H2 Antihistamines

H2 antihistamines compete with Histamine for binding at H2 receptors. The most commonly used in MCAS is famotidine.

Mechanism

By blocking H2 receptors on gastric parietal cells, these drugs reduce gastric acid secretion — which is why they were originally developed as anti-ulcer medications. In the MCAS context, they also block H2-mediated cardiac effects (tachycardia, increased contractility) and immune modulation.

Why They’re Part of MCAS Treatment

H2 blockade addresses symptoms that H1 Antihistamines don’t cover:

• Gastric acid hypersecretion (reflux, heartburn, nausea)
• Some cardiac effects of histamine
• Immune cell modulation

The combination of H1 + H2 blockade is more effective than either alone because they cover different receptor populations and different tissue effects of the same molecule.

Famotidine vs. Others

Famotidine is generally preferred. Ranitidine (Zantac) was widely used but was withdrawn from many markets due to NDMA (a probable carcinogen) contamination concerns. Cimetidine is an older H2 blocker with more drug-drug interactions (it inhibits several cytochrome P450 enzymes) and is less commonly used.