Cardiovascular Effects of the Cyclooxygenase Inhibitors

Abstract

C yclooxyenase (COX)-2 selective inhibitors were developed to create a new class of nonsteroidal antiinflammatory drugs (NSAIDs) with properties similar to those of nonselective NSAIDS but without their potential COX-1-mediated gastrointestinal toxicities. 1,2 Studies of the various COX-2 selective inhibitors have shown that they are in fact associated with a significantly lower risk of upper and lower gastrointestinal complications than traditional NSAIDs, except in patients who are taking concomitant low-doses of aspirin.Recent evidence also suggests that some doses of the COX-2 selective inhibitors, and perhaps some traditional NSAIDs as well, are associated with an increased risk of adverse cardiovascular (CV) events. Reports of a higher incidence of myocardial infarction (MI) among patients with arthritis taking high doses of the COX-2 selective inhibitor rofecoxib compared with those taking the NSAID naproxen 2-4 have had heightened concerns since 2001 regarding selective COX-2 inhibitor safety. In addition, in early 2005, elevated CV event rates were reported in patients with spontaneous adenomatous polyps who were taking high doses of celecoxib compared with placebo 5 and in patients who received parenteral parecoxib followed by oral valdecoxib versus placebo immediately after coronary artery bypass graft surgery. 6 This article represents a compilation of the data concerning the effects of both nonselective and selective NSAIDs on blood pressure (BP), particularly in patients with hypertension and/or on antihypertensive agents. Subsequently, the impact that the COX inhibitors have on CV events from several recent clinical trials for the treatment of arthritis or for cancer prevention, as well as from selected large observational studies, is discussed. CV Pharmacology of COX InhibitionCOXs participate in numerous physiological functions and human pathological disorders. The COX-1 isoform is constitutively expressed in most tissues where it regulates the synthesis of prostaglandins. COX-1 is the only form of the enzyme in mature platelets and is also expressed in the vascular endothelium, the gastrointestinal epithelium, brain, spinal cord, and kidney. The COX-2 isoform plays an important role in induction of inflammation in response to injury, as well as later repair of inflammation. It is noteworthy that COX-2 may be induced by bacterial endotoxins, cytokines, and growth factors and is expressed in atherosclerotic plaques, during angiogenesis, during wound healing, and in a variety of epithelial cell cancers. [7][8][9] In addition, COX-2 is constitutively expressed in the macula densa and renal medullary interstitium. 10,11 As discussed below, one result of COX-2 inhibition is a reduction in natriuresis and the development of hypertension in susceptible populations. The COX isoenzymes are similar in structure, but the substrate-binding channel of COX-2 contains a side pocket that is absent in COX-1. This structural difference has allowed for the design and development of COX inhibitors with side chains ...

Analysis and detection of dental prescribing errors at Primary Health Care Units in Brazil

“…The high number of prescriptions without specification of the salt of diclofenac could potentially result in harmful consequences, as it is well known that medications with sodium should be used with precaution in patients with hypertension [28]. Therefore, the omission of this information by dentists may transfer the responsibility of drug selection to the pharmacy.…”

Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats

“…COX-1, a known target of low-dose aspirin, is constitutively expressed in most tissues to regulate the synthesis of prostaglandins. Although COX-2 is induced as part of the inflammatory response, COX-2 has recently been reported to be constitutively expressed in the vascular endothelium [20,[23][24][25] . COX-2 is increased in blood vessels of individuals with cardiovascular risk factors [26] .…”

Treatment strategies for osteoarthritis patients with pain and hypertension

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