Narrated PUD

Chapter 77: 

Chapter 77 Drugs for Peptic Ulcer Disease

Peptic Ulcer Disease: 

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

Slide 3: 

Fig. 77-1. 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. (NSAIDs = nonsteroidal anti-inflammatory drugs.)

Pathogenesis of Peptic Ulcers: 

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: 

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)

Pathogenesis of Peptic Ulcers: 

Pathogenesis of Peptic Ulcers Aggressive Factors Helicobacter pylori, also known as H. pylori 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.

Pathogenesis of Peptic Ulcers: 

Pathogenesis of Peptic Ulcers Aggressive factors 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: 

Pathogenesis of Peptic Ulcers Summary of ulcer development Most common cause Infection with H. pylori 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: 

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: 

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

3 Ways Antiulcer Drugs Work: 

3 Ways Antiulcer Drugs Work

Drug Selection: H. pylori–Associated Ulcers : 

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: 

Drug Selection: NSAID-Induced Ulcers Prophylaxis Risk factors for ulcer development (over 60 years old, history of ulcers, high-dose NSAID therapy) Misoprostol and PPIs Treatment H 2 receptor blockers and PPIs are preferred method. Discontinue NSAIDs, if possible.

Nondrug Therapy: 

Nondrug Therapy Diet Traditional “ ulcer diet ” does not accelerate healing. No convincing evidence exists 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: 

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: 

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

H. pylori Treatment: 

H. pylori Treatment Minimum of two antibiotics prescribed to decrease risk for developing resistance Amoxicillin Clarithromycin Bismuth compounds Tetracycline Metronidazole Tinidazole

Antibiotic Regimen: 

Antibiotic Regimen 2007 ACG updated guidelines for managing H. pylori Use minimum of two antibiotics, preferably three Antisecretory agent (PPI, H 2 antagonist) Barriers to compliance Can require up to 12 pills/day (14 days) GI side effects Expensive (about $200)

Histamine2-Receptor Antagonists: 

Histamine 2 -Receptor Antagonists Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid)

Histamine2-Receptor Antagonists: 

Histamine 2 -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

Slide 22: 

Fig. 77-2. A model of the regulation of gastric acid secretion showing the actions of antisecretory drugs and antacids. Production of gastric acid is stimulated by three endogenous compounds: (1) acetylcholine (ACh) acting at muscarinic (M) receptors; (2) histamine (Hist) acting at histamine 2 (H 2 ) receptors; and (3) gastrin (Gast) acting at gastrin (G) receptors. As indicated, all three compounds act through intracellular messengers—either calcium (Ca ++ ) or cyclic AMP (cAMP)—to increase the activity of H + ,K + -ATPase, the enzyme that actually produces gastric acid. Prostaglandins (PG) decrease acid production, perhaps by suppressing production of intracellular cAMP. The actions of histamine 2 -receptor antagonists (H 2 RAs), proton pump inhibitors (PPIs), and other drugs are indicated. (P = prostaglandin receptor.)

Cimetidine (Tagamet): 

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

Cimetidine (Tagamet): 

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

Cimetidine (Tagamet): 

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

Ranitidine (Zantac): 

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): 

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): 

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 OTC – to treat heartburn, acid indigestion, sour stomach

Famotidine (Pepcid): 

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

Nizatidine (Axid): 

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: 

Proton Pump Inhibitors Most effective drugs for suppressing secretion of gastric acid Therapeutic uses Gastric/duodenal ulcers GERD Well tolerated Selection of PPI based on cost and prescriber preference

Omeprazole (Prilosec): 

Omeprazole (Prilosec) First proton pump inhibitor available Actions and characteristics Inhibits gastric secretion Short half-life Used for short-term therapy Adverse effects Headache Gastrointestinal effects

Slide 33: 

Fig. 77-2. A model of the regulation of gastric acid secretion showing the actions of antisecretory drugs and antacids. Production of gastric acid is stimulated by three endogenous compounds: (1) acetylcholine (ACh) acting at muscarinic (M) receptors; (2) histamine (Hist) acting at histamine 2 (H 2 ) receptors; and (3) gastrin (Gast) acting at gastrin (G) receptors. As indicated, all three compounds act through intracellular messengers—either calcium (Ca ++ ) or cyclic AMP (cAMP)—to increase the activity of H + ,K + -ATPase, the enzyme that actually produces gastric acid. Prostaglandins (PG) decrease acid production, perhaps by suppressing production of intracellular cAMP. The actions of histamine 2 -receptor antagonists (H 2 RAs), proton pump inhibitors (PPIs), and other drugs are indicated. (P = prostaglandin receptor.)

Other Antiulcer Drugs: 

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

Sucralfate (Carafate): 

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

Misoprostol (Cytotec): 

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: 

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 renal-impaired patients