Thioguanine
Mechanism :
Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase and is itself converted to 6-thioguanylic acid (TGMP). This nucleotide reaches high intracellular concentrations at therapeutic doses. TGMP interferes at several points with the synthesis of guanine nucleotides. It inhibits de novo purine biosynthesis by pseudo-feedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase-the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis.
Indication :
- Acute lymphoblastic leukemia
- Lymphoma
- Myeloid leukemia
- Chronic granulocytic leukemia
Contraindications :
Thioguanine should not be used in patients whose disease has demonstrated prior resistance to this drug. It is possible that patients of Lesch-Nyhan syndrome may be resistant to the drug. Consideration should be given to reducing the dosage in patients with impaired hepatic or renal function.
Dosing :
2-3 mg/kg/day orally.
Adverse Effect :
Stomatitis, anorexia, nausea, vomiting, gastric-intestinal intolerance, intestinal necrosis and perforation associated with veno-occlusive disease of the liver, myelosuppression, loss of vibration sense, unsteady gait, liver function abnormalities, hyperuricemia, nephrotoxicity.
Interaction :
Mercaptopurine: There is usually complete cross-resistance.
Aminosalicylate Derivatives (e.g., Olsalazine, Mesalazine, or Sulfasalazine): Should be administered with caution to patients receiving concurrent thioguanine therapy.
Hepatic Dose :
No dose adjustment recommended as it undergoes minimal hepatic metabolism. However use with caution and monitor as abnormal liver function tests have been reported.