Rheumatoid Arthritis Flashcards
What is RA?
- Chronic inflammation of synovial joints
- Autoimmune
- progressive
- symmetric
What are some Biomarkers you can use?
↑Erythrocytes sedimentation rate (ESR)
- ↑ C-reactive protein (CRP)
- Rheumatoid factor – antibody in 75% of causes
- HLA typing – antibodies associated with ↑ risk
- Antinuclear antibodies (ANA)
- Cyclic citrullinated Peptide (CCP) - inflammation
Hydroxychoroquine
MOA
1st line in mild disease: Synthetic DMARDS Antimalarial Drug 1. ↓ IL-1 synthesis 2.↓ phospholipase A2 (prevents PG production) 3.↓chemotaxis 4.Causes DNA intercalation (stopping cell division)
Hydroxychoroquine
Adverse effects:
EYES! Retinal toxicity
Get an eye check yearly**
- blurred vision, headache, dizziness
- lichenoid skin eruptions (rash)
- bleaches hair/ falls out
Sulfasalazine
Pyralin EN
MOA
5-ASA
- decrease PG synthesis
- decrease migration of inflammatory cells
- decrease leukotriene synthesis
Sulfasalazine
Adverse
GI, reversible male infertility, yellow-orange discharge of body fluids
Methotrexate
MOA
- Folic acid inhibitor
- dihydrofolate reductase inhibitor
- prevents purine synthesis
- Because inflammatory cells are dividing so rapidly they require MORE purine
- no purine = no inflammatory cells
- immunosupressants - ↓IL-1
- less macrophages
- ↓inflammatory response
Methotrexate
Dose
- 7.5-15mg / WEEK (low dose)
- onset 1-2 months
- can divide weekly dose over two days if needed
FOLATE:
- Must take with FOLATE to reduce S/E
- Must be 24hrs apart
- 1mg daily or 5-10mg weekly
Methotrexate
Adverse
-Myelosuppression
(↓bone marrow/RBC/ WBC)
- Thrombocytopenia (low platelets)
- Mucositis (mucus inflamed)
- photosensitivity**
-pulmonary fibrosis
(if people complain of coughing!)
- Hepatic portal fibrosis
- ↑risk of lung cancer, non-hodgkin’s disease (cancer in lymph system), melanoma
- nausea, vomiting, stomatitis
Leflunomide
MOA
Pyrimidine Synthase inhibitor
- inhibits dihydroorate dehydrogenase (DHODH)
- in lymphocytes
- immunosuppressant
Used only when methotrexate is not suitable
Gold Salts
MOA
Synthetic DMARDs
- ↓lymphocyte proliferation
- ↓activity of lysosomal enzymes
- ↓production of 02 radicals
- ↓ chemotaxis
- ↓Mast cell release
Other use for D-Penicillamine
-also used in metal poisoning/ Wilson’s disease because of Chelating ability
D-Penicillamine
MOA
Hydrolysis of Penicillin
-decrease collagen formation
-and decreases rheumatiod factors
(unique ability)
What does DMARDS Mean?
Disease-modifying antiartheumatic drugs
Etanercept
MOA
Biological DMARDS
Anti-TNFa Drugs
-Stops TNF binding to receptors causing inflammation response
-Combine with methotrexate
Adverse effects of Biological DMARD Anti-TNF
site reaction = itching, swelling
- metastatic melanoma risk
- allergic reaction
-TNF is important for immune system, shutting this down = prone to dormient infections eg Hep B and TB
What are the baseline monitoring for TNF-a drugs
aim four top 4
Baseline monitoring
- Full blood picture
- vaccination status
- latent disease
- screen for cancer
- Liver function (ALT and AST)
- Creatinine clearance
Infliximab
-special points
Monoclonal fusion protein
- non-humanised (25% is made from mice)
- body will remove this quickly
Adalimumab
-speical points
Fully humanises (no mice)
(no antibody response)
-good for psoriasis
-can cause hyperlipidaemia
Certolizumab Pegol
Special points
Add PEG to the molecule = bigger
Lasts longer in body
Tofacitinib
MOA
Janus Kinase Inhibitor
- stops proinflammatory things
- prevention of cell proliferation
- may induce apoptopic pathways ↓ lymphocytes
What is Anakinra?
Kineret
Interluekin-1 receptor antagonist
DO NOT use with TNF drugs
what is Tocilizaumab?
Acetemre
used in juvenile idiopathetic arthritis
What is the role of Corticosteroids in RA?
immunosupressant - used for Flare ups and when starting DMARDs (waiting for them to work)
