This document summarizes peptic ulcers, including their causes, symptoms, complications, and treatment. Peptic ulcers are chronic inflammatory conditions involving the stomach and duodenum caused by excess acid and pepsin. Common symptoms include abdominal pain and bleeding. Untreated ulcers can lead to complications like bleeding, infection, or obstruction. Various factors like heredity, diet, medications, and infections contribute to ulcer development. Treatment involves reducing acid secretion using proton pump inhibitors, H2 blockers, or antacids. Animal models are used in research to study ulcer development and potential new treatments.

1. ANTIULCER:
• PEPTIC ULCER: It is a chronic inflammatory
condition involving a group of disorders
characterized by ulceration in regions of upper
gastrointestinal tract where parietal cells
secret pepsin and hydrochloric acid or
duodenal mucosa occurring at the site where
the mucosal epithelium is exposed with acid
and pepsin

5. • Signs and symptoms: Here in peptic ulcer diseases
patients can be asymptomatic or experience anorexia,
nausea, vomiting, bleaching and blotting and heart
burn or epigastric pain.
Etiology of chronic ulceration:
• Heredity: Patients with peptic ulcer often have a family
history of the diseases. This is particularly the case with
duodenal ulcers which develop below the age of 20
years. The gastric ulcer patients have 3 times the
expected number of gastric ulcer but duodenal ulcer
occurs with the same frequency amongst relatives as in
the general population.

6. • Acid-pepsin Vs mucosal resistance:
• The immediate cause of peptic ulceration is
digestion of the mucosa by acid and pepsin of
the gastric juice. But the sequence of events
leading to this is unknown. Digestion by acid
and pepsin cannot be the only factor involved,
since the normal stomach is obviously capable
of resisting digestion by its own secretion. The
concept of ulcer etiology may be written as
“acid plus pepsin Vs mucosal resistance”.

8. • Gastric hyper secretion:
• Ulcer occurs only in the presence of acid and
pepsin. They are never found in achlorhydric
patients such as those with pernicious
anaemia. Peptic ulcer is the most common
gastrointestinal disorder in clinical practice.
Considering the side effects like arrhythmias,
gynacomastia and haematopoietic changes of
synthetic drugs hence there usage for a
chronic period is restricted.

9. COMPLICATIONS:
• Left untreated, peptic ulcers can result in:
• Internal bleeding. Bleeding can occur as slow
blood loss that leads to anemia or as severe
blood loss that may require hospitalization or
a blood transfusion. Severe blood loss may
cause black or bloody vomit or black or bloody
stools.

10. • Infection. Peptic ulcers can eat a hole through
(perforate) the wall of your stomach or small
intestine, putting you at risk of serious
infection of your abdominal cavity
(peritonitis).
• Obstruction. Peptic ulcers can block passage
of food through the digestive tract, causing
you to become full easily, to vomit and to lose
weight through either swelling from
inflammation or scarring

11. DIFFERENT FACTORS RELATED TO ACID SECRETION:
• General factors: Vagal hormonal effect, histamine
and epinephrine, insufficient circulation, shock
and general ischemia increase the secretion.
•
• Constitutional and environmental factors i.e. sex,
age, temperature, family history, social class,
geographical differences; occupation may also
influence the acid release.
• Local factors in stomach.

12. • Aggressive factors: HCl, pepsin, refluxed bile,
NSAIDs, alcohol, pancreatic proteolytic
enzymes, ingested irritants, bacterial toxins,
physiochemical trauma; all of these factors
increase the acid secretion.
• Digestive factors: Mucus, bicarbonates, blood
flow, resolution of epithelium, the current
status of therapy.

14. Classification of drugs used in peptic
ulcer:
• DRUGS THAT INHIBIT GASTRIC AICD
SECREATION
• DRUGS THAT NEUTRALIZE GASTIC ACID(
ANTACID)
• ULCER PROTECTIVE
• ANTI- H.PYROLI DRUGS

15. Drugs that inhibit gastric acid
secreation:
• H2 Receptor blocker- Cimetidine, Ranitidine,
Famotidine
• Proton pump inhibitor – Omeprazole,
pantoprazole, esomeprazole
• Anticholinergics- Pirenzepine
• Prostaglandin analoges - Mesoprostol

16. 2. Antacids
• Systemic:
Eg: sodium bicarbonate, sodium citrate
• Non systemic:
Eg: Magnesium hydroxide, alluminium
hydroxide gel

17. • 3. Ulcer protective: - Sucralfate
colloidal bismuth sulfate
• 4. Anti H.Pylori drugs:
amoxicilline
tinidazole

18. ANIMAL MODELS IN EXPERIMENTAL PEPTIC
ULCER:
• Studies on animal models helps to understanding the aetiology and
screening of anti-ulcer agents.
• IN-VIVO MODELS:-
• Ethanol-induced ulcers
• Cold restraint stress-induced ulcers
• Stress-induced gastric ulceration
• Pylorus ligated (PL)-induced ulcers
• Acetic acid-induced ulcers
• Histamine- induced ulcers
• Indomethacin -induced ulcers
• Serotonin- induced ulcer
• Aspirin-induced ulcers
• Reserpine -induced ulcers

19. • In- vitro models:-
1. [I125 ] Gastrin Binding Assay
2. Tiotidine Binding Assay
3. H+/K+- ATPase Inhibiting Assay

20. Alcohol induced gastric ulcer:
• PRINCIPLE:
Alcohol being a necrotizing agent, damage the
superficial epithilial layer and inhibits the
release of mucosal prostraglandins.

21. • PROCEDURE:
Wistar rats of 150-200 gm are taken, fasted for 18
hours before experiment , water ad libitum
Rats are given test drugs or standard drugs orally,
30 min later 1ml/200gm of 99.8 % ethanol is
administered orally
After 1 hours rat are sacrified and stomach are
disected out, severity score and ulcer index are
calculated

22. • Witt el al. (1985) describes a method to quantify
the extend of ethanol induce lessions.
• Using a transmission densiometer tho measure
the opticaldensity of photoghrahic negetives of
gastric mucosa.
• Damage area has lower optical density values.
ADVANTAGE:
Gastric lesions are examined after 1 hours of
ethanol administration
Reproduceable method to prouce gastric lesions in
experimental animals.

23. PYLORUS LIGATION IN RAT
• PRINCIPLE:
• Pylorus was ligated for certain period of time
and accumulation of gastric acid cause
ulceration.

24. PROCEDURE
• Wistar male rat was taken of 180-200gm and
was kept for fasting for 48hrs
• Under anaesthesia 1 inch midline abdominal
incision is given below the xiphoid process
• Pylorus is ligated without damaging the blood
supply

25. • Stomach is replaced and abdominal wall is closed
with suture. Test compund are given orally or
injected by SC
• About 17-19 hr later of ligation the rats are
sacrified and the stomach is dissected out
• The content of stomach are drained into
graduated centrifugation tube and send for the
study of volume, pH , free radical acid, total
acidity , prostraglandin,mucin, total carbohydrate
and protein ration

26. • Stomach is opened on greater curvature and
pined on cork plate, its inner surface is
examined for ulceration under occular
microscope
• The ulcer index is calculated and severity is
marked

27. EVALUATION:
• 0 = No ulcer
• 1 = Superficial ucler
• 2 = Deep ulcer
• 3 = perforation
• ULCER INDEX (U1)=
U1 = (UN +US +UP )10 -1

28. • UN = Average no. Of ucler per animal
• US = Aversge of severity scores
• UP = Percentage of animals with ulcer

29. STRESS ULCER MODEL:
• HANSON AND BRODIE,1960
• PRICIPLE:
Stress produce a significant role in the
pathogenesis of gastric ulcer.
PROCEDURE:
Albino rates(150-200) are taken and fasted for
36 hrs

30. • Drugs are administered orally or
subcutaneously and 30 min later the rats are
subjected to restraint
• For restraint rats are kept in a piece of
galvanized steel window screen of appropriate
size.to restrain the rat the limbs where kept
together in pair and tighten with adhesive
tape and were kept for 24 hrs

31. • Rats where then sacrified and stomach was
dissected.
• Ulcer index and ulcer severity was
determined.

32. HISTAMINE INDUCED GASTRIC ULCER:
• Gastric acid secreation increase by
administration of histamine intraperitoneally
• PROCEDURE:
• Guinea pig of 300- 400 g is taken
• Fasted for 36 hrs before experiment

33. • 1 ml of histamine acid phosphate (50 mg base)
was administered i.p.
• Promethazine HCl was administered i.p. 15
min before and 15 min after histamine to
protect animal from histamine toxicity
• The standard/ test drug are administered
orally or s.c 45 min before the histamine
injection

34. • 4 hrs later the guinea pig is sacrified and the
stomach is dissected out.
• Stomach was open with greater curvature and
ulcers were identified.
• ULCER SCORRING :
• TYPE 0 = No vissible ulcer
• TYPE I = 10 or less ulcer , 1-3 mm diameter
• TYPE 2 = 11 or more ulcer , 1 – 3 mm diameter

35. • TYPE 3 = 1 or more ulcer, 4-6 mm diameter
• TYPE 4 = 1 or more ulcer , 7 mm or more
diameter
• TYPE 5 = perforation to gastric wall
ADVANTAGE:
• Produce 100 % gastric ulceration
• Increase volume of gastric acid secretion
• Marked enhancement of free and total acidity

36. IN- VITRO
• [ 125I ]GASTRIN BINDING ASSAY:
• Gastrin( G cell of gastric antrum)
• Bind to CCK2 receptor of parential cell =
release HCl
• Bing CCK2 receptor of ECL cell = release
histamine– act on H2 receptor – release HCl
• Compound withgastrin receptor antagonist
can be potent antiulcer agent

37. PROCEDURE:
isolation of fundic gland from guinea pig
stomach
Incubated with50ul gastrin
1. In buffer alone ( for total binding)
2. In presence of unlabeled gastrin ( for non
specific binding)
3. In presence of test compound ( for specific
binding) for 90 min at 37 ̊C

38. • Ice cold buffer, in microcentrifudge tube is
layered with incubated mixture,centrifudge
for 5 min at 10,000 g
• Radioactivity is quantified in pellet after
decant of supernant

39. EVALUATION:-
• The total binding , non specific binding and
specific binding is been determined
• Percentage of specially bounded [125 I] Gastrin
displaced by given concentration of the test
compound calculated
• The higher the displace of [125 I] gastrin , the
more the antagonistic effect of the test drug.

40. Tiotidine binding assay:
• H2 receptor blocker
• Assay is done using cerebral cortex homogenate
obtained from guinea pig
• PROCEDURE:
• Cerebral cortex homogenate is incubatedwith
tiotidine for 90 min at 4 ̊C in the presence of
- Na2HPO4/KH2PO4 buffer alone( to determine total
binding)

41. • Unlabeled ranitidine and buffer( to determine
non specific binding)
• Test compound in buffer ( for competition
assay)
• 5 ml of ice cold phosphate buffer is added to
terminate the incubation
• Subsequently reaction mixture is filtered
under vaccum through glass fiber filters which
are presoaked within buffer.

42. • Filters are then washed with ice cold
phosphate buffer twice
• Radioactivity is measured by scintillation
counting.
• EVALUATION:
• Specific binding is calculated
• Specific binding = total binding – non specific
binding

43. H+ / K+ -ATPase binding assay:
• It is the final step in the synthesis of acid of
pariental cell.
• PROCEDURE:
• Homogenate of 80 ng Microsomal gastric H+ /
K+ -ATPase( pig gastric mucosa) incubated with
100ul buffer , 1mM ATP and test compound in
microtitre plate for 30 min at 37 ̊C

44. • Reaction is stopped by adding malachite green
(colorimetric agent)
• After 10 sec, 15 % of sodium citrate is added
for 45 min.
• Release of orthophosphate by ATP is
quantified by colorimeter.

45. EVALUATION:
• Percentage inhibition is calculated
• Lesser the orthophosphate release , more is
the inhibition done by test compound