Penicillamine (Cuprimine) can be used to treat acute, severe rheumatoid arthritis, producing reductions in joint pain, edema, and stiffness. The response to penicil-lamine is usually delayed (4-12 weeks), and remissions can last several months after withdrawal of treatment. Radiographic evidence of this drug's efficacy is limited; thus, penicillamine is seldom used to treat rheumatoid arthritis. The mechanism of action of penicillamine is unknown, but some evidence suggests that it may involve the inhibition of angiogenesis, synovial fibroblast proliferation, or transcriptional activation. Because penicillamine can chelate copper and promote its excretion, it is used to treat Wilson's disease (hepatolen-ticular degeneration) and has also been used in mercury and lead intoxication.
Penicillamine is readily absorbed from the GI tract and is rapidly excreted in the urine, largely as the intact molecule. Gradually increasing its dose minimizes side effects, which necessitate discontinuance of penicil-lamine therapy in perhaps one-third of patients. The most common side effects are maculopapular pruritic dermatitis, GI upset, loss of taste sensation, mild to occasionally severe thrombocytopenia and leukopenia, and mild proteinuria, which at times may progress to the nephritic syndrome. Discontinuance of therapy usually results in a rapid disappearance of side effects.
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