Cyclosporine in organ transplantation

Morales JM, Munoz MA, Fernandez Zatarain G, Garcia Canton C, Garcia Rubiales MA, Andres A, Aguado JM, Gonzalez Pinto I. Reversible acute renal failure caused by the combined use of foscarnet and cyclosporin in organ transplanted patients. Nephrol Dial Transplant 1995 10(6) 882-3. 

Mycophenolic acid, formed from mycophenolate mofetil, inhibits inosine monophosphate dehydrogenase in the de novo pathway of purine synthesis. This action suppresses both B and T lymphocyte aetivation. Mycophenolate mofetil is used both individually and in eombination with cyclosporine in organ transplants. The answer is (C). 

These are the agents used to suppress the immunity. The drugs like azathioprine and cyclosporin A are used chiefly to prevent rejection in organ transplantation. They are also used for treatment of autoimmune disease. 

Goa KL. Cyclosporin an updated review of the pharmacokinetic properties, clinical efficacy and tolerability of a microemulsion-based formulation (neoral)l in organ transplantation. Drugs. 2001 61 1957-2016. 

The immunomodulator cyclosporin was originally isolated from a soil fungus, Trichoderma polysporum (see Chapter 40). This compound was a major breakthrough for organ transplantation, because it suppressed immunological rejection of the transplanted organ. Tacrolimus (FK-506), a secondary metabolite of Streptomyces tsukabaensis, was approved in 1994 for use as an immunosuppressant in organ transplantation (De Smet, 1997). 

Several of these bioactive natural products have been successfully developed as therapeutics for clinical use. For example, Cyclosporin A is a fungal decapeptide principally used to suppress immune rejection in organ transplant patients. Mevinolin and compatin both control cholesterol synthesis in human. The search for enzyme- or receptor-targeted microbial products does not limit itself to medical use. Several commercially important antibiotics such as Nikkomycin and Avermectin have been found for agricultural applications in recent years. 

Oellerich M, Armstrong VW, Kahan B et al. Lake Louise Consensus Conference on cyclosporin monitoring in organ transplantation Report of the consensus panel. Ther Drug Monit 1995 17 642-54. 

Cyclosporine is an endecapeptide isolated from fungi. It is an immunosuppressive used to prevent rejection in organ transplantation. Studies have been carried out to investigate the effectiveness of inhalation of this compound in patients receiving lung transplants. Very rapid peak plasma levels were observed followed by a slow phase but the interpretation of this behavior is compromised by the low aqueous solubility of this compound. ... 

Azurdia RM, Graham RM, Weismann K, Guerin DM, Parslew R. Acne keloidalis in Caucasian patients on cyclosporin following organ transplantation. Br J Dermatol 2000 143(2) 465-7. 

Capone D, Aiello C, Santoro GA, Gentile A, Stanziale P, D Alessandro R, Imperatore P, Basile V. Drug interaction between cyclosporine and two antimicrobial agents, josa-mycin and rifampicin, in organ-transplanted patients. Int J Clin Pharmacol Res 1996 16(2-3) 73-6. 

At much lower concentrations still, below the cmc, both single- and doublechain cationic surfactants do not destroy cells. Radio-labelling studies show that the process of adsorption follows a Langmuir isotherm, i.e it is a physicochemical effect. At concentrations 10 to 100 times lower than the cmc, these surfactants are potent immunosuppressants [48, 49], as potent or more than cyclosporin A, the drug of choice in organ transplants. 

Bantle JP, Pallet MS, Boudreau RJ, Ollvarl MT, Ferris TF. Long-term effects of cyclosporine on renal function in organ transplant recipients. J Lab Clin Med 1990 115 233-240. 

Immunosuppressants are drugs capable of suppressing immune responses. They are used to treat autoimmune disease, aUergy, multiple myeloma, and chronic nephritis, and in organ transplantation. For example, immunosuppressants that are used to provide maintenance immunosuppression in solid organ and bone marrow transplant patients include cyclosporine, everoHmus (Ever), mycophe-nolic acid (MPA), Siro, and Tac (Figure 33-13). 

Misoprostol may also prove useful in the treatment of postpartum hemorrhage and has also been used in organ transplantation. For example, it has been reported to improve kidney function in cyclosporin-treated patients who have received renal transplants (334). 

The interaction between ketoconazole and cyclosporine has been exploited in order to reduce drug costs associated with administration of cyclosporine following organ transplantation. Relative to ketoconazole and itraconazole, fluconazole appears to be intermediate in its ability to inhibit human cytochromes P450. The magnitude of fluconazole-induced inhibition of cyclosporine metabolism appears, however, to depend on the dosage of fluconazole. 

KT Kivisto, et al. Therapeutic cyclosporine monitoring. Comparison of radioimmunoassay and high performance liquid chromatography methods in organ transplant recipients. Ther Drug Monit 12 353, 1990. 

The efficacy of tacrolimus as a primary immunosuppressant for the prophylaxis of rejection and for rescue therapy following failure of conventional cyclosporin-based rejection prophylaxis has been demonstrated in numerous clinical studies in adults and pediatrics using various types of combination therapy since 1989. Tacrolimus is now well established not only as a primary immunosuppressant in organ transplantation but also an excellent rescue agent for patients experiencing posttransplant rejection while on cyclosporin-based regimens [44]. 

Cyclosporine is effective in organ transplantation. The immunosuppressant action of the drug appears to be due to... 

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