What Is Azathioprine?

Azathioprine is an immunosuppressive drug, meaning it weakens the immune system to treat diseases in which this system is mistakenly active.

The immune system is a natural mechanism in the body that has the function of defending us against pathogens and infections. However, there are some diseases that develop because this system recognizes as foreign some natural substance or body structure that it shouldn’t, and attacks it. In these situations, this system must be weakened so that it stops attacking these structures.

Azathioprine is actually a prodrug. That is, this drug is administered and absorbed correctly, but until it is metabolized and converted into another molecule, 6-mercaptopurine, it does not trigger any effect.

It is used to treat conditions such as Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, multiple sclerosis and autoimmune hepatitis.

In addition, it was widely used to perform organ transplants, along with other immunosuppressive agents, so that the body would not recognize the new organ as foreign. However, it is no longer used for this last indication.

Pharmacokinetics: what happens to azathioprine in the body?

Pharmacokinetics includes the processes of absorption, distribution, metabolism and elimination of a drug. In this sense, azathioprine can be administered in two ways: orally or intravenously.

When administered orally, it should be borne in mind that the tablets must not be broken, must be taken whole and accompanied by food. In cases where azathioprine cannot be administered orally, intravenous administration will be used.

On oral administration, azathioprine is absorbed from the upper gastrointestinal tract. It is then distributed throughout the body, and derivatives of this drug have been found in the brain in rat studies.

Upon reaching the liver, it is metabolized to 6-mercaptopurine, the active metabolite  that triggers the immunosuppressive action. However, plasma levels of azathioprine and 6-mercaptopurine do not correlate well with the therapeutic efficacy or toxicity of this drug.

In addition to 6-mercaptopurine, azathioprine is also metabolized to other molecules, such as 6-thiuric acid, although this is not active. Finally, both the unmetabolized drug and the resulting metabolites are excreted in the urine.

How does azathioprine work in the body?

Today,  the mechanism of action by which this immunosuppressant exerts its effect  on the body  is not exactly known. However, different hypotheses were described, among which we found the following:

• 6-mercaptopurine is  considered  a purine antimetabolite, that is, it interrupts the synthesis of purines, necessary for the synthesis of DNA. This action would cause the cells of the immune system to weaken, thus giving rise to the immunosuppressive effect.
• The active metabolite of azathioprine could alkylate the sulfur groups, which would lead to DNA damage in immune cells.
• Another of the proposed hypotheses is the  inhibition of different nucleic acid synthesis pathways. The consequence of this interruption in the growth and proliferation of cells involved in the immune response would weaken this defense system and justify the action of azathioprine.

• Finally, it is believed that the DNA of cells of the immune system is damaged by the  incorporation of residues of purine analogues.

Adverse Reactions of Azathioprine

Like all drugs on the market, azathioprine is not exempt from causing a series of adverse effects.  We understand adverse effects as all unwanted and unintended events that occur as expected in treatment with a drug.

In this sense, among the  most frequently reported adverse reactions  during the studies carried out are:

• Digestive problems.
• Neutropenia.
• Pancreatitis.
• Hepatitis.

Conclusion

Azathioprine is a drug widely used in autoimmune diseases. However, as it can cause a number of adverse effects, it is important to discuss with your doctor any doubts or known allergic reactions to medications, in order to avoid complications.