藥物的肝臟毒性，消化系統(tǒng)用藥高分飛

1、Drugs Affecting Gastrointestinal Function,Gao Fen-Fei,OUTLINE,Peptic UlcerDigestionVomitingDiarrheaBileReview-Questions,Ulcer-Background,20世紀(jì)初，與應(yīng)激、生活、飲食等有關(guān)，故主張鎮(zhèn)靜、休息、飲食治療。1910年，Schwarz提出”No Acid No Ulcer” 1971年，Bla

2、ck等發(fā)現(xiàn)H2受體。1976年，第一代H2受體拮抗劑西咪替丁用于臨床——第一次革命。諾貝爾獎。 20世紀(jì)80年代中期，質(zhì)子泵抑制劑（proton pump inhibitor，PPI）奧美拉唑問世。 1983年，澳大利亞學(xué)者Warren與Marshall分離出Hp，病因觀念轉(zhuǎn)變，再一次革命。根治成為可能。2005年，獲諾貝爾獎。,Introduction of Ulcer,Epidemiologyincidence of a di

3、sease: 10%-12%Europe and America: DU > GU; Japan: GU > DU EtiologyGeneral consideration: No Acid No UlcerMain Destroy Factors: ①HCl, ②Pepsin, ③HpProtective Barrier: Mucus-HCO3-,Pathogenesis of Peptic Ulcer,Rev

4、iew,How is the secretion of gastric acid adjusted ?What is the mechanism of secretion of gastric acid ?,How to treat peptic ulcer ?,Anti-ulcer Targets,HClMucusHp,,,Anti-ulcer Classification,Antacids--- Neutralize HC

5、lGastric Antisecretory Drugs HCl secretionAntagonize Rs. on Parietal Cell--- H2,M3, GInhibitor of H+-PumpProtectors of MucosaAgents kill HP,,Ⅰ. Antacids,Mechanism:Alkalizer

6、s——To Neutralize HClAgents:Mg(OH)2 Al(OH)3 CaCO3 NaHCO3Adverse Effect:Systemic alkalosis, Diarrhea , CO2,Major constituents of antacids,Ⅱ.1.⑴ H2-R Antagonists,Mechanism:Pharmacologic Effects:Basal gastric a

7、cid nocturnal secretionAgents:Cimetidine， Ranitidine， FamotidineAdverse Effect:Gynecomastia, prolactin , CYP450 , headache,,,,,Ⅱ.1.⑵ Antimuscarinic Agents,Mechanism:Blocking M3-R on Parietal Cell, M-R on

8、 ECL cell and G cellPharmacologic Effects:HCl spasmolysisAgents:Atropine ，ProbanthinePirenzepine - M1,M2-R selectionAdverse Effect:,,Ⅱ.1.⑶ Antagonist of G-R,Mechanism:Competing Gastrin-R on Parietal CellPh

9、armacologic Effects:HCl Mucosal Agents:ProglumideAdverse Effect:,,,Ⅱ.2. Proton Pump Inhibitors,Mechanism:H+,K+-ATPase H+ K+ Pharmacologic Effects:HCl & Hp

10、Agents:Omeprazole（losec）LansoprazolePantoprazole，RabeprazoleAdverse Effect:,,,,,Ⅲ. Mucosal Protective Agents,Derivatives of Prostaglandin: Misoprostol (PGE1), EnprostilMechanism: HCl ; PepsinMucus-HCO3- ;

11、 Cytoprotective effectPharmacologic Effects:Prevention of ulcers iduced by NSAIDsContraindication：Women with childbearing,,,,2. SucralfateMechanism: Polymerization & gelatine barrier PGE2

12、 Mucus-HCO3- HpPharmacologic Effects:Effective in Duodenal UlcersNotice:Acid pHEmpty stomach,,,,,3. CBS Mechanism: Pepsin PGE1 Mucus-HCO3-

13、 CoatingHp （disputed）4. Teprenone5. Marzulene,,,,,,Ⅳ. Anti-Hp Drugs,90% DU,70% GU --- Helicobacter pylori (G-)Anti-Ulcer Agents:Bismuth CompoundsProton Pump InhibitorssucralfateAntibacterial Drugs:Amo

14、xicillinGentamicinMetronidazole,Combination Therapy,Therapy of triadOverseaPPI + two Antibacterial DrugsDomesticCBS + PPI or H2-R Antagonist + Antibacterial Drug,Digestion Aids,Contents of Digestive Juice:PepsinP

15、ancreatinHelpful Bacterias in Bowel:biofermin,Antiemetic Drugs and Drugs Promoting Gastrointestinal Motility,Medulla Oblongata Vomiting Center,Stimuli,,Chemoreceptor Trigger Zone,,Stomach and Abdomminal Musculature,,P

16、athogenesis of Vomiting,延髓嘔吐中樞,,,,刺激,,,晃動,,Antagonists of Receptors of H1: Nucleus of tractus solitarius, vestibulocerebellar pathway——Diphenhydramine, DimenhydrinateM : Nucleus of tractus solitarius, CTZ——Scopolamin

17、eD2 : CTZ, Nucleus of tractus solitarius, Stomach, Small intestine——Thiethylperazine，Metoclopramide 5-HT3 : Stomach, Small intestine, CTZ, Nucleus of tractus solitarius——Ondansetron，Granisetron Prokinetics：Metoclopra

18、mide Blocking GastrointestinalDomperidone D2-RCisapride：Ach release↑,,Antidiarrheal Drugs and Adsorbents,Opium preparation and DerivativesOpiate receptors in Gastrointestinal tract → tone↑mot

19、ility↓（μ），secretion↓（δ），Ach release ↓Loperamide： Derivatives of HaloperidolAstringentsTannalbinBismuth subsalicylate, Bismuth subcarbonateAdsorbantsMedicinal CharcoalKaolin,Laxatives,Contact catharticsIrritant or

20、 stimulant → intestinal motility↑Phenolphthalein, Rhubarb, Senna, Castor oilOsmotic laxativesnonabsorbable → distending → peristalsisMgSO4, Na2SO4, Lactulose, Celluloses Surface-active agentsLubricating, Stool soft

21、enLiquid paraffin,Choleretic drug,Cholic AcidHMG-CoA reductase (rate limiting enzyme)↓ → bile salt↑，cholesterol ↑Chenodiol (Chenodeoxycholic acid)MgSO4cholecystokinin ↑Cinametic acidAnethol trithione,Review-Questi