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Encyclopedia > Immunosuppressive drug
For a list of immunosuppressive drugs, see the transplant rejection page.

Immunosuppressive drugs or immunosuppressants are drugs that are used in immunosuppressive therapy to inhibit or prevent activity of the immune system. Clinically they are used to: Shortcut: WP:CU Marking articles for cleanup This page is undergoing a transition to an easier-to-maintain format. ... This Manual of Style has the simple purpose of making things easy to read by following a consistent format — it is a style guide. ... Transplant rejection occurs when the immune system of the recipient of a transplant attacks the transplanted organ or tissue. ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Immunosuppression is the medical suppression of the immune system. ... The immune system protects the body from infection by pathogenic organisms. ...

These drugs are not without side effects and risks. Because the majority of them act non-selectively, the immune system loses its ability to successfully resist infections and spreading of malignant cells. There are also other side effects, like hypertension, dyslipidemia, hyperglycemia, peptic ulcers, liver and kidney injury. The immunosuppressive drugs also interact with other medicines and affect their metabolism and action. Transplant rejection occurs when the immune system of the recipient of a transplant attacks the transplanted organ or tissue. ... Transplant redirects here. ... Grays Anatomy illustration of cells in bone marrow. ... The heart and lungs, from an older edition of Grays Anatomy. ... The kidneys are bean-shaped excretory organs in vertebrates. ... The liver is an organ in some animals, including mammals (and therefore humans), birds, and reptiles. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Rheumatoid arthritis (RA) is traditionally considered a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ... Myasthenia gravis (sometimes abbreviated MG; from the Greek myastheneia, lit. ... H&E section of non-caseating granuloma seen in the colon of someone affected by Crohns disease. ... Adverse effect, in medicine, is an abnormal, harmful, undesired and/or unintended side-effect, although not necessarily unexpected, which is obtained as the result of a therapy or other medical intervention, such as drug/chemotherapy, physical therapy, surgery, medical procedure, use of a medical device, etc. ... An infection is the detrimental colonization of a host organism by a foreign species. ... It has been suggested that Cancerous tumor be merged into this article or section. ... Arterial hypertension, or high blood pressure is a medical condition where the blood pressure is chronically elevated. ... Hypercholesterolemia (literally: high blood cholesterol) is the presence of high levels of cholesterol in the blood. ... Hyperglycemia or High Blood Sugar is a condition in which an excessive amount of glucose circulates in the blood plasma. ... A benign gastric ulcer (from the antrum) of a gastrectomy specimen. ... Overview of the citric acid cycle The citric acid cycle, one of the central metabolic pathways in aerobic organisms. ...


Immunosuppressive drugs can be classified into four groups:

Contents

Glucocorticoids

General information: Glucocorticoid. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger similar effects. ...


In pharmacologic (supraphysiologic) doses, glucocorticoids are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. An allergy can refer to several kinds of immune reactions including Type I hypersensitivity in which a persons body is hypersensitised and develops IgE type antibodies to typical proteins. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Transplant rejection occurs when the immune system of the recipient of a transplant attacks the transplanted organ or tissue. ... Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...


Immunosuppressive mechanism

Glucocorticoids suppress the cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-γ, the most important of which is the IL-2. Smaller cytokine production reduces the T cell proliferation. Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages and NK-cells, the production of antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. ... Interleukin-1 (IL-1) is secreted by the macrophages, monocytes and dendritic cells. ... Interleukin-2 (IL-2) is an interleukin, a type of biological response modifier, a substance that can improve the bodys natural response to disease. ... Interleukin-3 (IL-3) is an interleukin, a type of biological signal (cytokine) that can improve the bodys natural response to disease as part of the immune system. ... Interleukin-4, abbreviated IL-4, is a Cytokine that stimulates the proliferation of activated B-cells, T-cells, and differentiation of CD4+T-cells into Th2 cells, among other effects. ... ... Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. ... Interleukin-8 (IL-8) is a chemokine produced by macrophages and other cell types such as epithelial cells. ... Cytokines is a group of proteinaceous signalling compounds that like hormones and neurotransmitters are used extensively for inter-cell communication. ... T cells are a subset of lymphocytes that play a large role in the immune response. ...


Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and of IL-2 receptors. This diminishes both B cell clone expansion and antibody synthesis. Humoral immunity is the aspect of immunity that is mediated by secreted antibodies, produced in the cells of the B lymphocyte lineage (B cell). ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... The Interleukin-2 Receptor (IL-2R) is heterotrimeric protein expressed on the surface of certain immune cells, such as lymphocytes, that binds and responds to a cytokine called interleukin 2. ... Schematic of antibody binding to an antigen An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...


Antiinflammatory effects

Glucocorticoids influence all types of inflammatory events, no matter what their cause. They induce the lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. Illustration of a cell membrane The cell membrane, also called the plasma membrane or plasmalemma, is a semipermeable lipid layer surrounding the cytoplasm of all living cells. ... A phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances. ... In biochemistry, a substrate is a molecule which is acted upon by an enzyme. ... Arachidonic acid is a polyunsaturated fatty acid with twenty carbons and four cis double bonds, the first at the omega-6 position (20:4n-6). ... In biochemistry, eicosanoids are a class of oxygenated hydrophobic molecules that largely function as autocrine and paracrine mediators. ... Cyclooxygenase (COX) is an enzyme (EC 1. ...


Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. White Blood Cells is also the name of a White Stripes album. ... Types of epithelium This article discusses the epithelium, an animal anatomical structure. ... Schematic of cell adhesion The study of cell adhesion is part of cell biology. ... It has been suggested that this article or section be merged with Immigration. ... Chemotaxis is a kind of taxis, in which bodily cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. ... Phagocytosis (literally cell-eating) is a form of endocytosis wherein large particles are enveloped by the cell membrane of a (usually larger) cell and internalized to form a phagosome, or food vacuole. ... Respiratory burst is the rapid release of reactive oxygen species (superoxide radical and hydrogen peroxide) from different types of cells. ... In blood coagulation, tissue plasminogen activator (tPA) is an enzyme (EC 3. ... Chemokines are a family of pro-inflammatory activation-inducible cytokines, or small protein signals secreted by cells. ... Neutrophil granulocytes (commonly referred to as neutrophils) are a class of white blood cells and are part of the immune system. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, makros = long, phagein = eat) are white blood cells, more specifically phagocytes, acting in the nonspecific defense as well as the specific defense system of vertebrate animals. ... A mast cell (or mastocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. ...


Cytostatics

General information: Chemotherapy Chemotherapy is the use of chemical substances to treat disease. ...


Cytostatics inhibit cell division. In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells. Due to their highest effectiveness, purine analogs are most frequently administered. Chemotherapy is the use of chemical substances to treat disease. ... This does not cite its references or sources. ... Purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. ...


Alkylating agents

The alkylating agents used in immunotherapy are nitrogen mustards (cyclophosphamide), nitrosoureas, platinum compounds and others. Cyclophosphamide is probably the most potent immunosuppressive compound. In small doses, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune hemolytic anemias, Wegener's granulomatosis and other immune diseases. High doses cause pancytopenia and hemorrhagic cystitis. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. ... Airborne exposure limit 0. ... Urea streptozotocin ENU Nitrosourea compounds are compounds that include a nitroso (R-NO) group and a urea. ... General Name, Symbol, Number platinum, Pt, 78 Chemical series transition metals Group, Period, Block 10, 6, d Appearance grayish white Atomic mass 195. ... Hemolysis (alternative spelling haemolysis) literally means the excessive breakdown of red blood cells. ... In medicine (rheumatology), Wegeners granulomatosis is a form of vasculitis that affects the lungs, kidneys and other organs. ... Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets. ...


Antimetabolites

Antimetabolites interfere with the synthesis of nucleic acids. These include: An antimetabolite is a chemical with a similar structural to a substance (a metabolite) required for normal biochemical reactions, yet different enough to interfere with the normal functions of cells, including cell division. ...

Folic acid and folate (the anion form) are forms of a water-soluble B vitamin. ... Methotrexate (rINN) (IPA: ), abbreviated MTX and formerly known as amethopterin, is an antimetabolite drug used in treatment of cancer and autoimmune diseases. ... Purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. ... Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohns disease. ... Mercaptopurine: chemical structure Mercaptopurine (also called 6-MP or by its brand name Purinethol®) is an immunosuppressive drug used to treat leukemia. ... Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring [1]. It is isomeric with two other forms of diazine. ...

Methotrexate

Methotrexate is a folic acid analogue. It binds dihydrofolate reductase and prevents synthesis of tetrahydrofolate. It is used in the treatment of autoimmune diseases (for example rheumatoid arthritis) and in transplantations. Methotrexate (rINN) (IPA: ), abbreviated MTX and formerly known as amethopterin, is an antimetabolite drug used in treatment of cancer and autoimmune diseases. ... Folic acid and folate (the anion form) are forms of a water-soluble B vitamin. ... Categories: Biochemistry stubs | EC 1. ... Folic acid and folate (the anion form) are forms of a water-soluble B vitamin. ...


Azathioprine and Mercaptopurine

Azathioprine, is the main immunosuppressive cytotoxic substance. It is extensively used to control transplant rejection reactions. It is nonenzymatically cleaved to mercaptopurine, that acts as a purine analogue and an inhibitor of DNA synthesis. Mercaptopurine itself can also be administered directly. Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohns disease. ... Mercaptopurine: chemical structure Mercaptopurine (also called 6-MP or by its brand name Purinethol®) is an immunosuppressive drug used to treat leukemia. ...


By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity. It is also efficient in the treatment of autoimmune diseases. Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages and NK-cells, the production of antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. ... Humoral immunity is the aspect of immunity that is mediated by secreted antibodies, produced in the cells of the B lymphocyte lineage (B cell). ...


Cytotoxic antibiotics

Among these, dactinomycin is the most important. It is used in kidney transplantations. Other cytotoxic antibiotics are anthracyclines, mitomycin C, bleomycin, mithramycin. Actinomycin is any of a class of polypeptide antibiotics isolated from soil bacteria of the genus Streptomyces. ... Anthracycline - Wikipedia, the free encyclopedia /**/ @import /skins-1. ... The mitomycins are a family of aziridine-containing natural products isolated from One of these compounds, mitomycin C, finds use as a chemotherapeutic agent by virtue of its antitumour antibiotic activity. ... Bleomycin is an anti-cancer agent. ... Mithramycin is an anti-neoplastic antibiotic. ...


Antibodies

Antibodies are used as a quick and potent immunosuppression method to prevent the acute rejection reaction. Schematic of antibody binding to an antigen An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...


Polyclonal antibodies

Heterologous polyclonal antibodies are obtained from the serum of animals (e.g. rabbit, horse) and injected with the patient's thymocytes or lymphocytes. The antilymphocyte (ALG) and antithymocyte antigens (ATG) are being used. They are part of the steroid-resistant acute rejection reaction and grave aplastic anemia treatment. However, they are primarily added to other immunosuppressives to diminish their dosage and toxicity. They also allow transition to cyclosporine therapy. Polyclonal antibodies are antibodies that are derived from different B-cell lines. ... Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... Genera Pentalagus Bunolagus Nesolagus Romerolagus Brachylagus Sylvilagus Oryctolagus Poelagus Rabbits are small mammals in the family Leporidae of the order Lagomorpha, found in many parts of the world. ... Binomial name Equus caballus Linnaeus, 1758 The horse (Equus caballus, sometimes seen as a subspecies of the Wild Horse, Equus ferus caballus) is a large odd-toed ungulate mammal, one of ten modern species of the genus Equus. ... Thymocytes are T cell precursors which develop in the thymus. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... Aplastic anemia is a condition where the bone marrow does not produce enough, or any, new cells to replenish the blood cells. ...


Polyclonal antibodies inhibit T lymphocytes and cause their lysis, which is both complement mediated cytolysis and cell-mediated opsonization followed by removal of reticuloendothelial cells from the circulation in the spleen and liver]]. In this way, polyclonal antibodies inhibit cell-mediated immune reactions, including graft rejection, delayed hypersensitivity (i.e. tuberculin skin reaction), and the graft-versus-host disease (GVHD), but influence thymus-dependent antibody production. Lysis (Greek lusis from luein = to separate) refers to the death of a cell by bursting, often by viral or osmotic mechanisms that compromise the integrity of the cellular membrane. ... A complement protein attacking an invader. ... An opsonin is any molecule that acts as a binding enhancer for the process of phagocytosis. ... Diagram of the human circulatory system. ... The spleen is a ductless, vertebrate gland that is closely associated with the circulatory system, where it functions in the destruction of old red blood cells in holding a reservoir of blood. ... Hypersensitivity is an immune response that damages the bodys own tissues. ... Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...


Currently (March 2005) there are two preparations available to the market: Atgam (R), obtained from horse serum, and Thymoglobuline (R), obtained from rabbit serum.Polyclonal antibodies affect all lymphocytes and cause general immunosuppression possibly leading to post-transplant lymphoproliferative disorders (PTLD) or serious infections, especially by cytomegalovirus. To reduce these risks, treatment is provided in a hospital where adequate isolation from infection is available. They are usually administered for five days intravenously in the appropriate quantity. Patients stay in the hospital as long as three weeks to give the immune system time to recover to a point where there is no longer a risk of serum sickness. ← - 2005 : January - February - March - April - May - June - July - August - September - October - November - December- → Deaths in March • 31 – Terri Schiavo • 30 – Mitch Hedberg • 29 – Johnnie Cochran • 27 – Wilfred Bigelow • 26 – Paul Hester • 26 – James Callaghan • 21 – Jeff Weise • 21 – Bobby Short • 19 – John De Lorean • 18 – Gary Bertini • 17 – George F... Post-transplant lymphoproliferative disorder (PTLD) is the name given to a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant. ... Species see text Cytomegalovirus (CMV), is a genus of Herpes viruses; in humans the species is known as Human herpesvirus 5 (HHV-5). ... Serum sickness is a reaction to an antiserum derived from an animal source. ...


Because of a high immunogenicity of polyclonal antibodies, almost all patients have an acute reaction to the treatment. It is characterized by fever, rigor episodes and even anaphylaxis. Later during the treatment, some patients develop serum sickness or immune complex glomerulonephritis. Serum sickness arises seven to fourteen days after the therapy has begun. The patient suffers from fever, joint pain and erythema that can be soothed with the use of steroids and analgesics. Urticaria (hives) can also be present. It is possible to diminish their toxicity by using highly purified serum fractions and intravenous administration in the combination with other immunosuppressants, for example calcineurin inhibitors, cytostatics and cortisteroids. The most frequent combination is to simultaneously use antibodies and cyclosporine. Patients gradually develop a strong immune response to these drugs, reducing or eliminating their effectiveness. This page is a candidate to be copied to Wiktionary using the Transwiki process. ... An analogue medical thermometer showing the temperature of 38. ... For the medical term see rigor (medicine) Rigour (American English: rigor) has a number of meanings in relation to intellectual life and discourse. ... In medicine, anaphylaxis is a severe and rapid multi-system allergic reaction. ... In medicine, arthralgia (literally: joint pain, from arthros = joint and -algia denoting pain) is the presence of painful joints in the absence of frank arthritis. ... Erythema is an abnormal redness of the skin caused by capillary congestion. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ...


Monoclonal antibodies

Monoclonal antibodies are directed towards exactly defined antigens. Therefore, they cause fewer side effects. Especially significant are the IL-2 receptor (CD25) and CD3 directed antibodies. They are used to prevent the rejection of transplanted organs, but also to track changes in the lymphocyte subpopulations. It is reasonable to expect similar new drugs in the future. Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. ... The Interleukin-2 Receptor (IL-2R) is heterotrimeric protein expressed on the surface of certain immune cells, such as lymphocytes, that binds and responds to a cytokine called interleukin 2. ...


T-cell receptor directed antibodies

OKT3 (R) is presently the only approved anti-CD3 antibody. It is a mouse anti-CD3 monoclonal antibody of the IgG2a type that prevents T-cell activation and proliferation by binding the T-cell receptor complex present on all differentiated T cells. As such, it is one of the most potent immunosuppressive substances and is clinically used to control the steroid and/or polyclonal antibodies resistant acute rejection episodes. For acting more specifically than polyclonal antibodies, it is also used preventively in transplantations. T cells belong to group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity. ...


Presently, the OKT3's action mechanism is not yet sufficiently understood. It is known that the molecule binds TCR/CD3, the T-cell receptor complex. During the first few administrations, this binding non-specifically activates T cells, leading to a serious syndrome 30 to 60 minutes later. It is characterized by fever, myalgia, headache and artralgia. In some cases, it progresses to a life-threatening reaction of the cardiovascular system and the central nervous system needing a lengthy therapy. Past this period, CD3 (R) blocks the TCR - antigen binding and causes conformation change or the removal of the entire TCR3/CD3 from the T-cell surface. This lowers the number of T cells, perhaps by sensitising them for the uptake by the reticular epithelial cells. The cross-binding of CD3 molecules also activates an intracellular signal, causing the T cells' anergy or apoptosis, unless they receive another signal through a costimulatory molecule. CD3 antibodies also shift the balance from Th1 to Th2 cells.


Deciding whether to use OKT3(R) in the treatment, it is therefore necessary not only to consider its great effectiveness, but also its toxic side effects: the risk of excessive immunosuppression and the risk that the patient develops neutralizing antibodies against the drug, making it inefficacious. Although CD3(R) antibodies act more specifically than polyclonal antibodies, they lower the cell-mediated immunity significantly, predisposing the patient to opportunistic infections and malignancies.


IL-2 receptor directed antibodies

Interleukin-2 is an important immune system regulator necessary for the clone expansion and survival of activated lymphocytes T. Its effects are mediated by the trimer cell surface receptor IL-2a, consisting of the α, β and γ chains. The IL-2a (CD25, T-cell activation antigen, TAC) is expressed only by the already activated T lymphocytes. Therefore, it is of special significance to the selective immunosuppressive treatment and the research has been focused on the development of effective and safe anti-IL-2 antibodies. By the use of the recombinant gene technology, the mouse anti-Tac antibodies have been modified leading to the presentation of two himeric mouse/human anti-Tac antibodies in the year 1998: basiliximab (Simulect (R)) and daclizumab (Zenapax (R)). These drugs act by binding the IL-2a receptor's α chain, preventing the IL-2 induced clonal expansion of activated lymphocytes and shortening their survival. They are used in the profilaxis of the acute organ rejection after the bilateral kidney transplantation, both being similarly effective and with only few side effects. Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ...


Drugs acting on immunophilins

Cyclosporin

General information:cyclosporin ...


Together with tacrolimus, cyclosporin is a calcineurin inhibitor. It has been in use since 1983 and is one of the most widely used immunosuppressive drugs. It is a fungal peptide, composed of 11 amino acids. Tacrolimus (also FK-506 or Fujimycin) is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. ... ... Calcineurin (CN) is a protein phosphatase also known as protein phosphatase 2B (PP2B). ... 1983 (MCMLXXXIII) was a common year starting on Saturday of the Gregorian calendar. ...


Cyclosporin is thought to bind to the cytosolic protein cyclophilin (an immunophilin) of immunocompetent lymphocytes, especially T-lymphocytes. This complex of cyclosporin and cyclophilin inhibits calcineurin, which under normal circumstances induces the transcription of interleukin-2. The drug also inhibits lymphokine production and interleukin release, leading to a reduced function of effector T-cells. Cyclophilins are proteins that bind to cyclosporin A, which is usually used to suppress rejection after internal organ transplants. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... Calcineurin (CN) is a protein phosphatase also known as protein phosphatase 2B (PP2B). ... Interleukin-2 (IL2) is an interleukin, a type of biological response modifier that can improve the bodys natural response to disease. ... Lymphokines are a subset of Cytokines that are produced by immune cells. ... Interleukins are a group of cytokines that were first seen to be expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The name is sort of a relic though; it has since been found that interleukins are produced by a wide variety of bodily...


Cyclosporin is used in the treatment of acute rejection reactions, but has been increasingly substituted with newer immunosuppressants, as it is nephrotoxic. Nephrotoxicity is a poisonous effect of some substances, both toxins and medication, on the kidney. ...


Tacrolimus (Prograf(TM), FK506)

Tacrolimus is a bacterial product (Streptomyces tsukubaensis). It is a macrolide lactone and acts by inhibiting calcineurin. Tacrolimus (also FK-506 or Fujimycin) is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. ...


The drug is used particularly in the liver and kidney transplantations, although in some clinics it is used in heart, lung and heart/lung transplants. It binds to an immunophilin, followed by the binding of the complex to calcineurin and the inhibition of its phosphatase activity. In this way, it prevents the passage of G0 into G1 phase. Tacrolimus is more potent than cyclosporin and has less pronounced side effects.


Sirolimus (Rapamune (Tm), Rapamicin)

Sirolimus is a macrolide lactone, produced by the actinomycetes Streptomyces hygroscopicus. It is used to prevent rejection reactions. Although it is a structural analogue of tacrolimus, it acts somewhat differently and has different side effects. Sirolimus is a relatively new immunosuppressant drug used to prevent rejection in organ transplantation, and is especially useful in kidney transplants. ... Orders Subclass Acidimicrobidae     Acidimicrobiales Subclass Actinobacteridae     Actinomycetales     Bifidobacteriales Subclass Coriobacteridae     Coriobacteriales Subclass Rubrobacteridae     Rubrobacterales Subclass Sphaerobacteridae     Sphaerobacterales The Actinobacteria or Actinomycetes are a group of Gram-positive bacteria. ...


Contrary to cyclosporine and tacrolimus that affect the first phase of the T lymphocyte activation, sirolimus affects the second one, namely the signal transduction and their clonal proliferation. It binds to the same receptor (immunophilin) as tacrolimus, however the produced complex does not inhibit calcineurin, but another protein. Therefore, sirolimus acts synergistically with cyclosporine and, in combination with other immunosuppressants, has few side effects. Indirectly it inhibits several T lympohocyte kinases and phosphatases, preventing the transmission of signal into their activity and the transition of the cell cycle from G1 to S phase. Similarly, it prevents the B cell differentiation to the plasma cells, which lowers the quantity of IgM, IgG and IgA antibodies produced. It acts immunoregulatory.


Other drugs

Interferons

General information:Interferon. To meet Wikipedias quality standards, this article or section may require cleanup. ...


IFN-β suppresses the production of Th1 cytokines and the activation of monocytes. It is used to slow down the progression of multiple sclerosis. IFN-γ is able to trigger lymphocytic apoptosis. A cell undergoing apoptosis. ...


Opioids

Prolonged use of opioids may cause immunosuppression by inhibiting the migration of leukocytes. An opioid is any agent that binds to opioid receptors, found principally in the central nervous system and gastrointestinal tract. ...


TNF binding proteins

A TNF-α (tumor necrosis factor alpha) binding protein is a monoclonal antibody or a circulating receptor such as infliximab (Remicade®), etanercept (Enbrel®), or adalimumab (Humira®) that binds to TNF-α and prevent it from inducing the synthesis of IL-1 and IL-6 and the adhesion of lymphocyte activating molecules. They are used in the treatment of rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and psoriasis. In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm that binds to a specific factor (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... It has been suggested that Infliximab (Remicade) be merged into this article or section. ... Etanercept (Enbrel®, co-marketed by Amgen and Wyeth) is a human recombinant, soluble tumor necrosis factor-alpha (TNFα) receptor. ... In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ... Rheumatoid arthritis (RA) is traditionally considered a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. ... H&E section of non-caseating granuloma seen in the colon of someone affected by Crohns disease. ...


TNF or the effects of TNF are also suppressed by various natural compounds, including curcumin (an ingredient in turmeric) and catechins (in green tea). Curcumin is the active ingredient of the Indian curry spice turmeric. ... Binomial name Curcuma longa Linnaeus Turmeric (Curcuma longa, also known as tumeric) is a spice commonly used in curries and other South Asian cooking. ... Green tea (绿茶) is tea that has undergone minimal oxidation during processing. ...


These drugs may raise the risk of contracting tuberculosis or inducing a latent infection to become active. Infliximab and adalimumab have label warnings stating that patients should be evaluated for latent TB infection and treatment should be initiated prior to starting therapy with them. Tuberculosis (abbreviated as TB for Tubercle Bacillus) is a common and deadly infectious disease caused by the mycobacterium Mycobacterium tuberculosis or Mycobacterium_bovis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system, lymphatic system, circulatory system, genitourinary system, bones and joints. ...


Mycophenolate

Mycophenolic acid acts as a non-competitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), which is a key enzyme in the de novo guanosine nucleotide synthesis. In contrast to other human cell types, lymphocytes B and T are very dependent on this process. Mycophenolic acid (INN) (IPA: ) or mycophenolate is an immunosuppresant drug used to prevent rejection in organ transplantation. ... The chemical structure of Guanosine Guanosine is a nucleoside comprising guanine attached to a ribose (ribofuranose) ring via a β-N9-glycosidic bond. ...


Small biological agents

FTY720 is a new synthetic immunosuppressant, currently in phase 3 of clinical trials. It increases the expression or changes the function of certain adhesion molecules (α4/β7 integrin) in lymphocytes, so they accumulate in the lymphatic tissue (lymphatic nodes) and their number in the circulation is diminished. In this respect, it differs from all other known immunosuppressants. FTY720 is a novel immunosuppressant drug that causes lymphopenia by redirecting lymphocytes from circulation to the lymph nodes. ... An integrin, or integrin receptor, is an integral membrane protein in the plasma membrane of cells. ... The human lymphatic system The lymphatic system is a complex network of lymphoid organs, lymph nodes, lymph ducts, and lymph vessels that produce and transport lymph fluid from tissues to the circulatory system. ...


External links

  • Pancreas-Kidney Transplantation: Drugs, a brief history of immunosuppressive drugs. Accessed on 21 August 2005.
  • WSAVA 2001 - Immunosuppressive drug therapy, from the veterinary point of view. By Mark Papich. Accessed on 21 August 2005.
  • Newer Immunosuppressive Drugs;A Review -Gummert et al. - J Am Soc Nephrol 10:1366-1380, 1999. Free full text at JASN. Accessed on 21 August 2005.
  • Principles and Practice of Monitoring Immunosuppressive Drugs. W.V.Armstrong, J Lab Med, 2002, 26 (1/2): 27-36. PDF. Accessed on 21 August 2005.
  • Are Immunosuppressive Drugs a Useful Adjuvant to Treatment of HIV with Antiretrovirals?. Hivandhepatitis.com. Accessed on 21 August 2005.
  • Immunosuppression. By Randy P Prescilla, MD; accessed on Emedicine.com on 21 August 2005
  • National Kidney Foundation: A to Z Health Guide, answers to some frequently asked questions about immunosuppression in renal transplatation for a layman. Accessed on 21 August 2005.
  • Immunosuppressants, Pharmacologic profile. Drugguide.com. Accessed on 21 August 2005.
  • Immunosuppressants, a collection of links at About.com. Accessed ob 21 August 2005.

  Results from FactBites:
 
Immunosuppressant Drugs - Definition, Purpose, Description, Recommended dosage, Precautions, Side effects, Interactions (2299 words)
Immunosuppressant drugs, which are also called anti-rejection drugs, are used to prevent the body from rejecting a transplanted organ.
People taking immunosuppressant drugs should avoid contact with anyone who has had a recent dose of oral polio vaccine, as there is a chance that the virus used to make the vaccine could be passed on to them.
Immunosuppressant drugs are also associated with a slightly increased risk of cancer because the immune system plays a role in protecting the body against some forms of cancer.
Treatments: Immunosuppressive drugs - WrongDiagnosis.com (412 words)
Immunosuppressants are usually longer-lasting drugs and work in a different manner, usually by interfering with the body's white blood cells (T-cells or B-cells).
Unfortunately, modern immunosuppressants are not specific and suppress all of the immune system, leaving the patient vulnerable to a variety of opportunistic infections that would normally be prevented by the immune system.
Immunosuppressants are given to transplant patients to prevent organ rejection and to patients with autoimmune diseases like lupus.
  More results at FactBites »

 
 

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