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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
Q

target dose of mtx

A

15mg/week within 4-6 weeks of initiation

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26
Q

target dose of sulfa

A

1g BD

27
Q

maximum dose of sulfa

A

3000mg/day

28
Q

max dose of mtx

A

25mg/week

29
Q

low dose gc for initiation of dmard

A

7.5 mg/day prednisolone up to 3 months

30
Q

ci of MTX

A

crcl <30, liver disease, immunodeficiency, blood dyscrasias

31
Q

ddi of mtx

A

nsaids/cox2i, ppi, probenecid, vaccines, alcohol

32
Q

se of mtx

A

gi (ND, anorexia)
liver (increased lfts, cirrhosis)
lungs (fibrosis)
haem (myelosupprx)
derm (tens/sjs)
hair loss

33
Q

ci of sulfasalazine

A

Sulfonamide allergies
Caution in G5PD deficiency

34
Q

moa of sulfasalazine

A

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
Q

ddi of sulfa

A

Iron, antibiotics, warfarin

36
Q

se of sulfa

A

GI: nausea, dyspepsia;
Rash;
Haem: Agranulocytosis associated with HLA-B08:01 & HLA-A31:01 (European);
Oligospermia (reversible), urine discoloration;
CNS: headache, dizziness

37
Q

hydroxychloroquine ci

A

Preexisting retinopathy
Caution in G6PD deficiency

38
Q

moa of hcq

A

Reduced MHC Class II expression and antigen presentation
Reduced TNF-α and IL1
Antioxidant activity

39
Q

which dmard has better tolerated side effects

A

hcq

40
Q

hcq ddi

A

CYP2C9 inhibitor: cimetidine
QT prolongation drugs: eg. ciprofloxacin

41
Q

hcq se

A

Generally tolerable.
retinopathy, hyperpigmentation, hypoglycemia, qt prolongation, hair loss

42
Q

leflunomide moa

A

Inhibits dihydroorotate dehydrogenase and hence decreases pyrimidine production.

Suppression of T,B cells.

Inhibits NF-kB activation of pro-inflammatory pathway (lymphocyte action)

43
Q

halflife of leflu / hcq

A

lefly -18d
hcq - 40d

44
Q

sulfaz main thing to look out for

A

retinopathy

45
Q

hcq moa

A

Reduced MHC Class II expression and antigen presentation

Reduced TNF-α and IL1

Antioxidant activity

46
Q

hcq target dose

A

200-400mg in one or two doses

47
Q

leflunomide avoid in

A

ALT>2xULN

48
Q

leflunomide ddi

A

cholestyramine, activated charcoal, rosuvastatin, warfarin, vaccines, alcohol

49
Q

leflunomide ae

A

ND, raised transaminases, alopecia, rash, headache, myelosupprx, weight gain

50
Q

add on therapy to mtx

A

hydroxychloroquine, sulfasalazine

51
Q

moa of bdmards

A

Binds to cytokines or their receptors to downregulate/inhibit their functions, which reduces immune & inflammatory responses

52
Q

moa of tsdmards (jaki)

A

Janus kinase (JAK) pathway inhibitor, blocks cytokine production via JAK/STAT-activation of gene transcription

53
Q

why is tofacitinib (jaki) not preferred

A

higher risk for major adverse cardiovascular events (MACEs) & malignancy for indivs with risk factors

53
Q

why is tofacitinib (jaki) not preferred

A

higher risk for major adverse cardiovascular events (MACEs) & malignancy for indivs with risk factors

54
Q

vaccinations required before initiation

A
  • Pneumococcal
  • Influenza
  • HepatitisB
  • Varicella zoster
55
Q

pre-tx screening

A

Complete all anti-TB Tx first
Check for Hep B/C, avoid if present

56
Q

when on anti tnf, cannot have…

A

hep b, live vax

57
Q

jaki ae

A

Immune: Cytopenia, immunosuppression, anaemia

Hyperlipidemia: incr in total, LDL, HDL, cholesterol, TG

58
Q

inflammatory markers

A

crp, esr

59
Q

which drug to avoid for liver issues

A

leflunomide

60
Q

how to dose adjust for mtx for patients crcl < 50

A

50% of dose; CI in crcl <30

61
Q

how to dose adj for mtx for pts AST/ALT > 3ULN

A

75% of dose

62
Q

how to dose adj for sulfa for eGFR <60

A

initiate at lower dose

63
Q

how to dose adj for sulfa for dialysis

A

250mg OD, up to 1g/day

msk 3154 (8 decks)

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