Azathioprine: Uses And Mechanism Of Action
Azathioprine is an immunosuppressive drug. It is used in cases where the immune system needs to be weakened because it is reacting abnormally and causes disease.
The immune system is a natural defense mechanism against pathogens and infections. In some cases, however, it is itself the cause of the disease; this happens when he mistakenly considers a substance or structure of the body to be foreign and begins to attack it. In these cases, the immune system needs to be dampened.
Azathioprine is a prodrug. This means that once taken and absorbed, it only releases its effect after being metabolized and converted into another molecule, 6-mercaptopurine.
The most frequent uses are the treatment of Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, multiple sclerosis and autoimmune hepatitis.
Until recently it was administered in organ transplants, together with other immunosuppressive agents, to avoid rejection reactions. However, it is no longer used for this indication.
Pharmacokinetics: How does azathioprine behave in the body?
Pharmacokinetics includes the processes of drug absorption, distribution, metabolism and elimination. Azathioprine can be taken in two ways, orally or intravenously.
The patient who takes this drug by mouth should remember that the tablet should not be broken; you will also need to ingest it with food. When azathioprine cannot be taken orally, it is given intravenously.
When taken orally, azathioprine is absorbed in the upper gastrointestinal tract, and then reaches the whole body (in some studies in mice, traces of the drug have been found in the brain).
Once it reaches the liver, it is metabolized into 6-mercaptopurine; it is the active metabolite that will trigger the immunosuppressive effect. However, plasma levels of azathioprine and 6-mercaptopurine are not correlated with the therapeutic efficacy or toxicity of this drug.
In addition to 6-mercaptopurine, azathioprine is also metabolized into other molecules such as 6-thiouric acid, although this is not active. At the end of the process, both the unmetabolized drug and the metabolites are excreted in the urine.
Effect of azathioprine
The mechanism of action of this immunosuppressant on the body is not yet fully known. The hypotheses in this regard are different:
- According to a first hypothesis, 6-mercaptopurine acts as a purine antimetabolite, that is, it blocks the production of the purines necessary to synthesize DNA. This action would weaken the immune cells resulting in an immunosuppressive effect.
- The active metabolite of azathioprine could alkylate sulfuric groups, damaging the DNA of immune cells.
- Another hypothesis is that azathioprine inhibits various nucleic acid synthesis pathways. By stopping the growth and multiplication of cells involved in the immune response, it weakens the defense system.
- Finally, it is thought that the DNA of the cells of the immune system is damaged following the incorporation of residues of purine thio-analogues.
Side effects of azathioprine
Like all drugs on the market, azathioprine can produce a number of adverse effects. Adverse effects are all those unwanted and unintended events that occur unexpectedly during treatment with a drug. The most frequently reported adverse reactions during clinical trials are:
- Digestive disorders.
- Neutropenia.
- Pancreatitis.
- Hepatitis.
Conclusion
Azathioprine is a widely used drug in the treatment of autoimmune diseases. As it can produce a number of side effects, it is important to clarify any concerns with your doctor, reporting any known allergic reactions to the medications, in order to avoid complications.
