What is the active metabolite of azathioprine?

What is the active metabolite of azathioprine?

Azathioprine (AZA) is a purine synthesis inhibitor converted in the body to the active metabolites 6-mercaptopurine and 6-thioinosinic acid.

What is azathioprine toxicity?

Abstract. Azathioprine therapy can cause acute myelosuppression. Toxicity is in part caused by the incorporation of azathioprine-derived 6-thioguanine nucleotides (6-TGN) into deoxyribonucleic acid (DNA). The enzyme thiopurine methyltransferase (TPMT) plays an important role in azathioprine catabolism.

Why is azathioprine cytotoxic?

The cytotoxicity of azathioprine is due, in part, to the incorporation of 6-TGN into DNA. 6-MP undergoes two major inactivation routes (Figure 1). One is thiol methylation, which is catalyzed by the enzyme thiopurine S-methyltransferase (TPMT), to form the inactive metabolite methyl-6-MP (6-MeMP).

Which enzyme does azathioprine inhibit?

Azathioprine inhibits purine synthesis. Purines are needed to produce DNA and RNA. By inhibiting purine synthesis, less DNA and RNA are produced for the synthesis of white blood cells, thus causing immunosuppression.

Is azathioprine a biologic?

Immunomodulators are another treatment option and include azathioprine, mercaptopurine, cyclosporine and methotrexate. The biologic class of drugs consists of the anti TNF alpha agents, which include infliximab, adalimumab and golimumab.

How is azathioprine excreted?

In humans, azathioprine is catabolized to a variety of oxidized and methylated derivatives, which are excreted by the kidneys; very little azathioprine or 6-mercaptopurine are excreted intact. At least 11 different metabolites have been identified, with the major one, 6-thiouric acid, found in urine.

Does azathioprine increase risk of infection?

(Because azathioprine is an immunosuppressive medicine, it can lower the number of white blood cells in your blood, increasing the chance of getting an infection.) Long-term use may increase the risk of developing some types of tumors.

Is azathioprine a carcinogen?

Azathioprine is carcinogenic via two mechanisms: – as an immunosuppressant, it is associated with post-transplant lymphoproliferative disorders that generally have a viral etiology; – because it causes 6-thioguanine to accumulate in patients’ DNA, it also contributes to cancer development by DNA damage.

Does azathioprine deplete B cells?

The effect of azathioprine on lymphocyte populations was dose dependent; high doses decreased the number of T- and particularly, B-cells, while smaller doses produced a selective depletion of B-cells.

Is azathioprine a prodrug?

Azathioprine is a prodrug that is non-enzymatically converted to 6-MP.

Is azathioprine a TNF blocker?

There are several drug treatments available that can induce and maintain remission in Crohn’s disease. These include immunosuppressant drugs (i.e., azathioprine/6-mercaptopurine and methotrexate) and anti–tumor necrosis factor (TNF) therapy (i.e., infliximab, adalimumab , and certolizumab).