SCREENING METHODS FOR ANTI ULCER DRUGS

PRESENTED BY: VENUMADHAV DEPT.OF PHARMACOLOGY

ULCER:

A break in skin or mucous membrane with loss of surface tissue, disintegration and necrosis of epithelial tissue Causes : due to the imbalance of aggressive and defensive factors. Aggressive factors: HCl, Pepsin, Bile and H.pyloi Defensive factors : Gastric mucosa, bi carbonate secretion, prostaglandins, nitric oxide, innate resistant of mucosal cells

Etiology
H.pylori Acid and pepsin NSAIDS Smoking Caffeine Alcohol Stress

Anti ulcer agents

Reduction of gastric acid secretion: H2 anti histamines

Proton pump inhibitors

Anti cholinergics Prostaglandin analogue

Neutralization of gastric acid

Systamic: Nonsystemic Ulcer protective

M.O.A of anti ulcer agents

1.

Screening methods:

Pylorus ligation in rats (SHAY rat) Stress ulcer through immobilization stress Stress ulcers by cold water immersion Indomethacin induced ulcers in rats Ethanol induced mucosal damage in rats

Pylorus ligation in rats(shay rat)

Female, wister rats of 150-170, starved 48hr Avoid coprophagy Ten animals per dose and as control Midline abdominal incision, pylorus is ligated Closed by sutures , test compound given orally or s.c Placed 19hr in plastic cylinder d-45mm,closed ends Animals are sacrificed in co2 anesthesia Abdomen is opened and ligature is placed around esophagus Stomach is removed and contents are drained to centrifuge tube Stomach is opened along the greater curvature pined to cork plate

scoring
0 - no ulcer 1 - superficial ulcer 2 - deep ulcer 3 - perforation ulcer index(UI)=UN+US+UP*10-1

Stress ulcer through immobalization stress:

Purpose: Procedure: 10 female wistar(150-170) Starved 24 hr prior Administered test and placebo Lowerand upper extermities fixed wrapped in a wire gaze Horizontaly dark at 200 c, 24hr Co2 anaesthesia, remove the stomach

STRESS ULCER BY COLD WATER IMMERSION

PROCEDURE: Groups of 10 wistard rats(150-200) Oral test drug, placed in restraint cages, 220c/1hr Inject i.v via tail vein with 30 mg/kg evans blue. After 10 min stomach is removed by co2 anaesthesia Formol saline is injected, storage overnight Then next day stomach are opend with greater curvature, washed. lesions(lengths) are measuerd. EVALUATION: inhibition of the lesion porduction is expressed as percentage value.

Indomethacin induced ulcer

8-10 wister rats(150-200g) Test-20mg/kg indomethacin, After 10 min oraly, test drug in 0.1%tween 80 6hr later , sacrifice in co2 ,stomaach is removed Stomach Inject formal saline, kept for over night Stomach is opened, examined under microscope