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https://read.qxmd.com/read/30710016/interactions-of-fatty-acids-nonsteroidal-anti-inflammatory-drugs-and-coxibs-with-the-catalytic-and-allosteric-subunits-of-cyclooxygenases-1-and-2
#1
REVIEW
William L Smith, Michael G Malkowski
Prostaglandin endoperoxide H synthases-1 and -2, commonly called cyclooxygenases-1 and -2 (COX-1 and -2), catalyze the committed step in prostaglandin biosynthesis-the conversion of arachidonic acid to prostaglandin endoperoxide H2 Both COX isoforms are sequence homodimers that function as conformational heterodimers having allosteric (Eallo) and catalytic (Ecat) subunits. At least in the case of COX-2, the enzyme becomes folded into a stable Eallo/Ecat pair. Some COX inhibitors ( i.e. nonsteroidal anti-inflammatory drugs and coxibs) and common fatty acids (FAs) modulate Ecat activity by binding Eallo...
February 1, 2019: Journal of Biological Chemistry
https://read.qxmd.com/read/30661313/phenotypes-of-severe-cutaneous-adverse-reactions-caused-by-nonsteroidal-anti-inflammatory-drugs
#2
Suh Young Lee, Young Hee Nam, Young Il Koh, Sae Hoon Kim, Sujeong Kim, Hye Ryun Kang, Min Hye Kim, Jun Gyu Lee, Jung Won Park, Hye Kyung Park, Hyen O La, Mi Yeong Kim, Seong Ju Park, Yong Eun Kwon, Jae Woo Jung, Sang Hyon Kim, Cheol Woo Kim, Min Seok Yang, Min Gyu Kang, Jin Yong Lee, Joo Hee Kim, Sang Heon Kim, Gyu Young Hur, Young Koo Jee, Hyun Jung Jin, Chan Sun Park, Yi Yeong Jeong, Young Min Ye
PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS)...
March 2019: Allergy, Asthma & Immunology Research
https://read.qxmd.com/read/30656820/risks-of-colorectal-neoplasms-and-cardiovascular-thromboembolic-events-after-the-combined-use-of-selective-cox-2-inhibitors-and-aspirin-with-5-years-follow-up-a-meta-analysis
#3
Peirong He, Chaohao Yang, Guian Ye, Huanqin Xie, Wuzhuang Zhong
AIM: To evaluate the association between selective COX-2 inhibitors (coxibs) and the risk of colorectal neoplasm and vascular events with and without low-dose aspirin. METHOD: We searched for randomized controlled trials and comparative studies in PubMed, EMBASE, and Cochrane Library databases using pertinent key terms. Risk ratios (RRs) were calculated for each study with a fixed- or random-effects model. RESULTS: Eight clinical studies with 44,566 subjects were eligible...
January 18, 2019: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://read.qxmd.com/read/30622375/post-translational-modifications-of-prostaglandin-endoperoxide-synthase-2-in-colorectal-cancer-an-update
#4
REVIEW
Rafael I Jaén, Patricia Prieto, Marta Casado, Paloma Martín-Sanz, Lisardo Boscá
The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2 (PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used...
December 28, 2018: World Journal of Gastroenterology: WJG
https://read.qxmd.com/read/30535850/-pharmacology-of-non-opioid-analgesics
#5
J Schneider, R Kreutz, J Bolbrinker
Due to high prescription rates as well as the frequent use as over the counter drugs, it is of interest to consider non-opioid analgesics when evaluating the quality and appropriateness of a given overall medication. This article sums up the basic pharmacology and main adverse effects of these analgesics. Non-opioids can be further classified according to their additional mechanisms of action besides analgesia. High-dose acetylsalicylic acid, traditional nonsteroidal anti-inflammatory drugs, and coxibs exhibit antipyretic and anti-inflammatory properties...
December 7, 2018: Der Schmerz
https://read.qxmd.com/read/30484341/the-cox-2-prostanoid-signaling-cascades-in-seizure-disorders
#6
Asheebo Rojas, Di Chen, Thota Ganesh, Nicholas H Varvel, Raymond Dingledine
Introduction:A robust neuroinflammatory response is a prevalent feature of multiple neurological disorders, including epilepsy and acute status epilepticus. One component of this neuroinflammatory reaction is the induction of cyclooxygenase-2 (COX-2), synthesis of several prostaglandins and endocannabinoid metabolites, and subsequent activation of prostaglandin and related receptors. Neuroinflammation mediated by COX-2 and its downstream effectors has received considerable attention as a potential target class to ameliorate the deleterious consequences of neurological injury...
November 28, 2018: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30383903/gastrointestinal-safety-of-coxibs-systematic-review-and-meta-analysis-of-observational-studies-on-selective-inhibitors-of-cyclo-oxygenase-2
#7
REVIEW
Luis Hermenegildo Martín Arias, Antonio Martín González, Rosario Sanz Fadrique, Esther Salgueiro Vázquez
Prior meta-analyses have shown a higher gastrointestinal risk of nonselective NSAIDs versus placebo and a lower gastrointestinal risk of coxibs versus nonselective NSAIDs. However, the available data about gastrointestinal risk for coxibs versus placebo are scarce. The aim of this study was to review the current evidence on the use of coxibs and to evaluate the risk of gastrointestinal adverse outcomes (GAO) associated with coxibs versus nonexposed. Search was conducted on PubMed and Embase databases. We selected cohort observational, case-control, nested case-control and case-crossover studies that reported the risk of GAO associated with coxibs versus nonexposed as relative risk (RR), odds ratio (OR), hazard ratio (HR) or incidence rate ratio (IRR)...
November 1, 2018: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30383755/risk-of-acute-myocardial-infarction-during-use-of-individual-nsaids-a-nested-case-control-study-from-the-sos-project
#8
Gwen M C Masclee, Huub Straatman, Andrea Arfè, Jordi Castellsague, Edeltraut Garbe, Ron Herings, Bianca Kollhorst, Silvia Lucchi, Susana Perez-Gutthann, Silvana Romio, René Schade, Tania Schink, Martijn J Schuemie, Lorenza Scotti, Cristina Varas-Lorenzo, Vera E Valkhoff, Marco Villa, Miriam C J M Sturkenboom
BACKGROUND: Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used. OBJECTIVES: To estimate the risk of AMI for individual NSAIDs. METHODS: A nested case-control study was performed from a cohort of new NSAID users ≥18 years (1999-2011) matching cases to a maximum of 100 controls on database, sex, age, and calendar time...
2018: PloS One
https://read.qxmd.com/read/30355818/in-vivo-evaluation-of-anti-inflammatory-activity-of-2-3-acetyl-5-4-chloro-phenyl-2-methyl-pyrrol-1-yl-4-methylsulfanylbutyric-acid
#9
Hristina Zlatanova, Stanislava Vladimirova, Ilia Kostadinov, Atanas T Bijev
BACKGROUND: Persisting inflammatory stimuli cause chronic inflammation recognized as the major factor contributing to the development of a number of diseases. One group of drugs used in the treatment of chronic inflammation is the group of non-steroidal anti-inflammatory drugs and, more specifically, the selective COX-2 inhibitors (coxibs). However, most of the coxibs were withdrawn from the market in view of their safety profile. In the present study, 2-[3-Acetyl-5-(4-chlorophenyl)- 2-methyl-pyrrol-1-yl]-4-methylsulfanyl-butyric acid (compound 3e), an Npyrrolylcarboxylic acid derivative structurally related to celecoxib, is evaluated for anti-inflammatory activity after single and multiple (14 days) administration using an animal inflammation model...
June 1, 2018: Folia Medica
https://read.qxmd.com/read/30295105/proton-pump-inhibitors-use-and-misuse-in-the-clinical-setting
#10
Vincenzo Savarino, Elisa Marabotto, Patrizia Zentilin, Manuele Furnari, Giorgia Bodini, Costanza De Maria, Gaia Pellegatta, Claudia Coppo, Edoardo Savarino
The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome...
October 8, 2018: Expert Review of Clinical Pharmacology
https://read.qxmd.com/read/30285927/-cardiovascular-risk-of-non-steroidal-anti-inflammatory-drugs
#11
Guillermo R Prozzi, Martín Cañás, Martín A Urtasun, Héctor O Buschiazzo, Cristian M Dorati, Perla Mordujovich-Buschiazzo
Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs. Both the analgesic and antiinflammatory effects, as well as the cardiovascular adverse effects, depend on the COX-2 inhibition. This paper reviews the available evidence of the increased risk of thrombotic events for both coxibs and traditional NSAID...
2018: Medicina
https://read.qxmd.com/read/30245627/raging-the-war-against-inflammation-with-natural-products
#12
REVIEW
Ali Attiq, Juriyati Jalil, Khairana Husain, Waqas Ahmad
Over the last few decade Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are the drugs of choice for treating numerous inflammatory diseases including rheumatoid arthritis. The NSAIDs produces anti-inflammatory activity via inhibiting cyclooxygenase enzyme, responsible for the conversation of arachidonic acid to prostaglandins. Likewise, cyclooxegenase-2 inhibitors (COX-2) selectively inhibit the COX-2 enzyme and produces significant anti-inflammatory, analgesic, and anti-pyretic activity without producing COX-1 associated gastrointestinal and renal side effects...
2018: Frontiers in Pharmacology
https://read.qxmd.com/read/30231067/risk-of-ischemic-stroke-and-the-use-of-individual-non-steroidal-anti-inflammatory-drugs-a-multi-country-european-database-study-within-the-sos-project
#13
Tania Schink, Bianca Kollhorst, Cristina Varas Lorenzo, Andrea Arfè, Ron Herings, Silvia Lucchi, Silvana Romio, René Schade, Martijn J Schuemie, Huub Straatman, Vera Valkhoff, Marco Villa, Miriam Sturkenboom, Edeltraut Garbe
BACKGROUND AND PURPOSE: A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication. METHODS: Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated...
2018: PloS One
https://read.qxmd.com/read/30176739/benefits-and-risks-of-nonsteroidal-anti-inflammatory-drugs-methodologic-limitations-lead-to-clinical-uncertainties
#14
Manas A Rane, Jennifer G Foster, Sarah K Wood, Patricia R Hebert, Charles H Hennekens
Nonsteroidal anti-inflammatory drugs (NSAIDs) include traditional (tNSAIDs), such as ibuprofen, naproxen, and diclofenac, as well as selective cyclooxygenase-2 inhibitors (COXIBs), principally celecoxib. COXIBs were developed to decrease gastrointestinal side effects. Recently, the US Food and Drug Administration strengthened its warning about the risks of non-aspirin NSAIDs on myocardial infarction and stroke. The Cyclooxygenase 2 and Non-Steroidal Anti-Inflammatory Drug Trialist collaboration conducted a comprehensive worldwide meta-analysis using individual patient data exploring the risks of various COXIBs and NSAIDs on cardiovascular disease (CVD)...
September 3, 2018: Therapeutic Innovation & Regulatory Science
https://read.qxmd.com/read/30153531/in-vitro-comprehensive-analysis-of-va692-a-new-chemical-entity-for-the-treatment-of-osteoarthritis
#15
Sara Cheleschi, Valentina Calamia, Mercedes Fernandez-Moreno, Mariangela Biava, Antonio Giordani, Antonella Fioravanti, Maurizio Anzini, Francisco Blanco
Selective cyclooxigenase (COX)-2 inhibitors were developed to prevent traditional non-steroidal anti-inflammatory drugs (tNSAIDs) gastro-intestinal adverse effects. VA692, a recently disclosed selective COX-2 inhibitor, structurally related to well-known marketed coxibs, showed anti-inflammatory, and anti-nociceptive properties. The aim of this study was to analyze the anti-inflammatory effect of VA692, in comparison with celecoxib. At this purpose we evaluated the pro-inflammatory cytokines and anti-oxidant enzymes gene expression, apoptosis and ROS production, and PGE2 release in chondrocytes (both primary cultures and immortalized T/C-28a2 cell line) treated with the two drugs...
August 25, 2018: International Immunopharmacology
https://read.qxmd.com/read/30149590/use-of-non-steroidal-anti-inflammatory-drugs-and-associated-gastroprotection-in-a-cohort-of-workers
#16
María Jesús Lallana, Cristina Feja, Isabel Aguilar-Palacio, Sara Malo, María José Rabanaque
BACKGROUND: This study describes the prevalence of non-steroidal anti-inflammatory drug (NSAID) use, and analyses prescribing patterns of NSAIDs and associated gastroprotection. METHODS: The study population consisted of 5650 workers at the General Motors automobile assembly plant in Zaragoza, Spain. NSAID prescription data for 2014 were obtained from the prescription database of Aragon (Spain). NSAID consumption was determined based on the number of defined daily doses purchased per year...
August 24, 2018: International Journal of Environmental Research and Public Health
https://read.qxmd.com/read/30148083/robenacoxib-in-the-treatment-of-pain-in-cats-and-dogs-safety-efficacy-and-place-in-therapy
#17
REVIEW
Kavitha Kongara, John Paul Chambers
Robenacoxib is a novel nonsteroidal anti-inflammatory drug (NSAID) of coxib class developed for the control of inflammation and pain in dogs and cats. It shows high selectivity for the cyclooxygenase-2 (COX-2) enzyme in rats, cats, and dogs. Robenacoxib is available in both injectable and tablet formulations. This review initially focuses on the preclinical pharmacology of robenacoxib in rats that includes its high affinity for COX-2 enzyme and weaker and rapidly reversible binding for COX-1 enzyme in in vitro and ex vivo models of inflammation and its pharmacokinetics in the blood and inflammatory exudate, selective tissue distribution, and safety...
2018: Veterinary medicine
https://read.qxmd.com/read/30139288/nsaid-induced-gastrointestinal-damage-and-designing-gi-sparing-nsaids
#18
REVIEW
Guillermo García-Rayado, Mercedes Navarro, Angel Lanas
NSAIDs are widely used to treat pain and rheumatic conditions, but they induce adverse events in different body systems, although the major, most frequent events occur in the upper and lower gastrointestinal (GI) tracts. Areas covered: This review is focused on damage caused by NSAIDs in the upper and lower GI tracts, the different mechanisms of damage and the GI-sparing NSAIDs designed to minimize adverse events based on understanding of these mechanisms. Expert commentary: Among the new NSAIDs, COX-2 selective inhibitors have been extensively investigated, and some were approved for human use...
October 2018: Expert Review of Clinical Pharmacology
https://read.qxmd.com/read/30072617/in-vivo-brain-imaging-biodistribution-and-radiation-dosimetry-estimation-of-11-c-celecoxib-a-cox-2-pet-ligand-in-nonhuman-primates
#19
J S Dileep Kumar, Bing Bai, Francesca Zanderigo, Christine DeLorenzo, Jaya Prabhakaran, Ramin V Parsey, J John Mann
COX-2 selective inhibitors (COXIBs) are non-steroidal anti-inflammatory drugs (NSAIDs), with fewer side effects compared with non-selective NSAIDs, and are used for the treatment of arthritis, headaches, and other inflammatory diseases of the brain and peripheral tissues. Radiolabeled COXIBs may permit positron emission tomography (PET) imaging of COX-2 localization and activity in diseases, enable monitoring of inflammatory processes, and determine target occupancy of COX-2 activity by NSAIDs, thus, accelerating the development of novel CIXIBs...
August 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/30066292/cardiovascular-and-gastrointestinal-safety-of-selective-cyclooxygenase-2-inhibitors-a-case-non-case-study
#20
Luis Hermenegildo Martin Arias, Antonio Martin Gonzalez, Rosario Sanz Fadrique, Esther Salgueiro, Maria Sainz
Background Coxibs cardiovascular (CV) safety continues being a current issue after rofecoxib worldwide withdrawal in 2004. Objective To evaluate the cardiovascular and gastrointestinal (GI) risk of coxibs through case/non-case study. Setting The Spanish Pharmacovigilance System for Human Use Drugs (FEDRA) and the Uppsala Monitoring Centre (VigiBase) databases. Method We identified adverse drug reactions (ADRs) cases reported under the MedDRA system organ classes of "cardiac disorders", "vascular disorders", "nervous system disorder" and "gastrointestinal disorders"...
August 2018: International Journal of Clinical Pharmacy
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