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26 Cards in this Set
- Front
- Back
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What is the overall function of immunosuppressant drugs?
What are they referred to as? |
Alter T and B cell function to inhibit tissue destruction of autoimmune diseases
Disease Modifying Anti Rheumatic Drugs (DMARD) |
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What are the two major classes of immunosuppressants and how do they differ? |
Nonbiologics: low MW, po/ia/topical administration, off patent=low cost
Biologics: IgG1 proteins (large), chimeric (xi) or humanized (mu) mabs, IV or SC administration, long t1/2 and high co$t |
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What are the classes of non-biologics? |
Antimalarials (hydroxychloroquine) 5-aminosalicylates (sulfasalazine) Purine/pyrimidine synthesis inhibitors (methotrexate, azathioprine) DNA alkylating agents (cyclophosphamide) Glucocorticoids (prednisone oral, triamcinolone intraarticular) JAK3 inhibitors |
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What are the classes on biologics? |
TNFa inhibitors (infliximab) CTLA-4 IgG (atabacept) antiCD20 B cell depleter (rituximab) |
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What is the mechanism and therapeutic use of antimalarials? |
Hydroxychloroquine
Accumulate in the lysosomes of B cells & fibroblasts
Used in SLE and RA; used in combo drugs |
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What is the noted interesting side effect of hydroxycholoroquine? |
Accumulation in and damage to the retina (thus requires othalmologic monitoring |
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What is the mechanism of sulfasalazine?
What patients are at risk of the worst side effect? |
Blocks NFkB signaling which leads to apoptosis of T cells.
Patients with G6PD deficiency are at heightened risk of hemolytic anemia (because the drug has a pro-oxidizing effect, and with less glutathione, RBC hemolysis is more likely) |
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What is the mechanism of purine/pyrimidine synthesis inhibitors?
Which drugs fall into this class? |
The drug is an analogue of DNA substrates and when used to make purines/pyrimidines, they deplete the store of nucleotides available and thus inhibit cell replication.
Purine synth inhibitors - methotrexate, azathioprine Pyrimidine synth inhib - leflunomide |
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What is the use of MTX?
How can it be administered?
Can it be used alone? |
Used for cancer treatment, or at 1/100th the dose can be used for arthritis
Both oral and parenteral formulations
Recommended first line therapy alone or with other DMARDs |
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What is the mechanism of MTX?
What are the side effects of MTX?
How is it related to kidney function? |
Inhibits the enzyme that makes a precursor to purines --> affects B cells
Mucositis, hepatotoxicity, teratogenicity
Reduced renal function increases MTX t1/2, thus dose adjustment required |
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What is the mechanism of azathioprine?
What are the relevant side effects?
When is dose adjustment required? |
Depletes precursor to purine synthesis in B and T cells (may have affect too on triggering T cell apoptosis)
Bone marrow suppression, infection, malignancy
Adjust dose in TPMT deficiency or when rx w/ allopurinol |
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What is the mechanism of leflunomide?
What affect is seen on it's half life? |
It's metabolite inhibits de novo pyrimidine synthesis.
Because of enterohepatic circulation, can have a very long T1/2 (hence black box warning); can soak it up with cholestyramine |
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What is the mechanism of cyclophosphamide?
What is of interest about the end metabolic product? |
Converted by CYP450 to a DNA alkylating metabolite which blocks T-cell replication, thus impaired T-cell function
Very toxic = mustard gas |
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What is the principle therapeutic use of cyclophosphamide?
What are the side effects? |
Used in combo w/ glucocorticoid to treat vasculitis
Side effects: bone marrow suppression, infertility, alopecia |
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What are the rheumatologic uses of glucocorticoids?
How are they administered? |
Anti-inflammatory and immunosuppresant effects
Short course or intraarticular injection for quick pain relief |
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What is the newest nonbiologic drug and what does it target? |
Tofacitinib inhibits JAK3 which is a kinase that releases cytokines that promote transcription in T and B cells |
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What is the prototype TNFa antagonist?
What are two other drugs in this category? |
Infliximab is a chimeric monoclonal antibody with a high affinity for TNFa that prevents it from getting to its target
Etanercept and adalimumab |
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What are the uses of TNFa antagonists
How are they administered?
What is the economic downside? |
Used in RA, psoriatic arthritis, psoriasis and ankylosing spondylitis
Administered IV or SC at home
Expen$ive |
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What are the side effects of TNFa antagonists? |
Infusion or injection reactions Respiratory infections or reactivation of TB Worsening of HF Development of antibodies by the body against the injected antibodies; work around by coadministration of MTX which inhibits B cells |
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What is the mechanism of atabacept?
How is it administered?
What is the economic downside? |
Binds to APC B7 and inhibits the interaction with T cell CD28 to prevent T cell activation
Administered in IV infusions
Expen$ive |
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What are the side effects of atabacept? |
IV infusion reactions Infection (don't coadminister TNFa inhibitors) Antagonism of immunizations |
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What is the mechanism of rituximab?
When is it indicated? |
Binds to CD20+ B cells and inactivates them because then they are subject to killing by other immune cells
B-cell non-Hodgkins, RA if unresponsive to TNFa antagonists |
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What are the recommendations for non biologics in RA? |
Monotherapy: MTX or lefluonomide preferred
Combo: 2=MTX+leflunomie, hydroxycholorquine or sulfasalazine; 3=MTX+H+S |
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What are the recommendations for biologics in RA?
Which biologic to start? |
One biologic + MTX after the failed response to non-biologics
Start with TNFa inhibitor |
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What are the recommendations for ankylosing spondylitis? |
NSAIDs, if refractory then TNFa antagonists |
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What are the recommendations for SLE? |
NSAIDs Glucocorticoids Hydroxycholorquine MTX, azathioprine or cyclophosphamide Mycophenolate Rituximab Beimumab |
