Term
| What are the 4 major classes of immunosuppressant drugs? |
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Definition
T cell suppressants
Antibody reagents
Cytotoxic drugs
Glucocorticoids |
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Term
Name some T cell suppressants.
(immunosuppressants) |
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Definition
Calcineurin inhibitors (Cyclosporine A, Tacrolimus)
Sirolimus (Rapamycin)
Abatacept/ Belatacept |
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Term
Name some Antibody reagents.
(immunosuppressants) |
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Definition
Anti-thymocyte globulin
Muromonab CD3
Daclizumab |
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Term
Name some Cytotoxic drugs.
(immunosuppressants) |
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Definition
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Term
T cell suppressants
uses and mechanism |
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Definition
use:
Organ transplants! (?and autoimmune dzs)
mech:
Inhibit activation of T helpers --> prevent activation and expansion of CD8 and CD4 T cells.
NFAT and AP1 are required for transcription of cytokines (IL-2, IL-4, GM-CSF). These little drugs control NFAT mediated transcription by blocking calcineurin/NFAT interaction.
A key step of this interaction is that calcineurin dephosphorylates NFAT. |
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Term
Calcineurin inhibitors (Cyclosporine A, Tacrolimus)
mech and side effects |
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Definition
T cell suppressants
mech:
Blocks cytokine production in T helper cells (NFAT/Calcineurin pathway).
Inhibit calcineurin, and therefore prevent NFAT dephosphorylation.
side effects:
HTN, renal dysfxn, DM, gingival hyperplasia |
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Term
Sirolimus (Rapamycin)
mech |
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Definition
T cell suppressants
mech:
Block activity of cytokines on effector cells (an mTOR in inhibitor).
Blocks cytokine signaling in CD8 T cells and B cells. Cytokines bind to these cells and activate mTOR, but this drug binds and inhibits mTOR and FKBP12 |
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Term
Abatacept/ Belatacept
mech and uses |
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Definition
T cell suppressants
mech:
Co-stimulatory blockade - blocking B7 (responsible for co stimulation) --> T cell anergy
Recall that the 2 stimuations a T cell needs to be activated are MHC II binding the TCR and B7 binding the CD28. Abatacept bind B7, blocking the co-stimulation, resulting in T cell anergy.
mech:
Belatacept is 10x stronger, used for kidney transplants
Abatacept - tx of rheumatoid arthritis |
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Term
Anti-thymocyte globulin.
uses and mech |
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Definition
an antibody reagent
uses:
Not typically used for long term therapy. A single dose given before transplant.
mech:
Decreases number of T cells:
Antibody to human lymphocytes made in horses. These antibodies destroy T cells by inducing complement deposition. If the patient responds too strongly the their complement could be depleted. |
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Term
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Definition
an antibody reagent
mech:
Decreases number of T cells:
Antibody to human T helper cells at the CD3. This prevents proper antigen presentation by antigen presenting cells (APCs) leading to a decrease in the number of T cells. |
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Term
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Definition
an antibody reagent
mech:
Decreases number of T cells:
Blocks cytokine signaling (an anti-IL2 receptor antibody), blocking subsequent activation of CD8 and other CD4 cells by blocking IL-2 signaling |
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Term
Mycophenolate mofetil
uses and mech |
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Definition
Cytotoxic drugs
use:
Immunosuppression and general cancer therapy. Immunosuppressant doses are lower.
mech:
Inhibit inosine monophosphate dehydrogenase (IMPDH), which is part of the de novo pathway of GTP synthesis. Lymphocytes rely on the de novo synthesis of GTP to a greater extent than other cell types when proliferating, so this drug preferentially inhibits the proliferation of lymphocytes. |
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Term
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Definition
Glucocorticoid
use: everything
mech:
Binds to intracellular steroid receptors -->stimulate production of IkB --> NF-kB suppression --> immune suppression
Only class of immunosuppressant that acts in multiple places. Affect lymphocyte trafficking (anti-adhesion), inhibit T cell proliferation, inhibit expression of cytokines, inhibit the fxn of macrophages and lymphocytes |
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Term
| List contraindications for Kidney Donors |
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Definition
Under 18
History of thromboembolism / thrombotic disease
Family history of renal disease
Microscopic hematuria
proteinuria
GFR <80
Active infection / any significant medical illness
Pregnant woman
Hypertension or pre-hypertension
Diabetes
Multiple renal vessels / renal vessel anomalies |
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Term
| List contraindications for Kidney Recipient |
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Definition
Active malignancy
chronic infection
active mental illness
severe heart dysfunction
cirrhosis
extreme obesity BMI > 35
substance abuse (treat first)
pelvic ulcer disease (treat first) |
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Term
Side effects of Calcineurin inhibitors
(T cell suppressant type immunosuppressant) |
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Definition
Hyper and hair:
Hyperplasia
Hyperkalemia
Hyperlipidemia
Hypertension
hyperglycemia
Hirsutism
Alopecia
Tremor
Nephrotoxicity
Cytochrome p450 → drug drug interactions |
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Term
Side effects of Sirolimus / mTOR inhibtors
(T cell suppressant type immunosuppressant) |
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Definition
Cytochrome p450 → drug drug interactions
Less nephrotoxic
Longer half life
Mouth ulcers
Wound healing problems |
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Term
| Side Effects of Anti-proliferative agents |
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Definition
Myelosupression ( bone marrow suppression)
Anemia
Thrombocytopenia (low platelets)
Leukopenia
Cholestatic hepatitis
GI (diarrhea, dyspepsia, nausea, vomiting) |
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Term
Side effects of Belatacept / co-stimulation blockers
(T cell suppressant type immunosuppressant) |
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Definition
GI (diarrhea, constipation, nausea, vomiting)
Anemia
leukopenia
Hypertension
Graft dysfunction
Pyrexia (fever)
Cough
Hypokalemia or hyperkalemia |
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