Proton pump inhibitors (PPIs) are pro-drugs that require acid activation. The therapeutic implication of this is:

• A They should be given after meals when parietal cells are most active, to maximise drug activation in the acid environment
• B They are equally effective when given at any time because they are converted to active sulphenamides in the systemic circulation
• C They should be administered 30–60 minutes before the first meal of the day to achieve maximum acid suppression, because only actively secreting H+/K+-ATPase pumps can activate PPIs ✓
• D Concurrent antacid use improves PPI efficacy by providing an alkaline environment for activation

Explanation

PPIs are weak bases (substituted benzimidazoles) that are unstable in acid and require enteric-coated formulations. After absorption, they accumulate in the acidic secretory canaliculi of actively secreting parietal cells, where they undergo acid-catalysed conversion to the active sulphenamide form, which irreversibly binds to the cysteine residue of H+/K+-ATPase. Only pumps actively secreting acid (stimulated by a meal) are accessible for this covalent inhibition; resting pumps are not. Therefore, PPIs should be taken 30–60 minutes before the first meal to catch the maximal wave of pump activation. Antacids raise luminal pH and if given simultaneously can reduce PPI absorption.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.