RANITIDINE Siddharth Shah Brand Name: Zantac (GlaxoSmithKline, Prescription); Zantac OTC (Boehringer Ingelheim, OTC) Chemical Name: N [2-[[[5-[(d imethylamino)methyl]-2-furanyl]met hyl]thio]ethyl]-N'- methyl-2-nitro-1,1-ethenediamine, HCl. Structure: Appearance: White to pale yellow, slightly bitter and a sulfur-like odor. Primary Use: Relieves ‘heartburn’ associated with acid indigestion and sour stomach. How Heartburn occurs: Cells called parietal cells are responsible for acid secretion in the stomach. If the sphincter of the stomach opens when it should not, to allow stomach juices to enter the esophagus, heartburn occurs. Shown above (right) are the parietal cells, the apical membrane being common between these cells and the stomach lumen. As seen, water and CO 2 are converted to carbonate ion (HCO3 - ) and a hydrogen ion (H + ) by carbonic anhydrase. The HCO3 - is exchanged at the basolateral membrane for a chloride ion by the Cl - /HCO3 - antiporter. This Cl - continues to the apical membrane and by virtue of its
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concentration gradient, diffuses into the stomach lumen. The H+, on the other hand,
is exchanged for a potassium ion (K +) expending ATP by the H+/K + ATPase at the
apical membrane. H+ thus enters the stomach lumen. This H+ and the Cl- constitute
the HCl in the stomach. The H+/K + ATPase is, however, not present at the apical
membrane surface at all times. It is transported to the apical membrane only after
histamine activation.
Parietal cells bear receptors for three stimulators of acid secretion, reflecting
neural, paracrine and endocrine control:
Acetylcholine
Gastrin
Histamine (H2 type receptor) – primary modulator.
The H2 receptor is a rhodopsin-like GPCR. Binding of histamine and activation of
the H2 receptor leads to activation of adenylate cyclase (AC). AC catalyzes the
conversion of ATP to cAMP. Elevated cAMP levels activate Protein Kinase A (PKA).PKA phosphorylates certain cytoskeletal proteins involved in transport of the H+/K +
ATPase to the apical membrane.
Mechanism of Action: Ranitidine is a H2 receptor antagonist. It competes with
histamine to bind reversibly to the H2 receptor. By preventing activation of the H2
receptor and the subsequent activation of PKA, ranitidine prevents transport of the
H+/K + ATPase to the apical membrane. Thus, stomach acidification is prevented.
Since the acids are no longer produced, none can enter the esophagus to cause
irritation. Thus, heartburn is prevented.
Ranitidine is found to provide relief from heartburn within 24 hours.