Lecture 3: UPPER GI Drugs (MOST QUESTIONS)

Question 1

Which drugs are H2 receptor antagonists?

Answer 1

• tidines

Cimetidine, Famotidine

Question 2

MOA for Cimetidine & Famotidine?

Answer 2

REVERSIBLY block H2 receptor on parietal cell–> directly block gastric acid release

(Histamine stimulates rel of Gastric acid)

Question 3

Which type of H2 receptor antagonist has significant drug-drug interactions? What are they?

Answer 3

Cimetidine has drug-drug interactions w/ CYPs, warfarin, 7 phenytoin

Question 4

What are 4 considerations w/ H2 receptor antagonists related to ADME?

Answer 4

1. Rapidly absorbed –> minimal protein binding
2. Eliminate by kidney –> decr dose in renal insufficieny
3. Can develop tolerance
4. Cross placenta (Categ B) –> safe in pregnancy

Question 5

Which type of H2 receptor antagonist has unique hormonal S/Es? What are they?

Answer 5

Cimetidine

1. Males –> gynecomastia, impotence
2. Females –> galactorrhea

Question 6

Which type of H2 receptor antagonists shown to have efficacy for?

When are they used prophylactically & why?

Answer 6

GERD & PUD

• used prophylactically after an acute event to prevent recurrence

Question 7

What other drug when administered w/Famotidine significantly reduces the incidence of ulcers?

Answer 7

NSAIDs

Note: suggested to use ppx, dose-dependent

Question 8

When do H2 receptor antagonists work best?

Answer 8

At night, when less gastrin and ACh is produced

Question 9

What is the drug prototype for PPIs (Proton Pump Inhibitors?

Answer 9

• prazoles

Omeprazole

Question 10

What is the MOA for Omeprazole?

Answer 10

1. Weak base that accumulates in the parietal cell
2. Active/protonated drug IRREV binds & inhibits the parietal cell proton pump
3. prolongs inhibition of gastric acid secretion

Question 11

What are 4 considerations w/ PPIs related to ADME?

Answer 11

1. Acid labile –> need enteric coating to enter stomach
2. Single daily dose decreases acid secretion for 2-3 days
3. Hepatic metabolism –> caution in liver Dz
4. Crosses placenta/Categ C

Question 12

What are the 4 S/Es for long term use of PPIs?

Answer 12

1. Incr risk of fractures
2. decr B12 abosorption
3. HYPOmagnesemia (rare)
4. CKD (rare)

Question 13

What dz are PPIs the 1st line drug for?

Answer 13

Zollinger-Ellison Syndrome

Question 14

What are the PPIs not typically used for?

Answer 14

Not good choice for occasional heartburn

Question 15

When are PPIs most effective?

Answer 15

Good control of acid during the day

OPPOSITE of H2 Antagonists

Question 16

What are the prototype Antacid drugs?

Answer 16

1. Magnesium Hydroxide - Mg(OH)2
2. Aluminum Hydroxide - Al(OH)3
3. Calcium carbonate - CaCO3

Question 17

MOA for antacids?

Answer 17

Weak bases that directly neutralize acid in the stomach

Question 18

When must antacids be given? Why?

Answer 18

AFTER A MEAL –> antacids need acid present to work

Question 19

Which types of antacids are typically combined? Why?

Answer 19

Mg(OH)2 combined with Al(OH)3 or CaCO3

Magnesium hydroxide = diarrhea producing
Al(OH)3 and CaCO3 = constipation producing

Question 20

What types of drugs do ALL antacids interfere with and why?

Answer 20

Acidic drugs (salicylates) & basic drugs (quinidines)

Antacids are eliminated by kidneys –> incr urinary pH

Question 21

What are antacids used?

Answer 21

1. Occasional heartburn
   (opposite of PPIs)
2. SYMPTOMATIC relief of PUD or GERD

Question 22

What are the 3 Mucosal Protective prototype drugs?

Answer 22

1. Sulcralfate
2. Bismuth Subsalicylate
3. Misoprostol

Question 23

MOA for Sulcralfate?

Answer 23

Forms a protective paste at low pH –> adheres to peptic ulcers and epithelial cells –> protects against acid/pepsin attack

Question 24

When must Sulcralfate be given? Why?

Answer 24

MUST BE GIVEN BEFORE A MEAL –> needs the acidic environment to form the protective paste

Question 25

What is the major problem w/Sulcralfate? Solution?

What can Sulcralfate not be given with?

Answer 25

Problem –> Sulcralfate can adsorb other drugs
Solution –> wait 2 hrs to give Sulcralfate

Cant be given w/antacids (they neutralize acid in the stomach)

Question 26

What is Bismuth Subsalicylate good for/why?

Answer 26

Good for H. pylori infections b/c its antimicrobial

Question 27

How does Bismuth Subsalicylate differ from Sucralfate?

Answer 27

Bismuth Subsalicylate binds selectively to ulcers

Question 28

AE for Bismuth Subsalicylate?

What age group is Bismuth Subsalicylate CI in? Why?

Answer 28

AE –> blackened tongue (bismuth = metal)

CI = kids –> Reyes syndrome

Question 29

What type of drug is Misoprostol?

What are its 2 MOA?

Answer 29

PGE1 analog

MOA

1. inhibits acid secretion of ECL and maybe parietal cells
2. increase mucus & HCO3 secretion (protective)

Question 30

When is Misoprostol CI? Why?

Answer 30

Pregnancy –> induces uterine contractions

Question 31

What are the 2 Antiemetic drug prototypes?

Answer 31

1. Metoclompramide

2. Ondansetron

Question 32

Metoclompramide MOA in CNS and peripherally?

Answer 32

CNS —> DA & 5-HT3 Antagonist

Peripherally –> 5-HT4 Agonist

Question 33

Why is Metoclompramide considered a prokinetic?

Answer 33

It enhances ACh release in myenteric plexus & improves intestinal smooth muscle response to ACh

Question 34

AEs for Metoclompramide?

Answer 34

1. D2 antagonist activity –> extrapyramidal Sxs (parkinsonism-like) & tradive dyskinesia
2. BBW: long term use –> IRREV dyskinesia (muscle spasms)

Question 35

Best use for Metoclompramide?

Answer 35

Chemotherapy induced N/V

Question 36

MOA for Ondansetron?

Answer 36

Selective: 5-HT3 receptor antagonist

Little/no effects on muscarinic/DA receptors

Question 37

When is Ondansetron most effective?

Answer 37

Most effective when given before chemo/surgery

Question 38

S/Es of Ondansetron?

Answer 38

Constipation, HA