Which medications in the drug class Immunosuppressants are used in the treatment of Sarcoidosis?

Updated: Sep 15, 2020
  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Answer

Immunosuppressants

These agents may be of benefit in patients whose conditions have not responded to steroids or in patients unable to tolerate prednisone.

Chlorambucil (Leukeran)

Chlorambucil is a bifunctional slow-acting aromatic nitrogen mustard derivative that interferes with DNA replication, transcription, and nucleic acid function by alkylation. It alkylates and cross-links strands of DNA. Alkylation takes place through the formation of a highly reactive ethylenimonium radical. The probable mode of action involves cross-linkage of the ethylenimonium derivative between two strands of helical DNA and subsequent interference with replication. Chlorambucil is known chemically as 4-[bis(2chlorethyl)amino]benzene butanoic acid.

The dosage must be carefully adjusted according to the response of the patient and must be reduced as soon as an abrupt fall in the white blood cell count occurs.

Azathioprine (Azasan, Imuran)

Azathioprine is an imidazolyl derivative of 6-mercaptopurine. Many of its biological effects are similar to those of the parent compound. Both compounds are eliminated rapidly from blood and are oxidized or methylated in erythrocytes and the liver. No azathioprine or mercaptopurine is detectable in urine 8 hours after it is taken.

Azathioprine antagonizes purine metabolism and inhibits the synthesis of DNA, RNA, and proteins. The mechanism whereby azathioprine affects autoimmune diseases is unknown. It works primarily on T cells. It suppresses hypersensitivities of the cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity tests are suppressed to a greater degree than antibody responses. It works very slowly; it may require 6-12 months of trial prior to effect. Up to 10% of patients may have idiosyncratic reactions disallowing use. Do not allow the WBC count to drop below 3000/μL or the lymphocyte count to drop below 1000/μL.

Azathioprine is available in a tablet form for oral administration or in 100-mg vials for intravenous injection.

Cyclophosphamide

Cyclophosphamide is a cyclic polypeptide that suppresses some humoral activity. It is chemically related to nitrogen mustards. It is activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.

Cyclophosphamide is biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. The interaction of phosphoramide mustard with DNA is considered cytotoxic.

When used in autoimmune diseases, the mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

In high doses, it affects B cells by inhibiting clonal expansion and suppression of the production of immunoglobulins. With long-term low-dose therapy, it affects T-cell functions.

Cyclosporine (Gengraf, Neoral, Sandimmune)

Cyclosporine is an 11-amino acid cyclic peptide and natural product of fungi. It acts on T-cell replication and activity.

It is a specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of the cell cycle is suggested.

Cyclosporine binds to cyclophilin, an intracellular protein, which, in turn, prevents the formation of interleukin 2 and the subsequent recruitment of activated T cells.

It has about 30% bioavailability, but there is marked interindividual variability. It specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that the drug be present during the first 24 hours of antigenic exposure.

Cyclosporine suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) for a variety of organs.

Infliximab (Remicade)

Infliximab neutralizes cytokine TNF-alpha and inhibits its binding to the TNF-alpha receptor. Mix it in 250 mL of normal saline for infusion over 2 hours. It must be used with a low-protein-binding filter (1.2 micron or less). Infliximab is indicated to reduce the signs and symptoms of active ankylosing spondylitis

Thalidomide (Thalomid)

Thalidomide is an immunomodulatory agent that may suppress excessive production of TNF-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration.


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