Immunosuppressives Flashcards
Which immune response is more easily suppressive?
Primary
Inhibition is more likely if therapy begins ______ exposure
before
Broad based, low affinity, no priming, early response
Innate
Antigen specific, primed, high affinity, later response, T and B cells
Adaptive
Broad spectrum
Glucocorticoids
Inhibit B and T cell proliferation
Mycophenolate mofetil, antiproliferative agents
Bind to and deplete T cells
Monoclonal antibodies
Inhibit T cell activation and cytokine production
Tacrolimus and cyclosporine
Uses of immunosuppressives (4)
- Prevent/Tx rejection after organ transplant
- Autoimmune dz
- Allergies and asthma
- Macular degeneration
SE Immunosuppressants (2)
- Infections
- Increased risk of lymphomas and other malignancies
Corticosteroids MOA (3)
- Inhibits T cell proliferation and response to cytokines (IL-2)
- Decreases size and lymphoid content of spleen
- Decrease response to antibodies
- Depress macrophage fxn
- Modify T helper cells
Corticosteroid Tx (4)
- Organ transplant
- Long term immunosuppress
- Prevention of rxn to other drugs
- Topical: dermatitis, psoriasis
Corticosteroid SE (6)
- Cushing’s like syndrome
- Suppressed immune system
- Suppress pituitary-hypothalamic axis
- Osteoporosis
- PUD
- Menstrual/reproductive
T- Cell Suppressants (3)
- Calcineurin Inhibitors (Cyclosporine, Tacrolimus)
- Sirolimus
- Pimecrolimus
Calcineurin Inhibitors (2)
- Cyclosporine
- Tacrolimus
Cyclosporine MOA (6)
- SELECTIVE inhibition of T lymphocytes
- Binds to specific receptor
- INHIBITS CALCINEURIN/T-CELL ACTIVATION
- Decrease formation of IL-1/IL-2
- Increases TGF-B
- Suppresses immune response
Does cyclosporine suppress bone marrow?
NO! thus it is better tolerated
Cyclosporine Drug Interactions
- CYP3A4 metabolism
- Narrow therapeutic range
- NO GRAPEFRUIT JUICE
Drugs that decrease concentration of Cyclosporine
- Phenobarbital
- Phenytoin
- Rifampin
Drugs that increase concentration of Cyclosporine
- Erythromycin
- Ketoconazole
- Verapamil
Cyclosporine Tx (4)
- Prevent rejection in organ transplant
- Maintenance after organ transplant
- Bone marrow transplant
- Autoimmune dz
Cyclosporine SE (6)
- RENAL TOXICITY!!!
- HTN
- GINGIVAL HYPERPLASIA
- Tremor, hirsutism
- Hyperlipid, hyperglycemia
- N/V/D, anorexia
FK506, Tacrolimus MOA (3)
- Inhibits T cell activation
- Decrease IL-2 and IL-4
- Similar to Cyclosporine (Less toxic)
FK506, Tacrolimus Tx
- Prevent rejection in transplantation, particularly in liver, kidney, and heart
FK506, Tacrolimus Admin
- IV
- Oral
- Topical
FK506, Tacrolimus SE (8)
- Nephrotoxic
- HTN
- HYPERGLYCEMIA
- Tremor, HA, insomnia
- GI (empty stomach, avoid grapefruit)
- Increased infections (skin CA)
- Narrow therapeutic range
- Drug interactions
Sirolimus MOA
- Inhibits proliferation of T and B-cells
Sirolimus SE (2)
- Increases cholesterol/triglycerides
- NO RENAL TOXICITY
Pimecrolimus Admin
- Topical for atopic dermatitis
- Does not thin/atrophy skin, but may irritate or burn
Mycophenolate-Mofetil MOA (2)
- Decreases DNA synthesis by inhibiting monophosphate dehydrogenase
- T and B-cells need this for PURINE synthesis
Mycophenolate-Mofetil Tx
- Prevent rejection after transplants (often combined with Tacrolimus)
Mycophenolate-Mofetil SE (3)
- Rash
- GI
- Infections
Thalidomide MOA
- Blocks TNFa
Thalidomide SE (3)
- TERATOGENIC!
- Drowsiness
- Neutropenia
Thalidomide Tx
- Prevents graft vs host rxn
Azathioprine MOA (2)
- Converted in vivo to 6-mercaptopurine
- INHIBITS PURINE SYNTHESIS
Azathioprine Tx (4)
- Prevents rejection in transplant pts
- Glomerulonephritis in lupus
- Severe RA
- In dental practice for random stuff
Azathioprine SE (7)
- Bone marrow suppression
- TERATOGENIC
- Increased infections
- Liver toxicity
- N/V/D
- Metabolized by Xanthine oxidase –> reduce dose if used w/ Allopurinol
Cyclophosphamide MOA (3)
- Direct effect on T and B cells
- Blocks response to new antigens
- Can inhibit established immune response
- Alkalating agent
Cyclophosphamide Tx (3)
- Organ transplant RESCUE
- Bone marrow transplant
- Severe autoimmune dz
Cyclophosphamide SE (6)
- Hemorrhagic cystitis
- N/V
- Bone marrow suppression
- Aspermia, infertility
- Bladder fibrosis, CA
- Alopecia
Methotrexate MOA
- Human dihydrofolate reductase inhibitor
Methotrexate Tx (5)
- Organ transplants
- Psoriasis
- Antineoplastic
- RA
- Severe asthma
Methotrexate SE (3)
- FETAL TOXICITY
- Alopecia
- Hepatotoxicity with chronic use
Antibody Immunosuppressives MOA
- Form antibodies against specific cells
Antibody Immunosuppressives SE
- Allergic rxn (chimeric or humanized mabs decrease SE)
Lymphocyte Immune Globulin, Antithymocyte, Globulin, Muromonab CD3 MOA (2)
- Antibodies to T cells or CD3 receptor on T cells
- Bind/inactivate circulating T cells
Lymphocyte Immune Globulin, Antithymocyte, Globulin, Muromonab CD3 SE (3)
- Allergic Rxn, rash (give with corticosteroids to decrease rxn)
- Chills, fever
- Hypotension
Daclizumab/Basiliximab MOA
- Bind to IL-2 receptor on activated T cells, inhibit IL-2 activation
Daclizumab/Basiliximab SE
- Humanized/chimeric reduce adv SE
- NO general immunosuppression
Daclizumab/Basiliximab Tx
- Used right after transplant - induction
Efalizumba MOA (3)
- CD-11a monoclonal
- Prevents binding to intercellular adhesion molecule (increased in psoriasis)
- PREVENTS T CELL ACTIVATION, but doesn’t destroy them
Alefacept MOA
- Binds to CD-2 receptor on cell surface, blocks T-cell activation
Alefacept and Efalizumab Tx
- Psoriasis
Drugs for Macular Degeneration (4)
- Bevacizumab, Ranibizumab
- Pegaptanib, Aflibercept
Pegaptanib, Aflibercept MOA
- Bind to VEGF-A
Drugs for Macular Degeneration MOA
- Decrease formation of new blood vessels
Drugs for Macular Degeneration Admin
- Intra-vitreous
Drugs for Macular Degeneration SE
- Thromboembolism
- Stroke, MI
Interleukin-2 MOA (2)
- Proliferation/differentiation of helper T and cytotoxic T cell
- Proliferation of B cells/macrophages
Interleukin-2 Tx (2)
- Renal cell carcinoma
- Malignant melanoma
Interleukin-2 SE (3)
- Pulmonary edema
- SEVERE HYPOTENSION
- Hematologic
Granulocyte Colony Stimulating Factor; Filgrastim MOA
- Human recombinant
Granulocyte Colony Stimulating Factor; Filgrastim Tx
- Severe neutropenia induced by stem cell transplant or chemo
Granulocyte Colony Stimulating Factor; Filgrastim Admin
- SC
Granulocyte Colony Stimulating Factor; Filgrastim SE (2)
- Bone pain
- Injection site rxn
Epoetin-alfa MOA
- Human recombinant form of erythropoetin
Epoetin-alfa Tx
- severe anemia induced by Zidovudine, interferon chemo or pts with kidney dz
Epoetin-alfa Admin
- SC
Epoetin-alfa SE (2)
- HTN
- Risk thrombosis/stroke
Interferons MOA (2)
- a/b response to viruses
- g increase T lymphocytes and NK cells (activates macrophages, increase expression of major histocompatibility antigens)
Interferon Tx (3)
- Hep C (a2b)
- Severe uveitis (a2b)
- MS (b1b)
Multiple Sclerosis
- Immune system attacks myelin around nerves –> weakness, difficulty walking
Multiple Sclerosis Drugs (4)
- Interferon b1b
- Glatiramer
- Fingolimod
- Dimethyl fumarate
Interferon b1b MS (2)
- Injected
- Decrease relapses
Glatiramer MS
- Antibodies bind to drug instead of nerve (decoy)
Corticosteroid (1)
Prednisone
Proliferation Signal Inhibitors (4)
- Sirolimus
- Pimecrolimus
- Mycophenolate Mofetil
- Thalidamide
Cytotoxic Agents (3)
- Azathioprine
- Cyclophosphamide
- Methotrexate
Immunomodulators (7)
- Interferone a2b
- Interferon b1b
- Interleukin-2
- G-CSF
- Erythropoetin
- Glatiramer
- Dimethyl fumarate
Immunosuppressives
- Corticosteroids
- T cell Suppressants
- Proliferation Signal Inhibitors
- Cytotoxic Agents
- Antibodies
Two drugs that inhibit S phase?
Doxorubicin, Cisplatin
What drug affects G2 and M phase?
Bleomycin and Paclitaxel
What two drugs affect M phase?
Vinblastine, Vincistine
What drug affects G1 and M phase?
Mechlorethamine
What drug affects G and S phase?
5 FU
