Physiological Effects Of Nsaid On Inflammation

Inflammation occurs when the immune system's surveillance team identifies harmful intruders or irritants or when it's triggered by stimuli such as trauma, surgery or ischemia (low oxygen availability). The body treats the situation as police would a crime scene. Like an eye-witness to the crime, inflammation signals danger, increasing blood flow and vessel membrane permeability, and directing white blood cells to the location of the invasion. In the event that a prolonged inflammatory effect is undesirable, an non-steroidal anti-inflammatory drug (NSAID) may be used to counteract the activity.

Inflammation, Prostaglandins and NSAIDs

Inflammatory effect is managed in part by chemicals called prostaglandins. Prostaglandins are physiological compounds derived from fatty acids that behave in similar fashion to hormones. Enzymes are protein-based biological molecules that hasten the chemical reactions involved in the production of prostaglandins. The specific enzyme named cyclo-oxygenase-2 (COX-2) plays a key role in creating the prostaglandins that promote localized inflammation.
Though moderate, appropriately timed inflammation is essential for physiological health and protection of the human organism, prolonged or excessive prostaglandin activity characteristic of chronic inflammatory diseases such as rheumatoid and osteoarthritis, Alzheimer's disease, arteriosclerosis and cancer becomes detrimental. Consequential scarring and dysfunction of body tissues and joints as well as systemic body strain compromises health over time. Suppression of COX-2 activity minimizes the damage potential of chronic inflammation. NSAIDS temporarily inhibit the activity of COX-2, interrupting the cascade of events associated with inflammatory overkill.

Suppression Duration

The duration of suppression of COX-2 through NSAIDs is relatively short, meaning that to attain long-term suppression requires continued consumption of the drug. The salicylates, a subgroup of NSAIDs that includes aspirin, perform irreversible inhibition of COX-2, which results in a slightly longer anti-inflammatory effect than the second subgroup, called prostaglandin synthetase inhibitors (PSI), which perform shorter-acting reversible enzyme inhibition. PSI drugs include the well-recognized ibuprofen (Advil, Motrin) and naproxen (Aleve).
An undesirable physiological effect of prolonged NSAID use is stomach damage. NSAIDs negatively impact the stomach through inhibition of the cyclooxygenase-1 (COX-1) enzyme. COX-1, while chemically similar to COX-2, has no impact on inflammation. Rather, it is responsible for generating mucus and bicarbonate, which protect the internal lining of the stomach from exposure to cytotoxic substances. Inhibiting COX-1, though unavoidable when taking NSAIDs, is clearly undesirable, as stripping the stomach of its protective barriers may lead to ulcerations and other pathologies in the GI tract. (Reference 1) Unfortunately, NSAIDs are "non-selective" drugs, incapable of distinguishing between the physiological intricacies of COX enzymes and ultimately suppressing both.

Selective NSAIDs

Over recent years, drug companies have developed "selective" NSAID drugs, including the familiar prescription agents Celebrex, Bextra and Vioxx. These agents target only COX-2 enzymes, theoretically providing inflammatory relief without consequence to the stomach. While effective on chronic pain and inflammation, gastrointestinal bleeding similar to that observed in users of non-selective NSAIDs has been noted, as has been negative effects on heart health, which have raised questions and prompted lawsuits related to the products' safety.