C H A P T E R 5 7
Drugs affecting gastrointestinal secretions
897
G
astrointestinal (GI) disorders are among the most
common complaints seen in clinical practice. Many
products are available for the self-treatment of upset
stomach, heartburn or dyspepsia. The underlying causes
of these disorders can range from dietary excess, stress,
hiatus hernia, oesophageal reflux and adverse drug
effects to the more serious peptic ulcer disease. This
chapter addresses the major conditions often requir-
ing drug therapy: peptic ulcer disease and disorders
involving increased acid levels and digestive enzyme dys-
function (Box 57.1).
DRUGS USED TO TREAT GASTRO-
OESOPHAGEAL REFLUX DISEASE AND
ULCER DISEASE
Drugs typically used to affect GI secretions in treating
peptic ulcer disease and disorders involving increased GI
acid work to decrease GI secretory activity, block the
action of GI secretions, or form protective coverings
on the GI lining to prevent erosion from GI secretions.
Recent research studies have begun questioning the
effects that lowering acid levels might have on the home-
ostasis of the GI system and on total body homeostasis,
including calcium levels (see Box 57.2).
The drugs used to treat gastro-oesophageal reflux
disease (GORD) and ulcer disease include Histamine-2
(H
2
) antagonists, which block the release of hydrochlo-
ric acid in response to gastrin; antacids, which interact
with acids at the chemical level to neutralise them;
proton pump inhibitors, which suppress the secretion
of hydrochloric acid into the lumen of the stomach; GI
protectants, which coat any injured area in the stomach
to prevent further injury from acid; and prostaglandins,
which inhibit the secretion of gastrin and increase the
secretion of the mucus lining of the stomach, provid-
ing a buffer. Figure 57.1 depicts sites of actions of these
drugs used to treat GORD and ulcer disease. Box 57.3
highlights important considerations related to use of
these drugs across the lifespan.
H
istamine
-2
antagonists
Histamine-2 (H
2
) antagonists
(Table 57.1) block the
release of hydrochloric acid in response to gastrin. These
drugs include cimetidine (
Tagamet
), ranitidine (
Zantac
),
famotidine (
Pepcidine
) and nizatidine (
Nizac, Tazac
).
Therapeutic actions and indications
The H
2
antagonists selectively block H
2
receptors
located on the parietal cells. Blocking these receptors
prevents the release of gastrin, a hormone that causes
local release of histamine (due to stimulation of hista-
mine receptors), ultimately blocking the production of
hydrochloric acid. This action also decreases pepsin
production by the chief cells. H
2
receptor sites are also
found in the heart, and high levels of these drugs can
produce cardiac arrhythmias (see Adverse effects).
These drugs are used in the following conditions:
• Short-term treatment of active duodenal ulcer or
benign gastric ulcer (reduction in the overall acid level
can promote healing and decrease discomfort).
• Treatment of pathological hypersecretory conditions
such as Zollinger–Ellison syndrome (blocking the
overproduction of hydrochloric acid that is associated
with these conditions).
ULCER DISEASE
Erosions in the lining of the stomach and adjacent areas
of the GI tract are called
peptic ulcers
. People with
ulcers present with a predictable description of gnawing,
burning pain often occurring a few hours after meals.
Many of the drugs that are used to affect GI secretions
are designed to prevent, treat or aid in the healing of
these ulcers. The cause of chronic peptic ulcers is not
completely understood. For many years, it was believed
that ulcers were caused by excessive acid production, and
treatment was aimed at neutralising acid or blocking the
parasympathetic system to decrease normal GI activity
and secretions. Further research led many to believe that,
because acid production was often normal in people with
ulcers, ulcers were caused by a defect in the mucus lining
that coats the inner lumen of the stomach to protect it
from acid and digestive enzymes. Treatment was aimed
at improving the balance between the acid produced
and the mucus layer that protects the stomach lining.
Currently it is believed that chronic ulcers may also be
the result of infection by
Helicobacter pylori
bacteria.
Combination antibiotics have been found to be quite
effective in treating some people with chronic ulcers.
Acute ulcers, or “stress ulcers”, are often seen in
situations that involve acute physiological stress, such
as trauma, burns or prolonged illness. The activity of
the sympathetic nervous system during stress decreases
blood flow to the GI tract, leading to weakening of the
mucosal layer of the stomach and erosion by acid in
the stomach. Many of the drugs available for treating
various peptic ulcers act to alter acid-producing activities
of the stomach.
DIGESTIVE ENZYME DYSFUNCTION
Some people require a supplement to the production of
digestive enzymes. People with strokes, salivary gland
disorders, or extreme surgery of the head and neck may
not be able to produce saliva. Saliva is important in
beginning the digestion of sugars and proteins and is
essential in initiating the swallowing reflex. People with
common duct problems, pancreatic disease or cystic
fibrosis may not be able to produce or secrete pancreatic
enzymes. These enzymes may need to be administered to
allow normal digestion and absorption of nutrients.
■■
BOX 57.1
Major conditions for using drugs that
affect GI secretions
