Drugs for Arthritic Disease
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52 terms
Terms | Definitions |
|---|---|
 What are the drugs acting against circulating proinflammatory cytokines? | Infliximab, Adalimumab, Etanercept, and Anakinra |
| What is infliximab and how does it work? | human/mouse chimeric monoclonal IgG1 Ab, w/ human Fc and murine variable regions that bind soluble and transmembrane TNF-α |
| What are the uses of infliximab? | RA, Ankylosing spondylitis, Psoratic arthritis, Crohn's Dis, Ulcerative colitis, IBD |
| What is usually used in combination w/ infliximab? | methotrexate |
| Why might a serious infection, like TB, occur as a result of infliximab administration? | ↓ macrophage function |
| What are some common side effects of infliximab? | headache, fatique, abdominal pain, infusion reaction, upper respiratory/UTIs |
| What is a possible adverse effect when taking infliximab in combination w/ azathioprine? | T-cell lymphoma |
| What is the difference b/w infliximab and adalimumab structure? | Adalimumab is fully humanized monoclonal IgG1 ab (no murine component) |
| What are the uses of adalimumab? | Ankylosing spondylitis Crohn's disease Psoriasis with arthropathy |
| How does adalimumab work? | Fully human ab that blocks the interaction of TNF-α with TNF receptors on cell surfaces. Also: ↓ C reactive protein, ↓ ESR, ↓ IL-6, ↓ MMP-1 & MMP-3. |
| How might you have to adjust the dose of adalimumab after adding methotrexate to the drug regiment? | ↓ adalimumab (methotrexate ↑ t½) |
| What is the black box warning for adalimumab? | At risk for TB, invasive fungal infections, and other opportunistic infections. Adverse effects: exacerbates chronic CHF, serious infections, lupus-like syndrome. |
| How is adalimumab administered? | SQ every 14 days |
| What is the structure of Etanercept? | soluble, recombinant fully human TNF receptor fusion protein receptor (extracellular domain of the TNF-α receptor coupled to human IgG1) |
| How does etanercept work? | It inhibits the binding of TNF-α and TNF-β to their receptors, thus ↓ inflammation due to TNF-α. |
| What is etanercept used for? | moderate to severe RA psoriatic arthritis juvenile arthritis |
| What drug against proinflammatory cytokines is C/I in pts w/ MS? | etanercept |
| What is the structure of Anakinra? | recombinant form of Human IL-1 receptor antagonist |
| What is the main use of anakinra? | RA |
| What is a serious adverse effect of anakinra? | infection, ↓ WBCs |
| What are the miscellaneous DMARDs? | D-penicillamine Chloroquine/Hydroxychloroquine Sulfonamide plus salicylate (sulfasalazine) |
| What patients are given miscellaneous DMARDs? | NSAID non-responders non-compliant patients patients w/ serious GIT problems w/ NSAIDS and steroids patients whose joints are deteriorating rapidly Juvenile RA |
| What are some ways you evaluate the efficacy of a miscellaneous DMARD? | pain score articular index (size of joint) measure rf measure acute phase proteins test joint movement |
| What is the MoA of penicillamine? | unknown |
| Penicillamine is rarely used in the tx of RA now, what is its main use? | Wilson's disease |
| How is penicillamine administered? | oral |
| What are some major adverse effects of penicillamine? | *Blood dyscrasias-bone marrow suppression which may be fatal* hypersensitivity reactions Autoimmune disorders |
| If a patient on penicillamine develops proteinuria, what is the best next step? | alternate therapy (unwise to substitute this DMARD w/ another) |
| What are the second line drugs used in the tx of RA? | Hydroxychloroquine/chloroquine |
| What is chloroquines used for other than RA? | anti-malaria SLE |
| How does chloroquines work? | Suppresses the responsiveness of T- lymphocytes to mitogens Decreases leukocyte chemotaxis Stabilizes lysosomal membranes Inhibits DNA and RNA synthesis Reduce oxidative reactions |
| What is a major possible adverse effect of chloroquines? | irreversible retinal degeneration (dose and frequency related) |
| Besides RA, what is another use of sulfasalazine? | ulcerative colitis |
| Where is sulfasalazine metabolized to its active metabolite? | In the gut by bacteria. |
| What type of people would show increased effects with sulfasalazines? | slow-acetylators |
| How does sulfasalazines reduce inflammation? | cox inhibitor in the gut |
| What adverse effects of sulfasalazines occur in the first 3-6 months and then usually abate? | Leukopenia thrombocytopenia |
| What are the most common side effects of sulfasalazine? | nausea and vomiting diarrhea and anorexia |
| What are the major cytotoxic drugs? | methotrexate, azathioprine, leflunomide, cyclosporine |
| What is the most commonly prescribed DMARD? | methotrexate |
| How does methotrexate work? | inhibits DHFR |
| What is the difference in RA and cancer tx with methotrexate? | low dose in RA |
| What is given as an adjunct therapy in conjunction with methotrexate? | folate |
| What are some of the most common toxicities associated with long-term methotrexate therapy? | Nausea, vomiting, diarrhea, anorexia Leucopenia MTX lung Hepatotoxicity |
| What tests are mandatory when a pt is on methotrexate? | CBC's and LFT's (checking level of hepatoxicity) |
| How does azathioprine work? | inhibits PPRP synthase (purine synthesis) |
| How does leflunomide work? | inhibits dihydro-orotate DH (RTL of de novo pyrimidine synthesis) |
| What are the uses of leflunomide | moderate to severe RA psoriatic arthritis |
| Why does leftunomide decrease B and T cell proliferation? | B and T cells depend on de novo pyrimidine synthesis (can't recycle?). Leftunomide blocks this. |
| What are some adverse effects of leflunomide? | GI tox ↑ transaminases Rash and allergic reactions Reversible alopecia Headache Renal impairment |
| What drug is second line following methotrexate? | leflunomide |
| What are both methotrexate and leflunomide C/I in? | pregnancy! |
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