A previously used non steroidal anti-inflammatory drug, indomethacin, was commonly used for patients with inflammatory related diseases. However these patients experienced some serious side effects, particularly in the GI tract. Several studies were done, and finally the widely accepted mechanism causing these side effects was revealed: NSAIDs are non-selective COX inhibitors and are also particularly acidic. The combination of these things appears to be correlated with a topical effect and inhibition of COX-1 (which is known for secreting protective proteins, while COX-2 is recognized for its role in inflammation).
Because of the many potentially fatal side effects caused by typical NSAIDs, celecoxib was created. Celecoxib is a selective COX-2 inhibitor and is not especially acidic. Studies have shown celecoxib does not possess the same damaging potential as drugs like indomethacin, and appear to be much safer. So this sounds like a direct solution to the problem we had with indomethacin, right? At first glance it would seem that way, however more recent studies have shown Celebrex may cause an increase in cardiac risk. The drug has been compared to Vioxx, which was completely removed from the market because of dangerous side effects. There was even a cardiologist from Harvard Medical school, Dr. Elliott Antman, who distrusts Celebrex to the extent that he would go as far as recommending narcotics over Celebrex. While this seems extreme (especially considering the primary candidates are often elderly arthritis patients), there has been research showing an increase risk of heart disease with Celebrex. Still many doctors continue to prescribe Celebrex and believe it can help their patients deal with some unwanted inflammation. The belief most of these doctors have is that Celebrex is relatively safe to use in low doses, but the risk for heart disease increases significantly with higher doses. Realistically, only low doses are really necessary for most patients, which is probably why this drug is still on the market despite the controversy lasting almost 10 years. I think that all of the comparisons done with Celebrex and Vioxx are a major factor to what is scaring people and making them jump to conclusions that this drug is nowhere near safe (because of the reputation Vioxx has). Further studies will help in drawing a more defined conclusion, but for now it will remain a controversial issue (especially for the cardiologists).
Sources:
http://arthritis.webmd.com/news/20050217/study-low-dose-celebrex-poses-no-heart-risk
http://www.ahrp.org/infomail/05/02/01.php
From the article I had presented on the uses of NSAIDs, they had discussed a great deal about Celebrex. Celebrex does pose dangerous cardiovascular related risks which is why the American Heart Association only recommends its use if its absolutely necessary. The AHA emphasizes that Celebrex should be used in the lowest possible amount for the shortest time needed to abstain from the potential cardiac risks, which is what was mentioned in your post. If the pain associated with inflammatory diseases are that great to where Celebrex is necessary, the cardiovascular risks can possibly be overlooked if the drug is used in low doses.
ReplyDeleteThe COX-2 Inhibitors (such as Vioxx) do pose some cardiovascular risk due to the inhibitions of prostaglandin production, which are antithrombotic. Thus, they are particularly careful about the use of Celebrex or Vioxx at higher doses. However, as Janna pointed out, physicians don't usually increase the dose of celecoxib, but most likely add another drug.
ReplyDeleteI do disagree with Dr. Antman's use of narcotics, mainly because it does not actually target the inflammation but tries to treat a symptom (mainly pain). The narcotics are particularly addictive and actually can cause major CNS depression if not titrated correctly due to its narrow therapeutic window.
Though celecoxib has a serious adverse drug reaction, there is still much research that needs to be done to weigh the therapeutic and toxic effects of this drug, as well as it isomers.
The problem with Vioxx and Celebrex is that they affect Prostacyclin Synthase, which function to decrease blood clotting therefore interfering with platelet aggregation. These drugs, especially if they are used long term can cause blod clotting and serious risks of stroke and MIs.
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