Drug in Peptic Ulcer

General
A break in the mucosa of the stomach (gastric ulcer)
Damaging
or duodenum (duodenal ulcer)

Gastric
acid
Break in mucosa can cause pain, perforation,
Pepsin
bleeding & even death
Bile acids
Caused by an imbalance b/w the protective factors
H.pylori
& damaging factors in the GI mucosa

Factors

Protective
Mucus
Bicarbonate
Prostaglandins

Parietal cell contain receptor for:

o Gastrin (CCK-B)
o Histamine (H2)
o Acetylcholine (Muscarinic, M3)
When acetylcholine (from vagal postganglionic nerves) /
gastrin (released from antral Gcell into blood) bind to
parietal cell receptors

cytosolic Ca2+

Stimulates protein kinase that stimulate acid secretion from

H+/K+-ATPase on canalicular surface
In close proximity to parietal cell are gut endocrine,
enterochromaffin-like cell
o Have gastrin & acetylcholine receptor stimulate
histamine release
Histamine binds to H2 receptor on parietal cell

Activation of adenylyl cyclase

intracellular cyclic adenosine monophosphate (cAMP)

Activates protein kinase that stimulate acid secretion by

Cimetidin
e
H2
receptor
antagonist
s

Ranitidine
Famotidin
e
Nizatidine

Drugs in
Peptic
ulcer

Prostaglan
din
analogues

Omeprazo
le
Lansopraz
ole
Pantopraz
ole
Rabepraz
ole
Misoprost
ol

AntiCholinergic
agents

Pirenzepin
e

Proton
Pump
Inhibitors
(PPIs)

Antacids
Ulcer
protective

Sucralfat
e
Colloidal Bismuth
Subcitrate (CBS)

Drugs
H2 receptor

MOA
Block histamine induced

PK
Absorbed rapidly

AE/Advantages
Well tolerated by

o
o

Uses
Duodenal ulcer
Gastric ulcer

Dose
Cimetidin

antagonist
(1st group /
class for
peptic ulcer)

gastric secretion by binding

to H2 receptors
gastrin & Ach-induced
gastric acid secretion
Have antiulcerogenic effect.
Gastric ulcer due to stress
& drugs (NSAIDs,
cholinergic, histaminergic)
is prevented

PPI

It is inactive at neutral Ph

In the acidic environment of

the parietal cell canaliculi (pH
<5), PPI prodrug is converted
to a Sulfenamide, its active
form

from the small

intestine
Bioavailability is
60-80% due to 1st
pass hepatic
metabolism
Absorption is not
affected by
presence of food
in the stomach
Peak plasma
concentration in
1-3 hours
About 2/3 of a
dose is excreted
unchanged in
urine & bile, the
rest as oxidized
metabolites
Dose reduction is
needed in renal
failure

The oral
absorption of
omeprazole is
50% (unstable at
acidic pH), but as
the gastric pH
rises a higher

most patients
Adverse effects
occur in 5%. They
are generally mild
o Headache,
dizziness, bowel
upset, dries
mouth, rashes
o Confusion,
restlessness,
hallucinations,
delirium,
convulsions &
coma in some
patients.
Cimetidine (but
not other H2
blockers) has
antiandrogenic
effect:
o gynaecomastia,
loss of libido,
impotence &
temporary in
sperm count
Inhibit the final
step in gastric acid
secretion & have
overtaken H2
blockers
Powerful inhibitor
of gastric acid: can

o
o
o

Stress ulcers &

gastritis
Zollinger-Ellison
syndrome
Gastroesophagea
l reflux disease
(GERD)
Prophylaxis of
aspiration
pneumonia
Other uses
urticaria not
responding to H1
blockers

Peptic ulcer.
Required for antiH.pylori therapy.
Drugs of choice
for NSAIDs
induced gastric or
duodenal ulcers.

e 400 mg
BD or 800
mg at
bedtime
Ranitidine
150 BD or
300 mg
at
bedtime
Famotidin
e 20 mg
BD or 40
mg at
bedtime

Produce
dose
dependent
suppressio
n of
gastric
acid


The sulfenamide reacts
covalently w/ SH groups of the
H+K+ATPase enzyme

Inhibits the activity of the

proton pump irreversibly

Leads to nearly complete

suppression of acid secretion
For acid secretion to
resume, the parietal cells
must synthesize new
H+K+ATPase, which
requires approximately 18
hours.

Prostaglandi
n
analogue

PGE2 & PGI2 are produced

in GI mucosa & appear to
serve a protective role by
inhibiting acid secretion &
promoting mucus +
bicarbonate secretion

fraction (up to )
may be absorbed.
Bioavailability is
reduced by food,
should be taken
in empty
stomach.
It is highly
plasma protein
bound.
Rapidly
metabolized by
cytochrome P-450
in the liver &
metabolites
excreted in urine.
Inhibition of HCl
secretion occurs
within 1 h,
reaches max. at 2
h, is still half max.
at 24 h & lasts for
3 days

totally prevent HCl

secretion, w/o
much effect on
pepsin, intrinsic
factor, juice
volume & gastric
motility
AE
These are minimal:
nausea, loose
stools, headache,
abdominal pain,
muscle & joint
pain, dizziness (35%)
Rashes (1.5%),
leucopenia &
hepatic
dysfunction
infrequent.
On prolonged
treatment atrophic
gastritis has been
reported
occasionally
Diarrhea
Abdominal cramps
Uterine bleeding
Abortion
The need for
multiple daily

Control bleeding
from peptic ulcer
(more effective
than H2 blockers),
i.v. pantoprazole
preferred.
Gastroesophageal
reflux disease
(GERD).
Zollinger-Ellison
syndrome

Prevention of
NSAIDs-induced
peptic ulcer
However, PPIs
are more
effective, more

secretion;
w/o
anticholine
rgic / H2
blocking
action

200 g QID

Anticholinerg
ic agents

PGs inhibit gastrin

production & increase
mucosal blood flow
Natural PGs have a very
short half-life. A no. of PG
analogues with longer halflife have been developed
i.e. Misoprostol.
Ulcer healing in 4-8 weeks
but poor reliever of ulcer
pain
Pirenzepine. Selective
M1 cholinergic blocker

doses.
Patient
acceptability is
poor

Antacids

Sodium
bicarbona
te
Magnesiu
m

Antacids are weak bases

that react with gastric HCl
to form water & salt
Raise pH of gastric contents
Antacids do not acid
production
Acid-rebound occurs &

convenient,
better tolerated &
cheaper

Gastric
secretion is
reduced
without
producing
intolerable side
effects
Its therapeutic
dose range is
narrow side
effects occur
with slight
excess

Antacids are no
longer used for
healing peptic
ulcer.
They are now
employed only for
intercurrent pain

Usual
doses
inhibit
acid
secreti
on only
by 4050%
(less
than
H2
blocker
s)

hydroxide
Magnesiu
m
trisilicate
Aluminiu
m
hydroxide
gel
Calcium
carbonate
Sucralfate

gastric motility

CBS

It polymerizes at pH < 4 &

becomes a sticky gel like
material.
It strongly sticks to ulcer
base & remains there for 6
hr.
It precipitates surface
proteins at ulcer base &
acts as a physical barrier
preventing acid, pepsin &
bile from coming in contact
with the ulcer base
Increased secretion of
mucus & bicarbonate
through stimulation of
mucosal PGE2 production.
CBS & mucus form a
glycoprotein-Bi complex
which coats the ulcer &
acts as a barrier to HCl.
Detaches H. pylori from
the surface of mucosa &

Rarely used now

because of need for
4 large well timed
daily doses & the
availability of simpler
H2 blockers / PPIs.

It has no acid
neutralizing
action.
Very little
absorbed after
oral
administration

It is water soluble
but precipitates at
pH < 5

relief, acidity &

minor episodes of
heartburn
used on asneeded for
symptomatic
relief of dyspepsia

Diarrhea
Headache
Dizziness

Milk & antacids

should not be taken
concomitantly

Dose: 1 g
taken 1 hr
before 3
major meals
& at bed time
for 4-8 weeks

120 mg hr
before 3
major meals
& at bed time
for 4-8 weeks

directly kills this organism

which is involved in
causation of ulcer &
relapses.
AntiHelicobacter
pylori Drugs

Anti-H.pylori
therapy is
therefore now
recommended in
all ulcer patients
who test positive
for H. pylori
A number of 2
drug & 3 drug
regimens for 1-2
weeks have been
suggested

Lansopraz
ole 30 mg
+Amoxicill
in 1000
mg +
Clarithrom
ycin 500
mg
All given
twice daily
for 2
weeks.