Studies on the cimetidine resistant duodenal ulcer
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This thesis investigates why some patients with duodenal ulcer do not respond to blockade and how these patients should be treated. Part 1 examines the effect of cimetidi.'ne lg/day, cimetidine 2g/day and vagotomy on nocturnal gastric secretion in nonresponders. Cimetidine in either dose had no significant effect on volume of gastric secretion but nocturnal intragastric acidity did show a significant decrease. Vagotomy significantly decreased both volume and acidity of secretion. These findings suggest that nonresponse to cimetidine may be due to increased vagal drive. Part 2 investigates vagal function further by measuring nocturnal pepsin secretion in patients receiving cimetidine and ranitidine. Both H2~receptor antagonists increased nocturnal pepsin secretion despite reducing acid. Previous reports suggest cimetidine inhibits pepsin out¬ put. However, patients whose acidity is controlled well with cimetidine have a rise in pH which, as pepsin is unstable at high pH values may result in pepsin deactivation . Patients whose acidity is only poorly controlled with cimetidine, therefore, do not denature pepsin, and as blockade increases vagal drive, intragastric pepsin rises. Duodenal ulcer activity correlates well with pepsin output. Thus, combination of poor acidity control with rise in intragastric pepsin results in nonresponse. Studies were also performed to investigate the mechanism of incre¬ ased pepsin secretion. These suggested that histamine may inhibit vagal drive and, therefore, blockade may increase vagal release. Cimetidine in combination with atropine 4.8mg/day resulted in a significant re¬ duction of volume, acid and pepsin secretion. This latter result suggests that cimetidine should be combined with an anticholinergic agent to inhibit vagal drive and improve control of gastric secretion which theoretically should provide improved clinical response to medical treatment.