1. Pharmacotherapy of Gastric Acidity, Peptic Ulcer…

2. Introduction Defense mechanism of esophagus is the LES
Defense mechanism stomach are mucous lining and bicarbonate production (?)

3. Therapies…
Treat h. pylori with antimicrobial

4. Sites of therapeutic action
Histamine comes from ECL, mast cells, and neurons.
Medication should focus on these areas

5. 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.

6. PGE2 and PGI2
Chronic intake of Aspirins and NSAIDS are the usual causes of people going to the clinic due to ulcers

7. Proton Pump Inhibitors
Most potent drug to inhibit hyperacidity
Esomeprazole (Nexium)
Proton pump inhibitors are prodrugs (inactive)
Selectivity
Enhances absorption, distribution, metabolism, excretion.

8. Proton pump inhibitors
blank

9. 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

10. 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

11. 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

12. Proton Pump Inhibitors
Use with caution if px has hepatic disease
Studies are conflicting whether it has any adverse effects on liver

13. Proton Pump Inhibitors
Chronic intake of PPI can cause rebound phenomenon (?)

14. H2 Receptor Antagonists
Blocks histamine from binding to H2 receptors
Less potent than PPI
Can be taken even after a full meal

15. H2 Receptor Antagonists
Cheaper than PPI
Ranitidine (Ulcin)

16. H2 Receptor Antagonists
Has shorter duration compared to PPI
Given every 4-6 hours

17. H2 Receptor Antagonists
Adverse effects are rare
Cemetidine can cause reduced sperm count and impotence

18. 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)

19. Sucralfate
Used for mucosal inflammation or ulceration not responsive to acid suppression
Cheaper than PPI.
Usually used with H2 receptor blockers

20. Sucralfate Can cause aluminum overload  renal failure
Bezoars  undigested masses

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

22. antacids
blank

23. antacids
Best is combi of magnesium and aluminum hydroxide (Maalox)