Pharmacology · Proton pump inhibitors (PPIs)

Omeprazole !

Switches off the stomach acid pump long after it leaves the blood; used for reflux, ulcers, ulcer bleeding and, with antibiotics, to clear H. pylori.

Updated 2026-11-01

Class: Proton pump inhibitors (PPIs)
Transporter: Gastric H⁺/K⁺-ATPase (proton pump), α subunit
ATC code: A02BC01
WHO Model List of Essential Medicines

Gastric H⁺/K⁺-ATPase (proton pump), α subunitOmeprazole

The crystal is the pig gastric pump bound to vonoprazan, a reversible acid blocker; the figure highlights Cys813, the cysteine to which activated omeprazole bonds covalently.

Target in 3D: Gastric H⁺/K⁺-ATPase (proton pump), α subunit. PDB structure 5YLU (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Omeprazole is a prodrug and a weak base. It accumulates in the acidic secretory canaliculus of the parietal cell, where acid turns it into a reactive sulfenamide. This forms a disulfide bond with Cys813 on the luminal side of the H⁺/K⁺-ATPase and locks the pump, so it can no longer exchange K⁺ for H⁺. Acid output falls until new pumps are made.

Collects in the acidic canaliculus of the parietal cell
Acid converts it into a reactive sulfenamide
A disulfide bond to Cys813 locks the H⁺/K⁺ pump
Less acid: the oesophagus and ulcers heal

Pharmacokinetics

Absorption: Acid-sensitive, so it comes in delayed-release (enteric-coated) forms that release it in the small intestine.
Distribution: About 95% bound to plasma proteins.
Metabolism: Liver, mainly by CYP2C19 (to hydroxyomeprazole) and partly CYP3A4 (to omeprazole sulfone).
Elimination: Most of a dose leaves in the urine as inactive metabolites.
Half-life: About half an hour to an hour, but the effect lasts much longer because the pumps are blocked irreversibly.
Onset and duration: Acid output falls within about an hour of a dose; the effect builds up with repeated daily use.

Indications

Gastro-oesophageal reflux disease and erosive oesophagitis. Gastro-oesophageal reflux disease (GERD) →
Gastric and duodenal ulcers. Peptic ulcer disease →
H. pylori eradication, combined with amoxicillin and clarithromycin. Helicobacter pylori gastritis →
Gastrointestinal bleeding from peptic ulcer (listed for this use on the WHO Essential Medicines List). Upper gastrointestinal bleeding →
Zollinger–Ellison syndrome and other states of acid hypersecretion.

Adverse effects

Common

Headache
Abdominal pain, nausea and diarrhoea
Flatulence

Contraindications

Hypersensitivity to omeprazole or other benzimidazole PPIs
Use with rilpivirine, which needs gastric acid to be absorbed

Key interactions

Clopidogrel: Omeprazole reduces clopidogrel's active metabolite and its platelet inhibition; the combination is avoided.
Methotrexate (mainly high doses): Methotrexate levels may rise.
Drugs that need acid to be absorbed (iron salts, ketoconazole, itraconazole): Lower absorption and effect.
Diazepam, phenytoin and warfarin: More sedation with diazepam; phenytoin levels and INR are checked.

What is monitored

Magnesium and vitamin B12 with long-term use
Periodic review of whether treatment is still needed

Test yourself

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

Why must omeprazole reach acid to work, and where does that happen?

It is a prodrug; acid converts it into the reactive sulfenamide. This happens in the secretory canaliculus of the parietal cell, right next to the pump.

Which amino acid of the H⁺/K⁺-ATPase does activated omeprazole bond to, and what kind of bond is it?

Cysteine 813, through a covalent disulfide bond, which inactivates the pump irreversibly.

A patient on clopidogrel after a coronary stent is started on omeprazole. What is the concern?

Omeprazole inhibits CYP2C19, which turns clopidogrel into its active form, so platelet inhibition may be weaker.

Why can long-term omeprazole lead to vitamin B12 deficiency?

Gastric acid and pepsin free B12 from food proteins; with little acid, less B12 is released for absorption.

Add to my cards (4)

Amoxicillin

← Back to the class: Proton pump inhibitors (PPIs)

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 (MedlinePlus (U.S. National Library of Medicine), 2023); DailyMed - OMEPRAZOLE capsule, delayed release (DailyMed (U.S. National Library of Medicine), 2024); RCSB PDB - 5YLU: Crystal structure of the gastric proton pump complexed with vonoprazan (RCSB Protein Data Bank, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.