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# Proton pump inhibitors (PPIs)

The strongest acid reducers: they switch off the stomach's acid pump itself, so they work whatever triggers acid secretion.

Updated 2026-11-01

## What they are

Prodrugs that block the H⁺/K⁺-ATPase of the parietal cell, the final step of gastric acid secretion. They are the base of treatment for reflux, peptic ulcer and H. pylori eradication.

## Mechanism of action

PPIs are weak bases that collect in the very acidic secretory canaliculus of the parietal cell. There, acid converts them into a reactive sulfenamide that forms a disulfide bond with cysteines of the pump (Cys813 in all of them). The bond is irreversible, so acid secretion only returns as the cell makes new pumps; the effect outlasts the drug in the blood. Because they block the last step, they reduce acid driven by histamine, gastrin or acetylcholine alike.

Target: Gastric H⁺/K⁺-ATPase (proton pump)

## Key points

- They block the final step of acid secretion, so acid falls whatever the stimulus: histamine, gastrin or acetylcholine.
- Long-term use is linked to vitamin B12 deficiency, low magnesium, Clostridioides difficile diarrhoea, hip, wrist and spine fractures, and fundic gland polyps; regular review of whether they are still needed is part of good use.
- Omeprazole is metabolised mainly by CYP2C19 and reduces the active metabolite of clopidogrel; the combination is avoided.
- They lower the absorption of drugs that need gastric acid (iron salts, ketoconazole, itraconazole) and are contraindicated with rilpivirine.
- Potassium-competitive acid blockers such as vonoprazan act on the same pump and share the ATC group of the PPIs.

## Drugs in this class

- [**Omeprazole** Switches off the stomach acid pump long after it leaves the blood; used for reflux, ulcers, ulcer bleeding and, with… Gastric H⁺/K⁺-ATPase (proton pump), α subunit](https://durgical.com/en/pharmacology/omeprazole/)
- [**Pantoprazole** A proton pump inhibitor given by mouth or IV. It has fewer CYP interactions than omeprazole and does not weaken… Gastric H⁺/K⁺-ATPase (proton pump), α subunit](https://durgical.com/en/pharmacology/pantoprazole/)
- [**Esomeprazole** The S-isomer of omeprazole, a proton pump inhibitor given by mouth or IV. Like omeprazole, it inhibits CYP2C19 and is… Gastric H⁺/K⁺-ATPase (proton pump), α subunit](https://durgical.com/en/pharmacology/esomeprazole/)
- [**Lansoprazole** A proton pump inhibitor for ulcers, reflux and H. pylori. Its capsule granules can be sprinkled on soft food or given… Gastric H⁺/K⁺-ATPase (proton pump), α subunit](https://durgical.com/en/pharmacology/lansoprazole/)

## Others in the class

- esomeprazole
- lansoprazole
- dexlansoprazole
- pantoprazole
- rabeprazole

## Test yourself

Think of the answer, then tap the question to see it.

## Why does the acid-reducing effect of a PPI last far longer than its plasma half-life?

The drug binds the pump covalently and irreversibly; acid secretion only recovers as the parietal cell synthesises new pumps.

## Why do PPIs block acid regardless of whether it is stimulated by histamine, gastrin or acetylcholine?

All three pathways converge on the H⁺/K⁺-ATPase, the final step of acid secretion, which is the PPI target.

## Which three problems are associated with long-term PPI use?

Vitamin B12 deficiency, hypomagnesaemia and C. difficile infection (others: fractures, fundic gland polyps).

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Omeprazole: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a693050.html) (MedlinePlus (U.S. National Library of Medicine), 2023); [DailyMed - OMEPRAZOLE capsule, delayed release](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=934601b6-fbba-43c4-a8ef-7a7dfe9f9a51) (DailyMed (U.S. National Library of Medicine), 2024); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=A02BC01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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