H2 blockers or antagonists are medications developed in the mid 20th century that are essentially specialized antihistamines, which help to reduce stomach acid. Four of these drugs are now commonly available over the counter in many regions: cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®) and ranitidine (Zantec®). They are useful in the treatment of occasional indigestion or conditions like gastrointestinal reflux disease (GERD), and they have low incidence of side effects. H2 blockers may also have some off-label uses.
As the name implies, H2 blockers “block” the way the parietal cells in the stomach are affected by the body’s production of histamine, changing acid production in the stomach, which reduces acid levels. Regular antihistamines, like diphenhydramine (Benadryl®) don’t behave in the same manner. The difference is principally that H2 antagonists have specific action on the antihistamine receptors that are located in the stomach, which scientists who developed these medicines labeled as H2 receptors, thus differentiating them from H1 receptors that act during allergic reactions. By blocking the function of H2 receptors, the stomach produces correspondingly lower acid levels.
When H2 blockers were first sold in the 1970s by prescription, Tagamet® was the first drug to become available. It was relatively effective, but later drugs, especially ranitidine, proved to be more effective in acid reduction and had fewer overall side effects. The continued use of these drugs to treat things like occasional heartburn, indigestion or GERD, showed most had a fairly low side effect incidence, and most countries felt comfortable eventually releasing these drugs in over the counter form.
For conditions like GERD, H2 blockers eventually became less preferred with the development of another class of medications called proton-pump inhibitors (PPIs), which have a more curative effect on damage to the esophagus that may be caused by long-term acid reflux, and may provide longer symptom relief. When H2 blockers are used, they normally have to be taken two to three times a day to provide consistent acid blocking action, but many PPIs are used only once a day.
Determining exact drug interactions, contraindications or adverse effects of H2 blockers is challenging because each medicine is different. Those contemplating taking an H2 antagonist should consult with a physician or pharmacist to be certain the drug is appropriate based on all medical conditions or medicines used. Older H2 blockers like Tagamet® tend to have the heaviest side effect profile, while people using the newer medications like ranitidine may have fewer side effects. In general, all of these drugs may cause symptoms, though these are rare, like appetite suppression, nausea, diarrhea, loss of libido, erectile dysfunction, and confusion.
One of the off-label uses of some of the H2 antagonists is as appetite suppressant for dieting. Cimetidine or others could be taken before meals in larger than normal doses, but there’s little indication this is effective. Ranitidine is also occasionally used to treat allergic hives because unlike traditional antihistamines, it doesn’t cause significant drowsiness.