L16 - Immunosuppresive and immunomodulatory drugs Flashcards
Give three examples of glucocorticoid
Prednisone, prednisolone and methyprednisolone
What are the rapid effect of glucocorticoid
Rapid: produce a rapid, transient reduction in peripheral blood lymphocyte
What are the slow effects of glucocorticoid
Slow: Reduce the size and lymphoid content of the lymph nodes and spleen
Inhibit T cell poliferation, t cell dependent immunity and cytokine
What is the mode of action of glucocorticoid
The activated receptor formed a dimer
The binding to glucocorticosteroid response elements stimulate or inhibit the activity of an adjacent promoter which initiates or inhibit transcription of a gene
What are the clinicl use of glucocorticoid
GVHD following BMT
combined with other immunosuppressive agents to prevent transplant rejection
Give two examples of calcenurin inhibitors
Cyclosporin
Tacrolimus
What is the role of calcenurin in normal cells
Activation of T cell receptor -> Influx of calcium ions -> activation of calcineurin -> Production of nuclear factors -> Synthesis of interleukin 2
What are the pharmalogical properities of calcenurin inhibitors
Highly specific to T cell production with little effect on B cell
T cell dependent limb of antibody production is inhibited by preventing B cell to mature into plasma cell
What is the mode of action of cyclosporin
It binds onto cyclophilin
What is the mode of action of tacrolimus
It binds onto TKBP
What is the pharmacological property of cyclosporin
It has a low bioavailability and can be improved by the microemulsive form
It is rapidly distributed except in area of CSF
It is metabolised by CYP3A4 and excreted in bile
What is the pharmacologcial of tacrolimus
It is 10-100 times more potenet
What is the clinical usage of cyclosporin and tacrolimus
Cyclosporin - first line therapy in the prophylaxis and treatment of transplantation rejection
Tacrolimus - preventing rejection in solid organ transplant; GVHD when used in combination
Give two examples of poliferating signal inhibitors
Sirolimus
Everolimus
What is the pharmacological properties of poliferating signal inhibitors
Bioavailability only 15%
Metabolised by CYP3A4
Side effect - hyperlipidemia, myelosuppresant
What is the mode of action of PSI
It inds to FKBP and inhibit mTOR. This inhibit the poliferation of T cell at G1 phase
What is the clinical use of PSI
Use to prevent rejection of olid organ allografts
Used in combination with cyclosporin but with more nephrotoxicity
Give two examples of antimetabolites and cytotoxic drugs
Azathioprine
Mycophenolate mofetil
What is the pharmacological properties of azathioprine
It is a pro drug of 6-MP
It is metabolised and excreted in kidney
It can cause bone marrow suppresion, G.I. toxicity and cholestasis
What is the mode of azathioprine
AZA-> 6-MP -> thio-IMP -> thio-GMP -> thio-GTP -> inhibit DNA synthesis
What is the clinical use of azathioprine
Prevents transplant rejection
Treats autoimmune disease (Severe refractory rheumatoid arthritis)
What is the pharmacological property of mycophenolate mofetil
An antimetabolite which have replaced azathioprine
What is the mode of action of mycophenolate mofetil
It is a prodrug for mycophenolic acid
Since t and b lymphocyte has no salvage pathway, there will be no production when there is mycophenolate mofetil
What is the clinical use of MMF
Prolong graft survival
