Immunosuppressive Drugs Flashcards
What are the 7 targets of immunosuppressive drugs?
- Inhibition of gene expression
- Selective attack on clonally expanding cell populations
- Inhibition of intracellular Signaling
- Neutralization of cytokines and receptors required for T-cell activation
- Selective depletion of T cells or other immune cells
- Inhibition of co-stimulation by APCs
- Inhibition of lymphocytes target interaction
What is induction?
- when?
- toxicity
- Given at the time of transplantation
- Intense therapy and very toxic long term
**May include donor specific transfusion or irradiation as drug alternatives
What is maintenance?
- when?
- toxicity
Lower potency
- Taken All the time
- Tolerable in chronic use (but with side effects)
What is Rescue?
Intense and Effective administration of drugs
- chronically intolerable
- Given only in response to a rejection episode
T or F: drugs used to suppress the immune system at the time of transplant vary widely from patient to patient
True
What 3 types of drugs are given in the maintenance phase?
- Calcineurin Inhibitor
- Anti-proliferative (cell-cycle/mTOR inhibitors)
- Corticosteriod
What is the relatively immunogenicity of:
- Heart
- Liver
- Kidney
- Lung
Lung > Heart > Kidney > Liver
Coriticosteriods
- MOA
- Metabolism
- Therapy type
- Administration method
Prednisone/Methyprednisone
MOA:
Anti-inflammatory - prevents trascription of the IL-2 gene
Metabolism:
Hepatic
Therapy Type:
- Maintenance Immunotherapy
- Given in pulsed doses during rejection
Administration:
IV/PO
What drugs are administered during a rejection event?
Antilymphocytes antibodies
- Muromonab
- Thymogobulin
Corticosteroids - pulsed at high doses
Calcineurin Inhibitors
- MOA
- Metabolism
- Therapy type
- Administration method
Cyclosporine/Tachrolimus
MOA:
- PREVENT Cacineurin activation preventing NFAT from getting dephosphoylated and TRANSCRIBING THE IL-2 gene.
Metabolism:
Hepatic (CYP) - differences among race
Therapy Type:
Maintenance Immunotherapy
Administration:
IV/PO
IL-2 receptor antagonist
- MOA
- Metabolism
- Therapy type
- Administration method
Basiliximab
MOA:
Monoclonal antibody that blocks the IL-2 receptors (aka CD25)
Metabolism:
Not metabolized by liver - long acting
Therapy Type:
Induction agent
Administration:
IV
Anti-lymphocyte antibodies
- MOA
- Metabolism
- Therapy type
- Administration method
Muromonab, Thymoglobulin
MOA:
- Bind to CD3 domain to prevent activation of T-cells via TCR (monoclonal)
- Anti-thymocyte globulin (polyclonal antibody)
Metabolism:
Not metabolized by liver - long acting
Therapy Type:
- Induction Agent
- Used during Rejection episodes
Administration:
IV
Cell Cycle and mTOR inhibitors
- MOA
- Metabolism
- Therapy type
- Administration method
Asathioprine, Mycophenolate, Sirolimus
MOA:
1. Prevent Purine synthesis to prevent S phase completion and cell proliferation
- Purine antagonist
- Prevent mTOR from getting activated thus preventing protein synthesis (RESISTS IL-2 STIMUATION)
Metabolism:
1/2. Renal metabolism
3. Hepatic (CYP)
Therapy Type:
Maintenance Immunotherapy
Administration:
1/2. IV/PO
3. PO only
What agents are used during episodes of rejection?
- Corticosteriods
- prednisone - Anti-lypmocyte antibodies
- muromonab
- thymoglobuline
What are the side effects of ALL immunosuppressive drugs?
- Increased Risk of Cancer
2. Increased Risk of Opportunistic Infection
