2. BY PROF. AZZA EL-MEDANY DR. OSAMA YOUSIF

3. General Features & Conditions to use antirheumatic Low doses are commonly used early in the course of the disease Used when the disease is progressing & causing deformities Used when the inflammatory disease is not responding to NSAIDs Can not repair the existing damage, but prevent further deformity Have no analgesic effects Slow onset their effects take from 6 weeks up to 6 months to be evident

4. General Clinical Uses Treatment of rheumatic disorders Combination therapies are both safe & efficacious

5. Hydroxychloroquine Mechanism of action :  Trapping free radicals  Suppression of T lymphocyte cells

6. Pharmacokinetics Rapidly & completely absorbed following oral administration. Penetrates into C.N.S. & traverse the placenta Metabolized in liver

7. Pruritus GIT upset Discoloration of nail beds & mucous membranes Irreversible retinal damage Adverse Effects Headaches Blurred vision

8. Methotrexate Immunosuppressant drug Used mainly as chemotherapy for cancer treatment Doses of methotrexate as antirheumatic are much lower than those needed in cancer chemotherapy Given once a week

9. Mechanism of action  Inhibition of T-Cells ( cell-mediated immune reactions)

10. Nausea Liver cirrhosis Mucosal ulceration Acute pneumonia – like syndrome Adverse Effects Cytopenia

11. Biologic disease modifiers Genetically engineered drugs that are used to modify imbalances of the immune system in autoimmune diseases. Some of these agents block, or modify the activity of selected cells in the immune system, while others –including tocilizumab work by blocking certain messenger proteins known as cytokines, that send signals between those cells.

13. Classification of biologic disease modifiers  T-cell modulating drug ( abatacept )  B-cell cytotoxic agent ( rituximab )  Anti-IL-6 receptor antibody ( tocilizumab)  TNF- blocking agents ( infliximab)

14. Tocilizumab IL-6 receptor inhibitor Binds to membrane IL-6 receptors,blocking the activity of IL-6 in mediating signals Half-life is dose dependent (11-13 days ) Given as monthly IV infusion Used as monotherapy in adult with rheumatoid arthritis or in children over 2 years with systemic juvenile arthritis

15. Cont. Can be given in combination with methotrexate or other non biologic anti-rheumatic drugs in patients with active rheumatoid arthritis.

16. Side effects Severe infusion reactions Serious infections ( bacterial, tuberculosis,fungal Increase in cholesterol level Increase in liver enzymes Decrease in WBCs Blood tests will be used monthly for increase in cholesterol, liver enzymes & decrease in WBCs

17. Drug Interaction In combination of tocilizumab with some drugs such as cyclosporine or warfarin {IL-6 inhibits CYP450, this enzyme is essential for the metabolism of cyclosporine or warfarin. Tocilizumab which act as inhibitor for IL-6,resulting in restoring the activity of the enzyme }

18. Tumor necrosis factor –α (TNF- α ) blocking agents

19. Infliximab A chimeric antibody ( 25% mouse, 75% human)

20. Mechanism of action Binds to human TNF-α resulting in inhibition of its action as a mediator in inflammatory diseases

21. Infliximab Given as IV infusion over at least two hours Half-Life 8-12 days Given every 8 weeks regimen. Elicits up to 62% incidence of human antichimeric antibodies. Concurrent therapy with methotrexate decreases the prevalence of human antichimeric antibodies

22. Adverse effects Infections Upper respiratory tract infections Activation of latent tuberculosis Pancytopenia Infusion reactions

23. Comparison between NSAIDs & DMARDs DMARDs NSAIDs Slow onset of action used in chronic cases when deformity is exciting Arrest progression of the disease Prevent formation of new deformity Rapid onset of action used in acute cases to relief inflammation & pain No effect Can not stop formation of new deformity