List other examples of H2 antihistamines.
The FDA has requested the removal of ranitidine from the US market, because low levels of N-Nitrosodimethylamine (NDMA) were found in the medication. NDMA is thought to cause cancer.
Where are the histamine H2 receptors located, and what are the effects of histamine on H2 receptors?
Location of H2 receptors
Gastric parietal cells (oxyntic cells)
Vascular smooth muscle
Central nervous system
Histamine effects on H2 receptors
Increased gastric acid secretion
Positive inotropism and enhanced automaticity
Smooth muscle relaxation leading to vasodilatation
Describe the mechanism of action of H2 antihistamines.
Competitive, reversible antagonism of histamine H2 receptors (Gs protein-coupled receptor) on parietal cells → ↓ adenylyl cyclase activity → ↓ cAMP levels → ↓ protein kinase A activity → ↓ phosphorylation and activation of H+/K+ ATPase → ↓ gastric acid (H+) secretion
List side effects.
Almost all side effects are caused by cimetidine; side effects in other H2 blockers are rare.
Antiandrogenic effect (via release of prolactin) → erectile dysfunction, gynecomastia, low libido in men
Inhibition of cytochrome P450 (CYP2C19) → various drugs interactions, e.g., clopidogrel
Headaches, dizziness, confusion due to its ability to cross the blood-brain barrier
Can cross the placenta (but is considered safe)
Reduces renal creatinine excretion (along with ranitidine)
Anaphylactic shock (together with H1 antihistamines)
Symptomatic treatment of peptic ulcers: reduce the production of hydrochloric acid (less effective than PPIs )
Gastroesophageal reflux disease (GERD)