Flashcards in Pharm: GI disorders Deck (22)
describe the pumps/channels involved in HCl secretion by parietal cells
ATP dependent H/K exchanger pumps out protons
chlorine exits through chloride channels
Where do protons for stomach acid come from?
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
What biochemical change controls the ATP-dependent proton/K exchanger that helps generate stomach acid?
phosphrylation of the pump promotes activity
What three neurohormonal molecules promote phosphorylation/activation of the ATP-dependent H/K exchanger that generate stomach acid?
How does gastrin work (what cells are involved, what happens)
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
How does ACh affect ATP-dependent proton pump (H/K exchanger) that is responsible for production of stomach acid (include biochem pathway)
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
What role does histamine play in stomach acid secretion?
secreted by eneterochromaffin-like (ECL) cells
binds to H2 receptors on the basolateral membrane of parietal cells
adenylate cyclase activation
incr. cAMP dependent protein kinases
proton pump activation
What two facorts inhibit gastric acid secretion?
Prostaglandin E2 and somatostatin
How does prostaglandin E2 reduce gastric acid secretion?
inhibition of adenylate cyclase
How does somatostatin decrease gastric acid production?
1.inhibit gastrin release by G cells
2. inhibit histamine release by ECL cells
3. directly inhibit acid secretion by parietal cells
What is the first line drug that should be used to treat peptic ulcer disease caused by H. pylori infection?
clarithromycin (aka Biaxin)
What are four stategies/drug target for decreasing gastric acid production?
1. histamine H2 antagonists
2. proton pump inhibitor
4. anticholinergic drugs
How do histamine receptor antagonists work?
they competitively inhibit H2 receptors to decr. cAMP and cAMP dependent protein kinases
What are some H2 antagonists?
MUST KNOW: famotidine (pepsid)
may know: cimetidine/tagamet, ranitidine/zantac
What are the most important side effects of H2 antagonists
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)
How do proton pump inhibitors work?
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
What proton pump inhibitors should I know?
MUST know: pantoprazole/protonix
could know prilosec/omeprazole
What prostaglandin drug should I know, and how does it work?
inhibits gastric acid production by parietal cells
What antimuscarinic agent should I know for GI pharm? (less critical to know)
dicyclomine- decr. gastric acid production. rarely used
this is less important to know
What classes of drugs improve gastric resistance to erosion?
mucosal protective agents (sucralfate and colloidal bismuth)
Sucralfate: what is it? how does it work?
complex salt of sucrose sulfate and aluminum hydroxide
viscous gel that protects mucosal lining