Immunopharmacology

DR. SALVADOR 

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1st to have lympholytic property reduces the size and lymphoid content of the lymph nodes and spleen  on proliferating myeloid or erythroid stem cells in the bone marrow immunologic effects are probably

 rather than to direct cytotoxicity  than humoral immunity

idiopathic thrombocytopenic purpura and rheumatoid arthritis first-line immunosuppressive therapy for both solid organ and hematopoietic stem cell transplant recipients, with variable results asthma

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 Adrenal suppr ession Proximal muscle wasting Diabetes GI bleeding Fluid retention Serious viral, bacterial and fungal infection

Cyclosporine Tacrolimus

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graft-versus-host disease after hematopoietic stem cell transplantation kidney, pancreas, liver, and heart transplant ophthalmic solution: dry eye syndrome Inhaled cyclosporine: lung transplantation autoimmune disorders: uveitis, rheumatoid arthritis, psoriasis, and asthma

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Cyclosporine is a peptide antibiotic that appears to and blocks their activation binds to Cyclosporine and cyclophilin complex " inhibits calcineurin (necessary for the activation of a T-cell-specific transcription factor called w/c is involved in the synthesis of IL- 2 absorbed drug is primarily metabolized by the  in the liver

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nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism increased incidence of lymphoma and other cancers due to its release of

(FK 506) is an immunosuppressant macrolide antibiotic produced by binds to the blocking calcineurin tacrolimus is 10–100 times more potent than cyclosporine

preventing rejection in solid-organ transplant patients even after failure of standard rejection therapy considered a  (usually in combination with ) for graft-versus-host graft-versus-host disease. Tacrolimus ointment:

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nephrotoxicity, neurotoxicity, hyperglycemia, hypertension, hyperkalemia, and gastrointestinal complaints.

DR. SALVADOR 

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Sirolimus and its analogs

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immunosuppressant macrolide antibiotic produced by , resulting in an active complex that inhibits mTOR available only as an

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prophylaxis and as therapy for steroid-refractory acute and chronic graft-versus-host disease in hematopoietic stem cell transplant recipients

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semisynthetic derivative of inhibits

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Thalidomide is currently used in the treatment of initial diagnosis and for relapsed-refractory disease

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sedative drug that was withdrawn from the market in the 1960s because of its inhibits . It inhibits ! expression, and enhances cell-mediated immunity via interactions with T cells.

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profound  (especially thrombocytopenia), hepatotoxicity, diarrhea, hypertriglyceridemia, pneumonitis, and headache.

 isolated from the mold . , including mitogen and mixed lymphocyte responses, probably by

first-line drug for preventing or reducing in cardiac transplant recipients used as  of both acute and chronic graftversus-host diseases in hematopoietic stem cell transplant patients

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Toxicities include gastrointestinal disturbances (nausea and vomiting, diarrhea, abdominal pain) headache, hypertension, and reversible myelosuppression (primarily neutropenia).

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, alters adhesion molecule

The most important toxicity is

 Azathioprine Cyclophosphamide Leflunomide Hydroxychloroquine Other cytotoxic agents

prodrug of mercaptopurine and, like mercaptopurine, functions as an  much of the active material to 6-thiouric acid prior to excretion in the urine

maintaining renal allografts and may be of value in transplantation of other tissues.

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The chief toxic effect of azathioprine and mercaptopurine is bone marrow suppression, Hepatic dysfunction, manifested by very high serum alkaline phosphatase levels and mild jaundice

DR. SALVADOR 

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alkylating agent cyclophosphamide is

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In smaller doses: autoimmune disorders (including  and in patients with  and bleeding syndromes, autoimmune hemolytic anemia, antibody-induced pure red cell aplasia, and Wegener’s granulomatosis.

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carries considerable risk of pancytopenia and hemorrhagic cystitis

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elevation of liver enzymes with some risk of liver damage, renal impairment, and teratogenic effects.

inhibitor of pyrimidine synthesis

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available

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at present

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antimalarial agent with immunosuppressant properties. It is thought to endosomal compartments, thereby decreasing T-cell activation.

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only

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at present

including

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molecules by increasing the pH of lysosomal and

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useful in idiopathic thrombocytopenic purpura refractory to prednisone.

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 primarily used as an antineoplastic agent for lymphoid malignancies, and produces a profound lymphopenia.

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 ALG acts  As a result of the destruction or inactivation of T cells , an

 ALG and ATG are and play a definite role in the management of solid organ and bone marrow transplantation

that circulate between the blood and lymph and

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occurs while

Local pain and erythema often occur at the injection site (type III hypersensitivity) Complexes of host antibodies with horse ALG may precipitate and localize in the glomeruli of the kidneys

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Treatment of acute renal allograft rejection and steroid-resistant acute cardiac and hepatic transplant rejection

NONE (as per Katzung)

DR. SALVADOR 

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 An approach of intravenous use of polyclonal human immunoglobulin immunoglobulin preparation (usually ) is

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safe and effective in Kawasaki’s disease systemic lupus erythematosus and refractory idiopathic thrombocytopenic purpura.

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The technique is based on the observation that a higher titer of antibodies against the

. Rho(D) immune globulin is a concentrated  the red cell.

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prophylactic treatment to prevent erythroblastosis fetalis

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found on normal and malignant B and T lymphocytes, NK cells, monocytes, macrophages, and a small population of granulocytes

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MOA: decreases in kinase activity, matrix metalloproteinase activity, and growth factor production, and increased apoptosis

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 and inhibits VEGF from binding to its receptor, especially on endothelial cells. treatment of patients with

treatment of patients with : slight risk of hepatitis B virus reactivation

: lymphopenia, neutropenia, anemia, and thrombocytopenia

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infrequent and consist of local discomfort at the injection site or, rarely, a slight temperature elevation

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 containing a

: lymphopenia, neutropenia, anemia, and thrombocytopenia

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reduction of T helper cells increase of regulatory T cells decreased spontaneous immunoglobulin production, Fc receptor blockade increased antibody catabolism, and idiotypic-anti-idiotypic interactions with “pathologic antibodies.

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MOA: It inhibits cell growth, induces apoptosis, decreases vascular growth factor production, and suppresses internalization of the EGFR

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recombinant DNA-derived, of the human epidermal growth factor

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receptor MOA: blocks the natural ligand from binding and down- regulates the receptor

relapsed or refractory low-grade or follicular B-cell nonHodgkin’s lymphoma and chronic lymphocytic leukemia and treatment of rheumatoid arthritis

DR. SALVADOR 

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murine Fab fragment from an anti- carcinoembryonic antigen (CEA) antibody labeled with that is used for imaging patients with metastatic colorectal carcinoma (immunoscintigraphy) to determine extent of disease

murine monoclonal antibody labeled with isotopic

completely human IgG1 approved for use in patients with

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murine monoclonal antibody specific for . It is coupled to isotopic (111In)

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another

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recombinant humanized Fab fragment that binds to TNF- !. It is coupled to a treatment of patients with

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MOA: decreases in kinase activity, matrix metalloproteinase activity, and growth factor production, and increased apoptosis approved for , polyarticular  juvenile idiopathic arthritis, ankylosing spondylitis and psoriatic arthritis. It may be used in combination with methotrexate in some patients with arthritis.

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monoclonal antibody and is complexed with

human IgG monoclonal antibody that also binds to soluble and membrane-associated TNF- ! treatment of patients with : slight risk of hepatitis B virus reactivation

monoclonal anti- body possessing human constant (Fc) regions and murine variable regions MOA: decreases in kinase activity, matrix metalloproteinase activity, and growth factor production, and increased apoptosis Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis, and psoriatic arthritis.

recombinant fusion protein composed of the extra- cellular domain of cytotoxic T-lymphocyte-associated antigen  fused to hinge, CH2, and CH3 domains of human IgG1 binds more tightly to

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chimeric mouse-human IgG1 that on activated lymphocytes. MOA: Both agents function as , blocking IL-2 from binding to activated lymphocytes, and are therefore immunosuppressive.

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engineered protein consisting of the CD2-binding portion of leukocytefunction-associated antigen-3 (LFA-3) fused to a human IgG1 Fc region (hinge, CH2, and CH3). treatment of patients with

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humanized IgG4 monoclonal antibody that binds to the ! ! " and !4"7 integrins expressed on the surfaces of all leukocytes except neutrophils, and inhibits the !4-mediated adhesion of leukocytes to their cognate receptor. treatment of patients with

DR. SALVADOR 

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anti-IgE recombinant humanized monoclonal antibody that is approved for the treatment of in adult and adolescent patients whose symptoms are refractory to inhaled corticosteroids MOA # receptor on basophils and mast cells, which suppresses IgE-mediated release of type I allergy mediators such as histamine and leukotrienes

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recombinant humanized IgG1 that binds to soluble and membraneassociated IL-6 receptors. who are refractory to other anti-TNF! biologicals.

is a of IL-12 and IL-23 cytokines.  It blocks  from binding to their receptors, therefore inhibiting receptor-mediated signaling in lymphocytes.

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murine-human monoclonal antibody that eceptor on activated platelets and inhibits fibrinogen, von  Willebrand factor, and other adhesion molecules from binding to activated platelets, thus preventing their aggregation

humanized IgG monoclonal antibody that component, thereby inhibiting the terminal pore-forming lytic activity of complement.

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recombinant human IgG1 Fab that binds to VEGFprevents new blood vessel formation by blocking VEGF from binding to its receptor

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human IgG2 monoclonal antibody specific for human RANKL Binding RANKL it inhibits the maturation of osteoclasts, the cells responsible for bone resorption

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monoclonal antibody that binds to the fusion protein of respiratory  the airways