title: Gastrointestinal damage from nonsteroidal anti-inflammatory drugs.
abstract: The mechanisms underlying the development of gastrointestinal (GI) damage by the NSAIDs differ considerably from drug to drug. Aside from environmental or intersubject influence (e.g., concurrent disease, physical or sociopsychologic stress, dietary and genetic status), the intrinsic pharmacokinetic and physicochemical differences in these drugs account for variations in their rate of absorption or uptake from the circulation into the GI mucosa. Differences in the preference for absorption in the different regions of the GI tract account for the propensity of these drugs to cause injury in those regions wherein they accumulate. Bacterial flora and food antigens may be particularly important in promoting injury in the lower intestinal tract, whereas in the sterile environment of the normal stomach these may have less significance (except in achlorhydric states). The multiple cellular actions of NSAIDs are reviewed and the consequences of inhibiting prostaglandin cyclo-oxygenase considered. Under some conditions, the excess production of vasoconstrictor leukotrienes/HETES relative to effects of cyclo-oxygenase inhibition is postulated to have particularly important consequences in the pathogenesis of mucosal injury by NSAIDs. These consequences are separate from the concept of prostaglandin deficiency previously suggested by others.
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001639:Bicarbonates / Q000378:metabolism; D004777:Environment; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D008084:Lipoxygenase / Q000096:biosynthesis; D009093:Mucus / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D013312:Stress, Physiological / Q000150:complications
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D005609:Free Radicals; D011453:Prostaglandins; D008084:Lipoxygenase