Arthritic simi
- 1. ANTI-ARTHRITIS AGENT Presented By – SMITA CHOUDHARY M.Pharm II Semester
- 2. ANTIARTHRITIC AGENTS Rheumatoid arthritis (RA) is a chronic disabling disease affecting around 1% of the population. Much progress has been made in recent years towards the identification of mediators that contribute to the pathogenesis of RA,and a numbers of studies have pointed to a pivotal role for tumour necrosis factor- apha(TNFa)in the disease process.Indeed,the success of biological inhibitors of TNFa (Elliott et al.1993,1994 a,b;Moreland et al.1997;Weinblatt et al.1999) in the clinic is a testament to the pathological significance of this cytokine in RA.
- 3. 1-ADJUVANT ARTHRITIS Adjuvant Arthritis Rat adjuvant arthritis is an experimental model of polyarthritis which has been widely used for preclinical testing of numerous anti-arthritic agents which are either under preclinical or clinical investigation or are currently used as therapeutics in this disease. Male Lewis rats (165-200 grams, 7/group) are generally used in studies of adjuvant arthritis. The disease develops in females but is much more variable in onset and severity. Animals should be allowed to acclimate for at least 3 days prior to initiation of experimentation.
- 4. Induction of adjuvant disease can be done with either Freunds complete (FCA) supplemented with mycobacterium or by injection of the synthetic adjuvant N, Ndioctylddecyl-N', N- bis(2-hydroxy-ethyl) propanediamine (LA)7. Adjuvant can be injected at the base of the tail or in one of the foot pads. If injection is into the footpad, it allows study of the acute inflammatory reaction in that local area as well as the immunological reaction that develops approximately 9 days later in the contralateral paw and various organs. Hind paw swelling is monitored from day 9 (onset of disease) to15 or greater depending on duration desired.
- 5. In the later stages of disease (day 12+), adjuvant arthritis rats are often relatively immobile due to severity of paw swelling and so require special care to insure that they have access to water and food. Treatments are initiated on day 0 (prophylactic model dosing) or day 8 (therapeutic model). Various stress-related factors including manipulations during the test period (pharmacokinetic sampling), frequency of dosing (QD vs BID) or type of vehicle used can influence the disease progression.
- 6. The newer biologic agents such as the interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptors also have activity in this model9-12. Demonstration of efficacy with IL- 1ra is dependent on maintaining sufficient blood levels for prolonged receptor antagonism either by continuous infusion methodologies or by the use of slow release vehicles.
- 7. 2.TERPENTINE OIL INDUCED EDEMA Terpentine induced a acute and non- immunological disease edema joint,preferably Albino rat used 0.2ml injected into the sinovial cavity the animal. In the right knee of animal after 30mins of the test drug administration. The diameter of joint is measured at an internal of one hours upto 6hrs by using micro meter screb gauge.
- 8. Terpentine oil induced joint edema character to increase the vascularity per aldehyde and marked vasodilation through the sequencial release of cytokines his,serotonin in early phase followed by kinin like (bradykinin) substance in the termident phase and PG in late phase. Inhibition of terpentine induced joint edema reflex overall anti-inflammatory of effect of the test drug.
- 9. PARAMETERS TO BE EQVALUATED- 1-% changed in joint diameter 2-X-Ray photography of joint 3-Histopathology of joints
- 10. 3.FORMALDEHYDE INDUCED ARTHRITIS Formaldehyde induced chronic non-immunological arthritis.HCHO is injected as a substance injection of 0.1ml of HCHO solution (20%). Similar dose of HCHO is repeated on drug three time. The test drug is adminiseredon day one 30min before the 30min administration of HCHO.The administration of test drug may continue up to 10-45 days.
- 11. Arthritis is assested to measuring the increase the paw diameter over a period of 10 days using micrometer screw gauze. It is one of the most suitable method to evaluation antiproferative activity and screened antiarthritis agents. HCHO induced by bi-phasic response presence early neurogenic compound and followed by a later tissue mediated response.Overall HCHO induced a proliferative global edema.
- 12. PARAMETER TO BE EQUAL EVALUATED- 1-% Change in paw diameter 2-X-ray 3-Histopathology of joints