Gastrointestinal side effects associated with NSAID and aspirin use range in severity from minor, superficial mucosal injury to ul-ceration, perforation, gastric outlet obstruction, and hemorrhage. These effects represent a substantial source of drug-induced morbidity and mortality among Americans. Hospitalizations resulting from gastrointestinal disorders are at least six times more frequent in patients with arthritis who are taking NSAIDs compared with patients who are not. Up to 20% of patients taking long-term traditional NSAIDs have gastroduodenal ulcers, which can be observed by endoscopy; between 2% and 4% have symptomatic gastric ulcers; and between 1% and 2% have ulcer complications.
COX-1/COX-2 NSAIDs impart gastrointestinal damage via topical injury as well as by a systemic effect resulting from COX inhibition and a decrease in prostaglandin production. Infection with Helicobacter pylori (H. pylori) is an independent risk factor for gastrointestinal injury in patients receiving NSAIDs.
Topical Mucosal Injury
Topical mucosal injury secondary to NSAID use may be minor (e.g., focal or diffuse injury, typically limited to superficial cells lining the gastric lumen) or major (e.g., involving superficial cells as well as deeper glandular structures). Topical injury occurs rapidly, with one study documenting acute mucosal erosions and hemorrhage within 30 minutes of a single 75-mg dose of aspirin. Minor injury usually undergoes quick repair via restitution, a continuous process involving migration of cells from the underlying gastric glands. Major topical injury may occur when NSAIDs, which are weak acids, diffuse across the gastric mucosal barrier and become ionized and sequestered in the mucosal cells, leading to cytotoxicity and an altered local immune response.
Mucosal adaptation and a reduction in major mucosal injury may occur with chronic administration of damaging agents. Despite this, most patients who receive chronic high-dose NSAIDs exhibit major mucosal injury, a phenomenon that suggests that the mu-cosal adaptation process might be overwhelmed by these agents and cannot impede or reverse the damage-inducing process.
Agents that affect COX not only inhibit this portion of the inflammatory response but also have widespread physiological results from a decreased production of the beneficial eicosanoids (e.g., PGI2, prostaglandin E2 [PGE2] and thromboxane A2). The depletion of eicosanoids by agents that inhibit COX-1 compromises a variety of physiological gastroprotective mechanisms, including mucosal blood flow, secretion of mucus and bi-carbonate, and maintenance of a hydrophobic mucosal sur-face. Blocking the formation of PGI2 and PGE2 also has important implications in vascular homeostasis. Both PGI2 and PGE2 are important vasodilators in renal vascular beds; therefore, their inhibition may increase renal vasoconstriction, leading to sodium and water retention, edema, and hypertension. cialis canadian pharmacy