Pain Relievers: Questions & Answers

Arthritis Expert Helps You Understand Risks From Pain Relievers

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Arthritis Expert Helps You Understand Risks From Pain Relievers

Feb. 18, 2005 -- After three days of meetings, an expert FDA panel has recommended that the pain relievers Bextra and Celebrex, also called Cox-2 drugs, remain on the market. They also recommended that Vioxx be allowed back on the market. WebMD turned to arthritis expert William Shiel, MD, chief medical editor of, a WebMD company, to help you understand the drugs and their risks.

The FDA is expected to officially act on these recommendations in the near future.

Is the concern with Cox-2 drugs only in elderly people?

While studies have shown heart risks in people 65 and over, the issues raised pertain to any patient with underlying risk factors for heart disease or stroke. This means not only the elderly may be at risk, but also those who have underlying heart disease or known blood vessel disease, such as atherosclerosis or calcification of blood vessels.

Caution might be also be used for those with high blood pressure and a tendency toward fluid retention (edema). It has been shown that all anti-inflammatory drugs (like ibuprofen and Cox-2 inhibitors) can worsen blood pressure or cause fluid retention. Patients should be monitored for such side effects. Similarly, in the elderly who are at risk for kidney problems or in any patient with kidney disease, anti-inflammatory drugs should be used cautiously with close monitoring of kidney function.

Are Cox-2 inhibitors better pain relievers than older, traditional anti-inflammatory drugs like ibuprofen and naproxen?

No. As a group, the benefit of these drugs lies in their lower frequency of stomach and intestinal side effects, not in their effectiveness. Clinical research has shown that the Cox-2 inhibitors are essentially equivalent to traditional anti-inflammatory drugs in effectiveness. Improved effectiveness has never been the point of these medications, nor have their respective manufacturers marketed them for that purpose.

Having said that, doctors are well aware that determining which patient is going to respond to which anti-inflammatory drug involves some trial and error. Therefore, it is convenient to have options when treating chronic pain or inflammation.


Some studies have shown that Cox-2 inhibitors have been overprescribed. To whom should these drugs be prescribed?

In particular, a recent study published in the Archives of Internal Medicine showed that doctors were using Cox-2 drugs in a wide variety of patients instead of specifically selecting patients at risk for stomach bleeding as the ideal candidates. It was suggested that marketing and promotion of the drugs lead to their use in an unnecessarily large group of patients. Moreover, patients may have requested them because of perceived benefits.

Drug treatment is always based on a risk vs. benefit analysis. In clinical practice, Cox-2 inhibitors are considered after weighing the benefits vs. the risks. As more research clarifies the risks and the groups of patients who are more prone to these risks, it will become easier for patients and doctors to choose medications optimally.

Currently, Cox-2 drugs are most suited for patients who have a history of stomach or intestinal bleeding or who are at risk for bleeding. Persons who are taking the blood-thinning medication Coumadin cannot take traditional anti-inflammatory drugs because of high bleeding risks. When an anti-inflammatory drug is necessary, Cox-2 inhibitors are permissible for this group of patients.

The risks and benefits of taking a medication must be evaluated in an individualized fashion for each patient. The decision to take a medication requires knowledge of the severity of the condition treated, risks of alternatives, underlying medical conditions, past medication experiences, affordability of the drug, and the patient's age to adequately appreciate the risks.

If someone stops taking a Cox-2 drug, is the adverse risk of heart attack or stroke permanent?

No. There is no evidence of a sustained adverse effect. The risk would only be expected to be present while taking the drug, not after it has been discontinued.

It is interesting to note that the heart attack and stroke risk detected in the Vioxx study (which led its manufacturer to pull it from the market) did not present itself in study participants until the drug was taken for at least 18 months. There was no increased risk of heart attack or stroke detected in study participants who took Vioxx for less than 18 months. This suggests the possibility of some metabolism or enzyme change that takes time to occur in the body.


Are Cox-2 inhibitors less likely to irritate the stomach than older anti-inflammatory drugs?

Cox-2 inhibitors (such as Celebrex and Bextra) do not inhibit the Cox-1 enzyme in the stomach and are thus thought to be less toxic to the stomach than traditional anti-inflammatory drugs (such as aspirin, ibuprofen, or naproxen). These traditional anti-inflammatory drugs, called nonselective Cox-1/Cox-2 inhibitors, inhibit both Cox-1 and Cox-2 enzymes. While inflammation is reduced by blocking Cox-2, the protective mucus lining of the stomach is also reduced when Cox-1 is blocked, which can cause stomach upset, ulcers, and bleeding.

Current evidence suggests that the selective Cox-2 inhibitors are less toxic to the stomach than traditional anti-inflammatory drugs. This effect is especially significant in persons who are at risk of stomach bleeding, such as those with a history of prior stomach bleeding or patients on blood-thinning medications.

WebMD Health News Reviewed by Brunilda Nazario, MD on February 18, 2005


SOURCE: William Shiel, MD, chief medical editor,, a WebMD company.

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