-
Cyclosporine
- Mechanism: inhibits calcineurin, preventing expression of IL-2, thereby inhibiting activation of CD4+ and CD8+ T-cells
- Pharmacology: variable absorption leading to unpredictable bioavailability; metabolized by CYP3A4
- Uses: organ transplants; GVHD; selected autoimmune diseases
- Toxicity: nephrotoxicity, neurotoxicity, hypertension, hirsutism, hyperlipidemia, gingival hyperplasia
-
Tacrolimus
- Mechanism: inhibits calcineurin, preventing expression of IL-2, thereby inhibiting activation of CD4+ and CD8+ T-cells
- Pharmacology: metabolized in liver
- Uses: prophylaxis after liver and kidney transplants; rescue therapy in graft rejection
- Toxicities: nephrotoxicity; neurotoxicity; hypertension; inhibition of beta cell function; increased risk fro malignant lymphoma
-
Sirolimus
- Mechanism: inhibits mTOR, preventing transcription and translation of genes involved in cellular proliferation thereby inhibiting B and T cell proliferation
- Pharmacology: metabolized by CYP3A4
- Uses: prevention of acute transplant rejection; prevents neointimal proliferation and restenosis after stent placement
- Toxicity: anemia, thrombocytopenia, and hyperlipidemia; contraindicated after liver transplantation; no risk of lymphoma
-
Mycophenolate mofetil
- Mechanism: inhibits de novo purine synthesis
- Pharmacology: prodrug; should not be administered with antacids containing magnesium or aluminium hydroxide
- Uses: solid organ transplant as a single agent or in combination
- Toxicity: diarrhea, leukopenia
-
Leflunomide
- Mechanism: inhibits de novo pyrimidine synthesis
- Pharmacology: prodrug; extremely long half-life
- Uses: active rheumatoid arthritis
- Toxicity: diarrhea, nausea, myelosuppression, severe hepatotoxicity (rare)
-
Thalidomide
- Mechanism: unknown
- Uses: multiple myeloma, erythema nodosum leprosum
- Toxicity: peripheral neuropathy, teratogenicity
-
Fingolimod
- Mechanism: binds to sphingosine-1 phosphate receptors to block migration of lymphocytes out of lymph nodes
- Uses: MS
- Toxicity: fatal infections
- Pharmacology: must be phosphorylated by sphingosine kinase 2
-
Daclizumab
- Mechanism: humanized monoclonal antibody against alpha chain (CD25) of the high affinity IL-2 receptor, inhibiting IL-2 mediated T-cell activation
- Use: in combo to reduce acute rejection in kidney and cardiac transplantation
-
Basiliximab
- Mechanism: chimeric monoclonal antibody against alpha chain (CD25) of the high affinity IL-2 receptor, inhibiting IL-2 mediated T-cell activation
- Use: in combo to reduce acute rejection in kidney and cardiac transplantation
- Toxicity: acute hypersensitivity reactions
-
Muromonab
- Mechanism: mouse monoclonal antibody directed against epsilon chain of the T-cell surface protein CD3, thereby blocking engagement of the T-ell receptor
- Use: reversal of acute rejection of heart, liver, and kidney transplants
- Toxicity: may non-specifically activate T cells upon first infusion; may cause hypersensitivity reactions
-
Etanercept
- Mechanism: neutralizes free TNF
- Uses: rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis
- Toxicity: demyelinating disease
-
Natalizumab
- Mechanism: humanized monoclonal antibody against alpha4 subunit of integrin that inhibits lymphocyte migration through endothelial cells
- Use: Crohn's, MS
- Toxicity: significant risk for JC virus-induced PML
-
Abatacept
- Mechanism: binds to CD80 and CD86 to block binding of CD28 and prevent T cell activation
- Uses: prevention of renal allograft rejection
-
Infliximab
- Mechanism: chimeric monoclonal antibody against TNF alpha
- Uses: Crohn's, UC, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis
- Toxicity: increased susceptibility to infection, reactivation of hepatitis B, malignancies, hepatotoxicity, development of anti-infliximab antibodies
-
Anakinra
- Mechanism: IL-1 receptor antagonist
- Use: rheumatoid arthritis
- Toxicity: increased susceptibility to serious bacterial infection
-
Methotrexate
Cytotoxic cancer chemotherapeutic used at lower concentrations to treat autoimmune disease
-
Azathioprine
- Mechanism: disrupts de novo purine synthesis; inhibits transcription
- Use: rheumatoid arthritis (in combo with prednisone +/- cyclosporine/tacrolimus)
- Toxicity: bone marrow suppression, GI distress
-
Glatiramer
- Mechanism: antigenically similar to myelin basic protein
- Use: remitting-relapsing MS
-
Antilymphocyte & antithymocyte globulin
- Mechanism: depletes peripheral T cells by blocking cell surface receptors and direct cytotoxicity
- Uses: prevention of transplant rejection, GVHD, aplastic anemia
- Toxicity: fever, chills, leukopenia, thrombocytopenia, skin reactions
-
Immune globulin (i.v.)
- Uses: to confer passive immunity; treatment of autoimmune disorders (like ITP)
- Mechanism: controversial/unknown
-
INF-beta
- Mechanism: exploit cells' natural anti-viral and anti-proliferative properties
- Use: MS
-
Epoetin alfa
- Mechanism: erythropoietin analogue that stimulates formation of rbcs
- Use: anemia
- Toxicity: stroke, CV side effects
-
Darbepoetin alfa
- Mechanism: longer half-life form of erythropoietin analogue that stimulates formation of rbcs
- Use: anemia
- Toxicity: stroke, CV side effects
|
|