L16 - Immunosuppresive and immunomodulatory drugs

Question 1

Give three examples of glucocorticoid

Answer 1

Prednisone, prednisolone and methyprednisolone

Question 2

What are the rapid effect of glucocorticoid

Answer 2

Rapid: produce a rapid, transient reduction in peripheral blood lymphocyte

Question 3

What are the slow effects of glucocorticoid

Answer 3

Slow: Reduce the size and lymphoid content of the lymph nodes and spleen
Inhibit T cell poliferation, t cell dependent immunity and cytokine

Question 4

What is the mode of action of glucocorticoid

Answer 4

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

Question 5

What are the clinicl use of glucocorticoid

Answer 5

GVHD following BMT

combined with other immunosuppressive agents to prevent transplant rejection

Question 6

Give two examples of calcenurin inhibitors

Answer 6

Cyclosporin

Tacrolimus

Question 7

What is the role of calcenurin in normal cells

Answer 7

Activation of T cell receptor -> Influx of calcium ions -> activation of calcineurin -> Production of nuclear factors -> Synthesis of interleukin 2

Question 8

What are the pharmalogical properities of calcenurin inhibitors

Answer 8

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

Question 9

What is the mode of action of cyclosporin

Answer 9

It binds onto cyclophilin

Question 10

What is the mode of action of tacrolimus

Answer 10

It binds onto TKBP

Question 11

What is the pharmacological property of cyclosporin

Answer 11

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

Question 12

What is the pharmacologcial of tacrolimus

Answer 12

It is 10-100 times more potenet

Question 13

What is the clinical usage of cyclosporin and tacrolimus

Answer 13

Cyclosporin - first line therapy in the prophylaxis and treatment of transplantation rejection
Tacrolimus - preventing rejection in solid organ transplant; GVHD when used in combination

Question 14

Give two examples of poliferating signal inhibitors

Answer 14

Sirolimus

Everolimus

Question 15

What is the pharmacological properties of poliferating signal inhibitors

Answer 15

Bioavailability only 15%
Metabolised by CYP3A4
Side effect - hyperlipidemia, myelosuppresant

Question 16

What is the mode of action of PSI

Answer 16

It inds to FKBP and inhibit mTOR. This inhibit the poliferation of T cell at G1 phase

Question 17

What is the clinical use of PSI

Answer 17

Use to prevent rejection of olid organ allografts

Used in combination with cyclosporin but with more nephrotoxicity

Question 18

Give two examples of antimetabolites and cytotoxic drugs

Answer 18

Azathioprine

Mycophenolate mofetil

Question 19

What is the pharmacological properties of azathioprine

Answer 19

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

Question 20

What is the mode of azathioprine

Answer 20

AZA-> 6-MP -> thio-IMP -> thio-GMP -> thio-GTP -> inhibit DNA synthesis

Question 21

What is the clinical use of azathioprine

Answer 21

Prevents transplant rejection

Treats autoimmune disease (Severe refractory rheumatoid arthritis)

Question 22

What is the pharmacological property of mycophenolate mofetil

Answer 22

An antimetabolite which have replaced azathioprine

Question 23

What is the mode of action of mycophenolate mofetil

Answer 23

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

Question 24

What is the clinical use of MMF

Answer 24

Prolong graft survival