Drugs Used in Peptic Ulcer

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 Peptic ulcer
A localized loss of gastric or duodenal mucosa leads to
the formation of peptic ulcer.
duodenal ulcer gastric ulcer

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 Pathogenesis of peptic ulcer
1. Aggressive factors
Helicobacter Pylori ( H. Pylori)
gastric acid and pepsin
2. Defensive factors
mucus-bicarbonate barrier
prostaglandins

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 H. pylori
In 1983, H. pylori was found by two
Australians, Marshall and Warren.
And the two men won the noble prize for
the important findings in 2005.
H pylori is most common cause of PUD
Secretes urease convert urea to
ammonia
Produces alkaline environment enabling
survival in stomach
Almost all duodenal and 2/3 gastric ulcer
pts infected with HP
Considered class 1 carcinogen gastric
cancer
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H. Pylori (48,000)

flagellum
flagellum

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The Nobel Prize in Physiology or Medicine (2005) was awarded jointly
to Barry J. Marshall and J. Robin Warren "for their discovery of the
bacterium Helicobacter pylori and its roleUploaded
in gastritis by:
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peptic ulcer disease"
J. Robin Warren (2005) Barry J. Marshall (2005)
 Classification of drugs :
. Agents eradicating helicobacter
pylori.

. Agents decreasing secretion of

gastric acid

. Agents protecting mucosal barrier

. Antacids
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Regulation of gastric acid secretion

Proglumide

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Drugs reducing secretion of gastric acid

(1) H2-receptor antagonists

(2) Inhibitors of the proton pump
(3Antimuscarinic agents)
(4) gastrin-receptor antagonists

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 H2-R antagonists
Cimetidine, Ranitidine, Famotidine , Nizatidine
MOA:
Competitively block the binding of histamine to
H2 receptor. Completely inhibit gastric acid
secretion induced by histamine.
Characteristics:
more effective than M-R antagonists;long
duration; high rate of healing up; rebound

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Regulation of gastric acid secretion

Proglumide

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 Cimetidine
Pharmacokinetics:
Absorption: p.o F=70%
Distribution: widely
Elimination: kidney
! Heptic microsomal enzyme inhibitor
inhibit all kinds of gastric acid secretion

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 Clinical uses
peptic ulcers :
effective in promoting healing of peptic ulcers.
400 mg bid 4W80% healing
Zollinger-Ellison syndrome : a fatal disorder in
which a gastrin-producing tumor causes
hypersecretion of gastric acid.
gastroesophageal reflux disorder
(GERD, heartburn):

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 Adverse reactions
1.The common side effects are:
headache, dizziness, diarrhea and muscular
pain, skin rash
2.CNS effects:
confusion, disorientation and hallucination
3. Endocrine system effects: gynecomastia,
impotency, galactorrhea

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 Ranitidine
Antisecretive effect is 10 times that of
Cimetidine .
Less effect on hepatic microsomal
metabolism system.
Longer duration and less antiandrogenic
effect

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 Famotidine
1) Antisecretive effect is 40 times that
of Cimetidine .
2) Have no effect on hepatic
microsomal metabolism system.

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 Inhibitors of the proton pump
Omeprazole, lansoprazole, pantoprazole

Pharmacological effects:
Inhibits H+ being transported to gastric lumen
through inhibiting the proton pump.
Potent and long-lasting effect: Can inhibit over
95% of gastric acid secretion.
Also inhibit release of peptin and H.P

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 Omeprazole - MOA
Its a Prodrug
Covalent binding with sulfhydryl
cysteines of HK ATPase
Irreversible inactivation of the pump
molecule

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 Pharmacokinetics - PPI
Given on an empty stomach ( before 30
minutes to 1 hour)
After absorption, they are distributed by
blood to parietal cell canaliculi
Half life is very short and only 1-2 Hrs
Still action persists for 24 Hrs to 48 hrs after a
single dose
Highly protein bound and rapidly
Metabolized by the
Excreted in Kidneys minimally

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 Adverse Effects
GIT: nausea, abdominal pain, constipation,
flatulence, and diarrhea
Prolonged use:
Gynaecomastia, erectile dysfunction
Leucopenia and hepatic dysfunction
Vitamin B12 deficiency
Hypergastrinemia which may promote the
growth of gastrointestinal tumors (carcinoid
tumors )

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 PPI contd.
Drug Interaction:
Inhibits metabolism of Warfarin,
Diazepam
Therapeutic uses:
1. Gastroesophageal reflux disease (GERD)
2. Peptic Ulcer
3. Zollinger ellison Syndrome
4. Prevention of recurrence of (NSAID) -
associated gastric ulcers in patients who
continue NSAID use.
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Antacids
Antacids are weak bases that neutralize gastri HCl.
the pH of the stomach contents.
the acid load delivered to the duodenum and
the activity of pepsin.
Antacids are given between meal and at bed time
when symptoms of hyperacidity
the presence of food in the stomach can prolong
their neutralizing capacity.

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1.Systemic Antacids:
Sodium bicarbonate(NaHCO3)
Acts rapidly
Neutralized gastric asid (HCl), to (CO2) and (NaCl).
Formation of CO2 results in gastric distention and
belching
that can be dangerous if ulcer is near perforation.
Unreacted alkali is absorbed and can raise the pH of
blood (systemic alkalosis) and the urine.
Absorption of NaCl may increase
sodium load and this may exacerbate fluid retention in
patients with hypertension and CHF.
The sudden release
of CO2 can cause rebound acidity.
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2. Non-systemic Antacids
are poorly absorbed from GIT
a) Buffer Type Non-systemic Antacids
Aluminium hydroxide
Magnesium trisilicate
Aluminium hydroxide can cause
constipation and
Magnesium trisilicate diarrhoea.

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b) Non-Buffer Type Antacids
(Calcium carbonate and
Magnesium hydroxide)
are powerful drugs with fast onset of action.
Calcium carbonate may cause
belching due to liberation of carbon dioxide.
It can cause constipation .
Magnesium hydroxide does not liberate
carbon dioxide but can cause diarrhoea.

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 Antacids
Capsules & Tablets:
Powders
Chewable tablets
Suspensions
Effervescent granules and tablets

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 Muscarinic antagonists
Pirenzepine and Telenzepine
Block the M1 class receptors
Reduce acid production
Abolish gastrointestinal spasm

Mechanism of action:
Reduce meal stimulated HCl secretion by reversible blockade of
muscarinic (M1) receptors on the cell bodies of the intramural
cholinergic ganglia

Unpopular as a first choice because of high incidence of

anticholinergic side effects (dry mouth and blurred vision)

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 Agents protecting mucosal barrier

(1)Prostaglandins
(2)Mucosal protective agents

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 Prostaglandin analogues -
Misoprostol
Actions:
Inhibit histamine-stimulated gastric acid secretion
Stimulation of mucin and bicarbonate secretion
Increase mucosal blood flow
Therapeutic uses:
Prevent ion of NSAID-induced mucosal injury
(rarely used because it needs frequent
administration 4 times daily)

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 Misoprostol
Doses: 200 mcg 4 times a day (Misoprost)
ADRs:
Diarrhoea and abdominal cramps
Uterine bleeding
Abortion
Exacerbations of inflammatory bowel disease and
should be avoided in patients with this disorder
Contraindications:
1. Inflammatory bowel disease
2. Pregnancy (may cause abortion)

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Sucralfate ulcer protective
Salt of sucrose complexed to sulfated
aluminium hydroxide (basic
aluminium salt)
MOA:
In acidic pH polymerises to viscous gel
that adheres to ulcer crater - more on
duodenal ulcer
Precipitates protein on surface proteins
and acts as physical barrier
Dietary proteins get deposited on this
layer forming another coat
Delays gastric emptying and causes
gastric PG synthesis protective action
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 Sucralfate contd.
Taken on empty stomach 1 hr. before meals
Concurrent antacids, H2 antagonist avoided (as
it needs acid for activation)
Uses:
NSAID induced ulcers
Patients with continued smoking
Topically burn, bedsore ulcers, excoriated skins
Dose: 1 gm 1 Hr before meals
ADRs: Constipation, hypophosphatemia
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 Bismuth subsalicylate
Pharmacological actions:
Undergoes rapid dissolution in the stomach
into bismuth and salicylates
Salicylates are absorbed
Bismuth coats ulcers and erosions protecting
them from acid and pepsin and increases
prostaglandin and bicarbonate production
Uses:
Treatment of dyspepsia and acute diarrhoea

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Mucosal protective agents
These compounds, known as cytoprotective
ones , have several actions that enhance
mucosal protection mechanisms, thereby
preventing mucosal injury, reducing
inflammation and healing existing ulcers.
clinical uses: NSAID-induced ulcer
adverse reactions: dose-dependent diarrhea,
stimulate uterus

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Misoprostol: a stable analog of PGE2
(1) inhibits secretion of gastric acid and stimulate
secretion of mucus and bicarbonate.
(2) dilate blood vessel of mucous membrane.
(3) currently the only agent approved for prevention
of gastric ulcers induced by NSAIDs.
(4)less effective than H2-receptor antagonists for
acute treatment of peptic ulcers.
(5)produces uterine contractions and is
contraindicated during pregnancy.

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Mucosal protective agents
Sucralfate
1)In water or acidic solutions it forms a viscous,
tenacious paste that binds selectively to ulcers or
erosions for up to 6 hours.
2)Also stimulates prostaglandin release and mucus and
bicarbonate output.
3)Promote effects of growth factors
4)Inhibit H.P
! Needs acid envioment; affects absorption of other
drugs

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Mucosal protective agents
colloidal bismuth subcitrate
1) binds to an ulcer crater, coating it and
protecting it from acid and pepsin.
2) Inhibits the activity of pepsin
3) increases mucous secretion
4) increase prostaglandin synthesis
5) helps to eradicate H. pylori

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 Antimicrobial agents
Optimal therapy of patients with peptic ulcer
disease who are infected with H.Pylori
requires antimicrobial treatment.
Eradication of H.Pylori results in rapid healing of
active peptic ulcers and low recurrence rates.

Metronidazole, tetracycline, amoxiciliin, etc.

Often combined with other drugs.

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