Dobrilla G, Amplatz S, Benvenuti S, Di Fede F, Thaler W
Divisione di Gastroenterologia, Ospedale Generale Regionale, Bolzano, Italia.
An Med Interna. 1991 Sep;8(9):461-5.
According to the traditional view gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanisms of action--antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents--thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing yield contradictory clinical results; morning and bedtime single administrations of H2-antagonists prove equiactive on ulcer healing, leading to a reappraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby apparently undermining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the protonpump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility.
按照传统观点，胃酸和胃蛋白酶是溃疡形成的必要条件。然而，抑制胃酸远非唯一成功的治疗方法，作用机制截然不同的药物——抗酸剂、H2拮抗剂、抗毒蕈碱药、细胞保护剂和局部保护剂——都能达到相似的愈合率，这表明发病机制是多因素的。即使是抗分泌化合物，胃酸与溃疡愈合之间的关系也令人困惑：抗酸剂在广泛不同的剂量下都证明有效；临床效果相当的哌仑西平和H2阻滞剂，其抗分泌功效却有很大差异；关于H2拮抗剂餐后早期与晚期给药的研究得出相互矛盾的临床结果；H2拮抗剂早晨和睡前单次给药对溃疡愈合的效果相同，这导致人们重新审视所谓夜间胃酸的重要性。尽管胶体铋和硫糖铝等溃疡封闭剂完全没有抗分泌活性，但它们与H2拮抗剂一样有效，这显然削弱了胃酸在发病机制中的主要致病作用。然而，随着质子泵阻滞剂奥美拉唑取得惊人的100%愈合率，情况又回到了原点，胃酸似乎再次成为发病机制中的主要因素。基于主要致病因素的特异性治疗可能是一个可行的方案，但目前，这仍然只是一个遥远的可能性。
