Approach for risk-free glucocorticoids

Abstract

Glucocorticoid (GC) preparations are used in medicine for more than 70 years as the most powerful antiinflammatory drugs, possessing also anti-allergic, immunosuppressive, and antitoxic properties. However, the administration of these unique preparations is associated with severe adverse effects and difficulty and sometimes impossibility of their withdrawal. These adverse effects are manifestations of hormonal features of GC preparations. For reducing the risk associated with GC therapy two approaches are used: 1) synthesis of GC preparations with the improved therapeutical properties, and 2) the careful choosing patients to be treated with GCs, accurate decreasing the dose, medicamentous preventing the adverse effects. However, the problem of adverse effects still exists. GC hormones (and GC preparations!) are directly or indirectly participate in regulation of virtually all metabolic reactions, and this made it possible to propose the third approach: to take into account just the hormonal feature of GC preparations for optimizing their dose and regimen. The hepatic enzyme tyrosine aminotransferase (TAT) is the well-known example of the regulatory action of GCs. The TAT activity determines the blood level of tyrosine. Thus, blood tyrosine may be used for monitoring GC therapy. This proposal is based on the literature data of tyrosine metabolism and is supported by own observations in systemic lupus erythematosus, bronchial asthma, congenital adrenal hyperplasia in children, and also by experiment with adrenalectomy in rats.