1. Gastrointestinal drugs Department of Pharmacology Tang Huifang ( 汤慧芳 ) Email: tanghuifang@zju.edu.cn

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

3. Pathogenesis of peptic ulcers Infection with Hp ; Infection with Hp ; Increased gastric acid secretion; Increased gastric acid secretion; Inadequate mucosal defense to gastric acid. Inadequate mucosal defense to gastric acid. Treatment approaches approaches Eradicating Hp ; Eradicating Hp ; Neutralizing gastric acid, or reducing secretion of the acid; Neutralizing gastric acid, or reducing secretion of the acid; Protecting the gastric mucosa from damage. Protecting the gastric mucosa from damage. Peptic ulcers and treatment Part 1. Drugs used for peptic ulcers

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

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

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

7. 3. Adverse effects (1) Constipation and stomach cramp (salt of aluminum) (2) Diarrhea (salt of magnesium) (3) Hypercalcium which can cause renal failure (Calcium) (4) Hypernatremia (sodium-containing antacids) 4. Drug interactions Avoid concurrent administration of antacids and a variety of drugs. Avoid concurrent administration of antacids and a variety of drugs. (1) Affect rates of dissolution and absorption, bioavailbility, and renal elimination of many drugs (2) By binding to drugs (for example, tetracycline 四环 素 ), form insoluble complexes that are not absorbed Drugs used for peptic ulcers

8. Adminstration and dosage (1) Take antacids 1 h and 3 h after meals Seven times a day after meals and at bedtime. (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 Drugs used for peptic ulcers

9. Ⅱ. Drugs inhibiting gastric acid secretion Drugs used for peptic ulcers ① Muscarinic receptor antagonists ② H 2 receptor antagonists ③ Gastrin receptor antagonists ④ H + -K + -ATPase inhibitors (proton pump inhibitors)

10. Sucralfate carbonoxolone misoprostol atropine

11. A. Muscarinic receptor antagonists (M receptor blocker): Drugs most in use: Atropine( 阿托品 ) Atropine( 阿托品 ) Propantheline bromide( 溴丙胺太林 ) Propantheline bromide( 溴丙胺太林 ) Pirenzepine( 哌仑西平 ) Pirenzepine( 哌仑西平 ) Telenzepine( 替仑西平 ) Telenzepine( 替仑西平 )

12. Drugs used for peptic ulcers Atropine( 阿托品 ) Non-selective M receptor blocker: Block M 1, M 2, M 3, M 4, and M 5 receptors. Block M 1, M 2, M 3, M 4, and M 5 receptors. Block M3 receptor in Parietal cells( 壁细胞 ) Block M1 receptor in ganglion Block M receptors in ECL and G cells.

13. Pirenzepine( 哌仑西平 ) Drugs used for peptic ulcers Selective M receptor blocker: Selective M receptor blocker: Only block M 1 and M 2 - receptors. Only block M 1 and M 2 - receptors.

14. Sucralfate carbonoxolone misoprostol

15. 1. Pharmacological effects high affinity for M 1 - and low affinity for M 2 -receptors of the smooth muscle of the ileum and urinary bladder. 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 the secretion of HCl. blocking of M 1 -muscarinic receptors in autonomic ganglia, inhibiting the secretion of HCl. 2. Clinical uses: peptic ulcers 3. Adverse effects Atropine-like effects, at larger doses. Atropine-like effects, at larger doses. Drugs used for peptic ulcers Telenzepine( 替仑西平 )

16. B. H 2 receptor antagonists: Cimetidine ( 西咪替丁 ) Ranitidine ( 雷尼替丁 ) Drugs used for peptic ulcers

17. Sucralfate carbonoxolone misoprostol

18. Cimetidine( 西咪替丁 ) 1. Pharmacological effects Blocking H 2 receptors, decreasing H + secretion Blocking H 2 receptors, decreasing H + secretion 2. Clinical uses (1) Duodenal and gastric ulcer: (1) Duodenal and gastric ulcer: —— relieving symptoms, promoting healing of ulcers, and preventing ulcers. —— relieving symptoms, promoting healing of ulcers, and preventing ulcers. (2) Zollinger-Ellison syndrome (2) Zollinger-Ellison syndrome (3) Reflux esophagitis; (3) Reflux esophagitis; (4) Acute stress ulcers, etc. (4) Acute stress ulcers, etc. Drugs used for peptic ulcers

19. 3. Adverse effects (1)Side effects: constipation, diarhoea, tiredness, muscular pain, etc. (1)Side effects: constipation, diarhoea, tiredness, muscular pain, etc. (2)CNS effects: headache, dizziness, hal-lucination, etc. (elderly, long-term uses) (2)CNS effects: headache, dizziness, hal-lucination, etc. (elderly, long-term uses) (3)Endocretion effects: antiandrogen, (3)Endocretion effects: antiandrogen, gynecomastia( 男性乳房发育 ), galactorrh- ea( 溢乳 ), reduced sperm count, and male sexual dysfunction gynecomastia( 男性乳房发育 ), galactorrh- ea( 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, etc. Inhibiting hepatic P 450 : raising plasma concentrations of warfarin, phenytoin, diazepam, propranolol, quinidine and theophylline, etc. Drugs used for peptic ulcers

21. 5. Elimination Urinary excretion is the principal route of elimination of cimetidine, the dose should be modified in patients with renal impairment. Drugs used for peptic ulcers

22. Other H 2 receptor antagonists: Ranitidine( 雷尼替丁 ) Similar to cimetidine, but 5 ～ 10 times more potent, longer acting; Similar to cimetidine, but 5 ～ 10 times more potent, longer acting; Minimal side effects, no antiandrogenic and prolactin-stimulating effects, less inhibiting P 450. Minimal side effects, no antiandrogenic and prolactin-stimulating effects, less inhibiting P 450. Famotidine( 法莫替丁 ) Similar to ranitidine, but 4 ～ 8 times more potent. Similar to ranitidine, but 4 ～ 8 times more potent. Nizatidine( 尼扎替丁 ) The potent is similar to ranitidine. The potent is similar to ranitidine. Bioavailability is near 100%, principally eliminated by kidney Bioavailability is near 100%, principally eliminated by kidney Drugs used for peptic ulcers

23. 4 种 H 2 - 受体阻断药的比较 西咪替丁 2 1 400mg, bid 1 雷尼替丁 2-3 5-10 150mg, bid 0.1 法莫替丁 2.5-4 40 20mg, bid 0 尼扎替丁 2 5-10 150mg, bid 0 药 名 t 1/2 (h) 相对抑酸活力 剂 量 对肝药酶抑制

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

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

26. 质子泵的分子构型

27. 1. Pharmacological effects (1)Inhibiting gastric acid secretion by various stimuli(such as: histamine, gastrin, aspirin, ethanol, stress, etc.) (1)Inhibiting gastric acid secretion by various stimuli(such as: histamine, gastrin, aspirin, ethanol, stress, etc.) (2)Inhibiting Hp. (2)Inhibiting Hp. (3) protection for gastric mucosa 2. Clinical uses (1)Highly effective for duodenal and gas-tric ulcer: relieving symptoms, and (1)Highly effective for duodenal and gas-tric ulcer: relieving symptoms, and promoting healing of ulcers promoting healing of ulcers Used with antimicrobial agents to eradicate Hp. Used with antimicrobial agents to eradicate Hp. (2)Reflux esophagitis; (2)Reflux esophagitis; (3)Zollinger-Ellison syndrome (3)Zollinger-Ellison syndrome Drugs used for peptic ulcers

28. 3. Adverse effects (1)Side effects: (1)Side effects: Less, such as: nausea, headache, diarrhoea, constipation and rash occur. Less, such as: nausea, headache, diarrhoea, constipation and rash occur. (2)Increase of gastric carcinoid tumor (2)Increase of gastric carcinoid tumor (3)Others: (3)Others: hypersensitivity, gynecomastia( 男性乳房发 育 ) hypersensitivity, gynecomastia( 男性乳房发 育 ) 4. Drug interactions Inhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam, etc. Inhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam, etc. Drugs used for peptic ulcers

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

30. t 1/2 有效抑酸 剂量 对肝药 t 1/2 有效抑酸 剂量 对肝药 (h) 时间 (h) (mg/d) 酶影响 (h) 时间 (h) (mg/d) 酶影响 奥美拉唑 1.0 12 ～ 24 20 ～ 40 + 兰索拉唑 1.5 24 30  潘托拉唑 1.3 24 20 ～ 40  雷贝拉唑 1.0 24 20  几种质子泵抑制剂的比较 药 名 Drugs used for peptic ulcers

31. 丙谷胺 (Proglumide) 本品可与胃泌素竞争受体而抑制胃酸分泌 ; 也能促进黏液合成, 增强胃黏膜的黏液 - HCO 3 - 盐屏障, 从而发挥抗溃疡病的作用. 本品可与胃泌素竞争受体而抑制胃酸分泌 ; 也能促进黏液合成, 增强胃黏膜的黏液 - HCO 3 - 盐屏障, 从而发挥抗溃疡病的作用. 本品口服吸收迅速, 生物利用度为 60% ～ 74%, 达峰时间为 2h. 本品口服吸收迅速, 生物利用度为 60% ～ 74%, 达峰时间为 2h. 胃泌素受体阻断药 :

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

33. Sucralfate Bismuch, etc. misoprostol

34. Misoprostol 米索前列醇 A prostaglandin E analogues Drugs used for peptic ulcers

35. 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 Only approved for the prevention of NSAIDs-induced gastric Ulcer. 3. Adverse effects Side effects (13%):abdominal pain, diarrhea, nausea, headache, etc. Contraindicated in pregnancy women (Abortifacient 堕胎 property) (Abortifacient 堕胎 property) Drugs used for peptic ulcers

36. Sucralfate A sulfated disaccharide （二糖） complex of aluminum hydroxide Drugs used for peptic ulcers

37. 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. Take sucralfate 1 hour before meals Four times a day before meals and at bedtime 3. Adverse effects Constipation occurs in 2% due to the aluminum salt, not together with alkaline agents Drugs used for peptic ulcers

38. 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 Drugs used for peptic ulcers

39. 2. Clinical uses 1) Treatment of dyspepsia, 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, confusion, seizures). Bismuth Compounds Drugs used for peptic ulcers

40. Smectite( 蒙脱石 ) 1)Bind to the glycoprotein in the mucus to increase its coverage ability, enhancing cell restitution, antimicrobial activity against H pylori. 2) Use for acute or chronic diarrhea and ulcer. Drugs used for peptic ulcers

41. Ⅳ. Antimicrobial(anti-Hp) drugs 1. Anti-ulcer drugs: H + -K + -ATPase inhibitors; bismuch( 铋 剂 ); sulralfate( 硫糖铝 ), etc. H + -K + -ATPase inhibitors; bismuch( 铋 剂 ); sulralfate( 硫糖铝 ), etc. Weaker, combined with antimicrobial drugs. 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. Metronidazole( 甲硝唑 ); Amoxicillin( 阿 莫西林 ); Tetracycline( 四环素 ); Gentamicin ( 庆大霉素 ); Clarithromycin( 克拉霉素 ), etc. Drugs used for peptic ulcers

42. Sucralfate Bismuch, etc. misoprostol

43. HP 根除治疗方案的变化 -- 第四次全国幽门螺杆菌感染处理共识报告（ 2012 年） 我国 HP 感染率总体上仍然很高，成人感染率在 40- 60% 。 推荐用于根除治疗的 6 种抗菌药物中，甲硝唑耐药率 已达到 60%-70% ，克拉霉素达 20%--38% ，左氧氟沙 星达到 30%--38% ，耐药显著影响根除率。 羟氨苄青霉素、呋喃唑酮和四环素的耐药率仍很低 （ 1%-5% ） 。 因此标准三联疗法（ PPI+ 克拉霉素 + 羟氨苄 ) 或 （ PPI+ 克拉霉素 + 甲硝唑）根除率已低于或远低于 80% 。 共识： 推荐四联： PPI+ 铋剂 +2 种抗菌药物 抗菌药物组成： – 羟氨苄青霉素 + 克拉霉素 – 羟氨苄青霉素 + 左氧氟沙星 – 羟氨苄青霉素 + 呋喃唑酮 – 四环素 + 甲哨唑或呋喃唑酮新进展

44. 青霉素过敏者推荐的抗菌药物组成方案： – 克拉霉素 + 左氧氟沙星 – 克拉霉素 + 呋喃唑酮 – 四环素 + 甲硝唑或呋喃唑酮 – 克拉霉素 + 甲硝唑 疗程： 10d--14d ，放弃 7d 方案。 新进展

45. Gastrointestinal drugs Part2 Modulators of gastrointestinal functions

46. Abnormalities of gastrointestinal functions Nausea and vomitingConstipation Diarrhea Modulators of gastrointestinal functions

47. Contents Ⅰ. Promoting digestive drug( 助消化药 ) Ⅱ. Antiemetic and prokinetic drugs 1.antiemetic drugs( 止吐药 ) 1. antiemetic drugs( 止吐药 ) 2. prokinetic drugs( 胃动力药 ) 2. prokinetic drugs( 胃动力药 ) Ⅲ. Drugs for treatment of diarrhea 1. antimotility drugs( 抗蠕动药 ) 1. antimotility drugs( 抗蠕动药 ) 2. astringents( 收敛药 ) 2. astringents( 收敛药 ) 3. absorbants( 吸附药 ) 3. absorbants( 吸附药 ) Ⅳ. Laxatives 1. contact(stimulant) laxatives 1. contact(stimulant) laxatives 2. osmotic laxatives 2. osmotic laxatives 3. faecal softners(emollients) 3. faecal softners(emollients)

48. Ⅰ. Promoting digestive drug Pepsin( 胃蛋白酶 ) Pepsin( 胃蛋白酶 ) Pancreatin( 胰酶 ) Pancreatin( 胰酶 ) Lactasin( 乳酶生, Biofermin, 表飞 鸣 ) etc. Lactasin( 乳酶生, Biofermin, 表飞 鸣 ) etc. Modulators of gastrointestinal functions

49. Ⅱ. Antiemetic and prokinetic drugs 1. Antiemetic drugs( 止吐药 ) 1. Antiemetic drugs( 止吐药 ) H 1 receptor antagonists(H 1 受体阻断药 ): H 1 receptor antagonists(H 1 受体阻断药 ): Diphenhydramine( 苯海拉明 ); Diphenhydramine( 苯海拉明 ); Dimenhydrinate( 茶苯海明 ); Dimenhydrinate( 茶苯海明 ); Meclozine( 美克洛嗪 ) Meclozine( 美克洛嗪 ) M receptor antagonists(M 受体阻断药 ): M receptor antagonists(M 受体阻断药 ): Scopolamine ( 东莨菪碱 ) Scopolamine ( 东莨菪碱 ) D 2 receptor antagonists(D 2 受体阻断药 ): D 2 receptor antagonists(D 2 受体阻断药 ): Chlorpromazine ( 氯丙嗪 ) Chlorpromazine ( 氯丙嗪 ) 5-HT 3 receptor antagonists(5-HT 3 受体阻断药 ): 5-HT 3 receptor antagonists(5-HT 3 受体阻断药 ): Ondansetron( 昂丹司琼 ) Ondansetron( 昂丹司琼 ) Grasetron( 格拉司琼 ) Grasetron( 格拉司琼 ) Tropisetron( 托烷司琼 ) Tropisetron( 托烷司琼 ) Modulators of gastrointestinal functions

50. 2. Prokinetic drugs( 胃动力药 ) 2. Prokinetic drugs( 胃动力药 ) Metoclopramide( 甲氧氯普胺, 胃复安, 灭吐灵 ) Metoclopramide( 甲氧氯普胺, 胃复安, 灭吐灵 ) D 2 receptor block: antiemetic effects(CTZ), and promoting GI motility. D 2 receptor block: antiemetic effects(CTZ), and promoting GI motility. Adverse effects: CNS reactions, extrapyra-midal effects, etc. Adverse effects: CNS reactions, extrapyra-midal effects, etc. Domperidone( 多潘立酮, 吗丁啉 ) Domperidone( 多潘立酮, 吗丁啉 ) D 2 receptor block: promoting GI motility. D 2 receptor block: promoting GI motility. Adverse effects: headache, prolactin , gastric acid  Adverse effects: headache, prolactin , gastric acid  Cisapride( 西沙比利 ) Cisapride( 西沙比利 ) 5-HT4 receptor activitor, ACh release  : promoting intestinal & colon motility. 5-HT4 receptor activitor, ACh release  : promoting intestinal & colon motility. Modulators of gastrointestinal functions

51. GI tract smooth muscle cells NANC neuron Cholinergic neuron Post-ganglionic primary motor neuron Prokinetic drugs

52. Metoclopramide 甲氧氯普胺 Mechanism of action 1) Block D2 receptor, to stimulate 5-HT4 receptors and enhance coordinated 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. Modulators of gastrointestinal functions

53. Adverse effects 1) Fatigue, dizziness, faintness 2) Various extrapyramidal syndromes caused by its central anti-dopaminergic activity. Parkinsonism (reversible) tardive dyskinesia (irreversible) 3) Increased serum prolactin levels (chronic uses) Metoclopramide Modulators of gastrointestinal functions

54. Domperidone 多潘立酮 Mechanism of action A peripherial dopamine antagonist, has no procholinergic Effects Clinical uses 1) Used for treatment of diabetic gastroparesis gastroesophageal reflux disease 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 Increased serum prolactin levels (6% of patients) Rare cases of prolongation of QT interval. Modulators of gastrointestinal functions

55. Ⅲ. Drugs for treatment of diarrhea ( 止泻药 ) 1. Antimotility drugs( 抗蠕动药 ) : 1. Antimotility drugs( 抗蠕动药 ) : agonists for  receptors in GI tract agonists for  receptors in GI tract Opium preparations( 阿片制剂 ) Opium preparations( 阿片制剂 ) Diphenoxylate( 地芬诺酯 ): Diphenoxylate( 地芬诺酯 ): CNS effects at larger doses. CNS effects at larger doses. 2. Astringents( 收敛药 ) : Tannalbin( 鞣酸蛋白 ) Tannalbin( 鞣酸蛋白 ) Bismuch subsalicylate( 次硅酸铋 ) Bismuch subsalicylate( 次硅酸铋 ) Bismuch subcarbonate( 次碳酸铋 ) Bismuch subcarbonate( 次碳酸铋 ) 3. Absorbants( 吸附药 ) : 3. Absorbants( 吸附药 ) : Medical charchol( 药用炭, 活性炭 ) Medical charchol( 药用炭, 活性炭 ) Agysical( 矽炭银 ) Agysical( 矽炭银 ) Modulators of gastrointestinal functions

56. 1. Antimotility drugs: Mechanisms: Agonists for  receptors in GI tract (1) Opium preparation 阿片制剂 (1) Opium preparation 阿片制剂 (2) Diphenoxylate 地芬诺酯 (2) Diphenoxylate 地芬诺酯 Diphenoxylate dose not cross the blood-brain-barrier as easly as most opioids do and is relatively selective for peripheral opioid receptors. Has CNS effects at larger doses) Anti-diarrheals Modulators of gastrointestinal functions

57. Anti-diarrheals 1. Antimotility drugs: Loperamide 洛哌丁胺 It is two to three times potent than diphenoxylate, and its action is more rapid in onset and more prolonged. Use for acute or chronic diarrhea but not induced by infection. It has less CNS or cardiovascular effects It has less CNS or cardiovascular effects. Modulators of gastrointestinal functions

58. Ⅳ. Laxatives( 泻药 ) 1. Stimulant laxatives( 刺激性泻药 ) Phenolphthalein( 酚酞 ) Phenolphthalein( 酚酞 ) Bisacodyl( 必沙可啶 ) Bisacodyl( 必沙可啶 ) Rhubarb( 大黄 ) 、 Senna( 番泻叶 ), etc. Rhubarb( 大黄 ) 、 Senna( 番泻叶 ), etc. 2. Osmotic laxatives( 渗透性泻药 ) Magnesium sulfate( 硫酸镁 ); Magnesium sulfate( 硫酸镁 ); Sodium sulfate( 硫酸钠 ); Sodium sulfate( 硫酸钠 ); Lactulose( 乳果糖 ); Lactulose( 乳果糖 ); Sorbitol( 山梨醇 ); Sorbitol( 山梨醇 ); Glycerol( 甘油 ); Glycerol( 甘油 ); Celluloses( 纤维素类 ) Celluloses( 纤维素类 ) 3. Faecal softners( 粪便软化药, emollients) Liquid paraffin( 液体石蜡 ) Liquid paraffin( 液体石蜡 ) Modulators of gastrointestinal functions

59. Laxatives 1. Stimulant laxatives( 刺激性泻药 )1. Stimulant laxatives( 刺激性泻药 ) Phenolphthalein 酚酞 Phenolphthalein 酚酞 ( No longer used because of concerns about carcigenicity) ( No longer used because of concerns about carcigenicity) Bisacodyl 必沙可啶 Bisacodyl 必沙可啶 (It is active after deacetylation, stimulating enteric nerves to cause colonic mass movements; increases fluid and NaCl secretion. ) (It is active after deacetylation, stimulating enteric nerves to cause colonic mass movements; increases fluid and NaCl secretion. ) Modulators of gastrointestinal functions

60. Laxatives Anthraquinones 蒽醌类（中药成分） promote colon movements promote colon movements Cascara （鼠李皮） Rhubarb （大黄） Senna （番泻叶） Modulators of gastrointestinal functions

61. 2. Osmotic laxatives( 渗透性泻药 ) 1) Salt laxatives: magnesium sulfate 硫酸镁 ; sodium sulfate 硫酸钠； 1) Salt laxatives: magnesium sulfate 硫酸镁 ; sodium sulfate 硫酸钠； Laxatives These agents contain ions that are only slowly absorbed from the intestine. These ions retain fluid in the bowel lumen and cause a large volume of fluid to enter the colon. magnesium sulfate Modulators of gastrointestinal functions

62. 2. 2. Osmotic laxatives( 渗透性泻药 ) 2) Lactulose 乳果糖 ; 2) Lactulose 乳果糖 ; Laxatives In the small bowel, it is resistant to hydrolysis and has an osmotic effect. In the large intestine, lactulose is acted upon by the endogenous flora with the production of lactic acid, Lactic acid also has an osmotic effect. It is used to reduce ammonia blood levels in the prevention and treatment of hepatic encephalopathy Modulators of gastrointestinal functions

63. 3. Laxatives that decrease absorption Liquid petrolatum ( Lubricate the fecal mass, prevent excessive dehydration of the material, and may inhibit water reabsorption by coating the gut wall) Modulators of gastrointestinal functions