Are All COX-2 Inhibitors Created Equal?

Chang, Ingrid J.; Harris, Raymond C.

doi:10.1161/01.hyp.0000153049.77150.d7

Cited by 12 publications

(11 citation statements)

References 28 publications

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“…121 These characteristics may contribute to observed differences of the effect across various COX-2 inhibitors. Consistent with evidence that rofecoxib has stronger COX-2 selectivity than other COX-2 inhibitors, 120 our results indicate sub-stantially different effects between rofecoxib and other agents in its class. Notably, we found a higher risk of renal dysfunction, hypertension, and peripheral edema with rofecoxib, whereas in contrast, we found lower risk of hypertension and renal dysfunction with celecoxib and no effect with other agents.…”

Section: Commentsupporting

confidence: 90%

“…23,25,118,119 However, a class effect for all COX-2 inhibitors has previously remained unclear. 120 Although all study agents are considered selective COX-2 inhibitors, the various agents are known to somewhat differ in terms of potency and specificity of COX-2 inhibition as well as their respective pharmacokinetics and metabolism in the human body. 121 These characteristics may contribute to observed differences of the effect across various COX-2 inhibitors.…”

Section: Commentmentioning

confidence: 99%

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Adverse Effects of Cyclooxygenase 2 Inhibitors on Renal and Arrhythmia Events

Zhang

Ding

Song³

2006

JAMA

309

169

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Section: Commentsupporting

confidence: 90%

Section: Commentmentioning

confidence: 99%

Adverse Effects of Cyclooxygenase 2 Inhibitors on Renal and Arrhythmia Events

Zhang

Ding

Song³

2006

JAMA

309

169

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“…The effective halflife of the former drug is longer, which may be responsible for the increased side effects when both drugs are administered once per day. However, it also is possible that non-"class" effects of the drugs may be a factor because the chemical structures are different, with celecoxib being a sulfonamide and rofecoxib a sulfone (121). Further modifications of these drugs in the future may provide agents with fewer renal side effects.…”

Section: Effects Of Cox-2 Inhibitors In Proteinuric Statesmentioning

confidence: 99%

Update on Cyclooxygenase-2 Inhibitors

Harris

Breyer

2006

Clinical Journal of the American Society of Nephrology

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Nonsteroidal anti-inflammatory drugs represent the most commonly used medications for the treatment of pain and inflammation, but numerous well-described side effects can limit their use. Cyclooxygenase-2 (COX-2) inhibitors were initially touted as a therapeutic strategy to avoid not only the gastrointestinal but also the renal and cardiovascular side effects of nonspecific nonsteroidal anti-inflammatory drugs. However, in the kidney, COX-2 is constitutively expressed and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in mediation of renin release, regulation of sodium excretion, and maintenance of renal blood flow. This review summarizes the current state of knowledge about both renal and cardiovascular side effects that are attributed to COX-2 selective inhibitors.Clin J Am Soc Nephrol 1: 236 -245, 2006236 -245, . doi: 10.2215 N onsteroidal anti-inflammatory drugs (NSAID) are the most commonly used class of medications for the treatment of pain and inflammation and represent one of the most common classes of medications used worldwide, with an estimated usage of Ͼ30 million per day (1). Nonselective NSAID inhibit both constitutive cyclooxygenase-1 (COX-1) and inducible cyclooxygenase-2 (COX-2), the rate-limiting enzymes that are involved in production of prostaglandins and thromboxane. In addition to their role in inflammation, prostaglandins are important regulators of vascular tone, salt and water balance, and renin release, and nonselective NSAID exhibit adverse effects, including salt retention and reduced GFR, which may elevate BP or make pre-existing hypertension worse (2). It has been estimated that as many as 2.5 million Americans experience NSAID-mediated renal effects yearly (3). Risk factors that predispose to NSAID-induced renal functional alterations include age Ͼ65 yr, cardiovascular disease, diabetes, male gender, high NSAID dosage, and concurrent use of other nephrotoxic drugs (3). Up to 20% of patients who take nonselective NSAID and have more than one of these risk factors may manifest alterations in renal function.In addition to renal side effects, nonselective NSAID have long been known to predispose to gastrointestinal (GI) toxicity. It has been estimated that one third of patients who taking long-term nonselective NSAID develop endoscopically proven gastric or duodenal ulcers (4). The risk for serious bleeding from these lesions is somewhat lower, with approximately 100,000 hospitalizations for GI complications of NSAID (5). One study estimated that nonselective NSAID-induced GI abnormalities constitute the 15th leading cause of death in the United States (6). The premise that COX-1 performs cellular "housekeeping" functions for normal physiologic activity and is the predominant isoform expressed in platelets and the GI tract, whereas COX-2 acts at inflammatory sites, led to the development of COX-2 selective inhibitors. It also was originally hypothesized that the renal effects of nonselective NSAID were also linked to COX-...

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“…Introduction of selective coxibs (celecoxib, rofecoxib, etoricoxib, lumiracoxib, valdecoxib) held a promise of improved treatment of arthritis without gastrointestinal effects associated with non steroidal antiinflammatory drugs (NSAIDs) [49][50][51]. However, there is little comparative clinical pharmacology available of these compounds ( Table 1), and the incidence of adverse events, specially regarding thrombogenicity, is controversial [52][53][54].…”

Section: Cox-2: a Therapeutic Target In Human Atherosclerosis?mentioning

confidence: 99%

Monocyte Cyclooxygenase-2 Activity: A New Therapeutic Target for Atherosclerosis?

Paramo

Rodríguez

Beloqui

et al. 2005

CDTCHD

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It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases of leukocyte recruitment to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. COX-2 has been detected in macrophages, smooth muscle cells and endothelial cells in human atherosclerotic lesions. Several studies have also reported the presence of COX-2 in the shoulder region of atherosclerotic plaques, mainly colocalizing with macrophages and MMPs, enzymes that are involved in the destabilization of atherosclerotic plaques, leading to rupture and atherothrombotic syndromes (i.e. acute myocardial infarction). We have recently assessed monocyte COX-2 activity and the production of PGE(2) in a population of apparently healthy subjects free from clinically overt atherosclerosis. We found an association between increased PGE(2) and increasing number of cardiovascular risk factors and carotid intima-media thickness, a noninvasive surrogate marker of atherosclerosis, independently of traditional and non traditional cardiovascular risk factors. Our findings support the notion that the COX-2/PGE(2)axis may have a role in atherosclerosis, and this might be an attractive therapeutic target. COX-2 inhibitors, collectively called coxibs (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise of improved treatment of arthritis without the gastrointestinal side effects associated with aspirin and other nonsteroidal anti-inflammatory drugs. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk. Only well designed large scale clinical trials can provide the answer as to the net effect of selective COX-2 inhibition on cardiovascular events before this new class of anti-inflammatory drugs can be incorporated into the armamentarium of atherosclerosis.

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Are All COX-2 Inhibitors Created Equal?

Cited by 12 publications

References 28 publications

Adverse Effects of Cyclooxygenase 2 Inhibitors on Renal and Arrhythmia Events

Adverse Effects of Cyclooxygenase 2 Inhibitors on Renal and Arrhythmia Events

Update on Cyclooxygenase-2 Inhibitors

Monocyte Cyclooxygenase-2 Activity: A New Therapeutic Target for Atherosclerosis?

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