Drugs for Gastrointestinal Tract Disorders 消化系统药物 Classification(分类) Drugs that inhibit gastric acid secretion ·Antacids Cytoprotective drugs Drugs for H.pylori infection ·Digestants Laxatives,catharitics Antidiarrheal agents ·Antiemetic agents 1
1 Drugs for Gastrointestinal Tract Disorders 消化系统药物 Classification (分类) • Drugs that inhibit gastric acid secretion • Antacids • Cytoprotective drugs • Drugs for H. pylori infection • Digestants • Laxatives, catharitics • Antiemetic agents • Antidiarrheal agents
Drugs that inhibit gastric acid 胃酸分祕抑制药 Blood Gastric lumen Epithelial cell上皮细胞 Sucralfate Cytoprotective effect Mucus- Mucus Bicarbonate一 Bicarbonate Misoprostol Parietal cell壁细胞 PG CAMP④ Protein kinases Histamine- H2 质子泵 H Cimetidine, Lansoprazole and famotidine, omeprazole ATPase Aluminum and and ranitidine K hydroxides and calcium Acetylcholine- -M3 carbonate ⑧ Gastrin G 2
2 Drugs that inhibit gastric acid 胃酸分泌抑制药 质子泵 壁细胞 上皮细胞
奥美拉唑Omeprazole Proton Pump Inhibitor(PPL,质子泵抑制剂 A proton pump inhibitor used in the treatment of peptic ulcer disease(PUD),gastroesophageal reflux disease (GORD/GERD),laryngopharyngeal reflux(LPR)and Zollinger-Ellison syndrome. Weak base that enters parietal cells easily A prodrug that is activated in low pH(applies to all PPIs). CYP2C19 metabolized;T=1 h,effect lasts 24-48 h. Other Proton Pump Inhibitor(其它质子泵抑制剂) 兰索拉唑Lansoprazole 泮托拉唑Pantoprazole 雷贝拉唑Rabeprazole 埃索美拉唑Esomeprazole 3
3 奥美拉唑 Omeprazole A proton pump inhibitor used in the treatment of peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD), laryngopharyngeal reflux (LPR) and Zollinger–Ellison syndrome. Weak base that enters parietal cells easily A prodrug that is activated in low pH (applies to all PPIs). CYP2C19 metabolized; T ½ = 1 h, effect lasts 24-48 h. Proton Pump Inhibitor (PPI, 质子泵抑制剂) 兰索拉唑 Lansoprazole Other Proton Pump Inhibitor (其它质子泵抑制剂) 泮托拉唑 Pantoprazole 雷贝拉唑 Rabeprazole 埃索美拉唑 Esomeprazole
H2 receptor blocker(H2受体阻断剂) CH2-CH2-NH2 HO CH2-CH2-NH2 N N ○ Histamine Serotonin CH2一N CHa CH2SCH2CH2N =CNHCH3 N N HN一C=N CHa Cimetidine Ondansetron Cimetidine(西咪替丁) A histamine H2-receptor antagonist that inhibits the production of acid in the stomach.It is largely used in the treatment of heartburn and peptic ulcers.Approved in 1976,it is marketed under the trade name Tagamet. Cimetidine is a known inhibitor of many isozymes of the cytochrome P450 enzyme system,specifically CYP1A2, CYP2C9,CYP2C19,CYP2D6,CYP2E1,and CYP3A4. This inhibition forms the basis of the numerous drug interactions that occur between cimetidine and other drugs.For example,cimetidine may decrease metabolism of some drugs. 4
4 H2 receptor blocker (H2 受体阻断剂) A histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. Approved in 1976, it is marketed under the trade name Tagamet. Cimetidine is a known inhibitor of many isozymes of the cytochrome P450 enzyme system, specifically CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. This inhibition forms the basis of the numerous drug interactions that occur between cimetidine and other drugs. For example, cimetidine may decrease metabolism of some drugs. Cimetidine (西咪替丁)
哌仑西平Pirenzepine Pirenzepine is used in the treatment of peptic ulcers,as it reduces gastric acid secretion and reduces muscle spasm.It is in a class of drugs known as muscarinic receptor antagonists(M receptor blockers). Acetylcholine is the neurotransmitter of the parasympathetic nervous system which initiates the rest-and-digest state (as opposed to fight-or-flight),the result being an increase in gastric motility and digestion. It has no effects on the brain and spinal cord as it cannot diffuse through the blood-brain barrier. Antacids 抗酸药 5
5 哌仑西平 Pirenzepine Pirenzepine is used in the treatment of peptic ulcers, as it reduces gastric acid secretion and reduces muscle spasm. It is in a class of drugs known as muscarinic receptor antagonists (M receptor blockers). Acetylcholine is the neurotransmitter of the parasympathetic nervous system which initiates the rest-and-digest state (as opposed to fight-or-flight), the result being an increase in gastric motility and digestion. It has no effects on the brain and spinal cord as it cannot diffuse through the blood-brain barrier. Antacids 抗酸药
氢氧化铝Aluminium hydroxide 校游 This compound is used as an antacid.The hydroxide reacts with excess acid in the stomach,reducing its acidity.This decrease of acidity of the contents of the stomach may in turn help to relieve the symptoms of ulcers,heartburn or dyspepsia.It can also cause constipation and is therefore often used with magnesium hydroxide or magnesium carbonate,which have counterbalancing laxative effects.It is also used to control phosphate(phosphorus)levels in the blood of people suffering from kidney failure. Cytoprotective Drugs 粘膜保护药 6
6 氢氧化铝 Aluminium hydroxide This compound is used as an antacid. The hydroxide reacts with excess acid in the stomach, reducing its acidity. This decrease of acidity of the contents of the stomach may in turn help to relieve the symptoms of ulcers, heartburn or dyspepsia. It can also cause constipation and is therefore often used with magnesium hydroxide or magnesium carbonate, which have counterbalancing laxative effects. It is also used to control phosphate (phosphorus) levels in the blood of people suffering from kidney failure. Cytoprotective Drugs 粘膜保护药
Blood Epithelialcell上皮细胞 Gastric lumen Sucralfate Cytoprotective effect Mucus- Mucus 粘膜保护 Bicarbonate- Bicarbonate PG( Misoprostol Parietal cell壁细胞 ⊙ -Protein kinases Histamine ④ H Cimetidine, famotidine. Lansoprazole and omeprazole ATPas Aluminum and and ranitidine magnesium hydroxides and calcium Acetylcholine carbonate Gastrin G 米索前列醇Misoprostol Agonist for the EP3 receptor Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug(NSAID)induced gastric ulcers.It acts upon gastric parietal cells,inhibiting the secretion of gastric acid via G-protein coupled receptor mediated inhibition of adenylate cyclase,which leads to decreased intracellular cAMP levels and decreased proton pump activity at the apical surface of the parietal cell. Misoprostol also promotes mucus and bicarbonate secretion from epithelial cells,which protects gastric lumen surface. 7
7 粘膜保护 壁细胞 上皮细胞 米索前列醇 Misoprostol Misoprostol is a drug that is used for the prevention of non steroidal anti inflammatory drug (NSAID) induced gastric ulcers. It acts upon gastric parietal cells, inhibiting the secretion of gastric acid via G-protein coupled receptor mediated inhibition of adenylate cyclase, which leads to decreased intracellular cAMP levels and decreased proton pump activity at the apical surface of the parietal cell. Misoprostol also promotes mucus and bicarbonate secretion from epithelial cells, which protects gastric lumen surface. Agonist for the EP3 receptor
硫糖铝Sucralfate 401 枸橼酸铋钾Bismuth potassium citrate 胶体果胶铋Colloidal bismuth pectin 替普瑞酮Teprenone 人人人人人人人人 Drugs for Helicobacter pylori infection 抗幽门螺旋杆菌药 8
8 硫糖铝 Sucralfate 枸橼酸铋钾 Bismuth potassium citrate 胶体果胶铋 Colloidal bismuth pectin 替普瑞酮 Teprenone Drugs for Helicobacter pylori infection 抗幽门螺旋杆菌药
The discovery of H.pylori as a major cause for peptic ulcer It was Robin Warren,a pathologist working in Perth,who first noted that spiral bacteria colonized the lower part of the stomach(antrum)in about half of the patients from which he had taken biopsies.Crucially,he noted that inflammation of the mucosal lining of the stomach(gastritis)always appeared close to the location of the spiral bacteria.Intrigued by these findings,Barry Marshall,a young clinical fellow,teamed up with Warren (picture),and together they assayed stomach biopsies from 100 patients. The first time that Marshall and Warren presented their work at a national meeting in Australia,it was rejected outright.Whereas Warren was too shy to push their remarkable findings,Marshall had a missionary's zeal and vigorously defended their research.In order to convince the reluctant medical community of the robustness of their discovery,Marshall did the ultimate experiment.He drank a culture of H.pylori,developed acute gastritis and then successfully treated the illness with antibiotics. 9
9 It was Robin Warren, a pathologist working in Perth, who first noted that spiral bacteria colonized the lower part of the stomach (antrum) in about half of the patients from which he had taken biopsies. Crucially, he noted that inflammation of the mucosal lining of the stomach (gastritis) always appeared close to the location of the spiral bacteria. Intrigued by these findings, Barry Marshall, a young clinical fellow, teamed up with Warren (picture), and together they assayed stomach biopsies from 100 patients. The first time that Marshall and Warren presented their work at a national meeting in Australia, it was rejected outright. Whereas Warren was too shy to push their remarkable findings, Marshall had a missionary's zeal and vigorously defended their research. In order to convince the reluctant medical community of the robustness of their discovery, Marshall did the ultimate experiment. He drank a culture of H. pylori, developed acute gastritis and then successfully treated the illness with antibiotics. The discovery of H. pylori as a major cause for peptic ulcer
No single drug cures Helicobacter pylori infection.Treatment involves taking several medications for 7 to 14 days. Most of the treatment regimens include a proton pump inhibitor. This medication decreases the stomach's production of acid, which allows the tissues damaged by the infection to heal. Examples of proton pump inhibitors include lansoprazole (Prevacid@)omeprazole (Prilosec@)pantoprazole (Protonix@) rabeprazole (AcipHexR)and esomeprazole (NexiumR). Two antibiotics are generally recommended;this reduces the risk of treatment failure and antibiotic resistance.Example: clarithromycin and amoxicillin. Digestants 助消化药 10
10 No single drug cures Helicobacter pylori infection. Treatment involves taking several medications for 7 to 14 days. Most of the treatment regimens include a proton pump inhibitor. This medication decreases the stomach's production of acid, which allows the tissues damaged by the infection to heal. Examples of proton pump inhibitors include lansoprazole (Prevacid®) omeprazole (Prilosec®) pantoprazole (Protonix®) rabeprazole (AcipHex®) and esomeprazole (Nexium®). Two antibiotics are generally recommended; this reduces the risk of treatment failure and antibiotic resistance. Example: clarithromycin and amoxicillin. Digestants 助消化药
