Progression of Acid Reflux and Ulcer Disease Therapeutics

Over a period of 23 years, between 1977 and 2001, the treatment of acid reflux and ulcer disease was literarily transformed, first with the four histamine H2 receptor antagonists, starting with Tagamet (cimetidine), approved on August 16, 1977, followed by the five proton pump inhibitors, starting with Prilosec (omeprazole), approved on September 14, 1989. Stated differently, there were 23 years from Tagamet (the first of the H2 antagonists) to Nexium (the last of the PPI’s) approvals. Of special interest is that there was no overlap in the periods of active registration of these two pharmacologic classes, 1977 – 1988 (10 years and 8 months) for the four H2 antagonists and 1989 – 2001 (11 years and 5 months) for the five PPI’s, as is illustrated in the accompanying graph (click on H2 Antagonists and Proton Pump Inhibitors). Also, interestingly, combination of drugs of these two pharmacologic classes seems to improve acid control.

Another important development was the discovery of the role H. Pylori plays in the pathogenesis of gastric ulcer in the 1980’s, and the subsequent use of specific anti H. Pylori antibiotics, such as clarithromycin, amoxicillin or metronidazole. An ongoing therapeutic mainstay has involved the various antacids, first described in the mid 19th century, although their use extends back centuries.

The anticholinergic agents Banthine (methantheline) and Pro-Banthine (propantheline) had both been approved in the early 1950’s, but have been replaced by the above therapeutics. In addition, past treatments of gastric and duodenal ulcers had included several surgical procedures, such as vagotomy, partial and hemi-gastrectomy, pyloroplasty and gastrojejunostomy.

Refer to page 10 of Progression Of Modern Therapeutics (2013) available under Reports on this website.