Upper GI pharmacology

Question 1

2. Describe the possible side effects and drug interactions of PPIs and H2 antagonists.

Answer 1

PPI- hypergastrinemia, cyp 450 inhibitor

H2- gynecomastia, mental status changes in elderly

Question 2

3. Explain the rationale for antibiotic therapy of peptic ulcers.

Answer 2

H. Pylori

Question 3

6. Describe the site and mechanism of action of major prokinetic agents and list their side effects.

Answer 3

diarrhea

Question 4

7. Describe the site and mechanism of action and the relative efficacy of the major antiemetic agents and list their side effects.

Answer 4

drowsiness, constipation,

Question 5

omeprazole DDI

Answer 5

clopidogrel

Question 6

cimetidine s/e

Answer 6

gynecomastia, mental status changes, possible tolerance with continued use

Question 7

Sucralfate

Answer 7

Sulfated disaccharide Al+++ salt  binds necrotic tissue forming protective barrier

Activated by acidic pH – give on empty stomach – 2-4 / day

Not absorbed – few side effects – constipation

Diminishing use

Question 8

Misoprostol

Answer 8

Prostaglandin analog - acts on epithelial cell   H+ secretion -  mucus-bicarbonate

Indicated for NSAID-induced ulcers

Side effects limit use – diarrhea, uterine cramping, contraindicated in pregnancy

Question 9

Calcium (as carbonate [Tums])

Answer 9

Rapid, prolonged neutralization  rebound secretion

Safe - not for chronic use (but OK as Ca++ supplement)

Constipation - hypercalcemia - renal calculi possible

Question 10

Magnesium (as hydroxide [Milk of Magnesia])

Answer 10

Osmotic diarrhea – used to counteract Al+++ or Ca++-induced constipation (Maalox - Mylanta)

Avoid if renal disease  retention of Mg++ ions

Question 11

Aluminum (hydroxide [Amphojel], carbonate [Basaljel])

Answer 11

Widely used, binds phosphate in gut (used in CKD)

Main side effect is constipation

Chronic intake may lead to CNS toxicity

Question 12

drug causes of gastroparesis

Answer 12

Ca2+, opiates, calcium channel blockers

Question 13

pro kinetics for gastroparesis

Answer 13

Metoclopramide - FDA black box warning
D2 antagonist, 5-HT4 agonist, 5-HT3 antagonist
Domperidone - Canada/Mexico
Doesn’t cross BBB, but cardiac side effects
Anti-emetics-e.g. Compazine (prochlorperazine)
Erythromycin – IV to “kick start”; less effective po with side effects concern

Question 14

Metoclopramide (Reglan®)

Answer 14

Dopamine antagonist  blocks presynaptic inhibition of ACh release

 in coordinated contractions  enhance transit

Approved for not > 12 weeks

Additional benefit of antiemetic effect at chemoreceptor trigger zone (weak 5HT3 antagonist)  relief of n/v

Somnolence, dystonic reactions, tardive dyskinesias [Boxed warning]

Question 15

Tegaserod (Zelnorm®) - Cisapride (Propulsid®)

Answer 15

5HT4 receptor agonists  direct stimulation of ACh release

↑ coordinated contractions-transit in esophagus, stomach

Reduces bloating of irritable bowel syndrome (IBS)

Cisapride  life-threatening arrhythmias (↑ QT interval) - restricted

Tegaserod  linked to strokes, MI, angina - restricted