The evolution of peptic ulcer therapy. A role for temporal control of drug delivery.

The treatment of acid peptic disease has involved a series of attempts to control gastric acid secretion in order to heal and to prevent recurrence of duodenal ulcers. Early treatment attempted to heal by neutralizing gastric acid with diet modification, the Sippy diet, and Doll's milk drip. Just before the turn of the century, surgeons began performing gastric resections. In 1943, Dr. Lester Dragstedt performed the first truncal vagotomy to limit cholinergic stimulation of gastric acid secretion. This led to surgery that combined gastric resections with vagotomy. In 1970, the first parietal cell vagotomy was performed. This microsurgical technique limited vagal initiation of acid secretion while minimizing the impact on other gastrointestinal functions. By the 1960s, pharmacological intervention included antacids to neutralize acid and anticholinergics to reduce the amount of acid produced. These treatments varied in their effectiveness, and some of them caused significant side effects. In 1976, treatment of acid peptic disease began a new phase with the introduction of the first H2 receptor antagonist, cimetidine. Ranitidine, the second H2 receptor antagonist, produced greater acid suppression in the morning and at night with bid dosing than cimetidine with quid dosing. The knowledge that there is a circadian pattern in acid production, with higher levels between 10 PM and 2 AM, resulted in the development and use of a single evening dose of ranitidine. Ongoing research continues to investigate the effects of dose timing and the influence of more potent acid-suppressing agents. Finally, the issue of maintenance therapy and gastric acid secretion was addressed. The clinical advantage that ranitidine has over cimetidine in the prevention of ulcer recurrence can be attributed to its control of nocturnal acid suppression.