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Pharmacotherapy of Rheumatoid arthritis
- 2. INTRODUCTION • RA is a chronic, progressive, autoimmune, inflammatory disease affecting joints • Mediators of inflammation released initiate inflammatory process
- 3. CLASSIFICATION I. NSAIDs II. DMARDs A. Immunosuppressants – Methotrexate – Cyclophosphamide – Azathioprine – Cyclosporine – Leflunomide – Chloroquine, Hydroxychloroquine
- 4. B. Biological agents- • Etanercept • Infliximab • Adalimumab • Certolizumab • Golimumab TNFα blockers • Abatacept Inhibitors of T cell activation • AnakinraIL1 antagonist • Rituximab Anti B lymphocyte antibody • KanakinumabIL1 B antibody • TocilizumabIL6 antagonist
- 5. • First line drugs • Symptomatic relief • Toxicity with long term use • Eg- Aspirin, Ibuprofen, Naproxen, Diclofenac, Piroxicam I. NSAIDs
- 6. • For patients who do not obtain satisfactory relief from NSAIDs • Capable of arresting progress of disease • Effects take 6wks to 6 months • Also called SAARDs II. DMARDs
- 7. 1. METHOTREXATE MECHANISM OF ACTION Increases adenosine levels Inhibits cytokines Suppresses cells in inflammation, stimulates apoptosis Inhibits DHFR DOSE- ALLTREX 2.5MG TAB, 5mg/ml VIAL CARDITREX 2.5mg TAB, 25mg VIAL
- 9. 2. AZATHIOPRINE • Purine analogue • Prodrug • Converted to 6-thioguanine in body • Suppresses cell mediated immunity • Alternative to methotrexate DOSE- AZORAN 25mg tab AZAP 50mg tab
- 10. 3. CYCLOPHOSPHAMIDE • Alkylating agent • Inhibits T and B cell function • Orally in RA, autoimmune diseases DOSE- • CYPHOS, NEOPHOS 200,500mg, 1g inj • ONCOMIDE 50mg tab, 200,500mg, 1g vial
- 11. 4. LEFLUNOMIDE Prodrug Active metabolite inhibits T cell proliferation and productionof autoantibodies by B cells Orally effective T1/2- 5-40days ADR- Diarrhoea, wt gain, hypertension, alopecia
- 12. 5. HYDROXYCHLOROQUINE, CHLOROQUINE • Antimalarial drugs useful in RA • Can accumulate in tissues leading to toxicity • Side effect- retinal damage • Dose- CADIQUIN 250, 500mg tab, LAROVER 250mg tab
- 13. a) TNFα blocking agents (i) Infliximab Monoclonal antibody Slows progression of RA IV infusion 3- 5mg/kg every 8hr T1/2- 9- 12days ADR- Nausea, headache, rash, cough REMICADE 10mg vial
- 14. (ii) Etanercept •Recombinant fusion protein •50mg weekly SC, REMICADE 10mg vial (iii) Adalimumab •Anti TNF monoclonal antibody •SC 40mg/wk
- 15. b) Inhibitor of T cell activation- Abatacept •T1/2- 13-16 days •IV infusion- 800- 1000mg •Repeated 2 and 4wks c) IL1 antagonist- Anakinra •Pts not resp to DMARDs
- 16. d) Anti B lymphocyte antibody- Rituximab • Monoclonal antibody • Suppress inflammation e) IL6 antagonist- Tocilizumab • Binds to IL6 • Blocks its action
- 17. a) Gold salts • Not preferred- toxicity • Eg- Auranofin, Aurathiomalate MOA- Depress cell mediated immunity DOSE- 6mg/day, GOLDAR 3mg tab ADR- Hepatotoxicity, Nephrotoxicity, Dermatitis, Encephalitis III. OTHER ANTI RHEUMATIC DRUGS
- 18. b) d-Penicillamine • Metabolite of penicillin • Toxicity- same as gold, not preferred c) Sulphasalazine • Anti inflammatory • ADR- GI upset, skin rashes • Dose- 500-1000mg bd-tds • IWATA 500mg tab