Calcineurin Inhibitors & Immunosuppressants

Calcineurin Inhibitors & Immunosuppressants

1. Definition & scope

• Immunosuppressants are drugs that inhibit cellular and/or humoral immune responses; their major use is in organ transplantation and autoimmune disease (KDT 8e Ch.65, p.937).
• Calcineurin inhibitors (CNIs) — cyclosporine and tacrolimus — are among the most effective immunosuppressants in routine use; they target intracellular signalling pathways triggered by T-cell receptor (TCR) activation and form the backbone of most maintenance immunosuppressive regimens (G&G 14e Ch.39, pp.771–4; DiPiro 12e Ch.109, p.1457).
• Four major drug classes covered for transplantation: glucocorticoids, calcineurin inhibitors, antiproliferative/antimetabolic agents, and biologicals (antibodies/fusion proteins) (G&G 14e Ch.39, p.769).
• Two intrinsic limitations of all immunosuppressant therapy: (a) increased risk of bacterial, fungal, viral (especially CMV) and opportunistic infections; (b) increased risk of lymphomas and related malignancies after a long latency due to weakened immunological surveillance (KDT 8e Ch.65, p.945).
• A core design principle: most regimens combine 2–4 drugs with synergistic, non-overlapping mechanisms, each directed at a different molecular target — allowing lower doses of each agent and thereby limiting drug-specific toxicities while maximising immunosuppression (G&G 14e Ch.39, p.770; DiPiro 12e Ch.109, p.1466).