Leflunomide inhibits which enzyme to exert its effects?

• A. Chloroquine
• B. Mesalazine
• C. Leflunomide
• D. Etanercept

Answer: (C)

The main idea is that Leflunomide works by blocking a specific enzyme essential for making new pyrimidine building blocks. It is a prodrug that is converted to an active metabolite which inhibits dihydroorotate dehydrogenase (DHODH). DHODH is a key enzyme in the de novo synthesis of pyrimidines, the nucleotides needed to produce DNA and RNA. When DHODH is inhibited, cells can’t efficiently synthesize new pyrimidines, so rapidly dividing cells—especially activated T and B lymphocytes—have limited DNA synthesis and proliferate less. This dampens the immune response and reduces inflammation, which is why Leflunomide is used in autoimmune conditions.