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Disease Modifying Anti-Rheumatic Drugs (DMARDs)

Disease Modifying Anti-Rheumatic Drugs (DMARDs). Alistair Ward 22/04/13. Aim of Teach. Rheumatoid Management Ladder. Symptomatic Treatment. Methotrexate. Contra-indicated or No Response. Rituximab (alone, or with leflunomide ). TNF α inhibitors. Methotrexate. Mechanism of Action

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Disease Modifying Anti-Rheumatic Drugs (DMARDs)

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  1. Disease Modifying Anti-Rheumatic Drugs(DMARDs) Alistair Ward 22/04/13

  2. Aim of Teach

  3. Rheumatoid Management Ladder Symptomatic Treatment Methotrexate Contra-indicated or No Response Rituximab (alone, or with leflunomide) TNF α inhibitors

  4. Methotrexate • Mechanism of Action • Anti-Folate (Di-hydrate folatereductase inhibitor) • Interactions • Trimethoprim • NSAIDs • Nitrous Oxide (GA) • Clozapine (increased risk of agranulocytosis) • PPIs

  5. Methotrexate Side Effects • Common • Nausea and Diarrhoea • Rare • Neutropaenia • Hepatotoxiticity • FibrosingAlveolitis (Methotrexate Lung) Monitoring • FBC - Bone Marrow Suppression • LFTS - Liver Cirrhosis • FBC and LFT weekly for 4 weeks, fortnightly for 4 weeks then monthly throughout treatment • Pulmonary Function Tests – Pulmonary Fibrosis • Baseline CXR

  6. Methotrexate Contra-Indications • Pregnancy

  7. TNF-α Inhibitors(e.g. adalimumab, rituximab infliximab) Mechanism of Action TNF-α inhibitors are antibodies against Tissue Necrosis Factor Alpha (TNF-α). Normally TNF-α causes: • Release of pro-inflammatory cytokines; IL-1, IL-6, IL-8 • Increased migration of adhesion molecules by fibroblasts and increased leukocyte migration into inflamed tissues

  8. TNF-α Inhibitors(e.g. adalimumab, rituximab infliximab) Interactions Live vaccines • MMR • Rabies • Polio • BCG • Typhoid Side Effects • Immunosuppression • Injection site reactions • Exacerbation of Heart Failure • Theoretical increased risk of malignancy

  9. TNF-α Inhibitors(e.g. adalimumab, rituximab infliximab) Monitoring • Latent infections e.g. TB, Hep-B Contra-indications • Severe infection

  10. Fun Fact

  11. Leflunomide Mechanism of Action • Suppresses immunoglobulin production Interactions • Live vaccines • Warfarin • Phenytoin Side Effects • Rash • Ulcers • Diarrhoea • Increased BP • Myelosuppression • Hepatoxicicty

  12. Leflunomide Monitoring • FBC • LFTs Contraindications • Pregnancy NB: Washout procedure in case of conception want (both men and women) or adverse reaction • Colestyramine or activated charcoal

  13. Azathioprine Mechanism of Action • Inhibits production of immunoglobulins by B-lymphocytes Interactions • Allopurinol inhibits xanthine oxidase. • Xanthine oxidase is needed to metabolise azathioprine. Side Effects • Bone marrow suppression • Nausea • Rash • LFTs

  14. Azathioprine Monitoring • ThiopurineMethyltransferase (TPMT) metabolises azathioprine and therefore mercaptopurine. • Consider measuring levels of TPMT before treatment to reduce risk of myelosuppression • FBC Contraindications • Hypersensitivity to mercaptopurine

  15. Summary Slide

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