Nonsteroidal Anti-Inflammatory Drugs and Inflammatory Bowel Disease

Nonsteroidal anti-inflammatory drugs (NSA!Ds)adversely affect the entire gastrointesrinal tract.The small intestinal side effects of NSAIDs arc well-characterized and are a source of bleeding and protein loss which contributes co iron deficiency and hypoalbuminE>mia, respectively.NSAIDs rarely cause strictures, but these may be pathognomic when they occur.There arc only isolated reports of small intestinal perforations and massive bleeding.The pathogenesis ofNSAID cnteroparhy can be divided into two stages.The first stage is characterized by specific biochemical damage, principally to cmerocyte mitochondria, followed by inhibition of generation of reparative prostaglandins.Collectively this causes a breach in mucosa!integrity with increased intestinal permeability, which leads Lo the second, nonspecific tissue stage, representing an interplay between luminal aggressive tactors and mucosa!defences.This results in inflammation and macroscopic damage.The large intestine is not subjected co the same type of damage, presumably because of the completeness of drug absorption from the small intestine.However, NSAIDs have been implicated in colonic perforations and bleeding, diverticulitis and occasionally colitis.NSAIDs arc recognized as one of four mam causes of relapse in inflammatory bowel disease (IBO), all of which may have the potential to increase intestinal permeability.Extensive studies in patients with Crohn's disease -including sequential changes in intestinal inflammation, intestinal permeability and T cell activation in response to treatment with elemental diets, along with comparative studies on the site ufneutrophil chemoattractants in lBD and NSAID enteropathy -suggest that the clinical spectrum of Crohn's disease can be viewed as two separate events.It is suggested that the relapse of Crohn's disease ( with ia; unchecked inflammation) involves mechanisms identical to the nonspecific second stage of NSAID enteropathy, fundamentally unrelated to the Departments of Clnucal B1ocl1emistry and Medicine, King's College ~clwol of Medicine and Dentistry, London, LI