H2-Receptor Antagonists

H₂-receptor antagonists (cimetidine, famotidine, nizatidine, ranitidine) provide symptom relief from dyspepsia¹ and allow healing of acid-related disease by reducing the volume and acidity of gastric secretion. When compared to cimetidine, ranitidine may be more effective for nocturnal symptoms and also has a less potential for side effects and interactions. H₂-receptor antagonists are less effective than proton pump inhibitors for treating gastric and duodenal ulcers.

NICE have published guidelines for the management of dyspepsia:²

• Gastric and duodenal ulceration:
  • Double dose H₂-receptor antagonists are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers.³ H₂-receptor antagonist therapy can also promote healing of NSAID-associated ulcers (particularly duodenal).
  • Maintenance treatment with low doses has largely been replaced in Helicobacter pylori positive patients by eradication regimens.
  • Maintenance treatment may occasionally be used for those with frequent severe recurrences and for the elderly who suffer ulcer complications.
  • Treatment has not been shown to be beneficial in haematemesis and melaena, but prophylactic use reduces the frequency of bleeding from gastroduodenal erosions in hepatic coma, and possibly in other conditions requiring intensive care.
  • Proton pump inhibitors have been shown to be more effective at treating gastric and duodenal ulcers than H₂-antagonists.⁴
• Reflux oesophagitis:
  • Treatment reduces the risk of acid aspiration in obstetric patients at delivery (Mendelson's syndrome).
  • Proton pump inhibitors are more effective than H₂-antagonists in relieving heartburn in patients with gastro-oesophageal reflux disease.⁵
• Zollinger-Ellison syndrome:
  • High doses of H₂-receptor antagonists have been used in Zollinger-Ellison syndrome, but a proton pump inhibitor is preferred.
• Urticaria:
  • If optimal doses of H₁ antihistamines do not provide adequate control, there is evidence that the addition of an H₂-receptor antagonist may have some additional benefit in reducing symptoms of pruritus and the number and duration of weals.⁶

H₂-receptor antagonists should be used with caution in:

• Renal impairment
• Pregnancy
• Breast-feeding

H₂-receptor antagonists might mask symptoms of gastric cancer, which is particularly relevant when prescribed for patients who are middle-aged or older.

Cimetidine but not other H₂-antagonists (famotidine, nizatidine, and ranitidine do not share the drug metabolism inhibitory properties of cimetidine) may:

• Impair metabolism of drugs (eg, diazepam, phenytoin, warfarin and theophylline) that are oxidised by similar iso-enzymes of the cytochrome P450 system.
• Reduce hepatic clearance of certain drugs, including propranolol and labetalol.

Although side effects are uncommon, they are more likely to occur in patients with impaired renal function.

• Central nervous system (e.g. dizziness, depression, headache and confusion) occur more frequently in the elderly.
• Gastrointestinal disturbances, altered liver function tests (rarely liver damage).
• High dose cimetidine, nizatidine and ranitidine are occasionally associated with male gynaecomastia and impotence.
• Speculation but no evidence of increased risk gastric carcinoma.

Rare side-effects include:

• Acute pancreatitis
• Bradycardia
• Hypersensitivity reactions (including fever, arthralgia, myalgia, anaphylaxis)
• Blood disorders (including agranulocytosis, leucopenia, pancytopenia, thrombocytopenia)
• Skin reactions (including erythema multiforme and toxic epidermal necrolysis)