Antibiotics immunosuppressive action

Rapamycin (sirolimus), a macrolide antibiotic, has been used recently in organ transplantation for its potent immunosuppressive actions by inhibiting both cytokine mediated and growth factor mediated proliferation of smooth muscle cells and lymphocytes [55, 56]. In the RAVEL trial of non-acute single vessel lesions, the Sirolimus-eluting stent was compared to bare metal stent (BMS) in a 1 1 fashion [57]. One-year major adverse cardiovascular events and 6 month neointimal proliferation as assessed by late luminal loss (-0.01 0.33 mm in Sirolimus stent versus 0.80 0.53 mm in BMS) were improved. The Sirolimus-eluting stent thus virtually eliminated in-stent restenosis with no evidence of edge effect, dissection, or in-stent thrombosis. 

Tacrolimus, another antibiotic with immunosuppressant actions, does not bind to cyclophilin, but acts similarly to cyclosporine to inhibit caldneurin. 

Thiamphenicol is a chemical analogue of chloramphenicol with a rather low in vitro performance against many pathogens, including Salmonellae and E. coli. Though the antibiotic possesses haematotoxic properties and also has a pronounced immunosuppressive action, proven cases of thiamphenicol-induced fatal bone marrow aplasia have not so far been recorded. 

Mercaptopurine [6-MP] (Purinethol) [Antineoplastic/ Antimeta lite] Uses Acute leukemias, 2nd-line Rx of CML NHL, maint ALL in children, immunosuppressant w/ autoimmune Dzs (Crohn Dz) Action Antimetabolite, mimics hypoxanthine Dose Adults. 80-100 mg/mVd or 2.5-5 mg/kg/d maint 1.5-2.5 mg/kg/d Peds. Per protocol X w/ renal/hepatic insuff on empty stomach Caution [D, ] Contra Severe hepatic Dz, BM suppression, PRG Disp Tabs SE Mild hematotox, mucositis, stomatitis, D rash, fever, eosinophilia, jaundice. Hep Interactions T Effects W/ allopurinol T risk of BM suppression W/ trimethoprim-sulfamethoxazole X effects OF warfarin EMS May falsely T glucose OD May cause NA and liver necrosis symptomatic and supportive Meropenem (Merrem) [Antibiotic/Carbapenem] Uses lntra-abd Infxns, bacterial meningitis Action Carbapenem X cell wall synth, a [3-lactam Dose Adults. 1 to 2 g IV q8h Peds. >3 mo, <50 kg 10-40 mg/kg IV q 8h in renal insuff Caution [B, ] Contra [3-Lactam sensitivity Disp Inj 500 mg, 1 g SE Less Sz potential than imipenem D, thrombocytopenia Interactions T Effects W/ probenecid EMS Monitor for signs of electrolyte disturbances and... 

Although it is not chemically related to cyclosporine, tacrolimus (6.7) has a similar mechanism of action. Tacrolimus is an immunosuppressant macrolide antibiotic derived from Streptomyces tsukubaenis. Like cyclosporine, tacrolimus inhibits the same cytoplasmic phosphatase, calcineurin, which catalyzes the activation of a T-cell-specific transcription factor (NF-AT) involved in the biosyntheses of interleukins such as IL-2. Sirolimus (6.8) is a natural product produced by Streptomyces hydroscopicus, it blocks the ability of T cells to respond to cytokines. 

Tacrolimus (FK 506) is an immunosuppressant macrolide antibiotic produced by Streptomyces tsukubaensis. It is not chemically related to cyclosporine, but their mechanisms of action are similar. Both drugs bind to cytoplasmic peptidyl-prolyl isomerases that are abundant in all tissues. While cyclosporine binds to cyclophilin, tacrolimus binds to the immunophilin FK-binding protein (FKBP). Both complexes inhibit calcineurin, which is necessary for the activation of the T-cell-specific transcription factor NF-AT. 

Cyclospasmol cyclandelate. cyclosporin [ban] (ciclosporin [inn.jan] cyclosporine [usan] cyclosporin A Neoral Sandimmune ) is a cyclic polypeptide ANTIBIOTIC, possessing IMMUNOSUPPRESSIVE properties (with a specific action on T-lymphocytes). It also has ANTIFUNGAL activity and can be used clinically as an immunosuppressant after transplant surgery, and to treat severe autoimmune diseases including rheumatoid arthritis, cyclosporin A cyclosporine, cyclothiazide [ban. inn. usan] is a (thiazide) diuretic which can be used in ANTIHYPERTENSIVE therapy, cyclovalone [inn] (DVC) is a cyclohexanone, a choleretic... 

Sirohmus (SRL), also known as rapamycin, is another immunosuppressive macrolide antibiotic that is structurally similar to TAG. It represents the first in the newest class of immunosuppressants, with a unique mechanism of action. The potential of SRL to decrease the incidence of chronic rejection remains to be seen. 

This section covers compounds that were reported relatively recently. The mechanism of action of these compounds is reasonably understood. The compounds in this section have been sorted by their biological activity and their potential utility in the clinic. The class of compounds include immunosuppressants (rapamycin and FK506), antitumor agents (geldanamycin to echinomycin), antiinflammatory agents (efomycin), antiobesity agents (lipstatin), and antibiotics (streptogramins to platensimycin). 

FK506 (tacrolimus), a natural product of Streptomyces tukubaensis, is a 23-membered macrolide antibiotic that contains a unique hemiketal-masked, a,P-diketo amide moiety (Fig. 1) [1]. It has a mode of action and toxicity profile similar to those of cyclosporin A (CsA), an immunosuppressive cyclic undecapeptide produced by Tolypocladium inflatum (Fig. 1), which has been used clinically for two decades to prevent rejection on transplantation of organs, such as kidney, heart, liver, and bone marrow. The use of CsA has led to a remarkable increase of survival of all organ allografts and has fueled a dramatic increase in the number of kidney, liver, cardiac, and bone marrow transplants [2]. Thus, CsA has revolutionized transplantation surgery, both in terms of efficiency and quality of life of the patient. FK506 is said to be a more potent immunosuppressant than CsA and was approved for the treatment and prevention of kidney transplant rejection. 

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