IMMUNOSUPPRESSIVE DRUGS

• drugs that suppress, or reduce, the strength of

the body’s immune system.
• make the body less likely to reject a
transplanted organ
• These drugs are called anti-rejection drugs.
• treat autoimmune disorders
IMMUNOSUPPRESSIVE DRUG CATEGORIES

• Corticosteroid- prednisolone
• Calcineurin inhibitors- Tacrolimus,
Cyclosporine
• mTOR inhibitor- Sirolimus
• Inhibitors of nucleotide synthesis (IMDH
inhibitor)- Azathioprine, Mycophenolate acid
 Corticosteroids
• prevent production of cytokines and
vasoactive substances, including interleukin
(IL)–1, IL-2, IL-6, tumor necrosis factor-α,
chemokines, prostaglandins, major
histocompatibility class II, and proteases
• Azathioprine is a prodrug which is converted
to 6-mercaptopurine and metabolised to
cytotoxic thioguanine nucleotides which are
responsible for immunosuppression and
inhibiting DNA synthesis.
• Both cell-mediated and antibody-mediated
immune reactions are depressed.
 Cyclosporine
• agent is used for induction and maintenance
immunosuppression. It is a polypeptide of 11
amino acids of fungal origin and a prodrug
that binds to cyclophilin; complex inhibits
calcineurin phosphatase and T-cell activation
by dephosphorylation of inactive nuclear
factor of activated T cells (NF-AT). Therefore, it
prevents the production of IL-2 via calcineurin
inhibition.
• Tacrolimus
• Tacrolimus is a macrolide antibiotic and is
active against helper T cells, preventing the
production of IL-2 via calcineurin inhibition
• Sirolimus, also called rapamycin, is a macrolide product of a soil
fungus found on Easter Island. This agent is used for maintenance
immunosuppression and chronic rejection. Everolimus is a
rapamycin analog with a similar mechanism of action and adverse
effect profile.
• The mode of action of sirolimus is to bind the cytosolic protein-
FKBP12 in a way similar to tacrolimus. Unlike the tacrolimus-FKBP12
complex, which inhibits calcineurin, the sirolimus-FKBP12 complex
inhibits the mTOR pathway by directly binding the mTOR Complex1
(mTORC1). This complex inhibits signal 3 by stopping translation of
the RNA and preventing the progression from G1 phase to the S
phase of DNA synthesis. It also inhibits IL-2– and IL–4-dependent
proliferation of T and B cells.
 Mycophenolate acid
• inhibits the enzyme inosine monophosphate
dehydrogenase (IMDH; required for guanosine
synthesis) and impairs B- and T-cell
proliferation, sparing other rapidly dividing
cells (because of the presence of guanosine
salvage pathways in other cells). This agent is
used for maintenance immunosuppression and
chronic rejection.
• Cyclophosphamide is in the alkylating agent
and nitrogen mustard family of medications It
works by interfering with the duplication of
DNA and the creation of RNA.. Used to treat
autoimmune diseases