Heartburn. It’s an unpleasant burning feeling in your throat and chest that occasionally happens for some individuals after eating. Frequent occurrence, two or more days a week, may be a sign of gastroesophageal reflux disease (GERD) which should be treated. There are several medications called histamine (H₂) receptor antagonists (H₂RA) available by prescription or over the counter (OTC) to treat heartburn and other gastronintestinal conditions. Millions of people take these drugs daily, but how do they work?
 

Pathophysiology

When we eat, gastric acid is secreted to aid in digestion. Certain endogenous substances, primarily histamine, but also acetylcholine and gastrin, attach to receptors on the surface of parietal cells. These substances activate the enzyme adenyl cyclase, which converts adenosine triphosphate (ATP) to the intracellular catalyst cyclic adenosine monophosphate (cAMP). The cAMP ultimately stimulates proton-pump (H/K ATPase) activity. The pump catalyzes the exchange of extracellular potassium (K) ions for intracellular hydrogen (H⁺) ions. When the H⁺ ions combine with extracellular chloride (Cl) ions excreted by gastric cells at a different site, the result is hydrochloric (HCl), or gastric, acid. The mucous lining of the stomach protects it from the acid. However, when the lower esophageal sphincter at the junction of the esophagus and stomach is weakened or does not close properly, it may allow a backflow or “reflux” of acid into the esophagus, which does not have a protective mucous lining.
 

How Do H₂ Receptor Antagonists Work?

H₂Ras, or H₂-receptor blockers, competitively bind to H₂-receptor sites on the surface of parietal cells and inhibit the common pathway that histamine and other substances must travel to stimulate proton-pump activity and promote gastric acid secretion. This results in reduced gastric acid secretion, gastric volume, and hydrogen ion concentration.

Indications & Formulations (Facts and Comparisons, 2020)

H₂ blockers are approved by the U.S. Food and Drug Administration (FDA) for short-term use to treat a variety of gastric disorders outlined in the table below. Three medications are currently approved: cimetidine, famotidine, and nizatidine. Famotidine and cimetidine are available either OTC or by prescription. Nizatidine is available by prescription only. OTC and prescription ranitidine (Zantac) formlations have been removed from the U.S. market due high levels of a contaminant known as N-Nitrosodimethylamine (NDMA), a human carcinogen (FDA, 2020).

 

Histamine H2 Antagonists Indications (Facts and Comparisons, 2020)
Indication	Cimetadine (Tagamet)	Famotidine (Pepcid)	Nizatidine (Axid)
Benign gastric ulcer treatment	+	+	+
Duodenal ulcer treatment	+	+	+
Duodenal ulcer maintenance	+	+	+
GERD	+	+	+
Heartburn	+	+
Pathological hypersecretory conditions	+
Formulations
Tablet	+	+	+
Oral powder for suspension		+
Intravenous solution		+

Nursing Considerations (Nugent, Falkson & Terrell, 2022; Facts and Comparisons, 2020)

H₂RAs take effect in approximately 60 minutes with a duration of action ranging from 4 to 10 hours. H₂RAs are commonly taken once or twice daily. They may be taken with antacids (i.e., aluminum hydroxide, calcium carbonate, magnesium hydroxide) if faster relief is needed, however they should not be taken with other acid reducing medications (i.e., proton pump inhibitors). When taking H₂ blockers over-the-counter, advise your patients to stop use if they develop trouble or pain when swallowing food, vomiting with blood, or bloody or black stools. Patients should not self-treat with H2RAs for more than two weeks without consulting their primary care provider.
 
For complete information, please consult the drug’s specific package insert or the Nursing2024 Drug Handbook® + Drug Updates.
 

References
 
NIH (2018). Histamine Type-2 Receptor Antagonists. https://www.ncbi.nlm.nih.gov/books/NBK547929/
 
Facts and Comparisons (2020, April 21). Histamine H2 Antaonistis. https://fco.factsandcomparisons.com/lco/action/doc/retrieve/docid/fc_dfc/5545954?cesid=6uZ7eFqaDhR 
 
Nugent, C.C., Falkson, S.R. & Terrell, J.M. (2022, December 11). H2 Blockers. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK525994/
 
U.S. Food and Drug Administration (2020, April 1). FDA Requests Removal of All Ranitidine Products (Zantac) from the Market. https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market