A/38. Drugs used in peptic ulcer diseases. Pharmacotherapy of peptic ulcer diseases.

Question 1

Drugs need to know in this topic

Answer 1

(es)omeprazole

pantoprazole

famotidine

sucralfate

MgO magnesium oxide

Al2(OH)3

aluminum-hydroxide

Question 2

Magnesium hydroxide (Mg[OH]2)

Aluminum hydroxide (Al[OH]3)

Answer 2

Antacids Weak bases that neutralize stomach acid by reacting with protons in the lumen of the gut

1. Oral
2. Poorly absorbed from the bowel

Magnesium hydroxide (Mg[OH]2)

1. Symptomatic relief of dyspepsia and heartburn Side
   effects: diarrhea

Aluminum hydroxide (Al[OH]3)

1. Symptomatic relief of dyspepsia and heartburn Side
   effects: constipation

Question 3

Famotidine

Answer 3

• *H2-receptor antagonists**
  1. Competitive inhibitors of H2-receptors → indirect effect on proton pump activity → decrease gastric acid secretion (mainly nocturnal acid secretion)
  2. No H1, autonomic or anti-motion sickness effects (compared to H1 blockers)
  3. Acid suppressing effect is milder compared to proton pump inhibitors

1. Oral, parenteral
2. Duration of action 12-24 h’
3. Metabolism by hepatic CYP450
   (affected by drugs that induce/inhibit hepatic metabolism)
4. Inhibitors of cytochrome P450 enzymes (cimetidine most potent)
5. GERD
6. Peptic ulcer disease (PUD)
7. H. pylori associated ulcers (part of eradication regimen)
8. NSAID’s induced ulcers
9. Prophylaxis against stress-related mucosal injury
10. Zollinger-Ellison syndrome
    * *Side effects:**
11. GI distress
12. Antiandrogenic effects (gynecomastia, decreased
    libido) , mainly with cimetidine
13. Confusion, agitation (in the elderly)
14. Milder drug-interactions, milder side effects

Question 4

Esomeprazole

Pantoprazole

Omeprazole (not in the list)

Answer 4

• *Proton pump inhibitors (PPI’s)**
  1. Irreversible, direct inhibitors of the proton pump (K+/H+ antiport) in gastric parietal cells
  2. 1st-line agents, most effective in reducing stomach acidity

1. Oral, IV
   (oral formulation should be administered on empty stomach)
2. Hepatic metabolism
3. Prodrug; activation occurs inside parietal cell

**Omeprazole is an inhibitor of cytochrome P450 enzymes**
(effect on: clopidogrel, warfarin, phenytoin, diazepam, cyclosporine)
#Clopidogrel → bioactivation of prodrug is inhibited

1. GERD
2. Peptic ulcer disease (PUD)
3. H. pylori associated ulcers (part of eradication regimen)
4. NSAID’s associated ulcers
5. Prophylaxis against stress-induced mucosal injury
6. Zollinger-Ellison syndrome
   Side effects:
7. Diarrhea, abdominal pain
8. Headaches
9. Decrease in oral bioavailability of vitamin-B12, iron, digoxin,
   ketoconazole
10. Increased risk of respiratory and enteric infections
11. Hypergastrinemia (loss of negative feedback of H+ on D-cells, may lead to ECL and parietal cells hyperplasia)

Question 5

Sucralfa

Answer 5

• *Mucosal-protective agents**
  1. Aluminium sucrose sulphate; polymerizes on gastrointestinal luminal surface to form a protective gel-like coating of ulcer beds
  2. Enhances PGE synthesis, stimulates mucus and bicarbonate secretion, enhances mucosal defense and repair

Question 6

Peptic ulcer disease – definition

Answer 6

1. The term encompasses both gastric and duodenal ulcers.
2. Ulcers are defined as breaks in the mucosal surface > 5 mm in size, with depth penetrating to the submucosa.
3. May be acute or chronic, both penetrate the muscularis mucosae, but acute ulcer shows no evidence of fibrosis.
4. Erosions do not penetrate the muscularis mucosae.
5. Duodenal ulcers and gastric ulcers share many common features in terms of pathogenesis, diagnosis, and treatment.

Question 7

Therapy of H. pylori

Answer 7

Triple therapy

1. Bismuth subsalicylate
2. Metronidazole
3. Tetracycline
4. Omeprazole
5. Clarithromycin
6. Amoxicillin or Metronidazole

Quadruple therapy

1. Bismuth subsalicylate
2. Omeprazole
3. Metronidazole
4. Tetracycline