消化系统药物11幻灯片.pptVIP

Digestive System Agents Anti-ulcer Agents Antiemetics Prokinetics 5.1 Anti-ulcer Agents Development, Classification and Mechanism of Action H2 -Receptor Antagonists Proton Pump Inhibitors，PPI Strategies for Treating GI Ulcers Inhibit gastric acid production H2-receptor antagonists Proton pump inhibitors Increase mucus production PGE1 analog Protect damaged areas from secreted acid Neutralize secreted acid Antibacterial agents to treat Helicobacter pylori infection Agents that Neutralize Secreted Acid Antacids: Aluminum hydroxide (Amphojel) Calcium carbonate (Tums) Common side effects: Constipation (aluminum, calcium salts) Acid rebound Antibacterial Agents Helicobacter pylori may play a role in GI ulceration in some animals Traditional triple therapy: Amoxicillin Metronidazole (Flagyl) Agent to decrease acid production H2-receptor antagonist Proton pump inhibitor H2 -Receptor Antagonists Histamine and receptor Pharmacology of H2 -Receptor Antagonists Development and Therapy Agents of H2 -Receptor Antagonists SAR Specific Agents Histamine Histamine Receptor H2 Antagonist Pharmacological Effects Competitive antagonists at the H2 receptors Inhibits secretory function of gastric mucosa. Few other effects than those on gastric secretion. Reduces gastric acid volume concentration of pepsin H2 Receptor Antagonist H2 Receptor Antihistamines (cont) Model: H2 Receptor Binding SAR of H2 Receptor Antihistamines Cimetidine Cimetidine H2-receptor antagonist Inhibits the production of acid in the stomach and widely used for the treatment of heartburn and peptic ulcers. Metabolism First pass metabolism, oral bioavailability about 50% Ranitidine Hydrochloride Ranitidine Hydrochloride Mostly widely used in the treatment of peptic ulcer disease and gastroesophageal reflux disease Improved tolerability profile (i.e. fewer adverse drug reactions), longer-lasting action, and ten times the activity of cimetidine. Hepatic metabolism and renal excretion Pr