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GASTROINTESTINAL AND ANTIEMETIC DRUGS
DRUGS FOR PEPTIC ULCER (PUD) AND GASTROESOPHAGEAL REFLUX DISEASE (GERD)
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
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
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•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•Aggressive factors•Helicobacter pylori,also known as H. pylori (cont’d)•60%–70% of patients with PUD have H. pyloriinfection•H. pylorimay also promote gastric cancer•Duodenal ulcers are much more common among people with H. pyloriinfection 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•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
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
PEPTIC ULCER DISEASE (PUD)Duodenal ulcers •Occurs in 30-55 yrs of age•More common in males•Ulcers are five times more common in the duodenum than in the stomach.