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Evaluation of anti inflammatory drugs

This is a ppt depicting evaluations of anti-inflammatory drugs by Dr. Jill Pd Dr.D.Y.Patil Med college Pimpri,Pune

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Evaluation of anti inflammatory drugs

  1. 1. Evaluation of Anti-inflammatory drugs SEMINAR ON PRESENTER : Dr. Jill Mathew Dated :04/09/2013
  2. 2.  Inflammation is a protective response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult  Pfizer took about 18 years to develop the anti- inflammatory drug piroxicam, which was launched in 1980 during the “golden age of rational drug discovery”
  3. 3. CARDINAL SIGNS OF INFLAMMATION 1 2 34 5
  4. 4.  Acute: vasodilatation & increased capillary permeability  Delayed: infiltration of leukocytes and phagocyte cells  Chronic proliferative: tissue degeneration and fibrosis
  5. 5. (1) Recognition of the injurious agent (2) Recruitment of leukocytes (3) Removal of the agent (4 ) Regulation of the response (5) Resolution
  6. 6. ICAM-1 and VCAM-1
  7. 7. MEDIATOR VASO DILATATION VASCULAR PERMEABILTY CHEMOTAXIS PAIN Histamine ++ _ + Serotonin +/- _ + Bradykinin +++ _ +++ Prostaglandins +++ +++ + Leukotrienes - +++ _
  8. 8.  Animals used: Albino Guinea pigs  Test drug is administered -30 min before exposure  Duration of exposure to UV –B rays : 20 sec  Area of exposure : Depilated skin  Degree of erythema estimated after 2 hours visually on a scale 0-4  ADVANTAGE : Pure measure of the vasodilatory phase  Drawback: Accurate measurement of reaction not obtained, variability of response  DRUGS EFFECTIVE : NSAIDS like Phenyl butazone, Aminopyrene, Aspirin and Sodium salicylate
  9. 9. Area 2: treated with topical H 1 antagonist (1.5% chlorphenoxamine hydrochloride in the same cream base, Allergex, Epico) twice daily. Area 1: used as a control area and was exposed to -UVB and treated with cream base only twice daily. Area 3: treated with topical H 2 antagonist (2% famotidine in the same cream base) twice daily
  10. 10.  Rat-paw edema (Acute and Subacute phases) Drugs: Carrageenan (1%, 0.1 ml SC.), indomethacin 2 mg/kg IP  Site : Subplantar region of left hind paw Experimental injury cascade of events
  11. 11.  Biphasic  1 – release of histamine,5 HT and kinins  2- release of prostaglandins  Parameter : Paw volume up to the ankle joint is measured in treated and untreated groups before and after carrageenan
  12. 12.  Advantage: Simple ,easy, short lasting and reproducible  Disadvantage : Non –specific and difficult to quantify and examine cells & their modification by anti- inflammatory drugs Avoid in both the hind paws because of unalleviated pain and deformity
  13. 13.  % of edema produced by carrageenan alone = A – B X 100 = X % B  % of edema produced by carrageenan after treatment with drug = C – D X 100 = Y % D  % reduction of edema by drug = X –Y= %
  14. 14. 1. Carrageenan – COX 2. Mustard 3. Dextran 4. Egg-white Phlogistic agents 5. Compound 48/80 6. Yeast, Zymosan-LOX 7. Serotonin, histamine 8. Kaolin 9. Substance –p, nystatin, glass powder, cobra venom
  15. 15.  an instrument for measuring changes in volume within an organ whole body or limb  The mercury displacement due to dipping of the paw can be directly read from the scale attached to the mercury column
  16. 16. TUBE A TUBE B RAT PAW IS IMMERSED INTO THE TUBE ‘A’ & THE READING IS CHECKED THROUGH THE TUBE ‘B ’ SOME SET UPS HAVE A DIGITAL DISPLAY ATTACHED TO IT
  17. 17.  Inducer of arthritis:  Silver nitrate in the tibiotarsal joint of rats  Intra articular talc injections in pigeons  Locomotor activity with inflammed paws is impaired  Drugs effective: NSAIDS, steroids ,DMARDS  Anti-histamines
  18. 18.  Induction of Pleurisy:  Carrageenan , turpentine, Evan’s blue, Arabic gum, glycogen, dextran , antigens , microbes, mast cell degranulators  Advantage: Quantitation of anti-inflammatory activity and M.O.A of new test drug  Drugs effective: Steroid, NSAIDS & Gold  Index of activity of drug: The volume of exudate is decreased
  19. 19. 1. Croton oil induced ear edema ( Croton tiglium) 2. TPA-induced ear edema - Protein kinase C , NF-кB , phospholipase A2 PG 3. Arachidonic acid induced ear edema 4. Xylol induced ear edema
  20. 20.  Predictable model for topical anti-inflammatory drugs  Inflammatory response measured by increase in ear plug weight & thickness at single time interval( at 6 hours)  Drugs tested : Steroids and NSAIDS
  21. 21. Right -Control
  22. 22.  Std duration (27 sec) and Std intensity (55◦C) thermostatically controlled water to the shaved abdomen of rat Resultant edema can be measured by excising skin
  23. 23. Egg albumin or horse serum Passively sensitized by antibodies Intra-dermal injection of Ag or Ab is made Inflammatory reaction ASSESSMENT : by dye leakage or edema  Drugs effective :Cortisone , Salicylates
  24. 24.  To study repair phase characterized by fibroblast proliferation and blood vessel formation  Suppression of granulation tissue parallels with anti-inflammatory activity
  25. 25.  For measurement of activity of anti- inflammatory drugs on proliferative component of ‘subacute & chronic inflammatory processes’ 
  26. 26.  Sterile Cotton pellets (wt :5mg -50mg )  sc sites of axilla , back ,groin  Duration : 1-14 days  Pellet along with granuloma removed and weighed  Weight of granulomatous tissue =  Dry weight of granuloma cotton -initial weight of cotton pellet  Drugs effective: corticosteroids
  27. 27.  Immunologically mediated model of chronic inflammation  It a delayed HS response to mycobacterial Ag
  28. 28.  Induction of Arthritis : Subplantar injection of Freund’s complete adjuvant or mycobacteria suspended in oil  Day 1 Day 4-5 Day 7  Local reaction Peak Systemic disease  Parameters : Foot thickness, wt, grip strength , deformity measured  Evaluation of chronically administered drug against inflammation  Drugs effective: Steroids ,Immunosuppressants, gold ,d-penicillamine
  29. 29.  Chronic exposure to foreign bodies like contact lenses leads to GPC  Levels of IL3,IL 4,IL5 ,Ig G, Ig E and Ig M is increased in Tears  Procedure : A sterile needle is inserted directly into conjunctiva of unsensitized animal  Pricking results in high number of neutrophil infiltration
  30. 30.  VCAM-1,ICAM-1 and E-selectin are derived from HUVEC ,HDMEC cell lines  Cell based ELISA –assay
  31. 31. HUVEC, HMEC TNF-ἀ as reagent Test drug 20 min BCECF labeled WBC 20 min No drug Adherent cells are lysed and fluorescence measured at 485 nm in ELISA reader
  32. 32.  Thrombin activated human platelets Incubated with drug at 20 0 C for 10 min & mixed with Neutrophils at a ratio 10:1 Index of activity : Neutrophils with 2 or more and one or no adherent platelets are counted Test drug : Blocks Adhesion Drugs effective : NSAID ,chloroquine
  33. 33.  Dianzani etal  the PMNs are challenged by FMLP to generate 02- for screening anti-inflammatory compounds  Superoxide production was measured spectrophotometrically by measuring the superoxide dismutase inhibitable reduction  Drugs effective: Anti-oxidant drugs
  34. 34.  Stimulates A and C fibers producing pain  Lowers BP by vasodilatation  Test : detects compounds that inhibit binding of 3 H- Bradykinin in membrane preparation of guinea pig ileum Evaluation: specific binding= total binding- nonspecific binding % inhibition:100- specific binding
  35. 35.  Leptin is a proinflammatory cytokine  Circulating leptin levels are increased upon infectious and inflammatory stimuli such as LPS, turpentine, and cytokines  Leptin increased statin inhibitible free radical and cholestrol production invitro  CRP increased in obesity and reduced by statin  JUPITER TRIAL, Leptin and Insulin resistance  Fructose fed rat is a model of metabolic syndrome.
  36. 36. The compounds were found to be useful in OA,RA and Psoriasis A HAPPY TEACHERS DAY TO ALL TEACHERS ON BEHALF OF US

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