Confounding of the Comparative Safety of Prenatal Opioid Agonist Therapy.

Pub Med: Keyword Buprenorphine - August 23, 2016 - 6:01am

Confounding of the Comparative Safety of Prenatal Opioid Agonist Therapy.

J Addict Res Ther. 2015 Dec;6(4)

Authors: Brogly SB, Hahn KA, Diaz SH, Werler M

Abstract
Prenatal opioid agonist therapy with methadone or buprenorphine prevents maternal illicit opioid use and withdrawal and improves pregnancy outcomes compared to heroin use alone. Historically, methadone has been the first-line opioid agonist therapy for pregnant opioid dependent women; in recent years buprenorphine has become first-line treatment for some opioid dependent pregnant women. While there is some evidence of better outcomes in neonates exposed to buprenorphine vs. methadone, the effect of confounding from differences in women who use buprenorphine and methadone has not been carefully examined in most studies. This review explores mechanisms by which confounding can arise in measuring associations between prenatal buprenorphine vs. methadone exposure on neonatal outcomes using a graphical approach, directed acyclic graphs. The goal of this paper is to facilitate better understanding of the factors influencing neonatal abstinence syndrome and accurate assessment of the comparative safety of opioid agonist therapies on the neonate.

PMID: 27547489 [PubMed - as supplied by publisher]

Real-time application of the Rat Grimace Scale as a welfare refinement in laboratory rats.

Pub Med: Keyword Buprenorphine - August 18, 2016 - 6:29am

Real-time application of the Rat Grimace Scale as a welfare refinement in laboratory rats.

Sci Rep. 2016;6:31667

Authors: Leung V, Zhang E, Pang DS

Abstract
Rodent grimace scales have been recently validated for pain assessment, allowing evaluation of facial expressions associated with pain. The standard scoring method is retrospective, limiting its application beyond pain research. This study aimed to assess if real-time application of the Rat Grimace Scale (RGS) could reliably and accurately assess pain in rats when compared to the standard method. Thirty-two male and female Sprague-Dawley rats were block randomized into three treatment groups: buprenorphine (0.03 mg/kg, subcutaneously), multimodal analgesia (buprenorphine [0.03 mg/kg] and meloxicam [2 mg/kg], subcutaneously), or saline, followed by intra-plantar carrageenan. Real-time observations (interval and point) were compared to the standard RGS method using concurrent video-recordings. Real-time interval observations reflected the results from the standard RGS method by successfully discriminating between analgesia and saline treatments. Real-time point observations showed poor discrimination between treatments. Real-time observations showed minimal bias (<0.1) and acceptable limits of agreement. These results indicate that applying the RGS in real-time through an interval scoring method is feasible and effective, allowing refinement of laboratory rat welfare through rapid identification of pain and early intervention.

PMID: 27530823 [PubMed - as supplied by publisher]

NIDA Clinical Trials Network CTN-0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT): Study design and rationale.

Pub Med: Keyword Buprenorphine - August 16, 2016 - 8:29am
Related Articles

NIDA Clinical Trials Network CTN-0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT): Study design and rationale.

Contemp Clin Trials. 2016 Aug 10;

Authors: Lee JD, Nunes EV, Mpa PN, Bailey GL, Brigham GS, Cohen AJ, Fishman M, Ling W, Lindblad R, Shmueli-Blumberg D, Stablein D, May J, Salazar D, Liu D, Rotrosen J

Abstract
INTRODUCTION: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays.Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification.Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized.This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies.
METHODS: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients.Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX.
RESULTS: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase.Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms).Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness.
CONCLUSIONS: XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance.Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed.
CLINICAL TRIAL REGISTRATION: NCT02032433.

PMID: 27521809 [PubMed - as supplied by publisher]

Exaggerated acquisition and resistance to extinction of avoidance behavior in treated heroin-dependent men.

Pub Med: Keyword Buprenorphine - August 16, 2016 - 8:29am
Related Articles

Exaggerated acquisition and resistance to extinction of avoidance behavior in treated heroin-dependent men.

J Clin Psychiatry. 2016 Mar;77(3):386-94

Authors: Sheynin J, Moustafa AA, Beck KD, Servatius RJ, Casbolt PA, Haber P, Elsayed M, Hogarth L, Myers CE

Abstract
OBJECTIVE: Addiction is often conceptualized as a behavioral strategy for avoiding negative experiences. In rodents, opioid intake has been associated with abnormal acquisition and extinction of avoidance behavior. Here, we tested the hypothesis that these findings would generalize to human opioid-dependent subjects.
METHOD: Adults meeting DSM-IV criteria for heroin dependence and treated with opioid medication (n = 27) and healthy controls (n = 26) were recruited between March 2013 and October 2013 and given a computer-based task to assess avoidance behavior. For this task, subjects controlled a spaceship and could either gain points by shooting an enemy spaceship or hide in safe areas to avoid on-screen aversive events. Hiding duration during different periods of the task was used to measure avoidance behavior.
RESULTS: While groups did not differ on escape responding (hiding) during the aversive event, heroin-dependent men (but not women) made more avoidance responses during a warning signal that predicted the aversive event (analysis of variance, sex × group interaction, P = .007). Heroin-dependent men were also slower to extinguish the avoidance response when the aversive event no longer followed the warning signal (P = .011). This behavioral pattern resulted in reduced opportunity to obtain reward without reducing risk of punishment. Results suggest that, in male patients, differences in avoidance behavior cannot be easily explained by impaired task performance or by exaggerated motor activity.
CONCLUSIONS: This study provides evidence for abnormal acquisition and extinction of avoidance behavior in opioid-dependent patients. Interestingly, data suggest that abnormal avoidance is demonstrated only by male patients. Findings shed light on cognitive and behavioral manifestations of opioid addiction and may facilitate development of therapeutic approaches to help affected individuals.

PMID: 27046310 [PubMed - indexed for MEDLINE]

Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.

Pub Med: Keyword Buprenorphine - August 12, 2016 - 10:02am

Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.

Eur J Clin Pharmacol. 2016 Aug 10;

Authors: Fihlman M, Hemmilä T, Hagelberg NM, Kuusniemi K, Backman JT, Laitila J, Laine K, Neuvonen PJ, Olkkola KT, Saari TI

Abstract
PURPOSE: This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine.
METHODS: We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured.
RESULTS: Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC0-∞) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P < 0.001), its peak concentration (Cmax) 1.37-fold (P < 0.013) and half-life (t ½ ) 1.37-fold (P < 0.001). Posaconazole increased the AUC00-∞ of buprenorphine 1.25-fold (P < 0.001). Most of the plasma norbuprenorphine concentrations were below the limit of quantification (0.05 ng/ml). Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P < 0.001) but there was no quantifiable parent buprenorphine in urine. Plasma buprenorphine concentrations correlated with the pharmacological effects, but the effects did not differ significantly between the phases.
CONCLUSIONS: Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance.

PMID: 27510521 [PubMed - as supplied by publisher]

Crushed Buprenorphine or Buprenorphine-Naloxone for Opioid Dependency: A Review of the Clinical Effectiveness and Guidelines

Pub Med: Keyword Buprenorphine - August 12, 2016 - 10:02am

Crushed Buprenorphine or Buprenorphine-Naloxone for Opioid Dependency: A Review of the Clinical Effectiveness and Guidelines

Book. 2016 07 18

Authors:

Abstract
The purpose of this report is to review the clinical effectiveness and safety of sublingual crushed buprenorphine or crushed buprenorphine-naloxone for treating opioid dependency, compared to the uncrushed products, and to review the evidence-based guidelines regarding the administration of crushed buprenorphine or crushed buprenorphine-naloxone.


PMID: 27512740

Neurobiology of opioid dependence in creating addiction vulnerability.

Pub Med: Keyword Buprenorphine - August 11, 2016 - 6:57am

Neurobiology of opioid dependence in creating addiction vulnerability.

F1000Res. 2016;5

Authors: Evans CJ, Cahill CM

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

PMID: 27508068 [PubMed]

Enzymatic assays for detecting lactose and sucrose in urine to reveal intravenous drug abuse with emphasis on buprenorphine.

Pub Med: Keyword Buprenorphine - August 10, 2016 - 6:52am

Enzymatic assays for detecting lactose and sucrose in urine to reveal intravenous drug abuse with emphasis on buprenorphine.

Drug Test Anal. 2016 Aug 9;

Authors: Keltanen T, Mariottini C, Walta AM, Rahikainen AL, Ojanperä I

Abstract
Buprenorphine and methadone are commonly used medications for opioid maintenance treatment (OMT), using sublingual and oral administration, respectively. Although beneficial for OMT, these drugs can also be abused by intravenous administration. In intravenous abuse cases, the adjuvants lactose and sucrose are excreted in urine without hydrolysis to monosaccharides, since there are no disaccharidases in the blood. We validated enzymatic methods for the analysis of lactose and sucrose in urine. The analytical performance of both assays was considered appropriate for detecting intravenous drug abuse. The principle was proven by analyzing 93 postmortem (PM) urine samples for lactose, following comprehensive toxicological drug screening. In addition, 32 clinical urine samples from potential drug abusers were analyzed to assess the effect of PM changes on the assay. The mean level of lactose was low in clinical samples and relatively low in PM samples in which no drugs were found. Markedly elevated levels were seen in many of the buprenorphine positive samples, suggesting intravenous administration. Enzymatic methods could provide a simple and cost effective way to assess the intravenous administration of OMT drugs or drugs of abuse. Very high levels of glucose in urine may interfere with the assays. Furthermore, other causes for elevated urine disaccharides, such as hypolactasia and increased intestinal permeability, need to be considered in the interpretation of the results.

PMID: 27504930 [PubMed - as supplied by publisher]

The Availability of Ancillary Counseling in the Practices of Physicians Prescribing Buprenorphine.

Pub Med: Keyword Buprenorphine - August 10, 2016 - 6:52am

The Availability of Ancillary Counseling in the Practices of Physicians Prescribing Buprenorphine.

J Addict Med. 2016 Aug 8;

Authors: Barry DT, Fazzino T, Necrason E, Ginn J, Fiellin LE, Fiellin DA, Moore BA

Abstract
OBJECTIVE: We set out to examine physicians' perceptions of the provision of ancillary services for opioid dependent patients receiving buprenorphine.
METHODS: An e-mail invitation describing the study was sent out by the American Society of Addiction Medicine to its membership (approximately 3700 physicians) and other entities (for a total of approximately 7000 e-mail addresses). E-mail recipients were invited to participate in a research study funded by the National Institutes on Drug Abuse involving completion of an online survey; 346 physicians completed the survey.
RESULTS: The majority of the 346 respondents were internal or family medicine (37%), or addiction medicine providers (30%), who were practicing in urban (57%) or suburban settings (27%). Most respondents reported either offering (66%) or referring patients for ancillary counseling (31%). Interventions that were most frequently offered or referrals provided were individual counseling (51%) and self-help groups (63%), respectively. Counseling availability differed significantly by provider specialization for any, individual, group, family or couples, and self-help groups.
CONCLUSIONS: Generally, respondents reported compliance with ancillary counseling requirements for buprenorphine treatment of opioid use disorder. In addition to examining the efficacy of a variety of ancillary counseling services for patients receiving opioid agonist treatment, further research should examine physicians' attitudes toward the role of such counseling in buprenorphine treatment. Although the study sample was relatively large, the generalizability of the findings is unclear, suggesting that further investigation of the availability of ancillary counseling in buprenorphine treatment among a larger nationally representative sample of providers may be warranted.

PMID: 27504926 [PubMed - as supplied by publisher]

Efficacy of Full µ-Opioid Receptor Agonists is not Impaired by Concomitant Buprenorphine or Mixed Opioid Agonists/Antagonists - Preclinical and Clinical Evidence.

Pub Med: Keyword Buprenorphine - August 10, 2016 - 6:52am

Efficacy of Full µ-Opioid Receptor Agonists is not Impaired by Concomitant Buprenorphine or Mixed Opioid Agonists/Antagonists - Preclinical and Clinical Evidence.

Drug Res (Stuttg). 2016 Aug 9;

Authors: van Niel JC, Schneider J, Tzschentke TM

Abstract
Buprenorphine and the mixed agonists/antagonists nalbuphine and pentazocine, formerly classified as µ-opioid (MOP) receptor antagonists, have more recently been shown to be partial to full agonists of the human MOP receptor. These receptors do not necessarily have to be maximally activated for a full physiological response. Partial agonists can also sufficiently stimulate signaling processes leading to a full analgesic response, as shown by the effectiveness of buprenorphine, nalbuphine and pentazocine in animal pain models and in clinical settings where these drugs induce analgesia with full efficacy without a ceiling effect. Submaximal doses of MOP receptor analgesics combined with submaximal doses of buprenorphine, pentazocine, or nalbuphine result in additive to over-additive antinociceptive effects in animal experiments. Only when doses are given that exceed the therapeutic dose range may the antinociceptive effect be reduced to the effect of either opioid alone. The analgesic effects of pentazocine and nalbuphine combined with morphine are reported to be additive or over-additive in various clinical pain conditions. Buprenorphine, which clinically behaves as a full MOP receptor agonist for pain relief, can be combined with full opioid agonists without precipitating withdrawal. Thus, the overall evidence on the analgesic effects of buprenorphine, pentazocine or nalbuphine combined with opioid analgesics under various clinical pain conditions contradicts the consensus that these compounds diminish MOP receptor analgesia when co-administered with a full MOP receptor agonist.

PMID: 27504867 [PubMed - as supplied by publisher]

Transdermal Buprenorphine Patches for Postoperative Pain Control in Abdominal Surgery.

Pub Med: Keyword Buprenorphine - August 10, 2016 - 6:52am

Transdermal Buprenorphine Patches for Postoperative Pain Control in Abdominal Surgery.

J Clin Diagn Res. 2016 Jun;10(6):UC05-8

Authors: Kumar S, Chaudhary AK, Singh PK, Verma R, Chandra G, Bhatia VK, Singh D, Bogra J

Abstract
INTRODUCTION: Buprenorphine is a semi-synthetic derivative of thebaine; its low concentration is sufficient to provide effective pain relief.
AIM: To evaluate the efficacy of transdermal buprenorphine patch in postoperative pain management.
MATERIALS AND METHODS: After ethical approval and taking informed consent from the patients, they were randomized into three groups (n=30 in each group) using a computer generated random number table. Group A: placebo patch; Group B: buprenorphine (10mg) patch and Group C: buprenorphine (20mg) patch. Haemodynamic and analgesic effects were compared by using analysis of variance (ANOVA) followed by Turkey's post hoc test. The proportion of side effects was compared using the Chi-square test.
RESULTS: Haemodynamic changes were not statistically different in all the three groups A, B and C, whereas at the end of surgery VAS score of Group A subjects was significantly higher (4.93±0.98) as compared to Group B (1.73±0.64) and Group C (1.40±0.50). On 2(nd) postoperative day, no pain was reported by the Group C patients and on 4(th) day after surgery, no pain was reported by Group B patients.
CONCLUSION: The transdermal buprenorphine patch (20mg) was effective in attenuating postoperative pain, maintaining haemodynamic stability requiring no rescue analgesia, with fewer postoperative rescue analgesic requirements in low dose of buprenorphine patch (10mg) group.

PMID: 27504383 [PubMed]

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

Pub Med: Keyword Buprenorphine - August 9, 2016 - 6:45am

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

Subst Abuse Rehabil. 2016;7:99-105

Authors: Hämmig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, Dürsteler KM, Vogel M

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

PMID: 27499655 [PubMed]

Using the mouse grimace scale and behaviour to assess pain in CBA mice following vasectomy.

Pub Med: Keyword Buprenorphine - August 9, 2016 - 6:45am

Using the mouse grimace scale and behaviour to assess pain in CBA mice following vasectomy.

Appl Anim Behav Sci. 2016 Aug;181:160-165

Authors: Miller AL, Kitson GL, Skalkoyannis B, Flecknell PA, Leach MC

Abstract
Mice used in biomedical research should have pain reduced to an absolute minimum through refinement of procedures or by the provision of appropriate analgesia. Vasectomy is a common and potentially painful surgical procedure carried out on male mice to facilitate the production of genetically modified mice. The aim of our study was to determine if 0.05 mg/kg buprenorphine would ameliorate pain associated changes following abdominal vasectomy and to determine if the mouse grimace scale is an appropriate tool for the assessment of pain in this model. Eight male CBA mice underwent abdominal vasectomy as part of a genetically modified mouse-breeding programme. Here we assessed pain using a previously validated behaviour-based method and the mouse grimace scale. All mice received buprenorphine (0.05 mg/kg s.c.) pre-surgery. Behaviour and grimace scores were compared between baseline (pre-surgery), 30 min, 5 h, 24 h and 25 h post surgery. Following 24 h post-op, all mice were administered 5 mg/kg meloxicam (s.c.) as additional analgesia. Significant increases in specific pain behaviours and mouse grimace scale score were found 30 min post surgery. At 5 h post surgery, scores were returning to baseline levels. Frequency of rearing was significantly decreased at both 30 min and 5 h post surgery compared to baseline, demonstrating a longer lasting change in normal exploratory behaviour. Buprenorphine (0.05 mg/kg) was ineffective at ameliorating these pain-associated changes in CBA mice and should be considered inadequate at this dose. By 24 h post surgery, pain associated behaviours, grimace scale and rearing had all returned to baseline levels. There was no change in pain behaviours or MGS following administration of meloxicam indicating that an additional dose of meloxicam does not appear to offer benefit at this point. Using the mouse grimace scale to assess pain in mice, appeared to be effective in the immediate post vasectomy period in CBA mice demonstrating the same duration of increased score as the pain associated behaviours.

PMID: 27499567 [PubMed - as supplied by publisher]

Evaluation of the vaginal flora in pregnant women receiving opioid maintenance therapy: a matched case-control study.

Pub Med: Keyword Buprenorphine - August 9, 2016 - 6:45am
Related Articles

Evaluation of the vaginal flora in pregnant women receiving opioid maintenance therapy: a matched case-control study.

BMC Pregnancy Childbirth. 2016;16(1):206

Authors: Farr A, Kiss H, Hagmann M, Holzer I, Kueronya V, Husslein PW, Petricevic L

Abstract
BACKGROUND: Vaginal infections are a risk factor for preterm delivery. In this study, we sought to evaluate the vaginal flora of pregnant women receiving opioid maintenance therapy (OMT) in comparison to non-dependent, non-maintained controls.
METHODS: A total of 3763 women with singleton pregnancies who underwent routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0 gestational weeks were examined. Vaginal smears were Gram-stained, and microscopically evaluated for bacterial vaginosis, candidiasis, and trichomoniasis. In a retrospective manner, data of 132 women receiving OMT (cases) were matched for age, ethnicity, parity, education, previous preterm delivery, and smoking status to the data of 3631 controls. The vaginal flora at antenatal screening served as the primary outcome measure. Secondary outcome measures were gestational age and birth weight.
RESULTS: In the OMT group, 62/132 (47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and 31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 % CI, 0.33-0.71); p < 0.001]. Candidiasis occurred more frequently in OMT women than in controls [OR 2.11 (95 % CI, 1.26-3.27); p < 0.001]. Findings were inconclusive regarding bacterial vaginosis (± candidiasis) and trichomoniasis. Compared to infants of the control group, those of women with OMT had a lower mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006].
CONCLUSIONS: Pregnant women with OMT are at risk for asymptomatic vaginal infections. As recurrent candidiasis is associated with preterm delivery, the vulnerability of this patient population should lead to consequent antenatal infection screening at early gestation.

PMID: 27495167 [PubMed - in process]

Anti-inflammatory effect of dual nociceptin and opioid receptor agonist, BU08070, in experimental colitis in mice.

Pub Med: Keyword Buprenorphine - August 9, 2016 - 6:45am
Related Articles

Anti-inflammatory effect of dual nociceptin and opioid receptor agonist, BU08070, in experimental colitis in mice.

Eur J Pharmacol. 2015 Oct 15;765:582-90

Authors: Zielińska M, Ben Haddou T, Cami-Kobeci G, Sałaga M, Jarmuż A, Padysz M, Kordek R, Spetea M, Husbands SM, Fichna J

Abstract
Endogenous opioid and nociceptin systems are widely distributed in the gastrointestinal tract where they seem to play a crucial role in maintaining the intestinal homeostasis. The aim of our study was to assess whether activation of nociceptin (NOP) and µ-opioid (MOP) receptors by a mixed NOP/MOP receptor agonist, BU08070, induces anti-inflammatory response in experimental colitis. The anti-inflammatory effect of BU08070 (1 mg/kg i.p.) was characterized in the mouse model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, based on the assessment of the macroscopic and microscopic total damage scores and determination of myeloperoxidase (MPO) activity and TNF-α level in the colon. The effect of BU08070 on cell viability and NF-κB was characterized in THP-1 Blue cell line. The antinociceptive activity of BU08070 was examined in mustard oil-induced mouse model of abdominal pain. A potent anti-inflammatory effect of BU08070 (1 mg/kg i.p.) was observed as indicated by decrease in macroscopic damage score (1.88±0.39 vs. 5.19±0.43 units in TNBS alone treated mice), MPO activity (2.29±0.37 vs. 9.64±2.55 units) and TNF-α level in the colon (35.85±2.45 vs. 49.79±3.81 pg/ml). The anti-inflammatory effect of BU08070 was reversed by selective NOP and MOP receptor antagonists. BU08070 produced concentration-dependent inhibition of TNF-α and LPS-induced NF-κB activation. BU08070 exerted antinociceptive action in mice with experimental colitis. In conclusion, BU08070 significantly reduced the severity of colitis in TNBS-treated mice compared with controls. These results suggest that BU08070 is a potential therapeutic agent for inflammatory bowel diseases therapy.

PMID: 26404500 [PubMed - indexed for MEDLINE]

Treatment of Opioid-Use Disorders.

Pub Med: Keyword Buprenorphine - August 7, 2016 - 11:29am
Related Articles

Treatment of Opioid-Use Disorders.

N Engl J Med. 2016 Jul 28;375(4):357-68

Authors: Schuckit MA

PMID: 27464203 [PubMed - indexed for MEDLINE]

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

Pub Med: Keyword Buprenorphine - August 5, 2016 - 6:14am

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

Transcult Psychiatry. 2016 Aug 3;

Authors: Mendoza S, Rivera-Cabrero AS, Hansen H

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

PMID: 27488225 [PubMed - as supplied by publisher]

Relative Contribution of Adjuvants to Local Anesthetic for Prolonging the Duration of Peripheral Nerve Blocks in Rats.

Pub Med: Keyword Buprenorphine - August 3, 2016 - 2:03pm
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Relative Contribution of Adjuvants to Local Anesthetic for Prolonging the Duration of Peripheral Nerve Blocks in Rats.

Reg Anesth Pain Med. 2016 Aug 1;

Authors: Buvanendran A, Kroin JS, Li J, Moric M, Tuman KJ

Abstract
BACKGROUND AND OBJECTIVES: A chemically compatible, safe 4-drug multimodal formulation of bupivacaine combined with 3 adjuvants (clonidine, buprenorphine, and dexamethasone) has been proposed for long-lasting single-injection peripheral nerve blocks in patients. However, the relative importance of each of the adjuvants of the 4-drug formulation in producing long-lasting nerve blocks has not been determined. The aim of this study in rats was to determine which adjuvants (clonidine, buprenorphine, or dexamethasone) are essential for producing a long-lasting nerve block.
METHODS: After baseline sensory and motor responses were recorded, 0.1 mL of drug solution was injected into the sciatic notch of rats. Animals were reevaluated at 10-minute intervals after injection for the absence or presence of sensory and motor response in the sciatic nerve. The 4-drug formulation of 0.25% bupivacaine plus all 3 adjuvants (clonidine, buprenorphine, and dexamethasone), 0.25% bupivacaine with 1 or 2 of the adjuvants added separately, and 0.25% bupivacaine alone were compared for duration of nerve block.
RESULTS: The 4-drug multimodal solution produced a longer duration of sensory and motor nerve block than 0.25% bupivacaine alone (P < 0.0001). Bupivacaine plus clonidine also produced a longer duration of nerve block than 0.25% bupivacaine alone (P = 0.0157), but bupivacaine plus buprenorphine or bupivacaine plus dexamethasone did not prolong nerve block compared to bupivacaine alone. There was no difference (P = 0.1414) in the duration of nerve block between the 4-drug multimodal solution versus bupivacaine plus clonidine.
CONCLUSIONS: This animal study confirmed that the 4-drug multimodal formulation proposed for clinical nerve block produces superior duration of action compared to local anesthetic alone. This rat sciatic nerve model also indicated that one of the 3 adjuvants, clonidine, could by itself account for the extended duration of nerve block of bupivacaine.

PMID: 27483415 [PubMed - as supplied by publisher]

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