COX-2 inhibitors and cardiovascular risk

2006 ◽  
Vol 96 (10) ◽  
pp. 401-406 ◽  
Author(s):  
Muhammad Marwali ◽  
Jawahar Mehta
Keyword(s):  
Side Effects ◽  
Meta Analysis ◽  
Randomized Design ◽  
Cardiovascular Morbidity And Mortality ◽  
Long Time ◽  
Gastrointestinal Side Effects ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

SummaryEven though non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for a long time, the search continues for anti-inflammatory drugs with few side-effects. COX-2 inhibitors are currently most debated, because they have less gastrointestinal side effects but have been linked to increased cardiovascular morbidity and mortality, presumably related to thrombotic events. This has brought about the withdrawal of rofecoxib and other COX-2 inhibitors from the market. Although the results of several large studies with prospective, randomized design and meta-analysis of different trials have led to the demise of many popular COX-2 inhibitors, yet the conclusion seems to be rather simplistic. This review presents evidence from basic biology and clinical studies with the expectation that a balanced position, particularly in relation to increase in cardiovascular events, may be elucidated.

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 Role of Anti-inflammatory Drugs in the Colorectal Cancer

2019 ◽  
Vol 55 (3) ◽  
pp. 168-180
Author(s):  
Oumer Sada ◽  
Kemal Ahmed ◽  
Aliye Jeldo ◽  
Mensur Shafi
Keyword(s):  
Colorectal Cancer ◽  
Relative Risk ◽  
Meta Analysis ◽  
Data Sources ◽  
High Dose ◽  
Adjusted Relative Risk ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

Objective: The objective of this review was to systematically review and synthesize evidence regarding benefits of using nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of colorectal cancer (CRC). Data Sources: The data sources were MEDLINE, PubMed, NEJM, Google Scholar, and Google searches of references from relevant and eligible trials. Review Methods: We screened abstracts and full-text articles of identified references for eligibility and reviewed randomized controlled trials, cohort studies, and meta-analysis for evidence on benefits of using NSAIDs in CRC treatments. For all extracted data, completeness and relevance were checked. Results: The risk of any adenoma among frequent NSAID users was 26.8% vs 39.9% among placebo subjects who later used NSAIDs sporadically (adjusted relative risk = 0.62, 95% confidence interval [CI] = 0.39-0.98; P trend with NSAID use frequency = .03). Long-term use of aspirin reduces the risk of CRC. Aspirin also reduces the incidence of colon adenomas and mortality, especially when used for >10 years. Rofecoxib is associated with the reduction of CRC; however, it was associated with cardiovascular risk (with an overall unadjusted relative risk of 1.50 [95% CI = 0.76-2.94; P = .24]). Adenoma Prevention with Celecoxib trial shows that, for patients of all genotypes, the estimated cumulative incidence of one or more adenomas by year 3 was 59.8% for those randomized to placebo as compared with 43.3% for those randomized to low-dose (200 mg, twice daily) celecoxib (relative risk [RR] = 0.68; 95% CI = 0.59-0.79; P < .001) and 36.8% for those randomized to high-dose (400 mg, twice daily) celecoxib and 60.7% in placebo group (RR = 0.54; 95% CI = 0.46-0.64; P < .001). Conclusions: The use of COX-2 inhibitors both prior to and after diagnosis of CRC seemed to be mildly associated with the reduction in mortality of patients with CRC. Some literatures state that COX-2 inhibitors might play a synergistic role in adjuvant chemotherapy of FOLFOX regimen. Celecoxib was found to increase the radiosensitization of colon cancer cells.

scholarly journals Non-steroidal anti-inflammatory drugs: an overview

2019 ◽  
Vol 9 (1-s) ◽  
pp. 442-448 ◽  
Author(s):  
Kasturi Jahnavi ◽  
Palla Pavani Reddy ◽  
Bakshi Vasudha ◽  
Boggula Narender
Keyword(s):  
Side Effects ◽  
Gastrointestinal Haemorrhage ◽  
Cyclooxygenase Inhibitors ◽  
Full Spectrum ◽  
Analgesic Effects ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Musculoskeletal Trauma ◽  
Cox 2 Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) including both traditional non-selective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX path way in the generation of inflammation and in the biochemical recognition of pain. NSAIDs are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs). Their use is associated with the side effects such as gastrointestinal and renal toxicity. They are the most commonly employed first line drugs for all these conditions and many others-like musculoskeletal trauma, minor aches and pains, and dysmenorrhoea. The therapeutic anti-inflammatory action of NSAIDs is produced by the inhibition of COX-2, while the undesired side effects arise from inhibition of COX-1 activity. Thus, it was though those more selective COX-2 inhibitors would have reduced side effects. Based upon a number of selective COX-2 inhibitors (Rofecoxib, Celecoxib etc.) were developed as safer NSAIDs with improved gastric safety profile. Several newer applications like prophylaxis of stroke with aspirin are now common place. Use of these drugs for the prophylaxis of conditions like Alzheimer’s disease and colorectal cancer is being evaluated. Unfortunately, they have several toxicities ranging from minor heartburn to severe gastrointestinal haemorrhage and perforation. Therefore, newer NSAIDs have been introduced in recent years to circumvent this problem. In preliminary studies, these have shown better safety, efficacy, and tolerability but the full spectrum of adverse reactions of these drugs is yet to be fully known. This review can be used for further research as well as clinical purpose. Keywords: Non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase inhibitors, prostaglandins, aspirin.

scholarly journals Safety of selective non-steroidal anti-inflammatory drugs: analysis of the last years data

The Clinician ◽  
2020 ◽  
Vol 14 (1-2) ◽  
pp. 91-99
Author(s):  
N. A. Shostak ◽  
A. A. Klimenko ◽  
N. A. Demidova ◽  
D. A. Anichkov
Keyword(s):  
Heart Failure ◽  
Gastrointestinal Tract ◽  
Side Effects ◽  
Adverse Events ◽  
Gastrointestinal Complications ◽  
Increased Risk ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used pain relievers. However, their use often threatens with serious undesirable effects, associated mainly with damage to cardiovascular system (CVS), gastrointestinal tract, kidneys and liver. Contraindications to NSAIDs prescription are clearly regulated, algorithms for their personalized appointment are determined taking into account risk factors for cardiovascular and gastrointestinal adverse events. The severity of NSAIDs side effects is mainly due to the selectivity to cyclooxygenase-2 (COX-2), as well as the physicochemical properties of various drugs. Cardiovascular adverse events differ among various NSAIDs both within commonly used drugs and among COX-2 inhibitors. It is well known that NSAIDs selective for COX-2 are safer in terms of the effect on the gastrointestinal tract than non-selective drugs. A meta-analysis showed that relatively selective COX-2 inhibitors (meloxicam, etodolac) were associated with a comparable risk of developing symptomatic ulcers and ulcers identified by endoscopy, and safety and tolerability profiles of the drugs were similar.All NSAIDs are associated with cardiovascular toxicity, however, different drugs have significant risk differences. The mechanism of NSAIDs cardiovascular adverse effects is associated with an increase of blood pressure, sodium retention, vasoconstriction, platelet activation, and prothrombotic state. It has been shown that the risk of cardiovascular adverse events when taking COX-2 inhibitors (celecoxib, etoricoxib) significantly increases. According to a study of more than 8 million people, it was found that the risk of myocardial infarction was increased in patients taking ketorolac. Further, highest to lowest risk authors list indomethacin, etoricoxib, rofecoxib (not currently used), diclofenac, a fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen. When taking NSAIDs, the risk of heart failure decompensation increases, and it turned out to be the greatest for ketorolac, etoricoxib, and indomethacin. Meloxicam, aceclofenac, ketoprofen almost did not increase heart failure risk. It should be noted that when using the drugs (except for indomethacin and meloxicam), there is a tendency to increase the total cardiovascular and renal risks with increasing doses. Thus, it is obvious that a very careful approach is required when choosing NSAIDs. If there is an increased risk of gastrointestinal complications associated with NSAIDs, selective NSAIDs are preferred, with both coxibs and traditional selective NSAIDs showing the best safety profile in the studies. To minimize cardiovascular side effects specialists should consider the risk level of cardiovascular complications, as well as results of large clinical studies where particular NSAIDs are compared.

Risks of Cardiovascular Disease and Beyond in Prescription of Nonsteroidal Anti-Inflammatory Drugs

2019 ◽  
Vol 25 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Manas A. Rane ◽  
Alexander Gitin ◽  
Benjamin Fiedler ◽  
Lawrence Fiedler ◽  
Charles H. Hennekens
Keyword(s):  
Cardiovascular Disease ◽  
Side Effects ◽  
Health Care Providers ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Care Providers ◽  
Relieve Pain ◽  
Gastrointestinal Side Effects ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin, naproxen, diclofenac, and ibuprofen, as well as selective cyclooxygenase 2 inhibitors such as celecoxib. Their use is common, as well as their side effects which cause 100 000 hospitalizations and 17 000 deaths annually. Recently, the US Food and Drug Administration strengthened its warning about the risks of cardiovascular disease (CVD) attributed to nonaspirin NSAIDs. Methods: When the sample size is large, randomization provides control of confounding not possible to achieve with any observational study. Further, observational studies and, especially, claims data have inherent confounding by indication larger than the small to moderate effects being sought. Results: While trials are necessary, they must be of sufficient size and duration and achieve high compliance and follow-up. Until then, clinicians should remain uncertain about benefits and risks of these drugs. Conclusions: Since the totality of evidence remains incomplete, health-care providers should consider all these aforementioned benefits and risks, both CVD and beyond, in deciding whether and, if so, which, NSAID to prescribe. The factors in the decision of whether and, if so, which NSAID to prescribe for relief of pain from inflammatory arthritis should not be limited to risks of CVD or gastrointestinal side effects but should also include potential benefits including improvements in overall quality of life resulting from decreases in pain or impairment from musculoskeletal pain syndromes. The judicious individual clinical decision-making about the prescription of NSAIDs to relieve pain based on all these considerations has the potential to do much more good than harm.

scholarly journals Peran Kurkumin Sebagai Terapi Pada Osteoartritis

2020 ◽  
Vol 2 (1) ◽  
pp. 106-110
Author(s):  
Rilianda Abelira
Keyword(s):  
Peptic Ulcer ◽  
Side Effects ◽  
Old Age ◽  
Cyclooxygenase 2 ◽  
Tnf Α ◽  
The World ◽  
Inflammatory Drugs ◽  
Digestive Disorders ◽  
Cox 2 ◽  
Anti Inflammatory

Osteoartritis (OA) merupakan salah satu penyakit penyakit degeneratif atau geriatri yang disebabkan adanya inflamasi yang melibatkan kartilago, lapisan sendi, ligamen, dan tulang yang akibatnya dapat menyebabkan nyeri dan kekakuan pada sendi. Epidemiologi OA di didunia sekitar 15% dengan usia diatas 65-75 dan diperkirakan pada tahun 2020 penderita osteoarthritis akan meningkat 11,6 juta penderita. Kejadian OA di Indonesia dari tahun 1990 hingga 2010 telah mengalami peningkatan sebanyak 44,2% dan berdasarkan usia di Indonesia cukup tinggi dengan 65% pada usia tua (lansia) atau lebih dari 61 tahun. Pengobatan secara farmakologis untuk OA dengan menggunakan Obat Anti Inflamasi Non-Steroid (OAINS) salah satu contohnya adalah meloksikam. Namun, efek samping penggunaan OAINS dapat menimbulkan beberapa masalah seperti timbulnya ulkus peptikum dan gangguan pencernaan. Hal ini menyebabkan sedang dikembangkannya pengobatan herbal untuk OA yang harapannya dapat menjadi pengobatan utama dalam mengatasi OA dengan menggunakan kurkumin. Kurkumin berperan sebagai antiinflamasi dalam kunyit putih dengan menurunkan aktivitas cyclooxygenase 2(COX-2), lipoxygenase dan menghambat produksi sitokin seperti TNF-α, interleukin (IL). Osteoarthritis (OA) is a degenerative or geriatric disease that is caused by inflammation involving cartilages, joint lining, ligaments, and bones which can cause pain and stiffness in the joints. Epidemiology of OA in the world around 15% with ages above 65-75 and it is estimated in 2020, osteoarthritis will increase by 11.6 million. The incidence of OA in Indonesia from 1990 to 2010 has increased by 44.2% and by age in Indonesia is quite high with 65% in old age (elderly) or more than 61 years. Treatment for OA is using non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam. However, side effects of NSAID use can cause several problems such as the emergence of peptic ulcer and digestive disorders. This has led to the development of herbal treatments for OA which hopes to become the main treatment in overcoming OA by using curcumin. Curcumin acts as an anti-inflammatory in white turmeric by reducing the activity of cyclooxygenase 2 (COX-2), lipoxygenase and inhibiting the production of cytokines such as TNF-α, interleukin (IL).

2-Substituted Benzoxazoles as Potent Anti-Inflammatory Agents: Synthesis, Molecular Docking and In Vivo Anti-Ulcerogenic Studies

2021 ◽  
Vol 18 ◽  
Author(s):  
Iqra Hamid ◽  
Humaira Nadeem ◽  
Sameen Fatima Ansari ◽  
Sonia Khiljee ◽  
Inzamam Abbasi ◽  
...  
Keyword(s):  
Side Effects ◽  
Therapeutic Interventions ◽  
Binding Potential ◽  
Spectroscopic Techniques ◽  
Standard Drug ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Protein Pocket

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the commonly used therapeutic interventions of inflammation and pain that competitively inhibit the cyclooxygenase (COX) enzymes. Several side effects like gastrointestinal and renal toxicities are associated with the use of these drugs. The therapeutic anti-inflammatory benefits of NSAIDs are produced by the inhibition of COX-2 enzymes, while undesirable side effects arise from the inhibition of COX-1 enzymes. Objectives: In the present study, a new series of 2-substituted benzoxazole derivatives 2(a-f) and 3(a-e) were synthesized in our lab as potent anti-inflammatory agents with outstanding gastro-protective potential. The new analogs 2(a-f) and 3(a-e) were designed depending upon the literature review to serve as ligands for the development of selective COX-2 inhibitors. Methods: The synthesized analogs were characterized using different spectroscopic techniques (FTIR, 1HNMR, 13CNMR) and elemental analysis. All synthesized compounds were screened for their binding potential in the protein pocket of COX-2 and evaluated for their anti-inflammatory potential in animals using the carrageenan-induced paw edema method. Further 5 compounds were selected to assess the in vivo anti-ulcerogenic activity in an ethanol-induced anti-ulcer rat model. Results: Five compounds (2a, 2b, 3a, 3b and 3c) exhibited potent anti-inflammatory activity and significant binding potential in the COX-2 protein pocket. Similarly, these five compounds demonstrated a significant gastro-protective effect (p<0.01) in comparison to the standard drug, Omeprazole. Conclusion: Depending upon our results, we hypothesize that 2-substituted benzoxazole derivatives have excellent potential to serve as candidates for the development of selective anti-inflammatory agents (COX-2 inhibitors). However, further assessments are required to delineate their underlying mechanisms.

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