DMARDs

Question 1

What is more effective: methotrexate + etanercept or Methotrexate+sulfasalazine+hydroxychloroquine?

Answer 1

no difference between triple non-biologic therapy and biologic treatment. Evidence shows you can go with the cheaper, triple therapy option

Question 2

What is mechanism of Methotrexate?

Answer 2

immunosuppression by inhibition of AICAR transformylase, which increases AICA riboside, which inhibits adensoine deaminase, resulting in increased adenosine, resulting in lymphocyte prolif inhibition and IL-1,TNF, and INFg suppression. Increases IL-4 and impairs release of histamine and neutrophil chemotaxis.

Question 3

What effect does AICAR transformylase have on AICA?

Answer 3

it reduces AICA levels normally

Question 4

What is the relationship between AICA levels and RA?

Answer 4

high AICA levels correlate with decreased RA symptoms. Methotrexate increases AICA by inhibiting AICAR

Question 5

How does methotrexate stay in cells?

Answer 5

it undergoes polyglutamation as soon as it enters cells.

Question 6

Adverse effects of methotrexate?

Answer 6

susceptibility to disease and neoplasm. Teratogen, and pulmonary toxicity. Severe GI toxicity and PUD/ulcerative colitis possible when given with NSAIDs

Question 7

What is MOA of sulfasalazine?

Answer 7

metabolized to active sulfapyridine and mesalamine by bacteria in colon. Mesalamine is anti-inflammatory and inhibits PG and LT production.

Question 8

Adverse effects of sulfasalazine?

Answer 8

potentially fatal blood dyscrasias

Question 9

What is MOA of leflunomide?

Answer 9

active metabolite is A77 1726 which inhibits DHODH (dihydroorotate dehydrogenase, which normally catalyzes de novo pyrimidine synthesis. Without it, T and B lymphocytes enter arrested cell cycles and Ig production is halted.

Question 10

Adverse effects of leflunomide?

Answer 10

hepatotoxicity with chronic use.

Question 11

What is MOA of hydroxychloroquine?

Answer 11

anti-malarial, increases intracellular vacuole pH and alres processes like protein degradation by acidic hydrolases in lysosomes. Antigenic proteins can not be digested and presented on MHC class II proteins, this inhibits CD4 stimulation.

Question 12

Contraindications of hydroxychloroquine?

Answer 12

can not give in ocular disease because drug causes corneal opacities

Question 13

MOA of abatacept?

Answer 13

human CTLA4/IgG1 Fc fragment that binds CD80 and CD86 to prevent T cell co-stim signal from engaging with CD28

Question 14

MOA of adalimumab?

Answer 14

TNF-a monoclonal antibody that binds TNF-alpha and blocks its interaction with the p55 and p75 cell surface receptors

Question 15

MOA of anakinra?

Answer 15

recombinant human IL-1Ra (receptor antagonist) that competitively inhibits IL-1a and IL1-b binding to IL-1R1

Question 16

MOA of certolizumab?

Answer 16

Fab fragment of TNFa antibody that neutralizes membrane-associated and soluble TNFa

Question 17

MOA of etancercept?

Answer 17

extracellular ligand-binding protein of p75 TNF receptor linked to human IgG Fc. Endogenous p75 acts as a TNF antagonist. recombinant TNFR p75 bound to the Fc fragment of IgG1. Inactivates TNF but does not affect TNF production or serum levels.

Question 18

MOA of golimumamb?

Answer 18

TNFa antibody binds to and neutralizes both soluble and transmembrane TNFa

Question 19

MOA of infliximab?

Answer 19

chimeric mouse-hman IgG1 monoclonal antibody against TNFa neutralizes both soluble and transmembrane TNFa

Question 20

MOA of rituximab?

Answer 20

chimeric mouse-human IgG1 monoclonal antibody against CD20 receptor on B-cells. Fab domain binds CD20 and Fc causes B cell lysis.

Question 21

MOA of toclizummab?

Answer 21

IL-6 receptor antibody

Question 22

Which biologics can cause congestiv eheart failure?

Answer 22

adalimumab, golimumab, infliximab and rituximab.

Infliximab is worst.

Question 23

What must women taking rituximab do?

Answer 23

use reliable contraception and avoid pregnancy up to 6 months after stopping treatment