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54 MSK > Rheumatoid arthritis > Flashcards

Rheumatoid arthritis Flashcards

1
Q

How does MTX cause bone marrow suppression and GI disturbances?

A

MTX inhibits dihydrofolate reductase (DHFR), reducing levels of tetrahydrofolate and thus synthesis of purines and pyrimidines. This inhibition leads to decrease in production of DNA, RNA & certain AAs, ultimately disrupting growth and pro-life of rapidly divings cells such as those found in bone marrow and walls of GIT.

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2
Q

Clinical presentation of RA

A
  1. Pain
  2. Swelling
  3. Redness and warm
    4. Early morning stiffness >30 min
    5. Symmetrical polyarthritis
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3
Q

Laboratory findings 1

A

Autoantibodies
- Rheumatoid factor RF +(ve)
- Anti citrullinated peptide antibodies ACPA , anti-CCP assays (+ve)

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4
Q

Laboratory findings 2

A

ESR increase
CRP increase

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5
Q

Laboratory findings 3

A

Hg decrease
Platelets increase
WBC increase

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6
Q

Diagnosis of RA

A

At least 4 of:
1. Early morning stiffness >1 hour >6 weeks
2. Swelling of >3 joints >6 weeks
4. Swelling of wrist/MCP/PIP joints >6 weeks
5. Rheumatoid nodules
6. +ve RF &/ anti-CCP tests
7. Radiographic changes

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7
Q

Drugs used in RA

A
  1. NSAIDs
  2. Glucocorticoids
  3. DMARDs
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8
Q

Drug class of MTX

A

csDMARDs

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9
Q

Drug class of Adalimumab

A

bDMARDs

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10
Q

Drug class of Tofacitinib

A

tsDMARDS

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11
Q

Drug class of Infliximab

A

bDMARDs

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12
Q

Drug class of Etanercept

A

bDMARDs

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13
Q

Drug class of Golimumab

A

bDMARDs

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14
Q

Drug class of Anakinra

A

bDMARDs (not available in SG)

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15
Q

Drug class of Rituximab

A

bDMARDs

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16
Q

Drug class of Abatacept

A

bDMARDs (not available in SG)

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17
Q

1st line treatment of RA

A

MTX monotherapy
Short term low-dose GC can be added when initiating

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18
Q

Dose of MTX

A

Initiation : 7.5mg once weekly
2.5-5mg/week increment every 4-12 weeks
Target: 15mg/week

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19
Q

What needs to be co-prescribed with MTX? Why?

A

Folic acid 5mg/week
Rescue therapy: Folic acid, a synthetic form of the naturally occuring vitamin B9, helps prevent MTX-induced side effects by counteracting the reduced level of tetrahydrofolate.

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20
Q

Dose adjustment of MTX

A

CrCl<50ml/min: 50%
CrCl<30ml/min: AVOID

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21
Q

SE/cautions of MTX

A

GI: N/V, diarrhoea
Increases liver transaminase
Myelosuppression
TENS/SJS
Teratigenic

22
Q

Monitoring of MTX

A

FBC
LFT (AST, ALT, albumin, bilirubin)
SCr

23
Q

MOA of sulfasalazine

A

Modulates leukotrienes
Inhibit TNF

24
Q

CI of sulfasalazine

A

Sulfonamides allergies
Caution in G6PD deficiency

25
Q

MOA of hydroxychloroquine

A

Inhibits locomotion of neutrophils, chemotaxis of eosinophils, complement-dependent antigen-antibody reactions

26
Q

MOA of leflunomides

A

Decrease lymphocyte action

27
Q

Dose adjustment of leflunomides

A

ALT>2x ULN: AVOID

28
Q

CI of hydroxychloroquine

A

Pre-existing retinopathy
G^PD deficiency

29
Q

Caution for leflunomides

A

Very long half life
Requires wash out by cholestyramine
Teratogenic

30
Q

On MTX, but not at target

A

Add bDMARD/tsDMARD

31
Q

With bDMARDs/tsDMARDs, not at target

A

Switch to bDMARD or tsDMARD of different class

32
Q

MOA of bDMARD

A

Binds to cytokines or their receptors to down regulate or inhibit their functions, which reduces immune and inflammatory responses

33
Q

MOA of tsDMARD

A

Binds to JAK proteins inside cells to prevent JAKs from transphosphorylating the associated cytokine and growth factor receptor

34
Q

DMARDs with TNF-alpha target

A
  1. Adalimumab
  2. Etanercept
  3. Golimumab
  4. Infliximab
35
Q

DMARDs with IL-1 target

A

Anakinra

36
Q

DMARDs with IL-6 target

A

Tocilizumab

37
Q

DMARDs with CD20 target

A

Rituximab

38
Q

DMARDs with CD28 target

A

Abatacept

39
Q

Initiating DMARDs

A
  1. Pre-treatment screening
    - TB
    - Hepatitis B&C
  2. Vaccination
    - Pneumococcal
    - Influenza
    - Hepatitis B
    - Varicella zoster
  3. Laboratory screening
    - FBC
    - LFT
    - Lipid panel
    - SCr
40
Q

Safety concerns of bDMARDs/tsDMARDs 1

A

Injection site/infusion reaction

41
Q

Safety concerns of bDMARDs/tsDMARDs 2

A

Myelosuppression
- Monitor FBC with WBC differentials & platelet count

42
Q

Safety concerns of bDMARDs/tsDMARDs 3

A

Infections
- URTI, TB, opportunistic infections

43
Q

Safety concerns of bDMARDs/tsDMARDs 4

A

Malignancy risk

44
Q

Safety concerns of bDMARDs/tsDMARDs 5

A

Autoimmune diseases

45
Q

Safety concerns of bDMARDs/tsDMARDs 6

A

CVD
- HF (Avoid TNF-a inhibitors in NYHA class III & IV), HTN

46
Q

Safety concerns of bDMARDs/tsDMARDs 7

A

Hepatic
- Monitor LFT

47
Q

Safety concerns of bDMARDs/tsDMARDs 8

A

Metabolic effects
- Hyperlipidemia: monitor lipid panel

48
Q

Safety concerns of bDMARDs/tsDMARDs 9

A

Pulmonary diseases

49
Q

Safety concerns of bDMARDs/tsDMARDs 10

A

GI perforation
- Especially IL-6 & JAK inhibitors

50
Q

Safety concerns of bDMARDs/tsDMARDs 11

A

Thrombosis
- Especially IL-6 & JAK inhibitors

54 MSK (6 decks)

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