Chapter 11

Immunosuppressants and Antimetabolites

Ana Molina-Ruiz and Marta Mazaira-Fernández

Abstract

Dermatologists are often required to prescribe immunosuppressive agents for the treatment of serious and recalcitrant dematoses. Azathioprine, cyclophosphamide, methotrexate, and cyclosporine are the immunosuppressive agents most commonly used by dermatologists. The immunosuppressive drugs act by a variety of mechanisms. In general, the precise mechanisms responsible for most therapeutic benefits observed with these agents are understood only partially. Unlike biologic agents that selectively inhibit a proinflammatory cytokine and/or block its receptor, the immunosuppressive drugs interfere with combinations of critical pathways in the inflammatory cascade. Among the immunosuppressive drugs, several are "cytotoxic", causing either cell death or impaired proliferation; such drugs include cyclophosphamide, chlorambucil, methotrexate, and azathioprine. Other drugs suppress the immune system by inhibiting the proliferation or function of lymphocytes. This class includes drugs such as cyclosporine and tacrolimus, which specifically target calcineurin and thereby inhibit the production of interleukin-2 by activated T-lymphocytes. Others prevent lymphocyte proliferation by inhibiting nucleotide synthesis, for example, mycophenolate mofetil blocks the synthesis of purine. Finally glucocorticoids have many effects upon innate and acquired immunity. Familiarity with disease-specific clinical efficacy, side-effect profile, and dosage allows the successful and judicious use of these drugs in dermatologic disorders. This chapter summarizes the characteristics of systemic immunosuppressive agents commonly used in dermatology.

Total Pages: 286-365 (80)

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