All of the following are true statements EXCEPT:
Tacrolimus (FK506)- It is a newer immunosup- pressant chemically different from cyclosporine, but having the same mechanism of action, and is -100 times more potent. It binds to a different cytoplasmic immunophilin protein labelled 'FKBP', but the subsequent steps are the same, i.e. inhibition of helper T cells calcineurin. Tacrolimus is administered orally as well as by i.v. infusion. Oral absorption is variable and decreased by food. It is metabolized by CYP3A4 Section 14 and excreted in bile with a longer tlh of 12 hour. Therapeutic application, clinical efficacy as well as toxicity profile are similar to cyclosporine. It is paicularly valuable in liver transplantation because its absorption is not dependent on bile. Because ofmorepotentaction, itis also suitable for suppressing acute rejection that has set in. Hypeension, hirsutism and gum hyperplasia are less marked than cyclosporine, but tacrolimus is more likely to precipitate diabetes, cause neurotoxicity, alopecia and diarrhoea. Dose limiting toxicity renal toxity. Mycophenolate mofetil- Prodrug of mycophenolic acid which selectively inhibits inosine monophosphate dehydrogenase an enzyme essential for the de novo synthesis of guanosine nucleotides in the T and B cells (these cells, unlike others, do not have the purine salvage pathway). Lymphocyte prolife- ration, antibody production and cell-mediated immunity are inhibited. As 'add on' drug to cyclosporine + glucocoicoid in renal transplan- tation, it has been found as good or even superior to azathioprine, but should not be combined with azathioprine. It can help to reduce the dose of cyclosporine and thus its toxicity. Vomiting, diarrhoea, leucopenia and predisposition to CMV infection, g.i. bleeds are the prominent adverse effects. ESSENTIAlS of MEDICAL PHARMACOLOGY SIXTH EDITION -KD TRIPATHI Page 853
Sirolimus acts by inhibiting the action of 1L-2
Tacrolimus inhibits calcineurin pathway
Mycophenolate acts by inhibiting GMP dehydrogenase
Cyclosporince is an integeral component of transplant rejection regimen
Immunomodulators