Drug class antimetabolite mechanism of action drugs of this class alter rna and dna, building blocks of all cells, resulting in blunting of the immune system. The use of azathioprine for inhibition of renal homograft rejection is well established, the mechanisms for this action are somewhat obscure. The drug suppresses hypersensitivities of the cellmediated type and causes variable alterations in antibody production. The side chain allows azathioprine to be less toxic than 6mp. Both agents have a slow onset of action three to six months for full effect. An understanding of the role of tpmt in the overall metabolism of thiopurines and its mechanisms of action is critical to optimizing and individualizing ibd ther. Immunosuppressants mechanisms of action and monitoring. The mechanism of action of azathioprine is as a nucleic acid synthesis inhibitor. Your doctor will test the level of your enzymes before starting treatment see below. Azathioprine aza is an immunosuppressive agent that is widely used in inflammatory rheumatic diseases, including ra, where there is evidence to support its. Imuran azathioprine, an immunosuppressive antimetabolite, is available in tablet form for oral administration.
The first metabolic step that azathioprine undergoes in the body is the conversion to 6mercaptopurine 6mp. It may also interfere with cellular metabolism and inhibit mitosis. Azathioprine also may integrate into nucleic acids, resulting in chromosome breakage, nucleic acid malfunction, or the synthesis of faulty proteins. If your institution subscribes to this resource, and you dont have a myaccess profile, please contact your librarys reference desk for information on how to gain access to this resource from offcampus. Aza and its metabolites act as purine antagonists, which. Learn about drug interactions between azathioprine oral and mesalamine oral and use the rxlist drug interaction checker to check drug combinations. Nov 10, 2019 azathioprine may diminish the therapeutic effect of vaccines live. Thiopurines ie, azathioprine aza and mercaptopurine, also known as 6mercaptopurine, 6mp exert a glucocorticoidsparing effect for patients with inflammatory bowel disease ibd who cannot maintain remission when glucocorticoids are tapered and withdrawn. Azathioprine and longwave ultraviolet light have been shown to have a synergistic clastogenic effect in patients treated with azathioprine for a range of disorders. The enzyme thiopurine smethyltransferase tpmt is responsible for various activation and deactivation steps in azathioprine s mechanism of action. In this issue of gut, benhorin et al propose an innovative explanation for the well known phenomenon of the delayed onset of action of thiopurines see page 396. It is converted into 6mercaptopurine in the body where it blocks purine metabolism and dna synthesis. It is primarily metabolized in the liver where its side chain is removed.
Exploring the mechanism of action of azathioprine aza in ibd. Apr 15, 2003 over the past 50 years, azathioprine has been used in the treatment of hematologic malignancies, rheumatologic diseases, solid organ transplantation, and inflammatory bowel disease. Azathioprine and 6mercaptopurine are thiopurines, and azathioprine is an imidazolyl derivative of 6mercaptopurine. They are used to maintain remission in crohns disease and ulcerative colitis. Experts opinion on the practical use of azathioprine. Tacrolimus is a calcineurin inhibitor which has a similar mechanism of action to cyclosporin, reducing tcell differentiation.
The precise mechanism of action of thiopurine drugs remains unclear despite more than 40 years of use. Understanding the delayed onset of action of azathioprine. Understanding the delayed onset of action of azathioprine in. The fda recommends tpmt genotyping be performed before starting treatment with azathioprine, so that the risk for toxicity can be identified, and the starting dose of azathioprine can be reduced, or an alternative therapy can be used daily mednih. Azathioprine aza is a prodrug that is metabolized to its active component 6 mercaptopurine 6mp, a purine antagonist that. Other kidney diseases treated with this medication, continued. The drug is a purine analog, and the accepted mechanism of action is at the level of dna 1, 3. Azathioprine is metabolized in the liver before becoming active. One metabolic pathway is through its conversion to mercaptopurine, the active metabolite of mercaptopurine being 6thioinosinic acid.
The chemical classification of azathioprine is nucleoside analog, and purines. Azathioprine and photosensitivity reactions an update. Azathioprine is an immunosuppressive medicine, which means that it decreases the action of your bodys immune system. You can manage this and all other alerts in my account. Other proposed mechanisms of action include inhibition of several immune and inflammationrelated genes involved in intestinal inflammation. Azathioprine is a prodrug a precursor of a drug which is converted in the body to its active form called mercaptopurine. Azathioprine and mercaptopurine are thiopurines, and azathioprine is an imidazolyl derivative of mercaptopurine.
Find out what health conditions may be a health risk when taken with azathioprine oral. All generic drug interactions for azathioprine oral lists will include brand and generic names. Azathioprine aza, sold under the brand name imuran among others, is an. Each scored tablet contains 50 mg azathioprine and the inactive ingredients lactose, magnesium stearate, potato starch, povidone, and stearic acid. Over the past 50 years, azathioprine has been used in the treatment of hematologic malignancies, rheumatologic diseases, solid organ transplantation, and inflammatory bowel disease. Azathioprine is metabolised to 6mercaptopurine which in turn is inactivated by the action of xanthine oxidase the target of allopurinol. Besides the development of new drugs with new mechanisms of action for patients who do not respond to conventional therapies, several studies have been conducted to evaluate the best strategies to optimise response and remission.
Azathioprine may diminish the therapeutic effect of vaccines live. Azathioprine fda prescribing information, side effects and uses. The dosing and levels of immunosuppressive medications were standardized for all patients included in this study. Azathioprine aza is the 1methyl4nitro5imidazolyl derivative of thioguanine, a purinemimic antimetabolite. Azathioprineinduced severe bone marrow toxicity a report of 3 cases likai lo1 chihming hung1 yufu chen1 wangcheng ko1 tsenfang tsai2 chiayu chu2 dermatologists have been using azathioprine as a steroid sparing agent for the treatment of various dermatoses including photodermatoses, immunobullous diseases, psoriasis and ec. Usually administered orally it is well absorbed by the gastrointestinal tract.
Mechanism of action of azathioprine questioned you will receive an email whenever this article is corrected, updated, or cited in the literature. The drug may interfere with coenzyme functioning, thereby decreasing cellular. Azathioprine antagonizes purine metabolism and may inhibit synthesis of dna, rna, and proteins. Azathioprine decreases the metabolism of purines and may inhibit dna and rna synthesis as well. It is wellabsorbed from the gastrointestinal tract and has a serum halflife of 0. Immunosuppressive,an analogue of mercaptopurine action suppresses cellmediated hypersensitivities. The mechanisms whereby azathioprine affects autoimmune diseases are not known. Pdf exploring the mechanism of action of azathioprine aza. If your institution subscribes to this resource, and you dont have a myaccess profile, please contact your librarys reference desk for information on how to. Azathioprines mechanism of action remains to be elucidated, but suggested mechanisms for its immunosuppressive properties include. The fda recommends tpmt genotyping be performed before starting treatment with azathioprine, so that the risk for toxicity can be identified. The drug suppresses hypersensitivities of the cellmediated type and causes variable alterations in. Morris, in kidney transplantationprinciples and practice seventh edition, 2014. Azathioprine imuran side effects, dosage, interactions.
Azathioprine fda prescribing information, side effects. But lowering your immune function may make you more susceptible to infection. Its mechanism of action is likely due to incorporation of thiopurine analogues into the dna structure, causing chain termination and cytotoxicity. Azathioprinea purine nucleoside analog which acts as an antimetabolite by interfering with dna and rna synthesisis one of the immunosuppressive drugs recommended for this purpose. The exact mechanism of action of azathioprine is not known. Azathioprine is an antimetabolite, 6mercaptopurine 6mp with an additional side chain.
Recent knowledge in the field of apoptosis and a better insight into, as well as a rapid. The immunosuppressive effects of azathioprine involve a greater suppression of delayed hypersensitivity and cellular cytotoxicity tests than of antibody responses. Webmd provides common contraindications for azathioprine oral. Toward the definition of the mechanism of action of. Azathioprines mechanism of action is not entirely understood but it may be related to inhibition of purine synthesis, along with inhibition of b. Rna in c o rp o ratio n suppression of proliferation this mechanism of action in ibd would lead to.
The use of azathioprine for inhibition of renal homograft rejection is well established, the mechanism s for this action are somewhat obscure. By interrupting the immune process, azathioprine reduces inflammation and slows joint damage caused by rheumatoid arthritis. Adalimumab and azathioprine combination therapy for crohn. Pdf exploring the mechanism of action of azathioprine.
They thereby contribute to an improved insight into the exact mode of action of the classic immunosuppressive drug azathioprine. Azathioprine, a prodrug, is metabolized in the liver to 6mp also known as mercaptopurine, an antimetabolite that inhibits the enzyme responsible for purine synthesis, preventing dna synthesis and, therefore, cell proliferation. It is used to treat patients who have undergone kidney transplantation and for diseases in which modifying the activity of the immune system is important. Suppression of tcell effects, including ablation of tcell. Azathioprine has a deleterious effect on the bone health of. Although corticosteroids and drugs such as azathioprine still have a role, there is increasing use of newer potent immunosuppressants.
Jan 01, 2020 the use of azathioprine for inhibition of renal homograft rejection is well established, the mechanism s for this action are somewhat obscure. Allopurinol can correct this imbalance, allowing a slightly larger number of people to tolerate thiopurines. Azathioprine is the most widely used immunosuppressive treatment in multiple sclerosis ms. Adalimumab and azathioprine combination therapy for crohns. Drug interactions are extensive, and are as follows. One metabolic pathway is through its conversion to 6mercaptopurine, the active metabolite of. Like other immunosuppressants, it suppresses the proliferation of t and b lymphocytes, types of white blood cells that are part of the immune system and defend the body against both infectious diseases and foreign materials. Pharmacology and mechanism of action rheumatoid arthritis. Ibd pathogenesis genetic predisposition bacterial antigens activation of the mucosal immune system crohn. Lowdose azathioprine 3 mgkgday or less is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. The enzyme thiopurine smethyltransferase tpmt is responsible for various activation and deactivation steps in azathioprines mechanism of action. Azathioprine is an immunosuppressive antimetabolite prodrug.
Expression profiling reveals an inhibitory effect of aza on inflammatory cytokine gene expression in activated t cells. By inhibiting several enzymatic pathways required for the synthesis of deoxyribonucleic acid dna, azathioprine decreases the number of lymphocytes a type. The exact mechanism of immunosuppressive action is unknown since the exact mechanism of the immune response itself is complex and not completely understood. Comparison of sirolimus with azathioprine in a tacrolimus.
Allopurinol should not be given to people who are allergic to it. Azathioprine oral interactions with other medication. Pdf azathioprine for multiple sclerosis researchgate. Azathioprine, 6mercaptopurine in inflammatory bowel disease. Both in vitro and in vivo, azathioprine is metabolized to 6mp through reduction by glutathione and other sulphydrylcontaining compounds and then enzymatically converted into 6thiouric acid, 6methylmp, and 6thioguanine 6tg 1, 3. Diseases treated with this medication this medication is primarily used to prevent kidney transplant rejection and to treat severe rheumatoid arthritis.
Azathioprine, immunosuppressive drug that is used to treat rheumatoid arthritis and to suppress the bodys rejection of transplanted organs. Azathioprine a purine nucleoside analog which acts as an antimetabolite by interfering with dna and rna synthesisis one of the immunosuppressive drugs recommended for this purpose. Imuran azathioprine dose, indications, adverse effects. Commonly occurring adrs with azathioprine are gastrointestinal symptoms, hypersensitivity reactions and immunosuppression related infection 1. Azathioprine is the generic form of the brandname drug imuran, which is used along with other medicines to prevent organ rejection after a kidney transplant. Recent knowledge in the field of apoptosis and a better insight into, as well as a rapid increase in their use in several important areas of clinical medicine justify this appraisal.162 976 956 795 1443 768 227 862 1162 1193 863 717 1026 985 249 1169 312 555 1041 1351 1029 1413 549 450 754 349 1090 1067 711 229 1277 382 1420