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 Effects of selective inhibition of cyclooxygenase and lipooxygenase pathways in follicle rupture and ovulation in the rat

Reproduction ◽  
2006 ◽  
Vol 132 (4) ◽  
pp. 571-577 ◽  
Author(s):  
M Gaytán ◽  
C Bellido ◽  
C Morales ◽  
J E Sánchez-Criado ◽  
F Gaytán
Keyword(s):  
Selective Inhibition ◽  
Spatial Targeting ◽  
Follicle Rupture ◽  
Immature Rats ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

Treatment with non-steroidal anti-inflammatory drugs, either non-selective or selective cyclooxygenase-2 (COX-2) inhibitors, consistently impairs ovulation, indicating the essential role of COX-2/prostaglandins in the ovulatory process. Indomethacin, a potent inhibitor of both COX-1 and COX-2, induced several ovulatory alterations, consisting of a decrease in the number of oocytes effectively ovulated, trapping of oocytes inside the luteinized follicle, as well as abnormal follicle rupture at the basolateral sides, with release of the oocyte and follicular fluid to the interstitium. Yet, the precise role of prostaglandins in ovulation and whether some of the ovulatory defects induced by indomethacin are due to interference with additional components of the ovulatory cascade, beyond prostaglandin synthesis, are not completely understood. We have used gonadotrophin-primed immature rats to analyse whether, compared to indomethacin, selective inhibition of COX-2, with or without concomitant inhibition of COX-1, or selective inhibition of the lipooxygenase (LOX) pathway, induce similar ovulatory alterations. Immature rats (27 days of age) were injected PMSG (10 IU), and 48 h later hCG (10 IU) subcutaneously, and different anti-inflammatory drugs. Animals were killed at 21 h after hCG injection. Rats treated with the selective COX-2 inhibitor NS398 (10 mg/kg body weight, (bw)) showed alterations in follicle rupture as those treated with indomethacin (0.5 mg/rat), albeit affecting a lower number of follicles, irrespective of the concomitant inhibition of COX-1 with the selective inhibitor SC560 (10 mg/kg bw). Rats treated with the LOX inhibitor NDGA (300 mg/kg bw) did not show ovulatory alterations. These data indicate that the characteristic alterations of follicle rupture induced by indomethacin, are also induced by selective COX-2 inhibitors, strengthening the contention that prostaglandins play a crucial role in the spatial targeting of follicle rupture at the apex.

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 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.

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.

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 Anti-inflammatory drugs with therapeutic effects and drug regulators

2021 ◽  
pp. 30-39
Author(s):  
Prateek Paul ◽  
Manvi .
Keyword(s):  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Negative Effects ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Cox 1

For prostaglandin production, the enzyme cyclooxygenase (COX) is required. The two COX isoforms are constitutive COX-1 (which is responsible for physiological functions) and inducible COX-2 (involved in inflammation). COX inhibition explains both the medicinal (inhibition of COX-2) and negative effects (inhibition of COX-1) effects of non-steroidal anti-inflammatory medicines (NSAIDs). Nonsteroidal anti-inflammatory medicines (NSAIDs) act by blocking the enzyme cyclooxygenase (COX), which produces prostaglandins (PGs). To a greater or lesser extent, they share similar side effects, such as stomach and renal toxicity. According to a recent study, there are at least two COX isoenzymes. COX-1 is a naturally occurring enzyme that creates prostaglandins (PGs), which protect the stomach and kidneys. Aspirin's well-known anti-cancer impact could also be related to its influence on COX-2, which is expressed in this condition. As a result, selective COX-2 inhibitors may have new therapeutic potential as anticancer drugs, as well as in preventing premature labor and maybe reducing the progression of Alzheimer's disease.

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.

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