Transplant rejection immunosuppression

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. 

Answer Cyclosporine is an immunosuppressant drug used to prevent transplant rejections. Though an oral formulation is available, it has low bioavailability (very httle reaches the systemic circulation as intact drug). Diltiazem will inhibit cytochrome P450 3A4 in the gut. CYP3A4 is the... 

Cyclosporine (Sandimmune) is a potent inhibitor of antibody- and cell-mediated immune responses and is the immunosuppressant of choice for the prevention of transplant rejection. It also has application in the treatment of autoimmune diseases. 

The first monoclonal antibody—OKT3 or Orthoclone—was designed to be immunosuppressive and to reduce the likelihood of transplant rejection. Now monoclonal antibodies are used to treat a wide range of diseases, including arthritis, certain kind of cancers, and microbial and viral infections. 

Organ transplants Prevention and treatment of rejection (immunosuppression)... 

Some drugs are designed to specifically interfere with the immune system, to protect against transplant rejection. These are immunosuppressive drugs such as cyclosporin and rapamycin. Cyclosporin interferes with the maturation of T and B cells. 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

Antibodies that block the interleukin-2 receptor, thus preventing interleukin-2 from activating T lymphocytes, have also been developed.24,62 These antiinterleukin-2 receptor agents, such as basiliximab (Simulect) and daclizumab (Zenapax), may be helpful in reducing the incidence of acute transplant rejection.13 Antibodies seem to be especially useful in the initial (induction) phase of antirejection treatment because these drugs can delay or supplant the use of more toxic immunosuppressants such as the glucocorticoids and calcineurin inhibitors (cyclosporine and tacrolimus).3,56... 

Sirolimus (Rapamycin, Rapamune ), a natural macrocyclic lactone, is a potent immunosuppressive agent. It was developed by Wyeth-Ayerst Laboratories (Philadelphia, Pennsylvania, U.S.A.) and approved by the Food and Drug Administration for the prophylaxis of renal transplant rejection in 1999 (28,29). Sirolimus has its roots in Easter Island, where an actinomycete streptomyces hygroscopicus was found that produced a novel macrolide antibiotic with potent antibiotic, potent antifungal, immunosuppressive, and antimitotic activities. 

Rapamycin (Rapamune, Wyeth-Ayerst Laboratories) is a natural macrocyclic lactone with a potent immunosuppressive and antiproliferative effect that was approved by the Food and Drug Administration for the prophylaxis against renal transplant rejection,... 

Easter Island (Rapa Nui) first discovered and characterized by Sehgal in 1975 (38), Initially identified as an antifungal agent, the compound was subsequently found to posses potent immunosuppressive activities, initially demonstrated through its ability to prevent adjuvant-induced arthritis and experimental allergic encephalomyelitis in rodent models. As a potent immunosuppressive agent, sirolimus has been developed and marketed by Wyeth Pharmaceuticals for the prevention of renal transplant rejection (Rapamune ) (39). 

Immunosuppression or enhancement can be associated with two distinct groups (1) Drugs intended to modulate immune function for therapeutic purposes (e.g. to prevent organ transplant rejection) where adverse immunosuppression can be considered exaggerated pharmacodynamics. (2) Drugs not intended to affect immune function but cause immunotoxicity due, for instance, to necrosis or apoptosis of immune cells or interaction with cellular receptors shared by... 

Drug-mediated suppression of transplant rejection entails long-term treatment. Protracted immunosuppression carries an in-Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

Sirolimus (rapamycin) is another macrolide, produced by Streptomyces hydroscopi-cus. Its immunosuppressant action, evidently, does not appear to involve inhibition of calcineurin. It forms a complex with the FK protein, imparting a special conformation on it and the complex then inhibits the mTOR (mammalian target of rapamycin) phosphatase. The latter operates in the signaling path leading from the interleukin-2 receptor to activation of mitosis in lymphocytes. Thus, sirolimus inhibits lymphocyte proliferation. It is approved for the prevention of transplant rejection. 

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