Immunosupression Flashcards
Corticosteroid MoA
Binds to intracellular receptor
Prevent IL-1 and IL-6 production by macrophages
Inhibits T cell activation
Azathioprine MoA
cleaved to 6MP 6MP further cleaved to TIMP which is cleaved by TMPT into 6-MeMP and 6-TGN 6MeMP- inhibits de novo purine synthesis 6-TGN incorporates into DNA decreases DNA and RNA synthesis suppresses inflammatory cytokines
Azathioprine TMPT polymorphism
Highly polymorphic
Low TMPT increases risk of myleosupression
Calcineurin inhibitors examples
Ciclosporin and tacrloimus
Calcineurin inhibitor MoA
Bind to own binding proteins then form complex with calcineurin
inhibit IL-2 production and receptor expression
decrease T cell activation
Calcineurin inhibitors DDI
potent CYP 450 inhibitor
Mycophenolate mofetil MoA
Inhibits inosine monophosphate dehydrogenase
decrease guanosine synthesis
impaired T and B cell proliferation (spares rapidly dividing cells)
Cyclophosphamide MoA
cross links DNA so it can’t replicate
supressess T and B cell activity- alkylating agent
Cyclophosphamide ADR
haemorrhagic cystitis (metabolite is toxic to bladder)
Methotrexate MoA (unclear for non-malignant disease)
Reversibly inhibits dihydrofolate reductase
Inhibits synthesis of DNA, RNA and proteins
greater toxicity to rapidly dividing cells
Methotrexate specific ADR
Teratogenic
Abortifacent- used in termination of pregnancy
Sulfasalazine MoA
Inhibits T cell production
Inhibits IL 2 production
decrease neutrophil chemotaxis
Anti TNF alpha example
Adamumab, Infliximab
Anti TNF alpha MoA
Monoclonal antibody
blocks TNF alpha
decrease inflammation & angiogenesis
Anti TNF alpha risks
TB reactivation- TNF alpha is essential in development and maintenance of granulomata in TB
screen for TB before
