Drugs Acting On

Gastrointestinal Tract

Professor Kassim Al-Saudi,

M.B.,Ch.B.,Ph.D.

OBJECTIVES

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:

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

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

Defensive Factors

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

Aim of Treatment

Relief Symptoms
Heal Ulcer
Prevent recurrence
Prevent complications

Lifestyle measures

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

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
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
Patients

who have documented H. pylori infection and:

Definitely

had or has a duodenal or stomach ulcer

Have had stomach lymphoma or family hx of stomach
cancer
Consider

treatment if:

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

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
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

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:

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

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:

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:

May interfere with the metabolism of

diazepam, phenytoin, and warfarin.
May also interfere with drugs that depend
on gastric pH for absorption.

Adverse reactions:

Abdominal pain, diarrhea, nausea, and

vomiting

Pharmacological therapy
PPIs

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

% esophagitis cases healed

PPIs are the most effective

drugs for the initial
treatment of GERD
100
PPIs
80
60

H2RAs

40

Placebo

20
0

4
6
8
Weeks of treatment

10

12

p < 0.0005

H2-RECEPTOR
ANTAGONISTS

Commonly prescribed anti-ulcer drugs

include:
Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid)

H2-RECEPTOR
ANTAGONISTS
Pharmacokinetics:

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:

Block histamine from stimulating the acidsecreting parietal cells of the stomach.

H2-RECEPTOR
ANTAGONISTS
Pharmacotherapeutics:

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:

Cimetidine inhibits metabolism of ethyl

alcohol in the stomach resulting in higher
blood alcohol levels.

Adverse reactions:

Headache, diarrhea, and rash

Prevention of ulcers in NSAID

Users

*
*

* 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

ANTACIDS

Over-the-counter medications that include:

Magnesium hydroxide and aluminum
hydroxide
Sodium bicarbonate
Calcium carbonate
Simethicone

ANTACIDS
Pharmacokinetics:

Work locally in the stomach by neutralizing

gastric acid.
Distributed throughout the GI tract; eliminated
primarily in the feces.

Pharmacodynamics:

Reduce the total amount of acid in the GI tract.

ANTACIDS
Pharmacotherapeutics:

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:

All antacids can interfere with the

absorption of oral drugs given at the same
time.

Adverse reactions:

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

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
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