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systemic steroids MOA
mimic the action of cortisol, an endogenous clucocorticoid (turns immune activity/inflammation down). catabolic effects (hyperglycemia, hypercalcemia, muscle breakdown), inflammatory effects (incr neutrophil counts but decr their migration into tissue, decr all other counts)
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systemic steroids other SE
weight/water gain (moon face), skin (thin skin, violaceous striae/stretch marks, ulcers), avascular necrosis of the hips, Cushing's, adrenal suppression
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mineralcorticoids v glucocorticoids
dexamethasone only antiinflammatory (glucocorticoid), no mineralcorticoid. prednisone is a glucocorticoid with minimal mineralcorticoid activity.
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B-cell biologics
destroy or interfere with B cell's ability to mount an immune response. CD20 induces apoptosis and is found in 90% of B-cell neoplasms.
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B-cell biologics kinetics
T1/2 dependant on how many CD20 receptors available to bind and take drug out of circulation. takes 9-12 months for counts to recover.
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B-cell biologics SE
infusion rxns, progressive multifocal leukoencephalopathy (due to infection)
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T-cell biologics targets
CD3, CD25, CD11a, LFA-3 (aka CD58), CD28
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T-cell biologics SE
strong inflammatory reaction (cytokine-release syndrome) often occurs with the first dose of OKT3 (newer drugs have been designed to be nonactivating so as to avoid this problem).
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mixed biologic targets
CD52, IL6
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mixed biologic indications
alemtuzumab CA, transplant. tocilizumab doesn't destroy lymphocytes, so only use is RA.
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mixed biologic SE
alemtuzumab pancytopenia. tocilizumab hypercholesterolemia, elevated LFTs, neutropenia.
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tumor necrosis factor-alpha inhibitors MOA
TNFa is produced by macrophages/inflammatory cells, promotes inflammation, apoptosis. inhibitors blunt this effect. high TNFa levels are often in autoimmune diseases.
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tumor necrosis factor-alpha inhibitors kinetics
injected every 2-4 wks
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amtimetabolites MOA
azathioprine mimics nucleotides, gets incorporated and inhibits further synthesis of DNA/RNA. mycophenolate inhibits enzymes that create nucleotides, inhibiting DNA/RNA synthesis.
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antimetabolites kinetics
metabolism linked to TPMT activity (thiopurine methyltransferase)
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antimetabolites contraindications
mycophenolate pregnancy (azathioprine is OK)
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antimetabolites interactions
azathioprine metabolized to mercaptopurine, which is metabolized by xanthine oxidase (an enzyme important in gout) -- therefore allopurinol, a xanthine oxidase inhibitor, is a significant interaction
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antimetabolites SE
messes with systems that have high cell turnover
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calcineurin inhibitors MOA
binds and inhibits the actions of calcineurin (the upregulation of IL-2 receptors, activators of T-cells)
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calcineurin inhibitors kinetics
cyclosporine narrow therapeutic index (100-400ng/mL), monitor trough levels. metabolized by CYP3A4.
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calcineurin inhibitors SE
nephrotoxicity/HTN (especially cyclosporine), CNS problems (especially tacrolimus). cyclosporine hirsutism, gum hyperplasia. tacrolimus hyperglycemia, alopecia.
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target of rapamycin (mTOR) inhibitors MOA
binds and inhibits mTOR, stopping cell cycle progression. immunosuppressant/antineoplastic effects include inhibition of VEGF, proliferation, activation, and possibly more.
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target of rapamycin (mTOR) inhibitors indication
transplant medicine
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target of rapamycin (mTOR) inhibitors interactions
mTOR inhibitors + calcineurin inhibitors = greater risk of nephrotoxicity
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target of rapamycin (mTOR) inhibitors SE
messes with systems that have high cell turnover. also interstitial pneumonitis, metabolic effects (hyperglycemia, hyperlipidemia)
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glatramoids MOA
competes for binding to MHC II molecules on antigen presenting cells, and induces Th suppressor cells. these antiinflammatory factors may facilitate remyelination and provide a protective effect for axons.
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