Upper GI pharm

Question 1

misoprostol site of action

Answer 1

prostaglandin analog –> epithlial cell (mucus and bicarb), parietal cell (blocks cAMP –> blocked H secretion)

Question 2

PPIs

Answer 2

omeprazole (prilosec), Lansoprazole (prevacid)

Question 3

PPI mechanism of action

Answer 3

prodrug –> activated by H in parietal cells –> trapped in acidic secretory canniliculi –> irreversible inactivation of H/K ATPase

Question 4

PPI absorption

Answer 4

rapid, highly protein-bound. bioavailability improved with enteric coating or NaHCO3.

give 1 hour before meals

Question 5

PPI metabolism

Answer 5

first pass = CYP450

no accumulation in chronic renal failure

Question 6

Indications for PPI

Answer 6

GERD, PUD, NSAID-induced ulcers, prevention of stress gastritis in ICU, Zollinger-Ellison syndrome

Question 7

ADRs of PPIs

Answer 7

usually mild

Question 8

DDIs of PPIs

Answer 8

omaprazole may inhibit conversion of antiplatelet agent clopidogrel to active form

Question 9

H2 receptor antagonists

Answer 9

Ranitidine (Zantac), Cimetidine (Tagamet), Famotidine (Pepcid), Nizatidine (Axid)

Question 10

H2 blocker use

Answer 10

best for blocking NOCTURNAL acid secretion

GERD, PUD, stress-related gastritis

Question 11

H2 blocker absorption

Answer 11

rapid

Question 12

H2 blocker metabolism

Answer 12

some hepatic metabolism, but no dosage adjustment for liver disease

renal excretion (dosage reduction if ipaired renal function)

Question 13

H2 blocker side effects

Answer 13

generally well-tolerated. dizziness, diarrhea, constipation, headache

cimetidine can lead to mental status change and/or endocrine changes (gynecomastia, galactorrhea, decreased sperm count)

Question 14

H2 blocker DDIs

Answer 14

cimetidine inhibits P450; all antisecretory agents –> increased gastric pH –> decreased ketoconazole absorption

Question 15

Sucralfate mechanism of action

Answer 15

binds necrotic ulcer tissueand forms protective barrier –> blocked hydrolysis of mucosal proteins by pepsin

Question 16

Sucralfate activation

Answer 16

pH less than 4 (don’t administer with antacids, H2 blockers)

Question 17

Sucralfate use

Answer 17

adjunct in ulcer tx

Question 18

Misoprostol absorption

Answer 18

rapid –> 30 minute onset

Question 19

Misoprostol half-life

Answer 19

30 min –> TID/QID dosing

Question 20

Misoprostol use

Answer 20

NSAID-induced GI ulceration

Question 21

Misoprostol side effects

Answer 21

diarrhea (promotes fluid secretion), uterine cramping

contraindicated in pregnancy

Question 22

Gastric antacids mechanism

Answer 22

rapidly raises pH of stomach to 4-5 (above pepsin optimum pH). pH 7 –> rebound acid secretion via increased gastrin release

Question 23

gastric antacids pharmacokinetics

Answer 23

absorption: NaHCO3 > Al, Mg, Ca antacids

Question 24

gastric antacid side effects

Answer 24

Ca and Al –> constipation

Mg –> diarrhea

Question 25

Prokinetic agent uses

Answer 25

bowel motility disorders (achalasia of esophagus, gastroparesis), symptom relief of esophagitis associated with GERD

Question 26

mechanisms of promotility drugs

Answer 26

direct/indirect agonists at smooth muscle M3 receptors

Question 27

Erythromycin mechanism

Answer 27

agonist at excitatory neural and smooth mucle motilin receptors

Question 28

Cisapride mechanism

Answer 28

agonist at excitatory neural 5-HT4 receptors on enteric nervous system cholinergic motor neurons

Question 29

Metoclopramide mechanism

Answer 29

antagonist at presynaptic D2 receptors --| Ach release

Question 30

Neostigmine mechanism

Answer 30

inhibits hydrolysis of Ach by AChE

Question 31

Bethanechol mechanism

Answer 31

agonist at excitatory M3 smooth muscle receptors

Question 32

Metoclopramide pharmacokinetics

Answer 32

rapid absorption --> peak effects in 1h | metabolized to sulfate and glucuronide conjugates --> urinary excretion

Question 33

Cisapride side effects

Answer 33

life-threatening arrythmias from prolonged QT

Question 34

metoclopramide side effects

Answer 34

D2 block --> somnolence, dystonic reactions, tardive dyskinesia