Chapter: Modern Pharmacology with Clinical Applications: Antiinflammatory and Antirheumatic Drugs

Gold Compounds Drugs

Gold compounds (chrysotherapy) are the oldest of the DMARDs in use to treat rheumatoid arthritis.

Gold Compounds

Gold compounds (chrysotherapy) are the oldest of the DMARDs in use to treat rheumatoid arthritis. Pa-rentally administered gold is generally believed to be somewhat less effective than methotrexate; oral gold is less effective than parenteral preparations. Gold com-pounds take several months to produce a measurable effect. Among patients who can tolerate this therapy, some benefit will be obtained in about 80%, and complete remission will be induced in 20% of cases. Remissions are maintained for varying periods after discontinuing ther-apy, with a relapse rate as high as 80%. Relapse is usually less severe in such patients, and a second course of gold therapy usually produces beneficial effects.

Basic Pharmacology

The gold preparations available in the United States in-clude two preparations administered via intramuscular injection: gold sodium thiomalate (GSTM, Myochrysine, Aurolate) and aurothioglucose (gold sodium thioglu-cose, GSTG, Solganal), and an oral preparation, aura- nofin (Ridaura). Although called gold salts, these com-pounds contain monovalent gold bound to sulfur, a bond that is at least partly covalent.

The mechanism by which gold compounds produce their antiarthritic effects is not known. Since gold ther-apy can suppress the increased phagocytic activity that occurs in rheumatoid arthritis, the antirheumatic activ-ity of gold preparations may involve the inhibition of ei-ther antigen processing by macrophages or lysosomal enzyme release in the joint. Gold preparations also di-rectly inhibit certain lysosomal enzymes found in poly-morphonuclear leukocytes and macrophages.

Generally, 2 months of multiple dosing of gold compounds is required to reach steady-state levels. Auranofin therapy produces lower steady-state blood gold concentrations than does treatment with par-enteral gold compounds, but it also produces a lower in-cidence of adverse effects.

Adverse Effects

Toxic manifestations of gold therapy are most common after a minimal total amount (200–300 mg) of gold has been administered. Serious reactions necessitating dis-continuance of therapy or antidotal therapy are en-countered in perhaps 5% of the patients.

Both oral and parenteral gold therapy frequently produces dermatitis, usually preceded and accompanied by pruritus. Stomatitis may accompany dermatitis, which may be preceded by a metallic taste in the mouth of the patient. Blue or gray skin discoloration can arise from gold deposition in that tissue, and photosensitivity may also occur. Unlike parenteral gold compounds, au-ranofin does not accumulate appreciably in the skin. Auranofin, but not the parenteral gold preparations, most frequently causes diarrhea (about 50%), abdomi-nal pain, nausea, and anorexia.

Mild proteinuria is fairly common and does not al-ways require discontinuance of therapy; however, se-vere proteinuria may indicate a toxic nephritis. The pro-teinuria is usually reversible when gold administration is stopped. Hepatotoxicity has also been reported. Fatalities from gold therapy have been reported, usually a consequence of a blood dyscrasia. The most common hematological abnormality is eosinophilia. Serious blood dyscrasias, such as thrombocytopenia, agranulo-cytosis, and hypoplastic or aplastic anemia, are rare.

To complement steroidal and other measures used in treating gold toxicity, it may be necessary to hasten the elimination of gold from the body. Appropriate chelating agents include dimercaprol and penicillamine . The proper administration of either of these agents markedly increases the excretion of gold and alleviates the signs and symptoms of gold toxicity.

Contraindications and Drug Interactions

Gold compounds are contraindicated for use in patients with systemic lupus erythematosus, Sjögren’s syndrome, severe debilitation, or uncontrolled congestive heart failure or hypertension. Caution must be used in ad-ministering gold compounds to individuals who have conditions that might increase their susceptibility to gold toxicity: blood dyscrasias, immunosuppression, re-nal disease, hepatic disease, skin diseases, or inflamma-tory bowel disease. Animal studies have shown adverse effects on reproduction; gold compounds may distribute to breast milk and are therefore contraindicated for women who are breast-feeding.

Gold should be used cautiously in patients receiving drugs that can also cause nephrotoxicity. Interactions between gold compounds and penicillamine may result in severe hematological and renal side effects.

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