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Summary Immunosuppresant Drugs
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This is a summary table containing the different immunosuppressant drugs and their pharmacological characteristics.
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Immunosuppressive TherapyMOA CLINICAL USES TOXICITY DESC
reduce size and lymphoid content of lymph 1st line therapy for solid organ and HSC 1st hormonal agents recognized as
Glucocorticoids
nodes and spleen transplant recepients having lympholytic properties
interfere w/ cell cycle of activated thrombocytopenic purpura, RA, allergic rxns,
no effect on cells in BM
lymphocytes asthma
cytotoxic to certain subset of T cells
Calcineurin Inhibitors
a peptide antibiotic that binds to cyclophilin, nephrotoxicity, hypertension, hyperglycemia,
human organ transplantation, GVH dse after
Cyclosporine then inhibit calcineurin, blocking activation of liver dysfunction, hyperkalemia, altered
HSC transplantation, selected autoimmune d/os
T cells mental status, seizures, hirsutism
little toxicity to BM and drug induces TGF-B
inhibits gene transcription of IL-2, IL-3, IFN-y cadaveric transplantation of some organs
(tumor invasion & metastasis)
prophylactic regimen to prevent GVH Increased incidence of Lymphoma (Kaposi's
(+Methotrexate) sarcoma, skin ca)
solid organ transplantation; standard
binds to immunophilin FKBP --> inhibit nephrotoxicity, neurotoxicity, hyperglycemia, macrolide antibiotic produced by
Tacrolimus (FK506) prophylactic agent for GVH (+ Methotrexate,
calcineurin hypertension, hyperkalemia, GIT complaints Streptomyces tsukubaensis
MMF)
atopic dermatitis and psoriasis (topical)
Proliferation Signal Inhibitors newer class
solid organ allografts; prophylaxis and therapy
bind to immunophilin FK506-BP-12 --> block
Sirolimus for steroid-refractory acute and chronic GVH
molecular target of mTOR
disease
blockade of mTOR inhibits interleukin-driven
T cell proliferation; also B cell prolifration and uveoretinitis (topical) oral; half-life: 60hrs
Ab prodxn
myelosuppression (thrombocytopenia),
addt'l agent for chronic cardiac allograft
Everolimus " hepatotoxic, diarrhea, hyperTAG, under investigation
vasculopathy
pneumonitis, headache
inhibits JAK enzymes (hematopoiesis,
Tofacitinib (Xeljanz) immune cell fx in response to cytokine or GF adults - moderate to severe RA
signaling)
reduce NK cells, serum Ig, CRP
oral & IV; 1st line drug for chronic allograft semisynthetic derivative of
inhibits de novo synthesis of purines -- GIT disturbances, headache, HTN,
Mycophenolate mofetil vasculopathy in cardiac transplant -- mycophenolic acid from mold
inhibits T and B cell responses reversible myelosuppression (neutropenia)
antiproliferative properties Penicillium glaucus
prophylaxis and tx for acute & chronic GVH in
HSC transplant
newer: lupus nephritis, RA, IBD, derma d/os
inhibits angiogenesis, enhance cell-mediated multiple myeloma, leprosy (erythema nodosum teratogenesis, peripheral neuropathy,
Thalidomide immunity; anti-inflammatory & leprosum), skin manifestations of lupus constipation, rash, fatigue, hypothyroidism, oral sedative drug
immunomodulatory effects erythematosum deep-vein thrombosis
inhibits TNF-a, reduce phagocytosis by withdrawn -- teratogenic
neutrophils (phocomelia)
inc IL-10, alters adhesion molecule
expression
regulate cytokines and affect T cell immunomodulatory derivatives -
IMids
proliferation much more potent
Lenalidomide myelodysplastic syndrome less toxic oral
anti-angiogenic activity, inhibition of TNF-a,
Pomalidomide stimulation of apoptosis and cytotoxic T cell
activity
Cytotoxic agents
prodrug of mercaptopurine;
antagonist of purine metabolism -- inhibition acute glomerulonephritis in SLE; RA; Crohn's; BM suppression, skin rashes, fever, hepatic
Azathioprine converted by xanthine oxidase to 6-
of DNA, RNA, and protein synthesis MS; ITP (prednisone-resistant), AIHA dysfx, diarrhea
thiouric acid
SLE, acquired FXIII antibodies and bleeding
alkylating agent; destroys proliferating hemorrhagic cystitis - prevented w/ mesna;
Cyclophosphamide syndromes, AIHAs, pure red cell aplasia,
lymphoid cells and alkylate resting cells cardiotoxicity, electrolyte disturbances
Wegener's granulomatosis
Pyrimidine synthesis Inhibitors
inhibit mitochondrial dihydyroorotate
elevation of liver enzymes, renal impairment,
Leflunomide dehydrogenase -- dec lymphocyte activation; RA oral
teratogenic, CVS effects (tachy, angina)
anti-inflamm and immunomodulatory effect
has antiviral activity
same as above; dec number of lymphocytes CI in pregnancy, severe liver dse, active metabolite of leflunomide; long
Teriflunomide relapsing remitting MS
in CNS neutropenia, thrombocytopenia half-life of several weeks
inc pH of lysosomal and endosomal
compartments -- suppress ic ag processing RA, SLE, GVH after allogeneic stem cell
Hydroxychloroquine anti-malarial agent
and loading of peptides into MHC class II -- transplantation
decrease T cell activation
Methotrexate RA, GVH
Vincristine ITP refractory to prednisone
bind to microtubule units w/in cell -- prevent
Vinblastine mast cell degranulation -- prevent release of
histamine
adenosine deaminase inhibitor;
steroid-resistant GVH; preparative regimens
Pentostatin antineoplastic agent for lymphoid profound lymphopenia
prior to transplant; severe immunosuppression
malignancies
activate NRF-2 transcriptional pathways -
reduction of oxidative stress, protect the flushing, abdominal pain, inc hepatic
Dimethyl fumarate (DMF) relapsing-remitting MS methyl ester of fumaric acid
nerve cells from inflammation; significant enzymes, eoosinophilia
lymphopenia
downregulates the immune response to
skin hypersensitivity, lipoatrophy, skin mixture of synthetic polypeptides and
Glatiramer acetate myelin antigens by induction and activation "
necrosis at injection site four amino acids
of supppressor T cells that migrate to CNS
S1P receptor modulator - controls release of cardiac toxicity, bradycardia, QT
Fingolimod hydrochloride (FH) " from fungal metabolite myriocin
lymphocytes from lymphnodes and thymus prolongation
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