MSK: DMARDs Flashcards
What drugs are first-line for Rheumatoid arthritis?
NSAIDs
- acetaminophen
- -opoids are generally not necessary
MOA of glucocorticoids?
block transcription of NF-kB and AP1 transcription factors
-decreases immune cell and inflammatory cytokine (IL-1) production=anti-inflammatory
What is the clinical application of glucocorticoids in rheumatoid arthritis?
Relieves pain and inflammation while waiting for other DMARDs to kick in
-also treats flares of RA
ROI of glucocorticoids?
PO, IM, or intra-articular
What are some adverse effects of glucocorticoids?
Adrenal insufficiency*
Cushing syndrome*
Hypothyroidism
Diabetes mellitus
And many more
What gene is activated by glucocorticoids to inhibit Phospholipase A2 (PLA2)?
Lipocortin
How long are glucocorticoids effective for in RA?
usually < 6 months
-not used on chronic basis, only for flares
How many joints are inflammed in mild RA?
< or =5 joints
-any more it becomes moderate-severe
MOA of methotrexate?
Inhibits dihydrofolate reductase
-causes thymineless death of cells
What is the overcomplex mechanism of action for methotrexate that Wolff has listed?
Results in AICAR buildup, which binds to purinergic GPCRs on cell surfaces and has anti-inflammatory effects
Is methotrexate fast or slow onset?
Faster onset than other DMARDs; evident in 3-6 weeks
-works for 80% of patients
ROI for methotrexate?
Once per week oral or injection
What should you supplement patients on when giving methotrexate?
Folate
Are there many adverse effects with methotrexate? If so, what are they?
Yeah, high doses have many life threatening effects
- Bone marrow suppression
- hepatic fibrosis
- GI ulceration
Is methotrexate safe during pregnancy?
Absolutely not
MOA of hydroxychloroquine
Is lipophilic and accumulates in lysosomes where it is protonated, which results in even higher concentrations
-disrupts MCH II presentation
Clinical uses of hydroxychloroquine
Antimalarial
Often combined with methotrexate or sulfasalazine
Is hydroxychloroquine safe during pregnancy?
Yes
How long is the half life of hydroxychloroquine?
23 days
How can you speed up the benefits of hydroxychloroquine?
use a loading dose
What is the toxicity associated with hydroxychloroquine?
retinal damage
-low doses carry less of this risk
MOA of sulfasalazine
Metabolized into sulfapyridine to cause immunosuppression
-doesnt list how?
Clinical application of sulfasalazine
Used as monotherapy for RA or combined with hydroxychloroquine and/or methotrexate (triple therapy)
Is sulfasalazine safe in pregnancy?
Seems okay, but not studied well
Adverse effects of sulfasalazine?
GI side effects (N/V, Diarrhea)
Sulfa drug–watch for allergies
MOA of leflunomide
inhibits mito enzyme dihydroorotate dehydrogenase
-blocks synthesis and inhibits T cell proliferation
Clinical use of leflunomide?
Alternative DMARD to methotrexate
-second line
What is the half life of leflunomide?
16.5 days, so loading dose is needed
What are the most common adverse effects of leflunomide?
diarrhea, URI, reversible alopecia, rash and nausea
Can biologic DMARDs be combined with other biologics?
No! Can be combined with other non-biologic DMARDs though
What are the pros and cons of the biologic DMARDs?
Pros: Faster onset and high rate of response
Cons: expensive and increase risk of adverse events
What do the following suffixes mean:
- cept
- mab
- ximab
- zumab
- umab
- cept=fusion of a receptor to Fc region of IgG
- mab=monoclonal antibody
- ximab=chimeric ab
- zumab=humanized mAb
- umab=human mAb origin
TNF antagonists MOA?
Work by neutralizing TNF
-great for RA, after non-biologics
Clinical indications for TNF-a antagonists
Moderate to severe RA
-after non-biologics did not work
What other drug is TNF-antagonsits combined with?
Methotrexate
Adverse effects of TNF antagonists
Immunosupression
-TB
Severe allergic rxns
What drugs are the TNF inhibitors?
Etanercept (SubQ QD or BID)
Infliximab (IV every 6 weeks)
Adalimumab (SubQ biweekly)
MOA of rituximab
monoclonal Ab directed at CD20 on B cells
-depletes B cells to decrease levels of autoantibodies
What other drug is rituximab combined with?
methotrexate
What autoantibodies improves the likelihood of ritixumab working?
Rheumatoid factor and Anti-CCP
What adverse effects are associated with rituximab?
Infusion reactions and serum sickness
MOA of abatacept
prevents CD28 from binding to CD80/56
Clinical applications of abatacept
Moderate to severe RA
-can be combined with non-biologic DMARDs
Adverse reactions of abatacept
Generally well tolerated
-headache, URI, nausea
Can increase chance of infections
MOA of tocilizumab
humanized anti-IL6 receptor Ab
-blocks receptor limiting inflammation
Clinical application of tocilizumab
Moderate to severe RA after other drugs havent worked
-can be used alongside methotrexate
Adverse effects of toxilizumab
URIs*-most common
Life threatening infections (TB)
MOA of tofacitinib
inhibits JAK3
-decreases DNA transcription of cytokines and T/B cells
Clinical application of tofacitinib
Moderate to severe RA after other drugs havent worked
-can be used alongside methotrexate
ROI of tofacitinib
Oral
Is tofacitinib an expensive drug?
Yes, $2055 a month
Adverse effects of tofacitinib
Fatal infections with opportunistic infections
Can increase malignancies
MOA of anakinra
Recombinant drug of human IL-1 receptor antagonist
-decrease inflammation
Clinical use of anakinra?
Moderate to severe RA after other drugs haven’t worked
considered less effective than other DMARDs
Adverse effects of anakinra
Increase incidence of serious infections
Hypersensitivity reactions
Which drug directly decreases the amount of IL-17 and IFN-y and the CD4+ T cell population?
Tofacitinib (JAK3 inhibitor)
