Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications in the world.

First clinically introduced in 1989, the medicines suppress acid production in the stomach and are used in the treatment of many conditions, such as:

• Dyspepsia
• Peptic ulcer disease
• Helicobacter pylori therapy
• Gastro-oesophageal reflux disease (GERD or GORD)
• Barrett’s Oesophagus

Widely used PPIs include esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. They can come as capsules, tablets, granules or as a liquid and come under brand names, such as Nexium, Prevacid, Prilosec, Protonix and Pariet.

How do PPIs work?

The proton pump – also known as H+/K+-ATPase pump – is primarily responsible for the acidification of the stomach contents.

Proton pump inhibitors reduce the production of acid by blocking the H+/K+ ATPase enzyme that produces acid in the wall of the stomach.

PPIs bind to proton pumps in the stomach, thereby suppressing acid production. If you are up for a more scientific description of how PPIs work exactly, you can find more details in this research review.

PPIs

People are advised to take PPIs on an empty stomach, at least a half-hour before the first meal of the day.

Do PPIs always work?

It is estimated that between 10 and 40 per cent of patients with GORD fail to show improvements with their symptoms after taking PPIs – this is referred to as refractory reflux.

Read our guide to refractory reflux here.

Interaction with other medication

People who take PPIs may need to limit or avoid their exposure to certain medicines or foods due to potential interactions.

Problem with PPIs

Although initially designed to be taken only for weeks or months, millions of people have been on PPIs for years.

Adverse side effects are usually mild and reversible and include headache, diarrhoea, nausea, abdominal pain, constipation, dizziness and skin rashes.

However, there are growing concerns about long term treatment with PPIs. In recent years, studies have associated long-term use of the medication with a variety of serious adverse effects. Such as:

• Clostridium difficile infection
• Pneumonia
• Increased risk of bone fractures
• Hypomagnesaemia
• Vitamin B12 deficiency
• Increased mortality in older patients
• Decreased iron absorption

PPIs are also the subject of multiple pending lawsuits claiming the drugs have caused a number of health issues.

You can read our ‘Heartburn drugs linked to deadly health issues blog’ from 2019 here.

25 Years of Proton Pump Inhibitors: A Comprehensive Review