Transplantation immunosuppression

After transplantation, immunosuppression must be used to prevent host rejection of the graft liver, usually with prednisone and tacrolimus or cyclosporine. Tacrolimus and cyclosporine are calcineurin inhibitors and require drug level monitoring because of a narrow therapeutic range and significant toxicity, including renal failure and neurotoxicity. 

Ingle GR, Shah T. (2005) Enteric-coated mycophenolate sodium for transplant immunosuppression. Am J Health-System Pharm (AJHP) 62 2252-2259. 

Glucocorticoids are widely used as drugs to treat arthritis and dermatitis. In pharmacological doses, they are used to suppress various allergic, inflammatory and autoimmune diseases. They are also administered as post-transplant immunosuppressants. Nevertheless, they do not prevent infection and they also inhibit subsequent regenerative processes. Excessive glucocorticoid levels have side effects on many systems, such as the inhibition of bone formation, delayed wound healing, muscle weakness and an increased risk of infection. 

Role of Disease Severity or Prognosis. It is also useful to know that the prevalence of poor compliance is seemingly irrespective of prognosis, e.g. with post-transplant immunosuppressants (Didlake et al.. 

Tanabe K, Tokumoto T, Ishida H, Ishikawa N, et al. 2004. Excellent outcome of ABO-incompatible living kidney transplantation under pre transplantation immunosuppression with tacrolimus, mycophenolate mofetil and steroid. Transpl Proc. 36 2175-2177. 

Organ transplant Immunosuppression Transplantation of liver, kidney, heart, and so forth... 

Muromonab Orthoclone OKT 3 Prophylaxis of rejection after heart transplantation immunosuppression 1986/1992... 

Azathioprine, a prodrug converted to 6-mercaptopurine, is widely used as a post-transplant immunosuppressant and in various autoimmune or chronic inflammatory disorders, such as rheumatoid arthritis, dermatomyositis, systemic lupus eiythematosus, skin diseases, and inflammatory bowel diseases. 

Kowdley KV, Keeffe EB. Hepatotoxicity of transplant immunosuppressive agents. Gastroenterol Clin North Am 1995 24(4) 991-1001. 

Cyclosporine was approved for transplant immunosuppression in 1983. It is administered to prevent organ rejection after transplant of kidney, liver, lung, heart, or bone marrow. In addition, it has been given to patients with nephrotic syndrome, rheumatoid arthritis, psoriasis, severe Crohn s disease, and for other medical conditions. 

Transplant immunosuppression must be balanced in terms of graft and patient survival (the prevention of rejection versus the risk of adverse effects associated with therapy, including life-threatening infection or malignancy). A multidrug approach is rational from the immunomechanistic viewpoint because the agents... 

Ingle GR, Sievers TM, Hold CD SiroUmus Continuing the evolution of transplant immunosuppression. Ann Pharmacother 2000 34 1044. 

In 1989 tacrolimus (FK 506), a second caldneurin inhibitor started its clinical journey [8]. Tacrolimus has an immunosuppressive effect approximately 100 times more potent than CsA and early clinical trials demonstrate that FK 506 was effective in reversing refractory acute rejection in renal, liver and heart transplantation. Subsequently, this drug showed to be at least as effective as CsA in the primary immunosuppression schedules for solid organ and bone marrow transplantation and, similarly to CsA, proved to be a valuable alternative in the treatment of autoimmune diseases [3,9-11]. At the moment, FK 506 is considered the only drug that can substitute CsA in primary immunosuppression schedules and it is currently used in almost 60% of liver transplantation immunosuppressive prescriptions. 

Chocair PR, Duley JA, Cameron IS, Arap S, lanhez L, Sabbaga E, Siimnonds HA Does low-dose allopurinol, with azathioi ine, cyclosporin and rednisolone, improve renal transplant immunosuppression Adv Exp Med Biol (1994) 370,205-8. 

R345 S. Gabarti, P. F. Halloran and J. Friedewald, Managing Risk in Developing Transplant Immunosuppressive Agents The New Regulatory Environment ,... 

Late episodes of acute rejection are uncommon, and usually relate to poor patient compliance or inadequate levels of immunosuppression. The pathophysiology of chronic rejection is poorly understood, and can lead to graft loss. The incidence of chronic rejection has fallen progressively to approximately 5% over the past 10 years. Over-immunosuppression can lead to opportunistic bacterial infections and increased incidence of malignant disorders. Opportunistic infections such as legionellosis, nocardiosis, and tuberculosis occur between the 1st and I2th month post-transplant. Immunosuppressive treatment can be associated with Epstein Barr virus infection, and the development of post-transplantation lymphoproliferative disorder (Fig. 4.1.8). 

Cassivi SD, LiuM, Boehler A, Tanswell AK, Slutsky AS, Keshavjee S, Todd STRJ. Transgene expression after adenovirus-mediated retransfeetionofrat lungs is increased and prolonged by transplant immunosuppression. J Thorac Cardiovasc Surg 1999 117(1) 1-7. 

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