PHARM: Antacids and H. Pylori Eradication Flashcards
What type of drugs are weak bases that neutralize gastric acid?
antacids
What are antacids used for?
heartburn (quick acting with short duration)
What is the pharmacokinetic difference between systemic and non-systemic antacids?
systemic antacids are absorbable, non-systemic antacids are NOT absorbable
What is an example of a systemic antacid?
sodium bicarbonate
What is the stipulation for the use of sodium bicarbonate?
only for SHORT TERM USE—long term leads to sodium and water retention (altering the systemic acid-base balance)
What are some examples of non-systemic antacids?
aluminum, magnesium or calcium salts
What types of non-systemic antacids lead to constipaton?
Al- and Ca2+ containing antacids
What are some types of non-systemic antacids that lead to diarrhea?
Mg2+ containing antacids
What is the only known physiological role of H2 receptors?
stimulate secretion of HCl by the gastric parietal cells
What cells in the stomach release histamine?
ECL cells
How do the products of the ECL cells (histamine) get to the H2 receptors in the stomach?
paracrine
What does binding of histamine to H2 receptors cause?
cAMP cascade that leads to increased acid secretion from the membrane-bound molecules of the H+/K+ ATPase
Why do H2 blockers not solve all the acid problems in the stomach?
parietal cells can also be stimulated by neurocrine (vagal) stimulation or endocrine (gastrin) pathways that are NOT affected by these drugs
What do the H2 blockers end with?
“tidine”
when do you take H2 receptor blockers?
before bed
When do H2 blockers have their peak action
during the resting or “basal” state of the stomach (overnight)
Why are H2 blockers not as effective during the day?
inhibitory effects are partly overcome by stimulatory effect of food on acid secretion (would need to take multiple pills)
How does physiological tolerance occur in those taking H2 receptor blockers?
up-regulation of the receptor develops after a few days of continuous dosing
What H2 receptor blocker poses problems due to CYP inhibiton?
cimetidine
Which cimetidine DDIs are of physiological importance? Why is this?
phenytoin
warfarin
theophylline
These drugs have narrow therapeutic indexes and their concentrations increase to toxic levels if given with cimetidine
What are the indications for H2 blockers?
- GERD patients with MILD symptoms ONLY
- Is used in seriously ill patients in ICU to prevent stress-related upper GI bleeds
Which drug class is a racemic mixture of R- and S- enantiomers that is typically enterically coated (because the drugs are acid labile and must be protected from gastric acid)?
PPIs
What is the ending of PPIs?
“prazoles”
Which PPIs are NOT mixtures of R- and S- enantiomers?
Esomeprazole (purified S-enantiomer of omeprazole)
Dexlansoprazole (purified R-enantiomer of lansoprazole)
What is the name of immediate release omeprazole that is mixed with sodium bicarbonate?
Zegerid
What is special about Zegerid compared to other PPIs?
it is the only PPI that does NOT have an enteric coating
What is the path of a PPI after swallowing?
enteric coating of drug removed by acid in stomach (delayed release), drug absorbed and distributed within the body, drug preferentially taken up by PARIETAL cells
True or false: PPIs have a short elimination half life and a very short duration of action.
FALSE: short elimination half-life, but since effect is IRREVERSIBLE, the duration of action is much longer.
When do you give a PPI?
early morning 30-60 minutes before food
Why do H2 blockers and PPIs have a different dosage schedule?
PPIs block acid secretion both in the basal state AND in response to food stimulation
Does tolerance develop with PPIs?
NO
How does a PPI work?
PPI taken up by parietal cells→ become protonated→ excreted via the luminal aspect of the parietal cells and undergo chemical conversion to sulfenamide→ form covalent –SH bonds with cysteine residues of membrane bound proton pump to IRREVERSIBLY terminate its action
When can acid secretion be recovered with PPI use?
only after synthesis of new proton pumps
Who should get lower doses of PPIs than usual?
patients with hepatic dysfunction
What is a possible side effect of PPIs?
rebound hypersecretion of acid after stopping therapy
What is the PPI that leads to CYP- mediated DDIs?
omeprazole (CYP inhibitor)
What are the two DDIs of omeprazole (CYP-wise)?
phenytoin and warfarin
Why should you NOT take clopidogrel with omeprazole or esomeprazole?
may reduce the anti-platelet effect by slowing the conversion of clopidogrel to its active metabolite
What are the indications for PPIs?
- GERD
- PUD (helps heal duodenal ulcers)
- NERD
- Helpful after episode of ulcer bleeding
What is the first question that should be asked when a patient has PUD?
whether or not the patient is infected with H. pylori.
When do people acquire an H. pylori infection?
childhood
If a patient with PUD is NOT infected with H. pylori, what is the most likely cause?
NSAID or aspirin use
What drug is used to treat H. pylori negative PUD?
PPIs
What is REQUIRED to eradicate H. pylori?
You need to administer 2 or 3 antibiotics combined with an acid-suppressing drug (which improves the performance of antibiotics)!
What is the major type of triple therapy in H. pylori infection?
Clarithromycin-based triple therapy (PPI + clarithromycin + amoxicillin (or metronidazole if penicillin allergy)
What is the major quadruple therpay for H. pylori infection?
Bismuth-based quadruple therapy:
PPI (or H2RA) + bismuth + metronidazole + tetracycline
What are the major reasons 25-30% of patients have persistent H. pylori infection after treatment?
poor compliance
antimicrobial resistance
Which antibiotics are H. pylori always susceptible to?
amoxicillin
tetracycline
What should you do if a patient fails triple or quadruple therapy?
you CANNOT re-prescribe the same combination (but you can use amoxicillin or tetracycline in the new combinations)
Which is the antibiotic with the biggest problem with H. pylori resistance?
clarithromycin
