Thiopurines (Azathioprine/6-MP) in UC
If mesalamine type medications fail to induce and maintain a remission of UC then other medications are required. Corticosteroids, such as prednisone, are able to induce remission, but are not appropriate for long-term maintenance of remission due to significant side effects such as osteoporosis, weight gain, acne, elevated sugars, exacerbation of psychiatric illness, and insomnia.
In this case, use of the thiopurine drugs azathioprine (AZA) and 6-mercaptopurine (6-MP), is appropriate. Azathioprine is a pro-drug which the body immediately breaks down to 6-MP. Azathioprine is 50% 6-MP by weight, so the dose of azathioprine is twice 6-MP, but the two drugs are otherwise identical.
The mechanism of action is not fully understood, but AZA/6-MP are thought to block DNA synthesis and decrease the number and function of white blood cells. They can take one to three months to take effect, so they are not practical for induction of remission, but are effective at maintaining remission.
Your doctor may test you for thiopurine methyltransferase (TPMT) before starting AZA/6-MP. TPMT is one of the enzymes that metabolizes 6-MP. There are three levels of TPMT enzyme function: normal; intermediate; and low. These are based upon whether a person has two normal genes, one normal gene, or no normal genes for the enzyme, respectively. Patients with intermediate or low functioning TPMT have a higher risk of developing bone marrow suppression resulting in low white blood cell count and an increased risk of infection. They require lower doses of medication and closer monitoring of laboratory tests for side effects.
A test can be performed to measure the level of AZA/6-MP metabolites in the blood stream. Levels of 6-TG and 6-MMP are predictive of symptom response and toxicity and can be used to help guide dosing.
Next week I will review the adverse effects of AZA/6-MP, which needlessly frighten many patients.
Comments
Doctor can you please send me the doses of AZATHIOPRINE
when given to an ulcerative colitis patient. Send me in detail how the doses should be given and side-effects of continuing with this drug.
What is the most recent research going on this field. Also since their is no cure for ulcerative colitis tell me is there any other alternative treatment.
Posted by: Y.S. | January 7, 2008 4:42 PM
My wife is suffering from ulcerative colitis since 1990 and has been taking sulfasalazine and steroid treatment with local enema but now she is not responding to the treatment and relapses are very early and frequent with daily motions exceed 30 to 35 per day with bleeding per rectum and abdominal pain.
What are the prospects of surgery like left hemicolectomy with colorectal anastomosis?
I
Posted by: Y.S. | January 7, 2008 4:50 PM