(FETT) Histamine Receptor Antagonist

GI Agents

RANITIDINE

H2 antihistamine

• Ranitidine

  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.

• Famotidine

• Nizatidine

• Cimetidine

• Location of H2 receptors

  • Gastric parietal cells (oxyntic cells)

  • Vascular smooth muscle

  • Neutrophils

  • Central nervous system

  • Heart

  • Uterus

• Histamine effects on H2 receptors

  • Increased gastric acid secretion

  • Positive inotropism and enhanced automaticity

  • Smooth muscle relaxation leading to vasodilatation

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

• Almost all side effects are caused by cimetidine; side effects in other H2 blockers are rare.

• Cimetidine

  • 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)

• Gastritis

• Zollinger-Ellison syndrome

• Pregnancy, since cimetidine is known to cross the placental barrier

• Nursing mothers

• Children

Drink a glass of H2O before dining: H2 blockers need to be taken before dinner.