Table 1.
Maintenance immunosuppressive therapies in transplantation and autoimmune disease.
| Drugs | Mechanisms | Side effects |
|---|---|---|
| Azathioprine | Inhibits purine and DNA synthesis, inhibits cell proliferation | Bone marrow depression, opportunistic infection, macrocytosis and liver toxicity |
| Cyclosporine | Binds to cyclophilin, inhibits calcineurin phosphatase, blocks NF-AT dephosphorylation, blocks IL-2 transcription and T-cell activation | Hypertension, hyperlipidemia, nephrotoxicity, hepatotoxicity, pancreatitis, peptic ulcers, thrombotic microangiopathy, opportunistic infection, neurotoxicity, tremor, gingival hyperplasia and hirsutism |
| Methotrexate | Irreversibly inhibits DHFR, blocks folic acid synthesis, interferes with synthesis of DNA, RNA, thimidylates and proteins | Pulmonary fibrosis, hepatitis, anemia, neutropenia, hair loss, gastrointestinal symptoms and dermatitis |
| Mycophenolate mofetil | Inhibits inosine-monophosphate dehydrogenase, inhibits purine synthesis and blocks cell proliferation | Gastrointestinal symptoms, bone marrow depression, opportunistic infection in particular CMV and BK nephropathy |
| Sirolimus | Binds to FKBP12, inhibits mTOR and blocks IL-2-driven cell proliferation | Delayed graft function, delayed wound healing, mouth ulcers, pneumonitis, increased proteinuria, peripheral edema and hyperlipidemia |
| Steroids | Induces phospholipase A2 inhibitory proteins, inhibits arachidonic acid synthesis, inhibits prostaglandins and leukotrienes | Diabetes, delayed wound healing, peptic ulcers, psychosis, osteoporosis, infection, blurred vision, fluid retention, weight gain, acne and constipation |
| Tacrolimus | Binds to FKBP12, inhibits calcineurin phosphatase and blocks T-cell activation | Post-transplantation diabetes mellitus, nephrotoxicity, thrombotic microangiopathy and neurotoxicity |
| Fingolimod (FTY720) | Modulation of the spingosine-1-phosphate receptors | Adverse events reported in up to 10.7% of patients. All related to mechanism of action and include cardiovascular and infections. Isolated cases of ischemic stroke, vascular occlusion and encephalopathy have been reported [119,131] |
CMV: Cytomegalovirus; DHFR: Dihydrofolate reductase; NF-AT: Nuclear factor of activated T cell.