H2 receptor antagonists and night-time acid
Famotidine blocks the H2 receptor, the docking site where histamine, a natural messenger, tells the parietal cell (the acid-secreting cell of the stomach lining) to make acid.
Remember
Histamine is the main driver of basal acid secretion (the low steady output of acid between meals and overnight), so famotidine, which blocks the H2 receptor, works best for night-time symptoms.
Memory aid
H2 blockers close one door of three, and PPIs close the final gate
Famotidine blocks one of the three acid-stimulating pathways, whereas a PPI blocks the final common pathway.
Acid is made by parietal cells, the acid-secreting cells in the lining of the stomach. Three signals tell them to do so: histamine, gastrin (released from G cells in the lower stomach) and acetylcholine. Histamine comes from enterochromaffin-like (ECL) cells in the stomach wall and binds the H2 receptor on the parietal cell. That raises cAMP (cyclic AMP, a messenger inside the cell) and switches on the proton pump, the H+/K+ ATPase that pushes acid into the lumen.
Famotidine is an H2 receptor antagonist. It sits on the H2 receptor without activating it, so it competes with histamine for the receptor, and the block is competitive. Acid secretion falls by around 60 to 70% but is reduced rather than abolished, and one reason is that famotidine leaves the gastrin and acetylcholine receptors on the parietal cell working. A proton pump inhibitor (PPI) is more potent, because it blocks the pump that all three signals converge on.
Basal acid secretion is the low steady output of acid between meals and overnight. Histamine is the dominant driver of it, so blocking the H2 receptor has its biggest effect then. After a meal, gastrin and acetylcholine join in, so blocking histamine alone is less effective against meal-related acid.
Key facts
- Target
- the histamine H2 receptor on the parietal cell, which famotidine blocks competitively.
- Size of effect
- acid secretion falls by around 60 to 70%, which is less than with a PPI.
- Basal secretion
- the low steady acid output between meals and overnight, driven mainly by histamine.
- Still working
- the gastrin and acetylcholine receptors on the parietal cell, which famotidine does not block.
- Drug ending
- the ending tidine is shared by the H2 receptor antagonists (cimetidine, famotidine), whereas the proton pump inhibitors end in prazole.
- UK practice
- famotidine is the standard H2 receptor antagonist in current UK practice.
Exam traps
- Irreversible inhibition of the proton pump is how PPIs such as omeprazole work, not famotidine, which acts earlier in the pathway, at the histamine receptor.
- Antacids are weak bases that neutralise acid already in the stomach, whereas famotidine does not act in the stomach lumen but on the parietal cell, where it reduces how much acid is made.
- Gastrin mainly drives meal-related acid secretion, but famotidine does not block gastrin receptors: it blocks the histamine pathway, which matters more overnight.
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