Future Prospects for Anti-Ulcer Therapy: Acid Inhibitors versus Mucosal Protectives

Abstract

Present histamine H₂ antagonists together with omeprazole would appear to satisfy completely the range of medical needs for anti-secretory drugs. With the possible exception of gastrin antagonists, future developments in anti-secretory therapy are likely to present marketing rather than scientific challenges. The mechanism of action of protective drugs is largely unknown, so that no rationale exists on which to base the search for improved compounds in this category. Indeed, much of the clinical attraction for this approach has disappeared as a result of the disappointing clinical performance of prostaglandin analogues. Anti-secretory therapy is likely to dominate the anti-ulcer market, although protective drugs could assume importance in the event of long-term toxicity problems occurring in man, comparable to those found during animal carcinogenicity tests with potent, long-acting inhibitors. Opportunity exists in the future for the development of agents that act by increasing wound healing, since the quality of mucosal repair may contribute to the susceptibility of ulcers to relapse. Prevention of relapse is the most clearly definable target for new anti-ulcer drug research, although gastrointestinal cancer and inflammatory bowel disease constitute much more worthwhile therapeutic targets in terms of clinical need.

Key Words:

• Acid secretion
• H₂ antagonists
• H, K-ATPase inhibitors
• bismuth
• epidermal growth factor
• mucosal defense
• peptic ulcer disease
• prostaglandins
• sucralfate
• wound healing