Proton pump inhibitors

What are proton pump inhibitors?

Proton pump inhibitors (PPIs) are a group (class) of medicines that work on the cells that line the stomach, reducing the production of acid.

Types of proton pump inhibitors

PPIs include:

• Esomeprazole.

• Lansoprazole.

• Omeprazole.

• Pantoprazole.

• Rabeprazole.

What conditions are proton pump inhibitors used to treat?

PPIs are commonly used:

• To treat ulcers in the stomach and the part of the gut called the duodenum. Stomach and duodenal ulcers are far less common than they used to be in the Western world, partly because PPIs have become more widely available. However they still affect 5-10% of the worldwide population.

• To reduce acid reflux which may cause heartburn or inflammation of the gullet (oesophagitis). These conditions are sometimes called gastro-oesophageal reflux disease (GORD).

• As one part of treatment to get rid of Helicobacter pylori - a bacteria found in the stomach, which can cause ulcers.

• To help prevent ulcers or damage to the lining of the stomach associated with anti-inflammatory medicines called non-steroidal anti-inflammatory drugs (NSAIDs).

• In a rare condition called Zollinger-Ellison syndrome.

• In other conditions where it is helpful to reduce acid in the stomach.

PPIs usually work very well to reduce stomach acid and to treat the above conditions. They have significantly improved the quality of life of many people with these conditions since they first became available in the 1980s. They are commonly prescribed.

How do proton pump inhibitors work?

Upper gastrointestinal tract and acid

The stomach produces acid to help with the digestion of food and to kill germs (bacteria). This acid is corrosive so the body produces a natural mucous barrier which protects the lining of the stomach from being worn away (eroded).

In some people this barrier may have broken down allowing the acid to damage the stomach, causing inflammation or ulceration. In others there may be a problem with the muscular band at the top of the stomach (the sphincter) that keeps the stomach tightly closed. This may allow the acid to escape and irritate the gullet (oesophagus). This is called 'acid reflux' which can cause heartburn and/or inflammation of the gullet (oesophagitis).

PPIs stop some of the acid production from cells in the lining of the stomach. This can help to prevent ulcers from forming or assist the healing process. By decreasing the amount of acid, they can also help to reduce acid reflux-related symptoms such as heartburn.

They are called 'proton pump inhibitors' because they work by blocking (inhibiting) a chemical system called the hydrogen-potassium adenosine triphosphatase enzyme system (otherwise known as the 'proton pump'). This chemical system is found in the cells in the stomach lining that make stomach acid.

Proton pump inhibitors side-effects

Most people who take a PPI do not have any side-effects. However, side-effects occur in a small number of users. The most common side-effects are:

• Constipation.

• Diarrhoea.

• Wind (flatulence).

• Headaches.

• Feeling sick (nausea).

• Tummy (abdominal) pain.

• Being sick (vomiting).

A full list of side effects can be found in the leaflets that come with the medication.

Studies in the early 2020s showed that people taking PPIs are at increased risk of gastric cancer (cancer of the stomach). People with gastro-oesophageal reflux are also at increased risk of gastric cancer. Evidence suggests that PPIs reduce the risk of progression to oesophageal cancer in people with Barrett's oesophagus (a condition where the lining of the oesophagus changes and is more at risk of becoming malignant). Evidence also shows that there does not appear to be an increased risk of oesophageal or colorectal cancer with PPIs.

More recent studies (2023 and 2024) have suggested that there is no clear evidence to suggest that PPIs cause stomach cancer. It may be that people with conditions which make them more likely to be prescribed PPIs - for example, GORD or gastritis - are more prone to stomach cancer.

The authors of the recent studies have suggested that a large, randomised control trial should be set up to discover whether taking PPIs is associated with a higher risk of gastric cancer. However, in the meantime, the advice for most people (not those with Barrett's oesophagus) would be to only take PPIs as needed and to stop taking them or reduce the dose when they are not needed. People who need long term treatment for heartburn / reflux should also consider whether some of the older treatments (known as H2 blockers) might be sufficient to manage their symptoms as these have not been found to have an increased cancer risk.

PPIs have also been associated with an increased risk of bone fractures. Long-term use of higher dose PPIs has been shown to increase the risk of fractures, particularly hip fractures. It is thought that PPIs might reduce the absorption of calcium, thus reducing bone strength.

Taking a PPI can affect how well some medicines work and can occasionally cause serious 'drug reactions'.

This is particularly important with:

• The blood-thinning medicine warfarin.

• Medicine for epilepsy, called phenytoin (Epanutin®).

• Medicines called digoxin, methotrexate or cilostazol.

• Also, lansoprazole can possibly affect how well oral contraceptives might work.

When taking antacids (such as gaviscon or Rennies) it is important to avoid taking them at the same time as other medication including PPIs. This is because antacids can affect how well medication is absorbed.

Can I buy proton pump inhibitors?

Omeprazole, esomeprazole and pantoprazole can be bought over the counter at pharmacies, although certain doses and preparations still require a prescription. Rabeprazole and lansoprazole still require a prescription. Medical advice should be sought if requiring a PPI for more than four weeks. Tests might be needed, such as:

• Blood tests.

• A stool test for helicobacter pylori (a bacteria that lives in the stomach and can cause inflammation and ulceration).

• Or a gastroscopy (a camera passed through the gullet into the stomach).

How do I take proton pump inhibitors?

These are usually taken once or twice a day. The leaflet that comes with the particular PPI will advise on any other details of how they should be taken.

How quickly do proton pump inhibitors work?

Generally, PPIs are well absorbed by the body and may provide quick relief for some problems, for example for heartburn caused by acid reflux. However, if they are being taken for other reasons, such as to heal an ulcer, it may take longer for the medicines to have an underlying effect.

How long is treatment needed?

This can vary depending on the reason for taking a PPI. In some cases a doctor may prescribe a PPI that is taken 'as required' to relieve symptoms rather than every day. In some cases a regular dose taken each day is advised. Some people need PPIs for many years or for life (in conditions such as Barrett's oesophagus); other people will only need them for a few weeks.

Will my symptoms return after treatment with a proton pump inhibitor?

It is possible that symptoms might come back on stopping the medication. Further medical advice should be sought in these cases.

Stopping smoking, losing weight or maintaining a healthy weight, sleeping with the head of the bed raised slightly, eating smaller portions and eating fewer highly-processed foods all help reduce symptoms of GORD and therefore reduce the chances of needing to take PPIs for long periods of time.

Who should not take proton pump inhibitors?

PPIs may not be suitable for some people, for example, people with certain liver problems cannot take them. Pregnant women are advised to avoid them unless they are necessary, but there is no evidence of harm from omeprazole or esomeprazole in pregnancy. A full list of individuals who should not take a PPI is included with the information leaflet that comes in the medicine packet.

Other considerations when taking a proton pump inhibitor

Medical advice should be sought if symptoms worsen. Urgent medical advice should be sought by anyone experiencing any of the following problems which could indicate a serious gut disorder:

• Bringing up (vomiting) blood. This may be obviously fresh blood, but altered blood in vomit can look like ground coffee. Doctors call this 'coffee-ground vomit'.

• Blood in the stools (faeces). This may be obvious blood, or it may just make the stools black and tarry.

• Unintentional weight loss.

• Difficulty swallowing, including food getting stuck in the gullet (oesophagus).

• Persistent tummy (abdominal) pain or persistent vomiting.