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Histamine-2 Antagonists

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By Matt Vera BSN, R.N.

Histamine-2 (H2) receptor antagonists block the release of acid in response to gastrin or parasympathetic release.

Table of Contents

Histamine-2 Antagonist: Generic and Brand Names

Here is a table of the most commonly used H2 antagonists.

  • Histamine-2 antagonists (ends in -tidine)
    • cimetidine (Tagamet)
    • ranitidine (Zantac)
    • famotidine (Pepcid)
    • nizatidine (Axid)


Histamine-2 antagonists block the release of hydrochloric acid in response to gastrin.

  • These drugs include cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid).

Therapeutic actions

The desired actions of H2 antagonists include the following:

  • Selectively block H2 receptors located on the parietal cells.
  • Prevents the release of gastrin, a hormone that causes local release of histamine (due to stimulation of histamine receptors), ultimately blocking the production of hydrochloric acid.
  • Decreases pepsin production by the chief cells.


Histamine-2 antagonists are indicated for the following:

  • Short-term treatment of active duodenal ulcer or benign gastric ulcer.
  • Treatment of pathological hypersecretory conditions such as Zollinger-Ellison syndrome (blocking the overproduction of hydrochloric acid that is associated with these conditions).
  • Prophylaxis of stress-induced ulcers and acute upper GI bleeding in critical patients (blocking the production of acid protects the stomach lining, which is at risk because of decreased mucus production associated with extreme stress).
  • Treatment of erosive gastroesophageal reflux (decreasing the acid being regurgitated into the esophagus will promote healing and decrease pain).
  • Relief of symptoms of heartburn, acid indigestion, and sour stomach.


Cimetidine, ranitidine, and famotidine are available in oral and parenteral forms

OralVaries1-1.5 h4-5 h
IM, IVRapid1-1.5 h4-5 h
Half-life (T1/2)MetabolismExcretion
2 hoursLiverUrine

Contraindications and Cautions

The contraindications and cautions when using H2 antagonists include:

  • Allergy. The H2 antagonists should not be used with known allergy to any drugs of this class to prevent hypersensitivity reactions.
  • Pregnancy or lactation. Caution should be used during pregnancy or lactation because of the potential for adverse effects on the fetus or nursing baby.
  • Hepatic or renal dysfunction. Caution should be used in patients with hepatic or renal dysfunction, which could interfere with drug metabolism and excretion.
  • Prolonged or continual use. Care should also be taken if prolonged or continual use of these drugs is necessary because they may be masking serious underlying conditions.

Adverse effects

The adverse effects associated with H2 antagonists are:

  • CNS: Dizziness, confusion, headache, somnolence.
  • Cardio: Cardiac arrhythmias, cardiac arrest.
  • GI: Diarrhea.
  • Reproductive: Impotence.
  • Skin: Rash.
  • Misc: Gynecomastia.


Cimetidine, famotidine, and ranitidine can slow down the metabolism of the following drugs, leading to increased serum levels and possible toxic reactions:

Nursing Considerations

Nursing considerations for a patient using H2 antagonists include the following:

Nursing Assessment

Nursing assessment for a patient using H2 antagonists include:

  • Assess for possible contraindications and cautions: history of allergy to any H2 antagonists to prevent potential allergic reactions; impaired renal or hepatic function, which could affect the metabolism and excretion of the drug; a detailed description of the GI problem, including length of time of the disorder and medical evaluation to evaluate the appropriate use of the drug and possibility of underlying medical problems; and current status of pregnancy and lactation because of the potential for adverse effects on the fetus or newborn.
  • Perform a physical examination to establish baseline data before beginning therapy, determine effectiveness of the therapy, and evaluate for any adverse effects associated with drug therapy.
  • Inspect the skin for evidence of lesions or rash to monitor for adverse reactions.
  • Evaluate neurological status, including orientation and affect, to assess CNS effects of the drug and to plan for protective measures.
  • Assess cardiopulmonary status, including pulse, blood pressure, and electrocardiogram (if IV use is needed), to evaluate the cardiac effects of the drug.
  • Perform abdominal examination, including assessment of the liver, to establish a baseline and rule out underlying medical problem.
  • Monitor the results of laboratory tests, including liver and renal function tests, to predict changes in metabolism or excretion of the drug that might require dose adjustment.

Nursing Diagnosis

Nursing diagnosis related to the drug therapy might include the following:

Nursing Care Plans and Interventions

Nursing interventions for patients using H2 antagonists include:

  • Ensure therapeutic levels. Administer drug with or before meals and at bedtime (exact timing varies with product) to ensure therapeutic levels when the drug is most needed.
  • Prevent serious toxicity. Arrange for decreased dose in cases of hepatic or renal dysfunction to prevent serious toxicity.
  • Monitor IV doses carefully. Monitor the patient continually if giving IV doses to allow early detection of potentially serious adverse effects, including cardiac arrhythmias
  • Assess for potential drug-drug interactions. Assess the patient carefully for any potential drug-drug interactions if given in combination with other drugs because of the drugs effects on liver enzyme systems.
  • Provide patient’s comfort. Provide comfort, including analgesics, ready to access bathroom facilities, and assistance with ambulation, to minimize possible adverse effects.
  • Reorient patient thoroughly. Periodically reorient the patient and institute safety measures if CNS effects occur to ensure patient safety and improve and improve patient tolerance of the drug and drug effects.
  • Attend regular follow-ups. Arrange for regular follow-up to evaluate drug effects and the underlying problems.
  • Provide support. Offer support and encouragement to help patients cope with the disease and the drug regimen.
  • Educate the client. Provide patient teaching regarding drug name, dosage, and schedule for administration; importance of spacing administration appropriately as ordered; need for readily available access to bathroom; signs and symptoms of adverse effects and measures to minimize or prevent them.


Evaluation of a patient using H2 antagonists include:

  • Monitor patient response to the drug (relief of GI symptoms, ulcer healing, prevention of progression of ulcer).
  • Monitor for adverse effects (dizziness, confusion, hallucinations, GI alterations, cardiac arrhythmias, hypotension, gynecomastia).
  • Evaluate the effectiveness of the teaching plan (patient can name drug, dosage, adverse effects to watch for, and specific measures to avoid them).
  • Monitor the effectiveness of comfort measures and compliance with the regimen.

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Suggested reading and references for this Histamine 2 Receptor Antagonist Nursing Pharmacology Guide:

  • Lam, J. R., Schneider, J. L., Zhao, W., & Corley, D. A. (2013). Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Jama, 310(22), 2435-2442. [Link]
  • Karch, A. M., & Karch. (2011). Focus on nursing pharmacology. Wolters Kluwer Health/Lippincott Williams & Wilkins. [Link]
  • Katzung, B. G. (2017). Basic and clinical pharmacology. McGraw-Hill Education.
  • Lehne, R. A., Moore, L. A., Crosby, L. J., & Hamilton, D. B. (2004). Pharmacology for nursing care.
  • Smeltzer, S. C., & Bare, B. G. (1992). Brunner & Suddarth’s textbook of medical-surgical nursing. Philadelphia: JB Lippincott.
Matt Vera, a registered nurse since 2009, leverages his experiences as a former student struggling with complex nursing topics to help aspiring nurses as a full-time writer and editor for Nurseslabs, simplifying the learning process, breaking down complicated subjects, and finding innovative ways to assist students in reaching their full potential as future healthcare providers.

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