Nonsteroidal Anti-Inflammatory Drugs

Definition

Nonsteroidal anti-inflammatory drugs are medicines that relieve pain, swelling, stiffness, and inflammation.

Purpose

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for a variety of painful conditions, including arthritis, bursitis, tendinitis, gout, menstrual cramps, sprains, strains, and other injuries. They are also given to control the pain of cancer and the side effects of radiation therapy.

A group of researchers associated with the Women's Health Initiative reported in 2003 that regular use of aspirin, ibuprofen, and other NSAIDs may help to lower a woman's risk of developing breast cancer. Further clinical trials are needed, however, to confirm the group's findings.

Description

Nonsteroidal anti-inflammatory drugs relieve pain, stiffness, swelling, and inflammation, but they do not cure the diseases or injuries responsible for these problems. Two drugs in this category, ibuprofen and naproxen, also reduce fever. Some nonsteroidal anti-inflammatory drugs can be bought over the counter; others are available only with a prescription from a physician or dentist.

Among the drugs in this group are diclofenac (Voltaren), etodolac (Lodine), flurbiprofen (Ansaid), ibuprofen (Motrin, Advil, Rufen), ketorolac (Toradol), nabumetone (Relafen), naproxen (Naprosyn); naproxen sodium (Aleve, Anaprox, Naprelan); and oxaprozin (Daypro). They are sold as tablets, capsules, caplets, liquids, and rectal suppositories and some are available in chewable, extended-release, or delayed-release forms.

A newer group of NSAIDs known as COX-2 inhibitors are being used successfully to treat patients with allergic reactions to the older NSAIDs. Their name comes from the fact that they block an enzyme known as cyclooxygenase-2, or COX-2, which is involved in the inflammation pathway. The COX-2 inhibitors are also less likely to affect the patient's digestive tract. They include such drugs as celecoxib (Celebrex), rofecoxib (Vioxx), etoricoxib (Arcoxia), and valdecoxib (Bextra). With regard to cancer treatment, some studies indicate that the use of COX-2 inhibitors may postpone the need to prescribe narcotic medications for severe pain.

Recommended dosage

Recommended doses vary, depending on the patient, the type of nonsteroidal anti-inflammatory drug prescribed, the condition for which the drug is prescribed, and the form in which it is used. Always take nonsteroidal anti-inflammatory drugs exactly as directed. If using non-prescription (over-the-counter) types, follow the directions on the package label. For prescription types, check with the physician who prescribed the medicine or the pharmacist who filled the prescription. Never take larger or more frequent doses, and do not take the drug for longer than directed. Patients who take nonsteroidal anti-inflammatory drugs for severe arthritis must take them regularly over a long time. Several weeks may be needed to feel the results, so it is important to keep taking the medicine, even if it does not seem to be working at first.

When taking nonsteroidal anti-inflammatory drugs in tablet, capsule, or caplet form, always take them with a full, 8-ounce glass of water or milk. Taking these drugs with food or an antacid will help prevent stomach irritation.

Precautions

Nonsteroidal anti-inflammatory drugs can cause a number of side effects, some of which may be very serious (See Side effects). These side effects are more likely when the drugs are taken in large doses or for a long time or when two or more nonsteroidal anti-inflammatory drugs are taken together. Health care professionals can help patients weigh the risks of benefits of taking these medicines for long periods.

Do not take acetaminophen, aspirin, or other salicylates along with other nonsteroidal anti-inflammatory drugs for more than a few days unless directed to do so by a physician. Do not take ketorolac (Toradol) while taking other nonsteroidal anti-inflammatory drugs unless directed to do so by a physician.

Because older people are more sensitive than younger adults to nonsteroidal anti-inflammatory drugs, they may be more likely to have side effects. Some side effects, such as stomach problems, may also be more serious in older people.

Serious side effects are especially likely with one nonsteroidal anti-inflammatory drug, phenylbutazone. Patients age 40 and over are especially at risk of side effects from this drug, and the likelihood of serious side effects increases with age. Because of these potential problems, it is especially important to check with a physician before taking this medicine. Never take it for anything other than the condition for which it was prescribed, and never share it—or any other prescription drug—with another person.

Some nonsteroidal anti-inflammatory drugs can increase the chance of bleeding after surgery (including dental surgery), so anyone who is taking the drugs should alert the physician or dentist before surgery. Avoiding the medicine or switching to another type in the days prior to surgery may be necessary.

Some people feel drowsy, dizzy, confused, light-headed, or less alert when using these drugs. Blurred vision or other vision problems also are possible side effects. For these reasons, anyone who takes these drugs should not drive, use machines or do anything else that might be dangerous until they have found out how the drugs affect them.

Nonsteroidal anti-inflammatory drugs make some people more sensitive to sunlight. Even brief exposure to sunlight can cause severe sunburn, rashes, redness, itching, blisters, or discoloration. Vision changes also may occur. To reduce the chance of these problems, avoid direct sunlight, especially from mid-morning to mid-afternoon; wear protective clothing, a hat, and sunglasses; and use a sunscreen with a skin protection factor (SPF) rating of at least 15. Do not use sunlamps, tanning booths or tanning beds while taking these drugs.

Special conditions

People with certain medical conditions and people who are taking some other medicines can have problems if they take nonsteroidal anti-inflammatory drugs. Before taking these drugs, be sure to let the physician know about any of these conditions:

ALLERGIES. Let the physician know about any allergies to foods, dyes, preservatives, or other substances. Anyone who has had reactions to nonsteroidal anti-inflammatory drugs in the past should also check with a physician before taking them again.

PREGNANCY. Women who are pregnant or who plan to become pregnant should check with their physicians before taking these medicines. Whether non-steroidal anti-inflammatory drugs cause birth defects in people is unknown, but some do cause birth defects in laboratory animals. If taken late in pregnancy, these drugs may prolong pregnancy, lengthen labor time, cause problems during delivery, or affect the heart or blood flow of the fetus.

BREASTFEEDING. Some nonsteroidal anti-inflammatory drugs pass into breast milk. Women who are breastfeeding should check with their physicians before taking these drugs.

OTHER MEDICAL CONDITIONS. A number of medical conditions may influence the effects of nonsteroidal anti-inflammatory drugs. Anyone who has any of the conditions listed below should tell his or her physician about the condition before taking nonsteroidal anti-inflammatory drugs.

• stomach or intestinal problems, such as colitis or Crohn's disease
• liver disease
• current or past kidney disease ; current or past kidney stones
• heart disease
• high blood pressure
• blood disorders, such as anemia, low platelet count, low white blood cell count
• bleeding problems
• diabetes mellitus
• hemorrhoids, rectal bleeding, or rectal irritation
• asthma
• Parkinson's disease
• epilepsy
• systemic lupus erythematosus

• diseases of the blood vessels, such as polymyalgia rheumatica and temporal arteritis
• fluid retention
• alcohol abuse
• mental illness.

People who have sores or white spots in the mouth should tell the physician about them before starting to take nonsteroidal anti-inflammatory drugs. Sores or white spots that appear while taking the drug can be a sign of serious side effects.

SPECIAL DIETS. Some nonsteroidal anti-inflammatory drugs contain sugar or sodium, so anyone on a low-sugar or low-sodium diet should be sure to tell his or her physician.

SMOKING. People who smoke cigarettes may be more likely to have unwanted side effects from this medicine.

USE OF CERTAIN MEDICINES. Taking nonsteroidal anti-inflammatory drugs with certain other drugs may affect the way the drugs work or increase the risk of unwanted side effects. (See Interactions.)

Side effects

The most common side effects are stomach pain or cramps, nausea, vomiting, indigestion, diarrhea, heartburn, headache, dizziness or lightheadedness, and drowsiness. As the patient's body adjusts to the medicine, these symptoms usually disappear. If they do not, check with the physician who prescribed the medicine.

Serious side effects are rare, but do sometimes occur. If any of the following side effects occur, stop taking the medicine and get emergency medical care immediately:

• swelling or puffiness of the face
• swelling of the hands, feet, or lower legs
• rapid weight gain
• fainting
• breathing problems
• fast or irregular heartbeat
• tightness in the chest

Other side effects do not require emergency medical care, but should have medical attention. If any of the following side effects occur, stop taking the medicine and call the physician who prescribed the medicine as soon as possible:

• severe pain, cramps, or burning in the stomach or abdomen
• convulsions
• fever
• severe nausea, heartburn, or indigestion
• white spots or sores in the mouth or on the lips
• rashes or red spots on the skin
• any unusual bleeding, including nosebleeds, spitting up or vomiting blood or dark material
• black, tarry stool
• chest pain
• unusual bruising
• severe headaches

A number of less common, temporary side effects are also possible. They usually do not need medical attention and will disappear once the body adjusts to the medicine. If they continue or interfere with normal activity, check with the physician. Among these side effects are:

• gas, bloating, or constipation
• bitter taste or other taste changes
• sweating
• restlessness, irritability, anxiety
• trembling or twitching

Some patients who have had problems with side effects from NSAIDs may benefit from acupuncture as an adjunctive treatment in pain management. A recent study done in New York found that older patients with lower back pain related to cancer reported that their pain was relieved by acupuncture with fewer side effects than those caused by NSAIDs.

Interactions

Nonsteroidal anti-inflammatory drugs may interact with a variety of other medicines. When this happens, the effects of the drugs may change, and the risk of side effects may be greater. Anyone who takes these drugs should let the physician know all other medicines he or she is taking. Among the drugs that may interact with nonsteroidal anti-inflammatory drugs are:

• blood thinning drugs, such as warfarin (Coumadin)
• other nonsteroidal anti-inflammatory drugs
• heparin
• tetracyclines
• cyclosprorine

• digitalis drugs
• lithium
• phenytoin (Dilantin)
• zidovudine (AZT, Retrovir).

NSAIDs may also interact with certain herbal preparations sold as dietary supplements. Among the herbs known to interact with NSAIDs are bearberry (Arctostaphylos uva-ursi ), feverfew (Tanacetum parthenium ), evening primrose (Oenothera biennis ), and gossypol, a pigment obtained from cottonseed oil and used as a male contraceptive. In most cases, the herb increases the tendency of NSAIDs to irritate the digestive tract. It is just as important for patients to inform their doctor of herbal remedies that they take on a regular basis as it is to give the doctor a list of their other prescription medications.

KEY TERMS

Anemia— A lack of hemoglobin—the compound in blood that carries oxygen from the lungs throughout the body and brings waste carbon dioxide from the cells to the lungs, where it is released.

Bursitis— Inflammation of the tissue around a joint.

Colitis— Inflammation of the colon (large bowel.

COX-2 inhibitors— A class of newer NSAIDs that are less likely to cause side effects in the digestive tract. COX-2 inhibitors work by inhibiting the production of cyclooxygenase-2, an enzyme involved in inflammation.

Inflammation— Pain, redness, swelling, and heat that usually develop in response to injury or illness.

Salicylates— A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain, reduce inflammation, and lower fever.

Tendinitis— Inflammation of a tendon, which is a tough band of tissue that connects muscle to bone.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Drug Therapy in the Elderly." Section 22, Chapter 304 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Pelletier, Dr. Kenneth R. The Best Alternative Medicine, Part I: Western Herbal Medicine. New York: Simon and Schuster, 2002.

Wilson, Billie Ann, RN, PhD, Carolyn L. Stang, PharmD, and Margaret T. Shannon, RN, PhD. Nurses Drug Guide 2000. Stamford, CT: Appleton and Lange, 1999.

PERIODICALS

Birbara, C. A., A. D. Puopolo, D. R. Munoz, et al. "Treatment of Chronic Low Back Pain with Etoricoxib, A New Cyclo-Oxygenase-2 Selective Inhibitor: Improvement in Pain and Disability—A Randomized, Placebo-Controlled, 3-Month Trial." Journal of Pain 4 (August 2003): 307-315.

Gordon, D. B. "Nonopioid and Adjuvant Analgesics in Chronic Pain Management: Strategies for Effective Use." Nursing Clinics of North America 38 (September 2003): 447-464.

Graf, C., and K. Puntillo. "Pain in the Older Adult in the Intensive Care Unit." Critical Care Clinics 19 (October 2003): 749-770.

Harris, R. E., R. T. Chlebowski, R. D. Jackson, et al. "Breast cancer and Nonsteroidal Anti-Inflammatory Drugs: Prospective Results from the Women's Health Initiative." Cancer Research 63 (September 15, 2003): 6096-6101.

Hatsiopoulou, O., R. I. Cohen, and E. V. Lang. "Postprocedure Pain Management of Interventional Radiology Patients." Journal of Vascular and Interventional Radiology 14 (November 2003): 1373-1385.

Meng, C. F., D. Wang, J. Ngeow, et al. "Acupuncture for Chronic Low Back Pain in Older Patients: A Randomized, Controlled Trial." Rheumatology (Oxford) 42 (December 2003): 1508-1517.

Perrone, M. R., M. C. Artesani, M. Viola, et al. "Tolerability of Rofecoxib in Patients with Adverse Reactions to Nonsteroidal Anti-Inflammatory Drugs: A Study of 216 Patients and Literature Review." International Archives of Allergy and Immunology 132 (September 2003): 82-86.

Raffa, R. B., R. Clark-Vetri, R. J. Tallarida, and A. I. Wertheimer. "Combination Strategies for Pain Management." Expert Opinion in Pharmacotherapy 4 (October 2003): 1697-1708.

Small, R. C., and A. Schuna. "Optimizing Outcomes in Rheumatoid Arthritis." Journal of the American Pharmaceutical Association 43, no. 5, Supplement 1 (September-October 2003): S16-S17.

Stephens, J., B. Laskin, C. Pashos, et al. "The Burden of Acute Postoperative Pain and the Potential Role of the COX-2-Specific Inhibitors." Rheumatology (Oxford) 42, Supplement 3 (November 2003): iii40-iii52.

ORGANIZATIONS

U. S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857. (888) 463-6332. 〈http://www.fda.gov〉.

Nonsteroidal anti-inflammatory drugs

Definition

Nonsteroidal anti-inflammatory drugs are medicines that relieve pain , swelling, stiffness, and inflammation.

Description

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for a variety of painful conditions, including arthritis, bursitis, tendonitis, gout, menstrual cramps, sprains , strains , and other injuries.

Although the NSAIDs are often discussed as a group, not all are approved for use in children. As of 2004, the following drugs are approved for pediatric use:

• Ibuprofen (Advil, Motrin, Nuprin).
• Indomethicin (Indocin), not recommended for children under the age of 14 except in circumstances that warrant the risk. Indomethicin has special application in some infants born with heart problems.
• Ketoprofen (Orudis, Oruvail), not given to children under the age of 16 unless directed by a physician.
• Ketorolac tromethamine (Toradol), not approved for use in children but has been reported safe by some pediatric authorities.
• Meclofenamate sodium, safety and efficacy in children under 14 years of age has not been established.
• Mefenamic acid (Ponstel), safety and efficacy in children under 14 years of age has not been established.
• Naproxen (Aleve, Anaprox, Naprosyn), safety and efficacy in children under two years of age has not been established.
• Tolmetin sodium (Tolectin), safety and efficacy in children under two years of age has not been established.

Other NSAIDs have been used in pediatric therapy, but should not be considered as first choice for treatment of children or adolescents.

A new class of NSAIDs, called COX-2 inhibitors, have a lower risk of causing ulcers than do the traditional NSAIDs. These drugs may be appropriate for use in older teenagers but have not been approved for use in younger children, and there is some evidence that they are inappropriate for infants.

General use

Nonsteroidal anti-inflammatory drugs relieve pain, stiffness, swelling, and inflammation, but they do not cure the diseases or injuries responsible for these problems. Two drugs in this category, ibuprofen and naproxen, also reduce fever . Some nonsteroidal anti-inflammatory drugs can be bought without a prescription; others are available only with a prescription from a physician or dentist.

Precautions

Children with certain medical conditions and those who are taking some other medicines can have problems if they take nonsteroidal anti-inflammatory drugs. Before giving children these drugs, parents need to let the physician know about any of the following conditions.

Allergies

The physician needs to know about any allergies to foods, dyes, preservatives, or other substances. For children who have had reactions to nonsteroidal anti-inflammatory drugs in the past, parents should check with a physician before having these drugs prescribed again.

Pregnancy

Teens and young women who are pregnant or who plan to become pregnant should check with their physicians before taking these medicines. Whether nonsteroidal anti-inflammatory drugs cause birth defects in people is unknown, but some do cause birth defects in laboratory animals. If taken late in pregnancy, these drugs may prolong pregnancy, lengthen labor time, cause problems during delivery, or affect the heart or blood flow of the fetus.

Breastfeeding

Some nonsteroidal anti-inflammatory drugs pass into breast milk. Women who are breastfeeding their babies should check with their physicians before taking these drugs.

Other medical conditions

A number of medical conditions may influence the effects of nonsteroidal anti-inflammatory drugs. Parents of children and teens who have any of the conditions listed below should tell their physician about the condition before having nonsteroidal anti-inflammatory drugs prescribed.

• stomach or intestinal problems, such as colitis or Crohn's disease
• liver disease
• current or past kidney disease or current or past kidney stones
• heart disease
• high blood pressure
• blood disorders, such as anemia, low platelet count , low white blood cell count
• bleeding problems
• diabetes mellitus
• hemorrhoids, rectal bleeding, or rectal irritation
• asthma
• epilepsy
• systemic lupus erythematosus
• diseases of the blood vessels, such as polymyalgia rheumatica and temporal arteritis
• fluid retention
• alcohol abuse
• mental illness

Side effects

The most common side effects are stomach pain or cramps, nausea , vomiting , indigestion, diarrhea , heartburn, headache , dizziness or lightheadedness, and drowsiness. As the patient's body adjusts to the medicine, these symptoms usually disappear. If they do not, the physician who prescribed the medicine should be contacted.

Serious side effects are rare, but do sometimes occur. If any of the following side effects occur, patients should stop taking the medicine and get emergency medical care immediately:

• swelling or puffiness of the face
• swelling of the hands, feet, or lower legs
• rapid weight gain
• fainting
• breathing problems
• fast or irregular heartbeat
• tightness in the chest

Other side effects do not require emergency medical care, but should have medical attention. If any of the following side effects occur, patients should stop taking the medicine and the physician who prescribed the medicine should be called as soon as possible:

• severe pain, cramps, or burning in the stomach or abdomen
• convulsions
• fever
• severe nausea, heartburn, or indigestion
• white spots or sores in the mouth or on the lips
• rashes or red spots on the skin
• any unusual bleeding, including nosebleeds and spitting up or vomiting blood or dark material
• black, tarry stool
• chest pain
• unusual bruising
• severe headaches

A number of less common, temporary side effects are also possible. They usually do not need medical attention and will disappear once the body adjusts to the medicine. If they continue or interfere with normal activity, the physician should be contacted. Among these side effects are:

• gas, bloating, or constipation
• bitter taste or other taste changes
• sweating
• restlessness, irritability, anxiety
• trembling or twitching

Interactions

Nonsteroidal anti-inflammatory drugs may interact with a variety of other medicines. When interaction occurs, the effects of the drugs may change, and the risk of side effects may be greater. Physicians prescribing this drug should know all other medicines the patient is already taking. Among the drugs that may interact with nonsteroidal anti-inflammatory drugs are:

• blood thinning drugs, such as warfarin (Coumadin)
• other nonsteroidal anti-inflammatory drugs
• heparin
• tetracyclines
• cyclosprorine
• digitalis drugs
• lithium
• phenytoin (Dilantin)
• zidovudine (AZT, Retrovir)

NSAIDs may also interact with certain herbal preparations sold as dietary supplements. Among the herbs known to interact with NSAIDs are bearberry (Arctostaphylos uva-ursi ), feverfew (Tanacetum parthenium ), evening primrose (Oenothera biennis ), and gossypol, a pigment obtained from cottonseed oil and used as a male contraceptive. In most cases, the herb increases the tendency of NSAIDs to irritate the digestive tract. It is just as important for doctors to know which herbal remedies the patient is taking on a regular basis as it is for doctors to know the other prescription medications which are being taken.

Prevention

Many serious digestive system effects of NSAIDs can be prevented by taking mysoprostol (Cytotec), but this drug is only appropriate for patients with a high risk of ulcers. It is not called for when the NSAID is being used for a short period of time or in patients with other risk factors. Stomach upset can often be prevented by taking NSAIDs with food or milk.

Parental concerns

NSAIDs are very safe when used properly over a short period of time. They should not be used for longer periods or in larger doses than indicated on the label. If NSAIDs are to be used for prolonged periods, as in juvenile rheumatoid arthritis, there is a risk of potentially serious stomach and intestinal problems.

KEY TERMS

Anemia —A lack of hemoglobin, the compound in blood that carries oxygen from the lungs throughout the body and brings waste carbon dioxide from the cells to the lungs, where it is released.

Bursitis —Inflammation of the tissue around a joint.

Colitis —Inflammation of the colon (large bowel).

COX-2 inhibitors —A class of newer NSAIDs that are less likely to cause side effects in the digestive tract. COX-2 inhibitors work by inhibiting the production of cyclooxygenase-2, an enzyme involved in inflammation.

Inflammation —Pain, redness, swelling, and heat that usually develop in response to injury or illness.

Salicylates —A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain, reduce inflammation, and lower fever.

Tendonitis —Inflammation of a tendon, which is a tough band of tissue that connects muscle to bone.

Resources

BOOKS

Pelletier, Kenneth R. The Best Alternative Medicine, Part I: Western Herbal Medicine. New York: Simon and Schuster, 2002.

PERIODICALS

Gordon, D. B. "Nonopioid and Adjuvant Analgesics in Chronic Pain Management: Strategies for Effective Use." Nursing Clinics of North America 38 (September 2003): 447–464.

Small, R. C., and A. Schuna. "Optimizing Outcomes in Rheumatoid Arthritis." Journal of the American Pharmaceutical Association 43, no. 5, suppl. 1 (September-October 2003): S16–S17.

Stempak, D., et al. "Single-dose and steady-state pharmacokinetics of celecoxib in children." Clinical Pharmacological Therapy 72, no. 5 (November 2002): 490–497.

ORGANIZATIONS

U. S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857. Web site: <http://www.fda.gov>.

WEB SITES

Pediatric Rheumatology Online Journal. Available online at <www.pedrheumonlinejournal.org/> (accessed on September 29, 2004).

Nancy Ross-Flanigan Rebecca J. Frey, PhD Samuel Uretsky, PharmD

Nonsteroidal Anti-Inflammatory Drugs

Definition
Purpose
Description
Recommended dosage
Precautions
Interactions

Definition

Nonsteroidal anti-inflammatory drugs (NSAIDs) are medications other than corticosteroids that relieve pain, swelling, stiffness, fever, and inflammation. The most commonly used NSAIDs, including aspirin, ibuprofen, and naproxen, are available as over-the-counter (OTC) preparations; most, however, are prescription drugs. The use of NSAIDs for inflammation and low-grade pain is steadily increasing; in the early 2000s, these drugs accounted for 70 million prescriptions and 30 billion OTC purchases every year in the United States alone. They are one of the oldest classes of pain relievers, aspirin having been introduced for human use in 1829. One important reason why NSAIDs are so widely prescribed and recommended is that they have a very low rate of addiction.

Purpose

Nonsteroidal anti-inflammatory drugs are prescribed for a variety of painful conditions, including arthritis, bursitis, tendinitis, gout, menstrual cramps, sprains, strains, and other injuries. They may be used for treatment of postsurgical pain that is either too mild to require narcotic analgesics or follows a period of use of stronger analgesics. Ketorolac (Toradol) may be used in place of narcotics for treatment of acute pain in patients who should not receive narcotics.

Description

The nonsteroidal anti-inflammatory drugs are a group of agents that inhibit prostaglandin synthetase, thereby reducing the process of inflammation. As a group, they are all effective analgesics. Some, including the salicylates, ibuprofen, and naproxen, are also useful antipyretics (fever-reducers).

Although NSAIDs fall into discrete chemical classes, they are usually divided into the nonselective NSAIDs and the COX-2 specific agents. Among the nonspecific NSAIDs are diclofenac (Voltaren), etodo-lac (Lodine), flurbiprofen (Ansaid), ibuprofen (Motrin, Advil, Rufen), ketoprofen (Orudis), ketorolac (Tora-dol), nabumetone (Relafen), naproxen (Naprosyn), naproxen sodium (Aleve, Anaprox, Naprelan), and oxaprozin (Daypro). The only COX-2 specific drug remaining on the market in the United States as of 2007 is celecoxib (Celebrex); four other drugs in this class were withdrawn in the United States in 2004 because of reports that they increased patients’ risks

KEY TERMS

Ankylosing spondylitis— An autoimmune disorder of the joints in the spinal column, usually marked by pain and stiffness in the lower part of the spine.

Antipyretic— A medication that lowers fever.

Bursitis— Inflammation of the tissue around a joint.

Inflammation— Pain, redness, swelling, and heat that usually develop in response to injury or illness.

Metabolites— The chemicals produced in the body after nutrients, drugs, enzymes or other materials have been changed (metabolized).

Salicylates— A group of drugs that includes aspirin and related compounds; used to relieve pain, reduce inflammation, and lower fever.

Tendinitis— Inflammation of a tendon—a tough band of tissue that connects muscle to bone.

of heart attack and stroke, and a fifth in Australia in 2007 because of reports of increased risk of liver failure.

Nonselective NSAIDS inhibit both cyclooxyge-nase 1 and cyclooxygenase 2 (COX-2). Cyclooxyge-nase 1 is important for such body processes as platelet aggregation, the regulation of blood flow in the kidney and stomach, and the regulation of gastric acid secretion. The inhibition of cyclooxygenase 1 is considered the primary cause of NSAID toxicity, including gastric ulceration and bleeding disorders. COX-2 is the primary cause of pain and inflammation. Cele-coxib is a relatively selective COX-2 agent; it may cause the same adverse effects as the nonselective drugs, although with somewhat reduced frequency.

The analgesic activity of NSAIDs has not been fully explained. Antipyretic activity may be caused by the inhibition of prostaglandin E2 (PGE2) synthesis.

Although not all NSAIDs have approved indications for all uses, as a class, they are used for:

• ankylosing spondylitis
• bursitis
• dental pain
• fever
• gout
• headache
• juvenile arthritis
• pain from metastatic bone cancer
• mild-to-moderate postoperative pain
• osteoarthritis

• premenstrual syndrome (PMS)
• primary dysmenorrhea (painful menstrual periods)
• renal colic
• rheumatoid arthritis
• tendinitis

As of the early 2000s, NSAIDs have been studied for their potential effectiveness in lowering the risk of certain types of cancer, particularly colon, prostate, and ovarian cancers. More research needs to be done, however, to confirm the drugs’ ability to protect against cancer.

Recommended dosage

Recommended doses vary, depending on the patient, the type of nonsteroidal anti-inflammatory drug prescribed, the condition for which the drug is prescribed, and the form in which it is used. The patient is advised to consult specific sources for detailed information or ask a physician.

Precautions

The most common hazard associated with NSAID use is gastrointestinal intolerance and ulceration. This may occur without warning and is a greater risk among patients over the age of 65. The risk appears to rise with increasing length of treatment and increasing dose. Patients should be aware of the warning signs of gastrointestinal (GI) bleeding.

Allergic reactions are rare, but may be severe. Patients who have allergic reactions to aspirin should not be treated with NSAIDs.

Because NSAID metabolites are eliminated by the kidney, renal toxicity should be considered. Clinicians should monitor kidney function before and during NSAID use.

Among the NSAIDs that are classed as pregnancy category B are ketoprofen, naproxen, naproxen sodium, flurbiprofen, and diclofenac. Category C NSAIDs include Etodolac, ketorolac, mefenamic acid, meloxicam, nabu-metone, oxaprozin, tolmetin, piroxicam, and celecoxib. Breastfeeding is not advised while taking NSAIDs.

Many other rare but potentially serious adverse effects have been reported with NSAIDs. The consumer should consult specific references.

Interactions

Many drug interactions have been reported with NSAID therapy. The most serious are those that may affect the bleeding hazards associated with NSAIDs. Consumers are advised to consult specific references for further information. A partial list of interacting drugs includes:

• blood-thinning drugs such as warfarin (Coumadin)
• other nonsteroidal anti-inflammatory drugs
• heparin
• tetracycline antibiotics
• cyclosporine
• digitalis drugs
• lithium
• methotrexate
• phenytoin (Dilantin)
• zidovudine (AZT, Retrovir)

Resources

BOOKS

AHFS: Drug Information. Washington, DC: American Society of Healthsystems Pharmacy, 2002.

Howardell, Maynard J. Trends in COX-2 Inhibitor Research. New York: Nova Science Publishers, 2006.

Karch, A. M. Lippincott’s Nursing Drug Guide. Springhouse, PA: Lippincott Williams & Wilkins, 2003.

McCleane, Gary, and Howard Smith, eds. Clinical Management of Bone and Joint Pain. New York: Haworth Medical Press, 2007.

Neal, Michael J. Medical Pharmacology at a Glance, 5th ed. Malden, MA: Blackwell Publishing, 2005.

PERIODICALS

Barron, M. C., and B. R. Rubin. “Managing Osteoarthritic Knee Pain.” Journal of the American Osteopathic Association 107 (November 2007): ES21–ES27.

Funk, C. D., and G. A. Fitzgerald. “COX-2 Inhibitors and Cardiovascular Risk.” Journal of Cardiovascular Pharmacology 50 (November 2007): 470–479.

Green, G. A. “Understanding NSAIDs: From Aspirin to COX-2.” Clinical Cornerstone 3 (May 2001): 50–60.

Slattery, M. L., W. Samowitz, M. Hoffman, et al. “Aspirin, NSAIDs, and Colorectal Cancer: Possible Involvement in an Insulin-Related Pathway.” Cancer Epidemiology, Biomarkers and Prevention 13 (April 2004): 538–545.

Stock, D., P. A. Groome, and D. R. Siemens. “Inflammation and Prostate Cancer: A Future Target for Prevention and Therapy?” Urologic Clinics of North America 35 (February 2008): 117–130.

ORGANIZATIONS

U.S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA (1-888-463-6332). http://www.fda.gov/ (accessed April 1, 2008).

U.S. Pharmacopoeia (USP). 12601 Twinbrook Parkway, Rockville, MD 20852-1790. (800) 227-8772. http://www.usp.org/ (accessed April 1, 2008).

Samuel D. Uretsky, PharmD

Rebecca Frey, PhD

Norepinephrine seeAdrenergic drugs

Nose job seeRhinoplasty

Nosocomial infections seeHospital-acquired infections

NSAIDs seeNonsteroidal anti-inflammatory drugs

Nuclear magnetic resonance seeMagnetic resonance imaging

Nonsteroidal Anti-Inflammatory Drugs

Definition

Nonsteroidal anti-inflammatory drugs are medications other than corticosteroids that relieve pain, swelling, stiffness, and inflammation.

Purpose

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for a variety of painful conditions, including arthritis, bursitis, tendinitis, gout, menstrual cramps, sprains, strains, and other injuries.

Description

The nonsteroidal anti-inflammatory drugs are a group of agents inhibiting prostaglandin synthetase, thereby reducing the process of inflammation. As a group, they are all effective analgesics. Some, including the salicylates, ibuprofen, and naproxene, are also useful antipyretics (fever-reducers).

Although the NSAIDs fall into discrete chemical classes, they are usually divided into the nonselective NSAIDs and the COX-2 specific agents. Among the nonspecific NSAIDs are diclofenac (Voltaren), etodolac (Lodine), flurbiprofen (Ansaid), ibuprofen (Motrin, Advil, Rufen), ketorolac (Toradol), nabumetone (Relafen), naproxen (Naprosyn), naproxen sodium (Aleve, Anaprox, Naprelan), and oxaprozin (Daypro). The COX-2 specific drugs are celecoxib (Celebrex) and rofecoxib (Vioxx).

Nonselective NSAIDs inhibit both cyclooxygenase 1 and cyclooxygenase 2 (COX-2). Cyclooxygenase 1 is important for homeostatic maintenance, such as platelet aggregation, the regulation of blood flow in the kidney and stomach, and the regulation of gastric acid secretion. The inhibition of cyclooxygenase 1 is considered the primary cause of NSAID toxicity, including gastric ulceration and bleeding disorders. COX-2 is the primary cause of pain and inflammation. Note that both celecoxib and rofecoxib are relatively selective, and may cause the same adverse effects as the nonselective drugs, although with somewhat reduced frequency.

The analgesic activity of NSAIDs has not been fully elucidated. Antipyretic activity may be caused by the inhibition of prostaglandin E2 (PGE2) synthesis.

Although not all NSAIDs have approved indications for all uses, as a class, they are used for:

• ankylosing spondylitis bursitis
• fever
• gout
• headache
• juvenile arthritis
• mild to moderate pain
• osteoarthritis
• PMS
• primary dysmennorhea
• rheumatoid arthritis
• tendinitis

Recommended dosage

Recommended doses vary, depending on the patient, the type of nonsteroidal anti-inflammatory drug prescribed, the condition for which the drug is prescribed, and the form in which it is used. Consult specific sources for detailed information.

Precautions

The most common hazard associated with NSAID use is gastrointestinal intolerance and ulceration. This may occur without warning, and is a greater risk among patients over the age of 65. The risk appears to rise with increasing length of treatment and increasing dose. Patients should be aware of the warning signs of gastrointestinal (GI) bleeding.

Allergic reactions are rare, but may be severe. Patients who have allergic reactions to aspirin should not be treated with NSAIDs.

Because NSAID metabolites are eliminated by the kidney, renal toxicity should be considered. Clinicians should monitor kidney function before and during NSAID use.

Among the NSAIDs that are classed as pregnancy category B are ketoprofen, naproxen, naproxen sodium, flurbiprofen, and diclofenac. Etodolac, ketorolac, mefenamic acid, meloxicam, nabumetone, oxaprozin, tolmetin, piroxicam, rofecoxib, and celecoxib are category C. Breastfeeding is not advised while taking NSAIDs.

Many other rare but potentially serious adverse effects have been reported with NSAIDs. Consult specific references.

Interactions

Many drug interactions have been reported with NSAID therapy. The most serious are those that may affect the bleeding hazards associated with NSAIDs. A partial list of interacting drugs follows. Consult specific references for further information.

KEY TERMS

Bursitis— Inflammation of the tissue around a joint.

Inflammation— Pain, redness, swelling, and heat that usually develop in response to injury or illness.

Salicylates— A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain, reduce inflammation, and lower fever.

Tendinitis— Inflammation of a tendon—a tough band of tissue that connects muscle to bone.

• blood thinning drugs, such as warfarin (Coumadin)
• other nonsteroidal anti-inflammatory drugs
• heparin
• tetracyclines
• cyclosporine
• digitalis drugs
• lithium
• phenytoin (Dilantin)
• zidovudine (AZT, Retrovir)

Nonsteroidal Anti-Inflammatory Drugs

Definition

Nonsteroidal anti-inflammatory drugs are medications other than corticosteroids that relieve pain , swelling, stiffness, and inflammation.

Purpose

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for a variety of painful conditions, including arthritis, bursitis, tendinitis, gout, menstrual cramps, sprains, strains, and other injuries.

Description

The nonsteroidal anti-inflammatory drugs are a group of agents inhibiting prostaglandin synthetase, thereby reducing the process of inflammation. As a

group, they are all effective analgesics. Some, including the salicylates, ibuprofen, and naproxene, are also useful antipyretics (fever-reducers).

Although the NSAIDs fall into discrete chemical classes, they are usually divided into the nonselective NSAIDs and the COX-2 specific agents. Among the nonspecific NSAIDs are diclofenac (Voltaren), eto-dolac (Lodine), flurbiprofen (Ansaid), ibuprofen (Motrin, Advil, Rufen), ketorolac (Toradol), nabumetone (Relafen), naproxen (Naprosyn), naproxen sodium (Aleve, Anaprox, Naprelan), and oxaprozin (Daypro). The COX-2 specific drugs are celecoxib (Celebrex) and rofecoxib (Vioxx).

Nonselective NSAIDs inhibit both cyclooxygenase 1 and cyclooxygenase 2 (COX-2). Cyclooxygenase 1 is important for homeostatic maintenance, such as platelet aggregation, the regulation of blood flow in the kidney and stomach, and the regulation of gastric acid secretion. The inhibition of cyclooxygenase 1 is considered the primary cause of NSAID toxicity, including gastric ulceration and bleeding disorders. COX-2 is the primary cause of pain and inflammation. Note that both celecoxib and rofecoxib are relatively selective, and may cause the same adverse effects as the nonselective drugs, although with somewhat reduced frequency.

The analgesic activity of NSAIDs has not been fully elucidated. Antipyretic activity may be caused by the inhibition of prostaglandin E2 (PGE2) synthesis.

Although not all NSAIDs have approved indications for all uses, as a class, they are used for:

• ankylosing spondylitis
• bursitis
• fever
• gout
• headache
• juvenile arthritis
• mild to moderate pain
• osteoarthritis
• PMS
• primary dysmennorhea
• rheumatoid arthritis
• tendinitis

Recommended dosage

Recommended doses vary, depending on the patient, the type of nonsteroidal anti-inflammatory drug prescribed, the condition for which the drug is prescribed, and the form in which it is used. Consult specific sources for detailed information.

Precautions

The most common hazard associated with NSAID use is gastrointestinal intolerance and ulceration. This may occur without warning, and is a greater risk among patients over the age of 65. The risk appears to rise with increasing length of treatment and increasing dose. Patients should be aware of the warning signs of gastrointestinal (GI) bleeding.

Allergic reactions are rare, but may be severe. Patients who have allergic reactions to aspirin should not be treated with NSAIDs.

Because NSAID metabolites are eliminated by the kidney, renal toxicity should be considered. Clinicians should monitor kidney function before and during NSAID use.

Among the NSAIDs that are classed as pregnancy category B are ketoprofen, naproxen, naproxen sodium, flurbiprofen, and diclofenac. Etodolac, ketorolac, mefenamic acid, meloxicam, nabumetone, oxaprozin, tolmetin, piroxicam, rofecoxib, and celecoxib are category C. Breastfeeding is not advised while taking NSAIDs.

Many other rare but potentially serious adverse effects have been reported with NSAIDs. Consult specific references.

KEY TERMS

Bursitis —Inflammation of the tissue around a joint.

Inflammation —Pain, redness, swelling, and heat that usually develop in response to injury or illness.

Salicylates —A group of drugs that includes aspirin and related compounds. Salicylates are used to relieve pain, reduce inflammation, and lower fever.

Tendinitis —Inflammation of a tendon—a tough band of tissue that connects muscle to bone.

Interactions

Many drug interactions have been reported with NSAID therapy. The most serious are those that may affect the bleeding hazards associated with NSAIDs.

A partial list of interacting drugs follows. Consult specific references for further information.

• blood thinning drugs, such as warfarin (Coumadin)
• other nonsteroidal anti-inflammatory drugs
• heparin
• tetracyclines
• cyclosporine
• digitalis drugs
• lithium
• phenytoin (Dilantin)
• zidovudine (AZT, Retrovir)

Samuel D. Uretsky PharmD