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49 Cards in this Set
- Front
- Back
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5 Classic signs of Inflammation
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1. Rubor (Redness)
2. Dolor (Pain) 3. Calor (Heat) 4. Tumor (Swelling) 5. Functio lasea (Loss of function) |
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Innate (natural) immunity
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- Stereotyped response
- Broadly reactive - Relatively low affinity - Initiates, activates response to offending agent |
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Adaptive (learned) immunity
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- Specific response
- Neutralize or kill an agent - Ag specific - Requires priming |
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Methylprednisolone
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High dose IV for acute transplant rejection
Efficacious in GVHD Long-term use toxicity |
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Tacrolimus (FK508)
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More potent than cyclosporine
Calcineurin inhibitor Nephrotoxicity |
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Cyclosporine
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Calcineurin inhibitor
Inhibitor of T-cell mediated immunity Nephrotoxicity |
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Sirolimus (Rapamycin)
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Antiproliferator
Binds FKBP (like tacrolimus) Difference: Arrest cell division |
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Azathioprine
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Prodrug of mercaptopurine
Mercaptopurine inhibits gene translation (a purine analog) |
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Mycophenolic acid
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Antimetabolite
Inhibit inosine monophosphate dehydrogenase (IMPDH) |
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Mycophenolate mofetil
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Prodrug for mycophenolic acid
Higher bioavailability |
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Methotrexate
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Folate analog
Anticancer drug, rheumatoid arthritis, GVHD Cytotoxic and anti-inflammatory activity |
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Anti-thymocyte globulin (ATG)
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Polyclonal antibodies from rabbit injected with thymocyte
Antibodies to T-cell antigens Depletes circulating lymphocytes |
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Muromonab CD3 (OKT3)
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Mouse monoclonal Ab against Human CD3 (on T cells)
Depletes available pool of T cells |
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Daclizumab
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Humanized anti-CD25 mouse monoclonal antibodies
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Basiliximab
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Higher affinity than Daclizumab
Humanized anti-CD25 mouse monoclonal antibody Binds to IL-2 receptor on activated T cells |
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Glucocorticoid MOA
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Inhibition of activation of gene expression
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2 drugs that block intracellular signaling to suppress immunity/inflammation
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Cyclosporine
Tacrolimus |
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Montelukast, Zafirlukast
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Block LT1 Receptors
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Antihistamines
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Block H1 receptors
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Monoclonal antibodies to TNFalpha
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Infliximab, adalimumab
Chemical neutralization |
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Pseudoreceptor to TNFalpha
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Eternacept
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Drug that acts by costimulation modulation
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Abatacept
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NSAIDS
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Inhibition of cyclooxygenase
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Zileuton
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Inhibition of Lipoxygenase (prevent production of LTs)
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2 reasons to use immunosuppressive therapy
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1. Prevent transplant rejection
2. Treating autoimmune disease |
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Glucocorticoids
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Used WITH other immunosuppressive agents to prevent and treat transplant rejection
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Immunosuppressant efficacious in GVHD
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Methylprednisolone (high dose, IV)
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What does cyclosporine bind to?
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Cyclophilin
Calcineurin stays inactive NFAT is phospohorylated and inactive NFAT does not enter nucleus No production of IL-2 |
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Toxicity associated with cyclosporine
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Nephrotoxicity
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Rheumatoid arthritis treatment
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Cyclosporine
Methotrexate |
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Hirsutism and gum hyperplasia
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Cyclosporine
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Metabolism of Cyclosporine
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CYP3A (CYP450)
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Grapefruit juice
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Blocks CYP3A
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MOA of Tacrolimus
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Binds FKBP
Blocks IL-2 receptor signaling like cyclosporine |
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Metabolism of Tacrolimus
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CYP3A
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Major side effect of tacrolimus
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Nephrotoxicity
Neurotoxicity (headache, tremor, seizures) |
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Use of Sirolimus (Rapamycin)
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Prophylaxis in organ transplantation ESPECIALLY in patients with high risk for nephrotoxicity
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Drug of choice in patients high risk of nephrotoxicity (for organ transplant immunosuppression)
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Sirolimus (Rapamycin)
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Azathioprine side effects (2)
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1. Bone marrow suppression
2. Increased susceptibility to infection |
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Inosine monophosphate dehydrogenase (IMPDH)
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Rate-limiting enzyme in guanosine formation
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Preferential affects of mycophenolic acid
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Lymphocytes
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Why mycophenolates preferentially affect lymphocytes
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1. Lymphocytes depend on IMPDH for purine synthesis
2. Preferentially inhibits Type II IMPDH, highly expressed in lymphocytes |
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Do not use mycophenolate with which immunosuppressant
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Azathioprine
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Use of ATG (3)
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Induction of immunosuppression
Acute renal rejection Withdrawal of calcineurin inhibitors |
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Major side effect of anti-thymocyte globulin (ATG)
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Cytokine release syndrome
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Use of Muromonab CD3 (OKT3)
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Organ transplant rejection
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Major side effect of Muromonab CD3 (OKT3)
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Cytokine release syndrome
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Efalizumab
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Humanized IgG1 mAb against CD11a chain of lymphocyte function associated antigen
Blocks T-cell adhesion, trafficking, and activation Psoriasis |
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Monoclonal Ab for tx of psoriasis
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Efalizumab
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