1. Chapter 38 Gastrointestinal drugs

2. Hepatic, pacreatic and biliary disorders Ulcer disorders Abnormal mobility

3. Gastrointestinal drugs §Drugs used for peptic ulcers §Modulators of gastrointestinal functions

4. Gastrointestinal drugs Pathogenesis of peptic ulcers Infection with gram-negative Helicobacter pylori Increased gastric acid secretion Inadequate mucosal defense against gastric acid Treatment approaches Eradicating H. pylori infection Reducing secretion of gastric acid or neutralizing the acid Protecting the gastric mucosa from damage Peptic ulcers

5. Sucralfate carbonoxolone misoprostol Gastric structure related to peptic ulcer

6. Gastric acid secretion and regulation

7. §Antacids §Drugs affecting gastric acid secretion § Muscarinic receptor antagonists § H 2 receptor antagonists § H + -K + -ATPase inhibitors (proton pump inhibitors) § Gastrin receptor antagonists §Mucosal protective drugs §Antimicrobial drugs (Helicobacter pylori) A. Drugs used for peptic ulcers

8. §Antacids §Basic substances that reduce gastric acidity by neutralizing HCl §The hydroxide is the most common base but trisilicate, carbonate and bicarbonate ions are also used. §Aluminium, magnesium or sodium A. Drugs used for peptic ulcers

9. Sucralfate carbonoxolone misoprostol

10. §Drugs affecting gastric acid secretion §Muscarinic receptor antagonists A. Drugs used for peptic ulcers Pirenzepine 哌仑西平

11. §Pirenzepine （哌仑西平） §1. Pharmacological effects and clinical uses § high affinity for M 1 - and low affinity for M 2 -receptors of the smooth muscle of the ileum and urinary bladder. § blocking of M 1 -muscarinic receptors in autonomic ganglia, inhibiting HCl secretion §2. Adverse effects § Atropine-like effects, especially at larger doses §Other drugs §Telenzepine （替仑西平） §Atropine: atropine-like effects §Propantheline bromide ( 溴丙胺太林 ) A. Drugs used for peptic ulcers

12. Sucralfate carbonoxolone misoprostol

13. §H 2 receptor antagonists A. Drugs used for peptic ulcers Cimetidine 西咪替丁 cimetidine西咪替丁 ranitidine雷尼替丁

14. Cimetidine （西咪替丁） §1. Pharmacological effects § Blocking H 2 receptors, decreasing H + secretion §2. Clinical uses § Duodenal and gastric ulcer, reflux esophagitis: relieving symptoms, promoting healing of ulcers, and preventing ulcers § Zollinger-Ellison syndrome, acute stress ulcers, gastroesophageal reflux disease (heartburn) A. Drugs used for peptic ulcers

15. Sucralfate carbonoxolone misoprostol

16. 3. Adverse effects §(1) Side effects: constipation, diarhoea, tiredness, muscular pain, etc. §(2) CNS effects: headache, dizziness, confusion, hallucination, etc. (elderly, long-term uses)  (3) Endocretion effects: antiandrogen, gynecomastia ( 男 性乳房发育 ), galactorrhea ( 溢乳 ), reduced sperm count, and male sexual dysfunction §4. Drug interactions §Inhibiting hepatic P 450, raising plasma concentrations of warfarin, phenytoin, diazepam, propranolol, quinidine and theophylline A. Drugs used for peptic ulcers

18. Others Ranitidine 雷尼替丁 Longer acting; 4 ～ 10 times more potent Longer acting; 4 ～ 10 times more potent Minimal side effects, on antiandrogenic and prolactin- stimulating effects, not inhibiting P 450 Minimal side effects, on antiandrogenic and prolactin- stimulating effects, not inhibiting P 450 Famotidine 法莫替丁 Similar to ranitidine, but 3 ～ 20 times more potent Similar to ranitidine, but 3 ～ 20 times more potent Nizatidine 尼扎替丁 Bioavailability is near 100%, principally eliminated by kidney Bioavailability is near 100%, principally eliminated by kidney A. Drugs used for peptic ulcers

19. §H + -K + -ATPase inhibitors §( proton pump inhibitors ) A. Drugs used for peptic ulcers Omeprazole 奥美拉唑

20. §1. Pharmacological effects §(1) Inhibiting gastric acid secretion by various stimuli (histamine, gastrin, aspirin, ethanol, stress) §(2) Inhibiting H. pylori §2. Clinical uses §(1) Highly effective for duodenal and gastric ulcer, reflux esophagitis: relieving symptoms, promoting healing of ulcers §(2) Used with antimicrobial regimens to eradicate H. pylori A. Drugs used for peptic ulcers

21. Sucralfate carbonoxolone misoprostol

23. §3. Adverse effects §(1) Side effects: nausea, headache, diarrhoea, constipation and rash occur but are uncommon §(2) Increase of gastric carcinoid tumor: prolongated hypochlorhydria and secondary hypergastrinemia  (3) Others: gynecomastia ( 男性乳房发育 ), hypersensitivity §4. Drug interactions §Inhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam, etc. A. Drugs used for peptic ulcers

24. §Others  Lansoprazole 兰索拉唑  Pantoprazole 泮他拉唑  Rebeprazole 雷贝拉唑 A. Drugs used for peptic ulcers

25. §Mucosal protective drugs  Misoprostol 米索前列醇  Enprostil 恩前列素  Sucralfate 硫糖铝  Colloidal bismuth subcitrate 胶体次枸橼酸铋  Teprenone 替普瑞酮  Marzulene 麦滋林  Smectite 思密达  Proglumide 丙谷胺 A. Drugs used for peptic ulcers

26. Sucralfate Bismuch, etc. misoprostol

27. A. Drugs used for peptic ulcers Misoprostol 米索前列醇

28. A. Drugs used for peptic ulcers  Misoprostol 米索前列醇 §1. Pharmacological effects §Inhibiting gastric acid secretion §Promoting mucus and HCO 3 - secretion, and mucosal repair §2. Clinical uses §Ulcers, especially for NSAIDs-induced §3. Adverse effects §Side effects (13%): nausea, abdominal pain, diarrhea, headache, etc. §Contraindicated in pregnancy women

29. A. Drugs used for peptic ulcers §Antimicrobial drugs §(for Helicobacter pylori) §1. Anti-ulcer drugs § H + -K + -ATPase inhibitors; bismuch ; sulralfate § Weaker, combined with antimicrobial drugs §2. Antimicrobial drugs  metronidazole ( 甲硝唑 ) ; amoxicillin ( 阿莫西林 ) ;  tetracycline ( 四环素 ) ; gentamicin ( 庆大霉素 ) ;  clarithromycin ( 克拉霉素 )

30. Helicobacter pylori in the gastric mucosa

31. Sucralfate Bismuch, etc. misoprostol

32. B. Modulators of gastrointestinal functions gastrointestinal functions

33. B. Modulators of gastrointestinal functions gastrointestinal functions

34. B. Modulators of gastrointestinal functions §Antiemetic and prokinetic drugs antiemetic drugs § antiemetic drugs § prokinetic drugs §Drugs for treatment of diarrhea § antimotility drugs § astringents § absorbants §Laxatives § contact (stimulant) laxatives § osmotic laxatives § faecal softners (emollients)

35. B. Modulators of gastrointestinal functions §Antiemetic and prokinetic drugs §Antiemetic drugs §H 1 receptor antagonists: diphenhydramine 苯海拉明 ; § dimenhydrinate 茶苯海明 ; meclozine 美克洛嗪 §Muscarinic receptor antagonists: scopolamine 东莨菪碱 §D 2 receptor antagonists: chlorpromazine 氯丙嗪 §5-HT 3 receptor antagonists ： ondansetron 昂丹司琼 ; § grasetron 格拉司琼 ; tropisetron 托烷司琼

36. 孤束核

37. B. Modulators of gastrointestinal functions Ondansetron 昂丹司琼

38. B. Modulators of gastrointestinal functions §1. Pharmacological effects § Blocking 5-HT 3 receptor (central and peripheral) §2. Clinical uses Emesis induced by chemotherapy and radiotherapy in the patients with cancers § Emesis induced by chemotherapy and radiotherapy in the patients with cancers §3. Adverse effects § side effects: headache, constipation or diarrhea, etc.

39. 孤束核

40. §Prokinetic drugs  Metoclopramide 甲氧氯普胺 ( 胃复安，灭吐灵 ) § D 2 receptor block: antiemetic effects (CTZ), promoting GI motility (GI) § Adverse effects: CNS reactions, extrpyramidal effects, etc.  Domperidone 多潘立酮 ( 吗丁啉 ) § D 2 receptor block: promoting GI motility (GI) § Adverse effects: headache, prolactin , gastric acid   Cisapride 西沙必利  ACh release  : promoting intestinal and colon motility B. Modulators of gastrointestinal functions

41. Action sites of prokinetic drugs GI tract smooth muscle cells

42. B. Modulators of gastrointestinal functions §Drugs for treatment of diarrhea § Antimotility drugs: agonists for  receptors in GI tract § opium preparations § diphenoxylate 地芬诺酯（ CNS effects at larger doses) § loperamine 洛哌丁胺 § Astringents: § tannalbin 鞣酸蛋白 § bismuch subsalicylate; bismuch subcarbonate ( 铋制剂 ) §Absorbants ： § medical charchol 药用炭（活性炭） § agysical 矽炭银

43. B. Modulators of gastrointestinal functions §Laxatives §Contact (stimulant) laxatives § phenolphthalein 酚酞 § bisacodyl 必沙可啶 § anthraquinones 蒽醌类（中药成分） §Osmotic laxatives § magnesium sulfate 硫酸镁 ; sodium sulfate 硫酸钠； § lactulose 乳果糖 ; sorbitol 山梨醇 ; § glycerol 甘油 ; celluloses 纤维素类 §Faecal softners (emollients) § liquid paraffin 液体石蜡