Alex Rosenberg is an Intensivist who was working in a transplant centre last year. He gave this talk on immunosupression at last year's Bedside Critical Care Conference and managed to make a fairly dry subject seem understandable and relevant. Go to www.intensivecarenetwork.com for the podcast.
10. Antimetabolites
• Azathioprine
– Pro drug: metabolized to 6-MP
– Inactivated by TPMT.
– Interferes with purine synthesis and so inhibits
DNA replication.
– Adverse effects: myelosupression, GI symptoms
– Interacts with allopurinol.
11. • Mycophenolate
– Pro drug of mycophenolic acid.
– Blocks inosine monophosphate dehydrogenase.
– Selectively inhibits T & B lymphocyte clonal
expansion.
– Side effects: Diarrhoea, marrow suppression.
12.
13. Corticosteroids
• Immunosuppressive and anti-inflammatory.
• Inhibit transcription factors (IL2 / NFkB)
• Down regulate expression of graft self
molecules.
• Usually lifelong.
• First line treatment of acute rejection
14.
15. Proliferation Signal Inhibitors
• Sirolimus
– Streptomyces hygroscopicus – 1975 in Easter
Island.
– Binds to FK binding protein.
– Inhibits activation of mTOR.
– Prevents T and B cell proliferation
– Synergistic with CNIs
– Toxicities: Poor wound healing
17. To name a few….
• Basiliximab – anti CD25.
• Antithymocyte Globulin – CD 45 and multiple
others
• Muromonab – anti CD3
• Alemtuzumab – anti CD52
• Rituximab – anti CD20
• Bortezomib – proteasome inhibitor
three forms of renal injury including: 1) an acute renal dysfunction due to vasoconstriction of the afferent arteriole, 2) an thrombotic microangiopathy that leads to thrombotic thrombocytopenic purpura and hemolytic uremic syndrome 3) chronic interstitial fibrosis and arteriolar sclerosis associated with persistent deterioration of renal function