Chapter 78
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Transcript of Chapter 78
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Chapter 78
Drugs for Peptic Ulcer Disease
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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
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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.
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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
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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)
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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
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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
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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
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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
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Classes of Antiulcer Drugs Antibiotics Antisecretory agents Mucosal protectants Antisecretory agents that enhance mucosal
defenses Antacids
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Three Ways Antiulcer Drugs Work
Eradicate H. pylori (antibiotics)
Reduce gastric acidity(antisecretory agents, misoprostol)
Enhance mucosal defenses(sucralfate, misoprostol)
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Drug Selection: H. pylori–Associated Ulcers
Antibiotics Should be given to all patients with
gastric/duodenal ulcers and documented H. pylori Antisecretory agents
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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
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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
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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
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H. pylori Tests Noninvasive
Breath test Serum test Stool test
Invasive Endoscopic specimen obtained and evaluated
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H. pylori Treatment Minimum of two antibiotics (up to three)
prescribed to decrease risk of developing resistance Amoxicillin Clarithromycin Bismuth compounds Tetracycline Metronidazole Tinidazole
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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)
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Histamine2-Receptor Antagonists
Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid)
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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
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Fig. 78–2. A model of the regulation of gastric acid secretion showing the actions of antisecretory drugs and antacids.
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Cimetidine (Tagamet) Pharmacokinetics
Absorption slowed if taken with meals Crosses the blood-brain barrier with difficulty May cause some CNS side effects
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Cimetidine (Tagamet) Therapeutic uses
Gastric and duodenal ulcers Gastroesophageal reflux disease (GERD) Zollinger-Ellison syndrome Aspiration pneumonitis Heartburn, acid indigestion, and sour stomach
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Cimetidine (Tagamet) Adverse effects
Antiandrogenic effects CNS effects Pneumonia IV bolus: can experience hypotension and
dysrhythmias
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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
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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
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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
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Famotidine (Pepcid) Adverse effects
Does not bind to androgen receptors Possible increased risk for pneumonia caused by
elevation of pH
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Nizatidine (Axid) Actions much like those of ranitidine and
famotidine Therapeutic uses
Duodenal/gastric ulcers GERD, heartburn, acid indigestion, and sour
stomach
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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
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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
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Other PPIs Dexlansoprazole Rabeprazole Pantoprazole
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Other Antiulcer Drugs Sucralfate (Carafate) Misoprostol (Cytotec) Antacids
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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
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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
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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