Drugs Used in the Treatment of Gastrointestinal DiseasesYun-Bi Lu, PhD卢韵碧Dept. of Pharmacology,School of Medicine, Zhejiang Universityyunbi@1. Hepatic, pancreaticand biliary disorders2. Acid-peptic disorders3.Gastrointesinal motility Disorders4. Inflammatorybowel diseasesGastrointestinal drugs A. Drugs used for acid-peptic A. Drugs used fordisorders(抗消化性溃疡药) B. Modulators of gastrointestinal functions (消化功能调节药)Symptoms:Upper abdominal burning or hunger painEmesia(呕吐), belching (嗳气)The feature of peptic ulcer disease:High incidence, frequent Recurrence, Drugtherapeutics is the main way for treatment. Ulcer complicationUlcer bleeding (出血)Ulcer perforation (穿孔)Pyloristenosis(幽门狭窄)Canceration(癌变)Acid-peptic disorders1)Peptic ulcer disease (PUD)chronic inflammation due to Helicobacter pylori2) Drug-induced mucosal injury, especially bynon-steroidal anti-inflammatory drugs (NSAIDs)3) Acute stress ulcers （应激）4) Gastroesophageal reflux disease (GERD)5) Pathologic acid-hyper-secretory conditions (e.g.Zollinger-Ellison syndrome)Helicobacter pylori infectionGastroesophageal reflux disease (GERD)Abnormal reflux in the esophagusPeptic ulcerA.Drugs used for peptic ulcers ▪Antacids 抗酸药▪Drugs affecting gastric acid secretion抑制胃酸分泌药Muscarinic receptor antagonistsH2receptor antagonistsH+-K+ ·ATPase inhibitors (proton pump inhibitors) Gastrin receptor antagonists▪Antimicrobial drugs (Helicobacter pylori)抗菌药▪Mucosal protective drugs 黏膜保护药(Proton pump)Pharmacological effect×AntacidsNaHCO 3Mg(OH)2Mg 2S 3O 8Al(OH)3CaCO 3Sodium (bicarbonate )Salts of magnesium (carbonate, hydroxide,trisilicate )Salts of aluminum (aluminum hydroxide)Calcium (carbonate )2. Clinical usesnonprescription remedies for the treatment of dyspepsia(消化不良) symptom and minor episodes of heartburn.AntacidsAntacids3. Adverse effects•Constipation (salt of aluminum) 便秘•Diarrhea(salt of magnesium ) 腹泻Combination products such as maalox（氢氧化铝）•Hypercalcium which can cause renal failure(Calcium)•Hypernatremia(sodium-containing antacids)All antacids are generally regarded as safe in pregnancy.4.Drug interactions, Administration and dosage •To avoid or reduce drug interaction, other medication should NOT be taken within 1-2 hours of taking anantacids; (for example, tetracycline四环素),•Should not be taken continuously for more than 2weeks.铝碳酸镁片（达喜）[药品名称]通用名称：铝碳酸镁片[成份]本品每片含0.5克铝碳酸镁。
辅料为：玉米淀粉、甘草醇、糖精钠、硬脂酸镁、薄荷香精、香蕉香精。
[性状]本品为白色片。
[作用类别] 本品为抗酸与胃黏膜保护类非处方药药品。
[适应症]1．慢性胃炎。
2．与胃酸有关的胃部不适症状，如胃痛、胃灼热感（烧心）、酸性嗳气、饱胀等。
[规格] 0.5克[用法用量] 口服。
一次1-2片，一日3次。
餐后1－2小时、睡前或胃部不适时服用。
[不良反应] 偶见便秘、稀便、口干和食欲缺乏。
[禁忌]详情见说明书[注意事项]………..A.Drugs used for peptic ulcers ▪Antacids抗酸药▪Drugs affecting gastric acid secretion抑制胃酸分泌药Muscarinic receptor antagonistsH2receptor antagonistsH+-K+ ·ATPase inhibitors (proton pump inhibitors) Gastrin receptor antagonists▪Antimicrobial drugs (Helicobacter pylori)抗菌药▪Mucosal protective drugs 黏膜保护药cimetidine×(Proton pump)Cimetidine（西咪替丁）1. Pharmacological effects•Blocking H2 receptors, decreasing H+secretion; decreaseprotease secretion.•immunology modification(activate)Histamine →T cell H2receptor →histamine induced suppresser factor (HSF) →inhibit immuno logical function •Cardiac vascular function, depress HR and cardiac contractility in vitro (need relative high dose)A.Drugs used for peptic ulcersCimetidine（西咪替丁）2. Clinical uses▪Duodenal and gastric ulcer: relieving symptoms,promoting healing of ulcers, and preventing ulcers▪Acute stress ulcers (bleeding)▪Zollinger-Ellison syndrome, gastroesophageal reflux disease (heartburn)▪Immunology depression and tumor (assistant)Cimetidine（西咪替丁）3. Adverse effects▪Side effects: constipation, diarrhea, tiredness, muscular pain, etc.▪CNS effects: headache, dizziness, confusion,hallucination, etc.(elderly, long-term uses)▪Endocretion effects: antiandrogen, gynecomastia(男性乳房发育), galactorrhea(溢乳),reduced sperm count, and male sexual dysfunction▪Blood dyscrasias: rarely4.EliminationUrinary excretion, the dose should be modified in patients with renal impairment5. Drug interactionsOther H2receptor antagonists Ranitidine 雷尼替丁4～10 times more potent; Duration of action is comparable.Minimal side effects, weakly inhibiting CYP Famotidine法莫替丁Similar to ranitidine, but no inhibiting CYP Nizatidine尼扎替丁Bioavailability is near 100%, principally eliminated by kidneyOmepranzole×(the proton pump)Omeprazole(奥美拉唑)1. Pharmacological effects▪Inhibiting gastric acid secretion by various stimuli (histamine, gastrin, aspirin, ethanol, stress)▪Inhibiting H. pylori2. Clinical uses▪Duodenal and gastric ulcer:relieving symptoms, promoting healing of ulcers, used with antimicrobial regimens to eradicate H. pylori▪Reflux esophagitis▪Zollinger-ellison syndromeOmeprazole(奥美拉唑)3. Adverse effects▪Side effects: nausea, headache, diarrhea, constipation and rash occur but are uncommon▪Increase of gastric carcinoid tumor（肿瘤样增生）: prolongated hypochlorhydria and secondaryhypergastrinemia(only found by animal experiments)▪Others: gynecomastia(男性乳房发育),hypersensitivity 4.Drug interactions▪It is metabolized by hepatic P450 (CYP2C19);▪Inhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam, etc.M receptorantagonists×(the proton pump)×Proglumide丙谷胺▪Drugs affecting gastric acid secretion ▪Muscarinic receptor antagonistsAtropine 阿托品•Decrease gastric acid secretion by blockingM3receptor on parietal cell;•Decrease histamine release by blockingM1receptor on parasympathetic neuronal ganglion;M receptor on enterochromaffin-like cell (ECL cell);•Decrease gastrin release by blockingM receptor on G cell▪Pirenzepine（哌仑西平）1. Pharmacological effects and clinical uses▪High affinity for M1-and low affinity for M2-receptors of thesmooth muscle of the ileum and urinary bladder.▪Blocking of M1-muscarinic receptors in autonomic ganglia, inhibiting HCl secretion2. Adverse effects▪Atropine-like effects, especially at larger dosesOther drugs▪Telenzepine（替仑西平）▪Propantheline bromide (溴丙胺太林)A.Drugs used for peptic ulcers Mucosal protective drugsEffects:Protecting the gastric and duodenal mucosa from damage induced by acid and pepsin Misoprostol米索前列醇Sucralfate硫糖铝Colloidal bismuth subcitrate胶体次枸橼酸铋Misoprostol米索前列醇1. Pharmacological effects▪Inhibiting gastric acid secretion▪Promoting mucus and HCO-secretion, and mucosal repair32. Clinical usesOnly approved for the prevention of NSAIDs-induced gastric Ulcer.3. Adverse effectsSide effects (13%):, abdominal pain, diarrhea, headache, nausea etc.Contraindicated in pregnancy women(Abortifacient property)Sucralfate硫糖铝A sulfated disaccharide（二糖）complex of aluminum hydroxideSucralfate硫糖铝1. Pharmacological effects▪Binding to tissue proteins and forms a protective barrier ▪Enhancing cell restitution and re-epithelization.▪Weakly inhibiting H.Pylori growth.2. Clinical uses and Administration▪Duodenal ulcers (with proton pump inhibitors), seldom used.▪Take sucralfate1 hour before meals▪Four times a day before meals and at bedtime3. Adverse effects▪Constipation occurs in 2% due to the aluminum saltBismuth Compounds(铋剂) Colloidal bismuth subcitrate(CBS) 胶体次枸橼酸铋1. Pharmacological effects▪Probably coats ulcers and erosions, creating a protective layer against acid and pepsin▪Stimulate prostaglandin, mucus, and bicarbonate secretion▪Antimicrobial activity against H pylori2. Clinical uses▪Dyspepsia and acute diarrhea, ulcer.3.Adverse effects▪Blackening of the stool▪Bismuth toxicity: encephalopathy(铋剂神经毒性-急性可逆性脑病)A.Drugs used for peptic ulcers▪Mucosal protective drugs▪Misoprostol米索前列醇▪Enprostil恩前列素▪Sucralfate硫糖铝▪Colloidal bismuth subcitrate胶体次枸橼酸铋▪Teprenone替普瑞酮▪Marzulene麦滋林▪Smectite思密达A.Drugs used for peptic ulcers▪Antimicrobial drugs(for Helicobacter pylori)1. Anti-ulcer drug regimen▪H+-K+·ATPase inhibitors; bismuch; sulralfate（硫糖铝）▪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)Gastrointestinal drugs A. Drugs used for acid-peptic A. Drugs used fordisordersB. Modulators of gastrointestinalfunctions。