How do thiopurines work to stop cancer cells?

Thiopurine treatment causes the accumulation of 6-TG in DNA. A small fraction of incorporated 6-TG is methylated in a chemical methylation reaction with S-adenosylmethionine (SAM) the cellular donor of methyl groups in enzymatic reactions. DNA 6-meTG is not recognized to a significant extent by MGMT.

What do thiopurines do?

These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body’s immune system. Thiopurine drugs are used to treat some autoimmune disorders, including Crohn disease and rheumatoid arthritis, which occur when the immune system malfunctions.

Is mercaptopurine a chemotherapy?

Mercaptopurine is also called Xaluprine. It is a chemotherapy drug used to treat some types of leukaemia.

What is thiopurine toxicity?

Thiopurines present toxicity at distinct levels: myelosuppression, hepatotoxicity, pancreatitis and gastrointestinal intolerance, among others. Toxicity is an important cause of treatment cessation; in IBD, about 15% of patients discontinue thiopurines due to adverse events [4,5].

Is thiopurine an immunosuppressant?

Both Azathioprine and 6-Mercaptopurine (6-MP) belong to a group of drugs called thiopurines which are immunosuppressants. Thiopurines work by suppressing inflammation and slowing down the body’s immune response. They are also used to avoid rejection following organ transplantation.

What medications are thiopurines?

MN There are 3 types of thiopurines that have been used for inflammatory bowel disease (IBD) therapy: azathioprine, 6-mercaptopurine, and thioguanine. The first 2 are approved for the treatment of IBD, and the third has been tested in clinical trials.

How long can you stay on mercaptopurine?

Research suggests that the effectiveness of azathioprine and mercaptopurine does not diminish over time. While guidelines state that stopping treatment may be considered after four years for patients remaining in remission, many experts now believe thiopurine treatment should be continued indefinitely.

How long does it take for immune system to recover after mercaptopurine?

Recovery: 21-28 days. Liver toxicity . (see liver problems) Increased bilirubin, increased liver enzymes, jaundice, abdominal swelling (ascites). Increased with higher doses of drug.

What is the side effect of azathioprine?

Nausea, vomiting, or diarrhea. Flu-like symptoms (chills, aches, headache, or fatigue). Trouble urinating: pain, burning, constant urge, or frequent urination. Bloody, cloudy, or foul-smelling urine, or black, tarry stools.

What is thiopurine methyltransferase test?

TPMT genetic test (genotype)—an alternative test to TPMT enzyme activity level is a genetic test that can identify genetic variations in the TPMT gene. This genetic test identifies individual genetic differences associated with risk for thiopurine toxicity. Each person has two copies of the TPMT gene.

How are thiopurines metabolized?

Thiopurine metabolism The metabolism of MP involves three competing pathways: the first being degradation to TUA which is then excreted, the second is through methylation by TPMT into MeMP, and the third is the breakdown of MP into TIMP catalysed by HPRT. TIMP is then further metabolised via IMPDH into TGMP.