Gastric Drugs

Question 1

PPI MAO and Examples

Answer 1

-the activated form covalently binds cysteine 813 on extracellular domain of H-K ATPase which irreversibly inhibits acid prod

SO…

• effective for 24-48 hrs until new H-K ATPases can be produced
• Must take 20-30 min b/f meal so in blood when acid prod is stimulated

omeprazole, esomeprazole, lansoprazole, rabeprazole, etc

Question 2

PPI Coating and Metbolism

Answer 2

• Enteric coating so not broken down until alkaline SI –> blood stream –> accumulate in parietal cells; here they are activated by the acidic environment –> sulfenic acid
• Metabolism: use CYP450 (may dec clearance of benzos, warfarin, phenytoin, etc)

Question 3

PPI Side Effects

Answer 3

rare nausea, ab pain, constipation, flatulence, diarrhea

if chronic… inc risk of osteoporosis, CAP, C diff

Question 4

H2 Receptor Blockers (uses, MAO, examples)

Answer 4

• Mainly used for nocturnal acid secretion b/c most effective for basal acid secretion b/n feedings
• May use in conjugation w/ PPI if breakthrough nocturnal acid secretion
• MAO: rev competition w/ histamine for H2 receptor on basolateral parietal cell mem

cimetidine, ranitidine (Zantac), famotidine, nizatidine

Question 5

H2 Receptor Blocker Metabolism and Side Effects

Answer 5

• Metabolism: both liver and renal (reduce dose if prob w/ either)
• Side Effects: diarrhea, headache, drowsiness, fatigue, muscle pain, diarrhea (all rare)

**Cimetidine specifically binds androgen receptors and uses CYP450 so gynecomastia in men and drug interactions (used least)

Question 6

Antacid Composition

Answer 6

• Some form of alkaline compound to neutralize stomach acid + simethicone (surfactant that dec foaming and reflux)
• Ex: NaHCO3, Mg(OH)/Al(OH) - together as magaldrate - hydroxymag aluminate complex, Ca(HCO3)

Question 7

Side Effects of Various Antacids

Answer 7

• NaHCO3: creates alkaline and sodium load
• Mg(OH)/Al(OH): poorly absorbed so sustained effect; Al relaxes smooth muscle to delay emptying but Mg cancels this out; if renal insufficiency Al –> osteoporosis, encephalopathy, proximal myopathy

**Careful when using w/ other systemically absorbed drugs b/c Al and Mg may bind these drugs to form insoluble complexes (take antacid 2 hr before or after other drugs)

• Ca(HCO3): ab distention and belching; transient hypercalcemia; Ca++ toxicity if renal insufficiency, Ca stones, etc

Question 8

Sucralfate

Answer 8

• Sulfated polysaccharide w/ Al(OH)
• MAO: once in acid environment it crosslinks –> gel that adheres to epithelial cells and ulcer craters to prevent further breakdown by pepsin-mediate hydrolysis
• Side effects: constipation b/c Al

Question 9

Misoprostol

Answer 9

• Prostaglandin analogue - synthetic PGE1
• MAO: binds EP3 receptor on parietal cells –> G alpha i –> dec cAMP –> down-reg kinases –> dec activation of H/K ATPase
• Use b/f meal and not w/ antacids to inc efficacy
• Metabolism: first pass effect –> active misoprostol acid
• Side Effects: diarrhea (dose-dep but stops w/in 1 wk), ab pain, cramps
• DO NOT USE IF PREGNANT