GASTRO-INTESTINAL

AGENTS

BY
MERCY TONUI
KeMU
PHARMACOLOGY II
GASTROINTESTINAL TRACK
Drugs used in acid peptic diseases
Drugs stimulating gastrointestinal motility
(To cause diarrhea)  Laxatives
Antidiarrheal agents (to stop diarrhea)
Drugs used in the treatment of Irritable
Bowel Syndrome (IBS)
Drugs used to treat inflammatory bowel
disease (IBD)
Gastric acidity and Peptic
Ulcer Disease
Factors
Factors that
that
Factors
Factors that
that Protect
ProtectAgainst
Against
Increase
IncreaseAcidity
Acidity Acidity
Acidity
Peptic Ulcer Disease
Imbalance between defenses and aggressive factors

Defensive factors:
1. Mucus: continually secreted, protective effect
2. Bicarbonate: secreted from endothelial cells
3. Blood flow: good blood flow maintains
mucosal integrity
4. Prostaglandins: stimulate secretion of
bicarbonate and mucus, promote blood flow,
suppress secretion of gastric acid
Aggressive factors:
1. Helicobacter pylori: gram negative bacteria, live in
stomach and duodenum, may breakdown mucus layer
 inflammatory response to presence of the bacteria
also produces urease  forms CO2 and ammonia
which are toxic to mucosa

2. Gastric Acid: needs to be present for ulcer to form 

activates pepsin and injured mucosa

3. Decreased blood flow: causes decrease in mucus

production and bicarbonate synthesis, promote gastric
acid secretion

4. NSAIDS: inhibit the production of prostaglandins

5. Smoking: nicotine stimulates gastric acid production

Classes of Agents
1. Proton Pump Inhibitors
2. Histamine H2-Receptor
Antagonists
3. Prostaglandin Analogs
4. Cytoprotectants
5. Antacids
 1.
Proton Pump Inhibitors
(PPI’s)
Available PPIs
Esomeprazole (Nexium)
Lansoprazole (Laproton. Lapraz)
Omeprazole (Protop, Pumpitor, OGB)
Pantoprazole (Pantozol) (iv)
Rabeprazole (Pariet)
PPIs
1. Most potent suppressors of acid
secretion
24-48 hrinhibitor
2. Irreversible effects on acid suppression
of proton pump; blocks 98%
of acid secretion in all forms of ulcer and
hypersecretory Zollinger-Ellison syndrome.

 The drug is given in gelatin coated capsule to resist

breakdown in stomach acid. It reaches the intestine,
well absorbed, enters blood stream,reaches the
parietal cell.
 PPI Pharmacology

Omeprazole: prototype agent.

Activated only when pH decreases below 4
 the cationic configuration of drug bind to
the SH group of enzyme pump and
inactivate irreversibly.
Occurs only in parietal cell
 PPI – Pharmacokinetics
Available in enteric coated and granules filled
capsules form  oral route is preferable
Rapidly absorbed and Highly protein bound
(plasma bioavailability is ~50%)
Extensively metabolized in the liver by the
CYP2C19 and CYP3A4 isoenzymes*
Sulfated metabolites are excreted in the urine or
feces
Hepatic disease reduces the clearance of
 Therapeutics uses
Peptic ulcer
PPIs reduce the risk of bleeding from
an ulcer caused by aspirin and other
NSAIDs (a/c to the clinical study)
Zollinger-Ellison Syndrome
Treatment of GERD
Used with antimicrobial regimens to
eradicate H. pylori
 Common PPI Side Effects

CNS: headache, dizziness.

GI: diarrhea, abdominal pain, nausea,
vomiting, constipation, flatulence.
Musculoskeletal: back pain.
Respiratory: cough, upper respiratory tract
infection.
Rashes, leucopenia and hepatic dysfunction
(rare)
 Drug-Drug Interactions

Ketoconazole and Digoxin absorption is

decreased due to reduced acidity.
Omeprazole may inhibit the inhibits oxidation
of certain drugs, like diazepam, warfarin and
phenytoin metabolism
The activation of clopidogrel is interfered by
inhibiting CYP2C19
Oral omeprazole combined with sodium
bicarbonate for faster absorption
 Contraindications & cautions
In patients hypersensitive to drug or its
components.
Use cautiously in patients with hypokalemia and
respiratory alkalosis.

Nursing considerations
Tell patient to swallow tablets or capsules whole and not
to open, crush, or chew them.
Instruct patient to take drug 30 minutes before meals.
Caution patient to avoid hazardous activities if he gets
dizzy.
2. Histamine H2-
Receptor Antagonists
(H2RAs)
H2RAs

Have antiulcerogenic effect.

Reversibly compete with histamine
for binding to H2 receptors on the
basolateral membrane of parietal
cells
Less potent than PPIs but still
suppress acid by 70% over 24 hrs
Available H2RAs
H2 receptor blockers:
• Cimetidine (Open Gastric Bypass, iv)
• Dose: 300 mg, 4 times daily with meals
& at bedtime.
• First H2-blocker available Inhibits P450
Drug interaction
• Ranitidine (OGB, iv)
Dose: 150 mg 2 times daily .
Maintenance 150 mg at bed-time.
• Does not inhibit P450  fewer side
effects
• Famotidine
• Roxatidine
Pharmacokinetics
Rapidly absorbed after oral
administration
Serum concentrations peak in 1-3 hr
Therapeutic levels maintained up to 12
hrs
Small percentage is protein bound
10% to 35 % metabolized by the liver
Drugs and metabolites primarily
excreted by kidneys (**reduce doses in
renal disease)
1. inhibit 90% acid secretion in basal state as
well as food-induced and nocturnal acid
production.
2. they are helpful in healing gastric and
duodenal ulcers and prevent their
recurrence. Have benefits in preventing
increased gastric acid secretion in
Zollinger-Ellison syndrome.

3. Cimetidine Has several side effects, not a

choice now - Under Prescription.
Common H2RA Side Effects
Diarrhea
Headache
Drowsiness
Fatigue
Muscular pain
Constipation
Much less common
Confusion, delirium in the elderly
Associated with thrombocytopenia
Cimetidine anti-androgen effects… why?
And what happen if prescribed with
ketoconazole?
Drug-Drug Interactions
1. Inhibits CyP450: Inhibits the
metabolism of various drugs that
are concomitantly taken:
phenytoin, warfarin,
theophylinne, BZD.

2. These adverse effects are

relatively least with ranitidine and
famotidine
Contraindications:
- Children under 16 years.
- Lactation
- Impaired renal & hepatic function

Nursing considerations:
- Dilute for I.V. use ( 50 mg in 20 ml of 0.9%
Nacl) .
- Note any evidence of renal or liver disease.
- Obtain baseline liver & kidney function.
- Note for signs of infection .
- Adequate hydration for problem of diarrhea.
3. Prostaglandin Analogs:
Misoprostol
Protective Effects of Prostaglandins
PGE and PGI synthesized by gastric
2 2
mucosa
Acid-reducing effects
Cytoprotective effects
Contraindications with NSAIDS which
diminish prostaglandin formation by inhibition
of cyclooxygenase and lead to ulcer formation
Misoprostol: Cytotec synthetic analogues
Inhibit basal acid secretion (85-95%)
Inhibit stimulated acid secretion (75-85%)
Pharmacokinetics
Rapidly absorbed
Rapidly de-esterified to
misoprostol acid--the active
metabolite
Therapeutic effect peaks at 60-90
minutes after oral administration.
Plasma half lives - 3 hours
Side Effects

Diarrhea ± abdominal cramps

Begins within 2 weeks and often
resolves spontaneously in 1 week
Inflammatory bowel disease
Contraindicated during pregnancy
4. Sucralfate:
Carafate
 Introduction
Cytoprotective compounds,
Have several actions  which are enhance
mucosal protection mechanisms, thereby
Preventing mucosal injury
Reducing inflammation
Healing existing ulcers
Effectively heals duodenal ulcers
Long-term maintenance therapy to prevent their
recurrence
NB: This agent does not prevent NSAID-
induced ulcers, nor does it heal gastric
Common Side Effects
Constipation (2%)
Aluminum  hyphosphatemia:
Avoid in renal failure
May impair absorption of other
drugs: tetracycline, warfarin,
digitoxin, phenytoin  2 hr
interval
5. Antacids
 Antacids
Given orally 1-3 hrs after meals and bedtime
Mg+2 based preparations increase motility 
Diarrhea
Al+3 based preparations relax smooth muscle 
Constipation
Ca+2 based preparations release CO2  Belching,
nausea, distension, and flatulence.
Na content of antacids can be an important
consideration in patients with hypertension or
congestive heart failure***
Sodium Bicarbonate: NaHco3
Class: Alkalinizing agent , antacid ,
electrolyte
Nursing considerations:
- I.V. dose should be determined by Arterial
Blood Gases analysis.
- Should be administered. slowly.
- Periodically assess patient serum pH
during the therapy.
- Observer for signs of edema.
 Common Side Effects
Aluminum toxicity with renal disease 
Osteoporosis, encephalopathy,
osteomalacia
Hypercalcemia (Excessive intake of
calcium carbonate along with calcium
foods)
Calcium precipitation in the kidney
Impair absorption of some drugs  Take
2 hrs before or after other drugs : INH,
Antibiotic ulcer therapy:
Combinations must be used:
1. Bismuth (Scantoma, Stobiol®) – disrupts cell wall of
H. pylori
2. Clarithromycin – inhibits protein synthesis
3. Amoxicillin – disrupts cell wall
4. Tetracyclin – inhibits protein synthesis
5. Metronidazole – used often due to bacterial resistance
to amoxicillin and tetracycline, or due to intolerance by
the patient

Standard treatment regimen for peptic ulcer:

Omeprazole + amoxicillin + metronidazole
Laxatives
 Constipation
Abnormally infrequent and difficult
passage of feces through the lower GI tract
Symptom, not a disease
Disorder of movement through the colon
and/or rectum
Can be caused by a variety of diseases
(hemorrhoid, multipara) , drugs (opium,
aluminium antacids) or psychotics
Laxatives :
Bulk forming
Emollient
Hyperosmotic
Saline
Stimulant
Laxatives:
Mechanism of Action
Bulk forming
High fiber
Absorbs water to increase bulk
Distends bowel to initiate reflex bowel
activity
Examples:
psyllium (Mulax)
Methylcellulose, polycarbophil
Agar-agar
Laxatives:
Mechanism of Action
Emollient
Stool softeners and lubricants
Promote more water and fat in the
stools
Lubricate the fecal material and
intestinal walls
Examples:
Stool softeners: docusate sodium
Lubricants: mineral oil
Laxatives:
Mechanism of Action
Hyperosmotic
Increase fecal water content
Result: bowel distention, increased
peristalsis, and evacuation
Examples:
polyethylene glycol
sorbitol
glycerin
lactulose
 Glycerin Suppositories:
miscellaneous laxative
Onset 15-60 minutes.
Uses:
- To evacuate the colon prior to rectal & bowel
examination or surgery.
- To establish normal bowel function in patients
dependent on laxatives.
Contraindications:
-Anal fissure, fistula, ulcerative hemorrhoids.
 Laxatives:
Mechanism of Action
Saline
Increase osmotic pressure within the intestinal tract,
causing more water to enter the intestines
Result: bowel distention, increased peristalsis, and
evacuation
Saline laxative examples:
magnesium sulfate (Epsom salts, garam Inggris)
magnesium hydroxide
magnesium citrate
sodium phosphate
N.B. : The saline cathartics should be administered with
Uses:
- To empty the bowel prior to diagnostic or
surgical procedures.
- To eliminate parasites following anthelmintic
therapy.
- To remove toxic substances following poisoning.
Laxatives:
Mechanism of Action
Stimulant
Increases peristalsis via intestinal nerve
stimulation
Examples:
castor oil
senna
cascara
bisacodyl
Laxatives: Most Prominent Side
Effects
Bulk forming :Impaction, Fluid overload
Emollient : Skin rashes, Decreased
absorption of vitamins (ADEK  parafin )
Hyperosmotic : Abdominal bloating, Rectal
irritation
 Saline :Magnesium toxicity (with renal
insufficiency), Cramping, Diarrhea,
Increased thirst
 Stimulant : Nutrient malabsorption, Skin
rashes, Gastric irritation, Rectal irritation
Antidiarrheals
Causes of Diarrhea
Acute Diarrhea
Bacterial Chronic Diarrhea
Viral Tumors
Drug induced Diabetes
Nutritional Addison’s disease
Protozoal Hyperthyroidism
Irritable bowel
syndrome
Antidiarrheals
Drugs that decrease peristalsis,
thereby allowing fluid absorption
from the intestinal contents
Examples:
Anticholinergics
Protectants/adsorbents
Opiate-related agents
Probiotics
Metronidazole
Anticholinergics are used to treat tenesmus*
and vomiting
Examples:
Atropine
Aminopentamide
Isopropamide
Propantheline
Methscopolamine
Side effects include dry mucous membranes,
urine retention, tachycardia, and constipation
Protectants/adsorbents coat inflamed
intestinal mucosa with a protective layer
(protectants) or bind bacteria and/or digestive
enzymes and/or toxins to protect intestinal
mucosa from damaging effects (adsorbents)
Examples:
Bismuth subsalicylate (bismuth + aspirin-like
product)
Kaolin/pectin
Activated charcoal
Side effects include constipation
Opiate-related agents control diarrhea
by decreasing both intestinal secretions
and the flow of feces and increasing
segmental contractions
Examples:
Diphenoxylate
Loperamide
Paregoric
Side effects include CNS depression,
ileus, urine retention, bloat, and
constipation
Probiotics seed the GI tract with
beneficial bacteria; use is based on the
theory that some forms of diarrhea are
caused by disruption of the normal
bacterial flora of the GI tract
Must be refrigerated to maintain the
viability of the bacteria
Examples:
Plain yogurt with active cultures
Variety of trade-name products
A theory regarding the
development of diarrhea is that
anaerobic bacteria may increase
due to disruption of normal GI
flora
One way to treat this is to use an
antibiotic effective against
anaerobic bacteria
Metronidazole is an example of
an antibiotic used to treat diarrhea
Cost-effectiveness studies of Zinc
supplementation…
Zinc supplementation significantly
improved the cost-effectiveness of
standard management of diarrhoea for
dysenteric as well as non-dysenteric
illness.
Sufficient evidence to recommend the
inclusion of zinc into standard case
management of both types of acute
The new WHO-UNICEF recommended policies for
health professionals on the treatment of diarrhoea
1. Counsel mother to begin administering suitable home
fluids immediately upon onset of diarrhoea in a child
2. Treat dehydration with new low osmolarity ORS solution
(or with intravenous electrolyte solution in cases of severe
dehydration)
3. Emphasize continued feeding or increased breastfeeding
during, and increases feeding after, the diarrhoeal episode
4. Use antibiotics only when appropriate, i.e., in the presence
of bloody diarrhoea or shigellosis, and abstain from
administering anti-diarrhoeal drugs
5. Provide children with 20 mg per day of zinc
supplementation for 10-14 days (10 mg per day for
infants under six months old)
6. Advise mothers of the need to increase fluids and continue
feeding during future diarrheoal episodes
Zinc and Low-osmolarity ORS:
effective, safe and available
Drugs for pancreatic disorders

Digestants
 Pancreatin:
• Class: Digestant.
• Action: This mixture of enzymes (pancreatine , lipase,
& amylase) is obtained from hog pancreas. The
preparation increases digestion of food.
• Uses: Pancreatic deficiency as pancreatitis , cystic
fibrosis & pancreatectomy.
• Side effects:
• Rash, sneezing, lacrimation (allergic) .
• Holding tab. in mouth causes stomatitis &
ulceration of the mouth.
• High doses may cause hyperuricemia.
Gall stone drugs
• ursodiol (Actigall) dissolves radiolucent
noncalcified gallstones (cholelithiasis)
Emetics and Anti-emetics
 Emetics:
• These are used in cases of acute poisoning to
induce vomiting when it is desirable to empty
the stomach promptly & completely after
ingestion of toxic materials.

• Vomiting can be elicited either by direct action

on the chemoreceptor trigger zone in the
medulla or by indirect stimulation of the GIT.
 Apomorphine HCL:
• Class: Emetic .
• Action: is a synthetic derivative of morphine
which produce vomiting by
• stimulating the CTZ.
• Uses: In drug overdose. - Poisoning.
• Contraindications:
- Shock
- Drug induced CNS depression.
- Ingestion of corrosive substance as lye.
- Patients sensitive to morphine.
 Contd…
• Side effects: Depression , euphoria, tremors,
tachypnea .
• Overdose may lead to excessive emesis, cardiac
depression, respiratory depression, come and
finally death.
• Dose: 5-6 mg as a single dose.
• Nursing considerations:
- Before administration, give client 300 ml of water.
- Store solution in dark closed container.
- Have a naloxone available “ for respiratory
distress”.
- Note any sensitivity to morphine.
 Ipecac syrup:
• Class. : Emetic
• Action: An alkaloid extracted from Brazil root, acts both
locally on the gastric mucosa & centrally on the CTZ.

• N.B. : Ipecac syrup must not be confused with ipecac

fluid extract which is 14 times as potent.

• Uses: Drug overdose, poisoning to empty stomach.

• Contraindications:
- With corrosives, Unconscious patients, Shock,
Children under 6 months.
• Dose: 5-10 ml preceded or followed by 240 ml of water.
Anti-emetics
Nausea & vomiting can be caused by a variety of
conditions such as infections, drugs, motion,
organic disease or psychological factors.
The underlying cause of the symptoms must be
elicited before emesis is corrected.
The act of vomiting is complex.
Contd’…
The vomiting center in the medulla responds to
stimulation from many peripheral areas as well as
stimuli from CNS itself, the CTZ in the medulla,
the vestibular apparatus of the ear & the cerebral
cortex.
The selection of antiemetic depends on the cause
of the symptom as well as on the manner in which
the vomiting is triggered.
Many drugs used for other conditions such as
antihistamine, phenothiazines & barbiturates have
antiemetic properties & can be so used.
 Metoclopramide Hcl: (perinorm)
Action:
It is dopamine receptor antagonist acts
both centrally & peripherally,
Centrally due to the effect in the CTZ
(inhibition) , Peripherally it stimulate the
motility of the upper GIT without affecting
gastric & biliary or pancreatic secretions.
Contd…
Indications :
Digestive disorders leading to relief GIT pain ,
Dyspepsia & regurgitation in peptic ulcer, reflux
esophagitis & postanasthetic vomiting.
Nausea & vomiting as in chemotherapy.
Facilitate diagnostic procedure e.g. barium
meal.
Side effects:
GI disturbances, transient hypertension,
supraventricular tachycardia, dizziness &
extrapyramidal effect “convulsion”.
Contd…
Drug interaction:
Because of their antiemetic and antinauseant action the
antiemetics may mask overdose caused by other drugs.
Nursing considerations:
Take a complete history, if it is unusual occurrence or
if it is a recurring phenomenon.
Assess for other untoward symptoms as increased
intracranial pressure or intestinal obstruction
(antiemetic may mask signs of underlying pathology)
Caution the client that drug tends to cause drowsiness
& dizziness, advise him\her to avoid hazardous tasks.
 References

• Lippincott’s pharmacology
• Katzung’s pharmacology

• Internet sources
• PHARMACOLOGY FOR NURSES
Part II
Thank You
?