How Are H2 Blockers Different from Proton Pump Inhibitors (PPIs)?

H2 Blockers vs Proton Pump Inhibitors: Effects on Heartburn

assorted heartburn medications spilling from a bottle
What are the differences between H2 blockers and proton pump inhibitors (PPIs) for heartburn?. Photo©Petr Kazilek

How are H2 blockers different from proton pump inhibitors (PPIs) for the treatment of heartburn? Does one work faster than the other or last longer? What make your doctor choose one of these over the other?

H2 Blockers vs Proton Pump Inhibitors (PPIs)

You may be wondering why your doctor recommended and H2 blocker for your heartburn, whereas some you know was treated with a proton pump inhibitor (PPI) instead.

How do these medications work, and why might one be chosen over another for the treatment of acid reflux? Let's take a look at each of these classes of heartburn drugs and then compare their mechanism of action and other differences.

What are H2 Blockers

H2 blockers, or H2 receptor antagonists, are used often for heartburn. They block histamine 2, a compound which stimulates parietal cells found in the lining of the stomach to produce acid. Histamine 2 is only one of a number of stimuli that result in the production of acid.

What are Proton Pump Inhibitors?

Proton pump inhibitors (PPI) are potent medications which are used to decrease acid production in the stomach. They are used to treat heartburn as well as other conditions caused by excess stomach acid such as peptic ulcer disease. The proton pump is a molecule present in the parietal cells of the stomach which is responsible for pumping acid (hydrogen ions) into the stomach.

Proton pump inhibitors block the actions of this pump, preventing the acid which has been produced from entering the stomach.

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 - While H2 blockers and proton pump inhibitors both suppress gastric acid secretion, they work at different stages in the production of 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, 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 decreasing the amount of acid produced, though 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.
  • 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 PPI's 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.

    Choosing Between H2 Blockers and Proton Pump Inhibitors

    You may be wondering 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 a 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.

    Differences Between H2 Blockers

    As noted earlier, there are not only differences between these classes of medications, but differences between the individual drugs in each class. Drugs which are considered H2 blockers include:

    Differences Between Proton Pump Inhibitors

    There are also important differences between the proton pump inhibitors. Drugs which are considered proton pump inhibitors include:

    • Prilosec (omeprazole)
    • Prevacid (lanosoprazole)
    • Protonix (pantoprazole)
    • Nexium (esomeprazole)
    • Aciphex (rabeprazole)
    • Kapidex (dexlansoprazole)

    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.) Knowing this, some people find that there is a cost savings by using one instead of the other. If you do this, keep in mind that one tablet of the prescription drugs is often equivalent to two tablets of the over-the-counter preparations. Talk to your doctor or pharmacist before substituting one of these for the other. In addition, be aware of the possible side effects of antacid, such as the decrease in absorption of other medications, such as other heartburn medications, which may occur.

    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 as well 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 are requiring medications to manage your heartburn, make sure to see if any of these measures can improve your symptoms:


    Scarpignato, C., Gatta, L., Zullo, A., and C. Blandizzi. Effective and Safe Proton Pump Inhibitor Therapy in Acid-Related Diseases—A Position Paper Addressing Benefits and Potential Harms of Acid Suppression. BMC Medicine. Published Online 2016 Nov 9.

    Zhang, Y., Qing, L., He, B., Liu, R., and L. Zuo-Jing. Proton Pump Inhibitors Therapy vs H2 Receptor Antagonists Therapy for Upper Gastrointestinal Bleeding After Endoscopy: A Meta-Analysis. World Journal of Gastroenterology. 2015. 21(20):6341-6351.

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