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43 Cards in this Set
- Front
- Back
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Prednisone Indication
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Maintenance immunosuppression
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Methylprednisolone Indication
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Maintenance immunosuppression
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Prednisone/Methylprednisolone MOA
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Prevent T-cell activation by blocking cytokine production
• Inhibit macrophages • Redistribute lymphocytes • Block antigen recognition |
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Prednisone Route of Admin
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PO
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Prednisone/Methylprednisolone Side Effects
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Cushing’s syndrome, osteoporosis, myopathy, cataracts, glucose intolerance, hypercholesterolemia
Don’t withdraw abruptly |
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Antiproliferative Agents
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Azathioprine, Mycophenylate Mofentil
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Methylprednisolone Route of Admin
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IV
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Azathioprine Indication
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Maintenance immunosuppression
Lower doses also used in rheumatoid arthritis |
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Azathioprine MOA
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Metabolized into 6-mercaptopurine which disrupts purine incorporation into DNA
• Prevents proliferation of T-cells Metabolites are excreted in the urine |
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Azathioprine Side Effects
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BMS, hematological effects, infections, pancreatitis, hepatitis, cholestatic jaundice, interstitial pneumonitis, increased risk of neoplasia
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Important Azathioprine Interaction
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Interactions: increased levels with allopurinol causing increased neutropenia
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Mycophenolate
mofetil Indication |
Maintenance immunosuppression
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Mycophenolate
mofetil MOA |
Inhibits inosine monophosphate dehydrogenase in guanine synthesis
• Inhibits DNA synthesis in T and B cells • Hydrolyzed in GI to mycophenolic acid (active component) rapidly absorbed, glucoronidated, excreted in urine |
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Mycophenolate
mofetil Side Effects |
N/V/D, infections (CMV), sepsis, leukopenia, lymphoma, teratogenic, no hepatotoxicity
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Important Mycophenolate
mofetil Interactions |
antacids, cholestyramine, increases acyclovir
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Polyclonal Antibodies
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Lymphocyte Immune Globulin (ATGAM), Antithymocyte Globulin (ATG)
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Lymphocyte Immune Globulin (ATGAM)/Antithymocyte Globulin (ATG) Indication
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Used before transplant and early rejection
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Lymphocyte Immune Globulin (ATGAM) MOA
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Binds peripheral T-cells and wipes them out
Horse IgG’s against human T-cell antigens CD2, CD3, CD4, CD8, CD11a and CD18 |
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Lymphocyte Immune Globulin (ATGAM)/Antithymocyte Globulin (ATG) Side Effects
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Leukopenia, thrombocytopenia, fever, muscle pain, serum sickness
ATG is preferred in most situations because of less severe side effects |
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Antithymocyte Globulin (ATG) MOA
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Depletes circulating T-cells
Rabbit antibody against human T-cell antigens CD2, CD3, CD4, CD8, CD11a ,CD18, CD25, CD44, CD45, HLA clas I and II antigens |
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Monoclonal Antibodies
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Muromonab-CD3
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Muromonab-CD3 Indication
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Acute rejection
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Muromonab-CD3 MOA
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Inhibits signal transduction of antigen recognition
• Causes internalization of T-cell receptors, preventing recognition of antigens • Circulating T-cells decrease rapidly after injection Murine IgG2a antibody against CD3 on T-cells |
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Muromonab-CD3 Side Effects
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1st dose reaction → cytokine release syndrome
• Massive TNF-alpha, IL-2, IL-6 release • Severe flu-like symptoms (high fever, chills, tremor, myalgia) • Use glucocorticoids to reduce cytokine release before you give drug Pulmonary edema (monitor plasma volume), avoid in patients with history of seizures |
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IL-2 Receptor Antagonists
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Basiliximab
Daclizumab |
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Basiliximab/Daclizumab Indication
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Prophylaxis of acute rejection, maintenance immunosuppression
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Basiliximab/Daclizumab MOA
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Antibody against IL-2 CD25 receptor on activated T-cells
Prevents activated T-cell killing, does not deplete T-cells, mechanism not completely understood |
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Basiliximab/Daclizumab Side Effects
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Hematalogical infections, well-tolerated, anaphylactic reactions
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Calcineurin Inhibitors
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Tacrolimus, Cyclosporine
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Cyclosporine Indication
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Maintenance suppression (liver, heart, kidney, and other transplants, rheumatoid arthritis and psoriasis)
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Cyclosporine MOA
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Inhibits mRNA transcription of IL-2
Binds cyclophilin and inhibits calcineurin Prevents NF-AT from stimulating IL-2 transcription |
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Cyclosporine Side Effects
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Constriction of afferent artery at glomerulus, renal dysfunction
Pgp transport in BBB (CNS effects tremor) Hypertension (50% of renal, all heart) required treatment Diabetogenic (esp. with glucocorticoids) Hirsutism CYA3A interactions (increase or decrease) Monitor levels |
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Tacrolimus Indication
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Maintenance suppression and rescue in acute rejection
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Tacrolimus MOA
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Binds FKBP to inhibit actions of calcineurin
Prevents NF-AT activating IL-2 transcription |
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Tacrolimus Side Effects
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Nephrotoxicity, neurotoxicity (Tremor, headache, seizures), GI, hypertension, hyperglycemia, tumors and secondary infections
Damage pancreatic beta cells, diabetes CYPA3A4 metabolism Alopecia |
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Calcineurin Inhibitor that is protein bound & food decreases its absorption
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Tacrolimus
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mTOR inhibitors
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Sirolimus, Everolimus
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Everolimus Indication
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Approval in renal cell carcinoma after failure of Sunitib or Sorafeib
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Everolimus MOA
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Chemically related, shorter plasma half-life, shorter time to steady state, actions very similar to Sirolimus
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Sirolimus/Everolimus Side Effects
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Dyslipidemia
Thrombocytopenia Wound healing (lymphoceles → wait 1 month after transplant to start therapy) Interstitial pneumonitis, pulmonary infections Lymphoma BMS |
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Sirolimus MOA
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Binds to FKBP-12 and inhibits mTOR stimulated cell proliferation at G1-S phase transition
CYP3A4 metabolism (7 metabolites!) |
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Sirolimus Indication
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Acute rejection (renal transplants, not used in liver and lung transplants because of bronchial and hepatic artery stenosis)
Prophylaxis, used to limit use of calcineurin inhibitors Heart stents to prevent proliferative effects |
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Standard Triple Therapy
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Pre-Op: (Antibodies)
During: (Methylprednisolone) Post-Op: (Calcineurin Inh + GC + Antimetabolite/Sirolimus) |
