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Drugs Affecting Gastrointestinal Function

Drugs Affecting Gastrointestinal Function. Gao Fen-Fei. OUTLINE. Peptic Ulcer Digestion Vomiting Diarrhea Bile Review-Questions. Ulcer-Background. Epidemiology incidence of a disease: 10%-12% DU > GU (3:1) Etiology General consideration: No Acid No Ulcer

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Drugs Affecting Gastrointestinal Function

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  1. Drugs Affecting Gastrointestinal Function Gao Fen-Fei

  2. OUTLINE • Peptic Ulcer • Digestion • Vomiting • Diarrhea • Bile • Review-Questions

  3. Ulcer-Background • Epidemiology • incidence of a disease: 10%-12% • DU > GU (3:1) • Etiology • General consideration: No Acid No Ulcer • Main Destroy Factors: ①HCl, ②Pepsin, ③Hp • Protective Barrier: Mucus-HCO3- • Physiology • HCl: P-cell, H2, M1, G-R, H+-pump

  4. Anti-ulcer Targets • HCl • Mucus • Hp

  5. Anti-ulcer Classification • Antacids---NeutralizeHCl • Gastric Antisecretory Drugs HCl secretion • Antagonize Rs. on Parietal Cell--- H2,M3, G • Inhibitor of H+-Pump • Protectors of Mucosa • Agents killHP

  6. Ⅰ. Antacids • Mechanism: • Alkalizers——To Neutralize HCl • Agents: • Mg(OH)2 Al(OH)3 CaCO3 NaHCO3 • Adverse Effect: • Systemic alkalosis, Diarrhea , CO2

  7. Major constituents of antacids

  8. Ⅱ.1.⑴ H2-R Antagonists • Mechanism: • Pharmacologic Effects: • Basal gastric acidnocturnal secretion • Agents: • Cimetidine， Ranitidine， Famotidine • Adverse Effect: • Gynecomastia, prolactin , CYP450 , headache

  9. Ⅱ.1.⑵ Antimuscarinic Agents • Mechanism: • Blocking M3-R on Parietal Cell, M-R on ECL cell and G cell • Pharmacologic Effects: • HClspasmolysis • Agents: • Atropine ，Probanthine • Pirenzepine - M1,M2-R selection • Adverse Effect:

  10. Ⅱ.1.⑶ Antagonist of G-R • Mechanism: • Competing Gastrin-R on Parietal Cell • Pharmacologic Effects: • HClMucosal • Agents: • Proglumide • Adverse Effect:

  11. Ⅱ.2. Proton Pump Inhibitors • Mechanism: • H+,K+-ATPase H+ K+ • Pharmacologic Effects: • HCl & Hp • Agents: • Omeprazole（losec） • Lansoprazole • Pantoprazole，Rabeprazole • Adverse Effect:

  12. Ⅲ. Mucosal Protective Agents • Derivatives of Prostaglandin: Misoprostol (PGE1), Enprostil • Mechanism: • HCl ; Pepsin • Mucus-HCO3- ; • Cytoprotective effect • Pharmacologic Effects: • Prevention of ulcers iduced by NSAIDs • Contraindication： • Women with childbearing

  13. 2.Sucralfate • Mechanism: • Polymerization & gelatine barrier • PGE2Mucus-HCO3- • Hp • Pharmacologic Effects: • Effective in Duodenal Ulcers • Notice: • Acid pH • Empty stomach

  14. 3.CBS • Mechanism: • Pepsin • PGE1 Mucus-HCO3- • Coating • Hp （disputed） 4.Teprenone 5. Marzulene

  15. Ⅳ. Anti-Hp Drugs • 90% DU,70% GU --- Helicobacter pylori (G-) • Anti-Ulcer Agents: • Bismuth Compounds • Proton Pump Inhibitors • sucralfate • Antibacterial Drugs: • Amoxicillin • Gentamicin • Metronidazole

  16. Combination Therapy • Therapy of triad • Oversea • PPI + twoAntibacterial Drugs • Domestic • CBS + PPI or H2-R Antagonist + Antibacterial Drug

  17. Digestion Aids • Contents of Digestive Juice: • Pepsin • Pancreatin • Helpful Bacterias in Bowel: • biofermin

  18. Other areas CTZ Chemoreceptor trigger zone Vestibular apparatus Antiemetic Drugs and Drugs Promoting Gastrointestinal Motility • Nausea and Vomiting mechanism: Chemical stimuli 5-HT, D2, M1, H1 Stomach and Abdomminal Musculature Vomiting Center Vomiting

  19. Antagonists of Receptors of • H1:Nucleus of tractus solitarius, vestibulocerebellar pathway——Diphenhydramine, Dimenhydrinate • M : Nucleus of tractus solitarius, CTZ——Scopolamine • D2: CTZ, Nucleus of tractus solitarius, Stomach, Small intestine——Thiethylperazine，Metoclopramide • 5-HT3: Stomach, Small intestine, CTZ, Nucleus of tractus solitarius——Ondansetron，Granisetron • Prokinetics： • MetoclopramideBlocking Gastrointestinal • Domperidone D2-R • Cisapride：Ach release↑

  20. Antidiarrheal Drugs andAdsorbents • Opium preparation and Derivatives • Opiate receptors in Gastrointestinal tract → tone↑motility↓（μ），secretion↓（δ），Ach release ↓ • Loperamide： Derivatives of Haloperidol • Astringents • Tannalbin • Bismuth subsalicylate, Bismuth subcarbonate • Adsorbants • Medicinal Charcoal • Kaolin

  21. Laxatives • Contact cathartics • Irritant or stimulant → intestinal motility↑ • Phenolphthalein, Rhubarb, Senna, Castor oil • Osmotic laxatives • nonabsorbable → distending → peristalsis • MgSO4, Na2SO4, Lactulose, Celluloses • Surface-active agents • Lubricating, Stool soften • Liquid paraffin

  22. Choleretic drug • Cholic Acid • HMG-CoA reductase (rate limiting enzyme)↓ → bile salt↑，cholesterol ↑ • Chenodiol (Chenodeoxycholic acid) • MgSO4 • cholecystokinin ↑ • Cinametic acid • Anethol trithione

  23. Review-Questions • The classification of drugs used in the treatment of peptic ulceration. • the mechanisms and the agents of each.

  24. Good Bye!

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