pharmacotherapy of gastric acidity, peptic ulcer…
TRANSCRIPT
Introduction
• Defense mechanism of esophagus is the LES• Defense mechanism stomach are mucous
lining and bicarbonate production (?)
Sites of therapeutic action
• Histamine comes from ECL, mast cells, and neurons.
• Medication should focus on these areas
Gastric mucus
• Main function of mucus is to slow down ion diffusion
• Prostaglandins come from gastric mucosa. E2 and I2 stimulates secretion of mucus and bicarbonate.
• Anything that inhibits prostaglandin secretion (NSAIDS, steroids, alcohol) would decrease gastric mucus
• Tip: taking antacids the day after a drinking binge helps.
PGE2 and PGI2
• Chronic intake of Aspirins and NSAIDS are the usual causes of people going to the clinic due to ulcers
Proton Pump Inhibitors
• Most potent drug to inhibit hyperacidity• Esomeprazole (Nexium)• Proton pump inhibitors are prodrugs (inactive)– Selectivity– Enhances absorption, distribution, metabolism,
excretion.
Proton pump inhibitors
• Prodrugs are only activated in their intended environment– The acidic environment of the parietal cells– You don’t necessarily have to be hyperacidic
Proton Pump Inhibitors
• Inhibits the last step before acid secretion• Effect is prolonged– Can be taken just once a day
• Important: It has to be taken 30 minutes before a meal.– Otherwise, it won’t be absorbed into the parietal
cells– And acid would be secreted before prodrug is
activated therefore, pointless
Proton Pump Inhibitors
• Have to protect prodrug with enteric coating to keep stomach acids from degrading it before it makes it to the parietal cells
Proton Pump Inhibitors
• Use with caution if px has hepatic disease– Studies are conflicting whether it has any adverse
effects on liver
H2 Receptor Antagonists
• Blocks histamine from binding to H2 receptors• Less potent than PPI• Can be taken even after a full meal
H2 Receptor Antagonists
• Adverse effects are rare• Cemetidine can cause reduced sperm count
and impotence
Prostaglandin Analog: Misoprostol
• (mentioned in passing)• Can also protect stomach from increased acid
secretion and production of mucus• Very rapid absorption• Peaks after 30 minutes• Needs to be taken on an empty stomach• Contraindicated in pregnancy– Pregnancy related GERD usually use PPI (3rd
trimester)
Sucralfate
• Used for mucosal inflammation or ulceration not responsive to acid suppression
• Cheaper than PPI.– Usually used with H2 receptor blockers