NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND INFLAMMATORY BOWEL-DISEASE

Nonsteroidal anti-inflammatory drugs (NSAIDs)adversely affect the enti re gastrointestinal tract. The small intestinal side effects of NSAIDs are well-characterized and are a source of bleeding and protein loss which contributes to iron deficiency and hypoalbuminemia, respectively . NSAIDs rarely cause strictures, but these may be pathognomic when th ey occur. There are only isolated reports of small intestinal perforat ions and massive bleeding. The pathogenesis of NSAID enteropathy can b e divided into two stages. The first stage is characterized by specifi c biochemical damage, principally to enterocyte mitochondria, followed by inhibition of generation of reparative prostaglandins. Collectivel y this causes a breach in mucosal integrity with increased intestinal permeability, which leads to the second, nonspecific tissue stage, rep resenting an interplay between luminal aggressive factors and mucosal defences. This results in inflammation and macroscopic damage. The lar ge intestine is not subjected to the same type of damage, presumably b ecause of the completeness of drug absorption from the small intestine . However, NSAIDs have been implicated in colonic perforations and ble eding, diverticulitis and occasionally colitis. NSAIDs are recognized as one of four main causes of relapse in inflammatory bowel disease (I BD), all of which may have the potential to increase intestinal permea bility. Extensive studies in patients with Crohn's disease - including sequential changes in intestinal inflammation, intestinal permeabilit y and T cell activation in response to treatment with elemental diets, along with comparative studies on the site of neutrophil chemoattract ants in IBD and NSAID enteropathy - suggest that the clinical spectrum of Crohn's disease can be viewed as two separate events. It is sugges ted that the relapse of Crohn's disease (with its unchecked inflammati on) involves mechanisms identical to the nonspecific second stage of N SAID enteropathy, fundamentally unrelated to the cause of Crohn's dise ase. The basic cause may be found by exploring the mechanism for the i nappropriate severity of the acute inflammatory response to luminal ag gressive factors.