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PEPTIC ULCER
Definitions: Stomach or duodenal mucosal
lesions
Occurrence: due to imbalance between
aggressive factors and mucosal protective
mechanisms.
PEPTIC ULCER
Aggressive factors
Pepsin secretion - acid secretion
Protective factors
Prostaglandins (E2 & I2 )
Mucus/bicarbonate secretion
Mucosal blood flow
Rapid turnover of gastric mucosa
Risk factors
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H Pylori infections
Alcohol
Smoking
Diet
Drugs (NSAIDs, corticosteroids).
Stress
Genetic factors
Diseases (Zollinger Ellison Syndrome).
SYMPTOMS:

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Nausea – Vomiting – Anorexia
Upper abdominal pain.
Weight loss.
Heart burn.
COMPLICATIONS:
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Gastrointestinal hemorrhage
Chronic iron deficiency anemia
Pyloric stenosis
Perforation
Gastric secretions
1.
Pepsinogens (Chief cells).
2.
HCl and intrinsic factor (Parietal cells).
3.
Gastrin (G-cells).
4.
Mucus, bicarbonate (mucus-secreting cells).
Regulation of Gastric secretions
1.
2.
3.
Histamine (local hormone)
Acetylcholine (neurotransmitter).
Gastrin (hormone).
AIMS OF ULCER TREATMENT
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Promotion of ulcer healing.
Symptomatic relief of pain.
Prevention of recurrence (relapse).
Prevention of complications
DRUG TREATMENT OF PEPTIC ULCER
I. Gastric hyposecretory drugs.
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H2 receptor blockers
Muscarinic receptor blockers
Proton pump inhibitors
II. Eradication of H. pylori infections
To prevent relapse
DRUG TREATMENT OF PEPTIC ULCER
III. Mucosal cytoprotective agents.
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Sucralfate
Colloidal bismuth
Prostaglandin analogues
IV. Neutralizing agents (antacids).
Gastric hyposecretory drugs
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•
H2 receptor blockers
Muscarinic receptor blockers
Proton pump inhibitors
Decreasing gastric acidity can reduce
absorption of ketoconazole & iron
preparation, digoxin.
Proton Pump Inhibitors
Mechanism of action
Irreversible inhibition of proton pump (H+/ K+
ATPase) that is responsible for final step in
gastric acid secretion from the parietal cell.
PP inhibitors include:
 Omperazole
 Lansoprazole
 Pantoprazole
Illustration of Gastric secretion by parietal cells
Pharmacokinetics:
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They are prodrugs – taken orally.
are given as enteric coated capsules
They are rapidly absorbed from the intestine.
They are activated in the acidic medium of the
secretory parietal cell canaliculus.
They are inactivated if (combined with H2
receptor blockers).

Have long duration of action (> 12 h-24 h).

Once daily dose is sufficient
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Bioavailability is reduced by food.

Given 1 h before meal.
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Are metabolized in the liver by CytP450.

They are more potent than H2 receptor
blockers

Inhibits basal and stimulated-acid secretion.

Dose reduction is required in severe liver
failure.
USES
1. Zollinger Ellison syndrome (First choice).
2. Resistant severe peptic ulcer ( 4-8 weeks).
3. Reflux esophagitis.
4. Eradication of H. pylori.
ADVERSE EFFECTS
GIT disturbances: nausea, vomiting, diarrhea
 Achlorhydria.
 Hypergastrinaemia
 Gastric hyperplasia.
 Increased bacterial flora (nitrosamine)

H2 receptor blockers
Mechanism of action
 They competitively and reversibly block to H2
receptors on the parietal cells thus reduce
gastric secretion. They include:
-
Cimetidine
Ranitidine
Famotidine
Nizatidine
Pharmacokinetics
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Good oral absorption
Plasma half life (1-3 h).
Duration (4-12 h).
First pass metabolism (50% Except
Nizatidine 100 % bioavailability).
Given before meals.
Metabolized by liver.
Excreted mainly in urine.
Cross placenta & excreted in milk
Pharmacological actions:

Inhibit histamine, gastrin, cholinergic drug induced secretions.

Reduce basal and food-stimulated gastric
secretion.
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Reduce pepsin activity.

Promote mucosal healing & decrease pain
USES:
•
Duodenal Ulcer (6-8 weeks).
•
Benign gastric ulcer (8-12 weeks).
•
Reflux esophagitis
•
Zollinger Ellison Syndrome (large doses).
•
Pre-anesthetic medication (To prevent
aspiration pneumonitis).
•
Eradication of H. pylori infections.
Adverse Effects of H2 blockers:
1.
GIT disturbances: nausea, vomiting
2.
CNS effects:
Headache, dizziness, confusion (elderly –
renal or hepatic dysfunction).
3.
CVS effects
Bradycardia and hypotension (rapid I.V.)
Cimetidine has other adverse effects:
4.
Endocrine effects
 Antiandrogenic actions (gynecomasteia –
impotence)

5.
Galactorrhea in women.
Cytochrome P450 inhibitor: decrease
metabolism of oral anticoagulant, phenytoin,
benzodiazepines.
Precautions
1.
2.
Maintenance dose (Relapse may occur).
Dose reduction in severe renal or hepatic
failure and elderly.
ANTICHOLINERGIC DRUGS
1. Non selective muscarinic blockers:
Oxyphenonium, dicyclomine
Decreased gastric motility
- Delayed gastric emptying
- Heart burn
- Atropine like side effects.
-
2. Selective muscarinic blockers:
Pirenzepine - Telenzepine
 Blocks M1 receptors on the parietal cells.
 Selectively inhibit gastric acid secretion
 No effect on gastric motility
 Less side effects of cholinergic blockade.
 No effect on CNS.
 Dose : 50 mg bid for 4-6 weeks
Uses
1.Adjuvants to H2 receptor blockers.
2. decrease nocturnal pain in peptic ulcer.
Eradication Of H Pylori
Is a bacteria that causes chronic inflammation
of the inner lining of the stomach.
 Produce enzymes (tissue damage),
inflammation – ulcer.
 Duodenal ulcer - Gastric ulcer
 Risk factor for esophagus and stomach cancers.
 Eradication is important to prevent recurrence
of ulcer.

Helicobacter pylori in association with
gastric mucosa
Treatment
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Combined therapy is usually used.
– Clarithromycin, tetracycline, amoxicillin
– Proton pump inhibitors or H2 receptor
blockers.
– Bismuth compounds
– Metronidazole.
Resistance may develop to antibiotics.
Better eradication is obtained using proton
pump inhibitors & clarithromycin.
Treatment
The standard first-line therapy is "triple
therapy" consisting of proton pump inhibitors
as omeprazole and the antibiotics
clarithromycin and amoxicillin.
REGIMEN
DOSE
DURATION
Bismuth
Metronidazole
Tetracycline
525 mg qid
250 mg tid
500 mg qid
2 weeks
omeprazole
20 mg bid
500 mg bid
500 mg bid
1 week
20 mg bid
500 mg qid
500 mg bid
1 week
Metronidazole
Clarithromycin
omeprazole
Amoxacillin
Clarithromycin
omeprazole
Bismuth
Metronidazole
Amoxacillin
Tetracycline
or
20 mg bid
525 mg qid
500 mg qid
/ 500 mg qid
week
Mucosal protective agents.
1.
2.
3.
Sucralfate
Prostaglandin analogues.
Colloidal bismuth
Sucralfate
Sucrose octaphosphate + aluminium hydroxide
Mechanism of action
1.
In acidic pH, sucralfate dissociates into its
components.
2.
The negatively charged sucrose
octaphosphate binds with positively
charged protein molecules found in
damaged mucosa (Coat over the ulcer).
3.
Promote ulcer healing.
4.
Inhibition of pepsin.
3.
Stimulation of mucosal protective
mechanisms (mucous and bicarbonates
secretion).
Kinetics
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Orally, poor systemic absorption.

Duration (6 h).
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Excreted in feces.
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Avoid co-administration of antacid or H2
blocker.
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Bette taken on empty stomach.
Therapeutic Uses
 Benign gastric and duodenal ulcer.
 Chronic gastritis.
Adverse effects
 Constipation and dry mouth.
 Interferes with absorption of some drugs
tetracycline, theophyline, Tricyclic
antidepressant.
2. Misoprostol
 Prostaglandin Analogues (PGE1 )
  HCL secretion.
 Promote tight junction of gastric cells
prevent back diffusion of HCL.
  mucous and bicarbonate secretion.
blood flow of mucosa improve healing of ulcer.
Kinetics
Orally, 30 min.
is converted into active metabolite.
Excreted in urine- must be taken 3-4 times/day.
Therapeutic uses
 Prevention of NSAIDS-induced peptic ulcer.
Adverse Effects
 Abdominal cramps (sever colicky pain).
 Diarrhea.
 Uterine contraction dysmenorrhea or
abortion.
 Vaginal bleeding.
3. Colloidal Bismuth compounds
Bismuth subcitrate
Tripotassium dicitrato bismuthate.
Mechanism of Action
1.
It forms a precipitate with mucous cover the ulcer
with a protective coat that prevent effect of HCl.
2.
Promote healing of ulcer.
3.
Bactericidal effect against campylobacter pylori .
4.
Decrease activity of pepsin
5.
 Mucous & bicarbonate secretion.
Adverse Effects
1. Black stool.
2. Teeth discoloration.
3. Encephalopathy (in renal dysfunction).
USES
1. Triple therapy for eradication of H. pylori.
2.
Benign gastric & duodenal ulcer.
3. Traveller’s diarrhea
Drugs That Neutralize HCL (Antacids)
Drugs used to relief gastric pain associated
with hypersecretion of HCL.
Mechanism of Action
 Neutralization of HCL.
 Inhibition of pepsin (inactive at PH 5).
Therapeutic Uses
1. relief pain of peptic ulcer.
2. Dyspepsia.
I - Systemic Antacids
Sodium bicarbonate
NaHCO3 + HCL  NaCL + CO2.
Disadvantages
1. Rebound hyperacidity.
2.
Stomach distension due to CO2 liberation
 pain sensation.
3. Sodium load  salt and water retention
( # in cardiac patients).
4. Systemic alkalosis.
Calcium Carbonate
CaCO3+HCL  CaCl2 + H2O + CO2
Disadvantages
1. Liberation of CO2  stomach distension
2. 10% is absorbed  hypercalcemia.
3. Rebound hyperacidity.
4. Milk alkali syndrome (hypercalcemia, renal
failure).
II – Non Systemic Antacids
1. Aluminum Hydroxide Gel
2. Magnesium Trisilicate
Al (OH)3 + HCL  HCL3 + H2O.
Advantages
1.
Longer duration of action.
2.
Gradual neutralization of HCL  No
rebound hyperacidity.
3.
Adsorbs pepsin.
4.
Minimal change in acid base balance.
5.
No stomach distention
Disadvantages
Al (OH)3
1.
Constipation.
2.
Drug interaction:  absorption of
tetracycline, digoxin, iron.
Magnesium Trisilicate
1.
Diarrhea
2.
CNS depression (renal failure).
Alginates (Gaviscon)
Combine with antacids in reflux esophagitis
to increase adherence of mucus to
esophageal mucosa.