Differences Between PPIs and H2 Blockers for Heartburn

Comparing the Two Main Kinds of Medicines for GERD

Sick man taking antacid
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If you have heartburn, you probably wonder about the difference between the main medications used to treat it: proton pump inhibitors (PPIs) and H2 blockers. Both 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. Learn more about the differences, how they can help your heartburn, and why your doctor would recommend one over the other.

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) by a valve called the lower esophageal sphincter (LES). But several factors can weaken that valve including:

  • Eating foods that often trigger heartburn, such as acidic foods (for example, tomatoes and citrus fruits), spicy foods, or chocolate
  • Drinking alcohol or caffeine
  • Smoking cigarettes
  • Having certain medical conditions, such as diabetes and asthma
  • Having extra pressure on your abdomen (for example, obesity, pregnancy, or tight waistbands)

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.

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 (inhibiting it), acid secretion into the stomach is stopped.

Proton pump inhibitors are used to treat GERD, stomach and duodenal ulcerserosive esophagitis and Zollinger-Ellison syndrome. PPIs can be used alone or taken in combination with antacids. All PPIs are similar in how they work, and there is no evidence that suggests one is more effective than another. However, they differ in how they are broken down by the liver and how they interact with other medications. Additionally, the effects of some PPIs may last longer than others and may be taken less frequently.

PPIs include:

PPIs have a delayed onset of action while H2 blockers begin working within an hour. PPIs work for a longer period: most up to 24 hours, and the effects may last up to 3 days. H2 blockers, however, usually only work up to 12 hours.

H2 Blockers

The parietal cells in your stomach lining 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, true to their name, block these receptor sites and therefore reduce acid production.

H2 blockers include:

How Do H2 Blockers Differ from Proton Pump Inhibitors (PPIs)?

Though both H2 blockers and proton pump inhibitors both suppress gastric acid secretion, there are several ways in which these medications differ:

  • How they work: They work at different stages in the production of stomach acid. H2 blockers (histamine blockers) block one of the first stimuli for acid production. Proton pump inhibitors block the final step in the pathway of acid secretion in the stomach. In other words, the acid which has been produced (which may be reduced due to an H2 blocker) is prevented from arriving in the stomach.
  • Where they work: Both of these medications work in the parietal cells, which are the acid-producing cells in the lining of the stomach. H2 blockers work by blocking the histamine receptors in parietal cells to decrease the amount of acid produced (although there are other stimuli so that some acid is still produced). Proton pump inhibitors work by shutting down the proton pumps in these cells and preventing the acid from being secreted into the stomach.
  • How well they work: Proton pump inhibitors result in a greater suppression of acid than H2 blockers. This is because there are other stimuli, in addition to histamine 2, which stimulate the production of acid and H2 blockers only block histamine 2.
  • How soon they work: H2 blockers have a rapid onset of action, often working within an hour of taking the medication. Proton pump inhibitors, in contrast, have a delayed onset of action.
  • How long they last: H2 blockers may be effective for up to 12 hours after taking the medication. Proton pump inhibitors tend to last longer. Some PPIs last up to 24 hours, while others may have effects which last up to three days.
  • Side effects: Due to different mechanisms of action, the side effects of the two classes of medication differ as well, though both types of medication are usually well tolerated. Possible side effects also differ between the specific medications in each category. With H2 blockers, headache is most common. Proton pump inhibitors are in general very safe but are associated (in some studies but not all) with an increased risk of hip fractures. There are other possible side effects, and it is important to discuss these with your doctor before using any of these medications.

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.

Choosing Between H2 Blockers and Proton Pump Inhibitors

You may wonder why your doctor would choose one of these medications over another. Since proton pump inhibitors provide greater acid suppression, these are often needed for more severe symptoms.

The timing of the onset of action may also determine which medication your doctor will recommend. Since the H2 blockers work rapidly, they are often used when a person has a flare-up of their symptoms. Due to this rapid action, these medications can be used for those who have only occasional heartburn.

Since proton pump inhibitors take longer to begin working but have a greater effect, they are more often used for those who have chronic symptoms of heartburn to gain control over the symptoms.

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.

Prescription vs. Over-the-Counter Heartburn Medications

Many of the medications used for heartburn are available as both a prescription and as an over-the-counter medication. Though the drugs are the same, over-the-counter medications are available at a reduced dose (often one-half of the prescription dose). 

Talk to your doctor or pharmacist before substituting one of these for the other. Also, be aware of the possible side effects of antacids. They can decrease the absorption of other medications, including other heartburn medications.

Other Treatments for Heartburn

In addition to H2 blockers and proton pump inhibitors, many people also use antacids to help control their heartburn. Keep in mind that there are differences between individual antacids and talk to your doctor about which of these medications would be best for you. In addition to medications and lifestyle changes, some people require further treatments, such as surgery for hiatal hernias.

Beyond Medications for Heartburn

With all of the medications available to treat heartburn, we tend to forget about lifestyle changes that can help heartburn. If you require medications to manage your heartburn, make sure to see if any of these measures can improve your symptoms:

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. Along with medication, look at ways you can make healthy lifestyle changes that will also reduce your heartburn.


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