Foregut Pharmacology

Question 1

PPIs: MOA

Answer 1

Ex: Omeprazole (all end in “-azole”)

MOA:
•	Irreversibly bind proton pump
•	To function: pump needs to be active
•	Slow onset of action (hours) but long lasting (up to 12 hours)
•	Available OTC in full strength

Question 2

PPIs: uses

Answer 2

Heal ulcers
• H. pylori treatment: 2 weeks of PPI + (amoxicillin, clarithromycin OR amoxicillin, metro); and 8 weeks of ulcer therapy
• Must always document eradication
• Need to visually document gastric ulcer healing

• Erosive esophagitis & erosive gastritis/duodenitis
• Treat gastrinoma (Zollinge Ellison)

Question 3

PPIs: adverse effects

Answer 3

• Increase risk of C. difficile, GI infections, pulmonary infections
• Decreased Ca2+ absorption, osteoporosis risk, low magnesium
• Interacts with clopidegrel (anti-platelet medication)
• May cause abdominal pain, diarrhea

Question 4

H2-Histamine Receptor antagonists: MOA

Answer 4

Ex: Ranitidine, Cimetidine, Famotidien, Nizatidine (end in “-idines”)

MOA: 
•	Blocks histamine signaling pathway = reversibly competes with histamine for H2-receptor binding on parietal cells
•	Faster onset (15-20 min) 
•	But less potent effect
•	Available at ½ and full strength OTC

Question 5

H2-Histamine Receptor antagonists: Uses

Answer 5

• Strong enough to heal ulcers
• Most effective in suppressing nocturnal acid secretion
• Dyspepsia, heartburn, treating uncomplicated GERD

Question 6

H2-Histamine Receptor antagonists: adverse effects

Answer 6

• Low incidence
• Diarrhea, headache, drowsiness, fatigue, muscular pain, constipation, less commonly CNS effects

Cimetidine:
• Interacts with anticoagulation
• Can cause gynecomastia in me and galactorrha in women

Question 7

Prostaglandins: MOA

Answer 7

Ex: Misoprostol

MOA:
• Synthetic analog of PGE1
• Binds EP3 receptor on parietal cells → inhibits acid production
• Also = stimulates mucin and bicarbonate secretion; improves mucosal blood flow → cytoprotective effects

Question 8

Prostaglandins: uses

Answer 8

• When taken together, protects stomach from NSAIDs

Question 9

Prostaglandins: adverse effects

Answer 9

• Diarrhea (up to 30% of patients)

* Contraindicated in women of child-bearing age or during pregnancy → fetal loss

Question 10

Sucralfate: MOA

Answer 10

o The “super antacid”

MOA:
• An octasulfate of sucrose with aluminum hydroxide added
• Cross-links into viscous, sticky liquid → Sticks to inflamed areas
• Binds to both HCL and bile salts
• Also = cytoprotective → stimulates PG and epidermal growth factor (EGF) production
• Need to take 4x/day for full effect

Question 11

Sucralfate: adverse effects

Answer 11

• Constipation
• Aluminum poisoning if in renal failure
• Viscous layer can inhibit absorption of other drugs

Question 12

Antacids: types

Answer 12

• Aluminum = can constipate
• Magnesium = can cause diarrhea
• Calcium carbonate (Tums)

Question 13

Antacids: MOA

Answer 13

• Neutralizes acid
• Fast!
• Bind both HCl and bile salts

Question 14

Antacids: Adverse effects

Answer 14

• Alter gastric and urinary pH → altered rates of dissolution and absorption of other drugs (Need to take antacids 2 hours before other drugs)
• NaHCO3- = can cause alkalosis
• Bicarbonate and carbonate-containing antacids = release CO2 → belching, occasional nausea, abdominal distension, flatulence
• Mg2+ = laxative

Question 15

Describe the mechanism that accounts for the difference between the adverse effects of NSAIDs (both COX-1 and COX-2) on the gastrointestinal tract.

Answer 15

NSAIDs = inhibit prostaglandins

Selective COX-2 inhibitors
o Less upper GI toxicity (in short term use NOT taking with aspirin)
o If take with aspirin = same incidence of ulcers as with non-selective NSAIDs

Question 16

Metoclopramide: MOA

Answer 16

Facilitates Ach release from enteric neurons
• Suppresses inhibitory interneurons that use 5-HT
• Blocks dopamine recptors
Result: coordinated contractions = enhance transit and improves gastric emptying

Question 17

Metoclopramide: adverse effects

Answer 17

o In elderly: confusion at high doses

o Black box warning: Parkinson’s like and tardive dyskinesia (may be irreversible)

Question 18

Erythromycin

Answer 18

o Resembles GI messenger motilin → increases stomach emptying
o Only works at low dose
o Works best in IV form
o Side effect: tachphylaxis (diminished drug response = so limited utility)

Question 19

List 5 classes of antiemetics and the mechanisms responsible for their actions.

Answer 19

 5-HT3-receptor antagonists

Dopamine-receptor antagonists

Antihistamines – H1-histamine receptor blockers

Anticholinergics:

Dronabinol (delta-9-THC)

Question 20

Anti-emetics: 5-HT3-receptor antagonists

Answer 20

o Ondansetron
o Unclear if work at central or peripheral sites (or both)
o Highest 5-HT3 receptor concentrations in nucleus tractus solitarius (of vagus nerve) and chemoreceptor trigger zone
o Very well tolerated
o Adverse effects: constipation, diarrhea, headache, light-headedness

Question 21

Anti-emetics: Dopamine-receptor antagonists

Answer 21

o The phenothiazines: prochlorperazine (Compazine)

o Block D2-dopamine receptors in chemoreceptor trigger zone

Question 22

Anti-emetics: Antihistamines – H1-histamine receptor blockers

Answer 22

o Promethazine (Phenergan)
o Act on vestibular afferents and within brainstem
o Used: motion sickness and post-op emesis

Question 23

Anti-emetics: Anticholinergics:

Answer 23

o Scopolamine
o Prevent and treat motion sickness
o No role in chemotherapy-associated nausea

Question 24

Anti-emetics: Dronabinol (delta-9-THC)

Answer 24

o For cancer chemotherapy and refractory cases
o Adverse effects: tachycardia, conjunctival injection
o High doses can cause Cannabinoid induced cyclic vomiting syndrome