Antiulcer Drugs

This chapter discusses drugs used to

prevent and treat peptic ulcers, both
gastric and duodenal. These drugs
include tranquilizers, anticholinergics,
antacids, histamine2 blockers, proton
pump inhibitors (PPIs), a pepsin
inhibitor, and a prostaglandin analogue
antiulcer drug.
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Peptic ulcer is a broad term for an ulcer or erosion
that occurs in the esophagus, stomach, or duodenum
within the upper gastrointestinal (GI) tract. Ulcers are
more specifically named according to the site of
involvement: esophageal, gastric, or duodenal.
Duodenal ulcers occur 10 times more frequently than
gastric and esophageal ulcers. The release of
hydrochloric acid (HCl) from the parietal cells of the
stomach is influenced by histamine, gastrin, and
acetylcholine. Peptic ulcers occur when there is a
hypersecretion of HCl and pepsin, which erode the GI
mucosal lining.
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The gastric secretions in the stomach strive to
maintain a pH of 2 to 5. Pepsin, a digestive enzyme, is
activated at a pH of 2, and the acidpepsin complex of
gastric secretions can cause mucosal damage. If the
pH of gastric secretions increases to 5, the activity of
pepsin declines. The gastric mucosal barrier (GMB) is
a thick, viscous, mucous material that provides a
barrier between the mucosal lining and acidic gastric
secretions.

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An esophageal ulcer results from reflux of acidic
gastric secretions into the esophagus as a result of a
defective or incompetent cardiac sphincter. A gastric
ulcer frequently occurs because of a breakdown of the
GMB. A duodenal ulcer is caused by hypersecretion of
acid from the stomach passing into the duodenum
because of (1) insufficient buffers to neutralize gastric
acid in the stomach, (2) a defective or incompetent
pyloric sphincter, or (3) hypermotility of the stomach.
Gastroesophageal reflux disease (GERD) is
inflammation or erosion of the esophageal mucosa
caused by a reflux of gastric acid content from the
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stomach into the esophagus
 Predisposing Factors in
Peptic Ulcer Disease
The nurse needs to assist the patient in
identifying possible causes of the ulcer and

1 to teach ways to alleviate it. Predisposing

factors include mechanical disturbances,
genetic influences, bacterial organisms,
environmental factors, and certain drugs.
Healing of an ulcer takes 4 to 8 weeks.
Complications can occur as the result of
scar tissue.
“
Helicobacter pylori
Helicobacter pylori, a gram-negative bacillus, is
linked with the development of peptic ulcer and is
known to cause gastritis, gastric ulcer, and
duodenal ulcer. When a peptic ulcer recurs after
antiulcer therapy, and the ulcer is not caused by
nonsteroidal antiinflammatory drugs (NSAIDs)
such as aspirin or ibuprofen, the patient should be
tested for the presence of H. pylori, which may
have infected the gastric mucosa. In the past,
endoscopy and a biopsy of the gastric antrum
were needed to check for H. pylori. 7
“
Helicobacter pylori
One of the PPIs, such as omeprazole or
lansoprazole, is frequently used as a component
of combination drug therapy because each
suppresses acid secretion by inhibiting the
enzyme hydrogen or potassium adenosine
triphosphatase (ATPase), which makes gastric
acid. These agents block the final steps of acid
production. If triple therapy fails to eradicate H.
pylori, quadruple therapy using two antibiotics, a
PPI, and a bismuth or histamine2 (H2 ) blocker is
recommended. 8
 Gastroesophageal Reflux Disease GERD

“
also called reflux esophagitis, is an inflammation of
the esophageal mucosa caused by reflux of gastric
acid content into the esophagus. Its main cause is
an incompetent lower esophageal sphincter.
Smoking tends to accelerate the disease process.
Medical treatment for GERD is similar to the
treatment for peptic ulcers. This includes use of the
common antiulcer drugs to neutralize gastric
contents and reduce gastric acid secretion. Drugs
used in treatment include H2 blockers such as
famotidine and PPIs such as omeprazole,
lansoprazole, rabeprazole, pantoprazole, or 9
 Nonpharmacologic Measures for Managing
Peptic Ulcer and Gastroesophageal Reflux
Disease
• Nonpharmacologic measures, along
with drug therapy, are an important
part of treatment for a GI disorder.
Once the GI problem is resolved, the
patient should continue to follow
nonpharmacologic measures to
avoid recurrence of the condition.
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 Nonpharmacologic Measures for Managing
Peptic Ulcer and Gastroesophageal Reflux
Disease
• Avoiding tobacco and alcohol can decrease
gastric secretions. With GERD, nicotine
relaxes the lower esophageal sphincter,
permitting gastric reflux. Obesity enhances
GERD, so weight loss is helpful in decreasing
symptoms.

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 Nonpharmacologic Measures for Managing
Peptic Ulcer and Gastroesophageal Reflux
Disease
• The patient should avoid hot, spicy, and
greasy foods, which could aggravate the
gastric problem. Certain drugs like NSAIDs,
which include aspirin, should be taken with
food or in a decreased dosage.
Glucocorticoids can cause gastric ulceration
and should be taken with food. To relieve
symptoms of GERD, the patient should raise
the head of the bed, not eat before bedtime,
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and wear loose-fitting clothing
 Antiulcer Drugs
The seven groups of antiulcer agents are (1)
tranquilizers, which decrease vagal activity; (2)
anticholinergics, which decrease acetylcholine by
blocking the cholinergic receptors; (3) antacids, which
neutralize gastric acid; (4) H2 blockers, which block the
H2 receptor; (5) PPIs, which inhibit gastric acid
secretion, regardless of acetylcholine or histamine
release; (6) the pepsin inhibitor sucralfate; and (7) the
prostaglandin E1 analogue misoprostol, which inhibits
gastric acid secretion and protects the mucosa.
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 Tranquilizers
Tranquilizers have minimal effect in
preventing and treating ulcers; however,
they reduce vagal stimulation and
decrease anxiety. A combination of the
anxiolytic chlordiazepoxide and the
anticholinergic clidinium bromide may be
used in the treatment of ulcers. Adverse
effects may include edema, ataxia,
confusion, and agranulocytosis.
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 Anticholinergics
These drugs relieve pain by decreasing
GI motility and secretion. They act by
inhibiting acetylcholine and blocking
histamine and HCl. Anticholinergics delay
gastric emptying time, so they are used
more frequently for duodenal ulcers than
for gastric ulcers.

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 Anticholinergics
The anticholinergic propantheline bromide
inhibits gastric secretions in the treatment
of peptic ulcers. Anticholinergics should be
taken 30 minutes to 1 hour before meals
and at least 2 hours after the evening meal
for the bedtime dose to decrease acid
secretion that occurs with eating. Antacids
can slow the absorption of anticholinergics
and therefore should be taken 2 hours after
anticholinergic administration 16
 Antacids
Antacids promote ulcer healing by
neutralizing HCl and reducing pepsin
activity; they do not coat the ulcer. There are
two types of antacids: those that have a
systemic effect and those that have a
nonsystemic effect.

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 Antacids
Sodium bicarbonate, a systemically absorbed antacid,
was one of the first antiulcer drugs. Because it has
many side effects (sodium excess, causing
hypernatremia and water retention; metabolic alkalosis
caused by excess bicarbonate; and acid rebound
[excess acid secretion]), sodium bicarbonate is seldom
used to treat peptic ulcers.

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 Antacids
Calcium carbonate is most effective in
neutralizing acid; however, one-third to one-
half of the drug can be systemically
absorbed and can cause acid rebound.
Hypercalcemia and Burnett Syndrome.

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 Histamine2 Blockers
The histamine2 (H2) receptor antagonists,
or H2 blockers, are popular drugs used in
the treatment of gastric and duodenal
ulcers. Histamine2 blockers prevent acid
reflux in the esophagus (reflux esophagitis).
These drugs block the H2 receptors of the
parietal cells in the stomach thus reducing
gastric acid secretion and concentration.
Antihistamines used to treat allergic
conditions act against histamine1 (H1 ); they
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are not the same as H2 blockers.
 Histamine2 Blockers
Two H2 blockers—famotidine and
nizatidine—are more potent than cimetidine.
In addition to blocking gastric acid
secretions, they promote healing of the ulcer
by eliminating its cause. Their duration of
action is longer, decreasing the frequency of
dosing, and they have fewer side effects and
fewer drug interactions than cimetidine.
Prototype Drug Chart: Famotidine lists the
pharmacological data for famotidine, which
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is a frequently prescribed H2 blocker.
Proton Pump Inhibitors (Gastric
Acid Secretion Inhibitors, Gastric
Acid Pump Inhibitors)
PPIs suppress gastric acid secretion by
inhibiting the hydrogen/potassium ATPase
enzyme system located in the gastric
parietal cells. They tend to inhibit gastric
acid secretion up to 90% more than the H2
blockers (histamine antagonists). These
agents block the final step of acid
production.

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 Proton Pump Inhibitors (Gastric
Acid Secretion Inhibitors, Gastric
Acid Pump Inhibitors)
Omeprazole was the first PPI marketed, followed by
lansoprazole, rabeprazole, pantoprazole, esomeprazole, and
dexlansoprazole, a delayed-release oral capsule. These agents
are effective in suppressing gastric acid secretions and are
used to treat peptic ulcers and GERD. With lansoprazole, ulcer
relief usually occurs in 1 week. Rabeprazole is more effective
in treating duodenal ulcers than gastric ulcers, but it is most
effective for treating GERD and hypersecretory disease
(ZollingerEllison syndrome). Pantoprazole is prescribed to
treat short-term erosive GERD. Intravenous (IV) pantoprazole
is also reported as effective in treating Zollinger-Ellison
syndrome. 23
 Pepsin Inhibitors (Mucosal
Protective Drugs)
Sucralfate, a complex of sulfated sucrose and
aluminum hydroxide, is classified as a pepsin
inhibitor, or mucosal protective drug. It is
nonabsorbable and combines with protein to form
a viscous substance that covers the ulcer and
protects it from acid and pepsin. This drug does
not neutralize acid or decrease acid secretions.

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 Pepsin Inhibitors (Mucosal
Protective Drugs)
The dosage of sucralfate is 1 g, usually four times a day
before meals and at bedtime. If antacids are added to
decrease pain, they should be given either 30 minutes
before or 30 minutes after the administration of
sucralfate. Because sucralfate is not systemically
absorbed, side effects are few; however, it can cause
dry mouth, headache, drowsiness, dizziness, and
constipation.

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 Prostaglandin Analogue
Antiulcer Drug
Misoprostol, a synthetic prostaglandin analogue, is a
drug used to prevent and treat peptic ulcer. It appears
to suppress gastric acid secretion and to increase
cytoprotective mucus in the GI tract. It causes a
moderate decrease in pepsin secretion. Misoprostol is
considered as effective as cimetidine. Patients who
complain of gastric distress from NSAIDs such as
aspirin or indomethacin prescribed for long-term
therapy can benefit from misoprostol.

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THANKS!
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