Many of the NSAIDs currently in use have similar qualities and are grouped together. Many doctors call them "me too" medications because they are so similar in action. They do not contain any cortisone or its derivatives, hence the term nonsteroidal. They suppress inflammation, meaning that they reduce swelling, pain, tenderness, and redness as well as improve motion, hence the term, anti-inflammatory. Their exact modes of action are not known, but they seem to inhibit parts of a chemical cycle in the body that causes inflammation.

NSAIDs are the initial treatment of choice for most kinds of arthritis. They offer the best and safest help in reducing swelling and pain in joints and in managing fever. They usually begin to help in terms of weeks, though you can expect relief from fever within hours. However, sometimes they have to be given for months before improvement is apparent. In general, several NSAIDs will be tried before second-line drugs are considered.

The best known NSAID is aspirin, which is the original and oldest NSAID, in use since the last century before the Food and Drug Administration (FDA) was formed. For this reason aspirin has always been an over-the-counter drug. The other NSAIDs are prescription drugs except ibuprofen (Advil, Nuprin, and others), ketoprofen (Orudis KT, Actron), and naproxen (Aleve). Other NSAIDs must be approved by the FDA for use in people with arthritis. Acetaminophen (Tylenol and others) is considered a painkiller only and is also sold over the counter.

How NSAIDs are administered. All NSAIDs are administered by mouth, although aspirin is sometimes given by suppository. In Europe, suppositories are a popular way of administering NSAIDs because they reduce stomach pain and nausea, but they are less popular here because Americans are uncomfortable about administering drugs through the anus. Local irritation of the anal area is a possible side effect. At the moment, there are no NSAID skin-patch preparations, although the idea is good because skin patches allow even absorption. This will probably occur sometime in the future.

The NSAIDs differ markedly in how often they must be given. The most commonly used NSAIDs -- aspirin and the ibuprofen drugs -- have short blood-level times of a few hours. They must be given at least three or four times daily. Others such as Naproxen (Naprosyn) have longer blood-level times of twelve to fourteen hours after a dose and need to be given only two times daily. One drug, Feldene, has a half-life of greater than one day and can be given once daily.

Should NSAIDs be given with meals or between meals? Well, the drug level is higher if taken on an empty stomach, but stomach pain and nausea are also more frequent. Also, while a better drug level will be attained with between-meal dosage, it's easier for most people to remember to take the medicine at mealtimes. The specific time of day that medicine is given also matters. Most NSAIDs provide better results if given in higher doses at bedtime and in lower doses during the day. But with the short-acting medicines, daytime doses are just as necessary.

In short, if your medication is to be taken two times daily, take it at breakfast and at bedtime with a little food or milk. When medication once a day is possible, bedtime may be better. Also, when nausea is a problem, giving the evening dose at bedtime is better because the nausea occurs when you are asleep. No matter what they tell you, most NSAIDs keep fever down for no more than five hours regardless of the half-life of the medicine in the blood.

A definite concern to everyone is how long can NSAIDs be safely given? As far as anyone knows, they can be given for many years with no long-term dangers.

What type of relief to expect. NSAIDs have three main uses: to reduce swelling and inflammation; relieve pain; and reduce fever. NSAIDs improve fever the fastest. Reduction in an hour is frequent, though with JRA several hours may be necessary to control the high fever. Reducing pain in the joint is the next improvement, followed by reduced stiffness, reduced swelling and tenderness, and improvement of motion. Overall improvement in the joints can occur in a few days' time, but usually weeks and sometimes months can pass before noticeable improvement occurs. In fact, NSAIDs have allowed some patients to cut back on their intake of cortisone.

Until a few years ago, aspirin was the universal drug of choice for arthritis. However, since other NSAIDs have fewer side effects, the use of aspirin has been reduced. Also, because of Reye's syndrome, a terrible disease that affects the liver and brain of young children, its use has been severely restricted. Aspirin also causes liver function abnormalities in one in six children.

In the Physician's Desk Reference, there are more than thirty brands of NSAIDs listed that are on the market now, with perhaps twenty or more in the process of approval by the FDA. Part of the reason, of course, is the competitive spirit of our free economy, but another reason is that not everyone responds to a particular NSAID; therefore, several different ones are necessary. Some NSAIDs represent attempts to improve side effects such as headaches, drowsiness, or stomach pain and ulcers. Other NSAIDs can be given fewer times daily to increase compliance as mentioned.

When all things are considered, the treatment effects are the same with all the NSAIDs. No single one is clearly better than another. No single one has side effects that are absent in the others. The difference is that each person responds differently to each drug, and what helps one person will not help another. In addition, if one drug quits working, we need to be able to try another.

Every physician has a favorite NSAID that seems to work best for his or her patient. By using only a few NSAIDs, the doctor is more familiar with the dosage variations and usual side effects; this frequently results in better treatment than if she or he uses many NSAIDs on an infrequent basis and is not as familiar with individual variations of each one.

In general, NSAIDs should be given for one month before changing to another. There is a 50 percent chance that the first NSAID will be effective, and therefore a 50 percent chance for subsequent trials of different NSAIDs. It usually takes a trial of two or three NSAIDs before a safe and effective one is found. Usually a second-line drug is considered when two or three NSAIDs have been unsuccessful. If destructive arthritis appears or the disease worsens appreciably, second-line drugs are usually added.

Possible side effects of NSAIDs. The list of adverse effects of NSAIDs is long, but the major problems are few. The intestinal tract heads the list with nausea, abdominal pain, vomiting, and diarrhea. Anemia and blood or protein in the urine are next in frequency. Headache or drowsiness is infrequent. Changes in liver function frequently occur in children but not in adults who use aspirin, but changes in liver function are rare in children using the other NSAIDs.

About 5 percent of people receiving NSAIDs will have to discontinue them because of unacceptable side effects, particularly intestinal problems or anemia. A particular problem with aspirin is hemorrhaging in the intestinal tract in one in a hundred people taking aspirin.

The liver function tests used most often, called transaminase tests, monitor the enzymes the liver uses to break down chemicals in the body. The tests go by many names, but two are the SGOT and SGPT. They are done a few weeks after starting a new NSAID and every few months for a while to be sure that a particular medication is not injuring the liver. When the tests show results that are greater than two or three times normal, the doctor will usually tell you to stop the medicine and later may try to lower the daily dose to see if a lower dose will still help the arthritis and not cause the liver to function abnormally. Again, it's always a battle to find a medicine that helps the arthritis enough yet has minimal side effects.

NSAIDs cause anemia in 2 or 3 percent of people, though it's difficult to know whether the anemia is due to the arthritis or the medicine. Again, the usual sequence for a doctor to follow is to stop the medicine for a week or longer in order to see whether the blood count increases. The anemia can last for months or longer. The reason for the prolonged anemia is that the medication has depressed the blood-forming organs -- the bone marrow. You should pay attention to requests for a blood count safety check.

Urinalysis tests are used to check for blood or protein. When either is present in significant amounts in the urine specimen, it usually means that injury to the kidney has occurred. Aspirin rarely causes this type of problem; the injury more often occurs with one of the other NSAIDs. The same rules of stopping the drug, as mentioned above, apply here also.