Tx for acid-peptic diseases Flashcards
A person has H. pylori positive ulcers, what antimicrobials are the most effective?
Amoxicillin Clarithromycin Metronidazole/Tinidazole Rifabutin Tetracycline
What is the MoA of amoxicillin? Why is amoxicillin better than ampicillin/anti-pseudomonals to treat H. pylori?
Amoxicillin is a transpeptidase inhibitor…beta-lactam
Amoxicillin is more acid stable and has a higher oral availability than ampicillin
Anti-pseudomonals are not orally available
What is the MoA of clarithromycin? Why is clarithromycin better than the other macrolides for H. pylori treatment?
Clarithromycin binds to to 50S subunit…inhibits peptidyltransferase
Clarithromycin has the lowest MIC50 (Minimal Inhibitory Concentration needed to inhibit 50%) and is more acid stable
What is the MoA of metronidazole/tinidazole? What are the down sides to metronidazole? What are some drug interactions to pay attention to?
Metronidazole/tinidazole are reduced in bacteria to active form…forms random linkages in bacterial enzymes/proteins
H. pylori are often resistant to metronidazole
There are many side effects
Metronidazole increases anticoagulant effect of warfarin
Cimetidine decreases plasma clearance of metronidazole
What is the MoA of rifabutin? What are some side effects of rifabutin?
Rifabutin is a rifampin analog…prevents elongation of RNA
Hypersensitivity/fever, hepatotoxicity, induction of CYP450, orange/red body fluids
What is the MoA of tetracycline? What should NOT be given with tetracycline? What SHOULD be done 1-2 hours after taking tetracycline?
Tetracycline binds to 30S subunit…prevents tRNA from binding to A site
Antacids should NOT be given with tetracycline…decreases efficacy due to chelation
Patient should eat…decreases absorption –> higher concentration in the stomach
What are examples of H2 receptor blockers?
Cimetidine
Famotidine
Nizatidine
Ranitidine
-tidine
Which H2 drug has the most side effects?
Cimetidine may cause dizziness or headaches…it is also a CYP450 inhibitor
Which drugs are the most effective at reducing intragastric acidity? How do they do this?
Proton pump inhibitors are the most effective
Proton pump inhibitors IRREVERSIBLY block H/K ATPase
What are examples of proton pump inhibitors?
Omeprazole/esomeprazole
Rabeprazole
Lansoprazole
Pantoprazole
-prazole
What are examples of weak bases used to buffer stomach acid?
Aluminum Hydroxide
Calcium Carbonate
Magnesium Hydroxide
Sodium Bicarbonate
What causes the difference in efficacy of the antacids?
Degree of systemic absorption (systemic is bad)
Rate of dissolution and reactivity
Effects of cations and/or reaction products (Al–> constipation; Mg–> diarrhea; carbonate–> increased CO2–> gastric distention and belching…give simethicone)
When should antacids be used? Why?
Antacids should be used for intermittent dyspepsia
Rapid onset with short duration
Antacids do NOT prevent ulcer recurrence
Histamine blockers are used more often than antacids: what are the major differences?
Histamine blockers also have a relatively rapid onset, but have a longer duration and can somewhat prevent ulcer recurrence
When should PPIs be used? Why?
Zollinger-Ellison Syndrome
GERD
Ulcer treatment
PPIs have slow onset, very long duration, and are excellent at preventing ulcer recurrence
What two drugs are essentially band-aids that give the stomach epithelium time to heal?
Sucralfate and Bismuth
What is the MoA of sucralfate? When is it used?
Sucralfate stimulates secretion of PGs and bicarb…also recruit growth factors
Sucralfate is used in ICU…PPIs increase risk of pneumonia
What is a possible side effect of sucralfate?
Sucralfate causes constipation in 2-4% of patients…d/t aluminum salt
What is the MoA of bismuth?
Little antimicrobial activity…disrupts cell wall, prevents adhesion, and inhibits urease
Protects ulcer surface by coating it and stimulating secretion of PGs, mucous, and bicarb
What should be used to treat NSAID-induced ulcers?
Misoprostol is a synthetic PG
What is a neat thing for arthritis patients who have ulcers?
Misoprostol and NSAIDs can be given at the same time…pharmacokinetics are different enough
What are the down sides to misoprostol?
Increased intestinal electrolyte and fluid secretion –> dose dependent diarrhea, severe nausea, and cramping (10-20% of patients)
CANNOT give to pregnant women
What are the side effects of PPIs?
Alter absorption of other drugs/vitamins/minerals from the GI tract
Increase gastrin levels
If H. pylori not treated –> increased gastric inflammation
Rarely headache, diarrhea, ab pain, nausea or rash
Increased risk of respiratory and enteric infections
What is the difference between omeprazole and esomeprazole?
Omeprazole is racemic mixture (OTC)
Esomeprazole is only active S-isomer (prescription)
