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NSAIDs, such as aspirin, ibuprofen, and naproxen, are available over the counter and are prescribed in larger doses by physicians.

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Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as Over the Counter (OTC) pain relievers and are also prescribed by doctors in larger doses (prescription strength). NSAIDs reduce the production or release of prostaglandins, chemicals in the body responsible for inflammatory pain. Most NSAIDs are taken orally. There are many drugs, and the best drug varies from person to person. NSAIDs are nonspecific analgesics but are most commonly used
to treat musculoskeletal pains and headache. The most important side effect is peptic ulcer disease.

Nonsteroidal anti-inflammatory (NSAIDs) are a very diverse group of drugs. They all inhibit an enzyme called "cyclo-oxygenase" (COX). COX exists in many tissues and inhibition of this enzyme reduces the amount of chemicals known as "prostaglandins" in these sites. Prostaglandins have many roles, including the production of inflammation. Inhibition of COX by a NSAID, therefore, may reduce pain and inflammation.

There are at least two forms of COX. COX-1 is more involved in the normal functioning of organs like the stomach, while COX-2 is more involved when inflammation starts to occur. Most of the NSAIDs inhibit both COX-1 and COX-2. Recently, a few NSAIDs that selectively inhibit COX-2 have become available. These "COX-2 selective inhibitors" reduce the risks of some of the side effects associated with NSAID therapy.

NSAIDs that inhibit both COX-1 and COX-2 include:

Salicylates, like aspirin, diflunisal, choline magnesium trisalicylate, and salsalate
Proprionic acids, like ibuprofen (Motrin™), naproxen (Naprosyn™), fenoprofen, ketoprofen, flurbiprofen and oxaprozin
Acetic acids, like indomethacin (Indocin™), tolmetin, sulindac, diclofenac, ketorolac, and etodolac
Oxicams, like piroxicam (Feldene™)
Naphthlyalkanones, like nabumetone (Relafen™)
Fenamates, like mefenamic acid and meclofenamic acid
Pyrazoles, like phenylbutazone

The COX-2 selective inhibitors include:

celecoxib (Celebrex™)
meloxicam (Mobic™) when used at a lower dose.

There is large variation in the way patients respond to the NSAIDs. An individual may respond very well to some of these drugs and not at all to others. Some may be associated with side effects, whereas others are very well tolerated. The usual doses prescribed may be optimal in one case, but either too high or too low for another. Given all this variation, physicians often must try several of these drugs to identify the best one. Although usually a conventional dose is prescribed, the physician may decide to start with a relatively low dose and then increase the dose slowly to find the correct dose for the individual.

Side effects are relatively common with the NSAIDs. Gastrointestinal (GI) symptoms occur in about 10% of patients treated with the nonselective COX-1 and COX-2 NSAIDS, and ulcers occur in about 2%. The factors that have been associated with an increased risk of ulcers include advanced age, higher NSAID dose, administration of a corticosteroid drug along with the NSAID, a history of either ulcer disease or previous GI complications from NSAIDs, and probably heavy alcohol or cigarette use. Nausea and abdominal pain are poor predictors of serious GI toxicity and most patients who develop ulcers actually have no symptoms at all before the ulcer appears.

The risk of GI symptoms and ulcers also varies from drug to drug. In the large group of nonselective COX-1 and COX-2 NSAIDs, some are relatively less likely to cause these problems compared to the others. More importantly, the newer COX-2 selective drugs have been shown to reduce the risk of both GI symptoms and ulcer formation. The availability of these selective COX-2 selective drugs is widely considered to be an important advance for this reason. Still, there have not been enough scientific studies performed to know for sure whether the added cost of these drugs is balanced by their possible advantages. Most experts now feel that these drugs should be considered first-line at least for those patients who have a relatively increased risk of GI toxicity. The largest population for which this guideline would apply is the elderly.

The risk of ulcer also can be reduced by administering a so-called "gastroprotective" therapy along with the NSAID. The protective drugs include misoprostol; the so-called proton pump inhibitors, such as omeprazole and lansoprazole; and possibly higher doses of the H2 blockers, such as famotidine. Antacids can reduce symptoms but do not decrease ulcer risk.

All NSAIDs, including the selective COX-2 drugs, can cause renal toxicity and must be used cautiously in patients who have known kidney disease or may have kidney disease because of advanced age or a disease. The renal problems range from just swelling from fluid retention all the way to renal failure. Patients who receive these drugs should have kidney function monitored from time to time.

There may be an increased risk of heart problems or stroke in patients who are using NSAIDs. Therefore, low-dose aspirin should be taken by patients who are treated with either a nonselective NSAID or a COX-2 selective NSAID and who are at risk for a heart attack. The decision to treat with these drugs over a long period of time must be made case-by-case by a physician and patient after carefully weighing the risks and benefits.

The nonselective COX-1 and COX-2 NSAIDs inhibit the effects of platelets, which are cells in the blood stream that play an important role in clotting. Patients who take these drugs, therefore, have a relatively higher risk of bleeding. The selective COX-2 drugs have no effect on platelets.

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