immunosupressants

Question 1

AZATHIOPRINE

Answer 1

Azathioprine is a prodrug of mercaptopurine and, like mercaptopurine, functions as an antimetabolite. Although its
action is presumably mediated by conversion to mercaptopurine and
further metabolites
SAME MAO

Question 2

AZATHIPRINE WITH ALLUPURINOL

KINETICS

Answer 2

Azathioprine is well absorbed from the gastrointestinal tract and is metabolized primarily to mercaptopurine. Xanthine oxidase
converts much of the active material to 6-thiouric acid prior to
excretion in the urine.

inactivation depends on xanthine oxidase
for control of hyperuricemia should have the dose of azathioprine reduced to onefourth to one-third the usual amount to prevent excessive to

Question 3

AZATHIOPRINE CAUSES LYMPHOID CELL PROLIFERATION INTEREFERENCE

Answer 3

Azathioprine and mercaptopurine appear to produce immunosuppression by interfering with purine nucleic acid metabolism at
steps that are required for the wave of lymphoid cell proliferation
that follows antigenic stimulation. The purine analogs are thus
cytotoxic agents that destroy stimulated lymphoid cells
. Although
continued messenger RNA synthesis is necessary for sustained
antibody synthesis by plasma cells
these analogs appear to have
less effect on this process than on nucleic acid synthesis in proliferating cells. Cellular immunity as well as primary and secondary
serum antibody responses can be blocked by these agents.

Question 4

also used in

Answer 4

rheumatoid arthritis, Crohn’s Syndrome, glomerulonephritis

Question 5

side effects of azathioprine

Answer 5

The chief toxic effect of azathioprine and mercaptopurine is
bone marrow suppression, usually manifested as leukopenia,
although anemia and thrombocytopenia may occur. Skin rashes,
fever, nausea and vomiting, and sometimes diarrhea

Question 6

use of cyclosporine

Answer 6

successfully as the sole immunosuppressant for cadaveric transplantation of the kidney, pancreas, and liver, and it has proved
extremely useful in cardiac transplantation as well.
supress organ rejection after transplant.
In combination
with methotrexate, cyclosporine is a standard prophylactic regimen
to prevent GVH disease after allogeneic stem cell transplantation.
Cyclosporine has also proved useful in a variety of autoimmune
disorders, including uveitis, rheumatoid arthritis, psoriasis, and
asthma

Question 7

MAO OF CYCLOSPORINE

Answer 7

Cyclosporine is a peptide antibiotic that appears to act at
an early stage in the antigen receptor-induced differentiation of
T cells and blocks their activation. Cyclosporine binds to cyclophilin,
a member of a class of intracellular proteins called immunophilins.
Cyclosporine and cyclophilin form a complex that inhibits, calcineurin, which is necessary for the
activation of a T-cell-specific transcription factor. This transcription factor, NF-AT, is involved in the synthesis of interleukins (eg,
IL-2) by activated T cells. In vitro studies have indicated that
cyclosporine inhibits the gene transcription of IL-2, IL-3, IFN-γ,
and other factors produced by antigen-stimulated T cells

Question 8

SIDE EFFECTS OF CYCLOSPORINE

Answer 8

nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered
mental status, seizures, and hirsutism.