Non-steroidal anti-inflammatory drugs

2016 ◽  
Author(s):  
Lee S. Simon ◽  
Marc C. Hochberg
Keyword(s):  
Adverse Effects ◽  
The United States ◽  
Acute Gout ◽  
Diverse Group ◽  
Cox Inhibitors ◽  
Cardinal Characteristics ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Non-steroidal anti-inflammatory drugs (NSAIDs) are a chemically diverse group of compounds that share three cardinal characteristics: they are anti-inflammatory, analgesic, and antipyretic. They are approved by regulatory authorities for the treatment of patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute gout, and some forms of juvenile idiopathic arthritis. There are at least 20 chemically different NSAIDs currently available in Europe and the United States. These include not only the ‘traditional’ non-selective cyclooxygenase (COX) inhibitors that inhibit both the COX-1 and COX-2 enzymes but also the COX-2 selective inhibitors. This chapter gives a background of NSAIDs, including the mechanism of action, pharmacology and adverse effects (including hypersensitivity and gastrointestinal, cardiovascular thrombotic, and renal adverse effects), before summarizing the use of NSAIDs in patients with osteoarthritis.

Synthesis and evaluation of new benzimidazole-based COX inhibitors: a naproxen-like interaction detected by STD-NMR

RSC Advances ◽  
2015 ◽  
Vol 5 (61) ◽  
pp. 49098-49109 ◽  
Author(s):  
Luísa C. R. Carvalho ◽  
Daniela Ribeiro ◽  
Raquel S. G. R. Seixas ◽  
Artur M. S. Silva ◽  
Mariana Nave ◽  
...  
Keyword(s):  
Pharmacological Activity ◽  
Cox Inhibitors ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Std Nmr ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Non-steroidal anti-inflammatory drugs exert their pharmacological activity through inhibition of cyclooxygenase 1 and 2 (COX-1 and COX-2).

Evaluation of Novel New NSAIDs: A Review of COX-2 Inhibitors, with an Emphasis on Gastrointestinal Toxicity

1999 ◽  
Vol 12 (5) ◽  
pp. 401-411
Author(s):  
Julienne K. Kirk ◽  
Jennifer M. Hamilton ◽  
Kathy C. Phelps
Keyword(s):  
The United States ◽  
Similar Efficacy ◽  
Gastrointestinal Toxicity ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Control Pain ◽  
Cox 2 Inhibitors ◽  
Cox 1 ◽  
Gastrointestinal Ulceration

Identification of two isoforms of cyclooxygenase, COX-1 and COX-2, has initiated a revolution in the approach to pharmacologie pain management. It has been further determined that inhibition of COX-2 reduces inflammation, and inhibition of COX-1 compromises gastrointestinal mucosal integrity. As traditional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2, gastrointestinal ulceration can develop in association with the use of these agents to control pain and inflammation. An ideal NSAID would, therefore, inhibit COX-2 to provide anti-inflammatory effects while leaving COX-1, and, therefore, gastrointestinal mucosa, unaffected. Two selective COX-2 inhibitors have recently been approved in the United States. Celecoxib (Celebrex, G.D. Searle & Co.) and rofecoxib (Vioxxj, Merck & Co., Inc.) are indicated for the treatment of osteoarthritis. Also, celecoxib is approved for rheumatoid arthritis. Rofecoxib is also approved for the treatment of acute pain and dysmenorrhea. Both agents have displayed similar efficacy to traditional NSAIDs. In addition, endoscopically detected gastrointestinal ulceration is reduced versus older NSAIDs. Further evaluation of selective COX-2 inhibitors will elucidate long-term efficacy, safety, and potential reduction of health care dollars spent on hospitalization and treatment for NSAID-induced gastrointestinal toxicity.

scholarly journals Interactions of fatty acids, nonsteroidal anti-inflammatory drugs, and coxibs with the catalytic and allosteric subunits of cyclooxygenases-1 and -2

2019 ◽  
Vol 294 (5) ◽  
pp. 1697-1705 ◽  
Author(s):  
William L. Smith ◽  
Michael G. Malkowski
Keyword(s):  
Fatty Acids ◽  
Palmitic Acid ◽  
Direct Interaction ◽  
Cox Inhibitors ◽  
Prostaglandin Endoperoxide ◽  
Allosteric Effectors ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

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. However, the interactions and outcomes often differ between isoforms. For example, naproxen directly and completely inhibits COX-1 by binding Ecat but indirectly and incompletely inhibits COX-2 by binding Eallo. Additionally, COX-1 is allosterically inhibited up to 50% by common FAs like palmitic acid, whereas COX-2 is allosterically activated 2-fold by palmitic acid. FA binding to Eallo also affects responses to COX inhibitors. Thus, COXs are physiologically and pharmacologically regulated by the FA tone of the milieu in which each operates—COX-1 in the endoplasmic reticulum and COX-2 in the Golgi apparatus. Cross-talk between Eallo and Ecat involves a loop in Eallo immediately downstream of Arg-120. Mutational studies suggest that allosteric modulation requires a direct interaction between the carboxyl group of allosteric effectors and Arg-120 of Eallo; however, structural studies show some allosterically active FAs positioned in COX-2 in a conformation lacking an interaction with Arg-120. Thus, many details about the biological consequences of COX allosterism and how ligand binding to Eallo modulates Ecat remain to be resolved.

scholarly journals In silico study of anthocyanin and ternatin flavonoids for the treatment of inflammation-related diseases using molecular docking analysis

Food Research ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 780-785
Author(s):  
Y.T. Wijaya ◽  
A. Yulandi ◽  
A.W. Gunawan ◽  
Yanti
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Protein Crystal ◽  
Drug Candidate ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Inflammatory markers such as cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), and prostaglandin (PEG) are widely known as major targets in discovering natural anti-inflammatory drugs for the treatment of inflammationrelated diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are mostly used at present, however, some NSAIDS have been reported to cause gastrointestinal side effect due to ligand-protein interaction. Molecular docking is a promising tool to study such modes of interaction. In this study, we evaluated the potential use of anthocyanin and ternatin flavonoids as natural anti-inflammatory agents for treatment of inflammatory-related diseases using in silico molecular docking assay. Automated docking study using Protein-Ligand ANT System (PLANTS) and AutoDock Vina was performed with various ligand molecules, including ibuprofen, anthocyanin, and ternatin against the protein crystal structures of COX-1, COX-2, iNOS, and MPO. The in silico data demonstrated that ibuprofen bound effectively to the active site of COX-1 and MPO with minimum binding energy, yet the compound required more energy to bind the active site of COX-2. Ternatin flavonoid was bound to COX-2 and iNOS with minimum binding energy. In terms of binding energy, anthocyanin flavonoid was found to be effective for inhibiting COX-1, COX-2, and iNOS. These results suggested that anthocyanin and ternatin flavonoids may potentially be developed as anti-inflammatory drug candidate for the treatment of inflammatory-related diseases.

scholarly journals Motion – Cyclo-oxygenase-2 Selective Nonsteroidal Anti-Inflammatory Drugs are as Safe as Placebo for the Stomach: Arguments Against the Motion

2003 ◽  
Vol 17 (5) ◽  
pp. 335-338 ◽  
Author(s):  
Andreas Maetzel
Keyword(s):  
Low Dose ◽  
Traditional Nsaid ◽  
Suitable Alternative ◽  
Randomized Controlled ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Upper Gastrointestinal ◽  
Cox 1

Cyclo-oxygenase (COX) exists in two isoforms, COX-1 and COX-2, that direct the synthesis of prostaglandins, prostacyclin and thromboxane. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both isoenzymes, resulting in damage to the mucosa of the stomach and duodenum, but also in cardioprotection. Selective COX-2 inhibitors are less likely to damage the upper gastrointestinal tract, as has been shown by large, randomized, controlled trials. Specifically, the newer agents are superior to ibuprofen and naproxen in this regard, but celecoxib and diclofenac were not significantly different in patients who were not also taking low-dose acetylsalicylic acid. These studies did not include a placebo arm, however, and controlled comparisons of COX-2 inhibitors with placebo have not enlisted enough subjects to demonstrate conclusively that they are equally safe. Selectivity for the COX-2 isoform affords protection against upper gastrointestinal toxicity possibly at the expense of the cardioprotective effect of traditional NSAIDs. This might explain the higher rate of nonfatal myocardial infarction in patients who aregiven rofecoxib compared with naproxen. A traditional NSAID, combined with either misoprostol or a proton pump inhibitor, is still a suitable alternative to selective COX-2 inhibitors for the treatment of arthritis.

scholarly journals NSAIDs and heart failure: A dangerous relationship

2018 ◽  
Vol 88 (2) ◽  
Author(s):  
Raffaele Rotunno ◽  
Igino Oppo ◽  
Gabriele Saetta ◽  
Pietro Aveta ◽  
Sergio Bruno
Keyword(s):  
Heart Failure ◽  
Urinary Flow ◽  
Vascular Thrombosis ◽  
Cyclooxygenase 1 ◽  
Vasodilatory Action ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

One of the potential cardiotoxic action of anti-inflammatory drugs is the occurrence of heart failure (HF), due to their effects on fluid retention and blood pressure. The risk of hospitalization for HF is roughly doubled for both Coxibs, cyclooxygenase-1 (COX-1) and cyclooxygenase- 2 (COX-2) inhibitors, and all the conventional nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are also associated with a risk of vascular thrombosis, which for NSAIDs is different in relation to their different ability to inhibit COX-1 and COX-2. The cardiovascular toxicity of these drugs in the direction of HF follow different pathways respect to their related vascular thrombosis toxicity and involves, in particular, the renal prostaglandins, PGE2 and prostacyclin, mostly synthesized by COX-2. In the kidneys the PGs perform a direct vasodilatory action, e.g. by means of non-contrasting angiotensin mechanisms, and for this reason nimesulide effects on renal microcirculation are independent from the prevalence of intrarenal renin angiotensin aldosterone system (RAAS) activity. Conversely, nimesulide reduces sodium tubular urinary flow only in presence of intrarenal RAAS.

scholarly journals Modulation of smoke-induced DNA and microRNA alterations in mouse lung by licofelone, a triple COX-1, COX-2 and 5-LOX inhibitor

2019 ◽  
Vol 41 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Alberto Izzotti ◽  
Roumen Balansky ◽  
Rosanna T Micale ◽  
Alessandra Pulliero ◽  
Sebastiano La Maestra ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Cancer Chemoprevention ◽  
Mouse Lung ◽  
Preneoplastic Lesions ◽  
Dna And Rna ◽  
Bulky Dna Adducts ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Abstract Chronic inflammation plays a crucial role in the carcinogenesis process and, in particular, in smoking-related carcinogenesis. Therefore, anti-inflammatory agents provide an interesting perspective in the prevention of smoking-associated cancers. Among nonsteroidal anti-inflammatory drugs (NSAIDs), licofelone is a triple inhibitor of both cyclooxygenases (COX-1 and COX-2) and of 5-lipooxygenase (5-LOX) that has shown some encouraging results in cancer prevention models. We previously showed that the dietary administration of licofelone, starting after weanling, to Swiss H mice exposed for 4 months to mainstream cigarette smoke since birth attenuated preneoplastic lesions of inflammatory nature in both lung and urinary tract, and had some effects on the yield of lung tumors at 7.5 months of age. The present study aimed at evaluating the early modulation by licofelone of pulmonary DNA and RNA alterations either in smoke-free or smoke-exposed H mice after 10 weeks of exposure. Licofelone protected the mice from the smoke-induced loss of body weight and significantly attenuated smoke-induced nucleotide alterations by decreasing the levels of bulky DNA adducts and 8-hydroxy-2′-deoxyguanosine in mouse lung. Moreover, the drug counteracted dysregulation by smoke of several pulmonary microRNAs involved in stress response, inflammation, apoptosis, and oncogene suppression. However, even in smoke-free mice administration of the drug had significant effects on a broad panel of microRNAs and, as assessed in a subset of mice used in a parallel cancer chemoprevention study, licofelone even enhanced the smoke-induced systemic genotoxic damage after 4 months of exposure. Therefore, caution should be paid when administering licofelone to smokers for long periods.

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