H2 antagonists

H2 receptor antagonists for ulcers

When the stimulatory histamine H2 receptor is blocked, the production of the second messenger cAMP via the adenylate cyclase enzyme is inhibited. This decrease in cytosolic cAMP concentrations prevent the stimulation of protein kinase A and its subsequent phosphorylation of the H+/K+ ATPase that pumps acid into the gastric lumen.

H2 receptor antagonists were introduced for the treatment of peptic ulcer disease in the mid-1970s. They are very effective and relatively safe agents for the treatment of ulcer disease. Mostly, they reduce  basal (nocturnal) but also post-prandial acid secretion. By decreasing acid secretion, H2 receptor antagonists reduce ulcer pain and promote healing of the mucosa.

The effect of these drugs on acid secretion can be evaluated by aspiration of gastric contents and measuring their acidity, or by continuous 24-hour pH recording. Acid-reducing therapy is considered effective when it raises intragastric pH to levels > 4 for several hours.

Because of the short half-life and duration of action of these agents, more than once-daily administration is required to obtain 24-hour acid reduction. However, since both metabolized and unmetabolized product is excreted into the urine, dosage adjustments are required in patients with renal insufficiency. H2 receptor antagonists (particularly cimetidine) may also interfere with the metabolism of other drugs by inhibiting hepatic cytochrome P450 enzymes, so the possibility for drug interactions should be explored. Ranitidine is the most frequently prescribed H2 receptor antagonist.


Famotidine and ranitidine act as anti-ulcer drugs because of antagonism at the parietal cell of