Immunosuppressants consider

Secondary immunodeficiencies (9) are much more common than primary ones and frequently occur as a result of immaturity of the immune system in premature infants, immunosuppressive therapy, or surgery and trauma. Illnesses, particularly when prolonged and serious, have been associated with secondary immunodeficiencies, some of which may be reversible. Acquked immune deficiency syndrome (AIDS) (10—12) may be considered a secondary immunodeficiency disease caused by the human immunodeficiency vimses HIV-1 or HIV-2. Hitherto unknown, the disease began to spread in the United States during the latter part of the 1970s. The agent responsible for this infection has been isolated and identified as a retrovims. 

Heart transplantation represents the final option for refractory, end-stage HF patients who have exhausted medical and device therapies. Heart transplantation is not a cure, but should be considered a trade between a life-threatening syndrome and the risks associated with the operation and long-term immunosuppression. Assessment of appropriate candidates includes comorbid illnesses, psychosocial behavior, available financial and social support, and patient willingness to adhere to lifelong therapy and close medical follow-up.1 Overall, the transplant recipient s quality of life may be improved, but not all patients receive this benefit. Posttransplant survival continues to improve due to advances in immunosuppression, treatment and prevention of infection, and optimal management of patient comorbidities. 

Cyclosporine and tacrolimus belong to a class of immunosuppressants called the calcineurin inhibitors. These agents are considered by many to be the cornerstone of medical immunosuppression. The calcineurin inhibitors work by complexingwith cytoplasmic proteins (cyclosporine with cyclophylin and tacrolimus with FK binding protein 12). These complexes then inhibit calcineurin phosphatase, which results in reduced IL-2 gene transcription. The final outcome is a decrease in IL-2 synthesis and a subsequent reduction in T cell activation.7 11 20 21... 

Mycophenolate mofetil was approved by the FDA in 1995, and enteric-coated mycophenolic acid was approved in 2004. Both agents are considered to be adjunctive immunosuppressants. Mycophenolic acid acts by inhibiting inosine monophosphate deydrogenase, a vital enzyme in the de novo pathway of purine synthesis. Inhibition of this enzyme prevents the proliferation of most cells that are dependent on the de novo pathway for purine synthesis, including T cells.7,11,26-28... 

MPA derivatives have replaced azathioprine as the antiproliferative agent of choice in most organ transplant centers. The MPA derivatives generally are considered to provide a more specific immunosuppressive effect compared with azathioprine. Mycophenolate mofetil and enteric-coated mycophe-nolic acid have similar safety and efficacy data in renal transplant recipients. 

The third example considered the interaction of life-history traits (survival rates, fecundity, immunogenicity) with an environmental factor specific to parasites, namely the host immune system. Here phenotypic diversity in response to environmental conditions (host immunity) is not so readily apparent. To observe phenotypic diversity, different parasite lines need to be compared in their kinetics of infection and, to show immune-dependence, these must be complemented by control experiments in immunosuppressed hosts. Experiments seeking to select on this diversity... 

Selective immunosuppression in individuals suffering from the above conditions is likely best achieved by preventing the synthesis or functioning of IL-2. Cyclosporin A, one of the foremost immunosuppressive agents currently in use, functions by preventing IL-2 synthesis. A number of alternative approaches are now being considered or tested directly in clinical trials. These include ... 

In general, immunosuppression, expansion of regulatory cells, costimulatory blockade, or promotion of a Th2 cytokine milieu is considered to be supportive of disease control in T-cell regulatory disorders such as autoimmune disease and graft-versus-host disease (GvHD) [2]. In contrast, killer cells, a Thl cytokine milieu, or activated lymphocyte infusions support control of malignancy and infections. Maintaining a balance between the two... 

Presumably, any cytotoxic substance that destroys bone marrow and lymphoid tissue may be used as an immunosuppressant. Among these drugs, the most widely used primarily for autoimmune diseases are vincristine, methotrexate, and cytarabine. However, their use should be considered experimental. Only methotrexate is seriously and sufficiently recognized as an initial drug for treating rheumatoid arthritis. 

Pneumocystis carinii pneumonia - Prophylaxis in individuals who are immunosuppressed and considered to be at increased risk. 

Renal transplant patients have a higher prevalence of clinically significant hyperlipidemia. Accordingly, carefully consider the risk/benefit in patients with established hyperlipidemia before initiating an immunosuppressive regimen including sirolimus. 

Concurrent immunosuppressants Sirolimus has been administered concurrently with cyclosporine and corticosteroids. The efficacy and safety of the use of sirolimus in combination with other immunosuppressive agents have not been determined. Renai function impairment Mean serum creatinine was increased and mean glomerular filtration rate was decreased in patients treated with sirolimus and cyclosporine compared with those treated with cyclosporine and placebo or azathioprine controls. Monitor renal function during the administration of maintenance immunosuppression regimens including sirolimus in combination with cyclosporine, and consider appropriate adjustment of the immunosuppression... 

Renal function impairment Requires close monitoring and possibly frequent dosage adjustment. In patients with persistent high elevations of BUN and creatinine who are unresponsive to dosage adjustments, consider switching to other immunosuppressive therapy. 

The alkylating agents can be considered to be cell-cycle independent drugs. They are used for the management of leukemias, lymphomas, multiple myeloma and some carcinoma s and soft tissue tumors, generally as components of drug combination regimens. Cyclophosphamide is also used for its marked immunosuppressant properties. 

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