Bright-Asare P, Habte T, Yirgou B, Benjamin J
Digestive Diseases Research Center, King/Drew Medical Center, Los Angeles.
Drugs. 1988;35 Suppl 3:1-9. doi: 10.2165/00003495-198800353-00003.
Peptic ulcer develops when offensive factors overwhelm defensive processes in the gastroduodenal mucosa. Offensive factors include NSAIDs, hydrochloric acid-peptic activity, bile reflux, and some products of the lipoxygenase pathway such as leukotriene B4; whereas defensive processes are largely mediated by prostaglandins through poorly understood mechanisms uniformly termed cytoprotection. Cytoprotection, a physiological process working through the products of arachidonic acid metabolism, may result from the net effect of the protective actions of prostaglandins versus the damaging actions of leukotrienes. Some prostaglandins also have antisecretory effects. Therefore the peptic ulcer healing effects of prostaglandin analogues, all of which have significant antisecretory activity, may be more due to their antisecretory effects than primarily to their effects on mucosal defences. Certain drug-induced gastroduodenal lesions, e.g. NSAID-induced ulcers, which are often unresponsive to H2-receptor antagonists, have been healed and their recurrence prevented by the use of PGE1 and PGE2 analogues. All the prostaglandin analogues investigated to date in humans have the potential for inducing abortion, an important side effect which may limit their worldwide use. The optimal prostaglandin analogue for ulcer healing should not induce abortion and should be potently cytoprotective. The predominant damaging agent in the development of peptic ulcer disease is gastric hydrochloric acid. Thus, the worldwide established efficacy and safety of H2-receptor antagonists such as cimetidine, ranitidine, famotidine and most recently of roxatidine acetate suggest that these agents have become the standard by which other forms of anti-ulcer therapy should be judged.
当攻击因素超过胃十二指肠黏膜的防御过程时，消化性溃疡就会发生。攻击因素包括非甾体抗炎药、盐酸 - 胃蛋白酶活性、胆汁反流以及脂氧合酶途径的一些产物，如白三烯B4；而防御过程主要由前列腺素通过机制尚不清楚的统一称为细胞保护的过程介导。细胞保护是一种通过花生四烯酸代谢产物起作用的生理过程，可能是前列腺素的保护作用与白三烯的破坏作用的净效应所致。一些前列腺素还具有抗分泌作用。因此，前列腺素类似物的消化性溃疡愈合作用，所有这些都具有显著的抗分泌活性，可能更多是由于它们的抗分泌作用，而不是主要由于它们对黏膜防御的作用。某些药物引起的胃十二指肠病变，如非甾体抗炎药引起的溃疡，通常对H2受体拮抗剂无反应，使用PGE1和PGE2类似物已使其愈合并预防了复发。迄今为止在人类中研究的所有前列腺素类似物都有诱导流产的可能性，这是一个重要的副作用，可能会限制它们在全球的使用。用于溃疡愈合的最佳前列腺素类似物不应诱导流产，并且应具有强大的细胞保护作用。消化性溃疡疾病发展中的主要破坏因素是胃盐酸。因此，西咪替丁、雷尼替丁、法莫替丁以及最近的醋酸罗沙替丁等H2受体拮抗剂在全球范围内确立的疗效和安全性表明，这些药物已成为评判其他形式抗溃疡治疗的标准。
