Ribonucleotide diphosphate reductase inhibitors
Hydroxyurea, also called hydroxycarbamide, NH2-CO-NHOH, inhibit ribonucleotide-diphosphate reductase. This enzyme, in presence of iron and reduced HS groups converts monophosphate and diphosphate ribonucleotides (adenosine, guanosine, cytidine) into the corresponding deoxyribonucleotides: dADP, dGDP and dCDP which are, after being phosphorylated into triphosphate derivatives, used for the synthesis of DNA.
Role of ribonucleotide reductase
Hydroxyurea (Hydrea*) acts primarily on bone marrow and is used in chronic myelogenous leukemia, myelogenous splenomegaly and certain polycythemia of which thrombocythemia (hyperplaquettosis).
It is well absorbed after oral administration and is eliminated by the kidney.
Hydroxycarbamide can induce different hematological and digestive adverse effects. Resistance to its effect can result from an increased ribonucleotide-diphosphate reductase synthesis.