GI pharm Flashcards
What do -prazole drugs do?
proton pump inhibitors (e.g. omeprazole)
Which pathways agonize and antagonize the H+/K+ ATPase in the stomach?
Agonists: H2 (Gs); vagus M3 and gastrin (Gq)
Antagonists: PG and somatostatin (Gi)
What drug suffix denotes H2 antagonists used for peptic ulcer disease?
-tidine e.g. cimetidine
Get a table for 2 [H2] before you dine
Why don’t we target the parasympathetic pathway as a target for the treatment of PUD?
muscarinic antagonists are in the atropine family and thus would have atropine-like side effects (hot, mad, dry, red, blind)
What are the 3 effects of prostaglandins in the stomach?
- ↓ proton pump activity
- promote secretion of mucus which protects stomach
- enhance bicarb secretion to neutralize acid
What drug is the direct antidote to NSAID induced PUD?
MisoPROSTol (a PROSTaglandin PGE1 analog)
What treatments are available for gastrinomas (e.g. ZES)?
There are no gastrin antagonists, we use PPIs
How does sucralfate work in the tx of PUD?
it is a sticky gel that coats the ulcer crater, protecting it from further erosion by acids
What are antacids?
bases that neutralize free protons in the stomach
What two stimuli cause histamine release from ECL cells? Which receptors are involved?
- Gastrin (CCK-B receptor)
2. Vagal (M1)
Do H2 blockers affect gastric emptying time?
no
What are 3 applications for H2 inhibitors?
- PUD (both gastric and duodenal; less effective than PPIs)
- GERD
- ZES
What is the main mechanism by which cimetidine → side effects? What are they?
Inhibition of cyt p450 → anti-androgen effects → gynecomastia and ↓ libido in ♂
Note: cimetidine is also associated with confusion in the elderly
Are PPIs reversible or irreversible, and competitive or non-competitive inhibitors of the H+/K+ ATPase?
Irreversible; non-competitive → ↑ effectiveness
Besides outperforming H2 blockers in the treatment of GERD, PUD, and ZES, what is an additional application of PPIs?
part of treatment regimen for H. pylori
What is the treatment for H. pylori?
Omeprazole
Clarithromycin +/- Amoxicillin
What is the primary treatment of GERD?
PPIs
Is omeprazole a p450 inhibitor?
yes, though it is not in the mnemonic
What is the primary contraindication of misoprostol?
Anything with -prost- = prostaglandin = contraindicated in pregnancy → induce contractions → abortion by triggering labor
What should not be given with sucralfate for ulcers? Why?
don’t give antacids b/c sucralfate is a prodrug that requires acidic environment to turn into a protective gel lining
What is the medical term for pepto bismol?
bismuth subsalicylate
What is the mechanism of action of bismuth?
binds selectively to ulcer, coating and protecting it from acid and pepsin
When is bismuth primarily used?
as part of BMT regimen to eradicate H. pylori and prevent ulcer recurrence
BMT = bismuth, metronidazole, and tetracycline
What is the side effect of aluminum containing drugs? Mg2+ containing drugs?
Al: constipation
Mg: diarrhea
What are the drug interactions of antacids?
- ↑ pH of gut → ↑ absorption of drugs that are weak bases (deionizes them; e.g. quinidine)
- ↑ pH of gut → ↓ absorption of weak acids (ionizes them; e.g. warfarin)
- tetracycline chelates ions (e.g. Ca2+, Al+, Mg2+) in antacids → ionizing tetracycline → ↓ absorption of tetracycline and interfering with benefit of antacid
Which receptors does the vagus activate on ECL cells? on parietal cells?
M1 on ECL cells and M3 on parietal cells
Where is the chemoreceptor trigger zone (CTZ) in the brain? What is it responsible and what is special about its blood supply?
area postrema at the floor of the 4th ventricle; projectile vomiting; no good BBB as a circumventricular organ → drugs can readily reach receptors here
What 3 receptors are located in the chemoreceptor trigger zone (area postrema)?
agonists: D2 and 5HT3
antagonist: CB1 (cannabinoid)
What are the inputs into the vomiting center in the brain?
- chemoreceptor trigger zone
- vestibular system (CN VIII)
- pain afferents via spinal cord
How does the vestibular system interact with the vomiting center?
Motion → ACh release from CN VIII → M1 receptors in vomiting center
How does pain trigger vomiting?
Visceral/GI pain especially → GI afferents → release substance P → NK1 receptors in dorsal horn of spinal cord → stimulate vomiting center
How does ondansetron work?
antagonizes 5HT3 receptors in the CTZ
When is ondansetron used?
prevent vomiting in chemotherapy (esp. cisplatin), radiotherapy, and post-op
What is metocloparamide? What are its applications in the GI system?
D2 receptor antagonist; antiemetic in cancer chemotherapy, diabetic and post-op gastroparesis, prokinetic in GERD (before PPIs)
What drugs are used to treat motion sickness? What are the side effects?
- H1 antagonists (diphenhydramine, meclizine, promethazine) – not used b/c H1 blocking but b/c antimuscarinic
- Scopolamine - antimuscarinic
Side effects: atropine-like, sedation, anterograde amnesia
Which drug agonizes the CB1 receptor in the CTZ to prevent vomiting?
cannabinoids: dronabinol (THC)
Which drug antagonizes NK1 receptors (part of pain mediated vomiting path) in the spine?
aprepitant
What are neurokinins?
inflammatory mediators such as substance P and bradykinin that can also cause pain
How could octreotide theoretically be used in the treatment of ulcers?
It is a somatostatin analog that binds to the ST2 receptor on ECL cells, inhibiting histamine release
