Upper GI Pharmacology - Gauthier

Question 1

What stimuli cause parietal cells to increase acid production? How?

Answer 1

Signaling via M3 (ACh), CCK2 (Gastrin), or H2 (Histamine) cause upregulation of the H⁺/K⁺ ATPase via increasing cAMP or Ca²⁺

Question 2

How are prostaglandins cytoprotective of the GI tract?

Answer 2

1. Lowers ATPase activity by decreasing intracellular cAMP.
2. Stimulate epithelial production of mucous and bicarbonate ion.

Question 3

Describe the mechanism of action of proton pump inhibitors.

What are their indications?

Side effects?

Answer 3

Enter the secretory canaliculus of parietal cells, convert to a trapped isomer and irreversibly inactivate the ATPase.

For GERD, PUD, Zollinger-Ellison…any hypersecretory condition.

Few, but bone fracture and some infections with chronic use.

Question 4

Differentiate between Omeprazole, Esomeprazole, and Lansomeprazole.

What formulations are available?

Answer 4

Esomeprazole is the S-isomer of Omeprazole (normally racemic). Lansomeprazole is a different PPI that is available IV.

Administered as enteric-coated pill or with bicarbonate to prevent early activation.

Question 5

What is the mechanism of action of Cimetidine?

Which is preferable, it or Ranitidine?

How is resistance to these drugs developed?

Answer 5

Histamine receptor (H2) antagonism.

Ranitidine is preferable because Cimetidine inhibits hepatic P450s. (also higher potency, longer duration…)

Parietal cells can still be stimulated via the other receptors.

Question 6

What is the mechanism of action of Misoprostol?

What are its indications and side effects?

Answer 6

PGE1 agonist.

Formerly for NSAID-induced mucosal injury, now used only for its abortifacient effect. Side effects include cramping, diarrhea, exacerbation of IBD. Oh, and it’s dosing sucks (4/day)

Question 7

What is the mechanism of action of Sucralfate?

Side effects?

Answer 7

As a sulfated sucrose, forms a polymer gel which protects the epithelia from acid and stimulates PGs and EGF.

Side effects include constipation and disrupted drug absorption.

Question 8

What are the unique side effects to the antacids Al(OH)₃, Mg(OH)₂, and CaCO₃

Answer 8

Aluminum causes constipation.

Magnesium causes diarrhea.

Any carbonate antacid produces gas.

Question 9

Why shouldn’t antacids be taken within 2 hours of another drug?

What is simethicone?

Answer 9

By altering the gastric pH, they affect the absorption of other drugs.

Simethicone is a surfactant often added to antacids.

Question 10

What is the mechanism of action of Bismuth Subsalicylate?

Indication?

Side effects?

Answer 10

Not really known, but it binds the ulcer, promotes mucin and bicarbonate effects, and is antibacterial.

For traveler’s diarrhea (among others)

Black stools/tongue, and risk of Reye’s syndrome (salicylate)

Question 11

How is H. Pylori infection treated?

Answer 11

Triple therapy: A proton-pump inhibitor and two antibiotics (MCAT)

Question 12

What is the site of signaling for vomiting?

What is it influenced by?

Answer 12

The medullary vomiting center.

Many sensory centers (CTZ, cerebellum, STN) as well as higher centers.

Question 13

Distinguish between the mechanism of actions of Scopolamine and Dimenhydrinate.

What are they used for?

Answer 13

Scopolamine is an anti-muscarinic.

Dimenhydrinate is an H₁blocker (and also has anti-muscarinic activity).

Both are used for treatment of motion sickness.

Question 14

What are the sites and mechanisms of actions of Prochlorperazine and Metoclopramide?

Indications?

Side effects?

Answer 14

Both act on 5-HT₃receptors in the CTZ. Both reduce nausea, but metoclopramide is also a prokinetic (increases myenteric ACh).

Prochlorperazine is for “general use” nausea, while metoclopramide is labeled for diabetic gastroparesis and GERD.

Prochlorperazine causes restlessness. Metoclopramide causes drowsiness and dystonia.

Question 15

What is the site and indication for Ondansetron and Granisetron?

Answer 15

Both are 5-HT₃ receptor antagonists. They are indicated for treating chemotherapy-induced nausea.

Question 16

What is the name of the drug used for reducing chemotherapy-induced nausea by agonizing the cannabinol-1 receptor?

Answer 16

Dronabinol.

You can probably guess its side effects…

Question 17

What use do glucocorticoids like dexamethasone have in treatment of nausea?

Answer 17

Usually used in conjunction with other anti-emetics in the context of chemotherapy-induced nausea.

Question 18

Aprepitant is a ____ receptor antagonist used for ____. It is metabolized by _____. It is usually given in conjunction with a corticosteroid and a ____. It’s side effects are __________.

Answer 18

Substance P (NK₁) receptor antagonist.

Used for chemotherapy nausea/vomiting.

Metabolized by liver CYP3A4.

Given with corticosteroid and 5-HT₃ antagonist.

Side effects are fatigue, nausea (wat), constipation and hiccups.

Question 19

What (off-label) use does erythromycin have?

Answer 19

Causes massive gastric contractions, so can be used for (diabetic) gastroparesis. Patients won’t thank you for the incredible cramping and pants-shitting thoug.

Question 20

For each description, name the drug(s).

1. For motion sickness as a transdermal patch.
2. Histamine (1) receptor blocker.
3. Decreases basal acid secretion.
4. IV proton pump inhibitor.
5. Substance P receptor antagonist.
6. D₂ receptor antagonist.

Answer 20

1. Scopolamine
2. Dimenhydrinate
3. Cimetidine/Ramotidine
4. Lansoprazole
5. Aprepitant
6. Metoclopramide, Prochlorperazine