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https://www.readbyqxmd.com/read/28699646/review-of-opioid-pharmacogenetics-and-considerations-for-pain-management
#1
Aniwaa Owusu Obeng, Issam Hamadeh, Michael Smith
Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response...
July 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28693439/combatting-pain-after-orthopedic-trauma-surgery-perioperative-oral-extended-release-tapentadol-vs-extended-release-oxycodone-naloxone
#2
Gertrud Haeseler, Dirk Schaefers, Natalie Prison, Jörg Ahrens, Xiaofei Liu, Annika Karch
BACKGROUND: High post-operative pain scores after "minor" orthopedic/trauma surgery are in part attributed to inadequate prescription of opioid analgesics. Novel concepts aiming to achieve sufficient analgesia while minimizing opioid-related side effects by avoiding fluctuating plasma levels are based on perioperative oral administration of extended-release opioids beginning with the first dose pre-operatively. This is the first study to evaluate analgesic efficacy and side effect rates of extended-release tapentadol compared to oxycodone/naloxone following orthopedic/trauma surgery...
July 11, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28683172/opioids-for-cancer-pain-an-overview-of-cochrane-reviews
#3
REVIEW
Philip J Wiffen, Bee Wee, Sheena Derry, Rae F Bell, R Andrew Moore
BACKGROUND: Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol...
July 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28673386/polyglycerol-opioid-conjugate-produces-analgesia-devoid-of-side-effects
#4
Sara González-Rodríguez, Mohiuddin A Quadir, Shilpi Gupta, Karolina A Walker, Xuejiao Zhang, Viola Spahn, Dominika Labuz, Antonio Rodriguez-Gaztelumendi, Martin Schmelz, Jan Joseph, Maria K Parr, Halina Machelska, Rainer Haag, Christoph Stein
Novel painkillers are urgently needed. The activation of opioid receptors in peripheral inflamed tissue can reduce pain without central adverse effects such as sedation, apnoea, or addiction. Here, we use an unprecedented strategy and report the synthesis and analgesic efficacy of the standard opioid morphine covalently attached to hyperbranched polyglycerol (PG-M) by a cleavable linker. With its high-molecular weight and hydrophilicity, this conjugate is designed to selectively release morphine in injured tissue and to prevent blood-brain barrier permeation...
July 4, 2017: ELife
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
#5
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/28626504/comparing-healthcare-utilization-and-costs-among-medicaid-insured-patients-with-chronic-noncancer-pain-with-and-without-opioid-induced-constipation-a-retrospective-analysis
#6
Tope Olufade, Amanda M Kong, Nicole Princic, Paul Juneau, Rucha Kulkarni, Kui Zhang, Catherine Datto
BACKGROUND: Constipation is a common adverse effect of opioid use and has been associated with increased healthcare utilization and costs among patients receiving opioids for pain management. OBJECTIVE: To compare the healthcare utilization and costs of Medicaid patients with chronic noncancer pain with and without constipation who were receiving opioids. METHODS: This retrospective, claims-based study was conducted using data from the Truven Health MarketScan Medicaid Multi-State database...
April 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28597312/-management-of-chronic-pain-using-extended-release-tilidine-quality-of-life-and-implication-of-comedication-on-tilidine-metabolism
#7
C Wolfert, M Merbach, G Stammler, O Emrich, A M Meid, J Burhenne, A Blank, G Mikus
BACKGROUND AND OBJECTIVES: The synthetic opioid tilidine is often used in chronic pain treatment. However, the activation via metabolism in patients with concomitant medication and reduced liver or kidney function is not thoroughly investigated. We therefore studied pain treatment efficacy, health-related quality of live and the metabolism of tilidine in patients with chronic pain. METHODS AND MATERIALS: In all, 48 patients, who were on a stable dose of oral prolonged release tilidine for at least 7 days, were included in this observational multicenter study...
June 8, 2017: Der Schmerz
https://www.readbyqxmd.com/read/28588891/prevalence-and-clinical-features-of-opioid-induced-constipation-in-the-general-population-a-french-study-of-15-000-individuals
#8
P Ducrotté, J Milce, C Soufflet, C Fabry
BACKGROUND: Constipation is common during opioid therapy and can compromise analgesia. AIM: The aim of this article is to determine the prevalence and clinical characteristics of opioid-induced constipation (OIC) in France. METHODS: A questionnaire study was conducted in a representative sample of the French general population. Participants completed a 31-item questionnaire covering opioid use during the previous six months, and the occurrence of constipation (defined as <3 bowel movements per week, straining during defaecation, or both) during opioid treatment...
June 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28576452/naldemedine-versus-placebo-for-opioid-induced-constipation-compose-1-and-compose-2-two-multicentre-phase-3-double-blind-randomised-parallel-group-trials
#9
Martin Hale, James Wild, Jyotsna Reddy, Tadaaki Yamada, Juan Camilo Arjona Ferreira
BACKGROUND: Opioid-induced constipation is a frequent side-effect of opioid treatment, and standard interventions have limited or inconsistent efficacy. This study assessed the efficacy and safety of naldemedine, a peripherally acting μ-opioid receptor antagonist, for the treatment of opioid-induced constipation in patients with chronic non-cancer pain. METHODS: We report two double-blind, randomised, placebo-controlled trials in adults with chronic non-cancer pain and opioid-induced constipation...
May 30, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28576450/opioid-induced-constipation-reflections-on-efficacy-assessment
#10
Gerhild Becker, Waldemar Siemens
No abstract text is available yet for this article.
May 30, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28554659/naloxegol-an-opioid-antagonist-with-reduced-cns-penetration-mode-of-action-and-human-relevance-for-rat-testicular-tumours
#11
Håkan Andersson, Terri Mitchard, Nakpangi Johnson, Eike Floettmann
Naloxegol is an opioid antagonist which has been developed for the treatment of patients with opioid induced constipation. In the nonclinical safety program naloxegol was shown to have a very benign toxicity profile. In the rat, but not the mouse, 2-year carcinogenicity study a change in tumour pattern with an increase in testicular Leydig cell tumours (LCT) was observed after dosing at high (supra-pharmacological) concentrations. To establish the basis of the increase in LCT and to assess its potential relevance to humans, studies to exclude and potentially identify mode-of-action (MoA) were performed...
August 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28551445/decreasing-postoperative-narcotics-in-reconstructive-pelvic-surgery-a%C3%A2-randomized-controlled-trial
#12
Krista M L Reagan, David M O'Sullivan, Richard Gannon, Adam C Steinberg
BACKGROUND: Postoperative pain control is crucial to any successful recovery plan. Many currently used medication regimens are narcotic-focused. OBJECTIVE: The objective of our study was to evaluate the efficacy of a multimodal pain regimen after pelvic reconstructive surgery. STUDY DESIGN: The primary outcome measure was narcotic use. Secondary outcomes included pain, nausea, and constipation. Patients were randomized to either usual care postoperative treatment or multimodal pain regimen...
May 25, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28548207/pharmacometric-modeling-of-naloxegol-efficacy-and-safety-impact-on-dose-and-label
#13
N Al-Huniti, D Zhou, H Xu, S Aksenov, K H Bui, R Fox, G Helmlinger, D Stanski
Naloxegol is a peripherally acting μ-opioid receptor antagonist that was developed for the treatment of opioid-induced constipation. Modeling and simulation of naloxegol efficacy and tolerability informed selection of doses for phase III studies and provided comprehensive dosage recommendations for the naloxegol US package insert.
May 26, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28529168/opioids-in-gastroenterology-treating-adverse-effects-and-creating-therapeutic-benefits
#14
Michael Camilleri, Anthony Lembo, David A Katzka
The use of opioid medications on both an acute and chronic basis is ubiquitous in the United States. As opioid receptors densely populate the gastrointestinal tract, symptoms and side effects can be expected in these patients. In the esophagus, dysmotility may result, manifesting with dysphagia and a syndrome indistinguishable from primary achalasia. In the stomach, a marked delay in gastric emptying may ensue with postprandial nausea and early satiety. Postoperatively, particularly with abdominal surgery, opioid-induced ileus may ensue...
May 19, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28521200/patterns-of-kratom-use-and-health-impact-in-the-us-results-from-an-online-survey
#15
Oliver Grundmann
BACKGROUND: Kratom preparations have raised concerns of public health and safety in the US. Investigation into the demographics, perceived beneficial and detrimental effects of Kratom as well as common doses and purposes of its use are important to properly evaluate its potential health impact. METHODS: An anonymous cross-sectional online survey was conducted in October 2016 of 10,000 current Kratom users through available social media and online resources from the American Kratom Association...
May 10, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28515426/tolerability-of-opioid-analgesia-for-chronic-pain-a-network-meta-analysis
#16
Zengdong Meng, Jing Yu, Michael Acuff, Chong Luo, Sanrong Wang, Lehua Yu, Rongzhong Huang
Aim of this study was to study the tolerability of opioid analgesia by performing a network meta-analysis (NMA) of randomized-controlled trials (RCTs) which investigated effectiveness of opioids for the management of chronic pain. Research articles reporting outcomes of RCT/s comparing 2 or more opioid analgesics for the management of chronic pain were obtained by database search. Bayesian NMAs were performed to combine direct comparisons between treatments with that of indirect simulated evidence. Study endpoints were: incidence of adverse events, incidence of constipation, trial withdrawal rate, and patient satisfaction with treatment...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505689/-pain-management-in-palliative-care
#17
Martin B Steins, Corinna Eschbach, Matthias Villalobos, Michael Thomas
A consistent pain management together with treatment of dyspnoea belongs to the main issues in symptom control in particular in palliative thoracic oncology. Together with the medicamentous therapy the psychologic and social circumstances of the affected patients have to be considered as factors influencing the experience of pain. The therapeutic fundament according to the WHO guideline for cancer pain is the opiate based medicamentous adjustment combined with non-opioids. In principle, this should be performed preferably orally, as simply as possible, according to a fix drug schedule and individually adjusted to the needed dosage...
May 2017: Pneumologie
https://www.readbyqxmd.com/read/28504549/determination-of-naloxegol-in-human-biological-matrices
#18
Yan Li, Mark Hoffmann, Paul Severin
AIM: Naloxegol is an oral peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation. Sensitive, robust, bioanalytical methods were required to quantitate naloxegol in human biological matrices as part of the clinical development program. Results/methodology: Analytical plasma samples were prepared using Solid Phase Extraction (SPE) coupled with concentration. The method's linearity was established at 0.1-50 ng/ml with up to 100-fold dilution...
May 15, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28499731/discovery-of-n-substituted-endo-3-8-aza-bicyclo-3-2-1-oct-3-yl-phenol-and-phenyl-carboxamide-series-of-%C3%AE-opioid-receptor-antagonists
#19
Lan Jiang, David T Beattie, John R Jacobsen, Samuel Kintz, Glenmar P Obedencio, Daisuke Saito, Ioanna Stergiades, Ross G Vickery, Daniel D Long
Gastrointestinal dysfunction as a consequence of the use of opioid analgesics is of significant clinical concern. First generation drugs to treat these opioid-induced side-effects were limited by their negative impact on opioid receptor agonist-induced analgesia. Second generation therapies target a localized, peripherally-restricted, non-CNS penetrant drug distribution of opioid receptor antagonists. Herein we describe the discovery of the N-substituted-endo-3-(8-aza-bicyclo[3.2.1]oct-3-yl)-phenol and -phenyl carboxamide series of μ-opioid receptor antagonists...
May 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28493170/eluxadoline-a-review-in-diarrhoea-predominant-irritable-bowel-syndrome
#20
REVIEW
Gillian M Keating
Eluxadoline (Truberzi(®)) is an orally administered, minimally absorbed agent that acts locally in the gastrointestinal tract as a mixed µ-opioid receptor agonist and δ-opioid receptor antagonist. The randomized, double-blind, placebo-controlled, multinational, phase 3 IBS-3001 and IBS-3002 trials examined the efficacy of eluxadoline in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). The composite response rate (i.e. the proportion of patients with improvement in both worst abdominal pain and stool consistency on ≥50% of days; primary endpoint), was significantly higher in patients receiving eluxadoline 100 mg twice daily than in those receiving placebo after 12 and 26 weeks' therapy...
June 2017: Drugs
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