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Opioid tolerance

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https://www.readbyqxmd.com/read/28448398/intrathecal-morphine-versus-extended-release-epidural-morphine-for-postoperative-pain-control-in-pediatric-patients-undergoing-posterior-spinal-fusion
#1
Mindy Cohen, Jeannie Zuk, Nancy McKay, Mark Erickson, Zhaoxing Pan, Jeffrey Galinkin
BACKGROUND: Posterior spinal fusion for scoliosis is one of the most painful elective pediatric surgeries. Good postoperative pain control allows early ambulation and return of ability to tolerate oral intake. Options for analgesia in this patient population are suboptimal. We hypothesized that extended-release epidural morphine (EREM) would provide better pain control and less adverse effects compared to intrathecal (IT) morphine. METHODS: The primary outcome was total IV morphine consumption during 0-48 hours postoperatively...
April 24, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28445097/phase-iib-randomized-double-blind-placebo-controlled-study-of-naldemedine-for-the-treatment-of-opioid-induced-constipation-in-patients-with-cancer
#2
Nobuyuki Katakami, Koji Oda, Katsunori Tauchi, Ken Nakata, Katsunori Shinozaki, Takaaki Yokota, Yura Suzuki, Masaru Narabayashi, Narikazu Boku
Purpose This randomized, double-blind, multicenter study aimed to determine the dose of naldemedine, a peripherally-acting μ-opioid receptor antagonist, for future trials by comparing the efficacy and safety of three doses of naldemedine versus placebo in patients with cancer and opioid-induced constipation. Methods Patients ≥ 18 years old with cancer, an Eastern Cooperative Oncology Group performance status ≤ 2, who had been receiving a stable regimen of opioid analgesics for ≥ 2 weeks, had at least one constipation symptom despite laxative use, and no more than five spontaneous bowel movements (SBMs) during the past 14 days, were randomly assigned (1:1:1:1) to oral, once-daily naldemedine 0...
April 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28442580/ethanol-reversal-of-tolerance-to-the-antinociceptive-effects-of-oxycodone-and-hydrocodone
#3
Joanna C Jacob, Justin L Poklis, Hamid I Akbarali, Graeme Henderson, William L Dewey
This study compared the development of tolerance and its reversal by ethanol of two orally-bioavailable prescription opioids, oxycodone and hydrocodone, to that of morphine. Oxycodone (s.c) was significantly more potent in the mouse tail withdrawal assay than either morphine or hydrocodone. Oxycodone was also significantly more potent in this assay than hydrocodone when administered orally. Tolerance was seen following chronic subcutaneous administration of each of the three drugs and by the chronic administration of oral oxycodone, but not following the chronic oral administration of hydrocodone...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28426670/mice-expressing-a-hyper-sensitive-form-of-the-cb1-cannabinoid-receptor-cb1-show-modestly-enhanced-alcohol-preference-and-consumption
#4
David J Marcus, Angela N Henderson-Redmond, Maciej Gonek, Michael L Zee, Jill C Farnsworth, Randa A Amin, Mary-Jeanette Andrews, Brian J Davis, Ken Mackie, Daniel J Morgan
We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol...
2017: PloS One
https://www.readbyqxmd.com/read/28426507/peripartum-anesthetic-management-of-the-opioid-tolerant-or-buprenorphine-suboxone-dependent-patient
#5
Aileen Pan, Mark Zakowski
Opioid abuse and dependence continues to rise in both the general population and pregnancy, with opioid overdose deaths having quadrupled in the last 15 years. Illicit drug use in last 30 days of pregnancy was over 4% with almost 0.6% documented maternal opiate use at time of birth. The management of the opioid-tolerant, buprenorphine-dependent or methadone-dependent patient in the peripartum period is reviewed. Options for treatment of opioid dependence, acute pain management, and perioperative multimodal analgesia are discussed...
June 2017: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28417245/elbasvir-grazoprevir-a-review-in-chronic-hcv-genotypes-1-and-4
#6
Zaina T Al-Salama, Emma D Deeks
A fixed-dose combination tablet comprising the hepatitis C virus (HCV) NS5A inhibitor elbasvir and the HCV NS3/4A protease inhibitor grazoprevir (elbasvir/grazoprevir; Zepatier™) was recently approved for the treatment of chronic HCV genotype 1 and 4 infection in the EU and the USA. In phase III trials, 12 or 16 weeks of treatment with once-daily elbasvir/grazoprevir (fixed-dose tablet or as individual agents), taken with or without ribavirin, generally provided high rates of sustained virological response at 12 weeks (SVR12) in treatment-naive and -experienced adult patients with chronic HCV genotype 1a, 1b or 4 infection, including those with or without compensated cirrhosis, HIV co-infection, inherited blood disorders or chronic kidney disease or patients receiving opioid agonist therapy or of Japanese origin...
April 17, 2017: Drugs
https://www.readbyqxmd.com/read/28414496/impaired-psychomotor-function-and-plasma-methadone-and-levo-alpha-acetylmethadol-laam-concentrations-in-opioid-substitution-patients
#7
David A L Newcombe, Andrew A Somogyi, Felix Bochner, Jason M White
Tolerance to the psychomotor impairing effects of opioid drugs is expected to develop with repeated dosing, but may be incomplete. The relationship between plasma opioid concentration and psychomotor function in opioid-dependent patients was examined to determine whether impairment was more likely at the time of highest plasma drug concentration. Sixteen patients participating in a cross-over trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs)...
April 17, 2017: Experimental and Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28385341/enhancement-of-%C3%AE-opioid-receptor-desensitization-by-orexin-a-in-rat-locus-coeruleus-neurons
#8
S Mohammad Ahmadi Soleimani, Hossein Azizi, Narges Pachenari, Javad Mirnajafi-Zadeh, Saeed Semnanian
Opioids have always been used in clinical practice for pain management. However, development of tolerance to their effects following long term administration, seriously restricts further clinical use of these drugs. In this regard, μ-opioid receptor (MOR) desensitization, as an initial step in development of opioid tolerance, is of particular significance. Previous studies support the involvement of orexinergic system in development of opioid tolerance. Locus coeruleus (LC) nucleus has been shown to modulate pain and development of tolerance...
March 23, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28378462/targeting-multiple-opioid-receptors-improved-analgesics-with-reduced-side-effects
#9
REVIEW
Thomas Günther, Pooja Dasgupta, Anika Mann, Elke Miess, Andrea Kliewer, Sebastian Fritzwanker, Ralph Steinborn, Stefan Schulz
Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the μ-opioid receptor (μ receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the κ-opioid receptor (κ receptor), δ-opioid receptor (δ receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor)...
April 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28371835/effectiveness-and-safety-of-once-daily-extended-release-hydrocodone-in-individuals-previously-receiving-immediate-release-oxycodone-for-chronic-pain
#10
Joseph Pergolizzi, Maribeth Kowalski, Ellie He
Objectives. : This study evaluated the safety and effectiveness of a once-daily, single-entity, extended-release hydrocodone bitartrate (HYD) among patients with chronic noncancer and non-neuropathic pain who required opioid rotation from a previous analgesic regimen that primarily consisted of immediate-release (IR) oxycodone. Methods. : Post hoc analyses of a primary study that assessed HYD 20 to 120 mg over a 52-week period are presented. The primary study included a dose titration period (up to 45 days), a 52-week maintenance period, and an optional taper period (up to 14 days)...
March 28, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28368571/recent-advances-in-the-realm-of-allosteric-modulators-for-opioid-receptors-for-future-therapeutics
#11
Michael Remesic, Victor J Hruby, Frank Porreca, Yeon Sun Lee
Opioids, and more specifically μ-opioid receptor (MOR) agonists such as morphine, have long been clinically used as therapeutics for severe pain states but often come with serious side effects such as addiction and tolerance. Many studies have focused on bringing about analgesia from the MOR with attenuated side effects, but its underlying mechanism is not fully understood. Recently, focus has been geared toward the design and elucidation of the orthosteric site with ligands of various biological profiles and mixed subtype opioid activities and selectivities, but targeting the allosteric site is an area of increasing interest...
April 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28365372/endogenous-opioid-function-and-responses-to-morphine-the-moderating-effects-of-anger-expressiveness
#12
John W Burns, Stephen Bruehl, Christopher R France, Erik Schuster, Daria Orlowska, Melissa Chont, Rajnish K Gupta, Asokumar Buvanendran
Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n=89) and healthy controls (n=102) underwent ischemic pain induction under placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-out subscale. Endogenous opioid function x anger-out x pain status (chronic pain; healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance and pain intensity (McGill Sensory and Affective subscales) and side effects...
March 29, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28364251/allosteric-modulation-model-of-the-mu-opioid-receptor-by-herkinorin-a-potent-not-alkaloidal-agonist
#13
A F Marmolejo-Valencia, K Martínez-Mayorga
Modulation of opioid receptors is the primary choice for pain management and structural information studies have gained new horizons with the recently available X-ray crystal structures. Herkinorin is one of the most remarkable salvinorin A derivative with high affinity for the mu opioid receptor, moderate selectivity and lack of nitrogen atoms on its structure. Surprisingly, binding models for herkinorin are lacking. In this work, we explore binding models of herkinorin using automated docking, molecular dynamics simulations, free energy calculations and available experimental information...
March 31, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28363231/-management-of-adverse-effects-of-opioid-therapy
#14
Stefan Wirz
More than 6 million people in Germany suffer from chronic pain which greatly impairs their wellbeing. Often the only therapeutic option is to use class 2 or 3 analgesic opioids in the WHO classification, as class 1 analgesics may be toxic or of limited efficacy. However, the high incidence of opioid side effects leads to high discontinuation rates. Thus, the success of opioid treatment is also highly dependent on the management of the safety and tolerability of the treatment. Most opioid side effects, such as nausea and sedation, predominantly occur in the initial phase of therapy...
April 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28361126/pressure-sensitivity-and-phenotypic-changes-in-patients-with-suspected-opioid-induced-hyperalgesia-being-withdrawn-from-full-mu-agonists
#15
Ronald A Wasserman, Afton L Hassett, Steven E Harte, Jenna Goesling, Herbert L Malinoff, Daniel W Berland, Jennifer Zollars, Stephanie E Moser, Chad M Brummett
OBJECTIVES: To assess changes in phenotype and pressure sensitivity in patients with suspected opioid-induced-hyperalgesia (OIH) after transitioning to buprenorphine. METHODS: Twenty patients with suspected OIH were enrolled to transition to buprenorphine therapy. Patients completed validated self-report measures at baseline and at 1, 4, 8 weeks, and 6 months after initiation of buprenorphine along with quantitative sensory testing including measures of pressure pain threshold, pain tolerance and Pain 50 (a pain intensity rating)...
February 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28358754/open-label-study-of-injectable-extended-release-naltrexone-xr-ntx-in-healthcare-professionals-with-opioid-dependence
#16
Paul H Earley, Jacqueline Zummo, Asli Memisoglu, Bernard L Silverman, David R Gastfriend
OBJECTIVES: Healthcare professionals (HCPs) with opioid dependence are at risk for relapse and death, particularly in the first year of recovery; however, maintenance treatment with opioid agonists is controversial in this safety-sensitive group. We evaluated long-term safety, tolerability, and treatment outcomes of injectable, intramuscular, extended-release naltrexone (XR-NTX) in opioid-dependent HCPs. METHODS: This single-arm, multisite, open-label study was conducted in opioid-dependent HCPs who had been detoxified from opioids for at least 2 weeks...
March 29, 2017: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/28356897/novel-molecular-strategies-and-targets-for-opioid-drug-discovery-for-the-treatment-of-chronic-pain
#17
REVIEW
Keith M Olson, Wei Lei, Attila Keresztes, Justin LaVigne, John M Streicher
Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28353040/confounding-factors-associated-with-oral-mucositis-assessment-in-patients-receiving-chemoradiotherapy-for-head-and-neck-cancer
#18
Yih-Lin Chung, Newman N M Pui
PURPOSE: The aim of this study was to identify patient-centered, mucositis-associated adverse impact factors and events that might confound physician-assessed oral mucositis (OM) in head and neck cancer (HNC) patients receiving chemoradiotherapy. METHODS: This was a post hoc analysis of a previously conducted randomized trial to determine the efficacy of 5% phenylbutyrate mouthwash in preventing chemoradiotherapy-induced OM. This analysis identified patient-centered symptomatic, observable, and measurable factors that may confound physician scoring of the severity of OM during chemoradiotherapy...
March 28, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28352316/monocyte-chemoattractant-protein-1-contributes-to-morphine-tolerance-in-rats-with-cancer-induced-bone-pain
#19
Lei Liu, Xiu-Juan Gao, Chun-Guang Ren, Ji-Hua Hu, Xian-Wen Liu, Ping Zhang, Zong-Wang Zhang, Zhi-Jian Fu
Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28347772/bifunctional-opioid-nociceptin-hybrid-kgnop1-effectively-attenuates-pain-related-behaviour-in-a-rat-model-of-neuropathy
#20
Joanna Starnowska, Karel Guillemyn, Wioletta Makuch, Joanna Mika, Steven Ballet, Barbara Przewlocka
A bifunctional peptide containing an opioid and nociceptin receptor-binding pharmacophore, H-Dmt-D-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2 (KGNOP1), was tested for its analgesic properties when administered intrathecally in naïve and chronic constriction injury (CCI)-exposed rats with neuropathy-like symptoms. KGNOP1 significantly increased the acute pain threshold, as measured by the tail-flick test, and also increased the threshold of a painful reaction to mechanical and thermal stimuli in CCI-exposed rats...
March 24, 2017: European Journal of Pharmaceutical Sciences
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