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
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
an inhibitory enzyme that stops gastric acid secretion
mucus to lubricate the intestinal lining and avoid auto-
digestion
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
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
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 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