chapter 45- Immunosuppression Flashcards by Anna Woods

what drugs have the mechanism of action of inhibitor of IMPDH, the rate limiting enzyme in formation of guanosine

Mycophenolic acid, mycophenolate, mofetil, mycophenolate sodium

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what is the clinical application of mycophenolic acid

solid organ transplantation, lupus nephritis, rheumatoid arthritis, pemphigus

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what are the adverse effects of mycophenolic acid

HTN, peripheral edema, GI hemorrhage, leukopenia, myelosuppression

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what cells does mycophenolic acid ac on

primarily on lymphocytes

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what should you avoid concurrent admin of with use of mycophenolate mofetil

iron because it markedly reduces its bioavailability

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what is the clinical application of leflunomide

rheumatoid arthritis

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what are common adverse effects seen with leflunomide

interstitial lung disease, alopecia, diarrhea, rash

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what is a contraindication for leflunomide use

pregnancy

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what can be administered if you need rapid removal of leflunomide

cholestyramine

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what does leflunomide inhibit

dihydroorate dehydrogenase (DHOD)

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what does the leflunomide lead to the inhibition of

pyrimidine synthesis

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what is the clinical application of cyclosporine

keratoconjunctivitis (topical)

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what is the mechanism of action of cyclosporine

binds to cyclophilin, the resulting complex inhibits the phosphatase activity of calcineurin (involved in T cell activation)

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what interleukin does cyclosporine inhibition the production of

IL-2

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what drug can increase serum levels of cyclosporine

danazol and other androgens

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what can reduce serum cyclosporine level

Rifampin and St Jonns wort

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what are some adverse effects seen with cyclosporine

nephrotoxicity, HTN, neurotoxicity, hepatotoxicity, gingival hyperplasia, hirsutism

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what is a contraindication of topical cyclosporine use

active ocular infection

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what is the clinical application of tacrolimus

organ transplantation, atopic dermatitis

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what are some adverse effects with tacrolimus

nephrotoxicity, prolonged QT interval, lymphoma, alopecia, headache

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what is a contraindication for tacrolimus use

hypersensitivity to hydrogenated castor oil

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what is the mechanism of action of tacrolimus

binds to FK-binding protein (FKBP), which inhibits calcineurin

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what markedly reduces serum levels of tacrolimus

St. John’s Wort

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what is the clinical application of sirolimus

prophylaxis for renal transplant rejection; CAD (cardiac stents)

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what is the clinical application of everolimus

renal cell carcinoma; CAD (cardiac stents)

what are some adverse effects of sirolimus/everolimus use

thrombocytopenia, thrombotic microangiopathy, hyperlipidemia

what is the mechanism of action of sirolimus/everolimus

inhibition mTOR

what is the mechanism of action of etanercept

soluble TNF receptor dimer

what is the clinical application of etanercept

rheumatoid arthritis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis

what must people undergo screening for before using etanercept

what are contraindications for etanercept use

sepsis, HF

what is the mechanism of action of infliximab

monoclonal anti-TNF antibodies

what monoclonal anti-TNF antibody can be used to treat juvenile idiopathic arthritis

adalimmumab

what monoclonal anti-TNF antibody can be used to treat ulcerative colitis

infliximab

what is the major difference between infliximab, adalimumab/golumumab, and certolizumab

inf is a partially humanized mouse antibody against human TNF-alpha; adal/gol are fully human IgG antibodies against TNF-alpha; cert is a pegylated anti-TNF-alpha antibody fragment

what is the mechanism of action of ustekinumab

human IgG monoclonal antibody that binds the p40 protein subunit shared by Il-12 and IL-23

what is the clinical application of ustekinumab

plaque psoriasis

what are some adverse rxns with ustekinumab

increased risk of infection, reversible posterior leukoencephalopathy syndrome

how is ustekinumab administered

after initial loading dose, ustekinumab is admin subcutaneously every 3 months

what is the mechanism of action of anakinra

recombinant IL-1 receptor antagonist

what is the clinical application of anakinra

rheumatoid arthritis

what are some adverse effects seen with anakinra

neutropenia, increased risk of infection

what does anakinra significantly reduce

bony erosions, possibly by decreasing metalloproteinase release by synovial cells

what is the clinical application of rilonacept and canakinumab

cryopyrin-associated periodic fever syndrome (familial cold auto inflammatory syndrome and muckle-wells syndrome

what is the clinical application of tocilizumab

rheumatoid arthritis

what is the clinical application of antithymocyte globulin

renal transplantation, aplastic anemia

what is the clinical application of OKT3

organ transplantation

what is the mechanism of action of rilonacept

recombinant soluble IL-1 receptor Fc fusion protein

what is the mechanism of action of canakinumab

human IgG1 monoclonal antibody to IL-1beta

what is the mechanism of action of tocilizumab

recombinant humanized monoclonal antibody to IL-6 receptor

what is the mechanism of action of antithymocyte globulin

polyclonal rabbit or horse antibodies against human T-cell epitopes

what is the mechanism of action of OKT3

mouse monoclonal antibody against human CD3

what are some adverse rxns seen with rilonacept and canakinumab use

serious infection; infection site reaction and URIs

what administrations should be avoided with rilonacept and canakinumab use

patients with active, recurring or chronic infections; admin of live vaccines

what are some adverse rxns seen with tocilzumab

serious infections, GI perforation

how is tocilizumab administered

every 4 weeks as IV infusion

what are some adverse rxns seen with antithymocyte globulin

cytokine release syndrome, HTN, increased risk of infection

what is the cytokine release syndrome

fever, shaking chills, myalgia, headache

what are some adverse rxns seen with OKT3

can result in profound immunosuppression

what are some contraindications for antithymocyte globulin use

acute viral illness, history of allergy or anaphylaxis to rabbit or horse proteins

what are some contraindications for OKT3

heart failure, seizures, pregnancy/breastfeeding, uncontrolled HTN

what is the mechanism of action of rituximab

partially humanized anti-CD20 antibody

what is the mechanism of action of ofatumumab

fully human anti-CD20 antibody

what is the mechanism of action of daclizumab, basiliximab

antibodies to CD25, the high affinity IL-2 receptor

what is the mechanism of action of alemtuzumab

antibody to campath-1 (CD52), an antigen expressed on most mature lymphocytes and some lymphocyte precursors

what is the mechanism of action of alefacept

LFA-3/Fc fusion protein that interrupts CD2/LFA-3 signaling by binding to T-cell CD-2, leaving to inhibitor of T-cell activation

what is the mechanism of action of abatacept and belatecept

CTLA-4 analogues fused to an IgG1 constant region

what is the mechanism of action of natalizumab

monoclonal antibody against alpha-4 intern that inhibits immune cell interaction with cells expressing VCAM-1 and MadCAM-1

what is the mechanism of action of eculizumab

humanized antibody against C5, a complement protein that mediates late steps in complement activation and assembly of the MAC

what is the clinical application of rituximab

B-cell non-hodgkin lymphoma, RA, chronic lymphocytic leukemia

what is the clinical application of daclizumab, basiliximab

organ transplantation; prophylactic in renal transplant

what is the clinical application of alemtuzumab

B cell chronic lymphocytic leukemia

what are contraindications for alemtuzumab use

active systemic infection; underlying immunodeficiency

what is the clinical application of alefacept

psoriasis

what are some contraindications for alefacept use

HIV infection; low CD4-T cell count

what is the clinical application of abatacept

rheumatoid arthritis refractory to methotrexate or TNF-alpha inhibitors

what are some adverse effects seen with abatacept use

exacerbation of COPD, increased susceptibility to infection, nausea

what drugs should abatacept not be administered concurrently with

TNF-alpha inhibitors or anakinra

what is the clinical application of natalizumab

relapsing MS, crohn's disease

what is the clinical application of eculizumab

paroxysmal nocturnal hemoglobulinuria

what are some adverse reactions seen with natalizumab use

progressive multifocal leukoencephalopathy, depression, pneumonia

what are some contraindications for natalizumab use

history of PML

what are some adverse reactions seen witheculizumab usei

infections; headache, nasopharyngitis, back pain, nausea

what are some contraindications for eculizumab use

neisseria meningitides infection

what do all patients who discontinue eculizumab need to be monitored for

signs and symptoms of intravascular hemolysis, including eval for serum lactate dehydrogenase levels

What is the autoantigen seen in acute rheumatic fever

Streptococcal cell wall antigens that cross reaction with cardiac muscle

What is the autoantigen seen in autoimmune hemolytic anemia

Rh blood group antigens

What is the autoantigen seen in goodpasture's syndrome

Renal glomerular basement membrane collagen type 4

What is the autoantigen seen in immune thrombocytopenic purpura

Platelet GPIIB-IIIa

What is the autoantigen seen in mixed essential cryoglobulinemia

Rheumatoid factor IgG complexes

What is the autoantigen seen in SLE

DNA, histones, ribosomes, snRNP, scRNP

What is the autoantigen seen in experimental autoimmune encephalitis, MS

Myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein

What is the autoantigen seen in type 1 DM

Pancreatic beta cell antigens