thiopuriinien

Thiopuriines, a class of immunosuppressive and anticancer agents, are used to treat autoimmune diseases and to prevent organ transplant rejection. The principal members are azathioprine, 6-mercaptopurine (6-MP), and thioguanine. In Finnish medical terminology, the plural form thiopuriinien is used to refer to these compounds collectively.

Mechanism and metabolism: After administration, azathioprine is rapidly converted to 6-MP, which is further metabolized into active thio-nucleotide metabolites. These compounds inhibit de novo purine synthesis and can be incorporated into DNA and RNA, reducing the proliferation of rapidly dividing cells such as lymphocytes. Enzymes involved in thiopurine metabolism—HGPRT, TPMT, and xanthine oxidase (XO)—influence both efficacy and toxicity. TPMT activity varies genetically, and low activity increases the risk of bone marrow suppression. XO inhibition (for example by allopurinol) can raise thiopurine levels, necessitating dose adjustments.

Clinical use: Thiopurines are used to induce and maintain remission in inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), autoimmune hepatitis, and certain rheumatic and dermatologic conditions. They are also employed as part of immunosuppressive regimens in solid organ transplantation and in some hematologic malignancies.

Safety, monitoring, and interactions: Common adverse effects include bone marrow suppression, hepatotoxicity, pancreatitis, and gastrointestinal symptoms. Serious risks include infections from immunosuppression and rare hepatologic complications. Baseline and periodic complete blood counts and liver function tests are standard, with TPMT (and, in some populations, NUDT15) testing guiding initial dosing. Clinicians should monitor for signs of infection and educate patients about reporting fever or fatigue. Important drug interactions include allopurinol, which can amplify thiopurine toxicity.

History: Thiopuriines have been in clinical use since the mid-20th century, with azathioprine and 6-MP forming longstanding treatments for autoimmune diseases and leukemia.