured in multiple-reaction monitoring mode detecting two transitions per precursor ion. The total run time for both methods was about 15 min. Validation was performed according to the guidelines of the Society of Toxicological and Forensic Chemistry. The results of matrix effect determination were between 78% and 116%. The limits of detection and quantification for all drugs, except zopiclone, were less than 10 ng/mL and less than 25 ng/mL, respectively. Calibration curves ranged from 25 to 200 ng/mL for amphetamines, designer amphetamines, and benzoylecgonine, from 25 to 250 ng/mL for benzodiazepines, from 12.5 to 100 ng/mL for morphine, codeine, and dihydrocodeine, and from 5 to 50 ng/mL for buprenorphine and norbuprenorphine. Intraday and interday precision values were lower than 15%, and bias values within ± 15% were achieved. Turbulent flow chromatography needs no laborious sample preparation, so the workup is less time-consuming compared with gas chromatography-mass spectrometry methods. The methods are suitable for quantification of multiple analytes at the cutoff concentrations required for driving ability diagnostics in Germany.

  14. A hybrid liquid chromatography-mass spectrometry strategy in a forensic laboratory for opioid, cocaine and amphetamine classes in human urine using a hybrid linear ion trap-triple quadrupole mass spectrometer.

    Science.gov (United States)

    Dowling, Geraldine; Regan, Liam; Tierney, Julie; Nangle, Michael

    2010-10-29

    A rapid method has been developed to analyse morphine, codeine, morphine-3-glucuronide, 6-monoacetylmorphine, cocaine, benzoylegonine, buprenorphine, dihydrocodeine, cocaethylene, 3,4-methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and methadone in human urine. Urine samples were diluted with methanol:water (1:1, v/v) and sample aliquots were analysed by hybrid linear ion trap-triple quadrupole mass spectrometry with a runtime of 12.5 min. Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification and confirmation was carried out by library search with a developed in-house MS/MS library based on EPI spectra at a collision energy spread of 35±15 in positive mode and MRM ratios. The method was validated in urine, according to the criteria defined in Commission Decision 2002/657/EC. At least two MRM transitions for each substance were monitored in addition to EPI spectra and deuterated analytes were used as internal standards for quantitation. The reporting level was 0.05 μg mL(-1) for the range of analytes tested. The regression coefficients (r(2)) for the calibration curves (0-4 μg mL(-1)) in the study were ≥0.98. The method proved to be simple and time efficient and was implemented as an analytical strategy for the illicit drug monitoring of opioids, cocaines and amphetamines in criminal samples from crime offenders, abusers or victims in the Republic of Ireland. To the best of our knowledge there are no hybrid LC-MS applications using MRM mode and product ion spectra in the linear ion trap mode for opioids, cocaines or amphetamines with validation data in urine.

  15. Comparison between drug screening by immunoassay and ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry in post-mortem urine.

    Science.gov (United States)

    Sundström, Mira; Pelander, Anna; Ojanperä, Ilkka

    2015-05-01

    Immunoassay is currently the most common approach for urine drug screening. However, the continuous emergence of new psychoactive substances (NPS) and their low urinary concentrations have challenged the scope and sensitivity of immunoassays. Consequently, specialized toxicology laboratories rely more and more on mass spectrometry (MS) based techniques. Ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOF-MS) is an especially attractive technique for comprehensive drug screening. The objective was to compare the performances of immunoassay and UHPLC-HR-TOF-MS in terms of scope, flexibility, sensitivity, and reliability of substance identification. A total of 279 post-mortem urine samples were analyzed using a method representative of each technique. The immunoassay method was an Emit II Plus enzyme immunoassay for the following drug groups: amphetamines, benzodiazepines, buprenorphine, cannabis, and opiates. The UHPLC-HR-TOF-MS method was a recently published method covering hundreds of drugs: conventional drugs of abuse, abused prescription drugs, and NPS of various classes. UHPLC-HR-TOF-MS produced a lower number of false positive (FP) results for the drug groups covered by immunoassay. Many of the false negative (FN, n = 40) and FP (n = 22) immunoassay results were obviously due to the higher cut-off concentrations and interfering matrix, respectively. Moreover, the wider scope of UHPLC-HR-TOF-MS allowed detection of NPS and prescription drugs. UHPLC-HR-TOF-MS gave FP results related to a few particular substances. The future option of adjusting all compound-specific reporting parameters individually would allow the method's sensitivity and specificity to be fully exploited.

  16. Effects of μ-opioid receptor agonists in assays of acute pain-stimulated and pain-depressed behavior in male rats: role of μ-agonist efficacy and noxious stimulus intensity.

    Science.gov (United States)

    Altarifi, Ahmad A; Rice, Kenner C; Negus, S Stevens

    2015-02-01

    Pain is associated with stimulation of some behaviors and depression of others, and μ-opioid receptor agonists are among the most widely used analgesics. This study used parallel assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats to compare antinociception profiles for six μ-agonists that varied in efficacy at μ-opioid receptors (from highest to lowest: methadone, fentanyl, morphine, hydrocodone, buprenorphine, and nalbuphine). Intraperitoneal injection of diluted lactic acid served as an acute noxious stimulus to either stimulate stretching or depress operant responding maintained by electrical stimulation in an intracranial self-stimulation (ICSS). All μ-agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy agonists methadone and fentanyl were more potent at blocking acid-induced depression of ICSS than acid-stimulated stretching, whereas lower-efficacy agonists displayed similar potency across assays. All μ-agonists except morphine also facilitated ICSS in the absence of the noxious stimulus at doses similar to those that blocked acid-induced depression of ICSS. The potency of the low-efficacy μ-agonist nalbuphine, but not the high-efficacy μ-agonist methadone, to block acid-induced depression of ICSS was significantly reduced by increasing the intensity of the noxious stimulus to 5.6% acid. These results demonstrate sensitivity of acid-induced depression of ICSS to a range of clinically effective μ-opioid analgesics and reveal distinctions between opioids based on efficacy at the μ-receptor. These results also support the use of parallel assays of pain-stimulated and -depressed behaviors to evaluate analgesic efficacy of candidate drugs.

  17. Modulation of peripheral μ-opioid analgesia by σ1 receptors.

    Science.gov (United States)

    Sánchez-Fernández, Cristina; Montilla-García, Ángeles; González-Cano, Rafael; Nieto, Francisco Rafael; Romero, Lucía; Artacho-Cordón, Antonia; Montes, Rosa; Fernández-Pastor, Begoña; Merlos, Manuel; Baeyens, José Manuel; Entrena, José Manuel; Cobos, Enrique José

    2014-01-01

    We evaluated the effects of σ1-receptor inhibition on μ-opioid-induced mechanical antinociception and constipation. σ1-Knockout mice exhibited marked mechanical antinociception in response to several μ-opioid analgesics (fentanyl, oxycodone, morphine, buprenorphine, and tramadol) at systemic (subcutaneous) doses that were inactive in wild-type mice and even unmasked the antinociceptive effects of the peripheral μ-opioid agonist loperamide. Likewise, systemic (subcutaneous) or local (intraplantar) treatment of wild-type mice with the selective σ1 antagonists BD-1063 [1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine dihydrochloride] or S1RA [4-[2-[[5-methyl-1-(2-naphthalenyl)1H-pyrazol-3-yl]oxy]ethyl] morpholine hydrochloride] potentiated μ-opioid antinociception; these effects were fully reversed by the σ1 agonist PRE-084 [2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate) hydrochloride], showing the selectivity of the pharmacological approach. The μ-opioid antinociception potentiated by σ1 inhibition (by σ1-receptor knockout or σ1-pharmacological antagonism) was more sensitive to the peripherally restricted opioid antagonist naloxone methiodide than opioid antinociception under normal conditions, indicating a key role for peripheral opioid receptors in the enhanced antinociception. Direct interaction between the opioid drugs and σ1 receptor cannot account for our results, since the former lacked affinity for σ1 receptors (labeled with [(3)H](+)-pentazocine). A peripheral role for σ1 receptors was also supported by their higher density (Western blot results) in peripheral nervous tissue (dorsal root ganglia) than in several central areas involved in opioid antinociception (dorsal spinal cord, basolateral amygdala, periaqueductal gray, and rostroventral medulla). In contrast to its effects on nociception, σ1-receptor inhibition did not alter fentanyl- or loperamide-induced constipation, a peripherally mediated nonanalgesic opioid effect. Therefore

  18. Simultaneous analysis of some club drugs in whole blood using solid phase extraction and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Castro, André L; Tarelho, Sónia; Silvestre, Armando; Teixeira, Helena M

    2012-02-01

    The use of psychoactive substances to improve social relations and increase body energy, in Rave Culture, has raised many legal and health public concerns, both for illicit trade and consumption. Therefore, forensic toxicology plays an important role in this area, mainly linked to the detection and quantitation of these substances, both in vivo and in post-mortem samples. In fact, at the moment, forensic sciences have been under public authorities' scrutiny and critical look, due to the increasing attention of the media and public opinion, always applying for the use of scientific knowledge to help solving forensic cases. However, forensic toxicology results are only reliable to solve legal cases if all the analytical methodologies used are appropriately validated. In this work, a methodology for the extraction and analysis of 7-aminoflunitrazepam, buprenorphine, flunitrazepam, ketamine, methadone, phencyclidine (PCP) and d-propoxyphene was developed for whole blood samples, with solid phase extraction (SPE), using OASIS(®) MCX SPE columns, and gas chromatography coupled to mass spectrometry. The procedure presented here proved to be reliable, specific, selective and sensitive, with good LODs and LOQs and good precision.The adoption of a SPE procedure with an automatic SPE extraction device, allowed an increased level of automation in sample treatment, being contemporarily less time-consuming, increasing productiveness, and allowing good recovery and appropriate selectivity being, also, simple and reproducible. The simultaneous detection and quantitation of all compounds by the same extraction and detection methodology is crucial and has a great potential for forensic toxicology and clinical analysis.

  19. Escitalopram is associated with reductions in pain severity and pain interference in opioid dependent patients with depressive symptoms.

    Science.gov (United States)

    Tsui, Judith I; Herman, Debra S; Kettavong, Malyna; Anderson, Bradley J; Stein, Michael D

    2011-11-01

    Pain is common among opioid-dependent patients, yet pharmacologic strategies are limited. The aim of this study was to explore whether escitalopram, a selective serotonin reuptake inhibitor, was associated with reductions in pain. The study used longitudinal data from a randomized, controlled trial that evaluated the effects of escitalopram on treatment retention in patients with depressive symptoms who were initiating buprenorphine/naloxone for treatment of opioid dependence. Participants were randomized to receive escitalopram 10 mg or placebo daily. Changes in pain severity, pain interference, and depression were assessed at 1-, 2-, and 3-month visits with the visual analog scale, Brief Pain Inventory, and the Beck Depression Inventory II, respectively. Fixed-effects estimators for panel regression models were used to assess the effects of intervention on changes in outcomes over time. Additional models were estimated to explore whether the intervention effect was mediated by within-person changes in depression. In this sample of 147 adults, we found that participants randomized to escitalopram had significantly larger reductions on both pain severity (b=-14