Immunopharmacology Flashcards
What are the 4 classes of immunopharm drugs?
- calcineurin inhibitor
- mTOR inhibitor
- cytotoxic agent
- immunosuppressant antibodies
Name the drugs under each class.
- cyclosporine A, tacrolimus
- Sirolimus (rapamycin)
- azathioprine, MMF & MPS, Fingolimod
- polyclonal - lymphocyte & thymocyte antibodies
monoclonal
- Anti IL2R alpha
- CTLF4 Ig Fusion protein
- Anti BAFF mAb
- Anti TNF alpha
- Anti IL5
- Anti IL4 alpha
MOA
- binds to cyclophilin
- chaperone in immunosuppression// PPIase (peptidyl-prolyl cistrans isomerase) - CsA-cyclophilin complex inhibits calcineurin, a Ca2+-calmodulin Ser/Thr phosphatase
- prevent desphosp + translocation of NF-AT
- inhibits cytokine prdn (IL-2,TNFa,IFNgamma)
- inhibits T/B/CTL cells proliferation but primarily T cells
Use
oral/IV/ **ophthalamic
- transplants: kidney, liver, pancreas, heart
- uveitis, RA, psoarisis
Adverse effects
- hypertension, hyperlipidemia, hyperglycemia
- gum hyperplasia
- nephrotoxicity, neurotoxicity
MOA
- binds to immunophilin FKBP-12
- FKBP: chaperone in immunosuppr + PPIase
Use
oral/IV/**topical macrolide
- more potent than CsA
Adverse effects
- hypertension, hyperlipidemia, hyperglycemia
2. nephrotoxicity, neurotoxicity
MOA
- sirolimus:FKBP immunophilin complex
- binds & inhibits mTOR (ser/thr kinase)
- inhibiting 70kDa S6 kinase
- growth arrest from G1 to S phase
- maintain repressor activity of 4E-BP1
- inhibits cytokine-mediated proliferation of T & B cells
MOA
against receptors in immune system
Adverse effects
- hypertension, hyperlipidemia, hyperglycemia
2. nephrotoxicity, neurotoxicity
Use
- anti proliferative & anti angiogenic activities
- sirolimus-eluting coronary stents to prevent arterial restenosis
- gd combo: sirolimus + cyclosporine A but renal impairment
Adverse effects
- hypertension, hyperlipidemia, hyperglycemia
2. thrombocytopenia
*Azathioprine
other 2 include cyclophosphamide (alkylating) + methotrexate (DHFR inhib)
MOA
- prodrug–> converted to 6MP –> 6TG
2. 6TG impedes DNA synthesis, de novo purine synthesis –> decrease proliferation of lymphocytes
Use
- renal transplant &
2. other autoimmune disorders using triple therapy (calcineurin inhibitor + steroid + cytotoxic agent azathioprine)
Adverse effects
- bone marrow suppression: leukopenia, thrombocytopenia, anaemia
- bleeding
- GI toxicity
- lymphoma & neoplasia
MOA
- converted to mycophenolic acid
- inhibit preferentially type II (inducible) IMPDH
- inhibit de novo guanosine synthesis
Use
- less bone marrow suppression & GI toxicity than aza
- more selective T/B antiproliferative effects
- suppress antibody prdn
- inhibit leukocyte recruitment to graft site
Adverse effects
- diarrhoea
- neutropenia
- anemia
- hypertension
MOA
- prodrug phosph to FTY720P
- S1PR agonist
- activates S1P (1,3,4,5)
- S1P1 & 4 promotes chemokine mediated lymphocyte homing + decrease circulating lymphocyte
Use
multiple sclerosis
Adverse effects
- first dose negative cardiac chronotropic effect due to activation of S1P1,3 in SA nodal cells
*Polyclonal antibodies (non selective IgG)
lymphocyte antibody- atgam
thymocyte antibody- thymoglobulin
MOA
- opsonisation
- complement-dependent cytotoxicity
- ADCC
- depletion of t cells
- cross link TCR– anergy
Use
-
Adverse effects
- first dose effect cytokine release syndrome (fever, chills. hypotension)
- serum sickness/ thromobcytopenia/ leukopenia
- dev anti foreign IgG antibodies
- histiocytic lymphoma at site injection
