All are true for immunosuppressants except: (LQ)
|A||Sirolimus acts by T cell modification|
|B||Tacrolimus inhibits calcineurin pathway|
|C||Mycophenolate acts by inhibiting GMP dehydrogenase|
|D||Cyc1osporin is integral in transplant rejection regimen.|
Mycophenolate is a prodrug of mycophenolic acid which selectively inhibits inosine monophosphate dehydrogenase thus inhibiting lymphocyte proliferation, antibody production and cell mediated immunity. Available in oral & intravenous forms.
- Newer applications are lupus nephritis, RA & some skin conditions.
- Mech. of Action: enters target cells and binds to a protein cyclophilin forming a complex which inactivates calcineurin →↓ gene transcription of lL-2/3, INF-alpha → Response of T helper cells to antigenic stimulation fails
- Selectively ↓es cell mediated immunity
- S/E: Nephrotoxicity, ↑ in BP, Hyperkalemia Hepatotoxicty, precipitation of OM
- Hirsuitism, gum hyperplasia, tremors
i. Prevents graft rejection (most effective drug for it) ii. Autoimmune diseases (RA, IBO etc).
iii. Psoriasis iv. Aplastic anemia v. Rx of GVHO
Similar mechanism of action as cyclosporine but it binds to a different cytoplasmic protein called "FkBP"
- ↑ useful in liver transplantation
- ↑ potency
- ↓ hypertension, hirsuitism, Gum hyperplasia
Other immunosoppressants are:
Sirolimus: Binds immunophilins & (-) calcineurin (as do cyclosporine & tacrolimus)
- Doesn’t block lL production by activated T cells but instead blocks response of T cells to cytokines (C.f cyclosporine/Tacrolimus )
- Potent inhibitor of B cell proliferation and Ig production
- Topical sirolimus is used in some skin conditions and in combination with cyclosporine in the management of uveoretinitis.
a. (-) pyrimidine synthesis
b. Orally active
c. At present used only for RA
Toxicity: ↑ liver enzymes, renal impairment, teratogenicity, Angina, tachycardia
Others: Cyclophosphamide, Vincristine, Methotrexate, Cytarabine.