upper GI pharmacology

Question 1

1. Describe the site and mechanism of action and relative efficacy of the major antisecretory agents.

Answer 1

Proton pump inhibitors: Prodrug > diffuses into parietal cells > activated in canaliculi to sulfenamide > then “trapped” to irreversible inactivate H/K ATPase. Only inactivates active pumps.
H2 antagonists: reversible block of H2 receptors Proton pump inhibitors: Prodrug > diffuses into parietal cells > activated in canaliculi to sulfenamide > then “trapped” to irreversible inactivate H/K ATPase. Only inactivates active pumps.
H2 antagonists: reversible block of H2 receptors

Question 2

List proton pump inhibitors

Answer 2

omeprazole,lansoprazole,

Question 3

PPI pharmacokinetcs

Answer 3

Best before meal

Question 4

PPI uses

Answer 4

Most effective GERD agent, Faster relief than H2 antagonists for peptic ulcer dz, also used in NSAID induced ulcers, prevention of stress gastritis, zollinger-ellison syndrome

Question 5

PPI adverse effects/ DDIs

Answer 5

chronic use can cause increased fracture risk. Omeprazole inhibits activation of clopidogrel

Question 6

list H2 antagonists

Answer 6

Ranitidine, cimetidine.

Question 7

H2 antagonist uses

Answer 7

more rapid onset than PPIs in acute gastritis. Better at block of nocturnal acid secretion. Used in GERD (infrequent), peptic ulcer dz (PPIs are better)

Question 8

H2 antagonists pharmacokinetics

Answer 8

rapidly absorbed, renal excretion

Question 9

H2 antagonists adverse effects/DDIs

Answer 9

CNS dysfunction, gynecomastia (with chronic high dose cimetidine), inhbition of CYP450 (cimetidine)

Question 10

3. Explain the rationale for therapy of peptic ulcers.

Answer 10

PPI + antibiotics of H pylori positive. Also avoid NSAIDs and smoking, or chronic PPI use if NSAIDs necessary

Question 11

H Pylori treatment

Answer 11

first line: PPI BID + Clarithromycin + Amoxicillin (metronidazole) (triple therapy). Alternative/salvage therapy: PPI + Bismuth + Tetracycline + Metronidazole (quadruple therapy). Sequential therapy if resistance is concern: PPI + amoxicilin, followed by PPI + clarithromycin + tinidazole

Question 12

List cytoprotective agents and actions

Answer 12

sucralfate: binds necrotic tissue forming protective barrier. Misoprostol: prostaglandin analog that acts on epithelial cells to decrease acid secretion and increase mucus-bicarbonate. Limited by side effects (diarrhea, uterine cramping, contraindicated in pregnancy)

Question 13

5. Describe the general properties, primary ingredients, general mechanisms of action, and guidelines for use of antacids.

Answer 13

Rapidly raise pH of stomach to 4. Nonabsorbable and long acting. No adverse effects or DDIs.

Question 14

list gastric antacids and side effects

Answer 14

Calcium (tums): constipation, hypercalcemia. Aluminum: constipation, CNS toxicity. Magnesium: osmotic diarrhea.

Question 15

causes of gastroparesis

Answer 15

idiopathic, vagal nerve injury (post surgical), diabetes, med related (opiates, anticholinergics, Ca channel blockers)

Question 16

Meds for gastroparesis

Answer 16

prokinetic agents and antiemetics

Question 17

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

Answer 17

Metoclopramide: dopamine antagonist blocks presynaptic inhibition of Ach release. SE are dystonic reactions, tardive dyskinesias. Tegaserod-Cisapride: 5HT4 receptor agonist causes direct stimulation of Ach release. Cisapride causes life threatening arrhythmias and Tegaserod is linked to strokes, MI.

Question 18

MOA ondansetron

Answer 18

Block of serotonin (5-HT3) receptors at chemoreceptor trigger zone (CTZ in CNS), solitary tract nucleus, and on visceral afferents (GI tract).

Question 19

Prochloroperazine/metoclopramide MOA

Answer 19

dopamine receptor antagonists- anti emetic

Question 20

Meclizine MOA

Answer 20

antihistamine- anti emetic

Question 21

diphendyramine MOA

Answer 21

antihistamine- anti emetic