OPTIMIZING ACID SUPPRESSION FOR TREATMENT OF ACID-RELATED DISEASES

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacolog ical reduction of acid secretion is, therefore, the mainstay of curren t treatment, but the optimal degree of acid suppression remains incomp letely understood. This paper considers the ideal ways of assessing an d reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intraga stric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been succes sfully correlated with healing rates for duodenal ulcer, gastric ulcer , and gastroesophageal reflux disease. Three primary determinants of h ealing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, an d the duration of treatment. The order of importance of these determin ants varies depending on the disease. Data on 24-hr intragastric acidi ty should be accompanied whenever possible by data on 24-hr plasma gas trin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any ot her measurement of intragastric acidity. Comparative data sets in grou ps of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H-2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. H owever, in view of the importance of duration of treatment, healing ra tes with the H-2-receptor antagonists approach those obtained with pro ton pump inhibitors if treatment is continued for a longer time. In ga stroesophageal reflux disease in particular, although the optimal degr ee of acid suppression is not yet defined, the consistently superior p erformance of proton pump inhibitors demonstrates that increased suppr ession of acidity is clinically beneficial.