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NSAIDs

Non Steroidal Anti-Inflammatory Drugs (pronounced EN-seds)


Non Steroidal Anti-Inflammatory Drugs (NSAIDs) are medications which, as well as having pain-relieving (analgesic) effects, have the effect of reducing inflammation when used over a period of time. These pharmaceutical agents constitute one of the most widely used class of drugs, with more than 70 million prescriptions and more than 30 billion over-the counter tablets sold annually in the United States alone. 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.

The best known NSAID, is the original and oldest, aspirin, 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. The NSAID group includes aspirin, ibuprofen (marketed under the names Motrin and Advil) and naproxen (Aleve). It does not include acetaminophen (Tylenol), which is effective against pain and fever but not against inflammation — which is a major factor in certain types of pain, such as the ache of rheumatoid arthritis.

Uses

NSAIDs can be used as simple pain killers (analgesics), but paracetamol is usually preferable, as it is likely to have less unwanted effects, and costs less. They are most useful in conditions which cause inflammation. The anti-inflammatory effects may take from a few days to three weeks to come on, so it is worth persevering for a while before deciding that a NSAID is not going to help.

Uses of NSAIDs:

  • The commonest use of these drugs is for arthritis. Paracetamol is often adequate for osteoarthritis, but NSAIDs are particularly useful in the inflammatory forms of arthritis (eg rheumatoid arthritis) and, sometimes, in the more severe forms of osteoarthritis.

  • Back pain and sciatica. Ibuprofen has been clearly demonstrated to be helpful, and the other NSAIDs are also helpful.

  • Sprains, strains, and rheumatism.

  • Dental pain.

  • Post-operative pain.

  • Period pain (dysmenorrhoea) and heavy periods (menorrhagia).

  • Pain from kidney stones (renal colic).

  • To help reduce temperature in someone with a fever.

  • Migraine.

  • Other painful conditions, especially where there is inflammation.

  • A recent Dutch study suggested that regular and long-term use of some NSAIDs could reduce the risk of Alzheimer's disease by as much as 80 percent. Note that this is only one study.

  • Most NSAIDs also reduce the temperature in someone with a fever.

Properties

Aspirin is the only one that is proven to offer significant protection against heart disease by interfering with blood clot formation and probably acting in other ways we do not understand. If ibuprofen is taken also, studies have shown that it can lessen the effectiveness of an aspirin regimen. Most experts believe an occasional ibuprofen for, say, a headache should not significantly interfere with the heart protective effect of regular aspirin.

The NSAIDs work by affecting some chemicals in the body which cause inflammation, the prostaglandins. Unfortunately the same group of chemicals are involved in the stomach, and so the NSAIDs tend to cause indigestion, and may even cause duodenal or stomach ulceration.

As a result of this side-effect they cannot be used in someone with a history of peptic ulcer, except in exceptional circumstances, under close medical supervision. Also they would rarely be used and, if used, only with extra care, in somebody with heartburn or indigestion.

In general, the more effective a NSAID is at reducing inflammation, the more likely it is to cause indigestion. Sometimes your doctor will prescribe them along with something to cut down the risk of ulceration. There is even one medication that contains both components together.

There have been recent advances, in that some NSAIDs are said to be more specific in dealing with inflammation and less likely to irritate the digestive (gastro-intestinal) system, but nothing has yet overcome this problem altogether.

The drugs vary in strength and side effects. Usually, as with other medications, the more effective they are, the more side-effects they are likely to have. Aspirin, which originated from willow bark, has been around for a long time and is in many people's medicine chests. This is an anti-inflammatory analgesic.

Of the newer medications in this group, the one in widest general use is Ibuprofen, which is available over the counter in many countries. 

Adverse Reactions

There are many other potential side effects, but these vary according to the drug chosen and the individual taking it. The other side effects are far less likely to occur.

Specific allergy to a NSAID can be quite dramatic, with rash, swelling of the face, and sometimes difficulty breathing. (If this happens you should call for help urgently.) As with other drugs, if you get a reaction which you suspect to be a side effect, stop taking it and check with your doctor. Sometimes, if the reaction involves an itchy rash and or swelling, it is worth trying an antihistamine in the meantime.

Some people with asthma react to the NSAIDs by getting more wheezy. If this happens you should stop the drug, and use your usual asthma medication, calling the doctor if this does not work.

There are many other questions to consider in using these drugs — such as cost and safety. All NSAIDs (including aspirin, of course) can increase the risk for ulcers and bleeding in the gastro-intestinal system, though some newer ones available by prescription (such as Celebrex and Vioxx) are less likely to do so. However, for most people, the much lower cost of older NSAIDs like aspirin, Motrin, Advil and Aleve will make them the drugs of choice.

NSAIDs cannot be used in the following cases:

  • When patient has an allergy to aspirin or any NSAID

  • During pregnancy

  • During breast feeding

  • While patient is on blood thinning agents (anticoagulants)

  • Suffering from a defect of the blood clotting system (coagulation)

  • While patient has an active peptic ulcer

  • While patient is being treated for a fracture use should be monitored (see below).

Care is needed if you have:

  • Asthma

  • Liver impairment

  • Heart impairment

  • Kidney impairment

A further word of caution

Since there is knowledge that these medications can cause stomach upset, other drugs, such as antacids, are prescribed to alleviate those symptoms. And while these additional medications may provide symptom relief they do not prevent the underlying damage that is occurring.  And by hiding these symptoms antacids actually increase the chances of having a serious problem.

There is a problem with all COX-1 inhibitors in the NSAID (nonsteroidal anti-inflammatory drug) family -- this includes the vast majority of painkillers, such as aspirin, ibuprofen (Motrin and Advil), naproxen (Aleve) and many others -- and with rofecoxib (Vioxx), a COX-2 inhibitor in the newer subset of NSAIDs. All of these drugs blunt the effect of blood pressure medication, potentially producing an increase of up to 15 mm HG in the systolic reading -- the top number and the one doctors worry about in people over the age of 50. 

Also, some painkillers may impede the healing of fractured bones. In animal studies, broken bones failed to heal fully when treated with Cox-2 inhibitors -- prescription NSAIDs, including Vioxx and Celebrex. Older NSAIDs, such as ibuprofen and naproxen, also appear to delay healing. NSAIDs inhibit the activity of the enzyme essential for fracture healing.

Another important observation is that most people have no warning signs that these drugs are causing them internal damage before they ending up in the hospital with a serious medical condition.  And as we have seen from the statistics, approximately 10% of these hospitalizations end in death. The risk appears to be especially great in patients using diuretics. (Diuretics are chemical substances that help to rid the body of excess fluids. They do this by forcing the kidneys to excrete urine more frequently, and in greater amounts. Dieters use diuretics to assist in weight loss. Athletes use diuretics in a variety of ways, the most common being weight maintenance. Sports with weight restrictions (such as rowing or wrestling) show the largest concentration of diuretic use.)

“Overall death estimates are similarly disquieting. Conservative calculations, counting only excess deaths, indicate that about 7,600 deaths/year in the United States are attributable to NSAID use. The Food and Drug Administration suggests even higher figures, estimating NSAID use accounts for 10,000 to 20,000 deaths/year. These figures are comparable to Hodgkin’s disease or acquired immunodeficiency syndrome and represent a serious problem.”1

Forms

These drugs are available in nearly every form:

  • By mouth, they come in tablets, capsules or medicines. This is the most widely used form.

  • Some NSAIDs are available as injections. This form is used for the pain after surgical operations and also is very effective for the treatment of pain produced by kidney stones (renal colic).

  • Suppositories are available. These are often used for post operative pain and sometimes in chronic pain when the patient is unable to take medication by mouth.

  • Creams, gels and foams to apply to the skin. These are not felt to be as effective, but some people do get considerable relief from their use.

Although non-oral routes of administration avoid the direct irritation of the stomach, they do not avoid the indigestion and ulcer risks, as these are caused by the chemical once it is in the blood stream.

Common over the counter names include: ibuprofen (Advil®), naproxen (Aleve®), and aspirin (Bayer®).  Perscription brands include: celecoxib (Celebrex®), diclofenac (Voltaren®), etodolac (Lodine®), fenoprefen (Nalfon®), indomethacin (Indocin®), ketoprofen (Orudis®, Oruvail®), ketoralac (Toradol®), oxaprozin (Daypro®), nabumetone (Relafen®), sulindac (Clinoril®), tolmetin (Tolectin®), and rofecoxib (Vioxx® -- now withdrawn).

1 Fries James F., “NSAID Gastropathy: The Second Most Deadly Rheumatic Disease?  Epidemiology and Risk Appraisal”, Journal of Rheumatology, 1991, (Supplement 28), Vol. 18, pp. 6-10

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