03.01.6.1 Inhibition of the Proton Pumps

Probably, the best characterised pump is the proton pump. Acid secretion, via the proton pump, in the stomach is required for normal digestion. Dyspepsia (excessive acid secretion) is caused by bad cooking, overindulgence and anxiety, and can lead to acid-peptic disease. In acid-peptic disease there is an imbalance between the aggressive factors of the disease, which are the acid, pepsin, and the bacteria Helicobacter pylori, and the protective factors, such as bicarbonate, mucus, and prostaglandins. One way to restore the balance is to decrease the aggressive acid.

The proton pump is present on the parietal cells of the stomach, and is driven by the activity of an enzyme H⁺/K⁺ ATP-ase (Figure 3.15).

Figure 3.15 The proton pump (Copyright QUT, Sheila Doggrell)

The proton pump is stimulated by histamine, gastrin and acetylcholine. Regardless of what is stimulating the pump, the pump is inhibited by proton pump inhibitors (PPIs). This makes PPIs the most effective inhibitors of acid secretion. Omeprazole is the prototype PPI. There are other drugs that have names ending with prazole, and these are all PPIs.

The pharmacokinetic properties of the PPIs are interesting. They are prodrugs, requiring activation in an acidic environment. The only very acidic environment in the body is the stomach, and this is where the prazoles are activated, and this limits their action to the site, where they are required to act. Thus, there are no widespread unwanted effects with the PPIs.