GI Pharmacology — Gastric pH Drugs

Mechanism of Gastric Acid Secretion

• Simulation of secretion via
  • ↑Gastrin via gastrin receptors
  • ↑Ach via M1 rexeptors
  • Histamine via H2 Receptors
• receptors located on the basolateral membrane
• Ach and gastrin → ↑ in intracellular [Ca2+]
• H2 receptors are coupled via Gs to adenyl cyclase
• ↑ in Ca2+ and cAMP → ↑ protein kinase activity → ↑ hydrogen pump activity in the luminal membrane

Drug Classes

• PROTON PUMP INIHBITORS (eg, pantoprazole)
  • All are prodrugs
  • MOA
    • Converted to its active form in the low pH of stomach
    • Accumulates in the parietal cells after absorption
    • Binds to the H/K-ATPase anti-porter
    • Inhibiting the proton pump and causing potent and long lasting suppression of basal and stimulated gastric acid secretion.
  • PD:
    • ↓ acidity/gastric secretions, no change emptying/LOS tone
  • PK
    • A:
    • pKa ~4, lipophilic weak bases thus diffuse into acidic environments well (ie: parietal cell) thus attack secreting not quiesent pumps
    • ~50% oral bioavailability, best on empty stomach
    • D: High protein binding >90%
    • M: rapid first pass metabolism
    • E: t1/2 1.5hrs but irreversible H/KATPase bond lasts ~24hrs
• HISTAMINE-2 RECEPTOR ANTAGONISTS (eg; ranitidine)
  • Bind to the H2 receptor on the basolateral surface of the parietal cell to reduce H2-stimulated acid secretion from the H/K ATPase on the luminal side of the cell.
  • ↓ acidity/gastric secretions, no change emptying/LOS tone
  • PK
    • well orally absorbed, 50% first pass metabolism
    • poorly protein bound 15%
    • hepatic metabolism, does not induce p450
• MUSCARINIC ANTAGONISTS (eg, pirenzipine)
  • Relatively specific M3 receptor antagonist which reduces the acetylcholine-mediated stimulation of the proton pump
• ANTACIDS (eg, Mylanta, Gastrogel).
  • Weak bases which usually contain aluminium and/or magnesium compounds to chelate H+ ions

Gladwin 2016

Answer by Gladwin