Chapter 78

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 78

Drugs for Peptic Ulcer Disease

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 2

Peptic Ulcer Disease Definition

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


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.


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


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)



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



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


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


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


Classes of Antiulcer Drugs Antibiotics Antisecretory agents Mucosal protectants Antisecretory agents that enhance mucosal

defenses Antacids


Three Ways Antiulcer Drugs Work

Eradicate H. pylori (antibiotics)

Reduce gastric acidity(antisecretory agents, misoprostol)

Enhance mucosal defenses(sucralfate, misoprostol)


Drug Selection: H. pylori–Associated Ulcers

Antibiotics Should be given to all patients with

gastric/duodenal ulcers and documented H. pylori Antisecretory agents


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


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


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


H. pylori Tests Noninvasive

Breath test Serum test Stool test

Invasive Endoscopic specimen obtained and evaluated


H. pylori Treatment Minimum of two antibiotics (up to three)

prescribed to decrease risk of developing resistance Amoxicillin Clarithromycin Bismuth compounds Tetracycline Metronidazole Tinidazole


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)


Histamine2-Receptor Antagonists

Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid)


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


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


Cimetidine (Tagamet) Pharmacokinetics

Absorption slowed if taken with meals Crosses the blood-brain barrier with difficulty May cause some CNS side effects


Cimetidine (Tagamet) Therapeutic uses

Gastric and duodenal ulcers Gastroesophageal reflux disease (GERD) Zollinger-Ellison syndrome Aspiration pneumonitis Heartburn, acid indigestion, and sour stomach


Cimetidine (Tagamet) Adverse effects

Antiandrogenic effects CNS effects Pneumonia IV bolus: can experience hypotension and

dysrhythmias


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


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


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


Famotidine (Pepcid) Adverse effects

Does not bind to androgen receptors Possible increased risk for pneumonia caused by

elevation of pH


Nizatidine (Axid) Actions much like those of ranitidine and

famotidine Therapeutic uses

Duodenal/gastric ulcers GERD, heartburn, acid indigestion, and sour

stomach


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


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


Other PPIs Dexlansoprazole Rabeprazole Pantoprazole


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


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


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


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

Chapter 78

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