Disease-Modifying Anti-rheumatic Drugs (DMARDs) (Wolff)

Question 1

What are drugs of first choice for rheumatoid arthritis due to efficacy and rapid onset of action?

What is a drug of choice for additional pain relief?

Answer 1

1) NSAIDs

2) Acetaminophen

Question 2

Glucocorticoid receptors complexing with what transcription factors is a major indirect mechanism
for immunosuppression?

What is an inhibitor of PLA2 that is among the genes activated?

Answer 2

1) NF-κB and AP1

2) Lipocortin

Question 3

What are the clinical applications of glucocorticoids such as prednisone?

Answer 3

Treatment of RA by relieving pain and inflammation

while waiting for DMARD effects

Question 4

Prednisone has no biological effect until it is converted into what by the liver?

Answer 4

Prednisolone

Question 5

Using glucocorticoids for how long makes it more effective than either placebo or an NSAID?

Clinical experience suggests that glucocorticoids are effective for how long?

Answer 5

1) ≤ 1 month

2) ≤ 6 months

Question 6

What Nonbiologic DMARD accumulates in cells over multiple weeks and also blocks thymidylate synthase and 5-aminoimidazole-4- carboxamide ribonucleotide (AICAR)
transformylase?

Answer 6

Methotrexate

Question 7

The resulting AICAR due to methotrexate accumulation leads to an efflux of what?

This then binds to what on cell surface to exert anti-inflammatory effects?

Answer 7

1) Adenosine

2) Purinergic GPCRs

Question 8

Methotrexate acts faster than all other DMARDs with clinical effects evident in?

Answer 8

3-6 weeks

Question 9

What is the clinical application of methotrexate?

Answer 9

Drug of first choice for RA

Question 10

For treatment of RA, methotrexate should be adminstered?

Answer 10

Once per week, either orally or by injection

Question 11

While low doses of methotrexate are well-tolerated, what should patients be taking supplements of?

Answer 11

Folate

Question 12

What are life-threatening major toxicities associated

more with higher doses of methotrexate?

Answer 12

1) Bone marrow suppression
2) Hepatic fibrosis
3) GI ulceration
4) Pneumonitis

Question 13

Which Nonbiologic DMARD is a lipophilic weak base that accumulates in lysosomes?

Answer 13

Hydroxychloroquine

Question 14

In regard to the effects of hydroxychloroquine, the higher pH of the lysosomal vesicles in APCs limits the association of peptides with?

Answer 14

MHC class II molecules

Question 15

While hydroxychloroquine can slow disease progression, it has what caveat?

Answer 15

It has a delayed onset (3-6 months)

Question 16

What are the clinical applications for hydroxychloroquine?

Answer 16

1) Mild RA

2) Antimalarial

Question 17

What advantage does hydroxychloroquine have over methotrexate?

Answer 17

Hydroxychloroquine is considered safe to use during pregnancy

Question 18

What rare but serious adverse effect is seen with hydroxychloroquine?

Answer 18

Retinal damage

Question 19

What is the clinical application of the Nonbiologic DMARD sulfasalazine?

Answer 19

RA as monotherapy or apart of a triple therapy (w. hydroxychloroquine and methotrexate)

Question 20

What common toxicity is noted with sulfasalazine?

Answer 20

Derm reactions because its a sulfa drug

Question 21

What side effects of sulfasalazine are most commonly due to discontinuing use?

Answer 21

GI side effects

Question 22

What is the active moiety in patients with RA?

Answer 22

Sulfapyridine

Question 23

Which Nonbiologic DMARD exerts its effects by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase?

This has what effect on the pyrimidine known as
ribonucleotide uridine monophosphate pyrimidine (rUMP)?

Answer 23

1) Leflunomide

2) Blocks the synthesis of

Question 24

Leflunomide inhibits the proliferation of?

Answer 24

T cells

Question 25

What is the clinical application of leflunomide?

Answer 25

Second choice drug for RA

Question 26

What are common adverse effects of leflunomide?

Answer 26

1) Diarrhea 2) Respiratory infection 3) Alopecia

Question 27

As a general rule, Biologic DMARDs can be combined with non-biologic DMARDS, however?

Answer 27

Biologic DMARDs should never be combined together

Question 28

Between Biologic DMARDs and nonbiologic, which has a faster onset of action and higher rate of response?

Answer 28

Biologic DMARDs

Question 29

Which biologic DMARD is highly effective at reducing rheumatoid arthritis symptoms and disease progression by neutralizing an important immune mediator of joint injury?

Answer 29

Tumor Necrosis Factor Antagonists

Question 30

What are Tumor Necrosis Factor Antagonists indicated for?

Answer 30

Moderate to severe RA usually after traditional DMARDs have been ineffective

Question 31

Tumor Necrosis Factor Antagonists are often used in combination with?

Answer 31

Methotrexate

Question 32

All Tumor Necrosis Factor Antagonists pose risk of developing serious infections including?

Answer 32

TB

Question 33

Drugs that end with “-cept” refers to? Drugs that end with “-mab” indicates? Drugs that end with “ -ximab” indicates? Drugs that end with “-zumab” indicates? Drugs that end with “-umab” indicates?

Answer 33

1) Fusion of a receptor to the Fc part of human IgG1 2) Monoclonal antibody 3) Chimeric mAb 4) Humanized mAb 5) Human mAb origin

Question 34

Which TNF inhibitor is a soluble p75 TNF receptor fusion protein that consists of two p75 TNF receptors bound to the Fc portion of IgG? How is it administered?

Answer 34

1) Etanercept | 2) Once or twice weekly via subQ injection

Question 35

Which TNF inhibitor is a chimeric mAb directed against TNF? How is it administered?

Answer 35

1) Infliximab | 2) Intravenous infusion every six weeks

Question 36

Which TNF inhibitor is a recombinant fully human anti-TNF mAb? How is it administered?

Answer 36

1) Adalimumab | 2) SubQ injection every two weeks

Question 37

Which biologic DMARD is an antibody that targets CD20? This involves targeting of what cells?

Answer 37

1) Rituximab | 2) B cells

Question 38

What is the clinical application of rituximab?

Answer 38

Used in combination with methotrexate for RA

Question 39

What toxicity is noted with rituximab?

Answer 39

Severe infusion related hypersensitivity reactions

Question 40

Which biologic DMARD is a soluble fusion protein comprising CTLA-4 and the Fc portion of IgG1?

Answer 40

Abatacept

Question 41

Abatacept prevents the binding of what?

Answer 41

Prevents CD28 from binding to CD80/86

Question 42

What is the clinical application for abatacept?

Answer 42

Moderate to severe RA after TNF antagonist have failed

Question 43

Which biologic DMARD is an anti-human IL-6 receptor antibody of the IgG1 subclass?

Answer 43

Tocilizumab

Question 44

Tocilizumab has what effect? This limits the hepatic acute phase response and activation of?

Answer 44

1) Blocks the binding of IL-6 to its receptor | 2) T cells, B cells, macrophages, and osteoclasts

Question 45

What is the clinical application for tocilizumab?

Answer 45

Moderate to severe rheumatoid arthritis if other DMARDs and TNF alpha blockers have proven to be ineffective

Question 46

What are the most common adverse effects of tocilizumab?

Answer 46

Upper respiratory tract infections

Question 47

Which biologic DMARD is an inhibitor of the enzyme JAK3?

Answer 47

Tofacitinib

Question 48

Tofacitinib directly suppresses the production of? This suppresses the proliferation of?

Answer 48

1) IL-17 and IFNγ | 2) CD4+ T cells

Question 49

What is the clinical application for tofacitinib?

Answer 49

Moderate to severe rheumatoid arthritis that have poor response to methotrexate

Question 50

How is tofacitinib administered which is unusual among the biologic DMARDs?

Answer 50

Orally

Question 51

Which biologic DMARD is a recombinant, non-glycosylated version of human IL-1 receptor antagonist?

Answer 51

Anakinra

Question 52

Anakinra blocks the proinflammatory activity of?

Answer 52

IL-1

Question 53

What is the clinical application for anakinra?

Answer 53

Moderate to severe rheumatoid arthritis