Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Overview

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed pain medications worldwide in the treatment of pain and inflammation in many conditions.

Uses

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. These drugs also are effective in some neuropathic pain syndromes when used with other analgesics. NSAIDs are generally indicated for the symptomatic relief of the following conditions:

• Rheumatoid arthritis
• Osteoarthritis
• Acute gout
• Inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome)
• Dysmenorrhoea (painful menstruation)
• Headache and migraine
• Postoperative pain
• Mild-to-moderate pain due to inflammation and tissue injury
• Back pain and sciatica
• Sprains, strains, and rheumatism
• Dental pain
• Pain from kidney stones (renal colic)
• Fever
• Other painful conditions

Drugs in the class

NSAIDs comprise a large class of drugs with many different options. There are several different types of these madications:

• Salicylates: Aspirin (Ascriptin, Bayer, Ecotrin), diflunisal (Dolobid, Diflunisal Tablets), salsalate (Argesic SA, Disalcid, Salflex, Salsitab, Mono Gesic)
• Arylalkanoic acids: Diclofenac (Voltaren, Cataflam), indomethacin (Indocin)
• 2-Arylpropionic acids (profens): Ibuprofen (Advil, Motrin), ketoprofen (Orudis, Oruvail), naproxen (Naprosyn, Alleve), carprofen
• Pyrroles: Ketorolac (Toradol)
• Enolic acids (oxicams): Piroxicam (Feldene), meloxicam (Mobic)
• Sulphonanilides: Nimesulide
• Napthylalkanones: Nabumetone (Relafen)

Mode of action

NSAIDs work by suppressing the production of fatty acids called prostaglandins that cause inflammation and pain. They do this by blocking the action of an enzyme, cyclooxygenase (COX). This enzyme is responsible for converting precursor acids into prostaglandins.

In the periphery NSAIDs work by decreasing the sensitivity of the nociceptor to painful stimuli induced by heat, trauma, or inflammation. In the central nervous system, they are thought to function as antihyperalgesics and block the increased transmission of repetitive incoming signals to higher centers. In effect, they modulate perception of pain caused by repetitive stimulation from the periphery.

Possible side effects

NSAIDs may cause a number of side effects. The two main adverse drug reactions, associated with NSAIDs use, are gastrointestinal effects and renal effects. These effects are dose-dependent, and in many cases severe enough to pose the risk of ulcer perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy.

• Gastrointestinal side effects. The most common risk of NSAIDs is that they can cause ulcers and other problems in your esophagus, stomach, or small intestine. Common gastrointestinal side effects include: nausea, dyspepsia, vomiting, diarrhea, gastric ulceration, gastric bleeding. Risk of ulceration increases with duration of therapy, and with higher doses. To help protect the stomach, NSAIDs should always be taken with food or directly after a meal.
• High blood pressure and kidney damage. NSAIDs reduce the blood flow to the kidneys, which makes them work more slowly. When your kidneys are not working well, fluid builds up in your body. The more fluid in your bloodstream, the higher your blood pressure. If you take NSAIDs in high doses, the reduced blood flow can permanently damage the kidneys.
• Allergic reactions. NSAIDs can also cause extreme allergic reactions. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Many specialists recommend that people who have asthma stay away from any NSAID, especially if they have sinus problems or nasal polyps.

Use of aspirin in children and teenagers with chicken pox or influenza has been associated with the development of Reye's syndrome (a potentially fatal disease that causes numerous detrimental effects to many organs). Therefore, aspirin and nonaspirin salicylates (e.g. salsalate) should not be used in children and teenagers with suspected or confirmed chicken pox or influenza.

Indomethacin, ketoprofen and piroxicam appear to have the highest prevalence of gastrointestinal side effects, while ibuprofen (lower doses) and diclofenac appear to have lower rates.

Serious side effects are especially likely with one nonsteroidal anti-inflammatory drug, phenylbutazone. Patients of age 40 and over are especially at risk of side effects from this drug, and the likelihood of serious side effects increases with age.

Contraindications

NSAIDs should not be used in the following cases:

• Allergy to aspirin or any NSAID
• Aspirin should not be used under the age of 16 years
• During pregnancy
• During breast feeding
• On blood thinning agents (anticoagulants)
• Suffering from a defect of the blood clotting system (coagulation)
• Active peptic ulcer

Cost

Numerous NSAIDs are available as generics: diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate, naproxen, piroxicam, sulindac, and tolmetin. Only meloxicam (brand name: Mobic), nabumetone (Relafen), and oxaprozin (Daypro) are available by brand name only. Generic medications may be an equally effective and less expensive treatment option.

Conclusions

All NSAIDs are similarly effective. The choice of which NSAID to try first is usually empiric. If one doesn't provide adequate pain control, try switching to another. All NSAIDS when used chronically can result in the development of ulcers. Follow with your doctor closely and watch for signs or symptoms of gastrointestinal bleeding such as stomach pain and blood in the stools. Some NSAIDs are available in extended-release formulations that require less frequent dosing.

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