Calcineurin Inhibitors & Immunosuppressants

Introduction

• Immunosuppressants inhibit cellular and/or humoral immune responses; their major use is in organ transplantation and autoimmune disease.
• Calcineurin inhibitors (CNIs) — cyclosporine and tacrolimus — are the most effective agents in routine use and form the backbone of most maintenance regimens; they block intracellular signalling triggered by T-cell-receptor (TCR) activation.
• Four major drug classes are used for transplantation: glucocorticoids, calcineurin inhibitors, antiproliferative/antimetabolic agents, and biologicals (antibodies/fusion proteins).
• Most regimens combine 2–4 drugs with synergistic, non-overlapping mechanisms — each at a different molecular target — allowing lower doses of each and limiting drug-specific toxicity.
• Two intrinsic hazards of all immunosuppression: (a) increased infection risk (bacterial, fungal, viral — especially CMV — and opportunistic); and (b) increased lymphoma/malignancy risk after a long latency from weakened immune surveillance.