IMMUNOSUPPRESSIVE AGENTS

GLUCOCORTICOIDS (corticosteroids)

• The first hormonal agents  lympholytic properties

• Reduces the size and lymphoid content of the lymph
nodes and spleen
• Interfere with the cell cycle of activated lymphoid cells
• modulate allergic reactions
• Treatment of diseases like asthma
• Premedication for other agents (eg, blood products,
chemotherapy)
• Firstline immunosuppressive therapy for both solid
organ and hematopoietic stem cell transplant
 CALCINEURIN INHIBITORS:
Cyclosporine
• An immunosuppressive agent with efficacy in human
organ transplantation
• binds to cyclophilin  inhibits the gene
transcription of IL-2, IL-3, IFN-γ, and other factors
produced by antigen-stimulated T cells
• Intravenously or orally, though it is slowly and
incompletely absorbed (20–50%)
• Metabolized by the P450 3A enzyme
 Cyclosporine (2)

• Toxicities : nephrotoxicity, hyperten- sion,

hyperglycemia, liver dysfunction, hyperkalemia,
altered mental status, seizures, and hirsutism
• May be used alone or in combination
• For autoimmune disorders: uveitis, rheumatoid
arthritis, psoriasis, and asthma.
 CALCINEURIN INHIBITORS:
Tacrolimus
• An immunosuppressant macrolide antibiotic
produced by Streptomyces tsukubaensis
• Binds to FK-binding protein (FKBP)
• 10–100 times more potent than cyclosporine in
inhibiting immune responses
• For organ and stem cell transplantation
• Orally or intravenously
• Metabolized primarily by P450 enzymes in the liver
 Tacrolimus (2)

• Toxic effects : nephrotoxicity, neurotoxicity,

hyperglycemia, hypertension, hyper- kalemia, and
gastrointestinal complaints.
• Tacrolimus ointment :therapy of atopic dermatitis
and psoriasis
Mechanism of action of cyclosporine and tacrolimus
 MAMMALIAN TARGET OF RAPAMYCIN (mTOR)
INHIBITORS

• Sirolimus (rapamycin) as well as its analogs (called

“rapalogs”) such as everolimus and temsirolimus
• An immunosuppressant macrolide antibiotic
produced by Streptomyces hygroscopicus
• Effectively alone and in combination to prevent
rejection of solid organ allografts
• Sirolimus is available as an oral drug
• Topical sirolimus is also used in some dermatologic
disorder
• Toxicities : myelosuppression (especially
thrombocytopenia), hepatotoxicity, diarrhea,
hypertriglyceridemia, pneumonitis, and headache
Mechanism of action of sirolimus
 MYCOPHENOLATE MOFETIL

• Prodrug: is hydrolyzed to mycophenolic acid

• Isolated from the mold Penicillium glaucus
• Available in both oral and intravenous forms
• For solid organ transplant patients for refractory
rejection
• Toxicities: gastrointestinal disturbances (nausea and
vomiting, diarrhea, abdominal pain) headache,
hypertension, and reversible myelosuppression
(primarily neutropenia)
Mechanisme of action mycophenolate mofetil