scholarly journals Meloxicam in pain syndrome treatment of comorbid diseases patients

2021 ◽  
pp. 209-215
Author(s):  
O. A. Shavlovskaya ◽  
I. A. Bokova ◽  
N. I. Shavlovskiy
Keyword(s):  
Gastrointestinal Tract ◽  
Pain Syndrome ◽  
Cardiovascular Risks ◽  
Lower Back ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Comorbid Diseases ◽  
Per Oral ◽  
Cox 1

The issue nonsteroidal anti-inflammatory drugs (NSAIDs) use safety is associated with a high frequency of adverse events (AEs) from the gastrointestinal tract and cardiovascular risks. Patients with lower back pain (LBP) and osteoarthritis (OA), as a rule, have comorbid diseases, such as arterial hypertension (AH), coronary heart disease (CHD), gastrointestinal tract (GIT) diseases, which significantly complicates the appointment of NSAIDs. The main guideline in NSAIDs appointment is the selective ability to inhibit cyclooxygenase-1 and -2 (COX). The ratio of the activity of NSAIDs when blocking COX-1/COX-2 allows us to judge their potential toxicity. And, then higher the selectivity of NSAIDs, then lower its toxicity. For example, the ratio of COX-1/COX-2 in meloxicam is 0.33, diclofenac – 2.2, tenoxicam – 15, piroxicam – 33, indomethacin – 107. To the predominantly selective COX-2 NSAIDs include meloxicam, which has little effect on the GIT, the lowest relative risk (RR) of complications from the cardiovascular system (CVS). The therapeutic efficacy of meloxicam is comparable to piroxicam and diclofenac. A number of studies have shown the high efficacy of meloxicam, both with per oral (p/o) administration (7.5–15 mg/d), and with intramuscular (i/m) administration (1.5 ml), and when injected into trigger zones. Both with p/o and the injectable form of meloxicam has minimal GIT AEs and absence local reaction in the injection area. The drug can be recommended both as a combination therapy and prescribed in monotherapy.

Involvement of cyclooxygenase 2 (COX-2) in intrinsic tone of isolated guinea pig

1995 ◽  
Vol 73 (11) ◽  
pp. 1561-1567 ◽  
Author(s):  
L. Charette ◽  
C. Misquitta ◽  
J. Guay ◽  
D. Riendeau ◽  
T. R. Jones
Keyword(s):  
Guinea Pig ◽  
Time Course ◽  
Cyclooxygenase 2 ◽  
Maximal Response ◽  
Pharmacological Agents ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Indomethacin and related nonsteroidal anti-inflammatory drugs relax prostanoid-dependent intrinsic tone of isolated guinea pig trachea by inhibiting cyclooxygenase (COX). Recently, a second isoform of COX (COX-2) was discovered, which differed from COX-1 with respect to protein structure, transcriptional regulation, and susceptibility to inhibition by pharmacological agents. It is now known that indomethacin nonselectively inhibits COX-1 and COX-2, whereas NS-398 is a selective inhibitor of COX-2. In the present study we compared the activity of a selective (NS-398) and nonselective (indomethacin) COX-2 inhibitor on intrinsic tone of isolated guinea pig trachea. NS-398 ≥ indomethacin produced a reversal of intrinsic tone with a similar concentration-dependent (10 nM to 1 μM) time course (Tmax approximately 20–45 min), potency (EC50 1.7 and 5.6 nM, respectively), and maximal response. Contractions to cholinergic nerve stimulation (45 V, 0.5 ms, 0.1–32 Hz) and histamine were similarly modulated in tissues relaxed with the selective or nonselective COX-2 inhibitors. Immunoblot analyses showed that COX-2 protein synthesis was induced in both the cartilage and smooth muscle portions of the trachea during changes in intrinsic tone. These findings are consistent with pharmacological results and provide the first demonstration that prostanoid tone in isolated guinea pig trachea is dependent on COX-2 activity. The results also suggest that the activity of indomethacin in this preparation is likely related to COX-2 inhibition.Key words: cyclooxygenase 2, relaxation, guinea pig trachea, cyclooxygenase 1.

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).

scholarly journals Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Chris Walker
Keyword(s):  
Randomized Trials ◽  
Comparable Efficacy ◽  
Heart Attacks ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Isoform Selectivity ◽  
Meta Analyses ◽  
Cox 1 ◽  
Heterogeneous Class

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of arthritic conditions. Drugs in this heterogeneous class alleviate pain and inflammation by inhibiting cyclooxygenase-2 (COX-2). Cyclooxygenase-1 (COX-1) inhibition has traditionally been associated with increased gastrointestinal (GI) harm, whereas increased COX-2 selectivity has more recently become associated with greater risk of cardiovascular (CV) harm. When the entirety of data is considered, NSAIDs can be seen to exhibit a range of COX isoform selectivity, with all oral NSAIDs appearing to be associated with an increase in CV events. This review focuses on a comparison of the efficacy and the GI and CV safety profiles of three commonly used NSAIDs—celecoxib, etoricoxib, and diclofenac—using direct comparisons where available. While all three treatments are shown to have comparable efficacy, there are differences in their safety profiles. Both celecoxib and etoricoxib are associated with less GI harm than diclofenac despite the similarity of its COX-2 selectivity to celecoxib. Each of the three medicines under consideration is associated with a similar overall risk of CV events (fatal and nonfatal heart attacks and strokes). However, there are consistent differences in effects on blood pressure (BP), reported both from trials using ambulatory techniques and from meta-analyses of randomized trials, reporting investigator determined effects, with etoricoxib being associated with a greater propensity to destabilize BP control than either diclofenac or celecoxib.

Features of NSAIDs' use in pandemic. Gastroenterologist's view

2021 ◽  
Vol 1 (6) ◽  
pp. 32-34
Author(s):  
E. I. Sas
Keyword(s):  
Chronic Pain ◽  
Gastrointestinal Tract ◽  
Side Effects ◽  
Viral Infection ◽  
Mechanism Of Action ◽  
Clinical Course ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Inflammatory Changes ◽  
Cox 1

Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs used to treat acute and chronic pain associated primarily with inflammatory changes. This group of drugs is widely used in neurology, rheumatology, traumatology, etc. The main mechanism of action of the drugs is associated with the effect on cyclooxygenase-2 (COX-2) and blockade of the synthesis of pro-inflammatory prostaglandins (PG), as well as the effect on COX-1 and suppression of the synthesis of cytoprotective PG, which determines the possibility of side effects from the gastrointestinal tract. In the pandemic, the use of this group of drugs has increased many times over. Features of the clinical course of both the viral infection itself and the use of other drugs leads to a significant change in the pharmacodynamics and pharmacokinetics of NSAIDs, which may lead to the development of undesirable side effects.

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 Heterocyclic inflammation inhibitors

2004 ◽  
Vol 2 (1) ◽  
pp. 141-187 ◽  
Author(s):  
Sham Sondhi ◽  
Shefali Rajvanshi ◽  
Nirupma Singh ◽  
Shubhi Jain ◽  
Anand Lahoti
Keyword(s):  
Gastrointestinal Tract ◽  
Mode Of Action ◽  
Heterocyclic Compounds ◽  
Recent Developments ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

AbstractNon steroidal anti-inflammatory drugs are the most widely used medicines for relief of pain. These drugs have some side effects, particularly toxicity in the gastrointestinal tract and kidneys. Various approaches have been used for obtaining safer anti-inflammatory drugs. In this review we have summarized the recent developments in the following areas; (i) mode of action of NSAIDs (ii) Role of COX-1 & COX-2 in inflammation, (iii) Different approaches used to improve gastric tolerance i.e. chemical manipulation, formulation & co-administration, development of non specific (COX-1 & COX-2 inhibitors) and specific (COX-2 inhibitors) inflammation inhibitors, and development of inflammation inhibitors having a mode of action other than COX-1 & COX-2 inhibition. We have also focused on the safety of COX-2 inhibitors and the synthesis of heterocyclic compounds and their role as inflammation inhibitors.

scholarly journals PHARMACOEPIDEMIOLOGICAL STUDY OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND ITS EFFECTS ON CARDIOVASCULAR SYSTEM AMONG SELECTED AREAS OF CHITRADURGA.

2019 ◽  
Vol 8 (3) ◽  
Author(s):  
Tejaswini S. M. ◽  
Bharathi DR ◽  
Nataraj GR ◽  
Akza K Alex ◽  
Adarsh Mathew
Keyword(s):  
Cardiovascular Risk ◽  
Rural Areas ◽  
Urban Areas ◽  
Broad Class ◽  
Cardiovascular Risks ◽  
Pharmacoepidemiological Study ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide to treat pain and inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are a broad class of agents with analgesic and anti-inflammatory properties that inhibit the two recognized iso enzymes of prostaglandin G/H synthase (also known as cyclo -oxygenase (COX))—namely, COX 1 and COX 2. It is generally accepted that oral non-steroidal anti-inflammatory drugs (NSAIDs) can increase the risk of acute myocardial infarction. Randomized controlled trials of NSAIDs have been of limited use for assessing this rare adverse event, as they had small cohorts and poor generalizability. The trials excluded those at highest cardiovascular risk or with established cardiovascular disease. Objectives: 1. To assess the various classes of NSAID’S giving rise to cardiovascular risks. 2. To assess the prevalence of NSAID’s induced various cardiovascular risks. Materials and Methods: The study was carried out in selected areas of Chitradurga District. Results: 1. In our study, subjects who were having CVS risks were found to be the major users of Selective cox-2 inhibitor 20(27.7) followed by preferential cox-2 inhibitor 8(11.1)) and phenyl acetic acid 6(8.3). Among 401 subjects, 72 subjects were diagnosed as cardiovascular problem. The prevalence of NSAIDs induced cardiovascular problem was found to be 18% Conclusion: Our study concluded that prevalence of cardiovascular risk due to administration of NSAIDs more in rural areas than in urban areas. Key words: NSAIDs, CVS risks, Prevalence.

scholarly journals Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection

2021 ◽  
Author(s):  
Jennifer S. Chen ◽  
Mia Madel Alfajaro ◽  
Ryan D. Chow ◽  
Jin Wei ◽  
Renata B. Filler ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Replication ◽  
Cyclooxygenase 2 ◽  
Nsaid Treatment ◽  
Susceptibility To Infection ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Abstract Identifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 (COVID-19) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain and inflammation, could modulate both SARS-CoV-2 infection and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which mediate the production of prostaglandins (PGs). As PGs play diverse biological roles in homeostasis and inflammatory responses, inhibiting PG production with NSAIDs could affect COVID-19 pathogenesis in multiple ways, including: (1) altering susceptibility to infection by modifying expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2; (2) regulating replication of SARS-CoV-2 in host cells; and (3) modulating the immune response to SARS-CoV-2. Here, we investigate these potential roles. We demonstrate that SARS-CoV-2 infection upregulates COX-2 in diverse human cell culture and mouse systems. However, suppression of COX-2 by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 expression, viral entry, or viral replication. In contrast, in a mouse model of SARS-CoV-2 infection, NSAID treatment reduced production of pro-inflammatory cytokines and impaired the humoral immune response to SARS-CoV-2 as demonstrated by reduced neutralizing antibody titers. Our findings indicate that NSAID treatment may influence COVID-19 outcomes by dampening the inflammatory response and production of protective antibodies rather than modifying susceptibility to infection or viral replication. Importance Public health officials have raised concerns about the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating symptoms of coronavirus disease 2019 (COVID-19). NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are critical for the generation of prostaglandins – lipid molecules with diverse roles in homeostasis and inflammation. Inhibition of prostaglandin production by NSAIDs could therefore have multiple effects on COVID-19 pathogenesis. Here, we demonstrate that NSAID treatment reduced both the antibody and pro-inflammatory cytokine response to SARS-CoV-2 infection. The ability of NSAIDs to modulate the immune response to SARS-CoV-2 infection has important implications for COVID-19 pathogenesis in patients. Whether this occurs in humans and whether it is beneficial or detrimental to the host remains an important area of future investigation. This also raises the possibility that NSAIDs may alter the immune response to SARS-CoV-2 vaccination.

scholarly journals Cyclooxgenase-2 is induced by SARS-CoV-2 infection but does not affect viral entry or replication

2020 ◽  
Author(s):  
Jennifer S. Chen ◽  
Mia Madel Alfajaro ◽  
Jin Wei ◽  
Ryan D. Chow ◽  
Renata B. Filler ◽  
...  
Keyword(s):  
Cell Culture ◽  
Severe Acute Respiratory Syndrome ◽  
Human Cell ◽  
Viral Entry ◽  
Lung Inflammation ◽  
Human Cell Culture ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 1

AbstractIdentifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 (COVID-19) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain and inflammation, could modulate both SARS-CoV-2 infection and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which mediate the production of prostaglandins (PGs). PGE2, one of the most abundant PGs, has diverse biological roles in homeostasis and inflammatory responses. Previous studies have shown that NSAID treatment or inhibition of PGE2 receptor signaling leads to upregulation of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2, thus raising concerns that NSAIDs could increase susceptibility to infection. COX/PGE2 signaling has also been shown to regulate the replication of many viruses, but it is not yet known whether it plays a role in SARS-CoV-2 replication. The purpose of this study was to dissect the effect of NSAIDs on COVID-19 in terms of SARS-CoV-2 entry and replication. We found that SARS-CoV-2 infection induced COX-2 upregulation in diverse human cell culture and mouse systems. However, suppression of COX-2/PGE2 signaling by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 expression, viral entry, or viral replication. Our findings suggest that COX-2 signaling driven by SARS-CoV-2 may instead play a role in regulating the lung inflammation and injury observed in COVID-19 patients.ImportancePublic health officials have raised concerns about the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating symptoms of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). NSAIDs function by inhibiting the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). These enzymes are critical for the generation of prostaglandins, lipid molecules with diverse roles in maintaining homeostasis as well as regulating the inflammatory response. While COX-1/COX-2 signaling pathways have been shown to affect the replication of many viruses, their effect on SARS-CoV-2 infection remains unknown. We found that SARS-CoV-2 infection induced COX-2 expression in both human cell culture systems and mouse models. However, inhibition of COX-2 activity with NSAIDs did not affect SARS-CoV-2 entry or replication. Our findings suggest that COX-2 signaling may instead regulate the lung inflammation observed in COVID-19 patients, which is an important area for future studies.

scholarly journals Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

2006 ◽  
Vol 191 (1) ◽  
pp. 263-274 ◽  
Author(s):  
Simone Odau ◽  
Christoph Gabler ◽  
Christoph Holder ◽  
Ralf Einspanier
Keyword(s):  
Mrna Expression ◽  
Estrous Cycle ◽  
Luteal Phase ◽  
Cellular Level ◽  
Differential Distribution ◽  
Cyclooxygenase 1 ◽  
Epithelial Cell Layer ◽  
Cox 2 ◽  
Cycle Dependent ◽  
Cox 1

The aim of the present study was to investigate the enzymes for the local prostaglandin (PG) biosynthesis present in the bovine oviduct during the estrous cycle to influence early reproductive events. Bovine oviducts were classified into four phases: pre-ovulatory, post-ovulatory, early-to-mid luteal, and late luteal phase, subdivided further into ipsi- or contralateral site and separated into ampulla or isthmus. Oviductal cells were gained by flushing the oviductal regions. Quantitative real-time reverse transcriptase-PCR was performed for the secretory and cytosolic phospholipases A2 (sPLA2IB, cPLA2α, and cPLA2β) and cyclooxygenases (COX-1 and COX-2) as the first step enzymes of PG synthesis. COX-1 and cPLA2β showed significant highest mRNA expression around and before ovulation compared with the luteal phase respectively. sPLA2IB and cPLA2α mRNA expression was unregulated during the estrous cycle. Regional differences in mRNA content were found for sPLA2IB with higher mRNA expression in the ampulla than in the isthmus. Western blot analysis revealed the highest COX-1 protein content in the early-to-mid luteal phase. Immunohistochemistry demonstrated that COX-1 was localized in epithelial and smooth muscle cells, whereas COX-2 was only localized in epithelial cells. COX-2 showed a differential distribution within the epithelial cell layer suggesting a regulation on a cellular level, although the COX-2 mRNA and protein amounts did not vary throughout the estrous cycle. A COX activity assay of oviductal cells revealed that COX activity originated predominantly from COX-1 than from COX-2. Treatment of primary oviductal cells with 10 pg/ml 17β-estradiol or 10 ng/ml progesterone resulted in a higher expression of COX-2 and cPLA2α, but not of the other enzymes. The expression pattern of these enzymes suggests that an estrous-cycle dependent and region-specific PG synthesis in the bovine oviduct may be required for a successful reproduction.

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