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Understanding Anti-Inflammatory Medication - Part 2



Last week we discussed the process of inflammation as background to understanding the mechanism of action of anti-inflammatory medications.


A description was given of the biochemical processes that result in the signs and symptoms of inflammation: pain, redness, swelling and loss of function, if a localized process; headaches, fever, muscle and joint pain, if a systemic process.


There are two broad categories of drugs that treat inflammation, steroids and NSAIDs (non-steroidal anti-inflammatory drugs). Steroids (Cortisone, Prednisone, Medrol) are the most potent anti-inflammatory drugs available but if used chronically in therapeutic doses have potentially serious side effects. However, they can be used for short periods in low doses. If steroids had demonstrated a more acceptable safety profile, it is unlikely that NSAIDs would have been developed, but there are currently over two dozen drugs in this class with the most notable being ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and of course the very first NASID, aspirin. This class of medication is one of the most widely used in the world today.


Some basic biochemistry will assist you in understanding how NSAIDs work.


Our bodies function through millions of biochemical reactions that are mediated by special proteins called enzymes. Many of these reactions produce products necessary for health, but some produce substances that are undesirable. As mentioned last week, there are two important enzymes influenced to a variable degree by NASIDs, called COX-1 and COX-2. Both catalyze reactions that produce hormones called prostaglandins (PGs). The COX-1 enzyme is constantly active producing organ-protective PGs that function to insulate the lining of the stomach from acid irritation, balance the tendency for blood clotting, and assist in maintaining normal kidney function.


If a drug inhibits this enzyme, the protective PGs will not be produced, and this can lead to stomach ulcers, abnormal blood clotting with a tendency to bleeding, and kidney malfunction. The COX-2 enzyme is inactive until an inflammatory stimulus occurs. It is then activated and produces PGs that cause all of the inflammatory symptoms previously described, most problematic being pain. Drugs that inhibit the activity of the COX-2 enzyme improve pain and the other inflammatory symptoms.


Therefore, the ideal NSAID would be a strong inhibitor of the COX-2 enzyme and have minimal effect on COX-1. All of the NSAIDs have some inhibitory effects on both COX enzymes, but to varying degrees, and therefore can be divided into three categories: COX-1 selective (aspirin); non-selective, inhibiting COX-1 and 2 almost equally (ibuprofen, naproxen); and COX-2 selective (Celebrex, Vioxx). Two drugs, Voltaren (diclofenac) and Mobic (meloxicam) are in the non-selective group but do have more effect on COX-2 than the other drugs in this group.


Celebrex and Vioxx were released in early 2000 to much fan-fair with the hope that since they specifically and potently inhibited COX-2 with little effect on COX-1, they would provide better pain relief with minimal risk of side effects. Vioxx did provide superior pain relief but after a few short years on the market, it was noted to cause heart attacks, many fatal, and it was taken off the market.


There was concern about Celebrex causing similar problems, but the risk did not seem as great, so the FDA allowed continued marketing of the drug but with a ‘black box’ warning about potential cardiac side effects. Subsequently, an extensive clinical trial was completed with 24,000 participants over a four-year period with results showing that Celebrex, when compared to naproxen and ibuprofen, posed no greater risk for heart attack. The FDA is considering removing the ‘black box” warning.


In summary, all NSAIDs are relatively safe if used sporadically for short periods of time and at the recommended dosing. If chronic therapy is necessary in a patient with GI or kidney issues, Celebrex appears to be a safe choice for therapy (avoid if sulfur allergy). In a patient with cardiovascular disease, Naprosyn seems to be the safest. Ibuprofen would be a close second with two caveats: it has a tendency to elevate blood pressure more than the others and it can neutralize the cardio-protective effect of aspirin unless there is a 2-3-hour gap separating the time that the medications are taken. Mobic and Voltaren are very effective for arthritis pain because of enhanced COX-2 inhibition and lower GI side effects because of less inhibition of COX-1. However, liver and kidney function should be monitored.


Tylenol is not an NSAID and has very minimal benefits for arthritis pain although it is very safe to use. A little recognized pearl is the fact that Tylenol taken simultaneously with an NSAID significantly improves pain relief compared with the use of either alone. In fact, more than one trial has shown that naproxen 500mg with Tylenol 500mg or ibuprofen 600mg with Tylenol 500mg is more effective for relief of arthritis pain and some post- op pain than Percocet.


Hopefully, this information will assist you in making an informed decision, in consultation with your physician, about which NSAID to use if the need arises.



Dr. Tippett is the founder of Comprehensive Quality Healthcare Providers located at 1210 Commerce Dr. Suite 106, Greensboro, Ga. 30642. He can be reached at 706-510-3659. Visit his webpage at www.drtippett.com

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