Immunosuppression for AI Diseases Flashcards
What is the deal with autoreactive B-cells in RA?
They accumulate in the synovium producing and releasing cytokines (promote inflammation). They also produce auto-antibodies that result in immune complex formation with self antigens, promoting activation of immune cells (e.g. macrophages attack synovial cells) and initiating complement fixation
Discuss costimulation of T-cells.
T-cells require 2 signals for activation: Binding of MHC class II of the antigen-presenting cell to the TCR on the T-cell, and Binding of the costimulatory ligand (CD80/CD86) on the APC to the costimulatory receptor (CD28) on the T-cell.
Describe the mechanism of action of Abatacept.
It prevents costimulation of T-cells by preventing CD80/86 on APCs from binding CD28 on T-cells, resulting in T-cell hyporesponsiveness
What is the clinical indication for Abatacept?
RA that’s refractory to methotrexate and/or TNF-a inhibitors
What is the clinical indication for Tocilizumab, Rituximab, and Abatacept?
Immunosuppresion for RA in pts unresponsive to TNF-a inhibitors
Name the TNF-a inhibitors.
TNF - all consonants.
AEI - all vowels.
Adalimumab
Etanercept
Infliximab
What are the clinical indications for TNF-a inhibitors Adalimumab and Infliximab?
Immunosuppression useful for RA, ulcerative colitis, and Crohn’s dz
What is the clinical use for Etanercept?
Immunosuppression useful for many rheumatic syndromes, but less effective against IBDs compared with the other TNF-a inhibitors
What are the shared adverse effects associated with TNF-a inhibitors?
Activation of latent TB, increased opportunistic infection, lymphoma
*basal and squamous cell skin cancers w/ Adalimumab
What drugs are often combined with TNF-a inhibitors?
methotrexate, azathioprine, cyclosporine
Why is concurrent administration of methotrexate helpful when taking a TNF-a inhibitor?
It reduces the prevalence of antibody development against the drug
Describe the mechanism of action of Tocilizumab.
It neutralizes IL-6 receptor on immune cells, thus blocking activation of JAK-STAT pathway (responsible for transcription of genes for proinflammatory proteins)
Describe the mechanism of action of Rituximab.
It is a B-cell depletor; it recognizes CD20 on B-cell surfaces and binds to it depleting the fxn of B-cells
What is the role of B-cells in RA?
They are believed to be responsible for activating T-cell response and promoting inflammation
What drug metabolism-related effects are associated with Tocilizumab?
Because IL-6 normally suppresses some CYP expression in the liver, IL-6 suppression can lead to induction of those CYPs causing decreased therapeutic levels of drugs metabolized by them.
