Presentation on theme: "Drugs Affecting the Gastrointestinal System"— Presentation transcript:
1Drugs Affecting the Gastrointestinal System Caiying YEDepartment of Pharmacology, School of Basic Medicine,Peking Union Medical College
2Drugs Affecting the Gastrointestinal System AntiulcerantsDigestivesAntiemeticsPurgativesAntidiarrhealsCholagogues
3Peptic Ulcers Common disease，incidence rate: 10%~12%. Pathogenesis of ulcersAggressive Factors Defensive FactorsAcid,pepsinBile saltsDrugs (NSAIDs)H.pyloriMucus,bicarbonate layerBlood flow,cell renewalProstaglandinsPhospholipidFree radical scavengers
4Peptic Ulcers Therapy Purpose： Therapy is directed at enhancing host defense or eliminating aggressive factors; i.e., H. pylori.
5Drugs Used in Peptic Ulcers AntacidsInhibitors of gastric acid productionH2-receptor antagonistsProton pump inhibitorsMuscarinic antagonistsGastrin receptor antagonistMucosal ProtectantsAnti-Helicobacter pylori. drugsAcid Pump
6Drugs Used in Peptic Ulcers Antacids ：aluminum hydroxidemagnesium hydroxideH2- receptor antagonists ：cimetidineranitidineMuscarinic antagonists ：atropine
7Drugs Used in Peptic Ulcers Proton pump inhibitors ：omeprazoleGastrin receptor antagonist ：proglumideMucosal Protectants ：misoprostolAnti-Helicobacter pylori. Drugs ：antibiotics
8Antacids General characteristics Antacids are weak bases that are taken orally and that partially neutralize gastric acid and reduce pepsin activity.Antacids reduce the pain associated with ulcers and may promote healing. High doses are required for healing: 40 mEq of base seven times daily.
10H2-receptor antagonists Mechanism of actionCompetitively block the histamine (H2) receptor of acid-producing parietal cellsrendering cells less responsive to not only histamine but also to the stimulation of acetylcholine and gastrin.Also up to 90% inhibition of vagal stimulated and gastrin stimulated acid secretion.complete inhibition has not been shown
11H2-receptor antagonists Four FDA-approved:Cimetidine （Tagamet®）Ranitidine （Zantac®）Famotidine （Pepcid®）Nizatidine （Axid®）Roxatidine
12H2-receptor antagonists Therapeutic effects:Promote the healing of gastric and duodenal ulcersGastroesophageal reflux dz [GERD]Upper GI bleed [GIB]May be effective in stress ulcers & peptic esophagitis
14Muscarinic antagonists Atropine：Block the M1 class receptorsreduce acid productionabolish gastrointestinal spasmrelatively unpopular as a first choice because of high incidence of anticholinergic side effects (dry mouth and blurred vision)
17Omeprazole（losec） Irreversibly binds to H+/K+ ATPase Prevents H+ ion production & secrectionBlock all acid secretion = achlorhydriato return to normal must synthesize new H+/K+ ATPaseInhibit H. pylori
18Omeprazole（losec） Therapeutic uses Gastroesophageal reflux dz [GERD] Peptic ulcerInfection with H. pylori plus(Hp)Upper GI bleed [GIB]
22Misoprostol A congener of prostaglandin E1 PG’s: inhibit gastric acid secretionexhibit ‘cytoprotective’ activityenhance local production of mucus or bicarbonatepromote local cell regenerationhelp to maintain mucosal blood flow
23MisoprostolMisoprostol is approved for use in patients taking NASIDs who are at risk for gastric ulcersMisoprostol produces diarrhea and stimulation of uterine contraction.
25Agents Used in infection of Helicobacter Pylori Helicobacter pylori，HP
26Agents Used in infection of Helicobacter Pylori Aimed at eliminating H. pyloriBismuth ( Pepto-Bismol®)GentamicinAmotriptyline (Amoxil ® )ClarithromycinTetracycline (Achromycin V ®)Metronidazole (Flagyl ® )
27Proton pump inhibitors Agents Used in infection of Helicobacter Pylori AntacidsBefore 19701970~H2-receptor antagonistsProton pump inhibitors1980~Proton pump inhibitorsAgents Used in infection of Helicobacter Pylori1990~
29Antiemetic Drugs Vomiting reflex a coordinated reflex controlled by a bilateral vomiting center in the dorsal portion of the lateral reticular formation in the medullaPharmacologic interventionrelies on inhibition of inputs or depression of the vomiting center.
30Antiemetic Drugs Histamine1-receptor antagonist Cholinergic antagonist Dopamine antagonists :Metoclopramide Domperidone （motilium）[Therapeutic uses][Side effects]5-HT3 antagonistsCannabinoidsD2-receptor antagonist (periphery)A weaker antiemetic, fewer extrapyramidal effects.Accelerates gastric emptying; has little effect on the colon