Editorial: deja vu all over again—let the P‐CAB wars begin
Abstract
Gastric antisecretory therapy began after the discovery by subsequent Nobel recipient, Sir James Black, of the histamine H2 receptor on the basolateral surface of the parietal cell with the subsequent development of the histamine H2receptor antagonists (H2RAs). These drugs revolutionised the management of acidrelated diseases but were ultimately replaced by the proton pump inhibitors (PPIs) which block the final common pathway of gastric acid secretion. PPIs were more potent and more effective than the H2RAs, and were safe despite producing fasting and postprandial hypergastrinaemia.1,2 Omeprazole, the first PPI, was challenged in subsequent years by lansoprazole, pantoprazole, rabeprazole, esomeprazole and dexlansoprazole.2 However, PPIs need to be taken before meals, have a slow onset of action, pharmacodynamic variability between patients, a variety of putative longterm side effects, and cytochrome P450 interactions. (2) Although PPIs are currently the standard of care for most acidrelated diseases, there remains room for improvement.2 PPIs are prodrugs that undergo a conformational change in the acidic milieu of the secretory canaliculus exposing cysteine residues that bind covalently (irreversibly) with H+/K+ATPase alpha subunit cysteine residues blocking the enzyme and preventing ongoing H+/K+ exchange.2,3 In contrast, the newest class of antisecretory agents, the potassiumcompetitive acid blockers (PCABs), do so via competitive inhibition of potassium uptake which is…
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