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Disease –Modifying Antirheumatic drugs

Disease –Modifying Antirheumatic drugs . Slow Acting Anti-inflammatory Drugs ). BY. PROF. AZZA EL-MEDANY. DR. OSAMA YOUSF. OBJECTIVES. At the end of the lecture the students should Define DMARDs

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Disease –Modifying Antirheumatic drugs

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  1. Disease –Modifying Antirheumatic drugs 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. OBJECTIVES ( Continue) • Know some examples of drugs related to DMARDS. • Describe the mechanism of action , specific clinical uses , adverse effects & contraindications of individual drugs.

  5. General Features • Low doses are commonly used early in the course of the disease • Used when the disease is progressing & causing deformities • Used especially when the inflammatory disease does not respond to cyclooxygenase inhibitors • Can not repair the existing damage , but prevent further deformity • Have no analgesic effects • 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. Adverse Effects • Pruritus • Headaches • GIT upset • Blurred vision • Discoloration of nail beds & mucous membranes • Irreversible retinal damage

  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 polymorphonuclearchemotaxis • Inhibition of T-Cells ( cell-mediated immune reactions)

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

  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. Upper respiratory tract infections Pancytopenia Adverse effects Infections Activation of latent tuberculosis 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 lysosomalenzymez 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 phagocyticcells

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