H2-receptor antagonists

Key examples

• Ranitidine

 

Common indications

1. Peptic ulcer disease: for treatment and prevention of gastric and duodenal ulcers and NSAID-associated ulcers, although proton pump inhibitors (PPIs) are more effective and therefore usually preferred.
2. Gastro-oesophageal reflux disease (GORD) and dyspepsia: for relief of symptoms. PPIs are the main alternative, and are preferred in more severe cases.

 

Mechanisms of action

• Histamine H2-receptor antagonists (‘H2-blockers’) reduce gastric acid secretion. Acid is normally produced by the proton pump of the gastric parietal cell, which secretes H+ into the stomach lumen in exchange for drawing K+ into the cell. The proton pump is regulated, among other things, by histamine. Histamine is released by local paracrine cells and binds to H2-receptors on the gastric parietal cell. Via a second-messenger system, this activates the proton pump. Blocking H2-receptors therefore reduces acid secretion. However, as the proton pump can also be stimulated by other pathways, H2-blockers cannot completely suppress gastric acid production. In this respect they differ from PPIs, which tend to have a more complete suppressive effect.

 

Important adverse effects

• H2-blockers are generally well tolerated with few side effects. Most common among these are bowel disturbance (diarrhoea or, less often, constipation), headache and dizziness.

 

Warnings

• H2-blockers are excreted by the kidneys, so their dose should be reduced in patients with renal impairment. Like PPIs, they can disguise the symptoms of gastric cancer, so it is important not just to treat symptoms without considering and, if appropriate, investigating their cause.

Important interactions

• Ranitidine has no major drug interactions.