PPIs (Proton Pump Inhibitors)

What are PPIs?
What are PPIs used for?
How do PPIs work?
What are the side effects of PPIs?
What precautions are there for PPIs?
Use of PPIs in pregnancy
What medications do PPIs interact with?
PPIs and the elderly
How do you take PPIs?
What are the most common PPIs?

What are PPIs?

PPIs (proton pump inhibitors) Proton pump inhibitors (PPIs) are a commonly prescribed class of medications whose main action is to create a pronounced and long-lasting reduction of stomach acid production. They are used for the treatment of a number of medical conditions, most often for gastro-oesophageal reflux disease (also known as GORD or GERD). They are the most potent inhibitors of acid secretion available today. PPIs produce almost complete reduction of gastric acid secretion and are the drugs of choice for all but mild cases. Patients with severe symptoms often need prolonged treatment, often for years. Many PPIs have been proven to be very safe for short and long term use and have minimal side effects, even in elderly patients.

What are PPIs used for?

Common conditions include:

Gastro-oesophageal reflux disease (GORD)
Frequent heartburn and acid regurgitation
Oesophagitis
Duodenal and gastric ulcers
H. pylori eradication
Gastrointestinal lesions caused by using NSAIDs
Zollinger-Ellison syndrome

Virtual Medical Centre Video

Watch a video on Introduction to Heartburn

How do PPIs work?

The stomach produces acid to break down food, so it is easier for our bodies to digest them. In some people, this acid can be harmful to the lining of the stomach and the small bowel. This leads to a breakdown in the lining, causing indigestion, reflux and in some cases ulcers. The acid in the stomach is produced by the hydrogen-potassium-ATPase enzyme system, or the "proton pump". As the name suggests, PPIs stop acid being produced in the stomach by inhibiting the pump's ability to work. This markedly increase the pH of the stomach, and decreases the acidic irritation of the lining of the stomach and small bowel. This in turn provides symptomatic relief and allows the stomach and lower oesophagus to heal.

What are the side effects of PPIs?

PPIs are generally very well tolerated. The incidence of adverse effects is relatively low, affecting 1–3% of individuals. Adverse effects include:

More serious adverse effects, including liver dysfunction and visual disturbances, are infrequent but have been described. An increase in the risk of community-acquired pneumonia has also been noted. Due to the effect on calcium absorption, the risk of bone fractures may be indirectly increased.

Of major interest are the long term effects of PPIs. Long term cellular changes that take place in the stomach may be important in the development of stomach cancers. While the use of PPIs is not currently associated with an increased risk of stomach or colorectal cancer, further studies are required.

What precautions are there for PPIs?

PPIs should be used with care under certain conditions. Tell your doctor if you are:

Pregnant
Breastfeeding
Have liver conditions

Before starting PPI treatment, testing should be done to determine that no malignancy is present, as the symptoms of a malignancy may be masked with PPI use, leading to a delay in diagnosis.

Use of PPIs in pregnancy

All of the currently available PPIs are rated as pregnancy category B3, with the exception of rabeprazole (Pariet) which is categorised as B1.

There have been a number of scientific studies investigating the safety of PPIs in pregnancy. These have mostly studied the use of omeprazole (Losec), pantoprazole (Somac) and lansoprazole (Zoton), and have concluded that the use of PPIs in pregnancy is not associated with an increased risk of teratogenesis. However, despite their classification, the use of newer PPIs including rabeprazole (Pariet) and esomeprazole (Nexium) in pregnancy is not recommended due to the lack of scientific data.

What medications do PPIs interact with?

PPIs (proton pump inhibitors) Talk to your doctor before taking any other medicines or herbal remedies with a PPI. The actions of some drugs may be affected by using a PPI.

There are several ways in which a PPI may interact with other drugs, including affecting their absorption or their metabolism.

Drugs for which PPIs affect absorption include:

Antifungals: Ketoconazole (e.g. Nizoral), itraconazole
Digoxin
Antiretrovirals: Indinavir

Drugs for which PPIs affect metabolism include:

Antiepileptics: Phenytoin
Anticoagulants: Warfarin (e.g. Coumadin), clopidogrel (e.g. Plavix)
Sedatives: Diazepam (e.g. Valium)
Antibiotics: Clarithromycin, erythromycin
Antidepressants: Clomipramine, imipramine (e.g. Tofranil)

PPIs and the elderly

Interactions with other drugs must be considered in elderly patients, as adverse events are more likely to happen with this population. This is for several reasons. Elderly patients tend to be on more medications, and the more medications you are on, the more likely it is that two of them will interact with each other and change the effect.

Another reason is that as most medications are swallowed orally and digestion is started in the stomach, alterations to the environment within the stomach (such as what happens with a PPI) have the potential to change how much of another medication is absorbed. Talk to your GP about all of your medications and the possibility of interactions, as this may change which PPI is used to treat your condition.

The elderly are sometimes more susceptible to the adverse effects of drugs; however, clinical trials suggest that oral pantoprazole is safe and well tolerated in the elderly population for both short-term treatment of GORD and for longer term therapy of other conditions (e.g. ulcers, erosive oesophagitis).

How do you take PPIs?

These medications are available as tablets and capsules. People who have difficulty taking oral medications may use injections. The usual course is four weeks. If there is no improvement after four weeks, you may need to take them for longer, or your doctor may order further tests to determine what else may be helpful. The symptoms you experienced before taking a PPI may come back after you have stopped taking the medication. See your doctor immediately if you vomit blood, notice something that looks like coffee grounds in your vomit, or pass black tarry stools.

Until recently, these medications were only available though prescription. However, a two week course of Somac Heartburn Relief (pantoprazole) has now been made available through pharmacists.

What are the most common PPIs?

PPIs requiring a prescription from your doctor include:

Somac (pantoprazole)
Pariet (rabeprazole)
Losec (omeprazole)
Nexium (esomeprazole)
Zoton (lansoprazole)

PPIs available from a pharmacy without a precription include:

Somac Heartburn Relief (pantoprazole)

More information

For more information on acid reflux and heartburn and related investigations, treatments and supportive care, see Acid Reflux and Heartburn.

Reference

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