Immunosuppressants corticosteroids

Systemic fungal infections hypersensitivity to the drug IM use in ITP administration of live virus vaccines (eg, smallpox) in patients receiving immunosuppressive corticosteroid doses (see Warnings). 

Anti-inflammation, immunosuppression, corticosteroid replacement therapy PO 0 6-... 

Anti-inflammatory, immunosuppressant, corticosteroid replacement therapy Topical... 

Sirolimus has been used effectively alone and in combination with other immunosuppressants (corticosteroids, cyclosporine,... 

Nonspecific immunosuppressive therapy in an adult patient is usually through cyclosporin (35), started intravenously at the time of transplantation, and given orally once feeding is tolerated. Typically, methylprednisone is started also at the time of transplantation, then reduced to a maintenance dose. A athioprine (31) may also be used in conjunction with the prednisone to achieve adequate immunosuppression. Whereas the objective of immunosuppression is to protect the transplant, general or excessive immunosuppression may lead to undesirable compHcations, eg, opportunistic infections and potential malignancies. These adverse effects could be avoided if selective immunosuppression could be achieved. Suspected rejection episodes are treated with intravenous corticosteroids. Steroid-resistant rejection may be treated with monoclonal antibodies (78,79) such as Muromonab-CD3, specific for the T3-receptor on human T-ceUs. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-ceUs. 

Maintenance of remission of ulcerative colitis may be achieved with oral or topical aminosalicylates. Immunosuppressants such as azathioprine or 6-mercaptopurine can be used for unresponsive patients or those who develop corticosteroid dependency. 

Immunosuppressants such as azathioprine or 6-mercaptopurine can be used for unresponsive patients or those who develop corticosteroid dependency. Remission may be maintained in up to 58% of patients after 5 years of treatment.1,25 Intermittent infliximab dosing (5 mg/kg IV every 8 weeks) may be used to maintain disease remission and reduce the need for corticosteroids in patients with moderate to severe UC. Colectomy is an option for patients with progressive disease who cannot be maintained on drug therapy alone. 

The aminosalicylates, azathioprine, 6-MP, and infliximab are all viable options for treatment and maintenance of IBD in pediatric patients. Use of immunosuppressive therapy or infliximab may help reduce overall corticosteroid exposure. 

Azathioprine was originally approved by the FDA in 1968 as an adjunct immunosuppressant for use in renal transplant recipients. It is available in oral and IV dosage forms.11 Prior to the advent of cyclosporine, the combination of azathioprine and corticosteroids was the mainstay of immunosuppressive therapy. Over the past 10 years, the use of azathioprine has declined markedly due in large part to the success of the MPA derivatives, which are more specific inhibitors of T cell proliferation. 

Traditional triple-therapy immunosuppressive regimens have consisted of a calcineurin inhibitor, an antiproliferative or ToR inhibitor, and corticosteroids. In recent years, many protocols have focused on corticosteroid sparing or avoidance. Avoidance or sparing of corticosteroids has been supported in the literature, although more studies are needed to better characterize which patients should follow these protocols.36-39... 

Corticosteroids have various effects on immune and inflammatory response systems, although their exact mechanism of immunosuppression is not fully understood. It is generally believed that at high doses, the agents are directly lymphotoxic, and at lower doses, the corticosteroids act by inhibiting the production of various cytokines that are necessary to amplify the immune response.11... 

Treatment Discontinue or minimize immunosuppressants Surgical, radiologic, or antineoplastic therapy Do not abruptly withdraw corticosteroids... 

Topical corticosteroids are employed in some cases of bacterial keratitis. The suppression of inflammation may reduce corneal scarring. However, local immunosuppression, increased ocular pressure, and reappearance of the infection are disadvantages to their use. There is no conclusive evidence that they alter clinical outcomes. If the patient is already on topical corticosteroids when the keratitis occurs, discontinue use until the infection is eliminated.19... 

Corticosteroids Prednisone (or equivalent) 50-100 mg daily 5-7 days 3-4 days 0.5-3 mg/dL Monitor for hyperglycemia, insomnia, immunosuppression. 

Corticosteroids (e.g., beclomethazone, flunisolide, triamcinolone) have anti-inflammatory and immunosuppressant actions. These drugs are used prophylactically to prevent the occurrence of asthma in patients with frequent attacks. Because they are not useful during an acute attack, corticosteroids are prescribed along with maintenance bronchodilators. These drugs are also administered by inhalation. Cromolyn is another anti-inflammatory agent used prophylactically to prevent an asthmatic attack. The exact mechanism of action of cromolyn is not fully understood however, it is likely to involve the stabilization of mast cells. This prevents the release of the inflammatory mast cell mediators involved in inducing an asthmatic attack. Cromolyn has proven effective in patients with exercise-induced asthma. 

Corticosteroids have antiinflammatory and immunosuppressive properties. They interfere with antigen presentation to T lymphocytes, inhibit prostaglandin and leukotriene synthesis, and inhibit neutrophil and monocyte superoxide radical generation. 

Infliximab is used for moderate to severe active Crohn s disease in patients failing immunosuppressive therapy, in those who are corticosteroid dependent, and for treatment of fistulizing disease. A single, 5 mg/kg infusion is effective when given every day for 8 weeks. Additional doses at 2 and 6 weeks following the initial dose results in higher response rates. Adalimumab is effective in 54% of patients with moderate to severe Crohn s disease who have lost response to infliximab. The typical dosage is 160 mg subcutaneously initially, followed by 80 mg subcutaneously at week 2, with subsequent doses of 40 mg subcutaneously every other week thereafter. 

Natalizumab was approved by the U.S. FDA for the treatment of MS in November 2004, and is being evaluated in Phase 3 clinical trials for IBD and CD.105 Based on Phase 3 clinical trials in MS patients, natalizumab appeared to be safe, since an increased rate of infection was not observed after 1 year of treatment.106 The safety of combined treatment with immunosuppressants, other than short courses of corticosteroids, was not evaluated and was not recommended because of the potential for an increased risk of infections. Flowever, barely three months after its approval, natalizumab was voluntarily withdrawn from the MS market by its manufacturer and all ongoing clinical trials were suspended due to the occurrence of a rare neurological disease, progressive multifocal leukoencephalopathy (PML), in 3 out of approximately 3,000 patients enrolled in clinical trials (2 in MS and 1 in CD).107 108 109... 

The impacts of contaminants on the structure of the immune system can be assessed by examining white blood cell (WBC) numbers and the mass and cellularity of immune organs, although these indicators are usually not as sensitive as measures of immune function. Avian immunotoxicity studies frequently assess total and (or) differential WBC counts [79], and immunosuppression can be indicated by reduced numbers of WBCs or elevated WBC numbers caused by recurrent infections. An elevated heterophil to lymphocyte ratio can indicate altered immune status in response to corticosteroid stress hormones or other factors [78,7 9], Exposure to lead shot or lead acetate has been shown to alter total and (or) differential WBC numbers in Japanese quail (Coturnix coturnix) and mallards [81-83], In western grebes (Aechmophorus occidentalis) from California, concentrations of mercury in the kidney were positively correlated with heterophil... 

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

Several types of immunosuppression have also been tried. Azathioprine alone was found to have no effect on PBC [82], but additional benificial effects were found in combination with ursodeoxychohc add and corticosteroids [78]. Cyclosporin showed some success, espe-dally in corticosteroid-resistant autoimmune hepatitis [83], but its use is generally considerably hmited by severe side-effects. Corticosteroids were effective in the management of several types of autoimmune chronic active hepatitis [84,85] and in the management of acute al-cohohc hepatitis [86]. Their use, however, has to be brief hi order to minimize side-effects. In the treatment of PBC, corticosteroids alone were found to be toxic and had only limited efficacy [77]. 

Corticosteroids do not heal illnesses, but they are widely used in various conditions when it is necessary to utilize their anti-inflammatory, immunosuppressant, and mineralo-corticoid properties. In addition, they are used in replacement therapy for patients who have adrenal insufficiency. Corticosteroids can be used in vital situations for asthma, severe allergic reactions, and transplant rejections. They are effective in noninfectious granulomatous diseases such as sarcoidosis, collagen vascular disease, rheumatoid arthritis, and leukemia. Steroids are used as lotions, ointments, etc. in treating a number of dermatological and ophthalmologic diseases. 

Immunosuppression During therapy, do not use live virus vaccines (eg, smallpox). Do not immunize patients who are receiving corticosteroids, especially high doses, because of possible hazards of neurological complications and a lack of antibody response. This does not apply to patients receiving corticosteroids as replacement therapy. 

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... 

Organ rejection, prophylaxis Prophylaxis of acute organ rejection in patients receiving renal transplants. It is used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids. 

---