What Is Azathioprine?

Azathioprine is an immunosuppressive drug, that is, it weakens the immune system in order to treat diseases in which this system is equivocally active.

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

Azathioprine is, in particular, 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 effects.

This medicine is therefore used to treat diseases such as Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, multiple sclerosis, or autoimmune hepatitis.

In addition, it was previously widely used to perform organ transplants, along with other immunosuppressive agents, so that the body did not recognize the new organ as foreign. However, it is no longer used as much for the latter 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 must be borne in mind that the tablets should not be broken, they must be taken whole and with food. In cases where azathioprine cannot be administered orally, intravenous administration will be used.

Focusing on oral administration, azathioprine is absorbed from the upper gastrointestinal tract. Afterwards, it is distributed throughout the body, derivatives of this drug having been found in the brain in studies in mice.

Once it reaches the liver, it is metabolized to 6-mercaptopurine, which is the active metabolite that will trigger the immunosuppressive action. However, plasma levels of both 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 into other molecules, such as 6-thiuric acid, although this is not active. Finally, both the unmetabolized drug and the metabolites resulting from metabolism 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 have been described, among which we find the following:

• 6-Mercaptopurine is thought to be a purine antimetabolite, that is, it interrupts the synthesis of purines, necessary for DNA synthesis. This action would weaken the immune cells, thus appearing the immunosuppressive effect.
• The active metabolite of azathioprine could alkylate sulfuric groups, leading to DNA damage in immune system cells.
• Another of the proposed hypotheses is the inhibition of different pathways of nucleic acid synthesis. The consequence of this interruption of the growth and proliferation of the cells involved in the immune response would weaken this defense system and would justify the action of azathioprine.
• Finally, the DNA of immune system cells is thought to be damaged by the incorporation of purine thio-analog residues.

Adverse reactions of azathioprine

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

In this sense, among the adverse reactions that have been reported more frequently during the studies carried out are:

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

Conclution

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