UNIT III

Drugs Affecting the Gastrointestinal System

By: Muhammad Aurangzeb

Lecturer-INS/KMU
 Objectives

In this unit, learners will be able to:

• Discuss common symptoms/disorders for which gastrointestinal
drugs are used
• Explain drugs affecting gastrointestinal system, their mechanism
of action, indications
• Identify the expected and adverse reactions of gastrointestinal
drugs
• Discuss the nursing responsibility related to gastrointestinal
drugs
• Calculate the drugs dosage accurately.
The Gastrointestinal Tract
 Glands of the Stomach

• Cardiac: they primarily secrete mucus

• Pyloric: They secrete gastrin produced by their G
cells, also secrete mucus
• Gastric*gland secrete hydrochloric acid (HCl)
and intrinsic factor

* The cells of the gastric gland are the largest in

number and of primary importance when discussing
acid control
 Cells of the Gastric Gland

• Parietal cells
– Produce and secrete HCl
– Primary site of action for many acid-controller
drugs
 Hydrochloric Acid (HCl)

• Secreted by the parietal cells when stimulated by

food
• Maintains stomach at pH of 1 to 4
• Secretion also stimulated by:
– Large fatty meals
– Excessive amounts of alcohol
– Emotional stress
 Cells of the Gastric Gland (cont'd)

• Chief cells
– Secrete pepsinogen, a proenzyme
– Pepsinogen becomes pepsin when activated by
exposure to acid
– Pepsin breaks down proteins (proteolytic)
 Cells of the Gastric Gland (cont'd)

• Mucoid cells
– Mucus-secreting cells (surface epithelial cells)
– Provide a protective mucous coat
– Protect against self-digestion by HCl
Stomach Lining Basics
Gastric Gland
 Gastric Mucosal Barrier

•Surface mucosa cells in the pyloric region secrete a thick, alkaline-rich mucus that protects the
epithelium of the stomach and duodenum from harsh acid conditions of the lumen.

•This is known as the gastric mucosal barrier.

•This protective mucus barrier can be damaged by infection, certain drugs, and aspirin.
 Gastric Acid Secretion
• Parietal cells in the stomach secrete hydrochloric acid. Acid in the
stomach functions to kill bacteria, and to aid digestion by
solubilizing food. The acid is also important to establish the
optimal pH (between 1-4) for the function of the digestive
enzyme pepsin.
• A key protein for acid secretion is the H+/K+-ATPase (or proton
pump). This protein, which is present on membrane of parietal
cells, uses the energy derived from ATP hydrolysis to pump
hydrogen ions into the lumen in exchange for potassium ions.
• Acetylcholine is a neurotransmitter that is released by enteric
neurons. Histamine is a paracrine that is released from
ECL (enterochromaffin-like) cells. Gastrin is a hormone that is
released by G cells located in the gastric
epithelium. Somatostatin is also secreted by endocrine cells of the
gastric epithelium; it can act as either a paracrine or a hormone.
 Cont…
• Gastric acid secretion by parietal cells of the gastric
mucosa is stimulated by acetylcholine, histamine, and
gastrin
• The receptor-mediated binding of acetylcholine,
histamine, or gastrin results in the activation of
protein kinases, which stimulates the H+/K+–
adenosine triphosphatase (ATPase) proton pump to
secrete hydrogen ions in exchange for K+ into the
lumen of the stomach
• Receptor binding of prostaglandin E2 and somatostatin
diminish gastric acid production
• Histamine binding causes activation of adenylyl cyclase,
whereas binding of prostaglandin E2 inhibits it
• Gastrin and acetylcholine act by inducing an increase in
intracellular calcium levels
 Acid-Related Diseases

• Most common: hyperacidity

• Clients report symptoms of overproduction of HCl by
the parietal cells as indigestion, sour stomach,
heartburn, acid stomach
 Acid-Related Diseases (cont'd)

• PUD: peptic ulcer disease

• GERD: gastroesophageal reflux disease
• Helicobacter pylori (H. pylori)
– Bacterium found in GI tract of 90% of patients
with duodenal ulcers, and 70% of those with
gastric ulcers
– Combination therapy is used most often to
eradicate H. pylori
 Gastrointestinal Disorders

• Gastroesophageal Reflux Disease (GERD)

• Peptic Ulcer Disease (PUD)
• Nausea
• Emesis/ vomiting
• Diarrhea
• Constipation
 Gastro Intestinal Drugs

•Drugs used for:

1)Peptic ulcers and gastro-esophageal reflux

disease (GERD)

2) Nausea/vomiting especially Chemotherapy-

induced emesis

3) Diarrhea

4) Constipation
 Peptic Ulcer Disease
• Peptic ulcer disease (PUD) means the sore in the lining of
the stomach and the duodenum. An ulcer in the stomach is
known as a gastric ulcer while that in the first part of the
intestines is known as a duodenal ulcer.
Symptoms
• Burning pain in the stomach
• Nausea or vomiting
• Weight loss
• Anemia
• Malena ( the condition in which the stool color becomes
black )
• Loss of appetite
 Peptic Ulcer

•Causes of peptic ulcer:

– Infection with gram-negative Helicobacter pylori
– Regular use of non-steroidal anti-inflammatory drugs
(NSAIDs) (aspirin, diclofenac etc.)
– Severe physiologic stress: Stressful conditions that may
cause PUD include burns, central nervous system (CNS)
trauma, surgery, and severe medical illness.
This results in:
• Increased hydrochloric acid secretion
• Inadequate mucosal defense against gastric acid
NSAIDs induce ulcers by suppressing gastric prostaglandin
synthesis, reduction of gastric mucosal blood flow. 

Certain prostaglandins such as PGE2 and PGI2 inhibit gastric

secretion and help protect the stomach mucosa by
stimulating gastric mucus secretion. Currently, only
misoprostol (Cytotec) is available for clinical use.
 Treatment of peptic ulcer

1. Eradicating the H. pylori infection

2. Reducing secretion of gastric acid with the use of
proton pump inhibitors or H2-receptor antagonists
3. Providing agents that protect the gastric mucosa
from damage such as misoprostol and sucralfate
4. Neutralizing gastric acid with non-absorbable
antacids
•Antacids
•Mucosal protective agents
•Proton pump inhibitors
•H2-receptor antagonists
•Prostaglandins
•Antimicrobials
 Drugs which neutralize acid(Antacids):
Antacids attempt to chemically neutralize stomach
acids. These drugs contain a base such as carbonate or
hydroxide combined with aluminum, magnesium, or
calcium. The base combines with excess hydrogen ions
(H) in the stomach and thus increases the pH
 Mechanism of action of Antacids

• They achieve their effects by neutralizing gastric

acid, inhibiting gastric acid secretion or protect
gastric mucosa.
 Indications / Uses of antacids

• Indigestion.
• Reflux esophagitis,
• Pain and burning with peptic ulcer.
• Peptic ulcer.
 Drug which provide a physical barrier
Sucralfate (Ulsanic®)
Bismuth subsalicylate
Cytoprotective compounds
• Enhance mucosal protection mechanisms, preventing
mucosal injury, reducing inflammation, and healing
existing ulcers.
• Sucralfate (Carafate, Sulcrate). Sucralfate is a
disaccharide that exerts a cytoprotective effect on
the stomach mucosa. Sucralfate may form a
protective gel that adheres to ulcers and shields
them from the contents of the stomach.
Bismuth subsalicylate
• Effectively heals peptic ulcers
• Has antimicrobial actions
• Inhibits the activity of pepsin
• Increases secretion of mucus, and interact with necrotic
mucosal tissue to coat and protect the ulcer crater
 Drugs which decrease acid secretion

a. Proton Pump Inhibitors b. H2 receptor blockers

 PPI drugs inhibit the H/K -ATPase enzyme responsible for
secreting acid from gastric parietal cells of the stomach.
Common adverse effects
Headache
Nausea
Diarrhea
Abdominal pain
Fatigue
Dizziness
Constipation

For best results, take a PPI 30 minutes before you eat a heavy meal. This gives
the medication enough time to shut down the acid pumps that cause heartburn.
• Bind to the H+/K+-ATPase enzyme system (proton
pump) of the parietal cell and suppress the secretion
of hydrogen ions into the gastric lumen, inhibiting
gastric acid secretion
• The membrane-bound proton pump is the final step in
the secretion of gastric acid
• More effective than H2 antagonists in suppressing
gastric acid production and healing peptic ulcers
 PPIs are prodrugs with an acid-resistant enteric coating
to protect them from premature degradation by gastric
acid
 The coating is removed in the duodenum, and the
prodrug is absorbed and transported to parietal cells
 There, it is converted to the active form, which forms a
stable covalent bond with H+/K+-ATPase
 It takes about 18 hours for the enzyme to be
resynthesized
 At standard doses, all PPIs inhibit gastric acid
secretion by ~90%
 The superiority of the PPIs over the H2 antagonists
for suppressing acid production and healing peptic
ulcers has made them the preferred drugs for
◦ Stress ulcer treatment and prophylaxis
◦ Treating erosive esophagitis and active duodenal ulcer
◦ Long-term treatment of pathologic hypersecretory
conditions (e.g. Zollinger-Ellison syndrome)
 Approved for the treatment of GERD and have
gained favor over H2 antagonists

 PPIs reduce the risk of bleeding from an ulcer

caused by aspirin and other NSAIDs

 Used with antimicrobial regimens to eradicate H.

pylori
 Mechanism of action of H2 blockers
Histamine stimulates specific receptors on stomach parietal cells
to increase gastric acid secretion. These histamine receptors are
classified as H2 receptors. H2 antagonists, or blockers, prevent
the histamine activated release of gastric acid.
Side effects:
• headache
• nausea
• diarrhea
• abdominal pain
• dizziness,
• Constipation
• Cimetidine has been associated with gynaecomastia (breast
enlargement in men)and anti androgenic properties.
 Peptic ulcer

 Acute stress ulcers

 Gastroesophageal reflux disease (GERD)

 Prostaglandin E, produced by the gastric mucosa,
inhibits secretion of HCl and stimulates
secretion of mucus and bicarbonate
(cytoprotective effect)

 A deficiency of prostaglandins is involved in the

pathogenesis of peptic ulcers
 Misoprostol (Cytotec®)
◦ A stable analog of prostaglandin approved for the
prevention of gastric ulcers induced by NSAIDs
◦ Less effective than H2 antagonists and the PPIs for acute
treatment of peptic ulcers
◦ Has cytoprotective actions, but is clinically effective
only
at higher doses that diminish gastric acid secretion
 Misoprostol
◦ Like other prostaglandins, misoprostol produces uterine
contractions, dislodging of the fetus, and is
contraindicated during pregnancy

◦ Adverse effects: diarrhea and nausea

 Antimicrobial agents (For H. pylori)
• GERD is not associated with H. pylori infection and does not
respond to treatment with antibiotics
• Triple therapy consisting of a PPI combined with either
metronidazole or amoxicillin plus clarithromycin for 2 weeks
◦ (Amoxicillin, omeprazole, clarithromycin)
• Quadruple therapy of bismuth subsalicylate and
metronidazole, tetracycline plus a PPI, administered for a 2-
week course
• Treatment with a single antimicrobial drug is less effective,
results in antimicrobial resistance, and is absolutely not
recommended
 Increased motility of GIT and decreased absorption
of fluid are major factors in diarrhea

 Antidiarrheal drugs used to treat acute diarrhea

include
◦ Antimotility agents
◦ Adsorbents
◦ Agents that modify fluid and electrolyte transport
Antimotility agents
• Diphenoxylate
• Loperamide (Diacare®, Imodium®)
• Both are analogs of meperidine and have opioid-like actions
on the gut
• Activate presynaptic opioid receptors in the enteric nervous
system to inhibit ACh release and decrease peristalsis
• Lack analgesic effects at usual doses
Side effects: drowsiness, abdominal cramps, dizziness
Adsorbents
 Aluminum hydroxide
 Methylcellulose
 Used to control diarrhea
Act by adsorbing intestinal toxins or microorganisms
and/or by coating or protecting the intestinal mucosa
 Much less effective than antimotility agents and
 Can interfere with the absorption of other drugs
Agents that modify fluid and electrolyte transport
• Bismuth subsalicylate
• Used for traveler’s diarrhea
• Decreases fluid secretion in the bowel
• Its action may be due to its salicylate component as
well as its coating action
• Adverse effects may include black tongue and black
stools
 Constipation

Common condition caused by

• Diminished fluid intake
• Slow motility of waste material through large
intestine
• Certain foods, medications, diseases
 Constipation
•Usually effectively treated with dietary modification.
•Only if this fails should laxatives be used.

Therapy:
1. Bulking agents
2. Osmotic laxatives
3. Stimulant drugs
4. Stool softners
Laxatives
 Bulk Laxatives

-Increase in bowel content volume triggers stretch receptors in the intestinal wall
-Causes reflex contraction (peristalsis) that propels the bowel content forward

Psyllium (ispaghol)
Bran
Methylcellulose

•Insoluble and non-absorbable

•Non digestible

•Must be taken with lots of water!

(or it will make constipation worse)
 Saline and Osmotic Laxatives
-Effective in 1-3 hours
-Used to purge intestine (e.g. surgery, poisoning)
-Fluid is drawn into the bowel by osmotic force, increasing volume and
triggering peristalsis

•Nondigestible sugars and alcohols

•Lactulose (broken down by bacteria to acetic and lactic acid, which
causes the osmotic effect)

•Salts
•Milk of Magnesia (Mg(OH)2)
•Sodium Phosphates (used as enema)
•Sodium Citrate (used as enema)
 Stool Softners - Emollients

• It works by increasing the amount of water the stool

absorbs in the gut, making the stool softer and easier
to pass.
• Docusate sodium (surfactant and stimulant)
• Liquid Paraffin (oral solution)
• Glycerin suppositories

Docusate
 Irritant/Stimulant Laxatives-cathartics
-Increases intestinal motility
-Irritate the GI mucosa and pull water into the lumen
-Indicated for severe constipation where more rapid effect is required (6-8 hours)

•Castor Oil - From the Castor Bean

•Senna - Plant derivative
•Bisacodyl
•Lubiprostone -PGE1 derivative that stimulates chloride channels, producing
chloride rich secretions

Bisacodyl Senna Lubiprostone

 Antiemetics

• Antiemetics are the Drugs which prevent or

control the Vomiting/Nausea.
 Classification
Antieme
Ondansetron
•tics 5HT3 or
Antiemetic are the drugs event
Granisetron
Antagonists
which pr control the
Dolasetron
vomiting/nausea.
Domperidone
Prokinetics / Dopamine
Olanzapine
Antagonists
Metoclopramide
Cyclizine
Diphenhydramine
Meclozine Antihistamines
Promethazine
Hydroxyzine
Hyoscine & Dicyclomine Anticholinergics
 Mechanism of action

• 5HT3 Antagonists: They block serotonin receptors in CTZ and

Gastrointestinal tract So they can be used to treat post operative and
cytotoxic (Chemotherapy) drugs nausea/ vomiting.
• Prokinetics (Dopamine receptor (D2) Antagonists): They block the
dopamine receptors in CTZ also they promote gastrointestinal motility
& quicken gastric emptying.
• Antihistamines (H1 receptors antagonists): They block the histamine
neurotransmitter and they act by an effect on vomiting center and by
producing sedation.
• Anticholinergic: An Anticholinergic agents block the neurotransmitter
Acetyl choline in central and peripheral nervous system.
 Indications / Uses

• 5HT3 antagonists are used in management of

nausea vomiting associated with chemotherapy.
• Antihistamine such as diphen hydramine is used for
motion sickness and morning sickness.
• Metoclopramide is used for gastric emptying in
patient’s receiving tube feeding.
• Anticholinergic such as hyoscine, Dicyclomine are
useful in travel sickness.
Nursing Responsibilities regarding GI Drugs

• Give antacids at least one hour after meal and at least one
hour a part from enteric coated tablets.
• Always give combination of aluminum and magnesium
hydroxide because they make a balance (constipation effects
of aluminum with laxative effects of magnesium).
• Check antacids labels for sodium content and to use
only low sodium preparation.
• Teach the patient to avoid gastric irritants such as
smoking, alcohols, caffeine, NSAID’s because they
counteract the effect of drug.
 References

• Lippincott Illustrated Reviews: Pharmacology

Sixth Edition