Lecture 2: Anti-Ulcer Drugs

Question 1

What are the 5 families of Anti-Ulcer Drugs? (H/P/S/P/B)

Answer 1

H2 Receptor Antagonists (all end in “-tidine”)
Proton Pump Inhibitors (all end in “-prazole”)
Surface Acting Agents
PGE1 Analogs
Bismuth Compounds

Question 2

What are the 4 Histamine 2 Receptor Antagonists used to treat Ulcers? (C/F/N/R)

What is their MOA and what are they commonly used for?

Answer 2

Cimetidine, Famotidine, Nizatidine, Ranitidine

• reversibly inhibits H2 receptors on baso-lateral membrane of parietal cell
• used for relief of GERD symptoms; inhibits 20-50% of acid production (ulcers heal in 4-8+ weeks)

Question 3

What 2 rare adverse effects of Histamine 2 Receptor Antagonists? (GG/BD)

Answer 3

1. CIMETIDINE dec. testosterone binding to androgen receptors (gynecomastia and galactorrhea)
2. Blood Dyscrasias (neutropenia and thrombocytopenia)

VERY RARE; more likely with long-term, high-dosing; otherwise very well tolerated

Question 4

What two Histamine 2 Receptors Antagonists are CYP450 blockers?

Answer 4

CIMETIDINE is a prototypical inhibitor of CYP450 isoenzymes = LOTS of drug-drug interactions

• Ranitidine has 10% of CYP450 inhibition compared to cimetidine

Question 5

What is a relative contraindication of Histamine 2 Blocker usage?

Answer 5

PREGNANCY (use RANITIDINE only if necessary, then Famotidine)

Question 6

What are the 6 Proton Pump Inhibitors used to treat Ulcers? (O/E/L/D/P/R)

What is their MOA and which two are Isomers?

Answer 6

Omeprazole, Esomeprazole (ISOMER), Lansoprazole, Dexlansoprazole (ISOMER), Pantoprazole, Rabeprazole

MOA: covalently bind to H/K ATPase on parietal cell and inhibit gastric acid secretion (IRREVERSIBLE)
- takes several days to create new steady pump activity

• effects seen in several days (inhibits 50-90% of acid); if not healed in 4-8 weeks, check for H. PYLORI

Question 7

Aside from GI and CNS related adversities, what is the biggest additional risk associated with Proton Pump Inhibitor usage?

Answer 7

Clostridium Difficile-Associated Diarrhea

• rare but dangerous (watch out for it)

Question 8

Which PPI is a CYP450 inhibitor?

Answer 8

Omeprazole

Question 9

What is a relative contraindication of Proton Pump Inhibitor usage?

Answer 9

PREGNANCY (use LANSOPRAZOLE only if necessary, then use pantoprazole)

Question 10

What is a Surface Acting Agent used to treat ulcers?

What is its MOA and what is a common adverse effect?

Answer 10

Sucralfate (sulfated polysaccharide)
- octasulfate of sucrose with Al(OH)3 added

MOA: cross-linking (stomach acid interaction) that creates sticky polymer that adheres to epithelial cells around ulcer’s crater (BANDAID that prevents acid access to ulcer)

can also stim local prostaglandin and mucus production = cytoprotection

ADVERSE: constipation

Question 11

What are Relative Contraindications and Drug Interactions associated with Sucralfate use?

Answer 11

RC: severe renal failure due to Aluminum
- avoid aluminum-containing antacids (short times)

DI: possible; take 2-hours after other medications
- dosed QID, plan dosing methods accordingly

Question 12

What is a PGE-1 Analog used to treat Ulcers?

What is its MOA and what is its common indication of use?

What are two contraindications of use?

Answer 12

Misoprostol

MOA: provides protective prostaglandin to gastric mucosa and reduces gastric acid release from parietal cell (CYTOPROTECTION)

I: prevention of NSAID-induced gastric ulceration in patients at high-risk of ulcerations/complications (basically people on NSAIDS that CANNOT come off of them)

C: Pregnancy (only for off-label issues) and IBD

Question 13

What is a Bismuth Compound used to treat Ulcers?

What is its MOA, and what is the difference between OTC and Rx uses?

Answer 13

Bismuth subsalicylate (Pepto-Bismol)
   - also in combo pack for H. pylori

MOA: originally an anti-diarrheal agent that has well known ANTIMICROBIAL actions (can aid other antimicrobials); prevents microbial attachment to mucosa, enterotoxin inactivation, and cell wall disruption

OTC = alone for heartburn (reflux), indigestion, diarrhea
Rx = combo with antibiotics and acid suppressants
- H. pylori infections

Question 14

What are Adverse Effects and Drug Interactions associated with Bismuth Compounds?

Answer 14

AE: constipation and Black/Dark stool (regular formation)
- dose-related

DI: LOTS, take 2 hours after other medications

Question 15

What are 2 relative contraindications and absolute contraindications of Bismuth Compound usage?

Answer 15

RC: antiplatelets/anticoagulants and severe renal failure

AC: GI bleeding and salicylate hypersensitivity

Question 16

What is the typical combination treatment for H. pylori?

What is the current American College of Gastroenterology recommendation for treatment?

Answer 16

• at least 2 antibiotics and an acid reducer (PPI is frontline, but can use H2 antagonist if no PPI available)
• ACG recommends 10-14 day treatment with PPI, Clarithromycin, and either Amoxicillin/Metronidazole for treatment

Question 17

What can lead to false negative H. Pylori results?

Answer 17

• taking bismuth, antimicrobials, and some PPIs 4 weeks prior to performing Gastric Urease or Urea Breath-tests for H. pylori

Question 18

What is the difference between Triple Therapy and Quadruple Therapy treatments for H. Pylori?

Answer 18

TT: 14 days BID dosing
- PPI, Clarithromycin, Amoxicillin OR Metronidazole

QT: 10-14 days QID for everything NOT PPI (BID)
- PPI, Metronidazole, Tetracycline, Bismuth Subsalicylate

Question 19

What treatment should you pursue for H. pylori if triple-therapy treatment w/METRONIDAZOLE fails to eradicate infection?

Answer 19

• use a non-metronidazole containing quadruple therapy

Question 20

What option should you use if treating a pregnant patient WITHOUT H. pylori who has:

1. Moderate Symptoms
2. Severe Symptoms

Answer 20

1. consider ranitidine

2. consider lansoprazole

Question 21

What options do you have for H. pylori treatment if patient has:

1. PCN allergy (no amoxicillin)
2. Metronidazole resistance
3. Clarithromycin resistance

Answer 21

1. substitute Metronidazole
   
   • also consider Bismuth QUAD therapy
2. substitute Tetracycline
   
   • also consider QUAD therapy
   • Quad w/clarithromycin and amoxicillin
3. substitute either Tetracycline or Amoxcicillin
   
   • also consider Bismuth QUAD therapy