UNIT 06: DRUGS ACTING ON THE

GASTROINTESTINAL SYSTEM

DRUGS AFFECTING GASTROINTESTINAL SECRETIONS

DRUGS USED TO TREAT Antacids omeprazole DRUGS USED TO
GASTROESOPHAGEAL aluminum salts pantoprazole TREAT DIGESTIVE
REFLUX DISEASE AND calcium salts rabeprazole ENZYME
ULCER DISEASE magaldrate DYSFUNCTION
Gl Protectant
magnesium salts pancrelipase
Histamine- 2 Antagonists sucralfate
sodium bicarbonate saliva substitute
cimetidine
Prostaglandin
famotidine Proton Pump Inhibitors
misoprostol
nizatidine dexlansoprazole
ranitidine esomeprazole
lansoprazole

DRUGS USED TO TREAT GASTROESOPHAGEAL 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.

Histamine-2 Antagonists
Therapeutic Actions

The H2 antagonists selectively block H2 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 histamine receptors), ultimately blocking the production of hydrochloric acid. Also
decreases pepsin production by the chief cells. H2 receptor sites are also found in the heart, and
high levels of these drugs can produce cardiac arrhythmias.

Indications
 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)
 Prophylaxis of stress-induced ulcers and acute upper GI bleeding in critical patients (blocking the
production of acid protects the stomach lining, which is at risk because of decreased mucus production
associated with extreme stress)
 Treatment of erosive gastroesophageal reflux (decreasing the acid being regurgitated into the esophagus
will promote healing and decrease pain)
 Relief of symptoms of heartburn, acid indigestion, and sour stomach (over-the-counter preparations)

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Adverse Effects
GI effects of diarrhea or constipation; central nervous system (CNS) effects of dizziness, headache, somnolence,
confusion, or even hallucinations (thought to be related to possible H2 receptor effects in the CNS); cardiac
arrhythmias and hypotension (related to H2 cardiac receptor blocking; more commonly seen with intravenous or
intramuscular administration or with prolonged use); and gynecomastia (more common with long-term use of
cimetidine) and impotence.

Antacids
A group of inorganic chemicals that neutralize stomach acid.

Therapeutic Actions

Antacids neutralize stomach acid by direct chemical reaction.

Indications

 For the symptomatic relief of upset stomach associated with hyperacidity

 For the symptomatic relief of the hyperacidity associated with peptic ulcer, gastritis, peptic
esophagitis, gastric hyperacidity, and hiatal hernia
 Treatment of hyperphosphatemia
 Prevention of formation of phosphate urinary stones
 Relief of constipation

Adverse Effects

Acid–base and electrolyte imbalance, and acid rebound. Alkalosis with resultant metabolic
changes (nausea, vomiting, neuromuscular changes, headache, irritability, muscle twitching, and
even coma) may occur. The use of calcium salts may lead to hypercalcemia and milk-alkali
syndrome (seen as alkalosis, renal calcium deposits, or severe electrolyte disorders). Constipation
or diarrhea may result, depending on the antacid being used. Hypophosphatemia can occur with
the use of aluminum salts. Finally, fluid retention and heart failure can occur with sodium
bicarbonate because of its high sodium content.

Proton Pump Inhibitors

Therapeutic Actions

The gastric acid pump or proton pump inhibitors suppress gastric acid secretion by specifically
inhibiting the hydrogen–potassium adenosine triphosphatase (H+, K+- ATPase) enzyme system on
the secretory surface of the gastric parietal cells. This action blocks the final step of acid production,
lowering the acid levels in the stomach

Indications

 Short-term treatment of active duodenal ulcers

 Short-term treatment of GERD, erosive esophagitis, and benign active gastric ulcer
 For the long-term treatment of pathological hypersecretory conditions

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  As maintenance therapy for healing of erosive esophagitis and ulcers
 In combination with amoxicillin and clarithromycin for the treatment of H. pylori infection
 Relief of heartburn symptoms

Adverse Effects

Asthenia (loss of strength), vertigo, insomnia, apathy, and dream abnormalities may also be
observed. GI effects can include diarrhea, abdominal pain, nausea, vomiting, dry mouth, and
tongue atrophy. Upper respiratory tract symptoms, including cough, stuffy nose, hoarseness, and
epistaxis, are frequently seen. Other, less common adverse effects include rash, alopecia, pruritus,
dry skin, back pain, and fever. In preclinical studies, long-term effects of proton pump inhibitors
included the development of gastric cancer. Recent studies show an increase in bone loss in
patients using these drugs long term.

GI Protectant
Therapeutic Actions

Sucralfate forms an ulcer-adherent complex at duodenal ulcer sites, protecting the sites against
acid, pepsin, and bile salts.
Indications

 Short-term treatment of duodenal ulcers

 Maintenance of duodenal ulcers (at reduced dose) after healing in adults
 treatment of oral and esophageal ulcers due to radiation, chemotherapy, or sclerotherapy
 currently under investigation for treatment of gastric ulcers, gastric damage induced by
nonsteroidal anti-inflammatory drugs (NSAIDs)
 Prevention of stress ulcers in acutely ill individuals

Adverse Effects

Constipation is the most frequently seen adverse effect. Diarrhea, nausea, indigestion, gastric
discomfort, and dry mouth may also occur. Other adverse effects that have been reported with this
drug include dizziness, sleepiness, vertigo, skin rash, and back pain.

Prostaglandin
Therapeutic Actions

Prostaglandin E1 inhibits gastric acid secretion and increases bicarbonate and mucous production
in the stomach, thus protecting the stomach lining.

Indications

 Used to prevent NSAID-induced gastric ulcers in patients who are at high risk for
complications from a gastric ulcer (e.g., elderly or debilitated patients, patients with a past
history of ulcer)
 used in combination therapy with mifepristone as an abortifacient

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 Adverse Effects

GI effects—nausea, diarrhea, abdominal pain, flatulence, vomiting, dyspepsia, and constipation.

Genitourinary effects, which are related to the actions of prostaglandins on the uterus, include
miscarriages, excessive bleeding, spotting, cramping, hypermenorrhea, dysmenorrhea, and other
menstrual disorders. Women taking this drug should be notified, both in writing and verbally,
of these potential effects of this drug.

DIGESTIVE ENZYMES
Therapeutic Actions

Saliva substitute contains electrolytes and carboxymethylcellulose to act as a thickening agent in

dry mouth conditions. This makes the food bolus easier to swallow and begins the early digestion
process. Saliva substitute helps in conditions that result in dry mouth—stroke, radiation therapy,
chemotherapy, and other illnesses. The pancreatic enzymes are replacement enzymes that help the
digestion and absorption of fats, proteins, and carbohydrates.

Indications

 Aids digestion and absorption of fats, proteins, and carbohydrates in conditions that result
in a lack of this enzyme
 used as replacement therapy in patients with cystic fibrosis, chronic ductal obstruction,
pancreatic insufficiency, steatorrhea, or malabsorption syndrome and after pancreatectomy
or gastrectomy
 Aids in conditions resulting in dry mouth—stroke, radiation therapy, chemotherapy, and
other illnesses

Adverse Effects

Complications from abnormal electrolyte absorption, such as increased levels of magnesium,

sodium, or potassium. The adverse effects that most often occur with pancreatic enzymes are
related to GI irritation and include nausea, abdominal cramps, and diarrhea.

DRUGS AFFECTING GASTROINTESTINAL MOTILITY

LAXATIVES magnesium hydroxide Other Laxatives ANTIDIARRHEALS
Chemical Stimulants
magnesium sulfate lubiprostone bismuth subsalicylate
polycarbophil methylnaltrexone loperamide
bisacodyl
polyethylene glycol - opium derivatives
cascara
electrolyte solution GASTROINTESTINAL
castor oil
psyllium STIMULANTS IRRITABLE BOWEL
senna
Lubricants dexpanthenol SYNDROME DRUGS
Bulk Stimulants metoclopramide alosetron
docusate
lactulose tegaserod
glycerin
magnesium citrate hyoscyamine
( mineral oil

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 LAXATIVES
Laxative, or cathartic, drugs are indicated for the short-term relief of constipation; to prevent
straining when it is clinically undesirable (such as after surgery, myocardial infarction, or
obstetrical delivery); to evacuate the bowel for diagnostic procedures; to remove ingested poisons
from the lower GI tract; and as an adjunct in anthelmintic therapy when it is desirable to flush
helminths from the GI tract.

Chemical Stimulants
Therapeutic Actions

All of these agents begin working at the beginning of the small intestine and increase motility
throughout the rest of the GI tract by irritating the nerve plexus.

Indications

 Emptying of the gastrointestinal (GI) tract before some surgeries or diagnostic tests (e.g.,
barium enema)
 Prevention of constipation and straining after GI surgery, myocardial infarction (MI),
obstetrical delivery
 Short-term treatment of constipation
 Evacuation of the large intestine for diagnostic examination

Adverse Effects

Diarrhea, abdominal cramping, and nausea. Dizziness, headache, and weakness, are not uncommon
and may relate to loss of fluid and electrolyte imbalances that may accompany laxative use.
Sweating, palpitations, flushing, and even fainting have been reported after laxative use. A very
common adverse effect that is seen with frequent laxative use or laxative abuse is cathartic
dependence. This reaction occurs when patients use laxatives over a long period of time and the GI
tract becomes dependent on the vigorous stimulation of the laxative. Without this stimulation, the
GI tract does not move for a period of time (i.e., several days), which could lead to constipation and
drying of the stool and ultimately to impaction. Castor oil blocks absorption of fats (including fat-
soluble vitamins) and may lead to constipation from GI tract exhaustion when there is no stimulus
to movement.

Bulk Stimulants
Bulk stimulants (also called mechanical stimulants) are rapid-acting, aggressive laxatives that
cause the fecal matter to increase in bulk.

Therapeutic Actions

Bulk stimulants increase the motility of the GI tract by increasing the fluid in the intestinal contents,
which enlarges bulk, stimulates local stretch receptors, and activates local activity.

Indications

 Same as chemical stimulants

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 Adverse Effects

GI effects such as diarrhea, abdominal cramping, and nausea. CNS effects, including dizziness,
headache, and weakness, are not uncommon and may relate to loss of fluid and electrolyte
imbalances that may accompany laxative use. Sweating, palpitations, flushing, and even fainting
have been reported after laxative use. These effects may be related to a sympathetic stress reaction
to intense neurostimulation of the GI tract or to the loss of fluid and electrolyte imbalance. Patients
must use caution and take bulk laxatives with plenty of water. If only a little water is used, the
laxative may absorb enough fluid in the esophagus to swell into a gelatin-like mass that can
obstruct the esophagus and cause severe problems.

Lubricants
Sometimes it is desirable to make defecation easier without stimulating the movement of the GI
tract. This is done using lubricants. Patients with hemorrhoids and those who have recently had
rectal surgery may need lubrication of the stool.

Therapeutic Actions

Docusate has a detergent action on the surface of the intestinal bolus, increasing the admixture of
fat and water and making a softer stool. Glycerin is a hyperosmolar laxative that is used in
suppository form to gently evacuate the rectum without systemic effects higher in the GI tract.
Mineral oil is the oldest of these laxatives. It is not absorbed and forms a slippery coat on the
contents of the intestinal tract. When the intestinal bolus is coated with mineral oil, less water is
absorbed out of the bolus, and the bolus is less likely to become hard or impacted.

Indications

 Same as stimulants but preferred for patients with hemorrhoids and those who have
recently had rectal surgery

Adverse Effects

GI effects such as diarrhea, abdominal cramping, and nausea. In addition, leakage and staining may
be a problem when mineral oil is used and the stool cannot be retained by the external
sphincter. CNS effects, including dizziness, headache, and weakness, are not uncommon and may
relate to loss of fluid and electrolyte imbalances that may accompany laxative use. Sweating,
palpitations, flushing, and even fainting have been reported after laxative use. These effects are less
likely to happen with the lubricant laxatives than with the chemical or mechanical stimulants.

GASTROINTESTINAL STIMULANTS
Some drugs are available for more generalized GI stimulation that results in an overall increase in
GI activity and secretions. These drugs stimulate parasympathetic activity or make the GI tissues
more sensitive to parasympathetic activity.

Therapeutic Actions

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By stimulating parasympathetic activity within the GI tract, these drugs increase GI secretions and
motility on a general level throughout the tract. Metoclopramide works by blocking dopamine
receptors and making the GI cells more sensitive to acetylcholine, which leads to increased GI
activity and rapid movement of food through the upper GI tract. Metoclopramide is also being
studied for improvement of lactation. Dexpanthenol works by increasing acetylcholine levels and
stimulating the parasympathetic system.

Indications

 Relief of symptoms of gastroesophageal reflux disease

 Prevention of intestinal atony
 Prevention of nausea and vomiting after emetogenic chemotherapy or postoperatively
 Relief of symptoms of diabetic gastroparesis
 Promotion of gastrointestinal movement during small bowel intubation or promotion of
rapid movement of barium
 Currently under investigation for improvement of lactation

Adverse Effects

Nausea, vomiting, diarrhea, intestinal spasm, and cramping. Other adverse effects, such as
declining blood pressure and heart rate, weakness, and fatigue, may be related to
parasympathetic stimulation, extrapyramidal effects, and Parkinson-like syndrome.

ANTIDIARRHEALS
Antidiarrheals block stimulation of the GI tract for symptomatic relief from diarrhea.

Therapeutic Actions

Antidiarrheal agents slow the motility of the GI tract through direct action on the lining of the GI
tract to inhibit local reflexes (bismuth subsalicylate), through direct action on the muscles of the GI
tract to slow activity (loperamide), or through action on CNS centers that cause GI spasm and
slowing (opium derivatives).

Indications

 Relief of symptoms of acute and chronic diarrhea

 Prevention of reduction of volume of discharge from ileostomies
 Prevention and treatment of traveler’s diarrhea
 Preventing cramping and distention associated with dietary excess and some viral
infections

Adverse Effects

Constipation, distention, abdominal discomfort, nausea, vomiting, dry mouth, and even toxic
megacolon, are related to their effects on the GI tract. Other adverse effects that have been reported
include fatigue, weakness, dizziness, and skin rash. Opium derivatives are also associated with
lightheadedness, sedation, euphoria, hallucinations, and respiratory depression related to effect
on the opioid receptors.

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 IRRITABLE BOWEL SYNDROME DRUGS
The disorder is characterized by abdominal distress, bouts of diarrhea or constipation, bloating,
nausea, flatulence, headache, fatigue, depression, and anxiety. Underlying causes might be stress
related.

ANTIEMETIC AGENTS
ANTIEMETIC AGENTS Anticholinergics/ ondansetron Miscellaneous
Antihistamines palonosetron Agents
Phenothiazines
buclizine dronabinol
chlorpromazine Substance PI
cyclizine hydroxyzine
perphenazine Neurokinin
meclizine nabilone
prochlorperazine 1 Receptor
trimethobenzamide
promethazine 5- HT3 Receptor Blockers Antagonist
dolasetron aprepitant
Nonphenothiazine
metoclopramide
granisetron

One of the most common and most uncomfortable complaints encountered in clinical practice is
that of nausea and vomiting. Drugs used in managing nausea and vomiting are called antiemetics.
All of them work by reducing the hyperactivity of the vomiting reflex in one of two ways: locally, to
decrease the local response to stimuli that are being sent to the medulla to induce vomiting, or
centrally, to block the chemoreceptor trigger zone (CTZ) or suppress the vomiting center
directly.

Phenothiazines
Therapeutic Actions

Phenothiazines are centrally acting antiemetics that change the responsiveness or stimulation of
the CTZ in the medulla.

Indications

 Treatment of nausea and vomiting, including that specifically associated with anesthesia
 Treatment of severe vomiting
 Treatment of intractable hiccoughs, which occur with repetitive stimulation of the
diaphragm and lead to persistent diaphragm spasm

Adverse Effects

Drowsiness, dizziness, weakness, tremor, and headache are common adverse effects. Other, not
uncommon adverse effects include hypotension, hypertension, and cardiac arrhythmias.
Autonomic effects such as dry mouth, nasal congestion, anorexia, pallor, sweating, and urinary
retention often occur with phenothiazines. Patients should be cautioned that their urine may be
tinged pink to red-brown. This is a drug effect but can cause concern if the patient is not expecting
it. Endocrine effects such as menstrual disorders, galactorrhea, and gynecomastia have been
reported with phenothiazine use. Photosensitivity (increased sensitivity to the sun and ultraviolet

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light) is a common adverse reaction with these antiemetics. Patients should be advised to use
sunscreens and protective garments if exposure cannot be avoided.

Nonphenothiazine
The only nonphenothiazine currently available for use as an antiemetic is metoclopramide, which
acts to reduce the responsiveness of the nerve cells in the CTZ to circulating chemicals that induce
vomiting.

Refer to metoclopramide in previous chapters

Anticholinergics/Antihistamines
These drugs are anticholinergics that act as antihistamines and block the transmission of impulses
to the CTZ.

Refer to antihistamines in previous chapters

5-HT3 Receptor Blockers

Therapeutic Actions

The 5-HT3 receptor blockers block those receptors associated with nausea and vomiting in the CTZ
and locally.

Indications

 Treatment of severe nausea and vomiting associated with emetogenic chemotherapy,

radiation therapy, postoperative situations

Adverse Effects

Headache, dizziness, and myalgia related to their CNS effects. Pain at the injection site, rash,
constipation, hypotension, and urinary retention have also been reported.

Substance P/Neurokinin 1 Receptor Antagonist

Therapeutic Actions

It acts directly in the CNS to block receptors associated with nausea and vomiting with little to no
effect on serotonin, dopamine, or corticosteroid receptors.
Indications

 Treating the nausea and vomiting associated with highly emetogenic antineoplastic
chemotherapy

Adverse Effects

GI effects of diarrhea, constipation, and gastritis, nausea; anorexia; headache; and fatigue.

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