Lecture №12

Drugs affecting the digestive

system
 REDUCTION OF GASTRIC ACID SECRETION
• H2 ANTIHISTAMINES: Ranitidine,
Famotidine, Roxatidine
• PROTON PUMP INHIBITORS: Omeprazole,
Esomeprazole, Lansoprazole, Pantoprazole,
Rabeprazole, Dexrabeprazole
• ANTICHOLINERGIC DRUGS: Pirenzepine
Propantheline, Oxyphenonium
• PROSTAGLANDIN ANALOGUE: Misoprostol
 NEUTRALIZATION OF GASTRIC ACID
(ANTACIDS)
• SYSTEMIC: Sodium bicarbonate, Sod.
citrate
• NONSYSTEMIC: Magnesium hydroxide,
Mag. trisilicate, Aluminium hydroxide
gel, Magaldrate, Calcium carbonate
ULCER PROTECTIVES:
• Sucralfate, Colloidal bismuth subcitrate,
Rebamipide
ANTI-Helicobacter PYLORI DRUGS:
• Amoxicillin,
• Clarithromycin,
• Metronidazole,
• Tinidazole,
• Tetracycline
H. PYLORI
 EMETICS
1. Act on CTZ (The chemoreceptor
trigger zone) : Apomorphine
2. Act reflexly and on CTZ :
Ipecacuanha

Powdered mustard suspension or

strong salts solution may be used in
emergency.
 ANTIEMETICS
• Anticholinergics :
Hyoscine, Dicyclomine
• H1 antihistaminics:
Promethazine, Diphenhydramine,
Cinnarizine, etc.
• Neuroleptics (D2 blockers):
Chlorpromazine, Triflupromazine, etc.
• Prokinetic drugs:
Metoclopramide, Domperidone, etc.
• 5-HT3 antagonists
(5-hydroxytryptamine) :
Ondansetron, Granisetron , etc.
• NK1 (neurokinin) receptor antagonists:
Aprepitant, Fosaprepitant
• Adjuvant antiemetics : Dexamethasone,
Benzodiazepines, etc.
 LAXATIVES
1. Bulk forming - Dietary fibre:
Bran, Psyllium (Plantago),
Methylcellulose
2. Stool softener
Docusates, Liquid paraffin
3. Stimulant purgatives
(a) Diphenylmethanes
Phenolphthalein, Bisacodyl, Sodium
picosulfate
(b) Anthraquinones (Emodins) Senna,
Cascara sagrada
(c) 5-HT4 (5-hydroxytryptamine)
agonist Prucalopride
(d) Fixed oil Castor oil
 4. Osmotic purgatives
Magnesium salts: sulphate, hydroxide
Sodium salts: sulphate, phosphate
Sod. pot. tartrate
Lactulose
Gastric gland secretion is controlled by
the vagus nerve and also by some
hormones of the gastrointestinal tract
and other endogenous substances.
Thus, it is known that an increase in
vagal tone, as well as the release of
gastrin and histamine increases gastric
secretion. Anticholinergic,
antihistamine or antigastrin effects
decrease gastric juice secretion.
 DRUGS THAT DECREASE GASTRIC SECRETION
These agents are used for the treatment of
conditions associated with ulcerations of
gastric or duodenal mucosa as a result of a
disbalance between the erosive effect of
hydrochloric acid and pepsin and the
defensive mechanisms of the gastroduodenal
mucosa.
This is why management of this pathology
consists of a reduction in gastric secretion and
an increase in cytoprotective mechanisms.
Histamine H2-receptors activate G-
protein - adenylyl cyclase system.
This manifests as an increase in
the intracellular cAMP
concentration after H2-receptors
are stimulated by histamine.
This process provokes an
increase in the secretory activity
of the parietal cells of the gastric
mucosa.
RANITIDINE, FAMOTIDINE are used
as histamine H2-receptor blockers because
they possess significant efficacy and are
safe. From a chemical point of view the
blockers of histamine H2-receptors may be
considered the derivatives of histamine
HISTAMINE H2-RECEPTOR
BLOCKERS are competitive
histamine antagonists.
They affect histamine H2-receptors
of the parietal cells and
considerably reduce the secretion
of hydrochloric acid induced by
various stimulants. The basal
secretion of this acid is also
decreased. Gastric juice volume is
reduced.
 PROTON-PUMP INHIBITORS
• PPIs are a group of medications
whose main action is a pronounced
and long-lasting reduction of stomach
acid production.
• They are the most potent inhibitors of
acid secretion available.
PPIs are among the most widely sold
medications in the world, and the first
one, OMEPRAZOLE, is on the WHO List
of Essential Medicines, the safest and
most effective medicines needed in a
health system.
The drug is administered orally.
OMEPRAZOLE is absorbed quickly, the
duration of the effect is up to 2-3 days
 Indications for OMEPRAZOLE
• Treatment of Active duodenal ulcer
• Active benign gastric ulcer
• Symptomatic Gastroesophageal Reflux
Disease (GERD)
• Erosive esophagitis due to acid-
mediated GERD
• Helicobacter pylori eradication to reduce
the risk of duodenal ulcer recurrence
OMEPRAZOLE delayed-release capsules are
indicated for the long-term treatment of
pathological hypersecretory conditions (e.g.,
Zollinger-Ellison syndrome, multiple endocrine
adenomas and systemic mastocytosis) in adults
PANTOPRAZOLE also belongs to the
group of proton pump inhibitors.
Pharmacological properties and
indications are the same as for
omeprazole.
Similar drugs are LANSOPRAZOLE and
RABEPRAZOLE.
 Adverse Reactions
• Acute interstitial nephritis
• Clostridium difficile-Associated diarrhea
• Bone fracture
• Cutaneous and systemic lupus
erythematosus
• Cyanocobalamin (Vitamin B-12) deficiency
• Hypomagnesemia
•Fundic gland polyps
Proton pump inhibitors are
CONTRAINDICATED in patients
receiving rilpivirine-containing
products
A prostaglandin used as an
antiulcer drug is MISOPROSTOL (a
synthetic derivative of PGE1).
• It is active if administered orally.
• It is especially effective for the
prophylaxis of gastric mucosal
ulceration associated with
nonsteroidal antiinflammatory
drugs.
• It is reasonable to use such drugs
as gastroprotectors for the
treatment of ulcers
although they may cause diarrhoea in
many patients and this limits their
administration.

MISOPROSTOL should not be taken by

•pregnant women,
•anyone with a history of allergy to
prostaglandins.
 ANTACIDS
Antacids are often used to decrease the
excessive acidity of gastric juice.
They are bases that interact with the
hydrochloric acid of the gastric juice
and neutralize it.
SODIUM BICARBONATE is a swift
acting antacid. This drug has a
short-term effect.
• However it causes the formation
of CO2 in the stomach. This leads
to the dilation of the stomach
and, moreover, it can cause a
secondary increase in
hydrochloric acid secretion.
• SODIUM BICARBONATE is easily
soluble in water and well
absorbed, it can be a cause of
systemic alkalosis.
Magnesium preparations
include MAGNESIUM
HYDROXIDE and MAGNESIUM
TRISILICATE
Their effect develops more slowly
than that of sodium bicarbonate.
Magnesium hydroxide is 3-4 times
more active than sodium
bicarbonate.
Mg(OH)2 and 2MgO3SiO2(H2O)n
The formation of CO2 is not
seen with magnesium drugs
• Magnesium compounds are poorly
soluble. Only a small part of them is
absorbed from the intestine. They do
not usually cause a systemic effect.
However, in kidney pathology
hypermagnesaemia is possible.
• If taken in large doses, magnesium
compounds can cause a laxative effect.
• Magnesium trisilicate also possesses
adsorbing properties.
• ALUMINUM HYDROXIDE is an antacid
and an adsorbent. It does not produce
CO2 after interaction with hydrochloric
acid of the stomach. It does not cause
systemic alkalosis.
• It can cause constipation
 CaCO3
• Precipitated CALCIUM CARBONATE also
possesses antacid activity. Its interaction
with the hydrochloric acid of the
stomach leads to CO2 formation. The
effect of the drug develops very quickly.
• CALCIUM CARBONATE is poorly
absorbed from the gastrointestinal tract
and, therefore, it does not usually
produce a systemic effect.
• CALCIUM CARBONATE is poorly
absorbed from the gastrointestinal
tract and, therefore, it does not
usually produce a systemic effect.
• However, in large doses it can cause
hypercalcaemia and systemic
alkalosis. Sometimes CALCIUM
CARBONATE as well agent may be
the cause of constipation.
Maalox was a flavored liquid containing
aluminium hydroxide and magnesium
hydroxide, which acts to neutralize or reduce
stomach acid, for the purpose of relieving
symptoms indigestion, heartburn,
gastroesophageal reflux disease, or stomach
or duodenal ulcers.
• Maalox /Mylanta can be used as a
standalone antacid treatment or in
conjunction with prescription strength
medication such as proton pump
inhibitors and H2 blockers.
• In large doses, it can act as a laxative.
 ULCER PROTECTIVES
(GASTROPROTECTORS):
Gastroprotectors include the group of drugs
that act directly on the mucous membrane of
the stomach and, to a certain extent, prevent
damage caused by chemical or physical
factors (acids, alkali, enzymes, etc.).
Gastroprotectors are used to preserve the
structure and basic functions of the mucous
membrane. Usually such drugs are used to
treat gastric and duodenal ulcers.
 GASTROPROTECTIVE DRUGS may be
divided into two following groups:
• Drugs that create mechanical protection for
the mucous membrane (ulcer surface)
- SUCRALFATE, BISMUTH TRIPOTASSIUM
DICITRATE
• Drugs that increase the protective function
of the mucosal barrier and the resistance of
the mucosa to damaging factors
- REBAMIPIDE
 SUCRALFATE
Sucralfate is a viscous whitish-
yellow gel that consists of sulfated
sucrose saccharide and
polyaluminium oxide.
• Its polymerization occurs when
pH<4.0. i.e. in acidic environment.
It results in the production of a
sticky substance that covers the
ulcer.
• SUCRALFATE preserves viscosity
and adhesive properties even in
the duodenum. The drug interacts
with normal mucosa to a lesser
extent.
• The gel firmly covers the ulcers of the
stomach and duodenum for 6 h. The
drug is taken before meals and at
night.
• Since acid activates polymerization
of SUCRALFATE, it should not be
combined with antacids and H2-
blockers. It can cause adverse
effects such as constipation and
dryness in the oral cavity.
 bismuth tripotassium dicitrate
• It is a colloid suspension. After contact
with acid it produces white sediment
with a high affinity to glyco-proteins of
the mucosa, especially to the necrotic
mucosa of the ulcerated surface.
• The ulcer becomes covered with a
white protective layer of polymer-
glycoprotein complex.
The drug does not cause any adverse effects.
Presentation: Tablet
Strength: 120mg
Pack Size: 112 tablets
 REBAMIPIDE
Rebamipide is used to treat gastritis,
and also to help heal ulcers. It may also
help to reduce the harmful effects of
NSAIDs (nonsteroidal antiinflammatory
drugs) on the small intestine, and to
treat Behcet's disease.

100mg *3 times
daily – 2-8 weeks
 side effects
• Nausea, vomiting
• Stomach upset
• Diarrhea or other gastrointestinal
disturbances
• Muscle pain
• Abdominal pain
 EMETIC
The chemical substances that cause
vomiting influence chemoreceptors of the
trigger zone or stimulate the vomiting
center via a reflex. Agents that stimulate
dopamine receptors of this zone include
APOMORPHINE.
• The use of emetic drugs is very
limited. Sometimes, in acute
intoxications, if gastric lavage is not
possible, APOMORPHINE may be
used (it is injected subcutaneously).
• Also, APOMORPHINE is used for the
treatment of alcoholism to establish
a stable negative reflex reaction to
ethanol.
• Apomorphine is CONTRAINDICATED in
strong acidic and alkaline burns of the
stomach, in gastric and duodenal
ulcers, lung disorders associated with
possible bleeding and in severe
diseases of the heart.
• Apomorphine is not effective for
intoxication with vomiting center
suppressors (for example, drugs for
general anesthesia).
The main direction of
the effect of some
emetic and
antiemetic drugs
 ANTIEMETIC DRUGS-
The administration of antiemetic
drugs should be done according to
the genesis of vomiting.

Mediator systems that participate in the

regulation of the vomiting center.
There are data proving that along with
the blocking of dopamine receptors of
the trigger zone, THIETHYLPERAZINE
produces a direct suppressing effect on
the vomiting center.
 This is why this antiemetic drug can be
used more universally. It is well
tolerated.
Sometimes it may cause such ADVERSE
EFFECTS as dryness of the mouth,
sleepiness, tachycardia, hypotension
and parkinsonism if the drug is used
continuously.
• METOCLOPRAMIDE is an active
antiemetic drug that suppresses the
trigger zone.
• METOCLOPRAMIDE acts selectively; its
antiemetic effect is notfollowed by
general lethargy.
Another antagonist of dopamine
D2-receptors is DOMPERIDON.
It is used as an antiemetic and
prokinetic drug.
 GRANISETRON
Granisetron is a selective 5-
hydroxytryptamine 3 (5-HT3) receptor
antagonist with little or no affinity for
other serotonin receptors
 Indications for GRANISETRON
• Nausea and vomiting associated with
initial and repeat courses of
emetogenic cancer therapy, including
high-dose cisplatin.
• Nausea and vomiting associated with
radiation, including total body
irradiation and fractionated
abdominal radiation
 Indications for APREPITANT

Prevention of Chemotherapy
induced nausea and vomiting
 GALLSTONE DISSOLVING DRUGS
Cholesterol (CH) remains dissolved in
bile with the help of bile salts (salts of
cholic acid and chenodeoxycholic acid
conjugated with glycine and taurine)
• CHENODEOXYCHOLIC ACID
(CHENODIOL) and
URSODEOXYCHOLIC ACID
(URSODIOL) decrease CH content
of bile, enabling solubilization of
CH from stone surface.
• Dose: 450–600 mg daily in 2–3
divided doses after meals
• The drug helps DISSOLVE GALLSTONES
in those who cannot have gallbladder
surgery or who do not need the surgery.
• URSODIOL may be used with a
procedural device that fragments the
gallstone into smaller pieces; the
procedure, called lithotripsy, allows the
drug to dissolve the stones more
quickly.
• Dissolution of gallstones is a very slow
process: patient compliance is often poor.
However, medical treatment is now possible
in selected patients: Once treatment is
discontinued after stone dissolution,
recurrences are common, because bile
returns to its CH supersaturated state.
Repeat courses may have to be given.
• Because of these problems the pros and cons
of medical therapy must be weighed against
cholecystectomy
URSODIOL is also useful for certain
liver diseases of adults, children and
infants; the drug reduces itching and
other symptoms.
Antacids may interfere with the
absorption of URSODIOL .
Take URSODIOL at least 1 hour before
or 2 hours after an antacid dose!
 Side effects
• difficulty breathing • hives
• severe stomach area • diarrhea
pain • headache
• cough or sore throat • constipation
• hair loss or thinning • indigestion
• joint or muscle aches • nausea
 LAXATIVES
These are drugs that promote evolution
of bowels. A distinction is sometimes
made according to the intensity of
action.
• Laxative or aperient: milder action,
elimination of soft but formed stools.
• Purgative or cathartic: stronger action
resulting in more fluid evolution.
Many drugs in low doses act as laxative
and in larger doses as purgative.
 MECHANISM OF ACTION/ All
purgatives increase the water
content of the faeces by:
• A hydrophilic or osmotic action,
retaining water & electrolytes in the
intestinal lumen—increase volume of
colonic content & make it easily
propelled.
• Acting on intestinal mucosa, decrease
net absorption of water and
electrolyte; intestinal transit is
enhanced indirectly by the fluid bulk.
• Increasing propulsive activity as
primary action—allowing less time for
absorption of salt and water as a
secondary effect
• Psyllium is obtained from plantage ovate or
Psyllium plant. Psyllium plant grows in the
region which has good exposure to sunlight,
and the soils are well drained and sandy.
• The Botanical name of Psyllium husk is
Plantago Ovata, and it is better known as
Isabgol in India.
PSYLLIUM is mainly used as a dietary
fibre to relieve symptoms of both
constipation and mild diarrhea and
occasionally as a food thickener.
Research has shown lowering of blood
cholesterol levels in people with
elevated cholesterol, and lowering of
blood glucose levels in people with
type 2 diabetes.
 Psyllium Seeds

Psyllium Husk Powder

 Stool Softener Docusates (Dioctyl
sodium sulfosuccinate: DOSS)
It is an anionic detergent, softens the
stools by net water accumulation in the
lumen by an action on the intestinal
mucosa.
• It is a mild LAXATIVE; especially
indicated when straining at stools
must be avoided.
• Dose: 100–400 mg/day; acts in 1–3
days.
• As enema 50–150 mg in 50–100 ml
 side effects
• Cramps and abdominal pain can occur.
• It is bitter; liquid preparations may
cause nausea.
• Hepatotoxicity is feared on prolonged
use
 STIMULANT PURGATIVES
• They are powerful purgatives.
• They irritate intestinal mucosa and
thus were thought to primarily
stimulate motor activity.
 side effects, contraindications
• Routine and long-term use must be
discouraged, because it can produce
colonic atony.
• They can reflexly stimulate gravid
uterus, therefore are contraindicated
during pregnancy.
• Subacute or chronic intestinal
obstruction is another
contraindication.
Allergic reactions—
skin rashes and
Stevens-Johnson
syndrome have
been reported.
Senna is obtained from leaves and pods
of certain Cassia sp., while Cascara
sagrada is the powdered bark of the
buck-thorn tree.
These and a number of other plant
purgatives contain anthraquinone
glycosides, also called emodins.
Senna is most popularly used.
 age starting maximum
dosage dosage
adults and 2 tablets 4 tablets
children over 12 once a twice a
years of age day day
Regular use for 4–12 months causes
colonic atony and mucosal pigmentation
(melanosis).
LACTULOSE It is a semisynthetic
disaccharide of fructose and lactose
which is neither digested nor
absorbed in the small intestine—
retains water.
• In patients with hepatic encephalopathy,
lactulose causes reduction of blood NH3
concentration by 25–50%. The
breakdown products of lactulose are
acidic—lower the pH of stools. Ammonia
produced by bacteria in colon is
converted to ionized NH4+ salts that are
not absorbed.
• For this purpose 20 g or more may be
needed.
 side effects
• Flatulence and flatus is common,
cramps occur in few.
• Some patients feel nauseated by its
peculiar sweet taste.

• Hypersensitivity
• Low galactose diet