1、Gastrointestinal drugs,基础医学各论II,Hepatic, pacreatic and biliary disorders,Ulcer disorders,Abnormal mobility,Gastrointestinal drugs,Drugs used for peptic ulcersModulators of gastrointestinal functions,Gastrointestinal drugs,Peptic ulcers,Sucralfatecarbonoxolone,misoprostol,Gastric structure related to
2、 peptic ulcer,Gastric acid secretion and regulation,1. Antacids2. Drugs affecting gastric acid secretion Muscarinic receptor antagonists H2 receptor antagonists H+-K+-ATPase inhibitors (proton pump inhibitors) Gastrin receptor antagonists3. Mucosal protective drugs4. Antimicrobial drugs (Helicobacte
3、r pylori),A. Drugs used for peptic ulcers,Features of antacids Basic substances that reduce gastric acidity by neutralizing HClThe 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,Sucralfate
4、carbonoxolone,misoprostol,Drugs affecting gastric acid secretionMuscarinic receptor antagonists,A. Drugs used for peptic ulcers,Pirenzepine 哌仑西平,1. Pharmacological effects and clinical uses high affinity for M1- and low affinity for M2-receptors of the smooth muscle of the ileum and urinary bladder.
5、 blocking of M1-muscarinic receptors in autonomic ganglia, inhibiting HCl secretion2. Adverse effects Atropine-like effects, especially at larger dosesOther drugsTelenzepine（替仑西平）Atropine: atropine-like effectsPropantheline bromide (溴丙胺太林),A. Drugs used for peptic ulcers,Sucralfatecarbonoxolone,miso
6、prostol,H2 receptor antagonists,A. Drugs used for peptic ulcers,Cimetidine 西咪替丁,cimetidine西咪替丁,ranitidine雷尼替丁,1. Pharmacological effects Blocking H2 receptors, decreasing H+ secretion2. Clinical usesDuodenal and gastric ulcer, reflux esophagitis: relieving symptoms, promoting healing of ulcers, and
7、preventing ulcers Zollinger-Ellison syndrome, acute stress ulcers, gastroesophageal reflux disease (heartburn),A. Drugs used for peptic ulcers,Sucralfatecarbonoxolone,misoprostol,3. Adverse effects(1) Side effects: constipation, diarhoea, tiredness, muscular pain, etc.(2) CNS effects: headache, dizz
8、iness, 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 dysfunction4. Drug interactionsInhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam,
9、 propranolol, quinidine and theophylline,A. Drugs used for peptic ulcers,Other agentsRanitidine 雷尼替丁 Longer acting; 410 times more potentMinimal side effects, on antiandrogenic and prolactin-stimulating effects, not inhibiting P450Famotidine 法莫替丁 Similar to ranitidine, but 320 times more potentNizat
10、idine 尼扎替丁 Bioavailability is near 100%, principally eliminated by kidney,A. Drugs used for peptic ulcers,H+-K+-ATPase inhibitors( proton pump inhibitors ),A. Drugs used for peptic ulcers,Omeprazole 奥美拉唑,1. Pharmacological effects(1) Inhibiting gastric acid secretion by various stimuli (histamine, g
11、astrin, aspirin, ethanol, stress)(2) Inhibiting H. pylori2. 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,Sucralfatecarbo
12、noxolone,misoprostol,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) Other effects: gynecomastia (男性乳房发育), hypersensitivity4. Drug inte
13、ractionsInhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam, etc.,A. Drugs used for peptic ulcers,Other agents Lansoprazole 兰索拉唑 Pantoprazole 泮他拉唑 Rebeprazole 雷贝拉唑,A. Drugs used for peptic ulcers,Mucosal protective drugsMisoprostol 米索前列醇Enprostil 恩前列素Sucralfate 硫糖
14、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,SucralfateBismuch, etc.,misoprostol,A. Drugs used for peptic ulcers,Misoprostol 米索前列醇,A. Drugs used for peptic ulcers,1. Pharmacological effectsInhibiting gastric acid secretion
15、Promoting mucus and HCO3- secretion, and mucosal repair2. Clinical usesUlcers, especially for NSAIDs-induced3. Adverse effectsSide effects (13%): nausea, abdominal pain, diarrhea, headache, etc.Contraindicated in pregnancy women,A. Drugs used for peptic ulcers,Antimicrobial drugs (for Helicobacter p
16、ylori)1. Anti-ulcer drugs H+-K+-ATPase inhibitors; bismuch ; sulralfate Weaker, combined with antimicrobial drugs2. 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),Helicobacter pylori in the gastric mucosa,SucralfateBismuch, e
17、tc.,misoprostol,B. Modulators of gastrointestinal functions,B. Modulators of gastrointestinal functions,1. Antiemetic and prokinetic drugs antiemetic drugs prokinetic drugs2. Drugs for treatment of diarrhea antimotility drugs astringents absorbants3. Laxatives contact (stimulant) laxatives osmotic l
18、axatives faecal softners (emollients),B. Modulators of gastrointestinal functions,Antiemetic and prokinetic drugsAntiemetic drugsH1 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D2 receptor antagonists: chlorpromazine
19、氯丙嗪5-HT3 receptor antagonists：ondansetron 昂丹司琼; grasetron 格拉司琼; tropisetron 托烷司琼,孤束核,B. Modulators of gastrointestinal functions,Ondansetron 昂丹司琼,B. Modulators of gastrointestinal functions,1. Pharmacological effects Blocking 5-HT3 receptor (central and peripheral)2. Clinical uses Emesis induced by
20、chemotherapy and radiotherapy in the patients with cancers3. Adverse effects side effects: headache, constipation or diarrhea, etc.,孤束核,Antiemetic and prokinetic drugsProkinetic drugsMetoclopramide 甲氧氯普胺 (胃复安，灭吐灵) D2 receptor block: antiemetic effects (CTZ), promoting GI motility (GI) Adverse effect
21、s: CNS reactions, extrpyramidal effects, etc.,B. Modulators of gastrointestinal functions,Domperidone 多潘立酮 (吗丁啉) D2 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 gas
22、trointestinal functions,Action sites of prokinetic drugs,GI tract smooth muscle cells,B. Modulators of gastrointestinal functions,Drugs for treatment of diarrhea 1.Antimotility drugs: agonists for receptors in GI tract opium preparations diphenoxylate 地芬诺酯（CNS effects at larger doses) loperamine 洛哌丁
23、胺 2. Astringents: tannalbin 鞣酸蛋白 bismuch subsalicylate; bismuch subcarbonate (铋制剂) 3. Absorbants： medical charchol 药用炭（活性炭） agysical 矽炭银,B. Modulators of gastrointestinal functions,Laxatives1.Contact (stimulant) laxatives phenolphthalein 酚酞 bisacodyl 必沙可啶 anthraquinones 蒽醌类（中药成分）2.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3.Faecal softners (emollients) liquid paraffin 液体石蜡,
