Drugs Affecting the Gastrointestinal System

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 1012.
• Pathogenesis of ulcers
• Aggressive Factors
  Defensive Factors

• Mucus,bicarbonate layer
• Blood flow,cell renewal
• Prostaglandins
• Phospholipid
• Free radical scavengers

• Acid,pepsin
• Bile salts
• Drugs (NSAIDs)
• H.pylori

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

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 lt 3
• CNS lt 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
Lansoprazole
Omeprazole
Pantoprazole
20
Gastrin receptor antagonist

• Proglumide

21
Mucosal Protective Agents
22
Misoprostol

• A congener of prostaglandin E1
• PGs
• 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

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

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
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!