Nonsteroidal anti-inflammatory drug gastropathy at the new millennium: mechanisms and prevention

Abstract

Objectives: 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.