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3154 haem & MSK - nat > IC13.3, ic16 RA > Flashcards

IC13.3, ic16 RA Flashcards

1
Q

What are the cytokines involved in RA

A

TNF, IL1, IL6, IL17

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2
Q

What is the pathology of RA

A

Macrophage secretes TNF
TNF is the most important cytokine in inflammation, stimulate synovial fibroblast to secrete other cytokines and MMP (Matrix Metalloproteinase)
MMP and Neutrophils will break down cartilage, cause bone destruction

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3
Q

Symptoms of RA (7 points)

A

Pain
Swelling
Redness, warmth
Early morning stiffness > 30 mins
Systemic symptoms eg. General aching, Fatigue, Fever, Weight loss, Depression
Deformities eg. swan neck, boutonniere
Loss of function, ability to carry out ADL

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4
Q

What are the 4 types of lab findings for RA

A

Autoantibodies tests
Rheumatoid factor (RF): +ve
Anti-CCP assay: +ve
Patients may have either, so need do both

Acute phase response
Erythrocyte sedimentation rate (ESR): High
C-reactive protein (CRP): High

FBC
Hematocrit: Low
Platelets, WBC: High

X-ray
Not used for diagnosis
Monitor disease progression, late in course of disease
Monitor for narrowing joint space, erosion around margin of joint, hypertrophic synovial tissue

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5
Q

How to diagnose RA

A

At least 6 points in the American College of Rheumatology test
At least 6 weeks duration of symptoms
Joint involvement (single or multiple)
Acute phase reactants CRP, ESR
+ve RF or Anti-CCP test

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6
Q

Criteria for remission

A

6 months
At most 1 joint swollen or tender
CRP ≤ 1mg/dL (low inflammation)

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7
Q

What are the types of drugs used in RA

A

To reduce inflammation
NSAIDs (used before RA is diagnosed)
Glucocorticoids

Maintenance therapy
csDMARDs (Methotrexate, Sulfasalazine, Hydroxychloroquine, Leflunomide)
bDMARD (TNFa inhibitor, IL6 receptor antagonist, CD20)
tsDMARD (JAK inhibitor Tofa, Bari)

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8
Q

Principle for glucocorticoid use

what is the max duration

A

Given to bridge DMARD therapy, prescribed together
Eg. Prednisolone ≤ 7.5mg / day
Used for shortest duration possible

Max duration is 3 months, Taper and discontinue
Discontinue when b/tsDMARD started

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9
Q

Side effects of glucocorticoids

A

Osteoporosis / osteonecrosis
Insulin resistance
Gastric ulcer
Cataract, glaucoma
Increased CVD risk

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10
Q

For low disease activity, what DMARD to use?

Moderate - severe disease activity?

A

Low: Hydroxychloroquine or Sulfasalazine preferred

Mod - Severe: MTX monotherapy + short term glucocorticoid

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11
Q

What is the starting dose of Methotrexate

Target dose

A

7.5mg once a week
Give folic acid 5mg once a week, the next day

Target: 15mg a week

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12
Q

What is the MOA of Methotrexate

A

1) (major) Increase adenosine levels via ATIC inhibition
ATIC inhibition → Increased adenosine act on adenosine receptors
Immune response: Stop T cells production, inhibition of macrophage function
Anti-inflammatory: Decrease in pro-inflammatory cytokines

2) (minor) Inhibit dihydrofolate reductase → resulting in side effects
Inhibit DNA methylation, synthesis of DNA bases (Purine - AG, Pyrimidine - CUT), essential amino acid synthesis

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13
Q

Side effects of MTX (7 points)

A

Nausea, vomiting
Mouth, GI ulcers
Hair thinning
Liver: increased transaminases, cirrhosis
Myelosuppression
Photosensitivity (protect from light)
SJS / TEN

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14
Q

Contraindication of MTX

A

Pre-existing liver disease
Immunodeficiency
Blood dyscrasia
Pregnancy (teratogenic)
Avoid in CrCl < 30ml/min

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15
Q

Monitoring of MTX

A

FBC
LFT (AST, ALT, Albumin, Bilirubin)
SCr

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16
Q

Why is folic acid needed with MTX

A

Folate enters cells, converted to Dihydrofolate by Dihydrofolate reductase → Tetrahydrofolate → eventually produce DNA bases and amino acids

Methotrexate inhibit Dihydrofolate reductase, cause nausea, hairloss

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17
Q

Folic acid vs Folinic acid

A

Folic acid / Folate
Cheaper, but need higher doses

Folinic acid
Expensive, but more efficient

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18
Q

MOA of Sulfasalazine

Starting dose of Sulfasalazine

A

Metabolised to Sulfapyridine (active) and 5-aminosalicylic acid (5 ASA)

suppress T cell, B cell, macrophages
Decrease inflammatory cytokines IL1, 6, TNF

500mg 1-2x a day

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19
Q

Side effects of Sulfasalazine (7 points)

A

Nausea, vomiting
Headache, dizziness
Rash
G6PD Haemolytic anaemia
Neutropenia
Reversible infertility in men (Oligospermia)
Urine discolouration

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20
Q

Which csDMARD does not have hair loss / alopecia as side effect

A

Sulfasalazine

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21
Q

Contraindication of Sulfasalazine

A

Sulfonamide allergy
G6PD Deficiency

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22
Q

Which is the safest csDMARD for pregnancy

A

Sulfasalazine

23
Q

Dose of hydroxychloroquine

A

200-400mg a day

24
Q

Contraindication with hydroxychloroquine

A

Pre-existing retinopathy
G6PD deficiency

25
Q

Which drugs are contraindicated in G6PD deficiency

A

Sulfasalazine
Hydroxychloroquine

26
Q

What is the MOA of Hydroxychoroquine (3 points)

A

Reduce MHC class 2 expression and antigen presentation
Reduced TNF, IL1, cartilage resorption
Antioxidant activity

27
Q

Side effect of hydroxychloroquine

A

Nausea, vomiting
Stomach pain
Dizziness
Hair loss
Ocular toxicity (retinopathy)
Photosensitivity, hyperpigmentation
QT prolongation

28
Q

Monitoring for hydroxychloroquine

A

eye exam

29
Q

Indication of Hydroxychloroquine

A

Least potent, Best tolerated

30
Q

Which medication dont need to monitor FBC

A

Hydroxychloroquine

the rest need to monitor

31
Q

Leflunomide dose

A

Loading dose: 100mg a day for 3 days
Maintenance: 20mg a day

32
Q

MOA of Leflunomide

A

Converted to active metabolite Teriflunomide
Decrease pyrimidine synthesis
Inhibit T cell proliferation and B cell autoantibody production

33
Q

Which drugs decrease pyrimidine synthesis

A

Methotrexate and leflunomide

34
Q

Contraindications of Leflunomide (4 points)

A

ALT > 2x ULN: avoid use
Preexisting liver disease
Immunodeficiency
Pregnancy

35
Q

PK of Leflunomide

A

Has long half life (years after last dose)
Use Cholestyramine (bile salt binding resin) to remove Leflunomide

36
Q

Side effect of Leflunomide

A

Diarrhea
Increase transaminases
Alopecia (hair loss)
Weight gain
Myelosuppression (bone marrow suppression)
Teratogenic

37
Q

similarities between mtx and leflunomide

A

both teratogenic, myelosuppression, may cause alopecia, increase transaminases (so need to monitor liver)

38
Q

Monitoring of Leflunomide

A

FBC
LFT (ALT, AST, Albumin, Bilirubin)

39
Q

Which csDMARD can or cannot use with increased transaminase

A

Methotrexate: can use, 3x ULN just use 75% of dose

Leflunomide: cannot use, ALT 2x ULN

40
Q

What is the general MOA of bDMARD and tsDMARD

A

bDMARD are administered via SC injection or IV infusion
Bind to cytokine or receptors to downregulate their functions, which reduces immune and inflammatory responses

tsDMARD are administered orally
Bind to JAK proteins inside cells to prevent JAK from transphosphorylating the associated cytokine and growth factor receptor

41
Q

What are the bDMARDs

A

TNF-a (IAGE)
Infliximab
Adalimumab
Golimumab
Etanercept

IL6 - Tocilizumab

CD20 - Rituximab

42
Q

What are the tsDMARDs

A

Tofacitinib
Baricitinib

43
Q

What needs to be done before initiating ts/bDMARD (3 points)

A

Pre-treatment screening
Start after TB treatment
Avoid if have untreated Hep B or C

Vaccination before initiation
Pneumococcal
Influenza
Hep B
Varicella zoster / Herpes zoster

Lab testing
CBC with wbc, platelet count
LFT (ALT, AST, bilirubin, ALP)
Lipid panel
SCr

44
Q

When should ts/bDMARD be used

A

When patient does not achieve remission at 6 months

45
Q

What to look out for for each ts/bDMARD drug class

A

TNF-A
Monitor for anti drug antibodies
Avoid in heart failure

IL6 inhibitor (Tocilizumab)
GI perforation, thrombosis

JAK inhibitors
Higher risk of MACE
GI perforation, thrombosis
Malignancy risk

46
Q

Which TNF-a are IV, which are SC

A

IAGE
IG are iv
AE are sc

47
Q

What are contraindicated with TNF-a

A

Live vaccination
Hepatitis B
heart failure

48
Q

What is Anakinra

A

IL1 receptor antagonist
Protein which blocks IL1 receptor

49
Q

What is the MOA of Tofacitinib

A

Inhibit Jak 1 - 3
Block cytokine production by blocking JAK/STAT activation of gene transcription

50
Q

Side effect of Tofacitinib (3 points)

A

Immunosuppression
Opportunistic infections

Anaemia (jak 2)

Hyperlipidemia
Increase HDL, LDL, TG

51
Q

Which medications cannot be used together in RA

A

Glucocorticoids cannot be used together with b/tsDMARD, GC needs to be stopped when b/tsDMARD are started

bDMARDs and tsDMARDs should not be used together

52
Q

Why are JAK inhibitors last line?

A

Risk of MACE, malignancy, GI perforation, thrombotic events

53
Q

Should treatment be stopped after patient achieve remission after 6 months?

A

No, dont discontinue DMARD abruptly, may result in flare

54
Q

non pharm for RA

A

Patient education

Rest during flares, Exercise (to increase muscle strength) if no flare

Do range of motion exercises (similar to frozen shoulder)

Do aerobic exercise to reduce fatigue, pain, improve sleep

Avoid high intensity weight bearing exercises

Diet
Overcome anorexia, poor diet
Weight management if obese
Reduce inflammation eg. fish oil
Reduce ASCVD risk

3154 haem & MSK - nat (12 decks)

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