Prostaglandins: an overview of the worldwide clinical experience

Synthetic prostaglandins of the E series have cytoprotective and gastric antisecretory actions. Both actions are relevant to their therapeutic usefulness in treating and preventing gastrointestinal mucosal diseases. Controlled clinical studies have shown prostaglandins to be effective treatment for gastric and duodenal ulcer disease. Although used widely in dozens of foreign countries, however, prostaglandins have not been approved by the United States Food and Drug Administration for use in the treatment of peptic ulcer disease. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased incidence of gastric and duodenal ulcers, gastrointestinal bleeding, and increased morbidity and mortality. Misoprostol, a prostaglandin E1 analogue, is effective in preventing and treating NSAID-induced mucosal damage and has been approved by the Food and Drug Administration for the prevention of NSAID-associated gastric ulcers. Controlled studies have not provided convincing evidence that H2-receptor antagonists or sucralfate prevents NSAID-induced gastric ulcer. Preliminary clinical studies indicate that some E-prostaglandins may also be effective in treating and/or preventing stress ulcer, cystic fibrosis, and hepatorenal syndrome and in improving graft survival in renal transplant patients receiving cyclosporine. Additionally, in vitro and animal studies suggest that prostaglandins may have therapeutic value in inflammatory bowel disease, and they may promote cartilage repair by an inhibitory action on interleukin-1. The latter finding could be of major relevance in preventing cartilage destruction in rheumatic patients. Significant side effects associated with the clinical use of prostaglandins include mild to moderate diarrhea and stimulation of uterine contraction during early pregnancy. Prostaglandins are effective for the treatment of peptic ulcer disease and, to date, are the only effective therapy for preventing the total spectrum of NSAID-induced mucosal damage. These compounds may also prove effective in treating various inflammatory disorders.