1. Drugs Affecting the Gastrointestinal System
Caiying YE
Department of Pharmacology, School of Basic Medicine,
Peking Union Medical College

2. Drugs Affecting the Gastrointestinal System
Antiulcerants
Digestives
Antiemetics
Purgatives
Antidiarrheals
Cholagogues

3. Peptic Ulcers Common disease，incidence rate: 10%~12%.
Pathogenesis of ulcers
Aggressive Factors Defensive Factors
Acid,pepsin
Bile salts
Drugs (NSAIDs)
H.pylori
Mucus,bicarbonate layer
Blood flow,cell renewal
Prostaglandins
Phospholipid
Free radical scavengers

4. Peptic Ulcers Therapy Purpose：
Therapy is directed at enhancing host defense or eliminating aggressive factors; i.e., H. pylori.

5. Drugs Used in Peptic Ulcers
Antacids
Inhibitors of gastric acid production
H2-receptor antagonists
Proton pump inhibitors
Muscarinic antagonists
Gastrin receptor antagonist
Mucosal Protectants
Anti-Helicobacter pylori. drugs
Acid Pump

6. Drugs Used in Peptic Ulcers
Antacids ：
aluminum hydroxide
magnesium hydroxide
H2- receptor antagonists ：
cimetidine
ranitidine
Muscarinic antagonists ：atropine

7. Drugs Used in Peptic Ulcers
Proton pump inhibitors ：omeprazole
Gastrin receptor antagonist ：proglumide
Mucosal Protectants ：misoprostol
Anti-Helicobacter pylori. Drugs ：antibiotics

8. Antacids 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.

9. Antacids Magnesium hydroxide Magnesium trisilicate Aluminum hydroxide
Calcium carbonate
Sodium bicarbonate

10. H2-receptor antagonists
Mechanism of action
Competitively block the histamine (H2) receptor of acid-producing parietal cells
rendering 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

11. H2-receptor antagonists
Four FDA-approved:
Cimetidine （Tagamet®）
Ranitidine （Zantac®）
Famotidine （Pepcid®）
Nizatidine （Axid®）
Roxatidine

12. H2-receptor antagonists
Therapeutic effects:
Promote the healing of gastric and duodenal ulcers
Gastroesophageal reflux dz [GERD]
Upper GI bleed [GIB]
May be effective in stress ulcers & peptic esophagitis

13. H2-receptor antagonists
Side effect:
Overall low < 3%
CNS: < 1% total
headache, lethargy ，confusion, depression，hallucinations
ENDO：
Impotence ，increased prolactin ，gynecomastia
HEME:
Thrombocytopenia

14. Muscarinic antagonists
Atropine：
Block the M1 class receptors
reduce acid production
abolish gastrointestinal spasm
relatively unpopular as a first choice because of high incidence of anticholinergic side effects (dry mouth and blurred vision)

15. Proton pump inhibitors
H+,K+-ATPase (Proton Pump) inhibitor
Irreversible inhibition
Must synthesize new enzyme
Long duration
Omeprazole (Prilosec®)
Lansoprazole (Prevacid®)
Pantoprazole
Rabeprazole

16. Mechanism of Action

17. Omeprazole（losec） Irreversibly binds to H+/K+ ATPase
Prevents H+ ion production & secrection
Block all acid secretion = achlorhydria
to return to normal must synthesize new H+/K+ ATPase
Inhibit H. pylori

18. Omeprazole（losec） Therapeutic uses Gastroesophageal reflux dz [GERD]
Peptic ulcer
Infection with H. pylori plus(Hp)
Upper GI bleed [GIB]

19. Omeprazole
Lansoprazole
Pantoprazole

20. Gastrin receptor antagonist
Proglumide

21. Mucosal Protective Agents

22. Misoprostol A congener of prostaglandin E1 PG’s:
inhibit gastric acid secretion
exhibit ‘cytoprotective’ activity
enhance local production of mucus or bicarbonate
promote local cell regeneration
help to maintain mucosal blood flow

23. Misoprostol
Misoprostol is approved for use in patients taking NASIDs who are at risk for gastric ulcers
Misoprostol produces diarrhea and stimulation of uterine contraction.

24. Bismuth （Pepto-Bismol®）
Sucralfate
cytoprotective agent
stress ulcerations & PUD
inhibit H. pylori
Bismuth （Pepto-Bismol®）
inhibit pepsin activity

25. Agents Used in infection of Helicobacter Pylori
Helicobacter pylori，HP

26. Agents Used in infection of Helicobacter Pylori
Aimed at eliminating H. pylori
Bismuth ( Pepto-Bismol®)
Gentamicin
Amotriptyline (Amoxil ® )
Clarithromycin
Tetracycline (Achromycin V ®)
Metronidazole (Flagyl ® )

27. Proton pump inhibitors Agents Used in infection of Helicobacter Pylori
Antacids
Before 1970
1970~
H2-receptor antagonists
Proton pump inhibitors
1980~
Proton pump inhibitors
Agents Used in infection of Helicobacter Pylori
1990~

28. Digestives
                                          
Pepsin
Pancreatin
Lactasin

29. Antiemetic Drugs Vomiting reflex
a coordinated reflex controlled by a bilateral vomiting center in the dorsal portion of the lateral reticular formation in the medulla
Pharmacologic intervention
relies on inhibition of inputs or depression of the vomiting center.

30. Antiemetic Drugs Histamine1-receptor antagonist Cholinergic antagonist
Dopamine antagonists :
Metoclopramide Domperidone （motilium）
[Therapeutic uses]
[Side effects]
5-HT3 antagonists
Cannabinoids
D2-receptor antagonist (periphery)
A weaker antiemetic, fewer extrapyramidal effects.
Accelerates gastric emptying; has little effect on the colon

31. Thank you!