Vioxx and other COX-2 Inhibitors

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Category: Medications & Supplementation Published on Wednesday, 25 June 2008 Written by Yong Tsai, MD
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With the recent pulling off the market of Vioxx, patients are left doubting the safety of all COX-2 inhibitors, such as Bextra and Celebrex.

Patients ask: “Should I continue the treatment or see if I can go without it? If I take it, will I jeopardize my heart’s health?” While pharmaceutical and medical experts are trying to answer several questions: Is this occurrence and isolated Vioxx shortfall or is the inhibition of COX-2’s the cause? The fact is that even though Celebrex, Bextra and Vioxx belong to same category of COX-2 inhibitors, they are still different in structure and composition.

The majority of current studies that investigated side effects from Celebrex did not show an increased incidence of cardiovascular events as with the most recent Vioxx study did. However, to clarify the safety of all COX-2 inhibitors, further studies are definitely needed.

It was actually in the early 1990s, while studying the anti-inflammatory effects of gluco-corticosteroids, when scientists discovered two types of enzymes involved in prostaglandin production: cyclooxygenas-1 (COX-1) associated with protecting the digestive system from its own erosive acids and cyclooxygenas-2 (COX-2) associated with pain and inflammation.

Because aspirin was known to suppress the production of inflammatory substances that cause pain, swelling, and redness, commonly seen in arthritis, aspirin was viewed as the early choice treatment of arthritis until the emergence of traditional NSAIDs. Traditional NSAIDs became and are still a popular treatment defense against inflammation because of it’s even greater ability to inhibit the production of cycloxygenase, an enzyme that helps the body produce prostaglandins, especially for pain, swelling, and tenderness associated with arthritis.

However, prostaglandins also play an important role in protecting the stomach lining, promoting adequate blood clotting, regulating salt and fluid balance, and maintaining blood flow to the kidneys when function is impaired. And because aspirin and traditional NSAIDs, such as Advil, Aleve and Ibuprofen, not only reduce the “bad” prostaglandins to control inflammation, they also reduce the “good” prostaglandins that protect the stomach lining, this effect creates an increased risk of stomach irritation, stomach bleeding, fluid retention and decreased kidney function.

This is why COX-2 inhibitors gained such popularity; they were able to block only pro-inflammatory prostaglandins (the bad one), all while leaving the good prostaglandins (the stomach lining protectors) untouched, preventing stomach ulcers and bleeding. However, like traditional NSAIDs, they can still decrease kidney function and cause fluid retention. The question is “do they consequently block certain good prostaglandins, causing an increased risk of heart attack or stroke?”

So what is a person to do? Until new studies are completed, patients at low risk of cardiovascular complications, but with serious gastrointestinal complications, especially NSAID-induced, may benefit more from Cox-2 inhibitors. Those with high cardiovascular risk factors, but with low GI risk factors could consider traditional NSAID therapy. Finally, those unfortunate to have both a high cardiovascular and GI risk factors could consider a combined treatment of traditional NSAID with an acid suppressor (proton pump inhibitors (PPIs)) such as Prevacid, Protonix and Nexium.

Whatever treatment you decide, evaluating your risks and benefits with your physician seems to be the wisest move.

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