RHEUMATOID ARTHRITIS

● Debilitating disease
● less movement and activity of patient

PHARMACOLOGIC TX
1. SALICYLATES/ NSAIDS
● First line drugs for Rheumatoid arthritis
● Inhibits CoX, inhibits prostaglandin synthesis, no inflammation.
2. CORTICOSTEROIDS-
● oral and parenteral
● have systemic action= immunosuppressants (inhaled corticosteroids- oral
candidiasis, oral thrush)
3. DMARDS- DISEASE MODIFYING ANTI-RHEUMATIC DRUGS.
● Purpose is to prevent joint damage.
● Preserve the function of the joints.
● Reduce inflammatory factors (inhibit cytokines, interleukin)

○PURPOSE OF INFLAMMATORY CELLS

● to protect, they will migrate to the affected areas, they will attract other inflammatory
cells, if they accumulate, the cell will be activated and can be damaged.

EXAMPLES OF DMARDS
1. ○LEFLUNOMIDE
● Inhibit pyrimidine synthesis
● Inhibits nucleic acid synthesis
● Act in the immune function related to the production of inflammatory cells
● ADR- Liver damage, weight loss, immunosuppression (purpose is to suppress
immune, to inhibit function of inflammatory cells/factors-----
● C/I: methotrexate
2. ○ETANERCEPT
● inhibits TNF by binding to TNF-alpha and beta
● [(TNF-alpha-Tumor necrosis factor) cytokine inflammatory factor that could
stimulate COX, COX that will synthesizes prostaglandin and promotes
inflammation]
● Can be given with methotrexate.
3. ○INFLIXIMAB- binds to TNF-alpha, superior to methotrexate.
4. ○ANAKINRA-
● newest, interleukin-1 receptor antagonist.
● [INTERLEUKIN- produced by WBC/ leukocytes, regulation of immune response.]
WHEN THERE IS EXPOSURE TO ORGANISM (INFECTION)
○ (1st) WBC will release Interleukin and send signal to brain
○ (2nd) infection, fever because of the function of interleukin, produces
 prostaglandin and then increases temperature in the brain.
5. ○METHOTREXATE-
● Antimetabolite
● popular DMARS
● Dihydrofolate reductase inhibitor
● Inhibits DHF reductase, inhibit activation of folic acid,inhibit nucleic acid
synthesis, responsible for the formation of immune response, inflammatory genes
DHF-enzyme- responsible for the conversion of dihydrofolate---> tetrahydrofolate( active form of
folic acid [essential metabolite])-used to synthesize nucleic acids.

LESS FREQUENTLY USED:

1. ○GOLD preparations
● AU-symbol of gold
● oldest drug/ before
● it is also used in juvenile arthritis.
2. ○AZATHIOPRINE
● converted to 6-mercaptopurine (non-specific purine synthesis inhibitor)
● COMMON ADR: bone marrow suppression; causing aplastic anemia aka.
Pancytopenia (low levels of blood cells)
● *allopurinol can inhibit azathioprine metabolism*
● HOW??? Azathioprine converted to 6-MP, If there is xanthine oxidase, it will be
converted to thioxanthine. Allopurinol inhibits xanthine oxidase, inhibits
metabolism of azethioprine.
3. ○PENICILLAMINE
● chelating agent used in RA
● Reduces collagen formation
● (Collagen- part of the scar tissue, protein for the repair of the tissues)
4. ○CYCLOSPORINE
● Immunosuppressants
● bind to cyclophilin receptor, further inhibit calcineurin,
● THEREFORE, inhibits early stages of immune response
● (CALCINEURIN- intracellular phosphatase, involved in the activation of gene
encoding cytokine)