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Drugs Affecting the
Gastrointestinal System
Caiying YE
Department of Pharmacology,
School of Basic Medicine,
Peking Union Medical College
Drugs Affecting the
Gastrointestinal System
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Antiulcerants
Digestives
Antiemetics
Purgatives
Antidiarrheals
Cholagogues
Peptic Ulcers
• Common disease，incidence rate: 10%~12%.
• Pathogenesis of ulcers
Aggressive Factors
Defensive Factors
•Acid,pepsin
•Mucus,bicarbonate layer
•Bile salts
•Blood flow,cell renewal
•Drugs (NSAIDs)
•Prostaglandins
•H.pylori
•Phospholipid
•Free radical scavengers
Peptic Ulcers
Therapy Purpose：
Therapy is directed at
enhancing host defense or
eliminating aggressive
factors; i.e., H. pylori.
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
Drugs Used in Peptic Ulcers
Antacids
：
aluminum hydroxide
magnesium hydroxide
H2-
receptor antagonists ：
cimetidine
ranitidine
Muscarinic
atropine
antagonists ：
Drugs Used in Peptic Ulcers
• Proton pump inhibitors ：
omeprazole
• Gastrin receptor antagonist ：
proglumide
• Mucosal Protectants ：
misoprostol
• Anti-Helicobacter pylori. Drugs ：
antibiotics
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.
Antacids
• Magnesium hydroxide
• Magnesium trisilicate
• Aluminum hydroxide
• Calcium carbonate
• Sodium bicarbonate
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
H2-receptor antagonists
Four FDA-approved:
Cimetidine （Tagamet®）
Ranitidine （Zantac®）
Famotidine （Pepcid®）
Nizatidine （Axid®）
Roxatidine
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
H2-receptor antagonists
Side effect:
• Overall low < 3%
• CNS: < 1% total
headache, lethargy ，confusion, depression，
hallucinations
• ENDO：
Impotence ，increased prolactin ，gynecomastia
• HEME:
Thrombocytopenia
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)
Proton pump inhibitors
• H+,K+-ATPase (Proton Pump) inhibitor
• Irreversible inhibition
Must synthesize new enzyme
Long duration
Omeprazole (Prilosec®)
Lansoprazole (Prevacid®)
Pantoprazole
Rabeprazole
Mechanism of Action
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
Omeprazole（losec）
Therapeutic uses
• Gastroesophageal reflux dz [GERD]
• Peptic ulcer
• Infection with H. pylori plus(Hp)
• Upper GI bleed [GIB]
Omeprazole
Lansoprazole
Pantoprazole
Gastrin receptor antagonist
Proglumide
Mucosal Protective Agents
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
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.
• Sucralfate
 cytoprotective agent
 stress ulcerations & PUD
 inhibit H. pylori
• Bismuth （Pepto-Bismol®）
 inhibit pepsin activity
 inhibit H. pylori
Agents Used in infection of
Helicobacter Pylori
• Helicobacter pylori，HP
Agents Used in infection of
Helicobacter Pylori
Aimed at eliminating H. pylori
Bismuth ( Pepto-Bismol®)
Gentamicin
Amotriptyline (Amoxil ® )
Clarithromycin
Tetracycline (Achromycin V ®)
Metronidazole (Flagyl ® )
Before
1970
1970~
Antacids
H2-receptor antagonists
Proton pump inhibitors
1980~
1990~
Proton pump inhibitors
Agents Used in infection
of Helicobacter Pylori
Digestives
Pepsin
Pancreatin
Lactasin
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.
Antiemetic Drugs
• Histamine1-receptor antagonist
• Cholinergic antagonist
• Dopamine antagonists :
Metoclopramide
[Therapeutic uses]
[Side effects]
• 5-HT3 antagonists
• Cannabinoids
Domperidone （motilium）
D2-receptor antagonist (periphery)
A weaker antiemetic, fewer extrapyramidal
effects.
Accelerates gastric emptying; has little effect
on the colon
Thank you!