Does a coxib-associated thrombotic risk limit the clinical use of the compounds as analgesic, antiinflammatory drugs?

2006 ◽  
Vol 96 (10) ◽  
pp. 413-416 ◽  
Author(s):  
Thomas Hohlfeld ◽  
Sebastian Harder ◽  
Artur-Aron Weber
Keyword(s):  
Clinical Practice ◽  
Therapeutic Option ◽  
Benefit Assessment ◽  
Clinical Use ◽  
Antiinflammatory Drugs ◽  
Thrombotic Risk ◽  
Risk Benefit Assessment ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors

SummaryThe issue of the risk-benefit assessment of cyclooxygenase-2 (COX-2) inhibitors, as compared to traditional non-steroidal anti-inflammatory drugs (tNSAIDs), is far from being resolved. These compounds need to be carefully re-evaluated in order to avoid hasty conclusions, as it happened when COX-2 inhibitors were introduced into clinical practice. Several arguments support the concept, that COX-2 inhibitors remain a valuable therapeutic option at least for selected patients.

Does a coxib-associated thrombotic risk limit the clinical use of the compounds as analgesic anti-inflammatory drugs?

2006 ◽  
Vol 96 (10) ◽  
pp. 407-412 ◽  
Author(s):  
Debabrata Mukherjee
Keyword(s):  
Heart Disease ◽  
Cardiovascular Safety ◽  
Thrombotic Risk ◽  
Definitive Evidence ◽  
Multiple Risk Factors ◽  
Randomized Evaluation ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

SummaryNon-steroidal anti-inflammatory agents (NSAIDs) and selective cyclooxygenase (COX-2) inhibitors (coxibs) are commonly used as analgesic and anti-inflammatory agents.Selective COX-2 inhibitors or coxibs were primarily developed asa response to the gastrointestinal toxicity of conventional NSAIDs but may have other side effects. Currently available data suggests definite prothrombotic risk with the coxibs, and the magnitude of risk may vary with individual agents. Based on available data, coxibs should be restricted to use as 2nd-line, possibly as 3rd-line, agents for carefully chosen patients and randomized trials versus placebo or an accepted comparator must be performed to define the overall safety profile in diverse patient populations.The recently announced Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen (PRECISION) trial will assess the relative cardiovascular safety of three of the most commonly used pain relievers in the treatment of arthritis patients,ibuprofen,naproxen and celecoxib.The study will enroll patients with osteoarthritis, the most common form of arthritis, who have known coronary heart disease or who have multiple risk factors for heart disease and also some patients with rheumatoid arthritis. Patients will be followed for an average of two years to track the occurrence of serious cardiovascular events, including death, heart attack and stroke. This study should provide some definitive evidence of the relative cardiovascular safety of the available anti-inflammatory agents but would be even more useful if it included an arm where patients were treated with analgesics such as acetaminophen and/or moderate strength narcotics.

The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

2021 ◽  
Vol 28 ◽  
Author(s):  
Josiane Viana Cruz ◽  
Joaquín María Campos Rosa ◽  
Njogu Mark Kimani ◽  
Silvana Giuliatti ◽  
Cleydson Breno Rodrigues dos Santos
Keyword(s):  
Side Effects ◽  
Inflammatory Diseases ◽  
Structural Basis ◽  
Potential Inhibitor ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

scholarly journals COX-2: A Pivotal Enzyme in Mucosal Protection and Resolution of Inflammation

2006 ◽  
Vol 6 ◽  
pp. 577-588 ◽  
Author(s):  
John L. Wallace
Keyword(s):  
Digestive System ◽  
Intestinal Inflammation ◽  
Mucosal Protection ◽  
Cox Inhibitors ◽  
Gastrointestinal Injury ◽  
Inflammatory Drugs ◽  
Long Term Consequences ◽  
Cox 2 ◽  
Cox 2 Inhibitors

The discovery of a second form of cyclooxygenase, COX-2, led to a burst of research aimed at the development of nonsteroidal anti-inflammatory drugs that would not damage the gastrointestinal tract. In the years since, this promise has only been partially fulfilled. Selective COX-2 inhibitors cause less gastric damage than conventional, nonselective COX inhibitors, but their use is still associated with significant gastrointestinal injury, and with toxicity in the renal and cardiovascular systems. COX-2 is now recognized as a source of mediators that produce many beneficial and detrimental effects in the digestive system. In this review, the roles of COX-2 in mucosal defense and injury are discussed. Furthermore, contributions of COX-2–derived products to the long-term consequences of intestinal inflammation, including cancer, are reviewed.

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.

COMPARATIVE STUDY OF ANTI-INFLAMMATORY EFFECT OF ACECLOFENAC AND DICLOFENAC ON HUMAN BY CLINICAL TRIAL

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Amit Kumar Jha ◽  
Amit Kumar Jha
Keyword(s):  
Clinical Trial ◽  
Connective Tissue ◽  
Comparative Study ◽  
T Test ◽  
Complex Reaction ◽  
Antiinflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Inflammatory Effect

Various exogenous and endogenous stimuli incite a complex reaction in vascularized connective tissue called inflammation. Non sterodial antiinflammatory drugs are used to reduce inflammation Preferential COX-2 inhibitors namely diclofenac and aceclofenac was taken for my present work and anti inflammatory effect was compared with control and with each other. Student-t-test-was done to compare result. It was found that inflammation varied significantly across the three groups (P=000) compared to control, in~lammation was less in both diclofenac and aceclofenac (P=00). Reduction of inflammation with diclofenac was less, in comparision to aceclofenac at end. Aceclofenac is more efficacious than diclofenac. Keywords: Aceclofenac, diclofenac, Anti inflammatory effect

Angioedema Associated with Aspirin and Rofecoxib

2005 ◽  
Vol 39 (5) ◽  
pp. 944-948 ◽  
Author(s):  
Leisa L Marshall
Keyword(s):  
White Woman ◽  
Skin Testing ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Aspirin Therapy ◽  
Probability Scale ◽  
Antiinflammatory Drugs ◽  
Case Summary ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Auto Injector

OBJECTIVE: To report the probable association of angioedema with aspirin therapy and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib. CASE SUMMARY: A 44-year-old white woman, previously tolerant to aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs), developed angioedema of the lips after ingesting two 325-mg aspirin tablets during one day. The reaction occurred 3 hours after taking the second aspirin and resolved within 3 hours. Two weeks later, the patient took a 25-mg rofecoxib tablet for a sore throat, and she developed angioedema 51/2 hours later. Although the woman took 50 mg of diphenhydramine, the swelling did not subside. She repeated the diphenhydramine dose in the evening and, by noon the next day, 261/2 hours after the angioedema began, it was resolved. The patient's internist prescribed an epinephrine auto-injector and advised her to consult an allergist. With skin testing and oral rechallenge with aspirin, but not rofecoxib, the allergist determined the cause of the reactions to be aspirin-induced angioedema and selective COX-2 inhibitor intolerance. The Naranjo probability scale indicated that aspirin was a highly probable cause and rofecoxib was a probable cause of this patient's angioedema. DISCUSSION: Aspirin-induced angioedema and NSAID intolerance have been well documented. There are reports of both tolerance and intolerance to selective COX-2 inhibitors in patients with documented allergy-like reactions to aspirin and NSAIDs. CONCLUSIONS: Patients with aspirin and NSAID intolerance may develop intolerance to COX-2 inhibitors, especially with repeated exposure.

scholarly journals Nonsteroidal Anti-Inflammatory Drugs: A Potential Pharmacological Treatment for Intracranial Aneurysm

2019 ◽  
Vol 9 (1) ◽  
pp. 31-45 ◽  
Author(s):  
Courtney L. Fisher ◽  
Stacie L. Demel
Keyword(s):  
Nuclear Factor Κb ◽  
High Morbidity ◽  
Surgical Interventions ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Wall Sheer Stress ◽  
Cox 2 Inhibitors

Background: Saccular intracranial aneurysms (IAs) are outpouchings of the vessel wall of intracranial arteries. Rupture of IAs results in subarachnoid hemorrhage which is associated with high morbidity and mortality. Surgical interventions, such as clipping and coiling, have associated risks. Currently, there are no proven pharmacological treatments to prevent the growth or rupture of IAs. Infiltration of proinflammatory cytokines in response to increased wall sheer stress is a hallmark of IA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are being investigated as potential therapeutic agents for reduction in growth and/or prevention of IA through inhibition of inflammatory pathways. Summary: This review will discuss the role of NSAIDs in attenuating the inflammation that drives IA progression and rupture. There are two main subtypes of NSAIDs, nonselective COX and selective COX-2 inhibitors, both of which have merit in treating IA. Evidence will be presented which shows that NSAIDs inhibit several key inflammatory mediators involved in IA progression including nuclear factor-κB, tumor necrosis factor-α, and matrix metalloproteinases. In addition, the role of NSAIDs in limiting inflammatory cell adhesion to endothelial cells and attenuating endothelial cell senescence will be discussed. Key Messages: There is an abundance of basic science and preclinical data that support NSAIDs as a promising treatment for IA. Additionally, a combination treatment strategy of low-dose aspirin given concomitantly with a selective COX-2 inhibitor may result in a reduced side effect profile compared to aspirin or selective COX-2 inhibitor use alone. Several large clinical trials are currently planned to further investigate the efficacy of NSAIDs as an effective nonsurgical treatment for IAs.

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