peptic ulcer

1. Presented by:
Mohd akhtar
M.Pharm. (Pharmacology)

2.  Anatomy of Stomach
 Acid Peptic Disorders
 Peptic ulcer disease
 Comparison of Gastric & Duodenal ulcers
 Risk factors
 Symptoms
 Physiology of Acid secretion
 Treatment of peptic ulcer
 Summary

3. Muscularis
Serosa
Mucosa
Submucosa
FundicFundic
regionregion
Esophagus
Duodenum
AntrumAntrum
Layers
Parieta
l
cells
BodyBody
Pyloric
sphincter
Chief cells
Gastric pit

4.  Peptic Ulcers
• Gastric ulcer
• Duodenal Ulcer
 Gastro Esophageal Reflux Disease (GERD)
 Dyspepsia
 Stress Ulcers
 Gastric Cancers

5.  Peptic ulcer refers to an erosion of the mucosal
layer anywhere in the GI tract; however, it
usually refers to erosions in the stomach or
duodenum.
 Over 80% of peptic ulcers are caused by
Infection with the bacterium Helicobacter pylori.

6. Pathophysiology of Peptic UlcerPathophysiology of Peptic Ulcer
Disease (PUD)Disease (PUD)
Mucosal Defenses
• Bicarbonate
• Mucus
• Prostaglandin
• Growth factor
• Mucosal regeneration
Luminal Aggressors
• H. pylori
• NSAIDs
• Acid
• Pepsin

7. DUODENAL GASTRIC
INCIDENCE More common Less common
ANATOMY First part of duodenum –
anterior wall
Lesser curvature of
stomach
DURATION Acute or chronic Chronic
MALIGNANCY Rare Benign or malignant

9.  HELICOBACTER PYLORI Infection
 Non Steroidal Anti-inflammatory Drugs
 Steroid therapy
 Smoking
 Excess alcohol intake
 Genetic factors
 Zollinger Ellison syndrome – rare syndrome caused by
gastrin-secreting tumour
 Blood group O
 Hyperparathyroidism

10.  Nausea – Vomiting – Anorexia
 Epigastric pain after meal and during meal
 Intolerance of fatty food
 Heartburn
 Loss of weight
 Oral flatulence, bloating
 Pain radiating to the back

11. Feldman: Sleisenger & Fortran’s Gastrointestinal and Liver Disease, 7th
ed.

12.  Gastrointestinal hemorrhage
 Chronic iron deficiency anemia
 Pyloric stenosis
 Perforation
 peritonitis

13.  Bacteria
 Gram Negative spiral bacterium
 40% of patients >60 years are +ve for H.pylori
 Transmitted: possibly person to person
 Most common cause of antral gastritis
 Mechanism of gastric injury
 Adherence to epithelial cells
 Infects mucosa of stomach > inflammatory response >
gastritis > increased gastrin secretion > gastric
metaplasia > damage to mucosa > ulceration
 Cytotoxin

14.  Inhibits prostaglandin
synthesis (COX
inhibition)
 Disrupts functional
mucosal integrity
 ↓ mucosal blood flow
 ↓ cell regeneration
 Direct GI irritation
 Antiplatelet effect
(causing bleeding)
 ↑ acid (basal and
maximal stimulation)
secretion

16. ProglumideACh
PGE2
Histamine
Gastrin
Adenyl
cyclase
_
+
ATP cAMP
Protein Kinase
(Activated)
Ca++
+
Ca++
Proton pump
K+
H+
Gastric acid
Parietal cell
Lumen of stomach
AntacidOmeprazole
Ranitidine
H2M3
Misoprostol
_
_
_
_
+
PGE
receptor
+
+
Gastrin
receptor+
+
+
Cl-
K+

18.  Promotion of ulcer healing.
 Symptomatic relief of pain.
 Prevention of recurrence (relapse).
 Prevention of complications

19. I. Gastric hyposecretory drugs
 Proton pump inhibitors
 H2 receptor blockers
 Muscarinic receptor blockers
II. Eradication of H. pylori infections
 To prevent relapse
III. Mucosal cytoprotective agents
 Sucralfate
 Colloidal bismuth
 Prostaglandin analogues
IV. Neutralizing agents (antacids)

20. 1. Proton pump inhibitors
2. H2 receptor blockers
3. Muscarinic receptor blockers

21.  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
 Rabeprazole

22.  They are prodrugs – taken orally.
 Are given as enteric coated capsules
 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 (> 18 -24 hr).
 Bioavailability is reduced by food.
 Given 1 hr before meal.

23. PPIs are quite safe but may occur:
GIT disturbances: nausea, vomiting, diarrhoea
 Achlorhydria: increase the risk of enteric
infections due to Shigella, salmonella
 Hypergastrinaemia
 Gastric hyperplasia

24.  Mechanism of action
They competitively and reversibly block to H2
receptors on the parietal cells thus reduce gastric
secretion. They include:
H2 Receptor inhibitors include:
 Cimetidine
 Ranitidine
 Famotidine
 Nizatidine

25.  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

26. These are extremely safe drugs but may occur:
 nausea, vomiting,
 bradycardia and hypotension (rapid
I.V.)
 Gynecomasteia, impotence in male
 Galactorrhea in female on long term use
of cimitidine
 Decrease metabolism of oral anticoagulant,
phenytoin, benzodiazepines.

27. Acid (control)
H2 Block
PPI

28.  Mechanism of action
 Blocks M3 receptors on the parietal cells.
 Selectively inhibit gastric acid secretion
 Decreased gastric motility
 Delayed gastric emptying
Muscarinic blockers:
 Oxyphenonium
 Dicyclomine
 Pirenzepine
 Telenzepine

29. Treatment
Combined therapy is usually used.
 Clarithromycin, tetracycline, amoxicillin
 Proton pump inhibitors or H2 receptor
blockers
 Bismuth compounds
 Metronidazole
Resistance may develop to antibiotics so the
better eradication is obtained using proton
pump inhibitors, clarithromycin &
Amoxicillin.

30. The BEST among all the Triple therapy regimen is
Omeprazole/Lansoprazole - 20/30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin/Metronidazole -1gm/500 mg bd
Given for 14 days followed by P.P.I for 4 – 6 weeks.
Short regimens for 7 – 10 days not very effective.

31. REGIMEN DOSE DURATION
Bismuth
Metronidazole
Tetracycline
525 mg qid
250 mg tid
500 mg qid
2 weeks
omeprazole
Metronidazole
Clarithromycin
20 mg bid
500 mg bid
500 mg bid
1 week
omeprazole
Amoxacillin
Clarithromycin
20 mg bid
500 mg qid
500 mg bid
1 week
omeprazole
Bismuth
Metronidazole
Amoxacillin or /
Tetracycline
20 mg bid
525 mg qid
500 mg qid
500 mg qid
week

32. 1. Sucralfate
2. Prostaglandin analogs
3. Colloidal bismuth
 Bismuth subcitrate
 Tripotassium dicitrato bismuthate

33.  Sucralfate (aluminum hydroxide + sucrose)
 Form a sticky like gel over ulcer crater to
protect gastrointestinal mucosa and stimulates
prostaglandin synthesis
 It promote mucosal repair and ulcer healing
 It has no acid neutralising action and delay
gastric emptying
 Dose: 1 g QID

34.  Misoprostol is a prostaglandin E1 analog that
stimulates the secretion of mucus and
bicarbonates and inhibits acid secretion to a
minor degree.
 The drug has significant side effects, primarily
mild to moderate diarrhoea
 Is too costly to be used by most patients.

35. Drugs used to relief gastric pain associated with
hypersecretion of HCL and neutralize the gastric acid.
Mechanism of Action
Neutralization of HCL
Inhibition of pepsin (inactive at PH 5)
1. Systemic Antacids
Sodium bicarbonate
Calcium Carbonate
2. Non Systemic Antacids
Aluminum Hydroxide Gel
Magnesium Trisilicate

36.  Sodium bicarbonate
 Calcium Carbonate
NaHCO3 + HCL → NaCL + CO2
Disadvantages
 Rebound hyperacidity
 Stomach distension due to CO2 liberation
→ pain sensation
 Sodium load → salt and water retention
( # in cardiac patients)
 Systemic alkalosis

37.  Aluminum Hydroxide Gel
 Magnesium Trisilicate
Al (OH)3 + HCL → HCL3 + H2O
Advantages
 Longer duration of action.
 Gradual neutralization of HCL → No rebound
hyperacidity.
 Adsorbs pepsin.
 No stomach distention

38.  Due to the benign nature of duodenal ulcers
 When patients with duodenal ulcers require
surgery, it is usually one of three procedures:
 Vagotomy,
 Vagotomy with antrectomy,
 Pyloroplasty

39.  A peptic ulcer is a break in superficial epithelial
cells penetrating down to muscularis mucosa
 Duodenal > gastric ulcers
 H pylori is a predominant risk factor
 H pylori diagnosed by c urea breath test, stool
antigen or if validated serology, treated with
PAC500 or PMC250 regimen
 Complications of PUD can lead to acute
emergency of upper GI bleed