118 SEC TION II IMMUNOLOGY ‘ IMMUNOLOGY—IMMUNOSUPPRESSANTS

‘ IMMUNOLOGY—IMMUNOSUPPRESSANTS

Immunosuppressants Agents that block lymphocyte activation and proliferation. Reduce acute transplant rejection by
suppressing cellular immunity (used as prophylaxis). Frequently combined to achieve greater
efficacy with r toxicity. Chronic suppression q risk of infection and malignancy.

CD4 Basiliximab
–

FKBP +
CD3 Tacrolimus FKBP + Azathioprine
TCR IL-2R
Sirolimus
– (rapamycin)
Cyclophilin + 6–MP
– Mycophenolate
Cyclosporine – Calcineurin

NFAT–P NFAT mTOR –

–
PRPP
IMP amidotransferase
dehydrogenase
Proliferation
Glucocorticoids genes
Purine
T HELPER – – nucleotides
CELL
NF–κB De novo
T Inflammatory purine
NFA
cytokine genes synthesis
DNA replication

DRUG MECHANISM INDICATIONS TOXICITY NOTES

Cyclosporine Calcineurin inhibitor; Psoriasis, rheumatoid Nephrotoxicity,
binds cyclophilin arthritis hypertension,
Blocks T-cell activation hyperlipidemia,
by preventing IL-2 neurotoxicity, gingival Both calcineurin
transcription hyperplasia, hirsutism inhibitors are
highly nephrotoxic,
Tacrolimus (FK506) Calcineurin inhibitor; Immunosuppression Similar to cyclosporine, especially in higher
binds FK506 binding after solid organ q risk of diabetes doses or in patients
protein (FKBP) transplant and neurotoxicity; with r renal function
Blocks T-cell activation no gingival
by preventing IL-2 hyperplasia or
transcription hirsutism
Sirolimus (Rapamycin) mTOR inhibitor; binds “Pansirtopenia” Kidney “sir-vives.”
FKBP (pancytopenia), Synergistic with
Kidney transplant insulin resistance, cyclosporine
Blocks T-cell
rejection prophylaxis hyperlipidemia; Also used in drug-
activation and B-cell
specifically not nephrotoxic eluting stents
differentiation by
preventing response Sir Basil’s kidney
to IL-2 transplant

Basiliximab Monoclonal antibody; Edema, hypertension,

blocks IL-2R tremor

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 IMMUNOLOGY ‘ IMMUNOLOGY—IMMUNOSUPPRESSANTS SEC TION II 119

Immunosuppressants (continued)
DRUG MECHANISM INDICATIONS TOXICITY NOTES
Azathioprine Antimetabolite Rheumatoid arthritis, Pancytopenia 6-MP degraded by
precursor of Crohn disease, xanthine oxidase;
6-mercaptopurine glomerulonephritis, toxicity q by
Inhibits lymphocyte other autoimmune allopurinol
proliferation by conditions Pronounce “azathio-
blocking nucleotide purine”
synthesis
Mycophenolate Reversibly inhibits Glucocorticoid-sparing GI upset, Associated with
mofetil IMP dehydrogenase, agent in rheumatic pancytopenia, invasive CMV
preventing purine disease hypertension infection
synthesis of B and T Less nephrotoxic and
cells neurotoxic
Glucocorticoids Inhibit NF-κB Many autoimmune Cushing syndrome, Demargination
Suppress both B- and and inflammatory osteoporosis, of WBCs causes
T-cell function by disorders, adrenal hyperglycemia, artificial leukocytosis
r transcription of insufficiency, asthma, diabetes, amenorrhea, Adrenal insufficiency
many cytokines CLL, non-Hodgkin adrenocortical may develop if drug is
Induce T cell apoptosis lymphoma atrophy, peptic ulcers, stopped abruptly after
psychosis, cataracts, chronic use
avascular necrosis
(femoral head)

Recombinant cytokines and clinical uses

CYTOKINE AGENT CLINICAL USES
Bone marrow stimulation
Erythropoietin Epoetin alfa (EPO analog) Anemias (especially in renal failure)
Associated with q risk of hypertension,
thromboembolic events
Colony stimulating Filgrastim (G-CSF), sargramostim (GM-CSF) Leukopenia; recovery of granulocyte and
factors monocyte counts
Thrombopoietin Romiplostim (TPO analog), eltrombopag (think Autoimmune thrombocytopenia
“elthrombopag.” TPO receptor agonist) Platelet stimulator
Immunotherapy
Interleukin-2 Aldesleukin Renal cell carcinoma, metastatic melanoma
Interferons IFN-α Chronic hepatitis C (not preferred) and B, renal
cell carcinoma
IFN-β Multiple sclerosis
IFN-γ Chronic granulomatous disease

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