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Phar 504 > DMARDs in rheumatology > Flashcards

DMARDs in rheumatology Flashcards

1
Q

What are the two main actions of DMARDs

A

anti-inflammatory and immuno-modulatory actions

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2
Q

What drug is the most important anti-rheumatic drug and the cornerstone of combinatorial therapy

A

Methotrexate

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3
Q

How does methotrexate enter the cell

A

Reduced folate carrier

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4
Q

What is the enzyme that interacts with methotrexate when it enters the cell, what happens

A

Folypolyglutamate synthetase (FPGS), converts methotrexate to polyglutamated methotrexate (MTX-PG) causing the cell to be less likely to leave

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5
Q

What does MTX-PG do

A

Inhibits amino imidazole carboximide ribonucleotide transformylase (ATIC), inhibits thymidylate synthetase (TS), inhibit Dihydrofolate reductase (DHFR)

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6
Q

What is the MOA of methotrexate

A

Up-regulates adenosine, down regulates TS, inhibt DHFR

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7
Q

What are the consequences of up regulation of adenosine

A

Potent inhibition of inflammation, promotes transition from neutrophil-mediated infllmation to highly specific dendritic cell mediated response

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8
Q

What are consequences of down-regualtion of TS

A

disrupts pyrimidine synthesis and proliferation of anti-inflammatory cells

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9
Q

What are consequences of inhibiting DHFR

A

disruption of DNA synthesis and proliferation, inhibition of transmethylation

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10
Q

How should methotrexate be monitored

A

MTX-PG present in RBCs

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11
Q

What can be taken to deal with a folate deficiency due to MTX

A

Folate suplements on days methotrexate is not taken

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12
Q

What is the sulfasalazine

A

inhibit proinflammatory efffects of the arachidonic acid cascade, inhibit ATIC and DHFR, decreasing neutrophil activation, immunomodulatory

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13
Q

What is the immunomodulatory of sulfasalazine

A

inhibit T lymphocyte proliferation, natural killer cell activity, and B cell activation

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14
Q

What is the MOA of Leflunomide

A

Block Dihydroorotoate dehydrogenase (DHODH) decreasing pyrimidine biosynthesis, especially in mitogen-stimulate T cells

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15
Q

T/F: Methotrexate and Leflunomide are both drugs that are category X due to teratogenic embryolethal effects

A

True

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16
Q

What are the anti-malarial drugs

A

chlororquine,hydroxychloroquine

17
Q

What is the mechanism of hydroxychloroquine

A

Raise the pH within cytoplasmic vesicles causing the display of antigens by MHC to be reduced

18
Q

What class of drugs have become cornerstones for systemic lupus, vasculitis, polymyalgia rheumatics and myositis

A

Glucocorticoids

19
Q

What are strategies that inhibit cytokine action

A

monoclonal antibodies bind cytokines, monoclonal antibodies block the receptor, activation of anti-inflammatory pathways

20
Q

Which TNF receptor leads to cell death

A

TNFR1

21
Q

Which TNF receptor leads to proinflammatory cytokines

A

TNFR2

22
Q

Which monoclonal antibodies for rheumatoid arthritis binds to TNF alpha, which is humanized

A

Infliximab and Adalimumab, Humira

23
Q

Which monoclonal antibodies binds the TNFR

A

Enteracept

24
Q

Which antibody block co-stimulation for T cells

A

Abtacept

25
Q

What is the first phase for Rheumatoid arthritis management

A

Start methotrexate and glucocorticoid

26
Q

What is the second phase for rheumatoid arthritis management

A

add 2nd DMARD or biologic or JAK-inhibitor

27
Q

What is the third phase for rheumatoid arthritis

A

change or add biologic or JAK-inhibitor

28
Q

How does IL-6 contribute to rheumatoid arthritis

A

chemical messenger involved in destructive immune responses

29
Q

What are the Jak-Stat inhibitors used for RA

A

Baricitinib, Filgotinib, ABT-494

30
Q

What is sulfasalazine a pro drug for, what are their functions

A

5-Aminosalicyclic acid = anti-inflammatory, sulfapyridine = antibiotic

31
Q

What are the monoclonal antibody DMARDs that bind to TNF

A

etanerecpt, infliximab, Adalimumab

32
Q

Which monoclonal anitbody DMARD binds to B7 with IgG fused to the extracellular domain of CTLA-4

A

Abtacept/Orencia

33
Q

Which monoclonal antibody DMARD binds to CD20 on B cells

A

Rituximab

34
Q

Which monocloncal antibody DMARD binds IL-6 receptor

A

Tocilizumab

Phar 504 (34 decks)

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