PHARMACOTHERAPY

OF PEPTIC ULCER
DISEASE

Dr Harsha R
Assistant Professor
Department of Pharmacology

PHARMACOTHERAPY OF
ACID PEPTIC DISEASE

Dr Harsha R
Assistant Professor
Department of Pharmacology

Peptic ulcer disease

Peptic ulcer disease is one of the

common GI disorder in clinical practice

Peptic ulcer is defined as breach in

mucosa that occurs in part of GIT which
is exposed to gastric acid and pepsin i.e.
Stomach and Duodenum

Peptic ulcer Disease

1.

Gastric ulcer

2.

Duodenum ulcer

3.

Stress ulcers

4.

NSAIDs induced ulcer

Peptic ulcer disease

In all these condition at the end

MUCOSAL EROSION OR ULCERATION
develops

The exact etiology for development of

these ulceration is unknown.

It results probably due to imbalance

between the aggressive factors and the
defensive factors

Peptic ulcer disease

Gastric ulcer vs. Duodenal ulcer

Gastric ulcer

Duodenal ulcer

1.

Acid secretion is Normal

Acid secretion is higher

2.

Deficient mucosal defense plays

a key role in gastric ulcer

3.

H Pylori has a role

NSAIDs has a role

4.

Gastric ulcer tend to occur later

in life
With peak incidence reported in
6th decade

H Pylori has a role

Peptic ulcer disease

1st approach in treating any case of ACID

PEPTIC DISEASE ( GERD, GASTRIC
ULCER, DUODENAL ULCER, NSAIDs
Induced ulcer, Stress ulcer, non ulcer
dyspepsia) is reduction of gastric acid
secretion

Classification of drugs used

in APD
Drugs used to reduce gastric acid secretion

1. Drugs reducing gastric acid secretion ( Anti

secretory)

a)

Proton Pump Inhibitors( PPIs)

b)

H2 antihistamines

c)

Anti-cholinergic drugs

Proton Pump Inhibitors

Most widely prescribed acid suppressing

drugs world wide due to their
outstanding efficacy and safety.
PPIs have assumed a major role for the
treatment of acid peptic disorders

PPIs available for clinical use

Omeprazole ( Prototype)

Esomeprazole

Patoprazole

Rabeprazole

Dexrabeprazole

Lansoprazole

Dexlansoprazole

Omeprazole(Prototype drug)

Mechanism of Action
Uses
Adverse effects

Gastric gland

Gastric Parietal cell

Mechanism of action

PPIs are administered as Inactive

Prodrug.
Inactive Prodrug is acid labile
To protect this acid labile inactive prodrug
from rapid destruction- PPIs are
Enteric coated tablets
Delayed release tablets

Mechanism of action
PPIs- Enteric

Mechanism of action

This active drug molecule inside the

parietal cell will form a covalent
disulfide bond with H+ /K+ - ATPase
irreversibly inactivating the
enzyme.

Mechanism of action

Pharmacokinetics

All PPIs are administered orally in enteric

coated form or in delayed release
formulation.

Bioavailability: Of all PPIs is reduced by Food

All PPIs should be taken in Empty stomach,

followed one hour later by a meal to activate
the H+ /K+ - ATPase.

PPB: highly bound to Plasma Proteins

Uses

1.

Gastro esophageal reflux disease

2.

Peptic ulcer disease

A.

H pylori associated ulcer

B.

NSAID- associated ulcer

C.

Prevention of re-bleeding from peptic ulcer

3.

Non ulcer dyspepsia

4.

Prevention of stress releated mucosal bleeding

5.

Gastrinoma and other hyper secretory conditions

1. Gastro-esophageal reflux disease(GERD)

Gastro-esophageal reflux disease(GERD)

2. Peptic ulcer disease

A. Peptic ulcer disease- H pylori associated ulcer

OCA- Regimen

OCM- Regimen

OCT- Regimen

B. PUD-NSAIDs induced ulcer

NSAIDs are weak organic acids

NSAIDs induced ulcer

Aspirin and other NSAIDs inhibit

NSAIDs induced ulcer

NSAIDs induced ulcer

C. Prevention of rebleeding from peptic

ulcers

3. Non ulcer dyspepsia

PPIs have modest efficacy for treatment

of non ulcer dyspepsia
It benefits only 10-20% of patients having
non ulcer dyspepsia

4. Prevention of stress related Mucosal

bleeding

Adverse effects

PPIs are extremely safe

PPIs produce minimal adverse effects
PPIs are not teratogenic in animal
models
However safety during pregnancy has
not been established

Adverse effects

Adverse effects

Q1-Explain why proton pump inhibitors

should be administered on empty stomach?

PPIs to be taken 30 Minutes before

breakfast
PPIs to be taken in empty stomach then
one hour later patient is advised to take
food

Q2-Explain why PPIs are

administered once daily even
though they have short half life ?
Drug

Half life

Administration

Omeprazole

1hr

OD

Esomeprazole

1.5hr

OD

Lansoprazole

1-2hr

OD

Dexlansoprazole

1-2hr

OD

Pantoprazole

1-2hr

OD

Rabeprazole

1-2hr

OD

Paracetamol

6-8hr

3-4times a day

Rationale

Though PPIs have a short serum half life

of about 1-2hrs, acid inhibition is present
for up to 24hrs. This is due to Irreversible
inactivation of the proton pump (H+ /K+ ATPase)
The synthesis of new proton pump
(H+ /K+ - ATPase) will take around 1824hrs. Till then action of PPIs will last

Q3-Explain why PPIs are called hit

and run drugs?

After few hours of administration of PPIs ,

they are removed from the body but
their effect( Acid supressing effect)
continues

Esomeprazole

It is the S-enantiomer of omeprazole

Claimed to have higher oral
bioavailability
Claimed to have better acid supression
effect

Pantoprazole

It is similar in potency and clinical efficacy

to omeprazole
More acid stable
Higher bioavailability
It is also available for IV administration

Rabeprazole

This newer PPI is claimed to cause

fastest acid suppression
Potency and efficacy similar to
omeprazole

H2 blockers

Write a note on H2 Receptor Antagonist

Explain disadvantage of cimetidine

Rantidine is preferred over cimetidine in

peptic ulcer.

Rantidine is preferred over cimetidine in

clinical practice . Give reasons.

How does cimetidine differ from ranitidine?

H2 Receptor Antagonist

H2 Receptor Antagonist commonly referred as

H2 blockers

Before the advent of PPIs H2 blockers were the

first line of drugs in treating APD
Four H2 blockers are in clinical use

Cimetidine ( Prototype)

Ranitidine

Famotidine

Nizatidine : Roxatidine

Cimetidine( Prototype
drug)

MOA
Cimetidine vs Rantidine
Uses
Adverse effects

MOA

Because of structural similarity to

histamine , these drugs act selectively
by competitive blockade of parietal
cell H2 Receptor.

Tolerance : due to down regulation of

H2 receptor

Rebound phenomenon: May occur

MOA

MOA

When given in usual prescription dose all

H2

Receptor Antagonist inhibit 60-70% of total 24hr

acid secretion

H2 Receptor Antagonist are specially effective at

inhibiting Nocturnal acid secretion ( which
depends largely on histamine)

Modest impact on meal- stimulated acid

secretion ( which depends on Ach, Gastrin, and
histamine)

Q1-Rantidine vs
Cimetidine

Rantidine is 5 times more potent than

Cimetidine
Rantidine has longer duration of action with
greater 24hrs acid supression
No Anti- androgenic effect. Cimetidine has
Anti- androgenic effect it causes gyanecomastia
and reduced sperm count and impotence
Less Central nervous system effects:
Rantidine does not cross BBB , hence incidence of
CNS effects very less
Leeser drug interaction with Rantidine when
compared with cimetidine

Q2-Explain why cimetidine but not rantidine prolong

half life of concurrently administered drugs ?

Cimetidine inhibits several Cytochrome

P-450 isoenzymes- Drug metabolising
enzymes like CYP1A2, CYP2C9, CYP2D6.

Thus it can inhibit the metabolism of

various other drugs whose metabolism is
depended on these enzymes and increase
their concentration leading to toxicity.

Q2-Explain why cimetidine but not rantidine prolong

half life of concurrently administered drugs

Drug interaction seen with cimetidine

Phenytoin

Phenobarbitone

Sulfonylureas

Carbamazepine

Metronidazole

Uses

GERD

Peptic ulcer disease ( gastric ulcer,

duodenal ulcer, NSAIDs induced ulcer, Hplylori associated ulcer)

Non ulcer dyspepsia

Prevention of bleeding from stress

related gastritis

Antacids

Write a note on non systemic antacids?

As antacids magnesium trisilicate and

aluminium hydroxide are used in
combination. Give reason

Rationale for combination of antacids in

peptic ulcer therapy

Why are antacids not given along with

sucralfate in peptic ulcer?

Antacids

Antacids are weak bases that react with

gastric HCL to form salt and water

Or

Antacids are defined as basic substances

which neutralizes gastric acid and rises
gastric Ph

Antacid

Raising gastric Ph although is possible with

antacids , it is difficult to maintain it
continuously, because antacids acts for
only 30-60min

In spite of their limitation ( Short duration

of action), antacids are valuable as they
produce considerable, immediate
symptomatic relief in patients with APD

Antacid- classification

Non systemic antacid

1.

Aluminium hydroxide

2.

Magnesium hydroxide

3.

Magnesium trisilicate

4.

Calcium carbonate

Systemic antacid

1.

Sodium bicarbonate

Non systemic antacids

Non systemic antacids

Non systemic antacids

Q1-Rationale for using combination of two or more antacid

Magnesium
hydroxide

Aluminum
hydroxide

Combination
( magnesium
hydroxide +
aluminum hydroxide )

Onset of
action

Fast

Slow

Sustained

Effect on
intestine

Laxative

constipating

Will nullify each others

action: Bowl movement
least affected

Gastric
emptying

Hasten

Delay

Will nullify each others

action: gastric emptying
least affected

Dose

Can be
reduced

Reduced

Adverse effect minimal

Q2-Rationale for withholding drugs for

two hours after administration of antacids

Non systemic antacids forms complexes( weak

bases+ acid= non absorbablecomplex)
These complexes may decrease the absorption
of many drugs to varying extent
Tetracyclins
Diazepam
Phenytoin
Isoniazide
Ethambutol
Iron salts

Sucralfate

Write a note on sucralfate

Rationale for using sucralfate in peptic
ulcer disease
Explain the interaction between
sucralfate and antacids

Ulcer protective agents

Sucralfate

Is an octasulfate
Sucrose + Aluminium hydroxide ( Sucr+
alfate)
In acidic environment ,the drug
undergoes extensive cross- linking to
produce a viscous, sticky, polymer that
adheres to epithelial cell
It thus creates a physical barrier on
the ulcer base and prevent the ulcer
from the damaging effects of the acid
.

Sucralfate

Sucralfate action is entirely local

Sucralfate has no acid neutralising effect

Surcalfate is minimal absorbed after oral

administration

Ulcer healing dose of sucralfate is 1g to be

taken in empty stomach one hour before three
major meal and at bed time for 4-8 weeks

Q1-Explain the interaction between

sucralfate and antacids

PROSTAGLANDIN ANALOGUE

Misoprostol
Rationale for using prostaglandin
analogue in peptic ulcer
Uses of misoprostol

PROSTAGLANDIN
ANALOGUE

Misoprostol (PGE1)

Enprostil (PGE2)

Rioprostil (PGE2)

Rationale for using prostaglandin analogue in peptic ulcer

Misoprostol