Drug Therapy in the Heart Transplant Recipient

Abstract

Received March 16, 2004; revision received July 23, 2004; accepted September 30, 2004. Part I of this series describes the mechanisms and types of rejection and the intravenous immunosuppressive drugs commonly used for induction or antirejection therapy. In this article, we review the commonly used oral immunosuppressive drugs. Intravenous corticosteroid methylprednisolone is included in the discussion of corticosteroids. Table 1 gives trade names, pharmacology, necessary adjustments for renal or hepatic dysfunction, and dosing and general monitoring guidelines for drugs described in this section. Table 2 lists the major adverse effects of immunosuppressive drugs described in Parts I and II of this review and provides an estimate of their relative frequency. View this table: TABLE 1. Commonly Used Oral (and Intravenous) Immunosuppressive Drugs View this table: TABLE 2. Major Adverse Effects of Immunosuppressive Drugs Steroids, among the first immunosuppressive agents used in clinical transplantation, have remained an important component of induction, maintenance, and rejection regimens. ### Mechanism of Action Glucocorticoids are potent immunosuppressive and antiinflammatory agents (the Figure). They diffuse freely across cell membranes and bind to high-affinity cytoplasmic glucocorticoid receptors. The glucocorticoid receptor–steroid complex translocates to the nucleus, where it binds to a glucocorticoid response element within the DNA.1 The glucocorticoid receptor–steroid complex may also bind to other regulatory elements, inhibiting their binding to DNA. Both actions cause transcriptional regulation, thereby altering the expression of genes involved in immune and inflammatory response. Glucocorticoids affect the number, distribution, and function of all types of leukocytes (T and B lymphocytes, granulocytes, macrophages, and monocytes), as well as endothelial cells.2 The major effect on lymphocytes appears to be mediated by inhibition of 2 transcription factors, activator protein-1 and nuclear factor (NF) κ-B.3,4 This affects the expression of a number of genes, including those for growth factors, cytokines, CD40 ligand, GM-CSF, and adhesion and myosin heavy chain molecules.2 In nonlymphoid …