Ebook: Proton Pump Inhibitors

Inhibition of the proton pump in the parietal cells has been established as the main therapeutic principle in the treatment of acid-related diseases, such as peptic ulcer and gastro-oesophageal reflux. The proton pump inhi­ bitors are tailored for their purpose. They accumulate in the target cell, are activated by acid and bind strongly to the specific target - the proton pump. The clinical superiority of the proton pump inhibitors is due not only to their high efficacy but also to the long duration of the acid inhibition in comparison with other antisecretory drugs. At present when drug discovery mostly relies on identification and characterization of potential targets by genome research, molecular biology, combinatorial chemistry and automated screening, it seems worthwhile to present the development of the tITst proton pump inhibitor - omeprazol- starting from a chemical structure with an observed antisecretory effect but also severe toxic effects that had to be eliminated. As always, basic and applied research operate luind in hand to optimize the delicate balance be­ tween efficacy and safety of a new drug. This goal often involves time and many different specialists.

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This monograph contains a description of the discovery and development of a antisecretory therapy in the treatment of acid-related diseases: omeprazole, the first proton pump inhibitor. Overviews compare this and other proton pump inhibitors and discuss their pharmacology, including the mechanism of action, the effect on Helicobacter pylori infection, and the consequences of profound inhibition of gastric acid secretion. The pharmaceutic delivery system is described since it constitutes a special problem with this class of drugs. The clinical experience with proton pump inhibitors in acid-related diseases is reviewed with focus on gastro-esophageal reflux disease and peptic ulcer diseases including Helicobacter pylori and NSAID-induced ulcerations and Zollinger-Ellison syndrome. Finally, an overview is presented on the socio-economic impact of proton pump inhibitors in acid-related diseases emphasizing the important aspect of quality of life. The monograph is aimed at a broad readership with an interest in the development problems of this, at present, most commercially successful drug; the pharmacology of a "tailor-made" drug for a specific target; the therapeutic strategies in acid-related diseases; and the dramatic changes in the long-term outcome results of the treatment of peptic ulcer diseases where most patients now can be cured from the disease after only one week of drug therapy.