Initial Evaluation of a New Bismuth Compound in the Therapy of Peptic Ulcer with in Vivo Gastric Analysis.

THE MEDICAL therapy of peptic ulceration is at present most unsatisfactory. Some people draw a distinction between the medical treatment of gastric ulcer and that of duodenal ulcer, but we believe that this distinction is unimportant as the same general principles apply to both, apart from a few specific forms of treatment that we shall mention later. For practical clinical purposes therapy can be considered as applying to both types of ulcer and this view is shared by other authorities (Avery Jones, 1964; Lancet, 1962). A probable reason for the difficulty in applying specific therapy to peptic ulcer is the obscurity and controversy surrounding the underlying etiology. The roles of stress, hormonal dysfunction, acid hypersecretion, excessive pepsin production, lowered tissue resistance and bile regurgitation have all been considered and explored and these factors as xtiological agents all have their supporters (Lancet, 1962; Spira, 1956, 1964). The most widely accepted direct causal agent is hydrochloric acid in excess and much of present day therapy is aimed at "neutralising" this by means of antacids. In Great Britain alone there are over 100 antacid preparations or mixtures in common use. It is easy in the laboratory to demonstrate convincingly the acid neutralising effect of the antacids in common therapeutic use, and this has been done many times. Under these artificial conditions gastric emptying is not adequately allowed for, nor is the normal physiological production of more acid by the stomach. This further acid secretion may also be excessive in some cases due to over-reaction to the exciting influence of food on the stomach, or a temporary change in the gastric pH producing over compensation ('acid rebound'). Jn spite of this, there is little doubt that antacids do produce definite symptomatic relief particularly of pain, and this may be of sustained therapeutic benefit. The therapeutic virtues of antacids have mainly been demonstrated by clinical trials without conclusive in vivo evidence of sustained gastric neutralisation of hydrochloric acid, and it is clear from studies of gastric emptying that even if antacids were given in such quantities to have a significant effect on the acid in the stomach, it could only be transient due to the rate at which the antacid would be passed on into the duodenum. Thus there is some doubt as to how they produce the sustained pain relief that occurs in many patients. Further it has been shown that acid neutralisation does not accelerate healing in gastric ulcer even if the gastric pH is maintained above 4.0 throughout the 24 hours by means of a continuous milk drip (Doll, Friedlander and Pygott, 1956). Further it is known that in order to obtain a significant effect on gastric pH with alkalies, continuous tablet sucking is necessary and this cannot be done by the patient at night. If acid neutralisation is not then practicable in vivo, could pepsin neutralisation be an acceptable alternative therapeutic measure? Various workers have demonstrated that bismuth salts have the power of inhibiting the enzyme action of pepsin (Stephens, 1953; Bateson, 1958), and are not powerful antacids, thus avoiding possible acid rebound. For many years and especially in the 1930's, bismuth salts enjoyed great popularity as therapeutic agents in peptic ulceration, and some authorities have attributed the gradual rise in the incidence of peptic ulceration of recent years to the reduction in their use (Leak, 1963). In order to determine the validity of these postulates a preliminary survey has been carried out both clinically and biochemically. The purpose of this is to test firstly if bismuth salts have any therapeutic value, and secondly if they have any in vivo effect on the gastric contents.