Auranofin toxicity

Gold is used therapeutically in chronic inflammations as rheumatic arthritis (Ishida and Orimo 1994). The dose is given in the form ofa gold complex, such as gold sodium thiomalate and Auranofin toxic effects due to overdoses may appear. The most common method to monitor the therapeutic dose in serum or urine is GF-AAS. 

Gold compounds were first proved to be effective in a large double-blind trial in 1960. Because of their toxicity, they are used infrequently today. Their intramuscular formulations (aurothiomalate and aurothioglucose) contain 50% elemental gold. The oral formulation (auranofin) contains 29% elemental gold. 

These compounds have high bioavailability after intramuscular administration and tend to concentrate in synovial membranes, liver, kidney, spleen, lymph nodes, and bone marrow. One month after an intramuscular injection, 75-80% of the drug is eliminated from the serum, but intramuscular gold s total body half-life is approximately 1 year. Auranofin is only about 25% bioavailable. Gold compounds are excreted approximately 66% in the urine and 33% via the feces. There has generally been no correlation found between serum gold concentration and either efficacy or toxicity. 

Lupus er/thennatosus (affecting tlic skin) Photoprotection is essential. Potent adrenal steroid topically or intralesionally. Hydroxychloroquine or mepacrine. Monitor for retinal toxicity when treatment is long-term.Other agents include auranofin, aceiretin and in severe chilblain LE. thalidomide. A systemic disease, but discoid iupus erythematosus typicaily has no systemic manifestations. 

Auranofin is a triethylphosphine gold derivative for oral administration. It is in some respects strikingly different from the rest. Some 25% of an oral dose is absorbed through the intestinal wall and blood concentrations are some 15-25% of those reached with parenteral therapy. Auranofin is bound to cellular elements of the blood, is excreted mainly in the feces, and exhibits less tissue retention and total body gold accumulation than parenteral forms. It is more effective in acute inflammatory models and is a potent inhibitor of lysosomal enzyme release, antibody-dependent cellular toxicity, and superoxide production. Auranofin also affects humoral and cellular immune reactions. However, some have found auranofin to be rather less effective than parenteral gold. Auranofin is used in doses of 2-9 mg/day (generally 6 mg/day), which is less than the dose originally recommended. 

Auranofin has been associated with eosinophiha (range of incidence in various reports 0.1-13%). In a retrospective study of 82 patients with rheumatoid arthritis there was eosinophiha in 21% taking sodium aurothiomalate and 13% taking auranofin (33). However, early eosino-philia is not a rehable indicator of potential toxicity. 

Two patients developed fulminant colitis with toxic megacolon during treatment with auranofin (46,47). Both recovered completely within 4-6 weeks with supportive treatment, including high doses of prednisone. 

Mild and transient abnormalities in serum transaminase and alkaline phosphatase activities have been reported during therapy with auranofin (0.4%). This is noteworthy, since almost all patients were taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, which also can cause increases in transaminases. There has been a report of two cases of toxic hepatosis in patients taking auranofin (52). 

Answer C. Ocular toxicity is characteristic of chloroquine and hydroxychloroquine. Corneal deposits are reversible, but retinal pigmentation can ultimately lead to blindness. Patients will complain about GI distress, visual dysfunction, ringing in the ears (note that tinnitus aiso occurs in salicylism), and itchy skin. Hydroxychloroquine also promotes oxidative stress that can lead to hemolysis in G6PD deficiency. DMARDs include gold salts (e.g., auranofin), methotrexate, and etanercept, but thioridazine is a phenothiazine used as an antipsychotic it lacks anti-inflammatory effect, but does cause retinal pigmentation. 

Studies carried out at the Southern Research Institute indicated that auranofin at maximum non-toxic doses exhibited minimal activity in the P388 system and that continued treatment failed to reduce the tumor burden or prolong animal survival time. In contrast cisplatin both reduced tumor burden and prolonged animal survival (60). 

Dimercaptopropanol (dmp. Figure 1, also called British Anti-Lewisite) is thought to be useful for the treatment of toxic side effects arising from gold therapy (29). We report here studies on reactions of dmp with red cells treated with EtaPAuCl or auranofin. 

It is estimated that the dietary gold intake is < 7 J-g per day, and the absorption of gold compounds from the alimentary tract and skin is also poor (Iyengar etal. 2000). Of the more common medicinal gold compounds, only Auranofin - which shows good lipid solubility - can be absorbed through the intestine. The toxic symptoms appear as disorders in the digestive tract... 

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