Transcript Document

Drugs Acting On
Gastrointestinal Tract
Professor Kassim Al-Saudi,
M.B.,Ch.B.,Ph.D.
OBJECTIVES
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Identify classes of drugs used to improve GI
function.
Identify uses and varying actions of these
drugs.
Identify how these drugs are absorbed,
distributed, metabolized, and excreted.
Identify drug interactions and adverse
reactions to these drugs.
Be familiar with drug-induced hepatotoxicity
DRUGS AND THE GI SYSTEM
Classes of drugs used to improve GI
function include:
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Peptic ulcer drugs
Antiemetic and emetic drugs
Antidiarrheal drugs
Laxative drugs
Peptic Ulcer
•The term “peptic ulcer” refers to an ulcer in the
lower Oesophagus, stomach, duodenum
(commonly), jujenum and ileum (rarely)
• Gastric and duodenal ulcers may be acute
or chronic
• Acute ulcer shows no evidence of fibrosis
• Both penetrate the muscularis mucosae
• Erosions do not penetrate the muscularis
mucosae
Aetiology:
1- Infection – Helicobacter pylori (Gm –ve)
- 50% Industrialized
- 90% Developing (Childhood)
- Majority symptoms free
- 90% of DU patients and 70% of GU
patients are infected with H. pylori
2- Acid and Pepsin secretion
3- Mucosal defensive mechanism
Pathogenesis of Ulcers
Therapy is directed at enhancing host defense or
eliminating aggressive factors; i.e., H. pylori.
Aggressive
Factors
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Acid, pepsin
Bile salts
Drugs (NSAIDs)
H. pylori
Defensive Factors
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Mucus, bicarbonate
layer
Blood flow, cell renewal
Prostaglandins
Phospholipid
Free radical scavengers
Aim of Treatment
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Relief Symptoms
Heal Ulcer
Prevent recurrence
Prevent complications
Lifestyle measures
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Raise the head of the bed
Decrease fat intake
Avoid certain foods
Avoid lying down for 3 hours after eating
Stop smoking
Lose weight if appropriate
PEPTIC ULCER DRUGS
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Aimed at either eradicating H. pylori or
restoring balance between acid and
pepsin secretions and the GI mucosal
defense.
These drugs include: systemic antibiotics,
antacids, Histamine-2 (H2)-receptor
antagonists, proton pump inhibitors, and
other peptic drugs such as misoprostol
and sucralfate.
Eradication of H. pylori
Tests For Initial Diagnosis of
Infection
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Urea Breath Test and Stool Assay
 Non-invasive, sensitive and specific
Serology
 O.K. for initial diagnosis
 Fair sensitivity and specificity
Endoscopy Not necessary for diagnosis
Who Should Be Treated For
H. pylori Infection?
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Patients who have documented H. pylori
infection and:
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Definitely had or has a duodenal or stomach ulcer
Have had stomach lymphoma or family hx of
stomach cancer
Consider treatment if:
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Presence of “severe histologic” gastritis and H.
pylori infection
Ulcer-like dyspepsia in the absence of an ulcer or
prior to endoscopy in a young patient
FDA-Approved Treatment
Regimes for H. pylori Infection
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Omeprazole 20 mg BID + Clarithromycin 500 mg
BID + Amoxicillin 1 g BID for 10 days
Lansoprazole 30 mg BID +Clarithromycin 500 mg
BID + Amoxicillin 1 g BID for 10 days
Bismuth subsalicylate (Pepto Bismol) 525 mg QID
+ Metronidazole 250 mg QID + Tetracycline 500
mg QID X 14 days + H2 receptor antagonist x 4
wks
Known Factors Which Determine
Success of H. pylori Therapy
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Patient compliance or non-compliance
 Medicine complications or side effects
Antimicrobial resistance of infecting H. pylori strains
Duration of Therapy
Correct dosing
Clearance of H. pylori infection is not equivalent to
eradication.
Drugs Affecting Gastric Acid
Secretion
PROTON PUMP INHIBITORS
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Disrupt chemical binding in stomach cells
to reduce acid production, lessening
irritation and allowing peptic ulcers to heal.
These drugs include:
Omeprazole (Prilosec)
Rabeprazole (Aciphex)
Pantoprazole (Protonix)
Lansoprazole (Previcid)
Esomaprazole (Nexium)
PROTON PUMP INHIBITORS
Pharmacokinetics:
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Given orally in enteric-coated form to
bypass the stomach and are dissolved and
absorbed in the small intestine.
Highly protein-bound and are extensively
metabolized by the liver; eliminated in the
urine.
PROTON PUMP INHIBITORS
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Pharmacodynamics:
Block the last step in the secretion of
gastric acid by combining with hydrogen,
potassium, and adenosine triphosphate in
the parietal cells of the stomach.
PROTON PUMP INHIBITORS
Pharmacotherapeutics:
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Indicated for:
Short term treatment of gastric ulcers
Active duodenal ulcers and peptic ulcers
(H. pylori)
Erosive esophagitis
GERD
Hypersecretory states
PROTON PUMP INHIBITORS
Drug interactions:
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May interfere with the metabolism of
diazepam, phenytoin, and warfarin.
May also interfere with drugs that depend on
gastric pH for absorption.
Adverse reactions:
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Abdominal pain, diarrhea, nausea, and
vomiting
Pharmacological therapy –
PPIs
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Significantly more effective than H2RAs for
both symptom resolution and healing of
erosive esophagitis
Also effective in more severe cases of
GERD
Most patients respond well to standard
therapy, but some require prolonged and/or
high-dose treatment
PPIs are the most effective drugs for
the initial treatment of GERD
% esophagitis cases healed
100
PPIs
80
60
H2RAs
40
Placebo
20
0
2
4
6
8
Weeks of treatment
10
12
p < 0.0005
H2-RECEPTOR
ANTAGONISTS
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Commonly prescribed anti-ulcer drugs
include:
Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid)
H2-RECEPTOR
ANTAGONISTS
Pharmacokinetics:
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Absorbed rapidly and completely except for
famotidine; food and antiacids may reduce
absorption; distributed widely throughout the
body; metabolized by the liver; excreted
primarily in the urine.
Pharmacodynamics:
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Block histamine from stimulating the acidsecreting parietal cells of the stomach.
H2-RECEPTOR
ANTAGONISTS
Pharmacotherapeutics:
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Used therapeutically to:
Promote healing of duodenal and gastric
ulcers.
Provide long-term treatment of
pathological GI hypersecretory conditions.
Reduce gastric acid production and
prevent stress ulcers.
H2-RECEPTOR
ANTAGONISTS
Drug interactions:
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Cimetidine inhibits metabolism of ethyl
alcohol in the stomach resulting in higher
blood alcohol levels.
Adverse reactions:
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Headache, diarrhea, and rash
Prevention of ulcers in NSAID Users
Ulcer Recurrence (%)
30
20
10
Ranitidine 150 mg bid
n = 215
Omeprazole 20 mg qd
n = 210
16.3
*
5.2
5.7
*
0.5
0
Gastric Ulcer
Duodenal Ulcer
* p< 0.05
Antimuscarinic drugs
Pirenzepine, telenzepine
• M1 receptors antagonists :
Pirenzepine, telenzepine (a more potent
analog), reduce gastric acid secretion with
fewer adverse effects than atropine and
others.
• Contraindicated in some gastric ulcers as they
may slow gastric emptying and prolong the
exposure of the ulcer bed to acid.
ANTACIDS
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Over-the-counter medications that include:
Magnesium hydroxide and aluminum
hydroxide
Sodium bicarbonate
Calcium carbonate
Simethicone
ANTACIDS
Pharmacokinetics:
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Work locally in the stomach by neutralizing
gastric acid.
Distributed throughout the GI tract;
eliminated primarily in the feces.
Pharmacodynamics:
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Reduce the total amount of acid in the GI
tract.
ANTACIDS
Pharmacotherapeutics:
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Prescribed to relieve pain and promote
healing in peptic ulcer disease.
Also used to relieve symptoms of acid
indigestion, heart-burn, dyspepsia, or GERD.
Also used to prevent stress ulcers, GI
bleeding, and hyperphosphatemia in kidney
failure.
ANTACIDS
Drug interactions:
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All antacids can interfere with the
absorption of oral drugs given at the same
time.
Adverse reactions:
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Diarrhea, constipation, electrolyte
imbalances
Antacids
Mucosal Protective Agents
Bismuth Compounds:
Tripotassium dicitratobismuthate is a bismuth
chelate effective in healing gastric & duodenal
ulcers.
Low absorption has been reported
 Colloidal Bismuth Subcitrate (CBS) is used in
the management of gastric and duodenal
ulcers, and in combination with two
antibacterials for the eradication of H. pylori.
Sucralfate
• It is a complex of aluminium hydroxide
and sulphated sucrose but has minimal
antacid properties.
• May act by protecting the mucosa from
acid-pepsin attack in gastric and duodenal
ulcers.
OTHER PEPTIC ULCER
DRUGS
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Misoprostol (Cytotec) - Protects
against peptic ulcers caused by
NSAIDs by reducing the secretion of
gastric acid and by boosting the
production of gastric mucus.
NSAID Use in the Arthritis
Patient with a History of
Bleeding Ulcer
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Treating H. pylori is likely to be of benefit if
there was a duodenal ulcer;
test and treat for H. pylori is recommended.
Use COX2 Inhibitor
Add a PPI or Misoprostol