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What are the drugs acting against circulating proinflammatory cytokines?
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
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?
What is the difference b/w infliximab and adalimumab structure?
Adalimumab is fully humanized monoclonal IgG1 ab
(no murine component)
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?
(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.
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 are the miscellaneous DMARDs?
Sulfonamide plus salicylate (sulfasalazine)
What patients are given miscellaneous DMARDs?
patients w/ serious GIT problems w/ NSAIDS and steroids
patients whose joints are deteriorating rapidly
What are some ways you evaluate the efficacy of a miscellaneous DMARD?
articular index (size of joint)
measure acute phase proteins
test joint movement
What are some major adverse effects of penicillamine?
*Blood dyscrasias-bone marrow suppression which may be fatal*
If a patient on penicillamine develops proteinuria, what is the best next step?
(unwise to substitute this DMARD w/ another)
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)
What adverse effects of sulfasalazines occur in the first 3-6 months and then usually abate?
What are some of the most common toxicities associated with long-term methotrexate therapy?
Nausea, vomiting, diarrhea, anorexia
What tests are mandatory when a pt is on methotrexate?
CBC's and LFT's
(checking level of hepatoxicity)
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?
Rash and allergic reactions
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