What is the Difference Between a PPI and a H2 Blocker for Heartburn?

Comparing the Two Main Kinds of Medicines for GERD

Sick man taking antacid. Paul Bradbury/ GettyImages

If you have heartburn, you probably wonder about the difference between the main medications used to treat it:

  • ​Proton Pump Inhibitors (PPIs)
  • H2 Blockers 

What Causes Heartburn and What is Needed to Treat It?

Heartburn can be caused by a more ongoing condition called gastroesophageal reflux disease (GERD). GERD occurs when acid from the stomach backs up into the esophagus. Normally stomach acid and other contents are kept in the stomach (and out of the esophagus) from a valve called the  lower esophageal sphincter (LES).

But several factors can weaken that valve including:

Lifestyle modifications—quitting smoking, cutting out alcohol and foods that cause heartburn, and losing weight—are often the first line of treatment for heartburn. But sometimes medication is necessary, and that is where PPIs and H2 Blockers can help.

How These Medications Work

Both PPIs and H2 Blockers suppress gastric acid secretion. They are different, however, in how they do this. While PPIs shut down the proton pumps in the stomach, H2 Blockers work by blocking the histamine receptors in acid-producing cells in the stomach.

Proton Pump Inhibitors (PPIs)  

The proton pump is a molecule in certain cells of the stomach. It "pumps" acid into the stomach. It takes a non-acidic potassium ion out of the stomach and replaces it with an acidic hydrogen ion. This hydrogen ion is what makes things acidic. By putting more hydrogen ions into your stomach, the pump makes the contents of your stomach more acidic.

But by stopping the action of the pump, acid secretion into the stomach is stopped.

H2 Blockers

A cell in the stomach, called a parietal cell, makes acid. These cells are found in the stomach lining and are stimulated in a number of ways to produce acid.  One of these acid stimulants is histamine, which binds to histamine 2 receptors on the parietal cell. H2 Blockers reduce acid production by blocking these receptor sites.

How Fast and How Long These Medications Work

PPIs have a delayed onset of action, while H2 blockers begin working within an hour. That being said, PPIs work for a longer period of time—most last up to 24 hours and the effects may last up to three days. H2 Blockers, however, usually only work up to 12 hours.

Which Drugs are PPIs and Which Are H2 Blockers?

Proton Pump Inhibitors include:

H2 blockers include:

What Else Are H2 Blockers and PPIs Used to Treat?

It is good to know that in addition to heartburn (and more specifically, GERD), these medications are used to treat esophagitis and to reduce the symptoms of peptic ulcer disease.

They may also be used to treat other digestive disorders that can cause excess stomach acid.

What Medication Will My Doctor Recommend for My Heartburn?

If you have been recently diagnosed with GERD, speak with your doctor about a treatment plan. If you do not get relief with lifestyle changes, an 8-week trial of PPI therapy will likely be recommended.

If you continue to have symptoms after PPI therapy is discontinued, or if you have complications from your GERD (like erosive esophagitis), maintenance (longer-term) PPI therapy will likely be prescribed. Sometimes an H2-blocker, instead of a PPI, is recommended for maintenance therapy.

A Word from Verywell

If you have questions about your heartburn medication, please speak with your doctor. It is also important to take your medication as prescribed, including adhering to the correct dose and timing of intake (for example, taking your PPI 30 to 60 minutes prior to meal time). 


Katz PO, Gerson LB, Vela MF. Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2013;108:308-28.

U.S. Food and Drug Administration. Pharmacodynamic aspects of H 2-blockers versus proton pump inhibitors. 

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