Drugs Affecting the Gastrointestinal System Caiying YE Department of Pharmacology, School of Basic Medicine, Peking Union Medical College

Drugs Affecting the Gastrointestinal System Antiulcerants Digestives Antiemetics Purgatives Antidiarrheals Cholagogues

Peptic Ulcers Common disease，incidence rate: 10%~12%. Pathogenesis of ulcers Aggressive Factors Defensive Factors Acid,pepsin Bile salts Drugs (NSAIDs) H.pylori Mucus,bicarbonate layer Blood flow,cell renewal Prostaglandins Phospholipid Free radical scavengers

Peptic Ulcers Therapy Purpose： Therapy is directed at enhancing host defense or eliminating aggressive factors; i.e., H. pylori.

Drugs Used in Peptic Ulcers Antacids Inhibitors of gastric acid production H2-receptor antagonists Proton pump inhibitors Muscarinic antagonists Gastrin receptor antagonist Mucosal Protectants Anti-Helicobacter pylori. drugs Acid Pump

Drugs Used in Peptic Ulcers Antacids ： aluminum hydroxide magnesium hydroxide H2- receptor antagonists ： cimetidine ranitidine Muscarinic antagonists ：atropine

Drugs Used in Peptic Ulcers Proton pump inhibitors ：omeprazole Gastrin receptor antagonist ：proglumide Mucosal Protectants ：misoprostol Anti-Helicobacter pylori. Drugs ：antibiotics

Antacids General characteristics Antacids are weak bases that are taken orally and that partially neutralize gastric acid and reduce pepsin activity. Antacids reduce the pain associated with ulcers and may promote healing. High doses are required for healing: 40 mEq of base seven times daily.

Antacids Magnesium hydroxide Magnesium trisilicate Aluminum hydroxide Calcium carbonate Sodium bicarbonate

H2-receptor antagonists Mechanism of action Competitively block the histamine (H2) receptor of acid-producing parietal cells rendering cells less responsive to not only histamine but also to the stimulation of acetylcholine and gastrin. Also up to 90% inhibition of vagal stimulated and gastrin stimulated acid secretion. complete inhibition has not been shown

H2-receptor antagonists Four FDA-approved: Cimetidine （Tagamet®） Ranitidine （Zantac®） Famotidine （Pepcid®） Nizatidine （Axid®） Roxatidine

H2-receptor antagonists Therapeutic effects: Promote the healing of gastric and duodenal ulcers Gastroesophageal reflux dz [GERD] Upper GI bleed [GIB] May be effective in stress ulcers & peptic esophagitis

H2-receptor antagonists Side effect: Overall low < 3% CNS: < 1% total headache, lethargy ，confusion, depression，hallucinations ENDO： Impotence ，increased prolactin ，gynecomastia HEME: Thrombocytopenia

Muscarinic antagonists Atropine： Block the M1 class receptors reduce acid production abolish gastrointestinal spasm relatively unpopular as a first choice because of high incidence of anticholinergic side effects (dry mouth and blurred vision)

Proton pump inhibitors H+,K+-ATPase (Proton Pump) inhibitor Irreversible inhibition Must synthesize new enzyme Long duration Omeprazole (Prilosec®) Lansoprazole (Prevacid®) Pantoprazole Rabeprazole

Mechanism of Action

Omeprazole（losec） Irreversibly binds to H+/K+ ATPase Prevents H+ ion production & secrection Block all acid secretion = achlorhydria to return to normal must synthesize new H+/K+ ATPase Inhibit H. pylori

Omeprazole（losec） Therapeutic uses Gastroesophageal reflux dz [GERD] Peptic ulcer Infection with H. pylori plus(Hp) Upper GI bleed [GIB]

Omeprazole Lansoprazole Pantoprazole

Gastrin receptor antagonist Proglumide

Mucosal Protective Agents

Misoprostol A congener of prostaglandin E1 PG’s: inhibit gastric acid secretion exhibit ‘cytoprotective’ activity enhance local production of mucus or bicarbonate promote local cell regeneration help to maintain mucosal blood flow

Misoprostol Misoprostol is approved for use in patients taking NASIDs who are at risk for gastric ulcers Misoprostol produces diarrhea and stimulation of uterine contraction.

Bismuth （Pepto-Bismol®） Sucralfate cytoprotective agent stress ulcerations & PUD inhibit H. pylori Bismuth （Pepto-Bismol®） inhibit pepsin activity

Agents Used in infection of Helicobacter Pylori Helicobacter pylori，HP

Agents Used in infection of Helicobacter Pylori Aimed at eliminating H. pylori Bismuth ( Pepto-Bismol®) Gentamicin Amotriptyline (Amoxil ® ) Clarithromycin Tetracycline (Achromycin V ®) Metronidazole (Flagyl ® )

Proton pump inhibitors Agents Used in infection of Helicobacter Pylori Antacids Before 1970 1970~ H2-receptor antagonists Proton pump inhibitors 1980~ Proton pump inhibitors Agents Used in infection of Helicobacter Pylori 1990~

Digestives                                            Pepsin Pancreatin Lactasin

Antiemetic Drugs Vomiting reflex a coordinated reflex controlled by a bilateral vomiting center in the dorsal portion of the lateral reticular formation in the medulla Pharmacologic intervention relies on inhibition of inputs or depression of the vomiting center.

Antiemetic Drugs Histamine1-receptor antagonist Cholinergic antagonist Dopamine antagonists : Metoclopramide Domperidone （motilium） [Therapeutic uses] [Side effects] 5-HT3 antagonists Cannabinoids D2-receptor antagonist (periphery) A weaker antiemetic, fewer extrapyramidal effects. Accelerates gastric emptying; has little effect on the colon

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