Agent | Pharmacology | Molecular target | Molecular effect | Side effects |
---|---|---|---|---|
Corticosteroids | Increased bioavailability with hypoalbuminaemia and liver disease. | Cytosolic receptors. Heat shock proteins. | Blocks transcription of cytokine genes (eg IL-1, IL-2, IL-3, TNF-α, and IFN-γ). | Hypertension, glucose intolerance, dyslipidemia, osteoporosis. |
Cyclosporine | Lipid soluble, poor/variable oral absorption. Neoral has improved and more predictable bioavailability. | Binds cyclophylin. Inhibits calcineurin. | Inhibits IL-2 production. Stimulates TGF-β production. | Nephrotoxic effects, hypertension, dyslipidemia, glucose intolerance. |
Tacrolimus (FK506) | Better oral bioavailability than cyclosporin standard form | Binds FKBP-12. Inhibits calcineurin. | Inhibits IL-2 production. Antagonizes TGF-β. | Similar to cyclosporine but less hirsutism/gum enlargement. Up to 20% incidence of IDDM. |
 | Hepatic metabolism. |  |  |  |
Azathioprine | Hepatic metabolism to active product. | Metabolites bind DNA. | Inhibits purine synthesis, Blocks DNA and RNA synthesis. | Marrow suppression. |
MMF | Good bioavailability. Hepatic metabolism to form active product. | Inhibits inosine monophosphate dehydrogenase. | Blocks de novo pathway of purine synthesis (selective for lymphocytes). Blocks glycosylation. | Diarrhea/gastrointestinal upset. Cytomegalovirus. Increased but no reported. cases of PCP. |
Sirolimus | Lipid soluble. Poor oral bioavailability. | Binds FKBP-12. Blocks p70 S6 kinase. | Blocks IL-2-induced cell cycle. progression. | Hyperlipidemia. Thrombocytopenia. |