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48 Cards in this Set
- Front
- Back
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What are immunodrugs used for?
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inhibit cellular and humoral response
organ transplant autoimmune disease |
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4 Classes of Drugs
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1. Specific T Cell Inhibitors
2. Cytotoxic Drugs 3. Glucocorticoids 4. Antibodies |
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Specific T Cell Inhibitors
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Calcineurin inhibitors
Cyclosporine Tacrolimus |
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Cytotoxic Drugs
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Azathioprine
Methotrexate Mycophenolate Cyclophosphamide Chlorambucil (these are also used in cancer) |
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Glucocorticoids
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Prednisolone
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Antibodies
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Rho (D) immunoglobulin
etc. |
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What do glucocorticoids (prednisolone do?
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inhibit MHC expression which inhibits producoitn of L-1, IL-2, IL-6
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What do Cyclosporine and Tacrolimus do?
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inhibit antigen stimulated activation and proliferation of helper T cells (CD4) as well as expression of IL-2 and other cytokines
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What do cytotoxic drugs do?
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block proliferation and differentiation of T and B cells
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What do Antibodies do?
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bind to helper T cells and prevent their response to deplete them.
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Pg. 2 slide 2 in notes
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go over the interaction between APC and CD4
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Immunosuppression in organ transplantation steps (regime)
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1. Induction Regime
2. Common Regime 3. Maintanence Regime 4. Break through rejection |
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Induction Regime
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start before the transplant
Acute rejection likely from 2-12 weeks |
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Common Regimen
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cyclosporine + prednisolone+ azathlaprine (or MAB)
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Maintanence Regimen
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given for prolonged period of time may be life long
lower doses: one of the three drugs from common regime 2nd line are: mycophenolate cyclophosphamide, chlorambucil |
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Break Through Rejection
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high dose steroids--> taper it
risk of viral CMV, fungal, bacterial infectino and lymphomas |
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Cyclosporine
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immunosuppressant
post allogenic organ transplant Cyclosporine A is the main form |
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Cyclopsorine A
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cyclic nonribosomal peptide
from Tolypocladium inflatum Gams: fungus |
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allogenic
auto syngenic xeno |
same species
self indentical twin different species |
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Cyclosporine MOA
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binds with cyclophilin and inhibits calcineurin (cytoplasmic phosphate)
this in turn inhibits activation of T-cell transcription factor and leads to decreases in: IL-2, IL-3, and Interferon Gamma |
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Tacrolimus MOA
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similar to cyclosporine but does not bind to cyclophilin, but directly inhibits
calcineurin |
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Cyclosporine/Tacrolimus Uses
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1. in combination with steroids, cytotoxic agents or mycophenolate
2. (autoimmune diseases): Psoriasis, Atopic dermatitis, keratoconjunctivitis sicca, rarely in Rheumatoid arthritis 3. Ulcerative colitis who do not respond to steroids topical and systemic admins. |
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Cyclosporine AE, C/I and Interactions
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1. interacts with grapefruit: CYP is inhibited in Liver and GI by Cyclosporine and grapefruit
2. Gum Hyperplasia 3. Hyperglycemia 4. Numbness and Tingling 5. Nephrotoxicity and Hepatotoxicity 6. Cholelithiasis 7. HTN 8. Opportunistic fungal and viral infections |
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Cyclosporine G
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found to be less nephrotoxic than A
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Azathioprine
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immunosuppresant
organ transplant, autoimmune disease (RA), Crohn's disease, ulcerative colitis, ALL, AML Pro-drug: active metabolites are 6-mercaptopurine and 6-thionosinic acid |
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Azathioprine MOA
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inhibit purine synthesis necessary for the proliferation of cells (leukocytes)
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Azathrioprine AE/CI/Drug Interactions
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GI mucositis
supresses bone marrow and therefore increase in susceptibility to infection caution when used with allopurinol (purine analogue) TMPT (thiopurine S-methyltransferase) deactivates 6-mercaptopurine: therefore screen for genetic polymorphism of TPMT so there is not excessive drug toxicity |
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Azathrioprine AE/CI/Drug Interactions Continued
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Long Term AE: pregnancy---> potential hazard to fetus
Human carcinogen---> non-hodgkins lymphoma, squamous cell carcinoma of skin, hepatobiliary carcinomas and mesenchymal tumors |
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Methotrexate
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folic acid analog that inhibits DHFR
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Methotrexate Uses
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RA, Psoriasis, Carcinoma of Breast, lung, ovary, bladder and neck
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Methotrexate AE:
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Myelosuppression
GI Hemmorrhagic enteritis Neurotoxicity Hepatotoxicity |
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RHo(D) Immunoglobulin
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prevent antibody formation in rhesus negative women who have a rhesus positive baby
treating rhesus negative with Human IgG antibodies to red cell Rho(D) antigen Given within 72 hrs of delivery to preven hemolytic disease of newborn in later prgenancy |
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Monoclonal antibodies (mAbs)
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all end with mab
ex: infliximab |
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infliximab
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inhibits TNF alpha
Rheumatoid arthritis and Crohns |
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Abciximab
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inhibits the receptor GPIIb/IIIa on platelets
prevent coagulation in coronary angiography |
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Rituximab
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targets phosphoprotein CD20 on B-lymphocytes
non-hodgkins lymphoma |
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Daclizumab
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inhibits IL-2 on activated T-cells
acute rejection of kidney trasplants |
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Palivizumab
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inhibits RSV protein
RVS infection in children |
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Basiliximab
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inhibits IL-2 on activated T-cells
acute rejection of kidney transplant same as Daclizumab |
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Etanercept
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monoclonal antibody that does not end in mab
contains TNF receptor Rheumatoid Arthritis |
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Aldesleukin
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IL-2
promotes lymphocyte differentiation and NK's renal carcinoma and metastatic melanoma |
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IL-11
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improves platelet function
chemotherapy induced thrombocytopenia |
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Filgrastim
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G-CSF
stimulates proliferation and differentiation of granulocytes chemotherapy induced neutropenia---> bone marrow recovery |
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Sargramostim
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GM-CSF
stimulates granulocytes and macrophages BM recovery, after transplant adn after AML chemotherapy |
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Erythropoietin
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stimulates RBC production
anemia associated with chronic renal dysfunction chemotherapy adn radiation induced anemia |
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Interferon-alpha
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JAK-STAT signaling pathway
takes part in the regulation of cellular responses to cytokines of proliferation adn differentiation in combination with chemotherapy adn radiation (melanoma, leukemia, kaposis) Hepatitis C and B |
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Interferon-beta
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has anti-inflammatory properties
improves integrity of BBB in Multiple sclerosis |
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Interferon Gamma
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macrophage activating factor; enhances TNF
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