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Gastrointestinal drugs

Gastrointestinal drugs. Content. Part 1. Drugs used for peptic ulcers Part 2. Modulators of gastroenteric functions. Part 1. Drugs used for peptic ulcers. Drugs used for peptic ulcers. The Pathogenesis of peptic ulcers : 1. Infection with Helicobacter pylori ( Hp );

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Gastrointestinal drugs

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  1. Gastrointestinal drugs

  2. Content • Part 1. Drugs used for peptic ulcers • Part 2. Modulators of gastroenteric functions

  3. Part 1. Drugs used for peptic ulcers

  4. Drugs used for peptic ulcers The Pathogenesis of peptic ulcers: 1. Infection withHelicobacter pylori (Hp); 2. Increased gastric acid secretion; 3. Inadequate mucosal defense to gastric acid.

  5. Drugs used for peptic ulcers ▲ Infection withHpand peptic ulcers: Infection

  6. Drugs used for peptic ulcers Inflammation

  7. Drugs used for peptic ulcers Ulcers

  8. 罗宾·沃伦 巴里·马歇尔 巴里·马歇尔与罗宾·沃伦的这一研究成果获得2005年诺贝尔生理学或医学奖. 10月3日, 正在工作聚会的两位澳大利亚科学家得知自己获得2005年诺贝尔生理学或医学奖后举杯互相庆贺.

  9. Drugs used for peptic ulcers ▲Increased Gastric acid secretion 无酸，便无溃疡——1910年，Schiwatz (the proton pump) Basolateral membane

  10. Drugs used for peptic ulcers ▲Inadequate mucosal defense to gastric acid. Mucus-bicarbonate barrier

  11. Drugs used for peptic ulcers Peptic ulcers and treatment • Pathogenesis of • peptic ulcers • Infection with Hp; • Increased gastric acid secretion; • Inadequate mucosal defense to gastric acid. • Treatment • approaches • Eradicating Hp; • Neutralizing gastric acid, or reducing secretion of the acid; • Protectingthegastric mucosa from damage.

  12. Drugs used for peptic ulcers Classifiction of anti-ulcer drugs I.Antacids: neutralizing the acid II. Drugs suppressing gastric acid secretion ①Muscarinic receptor antagonists ②H2 receptor antagonists ③Gastrin receptor antagonists ④H+-K+-ATPase inhibitors (proton pump inhibitors) III. Antimicrobial drugs (Helicobacter pylori) IV. Mucosal protective drugs

  13. Drugs used for peptic ulcers Ⅰ. Antacids(抗酸药) • Basic substances that can reduce gastric acidity by neutralizing HCl; • Drugs most in use: Aluminium hydroxide(氢氧化铝), Magnesium hydroxide(氢氧化镁), Magnesium trisilicate(三硅酸镁), Magnesium oxide(氧化镁), etc. Composition resparation,such as: 复方氢氧化铝片（胃舒平),铝碳酸镁咀嚼片（达喜）

  14. Drugs used for peptic ulcers misoprostol Sucralfate carbonoxolone

  15. Drugs used for peptic ulcers (1) Antacids 1. Pharmacological effect Neutralizing gastric acid, diminish gastric acidity and inactivate pepsin（胃蛋白酶）activity 2. Clinical uses Used for peptic ulcer and acid-hypersecretory conditions.

  16. Drugs used for peptic ulcers 3. Adverse effects (1) Constipation and stomach cramp (salt of aluminum，松弛平滑肌) (2) Diarrhea (salt of magnesium) (3) Hypercalcium which can cause renal failure (Calcium) (4) Hypernatremia (sodium-containing antacids)

  17. Drugs used for peptic ulcers Adminstration and dosage (1) Take antacids 1 h and 3 h after meals (2) Should not be taken continuously for more than 3 m for ulcer (3) To help avoid or reduce drug interaction, other medication should not be taken within 1-2 hours of taking an antacids

  18. Drugs used for peptic ulcers Ⅱ. Drugs inhibiting gastric acid secretion A. Muscarinic receptor antagonists (M receptor blocker): Drugs most in use: Atropine(阿托品) Propantheline bromide(溴丙胺太林) Pirenzepine(哌仑西平) Telenzepine(替仑西平)

  19. Drugs used for peptic ulcers B. 4 种H2-受体阻断药的比较 西咪替丁2 1400mg, bid 1 雷尼替丁2-35-10150mg, bid 0.1 法莫替丁2.5-4 4020mg, bid 0 尼扎替丁 2 5-10150mg, bid 0 对肝药 酶抑制 相对抑 酸活力 药 名 剂　量 t1/2(h) 主要区别：药动学和引起药物相互作用的特性

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

  21. Drugs used for peptic ulcers Omepranzole × (the proton pump)

  22. Drugs used for peptic ulcers 1. Pharmacological effects (1)Inhibiting gastric acid secretion by various stimuli(such as: histamine, gastrin, aspirin, ethanol, stress, etc.) (2)Inhibiting Hp. (3) protection for gastric mucosa

  23. 2. Clinical uses (1)Highly effective for duodenal and gas-tric ulcer: relieving symptoms, and promoting healing of ulcers Used with antimicrobial agents to eradicate Hp . (2)Reflux esophagitis; (3)Zollinger-Ellison syndrome

  24. Drugs used for peptic ulcers 3. Adverse effects (1)Side effects: nausea, headache, diarrhoea, constipation and rash occur. (2)Others: gynecomastia(男性乳房发育) 4.Drug interactions Inhibiting hepatic P450,raising plasma concentrations ofwarfarin, phenytoin, diazepam,etc.

  25. Drugs used for peptic ulcers Others • Lansoprazole(兰索拉唑) • Pantoprazole(泮他拉唑) • Rebeprazole(雷贝拉唑)

  26. Drugs used for peptic ulcers 几种质子泵抑制剂的比较 t1/2有效抑酸 剂量 对肝药 (h)时间(h)(mg/d)酶影响 奥美拉唑1.012～2420～40 + 兰索拉唑1.52430 潘托拉唑1.32420～40 雷贝拉唑 1.02420 药　名

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

  28. misoprostol Sucralfate Bismuch, etc.

  29. Drugs used for peptic ulcers (3) Mucosal protective drugs Misoprostol米索前列醇 A prostaglandin E analogues

  30. Drugs used for peptic ulcers Misoprostol米索前列醇 1. Pharmacological effects Inhibiting gastric acid secretion Promoting mucus and HCO3- secretion, and mucosal repair 2. Clinical uses Only approved for the prevention of NSAIDs-induced gastric Ulcer. 3. Adverse effects Side effects (13%):abdominal pain, nausea, headache, etc. Contraindicated in pregnancy women (Abortifacient 堕胎 property)

  31. Drugs used for peptic ulcers (3) Mucosal protective drugs Sucralfate 硫酸蔗糖和氢氧化铝构成。PH<4，交联，聚合成有黏性的胶状聚合物，粘附于上皮细胞和基底膜达6个小时。

  32. Drugs used for peptic ulcers (3) Mucosal protective drugs Sucralfate 1. Pharmacological effects 1) Binding to mucosal surface and forms a protective barrier 2) Enhancing cell restitution and re-epithelization. 3) Weakly inhibiting H.Pylory growth. 4) Promote PGE2 production 5) Binding to pepsin and then reduce its activity 2. Clinical uses and Adminstration peptic ulcers, but with the advent of more effective agents (proton pump inhibitors); reflux esophagitis; mucosa impairment.

  33. Drugs used for peptic ulcers (3) Mucosal protective drugs Bismuth Compounds Colloidal bismuth subcitrate (CBS, 胶体次枸橼酸铋) Bismuth subslicylate 1. Pharmacological effects 1) Probably coats ulcers and erosions, creating a protective layer against acid and pepsin 2) Inhibit pepsin activity, stimulate prostaglandin, mucus, and bicarbonate secretion 3) Have direct antimicrobial activity against H pylori

  34. Drugs used for peptic ulcers Bismuth Compounds 2. Clinical uses 1) Treatment of dyspepsia（消化不良）, peptic ulcer, chronic gastritis. 2) Used in multidrug regimens for the eradication of H pylori infection. 3. Adverse effects Causes blackening of the stool, which may be confused with gastrointestinal bleeding Bismuth toxicity resulting in encephalopathy (ataxia, headaches).

  35. Drugs used for peptic ulcers Ⅳ. Antimicrobial(anti-Hp) drugs 1. Anti-ulcer drugs: H+-K+-ATPase inhibitors; bismuch(铋剂); sulralfate(硫糖铝), etc. 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), etc.

  36. misoprostol Sucralfate Bismuch, etc.

  37. Drugs used for peptic ulcers The best treatment regimen consists of a 7–14 day regimen of "triple therapy": Program 1 1) A proton pump inhibitor twice daily, 2) Clarithromycin 500 mg twice daily, 3) Amoxicillin 1 g twice daily. Daily for 7 d. For patients who are allergic to penicillin, metronidazole 500 mg twice daily should be substituted for amoxicillin. Program 2 1) Bismuth subsalicylate (2 tablets; 262 mg each), 2) Tetracycline (500 mg), 3) Metronidazole (250 mg), each taken four times daily for 14 days.

  38. Drugs used for peptic ulcers For patients with resistant infections, "quadruple therapy” • A proton pump inhibitor twice daily • 2) Bismuth subsalicylate (2 tablets; 262 mg each), • 3) Clarithromycin 500 mg twice daily, • 4) Amoxicillin 1 g twice daily • for 14 days.

  39. Gastrointestinal drugs Part2 Modulators of gastrointestinal functions

  40. Modulators of gastrointestinal functions Abnormalities of gastrointestinal functions Nausea and vomiting Constipation Diarrhea

  41. Contents Antiemetic and prokinetic drugs 1.antiemetic drugs(止吐药) 2. prokinetic drugs(胃动力药) Drugs for treatment of diarrhea 1. antimotility drugs(抗蠕动药) 2. astringents(收敛药) 3. absorbants(吸附药) Laxatives 1. contact(stimulant) laxatives 2. osmotic laxatives 3. faecal softners(emollients)

  42. 延脑的呕吐中枢，可接受来自催吐化学感受区（CTZ）、前庭器官、内脏等传入冲动而引发呕吐。已知CTZ含有丰富的多巴胺、组胺、胆碱受体，前庭器官有胆碱能、组胺能神经纤维与呕吐中枢相联。5-羟色胺的5-HT3亚型受体通过外周、中枢部位如孤束核也与呕吐有关。延脑的呕吐中枢，可接受来自催吐化学感受区（CTZ）、前庭器官、内脏等传入冲动而引发呕吐。已知CTZ含有丰富的多巴胺、组胺、胆碱受体，前庭器官有胆碱能、组胺能神经纤维与呕吐中枢相联。5-羟色胺的5-HT3亚型受体通过外周、中枢部位如孤束核也与呕吐有关。

  43. Modulators of gastrointestinal functions Antiemetic and prokinetic drugs 1. Antiemetic drugs(止吐药) H1 receptor antagonists(H1受体阻断药): Diphenhydramine(苯海拉明); Dimenhydrinate(茶苯海明); Meclozine(美克洛嗪) M receptor antagonists(M受体阻断药): Scopolamine(东莨菪碱) D2 receptor antagonists(D2受体阻断药): Chlorpromazine(氯丙嗪) 5-HT3 receptor antagonists(5-HT3受体阻断药): Ondansetron(昂丹司琼) Grasetron(格拉司琼) Tropisetron(托烷司琼)

  44. Modulators of gastrointestinal functions 2. Prokinetic drugs(胃动力药) Metoclopramide(甲氧氯普胺, 胃复安, 灭吐灵) D2 receptor block: antiemetic effects(CTZ), and promoting GI motility. Adverse effects: CNS reactions, extrapyra-midal effects, etc. Domperidone(多潘立酮, 吗丁啉) D2 receptor block: promoting GI motility. Adverse effects: headache, prolactin（泌乳素）, gastric acid 

  45. Modulators of gastrointestinal functions Prokinetic drugs Metoclopramide 甲氧氯普胺 Mechanism of action 1) Block D2 receptor, to stimulate 5-HT4 receptors and enhance transmission in cholinergic nerve plexues 2) An dopaminergic neuron antagonist in the central nervous system; at higher doses, 5-HT3 antagonist activity may also contribute to the anti-emetic effect. Clinical uses 1) Used for treatment of diabetic gastroparesis 2) Used for the prevention of nausea and vomiting associated with cancer chemotherapy or occurring post-operatively.

  46. Modulators of gastrointestinal functions Domperidone 多潘立酮 Mechanism of action A peripherial dopamine antagonist Clinical uses 1) Used for treatment of diabetic gastroparesis 2) Used for the prevention of nausea and vomiting induced by dyspepsia, chemotherapy, gastroesophageal reflux disease. Adverse effects Has few side effects because it can not cross the BBB 锥体外系不良反应少于甲氧氯普胺

  47. misoprostol Sucralfate Bismuch, etc.

  48. 对非甾体抗炎药引起的消化性溃疡有特效的药物是 ( ) A．Omeprazole B．Magnesium trisilicate（三硅酸镁） C．Misoprostol D．Sucralfate（硫糖铝） E．Domperidone（多潘立酮）

  49. Domperidone（多潘立酮）的止吐作用是通过阻断 ( ) A．5-HT3受体 B．M1受体 C．α1受体 D．多巴胺受体 E．H2受体

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