Comparison of COX Inhibitors

COX inhibition has different effects in different tissues: Prevents subsequent conversion of prostaglandins to thromboxane A2 and PGI2 Peripherally, inhibition of prostaglandin synthesis is anti-inflammatory Centrally, it is anti-pyretic In the stomach, it decreases mucous production and leads to mucosal ulceration

A Thousand Off-Target Effects of Targeted COX-2 Inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation by inhibiting cyclooxygenase (COX), although their use is limited by COX-1–mediated gastrointestinal side effects. COX-2 inhibitors were developed to circumvent these side effects but had complications. In one of the biggest controversies in pharmaceutical history, COX-2 inhibitors were found to double the risk of cardiovascular disease. Now, a study by Ahmetaj-Shala et al. points to kidney-generated inhibitors of nitric oxide synthase as a major culprit in these unwanted effects of COX-2 inhibition.

Cardiovascular Risk Associated With NSAIDs and COX-2 Inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain associated with a variety of medical conditions. Nonselective NSAIDs reversibly inhibit the enzyme cyclooxygenase (COX) in both of its isoforms, COX-1 and COX-2. An increased risk of cardiovascular events has been associated with the use of NSAIDs, especially of COX-2 selective NSAIDs. Current evidence suggests that naproxen, a nonselective NSAID, is associated with the lowest risk of cardiovascular events. Therefore, naproxen is the NSAID of choice in patients with high cardiovascular risk.

Cyclo-Oxygenase (COX) Inhibitors and Cardiovascular Risk: Are Non-Steroidal Anti-Inflammatory Drugs Really Anti-Inflammatory?

Cyclo-oxygenase (COX) inhibitors are among the most commonly used drugs in the western world for their anti-inflammatory and analgesic effects. However, they are also well-known to increase the risk of coronary events. This area is of renewed significance given alarming new evidence suggesting this effect can occur even with acute usage. This contrasts with the well-established usage of aspirin as a mainstay for cardiovascular prophylaxis, as well as overwhelming evidence that COX inhibition induces vasodilation and is protective for vascular function.

Cyclooxygenase Inhibition and Cardiovascular Risk

Owing to the widespread use of antiinflammatory drugs and the fact that the reported risks are cardiovascular in nature, we offer the readers of Circulation this special article. Our goals are to provide an overview of the relevant biology and pharmacology, to synthesize the data on the cardiovascular risks associated with antiinflammatory medications, to offer suggestions on strategies for prescribing these medications, and to make observations on the regulatory and research implications of the data and their interpretation.

How Bad Are the Cox-2 Inhibitors, Anyway?

Since Merck pulled Vioxx (rofecoxib) off the market, the big question has been whether its cardiovascular problems are specific or general. Do all COX-2 inhibitors have this liability? If so, do they all have it to the same extent? The analogy that comes to mind is the statins - all of them have been shown, at high enough dosages, to be associated with a potential for rhabdomyolosis, a serious muscle side effect. But Bayer's entry into the class, Baycol, showed it more than the others and had to be pulled.

Nonaspirin NSAIDs, Cyclooxygenase 2 Inhibitors, and the Risk for Stroke

Our results indicate an increased risk of stroke with current use of two highly selective coxibs, rofecoxib and valdecoxib, also shown to increase cardiovascular risk. These results also provide some reassurance about other specific NSAIDs regarding stroke risk.

Over-the-counter painkiller may increase risk of heart attacks

Considering only those NSAIDs that have been widely studied, the highest risk of cardiovascular events was shown with rofecoxib (Vioxx), diclofenac (Voltaren) and indomethacin (Indocid). Rofecoxib was withdrawn in 2004 and indomethacin is not commonly used, so the important result is the increased risk with diclofenac, which is available for non-prescription use.

What’s the Difference Between COX-2 Inhibitors and NSAIDs?

NSAIDs or Nonsteroidal anti-inflammatory drugs as their non-abbreviated name, are drugs that inhibit inflammation. They work by inhibiting two enzymes, Cyclooxygenase 1 and 2 (often shorted to COX 1 and COX 2). These enzymes produce small molecules that cause inflammation in our tissues (wherever that may be ie a knee or a back or your head).