GASTROINTESTINAL

PHARMACOLOGY

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INTRODUCTION
 The gastrointestinal tract (GIT) is subject to more
diseases and disorders than any other system of the body.
 Gastrointestinal disorders include gastro-esophageal
reflux disease (GERD), peptic ulcer disease (gastric and
duodenal), constipation & diarrhea, nausea & vomiting.
 Dyspepsia: upper abdominal pain/discomfort (fullness,
bloating, distension, nausea)
 Peptic ulcers: defects in mucosa extending through
muscularis mucosa
Prevalence
 PUD 5-10% lifetime

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 dyspepsia 25-40%
PEPTIC ULCER DISEASE (PUD)
 PUD- are chronic lesions that occur in any portion of the
GIT exposed to the aggressive action of acid-peptic
juices
Duodnal ulcer
Gastric ulcer
Stress ulcer
NSAIDs induced ulcer
Imbalance between cell destructive and cell protective
effects

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Protecting factors
 Mucus- thin protective layer
 Bicarbonate- secreted by the surface epithelial cells
 Mucosal blood flow- removes the acid that might diffuse
through the mucosa
 Prostaglandins- PGE2
 Dilution of gastric acid by food and secretion
 Alkalinization of gastric secretions by pancreatic juices
and bile.
 A competent pyloric sphincter which prevents the
regurgitation of the aggressive factors(bile acids and
pancreatic enzymes) in to the stomach.
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Aggressive Factors
 H. pylori
 Gastric Acid: needs to be present for ulcer to form =>
activates pepsin and injures mucosa
 Decreased blood flow: causes decrease in mucus
production and bicarbonate synthesis, promote gastric
acid secretion
 NSAIDS: inhibit the production of prostaglandins
↓ Mucus, ↓ bicarbonate, ↓ blood flow, ↓ proliferation of
cells and ↑ gastric acid secretion
 Smoking: nicotine stimulates gastric acid production

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  Many factors can disrupt the balance:
Activation of aggressive factors like acid, pepsin, bile,
H. pylori
Suppression of protective factors like mucus,
bicarbonates, prostaglandin, and blood flow
 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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GASTRO ESOPHAGEAL REFLUX DISEASE
(GERD)
Backflow of stomach acid into the esophagus
Main symptoms are irritation and burning in chest or throat.
Heartburn occurs after meals and worsens when lying
down.
More severe symptoms: difficulty swallowing, chest pain
 Lifestyle changes can help with management of GERD.

In some patients (~10%), the normal esophageal lining or

epithelium may be replaced with abnormal (Barrett's)
epithelium. This condition (Barrett's esophagus) has been
linked to cancer of the esophagus

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 Endoscope of Barrett’s Esophagus
(can become malignant - needs monitoring

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  Factors that increases GERD
 Food (fatty food, alcohol, caffeine)

 Smoking

 Obesity

 Pregnancy

 Gastric distension

 Medications like B-adrnergics, CCBs and nitrates

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Non pharmacologic treatment GERD and
PUD

 Cessation of smoking
 Withdrawal of gastric acid secretion stimulants such
as alcohol, caffeine and soft cola drinks

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Pharmacologic Treatment Of GERD And PUD
Anti-acids
H2 Receptor Blockers
Proton Pump Inhibitors
Mucosal Protective Agents
Anti-cholinergics
Prostaglandin Analogs
Anti-microbial Agents
drugs used in the prevention and treatment of peptic
ulcer disease act mainly to:
decrease cell-destructive effects,

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increase cell – protective effects or both
ANTIACIDS
Anti acids are alkaline in nature
React with HCl in the stomach
Produce less acidic and poorly absorbed salts
Raise the PH of gastric secretions
Raise PH by 3.5 neutralizes more than 90% of gastric acids
and indirectly inhibiting activity of pepsin (pepsin is inactive
above pH4)
 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;
13 it includes aluminum, magnesium and calcium compounds
ANTIACIDS……….
Gastric antacids differ in their potency, in onset of action,
duration of action and adverse effects produced.
Al compounds -Al(OH)3
have low neutralizing capacity
Slow onset of action
Can cause constipation
Rarely used alone
Used for patients with chronic renal failure and
hyperphosphatemia
 decreases the absorption of phosphates

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ANTIACIDS…………
Mg compounds (Mg(OH)2, Magnesium tri silicate
High neutralizing capacity
rapid onset of action , laxative effect
Mg trisilicate adsorb HCl and pepsin (physical action)
Cause diarrhea and hypermagnesemia
CI- renal failure
Ca compounds(Calcium Carbonate )
Rapid onset of action
May cause hypercalcemia
Cause rebound acid secretion due to Gastrin release in large
doses
Rarely used in PUD
Commonly used antiacids are combinations of Al and Mg
15 compounds like mallox, mylanta.
ANTIACIDS…………
All gastric antacids act chemically although some like
magnesium trisilicate can also act physically
Antacids act primarily in the stomach
Therapeutic uses
To prevent and treat PUD, GERD
To neutralize meal Stimulated acid secretion - Usually
taken 1 hour after meal
Beneficial in healing duodenal ulcer- in conjunction
with H2 - receptor antagonist

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ANTIACIDS…………
Antacids drug interactions
 Alter gastric pH
Decrease absorption of drugs which needs acidic
medium
E.g. ketoconazole /antifungal /
 Chelation with other drugs forming insoluble complex 
 absorption
 E.g. Tetracycline, fluoroquinolones, digoxin
Therefore, time gap (not less than 2 hrs.) is needed.

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H2 RECEPTOR BLOCKERS
Are the first class of highly effective drugs for acid peptic
disease.
Are highly selective to H2 receptors
 Inhibit secretion of gastric acid through competitive
inhibition of H2 receptors
 With gastric and duodnal ulcer, healing occurs within 4-8
weeks
 Adverse effects- occur infrequently with usual doses and
duration of treatment
 Suppresses 24 hour gastric secretion by 70%

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H2 RB…………..
Cimetidine
Cimetidine is the prototype of the group.
After oral absorption, peak plasma level reached in 1 or
1.5 hrs
Effective concentration is maintained for 6 hours
Caution for pregnant and lactating mothers as it crosses
placenta and found in milk
Acutely ill patients- IV cimetidine
MOA: competitively block the binding of histamine to H2
receptors thereby, decrease secretion of gastric acid.
Inhibit stimulated acid secretion (e.g. histamine,
19 insulin)
H2 RB…………..
Cimetidine……
Dose: - 400mg po bid or 800mg QD, IV 200mg
Adverse Effect
May alter the effects of other drugs through
interactions with CYP450(enzyme inhibitor), when it
is co-adminstered with warfarin, theophylline,
phenytoin, etc and the effects of the latter drugs is
enhanced because of inhibition of the metabolism of
them.
Sexual dysfunction, gynecomastia and menstrual
abnormality by inhibiting metabolism of estrogen
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Hepatotoxicity, Diarrhea, Dizziness
H2 RB…………..
Ranitidine
oral ranitidine reaches peak blood levels 1 to 3 hrs after
administration and is metabolized in the liver
5 times more potent than cimetidine
Action is more selective and long duration of action
Dose: - 150mg Bid or 300mg at bed time
Advantage
 Doesn't produce sexual dysfunction
 Doesn't interfere with hepatic Metabolism

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H2 RB…………..

Famotidine
About 40 times more potent than cimetidine
Well tolerated and posses fewer side effect
Doesn't interfere with Hepatic drug metabolism
Doses: - 20mg bid or 40mg once a day at bed time

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H2 RB…………..
Therapeutic uses
 Duodenal ulcer – rapid and marked pain relief occurs within 2-3
days. Ulcers heal at 4-8 weeks.
 Gastric ulcer – Healing rate is lower at 8 weeks (50-75%). It can
heal NSAIDs associated ulcers.
 Stress ulcers and gastritis
 Zollinger – Ellinson Sysndrome – Definitive treatment is surgical.
 Gastroesophageal reflux disease (GERD) – They are indicated in
mild or stage 1 of GERD.
 Prophylaxis of recurrent ulcer,
 Prophylaxis of aspiration pneumonia
 Antacids reduce absorption of all H 2 blockers (2hr gap is required).

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Proton-Pump inhibitor(PPI)
 Parietal cells secrete H+ ions which are accomplished by an
enzyme H+/K+- ATPase (serve as a proton pump,
exchanging K+ for H+ ions).
Omeprazole, esomeprazole, lansoprazole, pantoprazole
 More potent than H2–blocker
 Has longer duration of action
 Suppress gastric acid secretion more strongly
 Should be given about 30 min - 1hr before meals because
rate of absorption may be reduced by food.
If H2-receptor antagonist is needed, it should be taken well
after the PPI for best effect.
24 The H2 antagonists will reduce the activity of the proton
PPI……
PPIs are more effective, convenient & cheaper
MOA: irreversively bind to H+/K+-ATPase enzyme and
inactivate it
Therapeutic uses
 Peptic ulcer: relief of pain is rapid and excellent. Ulcer heals
at 2-4 weeks.
 Bleeding peptic ulcer: high dose IV PPI therapy
(pantoprazole 40-120mg/day)
 Stress ulcers
 GERD: stage 2 or 3 GERD. Omeprazole 20-60mg daily.
 Zollinger-Ellinson syndrome: PPIs are the drug of choice
for this disorder.
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PPI……
Adverse effects:
Nausea, loose stools, headache, abdominal pain, muscle
and joint pain, dizziness.
 Inhibit drug metabolizing enzyme,
 Prolonged complete suppression of the acid barrier to
bacteria entry into the body

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Mucosal Protective Agents
 Locally active agents help to heal gastric and duodenal
ulcers by forming a protective barrier between the ulcers
and gastric acid, pepsin, and bile salts.
 They do not alter the secretion of gastric acid.
 Sucralfate (carafate)
 A preparation of sulfated sucrose and Al(OH)3
 Can be used to prevent & treat PUD
 It requires an acid PH to activate
 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
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Mucosal Protective….
 Chelated Bismuth
(e.g. tripotassium, dicitratobismuthate)
 Protects the ulcer crater and allows healing
 Colloidal bismuth compounds additionally exert
bactericidal action against H.pylori.
 Should not be used repeatedly or for more than 2
months at a time
 Can cause black stools, constipation

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Prostaglandin E2 Analogs
Misoprostol
has both acid inhibitory and mucosal protective
properties.
Believed to stimulate mucus and bicarbonate secretion
and enhance mucosal blood flow.
In addition, it binds to a prostaglandin receptor on
parietal cells, reducing histamine-stimulated cAMP
production and causing modest acid inhibition.
Approved for prevention of gastric ulcers induced by
NSAIDs especially at anti-inflammatory doses.
It is less effective than H2 antagonists and the PPIs for

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acute treatment of peptic ulcers.
Misoprostol cont’d
 Cytoprotective actions are clinically observed only at
higher doses
 But not commonly used because of high side effects and
multiple daily dosing.
 Routine prophylactic use of misoprostol may not be
justified except in patients who are taking NSAIDs and
are at high risk of NSAID-induced ulcers, such as the
elderly or patients with ulcer complications.
 Adverse effects: abdominal cramp, diarrhoea, uterine
bleeding and abortion
 Contraindication- pregnancy
30  induce abortion, premature birth or birth defects.
Anticholinergic agents
E.g. Pirenzepine, Librax(Chlorediazepoxide + clindium)
 Major clinical indication is prevention & treatment
of peptic ulcer disease, Zollinger Ellison syndrome,
reflux esophagitis.
 Anticholinegic 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 empting and thereby prolong acid –
neutralizing effects, or with any anti-ulcer drug for
antispasmodic effect in abdominal pain.
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Anticholinergic…….
MOA:-
M1- receptor antagonist
decrease the acid secretion by reducing vagal activity
that result from stress
SE ; Anticholinergic side effects (anorexia, blurry
vision, constipation, dry mouth, sedation, dizziness,
headache)

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Anti-H. pylori Therapy
 >85% PUD caused by H. pylori
 Optimal therapy for patients with peptic ulcer disease
(both duodenal and gastric ulcers) who are infected with
H. pylori requires antimicrobial treatment.
 Eradication of H. pylori results in rapid healing of active
peptic ulcers and low recurrence rates.
 Successful eradication of H. pylori (80-90%) is possible
with various combinations of antimicrobial drugs.

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Anti H. pylori agents cont’d
 Antibiotic Ulcer Therapy - Used in Combinations
 Bismuth - Disrupts bacterial cell wall
 Clarithromycin - Inhibits protein systhesis
 Amoxicillin - Disrupts cell wall
 Tetracycline - Inhibits protein synthesis
 Metronidazole - used often due to bacterial
resistance to amoxicillin and tetracycline, or due to
intolerance by the patient

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Anti H. pylori agents cont’d
Triple Therapy 7- 14 day treatment - Effective 80-
85%
PPI-based 3-drug regimens (triple therapy)
Drug #1 Drug #2 Drug #3
Omeprazole 20 mg twice Clarithromycin Amoxicillin 1 g
daily 500 mg twice twice daily
or lansoprazole 30 mg twice daily or metronidazole
daily 500 mg twice
or pantoprazole 40 mg twice daily
daily
or esomeprazole 40 mg daily
or rabeprazole 20 mg daily

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Anti H. pylori agents cont’d
Quadruple Therapy - 7 day treatment, as efficacious
as triple therapy
Bismuth-based 4-drug regimens (quadruple therapy)

Drug #1 Drug #2 Drug #3 Drug #4

Omeprazole 40 mg BID Bismuth Metronidazole Tetracycline 500 mg
or lansoprazole 30 mg subsalicylate 250–500 mg QID
BID 525 mg QID QID or amoxicillin 500 mg
or pantoprazole 40 mg QID, or,
BID clarithromycin 250–
or esomeprazole 40 mg 500 mg QID
QD
or rabeprazole 20 mg
QD
or standard ulcer-healing
dosages of an
H2RA taken for 4–6
36
weeks
Anti H. pylori agents cont’d
 Initial treatment  triple therapy for 7 to 14 days
1. Omeprazole (20mg) bid
2. Clarithromycin (500mg) bid
3. Amoxicillin (1g) bid or [Metronidazole 500 mg bid]
 Quadruple treatment for Patients who failed to respond for
initial therapy (14days)
ÞPPI (BID), Metronidazole (QID), Tetracycline (QID),
Bismuth subsalicylate (QID)
 Treatment with a single antimicrobial drug is less effective (20
to 40 percent eradication rates), results in antimicrobial
resistance and is absolutely not recommended
 switching of antibiotics is also not recommended, do not
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substitute amoxicillin for ampicillin or erythromycin for
 Laxatives and cathartics (purgatives)
 Laxatives and cathartics are drugs used orally to
evacuate the bowels or to promote bowel elimination
(defecation).
The term laxative implies mild effects, and eliminative
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
38 Cathartic effect = 15-60ml
Laxatives cont…
 Laxative and cathartics are arbitrarily classified
depending on mode of action as:
Bulk forming laxatives:
include hydrophilic colloids such as psyllium, bran,
methylcellulose, etc.
Osmotic laxatives
Such as magnesium sulfate, magnesium hydroxide,
sodium phosphate, etc.
Stimulant (irritant) laxatives (cathartics):
Individual drugs are castor oil, bisacodyl,
phenolphthalein, cascara sagrada, glycerine, etc.
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Laxatives cont…
Fecal softeners
They have detergent – like property e.g. docusate.
Lubricant laxatives e.g. liquid paraffin (mineral oil).
It lubricates the intestine and is thought to soften stool
by retarding colonic absorption of fecal water.
 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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Laxatives cont…
Indications  
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
41 administered
Antidiarrheal
 Diarrhea, defined as the frequent expulsion of liquid or
semi liquid stools → hinders absorption of fluids and
electrolytes.
 In many instances, drug intervention is not required
because is a protective mechanism used in an attempt
by the body to flush out the offending pathogen or
agent.

 Antidiarrheal drugs may be given to relieve the

symptom (non-specific therapy) or may be given to treat
the underlying cause of the symptom (specific therapy).
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Antidiarrheal cont…
 For symptomatic treatment of diarrhea, opiates
and opiate derivatives are the most effective.
They decrease diarrhea by slowing propulsive
movements in small and large intestine.
Morphine is effective but not used because of serious
potential adverse effects, other synthetic drugs such
as diphenoxylate and loperamide are commonly used
  Adsorbent – demulcent products such as kaolin –
pectin preparation may be included in antidiarrheal
preparations, unfortunately, they may adsorb nutrient
and other drugs, including the antidiarrheal agents if
given concurrently
43 06/16/2023
Antidiarrheal cont…
 Anticholinergic agents e.g. atropine are occasionally
used to decrease abdominal cramping and pain
associated with diarrhea.
 Specific therapy may include the use of antibacterial,
which are recommended for use in carefully selected
cases of bacterial enteritis.
Severe diarrhea by salmonella, shigella,
campylobacter and clostridia species can be treated
by antibiotics (ampicillin, chloramphinicol, co-
trimoxazole etc.)

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Antidiarrheal cont…
Indications for use
1. Severe or prolonged diarrhea (>2-3 days)
2. When specific causes have been determined 
Glucose – electrolyte solution should be given in
severe cases for electrolyte and fluid replacement.
It contains:
Glucose 20 gm
NaCl 3.5gm
NaHCO3 2.5gm
KCl 1.5gm
Add water to 1000ml
45 06/16/2023
Anti-emetics
 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.
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Anti-emetics cont…
Nausea and vomiting are not diseases, but are only
indications of altered physiological conditions.
Antiemetic are drugs used to prevent or treat nausea
and vomiting.
 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, CTZ, cerebral cortex,
vestibular apparatus, or a combination of these.
 Antiemetic drugs are generally more effective in
prophylaxis than treatment.
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Anti-emetics cont…
Antiemetic drugs include:
1. Phenothiazines (neuroleptics) such as chlorpromazine
Acts on CTZ and vomiting center
Block dopamine receptors
Are effective in prevention or treating nausea and
vomiting induced by drugs, radiation therapy, surgery
and most other stimuli (e.g. pregnancy).
Are generally ineffective in motion sickness.
2. Antihistamines – such as promethazine, dimehydrinate
etc.
Are especially effective in prevention and treatment of
motion sickness (but they may cause concurrent
48 drowsiness, that may be troublesome for travellers)
Anti-emetics cont…
3. Miscellaneous antiemetic
Metoclopramide has both central and peripheral
antiemetic effects.
Centrally, metoclopoamide antagonizes the action of
dopamine.
Peripherally metoclopoamide stimulates the release of
acetylcholine, which in turn, increases the rate of
gastric emptying (used in esophapeal reflux)
Scopolamine, an anticholinergic drug is very effective in
reliving nausea & vomiting associated with motion
sickness.

49 06/16/2023
Anti-emetics cont…
Ondansetron- is serotonin antagonist (5-HT3
receptors) found on the afferent fibers of the vagus
nerve and in parts of the brain associated with CTZ
Controls chemical induced vomiting and nausea
Usually given in combination with dexamethasone
Ondansetron( 8mg QD or BID)
Now a days becoming popular and generic

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Drugs used to induce vomiting
 In case of poisoning with noncorrosive 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 by direct irritation of the upper gut and
on absorption, it also acts on CTZ

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Drugs used in the treatment of hemorrhoids
 Hemorrhoids are varicose veins of the anal canal which can be very
distressing for the sufferer.
 There is no pharmacological cure for this disorder, which is often self-
limiting, if not, may require surgical intervention.
 The use of drugs may however, hinder the sufferings:
Stool softeners may alleviate constipation; lessen straining
which can worsen the condition.
Local anesthetics (e.g. lignocaine, benzocaine) relieve pain
Corticosteroids (e.g. predniosolone) suppress inflammation, itching
& swelling
Vasoconstrictors (e.g. adrenaline, phenylephine) lessen venous
swelling
Astringent compounds (e.g. tannic acid) reduce swelling by
precipitating cell surface proteins.
52  Antihaemmorhoidal preparations contain one or more of these agents.
06/16/2023
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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 THANK
YOU

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