Mechanisms of NSAID-induced ulcerogenesis: structural properties of drugs, focus on the microvascular factors, and novel approaches for gastro-intestinal protection.
The multifactorial ulcer-producing actions of non-steroidal anti-inflammatory drugs (NSAIDs) are briefly reviewed and the main actions highlighted as the focus for potential strategies for reducing the ulcerogenic effects of these drugs. While some clinical benefits are evident from long-term clinical studies from application of PG analogues (misoprostol) and H+/K(+)-ATP-ase inhibitors (omeprazole) these are, ultimately, expensive approaches. Chemical structural properties of the NSAIDs underlying differences in their ulcerogenicity are analyzed with the objective of establishing the reasons for the low ulcerogenicity of some of these drugs (e.g. azapropazone). These studies serve as a basis for developing less gastrotoxic drugs in the future. In the studies we have undertaken analysis of the benefits of micronutrients and of modulating eicosanoid metabolism have been considered. The results of some clinical trials with micronutrients have proven encouraging. These and other approaches and pitfalls reported give further encouragement to explore the mechanisms of the protective effects of these latter agents and serve as a basis for future developments.
Department of Biomedical Sciences, McMaster University, Faculty of Health Sciences, Hamilton, Ontario, Canada.
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Rainsford
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000633:toxicity; D005753:Gastric Mucosa / Q000098:blood supply; D006801:Humans; D007413:Intestinal Mucosa / Q000098:blood supply; D008833:Microcirculation / Q000502:physiology; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000178:diet therapy / Q000503:physiopathology / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal