Despite their short half-lives (2 hours), Proton pump Inhibitors (PPIs) cause a prolonged suppression of acid secretion (up to 48 hours) because:

Ans. c. They irreversibly inhibit the proton pump molecule and hence, acid secretion requires synthesis of new proton pumps (Ref: Goodman and Gilman 12/e p1311; Katzung 12/e p1085-1087)Despite their short half-lives (2 hours), Proton Pump Inhibitors (PPIs) cause a prolonged suppression of acid secretion (up to 48 hours) because they irreversibly inhibit the proton pump molecule and hence, acid secretion requires synthesis of new proton pumps."Proton pump inhibitors (PPIs) are prodrugs that require activation in an acidic environment. After absorption into the systemic circulation, the prodrug diffuses into the parietal cells of the stomach and accumulates in the acid secretory cancliculi. Here, it is activated by the proton catalyzed formation of a tetracyclic sulfenamide, trapping the drug so that it cannot diffuse back across the canalicular membrane. The activated form then binds covalently with the sulfhydryl groups of cysteines in the H+K+ -ATPase, irreversibly inactivating the pump molecule. Acid secretion resumes only after new pump molecules are synthesized and inserted into the luminal membrane, providing a prolonged (up to 24 to 48 hour) suppression of acid secretion, despite the much shorter plasma half-lives (0.5-2 hour) of the parent compounds. Because they block the final step in acid production, the PPIs are effective in acid suppression regardless of other stimulating factors."- Goodman and Gilman 12/e p1311.Proton Pump InhibitorsMost potent antisecretory agents, substituted benzimidazoles, also known as the proton pump inhibitorsQ.Covalently bind to the catalytic subunit of the proton pump and negate all types of acid secretionQPPIs provide more complete inhibition of acid secretion than the H2-receptor antagonistsQ.Inhibition of acid secretion is also more prolonged because of the irreversible inhibition of the enzyme caused by the covalent bond to the proton pumpQ.PPIs are more effective during the day, generally prescribed before breakfastQ.PPIs require an acidic environmentQ within the gastric lumen in order to become activated and bind to the proton pump at the secretary canaliculus.Utilization of antacids or H2-receptor antagonists in combination with PPIs could have deleterious effects by promoting an alkaline environment and thereby preventing activation of the PPIQ.Consequently, antacids and H2-receptor antagonists should not be used in combination with PPIsQ.