In transplant patient

For the topical treatment of some chronic inflammatory skin diseases (like atopic dermatitis) immunosuppressive macrolides (like TRL and pimecrolimus) that permeate the inflamed epidermis are of benefit for patients. Severe side effects comparable to those after systemic application of TRL in transplanted patients (see above) have not been observed so far. For the treatment of psoriasis vulgaris these drugs are less effective. The CD2 antagonist alefacept may be a suitable alternative to allergic reactions. 

Cyclosporine is a cyclic polypeptide immunosuppressant typically used to prevent organ rejection in transplant patients. Its use is restricted to patients with fulminant or refractory symptoms in patients with active IBD. Significant toxicides associated with cyclosporine are nephrotoxicity, risk of infection, seizures, hypertension, and liver function test abnormalities.1,13,14... 

Elevated cholesterol levels in transplant patients are due to a culmination of factors such as age, genetic disposition, renal dysfunction, DM, proteinuria, body weight, and immunosuppressive therapy. Many of the immunosuppressive agents can produce elevations in serum lipid levels. 

Immunocompromised A condition in which the immune system is not functioning normally. This condition is seen in the very young, the very old, human immunodeficiency virus-infected individuals, and in transplant patients. An immunocompromised person is susceptible to opportunistic infections. 

Infectious disease studies are normally conducted over a short time, providing only snapshots and do not provide information on the consequence of chronic immunosuppression. The adverse health effects of chronic, low level immunosuppression have been addressed to some extent in transplant patients, primarily kidney transplants, who demonstrate an increase frequency of certain immunogenic tumors. 

GC regulate a wide variety of immune cell functions. GC modulate cytokine expression, adhesion molecule expression and immune cell trafficking, immune cell maturation and differentiation, expression of chemoattractants and cell migration, and production of inflammatory mediators and other inflammatory molecules [35], At pharmacological concentrations, GC are routinely used as immunosuppressive therapeutic agents in many acute and chronic inflammatory and autoimmune diseases, in transplant patients and in the treatment of leukemias and lymphomas [reviewed in 29].. 

Ceglarek U. et al., 2004. Rapid simultaneous quantification of immunosuppressants in transplant patients by turbulent flow chromatography combined with tandem mass spectrometry. Clin ChimActa 346 181. 

Ceglarek et al.45 reported the rapid simultaneous quantification of immmunosuppressants (cyclosporine A, tacrolimus, and sirolimus) in transplant patients by turbulent flow chromatography (TFC) coupled with HPLC-MS/MS. TFC is an online extraction technique involving the direct application of human plasma onto a turbulent flow column where protein is washed from the samples before the retained drug is backflushed onto an analytical column. 

Christians, U., Jacobsen, W. and Floren, L.C., Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients are the statins mechanistically similar Pharmacol. Ther., 1998, 80, 1-34. 

Ganciclovir IV is indicated for use only in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients and for the prevention of CMV disease in transplant patients at risk for CMV disease. 

The topical ophthalmic antiviral preparations appear to interfere with viral reproduction by altering DNA synthesis. Trifluridine is effective treatment for herpes simplex infections of the conjunctiva and cornea. Ganciclovir is indicated for use in immunocompromised patients with cytomegalovirus (CMV) retinitis and for prevention of CMV retinitis in transplant patients. Foscarnet is indicated for use only in AIDS patients with CMV retinitis. 

The principal advantage of MMF over alternative systemic immunosuppressive agents (e.g., methotrexate, cyclosporine) is its relative lack of hepatotoxicity and nephrotoxicity. Adverse effects produced by MMF most commonly include nausea, abdominal cramps, diarrhea, and possibly an increased incidence of viral and bacterial infections. Whether MMF may be associated with an increased long-term risk of lymphoma or other malignancies is controversial however, any such risk is likely to be lower in patients treated for skin disease with MMF monotherapy than in transplant patients treated with combination immunosuppressive therapy. 

Prevention of CMV disease in transplant patients IV 10 mg/kg/day in divided doses q 12h for 7-14 days, fhen 5 mg/kg/day as a single daily dose. 

Hollander A A, van Rooij J, Lentjes GW, et al. The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients. Clin Pharmacol Ther 1995 57(3) 318-324. 

Valacyclovir is generally well tolerated, although nausea, vomiting, or rash occasionally occur. At high doses, confusion, hallucinations, and seizures have been reported. AIDS patients who received high-dosage valacyclovir chronically (ie, 8 g/d) had an increased incidence of gastrointestinal intolerance as well as thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome this dose was associated with confusion and hallucinations in transplant patients. 

Little data in transplant patients has been generated. There is some data regarding famciclovir for treatment of recurrent hepatitis B following liver transplantation. 

Sirolimus is used for tissue transplantation where its major advantage over calci-neurin inhibitors is that it is not nephrotoxic. Chronic renal failure in transplant patients who have taken calcineurin inhibitors for the long term can be prevented by the administration of sirolimus. Steroid-free immunosuppression can be achieved by administering sirolimus alone or in combination with mycophenolate mofetil and cyclosporine or tacrolimus. Since impaired wound healing is one of its potential side effects, some transplant centers use sirolimus only after several weeks of surgery. 

Christians U, Sewing KF. 1993. Cyclosporin metabolism in transplant patients. Pharmacol Then 57 291-345. 

Ceglarek, U., Lembcke, J., Fiedler, G. M., Werner, M., Witzigmann, H., Hauss, J. P., and Thiery, J. (2004). Rapid simultaneous quantification of immunosuppressants in transplant patients by turbulent-flow chromatography combined with tandem mass spectrometry. Clin. Chim. Acta. 346 181-190. 

B. Legg, S. K. Gupta, and M. Rowland. A model to account for the variation in cyclosporin binding to plasma lipids in transplant patients. Ther. Drug Monit. 10 20-27 (1988). 

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