24.作用于消化系统的药物——山东大学药理学英文课件

1、 A benign, localized defect in the mucosa of any part of the gastrointestinal tract. duodenal ulcer gastric ulcer 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 hem

2、orrhage, perforation, obstruction and canceration. 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 ulcer1. Aggressive factors Helicobacter Pylori ( H. Pylori) ga

3、stric acid and pepsin 2. Defensive factors mucus-bicarbonate barrier prostaglandinsIn 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. “No H.P., no ulcer. And the two men won the noble prize

4、 for the important findings in 2005.flagellumPepsin can decompose protein molecule. But its activity is depended on the pH value. When local 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. The ep

5、ithelial layer of the mucosa is composed of tightly adjoined cells that are specialized for existence in an acid medium. Their tight junctions, synthesis of PGs and secretion of mucus and bicarbonate all contribute to maintenance of the epithelial barrier. mucus Prostaglandins are thought to enhance

6、 resistance to injury by maintaining blood flow to the mucosa. Thus 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 Have bee

7、n used for centuries in the treatment of patients with acid-peptic disorders. Were the mainstay of treatment for acid-peptic disorders until the advent of H2-receptor antagonists and proton pump inhibitors. weak bases : Mg(OH)2 , Al(OH)3 , CaCO3 , NaHCO3actions: 1) prevent injury from H+ 2) neutrali

8、ze gastric acid reduce gastric acidity reduce 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

9、)2 CaCO3 MgO1g药中和0.1 120 150 250 210 200 500N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打嗝打嗝; fla

10、tulence 肠胃胀气肠胃胀气; alkalemiaProglumide Drugs reducing secretion of gastric acid (1) H2-receptor antagonists (2) Antimuscarinic agents (3) Inhibitors of the proton pump (4) gastrin-receptor antagonistsCimetidine, Ranitidine, Famotidine , NizatidineActions Competitively block the binding of histamine t

11、o H2 receptor. Completely inhibit gastric acid secretion induced by histamine. characteristics: more effective than M-R antagonists;long duration; high rate of healing up; reboundProglumide Pharmacokinetics Absorption: p.o F=70% Distribution: widely Elimination: kidney ! Heptic microsomal enzyme inh

12、ibitor Action inhibit all kinds of gastric acid secretionpeptic ulcers : effective in promoting healing of peptic ulcers. 400 mg bid 4W80% healing after treatment is stopped, recurrence is common. This can be effectively prevented by eradication of . Zollinger-Ellison syndrome : a fatal disorder in

13、which a gastrin-producing tumor causes hypersecretion of gastric acid. In many patients, H2 receptor antagonists can effectively keep the acid secretion to safe levels so as to control symptoms related to excess acid secretion. gastroesophageal reflux disorder (GERD, heartburn): Because they act thr

14、ough stopping acid secretion, they may not relieve symptoms of heartburn for at least 45 minutes. Antacid will be more efficiently to neutralize secreted acid already in the stomach.1.the common side effects are headache, dizziness, diarrhea and muscular pain, skin rash2.CNS effects: confusion, diso

15、rientation and hallucination3. Endocrine system effects: gynecomastia, impotency, galactorrhea(溢乳) Ranitidine(雷尼替丁) 1) Antisecretive 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) Ant

16、isecretive effect is 40 times that of Cimetidine . 2) Have no effect on hepatic microsomal metabolism system. Nizatidine(尼扎替丁): Ebrotidine(乙溴替丁): 1) Expression of EGF and PDGFstimulate proliferation of epithelium 2) increase mucus secretion Omeprazole, lansoprazole, pantoprazole pharmacological effe

17、cts Inhibits H+ being transported to gastric lumen through inhibiting the proton pump. Potent and long-lasting effect: Can inhibit over 95% of gastric acid secretion. Also inhibit release of peptinProglumide peptic ulcer: was judged to be superior to H2-R antagonists Zollinger-Ellison syndrome: hear

18、tburn : the most effective agents.hemorrhage of upper digestive tract H.P infection 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

19、(高胃泌素血症高胃泌素血症) 5)cancerationOmeprazole Easily absorbed, but affected by food Is also heptic enzyme inhibitorlansoprazole second generationPantoprazole and rabeprazole third generation weak effect on heptic enzyme Muscarinic receptor stimulation increase gastrointestinal motility and secretion. So ch

20、olinergic antagonists can be used as adjuncts in the management of peptic ulcer disease and Zollinger-Ellison syndrome, particularly in patients refractory to standard therapies. Proglumide In contrast to the classic anticholinergics, the relatively specific M1-receptor antagonist, Pirenzepine is a

21、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: proglumide(丙谷胺) (1)Prostaglandins (2)Mucosal protective agents prostaglandins

22、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 prostaglandins is thought to be involved in the pathogenesis of peptic ulcers. These compounds, known as cytoprotective ones , have

23、several actions that enhance mucosal protection mechanisms, thereby preventing mucosal injury, reducing inflammation and healing existing ulcers.clinical uses: NSAID-induced ulcer adverse reactions: dose-dependent diarrhea, stimulate uterus (1) inhibits secretion of gastric acid and stimulate secret

24、ion of mucus and bicarbonate. (2) dilate blood vessel of mucous membrane. (3) currently the only agent approved 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 contraindic

25、ated during pregnancy.Sucralfate(硫糖铝硫糖铝)1)In water or acidic solutions it forms a viscous, 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! Needs acid envioment

26、; affects absorption of other drugscolloidal bismuth subcitrate (枸橼酸铋钾枸橼酸铋钾) 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. pyloriOptimal the

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

28、ve function Digestants Dilute hydrochloric acid Pepsin Pancretin biofermin Antiemetic and prokinetic agents Antiemetic and prokinetic agents Antiemetic agents 1. H1-receptor antagonist Dimenhydrinate (乘晕宁乘晕宁) 2. M-receptor antagonist scopolamine Metoclopramide(甲氧氯普胺甲氧氯普胺) mechanism 1) block D2-recep

29、tor in CTZ antinausea and antiemetic action 2) block gastrointestinal D2-receptor promote vermiculation肠蠕肠蠕动动 Clinical use: prevention of vomitting gastrointestinal reflux disease nonulcer dyspepsia impaired gastric emptying adverse reaction: extrapyramidal symptoms, especially dystonias张力障碍张力障碍 Dom

30、eperidone (多潘立酮多潘立酮) block gastrointestinal D2-receptor promote vermiculation Cisapride西沙必利西沙必利 DA, Ach, 5-HT4. 5-HT3 inhibitor ondansetron : used in the prevention of chemotherapy-induced and postoperative nausea and vomiting Granisetron(格拉司琼格拉司琼) Tropisetron托烷司琼托烷司琼 1.Opium receptor agonists Opium tincture Tincture camphor compound Diphenoxylate (苯乙哌啶苯乙哌啶) Loperamide洛哌丁胺洛哌丁胺Diphenoxylate(苯乙哌啶苯乙哌啶)Opioids are the most effective agents for relief of diarrhea. Is an analog of pethidine and have opioid-li