This Rheuma TV educational presentation by Dr. Sachin Dhote explains the pharmacology, pharmacodynamics, and mechanism of action of Leflunomide, a conventional synthetic DMARD (csDMARD) used in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA).
Key Highlights:
- Leflunomide is a prodrug rapidly converted to its active metabolite, teriflunomide (A77 1726).
- It reversibly inhibits dihydroorotate dehydrogenase (DHODH), blocking de novo pyrimidine synthesis.
- This suppresses activated T and B lymphocyte proliferation by causing Gā cell cycle arrest.
- At higher concentrations, it also inhibits protein tyrosine kinases and NF-ĪŗB signaling, reducing inflammatory cytokine production.
- Due to high protein binding and enterohepatic recirculation, it has a 14ā18 day half-life. Cholestyramine or activated charcoal washout is recommended before pregnancy or in cases of toxicity.