Hydroxyurea

Summary

Hydroxyurea is an antimetabolite drug that inhibits RNR, or ribonucleotide reductase. RNR is an enzyme that plays a role in the conversion of ribonucleotides to deoxyribonucleotides, so by inhibiting RNR, hydroxyurea decreases DNA synthesis and halts the cell cycle in the S phase. This property is particularly useful in targeting and preventing the growth of rapidly dividing cells, which is why hydroxyurea is used to treat myeloproliferative disorders. Additionally, hydroxyurea is used in the treatment of sickle cell disease. Hydroxyurea increases fetal hemoglobin, which is more resistant to sickling than adult hemoglobin.

Key Points

• Hydroxyurea
  • Mechanism
    • Inhibits ribonucleotide reductase (RNR)
      • Reduces DNA synthesis by inhibiting Pyrimidine Synthesis
      • S-phase specific
  • Clinical use
    • Myeloproliferative disorders
      • E.g. CML, polycythemia vera
    • Sickle cell anemia
      • Via increased fetal hemoglobin (HbF)
        • Mechanism is not understood but HbF is less prone to sickling than adult Hb