Adverse Effects of Non-Steroidal Anti-Inflammatory Drugs on the Gastrointestinal Tract. Part 1

Recent advances in our understanding of the mechanisms by which non-steroidal anti-inflammatory drugs (NSAIDs) alter the inflammation of arthritis also help to explain why NSAIDs often cause moderate to severe gastrointestinal (GI) side effects.

NSAIDs inhibit the activity of the enzyme cyclooxygenase found in many tissues. Cyclooxygenase converts arachidonic acid to molecules called prostaglandins. Prostaglandin production is critical for the normal function of the GI mucosa. Thus, NSAID inhibition of GI cyclooxygenase is correlated with the demonstrable adverse GI side effects when NSAIDs are employed as the primary medical therapy of arthritis.

The recent discovery of a second form of cyclooxygenase produced only at sites of inflammation led to the development of a class of cyclooxygenase inhibitors that would control the activities of inflammatory cells, and in theory, reduce the severity of concomitant GI reactions associated with conventional NSAID use. Thus, the cyclooxygenase produced constitutively (i.e., COX-1) would be spared by these new NSAIDs, whereas the cyclooxygenase type produced by human rheumatoid arthritis synovium or inflamed synovium of osteoarthritic joints (i.e., COX-2) would be inhibited. Since COX-2 biosynthesis is also stimulated by pro-inflammatory cytokines, which up-regulate the synthesis of extracellular matrix metalloproteinases, enzymes responsible for the destruction of cartilage and bone in arthritis, it followed that COX-2 inhibitors would be critical in the medical therapy of arthritis. Other strategies for suppressing cytokine activity, which contributes to arthritis symptoms, have been previously addressed.

The relative strength of NSAID inhibition of COX-1 and COX-2 have been extensively studied in order to establish effective dose and duration of use in clinical practice. In general, according to Drs. Paulus and Bulpitt, writing in the “Primer on the Rheumatic Diseases,” Edition 11, published by The Arthritis Foundation, the conventional NSAIDs, aspirin, indomethacin, tolmetin, naproxen, piroxicam and ibuprofen inhibit COX-1 at much lower concentrations than concentrations required to inhibit COX-2. By contrast, diclofenac and non-acetylated salicylate inhibit COX-1 and COX-2 approximately equally, whereas etodolac inhibits COX-2 at somewhat lower concentrations than concentrations required to inhibit COX-1.

People do not know when the urgent situation will happen. So, doctors and safety officials recommends you to have first aid kits in your workplace, office, car.