Acid suppression: proton pump inhibitors and H2 antagonists
How the parietal cell secretes acid, why PPIs are acid-activated irreversible prodrugs taken before breakfast, CYP2C19 effects and the clopidogrel question, H2 antagonist tachyphylaxis, and the mechanisms behind PPI hypomagnesaemia, B12 and iron deficiency, rebound acid and false test results.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- The parietal cell secretes acid through the H+/K+-ATPase, driven by histamine (H2), gastrin and acetylcholine (M3).
- PPIs block the pump itself, the final common step, so they suppress acid from every stimulus. H2 antagonists block only the histamine input.
- PPIs are acid-activated prodrugs that bind covalently. Timing before a meal matters; plasma half-life doesn't.
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Sources
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- Therapeutic Guidelines: GastrointestinalAU/NZTherapeutic Guidelines Limited, 2025
- Ranitidine: TGA safety alert and recallAU/NZTherapeutic Goods Administration, 2020
- Clopidogrel with or without omeprazole in coronary artery disease (COGENT)New England Journal of Medicine (Bhatt et al.), 2010
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C19 and proton pump inhibitor dosingClinical Pharmacology and Therapeutics (Lima et al.), 2021
- AGA clinical practice update on de-prescribing of proton pump inhibitorsGastroenterology (Targownik, Fisher, Saini), 2022;162:1334-42, 2022
- Last updated
- 14 November 2026
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