Rheumatoid Arthritits Flashcards
what is RA
Autoimmune attack on joints
Drugs and supplements for RA
- NSAIDs
- Glucocorticoid
- csDMARDs: Methotrexate, Sulfasalazine Hydroxychloroquine, Leflunomide
- tsDMARDs: Tofacitinib
- bDMARDs: TNF-alpha blockers, IL1 blocker, IL6 blocker
factors increasing risk of RA
- female (3:1 compared to male)
- Genetic (HLA-DR4 related antigen)
primary target area of RA
synovial tissues, bone erosion, joint deformity
MOA of methotrexate
folic acid analogue that has anti-proliferative effect on T cells that inhibits macrophage functions decreasing cytokines and other pro-inflammatory mediators due to:
- [major] increased adenosine levels due to 5-aminoimidazole 4 carboxamide ribonucleotide (AICAR) transformylase / IMP cyclohydrolase (ATIC) inhibition
- [minor] decrease pyrimidines due to inhibition of dihydrofolate reductase and hence thymidylate synthase
ADR of methotrexate
- N&V, GI and mouth ulcers
- hair thinning (minimise folinic acid)
- Myelosuppression, hepatotoxicity, pneumonitis, pulmonary fibrosis
who should avoid methotrexate
impaired renal function
MOA of sulfasalazine
- decrease IgA and IgM rheumatoid factors
- suppression of T and B cells and macrophages
- decreases inflammatory cytokines (IL-1beta, TNF-alpha, IL-6)
ADR of sulfasalazine
- N&V, GI discomfort
- cytopenia/ neutropenia
- oligospermia in men (reversible)
MOA of Leflunomide
- inhibit dihydroorotate dehydrogenase (decrease pyrimidine synthesis)
- anti-proliferative effects on T cells and inhibits B cell autoantibody production
- inhibits NF-kappaB activation of pro-inflammatory pathways
ADR of leflunomide
- N&V, GI discomfort
- myelosuppression, hepatotoxicity, pulmonary fibrosis
what should pre-pregnancy female do if they used to take leflunomide
wash out with cholestyramine 11 days before starting due to very long half life (detectable even years after last dose)
MOA of Tofacitinib
- Janus kinase (JAK) pathway inhibitor
- Blocks cytokine production by blocking JAK/STAT activation
ADR of Tofacitinib
- immunosuppression and hence opportunistic infections
- N&V, diarrhea
- dyslipidaemia, hyperlipidaemia, increase blood cholesterol, venous thromboembolism
- insomnia, HA
what should Tofacitinib avoid giving with
biological DMARDs (eg. TNF-alpha blockers, IL-1 blockers, IL-6 blockers)
MOA of hydroxychloroquine
- increase pH of intracellular vesicles (interferes with garbage processing and loading of antigens on to MHC II receptors for antigen presentation)
- Blocks toll-like receptor 9 (TRL9)
- shields endothelial annexing V, blocks anti-phospholipid antibodies
ADR of hydroxychloroquine
- N&V
- ocular toxicity (Bull’s eye maculopathy)
- cardiomyopathy
examples of TNF-alpha blockers
infliximab, adalimumab
examples of IL1 blockers
Anakinra
example of IL6 blockers
Tocilixumab
ADR of TNF- alpha blockers
- infection (hep B, TB)
- increased risk of lymphoma
- optic neuritis
- Leukopenia, aplastic anaemia
- exacerbation of multiple sclerosis
- drug induced lupus
- live vaccination CI
ADR of Anakinra
- injection site reactions
- infections due to immunosuppression
MOA of Tocilizumab
humanised chimeric mAb IgG1 directed against IL6R alpha chain, prevents binding of IL6 to IL6 alpha and IL6 signalling
ADR of tocilizumab
- immunosuppression resulting in risk in infections (esp URTI), leucopenia, neutropenia, fever
- skin eruptions, rashes, stomatitis (inflammation of mucous membrane of mouth)
- hypercholesterolaemia, HA, dizziness
