|
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.
|
