Pharmacological Approach to Gastric Acid Suppression: Past, Present, and Future

Abstract

Less than 2 centuries have elapsed since the identification of hydrochloric acid in the stomach. The clarification of the molecular mechanisms allowed the effective therapeutic suppression of gastric acid secretion. The spectacular advances in the treatment of acid-related disorders represent a synthesis of the contributions of several brilliant pharmacologists, basic scientists, and clinical physicians. Effective gastric acid suppressive therapy has dramatically improved the therapy and outcome of acid-related disorders. The introduction of proton pump inhibitors (PPIs) in clinical practice has significantly changed the medical management of upper gastrointestinal disorders. PPIs represent the “gold-standard” therapy in acid-related disorders. However, some challenges persist in the therapy of acid related diseases, including management of patients who respond inadequately to PPI therapy, more effective gastroprotection, or more powerful antisecretory treatment for the eradication of Helicobacter pylori infection. New antisecretory drugs are currently being developed and investigated to further provide a more effective and profound gastric acid secretion inhibition. The major advance has been the development of acid pump ­antagonists, the potassium channel acid blocking drugs (­P-CABs). Long-term studies comparing P-CABs with PPIs will help to define the exact place and safety profile of this class of drug in the management of acid-related disorders.

Different dose of new generation proton pump inhibitors for the treatment ofHelicobacter pyloriinfection: A meta-analysis

“…It was known that the differences in acid inhibition lead to different eradication rate and strong acid inhibition increases the efficacy of H. pylori . 42 – 44 Rabeprazole and esomeprazole could provide better control of gastric acid, leading an increase in pH value to the neutral range within a short time than older PPIs when they administered at the standard doses; thus, strengthened the effects of antibiotics. 45 – 47 In addition, 24-h intragastric pH monitoring had shown that 10 and 20 mg of rabeprazole twice daily have a comparable antisecretory effect on the median pH value and percent time of >4.0, >5.0, >6.0, and >7.0 for 24 h. 21 This might explain why the eradication rate in the high-dose group was not better than that in the standard-dose group.…”

Crosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicity

“…Compared to the Histamin H2-receptor antagonists, PPIs represent the gold-standard therapy in the gastric acidrelated disorders [51]. Omeprazole (a weakly basic compound, pKa ~4) is a gastric anti-secretory agent.…”

Amino acid conjugates of 2‐mercaptobenzimidazole provide better anti‐inflammatory pharmacology and improved toxicity profile

“…Similarly, the compound 4f and 4m produced a relatively moderate effect in reducing the intestinal fluid accumulation with a mean value of 125 ± 5 and 160.3 ± 1.6, respectively (Figure 4). These results of antisecretory effects indicate that 2‐mercapto‐benzimidazole derivatives reduce gastric secretions and can be a potential drug candidate for treating gastric ulcers (Herszényi, Bakucz, Barabás, & Tulassay, 2020).…”