H2 Blockers

Introduction and Mechanism of Action

• H2RAs, or H2 blockers, suppress gastric acid and are used to manage gastric conditions and prevent aspiration pneumonitis.^1,2
• Perioperative pulmonary aspiration is the aspiration of gastric contents during anesthesia induction, during a procedure, or in the immediate postoperative period. Link
• Complications of pulmonary aspiration include aspiration pneumonia, pneumonitis, and respiratory distress or failure.³
• Prevention of pulmonary aspiration is likely more effective when a combination of an H2RA and an antacid is used compared to the use of a single agent.⁴
• Gastric acid suppression by H2RAs
  • After a meal, gastrin stimulates histamine release from enterochromaffin-like cells.
  • Histamine binds to H2 receptors on gastric parietal cells, resulting in gastric acid release.
  • H2RAs reversibly bind to H2 receptors on gastric parietal cells, which inhibits histamine binding (competitive antagonist) and decreases gastric acid secretion.¹
  • Decreased gastric acid secretion leads to increased pH of stomach contents and reduced gastric volume, thereby decreasing the risk of pulmonary aspiration.²

Indications and Common Uses

• H2RAs are approved for gastroesophageal reflux disease (GERD), gastric or duodenal ulcers, heartburn or indigestion, gastric hypersecretion (such as Zollinger-Ellison syndrome), and stress ulcer prophylaxis.¹
• Off-label uses include esophagitis, gastritis, gastrointestinal bleeding, Helicobacter pylori eradication, stress ulcer prophylaxis in critically ill patients, and aspiration prophylaxis prior to anesthesia.^1,3,5
• Use in the perioperative period to reduce the risk of aspiration pneumonitis
• Pregnancy and labor
  • Caesarean section: H2RA should be administered as a premedication along with antacids (famotidine IV 20 mg IV, 60 – 90 minutes prior to induction).^2,6
  • Nondelivery obstetric procedures during pregnancy or early postpartum period (cerclage, external cephalic version, postpartum tubal ligation): H2RA (IV famotidine 20mg 60 – 90 minutes before induction, or 20mg PO night prior to surgery and morning of surgery) should be given in patients with GERD or beyond 18 weeks of pregnancy, along with prokinetic agent (metoclopramide) and nonparticulate antacid (to increase pH of gastric contents, decreasing pulmonary damage if aspiration does occur).^2,7
  • Nonobstetric surgery during pregnancy or the early postpartum period: consider giving H2RA prior to surgery if greater than 18 weeks of pregnancy.⁷
• Increased risk of pulmonary aspiration (emergency surgery, trauma, nonfasting, symptomatic GERD, gastroparesis or delayed gastric emptying, hiatal hernia, gastric outlet obstruction, esophageal pathology or esophagectomy, bowel obstruction, increased abdominal pressure)²
  • Consider H2RA (famotidine 20mg IV) 60 to 90 minutes prior to induction, along with an antacid.²
  • Patients regularly taking H2 blockers should continue to take them in the perioperative period. Intravenous (IV) formulations should be used in prolonged NPO states.⁸
• Patients without increased risk for pulmonary aspiration
  • H2RAs are not recommended for routine use prior to anesthesia.³

Formulations and Dosing

• In the United States, the H2RAs available by prescription or over the counter are famotidine, cimetidine, and nizatidine.¹
• Ranitidine (Zantac) has been withdrawn from the US marketplace due to unacceptably high levels of N-nitrosodimethylamine, a probable human carcinogen.^1,9
• Famotidine (Pepcid) is available as oral tablets, oral powder for suspension, combination formulations (calcium carbonate, magnesium hydroxide, or ibuprofen), and IV formulations.¹
  • IV formulation is approved for the treatment of active duodenal and gastric ulcers, short-term treatment of GERD, erosive or ulcerative esophagitis due to GERD, and gastric hypersecretion.¹
• Nizatidine is available as oral tablets and oral solution.¹
• Cimetidine is available as oral tablets, oral solution, and IV.¹
• Indication-specific dosing for H2RAs is listed in Table 1.

Pharmacokinetics and Drug Interactions

• Gastric relief typically occurs within 60 minutes with a duration of action of 4 to 10 hours.¹
• H2RAs are eliminated by hepatic and renal metabolism. Nizatidine clearance is significantly prolonged in renal disease.¹
• Nizatidine reaches peak plasma levels in 0.5 to 3 hours, famotidine in 1 to 3 hours, and cimetidine in 45 to 90 minutes.¹
• Concurrent antacid administration reduces absorption by 10-20 percent.⁹
• Food intake does not affect the absorption of H2RAs.⁹
• Cimetidine inhibits CYP1A2, CYP2C9, and CYP2D6, which can lead to drug interactions with medications metabolized by CYP450 enzymes.¹

Contraindications, Adverse Effects, and Special Populations

• There are no absolute contraindications to H2Ras, but they should be avoided in patients with known hypersensitivities to any H2RA formulation.¹
• H2RAs are generally well-tolerated, and toxicity is rare.¹
• Mild side effects include headache, fatigue, drowsiness, abdominal pain, constipation, and diarrhea.^1,6 Systemic effects of H2RAs are listed in Table 2.

Chronic Use

• Prolonged and high doses of cimetidine may result in gynecomastia, reduced sperm count, impotence, and galactorrhea.¹
• Regular use of H2RAs may lead to tachyphylaxis or tolerance, which can be prevented by intermittent use.¹
• Chronic use in patients over 50 years of age increases the risk of central nervous system effects.⁶
• Chronic use has been associated with B12 deficiency.⁹

Special Populations

• Renal impairment: If creatinine clearance is less than 30mL/min, reduce the famotidine dose by 50%. Cimetidine should not exceed 300mg every 12 hours. For patients with creatinine clearance 20 – 50mL/min, the nizatidine dose is 150mg once daily and 150mg every other day if creatinine clearance is less than 20mL/min.¹
• Hepatic impairment: No dosage adjustment for famotidine or nizatidine. Use cimetidine with caution due to the potential for medication interactions.¹
• Pregnancy: Although antacids are first-line agents for heartburn during pregnancy, H2 receptor antagonists may be used if needed (pregnancy category B).¹
• Breastfeeding mothers: No precautions for nizatidine or famotidine. Consider using agents other than cimetidine, as it may inhibit hepatic enzymes.¹
• Pediatric patients: H2RAs have been used safely in children and adolescents with heartburn symptoms not responsive to lifestyle changes.¹