RA Flashcards
location of RA
wrist, fingers, elbows, shoulders, hips, knees, ankles
diagnosis of RA
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
pathophysio of RA
T-cell mediated immune response,
inflammation,
release of proteases, prostaglandins,
destruction of articular cartilage and underlying bone
inflammatory cytokines involved in RA
IL-17, TNF, IL1, IL6
goals of therapy
at least 6 months of remission or low disease activity
maximise function
stop disease progression
symptoms of RA (esp in >60yo)
- Generalized aching/stiffness
- Fatigue
- Fever
- Weight loss
- Depression
what to use for patients with low disease activity
hydroxychloroquine, sulfasalazine (reduced immunosuppression)
examples of conventional dmards
mtx
sulfasalazine
hydroxychloroquine
leflunomide
examples of tnf alpha inhibitors
etanercept, infliximab, adalimumab
IL-1 receptor antagonist?
anakinra
IL-6 receptor antagonist?
tocilizumab
anti-cd20 b cell depleting mab
rituximab
jak inhibitor?
tofacitinib
what to take MTX with
PO folic acid 5mg/wk
what to avoid in CVS patients
anti-tnfa, jaki, IL6i
adverse effects of therapies
injection site reactions
myelosuppression
infections
malignancy risk
raised LFTs
AE specific to IL6i and JAKi
thrombosis, gi perforation
what to do before initiation of immunotherapy
- complete all anti-tb tx first
- screen for hep a/b and avoid tx
- screen for active infections
- cbc with wbc/platelets
- vax: pneumococcal, influenza, hep b, varicella
what to monitor during therapy
cbc - wbc, platelets (risk of myelosupprx)
lipids, scr, lft
non pharmaco mgmt of RA
physical activity and exercise
physio
rest inflamed joint
weight management
what activities to avoid for RA
weight bearing exercises
MOA of MTX
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
dosing of mtx
7.5mg once a week
increase every 4-12 weeks by 2.5-5mg
dosing of sulfa
initiate w 500 mg OD or BD, increase by 500 mg/week
target dose of mtx
15mg/week within 4-6 weeks of initiation
target dose of sulfa
1g BD
maximum dose of sulfa
3000mg/day
max dose of mtx
25mg/week
low dose gc for initiation of dmard
7.5 mg/day prednisolone up to 3 months
ci of MTX
crcl <30, liver disease, immunodeficiency, blood dyscrasias
ddi of mtx
nsaids/cox2i, ppi, probenecid, vaccines, alcohol
se of mtx
gi (ND, anorexia)
liver (increased lfts, cirrhosis)
lungs (fibrosis)
haem (myelosupprx)
derm (tens/sjs)
hair loss
ci of sulfasalazine
Sulfonamide allergies
Caution in G5PD deficiency
moa of sulfasalazine
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
ddi of sulfa
Iron, antibiotics, warfarin
se of sulfa
GI: nausea, dyspepsia;
Rash;
Haem: Agranulocytosis associated with HLA-B08:01 & HLA-A31:01 (European);
Oligospermia (reversible), urine discoloration;
CNS: headache, dizziness
hydroxychloroquine ci
Preexisting retinopathy
Caution in G6PD deficiency
moa of hcq
Reduced MHC Class II expression and antigen presentation
Reduced TNF-α and IL1
Antioxidant activity
which dmard has better tolerated side effects
hcq
hcq ddi
CYP2C9 inhibitor: cimetidine
QT prolongation drugs: eg. ciprofloxacin
hcq se
Generally tolerable.
retinopathy, hyperpigmentation, hypoglycemia, qt prolongation, hair loss
leflunomide moa
Inhibits dihydroorotate dehydrogenase and hence decreases pyrimidine production.
Suppression of T,B cells.
Inhibits NF-kB activation of pro-inflammatory pathway (lymphocyte action)
halflife of leflu / hcq
lefly -18d
hcq - 40d
sulfaz main thing to look out for
retinopathy
hcq moa
Reduced MHC Class II expression and antigen presentation
Reduced TNF-α and IL1
Antioxidant activity
hcq target dose
200-400mg in one or two doses
leflunomide avoid in
ALT>2xULN
leflunomide ddi
cholestyramine, activated charcoal, rosuvastatin, warfarin, vaccines, alcohol
leflunomide ae
ND, raised transaminases, alopecia, rash, headache, myelosupprx, weight gain
add on therapy to mtx
hydroxychloroquine, sulfasalazine
moa of bdmards
Binds to cytokines or their receptors to downregulate/inhibit their functions, which reduces immune & inflammatory responses
moa of tsdmards (jaki)
Janus kinase (JAK) pathway inhibitor, blocks cytokine production via JAK/STAT-activation of gene transcription
why is tofacitinib (jaki) not preferred
higher risk for major adverse cardiovascular events (MACEs) & malignancy for indivs with risk factors
why is tofacitinib (jaki) not preferred
higher risk for major adverse cardiovascular events (MACEs) & malignancy for indivs with risk factors
vaccinations required before initiation
- Pneumococcal
- Influenza
- HepatitisB
- Varicella zoster
pre-tx screening
Complete all anti-TB Tx first
Check for Hep B/C, avoid if present
when on anti tnf, cannot have…
hep b, live vax
jaki ae
Immune: Cytopenia, immunosuppression, anaemia
Hyperlipidemia: incr in total, LDL, HDL, cholesterol, TG
inflammatory markers
crp, esr
which drug to avoid for liver issues
leflunomide
how to dose adjust for mtx for patients crcl < 50
50% of dose; CI in crcl <30
how to dose adj for mtx for pts AST/ALT > 3ULN
75% of dose
how to dose adj for sulfa for eGFR <60
initiate at lower dose
how to dose adj for sulfa for dialysis
250mg OD, up to 1g/day
