Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

end of y3 > RA > Flashcards

RA Flashcards

1
Q

risk factors for RA

A

1) increased prevalence up to 70 yo
2) peak incidence 40 - 50 yo
3) women 3x more common
4) human leukocyte antigen: HLA-DRB1
5) family history

  • 3x higher odds if 1st degree
  • 2x higher odds if 2nd degree

6) smoking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

pathophysiology of RA

A

1) injury -> activation of macrophage in synovial tissue -> secretion of IL-8 and MCV1 -> recruit monocytes

2) monocytes differentiate into macrophage -> +ve feedback to recruit more monocytes -> stimulate release of TNF -> stimulate macrophages to produce

  • more chemokines and cytokines -> induce synovial fibroblast to secrete cytokines and break down connective basement membrane
  • IL-1 that binds to IL-1 receptor -> stimulate more cytokine secretion -> inflammation

3) neutrophils secrete toxic peroxidases and MPO -> further tissue breakdown
4) IL-6 important for recruitment of other cells and stimulate bone destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

clinical presentation of RA

A

1) inflammation
2) location: symmetrical polyarthritis

  • bilateral
  • small joints: knuckles, row of bones in front of it, wrist, some parts of toes
  • large joints: elbow, shoulder, hip, knees, ankles

3) morning stiffness > 30 mins
4) systemic symptoms

  • more present if > 60 yo
  • generalised aching/stiffness, fatigue, fever, weight loss, depression

5) extra-articular symptoms

  • eyes: Sjogren’s syndrome
  • heart: CAD
  • haematology: Fetty’s syndrome
  • skin: rheumatoid nodules
  • vascular: Rheumatoid vasculitis

6) deformities

  • swan neck (^ at first joint from fingernail), boutonniere (^ in middle joint)
  • loss of physical function and ability to carry out ADL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

lab finding for RA

A

1) autoantibodies

  • rheumatoid factor RF (+ve)
    ** not specific for RA, will show for all autoimmune disease
    ** not all RA pt will have +ve RF in early stage
  • anti-CCRP assays (+ve)

2) acute phase response

  • increase ESR, CRP

3) FBC

  • decreased haematocrit
  • increased platelet and WBC

4) radiologic

  • baseline for treatment efficacy monitoring
  • findings
    ** narrowing of joint space
    ** erosion around margin of joint
    ** hypertrophic synovial tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

diagnosis of RA

A

at least 4 of

1) early morning stiffness ≥ 1 hr for ≥ 6 wks
2) swelling of ≥ 3 joints for ≥ 6 wks
3) swelling of wrist/MCP/PIP joints for ≥ 6 wks
4) rheumatoid nodules
5) +ve RF +/- anti-CCRP test
6) radiographic change

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

goals of RA therapy

A

1) remission or low disease activity

  • ≥ 6 months of remission/low disease activity
  • Boolean 2.0 inclusion criteria for remission
    ** tender joint count (TJC) ≤ 1
    ** swollen joint count (SJC) ≤ 1
    ** CRP ≤ 1mg/dL
    ** patient global assessment ≤ 2cm
  • gradually taper dose after 6 months of remission

2) maximal functional improvement
3) Stop disease progression
4) prevent joint damage
5) alleviate pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

nonpharmaco for RA

A

1) patient education
2) psychosocial intervention

  • CBT for enhancing self-efficacy and QoL

3) rest inflamed joint, use splint to support joint and reduce pain

  • caution when promoting rest for fatigue symptoms, ensure no sedentary lifestyle

4) physical activities and exercise

  • range of motion exercises: preserve joint motion
  • increase muscle strength -> avoid contractures and muscle atrophy -> prevent decrease in joint stability and improve function
  • aerobic exercise: reduce fatigue and pain, improve sleep
  • avoid high intensity weight bearing exercises

5) physiotherapy, occupational therapy
6) nutrition and diet

  • overcome anorexia and poor dietary intake during RA
  • weight management if obese to reduce stress on weight-bearing joints
  • dietary intervention for reducing inflammation (fish oil) and ASCVD risk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

treatment for acute RA flares

A

1) NSAID

  • short term relief of pain and minor inflammation
  • can take PPi to reduce GI SE

2) glucocorticoid

  • low dose bridging therapy when initiating DMARD before DMARD take effect
    ** tapered and discontinued within 3 months
    ** discontinue if bsMARD/tsDMARD initiated
  • ≤ 7.5mg/day prednisolone up to 3 months
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

types of csDMARD

A

1) methotrexate
2) hydroxychloroquine
3) sulfasalazine
4) leflunomide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

initial treatment algorithm with csDMARD

A

1) moderate to high disease state

  • 1st line methotrexate
  • CI methotrexate: hydroxychloroquine, sulfasalazine, leflunomide

2) low disease state

  • hydroxychloroquine (best tolerated) -> sulfasalazine (less immunosuppressive) -> methotrexate (greater dosing flexibility and lower cost) -> leflunomide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

methotrexate dose

A
  • initiation dose 7.5mg once weekly
  • dose increment 2.5 - 5mg every 4-12 wks based on response
  • target dose 15mg/wk within 4-6 wks initiation
  • max dose 25mg/wk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

methotrexate MOA

A

1) major action

  • increase adenosine levels by AICAR transformylase and ATIC inhibition -> more adenosine acting on adenosine receptor -> anti-inflammatory effect

2) minor action

  • inhibit dihydrofolate reductase -> decrease pyrimidine synthesis and DNA methylation (cause GI effect and hair loss)
  • inhibit thymidylate synthetase

3) overall effect

  • increase extracellular adenosine level and activation of A2a receptor
  • anti-proliferative effect on T cells and inhibition of macrophage function
  • decrease in pro-inflammatory cytokines, adhesive molecules, chemotaxis, phagocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

methotrexate SE

A
  • N/V, mouth & GI ulcer, hair thinning
  • leukopenia, hepatic fibrosis, pneumonitis
  • increase transaminases, myelosuppression, TENS, SJS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

how to cope with methotrexate SE?

A

folic acid supplementation 5mg/wk 12 - 24 hr after methotrexate dose

  • SE caused by inhibition of dihydrofolate reductase
  • folic acid downstream of dihydrofolate reductase so bypass effects of dihydrofolate reductase inhibition = rescue methotrexate toxicity
  • can also use high dose of folate (cheaper)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

methotrexate CI/caution

A

avoid use if CrCl < 30

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

special population for methotrexate

A

X pregnant cuz teratogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

hydroxychloroquine dose

A
  • 200-400mg in 1-2 divided dose
  • max 5mg/kg/day
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

hydroxychloroquine MOA

A
  • reduce MHC class II expression and antigen presentation
  • reduced TNF-alpha and IL-1 and cartilage resorption
  • antioxidant activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

hydroxychloroquine SE

A

N/V, stomach pain, dizziness, hair loss, ocular toxicity (Retinopathy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

hydroxychloroquine CI

A

pre-existing retinopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

hydroxychloroquine caution

A

G6PD deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

sulfasalazine dose

A
  • initiate 500mg OD/BD
  • increase 500mg/wk until 1mg BD maintenance
  • max 3g/day
23
Q

sulfasalazine MOA

A

unknown, poorly absorbed, mediated by gut flora

24
Q

sulfasalazine SE

A

N/V, headache, rash, haemolytic anemia, neutropenia, reversible infertility in men

25
sulfasalazine CI
sulfonamide allergies
26
sulfasalazine caution
G6PD deficiency
27
leflunomide dose
- 100mg/day for 3 days then 20mg/day maintenance
28
leflunomide MOA
rapidly converted to active metabolite teriflunomide - inhibit dihydroorotate dehydrogenase - decrease in pyrimidine synthesis and growth arrest at GI phase - inhibit T cell proliferation and B cell production - inhibit NF-Kb activation pro-inflammatory pathway
29
leflunomide SE
D, increased transaminase, alopecia, weight gain, teratogenic, myelosuppression
30
leflunomide DDI
cholestyramine, activated charcoal
31
leflunomide caution
- very long t1/2 - cholestyramine (bile salt binding resin) wash out (e.g. pregnancy) - avoid use if ALT > 2x ULN
32
leflunomide special population
X pregnancy cuz teratogenic
33
what to do if csDMARD not enough to reach target?
- X rely on intraarticular glucocorticoid for symptomatic relief - if on methotrexate and not on target then ** add bDMARD/tsDMARD ** triple therapy: metho, hydroxy, sulfasala (lesser AE risk and cost) - if on bDMARD/tsDMARD and not on target then ** switch to another one of different class
34
bDMARD MOA
bind to cytokines or their receptors to downregulate/inhibit function -> reduce immune and inflammatory responses
35
tldr types of bDMARD
1) anti-TNF mab 2) IL-1R antagonist 3) anti IL-6 receptor mab
36
types of anti-TNF mab
infliximab (IV infusion), adalimumab (SC), etanercept (SC)
37
SE of anti-TNF-mab
1) respiratory infection, skin infection 2) increased risk of lymphoma 3) optic neuritis 4) exacerbation of multiple sclerosis 5) leukopenia, aplastic anaemia
38
anti-TNF mab CI
live vaccination, Hep B, HF patient
39
anti-TNF mab monitoring
screening for latent/active Tb
40
IL-1R antagonist types
anakinra (SC) - less active than anti-TNF
41
IL-1R antagonist MOA
bind to IL-1 receptor -> block signalling
42
IL-1R SE
infection, injection site reaction
43
anti IL-6 mab types
tocilizumab (IV)
44
anti IL-6 mab MOA
irreversible antagonist of IL-6 receptor
45
anti IL-6 receptor mab SE
- infections, skin eruptions, stomatitis, fever, neutropenia, increase ALT/AST - GI perforations - hyperlipidemia, interact w CYP (450, 3A4, 1A2, 2C9) substrates
46
types of tsDMARD
tofacitinib (PO)
47
what is tofacitinib
non-selective JAK inhibitor
48
MOA of tofacitinib
bind to JAK protein in cell -> prevent JAK from transphosphorylating associated cytokines and growth factors required -> block activation of JAK/STAT pathway -> inhibit gene transcription responsible for cytokines production
49
AE/precaution of tofacitinib
1) cytopenia 2) immunosuppression -> opportunistic infection - higher risk of herpes zoster esp in Asians 3) anaemia - affect JAK2 activation of erythropoietin 4) hyperlipidemia - increase everything cuz involved in metabolism 5) GI perforation
50
tofacitinib MACE and malignancy
1) CVS risk factors - > 65 yo - current/ex smoker - obesity - PMH of DM, HTN 2) risk factors for malignancy: history/current malignancy 3) risk factors for thromboembolic events - PMH of MI, HF, inherited blood clotting disorders, blood clot - use of combined hormonal contraceptives or hormone replacement therapy - undergoing major surgery, immobility
51
safety concerns for both bDMARD and tsDMARD
1) infection/injection site reaction 2) myelosuppression - monitor CBC & WBC differential and platelet count 3) infection 4) malignancy risk 5) autoimmune disease 6) cardiovascular disease (HF for TNF-alpha, HTN) 7) hepatic effect (monitor LFT) 8) metabolic effect (monitor lipid panel) 9) pulmonary disease 10) GI perforation (esp IL-6 inhibitor and JAK inhibitor, evaluate abdominal pain/repeated vomiting) 11) thrombosis (Avoid in pt w history of thrombotic events)
52
selection of bDMARD/tsDMARD
- X use more than 1 at the same time - CI ** hypersensitivity, severe infection, HF (TNF-alpha inhibitors)
53
what to do before initiating bDMARD/tsDMARD
1) prevent opportunistic infections - pre-treatment screening ** latent/active tb: start after completing anti-tb treatment ** Hep B, C: avoid if untreated disease detected - vaccination required before initiation ** pneumococcal, influenza, Hep B, varicella zoster/herpes zoster 2) lab screening/monitoring - CBC w differential WBC and platelet count - LFT: ALT, AST, bilirubin, ALP - lipid panel - SCr
54
monitoring for RA treatment
1) After initiating csDMARD - every 1 - 3 months - adjust treatment if no improvement by 3 months or target not reached by 6 month 2) if at target for ≥ 6 months (low disease activity/remission) - gradual discontinuation of DMARD ** no abrupt discontinuation to prevent flare ** if on triple therapy then gradual discontinuation of sulfasalazine over hydroxychloroquine ** if on methotrexate + bDMARD/tsDMARD then gradual discontinuation of methotrexate for better disease control

end of y3 (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions