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Low dose naloxone

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https://www.readbyqxmd.com/read/28641363/a-phase-iii-randomized-controlled-study-on-the-efficacy-and-improved-bowel-function-of-prolonged-release-pr-oxycodone-naloxone-up-to-160-80-mg-daily-vs-oxycodone-pr
#1
D Dupoiron, A Stachowiak, O Loewenstein, A Ellery, W Kremers, B Bosse, M Hopp
BACKGROUND: Oxycodone/naloxone (OXN PR) is a prolonged-release formulation containing oxycodone and naloxone in a 2:1 ratio. This study aimed to evaluate the tolerability and efficacy of doses up to OXN160/80 mg PR compared with oxycodone prolonged-release formulation (OxyPR) in a randomised controlled trial. METHODS: Two hundred and forty-three patients were randomised to treatment with OXN PR (n = 123) or OxyPR (n = 120) during the 5-week double-blind study...
June 22, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28631527/buprenorphine-naloxone-versus-methadone-and-lofexidine-in-community-stabilisation-and-detoxification-a-randomised-controlled-trial-of-low-dose-short-term-opiate-dependent-individuals
#2
Fergus D Law, Alison M Diaper, Jan K Melichar, Simon Coulton, David J Nutt, Judy S Myles
Buprenorphine/naloxone, methadone and lofexidine are medications with utility in the treatment of opiate withdrawal. We report the first randomised controlled trial to compare the effects of these two medications on withdrawal symptoms and outcome during opiate induction/stabilisation and detoxification. A double-blind randomised controlled trial was conducted in an outpatient satellite clinic of a specialist drug service. Eighty opiate dependent individuals meeting DSM-IV criteria for opiate dependence, using ⩽ ½ g heroin smoked/chased or ¼ g heroin injected or ⩽ 30mg methadone, with ⩽ 3 years of opioid dependency, underwent a short-term opiate treatment programme involving induction/stabilisation on methadone 30mg or buprenorphine/naloxone 4mg/1mg, followed by detoxification (where the methadone group was assisted by lofexidine)...
June 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28597483/international-patent-applications-for-non-injectable-naloxone-for-opioid-overdose-reversal-exploratory-search-and-retrieve-analysis-of-the-patentscope-database
#3
REVIEW
Rebecca McDonald, Øyvind Danielsson Glende, Ola Dale, John Strang
ISSUES: Non-injectable naloxone formulations are being developed for opioid overdose reversal, but only limited data have been published in the peer-reviewed domain. Through examination of a hitherto-unsearched database, we expand public knowledge of non-injectable formulations, tracing their development and novelty, with the aim to describe and compare their pharmacokinetic properties. APPROACH: (i) The PatentScope database of the World Intellectual Property Organization was searched for relevant English-language patent applications; (ii) Pharmacokinetic data were extracted, collated and analysed; (iii) PubMed was searched using Boolean search query '(nasal OR intranasal OR nose OR buccal OR sublingual) AND naloxone AND pharmacokinetics'...
June 8, 2017: Drug and Alcohol Review
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating
#4
Lisa R Goldberg, Stacey L Kirkpatrick, Neema Yazdani, Kimberly P Luttik, Olga A Lacki, R Keith Babbs, David F Jenkins, W Evan Johnson, Camron D Bryant
Genetic and pharmacological studies indicate that casein kinase-1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28559179/opioid-receptors-mediate-the-acquisition-but-not-the-expression-of-mitragynine-induced-conditioned-place-preference-in-rats
#5
Nurul H M Yusoff, Sharif M Mansor, Christian P Müller, Zurina Hassan
Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats...
May 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28553701/opioid-antagonists-with-minimal-sedation-for-opioid-withdrawal
#6
REVIEW
Linda Gowing, Robert Ali, Jason M White
BACKGROUND: Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. OBJECTIVES: To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications. SEARCH METHODS: We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science...
May 29, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28529359/the-journey-of-opioid-substitution-therapy-in-india-achievements-and-challenges
#7
Ravindra Rao
Opioids are one of the most problematic illegal substances globally. Opioid abuse is associated with complications in various spheres of the user's life, his/her family, and the society. Injecting drug use (IDU) is also linked to public health problems such as HIV infection and viral hepatitis. Medications form an important cornerstone in the treatment of opioid dependence. Treatment strategies such as "detoxification" alone or long-term treatment with opioid antagonist have limited acceptability and retention rates...
January 2017: Indian Journal of Psychiatry
https://www.readbyqxmd.com/read/28502631/a-brain-targeted-ampakine-compound-protects-against-opioid-induced-respiratory-depression
#8
Wei Dai, Dian Xiao, Xiang Gao, Xin-Bo Zhou, Tong-Yu Fang, Zheng Yong, Rui-Bin Su
The use of opioid drugs for pain relief can induce life-threatening respiratory depression. Although naloxone effectively counteracts opioid-induced respiratory depression, it diminishes the efficacy of analgesia. Our studies indicate that ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse respiratory depression without affecting analgesia at relatively low doses. Mice and rats were subcutaneously or intravenously injected with the opioid agonist TH-030418 to induce moderate or severe respiratory depression...
May 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28502630/new-opioid-receptor-antagonist-naltrexone-14-o-sulfate-synthesis-and-pharmacology
#9
Ferenc Zádor, Kornél Király, András Váradi, Mihály Balogh, Ágnes Fehér, Dóra Kocsis, Anna I Erdei, Erzsébet Lackó, Zoltán S Zádori, Sándor Hosztafi, Béla Noszál, Pál Riba, Sándor Benyhe, Susanna Fürst, Mahmoud Al-Khrasani
Opioid antagonists, naloxone and naltrexone have long been used in clinical practice and research. In addition to their low selectivity, they easily pass through the blood-brain barrier. Quaternization of the amine group in these molecules, (e.g. methylnaltrexone) results in negligible CNS penetration. In addition, zwitterionic compounds have been reported to have limited CNS access. The current study, for the first time gives report on the synthesis and the in vitro [competition binding, G-protein activation, isolated mouse vas deferens (MVD) and mouse colon assay] pharmacology of the zwitterionic compound, naltrexone-14-O-sulfate...
May 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28430384/pharmacokinetics-of-concentrated-naloxone-nasal-spray-over-first-30%C3%A2-minutes-post-dosing-analysis-of-suitability-for-opioid-overdose-reversal
#10
Gill Mundin, Rebecca McDonald, Kevin Smith, Stephen Harris, John Strang
BACKGROUND AND AIMS: Lack of non-injectable naloxone formulations has impeded widespread take-home provision for the prevention of heroin/opioid overdose deaths. For non-injectable formulations that are finally being investigated, rapid onset of action and sufficient bioavailability will be vital. We present analysis of data from a study of concentrated naloxone nasal spray formulations. Our aims are: to assess 1) pharmacokinetic properties and 2) suitability for overdose reversal in terms of naloxone absorption within 30 minutes post-dosing...
April 21, 2017: Addiction
https://www.readbyqxmd.com/read/28410920/potential-drug-interaction-with-opioid-agonist-in-the-setting-of-chronic-low-dose-opioid-antagonist-use
#11
James B Leonard, Vidya Nair, Christopher J Diaz, Jonathan B Penoyar, Penelope A Goode
Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis...
April 6, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28349575/low-dose-naloxone-for-prophylaxis-of-postoperative-nausea-and-vomiting-a-systematic-review-and-meta-analysis
#12
Robert W Barrons, Joseph Andrew Woods
STUDY OBJECTIVE: To determine whether postoperative administration of low-dose intravenous naloxone decreases the incidence of postoperative nausea and vomiting (PONV) and its impact on postoperative opioid requirements and pain scores. DESIGN: Meta-analysis of nine randomized controlled trials. PATIENTS: A total of 946 adult and pediatric patients who received low-dose intravenous naloxone for 24 hours after various surgeries. MEASUREMENTS AND MAIN RESULTS: Systemic literature searches of the Cochrane Central Register of Controlled Trials, Evidence-Based Medicine Reviews, PubMed, and Ovid MEDLINE databases were conducted...
May 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28336575/pharmacologic-profile-of-naloxegol-a-peripherally-acting-%C3%A2%C2%B5-opioid-receptor-antagonist-for-the-treatment-of-opioid-induced-constipation
#13
Eike Floettmann, Khanh Bui, Mark Sostek, Kemal Payza, Michael Eldon
Opioid-induced constipation (OIC) is a common side effect of opioid pharmacotherapy for the management of pain because opioid agonists bind to µ-opioid receptors in the enteric nervous system (ENS). Naloxegol, a polyethylene glycol derivative of naloxol, which is a derivative of naloxone and a peripherally acting µ-opioid receptor antagonist, targets the physiologic mechanisms that cause OIC. Pharmacologic measures of opioid activity and pharmacokinetic measures of central nervous system (CNS) penetration were employed to characterize the mechanism of action of naloxegol...
May 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28291086/opioid-type-respiratory-depressant-side-effects-of-cebranopadol-in-rats-are-limited-by-its-nociceptin-orphanin-fq-peptide-receptor-agonist-activity
#14
Klaus Linz, Wolfgang Schröder, Stefanie Frosch, Thomas Christoph
BACKGROUND: Cebranopadol is a first-in-class analgesic with agonist activity at classic opioid peptide receptors and the nociceptin/orphanin FQ peptide receptor. The authors compared the antinociceptive and respiratory depressant effects of cebranopadol and the classic opioid fentanyl and used selective antagonists to provide the first mechanistic evidence of the contributions of the nociceptin/orphanin FQ peptide and μ-opioid peptide receptors to cebranopadol's respiratory side-effect profile...
April 2017: Anesthesiology
https://www.readbyqxmd.com/read/28277185/changes-in-the-incentive-value-of-food-after-naltrexone-treatment-depend-on-a-differential-preference-for-a-palatable-food-in-male-rats
#15
Mariana Alvarado-Bañuelos, Eliana Barrios De Tomasi, Jorge Juárez
INTRODUCTION: Opioid antagonist treatments such as naltrexone (NTX) and naloxone reduce consummatory behavior of palatable food (PF) and other incentives. Meanwhile, a significant increase in alcohol consumption has been observed when it is offered immediately after ending NTX treatment, an effect apparently produced by increased opioidergic activity caused by up-regulation of opioid receptors. OBJECTIVE: On this basis we assessed changes in the consumption of PF after opioid antagonist treatment in rats with different preferences for that food...
March 23, 2016: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28275232/the-differential-effects-of-low-and-high-doses-of-apelin-through-opioid-receptors-on-the-blood-pressure-of-rats-with-renovascular-hypertension
#16
Mahboobeh Yeganeh-Hajahmadi, Hamid Najafipour, Farzaneh Rostamzadeh
The apelin/APJ system has an important role in the regulation of vascular tone and blood pressure. Opioid receptors (OPRs) are also important cardiovascular regulators and exert many of their effects by modulating the function of other G-protein-coupled receptors. The aim of this study was to analyze the interaction of apelin and the opioid system with respect to vascular responses to apelin in rats with renovascular hypertension (two-kidney, one clip (2K1C)). Homodynamic studies were carried out in 2K1C rats...
March 9, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28144724/pharmacokinetics-of-a-new-nasal-formulation-of-naloxone
#17
Ida Tylleskar, Arne Kristian Skulberg, Turid Nilsen, Sissel Skarra, Phatsawee Jansook, Ola Dale
PURPOSE: Nasal naloxone is wanted for bystander administration in opioid overdose and as a needle-free alternative for emergency medical personnel. Epidemiologic studies have indicated a therapeutic effect of bystander administration of low-concentration/high-volume formulations. The objective for this study was to describe the nasal pharmacokinetics of a new high-concentration/low-volume nasal formulation of naloxone. METHODS: This was an open, randomized triple crossover trial in healthy, human volunteers (n = 12) where two doses of nasal naloxone (0...
January 31, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28126501/hyperalgesic-and-hypoalgesic-mechanisms-evoked-by-the-acute-administration-of-ccl5-in-mice
#18
Sara González-Rodríguez, Miguel G Álvarez, Mario García-Domínguez, Ana Lastra, Rafael Cernuda-Cernuda, Alicia R Folgueras, María Teresa Fernández-García, Agustín Hidalgo, Ana Baamonde, Luis Menéndez
We show here that the intraplantar administration of CCL5 in mice produces hyperalgesia at low doses but activates compensatory antinociceptive mechanisms at doses slightly higher. Thus, the injection of 3-10ng of CCL5 evoked thermal hyperalgesia through the activation of CCR1 and CCR5 receptors, as demonstrated by the inhibitory effect exerted by the selective antagonists J113863 (0.01-0.1μg) and DAPTA (0.3-3μg), respectively. The prevention of this hyperalgesia by diclofenac (1-10μg), the inhibitors of COX-1 SC-560 (0...
January 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28078167/a-novel-strategy-for-attenuating-opioid-withdrawal-in-neonates
#19
Giovanni C Santoro, Samarth Shukla, Krishna Patel, Jakub Kaczmarzyk, Stergiani Agorastos, Sandra Scherrer, Yoon Young Choi, Christina Veith, Joseph Carrion, Rebecca Silverman, Danielle Mullin, Mohamed Ahmed, Wynne K Schiffer, Jonathan D Brodie, Stephen L Dewey
The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering. Consequently, we examined the efficacy of prenatal, low-dose and short-term vigabatrin (γ-vinyl GABA, GVG) exposure for attenuating these symptoms as well as the metabolic changes observed in the brains of these animals upon reaching adolescence...
August 2016: Journal of Addiction Research & Therapy
https://www.readbyqxmd.com/read/28059581/hot-and-cold-drugs-national-park-service-medication-stability-at-the-extremes-of-temperature
#20
Patil Armenian, Danielle Campagne, Geoff Stroh, Crystal Ives Tallman, William Z D Zeng, Thomas Lin, Roy R Gerona
STUDY OBJECTIVE: National Park Service (NPS) Parkmedics provide medical care in austere environments. The objective of this study was to evaluate the stability of specific medications used by Parkmedics at extremes of temperatures likely to be faced in the field. METHODS: This is a bench research study conducted in the laboratory setting over a 4-week period. Parenteral medications were separated into 4 temperature exposure groups: A) 45°C (hot); B) -20°C (cold); C) hot then cold temperatures alternating weekly; and D) cold then hot temperatures alternating weekly...
May 2017: Prehospital Emergency Care
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