Nonsteroidal anti-inflammatory drug gastropathy at the new millennium: mechanisms and prevention.
OBJECTIVE
Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxicity remains the most frequent adverse drug event in the United States. The objective of this review is to update clinicians in recent advances in basic and clinical investigation regarding the pathogenesis and management of NSAID gastropathy.


METHODS
Based upon an extensive review of the published literature and abstracts of key work within the past decade, the framework for new approaches to the prevention and treatment of NSAID-associated ulceration is summarized.


RESULTS
The pathophysiology of NSAID-induced injury to the GI tract is multifaceted and includes both prostaglandin-dependent and independent components. The pharmaceutical industry has capitalized on the identification of two different isoforms of cyclooxygenase, enabling the development of specific inhibitors of one isoform that minimizes prostaglandin-dependent mechanisms that contribute to NSAID-induced injury. Clinical trials support the efficacy and reduced toxicity of these agents. Because acid exacerbates the injury initiated by NSAIDs, potent acid suppressive therapy, typically with proton pump inhibitors, is another common approach to the treatment of NSAID-related dyspepsia as well as NSAID-induced ulcer disease.


CONCLUSIONS
Recent improvements in the understanding of NSAID-induced damage and new drug development have provided the opportunity for effective anti-inflammatory therapy with reduced GI toxicity. This illustrates the importance of identifying patients at risk for potential complications and the appropriate use of strategies to prevent and treat NSAID-induced complications.
Rich
M
M
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0362, USA.
Scheiman
J M
JM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004064:Digestive System / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D020011:Protective Agents / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D020011:Protective Agents; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases