What are the medications classified as H2 (histamine 2) receptor antagonists?

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H2 Receptor Antagonists: Medication List

The four H2 receptor antagonists available for clinical use are cimetidine, ranitidine, famotidine, and nizatidine. 1, 2, 3, 2

Available H2 Receptor Antagonist Medications

1. Cimetidine

  • An imidazole derivative that competitively inhibits histamine at H2 receptors of parietal cells 2
  • Peak levels occur 45-90 minutes after oral administration with a half-life of approximately 2 hours 2
  • Major limitation: Interacts with cytochrome P-450 hepatic enzyme system, affecting metabolism of other drugs 4, 5
  • Associated with increased risk of liver disease and gynecomastia 1
  • Least potent of the four H2RAs (famotidine is 40 times more potent on a weight basis) 4, 5

2. Ranitidine

  • Belongs to the basically substituted furans structural class 4, 5
  • Approximately 7 times more potent than cimetidine with longer duration of action 1
  • Does not have the antiandrogenic activity seen with cimetidine 6

3. Famotidine

  • Member of the guanidino-thiazole group 4, 5
  • Most potent H2RA: approximately 8 times more potent than ranitidine and 40 times more potent than cimetidine 4, 5
  • Does not interact with cytochrome P-450, avoiding drug-drug interactions 4, 5
  • Preferred agent for patients on clopidogrel plus aspirin because it does not interfere with clopidogrel metabolism 1
  • Longer duration of action than cimetidine or ranitidine 4, 5

4. Nizatidine

  • Belongs to the basically substituted thiazoles structural class 3, 4
  • Molecular formula C12H21N5O2S2 with molecular weight of 331.46 3
  • Does not have antiandrogenic activity like cimetidine 6

Pharmacologic Properties Common to All H2RAs

  • Suppress gastric acid production by 37% to 68% over 24 hours 6, 1
  • Acid-inhibiting effects last approximately 6 hours 1
  • Critical limitation: All develop tachyphylaxis within 6 weeks of treatment initiation, severely limiting long-term effectiveness 1
  • Work better as prophylactic rather than acute treatment, as they must be present before histamine binds to receptors 1
  • Generally well-tolerated with overall side-effect incidence of 2-3% 4, 5

Clinical Context

While all four medications are equally effective at usual recommended doses for mild GERD (>70% symptomatic improvement) 7, famotidine is the preferred choice in most clinical scenarios due to its superior potency, longer duration of action, lack of cytochrome P-450 interactions, and absence of antiandrogenic effects 1, 4, 5. The exception is when cost or availability dictates otherwise, as all four agents demonstrate similar efficacy for mild acid-related conditions 7.

References

Guideline

Histamine Type 2 Receptor Antagonists: Clinical Applications and Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Pharmacology of H2-receptor antagonists: an overview.

The Journal of international medical research, 1989

Research

What are the differences between the H2-receptor antagonists?

Alimentary pharmacology & therapeutics, 1987

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Efficacy of H2 receptor antagonists in the treatment of gastroesophageal reflux disease and its symptoms.

Canadian journal of gastroenterology = Journal canadien de gastroenterologie, 1997

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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