Lec 4 pharma
Rheumatoid Arthritis
⚫It is chronic autoimmune disease characterized by inflammation of joints and may affect
other organ systems.
✓ The exact cause is unknown. Genetic factors plays an important role.
✓ Activation of T cell, B cells and production
of autoantibodies leads to production of
mediators as TNF α and IL-1 which cause
joint inflammation, cartilage destruction,
bone erosion and deformity.
Pathophysiology
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Lec 4 pharma
Clinical manifestation:
A- Articular manifestation.
o Small joints of hands and feet are most commonly affected.
o In severe cases, larger joints as shoulder and knee are also affected.
o The affected joints become swollen, warm, painful and stiff.
o These manifestation increase in the morning (prominent feature).
B- Extra articular manifestation:
Other organs may be affected as lung, heart, kidney, liver.
Diagnosis:
1. Joint x-ray
2. Blood test for autoantibodies as rheumatoid factor.
❖ Management:
I-Steroidal anti-inflammatory drugs:
As corticosteroids ( prednisolone)
II-Non- steroidal anti-inflammatory drugs:
A-Rapidly acting anti – rheumatic drugs:
Large doses of NSAID are required they are used to relief pain and inflammation but
do not prevent joint destruction.
B- Slow acting anti-rheumatic drugs: Disease modifying anti-Rheumatic drugs (DMARDS):
- As it takes 6 weeks to 6 months to become evident. They are slow
acting if compared with NSAIDS.
1- Methotrexate 2-Chloroquine 3-Sulfasalazine
4-Leflunamide 5-Azathioprine 6-Cyclosporine
7-Gold salts
8-Monoclonal antibodies: a-Infliximab and Etanercept b-Rituximab
9- Anakinra
1- Methotrexate
-It is folic acid antagonist.
-It is one of 1st line drugs being used in RA cases.
-It inhibits multiple enzyme needed for activation of T-cells.
-It is given once weekly oral.
-Side effect:
hepatotoxicity- bone marrow depression- teratogenicity.
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2-Chloroquine
-It is antimalarial drug.
-It has role in the of RA as it decrease response of T- Cells to antigen and stabilize lysosomes.
-Side effects:
-Nausea, vomiting, Pruritis, Dermatitis.
-long term use cause retinopathy and ototoxicity.
3-Sulfasalazine:
-It is metabolized into 5-aminosalcylic acid which suppress T-cells and B-cells function.
-Side effects:
-Headache, Nausea, vomiting, Rash. – Neutropenia (rare).
4-Leflunamide :
-It suppress T-cells as it inhibit dihydroortate dehydrogenase leading to inhibition of pyrimidine
synthesis.
-Side effects:
-Diarrhea, Elevation in liver enzymes
6-Cyclosporine
-Potent inhibitor of T-cells as it inhibits phosphorylation of calcineurin which regulates nuclear
transcription factors in T-cells.
-Side effects: -Nephrotoxicity -Hepatotoxicity
7-Gold salts:
-It decrease release of inflammatory cytokines and inhibit phagocytosis
-Side effects: Dermatitis – nephrites
8-Monoclonal antibodies:
a-Infliximab and Etanercept:
-It block tumor necrosing factor α (TNFα)
-It does not cure RA, but it retard destruction of joints (it decrease signs and symptoms).
-Side effects:- Increase incidence of bacterial infection and cancers. - expensive
b-Rituximab:
-It is directed to CD20 antigen (trans membrane protein expressed on pre-B-lymphocyte).
9- Anakinra:
IL1 antagonist
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