Gastrointestinal drugs

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

Part 1. Drugs used for peptic ulcers

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

Infection ▲ Infection with Hp and peptic ulcers: Drugs used for peptic ulcers

Inflammation

Ulcers

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. 罗宾 · 沃伦 巴里 · 马歇尔

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

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

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

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

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 ), 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: 复方氢氧化铝片（ 胃舒平 ), 铝碳酸镁咀嚼片（达喜） 复方氢氧化铝片（ 胃舒平 ), 铝碳酸镁咀嚼片（达喜） Drugs used for peptic ulcers

Sucralfate carbonoxolone misoprostol Drugs used for peptic ulcers

(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 U sed for peptic ulcer and acid-hypersecretory conditions. U sed for peptic ulcer and acid-hypersecretory conditions. 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) 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 Drugs used for peptic ulcers

Ⅱ. Drugs inhibiting gastric acid secretion Drugs used for peptic ulcers 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 )

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

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

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

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 Drugs used for peptic ulcers

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

3. Adverse effects (1)Side effects: (1)Side effects: nausea, headache, diarrhoea, constipation and rash occur. (2)Others: (2)Others: gynecomastia( 男性乳房发育 ) 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

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

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 ～ ～ 40 + 兰索拉唑  潘托拉唑 ～ 40  雷贝拉唑  几种质子泵抑制剂的比较 药 名 Drugs used for peptic ulcers

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 ) Proglumide( 丙谷胺 ) Proglumide( 丙谷胺 ) Drugs used for peptic ulcers

Sucralfate Bismuch, etc. misoprostol

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

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. (3) Mucosal protective drugs 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 Drugs used for peptic ulcers

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). Bismuth Compounds 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. 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

Sucralfate Bismuch, etc. misoprostol

The best treatment regimen consists of a 7–14 day regimen of "triple therapy": 1) Bismuth subsalicylate (2 tablets; 262 mg each), 2) Tetracycline (500 mg), 3) Metronidazole (250 mg), each taken four times daily for 14 days. Program 2 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. Drugs used for peptic ulcers

1)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. For patients with resistant infections, "quadruple therapy” Drugs used for peptic ulcers

Gastrointestinal drugs Part2 Modulators of gastrointestinal functions

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

Contents Antiemetic and prokinetic drugs 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 ) 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 ) Laxatives Laxatives 1. contact(stimulant) laxatives 1. contact(stimulant) laxatives 2. osmotic laxatives 2. osmotic laxatives 3. faecal softners(emollients) 3. faecal softners(emollients)

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-HT 3 亚型受体通 过外周、中枢部位如孤束核也与呕吐有关。

Antiemetic and prokinetic drugs 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

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 （泌乳素） , gastric acid  Adverse effects: headache, prolactin （泌乳素） , gastric acid  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. 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 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 锥体外系不良反应少于甲氧氯普胺 Modulators of gastrointestinal functions

Sucralfate Bismuch, etc. misoprostol

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）

Domperidone （多潘立酮）的止吐作用是通过阻断 ( ) A ． 5-HT 3 受体 B ． M 1 受体 C ． α 1 受体 D ．多巴胺受体 E ． H 2 受体

抑酸作用最强的药物是 ( ) A ． Cimetidine （西米替丁） B ． Pirenzepine （哌仑西平） C. Omeprazole D. Sodium bicarbonate （碳酸氢钠）