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msk 3154 > RA > Flashcards

RA Flashcards

1
Q

location of RA

A

wrist, fingers, elbows, shoulders, hips, knees, ankles

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2
Q

diagnosis of RA

A

at least 4 of the following:
- early morning stiffness of at least 1h for minimally 6 weeks
- swelling of at least 3 joints for 6 weeks
- swelling of wrist/mcp/pip for 6 weeks
- rheumatoid nodules
- positive RF and/or anti-ccp tests
- radiographic changes

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3
Q

pathophysio of RA

A

T-cell mediated immune response,
inflammation,
release of proteases, prostaglandins,
destruction of articular cartilage and underlying bone

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4
Q

inflammatory cytokines involved in RA

A

IL-17, TNF, IL1, IL6

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5
Q

goals of therapy

A

at least 6 months of remission or low disease activity
maximise function
stop disease progression

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6
Q

symptoms of RA (esp in >60yo)

A
  • Generalized aching/stiffness
  • Fatigue
  • Fever
  • Weight loss
  • Depression
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7
Q

what to use for patients with low disease activity

A

hydroxychloroquine, sulfasalazine (reduced immunosuppression)

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8
Q

examples of conventional dmards

A

mtx
sulfasalazine
hydroxychloroquine
leflunomide

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9
Q

examples of tnf alpha inhibitors

A

etanercept, infliximab, adalimumab

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10
Q

IL-1 receptor antagonist?

A

anakinra

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11
Q

IL-6 receptor antagonist?

A

tocilizumab

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12
Q

anti-cd20 b cell depleting mab

A

rituximab

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13
Q

jak inhibitor?

A

tofacitinib

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14
Q

what to take MTX with

A

PO folic acid 5mg/wk

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15
Q

what to avoid in CVS patients

A

anti-tnfa, jaki, IL6i

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16
Q

adverse effects of therapies

A

injection site reactions
myelosuppression
infections
malignancy risk
raised LFTs

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17
Q

AE specific to IL6i and JAKi

A

thrombosis, gi perforation

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18
Q

what to do before initiation of immunotherapy

A
  1. complete all anti-tb tx first
  2. screen for hep a/b and avoid tx
  3. screen for active infections
  4. cbc with wbc/platelets
  5. vax: pneumococcal, influenza, hep b, varicella
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19
Q

what to monitor during therapy

A

cbc - wbc, platelets (risk of myelosupprx)

lipids, scr, lft

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20
Q

non pharmaco mgmt of RA

A

physical activity and exercise
physio
rest inflamed joint
weight management

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21
Q

what activities to avoid for RA

A

weight bearing exercises

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22
Q

MOA of MTX

A

Increased adenosine levels due to AICAR and ATIC inhibition.

Inhibits DHFR and thymidylate synthetase, decreasing DNA methylation, pyrimidine and purine synthesis.

hence inhibits cytokine production

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23
Q

dosing of mtx

A

7.5mg once a week
increase every 4-12 weeks by 2.5-5mg

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24
Q

dosing of sulfa

A

initiate w 500 mg OD or BD, increase by 500 mg/week

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25
target dose of mtx
15mg/week within 4-6 weeks of initiation
26
target dose of sulfa
1g BD
27
maximum dose of sulfa
3000mg/day
28
max dose of mtx
25mg/week
29
low dose gc for initiation of dmard
7.5 mg/day prednisolone up to 3 months
30
ci of MTX
crcl <30, liver disease, immunodeficiency, blood dyscrasias
31
ddi of mtx
nsaids/cox2i, ppi, probenecid, vaccines, alcohol
32
se of mtx
gi (ND, anorexia) liver (increased lfts, cirrhosis) lungs (fibrosis) haem (myelosupprx) derm (tens/sjs) hair loss
33
ci of sulfasalazine
Sulfonamide allergies Caution in G5PD deficiency
34
moa of sulfasalazine
Affect gut microflora, leading to decrease in: 1. Pro-inflammatory cytokines 2. Suppression of T,B cells, macrophages 3. Decreased IgA, IgM rheumatoid factors, leukotrienes. 4. Inhibit TNF
35
ddi of sulfa
Iron, antibiotics, warfarin
36
se of sulfa
GI: nausea, dyspepsia; Rash; Haem: Agranulocytosis associated with HLA-B*08:01 & HLA-A*31:01 (European); Oligospermia (reversible), urine discoloration; CNS: headache, dizziness
37
hydroxychloroquine ci
Preexisting retinopathy Caution in G6PD deficiency
38
moa of hcq
Reduced MHC Class II expression and antigen presentation Reduced TNF-α and IL1 Antioxidant activity
39
which dmard has better tolerated side effects
hcq
40
hcq ddi
CYP2C9 inhibitor: cimetidine QT prolongation drugs: eg. ciprofloxacin
41
hcq se
Generally tolerable. retinopathy, hyperpigmentation, hypoglycemia, qt prolongation, hair loss
42
leflunomide moa
Inhibits dihydroorotate dehydrogenase and hence decreases pyrimidine production. Suppression of T,B cells. Inhibits NF-kB activation of pro-inflammatory pathway (lymphocyte action)
43
halflife of leflu / hcq
lefly -18d hcq - 40d
44
sulfaz main thing to look out for
retinopathy
45
hcq moa
Reduced MHC Class II expression and antigen presentation Reduced TNF-α and IL1 Antioxidant activity
46
hcq target dose
200-400mg in one or two doses
47
leflunomide avoid in
ALT>2xULN
48
leflunomide ddi
cholestyramine, activated charcoal, rosuvastatin, warfarin, vaccines, alcohol
49
leflunomide ae
ND, raised transaminases, alopecia, rash, headache, myelosupprx, weight gain
50
add on therapy to mtx
hydroxychloroquine, sulfasalazine
51
moa of bdmards
Binds to cytokines or their receptors to downregulate/inhibit their functions, which reduces immune & inflammatory responses
52
moa of tsdmards (jaki)
Janus kinase (JAK) pathway inhibitor, blocks cytokine production via JAK/STAT-activation of gene transcription
53
why is tofacitinib (jaki) not preferred
higher risk for major adverse cardiovascular events (MACEs) & malignancy for indivs with risk factors
53
why is tofacitinib (jaki) not preferred
higher risk for major adverse cardiovascular events (MACEs) & malignancy for indivs with risk factors
54
vaccinations required before initiation
- Pneumococcal - Influenza - HepatitisB - Varicella zoster
55
pre-tx screening
Complete all anti-TB Tx first Check for Hep B/C, avoid if present
56
when on anti tnf, cannot have...
hep b, live vax
57
jaki ae
Immune: Cytopenia, immunosuppression, anaemia Hyperlipidemia: incr in total, LDL, HDL, cholesterol, TG
58
inflammatory markers
crp, esr
59
which drug to avoid for liver issues
leflunomide
60
how to dose adjust for mtx for patients crcl < 50
50% of dose; CI in crcl <30
61
how to dose adj for mtx for pts AST/ALT > 3ULN
75% of dose
62
how to dose adj for sulfa for eGFR <60
initiate at lower dose
63
how to dose adj for sulfa for dialysis
250mg OD, up to 1g/day

msk 3154 (8 decks)

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