Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

3154 MSK > RA > Flashcards

RA Flashcards

1
Q

pathophysiology of RA

genetics + environmental trigger

A

1) Citrullinated antigens picked up by APC
2) T cell mediated immune resp (T, B, macro, fibroblasts-like synoviocytes)
a. Inflamm cytokines IL17, TNF, IL1, IL6
b. Signal via JAKs
3) Inflamm respon + Recruit inflamm cells
a. Angiogenesis in synovium
b. Synovial proliferation
4) Release proteases & Prostaglandins
5) Destruction of articular cartilage & underlying bone

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

3 causes of articular destruction

A
  • Pannus invasion (thick, swollen synovial mem + granulation tissue)
    * Fibroblasts, inflamm cells, myofibroblasts
  • Incr RANKL on T cells (cytokines incr protein on T cell surface)
    * Binds to osteoclasts (Breakdown of bone)
  • Antibodies immune complex
    * Ab bind to target and form complexes
    * Activate complement system —– Rheumatoid factor (RF)
    * Target altered IgG Ab
    * Anti-cyclic citrullinated peptide Ab —– target citrullinated proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

cause of RA

A

Chronic systemic inflammatory autoimmune disease
Targets: synovial tissues, bone erosion, joint deformity

  • Immune complexes activated
    • Incr proliferation
    • Cytokine production (IL1, IL6, TNF, IFN-y, JAK-STAT pathway)
    • Adhesion and trafficking
  • B cells and T cells
  • Some phagocytes (neutrophils, macrophages)
    1. Production or metalloproteinases and other effector molecules
    2. Migration of polymorphonuclear cells
    3. Erosion of bone and cartilage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

presentation of RA

A
  • inflammation
    * worse than OA (pain, swell, erythematous, warm)
    * morning stiff > 30mins, symmetrical polyarthritis
  • systemic sx
    * general ache/ stiff, fatigue, weight loss, fever, depression
  • extra-articular complications
  • chronic = deformities (swan-neck, boutonniere, nodules, cyst)
  • loss of physical function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

extra-articular complication of RA

A

eye, heart, hematology, lung, renal, skin, vascular

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

lab findings of RA

A
  • autoAb (may be -ve at early state)
    ○ RF
    ○ Anti-CCP assays
  • Acute phase response (active disease/ inflamm)
    ○ ESR incr
    ○ CRP inr
  • FBC
    ○ Hematocrit decr
    ○ PLT incr
    ○ WBC incr
  • Radiologic x-rays/ MRI
    ○ Narrow 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
7
Q

diagnosis of RA

A
  • Hx, PE, labs, radiographs
  • ≥4 of following
    • Early morning stiffness ≥1hr x ≥6wks
    • Swelling of ≥3joints for ≥6wks
      ○ Polyjoints (large & small joints)
    • Swelling of wrist/ MCP/ PIP joints ≥ 6wks
    • Rheumatoid nodules
    • +ve RF/ anti-CCP tests
    • Radiographic changes

(may not be avail at early stage): RF, anti-CCP, radiographic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

tx goals

A
  • remission/ low disease activity (6mnths)
  • Boolean 2.0 criteria
    • Tender joint count ≤1
    • Swollen joint count ≤1
    • CRP ≤ 1mg/dL
      • Pt global assessment (10cm VAS ≤2cm)
  • SDAI, CDAI, DAS28
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

RA tx plan

A
  1. Anti-inflammatory agents
    • NSAID: short term relief of pain and stiffness (need PPI for GI SE)
    • CS: bridge anti-inflammatory therapy (DMARD slow onset) ≤3MNTHS
      ○ Slow withdrawal over wks - mnths to reduce ADR
  2. csDMARD (Methotrexate, sulfasalazine, leflunomide, hydroxychloroquine)
  3. bDMARD (TNF, ILRA, anti CTLA4, anti-CD20, anti-IL6 receptor)
  4. tsDMARD (jak-stat pathway)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

approach

A

1) csDMARD + NSAID (bridge 3mnths)

2) bDMARD added when pt on MTX but not at target

* TNFa tried first 
	○ Not rely on IA glucocorticoid for sx relief 
	○ Add bDMARD/ tsDMARD 
	○ Triple therapy (+hydroxy & sulfasalazine) 
		-  Less risk of ADR & lower costs 
* Try other class of bDMARD before ts DMARD

3) tsDMARD
* Gradual discontinuation of MTX or DMARD
* Dose reduction/ incr interval

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

monitor tx

A
  • Monitor freq in active disease (1-3mnths)
  • Adj tx if no improvement/target not reached by 6mnth
  • CBC, WBC, PLT (myelosupp)
  • LFT (hepatotoxicity)
  • Scr (MTX)
  • Lipid panel (part of bDMARD and tsDMARD - metabolic derangement)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

selection of bDMARD/ tsDMARD

A
  • pre-DMARD (screen/ tx infection)
  • Do not use >1 bDMARD/ tsDMARD at the same time
  • CI during selection
    ○ Hypersensitivity to components, form
    ○ Severe infections (sepsis, TB, opportunistic infections)
    ○ HF (TNFa i)
  • Anti-drug Ab may occur with TNF a inhibitor
    ○ Loss of efficacy
    ○ Switch to another class bDMARD (diff MOA) when fails / lack efficacy 3mnths
    ○ tsDMARD as last line (greater risk of MACE, malignancy)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

tsDMARD as last line (greater risk of major adverse CVS events, malignancy)
risk factors

A
  • CVS risk factors
    * > 65yo
    * hx for past/ current smoking
    * obesity
    * PMH of DM, HTN
  • malignancy risk factors (hx/ current)
  • thromboembolic risk
    * PMH of MI, HF, inherited blood clotting disorders, blood clot
    * use of CHC, HRT
    * undergoing major surgery
    * immobility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

bDMARD & tsDMARD safety concerns

A
  • inj site/ infusion rxn (acute vs delayed)
  • myelosupp (CBC, WBC, PLT)
  • infection (URTI, TB, hepatitis, opportunistic infection)
  • malignancy risk
  • autoimmune disease (SLE, lupus, demyelinating peripheral neuropathies)
  • CVS (HF =TNFa) (HTN = IL6, JAKi, TNFa)
  • pul disease/ toxicity (interstitial disease)
  • thrombosis (JAKi, IL6i)
  • hep (LFT)
  • metabolic (hyperlipidemia)
  • GI perforation (IL6, JAKi)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

GI perforation risk
CVS risk

A

GI: IL6i, JAKi, CD20 rituximab (onset 6day)
* diverticulitis
* > 65yo
* GC use
* NSAID use

CVS:
* HF: TNFa inhibitors
* HTN: IL6, JAKi

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

initiating bDMARD/ tsDMARD

A
  • Pre-tx screening (TB, Hep B & C)
  • vacc required before initiation (pneumococcal, influenza, hep B, varicella zoster)
  • lab screen (CBC, WBC, PLT, LFT, Lipid, Scr, preg)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

low disease activity/ remission

A
  • =/> 6mnths at target
    • Continuation of all DMARDs > reduction of dose/ gradual discontinuation but
    • Triple therapy: discontinue sulfasalazine > hydroxy
      ○ Lower ADR, better tx persistence
    • MTX + bDMARD/ tsDMARD
      ○ Gradual discontinuation of MTX or DMARD
      ○ Dose reduction/ incr interval
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

analgesics short term

A

3mnths
NSAID: inhibit PG synthesis
CS: anti-inflam, immunosuppressive
* PO < 7.5 mg prednisolone
* IA Q3 mnthly (< 2-3x/yr)
* discont if bMDARD/ tsDMARD started

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Methotrexate indication

A
  • 1st line choice DMARD therapy
    • Long term efficacy, acceptable toxicity, low cost
    • Assoc w/ sig. lower mortality
      • mod-high disease activity + ST analgesics
  • Combined with other sDMARDs for optimal effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

MOA of methotrexate

A
  1. Incr adenosine lvl, activate adenosine A2a receptor
    a. Inhibit 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/ IMP cyclohydrolase (ATIC)
    b. Anti-proliferative effects on T cells
    c. Inhibit macrophage functions
    d. Decr in pro-inflamm cytokines, adhesion molecules, chemotaxis, phagocytosis
  2. [minor action] Inhibit dihydrofolate reductase and thymidylate synthetase (decr folic acid, decr cell proliferation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

SE of methotrexate

A
  • ND, anorexia, stomatitis, LIVER, lung fibrosis, myelosupp, TENS/SJS
  • Reduction in folic acid, decr cell proliferation
    • NV, mouth & GI ulcer, hair thinning
    • Leukopenia, hepatic fibrosis, pneumonitis
  • Concomitant folic acid or folinic acid 12-24hr after methotrexate (decr toxicity)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

MTX dose

A

initiate 7.5mg once weeklu

titrate: 2.5-5mg/wkly (every 4-12wks based on resp)

TARGET: 15mg/day (within 4-6wks of initiate)
max: 25mg/wk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

folic acid dose

A

5mg/ wk

24
Q

CI of methotrexate

A

pre-exist liver disease/ AST/ALT > 3X ULN (75% dose)
immunodeficient
blood dyscrasias

teratogenic

crcl < 30ml/min (<50ml = 50% dose)

25
Q

DDI of methotrexate

A

NSAID/ COX2i (incr conc of MTX)
PPI (incr conc of MTX)
probenecid (incr conc of mTX)

vaccines (decr effect of vaccine)
alcohol (hepatotoxic)

26
Q

methotrexate monitor

A

sx: SOB, cough, NV, mouth sores, D, jaundice, skin , infection

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

27
Q

sulfasalzine MOA

A

Metabolised to sulfapyridine (active) + 5ASA
MOA: unknown, maybe mediated by effect on gut microflora
* Decr IgA and IgM rheumatoid factors
* Suppress T and B cells, macrophages
* Decr inflamm cytokines (IL1 b, TNF, IL6)

28
Q

sulfasalzine ADR

A

NV, headache, rash, infertility (reversible in M)
genitourinary, urine discolouration, headache, dizzy

hemolytic anemia, neutropenia (HLAB0801, HLA-A3101)

29
Q

CI for sulfasalazine

A
  • sulfonamide allergies
  • G6PD def

eGFR < 60ml/min: initiate at lower dose
dialysis: initiate 250mg OD ~ 1g/day

30
Q

monitor sulfasalazine

A

sx: NV, rash, infection
FBC

31
Q

leflunomide MOA

A
  • Converted to teriflunomide (active)
  • MOA: decr lymphocyte action
  • Inhibits dihydroorotate dehydrogenase
    - Decr pyrimidine synthesis and growth arrest at G1 phase
    - Inhibit T cell proliferation and B cell autoAB prodcution
    - Inhbit NF-kB activation pro-inflamm pathway
32
Q

leflunomide SE

A

D, elevation of liver enzymes, alopecia, weight gain, teratogenic, skin rash, headache, myelosupp

long t1/2 (even yrs detectable)
Wash out : Cholestyramine (bile salt binding resin) – before preg

33
Q

CI for leflunomide

A

ALT > 2X ULN
Teratogenic

34
Q

monitor in leflunomide

A

sx: D, hair loss, jaundice, infection

FBC, LFT (ast, alt, albumin, bilirubin)

35
Q

Hydroxychloroquine (best tolerated) MOA

A

inhibit chemotaxis of eosinophils, neutrophils, complement-dependent antigen-Ab reaction

Anti-malarial agent. Effective anti-inflamm agent in RA (but least potent DMARD)

MOA:
* Reduce MHC class II expression and APC
* Reduce TNF-a, IL1 and cartilage resorption
* Antioxidant activity

36
Q

SE of hydroxychloroquine

A

tolerable

SE: NV, stomach pain, hair loss, ocular toxicity (retinopathy)
photosensitive, hyperpig
hypogly, headache, dizzy, QT prolong

37
Q

dose adj in hydroxychloroquine

A

no specific dosage adj in renal/ hep
* metabolites excreted in urine (t1/2 40d)

C: preg

38
Q

monitor in hydroxychloroquine

A

eye exam- retinopathy (ophthalmoscopy)
G6PD def

39
Q

preg use what

A

Can use:
* Sulfasalazine (B), Hydroxychloroquine (C)
- both have risk of G6PD def

Cannot use: Teratogenic
* Methotrexate
* Leflunomide *req wash-out with cholestyramine, (long t½)

BMARD: TNFa inhibitors

40
Q

bDMARD eg
Better tolerated, add as adjunct so that csDMARD dose can be lowered

A
  • anti-TNF (infliximab, adalimumab, etanercept)
  • IL1R antagonist: Anakinra
  • Anti CTLA4 IG: Abatacept
  • Anti-CD20: rituximab
  • Anti-IL6 receptor mAb: tocilizumab
41
Q

Anti-TNF

A

1) Infliximab (chimeric 25%)
* Chimeric IgG1: binds TNFa
* IV infusion (hosp)

2) Adalimumab (human 100%)
* Fully human IgG1: Binds TNF-a
* SQ self admin

3) Etanercept (decoy TNFR2 receptor - IgG1 fusion protein intercepts TNF)
* Recombinant fusion protein
* Binds TNF-a and TNF-b
* SQ self admin

42
Q

TNF blockers indication

A

RA pt who do not respond well with sDMARD therapies
Combi with MTX for optimal effects

43
Q

TNF blockers ADR

A

resp infection and skin infection, incr risk of lymphoma, optic neuritis, exacerbation of multiple sclerosis, leukopenia, aplastic anemia

44
Q

TNF blocker CI + monitor

A

CI: live vaccination, Hep B
Monitor: screen for latent or active TB

hf iii,iv

45
Q

IL1R antagonist: Anakinra

A

○ Humanised. Recombinant IL1 receptor antagonist
* SQ (self admin)

○ Differ from endogenous prot by 1 methionine added to N-terminus. Not glycosylated

○ Competitive inhibitor of IL1, binds to IL1 receptor , block signalling
* Less effective than anti-TNF bDMARDs

46
Q

anakinra ADR

A

infections, INJ site rxn

47
Q

Anti CTLA4 IG: Abatacept MOA + SE

A

MOA: recombinant fusion protein w/ CTLA4-Fc IgG1.
* binds to CD80& CD86
* Prevents CD28 activation
* T cell therapy (IV or sc)
SE: resp infection in COPD, incr lymphoma incidence

48
Q

Anti-CD20: rituximab MOA + SE

A

MOA: chimeric mAb IgG1 directed at CD20 on pre- and mature B cells
* Depletes CD20+ B cells, block APC, autoAb and cytokine lvl
* B cell therapy (IV)

SE: rash (1st dose), resp infection in COPD
caution: GI perforation

49
Q

Anti-IL6 receptor mAb: tocilizumab MOA + SE

A

MOA: Humanised IgG1, binds to IL-6 receptor
* Prevent homodimerisation of IL6R b signalling

SE: infection, skin eruptions, stomatitis, fever, neutropenia, incr ALT/AST, hyperlipidemia

50
Q

tocilizumab DDI

A

Int. with CYP450, 3A4, 1A2, 2C9 substrates

Metabolised by proteolytic enzymes
by inhibiting IL6 = incr expression of CYP450 enzymes

51
Q
  1. tsDMARD (cytokine JAK-STAT pathway) indication
    Tofacitinib
A
  • Better response in combi with methotrexate in mod-severe RA
    □ Tofa + MTX ~ bDMARD + MTX
  • Mono if intolerance to methotrexate
  • In methotrexate and multiple bDMARD-refractory active RA
  • Approved for psoriatic arthritis (PsA)
  • DO NOT COMBINE WITH bDMARDs (only csDMARDs)
    □ Immunosupp risk

LAST LINE

52
Q

JAKi MOA (small molecule JKi)

A

Block cytokine production (stop JAK/ STAT activation of gene transcription)
□ Tyrosine kinase
□ Signal transducer and activator of transcription

Binds to JAK proteins inside cells to prevent JAKs from transphosphorylating associated cytokines & growth factor receptor

53
Q

JAKi ADR

A
  • Cytopenia (neut, lymphocytes, PLT, NK cells)
  • Immunosuppression (opportunistic infection – herpes zoster infection)
  • Anemia (JAK2 activation by erythropoietin)
  • Hyperlipidemia (incr total LDL, HDL, choelsterol, TG)
  • higher risk of major adverse cardiovascular events (MACEs) and malignancy
    * CVS, malignancy, thromboembolic events
54
Q

ROA of bDMARD & tsDMARD

A

TNFa: sc inj (except infliximab = IV)

IL1, CTLA4: sc inj
IL6, CD20: IV infusion

tofacitinib: PO

55
Q

non pharm

A
  • VACCINATION (TB, hep – pre-DMARD)
  • Pt education regarding RA & management
  • Psychosocial int
    • CBT (enhance self efficacy/ QOL)
  • Rest inflamed joint/ use splints to support joints & reduce pain
    • Caution – not to promote sedentary lifestyle
  • Physical activity & exercise (swim, no weight bearing exercises)
    • Maintain range of joint motion
    • Incr muscle strength
      ○ Avoid contractures & muscle atrophy
      ○ Maintain/ incr joint stability
      ○ Reduce fatigue & pain
    • Improve sleep
  • PT/OT (supervised exercise)
  • Nutritional & dietary counselling
    • Weight management if obese
    • Reduce inflamm (fish oil EPA/DHA 5.5mg OD)
    • Reduce ASCVD risk

3154 MSK (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions