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NMSP Week 4/5 > Disease-Modifying Anti-rheumatic Drugs (DMARDs) (Wolff) > Flashcards

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

1
Q

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?

A

1) NSAIDs

2) Acetaminophen

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2
Q

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?

A

1) NF-κB and AP1

2) Lipocortin

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3
Q

What are the clinical applications of glucocorticoids such as prednisone?

A

Treatment of RA by relieving pain and inflammation while waiting for DMARD effects

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4
Q

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

A

Prednisolone

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5
Q

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?

A

1) ≤ 1 month

2) ≤ 6 months

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6
Q

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

A

Methotrexate

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7
Q

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?

A

1) Adenosine

2) Purinergic GPCRs

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8
Q

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

A

3-6 weeks

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9
Q

What is the clinical application of methotrexate?

A

Drug of first choice for RA

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10
Q

For treatment of RA, methotrexate should be adminstered?

A

Once per week, either orally or by injection

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11
Q

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

A

Folate

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12
Q

What are life-threatening major toxicities associated more with higher doses of methotrexate?

A

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

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13
Q

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

A

Hydroxychloroquine

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14
Q

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

A

MHC class II molecules

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15
Q

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

A

It has a delayed onset (3-6 months)

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16
Q

What are the clinical applications for hydroxychloroquine?

A

1) Mild RA

2) Antimalarial

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17
Q

What advantage does hydroxychloroquine have over methotrexate?

A

Hydroxychloroquine is considered safe to use during pregnancy

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18
Q

What rare but serious adverse effect is seen with hydroxychloroquine?

A

Retinal damage

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19
Q

What is the clinical application of the Nonbiologic DMARD sulfasalazine?

A

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

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20
Q

What common toxicity is noted with sulfasalazine?

A

Derm reactions because its a sulfa drug

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21
Q

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

A

GI side effects

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22
Q

What is the active moiety in patients with RA?

A

Sulfapyridine

23
Q

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)?

A

1) Leflunomide

2) Blocks its synthesis

24
Q

Leflunomide inhibits the proliferation of?

A

T cells

25
Q

What is the clinical application of leflunomide?

A

Second choice drug for RA

26
Q

What are common adverse effects of leflunomide?

A

1) Diarrhea
2) Respiratory infection
3) Alopecia

27
Q

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

A

Biologic DMARDs should never be combined together

28
Q

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

A

Biologic DMARDs

29
Q

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

A

Tumor Necrosis Factor Antagonists

30
Q

What are Tumor Necrosis Factor Antagonists indicated for?

A

Moderate to severe RA usually after traditional DMARDs have been ineffective

31
Q

Tumor Necrosis Factor Antagonists are often used in combination with?

A

Methotrexate

32
Q

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

A

TB

33
Q

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?

A

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

34
Q

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?

A

1) Etanercept

2) Once or twice weekly via subQ injection

35
Q

Which TNF inhibitor is a chimeric mAb directed against TNF?

How is it administered?

A

1) Infliximab

2) Intravenous infusion every six weeks

36
Q

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

How is it administered?

A

1) Adalimumab

2) SubQ injection every two weeks

37
Q

Which biologic DMARD is an antibody that targets CD20?

This involves targeting of what cells?

A

1) Rituximab

2) B cells

38
Q

What is the clinical application of rituximab?

A

Used in combination with methotrexate for RA

39
Q

What toxicity is noted with rituximab?

A

Severe infusion related hypersensitivity reactions

40
Q

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

A

Abatacept

41
Q

Abatacept prevents the binding of what?

A

Prevents CD28 from binding to CD80/86

42
Q

What is the clinical application for abatacept?

A

Moderate to severe RA after TNF antagonist have failed

43
Q

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

A

Tocilizumab

44
Q

Tocilizumab has what effect?

This limits the hepatic acute phase response and activation of?

A

1) Blocks the binding of IL-6 to its receptor

2) T cells, B cells, macrophages, and osteoclasts

45
Q

What is the clinical application for tocilizumab?

A

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

46
Q

What are the most common adverse effects of tocilizumab?

A

Upper respiratory tract infections

47
Q

Which biologic DMARD is an inhibitor of the enzyme JAK3?

A

Tofacitinib

48
Q

Tofacitinib directly suppresses the production of?

This suppresses the proliferation of?

A

1) IL-17 and IFNγ

2) CD4+ T cells

49
Q

What is the clinical application for tofacitinib?

A

Moderate to severe rheumatoid arthritis that have poor response to methotrexate

50
Q

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

A

Orally

51
Q

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

A

Anakinra

52
Q

Anakinra blocks the proinflammatory activity of?

A

IL-1

53
Q

What is the clinical application for anakinra?

A

Moderate to severe rheumatoid arthritis

NMSP Week 4/5 (13 decks)

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