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1

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

PubMed Central

Objective: The objective of the current study was to explore the difference in treatment adherence to directly supervised buprenorphine and take-home buprenorphine/ naloxone combination for opioid substitution therapy. Urinalysis findings have been used to check treatment adherence on opioid substitution therapy agent. Additionally the study aimed to explore the misuse rate of buprenorphine/naloxone combination based on urinalysis findings. Design: Cross-sectional chart review Setting: Laboratory of a tertiary care drug dependence treatment center Participants: One-year laboratory urinalysis records of a tertiary care, drug-dependence treatment center in India were analyzed. All the urine samples of subjects on opioid substitution therapy with buprenorphine or buprenorphine/naloxone combination were included in the study. Measurements: Urinalysis using thin layer chromatography for buprenorphine and naloxone. In between group difference for treatment adherence on buprenorphine and buprenorphine/ naloxone combination was done using Mantel-Haenszel test. Results: A higher proportion of samples from subjects on buprenorphine/naloxone tested positive for buprenorphine as compared to subjects on buprenorphine. Twelve (7.6%) urine samples from patients on buprenorphine/naloxone tested positive for naloxone. Conclusions: The findings of the current study suggest that buprenorphine/naloxone combination has a higher adherence rate as compared to buprenorphine when used for opioid substitution therapy.

Jain, Raka

2012-01-01

2

Buprenorphine substitution treatment in France: drug users' views of the doctor-user relationship  

PubMed Central

The French system for drug substitution, or maintenance treatment, established in 1996, differs from the often strict conditions attached to methadone clinics in other countries. Because of the predominant role of general practitioners and the flexible prescription rules for Subutex® in France, the relationship between the physician and the drug user becomes a central element in the treatment. This article deals with the expectations that these users have of the physician, and their perception of his or her attitude towards them. In order to identify possible reasons for the absence of treatment compliance and of Subutex® misuse, it focuses on the users’ assessment of the physician’s response to the problems they report. This study, based on a diversified sample of 28 persons in treatment, showed 4 patterns of relationships between physicians and users, which differed in their focus: a) dosage, b) compliance, c) the person and d) obtaining a prescription. In all four case types, users had difficulty reporting other drug use or intravenous Subutex® injection within this relationship in which the stigma attached to drug dependence seems to reappear. Moreover, the lack of clarity about the treatment objectives and time frame limits the users’ ability to integrate the treatment into their lives and to commit themselves to it. The heterogeneity and fragility of the users’ situations are elements related to dependence that, during contact with the physician, require regular assessment of the individual’s situation and of the treatment objectives. This constant reappraisal of the situation with the physician should help to optimize the treatment and avoid the hiatus that can generate or continue “misuse.”

Guichard, Anne; Lert, France; Brodeur, Jean-Marc; Richard, Lucie

2007-01-01

3

Effect of buprenorphine dose on treatment outcome.  

PubMed

The goal of this meta-analysis is to provide evidence based information about proper dosing for buprenorphine maintenance treatment to improve treatment outcome. To be selected for the review and inclusion in the meta-analysis, articles had to be randomized, controlled, or double-blind clinical trials, with buprenorphine as the study drug; the length of buprenorphine maintenance treatment had to be 3 weeks or longer; doses of buprenorphine had to be clearly stated; outcome measures had to include retention rates in buprenorphine treatment; outcome measures had to include illicit opioid use based on analytical determination of drugs of abuse in urine samples as outcome variables; and outcome measures had to include illicit cocaine use based on analytical determination of drugs of abuse in urine samples as outcome variables. Twenty-nine articles were excluded because they did not meet the inclusion criteria. The authors present the results of 21 articles that met inclusion criteria. The higher buprenorphine dose (16-32 mg per day) predicted better retention in treatment compared with the lower dose (less than 16 mg per day) (P = .009, R(2) adjusted = 0.40), and the positive urine drug screens for opiates predicted dropping out of treatment (P = .019, R(2) Adjusted = 0.40). Retention in treatment predicted less illicit opioid use (P = .033, R(2) Adjusted = 0.36), and the positive urine drug screens for cocaine predicted more illicit opioid use (P = .021, R(2) Adjusted = 0.36). Strong evidence exists based on 21 randomized clinical trials that the higher buprenorphine dose may improve retention in buprenorphine maintenance treatment. PMID:22356665

Fareed, Ayman; Vayalapalli, Sreedevi; Casarella, Jennifer; Drexler, Karen

2012-01-01

4

Outpatient Opiate Detoxification Treatment with Buprenorphine  

Microsoft Academic Search

In an open study design, 50 opioid-dependent subjects (DSM-IV: 304.0) were investigated in a gradual detoxification treatment with buprenorphine. The study was performed at the drug addiction outpatient clinic of the Department of General Psychiatry at the University of Vienna. Subjects had to contact the outpatient clinic on a daily basis and buprenorphine was administered according to their clinical status.

K. Diamant; G. Fischer; C. Schneider; E. Lenzinger; L. Pezawas; S. Schindler; H. Eder

1998-01-01

5

Hypogonadism in men receiving methadone and buprenorphine maintenance treatment.  

PubMed

The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 +/- 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) <12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT <8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement. PMID:17971165

Hallinan, R; Byrne, A; Agho, K; McMahon, C G; Tynan, P; Attia, J

2007-10-30

6

Office-based buprenorphine treatment for opioid-dependent patients.  

PubMed

Opioid dependence is epidemic in the United States, with increasing numbers addicted to heroin and burgeoning abuse of prescription opioid analgesics. Buprenorphine, the most recent addition to the pharmacotherapies available to treat opioid dependence, is novel among the opioid pharmacotherapies because of its partial agonist properties. It has been placed on Schedule III and is available by prescription from a physician's office-based practice. This review briefly summarizes the research supporting buprenorphine as a treatment for opioid dependence--including its clinical pharmacology, formulation with naloxone to prevent diversion, clinical use in treatment of opioid dependence, and issues regarding its use in special populations. PMID:15764468

McCance-Katz, Elinore F

7

Buprenorphine and HIV primary care: new opportunities for integrated treatment.  

PubMed

Drug abuse and infection with human immunodeficiency virus (HIV) are associated with high rates of morbidity and mortality, but, because of medical, social, and legal factors, opiate addiction/dependence is a major obstacle to successful treatment of disease--for example, treatment of acquired immunodeficiency syndrome (AIDS) with highly active antiretroviral therapy. In an effort to improve the opportunity for treatment of drug abuse and HIV infection, the Forum for Collaborative HIV Research, in collaboration with the Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, the Centers for Disease Control and Prevention, and other agencies, presented a workshop entitled "Buprenorphine in the Primary HIV Care Setting." Participants reviewed and discussed current issues, such as the introduction of and sources for the provision of buprenorphine in HIV primary care settings and strategies for integrating treatment of HIV-infected drug abusers, all of which are covered in this supplement. PMID:17109302

Khalsa, Jag; Vocci, Francis; Altice, Frederick; Fiellin, David; Miller, Veronica

2006-12-15

8

Top Manager Effects on Buprenorphine Adoption in Outpatient Substance Abuse Treatment Programs  

PubMed Central

To examine the influence of top managers’ characteristics on the adoption of buprenorphine for opioid dependence among U.S. outpatient substance abuse treatment units, this investigation analyzed a cross-sectional national study of 547 such units in the 2004–2005 wave of the Drug Abuse Treatment System Survey. Administrators reported their demographics, training, and treatment orientation, as well as features of the unit and its pattern of use of buprenorphine. Nationally, 15.8% of programs offered any buprenorphine services. Greater adoption of buprenorphine correlated with directors’ younger age, longer tenure, male gender, and weaker endorsement of abstinence as the most important treatment goal. Availability of naltrexone and medical services also correlated positively with buprenorphine adoption. The authors conclude that leaders’ characteristics are related to the adoption of innovative practices in addiction treatment programs. Future work should examine whether leadership development for community addiction programs might speed up the diffusion of buprenorphine and other innovative, evidence-based practices.

Friedmann, Peter D.; Jiang, Lan; Alexander, Jeffrey A.

2013-01-01

9

Effect of Buprenorphine Dose on Treatment Outcome, a Literature Review and Meta-analysis  

Microsoft Academic Search

The goal of this meta-analysis is to provide evidence based information about proper dosing for buprenorphine maintenance treatment (BMT) to improve treatment outcome. In order to be selected for the review and inclusion in the meta-analysis, articles had to be: (1) Randomized, controlled, and\\/or double-blind clinical trials with buprenorphine as the study drug. (2) Length of buprenorphine maintenance treatment 3

Ayman Fareed; Sreedevi Vayalapalli; Jennifer Casarella; Karen Drexler

2012-01-01

10

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

PubMed Central

In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone®) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence.

Amass, Leslie; Ling, Walter; Freese, Thomas E.; Reiber, Chris; Annon, Jeffrey J.; Cohen, Allan J.; M.F.T.; McCarty, Dennis; Reid, Malcolm S.; Brown, Lawrence S.; Clark, Cynthia; Ziedonis, Douglas M.; Krejci, Jonathan; Stine, Susan; Winhusen, Theresa; Brigham, Greg; Babcock, Dean; L.C.S.W.; Muir, Joan A.; Buchan, Betty J.; Horton, Terry

2005-01-01

11

Brief v. Extended Buprenorphine Detoxification in a Community Treatment Program: Engagement and Short-Term Outcomes  

PubMed Central

Background Despite evidence supporting the efficacy of buprenorphine relative to established detoxification agents such as clonidine, little research has examined: (1) how best to implement buprenorphine detoxification in outpatient settings; and (2) whether extending the length of buprenorphine detoxification improves treatment engagement and outcomes. Objectives The current study examined the impact on (1) successful detoxification completion; (2) transition to longer-term treatment; and (3) treatment engagement of two different length opioid detoxifications using buprenorphine. Method The study compared data obtained from two consecutive studies of early treatment engagement strategies. In one study (n = 364), opioid-addicted participants entered treatment through a Brief (5-day) buprenorphine detoxification. In the other study (n = 146), participants entered treatment through an Extended (i.e., 30-day) buprenorphine detoxification. Results Results indicated a greater likelihood of successful completion and of transition among participants who received the Extended as compared to the Brief detoxification. Extended detoxification participants attended more counseling sessions and submitted fewer drug-positive urine specimens during the first 30 days of treatment, inclusive of detoxification, than did Brief detoxification participants. Conclusions Results demonstrate that longer periods of detoxification improve participant engagement in treatment and early treatment outcomes. Scientific Significance Current findings demonstrate the feasibility of implementing an extended buprenorphine detoxification within a community-based treatment clinic.

Katz, Elizabeth C.; Schwartz, Robert P.; King, Stuart; Highfield, David A.; O'Grady, Kevin E.; Billings, Timothy; Gandhi, Devang; Weintraub, Eric; Glovinsky, David; Barksdale, Wardell; Brown, Barry S.

2011-01-01

12

Developing and Implementing a New Prison-Based Buprenorphine Treatment Program  

PubMed Central

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 prison-initiated buprenorphine treatment in the United States, this manuscript focuses on how these obstacles were overcome through collaboration among correctional, treatment, and research personnel. Building on the present authors' work in developing prison-based methadone treatment, and considering the lack of experience in implementing corrections-based buprenorphine programs in the United States, this manuscript may serve as a guide for interested corrections officials, treatment providers, and researchers.

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

2010-01-01

13

Self-treatment: illicit buprenorphine use by opioid-dependent treatment seekers.  

PubMed

Outpatient-based opioid treatment (OBOT) with buprenorphine is an important treatment for people with opioid dependence. No quantitative empirical research has examined rationales for use of illicit buprenorphine by U.S. opioid-dependent treatment seekers. The current study sequentially screened OBOT admissions (n = 129) during a 6-month period in 2009. This study had two stages: (a) a cross-sectional epidemiological analysis of new intakes and existing patients already receiving a legal OBOT prescription (n = 78) and (b) a prospective longitudinal cohort design that followed 76% of the initial participants for 3 months of treatment (n = 42). The primary aims were to establish 2009 prevalence rates for illicit buprenorphine use among people seeking OBOT treatment, to use quantitative methods to investigate reasons for this illicit use, and to examine the effect of OBOT treatment on illicit buprenorphine use behavior. These data demonstrate a decrease in illicit use when opioid-dependent treatment seekers gain access to legal prescriptions. These data also suggest that the use of illicit buprenorphine rarely represents an attempt to attain euphoria. Rather, illicit use is associated with attempted self-treatment of symptoms of opioid dependence, pain, and depression. PMID:20434868

Schuman-Olivier, Zev; Albanese, Mark; Nelson, Sarah E; Roland, Lolita; Puopolo, Francyne; Klinker, Lauren; Shaffer, Howard J

2010-07-01

14

Buprenorphine augmentation in the treatment of refractory obsessive-compulsive disorder  

PubMed Central

Background: OCD is often refractory to treatment. There is a need for the development of new, non-invasive treatments for severe OCD. Rationale: There is evidence that opiates can be a useful adjunctive treatment in OCD. We summarise our experience with sublingual buprenorphine augmentation of standard pharmacological management of severe OCD. Methods: Patients were recruited from a standard psychiatric outpatient clinic and gave their consent to the treatment trial. The severity of the OCD was rated with the Y-BOCS. The buprenorphine was introduced to their existing medication regime at a low dose and the dose increased according to response. In order to gauge the reproducibility of the response the buprenorphine was withdrawn and then reintroduced once symptoms had returned. Results: 4 out of 7 patients with treatment resistant OCD showed a 30% reduction in the Y-BOCS score following buprenorphine augmentation. 3 of the responders were comorbid for other Axis 1 diagnoses. All of the responders had shown some improvement with SSRIs or clomipramine. Non-responders had not shown any improvement with either antidepressant or antipsychotic drugs. Typically improvement appeared within 2 days of initiating buprenorphine and waned within 1 to 2 days of its discontinuation. The dose of buprenorphine required varied between 400 µg and 600 µg a day. One responder managed on alternate day dosing. Reintroduction of buprenorphine resulted in symptom control within 2 to 3 days. The buprenorphine treatment was not associated with significant side-effects and the improvement was maintained without progressive dose escalation. Conclusions: Buprenorphine augmentation of standard treatment for OCD can result in clinically meaningful improvement in a proportion of refractory OCD cases. Further treatment trials are indicated.

Aziz, Victor; Briggs, Patrick; Kanakkehewa, Nimalee; Rawi, Omar

2013-01-01

15

Feasibility of Buprenorphine Maintenance Therapy Programs in the Ukraine: First Promising Treatment Outcomes  

Microsoft Academic Search

Background: Opiate substitution therapy (OST) in the Ukraine was not provided until 2004. As part of the introduction of OST, the first feasibility study was conducted in 2007. Six clinics in 6 cities were involved in providing OST and collecting data. Methods: A total of 151 opiate-dependent patients were given buprenorphine as a substitute, and a survey of substance use,

Michael Schaub; Emilis Subata; Victor Chtenguelov; Gundo Weiler; Ambros Uchtenhagen

2009-01-01

16

Using buprenorphine short-term taper to facilitate early treatment engagement  

Microsoft Academic Search

The U.S. Federal Food and Drug Administration approved buprenorphine for drug abuse treatment in 2002, and it became available for clinical use in early 2003. Maryhaven, a community treatment program, participated in a National Institute on Drug Abuse Clinical Trials Network trial evaluating buprenorphine–naloxone (BNX; Suboxone) short-term taper for medically managed opioid withdrawal and later adopted this treatment. In a

Gregory S. Brigham; Leslie Amass; Theresa Winhusen; Judy M. Harrer; Alvin Pelt

2007-01-01

17

Course and treatment of buprenorphine/naloxone withdrawal: an analysis of case reports.  

PubMed

Currently published information on buprenorphine-naloxone withdrawal recommends a gradually decreasing dosage over weeks to months. In this case report, abrupt cessation of buprenorphine/naloxone at various doses, and after variable durations of treatment, resulted in mild opiate withdrawal lasting over approximately 1-2 days that did not require additional opioid medication or only specific symptom-relieving, non-opioid, medications. Lengthy withdrawal regimens might prolong withdrawal symptoms unnecessarily, perhaps increasing the risk of re-addiction. Controlled studies of buprenorphine/naloxone withdrawal regimens over varying time frames would help to illuminate the most effective means of opioid discontinuation and inform clinical care. PMID:22882389

Westermeyer, Joseph; McCance-Katz, Elinore F

2012-07-24

18

Bringing buprenorphine-naloxone detoxification to community treatment providers: the NIDA Clinical Trials Network field experience  

Microsoft Academic Search

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

Leslie Amass; Walter Ling; Thomas E. Freese; Chris Reiber; Jeffrey J. Annon; Allan J. Cohen; Dennis McCarty; Malcolm S. Reid; Lawrence S. Brown; Cynthia Clark; Douglas M. Ziedonis; Jonathan Krejci; Susan Stine; Theresa Winhusen; Greg Brigham; Dean Babcock; Joan A. Muir; Betty J. Buchan; Terry Horton

2004-01-01

19

Consensus statement on office-based treatment of opioid dependence using buprenorphine  

Microsoft Academic Search

Buprenorphine and buprenorphine\\/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional organizations, researchers involved in monitoring, opioid treatment programs and the pharmaceutical industry met to synthesize and disseminate practical information to guide training, practice, monitoring, regulation and evaluation efforts with these medications. We performed a

David A. Fiellin; Herbert Kleber; Jeanne G. Trumble-Hejduk; A. Thomas McLellan; Thomas R. Kosten

2004-01-01

20

African American Patients Seeking Treatment in the Public Sector: Characteristics of Buprenorphine v. Methadone Patients  

PubMed Central

Background To expand its public-sector treatment capacity, Baltimore City made buprenorphine treatment accessible to low-income, largely African American residents. This study compares the characteristics of patients entering methadone treatment v. buprenorphine treatment to determine whether BT was attracting different types of patients. Methods Participants consisted of two samples of adult heroin-dependent African Americans. The first sample was newly-admitted to a health center or a mental health center providing buprenorphine (N=200), and the second sample was newly-admitted to one of two hospital-based methadone programs (N=178). The Addiction Severity Index (ASI) and the Friends Supplemental Questionnaire were administered at treatment entry and data were analyzed with logistic regression. Results BT participants were more likely to be female (p=.017) and less likely to inject (p=.001). Participants with only prior buprenorphine treatment experience were nearly five time more likely to enter buprenorphine than methadone treatment (p<.001). Those with experience with both treatments were more than twice as likely to enter BT (OR=2.7, 95% CI=1.11–6.62; p=.028). In the 30 days prior to treatment entry, BT participants reported more days of medical problems (p=.002) and depression (p=.044), and were more likely to endorse a lifetime history of depression (p<.001). Conclusion Methadone and buprenorphine treatment provided in the public sector may attract different patient subpopulations. Providing buprenorphine treatment through drug treatment programs co-located with a health and mental health center may have accounted for their higher rates of medical and psychiatric problems and appears to be useful in attracting a diverse group of patients into public-sector funded treatment.

Mitchell, Shannon Gwin; Kelly, Sharon M.; Gryczynski, Jan; Myers, C. Patrick; Jaffe, Jerome H.; O'Grady, Kevin E.; Olsen, Yngvild K.; Schwartz, Robert P.

2011-01-01

21

Brief buprenorphine detoxification for the treatment of prescription opioid dependence: A pilot study  

Microsoft Academic Search

We examined the feasibility of brief outpatient detoxification as a treatment for prescription opioid (PO) abusers. Fifteen PO-dependent adults were enrolled to receive buprenorphine stabilization, a 2-week buprenorphine taper, and subsequent naltrexone for those who completed the taper. Subjects also received behavioral therapy, urinalysis monitoring, and double-blind drug administration. Subjects provided 83.8%, 91.7% and 31.2% opioid-negative samples during stabilization, taper

Stacey C. Sigmon; Kelly E. Dunn; Gary J. Badger; Sarah H. Heil; Stephen T. Higgins

2009-01-01

22

Reimbursement and Practice Policies among Providers of Buprenorphine-naloxone Treatment  

Microsoft Academic Search

Physician acceptance of cash payment and low adherence to practice guidelines may contribute to buprenorphine-naloxone diversion. The purpose of this study was to investigate the clinical practice policies of physicians who provide office-based treatment for opioid dependence with buprenorphine-naloxone. Data were obtained from 31 of 71 practices surveyed (response rate 43.7%) that provided answers to at least some of the

Angela M. Wisniewski; Michael R. Dlugosz; Richard D. Blondell

2012-01-01

23

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

PubMed

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. PMID:15279124

Wesson, Donald R

2004-05-01

24

Clinical differences between opioid abuse classes ameliorated after 1 year of buprenorphine-medication assisted treatment.  

PubMed

This study compared the clinical and demographic profiles of three opioid-dependent user groups, and measured their response to 1 year of buprenorphine-medication assisted treatment. Opioid prescription, street, and combination (street + prescription) users completed the Addiction Severity Index multiple times over the course of one treatment year. Although groups differed on all measured demographics (P values <.05) and on six of seven Addiction Severity Index composite scores at induction (P values <.05), differences were ameliorated after 1 year. Findings highlight the disparities between the various opioid-dependent patient subpopulations and suggest that buprenorphine-medication assisted treatment is an effective treatment across user subtypes. PMID:22540432

Tkacz, Joseph; Severt, Jamie; Kassed, Cheryl; Ruetsch, Charles

2012-01-01

25

Buprenorphine treatment of opioid dependence: clinical trial of daily versus alternate-day dosing.  

PubMed

Buprenorphine, a mu-opioid partial agonist, has demonstrated efficacy for the treatment of opioid dependence comparable to that of methadone. The clinical utility of buprenorphine would be enhanced if it could be dosed on a less than daily basis. The current study is a parallel-group outpatient clinical trial of daily versus alternate-day dosing with 8 mg sublingual (s.l.) buprenorphine. Participants were randomly assigned to daily (n = 51) or alternate-day (n = 48) schedules of active medication administration for an 11-week double-blind trial. Patients assigned to alternate-day buprenorphine received placebo every other day. Primary outcome measures were retention in treatment and urine specimens positive for opiates. Clinic attendance, dose adequacy ratings, withdrawal symptomatology, and urine specimens positive for cocaine were secondary outcome measures. Neither endpoint analysis with the intent-to-treat sample nor time course analysis with treatment completers revealed any statistically significant differences between the dosing schedules on any outcome measure. Examination of 95% confidence intervals suggested a non-significant trend for the daily dosing schedule to have superior clinical efficacy at the dose tested. Nevertheless, these results are generally consistent with previous studies of less than daily dosing with buprenorphine and support the conclusion that an alternate-day dosing schedule can be effective in and acceptable to a substantial portion of patients. PMID:8746921

Johnson, R E; Eissenberg, T; Stitzer, M L; Strain, E C; Liebson, I A; Bigelow, G E

1995-11-01

26

Preliminary Assessment of a10Day Rapid Detoxification Programme Using High Dosage Buprenorphine  

Microsoft Academic Search

The original French therapeutic strategy for the treatment of opioid addiction was a rapid detoxification occasionally accompanied by treatment for withdrawal symptoms. In 1995, substitution therapy using opioids was introduced with the aim of maintenance, utilising methadone and the partial agonist buprenorphine, introduced in 1996. As well as being a maintenance agent, buprenorphine has been prescribed for rapid detoxification due

Jean Vignau

1998-01-01

27

Buprenorphine treatment: factors and first-hand experiences for providers to consider.  

PubMed

The viability of using buprenorphine to treat opiate dependence was well documented prior to federal approval in October 2002. What has been lacking in the literature is "hands-on" experience of providers from a clinical management and practice management perspective. This article adds to the knowledge base by providing information about buprenorphine treatment as well as anecdotes from patients treated by the authors, leading to a detailed list of factors worth considering for the treatment provider contemplating adding an opiate-addicted population to an existing treatment base. PMID:17439863

Meier, Bradley R; Patkar, Ashwin A

2007-01-01

28

Comment on "A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence During Pregnancy: Maternal and Neonatal Outcomes"  

PubMed Central

In a recent article, Lund et al sought to compare maternal and neonatal outcomes of various treatment regimens for opioid dependence during pregnancy.1 In their background, discussion the authors state that “In the United States buprenorphine plus naloxone [Suboxone®] … has been the preferred form of prescribed buprenorphine due to its reduced abuse liability relative to buprenorphine alone [Subutex®].” This claim is certainly consistent with the view of the firm that has manufactured and sold both products, Reckitt Benckiser. In September of 2011, the company announced that it was “… discontinuing distribution and sale of Subutex® tablets as we believe that mono product (product containing buprenorphine alone with no naloxone) creates a greater risk of misuse, abuse and diversion …”.2 Supporting evidence for the alleged “reduced abuse liability” appears to be lacking, however, and evidence cannot be located in the two references cited by Dr. Lund and his co-authors, which in fact are silent on the subject of abuse potential.3,4 In contrast, it has been reported that the transition to buprenorphine/naloxone from the mono formulation has been associated with “… no reduction in injection risk behaviors among IDUs.”5

Newman, Robert G.; Gevertz, Susan G.

2013-01-01

29

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes".  

PubMed

In a recent article, Lund et al sought to compare maternal and neonatal outcomes of various treatment regimens for opioid dependence during pregnancy.1 In their background, discussion the authors state that "In the United States buprenorphine plus naloxone [Suboxone(®)] … has been the preferred form of prescribed buprenorphine due to its reduced abuse liability relative to buprenorphine alone [Subutex(®)]." This claim is certainly consistent with the view of the firm that has manufactured and sold both products, Reckitt Benckiser. In September of 2011, the company announced that it was "… discontinuing distribution and sale of Subutex(®) tablets as we believe that mono product (product containing buprenorphine alone with no naloxone) creates a greater risk of misuse, abuse and diversion …".2 Supporting evidence for the alleged "reduced abuse liability" appears to be lacking, however, and evidence cannot be located in the two references cited by Dr. Lund and his co-authors, which in fact are silent on the subject of abuse potential.3,4 In contrast, it has been reported that the transition to buprenorphine/naloxone from the mono formulation has been associated with "… no reduction in injection risk behaviors among IDUs."5. PMID:23772177

Newman, Robert G; Gevertz, Susan G

2013-05-26

30

Preferences for clinic privileges, retail items and social activities in an outpatient buprenorphine treatment program  

Microsoft Academic Search

This study evaluated preferences for various clinic privileges, retail items, and social activities for use in an outpatient opioid dependence treatment program. Fifty-three opioid-dependent patients who received treatment with buprenorphine for at least 30 days rank ordered 11 clinic privileges, 19 retail items, and 8 social activities from the most desirable (a rank of 1) to the least desirable (a

Leslie Amass; Warren K. Bickel; John P. Crean; Stephen T. Higgins; Gary J. Badger

1996-01-01

31

Buprenorphine for opioid dependence.  

PubMed

As a treatment agent for opioid dependence, buprenorphine is a nearly ideal medication at our current stage of medication development. Unlike methadone, buprenorphine dosage can be rapidly adjusted with minimal potential for inducing severe consequences. In addition to its intrinsic safety, buprenorphine's relatively low abuse liability in the combination product (i.e., with naloxone as Suboxone) makes it even more acceptable in regulatory quarters as well as to prescribing physicians. The approval of buprenorphine as a pharmacotherapy for opioid dependence returns to physicians the ability to treat their opioid-dependent patients with an effective opioid-based treatment for the first time in nearly 100 years. Buprenorphine is an opioid, however, and potential for misuse remains, even in combination with naloxone. Whether buprenorphine will be increasingly accepted as a treatment for opioid-dependent patients depends on clinicians recognizing the advantages of its uniquely useful properties while still heeding the need to manage their patients' therapy with reasonable vigilance. PMID:19402772

Ling, Walter

2009-05-01

32

The evidence doesn't justify steps by state Medicaid programs to restrict opioid addiction treatment with buprenorphine.  

PubMed

Many state Medicaid programs restrict access to buprenorphine, a prescription medication that relieves withdrawal symptoms for people addicted to heroin or other opiates. The reason is that officials fear that the drug is costlier or less safe than other therapies such as methadone. To find out if this is true, we compared spending, the use of services related to drug-use relapses, and mortality for 33,923 Massachusetts Medicaid beneficiaries receiving either buprenorphine, methadone, drug-free treatment, or no treatment during the period 2003-07. Buprenorphine appears to have significantly expanded access to treatment because the drug can be prescribed by a physician and taken at home compared with methadone, which by law must be administered at an approved clinic. Buprenorphine was associated with more relapse-related services but $1,330 lower mean annual spending than methadone when used for maintenance treatment. Mortality rates were similar for buprenorphine and methadone. By contrast, mortality rates were 75 percent higher among those receiving drug-free treatment, and more than twice as high among those receiving no treatment, compared to those receiving buprenorphine. The evidence does not support rationing buprenorphine to save money or ensure safety. PMID:21821560

Clark, Robin E; Samnaliev, Mihail; Baxter, Jeffrey D; Leung, Gary Y

2011-08-01

33

Improvement in the Quality of Live in Heroin Addicts: Differences Between Methadone and Buprenorphine Treatment  

Microsoft Academic Search

Summary The main goals of opioid treatment in heroin addiction are to eliminate or reduce the use of heroin and other substances of abuse, to promote patients' social rehabilitation and to improve their quality of life. The purpose of this study is to evaluate the efficacy of buprenorphine and methadone on the quality of life of patients. These subjects were

Icro Maremmani; Pier Paolo Pani; Dina Popovic; Matteo Pacini; Joseph Deltito; Giulio Perugi

34

Developing and Implementing a New Prison-Based Buprenorphine Treatment Program  

ERIC Educational Resources Information Center

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…

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

2010-01-01

35

Compliance with buprenorphine medication-assisted treatment and relapse to opioid use.  

PubMed

Opioid dependence (OD), often characterized as a chronic relapsing disorder, affects millions of people worldwide. The purpose of this study was to examine the effect of compliance with buprenorphine on reducing relapse among a sample of patients in treatment for OD. Patients new to buprenorphine (N?= 703) completed the Addiction Severity Index (ASI) at baseline, and at 1, 2, and 3 months postbaseline. The ASI is a semistructured interview designed to measure problem severity in seven functional areas known to be affected by alcohol and drug dependence. Compliance was defined as taking buprenorphine medication on at least 22 of the past 28 days (80%), while relapse classification was based on resumed use of opioids during the follow-up period (months 2 and 3). Relapse was regressed onto demographic indicators, baseline ASI composite scores, and compliance with buprenorphine. Noncompliant patients were over 10 times more likely to relapse than those who were compliant (exp ?= 10.55;?p?< .001). Neither demographics nor baseline ASI composite scores were predictive of relapse (p's > .05). Compliance with medication-assisted treatment supports abstinence, essential for patient recovery. Understanding the factors that drive treatment compliance and noncompliance may assist providers in supporting patient compliance and recovery.? PMID:22211347

Tkacz, Joseph; Severt, Jamie; Cacciola, John; Ruetsch, Charles

2011-11-18

36

Lack of effect of single high doses of buprenorphine on arterial blood gases in the rat.  

PubMed

High dose buprenorphine, a potent semisynthetic agonist-antagonist for opiate receptors, is now used in substitution treatment of human heroin addiction. Deaths have been reported in addicts misusing buprenorphine. We determined the median lethal dose (LD(50)) and studied the effects of high doses of intravenous buprenorphine on arterial blood gases in rats. Male Sprague-Dawley rats were administered buprenorphine intravenously to determine the LD(50) using the up-and-down method. Subsequently, catheterized groups of 10 restrained rats received no drug, saline, acid-alcohol aqueous solvent (required to dissolve buprenorphine at a high concentration), or 3, 30, or 90 mg/kg of buprenorphine intravenously. Serial arterial blood gases were obtained over 3 h. The LD(50) determined in triplicate was 146.5 mg/kg (median of 3 series, range: 142.6-176.5). The mean dose received by surviving animals was 96.9 +/- 46.7 mg/kg. There was a significant effect of the acid-alcohol aqueous solvent on arterial blood gases. Excluding the solvent effect, 3, 30, and 90-mg/kg buprenorphine doses had no significant effects on arterial blood gases. The toxicity of intravenous buprenorphine in adult rats, assessed by the LD(50), is low. These data are consistent with a wide margin of safety of buprenorphine. The mechanism of death after the intravenous administration of a lethal dose of buprenorphine remains to be determined. PMID:11399802

Gueye, P N; Borron, S W; Risède, P; Monier, C; Buneaux, F; Debray, M; Baud, F J

2001-07-01

37

Symptomatic treatment of opiate withdrawal syndrome by low-dose buprenorphine in an in-patient setting  

Microsoft Academic Search

Summary The present study aims to assess the effectiveness of buprenorphine treatment in countering predictable withdrawal from street opiates in 68 opiate-addicts who requested admission to an in-patient opiate detoxification facility. Buprenorphine was administered at flexible doses, on a patient-blind clinical basis. Withdrawal was assessed by scoring a range of symptoms at the start of treatment (T0) and three more

Andrea Fuscone; Mariapia Correale; Mauro Romualdo; Walter Bianchi

38

Buprenorphine-Mediated Transition from Opioid Agonist to Antagonist Treatment: State of the Art and New Perspectives  

PubMed Central

Constant refinement of opioid dependence (OD) therapies is a condition to promote treatment access and delivery. Among other applications, the partial opioid agonist buprenorphine has been studied to improve evidence-based interventions for the transfer of patients from opioid agonist to antagonist medications. This paper summarizes PubMed-searched clinical investigations and conference papers on the transition from methadone maintenance to buprenorphine and from buprenorphine to naltrexone, discussing challenges and advances. The majority of the 26 studies we examined were uncontrolled investigations. Many small clinical trials have demonstrated the feasibility of in- or outpatient transfer to buprenorphine from low to moderate methadone doses (up to 60–70 mg). Results on the conversion from higher methadone doses, on the other hand, indicate significant withdrawal discomfort, and need for ancillary medications and inpatient treatment. Tapering high methadone doses before the transfer to buprenorphine is not without discomfort and the risk of relapse. The transition buprenorphine-naltrexone has been explored in several pilot studies, and a number of treatment methods to reduce withdrawal intensity warrant further investigation, including the co-administration of buprenorphine and naltrexone. Outpatient transfer protocols using buprenorphine, and direct comparisons with other modalities of transitioning from opioid agonist to antagonist medications are limited. Given its potential salience, the information gathered should be used in larger clinical trials on short and long-term outcomes of opioid agonist-antagonist transition treatments. Future studies should also test new pharmacological mechanisms to help reduce physical dependence, and identify individualized approaches, including the use of pharmacogenetics and long-acting opioid agonist and antagonist formulations.

Mannelli, Paolo; Peindl, Kathleen S.; Lee, Tong; Bhatia, Kamal S.; Wu, Li-Tzy

2012-01-01

39

Motivational Assessment of Non-Treatment Buprenorphine Research Participation in Heroin Dependent Individuals  

PubMed Central

Background Heroin abuse remains an important public health problem, particularly in economically disadvantaged areas. Insight into this problem is gained from interviewing addicted individuals. However, we lack systematic data on factors that motivate heroin users to participate in non-treatment research that offers both financial incentives (compensation) and non-financial incentives (e.g., short-term medication). Aim To better understand the relative importance of several types of personal motivations to participate in non-treatment buprenorphine research, and to relate self-motivations to social, economic, demographic and drug use factors. Methods Heroin dependent volunteers (N = 235 total; 57 female and 178 male; 136 African American, 86 Caucasian, and 13 Other) applied for non-therapeutic buprenorphine research in an urban outpatient setting from 2004–2008. We conducted a semi-structured behavioral economic interview, after which participants ranked 11 possible motivations for research participation. Results Although the study was repeatedly described as non-treatment research involving buprenorphine, participants often ranked some treatment-related motivations as important (wanting to reduce/stop heroin use, needing a medication to get stabilized/detoxify). Some motivations correlated with income, heroin use, and years since marketing of buprenorphine. Two dimensions emerged from principal component analysis of motivation rankings: (1) treatment motivation vs. greater immediate needs, and (2) commitment to trying alternatives vs. a more accepting attitude toward traditional interventions. In summary, heroin addicts’ self-motivations to engage in non-therapeutic research are complex – they value economic gain but not exclusively or primarily – and relate to variables such as socioeconomic factors and drug use.

Papke, Gina; Greenwald, Mark K.

2011-01-01

40

Suboxone® (Buprenorphine\\/Naloxone) as an Agonist Opioid Treatment in Spain: A Budgetary Impact Analysis  

Microsoft Academic Search

Objective: To evaluate the economic impact of buprenorphine\\/naloxone (B\\/N) as an agonist opioid treatment for opiate dependence. Methods: A budgetary impact analysis model was designed to calculate the annual costs (drugs and associated costs) to the Spanish National Healthcare System of methadone versus B\\/N. Data for the model were obtained from official databases and expert panel opinion. Results: It was

José Martínez-Raga; Francisco González Saiz; César Pascual; Miguel A. Casado; Francisco J. Sabater Torres

2010-01-01

41

Opioid drugs in maintenance and detoxification treatment of opiate addiction; proposed modification of dispensing restrictions for buprenorphine and buprenorphine combination as used in approved opioid treatment medications. Final rule.  

PubMed

This final rule amends the federal opioid treatment program regulations by modifying the dispensing requirements for buprenorphine and buprenorphine combination products approved by the Food and Drug Administration (FDA) for opioid dependence and used in federally certified and registered opioid treatment programs. In particular, this rule would allow opioid treatment programs more flexibility in dispensing take-home supplies of buprenorphine--removing restrictions on the time a patient needs to be in treatment in order to receive take-home supplies--after the assessment and documentation of a patient's responsibility and stability to receive opioid addiction treatment medication. Opioid treatment programs that use these products in the treatment of opioid dependence will continue to adhere to all other federal treatment standards established for methadone. PMID:23227572

2012-12-01

42

Brief Buprenorphine Detoxification for the Treatment of Prescription Opioid Dependence: A Pilot Study  

PubMed Central

We examined the feasibility of brief outpatient detoxification as a treatment for prescription opioid (PO) abusers. Fifteen PO-dependent adults were enrolled to receive buprenorphine stabilization, a 2-week buprenorphine taper, and subsequent naltrexone for those who completed the taper. Subjects also received behavioral therapy, urinalysis monitoring, and double-blind drug administration. Subjects provided 83.8%, 91.7% and 31.2% opioid-negative samples during stabilization, taper and naltrexone phases, respectively. Inspection of individual subject data revealed systematic differences in whether subjects successfully completed the taper without resumption of illicit opioid use. Post-hoc analyses were used to examine the characteristics of subjects who successfully completed the taper (Responders, n=5) versus those who failed to do so (Nonresponders, n=9). These pilot data suggest a subset of PO abusers may respond to brief buprenorphine detoxification, though future efforts should aim to improve outcomes, investigate individual differences in treatment response and identify characteristics that may predict those for whom longer-term agonist treatment is warranted.

Sigmon, Stacey C.; Dunn, Kelly E.; Badger, Gary J.; Heil, Sarah H.; Higgins, Stephen T.

2009-01-01

43

[Guidelines for substitution treatments in prison populations].  

PubMed

Care access for the drug addict patients in prison (in particular for the treatments of substitution) in France is very unequal from one establishment to another. This reflects the great variability of the practices of substitution and especially the absence of consensus on the methods of adaptation of these practices to the prison environment. Because of difficulties expressed by prisoners and medical staff on this subject and of stakes (let us recall that approximately 30% of the prisoners are dependent or abusers of one or more psychoactive substances), the formulation of recommendations or of a good practices guide of substitution in prison appeared necessary. Work that we detail here answers a ordering of the Advisory Commission of the Treatments of Substitution (September 2001) whose authors are members. It was presented at the session April 2003. It results from the confrontation of a review of the literature (including legal texts and official reports concerning substitution, the organization of the care in prison environment and the lawful framework), with a vast investigation. The latter was carried out near medical staff (22 prisons), penitentiary staff (3 prisons, 27 people met including directors of these establishments) and prisoners (7 establishments, 28 prisoners met) in the form of individual talks (semi-directing interviews with evaluation of the type of existing device and its knowledge by the penitentiary staff and the prisoners; statement of the suggestions, needs and requests of the medical, penitentiary staffs and of the prisoners). In the whole visited prisons, 7.8% (870) of the prisoners received substitution treatments (6.35% by buprenorphine, 1.44% by methadone), representing a proportion of substituted drug addicts (870 substituted for an evaluation of 3,350 prisoners drug addicts among the 11,168 prisoners of the 22 visited prisons) notably lower than that in free environment (56%, ie 96,000 substituted for an evaluated population of drug addicts for heroin of 160,000). There are however considerable variations (from 0 to 16.2%) of the proportion of substituted of one establishment for the other according to the type of prison, of its size, its localization and the type of medical device present. If a consensus exists for methadone (daily delivery with sanitary control), the organization of the care relating to the buprenorphine is extremely variable from one establishment to another, often putting in difficulty as well the medical teams as the prisoners. One recommendation is essential: the formulation of an individualized therapeutic project. Thirteen other recommendations are made in the following fields: renewal of substitution treatments, initiation of substitution treatments, urinary controls, methods of prescription, methods of delivery, co-prescriptions, global care, confidentiality, files, exits and transfers, extractions, formation, accompaniment of the teams. These recommendations being formulated, many medical concerns remain present and several questions open. The report of joint mission IGAS/IGSJ of June 2001 on the health of the prisoners underlines the principal persistent gaps: hygiene and public health, treatment of the mental disorders, the follow-up of the sexual delinquents, handling ageing, handicap and the end of lifetime. In the same way, the difficulties listed in prison environment concerning substitution are only the exacerbation of those existing outside: the misuses and traffics are common in free environment, risk reduction in prison, as outside, handle with obstacles related to the penalization of the drug use and can hardly evolve except questioning the law of 1970. The prison practice opens also questions: that of the "duration" of the substitution, frequently posed by the prisoners; concern to see the prison becoming a privileged place of access to the care, combining sanction and care whereas the law of 1970 allows the alternative (care or sanction); that of the clinic of the misuse, particularly "readable" in prison environment; and fina

Michel, L; Maguet, O

44

The effectiveness of community maintenance with methadone or buprenorphine for treating opiate dependence  

PubMed Central

Background Opiate dependence is a major health and social issue in many countries. A mainstay of therapy has been methadone maintenance treatment, but other treatments, particularly buprenorphine, are increasingly being considered. Aim To conduct a systematic review to synthesise and critically appraise the evidence on the effectiveness of community maintenance programmes with methadone or buprenorphine in treating opiate dependence. Method A systematic review of databases, journals and the grey literature was carried out from 1990–2002. Inclusion criteria were: community-based, randomised controlled trials of methadone and/or buprenorphine for opiate dependence involving subjects who were aged 18 years old or over. Results Trials were set in a range of countries, employed a variety of comparators, and suffered from a number of biases. The evidence indicated that higher doses of methadone and buprenorphine are associated with better treatment outcomes. Low-dose methadone (20 mg per day) is less effective than buprenorphine (2–8 mg per day). Higher doses of methadone (>50–65 mg per day) are slightly more effective than buprenorphine (2–8 mg per day). There was some evidence that primary care could be an effective setting to provide this treatment, but such evidence was sparse. Conclusion The literature supports the effectiveness of substitute prescribing with methadone or buprenorphine in treating opiate dependence. Evidence is also emerging that the provision of methadone or buprenorphine by primary care physicians is feasible and may be effective.

Simoens, Steven; Matheson, Catriona; Bond, Christine; Inkster, Karen; Ludbrook, Anne

2005-01-01

45

Entry into primary care-based buprenorphine treatment is associated with identification and treatment of other chronic medical problems  

PubMed Central

Background Buprenorphine is an effective treatment for opioid dependence that can be provided in a primary care setting. Offering this treatment may also facilitate the identification and treatment of other chronic medical conditions. Methods We retrospectively reviewed the medical records of 168 patients who presented to a primary care clinic for treatment of opioid dependence and who received a prescription for sublingual buprenorphine within a month of their initial visit. Results Of the 168 new patients, 122 (73%) did not report having an established primary care provider at the time of the initial visit. One hundred and twenty-five patients (74%) reported at least one established chronic condition at the initial visit. Of the 215 established diagnoses documented on the initial visit, 146 (68%) were not being actively treated; treatment was initiated for 70 (48%) of these within one year. At least one new chronic medical condition was identified in 47 patients (28%) during the first four months of their care. Treatment was initiated for 39 of the 54 new diagnoses (72%) within the first year. Conclusions Offering treatment for opioid dependence with buprenorphine in a primary care practice is associated with the identification and treatment of other chronic medical conditions.

2012-01-01

46

Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial  

Microsoft Academic Search

Background Expansion of access to eff ective treatments for heroin dependence is a worldwide health priority that will also reduce HIV transmission. We compared the effi cacy of naltrexone, buprenorphine, and no additional treatment, in patients receiving detoxifi cation and subsequent drug counselling, for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviours. Methods 126 detoxifi

Richard S Schottenfeld; Marek C Chawarski; Mahmud Mazlan

2008-01-01

47

The Cost of Integrated HIV Care and Buprenorphine/ Naloxone Treatment: Results of a Cross-Site Evaluation  

PubMed Central

Background Implementing integrated HIV and buprenorphine/ naloxone treatment requires cost estimates to plan and obtain funding. Methods We identified costs incurred at HIV clinical sites participating in a cross-site evaluation of integrated care that followed patients for 1 year. Costs include labor, overhead, and urine toxicology analyses (clinic perspective), buprenorphine/naloxone (payer perspective) and patient time and transportation (patient perspective). Sites provided resource utilization quarterly, and providers estimated time required for each activity. With site as the unit of analysis, results are reported as median (range) of average site costs in 2008 US dollars. Results The median number of monthly provider encounters for integrated care patients was 3.2 (1.5–13.3) compared with 1.7 (1.1–4.2) for similar patients not in integrated care, but integrated care patients had fewer physician encounters. Median monthly clinic costs per integrated care patient were $136 ($67–$677) for labor and overhead and $8 ($2–$23) for toxicology analyses, $22 higher than clinic costs for patients not in integrated care. Median monthly costs for buprenorphine/naloxone were $209 ($165–$272), and monthly patient costs in integrated care were $11 ($1–$54) higher. Conclusions Integrated HIV and buprenorphine/naloxone treatment requires different resources, including costs that are not third-party reimbursed. Implementing integrated care will require funding for training and for new staff such as buprenorphine coordinators, in addition to reimbursement for buprenorphine/naloxone. Further research is needed to identify potential cost offsets outside of the clinic setting.

Schackman, Bruce R.; Leff, Jared A.; Botsko, Michael; Fiellin, David A.; Altice, Fredrick L.; Korthuis, P. Todd; Sohler, Nancy; Weiss, Linda; Egan, James E.; Netherland, Julie; Gass, Jonathan; Finkelstein, Ruth

2012-01-01

48

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

ERIC Educational Resources Information Center

|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…

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

49

Consensus statement on office-based treatment of opioid dependence using buprenorphine.  

PubMed

Buprenorphine and buprenorphine/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional organizations, researchers involved in monitoring, opioid treatment programs and the pharmaceutical industry met to synthesize and disseminate practical information to guide training, practice, monitoring, regulation and evaluation efforts with these medications. We performed a review of the literature, training curricula and practice guidelines and commissioned manuscripts describing recently completed, or still in progress, studies or field experiences with BUP treatment. A consensus process generated fifteen statements: (1) The federal government should collect baseline data on opioid-related deaths and morbidity to assess the effect of BUP on public health, (2) the patient limit for group practices should apply to individual physicians rather than group practices, (3 and 4) telephone and Internet-based physician and pharmacist support is needed, (5) clinicians who provide psychosocial services to opioid dependent patients should be informed of the role of BUP, (6) opioid-dependent patients should be instructed to present for induction in mild withdrawal, (7) the existing Center for Substance Abuse Treatment guidelines provide a reasonable induction protocol, (8) physicians should be prepared to use ancillary medications with BUP induction, (9) a physician or nurse must be available to the patient during the induction period, (10) concurrent counseling and support services are necessary, (11) detoxification without appropriate followup addiction treatment leads to rapid relapse and is not as effective as maintenance, (12) pregnant opioid-dependent women should be treated using good clinical practice including specialist addiction care and prenatal care, (13) BUP induction and withdrawal treatment may benefit from different designations for payment, (14) take-home medication options should be tailored to patients' needs, (15) there is a need for clinical and policy research in unique patient populations. PMID:15450648

Fiellin, David A; Kleber, Herbert; Trumble-Hejduk, Jeanne G; McLellan, A Thomas; Kosten, Thomas R

2004-09-01

50

From morphine clinics to buprenorphine: regulating opioid agonist treatment of addiction in the United States.  

PubMed

The practice of prescribing opioid drugs for opioid dependent patients in the U.S. has been subjected to special government scrutiny for almost 100 years. From 1920 until 1964, doctors who used opioids to treat addicts risked federal and/or state criminal prosecution. Although that period ended when oral methadone maintenance was established as legitimate medical practice, public concern about methadone diversion and accidental overdose fatalities, combined with political pressure from both hostile bureaucracies and groups committed to drug-free treatments, led to the development of unprecedented and detailed Food and Drug Administration (FDA) regulations that specified the manner in which methadone (and later, levo-alpha-acetyl methadol, or levomethadyl acetate, (LAAM)) could be provided. In 1974, Congress gave the Drug Enforcement Administration (DEA) additional oversight of methadone treatment programs. Efforts to liberalize the FDA regulations over the past 30 years have been resisted by both the DEA and existing treatment providers. Additional flexibility for clinicians may evolve from the most recent effort to create an accreditation system to replace some of the FDA regulations. The development of buprenorphine, a partial opioid agonist, as an effective treatment for opioid addiction reopened the possibility for having a less burdensome oversight process, especially because of its reduced toxicity if ingested by non-tolerant individuals. New legislation, the Drug Addiction Treatment Act (DATA) of 2000, created an opportunity for clinicians with special training to be exempted from both federal methadone regulations and the requirement to obtain a special DEA license when using buprenorphine to treat addicts. Some details of how the DATA was developed, moved through Congress, and signed into law are described. PMID:12738346

Jaffe, Jerome H; O'Keeffe, Charles

2003-05-21

51

Buprenorphine use: the international experience.  

PubMed

The confluence of the heroin injection epidemic and the human immunodeficiency virus (HIV) infection epidemic has increased the call for expanded access to effective treatments for both conditions. Buprenorphine and methadone are now listed on the World Health Organization's Model Essential Drugs List. In France, which has the most extensive experience, buprenorphine has been associated with a dramatic decrease in deaths due to overdose, and buprenorphine diversion appears to be associated with inadequate dosage, social vulnerability, and prescriptions from multiple providers. Other treatment models (in the United States, Australia, Germany, and Italy) and buprenorphine use in specific populations are also reviewed in the present article. In countries experiencing a dual epidemic of heroin use and HIV infection, such as former states of the Soviet Union and other eastern European and Asian countries, access to buprenorphine and methadone may be one potential tool for reducing the spread of HIV infection among injection drug users and for better engaging them in medical care. PMID:17109307

Carrieri, Maria Patrizia; Amass, Leslie; Lucas, Gregory M; Vlahov, David; Wodak, Alex; Woody, George E

2006-12-15

52

Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone  

Microsoft Academic Search

background Office-based treatment of opiate addiction with a sublingual-tablet formulation of bu- prenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. methods We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate- addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4

Paul J. Fudala; T. Peter Bridge; Susan Herbert; William O. Williford; C. Nora Chiang; Karen Jones; Joseph Collins; Dennis Raisch; Paul Casadonte; R. Jeffrey Goldsmith; Walter Ling; Usha Malkerneker; Laura McNicholas; John Renner; Susan Stine; Donald Tusel

2003-01-01

53

Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options.  

PubMed

Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care. PMID:23092049

Bonhomme, Jean; Shim, Ruth S; Gooden, Richard; Tyus, Dawn; Rust, George

54

Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome  

Microsoft Academic Search

This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant

Hendree E. Jones; Rolley E. Johnson; Donald R. Jasinski; Kevin E. O’Grady; Christian A. Chisholm; Robin E. Choo; Michael Crocetti; Robert Dudas; Cheryl Harrow; Marilyn A. Huestis; Lauren M. Jansson; Michael Lantz; Barry M. Lester; Lorraine Milio

2005-01-01

55

Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome  

Microsoft Academic Search

This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant

E. Jonesa; Rolley E. Johnsona; Donald R. Jasinskib; Kevin E. O'Gradyc; Christian A. Chisholmd; Robin E. Choof; Michael Crocettie; Robert Dudase; Cheryl Harrowe; Marilyn A. Huestisf; Lauren M. Janssone; Michael Lantzd; Barry M. Lesterg; Lorraine Miliod

56

Effects of a High-Dose, Fast Tapering Buprenorphine Detoxification Program on Symptom Relief and Treatment Retention  

Microsoft Academic Search

A large number of patients with heroin dependency fail to enter a treatment program because of dropping out during or immediately after detoxification. This article presents an open study of symptom relief of 10 patients withdrawing from heroin with a high-dose rapid tapering buprenorphine detoxification protocol. It also presents a pseudo-experimental comparison between 208 patients treated with a clonidine\\/dextropropoxiphene detoxification

Tom Palmstierna

2004-01-01

57

Predictors of Abstinence: NIDA Multi-site Buprenorphine/Naloxone Treatment Trial in Opioid Dependent Youth  

PubMed Central

Objective To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal) assisted psychosocial treatment for opioid dependent youth Method Secondary analyses of data from 152 youth (ages 15–21) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification, both with weekly individual and group drug counseling. Logistic regression models were constructed to identify baseline and during-treatment predictors of opioid positive urines (OPU) at week-12. Predictors were selected based on significance or trend toward significance (i.e. p<0.1) and backward stepwise selection was used, controlling for treatment group, to produce final independent predictors at p ? 0.05. Results Youth presenting to treatment with past 30-day injection drug use (IDU) and more active medical/psychiatric problems were less likely to have a week-12 OPU. Those with early treatment opioid abstinence (i.e. weeks 1 and 2); and those who received additional non-study treatments during the study were less likely to have a week-12 OPU; and those not completing 12 weeks of treatment were more likely to have an OPU. Conclusions Youth with advanced illness (i.e. reporting IDU and additional health problems), and those receiving ancillary treatments to augment study treatment were more likely to have lower opioid use. Treatment success in the first 2 weeks and completion of 12 weeks of treatment were associated with lower rates of OPU. These findings suggest that youth with advanced illness respond well to Bup/Nal treatment, and identify options for tailoring treatment for opioid-dependent youth presenting at community-based settings.

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.

2013-01-01

58

Effects of buprenorphine and methadone in methadone-maintained subjects  

Microsoft Academic Search

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study

S. L. Walsh; H. L. June; K. J. Schuh; K. L. Preston; G. E. Bigelow; M. L. Stitzer

1995-01-01

59

Retention on buprenorphine treatment reduces emergency department utilization, but not hospitalization, among treatment-seeking patients with opioid dependence.  

PubMed

Drug users are marginalized from typical primary care, often resulting in emergency department (ED) usage and hospitalization due to late-stage disease. Though data suggest methadone decreases such fragmented healthcare utilization (HCU), the impact of buprenorphine maintenance treatment (BMT) on HCU is unknown. Chart review was conducted on opioid dependent patients seeking BMT, comparing individuals (n=59) who left BMT?7days with those retained on BMT (n=150), for ED use and hospitalization. Using negative binomial regressions, including comparison of time before BMT induction, ED utilization and hospitalization were assessed. Overall, ED utilization was 0.93 events per person year and was significantly reduced by BMT, with increasing time (retention) on BMT. BMT had no significant effect on hospitalizations or average length of stay. PMID:22534003

Schwarz, Ryan; Zelenev, Alexei; Bruce, R Douglas; Altice, Frederick L

2012-04-24

60

Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation  

SciTech Connect

High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD{sub 5}) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD{sub 5} was 10 mg kg{sup -1}. Norbuprenorphine 3 mg kg{sup -1} produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO{sub 2} (8.4 {+-} 0.9 versus 5.7 {+-} 0.1 kPa), decrease in arterial pH (7.25 {+-} 0.06 versus 7.44 {+-} 0.01), and hypoxia (8.3 {+-} 0.6 versus 11.1 {+-} 0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg{sup -1} norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for mu- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use.

Megarbane, Bruno [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France) and Reanimation Medicale et Toxicologique, Hopital Lariboisiere, 2 Rue Ambroise Pare, 75010 Paris (France)]. E-mail: bruno-megarbane@wanadoo.fr; Marie, Nicolas [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Pirnay, Stephane [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Laboratoire de Toxicologie, Prefecture de Police de Paris, 75012 Paris (France); Borron, Stephen W. [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France) and Departments of Emergency Medicine and Medicine - Occupational and Environmental Health, George Washington University, Washington, DC 22052 (United States); Gueye, Papa N. [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Risede, Patricia [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Monier, Claire [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Noble, Florence [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Baud, Frederic J. [INSERM U705, CNRS UMR 7157, Universite Paris VII, Hopital Fernand Widal, Paris (France); Reanimation Medicale et Toxicologique, Hopital Lariboisiere, 2 Rue Ambroise Pare, 75010 Paris (France)

2006-05-01

61

Buprenorphine for opiate addiction: potential economic impact  

Microsoft Academic Search

This study evaluated the potential economic impact of the buprenorphine\\/naloxone combination in the context of practice in the United States of America. In comparison to treatment provided through methadone clinics, buprenorphine\\/naloxone therapy in office practice may be associated with increased medication, physician, and nursing costs, but reduced costs for dispensing, toxicology screens, counseling and administration. It may also result in

Robert Rosenheck; Thomas Kosten

2001-01-01

62

Cognitive functioning in opioid-dependent patients treated with buprenorphine, methadone, and other psychoactive medications: stability and correlates  

PubMed Central

Background In many but not in all neuropsychological studies buprenorphine-treated opioid-dependent patients have shown fewer cognitive deficits than patients treated with methadone. In order to examine if hypothesized cognitive advantage of buprenorphine in relation to methadone is seen in clinical patients we did a neuropsychological follow-up study in unselected sample of buprenorphine- vs. methadone-treated patients. Methods In part I of the study fourteen buprenorphine-treated and 12 methadone-treated patients were tested by cognitive tests within two months (T1), 6-9 months (T2), and 12 - 17 months (T3) from the start of opioid substitution treatment. Fourteen healthy controls were examined at similar intervals. Benzodiazepine and other psychoactive comedications were common among the patients. Test results were analyzed with repeated measures analysis of variance and planned contrasts. In part II of the study the patient sample was extended to include 36 patients at T2 and T3. Correlations between cognitive functioning and medication, substance abuse, or demographic variables were then analyzed. Results In part I methadone patients were inferior to healthy controls tests in all tests measuring attention, working memory, or verbal memory. Buprenorphine patients were inferior to healthy controls in the first working memory task, the Paced Auditory Serial Addition Task and verbal memory. In the second working memory task, the Letter-Number Sequencing, their performance improved between T2 and T3. In part II only group membership (buprenorphine vs. methadone) correlated significantly with attention performance and improvement in the Letter-Number Sequencing. High frequency of substance abuse in the past month was associated with poor performance in the Letter-Number Sequencing. Conclusions The results underline the differences between non-randomized and randomized studies comparing cognitive performance in opioid substitution treated patients (fewer deficits in buprenorphine patients vs. no difference between buprenorphine and methadone patients, respectively). Possible reasons for this are discussed.

2011-01-01

63

Timing of buprenorphine adoption by privately funded substance abuse treatment programs: The role of institutional and resource-based inter-organizational linkages  

PubMed Central

Identifying facilitators of more rapid buprenorphine adoption may increase access to this effective treatment for opioid dependence. Using a diffusion of innovations theoretical framework, we examine the extent to which programs’ inter-organizational institutional and resource-based linkages predict the likelihood of being an earlier, later, or non-adopter of buprenorphine. Data were derived from face-to-face interviews with administrators of 345 privately funded substance abuse treatment programs in 2007–2008. Results of multinomial logistic regression models show that inter-organizational and resource linkages were associated with timing of adoption. Programs reporting membership in provider associations were more likely to be earlier adopters of buprenorphine. Programs that relied more on resources linkages, such as the detailing activities by pharmaceutical companies and the NIDA website, were more likely to be earlier adopters of buprenorphine. These findings suggest that institutional and resource-based inter-organizational linkages may expose programs to effective treatments, thereby facilitating more rapid and sustained adoption of innovative treatment techniques.

Savage, Sarah A.; Abraham, Amanda J.; Knudsen, Hannah K.; Rothrauff, Tanja C.; Roman, Paul M.

2011-01-01

64

Buprenorphine in the Treatment of Opiate Dependence: Its Pharmacology and Social Context of Use in the U.S  

Microsoft Academic Search

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

Donald R. Wesson

2004-01-01

65

Bioavailability of Buprenorphine from Crushed and Whole Buprenorphine (Subutex) Tablets  

Microsoft Academic Search

Background: Buprenorphine (Subutex) is the most abused opioid in Finland. In order to curb the abuse potential of this drug, many treatment centers and prisons crush Subutex tablets before administering them to patients. To date, there are no published studies comparing the efficacy and bioavailability of crushed and whole Subutex tablets. Methods: A total of 16 opioid-dependent patients stabilized on

Kaarlo Simojoki; Pirjo Lillsunde; Nicholas Lintzeris; Hannu Alho

2010-01-01

66

Tobacco addiction and smoking status in heroin addicts under methadone vs. buprenorphine therapy.  

PubMed

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. PMID:22690174

Pajusco, Benedetta; Chiamulera, Cristiano; Quaglio, Gianluca; Moro, Luca; Casari, Rebecca; Amen, Gabriella; Faccini, Marco; Lugoboni, Fabio

2012-03-16

67

Buprenorphine use in pregnant opioid users: a critical review.  

PubMed

Pregnancy in opioid users poses a number of problems to treating physicians. Most guidelines recommend maintenance treatment to manage opioid addiction in pregnancy, with methadone being the gold standard. More recently, buprenorphine has been discussed as an alternate medication. The use and efficacy of buprenorphine in pregnancy is still controversial. This article reviews the current database on the basis of a detailed and critical literature search performed in MEDLINE (206 counts). Most of the relevant studies (randomised clinical trials and one national cohort sample) were published in the last 2 years and mainly compared buprenorphine with methadone. Some studies are related to maternal outcomes, others to foetal, neonatal or older child outcomes. With respect to maternal outcomes, most studies suggest that buprenorphine has similar effects to methadone. Very few data from small studies discuss an effect of buprenorphine on neurodevelopment of the foetus. Neonatal abstinence syndrome is common in infants of both buprenorphine- and methadone-maintained mothers. As regards neonatal outcomes, buprenorphine has the same clinical outcome as methadone, although some newer studies suggest that it causes fewer withdrawal symptoms. Since hardly any studies have investigated the combination of buprenorphine with naloxone (which has been suggested to possibly have teratogenic effects) in pregnant women, a switch to buprenorphine monotherapy is recommended in women who become pregnant while receiving the combination product. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users. PMID:23775478

Soyka, Michael

2013-08-01

68

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

Microsoft Academic Search

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

Pekka Rapeli; Carola Fabritius; Hely Kalska; Hannu Alho

2009-01-01

69

Buprenorphine and opioid antagonism, tolerance, and naltrexone-precipitated withdrawal.  

PubMed

The dual antagonist effects of the mixed-action ?-opioid partial agonist/?-opioid antagonist buprenorphine have not been previously compared in behavioral studies, and it is unknown whether they are comparably modified by chronic exposure. To address this question, the dose-related effects of levorphanol, trans-(-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide (U50,488), heroin, and naltrexone on food-maintained behavior in rhesus monkeys were studied after acute and chronic treatment with buprenorphine (0.3 mg/kg/day). In acute studies, the effects of levorphanol and U50,488 were determined at differing times after buprenorphine (0.003-10.0 mg/kg i.m.). Results show that buprenorphine produced similar, dose-dependent rightward shifts of the levorphanol and U50,488 dose-response curves that persisted for ? 24 h after doses larger than 0.1 mg/kg buprenorphine. During chronic treatment with buprenorphine, the effects of levorphanol, U50,488, heroin, and naltrexone were similarly determined at differing times (10 min to 48 h) after intramuscular injection. Overall, results show that buprenorphine produced comparable 3- to 10-fold rightward shifts in the U50,488 dose-response curve under both acute and chronic conditions, but that chronic buprenorphine produced larger (10- to ? 30-fold) rightward shifts in the heroin dose-effect function than observed acutely. Naltrexone decreased operant responding in buprenorphine-treated monkeys, and the position of the naltrexone dose-effect curve shifted increasingly to the left as the time after daily buprenorphine treatment increased from 10 min to 48 h. These results suggest that the ?-antagonist, but not the ?-antagonist, effects of buprenorphine are augmented during chronic treatment. In addition, the leftward shift of the naltrexone dose-effect function suggests that daily administration of 0.3 mg/kg buprenorphine is adequate to produce opioid dependence. PMID:21051498

Paronis, Carol A; Bergman, Jack

2010-11-04

70

Buprenorphine and Opioid Antagonism, Tolerance, and Naltrexone-Precipitated Withdrawal  

PubMed Central

The dual antagonist effects of the mixed-action ?-opioid partial agonist/?-opioid antagonist buprenorphine have not been previously compared in behavioral studies, and it is unknown whether they are comparably modified by chronic exposure. To address this question, the dose-related effects of levorphanol, trans-(?)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide (U50,488), heroin, and naltrexone on food-maintained behavior in rhesus monkeys were studied after acute and chronic treatment with buprenorphine (0.3 mg/kg/day). In acute studies, the effects of levorphanol and U50,488 were determined at differing times after buprenorphine (0.003–10.0 mg/kg i.m.). Results show that buprenorphine produced similar, dose-dependent rightward shifts of the levorphanol and U50,488 dose-response curves that persisted for ?24 h after doses larger than 0.1 mg/kg buprenorphine. During chronic treatment with buprenorphine, the effects of levorphanol, U50,488, heroin, and naltrexone were similarly determined at differing times (10 min to 48 h) after intramuscular injection. Overall, results show that buprenorphine produced comparable 3- to 10-fold rightward shifts in the U50,488 dose-response curve under both acute and chronic conditions, but that chronic buprenorphine produced larger (10- to ?30-fold) rightward shifts in the heroin dose-effect function than observed acutely. Naltrexone decreased operant responding in buprenorphine-treated monkeys, and the position of the naltrexone dose-effect curve shifted increasingly to the left as the time after daily buprenorphine treatment increased from 10 min to 48 h. These results suggest that the ?-antagonist, but not the ?-antagonist, effects of buprenorphine are augmented during chronic treatment. In addition, the leftward shift of the naltrexone dose-effect function suggests that daily administration of 0.3 mg/kg buprenorphine is adequate to produce opioid dependence.

Bergman, Jack

2011-01-01

71

[Substitution therapy in drug addictions].  

PubMed

In France, so called "substitution treatments" for addiction are nicotine substitutes for tobacco dependence and buprenorphine, and methadone for opiate dependence. The word "substitution" participates to the uncertainty as to the objective of such treatments. From an addiction psychiatry perspective, these treatments are of interest as pharmacological treatments for maintenance of abstinence. In such a perspective they are not changing one substance of dependence for another. The goal is to reduce craving by low potential reinforcement medications. Conditions for success are a clarification of treatment goal with the patients, adequate dosing, and time. All medical doctors may prescribe buprenorphine for treatment of opiate dependence. Supervised daily dispensing in pharmacies is useful to increase compliance and collaboration, and avoid misuse and diversion. For tobacco dependence, nicotine patch must be clearly differentiated from other nicotine substitutes like gums and inhalers that have significant reinforcing effects. Because the patch is accessible without medical prescription, many patients are not sufficiently medically supervised and dropout frequently. For patients that cannot initially accept the behavioral changes associated to the goal of abstinence, it is legitimate to truly substitute them with less dangerous reinforcing substances. This possibility exists in France only for tobacco use that can be substituted to inhaled or chewed nicotine. It is possible that some reported misuse of buprenorphine and methadone are inadequate attempts to increase the reinforcing effects of these medications. PMID:12920942

Auriacombe, Marc; Fatseas, Mélina; Franques-Rénéric, Pascale; Daulouède, Jean-Pierre; Tignol, Jean

2003-06-15

72

Comparative Effects of Vasectomy Surgery and Buprenorphine Treatment on Faecal Corticosterone Concentrations and Behaviour Assessed by Manual and Automated Analysis Methods in C57 and C3H Mice  

PubMed Central

Establishing effective cage-side pain assessment methods is essential if post-surgical pain is to be controlled effectively in laboratory animals. Changes to overall activity levels are the most common methods of assessment, but may not be the most appropriate for establishing the analgesic properties of drugs, especially in mice, due their high activity levels. Use of drugs that can affect activity (e.g. opioids) is also a problem. The relative merits of both manual and automated behaviour data collection methods was determined in two inbred mouse strains undergoing vasectomy following treatment with one of 2 buprenorphine dose rates. Body weights and the effects of surgery and buprenorphine on faecal corticosterone were also measured. Surgery caused abnormal behaviour and reduced activity levels, but high dose buprenorphine caused such large-scale increases in activity in controls that we could not establish analgesic effects in surgery groups. Only pain-specific behaviour scoring using the manual approach was effective in showing 0.05 mg/kg buprenorphine alleviated post-vasectomy pain. The C57 mice also responded better to buprenorphine than C3H mice, indicating they were either less painful, or more responsive to its analgesic effects. C3H mice were more susceptible to the confounding effects of buprenorphine irrespective of whether data were collected manually or via the automated approach. Faecal corticosterone levels, although variable, were higher in untreated surgery mice than in control groups, also indicating the presence of pain or distress. Pain-specific scoring was superior to activity monitoring for assessing the analgesic properties of buprenorphine in vasectomised mice. Buprenorphine (0.01 mg/kg), in these strains of male mice, for this procedure, provided inadequate analgesia and although 0.05 mg/kg was more effective, not completely so. The findings support the recommendation that analgesic dose rates should be adjusted in relation to the potential severity of the surgical procedure, the mouse strain, and the individual animals' response.

Wright-Williams, Sian; Flecknell, Paul A.; Roughan, Johnny V.

2013-01-01

73

Training HIV Physicians to Prescribe Buprenorphine for Opioid Dependence  

ERIC Educational Resources Information Center

|Few HIV physicians are trained to provide buprenorphine treatment. We conducted a cross-sectional survey to assess the impact of an eight-hour course on the treatment of opioid dependence on HIV physicians' preparedness to prescribe buprenorphine. One hundred thirteen of 257 trained physicians (44%) provided HIV care. Post-course, the majority of…

Sullivan, Lynn E.; Tetrault, Jeanette; Bangalore, Deepa; Fiellin, David A.

2006-01-01

74

Attitudes toward buprenorphine and methadone among opioid-dependent individuals  

PubMed Central

Attitudes and beliefs about drug abuse treatment have long been known to shape response to that treatment. Two major pharmacological alternatives are available for opioid dependence: methadone, which has been available for the past 40 years, and buprenorphine, a recently-introduced medication. This mixed methods study examined the attitudes of opioid-dependent individuals toward methadone and buprenorphine. A total of 195 participants (n = 140 who were enrolling in one of 6 Baltimore area methadone programs and n = 55 who were out-of-treatment) were administered the Attitudes toward Methadone and toward Buprenorphine Scales and a subset (n = 46) received an ethnographic interview. In-treatment group had significantly more positive attitudes toward methadone than did the out-of-treatment group (p < .001), while they did not differ in their attitudes toward buprenorphine. Both groups had significantly more positive attitudes toward buprenorphine than methadone. Addressing these attitudes may increase treatment entry and retention.

Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; Peterson, James A.; Reisinger, Heather Schacht; Agar, Michael H.; Brown, Barry S.

2009-01-01

75

Disaccharides in urine samples as markers of intravenous abuse of methadone and buprenorphine.  

PubMed

Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict(®) and Subutex(®)). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes. PMID:24099717

Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie

2013-10-06

76

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

PubMed Central

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.

Balhara, Yatan Pal Singh; Jain, Raka

2012-01-01

77

Home Buprenorphine\\/Naloxone Induction in Primary Care  

Microsoft Academic Search

BACKGROUND  Buprenorphine can be used for the treatment of opioid dependence in primary care settings. National guidelines recommend directly\\u000a observed initial dosing followed by multiple in-clinic visits during the induction week. We offered buprenorphine treatment\\u000a at a public hospital primary care clinic using a home, unobserved induction protocol.\\u000a \\u000a \\u000a \\u000a METHODS  Participants were opioid-dependent adults eligible for office-based buprenorphine treatment. The initial physician visit

Joshua D. Lee; Ellie Grossman; Danae DiRocco; Marc N. Gourevitch

2009-01-01

78

Transdermal buprenorphine controls central neuropathic pain.  

PubMed

A 53-year-old male with peripheral sensorimotor neuropathy suffered an intracerebral hemorrhage resulting in right hemiparesis and hemisensory loss. Three months later, he developed constant and burning pain within the entire right side of his body. He was diagnosed with central pain syndrome and treated with antiepileptics and tricyclic antidepressants. Minimal analgesia was achieved, which was limited by intractable sedation and drowsiness. Patient was then treated with oral opioids (morphine and hydrocodone with acetaminophen) in escalating doses that produced cognitive impairment. After an opioid rotation was attempted, by switching morphine to transdermal fentanyl, there was no pain reduction or improved quality of life. A trial of buprenorphine was initiated, by administering transdermal patches in escalating doses in weekly intervals. Patient's pain was eventually successfully controlled with buprenorphine patch 60 ?g/h every 7 days. His self-reported Visual Analogue Scale pain scores decreased from an average of 8/10 to 2/10 or less. Patient's overall function and participation in home activities increased. Buprenorphine is a partial ?-receptor and a ?-? receptor antagonist known to block NMDA receptors and reduce hyperalgesia secondary to central sensitization.(1) Buprenorphine is also a partial agonist at the opioid receptor-like (ORL-1) receptor, which is found to be analgesic and antinociceptive at the level of the spinal cord.(1,2) The difference in analgesic responses between buprenorphine and other opioids may be due to different receptor G protein interactions and/or selective activation of neuronal K(ATP) channels by buprenorphine.(3) Deficient opening of K(ATP) channels has been shown to mediate neuropathic pain(4); therefore, activation of these channels by buprenorphine may contribute to its analgesic effect in neuropathic pain states wherein other opioids fail. More recently, there have been two case reports in which patients with neuropathic pain of different central etiology were successfully treated with buprenorphine.(5) Despite advances in understanding the pathology related to central pain, effective treatment options are limited. Buprenorphine may be an analgesic option for central pain management when opioids fail to reduce hypersensitivity or when patients exhibit intolerable side effects to other medications. PMID:23264319

Weiner, Michelle; Sarantopoulos, Constantine; Gordon, Eva

79

Home Buprenorphine/Naloxone Induction in Primary Care  

PubMed Central

ABSTRACT BACKGROUND Buprenorphine can be used for the treatment of opioid dependence in primary care settings. National guidelines recommend directly observed initial dosing followed by multiple in-clinic visits during the induction week. We offered buprenorphine treatment at a public hospital primary care clinic using a home, unobserved induction protocol. METHODS Participants were opioid-dependent adults eligible for office-based buprenorphine treatment. The initial physician visit included assessment, education, induction telephone support instructions, an illustrated home induction pamphlet, and a 1-week buprenorphine/naloxone prescription. Patients initiated dosing off-site at a later time. Follow-up with urine toxicology testing occurred at day 7 and thereafter at varying intervals. Primary outcomes were treatment status at week 1 and induction-related events: severe precipitated withdrawal, other buprenorphine-prompted withdrawal symptoms, prolonged unrelieved withdrawal, and serious adverse events (SAEs). RESULTS Patients (N?=?103) were predominantly heroin users (68%), but also prescription opioid misusers (18%) and methadone maintenance patients (14%). At the end of week 1, 73% were retained, 17% provided induction data but did not return to the clinic, and 11% were lost to follow-up with no induction data available. No cases of severe precipitated withdrawal and no SAEs were observed. Five cases (5%) of mild-to-moderate buprenorphine-prompted withdrawal and eight cases of prolonged unrelieved withdrawal symptoms (8% overall, 21% of methadone-to-buprenorphine inductions) were reported. Buprenorphine-prompted withdrawal and prolonged unrelieved withdrawal symptoms were not associated with treatment status at week 1. CONCLUSIONS Home buprenorphine induction was feasible and appeared safe. Induction complications occurred at expected rates and were not associated with short-term treatment drop-out. Electronic supplementary material The online version of this article (doi:10.1007/s11606-008-0866-8) contains supplementary material, which is available to authorized users.

Grossman, Ellie; DiRocco, Danae; Gourevitch, Marc N.

2008-01-01

80

Buprenorphine for Office-Based Treatment of Patients With Opioid Addiction  

Microsoft Academic Search

The Drug Addiction Treatment Act of 2000 (DATA 2000) was established to create a new paradigm for medication-assisted treatment of opiate addiction in the United States. Before enactment of DATA 2000, the use of opioid medications to treat opioid addiction was permissible only in federally approved treat- ment programs, ie, methadone clinics. The only medications permitted were Schedule II drugs

James J. Manlandro

81

Why buprenorphine is so successful in treating opiate addiction in France  

Microsoft Academic Search

In France, all registered medical doctors have been allowed to prescribe buprenorphine without any special education or licensing\\u000a since 1995. This has led to a rapidly increasing number of opiate-dependent users under buprenorphine treatment in primary\\u000a care. French physician compensation mechanisms, pharmacy services, and medical insurance funding all have contributed to minimizing\\u000a barriers to buprenorphine treatment. Approximately 20% of all

M. Fatseas; Marc Auriacombe

2007-01-01

82

Treatment of opioid-dependent adolescents and young adults with buprenorphine  

Microsoft Academic Search

Rising rates of opioid use among teenagers and young adults are a public health concern. Despite short durations of opioid\\u000a use compared with those of adults, youth with opioid dependence have a host of co-occurring conditions, including polysubstance\\u000a abuse, psychiatric disorders, hepatitis C infection, HIV risk, and high-risk sexual and criminal behaviors. Opioid-dependent\\u000a youth typically are offered outpatient\\/residential treatment with

Geetha A. Subramaniam; Marc J. Fishman; George Woody

2009-01-01

83

A combination of buprenorphine and naltrexone blocks compulsive cocaine intake in rodents without producing dependence.  

PubMed

Buprenorphine, a synthetic opioid that acts at both ? and ? opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at ? opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent ? opioid antagonist with weaker ? and ? antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block ? agonist-induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction. PMID:22875830

Wee, Sunmee; Vendruscolo, Leandro F; Misra, Kaushik K; Schlosburg, Joel E; Koob, George F

2012-08-01

84

A Combination of Buprenorphine and Naltrexone Blocks Compulsive Cocaine Intake in Rodents Without Producing Dependence  

PubMed Central

Buprenorphine, a synthetic opioid that acts at both ? and ? opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at ? opioid receptors raises its potential for creating opioid dependence in non–opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent ? opioid antagonist with weaker ? and ? antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block ? agonist–induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction.

Wee, Sunmee; Vendruscolo, Leandro F.; Misra, Kaushik K.; Schlosburg, Joel E.; Koob, George F.

2012-01-01

85

Postoperative Analgesie mit Buprenorphin  

Microsoft Academic Search

\\u000a Abstract  Thirty patients who had undergone elective anterolateral thoracotomy were studied in the surgical intensive care unit to compare\\u000a the analgesic effectiveness of i.v. self-administered buprenorphine (group A) with that of epidural administration (group\\u000a B) and of s.c. administration by a nurse of 0.3 mg buprenorphine every 3–4 h (group C, controls). Every 2 h the patients were\\u000a asked to record

J. Fähnrich; C. Castelano; E. Sturzenegger; B. Stoll; P. Uehlinger; S. Geroulanos

1990-01-01

86

Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal  

Microsoft Academic Search

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52,

Paul J Fudala; Jerome H Jaffe; Elizabeth M Dax; Rolley E Johnson; Rolley E Johnson PharmD

1990-01-01

87

Structural Determinants of Opioid and NOP Receptor Activity in Derivatives of Buprenorphine  

PubMed Central

The unique pharmacological profile of buprenorphine has led to its considerable success as an analgesic and as a treatment agent for drug abuse. Activation of nociceptin/orphanin FQ peptide (NOP) receptors has been postulated to account for certain aspects of buprenorphine’s behavioural profile. In order to investigate the role of NOP activation further, a series of buprenorphine analogues has been synthesised with the aim of increasing affinity for the NOP receptor. Binding and functional assay data on these new compounds indicate that the area around C20 in the orvinols is key to NOP receptor activity, with several compounds displaying higher affinity than buprenorphine. One compound, 1b, was found to be a mu opioid receptor partial agonist of comparable efficacy to buprenorphine, but with higher efficacy at NOP receptors.

Cami-Kobeci, Gerta; Polgar, Willma E.; Khroyan, Taline V; Toll, Lawrence; Husbands, Stephen M.

2011-01-01

88

Buprenorphine maintenance therapy in opioid-addicted health care professionals returning to clinical practice: a hidden controversy.  

PubMed

It remains controversial whether it is safe for recovering health care professionals to return to clinical practice after treatment for drug addiction. One specific component of reentry that remains particularly contentious is the use of pharmacotherapeutics, specifically buprenorphine, as opioid substitution therapy for health care professionals who wish to return to clinical work. Because health care professionals are typically engaged in safety-sensitive work with considerable consequences when errors occur, abstinence-based recovery should be recommended until studies demonstrate that it is safe to allow this population to practice while undergoing opioid substitution therapy. PMID:22386182

Hamza, Heather; Bryson, Ethan O

2012-03-01

89

Assessment of immunotoxicity of buprenorphine  

Microsoft Academic Search

Summary In order to use buprenorphine as an analgesic in immunological experiments, we have studied the potential immunotoxicity of buprenorphine. Three-week-old male Wistar Riv: TOX rats were subcutaneously treated with buprenorphine by injection of 0.1, 0.4, or 1.6 mg\\/kg body weight per day over a period of 4 weeks. Concentrations used were within the range for analgesia in rats. A

H. Van Loveren; N. Gianotten; C. F. M. Hendriksen; H. J. Schuurman; J. W. Van Der Laan

1994-01-01

90

Models for Integrating Buprenorphine Therapy into the Primary HIV Care Setting  

Microsoft Academic Search

Opiate dependence among human immunodeficiency virus (HIV)-infected patients has been associated with negative clinical outcomes, yet few affected patients receive appropriate and coordinated treatment for both conditions. The introduction of buprenorphine maintenance therapy into HIV care settings provides an opportunity for providers to integrate treatment for opiate dependence into their practices. Buprenorphine maintenance therapy has been associated with reductions in

Sanjay Basu; R. Douglas Bruce; Frederick L. Altice

2006-01-01

91

Unobserved versus observed office buprenorphine\\/naloxone induction: A pilot randomized clinical trial  

Microsoft Academic Search

Physician adoption of buprenorphine treatment of opioid dependence may be limited in part by concerns regarding the induction process. Although national guidelines recommend observed induction, some physicians utilize unobserved induction outside the office. The aim of this pilot randomized clinical trial was to assess preliminary safety and effectiveness of unobserved versus observed office buprenorphine\\/naloxone induction among patients entering a 12-week

Erik W. Gunderson; Xin-Qun Wang; David A. Fiellin; Benjamin Bryan; Frances R. Levin

2010-01-01

92

Buprenorphine-Naloxone Maintenance Following Release from Jail  

PubMed Central

Primary care is understudied as a re-entry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid dependent adults seeking buprenorphine/naloxone maintenance in an urban primary care clinic following release from jail vs. community referrals. Post-release patients were either; a) induced to buprenorphine in-jail as part of a clinical trial, or, b) seeking buprenorphine induction post-release. From 2007–2008, N=142 patients were new to primary care buprenorphine: n=32 post-release; n=110 induced after community referral and without recent incarceration. Jail-released patients were more likely African American or Hispanic and uninsured. Treatment retention rates for post-release (37%) vs. community (30%) referrals were similar at 48 weeks. Rates of opioid positive urines and self-reported opioid misuse were also similar between groups. Post-release patients in primary care buprenorphine treatment had equal treatment retention and rates of opioid abstinence vs. community-referred patients.

Lee, Joshua D.; Grossman, Ellie; Truncali, Andrea; Rotrosen, John; Rosenblum, Andrew; Magura, Steven; Gourevitch, Marc N.

2012-01-01

93

Transdermal buprenorphine in the management of persistent pain - safety aspects  

PubMed Central

By virtue of their efficacy, opioid analgesics have long been used for the treatment of both acute and chronic pain. Concerns regarding their safety and tolerability have frequently prevented this class of drugs achieving their full therapeutic potential, and their reported association with drug abuse and dependence has led to a reduced acceptance by many patients. Indeed, there is a variety of opioid-like side effects which are common to all members of the class, but some opioids have a more favourable safety profile than others. Buprenorphine is a semisynthestic opioid with a ?-agonistic and ?-antagonistic receptor-binding profile. Studies over the past two decades have shown buprenorphine to have a complex and unique pharmacological profile, which results in enhanced therapeutic benefits combined with a favourable safety profile. Having been underused before, the development of a new transdermal drug delivery system for buprenorphine has revived interest in this substance. Transdermal buprenorphine (Gruenenthal GmbH, Aachen, Germany) provides a noninvasive method of rate-controlled drug release ensuring constant and predictable serum buprenorphine levels over a prolonged period. This preparation has been shown to be advantageous for long-term treatment of chronic pain patients providing reliable pain control, few adverse events, and good patient acceptance.

Likar, Rudolf

2006-01-01

94

Buprenorphine Reduces Alcohol Drinking Through Activation of the Nociceptin/Orphanin FQ-NOP Receptor System  

PubMed Central

Background Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at ?-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. Methods Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. Results Similar to prototypical ?-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p < .01); in contrast, the two highest doses reduced it (p < .05). Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorphine (p < .001) but did not affect the inhibition of ethanol drinking induced by 3.0 mg/kg of buprenorphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 ?g/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine. Conclusions Buprenorphine has dualistic effects on ethanol drinking; low doses increase alcohol intake via stimulation of classic opioid receptors, whereas higher doses reduce it via activation of NOP receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism.

Ciccocioppo, Roberto; Economidou, Daina; Rimondini, Roberto; Sommer, Wolfgang; Massi, Maurizio; Heilig, Markus

2011-01-01

95

The Implementation of Buprenorphine/Naloxone in College Health Practice  

ERIC Educational Resources Information Center

|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.…

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

2008-01-01

96

Evaluation on drug dependence of buprenorphine 1  

Microsoft Academic Search

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

LIU Zhi-Min; LÜ Xian-Xiang; LIAN Zhi; GUO Ping; AN Xin

97

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

PubMed

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. The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three-day period of administration with a maximal effect at 39 h after the start of buprenorphine administration. One single injection of buprenorphine (0.1 mg/kg s.c.) followed by buprenorphine in the drinking water (0.056 mg/mL) induced an earlier onset of antinociception than buprenorphine in drinking water alone. In contrast, buprenorphine (0.1 mg/kg s.c.) injected every 8 h over a period of three days did not result in significant increases in paw withdrawal latency times. In conclusion, our results suggest that one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes. PMID:17430618

Jessen, L; Christensen, S; Bjerrum, O J

2007-04-01

98

Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?  

PubMed

Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence, the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research, the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate that buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that, to date, this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention. PMID:21948099

Blum, Kenneth; Chen, Thomas J H; Bailey, John; Bowirrat, Abdalla; Femino, John; Chen, Amanda L C; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R; Fornari, Frank; Downs, B William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

2011-09-24

99

Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?  

PubMed Central

Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that to date this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention.

Blum, Kenneth; Chen, Thomas JH; Bailey, John; Bowirrat, Abdulla; Femino, John; Chen, Amanda LC; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R.; Fornari, Frank; Downs, B.William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

2013-01-01

100

Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering  

ERIC Educational Resources Information Center

|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…

Greenwald, Mark K.

2008-01-01

101

Lack of effect of CYP3A4 inhibitor ketoconazole on transdermally administered buprenorphine  

Microsoft Academic Search

Objective: To evaluate the effect of ketoconazole on the pharmacokinetics of buprenorphine and its metabolites following application of a 10-mg buprenorphine transdermal system (BTDS).Methods: This was a randomized, double-blind, 2-treatment, 2-period crossover study with 20 healthy male and female subjects. Treatments: BTDS for 7 days with ketoconazole (200 mg po, bid) or placebo in crossover fashion.Results: The 90% confidence intervals

R. Noveck; S. Harris; A. El-Tahtawy; R. Kim; B. Reidenberg; J. Chung; D. Chen

2005-01-01

102

Urine specimen detection of concurrent nonprescribed medicinal and illicit drug use in patients prescribed buprenorphine.  

PubMed

Patients being treated with buprenorphine usually have a history of opioid dependence and may be predisposed to misuse of drugs. Concurrent drug misuse increases the risk of life-threatening drug interactions. This retrospective data analysis observed which nonprescribed and illicit drugs were most commonly detected in the urine of patients from pain management clinics taking buprenorphine with or without a prescription. GC, LC/MS and LC-MS-MS were used to quantify 20,929 urine specimens. The most prevalent illicit drug used in both the groups (prescribed and nonprescribed buprenorphine) was marijuana, followed by cocaine. The most prevalent nonprescribed medications abused by both the groups were benzodiazepines, followed by oxycodone and hydrocodone. The overall prevalence of illicit and nonprescribed drug use was significantly higher in subjects who used buprenorphine without a prescription versus prescribed use. Of the concurrent use of marijuana and cocaine with buprenorphine, cocaine is most concerning since it decreases exposure to buprenorphine (lower area under the concentration-time curve and maximum concentration). The concurrent use of nonprescribed benzodiazepines with buprenorphine can cause excess sedation leading to respiratory depression and even death. These findings highlight the importance of educating patients about these potential toxicities. Furthermore, pain providers should consider expanding the spectrum of drugs that they monitor in patients under treatment. PMID:24080973

Guo, Alexander Y; Ma, Joseph D; Best, Brookie M; Atayee, Rabia S

2013-09-29

103

Effect of Incarceration History on Outcomes of Primary Care Office-based Buprenorphine/Naloxone  

PubMed Central

Background Behaviors associated with opioid dependence often involve criminal activity, which can lead to incarceration. The impact of a history of incarceration on outcomes in primary care office-based buprenorphine/naloxone is not known. Objective The purpose of this study is to determine whether having a history of incarceration affects response to primary care office-based buprenorphine/naloxone treatment. Design In this post hoc secondary analysis of a randomized clinical trial, we compared demographic, clinical characteristics, and treatment outcomes among 166 participants receiving primary care office-based buprenorphine/naloxone treatment stratifying on history of incarceration. Main Results Participants with a history of incarceration have similar treatment outcomes with primary care office-based buprenorphine/naloxone than those without a history of incarceration (consecutive weeks of opioid-negative urine samples, 6.2 vs. 5.9, p?=?0.43; treatment retention, 38% vs. 46%, p?=?0.28). Conclusions Prior history of incarceration does not appear to impact primary care office-based treatment of opioid dependence with buprenorphine/naloxone. Community health care providers can be reassured that initiating buprenorphine/naloxone in opioid dependent individuals with a history of incarceration will have similar outcomes as those without this history.

Moore, Brent A.; Sullivan, Lynn E.; Fiellin, David A.

2010-01-01

104

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

PubMed

The effect of perioperatively administered buprenorphine analgesia on rats subjected to surgically induced global ischaemia was assessed. Rats supplied with buprenorphine, mixed in nut paste for voluntary ingestion, displayed significant reductions in postoperative excretions of faecal corticosterone, in both magnitude and variance. This is indicative of lowered stress levels and less inter-animal metabolic variation. Although corticosterone has been reported to modulate the extent of cerebral damage, histology of coronal sections exhibited no differences in the extent of the ischaemia 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 stress-associated confounding variables in the experimental animals. PMID:20952727

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

105

Behavioral drug and HIV risk reduction counseling (BDRC) with abstinence-contingent take-home buprenorphine: A pilot randomized clinical trial  

Microsoft Academic Search

This pilot randomized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment (BMT), provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine. After a 2-week buprenorphine and stabilization period, heroin dependent individuals (n=24) in Muar, Malaysia were randomly assigned to Standard Services BMT

M. C. Chawarski; M. Mazlan; R. S. Schottenfeld

2008-01-01

106

Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial  

Microsoft Academic Search

Background: We examined the effects of disulfiram versus placebo on cocaine dependence in buprenorphine-maintained subjects.Methods: Opioid and cocaine dependent subjects (n = 20) were induced onto buprenorphine maintenance, then randomized to disulfiram (250 mg q.d.; n = 11) or placebo (n = 9) treatment for 12 weeks.Results: Groups were comparable at baseline on demographic measures and on baseline measures of

Tony P George; Marek C Chawarski; Juliana Pakes; Kathleen M Carroll; Thomas R Kosten; Richard S Schottenfeld

2000-01-01

107

Onset, magnitude and duration of opioid blockade produced by buprenorphine and naltrexone in humans  

Microsoft Academic Search

Rationale: One therapeutic benefit of mu opioid agonist or antagonist maintenance is the resultant attenuation of the effects of illicit opioids. It is important\\u000a to characterize the development and duration of opioid blockade produced by buprenorphine, a novel opioid dependence pharmacotherapy.\\u000a Objective: This study characterized the ability of buprenorphine to attenuate opioid effects during treatment initiation and discontinuation\\u000a compared to

Kory J. Schuh; Sharon L. Walsh; Maxine L. Stitzer

1999-01-01

108

The history of the development of buprenorphine as an addiction therapeutic.  

PubMed

This paper traces the early 21st century success of the agonist-antagonist buprenorphine and the combination drug buprenorphine with naloxone within the broader quest to develop addiction therapeutics that began in the 1920s as the search for a nonaddictive analgesic. Drawing on archival research, document analysis, and interviews with contemporary actors, this paper situates the social organization of laboratory-based and clinical research within the domestic and international confluence of several issues, including research ethics, drug regulation, public attitudes, tensions around definitions of drug addiction, and the evolving roles of the pharmaceutical industry. The fervor that drove the champions of buprenorphine must be understood in relation to (1) the material work of research and pharmaceutical manufacturing; (2) the symbolic role of buprenorphine as a solution to numerous problems with addiction treatment evident by the mid-1970s; the destigmatization and individualization of addicts as patients; and (3) the complex configurations of public and private partnerships. PMID:22256949

Campbell, Nancy D; Lovell, Anne M

2012-01-18

109

Differential Activation of Pregnane X Receptor and Constitutive Androstane Receptor by Buprenorphine in Primary Human Hepatocytes and HepG2 Cells  

PubMed Central

Buprenorphine is a partial ?-opioid receptor agonist used for the treatment of opioid dependence that has several advantages over methadone. The principal route of buprenorphine disposition has been well established; however, little is known regarding the potential for buprenorphine to influence the metabolism and clearance of other drugs by affecting the expression of drug-metabolizing enzymes (DMEs). Here, we investigate the effects of buprenorphine on the activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR), as well as the induction of DMEs, in both HepG2 cells and human primary hepatocytes (HPHs). In HepG2 cells, buprenorphine significantly increased human PXR-mediated CYP2B6 and CYP3A4 reporter activities. CYP2B6 reporter activity was also enhanced by buprenorphine in HepG2 cells cotransfected with a chemical-responsive human CAR variant. Real-time reverse transcription-polymerase chain reaction analysis revealed that buprenorphine strongly induced CYP3A4 expression in both PXR- and CAR-transfected HepG2 cells. However, treatment with the same concentrations of buprenorphine in HPHs resulted in literally no induction of CYP3A4 or CYP2B6 expression. Further studies indicated that buprenorphine could neither translocate human CAR to the nucleus nor activate CYP2B6/CYP3A4 reporter activities in transfected HPHs. Subsequent experiments to determine whether the differential response was due to buprenorphine's metabolic stability revealed a dramatically differential rate of elimination for buprenorphine between HPHs and HepG2 cells. Taken together, these studies indicate that metabolic stability of buprenorphine defines the differential induction of DMEs observed in HepG2 and HPHs, and the results obtained from PXR and CAR reporter assays in immortalized cell line require cautious interpretation.

Li, Linhao; Hassan, Hazem E.; Tolson, Antonia H.; Ferguson, Stephen S.; Eddington, Natalie D.

2010-01-01

110

Influence of buprenorphine analgesia on post-operative recovery in two strains of rats.  

PubMed

The objective of this study was to establish an effective post-operative analgesic regimen for Sprague-Dawley (SD) and Dark Agouti (DA) rats. Buprenorphine (0.01 or 0.05 mg/kg), a partial mu opioid agonist, was administered subcutaneously immediately on completion of a standardized surgical procedure, involving anaesthesia, laparotomy and visceral manipulation. Two of the four treatment groups and the saline control group received a second injection 9 h later. Behavioural observations by three independent observers provided no information in assessing pain in this model. All rats lost weight, consumed less food and water after surgery. On the first day, both SD and DA rats receiving buprenorphine lost less weight than untreated control groups. Using weight loss as an efficacy criterion, low-dose buprenorphine, given once or twice, provided effective analgesia in SD rats. A higher single dose provided no additional benefit and a second dose was detrimental, reducing body weight and food intake. In DA rats, the high dose, given twice, appeared to be more effective than the lower dose. All DA cage cohorts consumed < 10% pre-operative food despite buprenorphine treatment, suggesting a higher dosage may be necessary. However, all SD and 80% DA rats who received no buprenorphine gained body weight on the second day, whereas most of the buprenorphine-treated rats continued to lose weight for another 2 days, despite increased food consumption by both strains. Buprenorphine may adversely affect intestinal function over a number of days due to its enterohepatic circulation; this effect may be more severe in DA rats. Adverse metabolic effects of buprenorphine and other opioids may preclude their use in the future if it can be shown that non-steroidal anti-inflammatory drugs (NSAIDs) provide equally effective analgesia. PMID:11459404

Jablonski, P; Howden, B O; Baxter, K

2001-07-01

111

Sublingual Buprenorphine for Chronic Pain: A Survey of Clinician Prescribing Practices.  

PubMed

OBJECTIVES:: Sublingual buprenorphine, with and without naloxone, is indicated for the treatment of opioid use disorders. Although not approved for pain, some evidence suggests it may be a safe and effective alternative to conventional opioid analgesics, particularly for those with addiction problems. This study surveyed pain specialists to examine the extent to which sublingual buprenorphine was prescribed for chronic pain and explore associated clinician attitudes and characteristics. METHOD:: A 36-item survey examining clinician attitudes and characteristics related to sublingual buprenorphine and other opioids was distributed to 1307 members of the American Pain Society, a multidisciplinary professional group. Members were provided a paper copy of the survey and URL to an online version. A follow-up letter was mailed after 2 weeks. RESULTS:: Overall, 230 completed surveys were returned (18.5%). Of clinicians who prescribed opioids for chronic pain (92.5%), 19.7% reported prescribing sublingual buprenorphine for chronic pain at least once; of these prescribers, 39.6% did not have a DEA X-waiver to prescribe sublingual buprenorphine for opioid dependence. Prescribers were more likely than nonprescribers to find sublingual buprenorphine effective for chronic pain. Prescribers were also significantly more likely to view sublingual buprenorphine as safer than full agonists in terms of addiction, overdose, and drug interaction. No differences emerged between prescribers and nonprescribers regarding perceptions of potential for drug diversion or in terms of overall opioid prescribing behaviors. DISCUSSION:: Results suggest that sublingual buprenorphine is indeed being used to treat chronic pain; however, the circumstances when this occurs are not entirely clear. PMID:23727654

Rosen, Kristen; Gutierrez, Antonio; Haller, Deborah; Potter, Jennifer S

2013-05-30

112

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

PubMed

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. (PsycINFO Database Record (c) 2013 APA, all rights reserved). PMID:23855333

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

2013-07-15

113

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

PubMed

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

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

2010-01-18

114

Using buprenorphine to facilitate entry into residential therapeutic community rehabilitation.  

PubMed

For opioid-dependent patients, the need for detoxification has been a barrier to entry into long-term residential treatment. This report describes a retrospective observational cohort study with the first 38 opioid-dependent patients entering First Step, a 14-day buprenorphine-naloxone (Suboxone) detoxification regimen integrated into a long-term residential therapeutic community (TC) program. Eighty-nine percent (34 of 38) of First Step patients completed a 14-day buprenorphine taper protocol, 50% (19 of 38) completed an initial 3- to 4-week stay, and 39% (15 of 38) completed at least 3 months of residential treatment at the TC. Retention did not differ significantly in a demographically matched concurrently admitted control group without impending opioid withdrawal, in which 65% (24 of 37) completed an initial 3- to 4-week stay (p = .20) and 57% (21 of 37) completed at least 3 months of treatment (p = .14). Withdrawal symptoms were mild, and there were no instances of precipitated withdrawal. The findings suggest the potential for buprenorphine to serve as a bridge, improving the viability of long-term residential treatment for managing opioid dependence. PMID:17306725

Collins, Eric D; Horton, Terry; Reinke, Katherine; Amass, Leslie; Nunes, Edward V

2006-11-21

115

A Comparison Between Low-Magnitude Voucher and Buprenorphine Medication Contingencies in Promoting Abstinence From Opioids and Cocaine  

Microsoft Academic Search

This study compared the relative efficacy of low-magnitude, contingent monetary vouchers, contingent buprenorphine medication, and standard counseling in promoting abstinence from illicit opioids and cocaine among opioid-dependent adults. Following an 8-week baseline period during which participants received buprenorphine maintenance treatment with no contingencies in place, 60 participants were randomly assigned to one of 3 treatment groups for 12 weeks: (a)

Anke Groß; Lisa A. Marsch; Gary J. Badger; Warren K. Bickel

2006-01-01

116

Buprenorphine in drug-facilitated sexual abuse: a fatal case involving a 14-year-old boy.  

PubMed

The first case involving repetitive sexual abuse linked to the use of buprenorphine is reported. Under the tradename Subutex, buprenorphine is largely used for the substitution management of opiate-dependent individuals, but it can also be easily found on the black market. A 14-year-old boy was found dead at the home of a well-known sex offender of minors. At the autopsy, no particular morphological changes were noted, except for pulmonary and visceral congestion. There was no evidence of violence, and no needle marks were found by the pathologist. Toxicological analyses, as achieved by liquid chromatography-mass spectrometry, demonstrated both recent and repetitive buprenorphine exposure in combination with nordiazepam. Buprenorphine concentrations were 1.1 ng/mL and 23 pg/mg in blood and hair, respectively. The boy's death was attributed to accidental asphyxia in a facilitated repetitive sexual abuse situation due to the combination of buprenorphine and benzodiazepines, even at therapeutic concentrations. The use of buprenorphine as a sedative drug was not challenged by the perpetrator. PMID:14607012

Kintz, Pascal; Villain, Marion; Tracqui, Antoine; Cirimele, Vincent; Ludes, Bertrand

2003-10-01

117

[Possibilities and limits of drug substitution treatment in ambulatory practice].  

PubMed

The controversial discussion about the use of methadone in the treatment of drug addicts has occupied specialists in West Germany for decades. Owing to the political pressure to find a solution to the drug problem, methadone has been an established place in the classical drug treatment system for a long time. Therefore, there has been a supplement (in 1991) to the guidelines of the N.U.B. that under special conditions, it is now possible, for a physician working in a practice or outpatient clinic to use methadone substitution as a routine procedure. The psychosocial care of the patient ist also very important in addition to the purely medical provision of a substitute drug which blocks the heroin hunger and helps prevent criminal activity. The profound dependence of a drug addict is not created primarily by the consumption of addictive substances but must be seen as the result of a severely disturbed personality development and treated accordingly. The individual context of the particular drug scene, scene behavior and jargon should also be taken into account. It is not sufficient to explain addiction and dependence by means of chemical formula or physiological processes. Thus, a substitution treatment always includes two crucial aspects: the soothing and protecting aspect of the medicine administered and the conflict and insight orientated aspect of the therapeutic commitment. The physician, the clinic employees and the social worker should be comprehensively and thoroughly qualified in order to deal with the equally wide-ranging demands of substitutions therapy. PMID:8928530

Siegel, I

1996-06-01

118

Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure  

PubMed Central

BACKGROUND Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. METHODS We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. RESULTS Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events. CONCLUSIONS These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.)

Jones, Hendree E.; Kaltenbach, Karol; Heil, Sarah H.; Stine, Susan M.; Coyle, Mara G.; Arria, Amelia M.; O'Grady, Kevin E.; Selby, Peter; Martin, Peter R.; Fischer, Gabriele

2010-01-01

119

Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble-films.  

PubMed

A sublingual soluble-film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid-dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone-induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction. PMID:21270789

Strain, E C; Harrison, J A; Bigelow, G E

2011-01-26

120

Buprenorphine tapering schedule and illicit opioid use  

PubMed Central

Aims To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. Design This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. Setting Eleven out-patient treatment programs in 10 US cities. Intervention Non-blinded dosing with Suboxone® during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. Measurements The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. Findings At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). Conclusion For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper.

Ling, Walter; Hillhouse, Maureen; Domier, Catherine; Doraimani, Geetha; Hunter, Jeremy; Thomas, Christie; Jenkins, Jessica; Hasson, Albert; Annon, Jeffrey; Saxon, Andrew; Selzer, Jeffrey; Boverman, Joshua; Bilangi, Richard

2011-01-01

121

Maternal Buprenorphine Dose, Placenta Buprenorphine and Metabolite Concentrations and Neonatal Outcomes  

PubMed Central

Buprenorphine is approved as pharmacotherapy for opioid dependence in non-pregnant patients in multiple countries, and is currently under investigation for pregnant women in the US and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in 5 term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships between maternal buprenorphine dose, placenta concentrations, and neonatal outcomes following controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (CV<27.5%, 4 locations), except for buprenorphine in 3 placentas. In 2 of these, buprenorphine was not detected in some locations and, in the 3rd placenta, was totally absent. Median (range) concentrations were buprenorphine 1.6ng/g (not detected to 3.2), norbuprenorphine 14.9ng/g (6.2 to 24.2), buprenorphine-glucuronide 3ng/g (1.3 to 5.0) and norbuprenorphine-glucuronide 14.7ng/g (11.4 to 25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15–70 fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration, and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome (NAS) onset and duration, and for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum NAS score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women.

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

2010-01-01

122

40 CFR 148.3 - Dilution prohibited as a substitute for treatment.  

Code of Federal Regulations, 2012 CFR

...Dilution prohibited as a substitute for treatment. 148.3 Section 148.3 Protection...ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE...Dilution prohibited as a substitute for treatment. The prohibition of § 268.3...

2012-07-01

123

Respiratory Rates and Arterial Blood-Gas Tensions in Healthy Rabbits Given Buprenorphine, Butorphanol, Midazolam, or Their Combinations  

PubMed Central

The objective of this study was to evaluate the respiratory effects of buprenorphine, butorphanol, midazolam, and their combinations in healthy conscious rabbits. Six adult female New Zealand white rabbits were anesthetized briefly with isoflurane by mask to allow placement of a catheter into the central ear artery. After a 60-min recovery period, a baseline arterial sample was obtained. Animals then were injected intramuscularly with either 0.9% NaCl (1 mL), buprenorphine (0.03 mg/kg), butorphanol (0.3 mg/kg), midazolam (2 mg/kg), buprenorphine + midazolam (0.03 mg/kg, 2 mg/kg), or butorphanol + midazolam (0.3 mg/kg, 2 mg/kg). Arterial blood gases were evaluated at 30, 60, 90, 120, 180, 240, and 360 min after drug administration. All drug treatments caused significant decreases in respiratory rate, compared with saline. Buprenorphine and the combinations of midazolam–butorphanol and midazolam–buprenorphine resulted in statistically significant decreases in pO2. No significant changes in pCO2 pressure were recorded for any treatment. Increases in blood pH were associated with administration of butorphanol, midazolam, and the combinations of midazolam–butorphanol and midazolam–buprenorphine. In light of these results, buprenorphine and the combinations of midazolam–buprenorphine and midazolam–butorphanol result in statistically significant hypoxemia in rabbits that breathe room air. The degree of hypoxemia is of questionable clinical importance in these healthy subjects. Hypoxemia resulting from these drug combinations may be amplified in rabbits with underlying pulmonary or systemic disease.

Schroeder, Carrie A; Smith, Lesley J

2011-01-01

124

Buprenorphine alters ethanol self-administration in rats: dose-response and time-dependent effects  

Microsoft Academic Search

Buprenorphine is a partial opioid agonist derived from thebaine and has high affinity for ? and ? opioid receptors. The present\\u000a study investigated dose-response (0.03, 0.15, 0.3, 3 mg\\/kg) and time-dependent effects of buprenorphine (1.5 or 4 h post-treatment)\\u000a on EtOH self-administration in outbred Sprague-Dawley rats. Freely feeding and drinking rats were trained to initiate EtOH\\u000a self-administration for 1 h

H. L. June; Charity R. Cason; Shen Hsing A. Chen; Michael J. Lewis

1998-01-01

125

Comparison of Buprenorphine and Meloxicam for Postsurgical Analgesia in Rats: Effects on Body Weight, Locomotor Activity, and Hemodynamic Parameters  

PubMed Central

Buprenorphine is administered to humans and animals for postoperative pain management, although its use is associated with complications. Alternative analgesics, including the nonsteroidal antiinflammatory meloxicam, are available, but information on their postoperative effects is limited. The objective of the present study was to compare buprenorphine (0.03 mg/kg SC twice daily for 3 d) with meloxicam (2 mg/kg SC initial dose followed by 1 mg/kg SC once daily for 2 d) by assessing parameters relating to postsurgical recovery in rats that underwent surgical implantation of radiotelemetric transducers. Rats treated after surgery with buprenorphine showed greater reductions in body weight, food consumption, locomotor activity, and nighttime heart rates than did meloxicam-treated rats. Buprenorphine and meloxicam treatments both had stimulatory effects on mean arterial pressure and daytime heart rate measurements, although effects on nighttime mean arterial pressure were greater in the buprenorphine-treated rats. In summary, the lesser physiologic changes associated with meloxicam, as compared with buprenorphine, suggest that meloxicam offers advantages for use as a postoperative analgesic after laparotomy and radiotelemetric transducer implantation in rats.

Bourque, Stephane L; Adams, Michael A; Nakatsu, Kanji; Winterborn, Andrew

2010-01-01

126

Molecular, anatomical, physiological, and behavioral studies of rats treated with buprenorphine after spinal cord injury.  

PubMed

Acute pain is a common symptom experienced after spinal cord injury (SCI). The presence of this pain calls for treatment with analgesics, such as buprenorphine. However, there are concerns that the drug may exert other effects besides alleviation of pain. Among those reported are in vitro changes in gene expression, apoptosis, and necrosis. In this investigation, the effect of buprenorphine was assessed at the molecular, behavioral, electrophysiological, and histological levels after SCI. Rats were injured at the T10 thoracic level using the NYU impactor device. Half of the animals received buprenorphine (0.05 mg/kg) for 3 consecutive days immediately after SCI, and the other half were untreated. Microarray analysis (n = 5) was performed and analyzed using the Array Assist software. The genes under study were grouped in four categories according to function: regeneration, apoptosis, second messengers, and nociceptive related genes. Microarray analysis demonstrated no significant difference in gene expression between rats treated with buprenorphine and the control group at 2 and 4 days post-injury (DPI). Experiments performed to determine the effect of buprenorphine at the electrophysiological (tcMMEP), behavioral (BBB, grid walking and beam crossing), and histological (luxol staining) levels revealed no significant difference at 7 and 14 DPI in the return of nerve conduction, functional recovery, or white matter sparing between control and experimental groups (p > 0.05, n = 6). These results show that buprenorphine (0.05 mg/kg) can be used as part of the postoperative care to reduce pain after SCI without affecting behavioral, physiological, or anatomical parameters. PMID:19653810

Santiago, José M; Rosas, Odrick; Torrado, Aranza I; González, María M; Kalyan-Masih, Priya O; Miranda, Jorge D

2009-10-01

127

Molecular, Anatomical, Physiological, and Behavioral Studies of Rats Treated with Buprenorphine after Spinal Cord Injury  

PubMed Central

Abstract Acute pain is a common symptom experienced after spinal cord injury (SCI). The presence of this pain calls for treatment with analgesics, such as buprenorphine. However, there are concerns that the drug may exert other effects besides alleviation of pain. Among those reported are in vitro changes in gene expression, apoptosis, and necrosis. In this investigation, the effect of buprenorphine was assessed at the molecular, behavioral, electrophysiological, and histological levels after SCI. Rats were injured at the T10 thoracic level using the NYU impactor device. Half of the animals received buprenorphine (0.05?mg/kg) for 3 consecutive days immediately after SCI, and the other half were untreated. Microarray analysis (n?=?5) was performed and analyzed using the Array Assist software. The genes under study were grouped in four categories according to function: regeneration, apoptosis, second messengers, and nociceptive related genes. Microarray analysis demonstrated no significant difference in gene expression between rats treated with buprenorphine and the control group at 2 and 4 days post-injury (DPI). Experiments performed to determine the effect of buprenorphine at the electrophysiological (tcMMEP), behavioral (BBB, grid walking and beam crossing), and histological (luxol staining) levels revealed no significant difference at 7 and 14 DPI in the return of nerve conduction, functional recovery, or white matter sparing between control and experimental groups (p?>?0.05, n?=?6). These results show that buprenorphine (0.05?mg/kg) can be used as part of the postoperative care to reduce pain after SCI without affecting behavioral, physiological, or anatomical parameters.

Santiago, Jose M.; Rosas, Odrick; Torrado, Aranza I.; Gonzalez, Maria M.; Kalyan-Masih, Priya O.

2009-01-01

128

A new highly specific buprenorphine immunoassay for monitoring buprenorphine compliance and abuse.  

PubMed

Urine buprenorphine screening is utilized to assess buprenorphine compliance and to detect illicit use. Robust screening assays should be specific for buprenorphine without cross-reactivity with other opioids, which are frequently present in patients treated for opioid addiction and chronic pain. We evaluated the new Lin-Zhi urine buprenorphine enzyme immunoassay (EIA) as a potentially more specific alternative to the Microgenics cloned enzyme donor immunoassay (CEDIA) by using 149 urines originating from patients treated for chronic pain and opioid addiction. The EIA methodology offered specific detection of buprenorphine use (100%) (106/106) and provided superior overall agreement with liquid chromatography-tandem mass spectrometry, 95% (142/149) and 91% (135/149) using 5 ng/mL (EIA[5]) and 10 ng/mL (EIA[10]) cutoffs, respectively, compared to CEDIA, 79% (117/149). CEDIA generated 27 false positives, most of which were observed in patients positive for other opioids, providing an overall specificity of 75% (79/106). CEDIA also demonstrated interference from structurally unrelated drugs, chloroquine and hydroxychloroquine. CEDIA and EIA[5] yielded similar sensitivities, both detecting 96% (22/23) of positive samples from patients prescribed buprenorphine, and 88% (38/43) and 81% (35/43), respectively, of all positive samples (illicit and prescribed users). The EIA methodology provides highly specific and sensitive detection of buprenorphine use, without the potential for opioid cross-reactivity. PMID:22417836

Melanson, Stacy E F; Snyder, Marion L; Jarolim, Petr; Flood, James G

2012-04-01

129

Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients  

Microsoft Academic Search

Co-dependence on opiates and cocaine occurs in about 60% of patients entering methadone treatment and has a poor prognosis. However, we recently found that desipramine (DMI) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients. Furthermore, contingency management (CM) has been quite potent in reducing cocaine abuse during methadone maintenance. To

Thomas Kosten; Alison Oliveto; Alan Feingold; James Poling; Kevin Sevarino; Elinore McCance-Katz; Susan Stine; Gerardo Gonzalez; Kishor Gonsai

2003-01-01

130

Safety and Effectiveness of Intravenous Morphine for Episodic Breakthrough Pain in Patients Receiving Transdermal Buprenorphine  

Microsoft Academic Search

Supplemental dosing of an opioid is the main treatment suggested to manage breakthrough pain in cancer patients. The intravenous route has been proven to be safe and effective, providing rapid analgesia in patients receiving oral morphine. Transdermal buprenorphine (TTS-BUP) is increasingly used in cancer pain management, but this drug has been labeled as a difficult drug to use in combination

Sebastiano Mercadante; Patrizia Villari; Patrizia Ferrera; Giampiero Porzio; Federica Aielli; Lucilla Verna; Alessandra Casuccio

2006-01-01

131

Postcastration analgesia in ponies using buprenorphine hydrochloride.  

PubMed

Buprenorphine has recently obtained UK Marketing Authorisation for horses. The analgesic effects are long lasting, and have considerable potential for postoperative pain relief. This observer blinded, randomised study aimed to evaluate postsurgical analgesia in ponies premedicated with buprenorphine prior to castration under intravenous anaesthesia. Ponies received either 0.01 mg/kg bodyweight (BW) buprenorphine (group B) or an equivalent volume of 5 per cent glucose (group C) given intravenously before induction of anaesthesia. Pain was assessed and recorded using dynamic interactive visual analogue scores (DIVAS 0-100) and a Simple Descriptive Scale (SDS 0-3) (high scores=most pain) before and 1, 3, 6, 9, 12 and 24 hours after anaesthesia. Rescue analgesia was given if DIVAS>40 mm. Data were analysed using the Mann-Whitney U test at P<0.05. Median (range) areas under the curve for DIVAS were 63 (0-383) mm hour in group B and 209 (0-391) mm hour in group C (P=0.0348). The SDS was lower in group B than in group C (P=0.038). Three group B and five group C animals required rescue analgesia. Buprenorphine did not produce any serious adverse effects. Buprenorphine at 0.01 mg/kg BW intravenously administered before anaesthesia provided near-comprehensive postoperative analgesia after surgical castration in ponies. PMID:23736517

Love, E J; Taylor, P M; Whay, H R; Murrell, J

2013-06-04

132

Major bone defect treatment with an osteoconductive bone substitute.  

PubMed

A bone defect can be provoked by several pathological conditions (e.g. bone tumours, infections, major trauma with bone stock loss) or by surgical procedures, required for the appropriate treatment. Surgical techniques currently used for treating bone defects may count on different alternatives, including autologous vascularized bone grafts, homologous bone graft provided by musculoskeletal tissue bank, heterologous bone graft (xenograft), or prostheses, each one of them dealing with both specific advantages and complications and drawbacks. The main concerns related to these techniques respectively are: donor site morbidity and limited available amount; possible immune response and viral transmission; possible animal-derived pathogen transmission and risk of immunogenic rejection; high invasiveness and surgery-related systemic risks, long post-operative. physical recovery and prostheses revision need. Nowadays, an ideal alternative is the use of osteoconductive synthetic bone substitutes. Many synthetic substitutes are available, used either alone or in combination with other bone graft. Synthetic bone graft materials available as alternatives to autogeneous bone include calcium sulphates, special glass ceramics (bioactive glasses) and calcium phosphates (calcium hydroxyapatite, HA; tricalcium phosphate, TCP; and biphasic calcium phosphate, BCP). These materials differ in composition and physical properties fro each other and from bone (De Groot in Bioceramics of calcium phosphate, pp 100-114, 1983; Hench in J Am Ceram Soc 74:1487-1510, 1994; Jarcho in Clin Orthop 157:259-278, 1981; Daculsi et al. in Int Rev Cytol 172:129-191, 1996). Both stoichiometric and non-stoichiometric HA-based substitutes represent the current first choice in orthopedic surgery, in that they provide an osteoconductive scaffold to which chemotactic, circulating proteins and cells (e.g. mesenchymal stem cells, osteoinductive growth factors) can migrate and adhere, and within which progenitor cells can differentiate into functioning osteoblasts (Szpalski and Gunzburg in Orthopedics 25S:601-609, 2002). Indeed, HA may be extemporarily combined either with whole autologous bone marrow or PRP (platelet rich plasma) gel inside surgical theatre in order to favour and accelerate bone regeneration. A case of bifocal ulnar bone defect treated with stoichiometric HA-based bone substitute combined with PRP is reported in here, with a 12-month-radiographic follow-up. PMID:19711008

Paderni, Stefania; Terzi, S; Amendola, L

2009-06-16

133

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

PubMed

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

Roose, Robert; Fuentes, Liza; Cheema, Mandeep

2012-05-15

134

Haemodynamic effects of buprenorphine after heart surgery.  

PubMed Central

The effect of buprenorphine on the cardiovascular system was examined in 11 patients during the period of reduced cardiac reserve after open-heart surgery. Within 10 minutes of giving the full analgesic dose (5 microgram/kg) intravenously the mean heart rate had fallen significantly by six beats/min. Although in two patients the mean arterial pressure fell by 24 mm Hg, there was no overall change in mean arterial pressure, cardiac output, or peripheral resistance. In a further six patients buprenorphine was used successfully as the sole analgesic after open-heart surgery. Buprenorphine appears to be safer than morphine for use in patients with reduced cardiac reserve and is of similar analgesic efficacy.

Rosenfeldt, F L; Houston, B; Thompson, D; Naqui, N; Malcolm, A D; Williams, B T; Coltart, D J

1978-01-01

135

Does buprenorphine maintenance improve the quality of life of opioid users?  

PubMed Central

Background & objectives: The quality of life (QOL) of substance abusers is known to be severely impaired. Information on impact of opioid maintenance treatment on the QOL of opioid dependent subjects though available from the developed countries, is lacking from India. This study was carried out to assess the impact of buprenorphine maintenance treatment on the quality of life (QOL) of opioid dependent subjects at nine months follow up. Methods: Based on specified inclusion criteria a total of 231 subjects were recruited from five participating centres across India. They received sublingual buprenorphine as a directly observed therapy along with brief psychosocial intervention (provided in groups of 8-10 subjects) after intake in to the study. The WHOQOL-BREF scale domain scores obtained at baseline were compared to domain scores at nine months follow up. Results: At nine months follow up, among the 64.1 per cent retained in buprenorphine maintenance, there was a significant (P<0.001) decline in opioid use from 24.9 ± 10.1 days at baseline to 1.7 ± 4.7 days at nine months follow up and improvements in score of the four WHOQOL-BREF domains (Physical, Psychological, Social relationships and Environment). Interpretation & conclusions: The results showed the beneficial effects of buprenorphine maintenance treatment in improving the QOL of opioid-dependent subjects at nine month follow up. These results point towards the need for an expanded nation-wide provision of buprenorphine maintenance treatment as a harm reduction strategy for the opioid dependent population.

Dhawan, A.; Chopra, A.

2013-01-01

136

Correlation between body weight changes and postoperative pain in rats treated with meloxicam or buprenorphine  

PubMed Central

It is essential to identify objective and efficient methods of evaluating postoperative pain in rodents. The authors investigated whether postoperative changes in rates of body weight gain could serve as a measure of the efficacy of meloxicam or buprenorphine analgesia in growing rats. Young adult male Lewis rats underwent general endotracheal anesthesia and thoracotomy and were treated postoperatively for 3 d with saline (no analgesia), buprenorphine (six doses of 0.1 mg per kg) or meloxicam (three doses of 1 mg per kg). The authors evaluated rats’ daily growth rates for 5 d after surgery and compared them with baseline (preoperative) growth rates. To discriminate between the effects of postoperative pain and other concurrent physiologic effects associated with anesthesia, thoracotomy or analgesia, the authors evaluated weight changes in multiple control groups. Treatment with buprenorphine in the absence of any other procedure or with anesthesia alone significantly affected rats’ body weight. Notably, growth rate was maintained at near normal levels in rats treated postoperatively with meloxicam. These findings suggest that growth rate might serve as an efficient index of postoperative pain after major surgical procedures in young adult rats treated with meloxicam but not in rats treated with buprenorphine.

Brennan, Matthew P.; Sinusas, Albert J.; Horvath, Tamas L.; Collins, J.G.; Harding, Martha J.

2009-01-01

137

Discriminative stimulus effects of buprenorphine in the rat  

Microsoft Academic Search

Buprenorphine, a potent ”low efficacy” or ”partial” morphine-like opioid agonist, has morphine-like discriminative effects\\u000a in animals and humans discriminating morphine or a related drug. The purpose of the present study was to characterize further\\u000a the discriminative effects of buprenorphine in subjects trained to discriminate buprenorphine itself. Rats trained to discriminate\\u000a between SC injections of saline and either 0.03 or 0.1

Stephen G. Holtzman

1997-01-01

138

Plasma concentrations of buprenorphine 24 to 72 hours after dosing  

Microsoft Academic Search

Background: This study evaluated plasma buprenorphine concentrations 24–72 h following sublingual administration of a dose of buprenorphine solution, ranging from 16 mg\\/70 kg to 44 mg\\/70 kg, administered on a daily or thrice-weekly schedule. Additionally, this study evaluated the effects of different thrice-weekly buprenorphine dose schedules on opiate use and withdrawal symptoms. Methods: Opiate dependent subjects (n=10) were maintained in

M. C. Chawarski; R. S. Schottenfeld; P. G. O’Connor; J. Pakes

1999-01-01

139

Facilitators and Barriers in Implementing Buprenorphine in the Veterans Health Administration  

Microsoft Academic Search

Opioid dependence is a chronic, relapsing disorder that deleteriously influences the health of those afflicted. Sublingual buprenorphine opioid agonist treatment (OAT) has been shown to be safe, effective, and cost-effective for the treatment of opioid dependence in nonspecialized, office-based settings, including the Veterans Health Administration (VHA). We sought to examine and describe provider-, facility-, and system-level barriers and facilitators to

Adam J. Gordon; Greg Kavanagh; Margaret Krumm; Rajeev Ramgopal; Sanjay Paidisetty; Minu Aghevli; Francine Goodman; Jodie Trafton; Joseph Liberto

2011-01-01

140

Double successful buprenorphine/naloxone induction to facilitate cardiac transplantation in an iatrogenically opiate-dependent patient.  

PubMed

Buprenorphine/naloxone is used for the treatment of opioid dependence. In the following case, a potential use for the medication combination is explored in the arena of transplant surgery. Psychiatry was consulted for a 29-year-old woman with iatrogenic opioid dependence after bilateral ventricular assist device placement for congenital cardiomyopathy. Her ejection fraction was less than 15% and she was considered a poor candidate for transplant due to drug-seeking behaviors. We transitioned her onto buprenorphine/naloxone to prevent abuse and control symptoms, qualifying her for cardiac transplant. After transplant, we coordinated care with cardiothoracic surgeons to restart buprenorphine/naloxone, and the patient has been stable for 8 months. PMID:22456493

Rodgman, Christopher; Pletsch, Gayle

2012-06-01

141

Patients' Reasons for Choosing Office-based Buprenorphine: Preference for Patient-Centered Care  

PubMed Central

Objectives To explore HIV-infected patients’ attitudes about buprenorphine treatment in office-based and opioid treatment program (OTP) settings. Methods We conducted in-depth qualitative interviews with 29 patients with co-existing HIV infection and opioid dependence seeking buprenorphine maintenance therapy in office-based and OTP settings. We used thematic analysis of transcribed audiorecorded interviews to identify themes. Results Patients voiced a strong preference for office-based treatment. Four themes emerged to explain this preference. First, patients perceived the greater convenience of office-based treatment as improving their ability to address HIV and other healthcare issues. Second, they perceived a strong patient-focused orientation in patient-provider relationships underpinning their preference for office-based care. This was manifest as increased trust, listening, empathy, and respect from office-based staff and providers. Third, they perceived shared power and responsibility in office-based settings. Finally, patients viewed office-based treatment as a more supportive environment for sobriety and relapse prevention. This was partly due to strong therapeutic alliances with office-based staff and providers who prioritized a harm reduction approach, but also due to the perception that the office-based settings were “safer” for sobriety, compared with increased opportunities for purchasing and using illicit opiates in OTP settings. Conclusions HIV-infected patients with opioid dependence preferred office-based buprenorphine because they perceived it as offering a more patient-centered approach to care compared with OTP referral. Office-based buprenorphine may facilitate engagement in care for patients with co-existing opioid dependence and HIV infection.

Korthuis, P. Todd; Gregg, Jessica; Rogers, Wendy E.; McCarty, Dennis; Nicolaidis, Christina; Boverman, Joshua

2010-01-01

142

The eŒect of substitution patterns on phonological treatment outcomes  

Microsoft Academic Search

It has been suggested that phonological learning in children with articulation disorders is inuenced by the variability or consistency of substitutes used for sounds that are excluded from the inventory. This proposal was based on a post- hoc analysis of children's pre-treatment inventories and substitution patterns, as well as their generalization patterns at the termination of phonological interven- tion. In

KAREN FORREST; MARY ELBERT; DANIEL A. DINNSEN

143

Fatal poisoning due to snorting buprenorphine and alcohol consumption  

Microsoft Academic Search

High dosage buprenorphine (Subutex®) has been prescribed as a replacement therapy for major opioid dependencies in France since 1996. However, several studies have underlined its lethal risk, especially when administered intravenously, or when combined with benzodiazepines, alcohol or other central nervous system depressants. We report three fatal buprenorphine-related poisonings after snorting, among outside protocol individuals, observed at the Forensic Medicine

Ophélie Ferrant; Frédérique Papin; Bénédicte Clin; Christian Lacroix; Elodie Saussereau; Jean-Emmanuel Remoué; Jean-Pierre Goullé

2011-01-01

144

Inè uence of buprenorphine analgesia on post-operative recovery in two strains of rats  

Microsoft Academic Search

Summary The objective of this study was to establish an effective post-operative analgesic regimen for Sprague-Dawley (SD) and Dark Agouti (DA) rats. Buprenorphine (0.01 or 0.05 mg =kg), a partial m opioid agonist, was administered subcutaneously immediately on completion of a standardized surgical procedure, involving anaesthesia, laparotomy and visceral manipulation. Two of the four treatment groups and the saline control

P. Jablonski; B. O. Howden; K. Baxter

145

Comparison of methadone and high dosage buprenorphine users in French care centres  

Microsoft Academic Search

Aims. In France, maintenance programmes for opiate users were adopted later than in other countri~s. Two maintenance treatments are available: methadone is only delivered in specialized centres while high dosage (HD) buprenorphine can be prescribed by al1 general practitioners and in specialized centres. The aim of this study was to compare the socio-demographic projiles, the practices and drug consumption patterns

Karine Barrau; Xavier Thirion; Joëlle Micallef; Christine Chuniaud-Louche; Béatrice Bellemin; Jean Louis San Marco

2001-01-01

146

Chemical profile of counterfeit buprenorphine vials seized in Tehran, Iran.  

PubMed

Buprenorphine, commonly known by the trademark Temgesic, is one of the most popular drugs of abuse among the opioid-addicted young individuals in Iran. Temgesic, Bungesic, etc. are the most popular and important illicit opioid drugs in Tehran's illicit drugs black market, and are now among the most widely abused by opioid addicts. Because of this, counterfeiting of this drug has increased in Tehran. In this study, the qualitative analysis of counterfeit buprenorphine by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) demonstrates the presence of diacetylmorphine, acetylcodeine and pheniramine, as well as the absence of buprenorphine. In conclusion, due to the absence of quality control and difficulties in differentiating counterfeit buprenorphine from genuine products, the use of counterfeit buprenorphine leads the opioid abusers to health risks. PMID:17646070

Soltaninejad, Kambiz; Faryadi, Mansoor; Akhgari, Maryam; Bahmanabadi, Leila

2007-07-23

147

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

PubMed

Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam treatment significantly reduced infarct volume and may be a confounder if used as an analgesic during MCAO surgery. Furthermore, investigation of behavioral profiles by using an automated behavioral scoring system showed that rearing and sniffing behaviors decreased as infarct volume increased. This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice. PMID:23582417

Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy; Kalliokoski, Otto; Hau, Jann; Johansen, Flemming F; Abelson, Klas Sp

2013-04-01

148

Effects of Buprenorphine and Meloxicam Analgesia on Induced Cerebral Ischemia in C57BL/6 Male Mice  

PubMed Central

Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam treatment significantly reduced infarct volume and may be a confounder if used as an analgesic during MCAO surgery. Furthermore, investigation of behavioral profiles by using an automated behavioral scoring system showed that rearing and sniffing behaviors decreased as infarct volume increased. This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice.

Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy; Kalliokoski, Otto; Hau, Jann; Johansen, Flemming F; Abelson, Klas SP

2013-01-01

149

Treatment of alprazolam withdrawal with chlordiazepoxide substitution and taper.  

PubMed

We describe the first case series (n = 6) of using chlordiazepoxide to accomplish a rapid, well-tolerated withdrawal from alprazolam. After abruptly discontinuing alprazolam, we substituted a 50-mg dose of chlordiazepoxide for each 1 mg of alprazolam (except for one elderly patient where we substituted 25 mg) and gave additional chlordiazepoxide doses (25-50 mg every 4-6 hours) as needed for the first 1-2 days of hospitalization. With this approach, the mean "substitution ratio" of chlordiazepoxide to alprazolam was 86 to 1. We then tapered chlordiazepoxide by an average of 10% each day over a 7- to 14-day period according to the symptoms manifested and tolerated by individual patients. No seizures or other serious side effects occurred. Incomplete cross-dependence, as described elsewhere in the literature, was not observed. The rapidity and familiarity of the method are advantages for inpatient units, but careful titration of dosage, diagnostic clarity, and extended follow-ups are necessary when applying this approach. PMID:7966502

Closser, M H; Brower, K J

150

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

PubMed Central

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.

Vadivelu, Nalini; Hines, Roberta L

2008-01-01

151

Methadone and Buprenorphine Prescribing and Referral Practices in US Prison Systems: Results from a Nationwide Survey  

PubMed Central

Background More than 50% of incarcerated individuals have a history of substance use, and over 200,000 individuals with heroin addiction pass through American correctional facilities annually. Opiate replacement therapy (ORT) with methadone or buprenorphine is an effective treatment for opiate dependence and can reduce drug-related disease and recidivism for inmates. Provision of ORT is nevertheless a frequently neglected intervention in the correctional setting. Objective and Methods We surveyed the 50 state; Washington, District of Columbia (DC); and Federal Department of Corrections' medical directors or their equivalents about their facilities' ORT prescribing policies and referral programs for inmates leaving prison. Results We received responses from 51 of 52 prison systems nationwide. Twenty-eight prison systems (55%) offer methadone to inmates in some situations. Methadone use varies widely across states: over 50% of correctional facilities that offer methadone do so exclusively for pregnant women or for chronic pain management. Seven states' prison systems (14%) offer buprenorphine to some inmates. The most common reason cited for not offering ORT was that facilities “prefer drug-free detoxification over providing methadone or buprenorphine.” Twenty-three states' prison systems (45%) provide referrals for some inmates to methadone maintenance programs after release, which increased from 8% in 2003; 15 states' prison systems (29%) provide some referrals to community buprenorphine providers. Conclusion Despite demonstrated social, medical, and economic benefits of providing ORT to inmates during incarceration and linkage to ORT upon release, many prison systems nationwide still do not offer pharmacological treatment for opiate addiction or referrals for ORT upon release.

Nunn, Amy; Zaller, Nickolas; Dickman, Samuel; Trimbur, Catherine; Nijhawan, Ank; Rich, Josiah D.

2009-01-01

152

The animal pharmacology of buprenorphine, an oripavine analgesic agent.  

PubMed Central

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

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

1977-01-01

153

Medicines and the drug control treaties: is buprenorphine for opioid addiction at risk of being lost?  

PubMed

Over the past century, a worldwide system for the control of drugs with abuse potential has developed through the adoption of a series of international treaties. The important multilateral conventions currently in force are the United Nations Single Convention on Narcotic Drugs, 1961 (Single Convention), the United Nations Convention on Psychotropic Substances, 1971 (Psychotropic Convention) and the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988. From the beginning, the aim of these drug control treaties has been to control the abuse and trafficking of substances with abuse potential while assuring that the availability of these drugs for medical and scientific purposes is not unduly restricted. There is activity in the World Health Organization and the International Narcotics Control Board to determine whether the international control of buprenorphine, a partial mu-opioid agonist used as an analgesic and for the treatment of opioid addiction, should be changed from the Psychotropic Convention to the Single Convention. This change would result in the classification and regulation of buprenorphine as a narcotic drug rather than a psychotropic substance. Such a move is unwarranted medically and scientifically and would provoke increased controls on buprenorphine that would fundamentally disrupt the medical practice of pain management and opioid replacement therapy around the world. The negative impact of inappropriate regulatory controls when licensed medicines come under such scrutiny are described. PMID:15181649

Costa E Silva, J A

2004-06-01

154

Sleep disordered breathing in patients receiving therapy with buprenorphine/naloxone.  

PubMed

Patients using chronic opioids are at risk for exceptionally complex and potentially lethal disorders of breathing during sleep, including central and obstructive apnoeas, hypopnoeas, ataxic breathing and nonapnoeic hypoxaemia. Buprenorphine, a partial ?-opioid agonist with limited respiratory toxicity, is widely used for the treatment of opioid dependency and chronic nonmalignant pain. However, its potential for causing sleep disordered breathing has not been studied. 70 consecutive patients admitted for therapy with buprenorphine/naloxone were routinely evaluated with sleep medicine consultation and attended polysomnography. The majority of patients were young (mean±sd age 31.8±12.3 years), nonobese (mean±sd body mass index 24.9±5.9 kg·m(-2)) and female (60%). Based upon the apnoea/hypopnoea index (AHI), at least mild sleep disordered breathing (AHI ?5 events·h(-1)) was present in 63% of the group. Moderate (AHI ?15- <30 events·h(-1)) and severe (AHI ?30 events·h(-1)) sleep apnoea was present in 16% and 17%, respectively. Hypoxaemia, defined as an arterial oxygen saturation measured by pulse oximetry, of <90% for ?10% of sleep time, was present in 27 (38.6%) patients. Despite the putative protective ceiling effect regarding ventilatory suppression observed during wakefulness, buprenorphine may induce significant alterations of breathing during sleep at routine therapeutic doses. PMID:23100497

Farney, Robert J; McDonald, Amanda M; Boyle, Kathleen M; Snow, Gregory L; Nuttall, R T; Coudreaut, Michael F; Wander, Theodore J; Walker, James M

2012-10-25

155

The Use of High Dosages of Transdermal Buprenorphine for Pain Management in Palliative Cancer Patients: A Case Study  

PubMed Central

Pain is a prevalent condition in patients with cancer, particularly in advanced stages of cancer. Although strong opioids are the mainstay of cancer pain management protocols, patients are often undertreated. Transdermal buprenorphine is currently available for the treatment of moderate to severe cancer pain and severe pain which does not respond to nonopioid analgesics; patch doses of 35, 52.5 and 70 µg/h are available (applied for up to 96 h), with no more than 2 transdermal patches at the same time, regardless of the strength. To date, there are no published reports in the literature of the use of high-dose transdermal buprenorphine (>140 µg/h). Herein, we present 2 cases of palliative cancer patients who received transdermal buprenorphine at doses titrated up to 210 and 175 µg/h, respectively, for the management of pain. Transdermal buprenorphine titrated to doses >140 µg/h provided adequate pain control and was well tolerated. Future studies to confirm these initial observations are warranted.

M.J. Clement, Paul; Beuselinck, Benoit; Van Beek, Karen; Georgette Mertens, P.; Cornelissen, Paul; Menten, Johan

2013-01-01

156

The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data  

PubMed Central

Most women using heroin are of reproductive age with major risks for their infants. We review clinical and experimental data on fetal, neonatal and postnatal complications associated with methadone, the current “gold standard”, and compare these with more recent, but limited, data on developmental effects of buprenorphine, and naltrexone. Methadone is a µ-opioid receptor agonist and is commonly recommended for treatment of opioid dependence during pregnancy. However, it has undesired outcomes including neonatal abstinence syndrome (NAS). Animal studies also indicate detrimental effects on growth, behaviour, neuroanatomy and biochemistry, and increased perinatal mortality. Buprenorphine is a partial µ-opioid receptor agonist and a ?-opioid receptor antagonist. Clinical observations suggest that buprenorphine during pregnancy is similar to methadone on developmental measures but is potentially superior in reducing the incidence and prognosis of NAS. However, small animal studies demonstrate that low doses of buprenorphine during pregnancy and lactation lead to changes in offspring behaviour, neuroanatomy and biochemistry. Naltrexone is a non-selective opioid receptor antagonist. Although data are limited, humans treated with oral or sustained-release implantable naltrexone suggest outcomes potentially superior to those with methadone or buprenorphine. However, animal studies using oral or injectable naltrexone have shown developmental changes following exposure during pregnancy and lactation, raising concerns about its use in humans. Animal studies using chronic exposure, equivalent to clinical depot formulations, are required to evaluate safety. While each treatment is likely to have maternal advantages and disadvantages, studies are urgently required to determine which is optimal for offspring in the short and long term.

Farid, W.O; Dunlop, S.A; Tait, R.J; Hulse, G.K

2008-01-01

157

Implementation of drug substitution therapy in Georgia.  

PubMed

The geopolitical uniqueness of the regional, socioeconomic situation and the existence of territories outside the control of the national government have facilitated the spread of drug use in Georgia. A special problem is injection of opiates, in particular heroin and Subutex (buprenorphine). It has been established that among registered HIV infected individuals the main route of transmission is injecting drug use. Although the prevalence of HIV among IDUs (injecting drug user) is only 1-3%, the high number of IDUs, and the high prevalence of hepatitis C in this population creates high risk of dramatic spread of HIV in Georgia. Beginning at the end of 2005, the GFATM (Global Fund against HIV/AIDS, Tuberculosis and Malaria) supported methadone substitution programmes in Georgia. At present, three programmes are functioning. At the same time, they involve 230 patients altogether. The studies carried out by the Research Institute on Addiction, with the aim to control the efficacy of pilot programmes have revealed a dramatic improvement of psychophysical state of patients, with very high rate of resocialization and decriminalization, significant diminishment of drug-related risky behaviour. Obtained results indicate high efficiency of methadone substitution programmes in Georgia, as an important tool both for treatment of opioid dependence and harm reduction. In order to obtain a more significant impact on public health substitution therapy programmes have to be further expanded. PMID:18935776

Todadze, Khatuna; Lezhava, Gela

2008-09-01

158

Acute Pain Management for Patients Receiving Maintenance Methadone or Buprenorphine Therapy  

PubMed Central

More patients with opioid addiction are receiving opioid agonist therapy (OAT) with methadone and buprenorphine. As a result, physicians will more frequently encounter patients receiving OAT who develop acutely painful conditions, requiring effective treatment strategies. Undertreatment of acute pain is suboptimal medical treatment, and patients receiving long-term OAT are at particular risk. This paper acknowledges the complex interplay among addictive disease, OAT, and acute pain management and describes 4 common misconceptions resulting in suboptimal treatment of acute pain. Clinical recommendations for providing analgesia for patients with acute pain who are receiving OAT are presented. Although challenging, acute pain in patients receiving this type of therapy can effectively be managed.

Alford, Daniel P.; Compton, Peggy; Samet, Jeffrey H.

2007-01-01

159

Treating Homeless Opioid Dependent Patients with Buprenorphine in an Office-Based Setting  

Microsoft Academic Search

Context  Although office-based opioid treatment with buprenorphine (OBOT-B) has been successfully implemented in primary care settings\\u000a in the US, its use has not been reported in homeless patients.\\u000a \\u000a \\u000a \\u000a Objective  To characterize the feasibility of OBOT-B in homeless relative to housed patients.\\u000a \\u000a \\u000a \\u000a Design  A retrospective record review examining treatment failure, drug use, utilization of substance abuse treatment services, and\\u000a intensity of clinical support by

Daniel P. Alford; Colleen T. LaBelle; Jessica M. Richardson; James J. O’Connell; Carole A. Hohl; Debbie M. Cheng; Jeffrey H. Samet

2007-01-01

160

[When is testosterone substitution a medically necessary treatment?].  

PubMed

The expert questioning of when a treatment with testosterone is medically necessary has increased by several 100% in the daily work of the insurance medical expert in the past years. The reason for this is that testosterone is prescribed a lot more often nowadays than it was 10 years ago. One can suspect that testosterone has become part of a popular lifestyle medication. However, the clinical meaning of the age-dependent decrease of testosterone in men is controversial. Unfortunately, there are only few study data about hypogonadism in ageing men. Testosterone treatment has a very narrow application field and is only medically necessary if the low testosterone level has been clinically proven as well as in a medical lab examination. This is decisive because testosterone treatment has numerous limitations of application and has a wide range of side effects. This article shows the controversy surrounding the discussion on testosterone treatment and the pitfalls of issuing the insurance medical expert's report. PMID:22808644

Hakimi, Rainer

2012-06-01

161

Buprenorphine in a Transdermal Therapeutic System - A New Option  

Microsoft Academic Search

Advanced patch technology has yielded a novel transdermal therapeutic system (TDS) for the rate-controlled systemic delivery of buprenorphine. Buprenorphine TDS is available in three strengths with release rates of 35, 52.5 and 70 mg\\/h over 72 h, corresponding to daily doses of 0.8, 1.2 and 1.6 mg, respectively. In total, 445 patients with chronic pain of malignant or non-malignant origin

2002-01-01

162

Simultaneous determination of buprenorphine, norbuprenorphine, and buprenorphine–glucuronide in plasma by liquid chromatography–tandem mass spectrometry  

Microsoft Academic Search

For the first time, an LC–MS–MS method has been developed for the simultaneous analysis of buprenorphine (BUP), norbuprenorphine (NBUP), and buprenorphine–glucuronide (BUPG) in plasma. Analytes were isolated from plasma by C18 SPE and separated by gradient RP-LC. Electrospray ionization and MS–MS analyses were carried out using a PE-Sciex API-3000 tandem mass spectrometer. The m\\/z 644?m\\/z 468 transition was monitored for

Aldo Polettini; Marilyn A Huestis

2001-01-01

163

Influence of naloxone on the postoperative analgesic and respiratory effects of buprenorphine  

Microsoft Academic Search

Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fraction 60%; Group BN) in the early postoperative period by means of the On-Demand Analgesia Computer (ODAC).

K. A. Lehmann; U. Reichling; R. Wirtz

1988-01-01

164

Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat  

Microsoft Academic Search

Summary The effects of oral administration of buprenorphine ('buprenorphine jello'), a partial ~t opioid agonist, oral naltrexone, a ~t antagonist and morphine, a J.1agonist, were investigated in rats following laparotomy. Food and water consumption and body weight were reduced in rats that underwent surgery. Rats undergoing anaesthesia alone showed only a small reduction in water consumption. Administration of oral buprenorphine

J. H. Liles; P. A. Flecknell; J. Roughan; I. Cruz-Madorran

1998-01-01

165

What Is Diversion of Supervised Buprenorphine and How Common Is It?  

Microsoft Academic Search

This study aimed to identify the practices of community pharmacists regarding the provision of buprenorphine for opioid dependence and explore behaviors pharmacists considered indicative of buprenorphine diversion. A cross-sectional survey of 669 community pharmacists authorized to dispense buprenorphine or methadone was conducted in New South Wales and Victoria, Australia. There was wide variation between pharmacies in the level of supervision

Adam R. Winstock; Toby Lea; Janie Sheridan

2009-01-01

166

Bone graft substitutes for the treatment of traumatic fractures of the extremities  

PubMed Central

Health political and scientific background Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures. Research questions The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed. Methods A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. Results 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevated high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference. The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. Discussion Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited. Conclusions The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided.

Hagen, Anja; Gorenoi, Vitali; Schonermark, Matthias P.

2012-01-01

167

Cannabis as an Adjunct to or Substitute for Opiates in the Treatment of Chronic Pain  

Microsoft Academic Search

There is a growing body of evidence to support the use of medical cannabis as an adjunct to or substitute for prescription opiates in the treatment of chronic pain. When used in conjunction with opiates, cannabinoids lead to a greater cumulative relief of pain, resulting in a reduction in the use of opiates (and associated side-effects) by patients in a

Philippe Lucas

2012-01-01

168

Shifts in opioid substitution treatment policy in Denmark from 2000-2011.  

PubMed

This article discusses how opioid substitution treatment policy has developed from 2000 to 2011 in Denmark. Empirically, it takes its point of departure in a stakeholder analysis including 17 qualitative interviews with stakeholders who have played important roles in this field. Analytically, it is inspired by Kingdon's concepts of agenda and policy window. Three major shifts are identified: a shift from psychosocial to medical thinking and practice, from an abstinence driven ideology to health care, and from perceptions of passive clients to user involvement. These shifts are discussed in relation to the legal context of substitute prescribing medicine. PMID:23952511

Frank, Vibeke Asmussen; Bjerge, Bagga; Houborg, Esben

2013-08-01

169

Can patients receiving opioid maintenance therapy safely drive? A systematic review of epidemiological and experimental studies on driving ability with a focus on concomitant methadone or buprenorphine administration  

Microsoft Academic Search

OBJECTIVE: To perform a systematic review of the present scientific literature on the treatment with methadone or buprenorphine related to (I) traffic accident risk in epidemiological studies and (II) to their effects on cognitive- and psychomotor functions of relevance to driving in experimental studies.METHODS: Searches for corresponding literature were conducted in MEDLINE, EMBASE and PsycINFO throughout March and June of

Maren Cecilie Strand; Bente Fjeld; Marianne Arnestad; Jørg Mørland

2012-01-01

170

Effects of d-Amphetamine and Buprenorphine Combinations on Speedball (Cocaine+Heroin) Self-Administration by Rhesus Monkeys  

Microsoft Academic Search

The simultaneous i.v. administration of heroin and cocaine, called a ‘speedball,’ is often reported clinically, and identification of effective pharmacotherapies is a continuing challenge. We hypothesized that treatment with combinations of a monoamine releaser d-amphetamine, and a mu partial agonist, buprenorphine, might reduce speedball self-administration by rhesus monkeys. Speedballs (0.01 mg\\/kg\\/inj cocaine+0.0032 mg\\/kg\\/inj heroin) and food (1 g banana-flavored pellets)

Nancy K Mello; S Stevens Negus

2007-01-01

171

Assessment of Carprofen and Buprenorphine on Recovery of Mice after Surgical Removal of the Mammary Fat Pad  

PubMed Central

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.

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

2010-01-01

172

Pattern of buprenorphine abuse among opioid abusers in Nepal  

PubMed Central

Background: Although buprenorphine abusers are a common clinical entity, literature on them is rare in Nepal. Aim: To assess whether injectable opioid abusers are any different a subgroup vis-a-vis brown sugar abusers in relation to their demographic and clinical profiles. Materials and Methods: Seventy-six opioid abusers, who were admitted over a period of one year, in our de-addiction center, were included in the present study. They were divided into two groups based on the history of the presence or absence of buprenorphine injection abuse in them. The demographic and clinical profiles of these two groups were studied and compared. Results: The most characteristic opioid abuse pattern was the abuse of brown sugar through inhalation (chasing). A total of 32 (42.1%) among them had a history of injectable drug abuse (IDU). Most characteristic buprenorphine abuse pattern seen was an evolution from injectable buprenorphine to triple injection to brown sugar abuse (Reverse Transition). Injection buprenorphine abusers, who attended our clinic, were older in age and had a history of a longer duration of abuse than their counterparts who abused opioid drugs through the inhalational route only. Their lifetime diagnosis revealed a polysubstance abuse pattern. They were more unstable, impulsive, and disorganized in their behavior pattern, suggestive of the presence of inadequate personality traits. There were high instances of injection-related side effects in the form of the presence of thrombophlebitis, HIV positivity, and clinical AIDS in them. Conclusion: Findings of the current research indicate the presence of a subgroup of patient population among opioid abusers with a history of injectable buprenorphine abuse, with characteristic personality traits, pattern of drug abuse, and associated physical complications resulting from it.

Aich, Tapas Kumar; Dhungana, Manoj; Khanal, Roshija

2010-01-01

173

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

PubMed Central

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.

Wapf, Victoria; Schaub, Michael; Klaeusler, Beat; Boesch, Lukas; Stohler, Rudolf; Eich, Dominique

2008-01-01

174

[Application of a seven-day buprenorphine transdermal patch in multimorbid patients on long-term ibuprofen or diclofenac].  

PubMed

The objective of this study was to evaluate the benefit of a seven-day buprenorphine transdermal patch for patients with chronic musculoskeletal pain previously receiving long-term treatment with ibuprofen or diclofenac alone. Data of a subgroup of 703 patients were analysed which were part of a multicenter observational study with 3,295 patients. These patients had previously received ibuprofen or diclofenac and were characterized by older age,the presence of gastrointestinal, cardiovascular, and renal risk factors and the existence of chronic musculoskeletal pain. The switch to the seven-day buprenorphine patch resulted in a clinically significant decrease of the mean pain intensity at rest during the day from 5.3 to 2.9, on physical effort during the day from 7.1 to 3.3, and at night from 4.9 to 1.9 at the end of the study (11-point NRS scale, pbuprenorphine due to the lack of cardiac, renal and gastrointestinal toxicity. Constant analgesia, improvement of daily activities and reduction of tablets were reported as important advantages of the seven-day patch. In conclusion, the seven-day buprenorphine patch is a valuable therapeutic option for patients with insufficient analgesia on long-term ibuprofen or diclofenac. PMID:21598463

Böhme, K; Heckes, B; Thomitzek, K

2011-01-13

175

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

PubMed

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. PMID:16044413

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

2005-10-01

176

Injection drug users' perceptions of drug treatment services and attitudes toward substitution therapy: A qualitative study in three Russian cities  

Microsoft Academic Search

This study explored injection drug users' (IDUs) perceptions of drug abuse treatment and treatment providers in three Russian cities as well as their attitudes toward opiate substitution therapy, which is currently not available in Russia. Data were collected from 121 qualitative interviews with IDUs conducted in 2003–2004. Negative perceptions of available treatments were related to poor treatment outcomes, judgmental service

Natalia Bobrova; Ron Alcorn; Tim Rhodes; Iurii Rughnikov; Elena Neifeld; Robert Power

2007-01-01

177

[Obstetrical peridural anesthesia with bupivacaine and buprenorphine. A randomized double-blind study in comparison with untreated controls].  

PubMed

Epidural anaesthesia with local anaesthetics has become a standard method of pain relief during labour. In recent years, spinal opiates, alone and in combination with local anaesthetics, have also been tried with varying degrees of success. Buprenorphine, a potent lipophilic opiate with long duration of action, has been used in several trials for caesarean section [3, 4, 6], but not yet in spontaneous labour. The aim of the present investigation was to evaluate epidural anaesthesia with bupivacaine alone and with bupivacaine+buprenorphine in comparison with no anaesthetic treatment in control parturients. METHODS. A total of 80 healthy women during labour at full term (age 18-38 years, weight 54-107 kg) were studied to evaluate the influence of 0.3 mg buprenorphine (group BB) vs placebo (group B) added to an initial dose of 15 ml plain bupivacaine 0.33% for lumbar catheter epidural anaesthesia. Plain bupivacaine 0.25% (10 ml) without any opiate admixture was used for reinjections. The control group was made up of 48 untreated parturients. After every injection, blood pressure, heart rate and respiratory rate were measured repeatedly, as were time intervals between injections, extent of blockade, duration of labour, actual and retrospective visual analogue pain score, and side effects such as pruritus, shivering or nausea and emesis. Maternal capillary blood gases were analysed three times during labour, and Apgar scores and venous and arterial umbilical blood gas analyses were obtained immediately after delivery. RESULTS. Admixture of buprenorphine 0.3 mg significantly increased the time interval between the first and second epidural doses (B: 162 +/- 47 vs BB: 224 +/- 64 min; mean, SD; Table 2) and significantly reduced the incidence of shivering (Table 9). The incidence of instrumental delivery was comparable in all groups (bupivacaine 32.5%, bupivacaine+buprenorphine 27.5%, control 21%; n.s.). No clinically relevant differences were observed between the epidural patients in onset and duration of the block (Fig. 1), analgesic efficacy (Fig. 2), duration of spontaneous labour (BB: 8.6 +/- 3.1 h, B: 8.5 +/- 2.9 h; n.s.) and vital functions of mothers and newborns. Although some statistically significant differences between the three groups were found in some parameters of the blood gas analyses (Table 7), the clinical condition of the newborns was always acceptable; Apgar scores were not significantly different. DISCUSSION AND CONCLUSIONS. The addition of buprenorphine to bupivacaine resulted in some advantages to the mother (reduced incidence of shivering) and the anaesthetist (time lapse before first reinjection was necessary) without jeopardizing the situation of the baby. Compared with untreated control parturients, retrospective pain scores during epidural anaesthesia with bupivacaine (with or without buprenorphine) were significantly lower. No clinically relevant disadvantages of epidural anaesthesia were observed. More studies are required to evaluate whether buprenorphine admixture allows a dose reduction of bupivacaine and could then claim clearer advantages than were found in the present investigation. PMID:1497132

Lehmann, K A; Stern, S; Breuker, K H

1992-07-01

178

Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis  

PubMed Central

Objective To quantify the effect of opiate substitution treatment in relation to HIV transmission among people who inject drugs. Design Systematic review and meta-analysis of prospective published and unpublished observational studies. Data sources Search of Medline, Embase, PsychINFO, and the Cochrane Library from the earliest year to 2011 without language restriction. Review methods We selected studies that directly assessed the impact of opiate substitution treatment in relation to incidence of HIV and studies that assessed incidence of HIV in people who inject drugs and that might have collected data regarding exposure to opiate substitution treatment but not have reported it. Authors of these studies were contacted. Data were extracted by two reviewers and pooled in a meta-analysis with a random effects model. Results Twelve published studies that examined the impact of opiate substitution treatment on HIV transmission met criteria for inclusion, and unpublished data were obtained from three additional studies. All included studies examined methadone maintenance treatment. Data from nine of these studies could be pooled, including 819 incident HIV infections over 23?608 person years of follow-up. Opiate substitution treatment was associated with a 54% reduction in risk of HIV infection among people who inject drugs (rate ratio 0.46, 95% confidence interval 0.32 to 0.67; P<0.001). There was evidence of heterogeneity between studies (I2=60%, ?2=20.12, P=0.010), which could not be explained by geographical region, site of recruitment, or the provision of incentives. There was weak evidence for greater benefit associated with longer duration of exposure to opiate substitution treatment. Conclusion Opiate substitution treatment provided as maintenance therapy is associated with a reduction in the risk of HIV infection among people who inject drugs. These findings, however, could reflect comparatively high levels of motivation to change behaviour and reduce injecting risk behaviour among people who inject drugs who are receiving opiate substitution treatment.

2012-01-01

179

Development of an enhanced formulation for delivering sustained release of buprenorphine hydrochloride.  

PubMed

To control the minimum effective dose, and reduce the number and quantity of administered potent drugs are unique features of advanced drug delivery in situ forming gel formulation. The efficacy, consistency, and increasing the application of existing injection therapies can be enhanced through optimization of controlled released systems by using FDA approved biodegradable PLGA (poly-d,l-lactide-co-glycolide) polymer. The purpose of this study was to develop different in situ forming implant (ISFI) formulations of buprenorphine hydrochloride for post treatment of drug addicts, acute and chronic pains. The drug releases from different ISFIs membranes with and without Tween 80 were compared over a period of time. Kinetic equation followed the Korsmeyer-Peppas model, as the plots showed high linearity. The influence of this additive on polymer properties was investigated using differential scanning calorimetry (DSC), and the membranes structure was studied by X-ray diffractometry (XRD) and scanning electron microscope (SEM). Data revealed that Tween 80 modified the drug release pattern using diffusion mechanism and decreased the glass transition temperature (T g) significantly. The degree of crystallinity was decreased after phase inversion which helps the dissolution of drug from membrane. The porosity of modified membranes was in accordance with release profiles. These findings suggest four different in situ forming implant formulations which can release various dose of the buprenorphine hydrochloride in a prolonged time. Also this surfactant can be an attractive additive for modifying the release rate of drugs from PLGA-based membrane drug delivery systems. PMID:23960766

Koocheki, S; Madaeni, S S; Niroomandi, P

2011-05-12

180

Development of an enhanced formulation for delivering sustained release of buprenorphine hydrochloride  

PubMed Central

To control the minimum effective dose, and reduce the number and quantity of administered potent drugs are unique features of advanced drug delivery in situ forming gel formulation. The efficacy, consistency, and increasing the application of existing injection therapies can be enhanced through optimization of controlled released systems by using FDA approved biodegradable PLGA (poly-d,l-lactide-co-glycolide) polymer. The purpose of this study was to develop different in situ forming implant (ISFI) formulations of buprenorphine hydrochloride for post treatment of drug addicts, acute and chronic pains. The drug releases from different ISFIs membranes with and without Tween 80 were compared over a period of time. Kinetic equation followed the Korsmeyer–Peppas model, as the plots showed high linearity. The influence of this additive on polymer properties was investigated using differential scanning calorimetry (DSC), and the membranes structure was studied by X-ray diffractometry (XRD) and scanning electron microscope (SEM). Data revealed that Tween 80 modified the drug release pattern using diffusion mechanism and decreased the glass transition temperature (Tg) significantly. The degree of crystallinity was decreased after phase inversion which helps the dissolution of drug from membrane. The porosity of modified membranes was in accordance with release profiles. These findings suggest four different in situ forming implant formulations which can release various dose of the buprenorphine hydrochloride in a prolonged time. Also this surfactant can be an attractive additive for modifying the release rate of drugs from PLGA-based membrane drug delivery systems.

Koocheki, S.; Madaeni, S.S.; Niroomandi, P.

2011-01-01

181

Motivational properties of buprenorphine as assessed by place and taste conditioning in rats  

Microsoft Academic Search

Buprenorphine, a mixed agonist-antagonist opioid with considerable analgesic activity, is currently indicated as a therapeutic\\u000a agent with low abuse potential. Nevertheless, buprenorphine abuse has been recently reported from some countries. Thus the\\u000a present experiments were performed to characterize further the motivational properties of buprenorphine in rats. Rewarding\\u000a and aversive effects were assessed by place preference and taste aversion conditioning, respectively.

M. Gaiardi; M. Bartoletti; A. Bacchi; C. Gubellini; M. Babbini

1997-01-01

182

Buprenorphine detection in hair samples by immunometric screening test: Preliminary experience  

Microsoft Academic Search

The recent introduction of buprenorphine use by the Drug Addiction Services has induced toxicology laboratories to develop new qualitative or semiquantitative screening assay for its determination in hair samples. The aim of this preliminary study was to verify the correlation between the buprenorphine intake and the immunometric screening test results (VMA-T Comedical and buprenorphine CEDIA\\/Thermo-Fisher\\/Microgenics reagents) and therefore their comparison

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

2010-01-01

183

Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects  

Microsoft Academic Search

Previous reports have demonstrated greater antinociception following administration of a buprenorphine\\/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects

J. L. Hay; S. F. La Vincente; A. A. Somogyi; C. B. Chapleo; J. M. White

2011-01-01

184

Stakeholders in opioid substitution treatment policy: similarities and differences in six European countries.  

PubMed

Based on the research papers within this special issue, this overview discusses similarities and differences in stakeholding in drug user opioid substitution treatment policy in Britain, Denmark, Italy, Austria, Poland, and Finland. It explores factors that have influenced stakeholder activity, including the importance of crisis, the impact of evidence, the availability of resources, the wider political context, the influence of moral frameworks and ideologies, and the pressure of external influences. The paper highlights the important differences in the emergence and evolution of stakeholder groups and in the political, cultural, and economic circumstances, which both constrain and enable their activities. PMID:23952506

Thom, Betsy; Duke, Karen; Frank, Vibeke Asmussen; Bjerge, Bagga

2013-08-01

185

Treatment of chronic sternal fistulae following cardiac surgery with a bone substitute.  

PubMed

Chronic sternal infection is a relatively rare complication following cardiac surgery that can cause high morbidity and mortality and can require repeated surgical procedures, including sternal resection, to resolve. However, preserving sternal integrity is essential, particularly in children. A variety of conservative treatments for this complication of cardiac surgery have been reported. Here, we report three cases of children in whom a bone substitute containing tricalcium phosphate and hydroxyapatite was used to fill sternal defects. After extensive surgical debridement, this method yielded primary wound closure with good resolution, preventing the recurrence of sternal infection. PMID:24049817

Lamas, M J; Centella, T

2013-06-01

186

Injection drug users' perceptions of drug treatment services and attitudes toward substitution therapy: a qualitative study in three Russian cities.  

PubMed

This study explored injection drug users' (IDUs) perceptions of drug abuse treatment and treatment providers in three Russian cities as well as their attitudes toward opiate substitution therapy, which is currently not available in Russia. Data were collected from 121 qualitative interviews with IDUs conducted in 2003-2004. Negative perceptions of available treatments were related to poor treatment outcomes, judgmental service providers, lack of psychologic services, and short lengths of stay in treatment. Positive perceptions were associated with receiving psychosocial care and nonjudgmental attitudes from providers. Most participants had heard about opiate substitution therapy, and some had treated themselves using methadone from the black market. Although respondents had doubts that opiate substitution therapy could work effectively in Russia, most agreed that this type of treatment would help IDUs function better in the society. PMID:17499960

Bobrova, Natalia; Alcorn, Ron; Rhodes, Tim; Rughnikov, Iurii; Neifeld, Elena; Power, Robert

2007-05-17

187

A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network  

Microsoft Academic Search

AIMS: The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network.\\u000aDESIGN: Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx,

Walter Ling; Leslie Amass; Steve Shoptaw; Jeffrey J. Annon; Maureen Hillhouse; Dean Babcock; Greg Brigham; Judy Harrer; Malcolm S. Reid; Joan A. Muir; Betty J. Buchan; Debbie Orr; George Woody; Jonathan Krejci; Douglas M. Ziedonis

2005-01-01

188

Clonazepam as Agonist Substitution Treatment for Benzodiazepine Dependence: A Case Report  

PubMed Central

Nowadays, the misuse of benzodiazepines (BZDs) is a cause for a serious concern among pharmacologically inexperienced patients, whether treated or untreated, that could lead to significant complications, including tolerance, dependence, and addiction. We present a case report in which an Italian patient affected by anxiety disorder and treated with BZDs presented a severe case of dependence on BZDs. We treated him according to an agonist substitution approach, switching from the abused BZD to a slow-onset, long-acting, high potency agonist (clonazepam), and looking at the methadone treatment model as paradigm. We decided to use clonazepam for its pharmacokinetic properties. The advantage of choosing a slow-onset, long-lasting BZD for the treatment of our patient was that it led us to a remarkable improvement in the clinical situation, including the cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning, and a better cognition level.

Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Bacciardi, Silvia; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

2013-01-01

189

Buprenorphine: dose-related effects on cocaine and opioid use in cocaine-abusing opioid-dependent humans  

Microsoft Academic Search

Fifteen subjects dependent on both opioids and cocaine completed an ascending and tapering schedule of buprenorphine dosing, with maintenance for 21 days at each dose of buprenorphine (4, 8, 12, 16 mg sublingual daily) during both ascending and tapering phases. Higher doses of buprenorphine led to greater reductions in opioid use: 64.7% of subjects were opioid abstinent for 3 weeks

Richard S. Schottenfeld; Juliana Pakes; Douglas M. Ziedonis; Thomas R. Kosten

1993-01-01

190

Clinical Experience with a Macroporous Synthetic Bone Substitute (Eurocer®) in the Treatment of the Patients with Bone Defects  

Microsoft Academic Search

\\u000a The treatment of bone defects was a major challenge and may still be a problem today. Due to the disadvantages with biologically\\u000a bone grafts there is a high clinical demand for synthetic bone substitution materials. The aim of this prospective study is\\u000a to reveal biocompatibility integration and extension of osseous healing for a biphasic synthetic ceramic bone substitute (Eurocer),\\u000a when

P. D. Sirbu; T. Petreus; Fl. Munteanu; M. Pertea; S. Lunca; V. Poroch; P. Botez

191

[The impact of substitution treatment by methadone among opiate-dependent subjects evaluated by Addiction Severity Index and by urine tests].  

PubMed

Methadone maintenance treatment (MMT) has been evaluated in the United States and in a few other countries. MMT has been developed in France since 1995, and over 5 000 patients receive this treatment. However no French study has yet been published on the efficacy of MMT as assessed by a validated scale. Retention in treatment for one year has been considered as a threshold to define maintenance of treatment benefits after discharge from a methadone program; determination of retention predictors is important. Over a three year period, we evaluated patients at admission and during treatment using the Addiction Severity Index (ASI), and urine drug screening was performed weekly; 95 patients (66 males and 29 females) were evaluated at intake. Their mean age was 30.2 5.5, and they had used opioids for a mean of 10.6 5.7 years. Their ASI severity scores for drugs were over 5, showing a clear need for treatment. Female patients differed from males only in the employment-finances ASI score; 43 patients completed at least one year of treatment, after which their drug and legal composite scores significantly improved. No significant changes in their consumption of cocaine, alcohol, benzodiazepines or cannabis were found, but they smoked fewer cigarettes at 12 months. Demographics, ASI severity scores, and history of suicide attempts did not differentiate one-year completers from dropouts (n=16). However, dropouts had used more buprenorphine and less methadone in the 30 days preceding their admission, and they received a lower dose of methadone during treatment. Our population is comparable to other French MMT populations; they enter treatment after a long history of opioid dependence. The improvement found on the ASI composite scores is also similar to the improvement described in other international studies. Dropouts in our study seem to be more treatment-resistant patients, in the sense that they had used more buprenorphine before intake and were not stabilized with it; and they may have had a more negative attitude towards methadone. PMID:12386547

Trémeau, F; Darreye, A; Khidichian, F; Weibel, H; Kempf, M; Greth, Ph; Schneider, J L; Wantz, C; Weber, B; Stépien, S; Macher, J P

192

Enzyme immunoassay validation for the detection of buprenorphine in urine.  

PubMed

A solid-phase enzyme immunoassay involving microtiter plates was proposed by Microgenics to screen buprenorphine in urine. The intra-assay precision at 10 ng/mL was 7.7% (coefficient of variation). The immunoassay was determined to have no cross-reactivity with codeine, dihydrocodeine, morphine, ethylmorphine, 6-monoacetylmorphine, methadone, pholcodine, propoxyphene, dextromoramide, and dextromethorphan at 1 and 10 mg/L. A low cross-reactivity (3% at 1 ng/mL) was observed at low concentrations of norbuprenorphine. After comparing this new immunological test (Singlestep ELISA) for 76 urine specimens with our validated high-performance liquid chromatography-electrospray mass spectrometry (HPLC-ES-MS) procedure, an optimum cutoff concentration of 2 ng/mL was determined for the kit. At this cutoff, the screening assay was able to determine more than 90% of true results with 43.4% true positives and 48.7% true negatives. Four positive urines (5.3%) were not confirmed by HPLC-ES-MS. In only one case, the negative urine test was confirmed as positive by HPLC-ES-MS (buprenorphine: 62.5 ng/mL). Buprenorphine concentrations determined by HPLC-ES-MS ranged from 1.2 to 1052 ng/mL. Of the four potential adulterants (hypochloride 50 mL/L, sodium nitrite 50 g/L, liquid soap 50 mL/L, and sodium chloride 50 g/L) that might be added to a positive urine specimen, none were able to cause a false-negative response by the immunoassay. The results of this study support the concept that the Singlestep ELISA for buprenorphine determination in urine should be considered as a new, valided screening procedure. PMID:12670004

Cirimele, V; Kintz, P; Lohner, S; Ludes, B

2003-03-01

193

Inhibition of ribonucleotide reductase by 2'-substituted deoxycytidine analogs: possible application in AIDS treatment.  

PubMed Central

After phosphorylation to the corresponding diphosphates, 2'-azido-2'-deoxycytidine and 2'-difluorocytidine act as powerful inhibitors of ribonucleotide reductase. Phosphorylation requires deoxycytidine kinase, an enzyme with particularly high activity in lymphoid cells. Therefore, the deoxycytidine analogs can be expected to inhibit the reductase with some specificity for the lymphoid system. Pretreatment of human CEM lymphoblasts with the analogs considerably increased the phosphorylation of 3'-deoxy-3'-azidothymidine (AzT). The increased phosphorylation of AzT is caused by a prolongation of the S phase of the cell cycle. Our results suggest the possibility of a combination of 2'-substituted deoxycytidine analogs with AzT in the treatment of AIDS. Gao et al. [Gao, W.-Y., Cara, A., Gallo, R. C. & Lori, F. (1993) Proc. Natl. Acad. Sci. USA 90, 8925-8928] have suggested the use of the ribonucleotide reductase inhibitor hydroxyurea for this purpose, since the resulting decrease in the size of deoxyribonucleotide pools decreases the processivity of the HIV reverse transcriptase. From our results it would appear that the 2'-substituted deoxycytidine analogs might be preferable to hydroxyurea.

Bianchi, V; Borella, S; Calderazzo, F; Ferraro, P; Chieco Bianchi, L; Reichard, P

1994-01-01

194

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

ERIC Educational Resources Information Center

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

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

2006-01-01

195

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

PubMed

In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing. PMID:23244551

Tenore, Peter L

2012-01-01

196

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

PubMed

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 (<0.5 µg/L) for buprenorphine and metabolites and positive for amisulpride. Although the cross-reactivity of amisulpride and 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. PMID:23471956

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

2013-03-06

197

Pain management after lumbar spinal fusion surgery using continuous subcutaneous infusion of buprenorphine  

Microsoft Academic Search

Purpose. The continuous subcutaneous infusion (CSI) technique is a simple, inexpensive method for managing postoperative pain. We examined the analgesic effects of CSI of buprenorphine in patients undergoing lumbar spinal fusion surgery. Methods. The patients were randomly assigned to one of three groups for postoperative pain management: control group (n = 17), high-dose buprenorphine group (BH group, n = 17),

Tomoyuki Kawamata; Yasumitsu Sato; Yukitoshi Niiyama; Keiichi Omote; Akiyoshi Namiki

2005-01-01

198

Illicit Use of Buprenorphine in a Community Sample of Young Adult Non-Medical Users of Pharmaceutical Opioids  

PubMed Central

BACKGROUND There is growing evidence about illicit use of buprenorphine in the U.S. The study aims to: 1) identify prevalence and predictors of illicit buprenorphine use in a community sample of 396 young adult (18-23 years old) non-medical users of pharmaceutical opioids; 2) describe knowledge, attitudes and behaviors linked to illicit buprenorphine use as reported by a qualitative sub-sample (n=51). METHODS Participants were recruited using respondent-driven sampling. Qualitative interview participants were selected from the larger sample. The sample (n=396) was 54% male and 50% white; 7.8% reported lifetime illicit use of buprenorphine. RESULTS Logistic regression analysis results indicate that white ethnicity, intranasal inhalation of pharmaceutical opioids, symptoms of opioid dependence, and a greater number of pharmaceutical opioids used in lifetime were statistically significant predictors of illicit buprenorphine use. Qualitative interviews revealed that buprenorphine was more commonly used by more experienced users who were introduced to it by their “junkie friends.” Those who used buprenorphine to self-medicate withdrawal referred to it as a “miracle pill.” When used to get high, reported experiences ranged from “the best high ever” to “puking for days.” Participants reported using buprenorphine/naloxone orally or by intranasal inhalation. Injection of buprenorphine without naloxone was also reported. CONCLUSION Our findings suggest that illicit buprenorphine use is gaining ground primarily among whites and those who are more advanced in their drug use careers. Continued monitoring is needed to better understand evolving patterns and trends of illicit buprenorphine use.

Daniulaityte, Raminta; Falck, Russel; Carlson, Robert G.

2011-01-01

199

Pharmacokinetic Interactions Between Buprenorphine/Naloxone and Tipranavir/Ritonavir in HIV-Negative Subjects Chronically Receiving Buprenorphine/Naloxone  

PubMed Central

HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid-dependence treatment medications can occur. HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacokinetic evaluation of open-label, twice daily tipranavir 500 mg co-administered with ritonavir 200 mg (TPV/r). Twelve subjects were enrolled and 10 completed the study. Prior to starting TPV/r, the geometric mean BUP AUC0-24h and Cmax were 43.9 ng?hr/mL and 5.61 ng/mL, respectively. After achieving steady-state with TPV/r (?7 days), these values were similar at 43.7 ng?hr/mL and 4.84 ng/mL, respectively. Similar analyses for norBUP, the primary metabolite of BUP, demonstrated a reduction in geometric mean for AUC0-24h [68.7 to 14.7 ng?hr/mL; ratio=0.21 (90% CI 0.19–0.25)] and Cmax [4.75 to 0.94 ng/mL; ratio=0.20 (90% CI 0.17–0.23)]. The last measurable NLX concentration (Clast) in the concentration-time profile, never measured in previous BUP/NLX interaction studies with antiretroviral medications, was decreased by 20%. Despite these pharmacokinetic effects on BUP metabolites and NLX, no clinical opioid withdrawal symptoms were noted. TPV steady-state AUC0-12h and Cmax decreased 19% and 25% respectively, and Cmin was relatively unchanged when compared to historical control subjects receiving TPV/r alone. No dosage modification of BUP/NLX is required when co-administered with TPV/r. Though mechanistically unclear, it is likely that decreased plasma RTV levels while on BUP/NLX contributed substantially to the decrease in TPV levels. BUP/NLX and TPV/r should therefore be used cautiously to avoid decreased efficacy of TPV in patients taking these agents concomitantly.

Bruce, R. Douglas; Altice, Frederick L.; Moody, David E.; Lin, Shen-Nan; Fang, Wenfang B.; Sabo, John P.; Wruck, Jan M.; Piliero, Peter J.; Conner, Carolyn; Andrews, Laurie; Friedland, Gerald H.

2009-01-01

200

High-sensitivity analysis of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in plasma and urine by liquid chromatography-mass spectrometry.  

PubMed

A new method using ultra-fast liquid chromatography and tandem mass spectrometry (UFLC-MS/MS) was developed for the simultaneous determination of buprenorphine and the metabolites norbuprenorphine, buprenorphine-3?-glucuronide, and norbuprenorphine-3?-glucuronide in plasma and urine. Sample handling, sample preparation and solid-phase extraction procedures were optimized for maximum analyte recovery. All four analytes of interest were quantified by positive ion electrospray ionization tandem mass spectrometry after solid-phase microextraction. The lower limits of quantification in plasma were 1pg/mL for buprenorphine and buprenorphine glucuronide, and 10pg/mL for norbuprenorphine and norbuprenorphine glucuronide. The lower limits of quantitation in urine were 10pg/mL for buprenorphine, norbuprenorphine and their glucuronides. Overall extraction recoveries ranged from 68-100% in both matrices. Interassay precision and accuracy was within 10% for all four analytes in plasma and within 15% in urine. The method was applicable to pharmacokinetic studies of low-dose buprenorphine. PMID:24095872

Regina, Karen J; Kharasch, Evan D

2013-09-08

201

Treating Homeless Opioid Dependent Patients with Buprenorphine in an Office-Based Setting  

PubMed Central

Context Although office-based opioid treatment with buprenorphine (OBOT-B) has been successfully implemented in primary care settings in the US, its use has not been reported in homeless patients. Objective To characterize the feasibility of OBOT-B in homeless relative to housed patients. Design A retrospective record review examining treatment failure, drug use, utilization of substance abuse treatment services, and intensity of clinical support by a nurse care manager (NCM) among homeless and housed patients in an OBOT-B program between August 2003 and October 2004. Treatment failure was defined as elopement before completing medication induction, discharge after medication induction due to ongoing drug use with concurrent nonadherence with intensified treatment, or discharge due to disruptive behavior. Results Of 44 homeless and 41 housed patients enrolled over 12 months, homeless patients were more likely to be older, nonwhite, unemployed, infected with HIV and hepatitis C, and report a psychiatric illness. Homeless patients had fewer social supports and more chronic substance abuse histories with a 3- to 6-fold greater number of years of drug use, number of detoxification attempts and percentage with a history of methadone maintenance treatment. The proportion of subjects with treatment failure for the homeless (21%) and housed (22%) did not differ (P?=?.94). At 12 months, both groups had similar proportions with illicit opioid use [Odds ratio (OR), 0.9 (95% CI, 0.5–1.7) P?=?.8], utilization of counseling (homeless, 46%; housed, 49%; P?=?.95), and participation in mutual-help groups (homeless, 25%; housed, 29%; P?=?.96). At 12 months, 36% of the homeless group was no longer homeless. During the first month of treatment, homeless patients required more clinical support from the NCM than housed patients. Conclusions Despite homeless opioid dependent patients’ social instability, greater comorbidities, and more chronic drug use, office-based opioid treatment with buprenorphine was effectively implemented in this population comparable to outcomes in housed patients with respect to treatment failure, illicit opioid use, and utilization of substance abuse treatment.

LaBelle, Colleen T.; Richardson, Jessica M.; O'Connell, James J.; Hohl, Carole A.; Cheng, Debbie M.; Samet, Jeffrey H.

2007-01-01

202

Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain.  

PubMed

There is a growing body of evidence to support the use of medical cannabis as an adjunct to or substitute for prescription opiates in the treatment of chronic pain. When used in conjunction with opiates, cannabinoids lead to a greater cumulative relief of pain, resulting in a reduction in the use of opiates (and associated side-effects) by patients in a clinical setting. Additionally, cannabinoids can prevent the development of tolerance to and withdrawal from opiates, and can even rekindle opiate analgesia after a prior dosage has become ineffective. Novel research suggests that cannabis may be useful in the treatment of problematic substance use. These findings suggest that increasing safe access to medical cannabis may reduce the personal and social harms associated with addiction, particularly in relation to the growing problematic use of pharmaceutical opiates. Despite a lack of regulatory oversight by federal governments in North America, community-based medical cannabis dispensaries have proven successful at supplying patients with a safe source of cannabis within an environment conducive to healing, and may be reducing the problematic use of pharmaceutical opiates and other potentially harmful substances in their communities. PMID:22880540

Lucas, Philippe

203

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

PubMed Central

Background Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial ?-opiod agonist and a ?-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. Methods A budgetary impact model was developed to estimate healthcare costs of the addition of B/N combination to the therapeutic arsenal for treating opioid dependent patients, during a 3-year period under the National Health System perspective. Inputs for the model were obtained from the specialized scientific literature. Detailed information concerning resource consumption (drug cost, logistics, dispensing, medical, psychiatry and pharmacy supervision, counselling and laboratory test) was obtained from a local expert panel. Costs are expressed in euros (€, 2010). Results The number of patients estimated to be prescribed B/N combination was 2,334; 2,993 and 3,589 in the first, second and third year respectively. Total budget is €85,766,129; €79,855,471 and €79,137,502 in the first, second and third year for the scenario without B/N combination. With B/N combination the total budget would be €86,589,210; €80,398,259 and €79,708,964 in the first, second and third year of the analyses. Incremental cost/patient comparing the addition of the B/N combination to the scenario only with methadone is €10.58; €6.98 and €7.34 in the first, second and third year respectively. Conclusion Addition of B/N combination would imply a maximum incremental yearly cost of €10.58 per patient compared to scenario only with methadone and would provide additional benefits.

2012-01-01

204

Opioid Dependence Treatment: Options In Pharmacotherapy  

PubMed Central

The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed.

Stotts, Angela L.; Dodrill, Carrie L.; Kosten, Thomas R.

2010-01-01

205

Tramadol induces conditioned place preference in rats: interactions with morphine and buprenorphine.  

PubMed

Surveys and drug surveillance have demonstrated that the abuse liability of tramadol is considerably low in the general population but appears to be higher in opiate addicts, and this difference could attribute to the poly-drug abuse of opioid addicts, although this hypothesis has not been tested in the laboratory. The present study examined the interactions between tramadol and a full ? opioid receptor agonist morphine or a partial ? opioid receptor agonist buprenorphine in a conditioned place preference (CPP) paradigm in rats. Rats were conditioned with tramadol (2-54 mg/kg, i.p.), morphine (0.125-8 mg/kg, s.c.), buprenorphine (0.01-0.316 mg/kg, s.c.) or a combination of a subeffective dose of tramadol (2mg/kg) with a subeffective dose of morphine or buprenorphine and the CPP effect was measured. The retention of CPP effect was also examined. Tramadol, morphine and buprenorphine all produced a dose-dependent and significant CPP. A smaller dose of tramadol (2mg/kg) enhanced morphine- and buprenorphine-induced CPP and shifted the dose-effect curves of both drugs leftward. In addition, the combination of tramadol with morphine or buprenorphine prolonged the retention of CPP. These findings indicate that tramadol potentiates the rewarding effects of morphine or buprenorphine largely in an additive manner and support the general contention that tramadol has relatively low abuse liability. PMID:22626615

Zhang, Min; Jing, Li; Liu, Qing; Wen, Rui-Ting; Li, Jun-Xu; Li, Yu-Ling; Gong, Qi; Liang, Jian-Hui

2012-05-22

206

Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.  

PubMed

Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects. PMID:20728384

Hay, J L; La Vincente, S F; Somogyi, A A; Chapleo, C B; White, J M

2010-08-21

207

Synthesis of N-substituted ?-hexonolactams as pharmacological chaperones for the treatment of N370S mutant Gaucher disease.  

PubMed

A series of N-substituted ?-hexonolactams have been designed and prepared by a concise route with a tandem ring-expansion reaction as the key step. Some of the N-substituted ?-hexonolactams show better enhancements to N370S mutant ?-glucocerebrosidase activity than NB-DNJ and NN-DNJ. Both the experimental results and computational studies highlight the importance of the carbonyl group for stabilizing protein folds in the mutant enzyme. The structure-activity relationships are also discussed. These novel N-alkylated iminosugars are promising pharmacological chaperones for the treatment of N370S mutant Gaucher disease. PMID:22286559

Wang, Guan-Nan; Twigg, Gabriele; Butters, Terry D; Zhang, Siwei; Zhang, Liangren; Zhang, Li-He; Ye, Xin-Shan

2012-01-27

208

Local and gap modes due to a substitutional impurity in alkali halides: One dimensional treatment  

Microsoft Academic Search

Local modes for substitutional impurity H in NaCl, NaBr and KCl have been calculated. Isotope shift for 35Cl and 37Cl substituted in KI has also been calculated. Good agreement with the experimental data has been obtained.

Shashi Bala; A. K. Ghatak; D. P. S. Malik

1972-01-01

209

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

SciTech Connect

In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg{sup -1} was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg{sup -1} buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P < 0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg{sup -1} buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.

Hreiche, Raymond [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Megarbane, Bruno [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France) and Assistance Publique-Hopitaux de Paris, Hopital Lariboisiere, Reanimation Medicale et Toxicologique, Universite Paris 7, 75010 Paris (France)]. E-mail: bruno-megarbane@wanadoo.fr; Pirnay, Stephane [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Laboratoire de Toxicologie, Prefecture de Police de Paris, 75012 Paris (France); Borron, Stephen W. [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Department of Surgery, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Monier, Claire [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Risede, Patricia [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Milan, Nathalie [Laboratoire de Toxicologie, Prefecture de Police de Paris, 75012 Paris (France); Descatoire, Veronique [INSERM U481, Faculte de Medecine Xavier Bichat, 75018 Paris (France); Pessayre, Dominique [INSERM U481, Faculte de Medecine Xavier Bichat, 75018 Paris (France); Baud, Frederic J. [INSERM U705, CNRS UMR 7157, Universite Paris 7, Universite Paris 5, Hopital Fernand Widal, 75010 Paris (France); Assistance Publique-Hopitaux de Paris, Hopital Lariboisiere, Reanimation Medicale et Toxicologique, Universite Paris 7, 75010 Paris (France)

2006-12-15

210

Effects of buprenorphine on intracerebral collagenase-induced hematoma in Sprague-Dawley rats.  

PubMed

We evaluated the effects of buprenorphine (0.05 mg/kg intraperitoneally) after collagenase-induced intracerebral hemorrhage in Sprague-Dawley rats. Methods of evaluation included serum biochemistry, behavioral tests (neurologic exam and rotarod treadmill), and histopathology. Serum biochemistry parameters showed no change after surgery in controls and buprenorphine-treated animals. At 48 h after collagenase injections, the performance of treated rats on the rotarod treadmill test was not significantly different from that of untreated rats, but the neurologic exams of treated rats showed significantly improved performance. Although the volume of the hematoma was reduced with buprenorphine, the number of necrotic neurons in the penumbra was significantly increased. These data indicate that administration of buprenorphine led to neurologic and histopathologic differences in a rat model of intracerebral hemorrhage, and data from such studies should be interpreted carefully if an opioid analgesic is used to minimize pain. PMID:17487946

Ferland, Catherine; Veilleux-Lemieux, D; Vachon, Pascal

2007-05-01

211

Ability to Work and Employability of Patients in Opioid Substitution Treatment Programs in Slovenia  

PubMed Central

Aim To assess the ability to work and employability of individuals taking part in opioid substitution treatment programs (OSTP). Methods The study was composed of two surveys. In the first survey, 237 of 480 patients enrolled in OSTP responded to the questionnaire about their employment status, opinion about employment, and perception of assignments before and during OSTP. In the second survey, 66 of 100 employers responded to the questionnaire on the occurrence, perception, and management of addiction problems in their companies. Results Unemployment rate in individuals enrolled in OSTP was 43.5% and decreased during OSTP by 10.5% (P?=?0.027). Irregular use of OSTP medications was the most important factor for unemployment (odds ratio, 2.44; P?=?0.016). OSTP was highly effective in achieving a positive change in patients’ perception of different kinds of assignments previously perceived as beyond their abilities. Thus, perception of mentally demanding assignments (P?

Bilban, Marjan; Kastelic, Andrej; Zaletel-Kragelj, Lijana

2008-01-01

212

Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells  

Microsoft Academic Search

A morphine alkaloid derivative, buprenorphine hydrochloride, induces apoptosis in NG108-15 cells. Apoptosis was detected mainly by apoptosis-specific DNA fragmentation and morphological changes. This apoptosis was dose-dependent and the time-course experiment indicated that DNA fragmentation occurred within 4 h after administration of buprenorphine hydrochloride. Specific inhibitors of the previously characterized apoptotic signal cascade as well as antagonists for opioid receptors were

Fumihiko Kugawa; Ken Arae; Akemichi Ueno; Masatada Aoki

1998-01-01

213

The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials  

Microsoft Academic Search

This study compared the neurological development of 4month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants. Participants were 30 buprenorphine-maintained women, 22 methadone-maintained women and 33 non opioid-dependent controls, and their infants. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study. Groups were matched for

Justine N. Whitham; Nicola J. Spurrier; Michael G. Sawyer; Peter A. Baghurst; John E. Taplin; Jason M. White; Andrea L. Gordon

2010-01-01

214

Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in human placenta by liquid chromatography mass spectrometry  

PubMed Central

A LCMS method was developed and validated for the determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in placenta. Quantification was achieved by selected ion monitoring of m/z 468.4 (BUP), 414.3 (NBUP), 644.4 (BUP-Gluc), and 590 (NBUP-Gluc). BUP and NBUP were identified monitoring MS2 fragments m/z 396, 414 and 426 for BUP, and 340, 364 and 382 for NBUP, and glucuronide conjugates monitoring MS3 fragments m/z 396 and 414 for BUP-Gluc, and 340 and 382 for NBUP-Gluc. Linearity was 1–50 ng/g. Intra-day, inter-day and total assay imprecision (% RSD) were <13.4%, and analytical recoveries were 96.2–113.1%. Extraction efficiencies ranged from 40.7–68%, process efficiencies 38.8–70.5%, and matrix effect 1.3–15.4%. Limits of detection were 0.8 ng/g for all compounds. An authentic placenta from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. BUP was not detected but metabolite concentrations were NBUP-Gluc 46.6, NBUP 15.7 and BUP-Gluc 3.2 ng/g.

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

2011-01-01

215

Evaluation of the physical properties of water treatment residue for use as a soil substitute compared with decomposed granite soil  

Microsoft Academic Search

To evaluate water treatment residue (WTR) as a soil substitute material, its physical properties were investigated and compared with decomposed granite soil (DGS). For comparison purposes, relative gas diffusivity (D\\/D0), saturated hydraulic conductivity (Ks), water retention curve, porosity and readily available water were measured for both the WTR and the DGS. The measured D\\/D0, Ks, water retention ability and porosity

Seok-Gon Park; Mizue Ohashi; Kiyoshi Kurosawa; Young-Jin Kim; Hisashi Yahata

2010-01-01

216

Generic substitution in the treatment of epilepsy: Case evidence of breakthrough seizures  

Microsoft Academic Search

Objective: There are concerns that generic and brand antiepileptic drugs (AEDs) may not be ther- apeutically equivalent. This study investigated how generic AED substitution may have negative consequences. Methods: Sixty-nine of 150 physicians who participated in a large survey on generic AED substi- tution completed a case review form regarding a patient who experienced a loss of seizure control due

M. J. Berg; R. A. Gross; K. J. Tomaszewski; W. M. Zingaro; L. S. Haskins

2008-01-01

217

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

PubMed

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

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

2011-08-31

218

Facts about Buprenorphine for Treatment of Opioid Addiction  

MedlinePLUS

... like heart disease or dia betes. A chronic disease is a medical condition for life. It cannot be cured, but it ... about addiction. They talked about it as a disease and not a moral failing …. I had a medical condition …. And that was a big relief for me ...

219

Evaluation of the One-Step™ ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens  

Microsoft Academic Search

A solid-phase enzyme immunoassay involving microtiter plates was recently proposed by International Diagnostic Systems corporation (IDS) to screen for buprenorphine in human serum. The performance of the kit led us to investigate its applicability in other biological matrices such as urine or blood, and also hair specimens. Low concentrations of buprenorphine were detected with the ELISA test and confirmed by

V Cirimele; S Etienne; M Villain; B Ludes; P Kintz

2004-01-01

220

Solvent substitution  

SciTech Connect

The DOE Environmental Restoration and Waste Management Office of Technology Development and the Air Force Engineering and Services Center convened the First Annual International Workshop on Solvent Substitution on December 4--7, 1990. The primary objectives of this joint effort were to share information and ideas among attendees in order to enhance the development and implementation of required new technologies for the elimination of pollutants associated with industrial use of hazardous and toxic solvents; and to aid in accelerating collaborative efforts and technology transfer between government and industry for solvent substitution. There were workshop sessions focusing on Alternative Technologies, Alternative Solvents, Recovery/Recycling, Low VOC Materials and Treatment for Environmentally Safe Disposal. The 35 invited papers presented covered a wide range of solvent substitution activities including: hardware and weapons production and maintenance, paint stripping, coating applications, printed circuit boards, metal cleaning, metal finishing, manufacturing, compliance monitoring and process control monitoring. This publication includes the majority of these presentations. In addition, in order to further facilitate information exchange and technology transfer, the US Air Force and DOE solicited additional papers under a general Call for Papers.'' These papers, which underwent review and final selection by a peer review committee, are also included in this combined Proceedings/Compendium. For those involved in handling, using or managing hazardous and toxic solvents, this document should prove to be a valuable resource, providing the most up-to-date information on current technologies and practices in solvent substitution. Individual papers are abstracted separated.

Not Available

1990-01-01

221

Substitution treatment in the era of "recovery": An analysis of stakeholder roles and policy windows in Britain.  

PubMed

Based on documentary analyses and interviews with twenty key informants in 2012, this paper analyses the shift in British drugs policy towards "recovery" from the perspectives of major stakeholders. The processes involved in reopening the debate surrounding the role of substitution treatment and its re-emergence on to the policy agenda are examined. Drawing on Kingdon's work on agenda-setting, the ways in which methadone maintenance was challenged and defended by key stakeholders in the initial phase of policy development and the negotiation of a "recovery" focus as the organizing concept for British drugs policy are explored. Study limitations are noted. PMID:23952509

Duke, Karen; Herring, Rachel; Thickett, Anthony; Thom, Betsy

2013-08-01

222

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

PubMed

Despite the frequent clinical use of buprenorphine in reptiles, its antinociceptive efficacy is not known. In a randomized, complete cross-over study, the antinociceptive efficacy of buprenorphine (0.2 mg/kg s.c.) was compared with hydromorphone (0.5 mg/kg s.c.), and saline (0.9% s.c. equivalent volume) in 11 healthy red-eared slider turtles (Trachemys scripta elegans). Additionally, buprenorphine at 0.1 and 1 mg/kg was compared with saline in six turtles. Hindlimb withdrawal latencies were measured after exposure to a focal, thermal noxious stimulus before and between 3 hr and up to 96 hr after drug administration. Buprenorphine did not significantly increase hindlimb withdrawal latencies at any time point compared with saline. In contrast, hydromorphone administration at 0.5 mg/kg significantly increased hindlimb withdrawal latencies for up to 24 hr. These results show that hydromorphone, but not buprenorphine, provides thermal antinociception in red-eared slider turtles. PMID:23082538

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

2012-09-01

223

Influence of oral buprenorphine, oral naltrexone or morphine on the effects of laparotomy in the rat.  

PubMed

The effects of oral administration of buprenorphine ('buprenorphine jello'), a partial mu opioid agonist, oral naltrexone, a mu antagonist and morphine, a mu agonist, were investigated in rats following laparotomy. Food and water consumption and body weight were reduced in rats that underwent surgery. Rats undergoing anaesthesia alone showed only a small reduction in water consumption. Administration of oral buprenorphine (0.5 mg/kg in flavoured gelatin) decreased the effects of surgery on body weight and water intake when compared to untreated (vehicle alone) controls. The magnitude of this beneficial effect was similar to that seen in previous studies using subcutaneous administration of buprenorphine. The fall in body weight and food and water intake following surgery was similar in the groups which received morphine and the control group which received vehicle (jelly). Neither the magnitude of the fall in body weight, and food and water intake, nor the behavioural scores differed between naltrexone and control (vehicle alone) rats following surgery. This suggests that the beneficial effects of partial agonist analgesics are mediated by a reduction in pain rather than by antagonism of endogenous opioids. Both anaesthesia and surgery caused changes in behaviour, but the major effects of buprenorphine in normal (unoperated) rats severely limited the value of behavioural parameters as a means of assessing possible beneficial effects of analgesic administration. PMID:9587897

Liles, J H; Flecknell, P A; Roughan, J; Cruz-Madorran, I

1998-04-01

224

Partial versus full agonists for opioid-mediated analgesia--focus on fentanyl and buprenorphine.  

PubMed

In contrast to other opioids, fentanyl and buprenorphine share a number of physicochemical properties that render both agents potentially suitable for transdermal delivery. However, there are significant differences between them in terms of their pharmacological profiles, as fentanyl is a full mu opioid receptor agonist capable of exerting a maximal response in certain tissues, while buprenorphine is a partial agonist unable to exert this maximum effect even at high doses. This review examines the hypothesis that partial opioid agonists would confer a number of benefits over full agonists, namely effective analgesia with a better tolerability and a lower propensity for addiction, with respect to fentanyl and buprenorphine. An attempt is also made to correlate clinical differences between these drugs with their respective agonist profiles and other differential pharmacokinetic/pharmacodynamic properties. Despite a dearth of directly comparative trials, the pharmacology of fentanyl and buprenorphine is well documented. Considerable data concerning buprenorphine suggest that the advantages initially espoused for partial opioid agonists are not borne out in clinical practice. Indeed, it may be postulated that full mu opioid agonists, particularly those with high selectivity and potency such as fentanyl, have a superior clinical profile and fulfill the above criteria more closely. Relative receptor binding, selectivity, potency and intrinsic efficacy of the opioids appear to be key determinants of their individual pharmacological profiles, contributing significantly to the heterogeneity of this class of analgesics. PMID:12461829

Zuurmond, W W; Meert, T F; Noorduin, H

2002-01-01

225

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

PubMed

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 policies and practices totally unsupported by scientific evidence and inquiry, officials in Russia have rendered narcology (and medical practice) insensitive to the alarming rates and continued spread of HIV, with its dire morbidity and mortality rates in the Russian Federation, turning their backs on all the other health problems posed by opiate use and dependence itself. PMID:18577225

Elovich, Richard; Drucker, Ernest

2008-06-24

226

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

PubMed Central

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 policies and practices totally unsupported by scientific evidence and inquiry, officials in Russia have rendered narcology ( and medical practice) insensitive to the alarming rates and continued spread of HIV, with its dire morbidity and mortality rates in the Russian Federation, turning their backs on all the other health problems posed by opiate use and dependence itself.

Elovich, Richard; Drucker, Ernest

2008-01-01

227

Effects of Indomethacin and Buprenorphine Analgesia on the Postoperative Recovery of Mice  

PubMed Central

Buprenorphine (Bup) is the most commonly used analgesic in mice, yet few objective assessments address its superiority for postsurgical recovery. In mice, IP implantation of a radiotelemetry device induces decreases in body weight (BW), food and water intake (FI, WI), core temperature (Tc), and activity levels that persist approximately 14 d in the absence of analgesia. To compare the efficacy of Bup with that of the nonsteroidal antiinflammatory drug indomethacin (Indo) for postsurgical recovery, male C57BL/6J mice were treated on the day of radiotelemetry implantation with Bup (0.3 mg/kg SC) or Indo (1 mg/kg SC) followed by treatment with Indo (1 mg/kg PO) on the next day (Bup–Indo versus Indo–Indo). Responses were compared between treatments in mice implanted with a radiotelemetry device and those that did not undergo surgery. Changes in BW, FI, WI, Tc, and activity were examined throughout 14 d of recovery. Indo–Indo was more efficacious in inhibiting postsurgical BW, FI, and WI reductions, compared with Bup–Indo. Bup also reduced BW and FI in the absence of surgery, indicating a nonspecific effect of this drug on these variables. Indo–Indo treatment was associated with higher activity levels during lights-on–to–lights-off transition periods compared with that observed with Bup–Indo. According to 5 objective measures of surgical recovery, our data suggest that Indo–Indo treatment is more efficacious than is Bup–Indo for postsurgical recovery of radiotelemetry-implanted mice.

Blaha, Michael D; Leon, Lisa R

2008-01-01

228

The use of buprenorphine as an analgesic after rodent embryo transfer.  

PubMed

Many researchers are reluctant to administer analgesia after rodent embryo transfer, primarily out of concern that analgesia will affect embryo implantation. According to the Animal Welfare Act and the Guide, however, embryo transfer constitutes major survival surgery and is likely to cause pain and distress despite its minimally invasive nature. The authors examined the effects of a single dose of the analgesic buprenorphine on mice that underwent embryo transfer. In mice treated with buprenorphine, the number of viable implanted embryos was typically equal to or greater than that in untreated mice. All mice seemed quiet, alert and active after surgery. PMID:18216800

Krueger, Karen L; Fujiwara, Yuko

2008-02-01

229

Risk Factors of Treatment-Limiting Anemia after Substitution of Zidovudine for Stavudine in HIV-Infected Adult Patients on Antiretroviral Treatment  

PubMed Central

Background Anemia is the main concern among patients using a zidovudine (AZT)-based antiretroviral treatment (ART). Some studies suggested weight-adjusted AZT dosing as a way to reduce toxicity. We analyzed the risk factors associated with AZT-induced anemia in a cohort using AZT as substitution for stavudine (D4T). Methods We retrospectively studied HIV-infected patients in a referral hospital in Phnom Penh, Cambodia between 2003 and 2011. Factors associated with AZT-related anemia requiring AZT-discontinuation within the first year after AZT initiation were analyzed using Cox regression. Results Overall, 1180 patients, 60.5% female, were included. At AZT initiation, the median hemoglobin was 12.7 g/dL (IQR 11.7–13.9), the median weight: 51 kg (IQR 45–58) and the median time on ART prior to AZT substitution: 1.4 years (IQR 1.0–2.0). Within one year follow-up, 139 patients (11.8%) developed anemia requiring AZT discontinuation. Overall, there was no independent association of body weight with AZT discontinuation. AZT discontinuation was associated with lower hemoglobin level when starting AZT; older age and taking D4T-based ART less than one year prior to AZT. In exploratory analysis, a linear increase in risk of grade 2–4 anemia with lower body weight was seen if starting AZT substitution within less than one year of D4T-based ART. Conclusion Our findings argue against the need of weight-based dosing of AZT to reduce anemia among patients using AZT as substitution for D4T. Whether this also applies to ART-naïve individuals remains to be assessed. Future studies with AZT dose reduction should assess efficacy and overall tolerance of AZT.

Phe, Thong; Thai, Sopheak; Veng, Chhunheng; Sok, Sopheak; Lynen, Lutgarde; van Griensven, Johan

2013-01-01

230

The politics of place(ment): problematising the provision of hepatitis C treatment within opiate substitution clinics.  

PubMed

The hepatitis C virus (HCV) epidemic is a significant public health challenge in Australia. Current initiatives to expand access to HCV treatment focus on opiate substitution therapy (OST) settings where the prevalence of hepatitis C among clients is high. In Australia, the provision of OST for many clients is via large clinics, with an estimated median of 150 clients per service. Conceptually informed by the work of Michel Foucault, our analysis of the proposed integrated treatment model focuses on the critical but overlooked question of organisational culture and power operating within OST. We argue that the specific context of OST not merely reflects but actively participates in the political economy of social exclusion via which the socio-spatial segregation and stigmatisation of the service user as 'drug user' is enacted. This paper analyses data collected from two samples during 2008/9: OST clients living in New South Wales, Australia and a range of OST health professionals working in Australian settings. In total, 27 interviews were conducted with current OST clients; 19 by phone and 8 face-to-face. One focus group and 16 telephone interviews were conducted with OST health professionals. Our analysis of key themes emerging from the interview data suggests that the successful introduction of HCV treatment within the OST clinic is not a given. We are concerned that particular areas of tension, if not explicit contradiction, have been overlooked in current research and debates informing the proposed combination treatment model. We question the appropriateness of co-locating a notoriously arduous, exacting treatment (HCV) within the highly surveillant and regulatory environment of OST. While applauding the intention to improve access to HCV care and treatment for people who inject drugs we caution against a treatment model that risks further entrenching (socio-spatial) stigmatisation amongst those already experiencing significant marginalisation. PMID:22133583

Rance, Jake; Newland, Jamee; Hopwood, Max; Treloar, Carla

2011-11-20

231

Artificial neural network assessment of substitutive pharmacological treatments in hospitalised intravenous drug users.  

PubMed

Artificial neural networks (ANNs) provide better solutions than linear discriminant analysis (LDA) to problems of classification and estimation involving a large number of non-homogeneous (categorical and metric) variables. In this study, we compared the ability of traditional LDA and a feed-forward back-propagation (FF-BP) ANN with self-momentum to predict pharmacological treatments received by intravenous drug users (IDUs) hospitalised for coexisting medical illness. When medical staff considered detoxification appropriate they usually suggested methadone (MET) and (or) benzodiazepines (BDZ). Given four different treatment options (MET, BDZ, MET+BDZ, no treatment) as dependent variables and 38 independent variables, the FF-BP ANN provided the best prediction of the consultant's decision (overall accuracy: 62.7%). It achieved the highest level of predictive accuracy for the BDZ option (90.5%), the lowest for no treatment (29.6), often misclassifying no treatment as BDZ. The LDA yielded a lower mean accuracy (50.3%). When the untreated group was excluded, ANN improved its absolute recognition rate by only 1.2% and the BDZ group remained the best predicted. In contrast, LDA improved its absolute recognition rate from 50.3 to 58.9%, maximum 65.7% for the BDZ group. In conclusion, the FF-BP ANN was more accurate than the statistical model (discriminant analysis) in predicting the pharmacological treatment of IDUs. PMID:11779684

Grassi, M C; Caricati, A M; Intraligi, M; Buscema, M; Nencini, P

2002-01-01

232

Switching from Transdermal Drugs: An Observational “N of 1” Study of Fentanyl and Buprenorphine  

Microsoft Academic Search

The aim of this study was to confirm that the concomitant presence of transdermal fentanyl (TTS FE) and buprenorphine (TTS BU) may be feasible without important consequences, using doses presumed to be equianalgesic. A prospective “N of 1” study was carried out in a sample of volunteers with cancer pain receiving stable doses of TTS FE or TTS BU, with

Sebastiano Mercadante; Giampiero Porzio; Fabio Fulfaro; Federica Aielli; Lucilla Verna; Corrado Ficorella; Alessandra Casuccio; Salvatore Riina; Giuseppe Intravaia; Salvatore Mangione

2007-01-01

233

Prenatal exposure to methadone and buprenorphine: A review of the potential effects on cognitive development  

Microsoft Academic Search

The amount of opioid users receiving opioid maintenance therapy has increased significantly over the last few years. As a result, an increasing number of children are prenatally exposed to long-lasting opioids such as methadone and buprenorphine. This article reviews the literature on the cognitive development of children born to mothers in opioid maintenance therapy. Topics discussed are the effects of

Carolien Konijnenberg; Annika Melinder

2011-01-01

234

Evaluation of a Sustained-Release Formulation of Buprenorphine for Analgesia in Rats  

PubMed Central

Preventing and minimizing pain in laboratory animals is a basic tenet of biomedical research and is warranted for ethical, legal, and scientific reasons. Postoperative analgesia is an important facet of pain management. A sustained-release formulation of buprenorphine was tested in rats for analgesic efficacy and plasma concentration over a 72-h time period. Rats were injected subcutaneously with either 1.2 mg/kg sustained-release formulation (Bup-SR), 0.2 mL/kg buprenorphine HCl (Bup-HCl), or an equivalent volume of sustained-release vehicle and tested in a thermal nociception model or a surgical postoperative pain model. In both models, Bup-SR showed evidence of providing analgesia for 2 to 3 d. Thermal latency response in rats that received the sustained-release formulation increased 28.4% and 15.6% compared with baseline values on days 1 and 2, respectively. Rats with a unicortical tibial defect and treated with Bup-SR showed similar willingness to bear weight on the hindlimbs as did negative-control animals (no surgery), demonstrated by counting vertical raises; rats treated with Bup-HCl had significantly fewer vertical raises than did control rats for 5 d after surgery. Plasma concentrations of buprenorphine remained over 1 ng/mL for 72 h after a single dose of Bup-SR. Taken together, the results indicate that this formulation of buprenorphine may be a viable option for treating postsurgical pain in laboratory rats.

Foley, Patricia L; Liang, Haixiang; Crichlow, Andrew R

2011-01-01

235

Differential pharmacological actions of methadone and buprenorphine in human embryonic kidney 293 cells coexpressing human ?-opioid and opioid receptor-like 1 receptors.  

PubMed

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human ?-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors. PMID:21671107

Lee, Cynthia Wei-Sheng; Yan, Jia-Ying; Chiang, Yao-Chang; Hung, Tsai-Wei; Wang, Hung-Li; Chiou, Lih-Chu; Ho, Ing-Kang

2011-06-14

236

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  

PubMed Central

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.

Sheard, Laura; Adams, Clive E; Wright, Nat MJ; El-Sayeh, Hany; Dalton, Richard; Tompkins, Charlotte NE

2007-01-01

237

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Project Study: protocol for a randomised controlled trial comparing methadone and buprenorphine for opiate detoxification  

PubMed Central

Background In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and 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 currently buprenorphine and methadone, both are recommended by national clinical guidelines. However, these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons. Methods/Design This study uses randomised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification, given in the context of routine care, within three UK prisons. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome will be abstinence status eight days after detoxification, as determined by a urine test. Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification. Trial registration Current Controlled Trials ISRCTN58823759

Sheard, Laura; Wright, Nat MJ; Adams, Clive E; Bound, Nicole; Rushforth, Bruno; Hart, Roger; Tompkins, Charlotte NE

2009-01-01

238

No detrimental effect from chronic exposure to buprenorphine on corticosteroid-binding globulin and corticosensitive immune parameters  

Microsoft Academic Search

Opioid drugs reportedly regulate the immune system via their effects on the hypothalamic– pituitary–adrenal (HPA) axis. The present study was carried out to assess the effects of chronic exposure to buprenorphine on HPA axis activation, corticosteroid-binding globulin (CBG), the main glucocorticoid (GC) carrier, and the immune system. Results show that buprenorphine, delivered by osmotic pump subcutaneously in C57BL\\/6 male mice

M D'Elia; J Patenaude; C Hamelin; D. R Garrel; J Bernier

2003-01-01

239

Mechanism-based PK\\/PD Modeling of the Respiratory Depressant Effect of Buprenorphine and Fentanyl in Healthy Volunteers  

Microsoft Academic Search

The objective of this study was to characterize the pharmacokinetic\\/pharmacodynamic (PK\\/PD) relationship of buprenorphine and fentanyl for the respiratory depressant effect in healthy volunteers. Data on the time course of the ventilatory response at a fixed PETCO2 of 50 mm Hg and PETO2 of 110 mm Hg following intravenous administration of buprenorphine and fentanyl were obtained from two phase I

A Yassen; E Olofsen; R Romberg; E Sarton; L Teppema; M Danhof; A Dahan

2007-01-01

240

No detrimental effect from chronic exposure to buprenorphine on corticosteroid-binding globulin and corticosensitive immune parameters.  

PubMed

Opioid drugs reportedly regulate the immune system via their effects on the hypothalamic- pituitary-adrenal (HPA) axis. The present study was carried out to assess the effects of chronic exposure to buprenorphine on HPA axis activation, corticosteroid-binding globulin (CBG), the main glucocorticoid (GC) carrier, and the immune system. Results show that buprenorphine, delivered by osmotic pump subcutaneously in C57BL/6 male mice during a 10-day period, caused a marked decrease in total corticosterone (CORT) levels at day 1 of exposure. CORT levels then increased with maximal values observed at day 5 of exposure. After day 5, total CORT levels gradually decreased and returned to control values. No significant changes were observed in CBG protein levels and mRNA expression in the liver. Since CBG levels remained unchanged, the percentage of free CORT values in buprenorphine mice did not differ from control values. Thus, the variations observed in the amount of free CORT were related only to changes measured in total CORT. These endocrine changes did not have a significant impact on the immune parameters measured. Total CD(4)+ and CD(8)+ splenic and thymic populations were not modulated by buprenorphine. However, splenocytes from mice exposed to buprenorphine after 5 days exhibited greater proliferation upon anti-TCR monoclonal antibody stimulation than saline-exposed mice. These results indicate that buprenorphine can be safely used because it did not have significant effects on GC availability for immune corticosensitive cells. PMID:14597216

D'Elia, M; Patenaude, J; Hamelin, C; Garrel, D R; Bernier, J

2003-11-01

241

Effect of tramadol use on three point-of-care and one instrument-based immunoassays for urine buprenorphine.  

PubMed

We report that use of the popular analgesic tramadol can cause false-positive urine buprenorphine results. We examined the extent of tramadol cross-reactivity in three point-of-care urine buprenorphine immunoassays (ACON, QuikStrip, and ABMC) and an instrument-based one (Cedia). We tested 29 urine samples from patients known to be taking tramadol. Ten different samples tested positive for urine buprenorphine by at least one immunoassay. Samples with positive buprenorphine screens by immunoassay were tested for total buprenorphine and total norbuprenorphine content by liquid chromatography-tandem mass spectrometry (LC-MS-MS), which confirmed that seven of the 10 positive samples were false-positives. The remaining three positive immunoassay samples had insufficient quantity for LC-MS-MS testing. No false-positives were detected with the ACON (10 ng/mL calibration cutoff) or the Cedia assay (using a 20 ng/mL calibration cutoff). All four false-positive Cedia results (using a 5 ng/mL cutoff) in this study tested negative using the ACON device. Our data suggest that tramadol use can cause false-positive urine buprenorphine immunoassays, and this effect appears to be assay-dependent. Tramadol interference with the Cedia assay is clinically relevant, especially if the 5 ng/mL calibration cutoff is used. PMID:18544218

Shaikh, Salima; Hull, Mindy J; Bishop, Kenneth A; Griggs, David A; Long, William H; Nixon, Andrea L; Flood, James G

2008-06-01

242

Benzene Substitutes.  

National Technical Information Service (NTIS)

The document identifies the most important potential benzene substitutes, determines their use in consumer products, and reviews the toxicology of these substances. The major benzene substitutes-cyclohexane, methylene chloride, and xylene, as well as ethy...

A. Mazella R. L. Malseed S. Scott S. Hunsicker D. Shellenberger

1978-01-01

243

Development of nanofibrous cellulose acetate/gelatin skin substitutes for variety wound treatment applications.  

PubMed

The major component of fibrous extracellular matrix of dermis is composed of a complex combination of proteins and polysaccharides. Electrospun cellulose acetate/gelatin might be an effective simulator of the structure and composition of native skin and during this study, we electrospun cellulose acetate/gelatin membranes in various compositions and their performance as a scaffold for either skin tissue engineering or as a wound dressing was evaluated. Skin treatment products, whether tissue-engineered scaffolds or wound dressings, should be sufficiently hydrophilic to allow for gas and fluid exchange and absorb excess exudates while controlling the fluid loss. However, a wound dressing should be easily removable without causing tissue damage and a tissue-engineered scaffold should be able to adhere to the wound, and support cell proliferation during skin regeneration. We showed that these distinct adherency features are feasible just by changing the composition of cellulose acetate and gelatin in composite cellulose acetate/gelatin scaffolds. High proliferation of human dermal fibroblasts on electrospun cellulose acetate/gelatin 25:75 confirmed the capability of cellulose acetate/gelatin 25:75 nanofibers as a tissue-engineered scaffold, while the electrospun cellulose acetate/gelatin 75:25 can be a potential low-adherent wound dressing. PMID:23640859

Vatankhah, Elham; Prabhakaran, Molamma P; Jin, Guorui; Ghasemi Mobarakeh, Laleh; Ramakrishna, Seeram

2013-05-01

244

Risk factors for neurodevelopmental deficits in congenital hypothyroidism after early substitution treatment.  

PubMed

Neurodevelopment in children with congenital hypothyroidism who receive early treatment is generally good. However, subtle neurological deficits still exist in some patients. The aim of this investigation was to evaluate factors that may influence neurodevelopmental outcome in congenital hypothyroidism patients. The developmental quotient (DQ) of 155 children with congenital hypothyroidism was evaluated at 24 months of age, using Gesell Developmental Schedules (GDS), and compared with that of 310 healthy controls. Mean DQ scores in congenital hypothyroidism patients were 7.5 points lower for adaptive behavior than in control patients (p < 0.01). Patients with severe congenital hypothyroidism had the lowest DQ scores compared with two other congenital hypothyroidism subgroups and controls (p < 0.01). Children with congenital hypothyroidism who also had a low level of serum T(4) at diagnosis or exhibited a longer thyroid stimulating hormone (TSH) normalization time had lower adaptive behavior scores (p < 0.0003). Bivariate correlation and multiple regression analyses found that the severity of congenital hypothyroidism and parental socioeconomic status correlated with DQ scores. TSH normalization time was negatively related to adaptive behavior scores (p < 0.01). Neurodevelopmental deficits in children with congenital hypothyroidism correlate with the severity of congenital hypothyroidism, TSH normalization time, and parental socioeconomic status. PMID:21467693

Huo, Kaiming; Zhang, Zhan; Zhao, Dehua; Li, Hezhou; Wang, Jun; Wang, Xinxia; Feng, Hongqi; Wang, Xiaoyang; Zhu, Changlian

2011-04-05

245

Blood Substitutes  

Microsoft Academic Search

\\u000a Blood substitutes have been developed to replace the transfusion of banked blood. Actually, it is unlikely that one singular\\u000a infusion fluid will ever replace all functions of whole blood. Indeed, “blood substitutes” merely substitute the O2-carrying function of red blood cells (RBC), so these substances should rather be referred to as “oxygen carrying blood substitutes”\\u000a or as “artificial oxygen carriers.

Andreas Pape; Oliver Habler

246

Buprenorphine transdermal system for opioid therapy in patients with chronic low back pain  

PubMed Central

OBJECTIVE: The present randomized, double-blinded, crossover study compared the efficacy and safety of a seven-day buprenorphine transdermal system (BTDS) and placebo in patients with low back pain of moderate or greater severity for at least six weeks. METHODS: Prestudy analgesics were discontinued the evening before random assignment to 5 ?g/h BTDS or placebo, with acetaminophen 300 mg/codeine 30 mg, one to two tablets every 4 h to 6 h as needed, for rescue analgesia. The dose was titrated to effect weekly, if tolerated, to 10 ?g/h and 20 ?g/h BTDS. Each treatment phase was four weeks. RESULTS: Fifty-three patients (28 men, 25 women, mean [± SD] age 54.5±12.7 years) were evaluable for efficacy (completed two weeks or more in each phase). Baseline pain was 62.1±15.5 mm (100 mm visual analogue scale) and 2.5±0.6 (five-point ordinal scale). BTDS resulted in lower mean daily pain scores than in the placebo group (37.6±20.7 mm versus 43.6±21.2 mm on a visual analogue scale, P=0.0487; and 1.7±0.6 versus 2.0±0.7 on the ordinal scale, P=0.0358). Most patients titrated to the highest dose of BTDS (59% 20 ?g/h, 31% 10 ?g/h and 10% 5 ?g/h). There were improvements from baseline in pain and disability (Pain Disability Index), Pain and Sleep (visual analogue scale), Quebec Back Pain Disability Scale and Short-Form 36 Health Survey scores for both BTDS and placebo groups, without significant differences between treatments. While there were more opioid-related side effects with BTDS treatment than with placebo, there were no serious adverse events. A total of 82% of patients chose to continue BTDS in a long-term open-label evaluation, in whom improvements in pain intensity, functionality and quality of life were sustained for up to six months without analgesic tolerance. CONCLUSION: BTDS (5 ?g/h to 20 ?g/h) represents a new treatment option for initial opioid therapy in patients with chronic low back pain.

Gordon, Allan; Rashiq, Saifudin; Moulin, Dwight E; Clark, Alexander J; Beaulieu, Andre D; Eisenhoffer, John; Piraino, Paula S; Quigley, Patricia; Harsanyi, Zoltan; Darke, Andrew C

2010-01-01

247

New insights into the pharmacological chaperone activity of c2-substituted glucoimidazoles for the treatment of Gaucher disease.  

PubMed

Mutations in acid ?-glucocerebrosidase (GCase) lead to the accumulation of the sphingolipid glucosylceramide, thereby resulting in Gaucher disease (GD). Active-site-specific competitive GCase inhibitors are effective pharmacological chaperones (PCs) that act as folding agents for mutant GCase folding in the endoplasmic reticulum. In this study, we prepared a series of glucoimidazole C2-substituent derivatives, and evaluated their inhibition and PC properties with GCase. A cell-based assay with patient-derived lymphoblasts (N370S or L444P mutations) demonstrated that administration of these compounds can significantly increase GCase activity. Interestingly, the 3,3-dimethyl-N-phenyl-4-amide-1-butyl-substituted moderate inhibitor 11 had the greatest effect on activity: 2.1-fold increase in N370S lymphoblasts at 2.5 ?M and 1.2-fold increase in L444P at 0.5 ?M following a three-day incubation. Computer docking studies and a protease protection assay were used to elucidate the ligand-enzyme interactions responsible for the chaperone activity of 11. Western blot and immuno-fluorescence assays verified restoration of GCase trafficking to the lysosome. Together, these results indicate that 11 is a promising PC for GD treatment and provide direct evidence of the mechanism of GCase chaperoning. PMID:23775891

Li, Zhonghua; Li, Tiehai; Dai, Shaoxing; Xie, Xiaoli; Ma, Xiaofeng; Zhao, Wei; Zhang, Weimin; Li, Jing; Wang, Peng George

2013-06-14

248

Clinical relevance of substitutions in the connection subdomain and RNase H domains of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-na?ve patients  

PubMed Central

Some mutations in the connection subdomain of the polymerase domain and in the RNase H domain of HIV-1 reverse transcriptase (RT) have been shown to contribute to resistance to RT inhibitors. However, the clinical relevance of such mutations is not well understood. To address this point we determined the prevalence of such mutations in a cohort of antiretroviral treatment-naïve patients (n=123) and assessed whether these substitutions are associated with drug resistance in vitro and in vivo. We report here significant differences in the prevalence of substitutions among subtype B, and non-subtype B HIV isolates. Specifically, the E312Q, G333E, G335D, V365I, A371V and A376S substitutions were present in 2–6% of subtype B, whereas the G335D and A371V substitutions were commonly observed in 69 and 75% of non-B HIV-1 isolates. We observed a significant decline in the viral loads of patients that were infected with HIV-1 carrying these substitutions and were subsequently treated with triple drug regimens, even in the case where zidovudine (AZT) was included in such regimens. We show here that generally, such single substitutions at the connection subdomain or RNase H domain have no influence on drug susceptibility in vitro by themselves. Instead, they generally enhance AZT resistance in the presence of excision-enhancing mutations (EEMs, also known as thymidine analogue-associated mutations, TAMs). However, N348I, A376S and Q509L did confer varying amounts of nevirapine resistance by themselves, even in the absence of EEMs. Therefore, our cohort establishes that several connection subdomain and RNase H domain substitutions typically act as pre-therapy polymorphisms.

Hachiya, Atsuko; Shimane, Kazuki; Sarafianos, Stefan G.; Kodama, Eiichi N.; Sakagami, Yasuko; Negishi, Fujie; Koizumi, Hirokazu; Gatanaga, Hiroyuki; Matsuoka, Masao; Takiguchi, Masafumi; Oka, Shinichi

2012-01-01

249

The effect of buprenorphine on the course of disease in laboratory rabbits infected with myxoma virus.  

PubMed

The only method of assessing the virulence of myxoma virus is to record survival times of rabbits inoculated with the virus. This raises ethical concerns about using animals in experiments where death is the end point. We investigated whether or not the opioid analgesic buprenorphine could be used in rabbits without compromising the myxoma virus virulence assay and on the presumption that animals may suffer pain during the course of the disease. Thirty, 5-month-old New Zealand White rabbits were divided into two groups stratified for weight and gender, and inoculated intradermally with 100 pfu of the Standard Laboratory Strain (SLS) of myxoma virus. At day 6 post infection (p.i.), when eyelid swelling was first seen, each animal in one group was treated with 0.03 mg/kg buprenorphine, subcutaneously, morning and evening until death. Animals in the other group were untreated. Animals were weighed daily and rectal temperatures taken morning and evening. Intake of food and water was assessed as was general demeanor including respiratory effort. There was no significant difference in mean survival time, weight change, or demeanor between the two groups. Increased respiratory effort was seen from day 10 p.i. in animals surviving up to and beyond that time but again there was no difference between groups. Animals treated with buprenorphine refused food and water a day earlier than untreated animals, and had lower temperatures immediately prior to death. It was concluded that the opiate analgesic buprenorphine can be used without compromising the current virulence assay for the SLS of myxoma virus in New Zealand White rabbits but that the clinical signs of myxomatosis that could be attributed to pain were not abrogated. PMID:10780844

Robinson, A J; Müller, W J; Braid, A L; Kerr, P J

1999-07-01

250

Degradable Bone Graft Substitute for Effective Delivery of Multiple Growth Factors in the Treatment of Nonunion Fractures.  

National Technical Information Service (NTIS)

Our hypothesis was that a degradable, thermally-responsive bone graft substitute, made from renewable sources, that effectively and simultaneously delivers osteogenic and angiogenic growth factors directly to the bone defect site can enhance repair of non...

J. Bush

2012-01-01

251

Biphasic bone substitute and fibrin sealant for treatment of benign bone tumours and tumour-like lesions  

Microsoft Academic Search

Purpose  Bone defects resulting from tumour resection or curettage are most commonly reconstructed with autologous bone graft which\\u000a is associated with limited availability and donor site morbidity. Recent research has focussed on synthetic biomaterials as\\u000a bone graft substitutes. The aim of this study was to assess the safety and efficiency of a bone substitute as an alternative\\u000a for autologous bone in

Stephan Reppenhagen; Johannes C. Reichert; Lars Rackwitz; Maximilian Rudert; Peter Raab; Guy Daculsi; Ulrich Nöth

252

Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy.  

PubMed

The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. PMID:23562407

Morgaz, J; Navarrete, R; Muñoz-Rascón, P; Domínguez, J M; Fernández-Sarmiento, J A; Gómez-Villamandos, R J; Granados, M M

2013-04-03

253

Effect of modern analgesic drugs (tramadol, pentazocine, and buprenorphine) on the bile duct sphincter in man.  

PubMed Central

Modern narcotic analgesic drugs, such as tramadol, pentazocine, and buprenorphine share similarities of molecular structure with morphine which is widely believed to cause spasm of the bile duct sphincter and so impede bile flow. This study assessed the effects of intravenously administered analgesics on bile duct sphincter motor activity measured by ERCP manometry. Ten minutes after pentazocine injection the duration of contractions and baseline pressure of the bile duct sphincter rose from 6.2 +/- 0.2 to 8.2 +/- 0.27 s and from 5.1 +/- 0.6 to 8.8 +/- 0.4 mmHg respectively. Tramadol, buprenorphine and saline showed no such effect. These data indicated that the effects of such drugs on bile duct sphincter function can be safely assessed by ERCP manometry and that pentazocine adversely affects the bile duct sphincter, whilst tramadol and buprenorphine do not. We consider therefore that pentazocine is not the premedication of first choice for endoscopic procedures involving the sphincter of Oddi and should also be avoided in patients with pancreatic and biliary disorders.

Staritz, M; Poralla, T; Manns, M; Meyer Zum Buschenfelde, K H

1986-01-01

254

P-15 small peptide bone graft substitute in the treatment of non-unions and delayed union. A pilot clinical trial  

Microsoft Academic Search

Treatment of non-unions and delayed unions often requires osteogenic material. Recently, a biomimetic bone matrix that simulates\\u000a the cellular environment of hard tissue, identified as P-15, was introduced to the orthopaedic community. A total of 22 patients\\u000a with mal-union or delayed union fractures was treated from June 2000 to October 2003 with P15- bone graft substitute (P15-BGS)\\u000a in the site

Francisco Gomar; Rafael Orozco; Jose Luis Villar; Federico Arrizabalaga

2007-01-01

255

Skin substitutes: An Indian perspective  

PubMed Central

There have been numerous alternatives developed to replace skin. These can either be permanent substitutes or temporary substitutes, which need to be replaced later by autologous grafts. These have been tried in recent times as an attempt to reduce the need or in the case of permanent substitutes ,altogether replace autologous skin grafts. However till date no ideal skin substitute has been developed. Various factors have to be considered while choosing one of these substitutes. In a developing country like India awareness and availability of these skin substitutes is not adequate considering the volume of cases that require this modality of treatment. Also there are skin substitutes developed in our country that need to be highlighted. This article is an attempt to review the vast array of skin substitutes that have been developed and consider their utility and feasibility for developing countries.

Singh, A. K.; Shenoy, Y. R.

2012-01-01

256

Substitute Solutions.  

ERIC Educational Resources Information Center

|In summer 1999, a group of Park City, Utah, school administrators, personnel directors, human-resource specialists, and substitute teacher coordinators brainstormed on improving the recruitment, training, and retention of substitute teachers. Providing effective preservice and on-the-job training and professional recognition are key suggestions.…

Jones, Kevin R.; Hawkins, Amber

2000-01-01

257

Italy's electronic health record system for opioid agonist treatment.  

PubMed

Electronic health record systems (EHRs) play an increasingly important role in opioid agonist treatment. In Italy, an EHR called the Multi Functional Platform (MFP) is in use in 150 opioid-agonist treatment facilities in 8 of Italy's 23 regions. This report describes MFP and presents 2010 data from 65 sites that treated 8145 patients, of whom 72.3% were treated with methadone and 27.7% with buprenorphine. Patients treated with buprenorphine compared to methadone were more likely to be male (p < .01) and younger (p < .001). Methadone compared to buprenorphine patients had a higher percentage of opioid-positive urine tests (p < .001) and longer mean length of stay (p = .004). MFP has been implemented widely in Italy and has been able to track patient outcomes across treatment facilities. In the future, this EHR system can be used for performance improvement initiatives. PMID:23518287

Serpelloni, Giovanni; Gomma, Maurizio; Genetti, Bruno; Zermiani, Monica; Rimondo, Claudia; Mollica, Roberto; Gryczynski, Jan; O'Grady, Kevin E; Schwartz, Robert P

2013-03-19

258

Cigarette smoking and short-term addiction treatment outcome  

Microsoft Academic Search

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

P. T. Harrell; I. D. Montoya; K. L. Preston; L. M. Juliano; D. A. Gorelick

2011-01-01

259

Use of 5-substituted nucleosides and/or prodrugs thereof in the resistance-free treatment of infectious diseases  

US Patent & Trademark Office Database

The present invention relates to the use of 5-substituted nucleosides and/or the prodrugs thereof together with at least one active substance in order to produce a drug or combination preparation for resistance-free therapy of infectious diseases caused by bacteria or protozoa.

2006-10-17

260

Pharmacokinetics of buprenorphine after single-dose subcutaneous administration in red-eared sliders (Trachemys scripta elegans).  

PubMed

Buprenorphine, a mu opioid receptor agonist, is expected to be a suitable analgesic drug for use in reptiles. However, to date, dosage recommendations have been based on anecdotal observations. The aim of this study was to provide baseline pharmacokinetic data in red-eared sliders (Trachemys scripta elegans) targeting a plasma level of 1 ng/ml reported effective for analgesia in humans. Serial blood samples were taken after subcutaneous injection of buprenorphine, and plasma buprenorphine levels were measured by radioimmunoassay. Pharmacokinetic parameters of a lower dose (0.02 mg/kg) injected into the forelimb were compared with a higher dose (0.05 mg/kg) given in the same forelimb as well as a lower dose (0.02 mg/kg) given in the hind limb of the same animals with 2 wk between studies. After administration of 0.05 mg/kg in the front limb, 85% of animals maintained the minimum effective plasma level for 24 hr, while only 43% of animals maintained this level after 0.02 mg/kg. After hind limb injection at 0.02 mg/kg, maximum plasma concentrations and areas under the buprenorphine concentration-time curve were less than 20% and 70%, respectively, of values after forelimb injection, consistent with substantial first pass extraction by the liver. Furthermore, a secondary rise in the buprenorphine level was found after having only a hind limb injection, probably from enterohepatic recirculation of glucuronidated drug. In conclusion, buprenorphine dosages of at least 0.075 mg/kg s.i.d. should be appropriate for evaluation of analgesia efficacy, and front limb administration may be preferable to hind limb administration for optimal drug exposure. PMID:19110701

Kummrow, Maya S; Tseng, Florina; Hesse, Leah; Court, Michael

2008-12-01

261

Blood substitutes.  

PubMed Central

With the development of modern methods of surgery, anaesthesia, and pre- and postoperative care the requirement for blood substitutes is continuously increasing. We present a review of the different blood substitutes which are already in clinical use or in an advanced stage of experimental investigation for possible practical administration. Our own clinical experience with dextrans and experimental studies on stroma-free haemoglobin and hydroxyethyl starch solutions are described.

Kostrzewska, E.

1976-01-01

262

Confirmatory analysis of buprenorphine, norbuprenorphine, and glucuronide metabolites in plasma by LCMSMS. Application to umbilical cord plasma from buprenorphine-maintained pregnant women.  

PubMed

An LCMSMS method was developed and fully validated for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) in 0.5mL plasma, fulfilling confirmation criteria with two transitions for each compound with acceptable relative ion intensities. Transitions monitored were 468.3>396.2 and 468.3>414.3 for BUP, 414.3>340.1 and 414.3>326.0 for NBUP, 644.3>468.1 and 644.3>396.3 for BUP-Gluc, and 590.3>414.3 and 590.3>396.2 for NBUP-Gluc. Linearity was 0.1-50ng/mL for BUP and BUP-Gluc, and 0.5-50ng/mL for NBUP and NBUP-Gluc. Intra-day, inter-day, and total assay imprecision (%RSD) were <16.8%, and analytical recoveries were 88.6-108.7%. Extraction efficiencies ranged from 71.1 to 87.1%, and process efficiencies 48.7 to 127.7%. All compounds showed ion enhancement, except BUP-Gluc that demonstrated ion suppression: variation between 10 different blank plasma specimens was <9.1%. In six umbilical cord plasma specimens from opioid-dependent pregnant women receiving 14-24mg/day BUP, NBUP-Gluc was the predominant metabolite (29.8+/-7.6ng/mL), with BUP-Gluc (4.6+/-4.8ng/mL), NBUP (1.5+/-0.8ng/mL) and BUP (0.4+/-0.2ng/mL). Although BUP biomarkers can be quantified in umbilical cord plasma in low ng/mL concentrations, the significance of these data as predictors of neonatal outcomes is currently unknown. PMID:19945361

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

2010-01-01

263

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

PubMed Central

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 <14.5%, and analytical recovery ranged from 94.1% to 112.3% for all analytes. Extraction efficiencies 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.

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

2009-01-01

264

TASTE CONDITIONING EFFECTS OF BUPRENORPHINE IN MORPHINE-NAIVE AND MORPHINE-EXPERIENCED RATS  

Microsoft Academic Search

Male Sprague–Dawley rats were injected daily with saline (morphine-naive rats) or 20 mg kg?1morphine (morphine-experienced rats), starting 15 days before the experiment. Subsequent taste conditioning indicated that 0.1 mg kg?1buprenorphine significantly decreased 0.025% saccharin consumption in morphine-naive, but not in morphine-experienced rats. A 10 mg kg?1dose of morphine gave similar results, whiled-amphetamine (0.75 mg kg?1) was consistently aversive. It was

M. GAIARDI; C. GUBELLINI; M. BARTOLETTI

1998-01-01

265

Is there a ceiling effect of transdermal buprenorphine? Preliminary data in cancer patients  

Microsoft Academic Search

Objective  The aim of this preliminary study was to explore the possibility of using higher doses of transdermal buprenorphine (TD-BUP)\\u000a than those commonly used and available as manufactured patches, which are based on the assumption that BUP may have a ceiling\\u000a effect that has never been determined yet.\\u000a \\u000a \\u000a \\u000a Materials and methods  Ten patients who were already receiving TD-BUP (70 ?g\\/h, which is about

Sebastiano Mercadante; Patrizia Ferrera; Patrizia Villari

2007-01-01

266

Influence of detomidine and buprenorphine on motor-evoked potentials in horses.  

PubMed

Horses need to be sedated before they are investigated by transcranial magnetic stimulation because of the mild discomfort induced by the evoked muscle contraction and the noise of stimulation. This paper describes the influence of a combination of detomidine (10 microg/kg bodyweight) and a low dose of buprenorphine (2.4 microg/kg) on the onset latency and peak-to-peak amplitude of magnetic motor-evoked potentials in normal horses. There were no significant differences between measurements of these parameters made before the horses were sedated and measurements made 10 and 30 minutes after the drugs were administered. PMID:12739602

Nollet, H; Van Ham, L; Gasthuys, F; Dewulf, J; Vanderstraeten, G; Deprez, P

2003-04-26

267

Hemodynamic and behavioral differences after administration of meloxicam, buprenorphine, or tramadol as analgesics for telemeter implantation in mice.  

PubMed

Cannulation of the common carotid artery for chronic, continuous radiotelemetric recording of aortic hemodynamic properties in mice is a highly invasive recovery surgery. Radiotelemetric recording, by its continuous nature, gives the most accurate measurements of hemodynamic variables in experimental animals, and is widely used in the study of cardiovascular diseases including hypertension. The American Heart Association has recommended data acquisition by radiotelemetric recording but did not provide guidelines regarding postoperative analgesic support. We assessed hemodynamic parameters, locomotor activity, food intake, and weight loss in radiotransmitter-implanted CD1 female mice receiving analgesic support during the first 48 h after surgery. The efficacy of analgesic support from the NSAID meloxicam was compared with that of the widely used opioid agonist buprenorphine and the related compound, tramadol. Meloxicam-treated mice recovered lost body weight more rapidly than did tramadol-or buprenorphine-treated mice. Furthermore, meloxicam-treated mice maintained circadian rhythm after surgery and had tighter regulation of mean arterial pressure than did tramadol- or buprenorphine-treated mice. Meloxicam was also superior with regard to food intake, locomotor activity, and limiting variance in hemodynamic parameters. This study indicates that when compared with buprenorphine and tramadol, meloxicam should be the postoperative analgesic of choice for radiotelemeter implantation in mice. PMID:24041211

Rätsep, Matthew T; Barrette, Valerie F; Winterborn, Andrew; Adams, Michael A; Croy, B Anne

2013-09-01

268

Effects of Buprenorphine Maintenance Dose on ?-Opioid Receptor Availability, Plasma Concentrations, and Antagonist Blockade in Heroin-Dependent Volunteers  

Microsoft Academic Search

The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease ?-opioid receptor (?OR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who were successively maintained on 32, 16, 2, and 0 mg daily buprenorphine (BUP) tablet doses. We

Mark K Greenwald; Chris-Ellyn Johanson; David E Moody; James H Woods; Michael R Kilbourn; Robert A Koeppe; Charles R Schuster; Jon-Kar Zubieta

2003-01-01

269

The Influence of Hyperbaric Oxygen Treatment on the Healing of Experimental Defects Filled with Different Bone Graft Substitutes  

PubMed Central

To assess potential effects of hyperbaric oxygen (HBOT) on artificial bone grafts, ? - Tricalcium phosphate (?-TCP) and calcium phosphate coated bovine bone (CPCBB) substitutes were applied to standard bone defects in rat tibiae. The control defects were left empty. Half of the animals received 60 minutes of 2.4 atmosphere absolute (ATA) of HBOT. Rats were sacrificed at one, two and four weeks. Bone healing was assessed histologically and histomorphometrically using light microscopy. The periosteum over the bone defects was examined ultrastructurally. Cardiac blood was collected to determine the serum osteocalcin levels. The HBOT increased new bone formation in the unfilled controls and ?-TCP groups and significantly decreased cartilage matrix and fibrous tissue formations in all groups. Active osteoblasts and highly organized collagen fibrils were prominent in the periosteum of ?-TCP and control groups. Serum osteocalcin levels also increased with HBOT. The healing of defects filled with CPCBB was similar to the controls and it did not respond to HBOT. These findings suggested that the HBOT had beneficial effects on the healing of unfilled bone defects and those filled with ?-TCP bone substitute but not with CPCBB, indicating a material-specific influence pattern of HBOT.

Sirin, Yigit; Olgac, Vakur; Dogru-Abbasoglu, Semra; Tapul, Leyla; Aktas, Samil; Soley, Sinan

2011-01-01

270

The influence of hyperbaric oxygen treatment on the healing of experimental defects filled with different bone graft substitutes.  

PubMed

To assess potential effects of hyperbaric oxygen (HBOT) on artificial bone grafts, ? - Tricalcium phosphate (?-TCP) and calcium phosphate coated bovine bone (CPCBB) substitutes were applied to standard bone defects in rat tibiae. The control defects were left empty. Half of the animals received 60 minutes of 2.4 atmosphere absolute (ATA) of HBOT. Rats were sacrificed at one, two and four weeks. Bone healing was assessed histologically and histomorphometrically using light microscopy. The periosteum over the bone defects was examined ultrastructurally. Cardiac blood was collected to determine the serum osteocalcin levels. The HBOT increased new bone formation in the unfilled controls and ?-TCP groups and significantly decreased cartilage matrix and fibrous tissue formations in all groups. Active osteoblasts and highly organized collagen fibrils were prominent in the periosteum of ?-TCP and control groups. Serum osteocalcin levels also increased with HBOT. The healing of defects filled with CPCBB was similar to the controls and it did not respond to HBOT. These findings suggested that the HBOT had beneficial effects on the healing of unfilled bone defects and those filled with ?-TCP bone substitute but not with CPCBB, indicating a material-specific influence pattern of HBOT. PMID:21326954

Sirin, Yigit; Olgac, Vakur; Dogru-Abbasoglu, Semra; Tapul, Leyla; Aktas, Samil; Soley, Sinan

2011-02-08

271

Evaluation of butorphanol tartrate and buprenorphine hydrochloride on the inflammatory reaction of the Sereny Test.  

PubMed

Invasion of the ocular epithelia of guinea pigs by virulent Shigella organisms, eliciting keratoconjunctivitis, is the basis of the Sereny Test (ST). This test has been used to ascertain the virulence of Shigella strains and more recently to screen candidate Shigella vaccines for efficacy. This test undoubtedly causes pain in test animals; however, recommendation for use of local analgesics/anesthetics has not been accepted because of concern that these topical agents may affect the ability of the Shigella organisms to invade the ocular epithelia or have a physiologic effect on the inflammatory process. Similarly, investigators are hesitant to use systemic analgesics in conjunction with the ST. Two blinded studies were conducted to evaluate the effects of selected systemic analgesics on the ST in outbred Hartley guinea pigs. Study 1 evaluated the recommended dosages for two systemic analgesics; study groups consisted of those receiving butorphanol tartrate (n = 16), those receiving buprenorphine hydrochloride (n = 16), and untreated controls (n = 5). Study 2 evaluated a low-dose buprenorphine hydrochloride group (n = 16) and an untreated control group (n = 5). All animals were inoculated with Shigella flexneri, strain 2a 2457T, onto the cornea and conjunctiva of each eye. At the onset of clinical signs, analgesics were administered to test groups. The degree of keratoconjunctivitis was evaluated per standard procedure; animals were weighed daily. After 7 days, animals were euthanatized and the eyes were removed for histologic morphometric evaluation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8277729

Swearengen, J R; Cockman-Thomas, R A; Davis, J A; Weina, P J

1993-10-01

272

Analgesic efficacy of buprenorphine in the presence of high levels of SDF-1?/CXCL12 in the brain.  

PubMed

Although morphine is often the best option for treating acute and chronic severe pain, its analgesic activity can be blocked in situations in which there are elevated levels of chemokines. Indeed, recently we have shown that elevated brain levels of the chemokine stromal cell-derived growth factor-1alpha (SDF-1?/CXCL12, the ligand of the HIV co-receptor CXCR4) diminish the antinociceptive effect of morphine. The purpose of the present study was to investigate whether such an effect is restricted to morphine or extends to other opioid medications such as buprenorphine. A sterilized stainless-steel C313G guide cannula was implanted into the periaqueductal grey (PAG), a brain region critical to the processing of pain signals, and a primary site of action of many analgesic compounds. The cold-water (-3°C) tail-flick test (CWT) was used to measure antinociception. Rats were pretreated with SDF-1?/CXCL12 administered into the PAG, and the antinociceptive actions of buprenorphine were measured. Direct infusion of SDF-1?/CXCL12 into the PAG failed to alter the antinociceptive action of buprenorphine. The presence of SDF-1?/CXCL12 in the PAG differentially alters the antinociceptive function of opioid medications. While it was able to diminish the antinociception induced by morphine (Adler et al., 2006), SDF-1?/CXCL12 did not affect the buprenorphine-induced antinociception. Buprenorphine appears to be more effective in the presence of high levels of SDF-1?/CXCL12 in the brain (which frequently occurs during neuroinflammatory conditions). PMID:21112161

Benamar, Khalid; Palma, Jonathan; Cowan, Alan; Geller, Ellen B; Adler, Martin W

2010-11-26

273

Liquid chromatographic-electrospray ionization mass spectrometric quantitative analysis of buprenorphine, norbuprenorphine, nordiazepam and oxazepam in rat plasma.  

PubMed

A liquid chromatographic-mass spectrometric method with electrospray ionization is presented for the simultaneous determination of buprenorphine, nordiazepam and their pharmacologically active metabolites, norbuprenorphine and oxazepam, in rat plasma. The drugs were extracted from plasma by liquid-liquid extraction and chromatographically separated using a gradient elution of aqueous ammonium formate and acetonitrile. Following electrospray ionization, the analytes were quantified in the single ion storage mode. The assay was validated according to current acceptance criteria for bioanalytical method validation. It was proved to be linear from 0.7 to 200 ng/ml plasma for buprenorphine, 1.0 to 200 ng/ml for norbuprenorphine, 2.0 to 200 ng/ml for nordiazepam, and from 5.0 to 200 ng/ml for oxazepam. The average recoveries of buprenorphine, norbuprenorphine, nordiazepam and oxazepam were 89, 39, 88 and 82%, respectively, with average coefficients of variation ranging from 1.8 to 14.3%. The limits of quantitation for these drugs were 0.7, 1.0, 2.0 and 5.0 ng/ml, respectively, with associated precisions within 17% and accuracies within +/-18% of the nominal values. Both the intra- and inter-assay precision values did not exceed 11.3% for the four analytes. Intra- and inter-assay accuracies lay within +/-15% of the nominal values. The validated method was applied to the determination of buprenorphine, norbuprenorphine, nordiazepam and oxazepam in plasma samples collected from rats at various times after intravenous administration of buprenorphine and nordiazepam. PMID:16554136

Pirnay, Stephane; Hervé, Françoise; Bouchonnet, Stéphane; Perrin, Bérengère; Baud, Frédéric J; Ricordel, Ivan

2006-03-22

274

Emotional Availability, Parental Self-Efficacy Beliefs, and Child Development in Caregiver-Child Relationships with Buprenorphine-Exposed 3-year-olds  

Microsoft Academic Search

Objective. The purpose was to compare emotional availability, maternal self-efficacy beliefs, and child developmental status in caregiver–child relationships with prenatally buprenorphine-exposed and nonexposed 3-year-old children. Design. We compared prenatally buprenorphine-exposed children living either with the biological mother (n = 7) or in foster care (n = 14) to nonexposed participants (n = 13). Emotional availability was coded from videotaped parent-child

Saara Salo; Kaisa Kivistö; Riikka Korja; Zeynep Biringen; Sarimari Tupola; Hanna Kahila; Satu Kivitie-Kallio

2009-01-01

275

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human ?-Opioid and Opioid Receptor-Like 1 Receptors  

Microsoft Academic Search

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on\\u000a adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human ?-opioid receptor (MOR)\\u000a and nociceptin\\/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity;\\u000a however, buprenorphine induced compromised AC inhibition. When naloxone was introduced

Cynthia Wei-Sheng Lee; Jia-Ying Yan; Yao-Chang Chiang; Tsai-Wei Hung; Hung-Li Wang; Lih-Chu Chiou; Ing-Kang Ho

276

Sensory Substitution  

NASA Astrophysics Data System (ADS)

The idea that the cutaneous surface may be employed as a substitute for the eyes and ears is by no means a modern notion. Although the sense of touch has long been considered as a surrogate for both the visual and auditory modalities, the focus of this chapter will be on the efforts to develop a tactile substitute for hearing, especially that of human speech. The visual system is our primary means of processing information about environmental space such as orientation, distance, direction and size. It is much less effective in making temporal discriminations. The auditory system is unparalleled in processing information that involves rapid sequences of temporal events, such as speech and music. The tactile sense is capable of processing both spatial and temporal information although not as effective in either domain as the eye or the ear.

Verrillo, Ronald T.

277

Substitute Teachers  

NSDL National Science Digital Library

Our lives are ones of uncertainty and surprise, yin and yang existences. Some things we can control and others we are powerless to command, even with the best intentions. Teachers are not exempt from emergencies, jury duty, and illness. Luckily, most schools plan for such incidents by having willing substitutes on hand. Teachers need to follow the Scout's motto to "be prepared" and keep the classroom running smoothly and efficiently for students and subs.

Swango, C. J.; Steward, Sally B.

2003-01-01

278

Substitution therapy for heroin addiction.  

PubMed

Substitution treatment for heroin addiction, defined here as maintenance prescribing of opioid agonist drugs to opioid dependent subjects, has increased in the last decade. The recent history of substitution treatment in five countries--Canada, the U.K., Australia, Israel, and France--is reviewed. In all five countries, the critical issues around substitution treatment are similar. The first key issue concerns the balance between making treatment accessible and attractive, and minimizing diversion to the black market. The second issue concerns the role of primary health care in delivering MMT. In general, there has been increasing involvement of primary health care, with training and support for practitioners. However, there remains uncertainty and official ambivalence over whether treatment should be restricted to specialist clinics and practitioners, or available through primary care. Most importantly, underlying these issues is the problem of stigma being associated with both addiction, and with substitution treatment. The underlying problem that treatment is often at odds with community values places enormous strains on substitution treatment, and makes the treatment system vulnerable to shifting community support and abrupt, politically-driven changes in policy. PMID:12180559

Bell, James; Dru, Alain; Fischer, Benedikt; Levit, Shabtay; Sarfraz, M Aamer

279

Structure-based epitope and PEGylation sites mapping of phenylalanine ammonia-lyase for enzyme substitution treatment of phenylketonuria  

Microsoft Academic Search

Protein and peptide therapeutics are of growing importance as medical treatments but can frequently induce an immune response. This work describes the combination of complementary approaches to map the potential immunogenic regions of the yeast Rhodosporidium toruloides phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) and to engineer the protein as a human therapeutic agent for the treatment of phenylketonuria (PKU), an inherited

Alejandra Gámez; Lin Wang; Christineh N. Sarkissian; Dan Wendt; Paul Fitzpatrick; Jeffrey F. Lemontt; Charles R. Scriver; Raymond C. Stevens

2007-01-01

280

History of reported sexual or physical abuse among long-term heroin users and their response to substitution treatment  

Microsoft Academic Search

Opioid-dependent individuals with a history of abuse have exhibited worse mental and physical health compared to those without such a history; however, the evidence regarding the influence of abuse histories on addiction treatment outcomes are conflicting.In the present study, we identified history of physical or sexual abuse at treatment initiation in relation to drug use and health among long-term opioid-dependent

Eugenia Oviedo-Joekes; Kirsten Marchand; Daphne Guh; David C. Marsh; Suzanne Brissette; Michael Krausz; Aslam Anis; Martin T. Schechter

2011-01-01

281

Coffee substitute  

US Patent & Trademark Office Database

A coffee-type beverage base is prepared by light roast method under 200.degree. C. and originated from grain and legume. This coffee substitute has a pleasant aroma, and can be used as a carrier of nutritional supplement or herb therapy as well as an additive of coffee, tea, or chocolate. This novel drink is especially suitable for individuals who suffer from conditions making them coffee intolerant, e.g., pregnancy, or those who suffer form hypoglycemia, hypertension, arrhythmia, insomnia, or gastric irritation.

2001-01-09

282

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

PubMed Central

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 screen and younger age at intake had a negative impact on retention and abstinence.

2011-01-01

283

Relative efficacy of cash versus vouchers in engaging opioid substitution treatment clients in survey-based research.  

PubMed

Concerns that cash payments to people who inject drugs (PWID) to reimburse research participation will facilitate illicit drug purchases have led some ethical authorities to mandate department store/supermarket vouchers as research reimbursement. To examine the relative efficacy of the two forms of reimbursement in engaging PWID in research, clients of two public opioid substitution therapy clinics were invited to participate in a 20-30 min, anonymous and confidential interview about alcohol consumption on two separate occasions, 4 months apart. Under the crossover design, at Time 1, clients of Clinic 1 were offered $A20 cash as reimbursement, while clients of Clinic 2 were offered an $A20 voucher; at Time 2, the form of reimbursement was reversed. Using clinic records to determine the denominator (number of clients dosed), we found that compared with clients offered a voucher, a significantly higher proportion of clients who were offered cash participated in the survey (58% (139/241) vs 74% (186/252); ?(2)=14.27; p=0.0002). At first participation, respondents most commonly reported planning to purchase food/drinks/groceries (68%), cigarettes (21%) and transport/fuel (11%) with their payments, with those reimbursed in cash more likely to report planning to fund transport/fuel (19% vs 1%; p<.01) and less likely to report planning to purchase food/drinks/groceries (62% vs 76%; p=0.02). Just three out of 155 cash participants reported planning to purchase illicit drugs with their payment. Results demonstrate that modest cash payments enhanced recruitment of this group, an important consideration given the challenges of delineating the parameters of a population defined by illegal activity, seemingly without promoting excessive additional drug use. PMID:23236087

Topp, Libby; Islam, M Mofizul; Day, Carolyn Ann

2012-12-12

284

Respiratory depression following administration of low dose buprenorphine as postoperative analgesic after fentanyl balanced anaesthesia.  

PubMed

Opioids are among the most ancient and widely used drugs in anaesthesiology. The pharmacology of opioid analgesics and their receptors is a complex and not fully understood matter; even more complex are the interactions between different classes of opioids at both molecular and clinical levels. We want to report here a clinical observation to emphasize the importance of the theoretical basis of anaesthesiology. This paper contains a clinical observation of respiratory depression following the administration of buprenorphine as postoperative analgesic after balanced anaesthesia with fentanyl. The observed case is interpreted in the light of the pharmacokinetics and pharmacodynamics of the different classes of opioid drugs (agonists, agonists-antagonists, antagonists) and of the interactions with their respective receptors. PMID:8880825

Zanette, G; Manani, G; Giusti, F; Pittoni, G; Ori, C

1996-01-01

285

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

PubMed

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 +/- 9.2microg/kg, ketamine 13.6 +/- 1.9 mg/kg and buprenorphine 0.5 +/- 0.06 microg/kg. Induction time was 3.1 +/- 1.4 min. This produced surgical anaesthesia for 21 +/- 4.2 min. Atipamezole 232 +/- 92 microg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 +/- 2.2 min. PMID:22135922

Jouber, K E; Serfontein, T; Scantlebury, M; Manjerovice, M B; Bateman, P W; Bennett, N C; Waterman, J M

2011-06-01

286

The synthesis of buprenorphine intermediates by regioselective microbial N- and O-demethylation reactions using Cunninghamella echinulata NRRL 1384  

Microsoft Academic Search

A biotransformation procedure, using the filamentous fungus Cunninghamella echinulata NRRL 1384, for the high yielding regioselective demethylation of a thebaine derivative to give intermediates for the synthesis of buprenorphine is reported. The thebaine derived substrate can be converted to a mixture of N-demethylated and N,O-demethylated products. Manipulation of the growth conditions of the organism and time of substrate addition resulted

Anthony M Abel; Andrew J Carnell; J. Alf Davis; Michael Paylor

2003-01-01

287

Effects of concurrent saccharin availability and buprenorphine pretreatment on demand for smoked cocaine base in rhesus monkeys  

Microsoft Academic Search

The effects of saccharin and the opioid partial agonist buprenorphine on cocaine base smoking were evaluated in five male rhesus monkeys. Monkeys completed a sequence of responding consisting of lever-press responses maintained under a fixed-ratio (FR) schedule followed by inhalation responses (FR5) on a smoking spout to gain access to a single delivery of volatilized cocaine base (1.0 mg\\/kg per

Sandra D. Comer; Vincent R. Hunt; Marilyn E. Carroll

1994-01-01

288

Physicochemical grounds for the substitution of nitrogen for argon during out-of-furnace treatment of high-carbon steel  

Microsoft Academic Search

Physicochemical grounds for the possibility of replacing of argon with nitrogen during blowing a metal in the course of degassing and in a ladle-furnace unit are obtained using a mathematical model of degassing steel for out-of-furnace treatment. According to the data of examining the model for adequacy, the calculation error does not exceed 1%. A numerical experiment demonstrates that the

I. V. Golub; A. P. Stovpchenko; L. V. Kamkina; Yu. S. Proydak

2009-01-01

289

Physicochemical grounds for the substitution of nitrogen for argon during out-of-furnace treatment of high-carbon steel  

Microsoft Academic Search

Physicochemical grounds for the possibility of replacing of argon with nitrogen during blowing a metal in the course of degassing\\u000a and in a ladle-furnace unit are obtained using a mathematical model of degassing steel for out-of-furnace treatment. According\\u000a to the data of examining the model for adequacy, the calculation error does not exceed 1%. A numerical experiment demonstrates\\u000a that the

I. V. Golub; A. P. Stovpchenko; L. V. Kamkina; Yu. S. Proydak

2009-01-01

290

Structure-based epitope and PEGylation sites mapping of phenylalanine ammonia-lyase for enzyme substitution treatment of phenylketonuria.  

PubMed

Protein and peptide therapeutics are of growing importance as medical treatments but can frequently induce an immune response. This work describes the combination of complementary approaches to map the potential immunogenic regions of the yeast Rhodosporidium toruloides phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) and to engineer the protein as a human therapeutic agent for the treatment of phenylketonuria (PKU), an inherited metabolic disorder. The identification of B and T cell epitopes on the PAL protein was performed by computational predictions based on the antigenicity and hydrophilicity of proteins, as well as by experimental epitope mapping using a PepSpots peptide array (Jerini AG). Human T cell epitope mapping was performed by applying the computational EpiMatrix algorithm (EpiVax, Inc.) for MHC Class I and Class II associated T cell epitopes on PAL, which predicts which sequences are associated with binding to several different HLA alleles, a requirement for antigen presentation and subsequent primary immune response. By chemical modification through PEGylation of surface lysine residues, it is possible to cover the immunogenic regions of a protein. To evaluate this strategy, we used mass spectrometry to determine which of the immunogenic epitopes are covered by the covalent PEGylation modification strategy. This approach has allowed us to determine whether additional lysines are needed in specific residue locations, or whether certain lysine residues can be removed in order to accomplish complete molecular coverage of the therapeutic enzyme. PMID:17560821

Gámez, Alejandra; Wang, Lin; Sarkissian, Christineh N; Wendt, Dan; Fitzpatrick, Paul; Lemontt, Jeffrey F; Scriver, Charles R; Stevens, Raymond C

2007-06-08

291

Differential Involvement of P-Glycoprotein (ABCB1) in Permeability, Tissue Distribution, and Antinociceptive Activity of Methadone, Buprenorphine, and Diprenorphine: In Vitro and In Vivo Evaluation  

PubMed Central

Conclusions based on either in vitro or in vivo approach to evaluate the P-gp affinity status of opioids may be misleading. For example, in vitro studies indicated that fentanyl is a P-gp inhibitor while in vivo studies indicated that it is a P-gp substrate. Quite the opposite was evident for meperidine. The objective of this study was to evaluate the P-gp affinity status of methadone, buprenorphine and diprenorphine to predict P-gp-mediated drug-drug interactions and to determine a better candidate for management of opioid dependence. Two in vitro (P-gp ATPase and monolayer efflux) assays and two in vivo (tissue distribution and antinociceptive evaluation in mdr1a/b (?/?) mice) assays were used. Methadone stimulated the P-gp ATPase activity only at higher concentrations, while verapamil and GF120918 inhibited its efflux (p <0.05). The brain distribution and antinociceptive activity of methadone were enhanced (p <0.05) in P-gp knockout mice. Conversely, buprenorphine and diprenorphine were negative in all assays. P-gp can affect the PK/PD of methadone, but not buprenorphine or diprenorphine. Our report is in favor of buprenorphine over methadone for management of opioid dependence. Buprenorphine most likely is not a P-gp substrate and concerns regarding P-gp-mediated drug-drug interaction are not expected.

HASSAN, HAZEM E.; MYERS, ALAN L.; COOP, ANDREW; EDDINGTON, NATALIE D.

2012-01-01

292

Treatment of chronic experimental Trypanosoma cruzi infections in mice with MK-436, a 2-substituted 5-nitroimidazole.  

PubMed Central

The antiprotozoal drug 3-(1-methyl-5-nitroimidazol-2-yl)-3a, 4,5,6,7,7a-hexahydro-1,2-benzisoxazole (MK-436) is highly efficacious for treating mice chronically infected with different strains of Trypanosoma cruzi. The compound was administered by gavage in two daily doses of 250 mg per kg body weight to 130 mice that had been infected for 90 to 400 days with either type II or III strains of T. cruzi. The following parasitological cure tests were carried out: xenodiagnosis, haemoculture, and inoculation of blood into newborn mice. Indirect immunofluorescence tests and histopathological studies were also performed. The results indicate that the drug is highly efficacious against chronic infection caused by both type II (cure rate, 90%) and type III strains (cure rate, 95.7%). Histopathological examinations showed complete clearance of the cardiac and muscular lesions in 36% of the mice infected with type II strains and a decrease in the intensity and extension of the lesions in mice infected with type III strains. Indirect immunofluorescence tests were persistently positive for all the mice 3-6 months after the treatment. Images Fig. 1 Fig. 2

Andrade, S. G.; Silva, R. C.; Santiago, C. M.

1989-01-01

293

Extensive Self-Harm Scarring: Successful Treatment With Simultaneous Use of a Single Layer Skin Substitute and Split-Thickness Skin Graft  

PubMed Central

Objective: Deliberate self-harm resulting in extensive skin scarring is a difficult clinical problem and is commonly associated with physical and sexual abuse or a known history of mental illness. Immediate hospital attendance often addresses the acute wound and current psychological state of patients; however, ongoing regret of these resulting scars present a problem to the patient and clinician. Deliberate self-harm to the skin leaves permanent and socially unacceptable scars in anatomically conspicuous areas and recognizable to others. Therefore, the aim was to offer a treatment to change these scars to that of an unknown entity. Methods: Six patients with extensive linear scars covering most of the forearm received surgical reconstruction. Patients were female aged between 18 and 47 years. Each patient had a history of psychosocial problems, and each had undergone psychiatric treatment. After an in-depth consultation and a further clinical psychological assessment, each individual was deemed suitable for reconstructive surgery. Scars were excised from the forearm en block, removing the majority of the affected area. Simultaneous use of a single layer skin substitute was used, covered by an autologous split-thickness skin graft. Negative pressure wound therapy was then applied immediately for 2 weeks after surgery. Results: The original scars were successfully converted to a socially and cosmetically acceptable appearance. Postoperative infection due to negative pressure wound therapy failure in one patient was the only complication reported. Conclusions: This case series highlights the utility of an innovative treatment for patients with DSH scarring resulting in aesthetic, psychological, and functional benefits.

Todd, Jodi; Ud-Din, Sara; Bayat, Ardeshir

2012-01-01

294

Opioid Maintenance Treatment during Pregnancy: Occurrence and Severity of Neonatal Abstinence Syndrome  

Microsoft Academic Search

Background: Opioid maintenance treatment (OMT) is widely used to treat pregnant women with a history of opioid dependence. This study investigated whether maternal methadone\\/buprenorphine dose and nicotine use in pregnancy affects the occurrence and duration of neonatal abstinence syndrome (NAS) in the infant. Methods: Forty-one pregnant women from OMT programmes in Norway who gave birth between January 2005 and January

Brittelise Bakstad; Monica Sarfi; Gabrielle K. Welle-Strand; Edle Ravndal

2009-01-01

295

Substituted isoquinolinones and quinazolinones  

US Patent & Trademark Office Database

The invention relates to substituted nitrogen containing bicyclic heterocycles of the formula (I) ##STR00001## wherein Z is CH.sub.2 or N--R.sup.4 and X, R.sup.1, R.sup.2, R.sup.4, R.sup.6, R.sup.7 and n are as defined in the description. Such compounds are suitable for the treatment of a disorder or disease which is mediated by the activity of MDM2 and/or MDM4, or variants thereof.

Berghausen; Joerg (Basel, CH); Buschmann; Nicole (Basel, CH); Furet; Pascal (Basel, CH); Gessier; Francois (Basel, CH); Lisztwan; Joanna Hergovich (Basel, CH); Holzer; Philipp (Basel, CH); Jacoby; Edgar (Basel, CH); Kallen; Joerg (Basel, CH); Masuya; Keiichi (Basel, CH); Soldermann; Carole Pissot (Basel, CH); Ren; Haixia (Shanghai, CN); Stutz; Stefan (Basel, CH)

2013-05-14

296

Bioengineered skin substitutes.  

PubMed

Bioengineered skin has great potential for use in regenerative medicine for treatment of severe wounds such as burns or chronic ulcers. Genetically modified skin substitutes have also been used as cell-based devices or "live bioreactors" to deliver therapeutics locally or systemically. Finally, these tissue constructs are used as realistic models of human skin for toxicological testing, to speed drug development and replace traditional animal-based tests in a variety of industries. Here we describe a method of generating bioengineered skin based on a natural scaffold, namely, decellularized human dermis and epidermal stem cells. PMID:23494436

Lei, Pedro; You, Hui; Andreadis, Stelios T

2013-01-01

297

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

PubMed Central

Purpose 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 ?-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/heat injury relative to placebo) for low-dose morphine was 0.01 (interquartile range: ?6.2; 9.9), 0.00 (?2.4; 2.1) for high-dose morphine, 0.03 (?1.8; 2.1) for low-dose buprenorphine, and 0.00 (?3.2; 1.1) for high-dose buprenorphine (P > 0.466). There were no significant differences in opioid responses between high and low pain-sensitive subjects (P > 0.286). High-dose buprenorphine, compared to placebo, was associated with a significantly enhanced action of the descending inhibitory pain control system (P = 0.004). Conclusion The present study, using multimodal testing technique, could not demonstrate any significant differences between morphine and buprenorphine in the profiles of antihyperalgesia and analgesia. Only high-dose buprenorphine was associated with a significant effect on the descending inhibitory pain control system.

Ravn, Pernille; Secher, Erik L; Skram, Ulrik; Therkildsen, Trine; Christrup, Lona L; Werner, Mads U

2013-01-01

298

Development and validation of a liquid chromatography–tandem mass spectrometry assay for the simultaneous quantification of buprenorphine, norbuprenorphine, and metabolites in human urine  

Microsoft Academic Search

A liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine\\u000a (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in human urine was developed and\\u000a fully validated. Extensive endogenous and exogenous interferences were evaluated and limits of quantification were identified\\u000a empirically. Analytical ranges were 5–1,000 ng\\/mL for BUP and BUP-Gluc and 25–1,000 ng\\/mL for NBUP and NBUP-Gluc. Intra-assay\\u000a and

Sherri L. Kacinko; Marta Concheiro-Guisan; Diaa M. Shakleya; Marilyn A. Huestis

2008-01-01

299

Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine.  

PubMed

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies. PMID:19653788

Chopra, Mohit P; Landes, Reid D; Gatchalian, Kirstin M; Jackson, Lisa C; Buchhalter, August R; Stitzer, Maxine L; Marsch, Lisa A; Bickel, Warren K

2009-08-01

300

Trends in the Use of Methadone and Buprenorphine at Substance Abuse Treatment Facilities: 2003 to 2011.  

National Technical Information Service (NTIS)

An estimated 2 million people in the United States are dependent upon or abuse opioids, including heroin and prescription opioids such as oxycodone and hydrocodone. Withdrawal from these drugs is generally so intense that those who are dependent upon them...

2013-01-01

301

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

Microsoft Academic Search

A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine\\u000a (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine,\\u000a cotinine, and trans-3?-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches\\u000a were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation\\u000a was achieved with a gradient mobile

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

2011-01-01

302

Skin Substitutes and Wound Healing  

Microsoft Academic Search

Medical science has vastly improved on the means and methods available for the treatment of wounds in the clinic. The production and use of various types of skin substitutes has led to dramatic improvements in the odds of survival for severely burned patients, but they have also shown promise for many other applications, including cases involving chronic wounds that are

F. A. Auger; D. Lacroix; L. Germain

2009-01-01

303

Oral buprenorphine is anti-inflammatory and modulates the pathogenesis of streptococcal cell wall polymer-induced arthritis in the Lew\\/SSN rat  

Microsoft Academic Search

Summary This study was carried out to determine an effective regimen for pain management in streptococcal cell wall (SCW)-induced arthritis in female Lew\\/SSN rats. Forty weanling rats (in 2 groups) were trained to accept disks of jelly as part of their dietary regimen. At 8 weeks of age weighing 150 g, SCW arthritis was induced and sublingual buprenorphine tablets were

D. Volker; M. Bate; R. Gentle; M. Garg

2000-01-01

304

Biologic and synthetic skin substitutes: An overview  

PubMed Central

The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing.

Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd. Yussof, Shah Jumaat

2010-01-01

305

Medically assisted recovery from opiate dependence within the context of the UK drug strategy: methadone and Suboxone (buprenorphine-naloxone) patients compared.  

PubMed

The focus of drug policy in the UK has shifted markedly in the past 5 years to move beyond merely emphasising drug abstinence towards maximising individuals' opportunities for recovery. The UK government continues to recognise the prescribing of narcotic medications indicated for opiate dependence as a key element of these individuals' recovery journey. This article describes a small, naturalistic comparison of the efficacy of the two most commonly prescribed opiate substitute medications in the UK--methadone hydrochloride (methadone oral solution) and Suboxone (buprenorphine-naloxone sublingual tablets)--for reducing current heroin users' (n = 34) days of heroin use, and preventing short-term abstainers (n = 37) from relapsing to regular heroin use. All patients had been prescribed either methadone or Suboxone for maintenance for 6 months prior to intake. Results showed that when controlling for a number of patient-level covariates, both methadone and Suboxone significantly reduced current users' days of heroin use between the 90 days prior to intake and at the 8-month follow-up, with Suboxone yielding a significantly larger magnitude reduction in heroin use days than methadone. Methadone and Suboxone were highly and equally effective for preventing relapse to regular heroin use, with all but 3 of 37 (91.9%) patients who were abstinent at intake reporting past 90-day point prevalence heroin abstinence at the 8-month follow-up. Overall, prescribing methadone or Suboxone for eight continuous months was highly effective for initiating abstinence from heroin use, and for converting short-term abstinence to long-term abstinence. However, the study design, which was based on a relatively small sample size and was not able randomise patients to medication and so could not control for the effects of potential prognostic factors inherent within each patient group, means that these conclusions can only be made tentatively. These positive but preliminary indications of the comparative efficacy of methadone and Suboxone for treating opiate dependence now require replication in a well-powered, randomised controlled trial. PMID:22703715

McKeganey, Neil; Russell, Christopher; Cockayne, Lucinda

2012-06-15

306

Nucleophilic Aromatic Substitution.  

ERIC Educational Resources Information Center

|Described is a microscale organic chemistry experiment which demonstrates one feasible route in preparing ortho-substituted benzoic acids and provides an example of nucleophilic aromatic substitution chemistry. Experimental procedures and instructor notes for this activity are provided. (CW)|

Avila, Walter B.; And Others

1990-01-01

307

Quinine substitutes in the confederate army.  

PubMed

During the Civil War, the unreliable supply and high cost of quinine forced the Confederate Army to use alternative treatments for malaria. Many quinine substitutes were mentioned in the literature of the time, but relatively few were advocated by Confederate officials and even fewer are described in surviving records. Medical supply officers often issued substitute remedies when quinine was requisitioned. Most alternative treatments were made from indigenous plants such as dogwood, willow (a constituent of which gave rise to aspirin), and tulip tree. High hopes were held for Georgia bark, which was thought to be closely related to cinchona, from which quinine was derived. Documentation of the effectiveness of quinine substitutes is scanty but is most plentiful for the external application of turpentine. The quinine substitutes were generally considered useful but not as effective as quinine. The Confederate Surgeon General's Office was active in seeking out and supplying troops with quinine substitutes. PMID:17615851

Hasegawa, Guy R

2007-06-01

308

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).  

PubMed

SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation--fentanyl and buprenorphine--fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2. The use of opioids in noncancer-related pain: Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3. The use of opioids in neuropathic pain: The role of opioids in neuropathic pain has been under debate in the

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

2008-05-23

309

Substitute Addiction: A Concern for Researchers and Practitioners  

ERIC Educational Resources Information Center

|An understanding of the role of substitute addictions remains unclear. This article examines the range and possible reward functions of substitute addictions. We suggest that prevention education and treatment need to take into account substitute addictions as an influential aspect of recovery. Research is needed to better understand the…

Sussman, Steve; Black, David S.

2008-01-01

310

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

PubMed Central

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 BUP) stabilization (4-8 weeks), and chronic administration (12-18 weeks), at trough (just prior to dosing) and peak (3 hours after dosing) plasma levels. Collection of the control group’s pain responses occurred twice during a single session, three hours apart. Baseline comparisons indicate that heroin-dependent individuals demonstrate significantly shorter latencies to threshold and tolerance for cold-pressor pain than the control group. Across pain stimuli and time points, little change in pain responses were found over time, the exception being cold pressor pain tolerance, for which hyperalgesia significantly increased at trough METH/BUP levels in both groups as they stabilized in treatment. We conclude that heroin-dependent individuals are hyperalgesic, and that once stabilized in treatment, are not different in pain responses regardless of treatment agent. The effects of non-pharmacologic therapy and previous heroin use may explain increased hyperalgesia found with treatment. Perspective To better understand the clinical phenomenon of OIH, this article describes experimental pain responses of heroin-dependent participants both prior to and over the course of maintenance therapy with methadone or buprenorphine. Hyperalgesia is present with illicit and treatment opioid use, and does not appear to appreciably improve over the course of treatment.

Compton, Peggy; Canamar, Catherine P.; Hillhouse, Maureen; Ling, Walter

2012-01-01

311

Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients  

Microsoft Academic Search

Up to 1999 more opioid dependent patients in Germany were substituted with codeine or dihydrocodeine (summarised as codeine) than with methadone. The current retrospective study compares the differences in detoxification treatment outcome for codeine-substituted patients, methadone-substituted patients and patients injecting illicit heroin. The study is based on the medical records of 1070 patients admitted consecutively for opioid and polytox detoxification

Markus Backmund; Kirsten Meyer; Dieter Eichenlaub; Christian G. Schütz

2001-01-01

312

Review of Bone Substitutes  

PubMed Central

Bone substitutes are being increasingly used in craniofacial surgery and craniomaxillofacial trauma. We will review the history of the biomaterials and describe the ideal characteristics of bone substitutes, with a specific emphasis on craniofacial reconstruction. Some of the most commonly used bone substitutes are discussed in more depth, such as calcium phosphate and hydroxyapatite ceramics and cements, bioactive glass, and polymer products. Areas of active research and future directions include tissue engineering, with an increasing emphasis on bioactivity of the implant.

Pryor, Landon S.; Gage, Earl; Langevin, Claude-Jean; Herrera, Fernando; Breithaupt, Andrew D.; Gordon, Chad R.; Afifi, Ahmed M.; Zins, James E.; Meltzer, Hal; Gosman, Amanda; Cohen, Steve R.; Holmes, Ralph

2009-01-01

313

Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of buprenorphine, norbuprenorphine, and metabolites in human urine  

PubMed Central

A liquid chromatography–tandem mass spec-trometry method for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in human urine was developed and fully validated. Extensive endogenous and exogenous interferences were evaluated and limits of quantification were identified empirically. Analytical ranges were 5?1,000 ng/mL for BUP and BUP-Gluc and 25?1,000 ng/mL for NBUP and NBUP-Gluc. Intra-assay and interassay imprecision were less than 17% and recovery was 93?116%. Analytes were stable at room temperature, at 4 °C, and for three freeze–thaw cycles. This accurate and precise assay has sufficient sensitivity and specificity for urine analysis of specimens collected from individuals treated with BUP for opioid dependence.

Kacinko, Sherri L.; Concheiro-Guisan, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

2009-01-01

314

Fast GC-MS method for the simultaneous screening of THC-COOH, cocaine, opiates and analogues including buprenorphine and fentanyl, and their metabolites in urine  

Microsoft Academic Search

A fast gas chromatography (GC)-MS method has been developed and validated for the simultaneous screening of different classes\\u000a of drugs of abuse in urine. Tetrahydrocannabinol metabolite, cocaine, opiates such as morphine, O-6-monoacetylmorphine (O-6-MAM), codeine, opioids such as buprenorphine, methadone, pentazocine, fentanyl and analogues and their main metabolites\\u000a can be detected and quantified after a simple liquid–liquid extraction in alkaline conditions

Sabina Strano-Rossi; Ana Maria Bermejo; Xavier de la Torre; Francesco Botrè

2011-01-01

315

Bone substitutes: new concepts  

Microsoft Academic Search

The filling of bone defects resulting from trauma or surgical resections of tumors requires bone grafts or bone substitutes. Bone substitute must be biocompatible, osteoconductive, and must present good mechanical properties. Among biomaterials classicaly used, calcium phosphate ceramic appear to be suitable alternatives to bone grafts. Calcium phosphate are known able to promote new bone formation on contact and have

D. Heymann; N. Passuti

1999-01-01

316

A combined liquid three-phase micro-extraction and differential pulse voltammetric method for preconcentration and detection of ultra-trace amounts of buprenorphine using a modified pencil electrode.  

PubMed

A combination of polytetrafluorethylene membrane-based liquid three-phase micro-extraction and voltammetry was used for the micro-separation and determination of buprenorphine. Type of the organic solvent used, pH levels of the donor and acceptor phases, salt concentration, extraction time, stirring rate, and electrochemical parameters as the essential factors affecting the liquid three-phase micro-extraction of buprenorphine were investigated. Differential pulse voltammetry exhibited two linear dynamic ranges of 1.0-109.0pmolL(-1) and 0.109nmolL(-1)-0.11µmolL(-1) of buprenorphine and the detection limit was found to be as low as 0.6pmolL(-1) of buprenorphine. Also, the effects of a number of common substances potentially interfering with selectivity were studied. The results indicate that the proposed method is highly selective and sensitive for buprenorphine detection in real samples such as human urine and plasma of both drug-addict and non-addict human subjects. PMID:24148523

Ensafi, Ali A; Khoddami, Elaheh; Rezaei, B

2013-08-19

317

Skin Substitutes and Uses Thereof.  

National Technical Information Service (NTIS)

The present invention relates to in vitro cultured skin substitutes, and in particular to improved methods for organotypic culture of skin substitutes. In some embodiments, the dermal equivalent of the skin substitute is lifted to air interface of the cul...

C. A. R. Ivarie L. A. Hoffman P. Barth

2004-01-01

318

1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases.  

PubMed

Adenosine receptors and monoamine oxidases are drug targets for neurodegenerative diseases such as Parkinson's and Alzheimer's disease. In the present study we prepared a library of 55 mostly novel tetrahydropyrimido[2,1-f]purinediones with various substituents in the 1- and 3-position (1,3-dimethyl, 1,3-diethyl, 1,3-dipropyl, 1-methyl-3-propargyl) and broad variation in the 9-position. A synthetic strategy to obtain 3-propargyl-substituted tetrahydropyrimido[2,1-f]purinedione derivatives was developed. The new compounds were evaluated for their interaction with all four adenosine receptor subtypes and for their ability to inhibit monoamine oxidases (MAO). Introduction of mono- or di-chloro-substituted phenyl, benzyl or phenethyl residues at N9 of the 1,3-dimethyl series led to the discovery of a novel class of potent MAO-B inhibitors, the most potent compound being 9-(3,4-dichlorobenzyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)-dione (21g, IC50 human MAO-B: 0.0629?M), which displayed high selectivity versus the other investigated targets. Potent dually active A1/A2A adenosine receptor antagonists were identified, for example, 9-benzyl-1-methyl-3-propargyl-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)dione (19f, Ki, human receptors, A1: 0.249?M, A2A: 0.253?M). Several compounds showed triple-target inhibition, the best compound being 9-(2-methoxybenzyl)-1-methyl-3-(prop-2-ynyl)-6,7,8,9-tetrahydro pyrimido [1,2-f]purine-2,4(1H,3H)-dione (19g, Ki A1: 0.605?M, Ki A2A: 0.417?M, IC50 MAO-B: 1.80?M). Compounds inhibiting several different targets involved in neurodegeneration may exhibit additive or even synergistic effects in vivo. PMID:24139167

Koch, Pierre; Akkari, Rhalid; Brunschweiger, Andreas; Borrmann, Thomas; Schlenk, Miriam; Küppers, Petra; Köse, Meryem; Radjainia, Hamid; Hockemeyer, Jörg; Drabczy?ska, Anna; Kie?-Kononowicz, Katarzyna; Müller, Christa E

2013-09-25

319

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

PubMed Central

Attitudes, perceived social norms and intentions were assessed for 376 counselors and 1083 clients from outpatient, methadone and residential drug treatment programs regarding four medications used to treat opiate dependence: methadone, buprenorphine, clonidine, and ibogaine. Attitudes, social norms and intentions to use varied by treatment modality. Methadone clients and counselors had more positive attitudes toward the use of methadone, while their counterparts in residential and outpatient settings had neutral or negative assessments. Across modalities, attitudes, perceived social norms, and intentions toward the use of buprenorphine were relatively neutral. Assessments of clonidine and ibogaine were negative for clients and counselors in all settings. Social normative influences were dominant across settings and medications in determining counselor and client intentions to use medications, suggesting that perceptions about beliefs of peers may play a critical role in use of medications to treat opiate dependence.

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

2009-01-01

320

Physician Substitutes (update)  

Center for Biologics Evaluation and Research (CBER)

Text Version... 1. The physician substitute must be a graduate of a recognized educational program such as nursing, emergency technician or physician assistant ... More results from www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation

321

Effects of heat treatment and substitution level on palatability and nutritional value of soy defatted flour in feeds for Coho Salmon, Oncorhynchus kisutch  

Microsoft Academic Search

An in vivo digestibility trial and a feeding trial were conducted to determine the extent to which heat treatment, nutritional quality, and palatability of hexane-extracted, defatted soy flour (SF) influenced growth of fingerling coho salmon. Heat treatment of SF (autoclave, 1.7 atm, 121°C) lowered trypsin units inhibited (TUI) from 181 to 1.8 after 20 min and lowered protein solubility from

Ronney E. Arndt; Ronald W. Hardy; Shozo H. Sugiura; Faye M. Dong

1999-01-01

322

The substitutability of reinforcers  

PubMed Central

Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included.

Green, Leonard; Freed, Debra E.

1993-01-01

323

The substitutability of reinforcers.  

PubMed

Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

Green, Leonard; Freed, Debra E

1993-07-01

324

Isovalent Substitution and Heat Treatment Control of Chain Oxygen Disorder, Structure and Tc in Y1-xSmxSrBaCu3O6+z  

NASA Astrophysics Data System (ADS)

We report here on the preparation, X-ray diffraction (XRD) with Rietveld refinement, AC susceptibility measurements and effect of heat treatments in Y1-xSmxSrBaCu3O6+z. Each sample was subject to two types of heat treatment: oxygen annealing [O] and argon annealing followed by oxygen annealing [OAO]. For the samples [O], as x increases from 0 to 1, the orthorhombicity ? decreases, together with Tc. However, for the samples [OAO], Tc generally increases with x as V decreases. This last evolution of Tc and V in opposite senses is unusual and it's observed for the first time. For a given x, the argon treatment increases V (for 0<=x<=1), Tc (for x >= 0.4) and the distance d[Cu(1)-(Sr/Ba)] for x < 0.5 and decrease it for x>0.5. Remarkable correlations were observed. A combination of several factors such as decrease in d[Cu (1)-O(1)] increase in cationic and chain oxygen ordering; the mobile hole content in the Cu(2)O2 plans (pSh) and in-phase purity for the [OAO] samples may account for the observed data.

Nafidi, A.; Bouallal, B.; El Kaaouachi, A.; Bellioua, M.; Sahsah, H.

2006-09-01

325

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

PubMed

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

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

2012-12-28

326

Sensory substitution in prosthetics.  

PubMed

Use of arm and hand prostheses may be essential for many amputees to facilitate activities of daily life and interaction with society. A major drawback that reduces the use of prostheses, however, is the lack of sensibility. Current strategies for sensory feedback in commercially available prostheses are based on force and slip sensors in the mechanical hand for independent grasp control in an opening and closing function. Developing principles for providing conscious sensibility is discussed, including new techniques where hearing is used as substitution for sensation based on sense substitution. PMID:11599215

Lundborg, G; Rosén, B

2001-08-01

327

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

Microsoft Academic Search

A simple isocratic reversed-phase high-performance liquid chromatographic method (RP-HPLC) was developed for the simultaneous determination of buprenorphine hydrochloride, naloxone hydrochloride dihydrate and its major impurity, noroxymorphone, in pharmaceutical tablets. The chromatographic separation was achieved with 10mmolL?1 potassium phosphate buffer adjusted to pH 6.0 with orthophosphoric acid and acetonitrile (17:83, v\\/v) as mobile phase, a C-18 column, Perfectsil Target ODS3 (150mm×4.6mm

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

2009-01-01

328

Online solid-phase extraction liquid chromatography–electrospray-tandem mass spectrometry analysis of buprenorphine and three metabolites in human urine  

Microsoft Academic Search

An online solid-phase extraction (SPE) liquid chromatography–electrospray tandem mass spectrometry (LC–ESI-MS\\/MS) method for the determination of buprenorphine (Bup), norbuprenorphine (nBup), buprenorphie-3-?-d-glucuronide (Bup-3-G) and norbuprenorphie-3-?-d-glucuronide (nBup-3-G) in human urine was developed and validated. A mixed mode SPE column with both hydrophilic and lipophilic functions was used for online extraction. A C18 column was employed for LC separation and ESI-MS\\/MS was utilized

An-Chan Liu; Tzuen-Yeuan Lin; Lien-Wen Su; Ming-Ren Fuh

2008-01-01

329

Generating query substitutions  

Microsoft Academic Search

We introduce the notion of query substitution, that is, gen- erating a new query to replace a user's original search query. Our technique uses modications based on typical substitu- tions web searchers make to their queries. In this way the new query is strongly related to the original query, contain- ing terms closely related to all of the original terms.

Rosie Jones; Benjamin Rey; Omid Madani; Wiley Greiner

2006-01-01

330

The Age of Substitutability  

ERIC Educational Resources Information Center

|Dwindling mineral resources might cause a shift from nonrenewable resources to renewable resources and inexhaustible elements such as iron and aluminum. Alternative energy sources such as breeder, fusion, solar, and geothermal power must be developed for production and recycling of materials. Substitution and, hence, living standards ultimately…

Goeller, H. E.; Weinberg, Alvin M.

1976-01-01

331

Performing Substitute Teaching  

ERIC Educational Resources Information Center

|Formal education is both a right and an obligation bestowed on young people in most all nations of the world. Teachers (adults) and students (youth) form a co-present dyadic contract that must be maintained within the classroom. Substitute teachers fill a role in sustaining the integrity of this teacher-student link, whenever teachers are absent.…

Bletzer, Keith V.

2010-01-01

332

EFFICIENT ATTACKS ON HOMOPHONIC SUBSTITUTION CIPHERS  

Microsoft Academic Search

Substitution ciphers are one of the earliest types of ciphers. Examples of classic substitution ciphers include the well-known simple substitution and the less well-known homophonic substitution. Although simple substitution ciphers are indeed simple - both in terms of their use and attacks; the homophonic substitution ciphers are far more challenging to break. Even with modern computing technology, homophonic substitution ciphers

Amrapali Dhavare

2011-01-01

333

Empirically supported substance abuse treatment approaches: A survey of treatment providers' perspectives and practices  

PubMed Central

To better understand the extent that empirically supported and promising substance abuse treatment approaches are implemented in community settings, treatment providers were surveyed regarding their perceptions and use of several psychosocial and pharmacological treatment interventions. Program directors (n=30) and staff members (n=331) from diverse community settings rated the effectiveness and extent of use of various treatment interventions, and provided information on program and workforce characteristics via self-administered questionnaires. On average, program directors and staff rated the psychosocial treatment interventions as effective, with the exception of vouchers/motivational incentives. About half of the treatment providers did not know the effectiveness of certain pharmacological treatments, including buprenorphine and naltrexone. Respondents from the majority of programs (55%–80%) reported using Motivational Enhancement Therapy, Community Reinforcement Approach, and Supportive Expressive Psychotherapy. The extent that programs used several of the treatment interventions was related to organizational training and information resources. The study findings provide important information regarding training and research dissemination efforts.

Herbeck, Diane M.; Hser, Yih-Ing; Teruya, Cheryl

2008-01-01

334

Substitutional carbon in germanium  

Microsoft Academic Search

Carbon impurities implanted into single-crystalline germanium are studied with infrared absorption spectroscopy and ion channeling. After implantation of 12C+ at room temperature and subsequent annealing at 350 °C, a sharp infrared absorption line is observed at 531 cm-1. When 12C+ is substituted by 13C+, the line shifts down in frequency to 512 cm-1 and co-implantation of 12C+ and 13C+ does

L. Hoffmann; J. C. Bach; B. Bech Nielsen; P. Leary; R. Jones; S. Öautberg

1997-01-01

335

[Primary health care and family medicine--possibilities for treatment of opiate addicts].  

PubMed

The global trend of promoting management and treatment of drug addicts in family physician offices is the result of the success of opioid agonist therapy. Studies have shown favorable results by shifting treatment into the hands of family physician. This process contributes to general health care of drug addicts and their health by linking different areas of health care, thereby providing comprehensive protection. Shifting treatment of addiction to family physician offices contributes to the elimination of treatment isolation and stigmatization, while further benefits are lower barriers to employment, increase in patient privacy and opportunity to provide health care. The aim of this study was to provide a concise overview of the knowledge from new clinical research over the past ten years on heroin addiction treatment in primary care. New research dealing with the approach to treating addicts indicates a direct link between receiving primary health care with a reduced likelihood of using heroin; furthermore, the main concerns of drug addicts for treatment are availability of more therapeutic programs, better functioning of existing programs, and improved staff relations towards them; final results and outcomes achieved by office and hospital treatment of drug addicts are similar and confirm the positive linear relationship between treatment duration and outcome. Studies comparing therapies show a positive effect of the adaptive methadone treatment maintenance model on the psychosocial factors; equal efficiency of treatment regardless of initiation with buprenorphine or with methadone; and equal effectiveness of levo-alpha-acetylmethadol treatment compared with methadone and diacetylmorphine as a good alternative for addiction therapy with previously unsatisfactory results. New studies on buprenorphine show equal effectiveness and cost of detoxification whether guided by a family physician or at the hospital; non-supervised therapy does not significantly influence the outcome, but is significantly cheaper; long-term therapy with buprenorphine in the doctor's office shows mild retention. PMID:23814972

Tiljak, Hrvoje; Nerali?, Ivana; Cerovecki, Venija; Kastelic, Andrej; Adzi?, Zlata Ozvaci?; Tiljak, Anja

2012-10-01

336

An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in african-americans.  

PubMed

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 ?-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. PMID:23612435

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

2013-04-23

337

A Comparative Clinical Study of the Effect of WeiniCom, a Chinese Herbal Compound, on Alleviation of Withdrawal Symptoms and Craving for Heroin in Detoxification Treatment  

Microsoft Academic Search

WeiniCom is a Chinese herbal compound. The purposes of this double blind study were to evaluate (1) the efficacy ofWeiniCom in reducing acute opioid withdrawal symptoms and craving, and (2) the side effects of WeiniCom, in each instance by comparing WeiniCom with buprenorphine, an established opioid detoxification treatment agent. Forty-two heroin addicts meeting the criteria of dependence in DSM-IV were

Wei Hao; Min Zhao

2000-01-01

338

Buprenorphine Modulates Methamphetamine-Induced Dopamine Dynamics in the Rat Caudate Nucleus  

Microsoft Academic Search

Methamphetamine (METH) abuse and addiction present a major problem in the United States and globally. Oxidative stress associated\\u000a with exposure to METH mediates to the large extent METH-evoked neurotoxicity. While there are currently no medications approved\\u000a for treating METH addiction, its pharmacology provides opportunities for potential pharmacotherapeutic adjuncts to behavioral\\u000a therapy in the treatment of METH addiction. Opioid receptor agonists

Frederico C. Pereira; Bobby Gough; Tice R. Macedo; Carlos F. Ribeiro; Syed F. Ali; Zbigniew K. Binienda

2011-01-01

339

Assessing Need for Medication-Assisted Treatment for Opiate-Dependent Prison Inmates  

PubMed Central

Individuals with a history of heroin dependence are overrepresented in American correctional facilities and 75% of inmates with a drug use disorder do not receive treatment during incarceration or after release. Medication-assisted treatment (MAT) with opiate agonists, such as methadone or buprenorphine, constitute standard of care; to guide planning for an expansion of drug treatment services in correctional facilities, a needs assessment was conducted at the Department of Correction and Rehabilitation (DCR) of Puerto Rico (PR). We report on the research process, the findings that informed our recommendations for the PCR to expand MAT for eligible inmates, and lessons learned.

Albizu-Garcia, Carmen E.; Caraballo, Jose Noel; Caraballo-Correa, Glorimar; Hernandez-Viver, Adriana; Roman-Badenas, Luis

2012-01-01

340

Sores -- Treatment  

MedlinePLUS Videos and Cool Tools

... called debridement. There are many different ways your healthcare provider may remove and clean off the dead ... substitute for the advice of a doctor or healthcare professional or a recommendation for any particular treatment ...

341

Substituted hydroxyapatites for bone repair.  

PubMed

Calcium phosphates such as hydroxyapatite have a wide range of applications both in bone grafts and for the coating of metallic implants, largely as a result of their chemical similarity to the mineral component of bone. However, to more accurately mirror the chemistry, various substitutions, both cationic (substituting for the calcium) and anionic (substituting for the phosphate or hydroxyl groups) have been produced. Significant research has been carried out in the field of substituted apatites and this paper aims to summarise some of the key effect of substitutions including magnesium, zinc, strontium, silicon and carbonate on physical and biological characteristics. Even small substitutions have been shown to have very significant effects on thermal stability, solubility, osteoclastic and osteoblastic response in vitro and degradation and bone regeneration in vivo. PMID:22389101

Shepherd, Jennifer H; Shepherd, David V; Best, Serena M

2012-03-03

342

[Vitreous substitutes as drug release systems].  

PubMed

Despite major improvements of vitreo-retinal surgical techniques proliferative vitreoretinopathy (PVR) remains a major challenge. Surgical therapy alone may not be sufficient in complicated cases of PVR. A combination of standard techniques such as pars plana vitrectomy with a vitreous substitute and a simultaneous adjuvant pharmacological treatment for the suppression of undesired proliferation of retinal cells and retinal scarring may be a promising therapeutic approach. However, due to the narrow therapeutic range and the short biological half-life of most anti-proliferative or anti-inflammatory drugs in the vitreous cavity, intravitreal slow-release systems for extended drug delivery are desirable. Vitrectomy for PVR normally requires a vitreous substitute. Consequently, a vitreous substitute that could also serve as a slow-release system for anti-proliferative or anti-inflammatory drugs would provide several advantages. This review gives an overview of recent developments of slow-release systems that may also be suitable as vitreous substitutes. Even standard internal tamponades such as silicone oils or gases may serve as extended drug-release systems under certain conditions. In the mean time polymerised hydrogels have been developed, which apart from providing an adequate tamponade effect, may facilitate an extended intravitreal release of various anti-proliferative and anti-inflammatory drugs for several weeks. PMID:19750422

Szurman, P; Frank, C; Kaczmarek, R T; Spitzer, M S

2009-09-11

343

Confidence in generic drug substitution.  

PubMed

Patients should have confidence that the generic drugs they are prescribed in the United States can be effectively substituted for the brand product or another generic product. Through new bioequivalence study designs for narrow therapeutic index (NTI) drugs and postapproval studies of generic substitution, the US Food and Drug Administration's (FDA's) ongoing generic drug regulatory science activities are designed to ensure successful generic substitution for all drug products. PMID:24048239

Lionberger, R; Jiang, W; Huang, S-M; Geba, G

2013-10-01

344

Silent nucleotide substitutions during evolution  

NASA Astrophysics Data System (ADS)

Silent nucleotide substitutions in evolution are found by comparing homologous sequences of DNA from different organisms. Silent changes are common in the third bases of codons, so that no change takes place in the specified amino acid. Silent changes average about half of the total nucleotide substitutions during evolution of protein-coding regions of genes. Nucleotide substitutions also take place during evolution in non-coding regions of DNA, such as in intervening sequences and in sequences that precede and follow codon regions in genes. Deletions and additions from events of recombination, in addition to nucleotide substitutions, are common in these non-coding regions.

Jukes, Thomas H.

1980-11-01

345

Sulfur-substituted tetrahedranes.  

PubMed

The stable sulfur-substituted tetrahedrane derivatives 2-4 were synthesized by the reaction of tris(trimethylsilyl)tetrahedranyllithium 1 with diphenyl disulfide, bis(4-nitrophenyl) disulfide, and bis(2,4-dinitrophenyl) disulfide, respectively, and characterized by both NMR spectroscopy and X-ray crystallography. Phenylsulfonyltetrahedrane 5 was prepared by the reaction of 2 and m-chloroperbenzoic acid. The UV-vis absorption spectra of 2-4 suggested an interaction of the ? orbital of the tetrahedrane core and the lone-pair electrons on the sulfur atom, whereas no interaction for 5 was found. Thermal reactions of 2 and 5 are also reported; 2 underwent fragmentation into two acetylene molecules, whereas 5 gave the corresponding cyclobutadiene. PMID:21728313

Ochiai, Tatsumi; Nakamoto, Masaaki; Inagaki, Yusuke; Sekiguchi, Akira

2011-07-07

346

Development and application of carbon nanotubes assisted electromembrane extraction (CNTs/EME) for the determination of buprenorphine as a model of basic drugs from urine samples.  

PubMed

In this work carbon nanotubes assisted electromembrane extraction (CNTs/EME) coupled with capillary electrophoresis (CE) and ultraviolet (UV) detection was developed for the determination of buprenorphine as a model of basic drugs from urine samples. Carbon nanotubes reinforced hollow fiber was used in this research. Here the CNTs serve as a sorbent and provide an additional pathway for solute transport. The presence of CNTs in the hollow fiber wall increased the effective surface area and the overall partition coefficient on the membrane; and lead to an enhancement in the analyte transport. For investigating the influence of the presence of CNTs in the SLM on the extraction efficiency, a comparative study was carried out between EME and CNTs/EME methods. Optimization of the variables affecting these methods was carried out in order to achieve the best extraction efficiency. Optimal extractions were accomplished with NPOE as the SLM, with 200V as the driving force, and with pH 2.0 in the donor and pH 1.0 in the acceptor solutions with the whole assembly agitated at 750rpm after 25min and 15min for EME and CNTs/EME, respectively. Under the optimized conditions, in comparison with the conventional EME method, CNTs/EME provided higher extraction efficiencies in shorter time. This method provided lower limit of detection (1ngmL(-1)), higher preconcentration factor (185) and higher recovery (92). Finally, the applicability of this method was evaluated by the extraction and determination of buprenorphine in patients' urine samples. PMID:23452789

Hasheminasab, Kobra Sadat; Fakhari, Ali Reza

2013-01-05

347

Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution  

Microsoft Academic Search

The effect of testosterone (T) substitution therapy on blood vessel functions in relation to cardiovascular disease has not been fully elucidated. In 36 newly diagnosed nonsmoking hy- pogonadal men (37.5 12.7 yr) endothelium-dependent flow- mediated vasodilatation (FMD; decreased in atherosclerosis) of the brachial artery was assessed before treatment and after 3 months of T substitution therapy (250 mg testosterone en-

MICHAEL ZITZMANN; MAIK BRUNE; EBERHARD NIESCHLAG

348

Stoichiometric carbon substitution in MgB2  

Microsoft Academic Search

Carbon has been substituted into the MgB2 lattice, forming the series Mg(B1-xCx)2, by heat treatments in sealed Ta tubes starting with elemental constituents. The superconducting transition temperature, TC, was measured by diamagnetic susceptibility. The superconducting transitions are sharp and the x-ray diffraction on the samples show only trace amounts of impurity phases. The C fraction that substitutes the B atoms

S. Jemima Balaselvi; N. Gayathri; A. Bharathi; V. S. Sastry; Y. Hariharan

2004-01-01

349

Resistance-induced antibiotic substitution  

Microsoft Academic Search

In many cases, physicians prescribe antibiotics without knowing whether an individual patient is infected with a susceptible or resistant pathogen. As the proportion of resistant organisms in a community increases, physicians substitute away from older-inexpensive drugs to newer, more expensive agents as first line therapy. This paper explores the implications of resistance-induced antibiotic substitution for epidemiological models to predict future

David H. Howard

2004-01-01

350

Treatment of opioid dependence in the setting of pregnancy.  

PubMed

Opioid dependence in the setting of pregnancy provides a distinct set of challenges for providers. Treatment plans must take into consideration psychiatric and medical comorbidities while balancing risks and benefits for the maternal-fetal dyad. Treatment is best offered through a comprehensive treatment program designed to effectively deliver opioid agonist maintenance treatment along with psychosocial and obstetric care. As misuse of prescription analgesics increases in the United States, identification of the problem in pregnancy will become more important because this misuse is expected to lead to an increased prevalence of opioid dependence in pregnancy. Buprenorphine as maintenance treatment of opioid dependence during pregnancy has promise and may offer some benefits, but more research is needed, especially regarding induction of actively addicted women during pregnancy. For the present, methadone maintenance remains the standard of care for agonist treatment of opioid dependence in pregnancy against which other treatments must be compared. PMID:22640765

Young, Jessica L; Martin, Peter R

2012-04-11

351

Buprenorphine Transdermal Delivery System in Adults with Persistent Noncancer-Related Pain Syndromes Who Require Opioid Therapy: A Multicenter, 5Week Run-in and Randomized, Double-Blind Maintenance-of-Analgesia Study  

Microsoft Academic Search

Objective: This study compared the efficacy and safety profile of buprenorphine transdermal delivery system (BTDS) and placebo in subjects with persistent noncancer-related pain who required opioid analgesics.Methods: This was a multicenter, double-blind, parallel-group study in adult subjects (age ?18 years) with at least a 2-month history of noncancer-related pain for which they received oral opioid combination agents. The study employed

Craig J. Landau; William D. Carr; Albert J. Razzetti; Nelson E. Sessler; Catherine Munera; Steven R. Ripa

2007-01-01

352

Wearable and implantable pancreas substitutes.  

PubMed

A lifelong-implanted and completely automated artificial or bioartificial pancreas (BAP) is the holy grail for type 1 diabetes treatment, and could be a definitive solution even for other severe pathologies, such as pancreatitis and pancreas cancer. Technology has made several important steps forward in the last years, providing new hope for the realization of such devices, whose feasibility is strictly connected to advances in glucose sensor technology, subcutaneous and intraperitoneal insulin pump development, the design of closed-loop control algorithms for mechatronic pancreases, as well as cell and tissue engineering and cell encapsulation for biohybrid pancreases. Furthermore, smart integration of the mentioned components and biocompatibility issues must be addressed, bearing in mind that, for mechatronic pancreases, it is most important to consider how to recharge implanted batteries and refill implanted insulin reservoirs without requiring periodic surgical interventions. This review describes recent advancements in technologies and concepts related to artificial and bioartificial pancreases, and assesses how far we are from a lifelong-implanted and self-working pancreas substitute that can fully restore the quality of life of a diabetic (or other type of) patient. PMID:22990986

Ricotti, Leonardo; Assaf, Tareq; Dario, Paolo; Menciassi, Arianna

2012-09-20

353

How Do Substitute Teachers Substitute? An Empirical Study of Substitute-Teacher Labor Supply  

ERIC Educational Resources Information Center

|This paper examines the daily labor supply of a potentially important, but often overlooked, source of instruction in U.S. public schools: substitute teachers. I estimate a sequential binary-choice model of substitute teachers' job-offer acceptance decisions using data on job offers made by a randomized automated calling system. Importantly, this…

Gershenson, Seth

2012-01-01

354

40 CFR Appendix A to Subpart G of... - Substitutes Subject to Use Restrictions and Unacceptable Substitutes  

Code of Federal Regulations, 2012 CFR

...G, App. A Appendix A to Subpart G of Part 82âSubstitutes Subject to Use Restrictions and Unacceptable Substitutes Refrigerants Unacceptable Substitutes End-use Substitute Decision Comments CFC-11 centrifugal chillers (retrofit)...

2012-07-01

355

Substitution and pooling in crowding.  

PubMed

Unless we fixate directly on it, it is hard to see an object among other objects. This breakdown in object recognition, called crowding, severely limits peripheral vision. The effect is more severe when objects are more similar. When observers mistake the identity of a target among flanker objects, they often report a flanker. Many have taken these flanker reports as evidence of internal substitution of the target by a flanker. Here, we ask observers to identify a target letter presented in between one similar and one dissimilar flanker letter. Simple substitution takes in only one letter, which is often the target but, by unwitting mistake, is sometimes a flanker. The opposite of substitution is pooling, which takes in more than one letter. Having taken only one letter, the substitution process knows only its identity, not its similarity to the target. Thus, it must report similar and dissimilar flankers equally often. Contrary to this prediction, the similar flanker is reported much more often than the dissimilar flanker, showing that rampant flanker substitution cannot account for most flanker reports. Mixture modeling shows that simple substitution can account for, at most, about half the trials. Pooling and nonpooling (simple substitution) together include all possible models of crowding. When observers are asked to identify a crowded object, at least half of their reports are pooled, based on a combination of information from target and flankers, rather than being based on a single letter. PMID:22160819

Freeman, Jeremy; Chakravarthi, Ramakrishna; Pelli, Denis G

2012-02-01

356

40 CFR 721.5867 - Substituted phenol.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Substituted phenol. 721.5867 Section 721.5867 ...Substances § 721.5867 Substituted phenol. (a) Chemical substance and significant...substance generically identified as substituted phenol (PMNs P-89-1125,...

2013-07-01

357

40 CFR 721.5867 - Substituted phenol.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted phenol. 721.5867 Section 721.5867 ...Substances § 721.5867 Substituted phenol. (a) Chemical substance and significant...substance generically identified as substituted phenol (PMNs P-89-1125,...

2010-07-01

358

40 CFR 721.4420 - Substituted hydroxylamine.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 false Substituted hydroxylamine. 721.4420 Section 721.4420...Substances § 721.4420 Substituted hydroxylamine. (a) Chemical substance and significant...identified generically as substituted hydroxylamine (PMN P-84-492) is subject...

2009-07-01

359

40 CFR 721.4420 - Substituted hydroxylamine.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted hydroxylamine. 721.4420 Section 721.4420...Substances § 721.4420 Substituted hydroxylamine. (a) Chemical substance and significant...identified generically as substituted hydroxylamine (PMN P-84-492) is subject...

2010-07-01

360

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2010 CFR

... 2009-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2009-07-01

361

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2010-07-01

362

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2013-07-01

363

Rare 2-Substituted Purine Nucleosides.  

National Technical Information Service (NTIS)

This project is concerned with the synthesis of rare 2-substituted purine nucleosides with therapeutic potential against RNA viruses. The goals were to develop rational procedures for the synthesis of the target molecules discussed in the proposal. Synthe...

V. Nair

1986-01-01

364

Nucleophilic Substitution by Benzodithioate Anions.  

ERIC Educational Resources Information Center

|Describes a two-session experiment designed to provide a good illustration of, and to improve student knowledge of, the Grignard reaction and nucleophilic substitution. Discusses the procedure, experimental considerations, and conclusion of this experiment. (CW)|

Bonnans-Plaisance, Chantal; Gressier, Jean-Claude

1988-01-01

365

Preclinical evaluation of skin substitutes.  

PubMed

The important requirements of a skin substitute such as water vapour permeability, adherence to the excised wound surface, oxygen permeability, mechanical properties, impermeability to micro-organisms and exudate soaking capacity have been highlighted. Two commercial synthetic skin substitutes, Bioclusive and Geliperm, have been used to establish the preclinical assessment procedures for skin substitutes. Two in vitro techniques, the 'Water Cup' and the 'Inverted Cup,' and two in vivo methods involving a 'Ventilated Hygrometer Chamber' system and an Evaporimeter have been employed to assess and compare the water vapour permeability of the skin substitutes under controlled conditions. An Evaporimeter, which is very simple to operate, provides more accurate results. A simple test has been designed to evaluate the early adherence of the skin substitutes to the excised wound surface of rats. The pulling force and the peeling force required to remove the membrane from the wound surface have been measured and these forces have been found to depend upon the composition of the membrane. An oxygen permeability cell has been fabricated which measures the dissolved oxygen permeability of the skin substitutes. The detection of oxygen is based on the electrocatalytic reduction of oxygen at the surface of a noble metal. The tensile properties of the skin substitutes have been measured by an International Standard procedure and both the skin prostheses are associated with some drawbacks. An in vitro method of testing the microbial permeability of the skin substitutes has been designed which simulates an oozing colonized wound that a skin substitute faces in cases of septicaemia. Both the test materials were impermeable to both bacteria and fungi and will provide an effective barrier. The effectiveness of the skin substitutes to absorb wound exudate from the wound surface has been evaluated by soaking the pieces of the membranes in water, plasma and serum and observing their weight gain. The soaking capacity depends upon the composition and nature of the material. The procedures developed have been employed to evaluate a hydrogel type synthetic skin substitute recently formulated in our laboratory. PMID:2275766

Nangia, A; Hung, C T

1990-10-01

366

Treatment  

Microsoft Academic Search

Few clinical issues have been more hotly contested than the treatment of ADHD, particularly the relative value of medication\\u000a versus behavioral\\/psychosocial treatments (DuPaul & Power, 2008; Toplak, Connors, Shuster, Knezevic, & Parks, 2008; Wauschbusch\\u000a & Hill, 2003). Treatment decisions are often complicated by biases reflecting media coverage of diagnostic and treatment controversies,\\u000a cultural background, previous experiences or anecdotal stories from

Stephen E. Brock; Shane R. Jimerson; Robin L. Hansen

367

1-((3 S,4 S)-4Amino1-(4-substituted-1,3,5-triazin-2-yl) pyrrolidin-3-yl)-5,5-difluoropiperidin-2-one inhibitors of DPP-4 for the treatment of type 2 diabetes  

Microsoft Academic Search

A 3-amino-4-substituted pyrrolidine series of dipeptidyl peptidase IV (DPP-4) inhibitors was rapidly developed into a candidate series by identification of a polar valerolactam replacement for the lipophilic 2,4,5-trifluorophenyl pharmacophore. The addition of a gem-difluoro substituent to the lactam improved overall DPP-4 inhibition and an efficient asymmetric route to 3,4-diaminopyrrolidines was developed. Advanced profiling of a subset of analogs identified 5o

Kim M. Andrews; David A. Beebe; John W. Benbow; David A. Boyer; Shawn D. Doran; Yu Hui; Shenping Liu; R. Kirk McPherson; Constantin Neagu; Janice C. Parker; David W. Piotrowski; Steven R. Schneider; Judith L. Treadway; Maria A. VanVolkenberg; William J. Zembrowski

2011-01-01

368

Stakeholders' role in contemporary "substitute drug" prescribing policies in Italy.  

PubMed

This article, part of a comparative research project (WP2) funded by FP7 ALICE RAP, is based upon a review of literature and documents and 18 individual interviews with Italian national stakeholders (SHs) conducted in 2012. The goal was to identify the main shifts in opioid "substitution drug" treatment policies and understand the role played by different SHs during the last 30 years. The study confirms that opioid "substitution drug" treatment is a particularly suitable theme for improving knowledge in the field of SH analysis, even if results show that changes in policies are mainly due to external factors rather than to the action of SHs. PMID:23952507

Beccaria, Franca; Rolando, Sara

2013-08-01

369

Lipid-based fat substitutes.  

PubMed

Fats and oils account for 38% of the total calories in the diet of Western populations, especially in the U.S. They provide the most concentrated source of energy, 9 kcal/g of a triacylglycerol molecule compared with 4 kcal/g provided by carbohydrate and protein. In response to consumer demands for low-calorie or calorie-free fats and their reluctance to give up the taste of fat, current research efforts have been directed toward the development of lipid-like fat substitutes. These fat substitutes contain the fatty acids found in conventional fats and oils, with all the physical and organoleptic properties of fats, but provide few or no calories in the diet. Some of the fat substitutes are modified triacylglycerols (glycerol backbone) with reduced digestion and absorption; others are digestible and nondigestible carbohydrate fatty acid esters and polyesters, respectively. Sucrose polyester (Olestra), a sucrose molecule esterified with six to either fatty acids, is the most studied of the lipid-based fat substitutes containing a carbohydrate backbone. If approved by the FDA, sucrose polyester will find application in almost all fat-containing foods. Specialty fats or fat substitutes targeted to certain individuals with special needs are being developed. Among these are the medium-chain triacylglycerols and structured lipids (glycerol backbone), or ¿nutraceuticals¿ with reduced absorption and medical applications. Enzyme biotechnology is another tool available to lipid chemists to selectively modify, esterify, transform, transesterify, and interesterify fats and oils or synthesize new lipids such as structured lipids of food, nutritional, and medical importance. These designer fats may be the trend in the future to produce medical lipids that do not occur normally in nature. The different types of lipid-based fat substitutes are reviewed with respect to their synthesis, analysis, metabolism, potential applications/uses, and the future of fat substitutes. PMID:8573281

Akoh, C C

1995-09-01

370

Anion substitution in zinc chalcogenides.  

PubMed

Anion substitution effects on the structure and energy of zinc chalcogenides were studied with the semiempirical molecular orbital method MSINDO. Cyclic clusters of different sizes were chosen as model systems. The convergence of the bulk properties of the perfect clusters with increasing cluster size was tested. Single and multiple substitution of oxygen atoms in zinc oxide by sulfur and of sulfur atoms in zinc sulfide by oxygen served to determine the energetics of substitution for these two cases. It was found that the substitution of oxygen by sulfur in ZnO is easier than the substitution of sulfur by oxygen in ZnS in agreement with experimental results. The interaction between two oxygen atoms vs. two selenium atoms in zinc sulfide was investigated. Oscillations of the cluster energy in dependence of the distance between the two doping atoms were observed. These are explained by the relative sites of the doping atoms in the crystal lattice. The magnitude of the oscillations is smaller in ZnS:Se than in ZnS:O, because the difference between the anion radii of S2- and Se2- is smaller than between S2- and O2-. This is also reflected in the band gap. PMID:16691570

Jug, Karl; Tikhomirov, Viatcheslav A

2006-07-30

371

Current and potential pharmacological treatment options for maintenance therapy in opioid-dependent individuals.  

PubMed

Opioid dependence, manifesting as addiction to heroin and pharmaceutical opioids is increasing. Internationally, there are an estimated 15.6?million illicit opioid users. The global economic burden of opioid dependence is profound both in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism and lost productivity. Opioid agonist medications, such as methadone and buprenorphine, that stabilize neuronal systems and provide narcotic blockade are the most effective treatments. Prolonged provision of these medications, defined as maintenance treatment, typically produces improved outcomes when compared with short-duration tapers and withdrawal. The benefits of opioid agonist maintenance include decreased illicit drug use, improved retention in treatment, decreased HIV risk behaviours and decreased criminal behaviour. While regulations vary by country, these medications are becoming increasingly available internationally, especially in regions experiencing rapid transmission of HIV due to injection drug use. In this review, we describe the rationale for maintenance treatment of opioid dependence, discuss emerging uses of opioid antagonists such as naltrexone and sustained-release formulations of naltrexone and buprenorphine, and provide a description of the experimental therapies. PMID:22235870

Tetrault, Jeanette M; Fiellin, David A

2012-01-22

372

Second and Third-Order Matching via Explicit Substitutions  

Microsoft Academic Search

The past few years have established the benefits of using explicit substitutions in the treatment of problems such as unification and matching related to higher-order automated deduction and the implementation of programming languages. Matching is a basic operation extensively used in computation and deduction. Second and third-order matching, in particular, provide an adequate environment for expressing pattern recognition and program

LEONARDO CAVALCANTI DE MOURA; FAIROUZ KAMAREDDINE; Bras ´ ilia

373

Differential silver carbonate staining of sister chromatids in BrdU-substituted chromosomes  

Microsoft Academic Search

Differential staining of sister chromatids in BrdU-substituted human chromosomes is demonstrated by an ammoniacal silver carbonate procedure. With this method the chromosomes exhibit a subchromatid structure. Because proteolytic treatment indicated that the silver carbonate binds the chromosome proteins, changes of these components may be inferred in the BrdU-substituted chromosomes. Sister chromatid exchanges could be identified.

V. J. Goyanes

1978-01-01

374

The Thermochromic Vanadium Dioxide I. Role of Stresses and Substitution on Switching Properties  

Microsoft Academic Search

The monoclinic tetragonal transition occurring at 341 K for VO2 vanadium dioxide and the corresponding switching of the optical properties can be affected in various ways by thermal treatments, substitution, and pressure. The transition in pure or substituted powdered samples is characterized by thermal analysis (DSC), X-ray (XRD) and neutron (NRD) diffractions, and infrared spectroscopy (IR). The influence of pressure

J. C. Rakotoniaina; R. Mokrani-Tamellin; J. R. Gavarri; G. Vacquier; A. Casalot; G. Calvarin

1993-01-01

375

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Butyl acrylate, polymer with substituted methyl styrene, methyl...Substances § 721.6920 Butyl acrylate, polymer with substituted methyl styrene, methyl...substance identified as butyl acrylate, polymer with substituted methyl styrene,...

2013-07-01

376

40 CFR 721.2577 - Copper complex of (substituted sulfonaphthyl azo substituted phenyl) disulfonaphthyl azo, amine...  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Copper complex of (substituted sulfonaphthyl...Specific Chemical Substances § 721.2577 Copper complex of (substituted sulfonaphthyl...chemical substances identified generically as copper complex of (substituted...

2013-07-01

377

Austronesian Nasal Substitution: A Survey  

Microsoft Academic Search

Nasal substitution, which replaces a base-initial obstruent with the homorganic nasal under pre²xation, is arguably the most prominent morphonological process seen in Austronesian languages, as it is an active part of the verbal morphology of most languages of the Philippines and western Indonesia, as well as Malagasy, Chamorro, and Palauan. Although a comparative overview of this process was provided by

Robert Blust

2004-01-01

378

Assessment of asbestos insulation substitutes  

Microsoft Academic Search

A state-of-the-art study of asbestos insulation alternatives has been conducted to identify the best substitute material for steam lines in power plants. A survey of utilities across the nation showed that calcium silicate is the most commonly employed material today, followed by mineral wool, fiberglass, and ceramic fibers. However, the calcium silicate was found to be dusty and to become

J. D. Fourroux; R. L. Jr. Frank; T. W. Jr. Newberry

1990-01-01

379

ADMISSIBLE SUBSTITUTIONS IN SEQUENT CALCULI  

Microsoft Academic Search

For first-order classical logic a new notion of admissible substitution is defined. This notion allows optimizing the procedure of the application of quantifier rules when logical inference search is made in sequent calculi. Our objective is to show that such a computer-oriented sequent technique may be created that does not require a preliminary skolemization of initial formulas and that is

A. V. Lyaletski

380

The French Experience – the Pharmacist, General Practitioner and Patient Perspective  

Microsoft Academic Search

High-dose buprenorphine (Subutex®) has been available in France as a maintenance treatment since February 1996. Results from a twice yearly survey of pharmacists, general practitioners (GPs) and patients themselves in the use of Subutex® appeared to be representative of the general substitution therapy situation in France. Results from May 1997 were encouraging, with improved relationships between pharmacists and patients, and

Jacques Bouchez; Jean Vignau

1998-01-01

381

Aqueous oxidation of substituted dihydroxybenzenes by substituted benzoquinones.  

PubMed

Strict anaerobic techniques, HPLC, and spectrophotometry are employed to explore rates of reaction between a series of substituted benzoquinone oxidants and substituted dihydroxybenzene reductants, which represent important redox-active moieties within natural organic matter (NOM). Benzoquinones and dihydroxybenzenes that lack electron-withdrawing substituents exhibit reversible reactions within the acidic range of natural waters. Initial rates for reversible reactions are proportional to [H+]-1, attributable to the greater reactivity of monoprotonated versus diprotonated dihydroxybenzene molecules. Reversible reactions are generally faster for pairs having higher thermodynamic driving force. Concentrations in reversible reactions eventually reach plateau values, which coincide with expected values calculated using standard reduction potentials. If a reactant benzoquinone possesses an electron-withdrawing substituent, reaction progress falls short of expected values. If a product benzoquinone possesses an electron-withdrawing substituent, reaction progress extends beyond what is thermodynamically predicted. Electron-withdrawing substituents raise the susceptibility of benzoquinones to side reactions such as the Michael addition reaction. PMID:16786688

Uchimiya, Minori; Stone, Alan T

2006-06-01

382

Effectiveness of drug tests in outpatients starting opioid substitution therapy.  

PubMed

We aimed to assess the effectiveness of drug tests for treatment retention in outpatients starting opioid substitution therapy. A retrospective cohort was created from the data of the French health insurance system database for the Midi-Pyrenees region. Patients starting opioid substitution treatment (OST) were included and followed for 18 to 30 months. Two groups of patients were defined: the drug test group (at least one drug test reimbursement) and a control group (no drug test reimbursement). The cohort included 1507 patients. During follow-up, 39 subjects (2.6%) had at least one drug test reimbursement. Mean treatment retention was 207 days in the control group and 411 days in the drug test group (p < 0.001). With a multivariate Cox model, drug tests were associated with treatment retention: hazard ratio 0.55 (95% CI: 0.38-0.80). Use of a drug test in follow-up of opioid substitution treatment, although rarely prescribed, significantly improved treatment retention. PMID:23337248

Dupouy, Julie; Dassieu, Lise; Bourrel, Robert; Poutrain, Jean-Christophe; Bismuth, Serge; Oustric, Stéphane; Lapeyre-Mestre, Maryse

2013-01-20

383

Dual functional selenium-substituted hydroxyapatite  

PubMed Central

Hydroxyapatite (HA) doped with trace elements has attracted much attention recently owing to its excellent biological functions. Herein, we use a facile co-precipitation method to incorporate selenium into HA by adding sodium selenite during synthesis. The obtained selenium-substituted HA products are needle-like nanoparticles which have  size and crystallinity that are similar to those of the pure HA nanoparticles (HANs) when the selenium content is low. HANs are found to have the ability to induce the apoptosis of osteosarcoma cells, and the anti-tumour effects are enhanced after incorporation of selenium. Meanwhile, the nanoparticles can also support the growth of bone marrow stem cells. Furthermore, the flow cytometric results indicate that the apoptosis induction of osteosarcoma cells is caused by the increased reactive oxygen species and decreased mitochondrial membrane potential. These results show that the selenium-substituted HANs are potentially promising bone graft materials in osteosarcoma treatment due to their dual functions of supporting normal cell growth and inducing tumour cell apoptosis.

Wang, Yanhua; Ma, Jun; Zhou, Lei; Chen, Jin; Liu, Yonghui; Qiu, Zhiye; Zhang, Shengmin

2012-01-01

384

Substance-related Problems and Treatment among MSM and Other Men in Chicago  

PubMed Central

This study compares a sample of urban MSM with a general population sample of men in the same city on self-reported problems with substance use indicative of dependence, and history of substance use treatment. Both samples were randomly selected using multistage probability methods. All participants completed Audio Computer-Assisted Self-Interviews (ACASI), including questions on substance use, problems related to substance use experienced in the past 12 months, and substance treatment. Problem use of alcohol, marijuana, and cocaine did not differ between samples. Compared to men in the general population sample, MSM were significantly more likely to experience problems related to the use of sedatives, tranquilizers, or prescription pain relievers. Among MSM, history of substance treatment was associated with a positive HIV test, and treatment usually preceded HIV diagnosis. Research is needed on effective methods for integrating HIV prevention for MSM into substance treatment settings, including physician-administered buprenorphine treatment for opiate addiction.

Mackesy-Amiti, Mary Ellen; Fendrich, Michael; Johnson, Timothy P.

2009-01-01

385

47 CFR 76.110 - Substitutions.  

Code of Federal Regulations, 2012 CFR

...Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.110 Substitutions. Whenever, pursuant...such community unit may, consistent with these rules and the sports blackout rules at § 76.111, substitute a program from...

2012-10-01

386

47 CFR 76.110 - Substitutions.  

Code of Federal Regulations, 2011 CFR

...Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.110 Substitutions. Whenever, pursuant...such community unit may, consistent with these rules and the sports blackout rules at § 76.111, substitute a program from...

2011-10-01

387

Assessment of asbestos insulation substitutes  

SciTech Connect

A state-of-the-art study of asbestos insulation alternatives has been conducted to identify the best substitute material for steam lines in power plants. A survey of utilities across the nation showed that calcium silicate is the most commonly employed material today, followed by mineral wool, fiberglass, and ceramic fibers. However, the calcium silicate was found to be dusty and to become brittle once exposed to elevated temperatures. Although it is asbestos-free, studies on its carcinogenicity are incomplete. Characteristic data on existing substitute materials is compiled and an optimum choice of insulation combination is configured. Potential cost savings of using this combination is evaluated for a major utility. A PC-based computer program is developed to assist utility personnel in selecting the proper insulation materials for steam lines. 31 refs., 8 figs.

Fourroux, J.D.; Frank, R.L. Jr.; Newberry, T.W. Jr. (Tennessee Valley Authority, Chattanooga, TN (USA))

1990-03-01

388

Introduction of low dose transdermal buprenorphine -- did it influence use of potentially addictive drugs in chronic non-malignant pain patients?  

PubMed

The aim was to study the introduction of the new low dose transdermal buprenorphine (LD-TD-BUP) in Norway, particularly with regard to former use and co-medication with other potentially addictive drugs. The nationwide Norwegian Prescription Database contains information on all prescription drugs dispensed to individual non-institutionalised patients, and we may follow all individuals who received LD-TD-BUP (Norspan) after marketing on the Norwegian market on 15/11/05. We studied all prescriptions of opioids and other potentially addictive drugs to patients receiving at least two LD-TD-BUP prescriptions during 2004-2006. Poisson regressions were run with concomitant use of addictive drugs (yes, no) as the endpoint. Overall, 1884, non cancer individuals received at least two prescription of LD-TD-BUP. Of these 91.7% received prescriptions of other opioids and 58.6% of them had also been prescribed benzodiazepines/carisoprodol before the prescription of LD-TD-BUP. Of the LD-TD-BUP users who received more than one prescription, 60% co-medicated with at least one other potentially addictive drug, and 24% with at least two. In the multivariate analysis, the variables associated with a higher likelihood of using co-medicated drugs were: previous use of benzodiazepines/carisoprodol relative risk RR=16.7 (95% CI 10.4-26.9), previous use of opioids RR=4.0 (1.9-8.7) and younger age 20-40 years RR=1.9 (1.6-2.3). So far, it is questionable whether the introduction of LD-TD-BUP actually has stabilised opioids consumption or whether it has complicated and increased the consumption of potentially addictive drugs. PMID:19095476

Skurtveit, Svetlana; Furu, Kari; Kaasa, Stein; Borchgrevink, Petter C

2008-12-17

389

Development and Clinical Evaluation Synthetic Skin Substitute as a Model of Skin Function.  

National Technical Information Service (NTIS)

Temporary skin substitutes, including human cadaver cutaneous allografts, porcine cutaneous xenografts, and amniotic membranes have become widely used in the treatment of thermally injured patients. The principal use of these biologic dressings is for tem...

N. S. Levine A. D. Mason B. A. Pruitt

1983-01-01

390

Preparation and Reactions of Substituted Ethenesulfenate Anions  

Microsoft Academic Search

Trans-alkyl and gem-silyl substituted ethenesulfenate anions result from the reaction of hexamethyldisilazide bases with anti-alkyl and anti-silyl substituted thiirane-S-oxides, respectively, via a stereoselective deprotonation process. The sulfenates can be captured at sulfur with certain alkyl halides or they can be converted to a series of substituted ethenesulfenic acid amides.

Adrian L. Schwan; Mitchell D. Refvik

1994-01-01

391

Substitutes for School Nurses in Illinois  

ERIC Educational Resources Information Center

|The purpose of this descriptive study was to explore utilization of nurse substitutes in the school setting in Illinois. The literature described personnel who staff the school health office in the absence of the school nurse and the barriers to obtaining nurse substitutes. There were no empirical studies conducted on school nurse substitutes in…

Vollinger, Linda Jeno; Bergren, Martha Dewey; Belmonte-Mann, Frances

2011-01-01

392

Generic Substitution of Narrow Therapeutic Index Drugs  

Microsoft Academic Search

Controversy regarding generic substitution of narrow therapeutic index drugs, especially antiepileptic drugs, has become a big debate lately. Some states are considering passing laws that will restrict the generic substitution of these narrow therapeutic index drugs. In fact, some states have already modified their laws to limit switching and generic substitution of these medications, requiring patient and prescriber consent before

Mays Putrus

393

Surgical-orthodontic management of an adult skeletal Class III malocclusion with canine substitution.  

PubMed

Management of missing lateral incisors requires thorough treatment planning and an interdisciplinary approach. Occlusion and alignment are significant considerations. Three treatment options are available for replacing missing lateral incisors: canine substitution, tooth-supported restorations, and single-tooth implants. The ideal treatment is the one that satisfies the esthetic and functional requirements of the patient. The pros and cons of the various treatment options must be meticulously analyzed before arriving at a decision. This article closely examines patient selection and illustrates the importance of interdisciplinary treatment planning in an adult treated with canine substitution and orthognathic surgery. PMID:22567650

Meeran, Nazeer Ahmed; Selvakumar, T; Parveen, M F Jaseema

2012-01-01

394

Cannabis as a substitute for alcohol and other drugs  

PubMed Central

Background Substitution can be operationalized as the conscious choice to use one drug (legal or illicit) instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients. Methods Anonymous survey data were collected at the Berkeley Patient's Group (BPG), a medical cannabis dispensary in Berkeley, CA. (N = 350) The sample was 68% male, 54% single, 66% White, mean age was 39; 74% have health insurance (including MediCal), 41% work full time, 81% have completed at least some college, 55% make less than $40,000 a year. Seventy one percent report having a chronic medical condition, 52% use cannabis for a pain related condition, 75% use cannabis for a mental health issue. Results Fifty three percent of the sample currently drinks alcohol, 2.6 was the average number of drinking days per week, 2.9 was the average number of drinks on a drinking occasion. One quarter currently uses tobacco, 9.5 is the average number of cigarettes smoked daily. Eleven percent have used a non-prescribed, non OTC drug in the past 30 days with cocaine, MDMA and Vicodin reported most frequently. Twenty five percent reported growing up in an abusive or addictive household. Sixteen percent reported previous alcohol and/or drug treatment, and 2% are currently in a 12-step or other recovery program. Forty percent have used cannabis as a substitute for alcohol, 26% as a substitute for illicit drugs and 66% as a substitute for prescription drugs. The most common reasons given for substituting were: less adverse side effects (65%), better symptom management (57%), and less withdrawal potential (34%) with cannabis. Conclusion The substitution of one psychoactive substance for another with the goal of reducing negative outcomes can be included within the framework of harm reduction. Medical cannabis patients have been engaging in substitution by using cannabis as an alternative to alcohol, prescription and illicit drugs.

2009-01-01

395

Current status of erythrocyte substitutes.  

PubMed Central

During the last two decades the search for alternatives to whole blood transfusions has led to promising developments in the field of erythrocyte substitutes. Hemoglobin solutions free of fragments of erythrocyte stroma and fluorocarbon emulsions are not blood-type-specific and appear likely to satisfy some proportion of our blood requirements. Both must be modified before becoming clinically useful. The oxygen affinity of the hemoglobin solution must be reduced and its intravascular persistence improved. Fluorocarbons cannot yet contribute significantly to the oxygen supply unless the patient breathes hyperbaric oxygen. Recent advances are leading to solutions for these problems.

Biro, G. P.

1983-01-01

396

Wanted: The perfect asbestos substitute  

SciTech Connect

The quest continues for commercially viable asbestos replacements. To date, no single product has emerged that is as inert, strong or incombustible as thin fibrous silicate mineral. Traditionally, asbestos has been woven into cloths and garments, compressed into boards, gaskets, and pipe coverings, and used as a filler and reinforcement in paint, asphalt, cement and plastic. Ever since health concerns began to surface about this fibrous mineral, industrial use has been on the wane. The paper describes the many materials being tested for various purposes as an asbestos substitute.

Not Available

1993-01-01

397

40 CFR 721.5930 - Phenylenebis[imino (chlorotriazinyl)imino(substituted naphthyl)azo(substituted phenyl)azo, sodium...  

Code of Federal Regulations, 2010 CFR

...imino (chlorotriazinyl)imino(substituted naphthyl)azo(substituted phenyl)azo, sodium salt (generic name). 721.5930 Section...imino (chlorotriazinyl)imino(substituted naphthyl)azo(substituted phenyl)azo, sodium salt...

2010-07-01

398

Biochemistry and pharmacology of 7?-substituted androstenediones as aromatase inhibitors  

Microsoft Academic Search

The inhibition of aromatase, the enzyme responsible for converting androgens to estrogens, is therapeutically useful for the endocrine treatment of hormone-dependent breast cancer. Research by our laboratory has focused on developing competitive and irreversible steroidal aromatase inhibitors, with an emphasis on synthesis and biochemistry of 7?-substituted androstenediones. Numerous 7?-thiosubstituted androst-4-ene-3,17-diones are potent competitive inhibitors, and several 1,4-diene analogs, such as

Robert W. Brueggemeier; Jill M. O'Reilly; Carl J. Lovely; Patrick J. Ward; Anne L. Quinn; David Baker; Michael V. Darby; Xin-Ju Gu; Nancy E. Gilbert

1997-01-01

399

Substituting objects from consciousness: A review of object substitution masking.  

PubMed

Object substitution masking (OSM) occurs when a sparse (e.g., four-dot), temporally trailing mask obscures the visibility of a briefly presented target. Here, we review theories of OSM: those that propose that OSM reflects the interplay between feedforward and feedback/reentrant neural processes, those that predict that feedforward processing alone gives rise to the phenomenon, and theories that focus on cognitive explanations, such as object updating. We discuss how each of these theories accommodates key findings from the OSM literature. In addition, we examine the relationship between OSM and other visual-cognitive phenomena, including object correspondence through occlusion, change blindness, metacontrast masking, backward masking, and visual short-term memory. Finally, we examine the level of processing at which OSM impairs target perception. Collectively, OSM appears to reflect the conditions under which the brain confuses two visual events for one when they are encoded with low spatiotemporal resolution, due to processing resources being otherwise occupied. PMID:23417271

Goodhew, Stephanie C; Pratt, Jay; Dux, Paul E; Ferber, Susanne

2013-10-01

400

Empirically supported substance abuse treatment approaches: a survey of treatment providers' perspectives and practices.  

PubMed

To better understand the extent that empirically supported and promising substance abuse treatment approaches are implemented in community settings, treatment providers were surveyed regarding their perceptions and use of several psychosocial and pharmacological treatment interventions. Program directors (n=30) and staff members (n=331) from diverse community settings rated the effectiveness and extent of use of various treatment interventions, and provided information on program and workforce characteristics via self-administered questionnaires. On average, program directors and staff rated the psychosocial treatment interventions as effective, with the exception of vouchers/motivational incentives. About half of the treatment providers did not know the effectiveness of certain pharmacological treatments, including buprenorphine and naltrexone. Respondents from the majority of programs (55%-80%) reported using Motivational Enhancement Therapy, Community Reinforcement Approach, and Supportive Expressive Psychotherapy. The extent that programs used several of the treatment interventions was related to organizational training and information resources. The study findings provide important information regarding training and research dissemination efforts. PMID:18207334

Herbeck, Diane M; Hser, Yih-Ing; Teruya, Cheryl

2007-12-23

401

Isovalent Substitution and Heat Treatments Control of T c, Chain Oxygen Disorder and Structural Phase Transition in High T c Superconductors (Y1- x Nd x )SrBaCu3O6+ z  

NASA Astrophysics Data System (ADS)

We report here on the preparation, X-ray diffraction with Rietveld refinement, AC magnetic susceptibility measurements and effect of heat treatments in (Y1- x Nd x )SrBaCu3O6+ z . Each sample was subject to two types of heat treatment: oxygen annealing [O] and argon annealing followed by oxygen annealing [AO]. For each x, the [AO] heat treatment increases the orthorhombicity ?=( b- a)/( b+ a) (for 0? x<1), T c (for x>0.2) and the distance d[Cu(1)-(Sr/Ba)] (decrease T c) for x<0.25 and decrease it (increase T c) for x>0.25. When x increase from 0 to 1, ? decreases to 0 with transition from orthorhombic to tetragonal structure. ?[O] decreases with T c[O]. However, T c[AO] decreases with ?[AO] until x=0.2, increases for x=0.4 and after it decreases by 9.8 K to 77.2 K for x=1 [AO]. Remarkable correlations were observed between T c( x) and the volume of the unit cell V( x); and between ?T c( x)= T c[AO]- T c[O] and ??( x). A combination of several factors such as decrease in d[Cu(1)-(Sr/Ba)]; increase in cationic and chain oxygen ordering; the number p sh( x) of holes by Cu(2)-O2 superconducting plans and in-phase purity for the [AO] samples may account for the observed data.

Morghi, R.; Nafidi, A.; Aboulkassim, A.; Chaib, H.; Charafi, H.; Ait Taleb, T.; Marí Soucase, B.; Mollar García, M.; Hartiti, B.; Chander Singh, K.; Khallouq, K.

2013-06-01

402

Safety and health policy considerations related to the use of buprenorphine\\/naloxone as an office-based treatment for opiate dependence  

Microsoft Academic Search

Opiate dependence remains a fundamental challenge confronting health delivery systems and is often characterized as a social and moral issue. The impact of this disorder on healthcare policy is changing with the increased incidence of HIV, hepatitis C, and tuberculosis infections in opiate-dependent patients. These medical illnesses have substantial effect on escalating healthcare costs, and, therefore, also affect healthcare policy

T. Peter Bridge; Paul J. Fudala; Susan Herbert; Deborah B. Leiderman

2003-01-01

403

Exfoliation and thermal transformations of Nb-substituted layered titanates  

SciTech Connect

Single-layer Nb-substituted titanate nanosheets of ca. 1 nm thickness were obtained by exfoliating tetrabutylammonium (TBA)-intercalated Nb-substituted titanates in water. AFM images and turbidity measurements reveal that the exfoliated nanosheets crack and corrugate when sonicated. Upon heating, the thermal transformation into anatase and further to rutile is retarded. This suppression of the phase transition upon higher valent substitution may promote technological applications of anatase thin films, hereunder development of films with TCO properties. Depending on the oxygen partial pressure during the transformation, the Nb-substitution into TiO{sub 2} provokes different defect situations and also electronic properties. At reducing conditions, Nb is incorporated as Nb{sup V} and an equivalent amount of Ti{sup IV} is transformed to Ti{sup III} as evidenced by XPS. Magnetic susceptibility data show accordingly paramagnetic behavior. For samples heated in air Ti{sup IV} and Nb{sup V} cations prevail, the latter is compensated by cation vacancies. {sup 93}Nb MAS NMR data prove that Nb is finely dispersed into the transformed (Ti,Nb)O{sub 2} oxide matrices without sign of Nb{sub 2}O{sub 5} (nano)precipitates. The Nb-O-Ti bonds and defects at cation sites are considered key factors for increasing the transformation temperatures for conversion of the nanosheets to anatase and finally into rutile. It is further tempting to link the delay in crystallization to morphology limitations originating from the nanosheets. The present work shows that layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment. - Graphical abstract: Layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment. Highlights: Black-Right-Pointing-Pointer Single layer Nb-substituted nanosheets were obtained by exfoliation of layered titanates. Black-Right-Pointing-Pointer Nb(V) successfully introduced into anatase and rutile solid solutions. Black-Right-Pointing-Pointer Anatase obtained from reconstructed nanosheets exhibit enhanced thermal stability. Black-Right-Pointing-Pointer Oxygen partial pressure influences the valence of Nb in heat-treated samples. Black-Right-Pointing-Pointer Deposition of oriented thin Ti(Nb)O{sub 2} layers by spray coating was demonstrated.

Song Haiyan; Sjastad, Anja O.; Fjellvag, Helmer; Okamoto, Hiroshi [Department of Chemistry and Centre for Materials Science and Nanotechnology, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo (Norway); Vistad, Ornulv B.; Arstad, Bjornar [SINTEF Materials and Chemistry, P.O. Box 124, Blindern, N-0314 Oslo (Norway); Norby, Poul, E-mail: pnor@risoe.dtu.dk [Department of Chemistry and Centre for Materials Science and Nanotechnology, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo (Norway); Materials Research Division, Riso National Laboratory for Sustainable Energy, Technical University of Denmark, P.O. Box 49, DK-4000 Roskilde (Denmark)

2011-12-15

404

Engineering bone tissue substitutes from human induced pluripotent stem cells.  

PubMed

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease. PMID:23653480

de Peppo, Giuseppe Maria; Marcos-Campos, Iván; Kahler, David John; Alsalman, Dana; Shang, Linshan; Vunjak-Novakovic, Gordana; Marolt, Darja

2013-05-07

405

Protein substitutes for PKU: What's new?  

Microsoft Academic Search

Summary: Protein substitutes are an essential component in the management of phenylketonuria. A series of studies at Birmingham Children's\\u000a Hospital have investigated their optimal dosage, timing and practical administration as well as the efficacy and tolerance\\u000a of novel protein substitutes. The key findings are as follows. (1) Lower dosages of protein substitute (1.2 g\\/kg per day of\\u000a protein equivalent) adversely

A. Macdonald; A. Daly; P. Davies; D. Asplin; S. K. Hall; G. Rylance; A. Chakrapani

2004-01-01

406

Immunohistological Changes in Dilated Cardiomyopathy Induced by Immunoadsorption Therapy and Subsequent Immunoglobulin Substitution  

Microsoft Academic Search

Background—Immunoadsorption (IA) and subsequent immunoglobulin (Ig) G substitution represent an additional therapeutic approach in dilated cardiomyopathy (DCM). It remains to be elucidated whether this treatment modulates myocardial inflammation, which is possibly a causal factor of ventricular dysfunction. Methods and Results—From 25 DCM patients (EF ,30%), 12 patients were randomized for IA therapy and subsequent IgG substitution at 1-month intervals until

Alexander Staudt; Frank Schäper; Verena Stangl; Andreas Plagemann; Marco Böhm; Kurt Merkel; Gerd Wallukat; Klaus D. Wernecke; Karl Stangl; Gert Baumann; Stephan B. Felix

2010-01-01

407

Allogeneic skin substitutes applied to burns patients  

Microsoft Academic Search

Early re-surfacing of burn wounds remains the ideal but is limited by the availability of skin graft donor sites. Cultured grafts overcome these problems and autologous keratinocytes can be grown in culture and placed on a dermal substitute, but this results in delay and requires two operations. We developed an organotypic skin substitute, which achieves cover in one procedure, and

J. Nanchahal; R. Dover; W. R. Otto

2002-01-01

408

Expedient preparation of trifluoromethyl-substituted benzofuranols.  

PubMed

Direct access to 3-trifluoromethyl-substituted benzofuranols is presented. The products are obtained in good yields from commercially available salicylaldehydes by using in situ generated trifluoromethyl diazomethane and boron trifluoride as an activator. As shown in a representative example, the products can be transformed into the corresponding trifluoromethyl-substituted benzofurans. PMID:22013956

Morandi, Bill; Carreira, Erick M

2011-10-20

409

Synthesis of 1-(dihydroxypropyl)-5-substituted uracils  

Microsoft Academic Search

Novel 1-(dihydroxypropyl)-5-substituted uracils were synthesized in the reaction of 1-(4-nitrophenyl)-5-substituted uracil derivatives with appropriate aminopropanediols under mild conditions. In the case of 3-amino-1,2-propanediol both racemic and enantiomerically enriched products were obtained. These compounds may be considered as new building blocks for oligonucleotide synthesis.

Andrzej Gondela; Krzysztof Walczak

2003-01-01

410

Amino acid substitution matrices from protein blocks  

Microsoft Academic Search

Methods for alignment of protein sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid with another. The most widely used matrices are based on the Dayhoff model of evolutionary rates. Using a different approach, we have derived substitution matrices from about 2000 blocks of aligned sequence segments characterizing more than

Steven Henikoff; Jorja G. Henikoff

1992-01-01