Pharm: GI disorders

Question 1

describe the pumps/channels involved in HCl secretion by parietal cells

Answer 1

ATP dependent H/K exchanger pumps out protons

chlorine exits through chloride channels

Question 2

Where do protons for stomach acid come from?

Answer 2

carbonic acid synthesized from water and carbon dioxide with the help of carbonic anhydrase. bicarb exchanged for Cl on the blood side of the parietal cell

Question 3

What biochemical change controls the ATP-dependent proton/K exchanger that helps generate stomach acid?

Answer 3

phosphrylation of the pump promotes activity

Question 4

What three neurohormonal molecules promote phosphorylation/activation of the ATP-dependent H/K exchanger that generate stomach acid?

Answer 4

1. gastrin
2. ACh
3. histamine

Question 5

How does gastrin work (what cells are involved, what happens)

Answer 5

gastrin secreted by G cells into blood
gastrin binds CCK receptors on basolateral parietal cells. mediate signal via phospholipase C. incr. in cytoplasmic Ca –> kinases (protein kinase C and calmodulin-dependent kinases) –> proton pump activation

Question 6

How does ACh affect ATP-dependent proton pump (H/K exchanger) that is responsible for production of stomach acid (include biochem pathway)

Answer 6

binds to M3 muscarinic receptors on parietal cells
activates phospholipase C
incr. in cytoplasmic Ca –> kinases (protein kinase C and calmodulin dependent kinases)–> proton pump activation

Question 7

What role does histamine play in stomach acid secretion?

Answer 7

secreted by eneterochromaffin-like (ECL) cells
binds to H2 receptors on the basolateral membrane of parietal cells
adenylate cyclase activation
incr. cAMP
incr. cAMP dependent protein kinases
proton pump activation

Question 8

What two facorts inhibit gastric acid secretion?

Answer 8

Prostaglandin E2 and somatostatin

Question 9

How does prostaglandin E2 reduce gastric acid secretion?

Answer 9

inhibition of adenylate cyclase

Question 10

How does somatostatin decrease gastric acid production?

Answer 10

1. inhibit gastrin release by G cells
2. inhibit histamine release by ECL cells
3. directly inhibit acid secretion by parietal cells

Question 11

What is the first line drug that should be used to treat peptic ulcer disease caused by H. pylori infection?

Answer 11

clarithromycin (aka Biaxin)

Question 12

What are four stategies/drug target for decreasing gastric acid production?

Answer 12

1. histamine H2 antagonists
2. proton pump inhibitor
3. Prostaglandin
4. anticholinergic drugs

Question 13

How do histamine receptor antagonists work?

Answer 13

they competitively inhibit H2 receptors to decr. cAMP and cAMP dependent protein kinases

Question 14

What are some H2 antagonists?

Answer 14

MUST KNOW: famotidine (pepsid)

may know: cimetidine/tagamet, ranitidine/zantac

Question 15

What are the most important side effects of H2 antagonists

Answer 15

CNS: headache, dizziness, confusion, hallucination (esp. in elderly
Drug interactions: metabolized by P450 (interacts with drugs like warfarin, phenytoin) and may reduce drugs that require gastric acid for absorption

other sides: diarrhea, inhibition of alcohol metab, antiandrogenic effects (gynecomastia, reduced sperm count)

Question 16

How do proton pump inhibitors work?

Answer 16

taken as a prodrug and conveted to active form in acid near parietal cells
covalent binding to cysteine residue (noncompetitive)
pump takes 18 hrs to replace

Question 17

What proton pump inhibitors should I know?

Answer 17

MUST know: pantoprazole/protonix
could know prilosec/omeprazole
prevacid/lansoprazole

Question 18

What prostaglandin drug should I know, and how does it work?

Answer 18

misoprostol

inhibits gastric acid production by parietal cells

Question 19

What antimuscarinic agent should I know for GI pharm? (less critical to know)

Answer 19

dicyclomine- decr. gastric acid production. rarely used

this is less important to know

Question 20

What classes of drugs improve gastric resistance to erosion?

Answer 20

antacids

mucosal protective agents (sucralfate and colloidal bismuth)

Question 21

Sucralfate: what is it? how does it work?

Answer 21

complex salt of sucrose sulfate and aluminum hydroxide

viscous gel that protects mucosal lining

Question 22

Colloidal bismuth: what is it? How does it work (3 things)

Answer 22

aka pepto-bismol. protects mucosal lining:

1. binds to gastric mucosal glycoproteins
2. induces secretion of sodium bicarbonate and prostaglandin (reduces acid)
3. inhibts H. pylori growth