Immunosuppressive Mechanisms of Transplant Drugs

The immune system plays a critical role in rejecting transplanted organs as foreign tissue. Immunosuppressant drugs work to suppress the immune system's response and prevent transplant rejection. There are several classes of drugs that function through different immunosuppressive mechanisms.

Calcineurin Inhibitors

Calcineurin inhibitors like cyclosporine and tacrolimus are considered the backbone of most Organ Transplant Immunosuppressant Drugs regimens. They inhibit calcineurin, a phosphatase essential for T-cell activation. Without calcineurin activity, T-cells cannot be stimulated by interleukins and other signals to proliferate and carry out immune responses against the transplanted organ. Cyclosporine was the first clinically effective immunosuppressant for organ transplant immunosuppressant drugs. Tacrolimus is more potent with fewer side effects than cyclosporine.

Antiproliferative Agents

Mycophenolate mofetil and mycophenolic acid work by selectively inhibiting inosine monophosphate dehydrogenase, an enzyme crucial for purine synthesis. This effectively blocks the proliferation of T and B lymphocytes, hindering both cell-mediated and antibody-mediated rejection. Azathioprine is an older antiproliferative immunosuppressant still used sometimes.

Corticosteroids

Glucocorticoids like prednisone are potent immunosuppressants that inhibit multiple aspects of immune responses. They act through the glucocorticoid receptor to repress expression of cytokines and adhesion molecules involved in lymphocyte migration and activation. Corticosteroids are often part of initial immunosuppressive therapy but must be tapered to avoid long-term side effects.

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