Pharmacology immunosuppressants

Barshes NR, Goodpastor SE, Goss JA. Pharmacologic immunosuppression. Front Biosci. 2004 9 411-420. 

Thiirane is more bactericidal than oxirane, and derivatives of 2-mei captomethylthiirane inhibit tuberculosis. The following pharmacological uses have been reported for compounds derived from thiirane derivatives gold complexes of the adducts of diethylphosphine and thiirane (antiarthritic), adducts of thiiranes and malononitrile (antibacterial, blood vessel dilators, muscle relaxants, sedatives), thermolysis products of thiirane 1-oxides and adducts of thiirane 1-oxides with sulfenyl chlorides (antibacterial), adducts of 2,3-diarylthiirene 1,1-dioxides with ynamines (antibacterial, parasiticidal), adducts of 2,3-diarylthiirene 1,1-dioxides with enamines (antifertility), adducts of p-aminophenylacetic esters with thiirane (immunosuppressants), adducts of amines and thiiranes (radioprotective drugs). 

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].. 

Pharmacology Tacrolimus is a macrolide immunosuppressant that prolongs the survival of the host and transplanted graft and inhibits T-lymphocyte activation, although the exact mechanism of action is not known. 

Pharmacology Sirolimus, a macrolide immunosuppressive agent, inhibits both T-lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (interleukin-2, -4, and -15) stimulation and also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK binding protein-12 (FKBP-12), to generate an immunosuppressive complex. 

Pharmacology Daclizumab is an immunosuppressive, humanized IgGI monoclonal antibody produced by recombinant DNA technology that binds specifically to the alpha subunit (Tac subunit) of the human high-affinity interleukin-2 (IL-2) receptor that is expressed on the surface of activated lymphocytes. Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. 

Pharmacology Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. The mechanism of action of tacrolimus in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. Pharmacokinetics ... 

Two molecular mechanisms for the interactions have been established. First, both hypericin and hy-perforin, two of the pharmacologically active constituents of the herb, cause induction of the enzyme CYP3A4 which is responsible for much of the metabolism of many commonly used drugs. Giving SJW to patients also taking the immunosuppressant, cyclosporine, which is metabolized primarily by CYP3A4, has led to near-rejection of transplanted organs as cyclosporine plasma concentrations fell due to increased metabolism. The same mechanism has led to reduced efficacy of indinavir in patients... 

Del Tacca M. Prospects for personalized immunosuppression pharmacologic tools - a review. Transplant Proc 2004 36(3) 687-9. 

The present primary mode of therapy for these diseases involves the use 5-amino-salicylate (5-ASA) products. Often patients require additional medications, including corticosteroids, to help induce remission and various immune modulators, such as azathioprine, 6-mercaptopurine or methotrexate, to maintain remission. In Crohn s disease certain antibiotics, such as metronidazole and ciprofloxacin, and infliximab Remi-cade), an anti-tumor necrosis factor-a(TNFa) antibody, also have been used. The pharmacology of antibiotics, immunosuppressive drugs, and corticosteroids is discussed in Chapters 43,57, and 60, respectively. 

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