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PHRM 864 Module 4 > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

Pharmacologic treatment

A

not able to cure pts or reverse the damage that’s been done
adjunct therapy: NSAIDs, corticosteroids
DMARDs, biologic agents anti-TNF, biologic agents (non-TNF)

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2
Q

NSAIDs

A

effective in reducing pain, swelling, and stiffness
do NOT alter disease progression
dose at anti-inflammatory doses
use in combo with DMARDs
ex. ibuprofen, naproxen, celecoxib (don’t use in pts with sulfa allergy!)
antinflammatory doses are higher

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3
Q

Corticosteroids

A

used for anti-inflammatory + immunosuppressive properties
not used as monotherapy
use in combo with DMARD
use in acute flares (to try and decrease the flare to save/preserve the DMARD)
use in pts with extra-articular manifestations
ex. prednisone
trying for lowest dose possible b/c of AEs, try to go for short term treatment

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4
Q

Corticosteroid AES

A

short term: hyperglycemia, gastritis, mood changes, elevated BP
long term: aseptic necrosis, cataracts, obesity, growth failure, osteoporosis

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5
Q

Monitoring parameters for corticosteroids

A

baseline: BP, BG
maintenance: BP q3-6mo, BG q3-6mo

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6
Q

Disease modifying anti-rheumatic drugs (DMARDs)

A

potential to decrease/prevent joint damage and preserve joint integrity
timing of initiation is critical
onset of action is delayed

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7
Q

DMARDs meds

A

methotrexate, sulfasalazine, hydroxychloroquine, leflunomide

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8
Q

Methotrexate

A

gold standard of treatment!
most predictable benefit
DMARD of choice and with best long-term outcome

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9
Q

Methotrexate MOA

A

inhibit dihydrofolic acid reductase (inhibits neutrophil adhesion and chemotaxis)

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10
Q

Methotrexate dosing

A

2.5mg tabs
dose: 7.5mg per WEEK by mouth or IM (up to 15-20 mg)
onset: 1-2 mo

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11
Q

MTX AEs

A

hematologic: bone marrow suppression
gastrointestinal: N/V/D, stomatitis, mucositis (taking with food helps) - folic acid supplementation 1mg/day to reduce sx
hepatic: cirrhosis, hepatitis, fibrosis
pulmonary: pneumonitis, fibrosis
dermatologic: rash, urticaria, alopecia
teratogenic: wait one cycle of BCP, wait 3 mo before considering conception

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12
Q

MTX contraindications

A

pregnancy, chronic liver disease (EtOH abuse), immunodeficiency, pre-existing blood dyscrasias, pleural/peritonal effusions, leukopenia/thrombocytopenia, CrCl< 40ml/min

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13
Q

MTX monitoring

A

baseline: CXR, CBC, SCr, LFTs, albumin
maintenance: CBC, SCr, LFT: <3mo: 2-4wks; 3-6mo: 8-12wks; >6mo: 12wks

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14
Q

Leflunomide MOA

A

prodrug
inhibit de novo biosynthesis of pyrimidines, interferes with tyrosine kinase activity, inhibits cell cycle progression

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15
Q

Leflunomide dosing

A

requires loading dose
teratogenic: use cholestyramine to clear from system b/c of it’s long t1/2 (16 days)

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16
Q

Leflunomide AEs

A

diarrhea, rash, alopecia, increased LFTs, teratogenicity

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17
Q

Leflunomide monitoring

A

CBC, SCr, LFT
baseline and maintenance: <3mo: 2-4wks; 3-6mo: 8-12wks, >6mo: 12wks

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18
Q

Sulfasalazine MOA

A

prodrug - cleaved in colon to sulfpyradine and 5-ASA
inhibits IL-1
do NOT use in pt with sulfa allergy!

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19
Q

Sulfasalazine AEs

A

gastrointestinal: N/V/D, anorexia
dermatologic: rash/urticaria/photosensitivity*
hematologic: leukopenia, thrombocytopenia; rare: hemolytic and aplastic anemia
caution for allergy

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20
Q

Sulfasalazine monitoring

A

CBC, SCr, LFT
baseline
maintenance: <3mo: 2-4wks; 3-6mo: 8-12wks; >6mo: 12wks

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21
Q

Hydroxychloroquine MOA

A

modification of cytokine infiltration in joint
used in earlier treatment (not as effective as others)

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22
Q

Hydroxychloroquine AEs

A

advantage: no myelosuppression, hepatic, renal toxicities*
ocular: retinal toxicity*; >70yo, cumulative dose >800g, night/peripheral changes
gastrointestinal: N/V/D (take w/ food)
dermatologic: increase skin pigment, rash, alopecia

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23
Q

Hydroxychloroquine monitoring

A

vision exam
baseline
every 6-12mo
“appealing” because really no monitoring

24
Q

Biologic response modifiers (biologic DMARDs)

A

TNF neutralizers: etanercept, infliximab, adalimumab, golimumab, certolizumab
all impact + neutralize TNF in different ways, if fail one, can try another in same class

25
Q

TNF neutralizers warnings/precautions

A

risk of infection
do not use in combo with IL-1 inhibitors or T-cell co-stimulation modulators (further increases risk of infection + AEs)
black box warnings, increased neurologic/demyelinating disorders, malignancies, congestive HF, hepatitis B reactivation, no concurrent live vaccine administration (TB testing to make sure no latent TB)

26
Q

TNF neutralizers AEs

A

HAs and rash, risk of infection (upper respiratory most common), injection site rxn, exarcerbations of CHF, risk of malignancy, risk of evidence of demyelinating disease

27
Q

Etanercept

A

binds to and inhibits TNF - binding occurs before the cytokine can interact with cell-surface TNF receptors that would produce an inflammatory response
SC!

28
Q

Infliximab

A

binds and inhibits TNF
IV!
indicated in combo with MTX, could be used as monotherapy

29
Q

Adalimumab

A

binds and inhibits TNF
for pts who have inadequate response to one or more DMARDs; can be used alone or in combo
SC every other week!

30
Q

Golimumab

A

binds and inhibits TNF
for moderate to severe RA; used in combo with MTX
SC once monthly!
monitor: CBC with PLT and LFTs

31
Q

Certolizumab

A

binds and inhibits TNF
for RA pts with moderate to severe disease; can be used alone or in combo with non-BRM DMARDs
SC!

32
Q

Anakinra

A

IL-1 inhibitor
for moderate to severe RA in pts who have failed one or more DMARDs; can use alone or in combo
SC!
do not use in combo with TNF agents or abatacept

33
Q

Anakinra AEs

A

injection site rxns, HA, N/V, flu-like sx, hypersensitivity to e.coli derived proteins, increased risk of serious infection, decreased neutrophils

34
Q

Anakinra monitoring

A

neutrophil count
prior to start, monthly for 3 mo, quarterly for up to one year

35
Q

Selective T-cell co-stimulation modulator

A

abatacept

36
Q

Abatacept

A

for moderate to severe RA; if had inadequate response to one or more DMARDs
monotherapy or in combo with DMARD (not with TNF inhibitors or IL-1 antagonists)
inhibits T-cell activation
IV!

37
Q

Abatacept warnings

A

do not use with TNF antagonists or IL-1 antagonists
increased risk of infection
no live vaccine administration
caution in pts with COPD*

38
Q

Abatacept AEs

A

HA, nausea, upper respiratory infection, nasopharingitis, infusion rxns, serious infection, malignancy

39
Q

IL-6 receptor inhibitors

A

tocilizumab (IV) and sarilumab (SC)
for moderate to severe RA after inadequate response to one or more DMARDs
alone or in combo with MTX or another DMARD

40
Q

IL-6 receptor inhibitors MOA

A

binds to soluble and membrane bound IL-6 receptors

41
Q

IL-6 inhibitor warnings

A

black box warning: serious infections*
contraindicated in pts with liver toxicity, thrombocytopenia, and neutropenia

42
Q

IL-6 inhibitor AEs

A

serious infection, liver toxicity, thrombocytopenia, neutropenia, lipid abnormalities, intestinal perforations (tocilizumab), infusion rxns (tocilizumab)

43
Q

IL-6 inhibitor monitoring parameters

A

neutrophil count - at 4-8wks then q3mo
platelet count - at 4-8wks then q3mo
LFTs - at 4-8wks then q3mo
lipid profile - after 4-8wks then q6mo

44
Q

Anti-CD20 antibody

A

rituximab
“last resort” - reserved for pts who have failed others; for moderate to severe RA; in those with inadequate response to TNF antagonists; used in combo with MTX
bind specifically to antigen CD20

45
Q

Rituximab dosing

A

IV
administer methylprednisolone 30 min before infusion to reduce infusion rxns

46
Q

Rituximab AEs

A

tumor lysis syndrome, mucocutaneous rxns, viral infection, hypersensitivity, renal toxicity, bowel obstruction, hep B reactivation, cardiac arrhythmia

47
Q

Rituximab monitoring

A

CBC with platelet, serum creatinine, vital signs (during infusions)

48
Q

Targeted synthetic DMARDs

A

janus kinase inhibitors

49
Q

Janus kinase inhibitors

A

these are oral agents!
for moderate to severe RA after inadequate response to TNF; used alone or in combo with MTX or another DMARD; NOT in combo with BRM, azathioprine, or cyclosporine

50
Q

Janus kinase inhibitors MOA

A

inhibits janus kinase

51
Q

JAK inhibitor meds

A

tofacitinib
baricitinib
upadacitinib

52
Q

JAK inhibitors warnings

A

cytochrome P450 interactions; do not use in hepatic impairment; risk of infection; risk of malignancy; major adverse CV events; thrombosis; GI perforations; no live vaccines
do NOT use if: Hgb < 9mg/dL, ANC < 1000 cells/mm^3, ALC < 500 cells/mm^3

53
Q

JAK inhibitors AEs and monitoring parameters

A

upper respiratory, HA, nausea
monitoring: lympocyte count, neutrophil count, Hgb, liver enzymes, lipid profile

54
Q

Combination therapy

A

drugs with different MOA; allows for decreased dosages and minimizes AEs; more effective in treating resistance; may provide dramatic slowing of progression; MTX most common in combo with other DMARDs

55
Q

Therapeutic decisions

A

treat to target approach
different considerations for stratification of patients: early RA vs established RA

PHRM 864 Module 4 (7 decks)

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