pathophysiology and pharmacotherapy of Rheumatoid arthritis

1. Presented by
Ved prakash panda
M.Pharm (pharmacology)

2.  Introduction
 Epidemiology
 Aetiology
 Pathophysiology
 Clinical menifestation
 Diagnosis
 Treatment

3.  Defination :rheumatoid arthritis is a long
term autoimmune disorder that primarily
affects joints. It typically result in swollen &
painful joints. Most commonly, the wrist &
hands are involved, with the same joints
typically involved on both sides of the body.
 Epidemiology: approximately 1% of the
population world wide is affected by
rheuatoid arthritis, with females being 3
times more commonly affected then men.

4.  Aetiology :
1. genetic factors contributes 60% of the risk
of developing the disease. A MHC antigen
HLA- DR4 is the major genetic factor.
2. Cigaratte smoking is a strong risk factor for
developing Rheumatoid arthritis
3. Synovial injury/ infection with joints leads
to cause of rheumatoid arthritis.
 As all the above factors cause modification
of auto antigen.

5.  Pathologically, RA is characterised by the
infiltration of variety of inflammatory cells into
the joints.
 Synovial membrane is made up of the cell called
fibroblast or synovocytes.
 Because of modification of auto antigen, this is
recognised by antigen presenting cell, which
activates APC to initiate an immune response.
 APC migrate to lymph nodes and activates T- cell
& B- cell.
 B- cell proliferate into plasma cell and produce
antigen against your own antibody, and migrate
to joint tissue.

7.  Macrophage in synovium secrete cytokines
like THF-alpha, IL-1, IL-6.
 Cytokines stimulate synovial fibroblast, they
are activated, proliferate & stimulate RANKL
expression which stimulate osteoblast activity
i.e bone erosion.
 Synovial fibroblast secrete protease causing
cartilage degradation.
 The synovial membrane becomes highly
vascularised & hypertrophied, creating a
pannus formation and inflamation.

8.  Clinical manifestation:
 Pain, stiffness & swelling of finger, thumbs,
wrists, knee & toes.
 Morning stiffness may last for 30min to
several hours.
 Symmetric arthritis
 Extraarticular features, including
osteoporosis, subcutaneous nodules.
 Ankylosis formation( fusion of bone in the
joints).

9.  Diagnosis:
 Blood test, x- rays for presence of synovitis &
erosion of bones or cartilage.
 Morning stiffness for at least 6 weeks
 Swelling of 3 or more joints for at least 6
weeks.
 Presence of positive rheumatoid factors, it is
an auto antibody present in 80% of patient
with rheumatoid arthritis and term as
seropositive.

10.  Treatment:
 Non-pharmacological treatment:
1. Physiotherapy is found to be effective in
treating both acute as well as chronic state.
2. Heat, cold & electrotherapy
3. Exercise
4. Surgeries:
Joint replacement procedure- Arthroplasty
Bonegrafting- artrodesis
Synovial membrane is removed- synovectomy

11.  4 main categories of drugs employed in the
management of rheumatoid arthritis:
1. NSAIDs
2. DMARD’S
3. GLUCOCORTICOIDS
4. BIOLOGICAL THERAPIES

12.  NSAIDs:
 Inhibition of cyclooxygenase(COX) enzyme
 NSAIDs inhibit production of inflammatory
prostanoids.
 Drugs:
 salicylates-aspirin
 Acetates- diclofenac
 Indoles-indomethacin
 Propionates-ibuprofen
 Cox-2 selective inhibitors:
 Celecoxib
 valdecoxib

13.  Disease modifying anti-rheumatic
agents(DMARDs):
 All DMARDs inhibit the release or reduce the
activity of inflamatory cytokines such as TNF-
alpha, IL-1,IL-2,IL-6.
 DRUGS:
 Sulfasalazine
 Methotrexate
 Cyclosporin
 Azarhiprine

14.  CORTICOSTEROIDS:
 Inhibit chemotaxis & migration of leukocyes
and activity of B & T cells.
 Drugs:
 Methylprednisolone.
 Triamcinlone acetonide.
 CYTOKINES INHIBITORS:
 TNF alpha- Inhibitors-Infliximab, Etanercept
 IL-1 Antagonist-Anakinra