Azathioprine as an oral corticosteroid sparing agent for asthmaSteroid-sparing agents definition of Steroid-sparing agents by Medical dictionary https: Agents in this group include auranofin, azathioprine, cycloSPORINE, gold salts, hydroxychloroquine, leflunomide, steroud, D-penicillamine, and sulfasalazine. A drug that is used to treat rheumatoid arthritis steroid sparing effect wikipedia acts more slowly but more effectively than nonsteroidal anti-inflammatory drugs. Such drugs include hydroxychloroquine, methotrexate, and tumor necrosis factor inhibitors. References in periodicals archive?
Steroid-sparing agents | definition of Steroid-sparing agents by Medical dictionary
Azathioprine AZA , sold under the brand name Imuran among others, is an immunosuppressive medication. Common side effect include bone marrow suppression and vomiting. Azathioprine was first made in In the United States, it is currently approved by the Food and Drug Administration FDA for use in kidney transplantation from human donors, and for rheumatoid arthritis. Azathioprine is used to prevent rejections of kidney or liver allografts , usually in conjunction with other therapies including corticosteroids , other immunosuppressants, and local radiation therapy.
Being a disease-modifying antirheumatic drug DMARD , azathioprine has been used for the management of the signs and symptoms of adult rheumatoid arthritis. Azathioprine has been used in the management of moderate to severe chronically active Crohn's disease,  to maintain clinical remission absence of disease activity in corticosteroid-dependent patients,  and to provide benefit in people with fistulizing Crohn's disease.
Azathioprine treatment is associated with an increased risk of lymphoma , but it is unclear if this is due to the drug or a predisposition related to Crohn's disease. It may also be used to prevent flares in those with ulcerative colitis. It is used as an add on therapy when steroid therapy is given by mouth for pemphigus and myasthenia gravis, as a "steroid-sparing" agent. It was shown to be very effective in eczema and atopic dermatitis in researches, even though it is not commonly used.
It was widely used for the treatment of multiple sclerosis until the first half of the s. Concerns about increased risk of malignancy has led to a decreased use, yet it is still used in maintenance treatment for patients who frequently relapse. A widely used therapy for idiopathic pulmonary fibrosis was azathioprine in combination with prednisone and N - acetylcysteine. A study showed that there were worse outcomes with this combination than with placebo.
Nausea and vomiting are common adverse effects, especially at the beginning of a treatment. Such cases are met with taking azathioprine after meals or transient intravenous administration. Side effects that are probably hypersensitivity reactions include dizziness, diarrhea, fatigue , and skin rashes. Hair loss is often seen in transplant patients receiving the drug, but rarely occurs under other indications. Because azathioprine suppresses the bone marrow , patients can develop anaemia and will be more susceptible to infection ; regular monitoring of the blood count is recommended during treatment.
Under FDA rules, like many other immunosuppressants, the use of this drug excludes eligibility for blood donation. It is listed by the International Agency for Research on Cancer as a group 1 carcinogen carcinogenic to humans.
The enzyme thiopurine S-methyltransferase TPMT is responsible for various activation and deactivation steps in azathioprine's mechanism of action. The first metabolic step that azathioprine undergoes in the body is the conversion to 6-mercaptopurine 6-MP; see Pharmacokinetics , which is itself an immunosuppressant prodrug.
Azathioprine is listed as a human carcinogen in the 12th Report on Carcinogens by the National Toxicology Program of U. Department of Health and Human Services , asserting that it is "known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.
Food and Drug Administration has required warnings to be placed on packaging with respect to increased risks of certain cancers. The risks involved seem to be related both to the duration and to the dosage used. People who have previously been treated with an alkylating agent may have an excessive risk of cancers if treated with azathioprine.
Epidemiological studies by International Agency for Research on Cancer IARC have provided "sufficient" evidence of azathioprine carcinogenicity in humans Group 1 ,  although the methodology of past studies and the possible underlying mechanisms are questioned.
The various diseases requiring transplantation may in themselves increase the risks of non-Hodgkin's lymphoma , squamous cell carcinomas of the skin, hepatobiliary carcinomas , and mesenchymal tumours to which azathioprine may add additional risks. Those receiving azathioprine for rheumatoid arthritis may have a lower risk than those undergoing transplantation. Cases of hepatosplenic T-cell lymphoma — a rare type of lymphoma — have been reported in patients treated with azathioprine.
The majority occurred in patients with inflammatory bowel disease. Adolescents and young adult males were the majority of cases. The FDA has required changes to the labeling to inform users and clinicians of the issue. The use of immunosuppressive medication including azathioprine in organ transplantation has been linked to increased rates of developing skin cancer.
Patients taking azathioprine were found to be abnormally sensitive to UVA light. Large single doses are generally well tolerated; a patient who took 7. Main symptoms of long-term overdosing are infections of unclear origin, mouth ulcers and spontaneous bleeding, all of which are consequences of the bone marrow suppression. Other purine analogues such as allopurinol inhibit xanthine oxidase , the enzyme that breaks down azathioprine, thus increasing the toxicity of azathioprine.
Azathioprine decreases the effects of the anticoagulant warfarin and of non-depolarizing muscle relaxants, but increases the effect of depolarizing muscle relaxants. Azathioprine can cause birth defects. This contrasts with the later-developed drugs tacrolimus and mycophenolate, which are contraindicated during pregnancy. Traditionally, as for all cytotoxic drugs , the manufacturer advises not to breastfeed whilst taking azathioprine. Highest blood plasma concentrations, counting not only the drug itself but also its metabolites, are reached after one to two hours; and the average plasma half-life is 26 to 80 minutes for azathioprine and three to five hours for drug plus metabolites.
Azathioprine is a prodrug , a substance that is not an active drug itself but is activated in the body. This happens in several steps; at first it is slowly and almost completely converted to 6-mercaptopurine 6-MP by reductive cleavage of the thioether — S —.
This is mediated by glutathione and similar compounds in the intestinal wall, the liver and on red blood cells, without the aid of enzymes. Azathioprine inhibits purine synthesis. By inhibiting purine synthesis, less DNA and RNA are produced for the synthesis of white blood cells , thus causing immunosuppression. Azathioprine is converted within tissues to 6-mercaptopurine 6-MP. Some 6-MP is converted in turn to 6-thioguanine by the addition of an amino group. Both 6-MP and 6-thioguanine are conjugated with ribose , and then phosphorylated to form the nucleotides thioinosinic acid and thioguanylic acid respectively.
Azathioprine is a thiopurine linked to a second heterocycle an imidazole derivative via a thioether. It is practically insoluble in water and only slightly soluble in lipophilic solvents such as chloroform, ethanol and diethylether. It dissolves in alkaline aqueous solutions, where it hydrolyzes to 6-mercaptopurine.
Azathioprine is synthesized from 5-chloromethylnitro-1 H -imidazole and 6-mercaptopurine in dimethyl sulfoxide DMSO.
Robert Schwartz investigated the effect of 6-MP on the immune response in and discovered that it profoundly suppresses the formation of antibodies when given to rabbits together with antigens.
Ciclosporin has now replaced some of the azathioprine use due to a longer survival time, especially in heart-related transplantations. From Wikipedia, the free encyclopedia. D Evidence of risk. S4 Prescription only CA: This section may be too technical for most readers to understand.
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