1. The document describes various screening models for evaluating potential anti-ulcer drugs, including the pylorus ligated rat model, stress ulcer models, and models using histamine, acetic acid, NSAIDs, reserpine, and cysteamine to induce gastric or duodenal ulcers. 2. The pylorus ligated rat model involves ligating the pylorus to cause ulceration from accumulated gastric acid, while stress ulcer models use restraint with or without cold water immersion to induce ulcers. 3. Additional models induce ulcers using substances like histamine, acetic acid, NSAIDs, reserpine, and cysteamine by various mechanisms like increasing acid secretion or

1. Screening methods for ulcer
(peptic & Duodenal )
Parv Dave
M.P.sem-3

2. List of contents
• Introduction
• Causes
• Signs and symptoms
• models

3. introduction
• A disruption of the mucosal integrity of the stomach and/or
duodenum leading to a local defect or excavation due to corrosive
action of acid or pepsin

4. Causes

5. Signs and symptoms
• A gnawing or burning pain in stomach between meals or at night
• Bloating
• Heartburn
• Nausea or vomiting
• Loss of appetite
• In severe cases, symptoms can include:
• Dark or black stool
• Vomiting blood or material that can look like coffee grounds
• Weight loss
• Severe pain in belly

6. Pathophysiology

8. Screening models
1.Pylorus Ligated Rat
2. Stress Ulcers:
• Restraint ulcers
• Water Immersion Induced Restraint Ulcers
• Cold and Restraint ulcers
• Restraint Plus Aspirin ulcers
• Swimming stress ulcers
3. Histamine Induced gastric ulcers in G. pigs
4. Acetic acid induced Chronic gastric ulcers

9. 5. Gastric mucosal damage by NSAIDs in rats.
• Aspirin
• Phenylbutazone
• Indomethacin
• Ibuprofen
6. Reserpine induced chronic gastric ulcers.
7. Serotonin induced gastric mucosal lesions
8. Cysteamine induced Duodenal Ulcer
9. Dimaprit induced Duodenal Ulcer

10. Pylorus Ligated Rat
Principle:
• Pylorus is ligated over a certain period of time
• Accumulation of gastric acid causes ulceration
Procedure:
• Wistar rats weighing 150-200 grams
• Fasting : 48 hours ; water ad libitum.
• Housed singly in cages with raised bottoms of wide wire mesh to avoid coprophagy.

11. • Under anaesthesia , a one-inch midline abdominal incision is done.
• Pylorus is ligated without damaging its blood supply.
• Stomach is replaced and abdominal wall closed
• Test compounds are given either orally or injected s.c.
• About 17-19 hours after pyloric ligation, rats are sacrificed and stomachs
are dissected out.

12. • Contents of the stomach are drained into a graduated centrifuge tube and
subjected to analysis for volume, pH, free and total acidity, mucin,
prostaglandin, total carbohydrate:protein ratio etc.
• Stomach is opened along the greater curvature.
• Its inner surface is examined for ulceration with a binocular microscope.
• The ulcer index is calculated and the Ulcer severity graded.

13. Ulcer index (Ui)
UN = Average number of ulcers per animal
US = Average of severity scores
UP = Percentage of animals with ulcers
UI = (UN + US + UP )× 10-1

14. ULCER SCORING :
• Type 0 : No visible ulcers
• Type 1 : 10 or less small ulcers, 1-3 mm in diameter
• Type 2 : 11 or more ulcers, 1-3 mm in diameter
• Type 3 : 1 or more ulcers, 4-6 mm in diameter
• Type 4 : 1 or more ulcers, 7 mm or more in diameter
• Type 5 : Perforation of the gastric wall

15. • Evaluation of the test
• Ulcer severity
0 = No ulcer
1 = Superficial ulcer
2 = Deep ulcer
3 = Perforation

16. Advantage:
• Evaluates anti-ulcer drugs with various mechanisms of action and
different doses.
Disadvantage:
• The ulcers localized in antrum of the stomach

17. Stress induced ulcer
• Gastrointestinal erosion is the one of the consistent finding in man
and in experimental animals subjected to different types of stress.
These ulcers appear to be the experimental of human stress ulcers.
• The major advantage of these preparation over pyloric ligated are
that they are technically simple, they do not require anaesthesia or
surgery
• they bring central nervous system into play and the lesions produced
by these methods are located in the glandular region of the rat
stomach.

18. i. Restraint- induced ulcers
Principle:
 Stress plays a significant role in the pathogenesis of gastric ulcers.
Procedure:
• Albino rats weighing 150-200 grams were taken
• Fasted for 36 hours before experiment
• Drug was administered orally or subcutaneously
• 30 min later animals were subjected to restraint

19. • For restraint, the rats were placed in a piece of galvanized steel window screen of
appropriate size.
• Screen was moulded around the animal and held in place with wire staples.
• To restrain the rats, the limbs were put together in pair and tightened with adhesive
tape.
• Rats were kept under restraint for 24 hours
• Rats were then sacrificed & their stomachs dissected out.
• Ulcer index and ulcer severity were determined.

20. ii. Cold water immersion induced ulcer
Principle:
 Exposure of cold conditions to restrained animals accelerates the occurrence of
gastric ulcers.
Procedure:
• Wistar rats weighing 150-200 grams are used.
• After fasting the animals for 16 hours, the test compound is administered orally

21. • Rats are then placed individually in restraint cages vertically, and then
immersed in water upto abdominal, at 22°C for 1 hour.
• Then rats are removed from the cages, dried
• Evan’s blue (30mg/kg) injected i.v. via the tail vein
• 10 min later, they are sacrificed
• The stomach is removed & ligated at both ends
• It is filled with Formol saline & kept overnight
• On the next day, the stomach is opened along the greater curvature and
examined for ulcerative lesions

22. • iii. Swimming stress ulcer
• Male wistar rats fasted for 24-36 hours are forced to swim inside the
vertical cylinders (height 30 cm, diameter 15 cm) containing water up
to 15 cm height maintained at 23° C
• Three hours after the stress, they are removed from the cylinders and
sacrificed by a blow on the head.
• The test drugs are administered 30 min prior to stress.

23. Histamine Induced gastric ulcers in G. pigs
Principle:
 Gastric acid secretion is increased when histamine is administered
intraperitoneally
Procedure:
• Guinea pig weighing 300-400 grams are taken
• Fasted for 36 hours before experiment; water ad libitum
• 1 ml of histamine acid phosphate (50 mg base) was administered i.p.

24. • The standard/test drugs were administered s.c. 45 minutes before
histamine injection.
• 4 hours after histamine injection, guinea pigs were sacrificed and
stomach dissected out.
• The gastric contents were subjected to analysis
• Stomach was opened along the greater curvature, ulcers were
identified.

25. Advantages:
• Produces 100% gastric ulceration
• Increased volume of gastric acid secretion
• Marked enhancement of free and total acidity.

26. Acetic Acid-induced gastric Ulcer
Principle:
Acetic acid enhances the ulceration in stomach by increasing the acidity of
stomach contents.
Procedure:
• Wistar rats weighing 150-200 grams are taken
• Fasted for 24 hours before experiment.
• Pentobarbital anaesthesia
• A cylindrical glass tube of 6 mm diameter : tightly placed upon the anterior serosal surface of
stomach 1 cm away from the pyloric end.

27. • 50% Acetic acid (0.06 ml per animal) was instilled into the tube and
allowed to remain for 1 minute on the gastric wall .
• After removal of Acetic acid solution, the abdomen was closed.
• Animals were caged and fed normally.
• Test drugs were given orally on Day 1 twice daily, 4 hours after application
of acetic acid and continued upto 10 days after induction of ulcer
• Animals were sacrificed after 18 hours of the last dose
to assess ulcer size and healing.
• Ulcer index and Severity score calculated.

28. Advantages:
• Simple procedure: resulting in ulcers of consistent size and severity at an
incidence of 100%.
• Resemble human ulcers in terms of both pathological features and healing
mechanisms.
• Relapse of healed ulcers is frequently observed,just as in peptic ulcer
patients.
Disadvantages:
• Submucosal injection produced ulcers penetrating entire gastric wall
& adherence of ulcer base to adjacent organs (mainly Liver).

29. Indomethacin-induced gastric lesions(NSAIDs)
Principle:
 NSAID induced gastric damage ; by blocking COX enzyme, endogenous
prostaglandin production inhibited.
Procedure:
 Rats fasted for 36 hours before Indomethacin administration (20 mg/kg, orally)
 30 min prior to the administration of the Indomethacin, standard/test drug is
administered.

30.  1 hour after Indomethacin administration
 Rats are sacrificed, their stomach dissected out
and examined for the number of lesions
under the microscope.
 Ulcer index and ulcer severity are determined.

31. Serotonin induced gastricmucosal lesions
• Principal:
• Reserpine produces severe hemorrhagic ulceration of the stomach
• which has been attributed to significant degranulation of gastric mast
cells and
• consequent liberation to histamine.

32. • Procedure:
• The animals are fasted for 24 h prior
• Gastric lesions are scarcely noticed at 0.5 h after serotonin injection
(ulcer index 1.2), but are obviously distinguishable at 1 hr (ulcer index
7.7) and reach maximum intensity at 4 h (ulcer index 15.2 ).
• The lesions are located mainly at the side of the greater curvature of
the corpus.
• The ulcer index decreases to 8.0 at 8 h and is maintained at this level
upto 24 h after
• serotonin injection

33. Reserpine induced chronic gastric ulcers
• Principle:
• Reserpine produces severe hemorrhagic glandular ulceration of the
stomach
• which has been attributed to significant degranulation of gastric mast
cells and consequent liberation to histamine.

34. • Procedure:
• 24 h fasted rats
• administered reserpine 5 mg/kg/day for 5 days and sacrificed after
two weeks.
• All the rats developed solitary chronic gastric ulceration.
• ulcers are oval or round situated at or round situated

35. Duodenal Ulcer

36. Cysteamine induced Duodenal Ulcer
Principle:
• Inhibition of alkaline mucus production
• Increased gastric acid secretion
• Increased serum gastrin levels
• Delayed gastric emptying

37. Procedure:
• Female Sprague-Dawley rats weighing 150-200 grams are taken
• Test drug and the standard drug are administered 45 min prior to
Cysteamine administration.

38. MODEL ANIMAL ROUTE DOSE DURATION
Cysteamine
induced
duodenal ulcers
(Cysteamine)
10% in N.S.
Sprague-
Dawley rats
150-200
grams
Orally
S.C.
28mg/100g
20mg/100g
3 times at intervals of 3.5
hours --> animals sacrificed
after 28 hours of 1st dose
2 times at 4 hours interval-
-> animals sacrificed after
40 hours of 1st dose

39. • Perforating duodenal ulcers are produced
• Located 2-4 mm from the pylorus, mainly on
the anterior wall of duodenum
• Necrotic material and acute inflammatory response
is present at ulcer crater

40. Advantages:
Ulcerogenesis is seen with one full dose of cysteamine.
Easily reproducible
Disadvantage:
• Ulcers, located on the anterior wall, frequently perforate, resulting in
peritonitis, or penetrate into the liver.
• A small ulcer is usually present on the posterior wall (“kissing ulcer”) of the
duodenum , penetrates the pancreas.

41. Dimaprit induced Duodenal Ulcer
Principle:
 H2 receptor agonist
 Induced gastric erosion in rats after single i.v. dose.
 Duodenal ulcer in guinea pigs after repeated s.c. dose.
Procedure:
• Wistar rats weighing 150-200 g or guinea pigs 250-300 g are taken
• Fasted for 24 hours before experiment; free access to water
• Test drug or standard drug is given orally 60 min before injecting Dimaprit in rats
and 30 min before injecting it in guinea pig.

42. • Dimaprit is given in a dose 100 mg/kg i.v. in rats and 2
mg/kg s.c. every hour for 6 hours in guinea pig.
• After 1 hour of Dimaprit injection, Animal is sacrificed and stomach
dissected out.
• Stomach is opened along the greater curvature and examined for
ulceration.

43. Treatment of ulcer

44. Reference
• Wolfgang H.Vogel, “Drug Discovery and Evaluation”, springer,2nd
eddition

45. Thank you