PHARMACOLOGY OF DRUGS FOR

GASTROINTESTINAL AND HEPATOBILIARY

DISEASES
Dr. Kwame B.N. BANGA, BSc, MPhil, PhD (Biochemistry, Pharmacology)
Associate Professor

Department of Pharmacology & Toxicology,

University of Ghana, College of Health Sciences,
School of Pharmacy, Legon, Accra, Ghana

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Learning objectives
After completing this lecture, the student will be able to:

• Describe different drugs used for treatment of gastrointestinal

diseases

• Understand the basic pharmacological principles of these drugs

• Know the adverse effects of these drugs

• Use the drugs rationally

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Introduction
• Pharmacologically treatable disorders of impairments of normal motility, digestion,
absorption, secretions of the gastrointestinal tract include
–– peptic ulcer
–– reflux esophagitis
–– Zollinger-Ellison syndrome
–– gastroparesis
–– constipation
–– diarrhoea
–– inflammatory diseases
–– infections.
• This lecture discusses different drugs used for treatment of these disorders.
• However, anti-infective drugs will be discussed in other lectures.

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Physiology & Pathophysiology of GIT diseases

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Introduction to the Digestive System

• Digestive system = Digestive tract + Accessory organs

 Process food into molecules (absorbed and utilized by the cells) and the
waste products are eliminated.
• Digestive tract or alimentary canal or gastrointestinal (GI) tract = a long continuous
tube that extends from the mouth to the anus.
 It includes the mouth, pharynx, esophagus, stomach, small intestine, and
large intestine.
 Tongue + teeth = accessory structures located in the mouth.
 Salivary glands, liver, gallbladder, and pancreas = major accessory organs
(play a role in digestion by secreting fluids into the digestive tract).
• Food undergoes three types of processes in the body:
 Digestion
 Absorption
 Elimination
Introduction to the Digestive System …

• Digestion + absorption occur in the digestive tract.

 After absorption, nutrients are available to all cells and are utilized in
metabolism.
• The digestive system prepares nutrients for utilization by body cells through 6
activities, or functions:
 Ingestion: food intake through the mouth).
 Mechanical digestion: breaking down large pieces of food into smaller
particles for chemical digestion; begins in the mouth with chewing or
mastication and continues with churning and mixing actions in the
stomach.
 Chemical Digestion: Carbohydrates, proteins, and fats are transformed into
glucose, amino-acids and fatty acids through a process called hydrolysis,
using water and digestive enzymes.
Introduction to the Digestive System …

 Movements:
o mouth => pharynx => esophagus = Deglutition or Swallowing
o Mixing movements occur in the stomach as a result of smooth muscle
contraction => Segmentation (repetitive contractions in small segments
of the digestive tract)
o Propelling food particles through the digestive tract => peristalsis
(rhythmic waves of contractions).

 Absorption: passage of simple molecules through cell membranes of the

lining in the small intestine into the blood or lymph capillaries.

 Elimination: Food molecules that cannot be digested or absorbed

(waste) are eliminated from the body through the anus, in the form of feces
=> Defecation or Elimination.
General Structure of the Digestive System

• Digestive tract ≈ 9 meters in length.

• Basic structure of the wall is the same throughout the entire length of the tube.

• Wall of the digestive tract has 4 layers:

 Mucosa

 Submucosa

 Muscular layer

 Serous layer or serosa

• Mucosa = innermost layer of the wall.
 Lines the lumen of the digestive tract.
 Mucosa = epithelium + underlying loose connective tissue layer (lamina
propria) + thin layer of smooth muscle (muscularis mucosa).
 In certain regions, mucosa develops folds => increase the surface area.
 Certain cells in the mucosa secrete mucus, digestive enzymes, and
hormones.
 Ducts from other glands pass through the mucosa to the lumen.
 In the mouth and anus, where thickness for protection against abrasion is
needed, the epithelium is stratified squamous tissue.
 The stomach and intestines have a thin simple columnar epithelial layer
for secretion and absorption.
• Submucosa = thick layer of loose connective tissue that surrounds the mucosa.
 Contains blood vessels, lymphatic vessels, and nerves. Glands may be
embedded in this layer.

• Smooth muscle = responsible for movements of the digestive tract

 Arranged in two layers (inner circular and outer longitudinal).
 Myenteric plexus is between the two muscle layers.

• Serosa = outermost layer of the digestive tract (connective tissue)

 Adventitia (above the diaphragm).
 Serosa (below the diaphragm)
Regions of the Digestive System

• Digestive system = a tube running from mouth to anus.

• Chief goal = to break down huge macromolecules (proteins, fats and starch),
which cannot be absorbed intact, into smaller molecules (amino acids, fatty
acids and glucose) that can be absorbed across the wall of the tube, and into the
circulatory system for dissemination throughout the body.
• Regions of the digestive system can be divided into two main parts:
 Alimentary tract and accessory organs.
 The alimentary tract of the digestive system is composed of the mouth,
pharynx, esophagus, stomach, small and large intestines, rectum and
anus.
 Associated with the alimentary tract are the following accessory organs:
salivary glands, liver, gallbladder, and pancreas.
Esophagus

• Esophagus = collapsible muscular tube that serves as a passageway between

the pharynx and stomach.
• It is posterior to the trachea and anterior to the vertebral column.
• It passes through an opening in the diaphragm, called the esophageal hiatus,
and then empties into the stomach.
• The mucosa has glands that secrete mucus to keep the lining moist and well
lubricated to ease the passage of food.
• Upper and lower esophageal sphincters control the movement of food into
and out of the esophagus.
• The lower esophageal sphincter is sometimes called the cardiac sphincter and
resides at the esophagogastric junction.
Stomach

• Receives food from the esophagus

• Located in the upper left quadrant of the abdomen. T
• Divided into: fundic, cardiac, body, and pyloric regions.
• Lesser and greater curvatures are on the right and left sides, respectively, of the
stomach.
Gastric Secretions

• Mucosal lining of the stomach = simple columnar epithelium with numerous

tubular gastric glands.
• Gastric glands open to the surface of the mucosa through tiny holes called gastric
pits.
• Four different types of cells make up the gastric glands:
 Mucous cells
 Parietal cells
 Chief cells
 Endocrine cells

• Secretions of the exocrine gastric glands (mucous, parietal, and chief cells) make up
the gastric juice.
• Products of the endocrine cells are secreted directly into the bloodstream and are not
a part of the gastric juice.
 Endocrine cells secrete the hormone gastrin, which functions in the
regulation of gastric activity.
Regulation of Gastric Secretions

• Regulation of gastric secretion is accomplished through neural and hormonal

mechanisms.
• Gastric juice is produced all the time but the amount varies subject to the regulatory
factors.
• Regulation of gastric secretions may be divided into cephalic, gastric, and intestinal
phases.
 Thoughts and smells of food start the cephalic phase of gastric secretion
 Presence of food in the stomach initiates the gastric phase
 Presence of acid chyme in the small intestine begins the intestinal phase.

Stomach Emptying
• Relaxation of the pyloric sphincter allows chyme to pass from the stomach into the
small intestine.
• The rate of which this occurs depends on the nature of the chyme and the receptivity
of the small intestine.
Stomach Lining Basics

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 Gastric Gland

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 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.

•These cells are stimulated by mechanical and chemical irritation and parasympathetic inputs.
•This protective mucus barrier can be damaged by bacterial and viral infection, certain drugs,
and aspirin.03/02/2024 Dr. Banga_PHMD 444_2021/2022 19
 Parietal Cell: Gastric Acid Secretion
H+

ECL: Enterochromaffin-like cell

D cell: Delta cells
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Chief Cell: Synthesis and Activation of Pepsin

HCl
+HCl

Pepsin
Pepsin

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Serotonin (5-Hydroxytryptamine)
• Key neurotransmitter in the intestine

• Present in abundance within the gut

• Most is stored in enterochromaffin cell granules

• Released by many stimuli - most potently by mucosal

stroking

• Serotonin stimulates enteric nerves to initiate

secretion and propulsive motility

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Serotonin Dysfunction in the Gut

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Small & Large Intestine

Small Intestine

• Extends from the pyloric sphincter to the ileocecal valve, where it empties
into the large intestine.
• The small intestine finishes the process of digestion, absorbs the nutrients,
and passes the residue on to the large intestine.
• The liver, gallbladder, and pancreas are accessory organs of the digestive
system that are closely associated with the small intestine.
• Divided into: duodenum, jejunum, and ileum.
• Follows the general structure of the digestive tract in that the wall has a
mucosa with simple columnar epithelium, submucosa, smooth muscle with
inner circular and outer longitudinal layers, and serosa.
• Absorptive surface area of the small intestine is increased by plicae circulares,
villi, and microvilli.
Small Intestine…

• Exocrine cells in the mucosa of the small intestine secrete mucus, peptidase,
sucrase, maltase, lactase, lipase, and enterokinase.
• Endocrine cells secrete cholecystokinin and secretin.

• The most important factor for regulating secretions in the small intestine is the
presence of chyme.
 This is largely a local reflex action in response to chemical and
mechanical irritation from the chyme and in response to distention of the
intestinal wall.
 This is a direct reflex action, thus the greater the amount of chyme, the
greater the secretion.
Large Intestine
• Large intestine is larger in diameter than the small intestine.
• It begins at the ileocecal junction, where the ileum enters the large intestine, and ends
at the anus.
• The large intestine consists of the colon, rectum, and anal canal.
• The wall of the large intestine has the same types of tissue that are found in other
parts of the digestive tract but there are some distinguishing characteristics.
 The mucosa has a large number of goblet cells but does not have any villi.
 The longitudinal muscle layer, although present, is incomplete.
 The longitudinal muscle is limited to three distinct bands, called teniae coli, that run the entire
length of the colon.
 Contraction of the teniae coli exerts pressure on the wall and creates a series of pouches, called
haustra, along the colon.
 Epiploic appendages, pieces of fat-filled connective tissue, are attached to the outer surface of the
colon.
• Unlike the small intestine, the large intestine produces no digestive enzymes.
 Chemical digestion is completed in the small intestine.
• Functions of the large intestine = absorption of water and electrolytes and
elimination of feces.
Rectum and Anus

• Rectum continues from the sigmoid colon to the anal canal and has a thick muscular
layer.
 It follows the curvature of the sacrum and is firmly attached to it by connective
tissue.
 Rectum ends about 5 cm below the tip of the coccyx, at the beginning of the anal
canal.

• Last 2 to 3 cm of the digestive tract is the anal canal (continues from the rectum and
opens to the outside at the anus).
 Mucosa of the rectum is folded to form longitudinal anal columns.
 Smooth muscle layer is thick and forms the internal anal sphincter at the superior
end of the anal canal.
 This sphincter is under involuntary control.
 There is an external anal sphincter at the inferior end of the anal canal.
 This sphincter is composed of skeletal muscle and is under voluntary control.
Accessory Organs

• The salivary glands, liver, gallbladder, and pancreas are not part of the digestive
tract, but they have a role in digestive activities and are considered accessory
organs.

Salivary Glands
• 3 pairs of major salivary glands (parotid, submandibular, and sublingual glands)
and numerous smaller ones secrete saliva into the oral cavity, where it is mixed
with food during mastication. Saliva contains water, mucus, and enzyme amylase.
• Functions of saliva include the following:
 It has a cleansing action on the teeth.
 It moistens and lubricates food during mastication and swallowing.
 It dissolves certain molecules so that food can be tasted.
 It begins the chemical digestion of starches through the action of amylase,
which breaks down polysaccharides into disaccharides.
Liver

• Located primarily in the right hypochondriac and epigastric regions of the

abdomen, just beneath the diaphragm.
• The largest gland in the body.
• Divided into two major lobes and two smaller lobes.
• Functional units of the liver = lobules with sinusoids (carry blood from the
periphery to the central vein of the lobule).
• Receives blood from two sources.
 Freshly oxygenated blood is brought to the liver by the common hepatic
artery from the abdominal aorta.
 Blood that is rich in nutrients from the digestive tract is carried to the liver by
the hepatic portal vein.
• Has a wide variety of functions and many of these are vital to life.
• Hepatocytes perform most of the functions attributed to the liver, but the
phagocytic Kupffer cells are responsible for cleansing the blood.
Liver…

• Liver functions include the following:

 secretion
 synthesis of bile salts
 synthesis of plasma protein
 storage
 detoxification
 excretion
 carbohyrate metabolism
 lipid metabolism
 protein metabolism
 filtering
Gallbladder
• Pear-shaped sac attached to the visceral surface of the liver by the cystic duct.
• Principal function of the gallbladder = to serve as a storage reservoir for bile.
 Bile is a yellowish-green fluid produced by liver cells.
 Main components of bile = water, bile salts, bile pigments, and cholesterol.
 Bile salts act as emulsifying agents in the digestion and absorption of fats.
 Cholesterol and bile pigments from the breakdown of hemoglobin are excreted
from the body in the bile.
Pancreas
• Has both endocrine and exocrine functions.
 Endocrine portion consists of the scattered islets of Langerhans, which secrete the
hormones insulin and glucagon into the blood.
 Exocrine portion is the major part of the gland. It consists of pancreatic acinar cells
that secrete digestive enzymes into tiny ducts interwoven between the cells.
• Pancreatic enzymes = anylase, trypsin, peptidase, and lipase.
• Pancreatic secretions are controlled by the hormones secretin and cholecystokinin.
SUMMARY:

• The digestive tract includes the digestive tract and its accessory organs, which process
food into molecules that can be absorbed and utilized by the cells of the body.
• Food undergoes three types of processes in the body: digestion, absorption, and
elimination.
• The digestive system prepares nutrients for utilization by body cells through six
activities, or functions: ingestion, mechanical digestion, chemical digestion, movements,
absorption, and elimination.
• The wall of the digestive tract has four layers or tunics: mucosa, submucosa, muscular
layer, and serous layer or serosa.
• Regions of the digestive system can be divided into two main parts: alimentary tract and
accessory organs.
• The alimentary tract of the digestive system is composed of the mouth, pharynx,
esophagus, stomach, small and large intestines, rectum and anus.
• Associated with the alimentary tract are the following accessory organs: salivary glands,
liver, gallbladder, and pancreas.
 ACID-PEPTIC DISEASES

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• Acid-peptic disease includes peptic ulcer (gastric and duodenal), gastroesophageal
reflux and Zollinger–Ellison syndrome.

• Peptic–ulcer disease is thought to result from an imbalance between cell-destructive

effects of hydrochloric acid and pepsin and cell-protective effects of mucus and
bicarbonate on the other side. Pepsin is a proteolytic enzyme activated in gastric acid,
also can digest the stomach wall.

• A bacterium, Helicobacter pylori is now accepted to be involved in the pathogenesis of

ulcer.

• In gastroesophageal reflux, acidic stomach content enters into the esophagus causing a
burning sensation in the region of the heart; hence the common name heartburn, or
other names such as indigestion, dyspepsia, pyrosis, etc.

• Zollinger-Ellison syndrome is caused a tumor of gastrin secreting cells of pancreas

characterized by excessive secretion of gastrin that stimulates gastric acid secretion.
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Peptic Ulcer Disease

Benign PUD: Normal gastric acid pro-

duction however the mucosal barrier is weak.

Malignant PUD: Excessive secretion of gastric

Acid that overwhelms the mucosal barrier.
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Dr. Banga_PHMD 444_2021/2022
• HCl is secreted by parietal cells of the gastric mucosa which contain receptors for
acetylcholine (M), histamine (H2) and gastrin (G) that stimulate the secretion.

• Antagonists of acetylcholine, histamine and gastrin inhibit acid secretion.

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Dr. Banga_PHMD 444_2021/2022
Therapeutic approaches
• These disorders can be treated by drugs, which are able to:
–– Neutralize gastric acid (HCl) e.g., magnesium hydroxide
–– Reduce gastric acid secretion e.g., cimetidine
–– Enhance mucosal defences e.g., sucralfate
–– Exert antimicrobial action against H.pylori e.g., clarithromycin

• The effective therapeutic approach of ulcer is based on the adage: “no acid, no ulcer”

• Anti–ulcer drugs: drugs used in the prevention and treatment of peptic ulcer disease
act mainly to decrease cell-destructive effects, increase cell–protective effects or
both.

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Anti- GIT Ulcer Drugs I: Proton Pump Inhibitors

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Proton Pump Inhibitors
• Mechanism of action:
–– Omeprazole, lansoprazole and related “–prazoles” are irreversible, direct
inhibitors of the proton pump (K+/H+ antiport) in the gastric parietal cell

• Uses:
–– More effective than H2 blockers in peptic ulcer disease (PUD)
–– Also effective in GERD and Zollinger-Ellison syndrome
–– Eradication regimen for H. pylori

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 Proton Pump Inhibitors

Lansoprazole

Omeprazole

Rebeprazole

Pantoprazole
Esomeprazole

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Anti- GIT Ulcer Drugs II: H2 receptor antagonists

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H2 Antagonists (Cimetidine, Ranitidine, Famotidine,
Nozatidine)
• Mechanisms of action:
–– Suppress secretory responses to food stimulation and nocturnal secretion of gastric
acid via their ability to decrease (indirectly) the activity of the proton pump.
–– Also partially antagonize HCl secretion caused by vagally or gastrin-induced release of
histamine from ECL-like cells (GI mast cells)
–– No effects on gastric emptying time
• Uses:
–– PUD (overall less effective than proton pump inhibitors)
–– Gastroesophageal reflux disease (GERD)
–– Zollinger-Ellison syndrome
• Side effects:
–– Cimetidine is a major inhibitor of P450 isoforms → drug interaction via ↑ effects
–– Cimetidine →↓ androgens → gynecomastia and ↓ libido
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Dr. Banga_PHMD 444_2021/2022
 H2 Antagonists

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Anti- GIT Ulcer Drugs III: Antacids & others

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Gastric acid neutralizers (antacids)
• Antacids are alkaline substances (weak bases) that neutralize gastric acid
(hydrochloric acid)

• They react with hydrochloric acid in the stomach to produce neutral or less acidic or
poorly absorbed salts and raise the PH of stomach secretion, and above PH of 4,
pepsin become inactive.

• Antacids are divided into systemic and non-systemic:

- Systemic, e.g., sodium bicarbonate are absorbed into body fluids and may alter
acid-base balance. It can be used in the treatment of metabolic acidosis.
- Non systemic, do not alter acid–base balance significantly. They are used as
gastric antacids; and include aluminium, magnesium and calcium compounds
e.g., Al(OH)3, MgS2O3 , Mg(OH)2, CaCO3)

• Side effects: Constipation (Al+++), diarrhea (Mg++); rebound hyperacidity

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Clinical Correlate: Antacids and Drug Absorption
• ↑ oral absorption of weak bases (e.g., quinidine)
• ↓ oral absorption of weak acids (e.g., warfarin)
• ↓ oral absorption of tetracyclines (via chelation)

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Anticholinergic agents (pirenzepine, dicyclomine)
• Muscarinic M1 acetylcholine receptor antagonist
• Blocks gastric acid secretions
• About as effective as H2 blockers
• Rarely used, primarily as adjunct therapy

• Major clinical indication is prevention & treatment of peptic ulcer disease (but also
Zollinger Ellison syndrome and reflux esophagitis).

• Anticholinergic drugs are not used alone in the treatment of peptic ulcer. However, they
are combined with H2-antagonists to further decrease acid secretion, with antacids to
delay gastric emptying and thereby prolong acid-neutralizing effects, or with any anti-
ulcer drug for antispasmodic effect in abdominal pain.
• Anticholinergic side effects (anorexia, blurry vision, constipation, dry mouth, sedation)
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 Prostaglandins
• Misoprostol

• PGE1 analog

• Stimulates Gi pathway, leading to decrease in gastric acid release

• Mechanism of action: PGE1 analog, which is cytoprotective →↑ mucus
and bicarbonate secretion and ↓ HCl secretion
• Uses: Previously for NSAID-induced ulcers, but PPIs are now used

• Side effects include diarrhea, pain, and cramps (30%)

• Do not give to women of childbearing years unless a reliable method Misoprostol

of
birth control can be DOCUMENTED
• Can cause birth defects, and premature birth

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Pharmacology of Drugs for gastroesophageal reflux
disease (GERD)

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Gastroesophageal Reflux Disease
(GERD)

Endoscope of Barrett’s Esophagus

(can become malignant - needs monitoring)

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Gastroesophageal Reflux Disease
(GERD)

Precipitants:

 Food (fatty food, alcohol, caffeine)

 Smoking
 Obesity
 Pregnancy

Usually chronic relapsing course

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 Mucosal Protective Agents
• Sucralfate (carafate)
• Can be used to prevent & treat PUD
• It requires an acid Ph to activate
• Forms sticky polymer in acidic environment and adheres to
the ulcer site, forming a barrier
• May bind with other drugs and interfere with absorption
• Give approximately 2 hours before or after other drugs
• Take on an empty stomach before meals

• Chelated Bismuth
• Protects the ulcer crater and allows healing
• Some activity against H. pylori
• Should not be used repeatedly or for more than 2
months at a time
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Helicobacter pylori

www.science.org.au/ nobel/2005/images/invasion.jpg

H. pylori are bacteria able to attach to the epithelial cells of the stomach
and duodenum which stops them from being washed out of the stomach.
Once attached, the bacteria start to cause damage to the cells by secreting
degradative enzymes, toxins and initiating a self-destructive immune
response.
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 Anti-H.pylori Therapy
• >85% PUD caused by H. pylori
• Antibiotic Ulcer Therapy - Used in Combinations
• Bismuth - Disrupts bacterial cell wall
• Clarithromycin - Inhibits protein systhesis
• Amoxicillin - Disrupts cell wall
• Tetracycline - Inhibits protein synthesis
• Metronidazone - Used often due to bacterial resistance to
amoxicillin and tetracycline, or due to intolerance

Triple Therapy - 7 day treatment - Effective 80-85%

Proton pump inhibitor + amoxicillin/tetracycline + metronidazone/clarithomycin

Quadruple Therapy - 3 day treatment, as efficacious as triple therapy

- Add Bismuth to triple therapy
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LAXATIVES AND CATHARTICS (PURGATIVES)

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 Constipation

• Usually effectively treated with dietary modification.

• Only if this fails should laxatives be used.
• The #1 cause of constipation in laxative abuse!

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

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 Laxatives

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 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
Bran
Methylcellulose

•Insoluble and non-absorbable

•Non digestible
•Must be taken with lots of water! (or it will make constipation worse)

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 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)
•Epsom Salt (MgSO4)
•Glauber’s Salt (Na2SO4)
•Sodium Phosphates (used as enema)
•Sodium Citrate (used as enema)
•Polyethylene glycol

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 Stool Softners - Emollients

•Docusate sodium (surfactant and stimulant)

•Liquid Paraffin (oral solution)
•Glycerin suppositories

Docusate
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 Irratant/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

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Laxative Abuse
•Most common cause of constipation!
•Longer interval needed to refill colon is misinterpreted as constipation
=> repeated use

•Enteral loss of water and salts causes release of aldosterone

=> stimulates reabsorption in intestine, but increases renal excretion of
K+
=> double loss of K+ causes hypokalemia, which in turn reduces
peristalsis.
=>This is then often misinterpreted as constipation
=> repeated laxative use
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03/02/2024 Dr. Banga_PHMD 444_2021/2022 64
• Laxatives and cathartics are drugs used orally to evacuate the bowels or to
promote bowel elimination (defecation).

• The term laxative implies mild effects, and elimination of soft formed stool.

• The term cathartic implies strong effects and elimination of liquid or semi
liquid stool.

• Both terms are used interchangeably because it is the dose that determines
the effects rather than a particular drug.
Example:- castor oil laxative effect= 4ml; Cathartic effect = 15-60ml

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Laxative and cathartics are arbitrarily classified depending on mode of action
as:
• Bulk-forming laxatives:
- substances that are largely unabsorbed from the intestine.
- They include hydrophilic colloids such as psyllium, bran, methylcellulose,
etc.
- When water is added, the substances swell and become gel-like which
increases the bulk of the fecal mass that stimulates peristalsis and
defecation.
- Osmotic laxatives such as magnesium sulfate, magnesium hydroxide,
sodium phosphate, etc. also belong to bulk–forming laxatives.
- These substances are not efficiently absorbed, thus creating a stronger
than usual solution in the colon which causes water to be retained.
- The increase in pressure and volume causes stimulation of peristalsis.

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• Stimulant (irritant) laxatives (cathartics):
- Substances that are themselves irritant or contain an irritant
substance to produce purgation.
- Individual drugs are castor oil, bisacodyl, phenolphthalein,
cascara sagrada, glycerin, etc.
- Strongest and most abused laxative products that act by
irritating the GI mucosa and pulling water into the bowel lumen.
- The feces is moved too rapidly, and watery stool is eliminated as
a result.
- Glycerin can be administered rectally as suppository only.

• Stool-wetting agents: surfactants

• Emollients (moisturizers): e.g., docusate, mineral oil

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Indications for use
Laxatives and cathartics are used:
1. To relieve constipation – bulk – forming
2. To prevent straining – stool softeners
3. To empty the bowel in preparation for bowel surgery or diagnostic
procedures (saline or stimulant)
4. To accelerate elimination of potentially toxic substances from the GI tract
(saline or stimulant)
5. To accelerate excretion of parasite after anthelmintic drugs (saline or
stimulant) have been administered.

• Constipation is a common problem in older adults and laxatives are often used or
overused.
• Non-drug measures to prevent constipation (e.g. increasing intake of fluid and
high–fiber foods, exercise) are much preferred to laxatives.
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 ANTIDIARRHOEALS

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 Diarrhea
•Caused by:
• Toxins
• Microorganims (shigella, salmonella, E.coli, campylobacter, clostridium difficile)
• Antibiotic associated colitis

• Indications for treatment

• >2-3 days
• Severe diarrhea in the elderly or small children
• Chronic inflammatory disease
• When the specific cause has been determined
Dr. Banga_PHMD 444_2021/2022
• Anti-motility Agents
Anti-Diarrheal Agents
• Reduce peristalsis by stimulating opioid receptors in the bowel
• Allow time for more water to be absorbed by the gut
• Morphine
• Codeine
• Diphenoxylate
• Loperamide
 40-50x more potent than morphine
 Poor CNS penetration
 Increases transit time and sphincter tone
 Antisecretory against cholera toxin and some E.coli toxin
 T½ 11 hours, dose: 4 mg followed by 2mg doses (16mg/d max)
 Overdose: paralytic ileus, CNS depression
 Caution in IBD (toxic megacolon)

• Contraindications for antidiarrheals

• Toxic Materials
• Microorganisms (salmonella, E.coli) Loperamide
Dr. Banga_PHMD 444_2021/2022
• Antibiotic associated
 Clostridium Difficile
•The major cause of diarrhea and colitis in patients exposed to antibiotics (~20%).
•Fecal - oral route of transmission
•Three steps to infection
• Alteration of normal fecal flora
• Colonic colonization of C. difficile
• Growth and production of toxins
• Infection can lead to formation of colitis and toxic megacolon

•Pharmacological Treatment
• Discontinue offending antibiotic
• Metronidazole (contraindicated in patients with liver or renal impairment)
• Vancomycin (contraindicated in patients with renal impairment)
Dr. Banga_PHMD 444_2021/2022
Antiflatulants

(Le Pétomane)

Dr. Banga_PHMD 444_2021/2022

Antiflatulants
•Used to relieve the painful symptoms associated with gas
•Simethicone (a detergent)
• Alters elasticity of mucus-coated bubbles, causing them to break
• Large bubbles -> smaller bubbles, and less pain
• Used often, but limited data regarding effectiveness

Simethicone

Dr. Banga_PHMD 444_2021/2022

 ANTIEMETICS

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Emesis
(Vomiting)

Dr. Banga_PHMD 444_2021/2022

 Emesis
(seeing something repulsive)
(motion sickness)

(Ingesting a toxin) Dr. Banga_PHMD 444_2021/2022

Antiemetic Mechanisms
The figure below shows the complexity of the emetic pathways with an impact on the
vomiting center and reveals the multiplicity of receptor types involved, including
those activated by ACh, DA, 5HT, histamine, and endogenous opiopeptides.

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 Syrup of Ipecac Emetic

• Prepared from the root of the ipecacuanha plant

• Induces emesis
• Side effects include drowsiness, diarrhea, and stomach ache
• Acceptable for use when:
• There is no contraindication to the use of ipecac
• There is substantial risk of serious toxicity to the victim
• There is no alternative therapy available or effective to decrease
gastrointestinal absorption (e.g., activated charcoal)
• There will be a delay of greater than 1 hour before the patient will arrive at
an emergency medical facility and ipecac syrup can be administered within
30-90 minutes of the ingestion
• Ipecac syrup administration will not adversely affect more definitive
treatment that might be provided at a hospital Dr. Banga_PHMD 444_2021/2022
Antiemetic Therapuetics •Muscarinic M1 receptor antagonist
•Scopolamine
•Side Effects:
•Dry Mouth
•Dizziness
•Restlessness
•Dilated Pupils
•Delirium at high doses
•Allergic Reaction
•Contraindications
•Kidney or liver disease
•Enlarged prostate
•Difficulty in urination / bladder problems
•Heart Disease
Dr. Banga_PHMD 444_2021/2022
•Glaucoma
Antiemetic Therapeutics •Histamine H1/Dopamine D2 receptor antagonist
•Phenothiazines
• Promethazine (Phenergan)
• Prochlorperazine (Compazine)
•Side Effects
•These drugs are neuroleptics (typical antipsychotics)
•Blurred vision
•Dry mouth
•Dizziness
•Restlessness
•Seizures
•Extrapyramidal effects - Tardive dyskinesia (long term treatment)
•Contraindications
•Allergy to phenthiazines
•Glaucoma
•Liver disease
•Prostate / bladderDr.problems
Banga_PHMD 444_2021/2022
 Antiemetic Therapuetics
•Serotonin 5-HT3 receptor antagonist
•Ondansetron (Zofran)
•Granisetron
•Excellent for chemotherapy induced nausea and vomiting

•Side Effects
•Very few common side effects - usually well tolerated
•Headache
•Constipation

•Rarely
•Hiccups
•Itchiness
•Transient blindness
Dr. Banga_PHMD 444_2021/2022
Antiemetic Therapeutic Sites - Summary
Cancer Chemotherapy Drugs

Dopamine agonists

Chemoreceptor
Trigger Zone
(CTZ)

Ondansetron Scopolamine
H1 Antihistamines
Phenothiazines

All

Ondansetron

Dr. Banga_PHMD 444_2021/2022

• Drugs used to prevent or treat nausea and vomiting.
- Nausea is an unpleasant sensation of abdominal discomfort accompanied
by a desire to vomit.
- Vomiting is the expulsion of stomach contents through the mouth
- Nausea may occur without vomiting and vomiting may occur without prior
nausea, but the two symptoms most often occur together.

• Vomiting occurs when the vomiting center in the medulla oblongata is stimulated.

• Dopamine and acetylcholine play a major role in stimulating the vomiting center.

• To a certain extent, vomiting is a protective mechanism which can result from various
noxious stimuli.

• Drugs used in nausea and vomiting belong to several different therapeutic classifications.

• Most antiemetic agents relieve nausea and vomiting by acting on the vomiting center,
chemoreceptor trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination
of these. 03/02/2024 Dr. Banga_PHMD 444_2021/2022 84
Drugs for Nausea and Vomiting
Drugs for nausea and vomiting include:

• 5HT3 (a serotonin receptor) antagonists: ondansetron (commonly used in cancer

chemotherapy), granisetron

• DA antagonists: prochlorperazine, metoclopramide (also used in cancer chemotherapy;

also prokinetic in GERD)

• H1 antagonists: diphenhydramine, meclizine, promethazine

• Muscarinic antagonists: scopolamine

• Cannabinoids: dronabinol

• NK1-receptor antagonist: aprepitant (NK1 is a receptor to substance P)

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Clinical Correlate: Opioid analgesics (e.g., morphine)
have duality of action: ↓ emesis by activating receptors that decrease pain
transmission and ↑ emesis by activating receptors in the CTZ.

Drugs used to induce vomiting

• In case of poisoning with non-corrosive agents, and assuming incomplete
absorption of the poison has taken place, induction of vomiting can be carried
out
• The drug used for this purpose is emetine, the active ingredient of
ipecacuanha (syrup of ipecac).
• Emetine induces direct irritation of the upper gut and acts on CTZ.

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Drugs used in inflammatory bowel disease
(ulcerative colitis and Crohn's disease)
• Ulcerative colitis is an inflammatory condition of the rectum and colon;
• Crohn's disease can involve the whole intestine.
• Both diseases can lead to pain and abdominal discomfort. Two groups of
drugs used to treat both conditions are
1. corticosteroids e.g. prednisolone
2. drugs related to sulphonamides e.g. sulfasalazine.

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