RA Drugs- DMARDs Flashcards Preview

Rheum/Musculoskeletal/Derm Week 1 > RA Drugs- DMARDs > Flashcards

Flashcards in RA Drugs- DMARDs Deck (75):
1

The treatment of RA is progressive. What do most clinicians start with?

a DMARD like METHOTREXATE with the addition of an NSAID and a corticosteroid

2

How is RA treated initiated in milder cases?

Hydroxychloroquine is preferred because of lower toxicity

3

What is considered in RA treatment after initial treatment failure?

a first-line biological agent such as Etanercept, Infliximab, Adalimumab, Golimumab, or Certolizumab

4

T or F. Experience shows that early, aggressive treatment with MTX and/or a biological agent results in longer disease-free remission, less joint destruction, and a better quality of life

T.

5

What are the results of Methotrexate use?

inhibition of lymphocyte
proliferation and suppression of several pro-inflammatory mediators (Il-1, IFN-y, and TNF) via tonic adenosine activation.

6

What process does Methotrexate undergo that helps retain it in the cell?

polyglutamation

7

High-dose methotrexate therapy is associated with what?

bone marrow suppression, although this may not be problematic at doses used in the treatment of arthritis.

8

How is Methotrexate metabolized?

hepatic (contraindicated with alcoholism, or other hepatic disease)

9

How is Methotrexate eliminated?

renal (hydrate and alkalination to avoid damage)

10

AEs of Methotrexate?

-opportunistic infection, tumor
-malignant lymphoma
-derm rxns
-severe GI toxicity -irreversible pulmonary fibrosis

11

What can increase the risk of Gi toxicity with methotrexate use?

concurrent NSAID use

12

Is Methotrexate safe in pregnancy or breast-feeding?

No, category X

13

T or F. Vaccinations should be avoided while on methotrexate

T. Ab response may be suboptimal

14

How is Sulfasalazine metabolized?

to sulfapyridine and melamine by colon bacteria which are then acetylated and hydroxylated in the liver (look out for slow acetylators)

15

How does Sulfasalazine help in RA?

anti-inflammatory properties from melamine, an inhibitor of PG and leukotriene production

16

How is Sulfasalazine eliminated?

renal

17

Contraindications of Sulfasalazine?

PMH of hypersensitivity to salicylate or sulfonamide drugs

18

AEs of Sulfasalazine?

fatal blood dyscrasia

19

How does Leflunomide work?

inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme that catalyzed a key step in de novo pyrimidine synthesis causing cell cycle arrest in T/B lymphocytes

20

Is Leflunomide safe in pregnancy?

no, category X

21

T or F. Leflunomide metabolites produce a uricosuric effect

T. that is, it increases the renal elimination of uric acid

22

How is Hydroxychloroquine used for RA treatment (note it is also used for malaria and SLE treatment)?

increases intracellular vacuole pH thus inhabiting the acidic cytoplasmic compartments required for antigenic protein digestion and peptide assembly with the alpha and beta chains of MCH class II proteins

23

AEs of Hydroxychloroquine?

-blood dyscrasia
-CNS toxicity (seizures, ototoxicity, polyneuritis)
-rarely causes coral opacities, retinopathy, or keratopathy

24

Contraindications to Hydroxychloroquine use?

-hepatic disease (concentrates in liver normally)
-ocular disease

25

Monitoring parameters for Methotrexate?

CBC with differential, LFT, serum creatine/BUN, pregnancy test

and serum uric acid

26

Monitoring parameters for Sulfasalazine?

CBC with differential, LFT, serum creatine/BUN and urinalysis

27

Monitoring parameters for Leflunamide?

CBC with differential, LFT, pregnancy test and serum electrolytes

28

Monitoring parameters for Hydroxychloroquine?

CBC and opthalmalogic exam

29

How do corticosteroids work?

Nf-kB, activator protein (AP)-1 and NF-AT all inhibited leading to reduced production of TNF-a, IL-1, and thus IL-6 AND



other mechanisms

30

Mechanism of some AEs of corticosteroids?

upregulation of receptor-activator of nuclear factor kB (RANKL) and macrophage colony-stimulating factor (MCF) and down regulation of osteoprotegerin

31

What does upregulation of RANKL and macrophage colony-stimulating factor (MCF) cause?

increased osteoclast production (and lifespan) leading to increased bone resorption early in GC treatment (and transiently)

32

How do GCs affect osteoblasts?

upregulate PPARy2 expression and decrease Wnt signaling leading to decreased osteoblastogenesis AND

upregulate caspase 3 expression

33

What is the effect of decreased osteoblast populations?

these effects are responsible for the LONG TERM state of decreased been formation that characteristic of GC-induced osteoporosis

34

T or F. In addition to suppressing symptoms/signs of early RA, GCs appear to possess disease-modifying effects, at least in early stage disease

T.

35

What are some things that can be done to prevent GC-induce osteoporosis?

-advice sufficient dietary intake of calcium, protein, and vitamin D

-weight-bearing exercise

-avoid alcohol and tobacco abuse

36

What treatment options are available to those chronically taking GCs to reduce risk of osteoporosis?

anti-osteoporotic therapy in those with fracture risk (measure height annually and assess BMD regularly)

37

AEs of high-dose GCs?

-Cushingoid (w/ HTN) syndrome
-diabetes mellitus
-cataracts
-growth retardation

38

Clinical studies clearly show that patients with rheumatoid arthritis are at increased
risk of _________ compared to the general population.

cardiovascular events. This might be due to the inflammatory condition that the patient is experiencing, but it could also be
attributed to adverse effects of drugs used in the treatment of the condition.

39

What is one way to avoid the general systemic effects of corticosteroids?

Administer such
drugs by injection, for example as intra-articular injection in the knee

40

T or F. Adverse effects of corticosteroids are both cumulative and daily dose dependent and can be influenced by the concurrent administration and other drugs such as DMARDs.

T. However, low-dose corticosteroids do not necessarily produce the myriad of adverse effects and may be used quite safely with routine clinical care.

41

Still, what should be monitored with low-dose GC?

osteoporosis, blood sugar levels, glaucoma and the presence of oedema.

42

What is Auranofin?

old RA drug composed of golf that suppressed inflammation but is accompanied by skin rash and GI dysfunction and is not sued anymore here

may have use in other diseases

43

What is Abatacept (Orencia)?

Fusion protein of human CTLA4/IgG1 Fc Fragment that binds CD80 and CD86 and prevents T-cell co-stimulatory signal engaging with CD28

44

What is Adalimumab (Humira)?

TNF-a monoclonal Ab, blocking its interaction with the p55 and p75 cell surface receptors

45

What is Anakinra?

recombinant human IL-1 receptor antagonist

46

What is Certolizumab peg?

Fab fragment of humanized TNF-a Ab the neutralized membrane-associated and soluble human TNF-a

47

What is Etancercept?

Extracellular ligand-binding portion of human p75 TNF receptor linked to part of human IgG Fc

48

What is the role of endogenous p75?

TNF antagonist

49

What is the effect of Etancercept (Enbrel)?

it binds to and inactivates TNF but does not affect TNF production or serum levels

50

What is Golimumab (Simponi)

Human-Derived TNF-a Ab (V and C regions) that binds to and neutralizes both soluble and transmembrane TNF-a

51

What is Infliximab (Remicade)?

Chimeric (mouse-human) IgGk monoclonal Ab against TNF-a that binds and neutralizes both soluble and transmembrane TNF-a

52

What is Tocilizumab (Actemra)?

Humanized IL-6 receptor-inhibiting monoclonal Ab that binds to soluble (serum and synovial fluid) and membrane-bound IL-6 and inhibits signaling

53

What is Rituximab (Rituxan)?

Chimeric monoclonal against CD20 on B cells

54

How does Rituximab work?

Fab domain binds CD20 and Fc domain recruits immune effectors to meidate B-cell lysis (ADCC, Ab-dependent, etc.)

55

Rules of thumb with biologics

-don't initiate treatment during infection
-may increase infection or malignancy risk

56

Which biologics can cause CHF or hypotension /angina/dysrhythmia?

-Infliximab (contraindicated)
-Adalimumab
-Golimumab
-Rituximab

57

Which biologics can cause a lupus-like presentation?

-Adalimumab
-Certolizumab
-Etanercept
-Infliximab

58

Stevens-Johnson syndrome (toxic epidermal necrolysis) has been infrequently reported with _____

Rituximab

59

What biologic may fuck with blood glucose tests?

Abatacept IV (contains maltose)

60

T or F. Women taking Rituximab must use reliable contraception while taking the drug and avoid pregnancy for 4-6 months after therapy

T. IgG crosses placenta and could deplete B-cells

61

Which biologics cannot be given SC?

-Infliximab
-Rituximab
-Tocilizumab

all others have the risk for injection site reactions with repeated injection given in the same spot

62

CBCs should be routinely given with which biologics? Why?

-Anakinra, Certolizumab, Rituximab, Tocilizumab

due to risk of blood dyscrasia

63

CBCs should be routinely monitored with which biologics? Why?

Golimumab, Infliximab, and Tocilimumab

64

Give a serum lipid profile with which biologic?

Tocilizumab

65

What is Tofacitinib (Xeljanz)?

Po JAK3/JAK1 inhibitor for mild-severe RA

66

What interleukins are blocked by Tofacitinib?

IL-2, 4, 7, 9, 15, and 21

67

AEs of Xeljanz?

increased HDL and LDL cholesterol, headache, UTIs, URTIs, nasopharyngitis

68

BBWs of Xeljanz?

-serious infections, including Tb and opportunistic
-Lymphoma

69

What is Apremilast (Otezla)?

an orally (CYP) active phosphodiesterase inhibitor (PDE4), giving rise to a reduction in pro inflammatory
mediators

70

Uses for Apremilast?

psoriatic arthritis (improves joint tenderness and swelling) and plaque psoriasis (redness/scaliness).

71

AES of Otezla?

Nausea, headache, weight loss (monitor!),

depression/suicidal ideation rarely

72

What drugs should be avoided in G6PD deficient patients?

Sulfasalazine and
Hydroxycloroquine

(look for hemolytic anemia)

73

What are the 4 mechanisms for the inhibition of TNF-a bearing cells by anti-TNF agents?

1. inhibition of TNF signaling
Destruction of TNFa bearing cells by:
2. CDC
3. ADCC and
4. outside-to-inside signal (reverse signaling)

74

What is TAILS?

TNF-a antagonist-induced lupus like syndrome thought to be due to release of antigenic particles during apoptosis, stimulating autoantibodies or by suppressing Th1

usually abates 1-6 months when drug stopped

75

T or F. TNF levels are elevated in CHF patients

T. BUT TNF-a antagonists only make it worse!!! AVOID