Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Prostaglandins are a family of chemicals that are produced by the cells of the body and have several important functions. They promote inflammation that is necessary for healing, but also results in pain, and fever; support the blood clotting function of platelets; and protect the lining of the stomach from the damaging effects of acid.

Prostaglandins are produced within the body's cells by the enzyme cyclooxygenase (COX). There are two COX enzymes, COX-1 and COX-2. Both enzymes produce prostaglandins that promote inflammation, pain, and fever. However, only COX-1 produces prostaglandins that support platelets and protect the stomach. Nonsteroidal anti-inflammatory drugs (NSAIDs) block the COX enzymes and reduce prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced. Since the prostaglandins that protect the stomach and support platelets and blood clotting also are reduced, NSAIDs can cause ulcers in the stomach and promote bleeding.

The following list is an example of NSAIDs available:

• aspirin
• celecoxib (Celebrex)
• diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)
• diflunisal (Dolobid - discontinued brand)
• etodolac (Lodine - discontinued brand)
• ibuprofen (Motrin, Advil)
• indomethacin (Indocin)
• ketoprofen (Active-Ketoprofen [Orudis - discontinued brand])
• ketorolac (Toradol - discontinued brand)
• nabumetone (Relafen - discontinued brand)
• naproxen (Aleve, Anaprox, Naprelan, Naprosyn)
• oxaprozin (Daypro)
• piroxicam (Feldene)
• salsalate (Disalsate [Amigesic - discontinued brand])
• sulindac (Clinoril - discontinued brand)
• tolmetin (Tolectin - discontinued brand)

NSAIDs are associated with several side effects. The frequency of side effects varies among NSAIDs.

Common side effects are

• nausea,
• vomiting,
• diarrhea,
• constipation,
• decreased appetite,
• rash,
• dizziness,
• headache, and
• drowsiness.

Other important side effects are:

• kidney failure (primarily with chronic use),
• liver failure,
• ulcers, and
• prolonged bleeding after injury or surgery.

NSAIDs can cause fluid retention which can lead to edema, which is most commonly manifested by swelling of the ankles.

WARNING: Some individuals are allergic to NSAIDs and may develop shortness of breath when an NSAID is taken. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID.

Use of aspirin in children and teenagers with chickenpox or influenza has been associated with the development of Reye's syndrome, a serious and sometimes fatal liver disease. Therefore, aspirin and non-aspirin salicylates (for example, salsalate [Amigesic]) should not be used in children and teenagers with suspected or confirmed chickenpox or influenza.

NSAIDs increase the risk of potentially fatal, stomach and intestinal adverse reactions (for example, bleeding, ulcers, and perforation of the stomach or intestines). These events can occur at any time during treatment and without warning symptoms. Elderly patients are at greater risk for these adverse events. NSAIDs (except low dose aspirin) may increase the risk of potentially fatal heart attacks, stroke, and related conditions. This risk may increase with duration of use and in patients who have underlying risk factors for heart and blood vessel disease. Therefore, NSAIDs should not be used for the treatment of pain resulting from coronary artery bypass graft (CABG) surgery.

NSAIDs are used primarily to treat inflammation, mild to moderate pain, and fever.

Specific uses include the treatment of:

• headaches,
• arthritis,
• ankylosing spondylitis,
• sports injuries, and
• menstrual cramps.

Ketorolac (Toradol) is only used for short-term treatment of moderately severe acute pain that otherwise would be treated with narcotics.

Aspirin (also an NSAID) is used to inhibit the clotting of blood and prevent strokes and heart attacks in individuals at high risk for strokes and heart attacks.

NSAIDs also are included in many cold and allergy preparations.

Celecoxib (Celebrex) is used for treating familial adenomatous polyposis (FAP) to prevent the formation and growth of colon polyps.

NSAIDs vary in their potency, duration of action, how they are eliminated from the body, how strongly they inhibit COX-1 versus COX-2 and their tendency to cause ulcers and promote bleeding. The more an NSAID blocks COX-1, the greater is its tendency to cause ulcers and promote bleeding. One NSAID, celecoxib (Celebrex), blocks COX-2 but has little effect on COX-1, and is therefore further classified as a selective COX-2 inhibitor. Selective COX-2 inhibitors cause less bleeding and fewer ulcers than other NSAIDs.

Aspirin is a unique NSAID, not only because of its many uses, but because it is the only NSAID that inhibits the clotting of blood for a prolonged period of time (4 to 7 days). This prolonged effect of aspirin makes it an ideal drug for preventing blood clots that cause heart attacks and strokes.

Most NSAIDs inhibit the clotting of blood for only a few hours. Ketorolac (Toradol) is a very potent NSAID and is used for moderately severe acute pain that usually requires narcotics. Ketorolac causes ulcers more frequently than other NSAID. Therefore, it is not used for more than five days. Although NSAIDs have a similar mechanism of action, individuals who do not respond to one NSAID may respond to another.

NSAIDs reduce blood flow to the kidneys and therefore reduce the action of diuretics ("water pills") and decrease the elimination of lithium (Eskalith, Lithobid) and methotrexate (Rheumatrex, Trexall). As a result, the blood levels of these drugs may increase as may their side effects.

NSAIDs also decrease the ability of the blood to clot and therefore increase bleeding. When used with other drugs that also increase bleeding (for example, warfarin [Coumadin]), there is an increased likelihood of serious bleeding or complications of bleeding. Therefore, individuals who are taking drugs that reduce the ability of blood to clot should avoid prolonged use of NSAIDs.

NSAIDs also may increase blood pressure in patients with hypertension (high blood pressure) and therefore antagonize the action of drugs that are used to treat hypertension.

NSAIDs increase the negative effect of cyclosporine on kidney function.

Persons who have more than three alcoholic beverages per day may be at increased risk of developing stomach ulcers when taking NSAIDs.