Pharmacotherapy of Gastric Acidity, Peptic Ulcer…

Introduction

• Defense mechanism of esophagus is the LES• Defense mechanism stomach are mucous

lining and bicarbonate production (?)

Therapies…

• Treat h. pylori with antimicrobial

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

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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

Proton Pump Inhibitors

• Chronic intake of PPI can cause rebound phenomenon (?)

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

• Cheaper than PPI• Ranitidine (Ulcin)

H2 Receptor Antagonists

• Has shorter duration compared to PPI• Given every 4-6 hours

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

Sucralfate

• Can cause aluminum overload renal failure• Bezoars undigested masses

antacids

• Need to titrate dose to relieve symtopms• It can cause accumulation of Al, Ca, and Mg

antacids

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antacids

• Best is combi of magnesium and aluminum hydroxide (Maalox)