MECHANISM OF ACTION • • • •
Gold salts accumulate in bone marrow, liver & spleen. Impairs macrophage function and cytokine activity which supresses phagocytosis and lysosomal enzyme activity. Inhibits PG synthesis and complement activation. Potentially acts by suppressing IgM antibody responses and formation of immune complexes as well as IL-1 generation.
CLINICAL NOTE •
Absorption decreased by food. Metabolised in the liver, excreted in urine and faeces
IMMUNOSUPPRESSANTS
METHOTREXATE MECHANISM OF ACTION • Folic acid antagonist that decreases inflammatory cells in the synovium • Reversibly inhibits dihydrofolate reductase • Leading to reduced intracellular levels of THF and therefore preventing the synthesis of purines and thymidine INDICATIONS • Reducing joint erosions in established and early rheumatoid arthritis CONTRAINDICATIONS • Renal dysfunction • Liver disease • Active infectious disease • Excessive alcohol consumption.
LEFLUNOMIDE MECHANISM OF ACTION • Pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase. • It undergoes biotransformation to active metabolite to inhibit the dihydroorotate dehydrogenase. • Prevents pyrimidine synthesis by specifically targeting lymphocyte proliferation. • Also inhibits osteoclast production and therefore slows progression.
INDICATIONS • Active rheumatoid arthritis as a disease-modifying antirheumatic drug (DMARD). • Active psoriatic arthritis.
