PUD

Question 1

What is the goal when treating PUD and other disorders of chronic inflammation (GERD, Gastritis, etc)?

Answer 1

Goal is to reduce inflammation

Question 2

What are the protective cells of GI tract?

Answer 2

Surface epithelial, mucosal neck, and stem cells

Question 3

What are the digestive cells of GI?

Answer 3

Parietal, chief, and endocrine cells

Question 4

Describe direct pathway of acid secretion

Answer 4

Ach, gastrin, histamine directly stimulate parietal cells to secrete acid

Question 5

Describe the indirect pathway of acid secretion

Answer 5

Ach and gastrin stimulate ECL cells –> histamine release –> acid secretion

Question 6

Half of this lecture is stuff we know from phys, micro, & path. Should you review these subjects for the test?

Answer 6

Yes.. So now we will move on to pharm stuff

Question 7

Whats the overall goal of PUD tx? (3)

Answer 7

1. Eradicate H. pylori with antibiotics
2. Relieve symptoms with anti-secretory drugs or antacids
3. Heal ulcers with PGs, bismuth, sucrasulfate

Question 8

What do antacids do?

Answer 8

Neutralize acid in the stomach (duh)

Question 9

What is the goal for antacid tx?

Answer 9

pH > 4

Question 10

What are the antacid drugs?

Answer 10

1. Maalox (Mg-Al hydroxide)
2. Gaviscon (Maalox + algenic acid)
3. Calcium carbonate (Tums)

Question 11

What are antacids used for?

Answer 11

1. Simple dyspepsia

2. Adjunctive with H2 blockers or PPIs

Question 12

When are antacids taken?

Answer 12

A few hours post meal or before bedtime

Question 13

What is probably the biggest consideration when prescribing antacids?

Answer 13

They can SIGNIFICANTLY affect the absorption of other drugs (b/c the increase the pH of the stomach). So you dont want to take them within a few hours of other drugs*****

Question 14

Maalox is a combo of Mg hydroxide and Al hydroxide. What do these things do?

Answer 14

Mg hydroxide causes diarrhea. Al hydroxide causes constipation. You mix them together to balance the AEs. (Mg: M for Mudbutt)

Question 15

What do H2 antagonists do? (3)

Answer 15

1. Block histamine receptors.
2. Inhibit basal, cephalic, and nocturnal gastric acid secretion.
3. Reduces volume and [H+] of gastric acid

Question 16

Name the H2 antagonists

Answer 16

• Cemetidine: 1x potency
• Ranitidine & Nizatidine: 4-10x potency
• Famotidine: 20-50x potency
• *All have same efficacy

Question 17

Are the H2 antagonist specific for the stomach or not?

Answer 17

Yes! Thats good because few AEs

Question 18

Unique thing about Cemetidine?

Answer 18

Inhibits CYPs –> drug interactions

Question 19

Unique thing about Ranitidine?

Answer 19

Alters other drug’s bioavailability via an unknown mechanism

Question 20

Unique thing about Famotidine?

Answer 20

Leads to decreased Theophylline clearance

**Theophylline treats COPD

Question 21

What do PPIs do?

Answer 21

Inhibit H+ pump at apical surface of parietal cells

• *More effective than H2 blockers b/c it is the final common pathway so can block 90% of acid secretion**
• *All orally active pro-drugs with long duration of action

Question 22

Name the PPIs

Answer 22

The prazoles: Omeprazole, Esomepraole, Lansoprazole

Question 23

How do these drugs get to their place of action?

Answer 23

Drug has enteric coating which allows release of prodrug into SI (in neutral pH of SI, PPI is stable) –> PPIs then absorbed into blood stream (lipid soluble) –> Carried in blood to parietal cells where acid pH ionizes & traps them –> Ionized drug irreversibly binds to H/K ATPase

Question 24

What is the result of PPIs binding to H/K ATPase?

Answer 24

Achlorhydria & no gastric acid secretion. The parietal cell must make new H/K ATPases (proton pumps)

Question 25

All PPIs inhibit which CYP? Which PPI is the weakest inhibitor of said CYP?

Answer 25

CYP2C19. Pantoprazole is the weakest inhibitor of the CYP

Question 26

What does the CYP inhibition do?

Answer 26

1. Decreases Clopidogrel efficacy | 2. Decreases bioavailability of anti-retrovirals

Question 27

Clinical uses of PPIs? (4)

Answer 27

1. Short term for active PUD 2. Managing ZE syndrome 3. Managing refractory GI ulcers 4. Management of GERD * *Basically all letters: PUD, ZE, GERD

Question 28

Name the cytoprotective agents (think BS)!

Answer 28

1. Bismuth subsalicylate | 2. Sucralfate

Question 29

What does Bismuth subsalicylate do? (4 things)

Answer 29

1. Increases mucous & HCO3 secretion 2. Decreases pepsin activity 3. Chelates protein at base of ulcer to form protective barrier from GA and pepsin 4. Inhibits H. pylori

Question 30

What is Bismuth subsalicylate effective for? (4 things)

Answer 30

"TUG- Diarrhea": Travelers diarrhea, Ulcers, GERD, diarrhea

Question 31

What does Sucralfate do?

Answer 31

Forms sticky gel that adheres to gastric epithelium protecting it from GA and pepsin **Think sucralfate = sucrose = sticky gel

Question 32

What is unique about Sucrasulfate as far as activity?

Answer 32

It is the only agent that requires ACIDIC pH for activity so it can protect against ulcers without need for alkalinization (alkalinizatoin can lead to bacterial overgrowth)

Question 33

What is unique about Sucrasulfate as far as who to use it on?

Answer 33

Bedridden pts!

Question 34

What antibiotics treat H. pylori

Answer 34

Clarithromycin, Amoxicillin, Tetracycline, Metronidazole, Furazolidine

Question 35

Clarithromycin MOA?

Answer 35

protein synthesis inhibitor (50S subunit)

Question 36

Amoxicillin MOA?

Answer 36

B-lactamase resistant B-lactam (watch for Pcn allergy)

Question 37

Metronidazole MOA?

Answer 37

Inh nucleic acid synthesis. It is a synthetic antibiotic for obligate anaerobes

Question 38

Furazolidone MOA?

Answer 38

Nitrofuran anti-bacterial and anti-protozoal

Question 39

Describe the triple or quad therapy for treating H. pylori

Answer 39

Give: 1. PPI 2. H2 blocker 3. Bismuth subsalicylate 4. One or two antibiotics * *For 10-14 days

Question 40

If Clarithromycin resistant, switch to?

Answer 40

Metronidazole

Question 41

If Metronidazole resistant, switch to?

Answer 41

Furazolidine