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NMSKP Exam II > MSK: DMARDs > Flashcards

MSK: DMARDs Flashcards

1
Q

What drugs are first-line for Rheumatoid arthritis?

A

NSAIDs

  • acetaminophen
  • -opoids are generally not necessary
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2
Q

MOA of glucocorticoids?

A

block transcription of NF-kB and AP1 transcription factors

-decreases immune cell and inflammatory cytokine (IL-1) production=anti-inflammatory

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3
Q

What is the clinical application of glucocorticoids in rheumatoid arthritis?

A

Relieves pain and inflammation while waiting for other DMARDs to kick in
-also treats flares of RA

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4
Q

ROI of glucocorticoids?

A

PO, IM, or intra-articular

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5
Q

What are some adverse effects of glucocorticoids?

A

Adrenal insufficiency*
Cushing syndrome*
Hypothyroidism
Diabetes mellitus

And many more

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6
Q

What gene is activated by glucocorticoids to inhibit Phospholipase A2 (PLA2)?

A

Lipocortin

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7
Q

How long are glucocorticoids effective for in RA?

A

usually < 6 months

-not used on chronic basis, only for flares

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8
Q

How many joints are inflammed in mild RA?

A

< or =5 joints

-any more it becomes moderate-severe

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9
Q

MOA of methotrexate?

A

Inhibits dihydrofolate reductase

-causes thymineless death of cells

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10
Q

What is the overcomplex mechanism of action for methotrexate that Wolff has listed?

A

Results in AICAR buildup, which binds to purinergic GPCRs on cell surfaces and has anti-inflammatory effects

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11
Q

Is methotrexate fast or slow onset?

A

Faster onset than other DMARDs; evident in 3-6 weeks

-works for 80% of patients

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12
Q

ROI for methotrexate?

A

Once per week oral or injection

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13
Q

What should you supplement patients on when giving methotrexate?

A

Folate

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14
Q

Are there many adverse effects with methotrexate? If so, what are they?

A

Yeah, high doses have many life threatening effects

  • Bone marrow suppression
  • hepatic fibrosis
  • GI ulceration
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15
Q

Is methotrexate safe during pregnancy?

A

Absolutely not

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16
Q

MOA of hydroxychloroquine

A

Is lipophilic and accumulates in lysosomes where it is protonated, which results in even higher concentrations

-disrupts MCH II presentation

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17
Q

Clinical uses of hydroxychloroquine

A

Antimalarial

Often combined with methotrexate or sulfasalazine

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18
Q

Is hydroxychloroquine safe during pregnancy?

A

Yes

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19
Q

How long is the half life of hydroxychloroquine?

A

23 days

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20
Q

How can you speed up the benefits of hydroxychloroquine?

A

use a loading dose

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21
Q

What is the toxicity associated with hydroxychloroquine?

A

retinal damage

-low doses carry less of this risk

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22
Q

MOA of sulfasalazine

A

Metabolized into sulfapyridine to cause immunosuppression

-doesnt list how?

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23
Q

Clinical application of sulfasalazine

A

Used as monotherapy for RA or combined with hydroxychloroquine and/or methotrexate (triple therapy)

24
Q

Is sulfasalazine safe in pregnancy?

A

Seems okay, but not studied well

25
Adverse effects of sulfasalazine?
GI side effects (N/V, Diarrhea) | Sulfa drug--watch for allergies
26
MOA of leflunomide
inhibits mito enzyme dihydroorotate dehydrogenase | -blocks synthesis and inhibits T cell proliferation
27
Clinical use of leflunomide?
Alternative DMARD to methotrexate | -second line
28
What is the half life of leflunomide?
16.5 days, so loading dose is needed
29
What are the most common adverse effects of leflunomide?
diarrhea, URI, reversible alopecia, rash and nausea
30
Can biologic DMARDs be combined with other biologics?
No! Can be combined with other non-biologic DMARDs though
31
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
32
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
33
TNF antagonists MOA?
Work by neutralizing TNF | -great for RA, after non-biologics
34
Clinical indications for TNF-a antagonists
Moderate to severe RA | -after non-biologics did not work
35
What other drug is TNF-antagonsits combined with?
Methotrexate
36
Adverse effects of TNF antagonists
Immunosupression -TB Severe allergic rxns
37
What drugs are the TNF inhibitors?
Etanercept (SubQ QD or BID) Infliximab (IV every 6 weeks) Adalimumab (SubQ biweekly)
38
MOA of rituximab
monoclonal Ab directed at CD20 on B cells | -depletes B cells to decrease levels of autoantibodies
39
What other drug is rituximab combined with?
methotrexate
40
What autoantibodies improves the likelihood of ritixumab working?
Rheumatoid factor and Anti-CCP
41
What adverse effects are associated with rituximab?
Infusion reactions and serum sickness
42
MOA of abatacept
prevents CD28 from binding to CD80/56
43
Clinical applications of abatacept
Moderate to severe RA | -can be combined with non-biologic DMARDs
44
Adverse reactions of abatacept
Generally well tolerated -headache, URI, nausea Can increase chance of infections
45
MOA of tocilizumab
humanized anti-IL6 receptor Ab | -blocks receptor limiting inflammation
46
Clinical application of tocilizumab
Moderate to severe RA after other drugs havent worked | -can be used alongside methotrexate
47
Adverse effects of toxilizumab
URIs*-most common Life threatening infections (TB)
48
MOA of tofacitinib
inhibits JAK3 | -decreases DNA transcription of cytokines and T/B cells
49
Clinical application of tofacitinib
Moderate to severe RA after other drugs havent worked | -can be used alongside methotrexate
50
ROI of tofacitinib
Oral
51
Is tofacitinib an expensive drug?
Yes, $2055 a month
52
Adverse effects of tofacitinib
Fatal infections with opportunistic infections Can increase malignancies
53
MOA of anakinra
Recombinant drug of human IL-1 receptor antagonist | -decrease inflammation
54
Clinical use of anakinra?
Moderate to severe RA after other drugs haven't worked considered less effective than other DMARDs
55
Adverse effects of anakinra
Increase incidence of serious infections Hypersensitivity reactions

NMSKP Exam II (4 decks)

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