Active Ingredients

Azathioprine – Effect, Application & Risks


Azathioprine is one of the immunosuppressive drugs and is widely used in organ transplants , autoimmune diseases and certain chronic inflammations . The active substance’s mode of action is mediated by inhibition of nucleic acid synthesis. Since the drug works with a delay, it is always used in organ transplants in combination with other immunosuppressants.

What is azathioprine?

Azathioprine is a drug for suppressing the immune system. It is used for excessive, misdirected or unwanted immune reactions of the organism. This applies to rejection reactions in organ transplants, autoimmune reactions and other misdirected immune reactions of the organism.

The active ingredient consists of a purine ring connected to the heterocyclic imidazole ring via a sulfur bridge. In the metabolism , this compound is subject to several degradation reactions, during which a variety of intermediate compounds (metabolites) are formed. Important metabolites are 6-mercaptopurine and 1-methyl-4-nitro-5-thioimidazole. 6-mercaptopurine passes through the cell membrane and is converted into other active and inactive metabolites. 6-mercaptopurine is the actual metabolite that intervenes in the nucleic acid metabolism.

It is an analogous purine base that can be incorporated into DNA or RNA instead of the physiological purine base . In addition, the formation of new purine bases is also inhibited as part of these metabolic processes. This leads to an overall inhibition of nucleic acid synthesis. The role of the other metabolite (1-methyl-4-nitro-5-thioimidazole) has not yet been clearly clarified.

Pharmacological action

As already mentioned, the active ingredient ensures the inhibition of nucleic acid synthesis via its metabolites. At the same time, this suppresses the formation of new cells, since the nucleic acids can no longer be provided in sufficient quantities. This applies in particular to cells and organs that are dependent on a higher rate of cell division.In order to react to foreign invaders, the immune system must react quickly and therefore quickly produce new immune cells, which then undergo further differentiation. Azathioprine therefore has an antiproliferative effect, i.e. it inhibits cell division. The necessary T – lymphocytes , natural killer cells and B-lymphocytes cannot then be produced in sufficient quantities. The secretion of the tumor necrosis factor TNF-alpha is also reduced.

However, azathioprine only reaches its full effectiveness after two to five months. Therefore, therapy with other faster-acting immunosuppressants, such as glucocorticoids or ciclosporin , must be started in order to be effective right from the start. The delayed action of azathioprine results from the slow reduction in nucleic acid concentration.

Medical Application & Use

Azathioprine has a wide range of applications. It is suitable for all areas of application that require suppression of the immune system. This applies to organ transplants, autoimmune reactions or allergic reactions. Improvements and weakening of inflammatory reactions can be achieved in almost all areas .

A particularly important area of ​​application is the use of the drug in organ transplants to weaken rejection reactions. Azathioprine is also used in diseases such as arthritis and diseases of the rheumatic circuit, in multiple sclerosis , sarcoidosis , myasthenia , lupus erythematosus , granulomatosis with polyangiitis , Behcet’s disease , Autoimmune Hepatitis or Idiopathic Interstitial Pneumonia .

Azathioprine is also often used for severe neurodermatitis . The same applies to such diseases as Crohn’s disease or ulcerative colitis . All of these are diseases that are caused by the immune system’s reaction to the organs of one’s own body.

Risks & side effects

In addition to the diverse areas of application, however, many contraindications , side effects , interactions and precautionary measures must also be observed. For example, in a relatively large proportion of the population (10 percent), the enzyme thiopurine methyltransferase (TPMT) has only a reduced effect. Thiopurine methyltransferase (TPMT) is responsible for the metabolism of 6-mercaptopurine. As already mentioned, 6-mercaptopurine can be incorporated into DNA or RNA as an analogous purine base instead of the physiological purine base and thus impede normal nucleic acid synthesis. Without the enzyme TPMT, this metabolite can no longer be broken down effectively and accumulates. This increases the toxicity of azathioprine.The reduced nucleic acid synthesis also weakens the repair mechanism on the DNA in the event of mutations . Therefore, exposure to solar radiation should be as low as possible during the treatment period in order to reduce the risk of skin cancer .

Other contraindications for the use of azathioprine are liver and kidney dysfunction , severe infections or damage to the bone marrow . Since azathioprine has an embryotoxic effect, it must not be used during pregnancy .

Sometimes there are unpleasant or even serious side effects. These include, among other things, a general feeling of illness, nausea , vomiting , loss of appetite , changes in the blood count with the development of anemia , leukopenia or thrombocytopenia . In rare cases, megaloblastic anemia can also occur. Megaloblastic anemia is a type of anemia that results from impaired DNA synthesis. In men, a reduction in the formation of germ cells can sometimes be observed. However, this phenomenon is reversible and only occurs during treatment.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.