Pharm of Peptic Ulcer Disease

Question 0

3 acid-promoting receptors on the parietal cell?

Answer 0

Ach
Gastrin
Histamine

Question 1

4 medical ways to treat peptic ulcer disease?

Answer 1

Inhibit acid production
Neutralize acid
Increase protective factors
Kill H. pylori

Question 2

Why does targeting the proton pump also affect pepsin?

Answer 2

Pepsin is only active at a pH below 4.
It gets irreversibly inactivated at pH 6.
Increasing pH with PPI disables pepsin and prevents autodigestion.

Question 3

What do PPIs do the proton pump?

Answer 3

Irreversibly inhibit them.

Question 4

What are the CAT aggressive factors for ulcers?

Answer 4

Caffeine
Alcohol
Tobacco
(C and T increase acid secretion, A is directly toxic to tissue)

Question 5

2 protective prostaglandins? What 3 things do they do?

Answer 5

PGE1 and PGE2
They increase bicarb,
increase mucous,
and increase blood flow.

Question 6

Are tight junctions an important protective factor?

Answer 6

Yes.

Question 7

What does the parietal cell “proton pump” actually do?

Answer 7

Exchanges H+ for K+, using ATP.

Question 8

How does the parietal cell deal with the excess of K+ that builds up?

Answer 8

There’s a Cl-, K+ symporter that brings them out of the cell.

Question 9

What impact to PGE1&2 directly have on parietal cells?

Answer 9

The bind to a GPCR that uses Gi, decreasing cAMP levels in the cell.

Question 10

What’s the major concern with cimetidine/Tagament (an H2 antagonist)?

Answer 10

P450 metabolism uses CYP3A4 -> lots of drug interactions.

esp Warfarin, phenytoin, diazepam

Question 11

Why do PPIs have such a long duration of effect despite having a short half life of 1-2 hours?

Answer 11

Irreversible inhibition of proton pump -> effect lasts for 24-36 hours.

Question 12

Do PPIs act from within the gut, or must they be absorbed systemically?

Answer 12

They must be absorbed systemically.

thus are formulated such that they won’t be destroyed by stomach acid…

Question 13

Major adverse effect of PPIs? (Theoretical one?)

Answer 13

Long term use -> weak bones due to impaired ability of osteoclasts to remodel bones (they can’t secrete acid).
(Theoretically may cause increased risk for gastrinoma, but this has never been seen in humans.)
(also… infections, due to less acid)

Question 14

Take-home point about antacid adverse effects?

Answer 14

You need to take way a lot to get effects. Effects are caused by ion that’s associated with the carbonate/bicarb/hydroxide.

Question 15

Generally, what’s the treatment for H. pylori?

Answer 15

2 ABx + PPI (+/- bismuth subsalicylate)

Question 16

Specifically, which ABx are used for H. pylori?

Answer 16

Clarithromycin or levofloxacin
plus
Amoxicillin or metronidazole

Question 17

5 things NSAIDs negatively impact related to ulcers?

Answer 17

Mucus
Bicarb
PGs
Blood flow
Direct epithelial injury

Question 18

What are 2 protective drugs for ulcers?

Answer 18

Misoprostol

Sucralfate

Question 19

What is misoprostol?

Answer 19

PGE 2 analogue.

Causes bloating, diarrhea, abortion.

Question 20

What is sucralfate?

Answer 20

Complex salt of sucrose and Aluminum hydroxide.

Stimulates bicarb and PGE2 production, prevents proteolysis - doesn’t have a direct effect on acid production.