Upper GI pharm Flashcards
misoprostol site of action
prostaglandin analog –> epithlial cell (mucus and bicarb), parietal cell (blocks cAMP –> blocked H secretion)
PPIs
omeprazole (prilosec), Lansoprazole (prevacid)
PPI mechanism of action
prodrug –> activated by H in parietal cells –> trapped in acidic secretory canniliculi –> irreversible inactivation of H/K ATPase
PPI absorption
rapid, highly protein-bound. bioavailability improved with enteric coating or NaHCO3.
give 1 hour before meals
PPI metabolism
first pass = CYP450
no accumulation in chronic renal failure
Indications for PPI
GERD, PUD, NSAID-induced ulcers, prevention of stress gastritis in ICU, Zollinger-Ellison syndrome
ADRs of PPIs
usually mild
DDIs of PPIs
omaprazole may inhibit conversion of antiplatelet agent clopidogrel to active form
H2 receptor antagonists
Ranitidine (Zantac), Cimetidine (Tagamet), Famotidine (Pepcid), Nizatidine (Axid)
H2 blocker use
best for blocking NOCTURNAL acid secretion
GERD, PUD, stress-related gastritis
H2 blocker absorption
rapid
H2 blocker metabolism
some hepatic metabolism, but no dosage adjustment for liver disease
renal excretion (dosage reduction if ipaired renal function)
H2 blocker side effects
generally well-tolerated. dizziness, diarrhea, constipation, headache
cimetidine can lead to mental status change and/or endocrine changes (gynecomastia, galactorrhea, decreased sperm count)
H2 blocker DDIs
cimetidine inhibits P450; all antisecretory agents –> increased gastric pH –> decreased ketoconazole absorption
Sucralfate mechanism of action
binds necrotic ulcer tissueand forms protective barrier –> blocked hydrolysis of mucosal proteins by pepsin
Sucralfate activation
pH less than 4 (don’t administer with antacids, H2 blockers)
Sucralfate use
adjunct in ulcer tx
Misoprostol absorption
rapid –> 30 minute onset
Misoprostol half-life
30 min –> TID/QID dosing
Misoprostol use
NSAID-induced GI ulceration
Misoprostol side effects
diarrhea (promotes fluid secretion), uterine cramping
contraindicated in pregnancy
Gastric antacids mechanism
rapidly raises pH of stomach to 4-5 (above pepsin optimum pH). pH 7 –> rebound acid secretion via increased gastrin release
gastric antacids pharmacokinetics
absorption: NaHCO3 > Al, Mg, Ca antacids
gastric antacid side effects
Ca and Al –> constipation
Mg –> diarrhea
Prokinetic agent uses
bowel motility disorders (achalasia of esophagus, gastroparesis), symptom relief of esophagitis associated with GERD
mechanisms of promotility drugs
direct/indirect agonists at smooth muscle M3 receptors
Erythromycin mechanism
agonist at excitatory neural and smooth mucle motilin receptors
Cisapride mechanism
agonist at excitatory neural 5-HT4 receptors on enteric nervous system cholinergic motor neurons
Metoclopramide mechanism
antagonist at presynaptic D2 receptors –| Ach release
Neostigmine mechanism
inhibits hydrolysis of Ach by AChE
Bethanechol mechanism
agonist at excitatory M3 smooth muscle receptors
Metoclopramide pharmacokinetics
rapid absorption –> peak effects in 1h
metabolized to sulfate and glucuronide conjugates –> urinary excretion
Cisapride side effects
life-threatening arrythmias from prolonged QT
metoclopramide side effects
D2 block –> somnolence, dystonic reactions, tardive dyskinesia
