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Rheum > drugs for rheumatoid arthritis and other rheum diseases > Flashcards

drugs for rheumatoid arthritis and other rheum diseases Flashcards

1
Q

NSAIDs major risk include (3)

A
  1. Gi bleed
  2. HTN and renal failure
  3. coronary vascular disease
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2
Q

NSAIDs facts to consider

  1. older adults
  2. testing
  3. higher CV risk
A
  1. older adults- use a proton pump inhibitors
  2. testing kidney function and blood pressure
  3. avoiding them with higher CV risk
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3
Q

NSAIDs is used as a first line therapy in RA

A

NOPE!!! not a drug modifying disease only used to treat symptomatic pain relief

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4
Q

which drug induces osteoporosis and thus increase risk of fracture

A

glucocorticoid

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5
Q

glucocorticoids increase infection?

A

yep, it is an immunosupressor

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6
Q

General principles of DMARDs:

  1. How fast do they work?
  2. infection risk?
  3. effect on would healing
  4. follow up needed?
  5. teratogenic?
  6. risk of malignancies?
A
  1. Slowly
  2. increased risk of infection
  3. probably no effect on wound healing
  4. regular clinical and laboratory follow-up
  5. yep a lot of them are teratogenic
  6. lymphoma is seen but it is might be confounding and it is really high disease activity that is the culprit
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7
Q

methotrexate in RA vs malignancies

A

much lower dose used in RA

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8
Q

first line therapy for RA

A

Methotrexate

** often used for peripheral inflammatory arthritis associated with SLE and other diseases

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9
Q

Methotrexate:

  1. MOA
  2. Side effects
  3. Monitor
  4. supplementation
A
  1. Binds to dihydrofolate reductase blocking purine synthesis but not sure how it works in RA
  2. side effects: liver damage, bone marrow suppression, pulm. fibrosis and highly teratogenic
  3. liver function tests and blood counts but also the occasional creatinine due to kidney clearance
  4. Folic acids which helps to limit side effects
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10
Q

do we need to abstain from alcohol with methotrexate?

A

yep

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11
Q

Often used as first line therapy when MTX is contraindicated (e.g. alcohol use) or not tolerated

A

leflunomide (LEF) and sulfasalazine (SSZ)

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12
Q

Mechanisms of action:

  1. LEF (leflunomide)
  2. SSZ (sulfasalazine)
A
  1. LEF: probably inhibits pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase
  2. SSZ: not clear
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13
Q

side effects difference between LEF and SSZ

A

LEF has the same side effects as methotrexate but SSZ does not have liver SE but can cause bone marrow suppression

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14
Q

is often used in combination with MTX and/or HCQ (‘triple therapy’)

A

SSZ

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15
Q

First line therapy for non-organ- and non-life-threatening manifestations of SLE
almost all those with SLE should be on HCQ
Often used for RA and other arthritides, especially in combination with other DMARDs

A

hydroxychloroquine

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16
Q

hydroxychloroquine MOA

A

poorly understood was originally developed as an antimalarial

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17
Q

hydroxychloroquine side effects

A

pretty safe!!! SE is to the eye, leading some retinopathy issues and it is irreversible but it is a cumulative effect

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18
Q

hydroxychloroquine can be used during pregnancy

A

yes!!!!!!

19
Q

2nd line or maintenance therapy for many non-life-threatening manifestations of SLE, vasculitides, and others
occasionally used for RA

A

azathioprine (AZA),

20
Q

used for organ- and life-threatening manifestations of SLE, vasculitides, and other autoimmune diseases

A

mycophenolate (MMF), and cyclophosphamide (CYC)

*** they are heavy hitters, only really used with increased risk of multiorgan failure

21
Q

Mechanisms of action pair azathioprine (AZA), mycophenolate (MMF), and cyclophosphamide (CYC) :

  1. antagonizes purine metabolism, inhibiting DNA synthesis
  2. inhibits inosine monophosphate dehydrogenase, inhibiting guanosine nucleotide synthesis, thus inhibiting DNA synthesis
  3. cross-links DNA strands by alkylation, inhibiting DNA synthesis
A
  1. AZA: antagonizes purine metabolism, inhibiting DNA synthesis
  2. MMF: inhibits inosine monophosphate dehydrogenase, inhibiting guanosine nucleotide synthesis, thus inhibiting DNA synthesis
  3. CYC: cross-links DNA strands by alkylation, inhibiting DNA synthesis
22
Q

Side effects: azathioprine (AZA), mycophenolate (MMF), and cyclophosphamide (CYC)

A

bone marrow suppression and risk of infection AZA«< MMF

23
Q

which other drug besides hydroxychloroquine can be used during pregnancy?

A

AZA

24
Q

Biologic agents

A

made in biologic system often are monoclonal ab

25
Q

Biologic agents are given how?

A

need to be injected or infused

26
Q

why are biologics not a first line therapy if they are generally as effective as MTX?

A

expensive

27
Q

biologics are used in combination with each other

A

noppe!!!

28
Q

Soluble TNF receptor fusion protein

A

etanercept

  • it is a distractor
29
Q

TNF antagonists

*****TNF, despite its name (Tumor Necrosis Factor), is a ubiquitous cytokine involved in the regulation of the immune response

A

binds/blocks soluble or cell surface TNF or TNF-receptor

30
Q

TNF antagonist compared to gcs how immunosuppressive is it?

A

less immunosuppressive than medium/high dose GCs

31
Q

major side effect of TNF antagonist

A

reactivation of latent TB

32
Q

MAb targeting the interleukin-6 (IL-6) receptor. IL-6 is a ubiquitous cytokine in inflammatory processes

A

tocilizumab:

33
Q

fusion protein targeting CD80/CD86, thus blocking interaction with CTLA4, a costimulatory signal required for full T cell activation

A

abatacept:

34
Q

MAb targeting CD20, a B-cell antigen

kills/depletes B-cells and pre-B cells

A

rituximab

35
Q

rituximab depletes B-cells, but NOT plasma cells

A

yep!! therefore there is still ab production

36
Q

side effect of rituximab (2)

A
  1. infusion reaction

2. PML

37
Q

targets IL-1
approved for RA but not used much as it is not very effective
seems to be very effective for ‘autoinflammatory’ diseases such as Familial Mediterranean Fever, the systemic form of JIA, and adult onset Still’s disease

A

anakinra

38
Q

targets BLyS
approved for minor symptoms of SLE
despite FDA approval, its efficacy is not clear

A

belimumab

39
Q

targets RANK-Ligand

approved for osteoporosis

A

denosumab

40
Q

targets IL-12 and IL-23

approved for psoriasis and psoriatic arthritis

A

ustekinumab

41
Q

targets the JAK/STAT pathway

first new oral approved to treat RA

A

tofacitinib

42
Q

inhibits phosphodiesterase 4

recently approved to treat psoriatic arthritis

A

apremilast

43
Q

principles of RA management

  1. start time of treatment
  2. Screening
  3. treat initially with
  4. disease not controlled
  5. goal of treatment
  6. maintenance
A
  1. start early- prolonged treatment with NSAIDs/GCs alone is not adequate
  2. screen for hep B/C and TB if starting a biologic. vaccinate if possible
  3. treat initially with MTX
  4. switch after 3-6 month trial
  5. goal of treatment is to lower disease activity or clinical remission
  6. continue appropriate vaccinations

Rheum (13 decks)

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