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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 78 Drugs for Peptic Ulcer Disease.

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Presentation on theme: "Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 78 Drugs for Peptic Ulcer Disease."— Presentation transcript:

1 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 78 Drugs for Peptic Ulcer Disease

2 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

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

4 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.4 Pathogenesis of Peptic Ulcers  Defensive factors  Mucus Secreted cells of the GI mucosa Secreted cells of the GI mucosa Forms a barrier to protect underlying cells from acid and pepsin Forms a barrier to protect underlying cells from acid and pepsin  Bicarbonate Secreted by epithelial cells of stomach and duodenum Secreted by epithelial cells of stomach and duodenum Most remains trapped in the mucus layer to neutralize hydrogen ions that penetrate the mucus 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 Poor blood flow can lead to ischemia, cell injury, and vulnerability to attack  Prostaglandins Stimulate the secretion of mucus and bicarbonate Stimulate the secretion of mucus and bicarbonate

5 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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 Gram-negative bacillus that can colonize in the stomach and duodenum Lives between epithelial cells and the mucus barrier Lives between epithelial cells and the mucus barrier  Escapes destruction by acid Can remain in GI tract for decades Can remain in GI tract for decades Half of the world infected, but most people do not develop symptomatic peptic ulcer disease (PUD) Half of the world infected, but most people do not develop symptomatic peptic ulcer disease (PUD)

6 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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 60%–70% of patients with PUD have H. pylori infection H. pylori may also promote gastric cancer 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 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 Eradication of the bacterium promotes healing of the PUD and minimized recurrence of PUD

7 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.7 Pathogenesis of Peptic Ulcers  Aggressive factors  Nonsteroidal anti-inflammatory drugs (NSAIDs) Inhibit the biosynthesis of prostaglandins Inhibit the biosynthesis of prostaglandins Decrease blood flow, mucus, and bicarbonate Decrease blood flow, mucus, and bicarbonate  Gastric acid Causes ulcers by directly injuring cells of the GI mucosa and indirectly by activating pepsin 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 Increased acid alone does not increase ulcers but is a definite factor in PUD  Pepsin Proteolytic enzyme in gastric juice Proteolytic enzyme in gastric juice  Smoking Delays ulcer healing and increases risk for recurrence Delays ulcer healing and increases risk for recurrence

8 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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 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 Additional factors must be involved: 50% harbor HP, but only 10% develop PUD  Second most common cause NSAIDs NSAIDs

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

10 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.10 Classes of Antiulcer Drugs  Antibiotics  Antisecretory agents  Mucosal protectants  Antisecretory agents that enhance mucosal defenses  Antacids

11 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.11 Three Ways Antiulcer Drugs Work Eradicate H. pylori (antibiotics) Reduce gastric acidity (antisecretory agents, misoprostol) Enhance mucosal defenses (sucralfate, misoprostol)

12 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Drug Selection: H. pylori– Associated Ulcers  Antibiotics  Should be given to all patients with gastric/duodenal ulcers and documented H. pylori  Antisecretory agents

13 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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 histamine 2 receptor blockers are not recommended  Discontinue NSAIDs, if possible

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

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

16 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.16 H. pylori Tests  Noninvasive  Breath test  Serum test  Stool test  Invasive  Endoscopic specimen obtained and evaluated

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

18 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.18 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)

19 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.19 Histamine 2 -Receptor Antagonists  Cimetidine (Tagamet)  Ranitidine (Zantac)  Famotidine (Pepcid)  Nizatidine (Axid)

20 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.20 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

21 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.21 Fig. 78–2. A model of the regulation of gastric acid secretion showing the actions of antisecretory drugs and antacids.

22 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.22 Cimetidine (Tagamet)  Pharmacokinetics  Absorption slowed if taken with meals  Crosses the blood-brain barrier with difficulty  May cause some CNS side effects

23 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.23 Cimetidine (Tagamet)  Therapeutic uses  Gastric and duodenal ulcers  Gastroesophageal reflux disease (GERD)  Zollinger-Ellison syndrome  Aspiration pneumonitis  Heartburn, acid indigestion, and sour stomach

24 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.24 Cimetidine (Tagamet)  Adverse effects  Antiandrogenic effects  CNS effects  Pneumonia  IV bolus: can experience hypotension and dysrhythmias

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

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

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

28 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.28 Famotidine (Pepcid)  Adverse effects  Does not bind to androgen receptors  Possible increased risk for pneumonia caused by elevation of pH

29 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.29 Nizatidine (Axid)  Actions much like those of ranitidine and famotidine  Therapeutic uses  Duodenal/gastric ulcers  GERD, heartburn, acid indigestion, and sour stomach

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

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

32 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.32 Other PPIs  Dexlansoprazole  Rabeprazole  Pantoprazole

33 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.33 Other Antiulcer Drugs  Sucralfate (Carafate)  Misoprostol (Cytotec)  Antacids

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

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

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


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