Drugs to Treat Gastrointestinal
Disorders
Clinical Indication
Prevention or management of gastric or duodenal
ulcers
Management of gastroesophageal reflux disease
(GERD)
Digestion and Acid Secretion
Stomach secretes hydrochloric acid (HCl) in
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anticipation of eating (psychostimulation)
response to distension from food mass
to break-up food prior to transfer to the intestines
during sleep to reduce bacterial growth
Duodenum secretes
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an inhibitory enzyme that stops gastric acid secretion
mucus to lubricate the intestinal lining and avoid autodigestion
Acid secretion is mediated by
Hormones, neurotransmitters, and histamine
Production of Ulcers
Ulcers, open sores in the mucosal lining, occur in
the stomach and intestines when
acid and pepsin activity is overactive
from emotional stimulation or alcohol
drugs inhibit mucus production(ulcerogenic)
predisposing factors are present such
as smoking, alcohol, vagal stimulation
presence of Helicobacter pylori bacteria
Symptoms of Ulcers
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Pain due to acid stimulation of nerve endings
Nausea
Vomiting
Loss of appetite
Blood loss through erosion of the mucosal
lining
• Anemia from chronic blood loss
• Hypotension and shock from blood loss
Treatment of Ulcers
Reduce gastric acid secretion (antisecretory)
antihistamines (H2-receptor antagonists)
prostaglandins
proton pump inhibitors
anticholinergic drugs
Reduce gastric acid irritation on mucosal lining
neutralize gastric acid (antacids)
Protective barrier/coat mucosal lining
sucralfate
Antibiotics
H2-Receptor Antagonists
Histamine receptors on the parietal cells
mediate the secretion of gastric acid and pepsin
H2-receptors are different than H1-receptors
that mediate hypersensitivity and allergic
reactions
Cimetidine, ranitidine, famotidine, nizatidine
These drugs differ in their potency and ability to affect
liver microsomal enzymes
Adverse Effects of H2- Antagonists
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Headache
Constipation
Reversable mental confusion
Disorientation in elderly
Elevated serum liver enzymes
(AST, ALT)
Prostaglandins
Prostaglandin receptors mediate bicarbonate
production and mucus secretion
Misoprostol
Inhibits the ulcerogenic effect of chronic
high dose NSAIDs
Adverse effects include
diarrhea
headache
nausea
flatulence
Should never be given during pregnancy or if the woman is
considering becoming pregnant due to abortifacient activity
Proton Pump Inhibitors
Proton pumps mediate the exchange of potassium
ions (K+) for hydrogen ions (H+) within parietal cells
Omeprazole, lansoprasole
Used for acute treatment of gastric ulcers and GERD,
and long-term treatment of hypersecretory conditions,
in combination with antibiotics for ulcer healing
Adverse effects include headache, nausea, diarrhea,
abdominal pain, constipation
Antacids
Sodium bicarbonate, magnesium hydroxide,
aluminum hydroxide, calcium carbonate
• Neutralize gastric acid
• Most are not absorbed into the circulation
• Small amounts of the ions (aluminum, magnesium, and
calcium) may be absorbed
• Short duration of action
• Cause acid rebound with chronic use
Adverse effects
Constipation
Sodium bicarbonate- fluid retention, increased blood
pressure
GERD: Gastric Stimulants
Induce contractions within the upper GI tract
• prevent reflux of acid into the esophagus
• promote gastric emptying
• move damaging substances away from the
esophagus
• Stimulate cholinergic receptors selectively
within the GI tract
metoclopramide, cisapride
Adverse effects
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GI Stimulants
Metaclopramide
Cisapride
Diarrhea
Dry mouth
Headache
Constipation
Dizziness
Abdominal pain
Restlessness
Rhinitis
Sinus tachycardia Sinus tachycardia
Hypersensitivity
Hypersensitivity
Contraindications
Cisapride combination with antifungal and antibacterial drugs
leads to cardiotoxic blood levels of cisapride
Patients with seizures or extrapyramidal symptoms or active
GI hemorrhage or perforation
Anticholinergic Antispasmodic Drugs
Irritable Bowel Syndrome (IBS)
Antispasmodic drugs relax intestinal smooth muscle
Dicyclomine, oxyphencyclimine
Anticholinergic drugs
Anisotropine, clindinium bromide, isopropamide,
methscopolamine, propanthelene
Special considerations:
Patients with glaucoma, tachyarrhythmias or bladder
Obstructions
Contraindications
Patients with narrow angle glaucoma, bowel obstruction
Vomiting (Emesis) Mechanism
Vomiting occurs by CNS stimulation of the
• chemoreceptor trigger zone (CTZ) and
• vomiting center (VC)
Stimulants include
• toxins, uremia
• electrolyte imbalance
• hormonal imbalance in pregnancy
• radiation & chemotherapy
• intense smell, memory, sight, motion
Antiemetics
Drugs that block vomiting are known as
antiemetics and include
• Antihistamines (H1-antagonists)
• Metoclopramide
• Anticholinergics
• Phenothiazines
• Serotonin antagonists
(ondansetron, granisetron)
• Phosphorylated carbohydrate (sugar) solution
Motility Agents
Clinical Indication
Antidiarrheal drugs
Prevent or interrupt increased intestinal motility causing
diarrhea
Laxatives
Prevent or interrupt decreased intestinal activity producing
constipation
Bowel Function
Increase in intestinal motility produces a watery
stool (diarrhea) through
• Stimulation of parasympathetic nervous system
• Irritation of mucosal lining (drugs or infection)
• Antibiotics that create an imbalance in normal intestinal flora
Decrease in intestinal motility produces compacted
stool difficult to expel (constipation) through
• Stimulation of the sympathetic nervous system especially
through anxiety and emotional triggers
• Daily diet inadequate in fiber and fluid intake
• Habitually ignoring the defecation reflex
Antidiarrheal Drugs
Adsorbents
Bind irritating substances for excretion
bismuth subsalicylate, kaolin and pectin, attapulgite
Anticholinergics
Inhibit parasympathetic nervous system, slow
intestinal motility facilitate water absorption
atropine, belladonna, scopolamine
Opiates and Narcotic derivatives
Are anticholinergic and induce muscle spasms
(spasmogenic)
difenoxin, diphenoxylate, loperamide, paregoric
Adverse Effects & Contraindication
Adverse effects
• Most frequent adverse effect is constipation
• Diphenoxylate may be absorbed and produce
dizziness, blurred vision, nausea, and rash
Contraindication
• Anticholinergic drugs should not be used in patients
with glaucoma because intraocular pressure may
increase
Laxatives and Cathartics
Emollients
Allow water to penetrate the fecal mass
mineral oil
Osmotic (saline) laxatives
Contain sodium ions that attract water into the feces
sodium phosphate salts, magnesium citrate, PEG-ES
Stimulants
Irritate the intestinal lining and promote histamine release
increasing intestinal motility
bisacodyl, castor oil, senna preparations
Stool softeners
docusate sodium, docusate calcium, docusate potassium
Swelling agents
Natural fibers or grains that soak up water and expand
bran, prunes, psyllium hydrophillic
Adverse Effects
Laxatives that contain sodium, phosphate,
or magnesium will be absorbed and excreted
through the kidneys. The absorbed ion load
may produce
• CNS depression
• Cardiac arrhythmias
• Edema in renal impaired patients
• Depressed muscle function
Osmotic laxatives can cause a large loss of water
leading to dehydration, especially in elderly patients