Recent advances in gastric ulcer therapeutics.
In developed countries at least, ulcers related to Helicobacter pylori infection are becoming rarer. However, ulcers associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) remain a major clinical problem, which has not been solved through the introduction of selective inhibitors of cyclooxygenase (COX)-2. Recent studies suggest that NSAID-induced ulcers can be prevented largely through co-administration of a proton pump inhibitor to block acid secretion in the stomach. In patients requiring aspirin therapy to prevent cardiovascular diseases, co-administration of aspirin plus a proton pump inhibitor was found to be safer than using another anti-platelet therapy that does not block gastric prostaglandin production (e.g. clopidogrel). Several recent papers have clarified further the contribution of COX-2 to gastric mucosal defence and to the healing of ulcers. In some circumstances, COX-2 produces a highly potent gastroprotective substance (15-R-lipoxin A(4)), and analogues of this substance could have therapeutic value for preventing gastric ulceration. Nitric oxide-releasing NSAIDs continue to show promise in terms of limiting damage to the gastrointestinal tract, even when given in combination with aspirin. Recent studies support the notion that platelets make a major contribution to ulcer healing, and the release of several key growth factors from platelets appears to be regulated by proteinase-activated receptors.
Wallace
John L
JL
Department of Pharmacology & Therapeutics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada. wallacej@ucalgary.ca
D017302:Annexins / Q000502:physiology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D051546:Cyclooxygenase 2 / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D044463:Receptor, PAR-1 / Q000502:physiology; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D014945:Wound Healing
D017302:Annexins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044463:Receptor, PAR-1; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2