1. Drugs for Peptic Ulcer Disease
Chapter 78
Drugs for Peptic Ulcer Disease 1

2. Peptic Ulcer Disease Definition Cause Group of upper GI disorders
Degrees of erosion of the gut wall
Severe erosion can be complicated by hemorrhage and perforation
Cause
Imbalance between mucosal and aggressive factors 2

3. Fig. 78–1. The relationship of mucosal defenses and aggressive factors to health and peptic ulcer disease. When aggressive factors outweigh mucosal defenses, gastritis and peptic ulcers result. 3

4. Pathogenesis of Peptic Ulcers
Defensive factors
Mucus
Secreted cells of the GI mucosa
Forms a barrier to protect underlying cells from acid and pepsin
Bicarbonate
Secreted by epithelial cells of stomach and duodenum
Most remains trapped in the mucus layer to neutralize hydrogen ions that penetrate the mucus
Blood flow
Poor blood flow can lead to ischemia, cell injury, and vulnerability to attack
Prostaglandins
Stimulate the secretion of mucus and bicarbonate 4

5. Pathogenesis of Peptic Ulcers
Aggressive factors
Helicobacter pylori, also known as H. pylori
Gram-negative bacillus that can colonize in the stomach and duodenum
Lives between epithelial cells and the mucus barrier
Escapes destruction by acid
Can remain in GI tract for decades
Half of the world infected, but most people do not develop symptomatic peptic ulcer disease (PUD) 5

6. Pathogenesis of Peptic Ulcers
Aggressive factors
Helicobacter pylori, also known as H. pylori (cont’d)
60%–70% of patients with PUD have H. pylori infection
H. pylori may also promote gastric cancer
Duodenal ulcers are much more common among people with H. pylori infection than among people who are not infected
Eradication of the bacterium promotes healing of the PUD and minimized recurrence of PUD 6

7. Pathogenesis of Peptic Ulcers
Aggressive factors
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Inhibit the biosynthesis of prostaglandins
Decrease blood flow, mucus, and bicarbonate
Gastric acid
Causes ulcers by directly injuring cells of the GI mucosa and indirectly by activating pepsin
Increased acid alone does not increase ulcers but is a definite factor in PUD
Pepsin
Proteolytic enzyme in gastric juice
Smoking
Delays ulcer healing and increases risk for recurrence 7

8. Pathogenesis of Peptic Ulcers
Summary of ulcer development
Most common cause
Infection with H. pylori (HP) is the most common cause of gastric and duodenal ulcers
Additional factors must be involved: 50% harbor HP, but only 10% develop PUD
Second most common cause
NSAIDs 8

9. Overview of Treatment Goals of drug therapy
Alleviate symptoms
Promote healing
Prevent complications
Prevent recurrence
Drugs do not alter the disease process; they create conditions conducive to healing 9

10. Classes of Antiulcer Drugs
Antibiotics
Antisecretory agents
Mucosal protectants
Antisecretory agents that enhance mucosal defenses
Antacids 10

11. Three Ways Antiulcer Drugs Work
Eradicate H. pylori
(antibiotics)
Reduce gastric acidity
(antisecretory agents, misoprostol)
Enhance mucosal defenses
(sucralfate, misoprostol) 11

12. Drug Selection: H. pylori–Associated Ulcers
Antibiotics
Should be given to all patients with gastric/duodenal ulcers and documented H. pylori
Antisecretory agents 12

13. Drug Selection: NSAID- Induced Ulcers
Prophylaxis
Risk factors for ulcer development (older than 60 years, history of ulcers, high-dose NSAID therapy)
Treatment
Proton pump inhibitors (PPIs) (eg, omeprazole) are preferred
Misoprostol is also effective, but can cause diarrhea
Antacids, sucralfate, and histamine2 receptor blockers are not recommended
Discontinue NSAIDs, if possible 13

14. Nondrug Therapy
Diet
Traditional “ulcer diet” does not accelerate healing
No convincing evidence indicates that caffeinated beverages promote ulcers or delay healing
Change eating pattern to 5–6 small meals a day (reduces pH fluctuations)
Avoid smoking, aspirin, other NSAIDs, and alcohol if a trigger 14

15. Evaluation of Therapy Monitor for relief of pain
Keep in mind: cessation of pain and disappearance of ulcer rarely coincide
Pain may subside before complete healing or may continue after healing
Radiologic or endoscopic examination of ulcer site
H. pylori tests 15

16. H. pylori Tests Noninvasive Invasive Breath test Serum test Stool test
Endoscopic specimen obtained and evaluated 16

17. H. pylori Treatment
Minimum of two antibiotics (up to three) prescribed to decrease risk of developing resistance
Amoxicillin
Clarithromycin
Bismuth compounds
Tetracycline
Metronidazole
Tinidazole 17

18. Antibiotic Regimen 2007 ACG updated guidelines for managing H. pylori
Use minimum of two antibiotics, preferably three
Antisecretory agent (PPI, H2 antagonist)
Barriers to compliance
Can require up to 12 pills/day (14 days)
GI side effects
Expensive (about $200) 18

19. Histamine2-Receptor Antagonists
Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid) 19

20. Histamine2-Receptor Antagonists
First-choice drugs for treating gastric and duodenal ulcers
Promote healing by suppressing secretion of gastric acid
All four equally effective
Serious side effects uncommon 20

21. Fig. 78–2. A model of the regulation of gastric acid secretion showing the actions of antisecretory drugs and antacids. 21

22. Cimetidine (Tagamet) Pharmacokinetics
Absorption slowed if taken with meals
Crosses the blood-brain barrier with difficulty
May cause some CNS side effects 22

23. Cimetidine (Tagamet) Therapeutic uses Gastric and duodenal ulcers
Gastroesophageal reflux disease (GERD)
Zollinger-Ellison syndrome
Aspiration pneumonitis
Heartburn, acid indigestion, and sour stomach 23

24. Cimetidine (Tagamet) Adverse effects Antiandrogenic effects
CNS effects
Pneumonia
IV bolus: can experience hypotension and dysrhythmias 24

25. Ranitidine (Zantac) Shares many properties of cimetidine
More potent, fewer adverse effects, causes fewer drug interactions than cimetidine (and has less ability to cross CNS)
Adverse effects
Significant ones uncommon
Does not bind to androgen receptors 25

26. Ranitidine (Zantac) Therapeutic uses
Short-term treatment of gastric/duodenal ulcers
Prophylaxis of recurrent duodenal ulcers
Treatment of Zollinger-Ellison syndrome and hypersecretory states
Treatment of GERD 26

27. Famotidine (Pepcid) Actions similar to those of ranitidine
Therapeutic uses
Short-term treatment of gastric/duodenal ulcers
Prophylaxis of recurrent duodenal ulcers
Treatment of Zollinger-Ellison syndrome and hypersecretory states
Treatment of GERD
Over-the-counter (OTC): to treat heartburn, acid indigestion, sour stomach 27

28. Famotidine (Pepcid) Adverse effects
Does not bind to androgen receptors
Possible increased risk for pneumonia caused by elevation of pH 28

29. Nizatidine (Axid) Actions much like those of ranitidine and famotidine
Therapeutic uses
Duodenal/gastric ulcers
GERD, heartburn, acid indigestion, and sour stomach 29

30. Proton Pump Inhibitors
Most effective drugs for suppressing secretion of gastric acid
Therapeutic uses: short term
Gastric/duodenal ulcers
GERD
Well tolerated
Selection of PPI based on cost and prescriber preference
Can increase the risk of serious adverse events, including fracture, pneumonia, acid rebound, and possibly intestinal infection with Clostridium difficile 30

31. Omeprazole (Prilosec)
First available proton pump inhibitor
Actions and characteristics
Inhibits gastric secretion
Short half-life
Used for short-term therapy
Adverse effects
Usually inconsequential with short-term use
Headache
Gastrointestinal effects
Pneumonia
Rebound acid hypersecretion
C. difficile infection
Gastric cancer 31

32. Other PPIs
Dexlansoprazole
Rabeprazole
Pantoprazole

33. Other Antiulcer Drugs Sucralfate (Carafate) Misoprostol (Cytotec)
Antacids 33

34. Sucralfate (Carafate)
Creates a protective barrier up to 6 hours
Therapeutic uses
Acute ulcers and maintenance therapy
Adverse effects
Constipation (in only 2% of patients)
Drug interactions
Minimal
Antacids may interfere with effects of sucralfate 34

35. Misoprostol (Cytotec)
Therapeutic uses
Only approved GI indication is prevention of gastric ulcers caused by long-term NSAID therapy
Adverse effects
Most common: dose-related diarrhea (13%–40%) and abdominal pain (7%–20%)
Contraindicated during pregnancy: category X
Significant actions need to be taken to ensure that pregnancy does not occur after therapy starts, and that patient is not pregnant at therapy initiation 35

36. Antacids
React with gastric acid to produce neutral salts or salts of low acidity
Decrease destruction of the gut wall by neutralizing acid
May also enhance mucosal protection by stimulating production of prostaglandins
Except for sodium bicarbonate, antacids do not alter systemic pH
Use with caution in patients with renal impairment 36