作用于消化系统的药物——山东大学药理学英文课件.ppt

1、Chapter 32drug used in digestive system,This chapter describes drugs used to treat these common medical conditions involving the gastrointestinal tract: peptic ulcers, dyspepsia, vomitting, diarrhea and constipation, etc.,Part Drugs Used in Peptic Ulcer,peptic ulcer,A benign, localized defect in the

2、 mucosa of any part of the gastrointestinal tract. duodenal ulcer gastric ulcer,Symptoms and complications,The most important symptom is abdominal pain and discomfort. The atypical symptoms are abdomen distention, inappetence, belching, reflux of gastric acid. The severe complications are hemorrhage

3、, perforation, obstruction and canceration.,Pathogenesis of peptic ulcer,although the pathogenesis of peptic ulcer disease is not fully understood, the theory that the balance between mucosal defense and injury is broken are recognized.,Pathogenesis of peptic ulcer 1. Aggressive factors Helicobacter

4、 Pylori ( H. Pylori) gastric acid and pepsin 2. Defensive factors mucus-bicarbonate barrier prostaglandins,Helicobacter Pylori ( H. Pylori),In 1983, H. pylori was found by two Australians, Marshall and Warren. Now, it is believed that H. pylori is the most important pathogenic factor to peptic ulcer

5、. “No H.P., no ulcer.” And the two men won the noble prize for the important findings in 2005.,H. Pylori (48,000),flagellum,H. Pylori on gastric mucosa(16,000),Actions of H. Pylori,gastric acid and pepsin,Pepsin can decompose protein molecule. But its activity is depended on the pH value. When local

6、 pH value elevates to 4, pepsin cant work well. Gastric acid is the key-factor of the formation of peptic ulcer. we can also say that “No acid, no ulcer.”,mucus-bicarbonate barrier,The epithelial layer of the mucosa is composed of tightly adjoined cells that are specialized for existence in an acid

7、medium. Their tight junctions, synthesis of PGs and secretion of mucus and bicarbonate all contribute to maintenance of the epithelial barrier.,mucus-bicarbonate barrier,mucus,Prostaglandins(PGs),Prostaglandins are thought to enhance resistance to injury by maintaining blood flow to the mucosa. Thus

8、 it also plays a major role in the maintenance of defensive mechanism.,Classification of drugs : .Antacids .Agents decreasing secretion of gastric acid . Agents protecting mucosal barrier .Agents eradicating helicobacter pylori,Antacids,Have been used for centuries in the treatment of patients with

9、acid-peptic disorders. Were the mainstay of treatment for acid-peptic disorders until the advent of H2-receptor antagonists and proton pump inhibitors.,Antacids,weak bases : Mg(OH)2 , Al(OH)3 , CaCO3 , NaHCO3 actions: 1) prevent injury from H+ 2) neutralize gastric acid reduce gastric acidity reduce

10、 peptic activity 3) protect face of ulcer( Mg2SiO8 Al(OH)3 ), Antacids NaHCO3+HCl Nacl+H2O+CO2 Mg2Si3O8+4HCl 2MgCl2+3SiO2 Al(OH)3+3HCl AlCl3+3H2O Mg(OH)2+HCl MgCl2+2H2O CaCO3+2HCl CaCl2+H2O+CO2 MgO+HCl MgCl2+H2O,表1、常用抗酸药的作用特点比较 NaHCO3 Mg2SiO8 Al(OH)3 Mg(OH)2 CaCO3 MgO 1g药中和0.1 120 150 250 210 200 50

11、0 N的HCl ml数 抗酸作用 弱快 弱慢 较强慢 较强快 较强快 最强 作用持续时间 短 长 较长 较长 较长 较长 保护溃疡面 无 有 有 无 无 无 收敛作用 无 无 有 无 有 无 产生CO2 有 无 无 无 有 无 （嗳气） 引起便秘 无 无 有 无 有 无 引起腹泻 无 有 无 有 无 有 引起碱血症 有 无 无 无 无 无,药物,特点,作用,side reactions: disorder of gastrointestinal track diarrhea; constipation; belching（打嗝）; flatulence （肠胃胀气）; alkalemia,Ag

12、ents reducing secretion of gastric acid,Regulation of gastric acid secretion,Proglumide,Drugs reducing secretion of gastric acid (1) H2-receptor antagonists (2) Antimuscarinic agents (3) Inhibitors of the proton pump (4) gastrin-receptor antagonists,H2-R antagonists,Cimetidine, Ranitidine, Famotidin

13、e , Nizatidine Actions Competitively block the binding of histamine to H2 receptor. Completely inhibit gastric acid secretion induced by histamine. characteristics: more effective than M-R antagonists;long duration; high rate of healing up; rebound,Regulation of gastric acid secretion,Proglumide,Cim

14、etidine(西咪替丁;甲氰咪胍):, Pharmacokinetics Absorption: p.o F=70% Distribution: widely Elimination: kidney ! Heptic microsomal enzyme inhibitor Action inhibit all kinds of gastric acid secretion,Clinical uses,peptic ulcers: effective in promoting healing of peptic ulcers. 400 mg bid 4W80% healing after tr

15、eatment is stopped, recurrence is common. This can be effectively prevented by eradication of H.Pylori.,Zollinger-Ellison syndrome: a fatal disorder in which a gastrin-producing tumor causes hypersecretion of gastric acid. In many patients, H2 receptor antagonists can effectively keep the acid secre

16、tion to safe levels so as to control symptoms related to excess acid secretion.,gastroesophageal reflux disorder (GERD, heartburn): Because they act through stopping acid secretion, they may not relieve symptoms of heartburn for at least 45 minutes. Antacid will be more efficiently to neutralize sec

17、reted acid already in the stomach.,Adverse reactions,1.the common side effects are headache, dizziness, diarrhea and muscular pain, skin rash 2.CNS effects: confusion, disorientation and hallucination 3. Endocrine system effects: gynecomastia, impotency, galactorrhea(溢乳),Ranitidine(雷尼替丁) 1) Antisecr

18、etive effect is 10 times that of Cimetidine . 2)Less effect on hepatic microsomal metabolism system. 3)Longer duration and less antiandrogenic effect,Famotidine(法莫替丁) 1) Antisecretive effect is 40 times that of Cimetidine . 2) Have no effect on hepatic microsomal metabolism system. Nizatidine(尼扎替丁):

19、 Ebrotidine(乙溴替丁): 1) Expression of EGF and PDGFstimulate proliferation of epithelium 2) increase mucus secretion,Inhibitors of the proton pump,Omeprazole, lansoprazole, pantoprazole pharmacological effects Inhibits H+ being transported to gastric lumen through inhibiting the proton pump. Potent and

20、 long-lasting effect: Can inhibit over 95% of gastric acid secretion. Also inhibit release of peptin and H.P,Regulation of gastric acid secretion,Proglumide,Clinical uses,peptic ulcer: was judged to be superior to H2-R antagonists Zollinger-Ellison syndrome: heartburn : the most effective agents. he

21、morrhage of upper digestive tract H.P infection,Adverse reactions extremely safe,1)G.I reactions: nausea,vomitting, diarrhea, abdominal pain etc. 2)NS: headache, swirl, insomnia, peripheral neuritis, etc. 3) overgrowth of bacteria: Increases in gastric bacterial concentrations. 4)hypergastrinemia(高胃

22、泌素血症) 5)canceration,Omeprazole Easily absorbed, but affected by food Is also heptic enzyme inhibitor lansoprazole second generation Pantoprazole and rabeprazole third generation weak effect on heptic enzyme,Antimuscarinic agents,Muscarinic receptor stimulation increase gastrointestinal motility and

23、secretion. So cholinergic antagonists can be used as adjuncts in the management of peptic ulcer disease and Zollinger-Ellison syndrome, particularly in patients refractory to standard therapies.,Regulation of gastric acid secretion,Proglumide,Antimuscarinic agents,In contrast to the classic antichol

24、inergics, the relatively specific M1-receptor antagonist, Pirenzepine is a good choice as an anti-secretory agent. Because it suppresses basal and stimulated gastric acid secretion at doses having a minimal effect on other organs (salivary glands, the heart and eye.),gastrin-receptor antagonists: pr

25、oglumide(丙谷胺), Agents protecting mucosal barrier,(1)Prostaglandins (2)Mucosal protective agents,Prostaglandins prostaglandins E2 and I2, produced by the gastric mucosa, inhibit secretion of gastric acid and stimulate secretion of mucus and bicarbonate (cytoprotective effect) . A deficiency of prosta

26、glandins is thought to be involved in the pathogenesis of peptic ulcers.,Mucosal protective agents,These compounds, known as cytoprotective ones , have several actions that enhance mucosal protection mechanisms, thereby preventing mucosal injury, reducing inflammation and healing existing ulcers. cl

27、inical uses: NSAID-induced ulcer adverse reactions: dose-dependent diarrhea, stimulate uterus,Misoprostol: a stable analog of PGE2,(1) inhibits secretion of gastric acid and stimulate secretion of mucus and bicarbonate. (2) dilate blood vessel of mucous membrane. (3) currently the only agent approve

28、d for prevention of gastric ulcers induced by NSAIDs. (4)less effective than H2-receptor antagonists for acute treatment of peptic ulcers. (5)produces uterine contractions and is contraindicated during pregnancy.,Mucosal protective agents,Sucralfate(硫糖铝) 1)In water or acidic solutions it forms a vis

29、cous, tenacious paste that binds selectively to ulcers or erosions for up to 6 hours. 2)Also stimulates prostaglandin release and mucus and bicarbonate output. 3)Promote effects of growth factors 4)Inhibit H.P ! Needs acid envioment; affects absorption of other drugs,Mucosal protective agents,colloi

30、dal bismuth subcitrate (枸橼酸铋钾) 1) binds to an ulcer crater, coating it and protecting it from acid and pepsin. 2) Inhibits the activity of pepsin 3) increases mucous secretion 4) increase prostaglandin synthesis 5) helps to eradicate H. pylori,Antimicrobial agents,Optimal therapy of patients with pe

31、ptic ulcer disease who are infected with H.Pylori requires antimicrobial treatment. Eradication of H.Pylori results in rapid healing of active peptic ulcers and low recurrence rates. Metronidazole, tetracycline, amoxiciliin, etc. Often combined with other drugs.,Section 2 Drugs modulating digestive

32、function Digestants Dilute hydrochloric acid Pepsin Pancretin biofermin, Antiemetic and prokinetic agents, Antiemetic and prokinetic agents Antiemetic agents 1. H1-receptor antagonist Dimenhydrinate (乘晕宁) 2. M-receptor antagonist scopolamine,3. dopamine antagonists:,Metoclopramide(甲氧氯普胺) mechanism 1

33、) block D2-receptor in CTZ antinausea and antiemetic action 2) block gastrointestinal D2-receptor promote vermiculation（肠蠕动）,Clinical use: prevention of vomitting gastrointestinal reflux disease nonulcer dyspepsia impaired gastric emptying adverse reaction: extrapyramidal symptoms, especially dyston

34、ias（张力障碍）,Domeperidone (多潘立酮) block gastrointestinal D2-receptor promote vermiculation Cisapride（西沙必利） DA, Ach, 5-HT,4. 5-HT3 inhibitor ondansetron : used in the prevention of chemotherapy-induced and postoperative nausea and vomiting Granisetron(格拉司琼) Tropisetron（托烷司琼）, Antidiarrheal agents Increas

35、ed motility of the gastrointestinal tract and decreased absorption of fluid are major factors in diarrhea. So antidiarrheals include anti-motility agents, adsorbents and drugs that modify fluid and salt transport.,1.Opium receptor agonists Opium tincture Tincture camphor compound Diphenoxylate (苯乙哌啶) Loperamide（