PHARM_PEPTICULCER/GERD Flashcards
what type of acetylcholine receptors are found on parietal cells which when activated promote acid secretion?
M3
both gastrin and the M3 receptor act through which type of G protein to promote acid secretion?
Gq
Histamine acts through what kind of G protein to activate adenylate cyclase and promote acid secretion?
Gs
somatostatin and prostaglandins act through what kind of G protein to inhibit adenylate cyclase and thus inhibit acid secretion?
Gi
what is the primary etiology of peptic ulcer disease?
H. Pylori
how can you diagnose an H. pylori infection?
blood antibody test or urea breath test
what are the 3 major overall goals for the treatment of peptic ulcer disease?
- eradication of H. pylori (abx-tetracycline, clarithromycin, metronidazole)
- relief of symptoms (antisecretory agents, antacids)
- healing of ulcerations (prostaglandin agonists, bismuth, sucrasulfate)
MOA of antacids
neutralize gastric acid in the stomach
how high do you need to get the pH if you want to prevent the transformation of pepsinogen to pepsin?
pH >4
what are the 3 main ingredients in antacids?
aluminum hydroxides
magnesium hydroxids
calcium carbonate
aluminum hydroxides can have what side effect?
constipation
magnesium hydroxides can have what adverse effect?
diarrhea
what are the therapeutic uses of antacids?
simple dyspepsia
adjuncts to primary therapy w/ H2 blockers or PPIs
when should you take antacids for them to be most effective?
1-3 hrs after a meal and at bedtime
H2 receptor antagonists MOA
highly selective competitive inhibitor of H2 receptor
- inhibit basal, food-stimulated, and nocturnal gastric acid secretion
- reduce both volume and concentration of acid secretion
name the most potent h2 receptor antagonist?
famotidine
how often does famotidine need to be administered?
once daily because it has a long half life
what if the only notable side effect of cimetidine?
inhibits CYP450
PPI MOA?
noncompetitive irreversible inhibitor of the H+/K+ ATPase enzyme
result–>achlorhydria-all gastric acid secretion is blocked
which 2 PPIs are effective orally b/c they have a long duration of action and are more powerful?
omeprazole & esomeprazole
which PPI is metabolized to a much lower extent by the cytochrome P450 system?
rabeprazole
how do the PPIs effectively reach their target tissue?
has enteric coating
- in neutral pH the PPI prodrug is stable
- lipid solubility permits absorption
- then carried by blood and diffuse into the secretory canaliculi, where the acid pH causes protonation and trapping of the drug near the proton pump
what are the clinical indications for PPIs?
short term treatment of PUD, management of ZES & in refractory gastric, esophageal and duodenal ulcers
-manage symptoms of GERD
how does bismuth subsalicylate work?
enhances secretion of mucus & bicarb
- inhibits pepsin activity
- chelates w/ proteins at the base of the ulcer crater and forms a protective barrier against acid and pepsin
- effective treatment of traveler’s diarrhea
how does sucralfate work>
forms sticky viscous gel that adheres to gastric epithelial cells protecting them from acid and pepsin
___________is the only agent in its calss that requires an acidic pH for its maximal activity
sucralfate
when does sucralfate need to be given to promote gastric healing?
given 1 hr before meals and at bedtime
which drug is used in H2-blocker or PPI-induced pneumonia in bedridden pts?
sucralfate
-when stomach becomes too basic this can reintroduce harmful bacteria
how does metochloparmide work?
dopamine-2 receptor blockers
-w/i GI tract blocking D2 receptors increases the local release of ACh via 5HT4-R agonism
name the 5 abx that are used to eradicate H. pylori
- clarithromycin
- amoxicillin
- tetracycline-2nd line
- metronidazole
- furazolidine-nitrofuran antibacterial & antiprotozoal
what are 2 conditions that cause a reflux episode to occur?
- GI contents must be ready to reflux
2. the anti-reflux mech. at the LES is compromised
name the 5 aspects of postural & dietary therapy of GERD?
- decrease gastric contents (size of meal)
- decrease weight
- bed elevation
- low fat diet
- avoid coffee, peppermint
what are the pharmacological actions of the dopamine-2 receptor blockers?
stimulates GI smooth muscle
increases amplitude of esophageal contractions
accelerates gastric emptying
increases LES pressure
MAIN ANTIREFLUX= ENHANCED GASTRIC EMPTYING
what are some of the side effects of dopamine-2 receptor blockers?
related to central dopaminergic antagonism like tardive dyskinesia
-prescribe for 1-2 wks only
what are the 2 classes of antisecretory drugs used to treat GERD?
H2 receptor blockers
proton pump inhibitors
