Leflunomide, mycophenolic acid and matrix metalloproteinase inhibitors.
Leflunomide inhibits dihydro-orotate dehydrogenase with secondary effects on interleukin 2, transforming growth factor alpha and antibody production. Published data show that it is effective at 10-25 mg/day. Leflunomide's side-effects include gastrointestinal toxicity, a low incidence of alopecia, elevated liver function test abnormalities and weight loss. Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase with secondary decreases on guanine nucleotides, DNA synthesis and inhibition of natural killer cell activity. At 1 or 2 g daily it is effective clinically, although it has little effect on erythrocyte sedimentation rate. Incidences of toxicity obtained from transplantation experience are principally gastrointestinal but also include a probable increase in viral infections, some myelosuppression and occasional cholestasis or pancreatitis. Matrix metalloproteinase inhibitors (MMPIs) are a diverse group of enzymes that are rapidly induced by inflammatory mediators. Some MMPIs are effective in rheumatoid arthritis. Their toxicities include gastrointestinal toxicity, sun sensitivity and rare systemic lupus erythematosus-like syndromes.
Furst
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Virginia Mason Research Center, Arthritis Clinical Research Unit, Seattle, WA 98101, USA.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077339:Leflunomide; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009173:Mycophenolic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D008666:Metalloendopeptidases; D000077339:Leflunomide; D009173:Mycophenolic Acid