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Opioid tolerance

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https://www.readbyqxmd.com/read/28226414/methylene-blue-for-the-treatment-of-intractable-pain-associated-with-oral-mucositis
#1
Carlos J Roldan, Kent Nouri, Thomas Chai, Billy Huh
Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develop intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative...
February 22, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28223843/the-use-of-rotation-to-fentanyl-in-cancer-related-pain
#2
Delia Dima, Ciprian Tomuleasa, Ioana Frinc, Sergiu Pasca, Lorand Magdo, Ioana Berindan-Neagoe, Mihai Muresan, Cosmin Lisencu, Alexandru Irimie, Mihnea Zdrenghea
Pain is commonly diagnosed with respect to cancer and heart diseases, being a major symptom in most neoplastic diseases. Uncontrolled pain leads to a decrease in the quality of life and an increase in the morbidity of the patient. Opioids represent the best analgetic supportive therapy and are frequently used in patients suffering from cancer and experiencing a high level of pain. Opioid treatment starts with a gradual titration of the dose until the minimum effective dose and the maximum tolerated dose are determined...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28214183/-misuse-and-dependence-on-prescription-opioids-prevention-identification-and-treatment
#3
B Rolland, D Bouhassira, N Authier, M Auriacombe, V Martinez, P Polomeni, G Brousse, R Schwan, P Lack, J Bachellier, S Rostaing, P Bendimerad, P Vergne-Salle, M Dematteis, S Perrot
Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#4
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28204957/insights-into-the-role-of-opioid-receptors-in-the-gi-tract-experimental-evidence-and-therapeutic-relevance
#5
James J Galligan, Catia Sternini
Opioid drugs are prescribed extensively for pain treatment but when used chronically they induce constipation that can progress to opioid-induced bowel dysfunction. Opioid drugs interact with three classes of opioid receptors: mu opioid receptors (MORs), delta opioid receptors (DOR), and kappa opioid receptors (KORs), but opioid drugs mostly target the MORs. Upon stimulation, opioid receptors couple to inhibitory Gi/Go proteins that activate or inhibit downstream effector proteins. MOR and DOR couple to inhibition of adenylate cyclase and voltage-gated Ca(2+) channels and to activation of K(+) channels resulting in reduced neuronal activity and neurotransmitter release...
February 16, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28190392/pi3k-akt-pathway-a-potential-therapeutic-target-for-chronic-pain
#6
Shu-Ping Chen, Ya-Qun Zhou, Dai-Qiang Liu, Wen Zhang, Anne Manyande, Xue-Hai Guan, Yu-Ke Tian, Da-Wei Ye, Deeq Mohamed Omar
Chronic pain is among the most disabling and costly disorders, with prevalence ranging from 10% to 55%. However, current therapeutic strategies for chronic pain are unsatisfactory due to our poor understanding of its mechanisms. Thus, novel therapeutic targets need to be found in order to improve these patients' quality of life. PI3K and its downstream Akt are widely expressed in the spinal cord, particularly in the laminae I-IV of the dorsal horn, where nociceptive C and Aδ fibers of primary afferents principally terminate...
February 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28183374/experiences-of-codeine-use-misuse-and-dependence-application-of-liese-and-franz-s-cognitive-developmental-model-of-substance-abuse
#7
Marie Claire Van Hout, Ian Norman, Eileen Rich, Michael Bergin
BACKGROUND: Misuse of codeine-containing medicines is an emerging public health issue. AIMS: We present the application of Liese and Franz's (1996) cognitive developmental model of substance abuse to the trajectory from legitimate codeine use for pain, towards that of therapeutic and other forms of misuse, and physical and psychological dependence. It illustrates a cognitive behavioural analysis of the experiences of codeine misusers - which 'surfaces' the specific beliefs, thoughts, emotions and behaviours of this group of hidden codeine dependent individuals, who are distinct and unique from other opioid-dependent cohorts...
February 10, 2017: Behavioural and Cognitive Psychotherapy
https://www.readbyqxmd.com/read/28182123/long-term-safety-and-analgesic-efficacy-of-buprenorphine-buccal-film-in-patients-with-moderate-to-severe-chronic-pain-requiring-around-the-clock-opioids
#8
Martin Hale, Veronica Urdaneta, M Todd Kirby, Qinfang Xiang, Richard Rauck
BACKGROUND: This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids. METHODS: The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients) or were recruited de novo for this study (n=61) were enrolled in this study...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28179123/spinal-or-supraspinal-phosphorylation-deficiency-at-the-mor-c-terminus-does-not-affect-morphine-tolerance-in-vivo
#9
Cherkaouia Kibaly, Hong-Yiou Lin, Horace H Loh, Ping-Yee Law
The development of tolerance to morphine, one of the most potent analgesics, in the management of chronic pain is a significant clinical problem and its mechanisms are poorly understood. Morphine exerts its pharmacological effects via the μ-opioid receptor (MOR). Tolerance is highly connected to G-protein-coupled receptors (GPCR) phosphorylation and desensitization increase. Because morphine desensitization previously has been shown to be MOR phosphorylation- and ß-arrestin2-independent (in contrast to agonists such as fentanyl), we examined the contribution of phosphorylation of the entire C-terminus to the development of antinociceptive tolerance to the partial (morphine) and full (fentanyl) MOR agonists in vivo...
February 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28177515/methadone-for-cancer-pain
#10
REVIEW
Alexander B Nicholson, Graeme R Watson, Sheena Derry, Philip J Wiffen
BACKGROUND: This is an updated review originally published in 2004 and first updated in 2007. This version includes substantial changes to bring it in line with current methodological requirements. Methadone is a synthetic opioid that presents some challenges in dose titration and is recognised to cause potentially fatal arrhythmias in some patients. It does have a place in therapy for people who cannot tolerate other opioids but should be initiated only by experienced practitioners. This review is one of a suite of reviews on opioids for cancer pain...
February 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28177167/ketamine-as-an-adjunct-to-opioids-for-acute-pain-in-the-emergency-department-a-randomized-controlled-trial
#11
Karen J Bowers, Kelly B McAllister, Meredith Ray, Corey Heitz
OBJECTIVES: This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids. 2) To measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids. 3) To compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids. 4) To monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids...
February 8, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
https://www.readbyqxmd.com/read/28167156/eluxadoline-demonstrates-a-lack-of-abuse-potential-in-phase-2-and-3-studies-of-patients-with-irritable-bowel-syndrome-with-diarrhea
#12
Reginald V Fant, Jack E Henningfield, Brooks D Cash, Leonard S Dove, Paul S Covington
BACKGROUND & AIMS: Eluxadoline is approved by the Food and Drug Administration for the treatment of adults with irritable bowel syndrome with diarrhea (IBS-D). Eluxadoline is a locally acting mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist. The abuse potential of eluxadoline was evaluated as part of the Phase 2 and 3 clinical trials assessing the efficacy, safety, and tolerability of the drug. METHODS: One Phase 2 (IBS-2001) and 2 Phase 3 (IBS-3001 and IBS-3002) randomized controlled trials enrolled patients meeting Rome III criteria for IBS-D...
February 3, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28162605/-364-morphine-tolerance-during-inflammatory-pain-role-of-delta-opioid-receptors-in-the-midbrain-periaqueductal-gray
#13
A Wilson-Poe, J Moron Concepcion
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28158929/the-analgesic-and-anti-inflammatory-effects-of-salvinorin-a-analogue-%C3%AE-tetrahydropyran-salvinorin-b-in-mice
#14
K F Paton, N Kumar, R S Crowley, J L Harper, T E Prisinzano, B M Kivell
BACKGROUND: Drugs activating the mu opioid receptor are routinely used to treat severe acute and chronic pain. Unfortunately, side effects including nausea, constipation, respiratory depression, addiction and tolerance can limit clinical utility. In contrast, kappa opioid receptor (KOPr) agonists, such as Salvinorin A (SalA), have analgesic properties with little potential for abuse. METHODS: We evaluated SalA and the novel analogue β-tetrahydropyran Salvinorin B (β-THP SalB) for the ability to modulate pain and inflammation in vivo...
February 3, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28155167/inhibition-of-snake-venom-metalloproteinase-by-%C3%AE-lactoglobulin-peptide-from-buffalo-bubalus-bubalis-colostrum
#15
Ashok Arpitha, M Sebastin Santhosh, A C Rohit, K S Girish, D Vinod, H S Aparna
Bioactive peptide research has experienced considerable therapeutic interest owing to varied physiological functions, efficacy in excretion, and tolerability of peptides. Colostrum is a rich natural source of bioactive peptides with many properties elucidated such as anti-thrombotic, anti-hypertensive, opioid, immunomodulatory, etc. In this study, a variant peptide derived from β-lactoglobulin from buffalo colostrum was evaluated for the anti-ophidian property by targeting snake venom metalloproteinases. These are responsible for rapid local tissue damages that develop after snakebite such as edema, hemorrhage, myonecrosis, and extracellular matrix degradation...
February 2, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28142305/effects-of-acute-and-repeated-treatment-with-the-biased-mu-opioid-receptor-agonist-trv130-oliceridine-on-measures-of-antinociception-gastrointestinal-function-and-abuse-liability-in-rodents
#16
Ahmad A Altarifi, Bethany David, Karan H Muchhala, Bruce E Blough, Hamid Akbarali, S Stevens Negus
RATIONALE: TRV130 (oliceridine; N-[(3-methoxythiophen-2-yl)methyl]-2-[(9 R)-9-pyridin-2-yl-6-oxaspiro[4.5]decan-9-yl]ethanamine) is a novel mu opioid receptor (MOR) agonist that preferentially activates G-protein versus β-arrestin signaling pathways coupled to MORs. Prevailing evidence suggests that TRV130 and other G-protein-biased MOR agonists may produce therapeutic analgesic effects with reduced adverse effects compared to existing MOR agonists. OBJECTIVES: This study compared the effects of acute and repeated TRV130 administration on measures of antinociception, gastrointestinal function, and abuse liability in rodents...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28139906/heteromer-induction-an-approach-to-unique-pharmacology
#17
Philip S Portoghese, Eyup Akgün, Mary M Lunzer
It is proposed that two types of opioid receptor heteromers exist: a) those that are constitutive and b) those that are induced by bivalent ligands. Mu opioid agonists interact with constitutive MOR-DOR heteromer to mediate tolerance and dependence. Bivalent ligand, MDAN21, is devoid of these adverse effects by virtue of its DOR antagonist pharmacophore. We propose that bivalent ligands MMG22 and MCC22 induce colocalized receptors to form heteromers (MOR-mGluR5 and MOR-CCR5, respectively) that do not occur naturally, thereby promoting unique pharmacology...
January 31, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28130265/effect-of-tamoxifen-and-brain-penetrant-pkc-and-jnk-inhibitors-on-tolerance-to-opioid-induced-respiratory-depression-in-mice
#18
Sarah L Withey, Rob Hill, Abigail Lyndon, William L Dewey, Eamonn Kelly, Graeme Henderson
Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound tolerance to the respiratory depressant effects of the drug (Hill et al., 2016, Neuropsychopharmacol 41:762-773). The aim of the present study was to investigate whether tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Jun N-terminal kinase (JNK). We found that whilst mice treated for up to six days with morphine developed tolerance, as measured by the reduced responsiveness to an acute challenge dose of morphine, administration of the brain-penetrant PKC inhibitors tamoxifen and calphostin C, restored the ability of acute morphine to produce respiratory depression in morphine-treated mice...
January 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28127938/an-open-label-randomized-bioavailability-study-of-alternative-methods-of-oral-administration-of-naloxegol-in-healthy-subjects
#19
Khanh Bui, Bruce Birmingham, Ulysses Diva, Bruce Berger
Naloxegol is a peripherally acting μ-opioid receptor antagonist approved as an orally administered tablet for the treatment of opioid-induced constipation. Patients with swallowing difficulties may benefit from alternative approaches to the oral administration of the whole-tablet formulation of naloxegol. This open-label, randomized, 4-period, 4-treatment, crossover, single-dose study (NCT02446171) evaluated the pharmacokinetic (PK) characteristics of crushed naloxegol 25-mg tablets (suspended in water) administered orally or by nasogastric tube and a naloxegol solution compared with the commercially available 25-mg tablet formulation in healthy volunteers...
January 27, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28121474/elevated-levels-of-dna-methylation-at-the-oprm1-promoter-region-in-men-with-opioid-use-disorder
#20
Ghasem Ebrahimi, Gholamreza Asadikaram, Hamed Akbari, Mohammad Hadi Nematollahi, Moslem Abolhassani, Gholamabbas Shahabinejad, Leyla Khodadadnejad, Mohammad Hashemi
BACKGROUND: The mu-opioid receptor, encoded by mu-opioid receptor gene (OPRM1), has an important role in the development of addiction to opioids. Its aberrant reduction on the cell membrane is responsible, at least in part, for tolerance and physical dependence. OBJECTIVES: The present study was designed to identify the relationship between opium consumption and epigenetic mechanisms involved in opium addiction. METHODS: Genomic DNA was extracted from the peripheral blood of 66 men with opium use disorder and 57 healthy men as a control group...
January 25, 2017: American Journal of Drug and Alcohol Abuse
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