Immunosuppressive Drugs

jmanderson's version from 2016-02-11 00:14

PowerPoint Objectives


Question Answer
hyperacute rejection latency and affected by drugs?hours latent, NOT affected by drugs
accelerated rejection latency and affected by drugs?days latent, NOT affected by drugs
Acute rejection latency and affected by drugs?days-months latent, affected by drugs
chronic rejection latency and affected by drugs?months-years latent, affect by drugs
Cyclosporine MOAbinds to cyclophilin (an immunophilin) this complex inhibits the cytoplasmic phosphatase, calcineurin, which is necessary for the activation of T-cell-specific transcription factor (NF-AT) which is involved in the synthesis of interleukins by activated T cells.
Cyclosporine CNS-AEsaltered mental status, seizures
Give the receptor upon which the proliferation signal inhibitors (sirolimus, everolimus) actbinds to immunophilin FK-506-binding protein 12 → active complex that blocks molecular target of rapamycin (mTOR) which blocks interleukin-driven T-cell activation (including angiogenesis, cell growth, metabolism)
what type of the immune response proliferation signal inhibitors (sirolimus, everolimus) block?Indication = Siro used for solid organ allografts (often in combination with other immunosuppressants). Topical used with cyclosporine for uveoretinitis. Stents containing sirolimus used to decrease rejection.
Give the specific treatment for which mycophenolate mofetil is the first-line agent.first line for preventing/reducing chronic allograft vasculopathy in cardiac transplant pts.
Explain what aspect of the immune response azathioprine acts for mercaptopurine that is an anti-metabolite. It interferes with PURINE METABOLISM at steps that are required for the wave of lymphoid cell proliferation that occurs after antigenic stimulation. Thus they block cellular immunity.
Cyclophosphamide MOAalkylating agent. Destroys proliferating lymphoid cells, but also alkylates resting cells (thus high doses can cause pancytopenia)
Give the drug given as an antidote to cyclophosphamide-caused hemorrhagic cystitis.Mesna
Give the specific effect and site of hydroxychloroquine actionantimalarial with immunosuppressant properties (suppresses intracellular Ag processing and peptide loading on MHC class II molecules). It does this by INCREASING PH IN LYSOSOME which will decrease T-CELL activation. Called ion-trapping.
hydroxychloroquine Indicationtreats and prevents Graft vs. Host disease after allogeneic stem cell transplant
Describe the type of immune cells affected by anti-lymphocyte globulin (ALG)destroys/inactivates T-CELLS which impairs delayed hypersensitivity and immunity
Give two adverse effects of ALG that occur because the humoral aspects of the immune system remain intact.Anaphylaxis and serum sickness (due to serum-reactive precipitating antibodies)
Give the mechanism descriptor that applies to both basiliximab and daclizumab.Interleukin-2 antagonists
Give the specific indication for both canakinumab and rilonacept.Cryoperin-associated periodic syndromes (genetic autoinflammatory syndromes defined by ‘gain-of-function’ mutations affecting the cryopryin protein)

HandOut Objectives


Question Answer
Autologous stem cell transplantationstem cells are removed from a person, stored, and later given back to the SAME PERSON.
Allogeneic stem cell transplantationdonor and recipient of stem cells are from a DIFFERENT PERSON
Describe the effect of IGIV used for Kawasaki’s disease.REDUCES SYSTEMIC INFLAMMATION and PREVENTS CORONARY ANAEURYSMS. Proposed MOA is reduction of T helper cells, Tregs, Ig production, FcRs, increased antibody catabolism, and idiopathic-anti-idiotypic interactions with “pathological antibodies”.
Explain the known immediate effect of leflunomide and teriflunomide.Block the enzyme dihydroorotate dehydrogenase, which plays a role in DNA/RNA synthesis. These drugs thus inhibit the proliferation of lymphocytes.
leflunomide and teriflunomide used to tx?inflammatory diseases such as multiple sclerosis, psoriatic arthritis, and rheumatoid arthritis
toxicities of leflunomideelevation of liver enzymes with risk of liver and kidney damage. They are teratogenic.
toxicity and what must be monitored for it with Dimethyl fumarate (DMF) treatmentLYMPHOPENIA may be significant, so monitoring of blood counts must be done regularly and drug is withheld if active infection is present.

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