DMARDs in rheumatology Flashcards
What are the two main actions of DMARDs
anti-inflammatory and immuno-modulatory actions
What drug is the most important anti-rheumatic drug and the cornerstone of combinatorial therapy
Methotrexate
How does methotrexate enter the cell
Reduced folate carrier
What is the enzyme that interacts with methotrexate when it enters the cell, what happens
Folypolyglutamate synthetase (FPGS), converts methotrexate to polyglutamated methotrexate (MTX-PG) causing the cell to be less likely to leave
What does MTX-PG do
Inhibits amino imidazole carboximide ribonucleotide transformylase (ATIC), inhibits thymidylate synthetase (TS), inhibit Dihydrofolate reductase (DHFR)
What is the MOA of methotrexate
Up-regulates adenosine, down regulates TS, inhibt DHFR
What are the consequences of up regulation of adenosine
Potent inhibition of inflammation, promotes transition from neutrophil-mediated infllmation to highly specific dendritic cell mediated response
What are consequences of down-regualtion of TS
disrupts pyrimidine synthesis and proliferation of anti-inflammatory cells
What are consequences of inhibiting DHFR
disruption of DNA synthesis and proliferation, inhibition of transmethylation
How should methotrexate be monitored
MTX-PG present in RBCs
What can be taken to deal with a folate deficiency due to MTX
Folate suplements on days methotrexate is not taken
What is the sulfasalazine
inhibit proinflammatory efffects of the arachidonic acid cascade, inhibit ATIC and DHFR, decreasing neutrophil activation, immunomodulatory
What is the immunomodulatory of sulfasalazine
inhibit T lymphocyte proliferation, natural killer cell activity, and B cell activation
What is the MOA of Leflunomide
Block Dihydroorotoate dehydrogenase (DHODH) decreasing pyrimidine biosynthesis, especially in mitogen-stimulate T cells
T/F: Methotrexate and Leflunomide are both drugs that are category X due to teratogenic embryolethal effects
True
What are the anti-malarial drugs
chlororquine,hydroxychloroquine
What is the mechanism of hydroxychloroquine
Raise the pH within cytoplasmic vesicles causing the display of antigens by MHC to be reduced
What class of drugs have become cornerstones for systemic lupus, vasculitis, polymyalgia rheumatics and myositis
Glucocorticoids
What are strategies that inhibit cytokine action
monoclonal antibodies bind cytokines, monoclonal antibodies block the receptor, activation of anti-inflammatory pathways
Which TNF receptor leads to cell death
TNFR1
Which TNF receptor leads to proinflammatory cytokines
TNFR2
Which monoclonal antibodies for rheumatoid arthritis binds to TNF alpha, which is humanized
Infliximab and Adalimumab, Humira
Which monoclonal antibodies binds the TNFR
Enteracept
Which antibody block co-stimulation for T cells
Abtacept
