Ask the Doctors by Eve Glazier, M.D. and Elizabeth Ko, M.D

High Doses of Pain Relievers Should Be Taken Infrequently

Dear Doctor: Which pain reliever is safer -- acetaminophen, ibuprofen, celecoxib or naproxen? It seems as if they all carry some risks.

Dear Reader: Pain is a symptom to which we can all relate. It's also an important indicator of possible injury within the body and should be acknowledged, not simply by taking medication, but also by understanding the cause of the pain. That said, one person's pain is different than another's, with some people needing greater pain relief.

So, if you need a medication for pain, what should you use? Let's look first at acetaminophen (Tylenol). Acetaminophen has been used since 1955; it is available in multiple products, works well for pain, and is for the most part safe. However, at high doses -- specifically, above 4,000 milligrams a day, or eight tablets of Extra Strength Tylenol -- the medication can cause liver damage, or even death, especially in those who are malnourished, drink alcohol in excess or consistently take more than 4,000 mg per day. Age is also a factor, as those over 40 have a greater risk of liver failure and death after over-dosage.

Ibuprofen (Advil, Motrin) has been used for pain since 1974. It is one of many medications classified as non-steroidal anti-inflammatory drugs (NSAID). NSAIDs work by inhibiting formation of mediators of pain and inflammation, and they're notably effective at decreasing inflammation in swollen joints related to arthritis.

Naproxen (Aleve) was first marketed in 1976 and works similarly to ibuprofen. But it has a longer half-life, giving it a longer-lasting effect. Both ibuprofen and naproxen decrease the formation of prostaglandins in the stomach. These chemicals produced by the body have hormonelike effects, protecting the stomach lining from acidity. The decrease of prostaglandins can injure the stomach lining, leading to stomach inflammation, ulcers and possibly severe bleeding.

Celecoxib (Celebrex) is a more selective NSAID and does not decrease prostaglandins in the stomach. This translates into significantly less likelihood of creating ulcerations.

All NSAIDs also reduce prostaglandins in the kidneys, which can lead to kidney injury. This injury becomes worse in people who have a history of chronic kidney disease, who are older, or who have congestive heart failure or cirrhosis.

Lastly, the chronic use of high-dose NSAIDs has been linked to an increased risk of heart attacks. Celecoxib may have a slightly greater risk of this than ibuprofen and naproxen, but a recent New England Journal of Medicine study looking at those who used NSAIDs chronically for arthritis found no difference in cardiovascular events between celecoxib and either ibuprofen or naproxen.

Of the drugs you listed, my feeling is that acetaminophen is the safest when used regularly. However, I would use acetaminophen at no higher doses than 4,000 mg per day and, if you were to use it regularly, I would recommend decreasing this amount to 2,000 to 3,000 mg per day.

The NSAIDs -- ibuprofen, naproxen and celecoxib -- are needed by some who have inflammatory arthritis, and they are good medications in the short-term. I would caution against consistent long-term use, especially at high doses and especially if you have any history of heart disease.

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