H2-Receptor Antagonists

H2-RAs such as cimetidine, famotidine, nizatidine and ranitidine are used to treat more severe GORD.

Mode of action

H2-RAs block histamine H2-receptors located in the parietal cell membrane and therefore directly and selectively reduce acid secretion from the parietal cells (Figure 3). If used at their recommended therapeutic doses, they reduce acid output by 50–60%; however, because acid secretion is also mediated through the gastrin and muscarinic receptors, substantial acid output is still observed.

Interaction of an H2-RA with the parietal cell
FIGURE 3 – Interaction of an
H2-RA with the parietal cell
(click to enlarge)

H2-RAs also partially decrease pepsin production through an unknown mechanism and reduce the volume of refluxate entering the oesophagus. They have no effect on LOS activity, oesophageal clearance or gastric emptying.

Efficacy

H2-RAs generally relieve reflux symptoms in approximately 50% of patients with GORD,[Klinkenberg-Knol et al. 1995] although their efficacy in healing oesophagitis is less clear and dependent on the severity of oesophagitis, they are more effective in less severe oesophagitis.

The primary indication for H2-RAs, however, is peptic ulceration. In this indication, all of the products produce symptomatic relief in 1–2 weeks, and 75% of ulcers are healed by a 4–8 week course. However, relapse is common, and 60–80% of patients may relapse within 1 year if not given maintenance treatment.

H2-RAs are effective in the rare hyperacid condition, Zollinger-Ellison syndrome.

Dosing

In general, H2-RAs can be taken less frequently than antacids due to more sustained acid suppression.

Dosing is usually twice daily for ulcer or oesophagitis 'healing' therapy. For maintenance therapy for dyspepsia and reflux, a single dose at bedtime usually suffices. Famotidine is a longer-acting drug and requires once-daily dosing only.

After therapy is completed, however, rebound hypersecretion of acid can occur, as the stomach is stimulated to over-produce acid to compensate for increased stomach pH.

Adverse effects

The H2-RAs in general are well tolerated, but have been associated with nonspecific side effects, such as headache, fatigue, diarrhoea, dizziness and skin rashes, the negative impact of which may outweigh the potential therapeutic benefits.

Uncommon adverse effects include:

  • Reversible liver damage
  • Gynaecomastia (breast development in males)
  • Possible impotence

In practice, fungal or bacterial overgrowth due to prolonged pH elevation has not proved to be a problem.

Precautions

H2-RAs are not generally recommended for use in pregnancy and during lactation, and most are not recommended for use in infants and children.

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