Immunosuppressant

Immunosuppressive agents are used to:

• Prevent the rejection of transplanted organs and tissues
• Treat autoimmune diseases or diseases that are most likely of autoimmune origin

Because the majority of them act non-selectively, the immune system is less able to resist infections and the spread of malignant cells.

Immunosuppressive drugs can be classified into five groups:

• Glucocorticoids
• Calcineurin inhibitors such as cyclosporin and tacrolimus
• Sirolimus derivatives such as everolimus, sirolimus
• Mycophenolate mofetil
  
• Antibodies
• Cytotoxics
  

Glucocorticoids:

• suppress cellular and humoral immune system
• anti-inflammatory effects

Calcineurin inhibitor - cyclosporin and tacrolimus

• Cyclosporin and tacrolimus block the action of calcineurin in activated T cells. This prevents production of interleukin-2 and other cytokines which normally stimulate T cell proliferation and differentiation.

• Common side effects include gingival hyperplasia, hirsutism and nephrotoxicity.

Sirolimus Derivatives:

• Bind to the same intracellular protein (FKBP-12 ), then blocks the activity of mammalian target of rapamycin (mTOR) kinase preventing cell cycle progression and cytokine-induced T and B cell proliferation.

• Common side effects include rash, neutropenia, proteinuria and interstitial lung disease.

Mycophenolate mofetil

• selectively suppresses lymphocyte proliferation and antibody formation by inhibiting inosine monophosphate dehydrogenase.

• Common side effects include GI symptoms.

Antibodies:

Antibodies are sometimes used as a quick and potent immunosuppressive therapy to prevent the acute rejection.

Includes:

• Polyclonal antibodies which inhibit T cell and cause lysis.
  
• Monoclonal antibodies which are directed towards exactly defined antigens.

Cytotoxics:

In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells.

includes:
Alkylating agents - such as cyclophosphamide, which is probably the most potent immunosuppressive compound.
Anti-metabolites

• Folic acid analog - such as methotrexate
• Purine analogs - azathioprine and mercaptopurine

Azathioprine can cause irreversible bone marrow failure for those with a particular polymorphism of the TPMT gene.

Drug interactions with allopurinol.