Immunosuppressives

Azathioprine

ALG (antilymphocytic globulin)
Antithymocytic Globulins
Rho (D) Immune Globulin (RhoGham)
Immune Globulin IV (IVIG)
Muromonab-CD3 (OKT3)

Cyclosporine
Tacrolimus
Sirolimus
Mycophenolate Mofetil

Etanercept
Infliximab
Daclizumab

MoA: inhibits PRPP synthetase and PRPP amidotransferase, inhibiting the de novo and salvage pathways; prevents clonal B & T cell proliferation;
Clinical Uses: prevents graft rejection; tx of autoimmune diseases such as RA, SLE, Crohn's disease and type 4 hypersensitivity rxns such as contact dermititis;
RoA: oral (MC), IV; small frequent doses are preferred vs. one large dose

Bone marrow suppression, leukopenia, thrombocytopenia anemia, hepatoxic/cholestasis;
DD Interaction: dosage must be reduced when given with allopurinol and mercaptopurine since these inhibit xanthine oxidase which metabolize azathioprine

MoA: binds to T-cells causing them to be destroyed by complement; blocks cellular immunity NOT antibody formation;
Clinical Uses: prophylaxis for kidney transplant and BMT rejection; tx of acute rejection following kidney transplant; tx of aplastic anemia in patients not suitable for BMT;
AE: anaphylaxis and serum sickness

MoA: contains cytotoxic antibodies to CD 2, 3, 4, 8, 11a, 18, 25, 44, 45 and HLA Class 1 & 2;
Clinical Uses: acute renal transplant rejection crises

MoA: suppresses Rh- mother's own antibody response to the fetus' Rh+ antigens;
Clinical Uses: passive immunity for the prevention of hemolytic disease of the newborn

MoA: polyclonal human IgG;
Clinical Uses: passive immunity; autoimmune diseases, Kawasaki's disease, SLE, refractory idiopathic thrombocytopenia purpura, Hep A, measles

MoA: monoclonal antibody to CD3 so it blocks antigen recognition; CD3 coreceptor;
Clinical Uses: acute renal allograft rejection crisis; also used in steroid resistant cardiac or hepatic allograft rejection;
AE: cytokine release syndrome: fever, dyspnea, wheezes, headache, hypotension, pulmonary edema; blood dyscrasias, hearing loss, HS rxns, impaired vision

MoA: binds to cyclophilin-A, inhibiting calcineurin, therefore inhibiting the transcription of IL-2 which reduces the function of effector T-cells; increased expression of TGF-B;
Clinical Uses: organ transplantation to prevent rejection of kidney, heart, liver, BMT, lung, and pancreas transplants; tx of GvHD in BMT recipients, uveitis, severe psoriasis, glomerular nephritis
RoA: oral, IV, IM; must be given for at least 2 weeks postop
AE: NEPHROTOXICITY, neurotoxicity, hyperuricemia, HTN, hepatotoxicity, gingival hyperplasia, osteoporosis, anorexia, GIT toxicity

MoA: binds to FKBP-12 to form a complex that inhibits Ca+2 stimulated phosphatase activity, therefore inhibiting calcineurin;
Clinical Uses: also a macrolide antibiotic; same uses as cyclosporine including atopic dermatitits; though it is 10-100x more potent than cyclosporine it may be given PRE-OP as it is not as nephrotoxic!!!
AE: nephrotoxicity, neurotoxicity, hyperkalemia, hyperglycemia, and diabetes; no effect on uric acid and LDL

MoA: combines with FKBP-12 but inhibits mTOR, a key enyzme in the G1-->S cell cycle progression so it arrests T cells in the G1 phase: blocks T cell response to cytokines and inhibits B cell proliferation and Ig production;
Clinical Uses: same as cyclosporine; also used in stents to reduce stenosis; tx of CAD;
AE: not nephrotoxic, however it is a myelosuppressant leading to leukopenia, hepatotoxicity, and thrombocytopenia

MoA: prodrug converted to MAP; inhibits inosine monophosphate dehydrogenase used in the de novo guanine nucleotide synthesis pathway, inhibiting T and B cell proliferation and functions;
Clinical Uses: prophylaxis of allogenic renal, hepatic, and cardiac transplant rejection; steroid refractory GvHD in hematopoetic stem cell transplant; SLE;
CI: PREGNANCY; also thought to reduce the efficacy of oral contraceptive pills;
AE: nausea, vomiting, diarrhea, abdominal pain, headache, HTN, leukopenia, and neutropenia

MoA: binds to TNF-alpha and prevents it from binding its real receptor;
Clinical Uses: RA; used in adjunct with methotrexate for cancer; experimentally used for immunosuppression and tx of psoriasis

MoA: TNF-alpha monoclonal chimeric antibody that binds to TNF-alpha and prevents the cytokine from binding to its receptors; inhibits IL-1 and IL-6, inhibits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes; no synthesis of PGs, or induction of acute phase liver proteins; inhibits activation of neutrophils and eosinophil activity;
RoA: IV;
Clinical Uses: RA (in adjunct with methotrexate), Crohn's disease;
AE: HS rxns, headache, and serum sickness

MoA: binds to IL-2 receptor on T-cells preventing activation of CD4 helper T-cells;
Clinical Uses: tx of acute rejection following kidney, heart, or liver transplants;
AE: dyspnea, fever, GI distress, hypotension, HTN, chest pain;
Warnings: increased mortality rates in cardiac allograft patients with combo tx using cyclosporine, mycoferolate mofetil, and corticosteroids