What is peptic ulcer ?

• Ulcer occurs in any part of the gastrointestinal

tract (GIT) which is exposed to gastric acid and
pepsin, i.e the stomach & duodenum

• Etiology – Not clearly known

• There are 2 factors – aggressive factors & the

defensive factors
 Aggressive factors
• Acid

• Pepsin

• Bile

• H.Pylori
 Defensive factors
Gastric mucus

Bicarbonate secretion

Prostaglandins

High mucosal blood flow

Innate resistance of the mucosal cells

Gastric ulcer & Duodenal ulcer
Regulation of Gastric acid secretion

• Enzyme H+K+ATPase ( Proton Pump) which

secreate H+ ions in the apical canaliculi of
parietal cells
• Activated by Histamine, Ach and Gastrin via its
own receptor
• Major dominant role is by histamine , activate
H2 receptor  increased HCL
 Peptic ulcer
• What are the goals of anti-ulcer therapy?

 Relief of pain
 Ulcer healing
 Prevention of complications (bleeding,
perforation)
 Prevention of relapse.
• Approaches for the treatment of peptic ulcer
are:
1.Reduction of gastric acid secretion
(a)H2 antihistamines: Cimetidine, Ranitidine,
Famotidine, Roxatidine
(b) Proton pump
inhibitors:
Omeprazole,
Esomeprazole,
Lansoprazole,
Pantoprazole,
Rabeprazole,
Dexrabeprazole
(c) Anticholinergic drugs:
Pirenzepine,
Propantheline,
Oxyphenonium

(d) Prostaglandin analogue:

Misoprostol
2. Neutralization of gastric acid (Antacids)

(a) Systemic:
Sodium bicarbonate,
Sodium citrate

(b) Nonsystemic:
Magnesium hydroxide,
Magnesium trisilicate,
Aluminium hydroxide gel,
Calcium carbonate
3.Ulcer protectives:
Sucralfate,
Colloidal bismuth subcitrate (CBS)

4. Anti-H. pylori drugs:

Amoxicillin,
Clarithromycin,
Metronidazole,
Tinidazole,
Tetracycline
 H2 ANTAGONISTS
• first class of highly effective drugs for acid-peptic
disease

• Four H2 antagonists cimetidine, ranitidine,

famotidine and roxatidine are available in India

• cimetidine, ranitidine and roxatidine –

competitive H2 blocker

• Famotidine – is a non-competitive H2 blocker

• Cimetidine was a first H2 blocker introduced

• prototype drug

• Not in the market because of its side effects

• H2 blockers markedly inhibits gastric secretion.

• All phase of acid secretion is suppressed in dose

dependent manner
• Basal nocturnal acid secretion is suppressed
more completely.

• The usual ulcer healing doses produce 60–70%

inhibition of 24 hr acid output.

• H2 blockers have antiulcerogenic effect.

• Gastric ulceration due to stress and drugs

(NSAIDs, cholinergic, histaminergic) is prevented.
 cimetidine
• cimetidine is well tolerated by most patients

• ADE < 5% of patients

• Side effects - Headache , dizziness , bowel upset

and dry mouth are generally mild

• Raid or high dose i.v injection can cause confusional

state, hallucination, convulsion, bradycardia, cardiac
arrhythmias or cardiac arrest
 Cimetidine is not used routinely
• It cross blood brain barrier and result in mental
state changes

• Inhibits binding of dihydrotestosterone to androgen

receptor that can manifest as impotence in males

• Inhibits the metabolism of estradiol and increase

serum prolactin levels on long term use
• It is potent inhibitor of CYP enzyme and can
increase plasma concentration of warfarin,
theophylline, phenytoin, carbamazepine and
many other drugs

• It is the least potent H2 blocker

 Ranitidine
• 5 times more potent than Cimetidine

• Longer duration of action with greater 24 hr

acid suppression is obtained clinically

• Cimetidine ADE is not seen with Ranitidine

• Famotidine – Most potent H2 blocker

• 5-8 times more potent than Ranitidine

• Anti-androgenic action is absent

• Low affinity for cytochrome P450  low

interaction with drug metabolism

• Incidence of adverse effects is low

 Lafutidine
• Second generation H2 blocker

• In addition to decreasing acid secretion by H2

blockage , it is claimed to enhance NO production
and improved gastric mucosal blood flow

• Gastro-protective effect by increasing mucus

production & Somatostatin release

• Indication – Dyspepsia, peptic ulcer & GERD

 USES – H2 blockers
• Peptic ulcer

• Non-ulcer dyspepsia

• Bleeding from stress ulcer and erosive gastritis

• Gastroesophageal reflux disease(GERD)

• Prophylaxis of aspiration pneumonia

• Urticaria
 Peptic ulcer
• H2 blockers are rarely used for treating peptic ulcer
because PPI acts faster, more complete relive of
pain

• High dose at bed time – dec. nocturnal secretion by

giving single bed time dose

• Maintenance therapy – during bed time – reduces

relapse rate in peptic ulcer
• H2 blockers – not used for ulcer caused
by NSAIDs & H.Pylori infection

• Non-ulcer dyspepsia:
Abdominal fullness & pain
Gas & bloating
Nausea
It is most functional
 Bleeding from stress ulcer and erosive
gastritis
• Hepatic coma , severe burns & trauma,
prolonged surgery, prolonged intensive care,
renal failure, asphyxia neonatorum are all
associated with gastric erosion and bleeding

• IV infusion – prevents the gastric lesions &

hemorrhage as well as promotes healing of
erosions
GERD – H2 blocker is indicated only in mild or
stage – I cases of GERD
Prophylaxis of aspiration pneumonia:
H2 blockers given preoperatively reduce the risk
of aspiration acidic gastric contents during
anesthesia & surgery
Urticaria:
H2 blockers have adjuvant beneficial action
certain cases of urticaria who do not responed
to H1 antagonist alone
 Proton Pump Inhibitor(PPI)
• Omeprazole – Prototype drug of PPI

• PPI > H2 blocker

• Dose dependent suppression of gastric acid

secretion

• Strong inhibitor of gastric acid both in resting as

well as the stimulated by food
• Omeprazole is inactive at neutral pH

• pH<5 it rearranges to two charged cationic

forms

• React covalently with SH group of H+K-ATPase

enzyme and inactivate irreversibly
• 2 molecules of omeprazole react with one
molecule of the enzyme

• Tightly bound to the H+K-ATPase enzyme by

covalent bonds.

• Acid secretion resumes only when new

H+K+ATPase molecules are synthesized
(reactivation half time 18 hours).

• Hit and run phenomenon

 PK - PPI
• All PPIs are enteric coated
• Oral bioavailability is 50% - acid liability
• Bioavailability of all PPIs is reduced by food
• Metabolized by CYP2C19 & CYP3A4
HCL inhibition starts 1 hr
Maximum inhibition 2 hrs
Half maximum 24 hrs
Inhibition Lasts for 2-3 days
 Adverse effects
• PPI has minimal side effects & very safe drug
• Nausea
• Loose stools
• Headache
• Abdominal pain
• Muscle & joint pain
• Dizziness
• Above symptoms complained by 3-5%
 Other PPI
• Esomeprazole
• Lanoprazole
• Pantoprazole
• Rabeprazole
• Dexrabeprazole
• Iiaprazole
 Uses of PPI
1. Peptic ulcer
2. Bleeding peptic ulcer
3. Stress ulcer
4. GERD
5. Zollinger-Elison syndrome
6. Aspiration pneumonia
 PPI -Peptic ulcer

• Omeprazole 20-40 mg OD more effective

than H2 blocker

PPI treatment
• Duodenal ulcer – 2 to 4 weeks ( depends )
• Gastric ulcer – 4 to 8 weeks

• PPI – DOC for NSAID induced gastric

/duodenal ulcers
 PPI – Bleeding peptic ulcer
• Acid enhances clot dissolution

• Suppression of gastric acid facilitate clot

formation reducing blood loss and rebleed

• High dose of IV PPI therapy for 3 days

• Stress ulcer - IV pantoprazole /
rabeprazole

Gastroesophageal reflux disease(GERD):

• PPIs are the drugs of choice
• Omeprazole produces more complete
round-the-clock inhibition of gastric acid
resulting in rapid symptom relief and is
more effective than H2 blockers
 Zollinger-Ellison syndrome:

• Islet cell” tumor of the pancreas

• Hypergastrinemia

• Gastric acid hypersecretion

• Consequences of acid hypersecretion :
– PUD, GERD [ with or without complications]
– Diarrhea, malabsorption
• Omeprazole is more effective than H2 blockers
in controlling hyperacidity in Z-E syndrome

• 60–120 mg/day or more (in 2 divided doses)

required for healing of ulcers

• Inoperable cases have been treated for >6

years with sustained benefit and no adverse
effects.
 ANTICHOLINERGICS
• Atropinic drugs reduce the volume of gastric juice

• Stimulated gastric secretion is less completely

inhibited.

• Effective doses (for ulcer healing) of nonselective

antimuscarinic drugs (atropine, propantheline,
oxyphenonium) invariably produce intolerable
side effects.
 PROSTAGLANDIN ANALOGUE
• PGE2 and PGI2
Role of PGs - cytoprotective
 Inhibition of acid secretion
 promoting mucus production
 Increasing HCO3¯ secretion
 inhibit gastrin release
 Increase mucosal blood flow
• Natural PGs have very short t½

• synthetic PGE1 – Misoprostol

• Major problems in the use of misoprostol are—

diarrhoea, abdominal cramps, uterine bleeding,
abortion. Patient acceptability is poor.

• Used in prevention & treatment of NSAID

associated gastrointestinal injury and blood loss.
 ANTACIDS
• These are basic substances which neutralize gastric
acid and raise pH of gastric contents.

• Antacids do not decrease acid production

• potency of an antacid - acid neutralizing capacity

(ANC)

• How much of antacid is required ?

 Systemic Antacids

• Sodium bicarbonate (1 g → 12 mEq HCl), &

Sodium citrate (1 g → 10 mEq HCl),

• water soluble, acts instantaneously, but the

duration of action is short. It is a potent
neutralizer pH may rise above 7.
 Systemic Antacids - Demerits
a) Absorbed systemically: large doses will induce
alkalosis.

(b) Produces CO2 in stomach → distention,

discomfort,belching, risk of ulcer perforation.

(c) Acid rebound occurs, but is usually short lasting.

(d) Increases Na+ load: may worsen edema and CHF.

Non-systemic Antacids
 Non-systemic Antacids
• insoluble and poorly absorbed basic compounds

• react in stomach to form the corresponding

chloride salt.

• chloride salt again reacts with the intestinal

bicarbonate so that HCO3¯ is not spared for
absorption—no acid-base disturbance occurs.
 Non-systemic Antacids
 Mag. Hydroxide (milk of magnesia)

 Magnesium trisilicate

 Aluminium hydroxide gel

 Magaldrate

 Calcium carbonate
 Mag. Hydroxide (1 g → 30 mEq HCl)

• low water solubility

• Aqueous suspension (milk of magnesia)

• low concentration of OH¯ ions and thus low

alkalinity.

• reacts with HCl promptly & Rebound acidity is mild

Magnesium trisilicate (1 g → 10 mEq HCl)
• 5% of administered Mg is absorbed
systemically— may cause problem if renal
function is inadequate

• Mg salts have a laxative action by generating

osmotically active MgCl2
 Aluminium hydroxide gel
• Al3+ ions relax smooth muscle  delays
gastric emptying.

• constipation occur due to its smooth muscle

relaxant and mucosal astringent action.

• Alum. hydrox. binds phosphate in the intestine

and prevents its absorption—
hypophosphatemia
• Magaldrate - hydrated complex of
hydroxymagnesium aluminate
• reacts rapidly with acid and releases alum.
hydrox.

• Calcium carbonate - liberates CO2 in the

stomach  distention and discomfort.
• greatest drawback of CaCO3 as an antacid is
that Ca2+ ions diffuse into the gastric mucosa
—> increase HCl production
 Milk alkali syndrome
• large quantity of milk was prescribed with
CaCO3

• syndrome characterized by headache,

anorexia, weakness, abdominal discomfort,
abnormal Ca deposits and renal stones due to
concurrent hypercalcaemia and alkalosis.
• It is rare now.
 Antacid combinations
(a) Fast acting (Mag. hydrox.) and slow acting (Alum.
hydrox.)
(b) Mag. salts are laxative & alum. salts are
Constipating bowel movement may be least
affected.
(c) Gastric emptying is least affected

(d) Dose of individual components is reduced;

systemic toxicity is minimized.
 ULCER PROTECTIVES
SUCRALFATE
• Basic aluminium salt of sulfated sucrose

• Sucralfate polymerizes at pH < 4 by cross

linking of molecules, assuming a sticky gel-like
consistency

• strongly adheres to ulcer base, especially

duodenal ulcer
• SUCRALFATE is
infrequently used
now because of
need for 4 large
well-timed daily
doses and the
availability of
• Dose: The ulcer healing
simpler and more
dose of sucralfate is 1 g
effective H2
taken in empty stomach
blockers/PPI
1 hour before the 3
major meals and at bed
time for 4–8 weeks.
 Colloidal bismuth subcitrate (CBS)
• water soluble but precipitates at pH < 5.

• MOA of CBS is not clear; probabilities are:

May increase gastric mucosal PGE2, mucus
and HCO3¯production
May precipitate mucus glycoproteins and coat
the ulcer base.
May detach and inhibit H.pylori directly
 ANTI-HELICOBACTER PYLORI DRUGS
• Gram negative
bacillus
• Attaches to the
surface epithelium
beneath the mucus
• High urease activity
• Produces ammonia
• H.Pylori can cause chronic gastritis, dyspepsia,
peptic ulcer, gastric lymphoma and gastric
carcinoma.
 Eradication of H. pylori infection

• Combination of PPI therapy + antimicrobial

therapy
• Single antibiotic drugs are not used because of
rapid development of resistance

Antimicrobials that are used clinically against

• Amoxicillin, clarithromycin, tetracycline and
metronidazole/tinidazole
 Anti-H.pylori one week Regimens
PPI AMOXICILLIN CLARITHROMYCI METRONIDAZOL
N E
Omeprazole (20 1 GM BD 500 MG BD -------
mg)
Esomeprazole ------- 250 MG BD 400 MG BD
(20 mg)
Lansoprazole (30 1 GM BD -------- 400 MG BD
mg)
Pantoprazole (40
mg)
Rabeprazole (20 500 MG TDS -------- 400 MG BD
mg)
 Two week-twice daily Regimens
PPI AMOXICILLIN CLARITHROMYCIN METRONIDAZOLE

Omeprazole (20 750 GM ----------- 400 MG

mg)

Lansoprazole (30 ------- 250 MG 400 MG

mg)

Pantoprazole (40 750 GM 500 MG --------

mg)
H.Pylori Kit
 US-FDA approved regimen is
Lansoprazole 30 mg
+
Amoxicillin 1000 mg
+
Clarithromycin 500 mg

all given twice daily for 2 weeks

 Quadruple therapy
CBS 120 mg QID +
tetracycline 500 mg QID +
metronidazole 400 mg TDS +
omeprazole 20 mg BD

is advocated for eradication failure cases

 GERD
• Stage 1: occasional heartburn (<3 episodes/
week), mostly only in relation to a
precipitating factor, mild symptoms, no
esophageal lesions

• Stage 2: > 3 episodes/week of moderately

severe symptoms, nocturnal awakening due to
regurgitation, esophagitis present or absent.
• Stage 3: Daily/chronic symptoms, disturbed
sleep,esophagitis/erosions/stricture/extra-
esophageal symptoms like laryngitis,
hoarseness, dry cough, asthma.

• Symptoms recur soon after treatment

stopped.
 Drugs for GERD
 Proton pump inhibitors (PPIs)

 H2 blockers

 Antacids

 Sodium alginate

 Prokinetic drugs
Sodium alginate
1. Name the most potent drug for peptic ulcer.
2. Mention the possible drug interactions with
antacids.
3. What is the rationals in giving a
combination of aluminium Hydroxide gel
and magnesium trisibirate.
4. Antacids should not be given along with
sucralfate why?
5. What bacteria is implicated in the etiology
of peptic ulcer?
6. Mention any one therapeutic regiment for
7. What are the advantages fo ranitidine compared to
cimetidine?
8. Which anti ulcer drug is preferred for NSAIDs
induced peptic ulcer.
9. Which anti ulcer drug is contra indicated in a
pregnant women.
10.What are the mechanism of actions of omeprazole
and cimetidine.
11.When should the antacids be given in relation to
the time of food.
12.What is the mechanism of action of misoprostal in
peptic ulcer?
13. Enumerate the uses of anti ulcer drug.
14. Why antacids are not suitable for long term
therapy?
15. Colloidal bismuth subcarbonate is an ulcer
protective and directly kills H. pylori : How
ever its use is restricted. Why?
16. Which of the anti ulcer drug known to
produce gastric cancer in rats on chronic
administration.
17. What is the treatment for stress induced
ulcer?
18. Between duodenal and gastric ulcer which
responds to anti ulcer treatment better?
19. Proton pump inhibitors, inhibit the pump;
inreversibily true or false.