Pharmacology of histamine 2 (H2) antagonists
Therapeutic actions
H2 antagonists or H2-blocker inhibit the action of histamine at the H2 receptors of the stomach, inhibiting gastric acid secretion and reducing total pepsin output; the resultant decrease in acid allows healing of ulcerated areas. See additional notes "Peptic Ulcer; assessment and management" and "Dyspepsia".
Clinical pharmacology
Dosing and indications
H2 receptor antagonists (H2RAs) are indicated for the short-term and maintenance treatment of active duodenal ulcers and benign gastric ulcers. They are also used in the treatment of pathologic hypersecretory conditions such as Zollinger-Ellison syndrome and erosive GERD. Additionally, H2RAs provide prophylaxis against stress-induced ulcers and acute upper GI bleeding in critically ill patients, as well as treatment for GERD, heartburn, acid indigestion, and sour stomach.
- "See, table 1" and cimetidine, famotidine, nizatidine and ranitidine for prescribing information (from priscriber's digital reference).
- Ranitidine (Zantac) withdrawn from market in 2020.
| Table (1). Recommended oral dosing of H2 antagonist for patients with normal renal function | |||
|---|---|---|---|
| Medication | Maintenance, duodenal ulcer | Active ulcer | GERD/erosive esophagitis |
| Cimetidine (Tagamet) | 400 mg HS | 800 mg HS (can divide BID for duodenal ulcer) up to 1600 mg HS (duodenal) or 300 mg QID (gastric) | 1600 mg divided BID or QID |
| Famotidine (Antodine) | 20 mg HS | 40 mg HS (can divide BID for duodenal ulcer) | 20 mg BID (GERD); 20 or 40 mg BID (erosive esophagitis) |
| Nizatidine (Nizatect) | 150 mg HS | 300 mg HS (duodenal ulcers) or divided BID (duodenal or gastric ulcers) | 150 mg BID |
| Ranitidine (Zantac) | 150 mg HS | 300 mg HS (duodenal ulcer) or 150 mg BID (duodenal or gastric ulcer) | 150 mg BID (GERD); 150 mg QID (erosive esophagitis) |
| Abbreviations: BID=twice daily; CrCl=creatinine clearance; GERD=gastroesophageal reflux disease; HS=at bedtime; QID=four times daily | |||
Contraindications
H2RAs are contraindicated in patients with an allergy to H2 antagonists and in those with impaired renal or hepatic function. They are classified as Category B during pregnancy, indicating they are considered safe for use.
Adverse effects
Adverse effects associated with H2RAs include
- CNS symptoms such as dizziness, somnolence, headache, confusion, hallucinations, peripheral neuropathy, and signs of brainstem dysfunction (dysarthria, ataxia, diplopia).
- Cardiovascular (CV) effects may include cardiac arrhythmias, arrest, and hypotension with intravenous use.
- Gastrointestinal (GI) adverse effects can manifest as diarrhea. Hematologic effects may present as increases in plasma creatinine and serum transaminase levels.
- Other potential effects include impotence (reversible with drug withdrawal), gynecomastia (with long-term treatment), rash, vasculitis, and pain at the intramuscular injection site.
Interactions
Interactions with H2RAs include an increased risk of decreased white blood cell counts when used with antimetabolites, alkylating agents, and other drugs known to cause neutropenia. There is also an increased risk of serum levels and toxicity for warfarin-type anticoagulants, phenytoin, beta-adrenergic blockers, alcohol, quinidine, lidocaine, theophylline, chloroquine, and certain benzodiazepines (such as alprazolam, chlordiazepoxide, diazepam, flurazepam, and triazolam), as well as nifedipine, pentoxifylline, tricyclic antidepressants, procainamide, and carbamazepine when taken concurrently with H2 antagonists.
Clinical considerations
| Table (2). Clinical considerations of H2RA | |
|---|---|
| Comment | |
| Assessment | History: Allergy to H2 antagonists, impaired renal or hepatic function, lactation. Physical: Skin lesions; orientation, affect; pulse, baseline ECG (continuous with IV use); liver evaluation, abdominal examination, normal output; CBC, LFTs, renal function tests. |
| Interventions | Administer drug with food and at bedtime. Decrease doses in renal and hepatic impairment. Administer IM dose undiluted, deep into large muscle group. Ensure ready access to bathroom. Provide comfort measures for rash, headache. Establish safety measures if CNS changes occur (side rails, accompany patient). Arrange for regular follow-up, including liver and renal function tests, to evaluate effects. |
Teaching points
- Take H2RA with food and at bedtime; therapy may continue for 4–6 weeks or longer.
- Take antacids exactly as prescribed; be careful of the time.
- Inform your health care provider about your cigarette smoking habits.
- Cigarette smoking decreases the effectiveness of these drugs.
- Have regular medical follow-up while on this drug to evaluate your response.
- Report sore throat, fever, unusual bruising or bleeding, tarry stools, confusion, hallucinations, dizziness, muscle or joint pain.
References
- Aronson, J. K., ed. (2016). "Histamine H2 Receptor Antagonists." In Meyler's Side Effects of Drugs (16th ed.), 751-753. Elsevier. https://doi.org/10.1016/B978-0-444-53717-1.00849-0.
- Nugent, C.C. and Terrell, J.M. (2019). H2 Blockers. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK525994.
