1. Slow Acting Anti-inflammatory Drugs )

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

3. OBJECTIVES At the end of the lecture the students should Define DMARDs Describe the classification of this group of drugs Describe the general advantages & criteria of this group of drugs Describe the general clinical uses

4. o Know some examples of drugs related to DMARDS. o Describe the mechanism of action, specific clinical uses, adverse effects & contraindications of individual drugs. OBJECTIVES ( Continue)

5. General Features Low doses are commonly used early in the course of the disease Used when the disease is progressing & causing deformities ( they stop the progress of the disease ) 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

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

7. Hydroxychloroquine Mechanism of action :  Stabilization of lysosomal enzyme activity  Trapping free radicals  Suppression of T lymphocyte cells

8. Pharmacokinetics Rapidly & completely absorbed following oral administration. Has a very large volume of distribution Penetrates into C.N.S. & traverse the placenta Metabolized in liver

9. Continue Some metabolic products retain antimalarial activity Both parent drug & metabolites are excreted in the urine The excretion rate is enhanced in acidic urine

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

11. Methotrexate Immunosuppressant drug Response to methotrexate occurs sooner than for other slow acting drugs. Doses of methotrexate are much lower than those needed in cancer chemotherapy Given once a week

12. Mechanism of action  Inhibition of polymorphonuclear chemotaxis  Inhibition of T-Cells ( cell-mediated immune reactions)

13. Nausea Liver cirrhosis Mucosal ulceration Acute pneumonia – like syndrome Adverse Effects Cytopenias

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

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

16. Mechanism of action Binds to human TNF-α resulting in inhibition of macrophage & T cell function

17. 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

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

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

20. SUMMARY DMARDs are used mainly in chronic cases of rheumatoid arthritis, when the disease is progresssing and forming deformity. They do not remove the existing damage but prevent further formation of deformities. They have no analgesic effect.

21. SUMMARY ( Continue) They are slow in onset needs weeks to manifest their effects. Hydroxychloroquine acts mainly through suppression of the activity of lysosomal enzymez and trapping free radicals. Its main adverse effects is irreversible retinal damage & hepatic toxicity.

22. CONTINUE Methotrexate acts mainly through suppression of phagocytic cells & T cells Its adverse effects are bone marrow depression & mucosal ulceration Infliximab is a chimeric TNF-α blocking agent. Given with methotrexate to reduce antichimeric effect

23. CONTINUE Its main adverse effects are upper respiratory tract infections & reactivation of latent TB,

24. CONTINUE Methotrexate acts mainly through suppression of phagocytic cells &