From the Guidelines
Hydroxyurea's mechanism of action (MOA) is myelosuppressive, meaning it suppresses the production of blood cells in the bone marrow [ 1 ].
Key Mechanism Details
- The exact mechanism involves inhibiting DNA synthesis, although the specific details of this process are not outlined in the provided evidence [ 1 ].
- This action is the basis for its use in treating conditions like polycythemia vera, where it helps reduce the excessive production of blood cells [ 1 ].
Administration and Monitoring
- Hydroxyurea is typically administered orally, with a starting dosage of 500 mg twice a day [ 1 ].
- The treatment duration is usually long-term, requiring regular monitoring of blood counts and other parameters to adjust the dose and minimize side effects such as anemia, neutropenia, oral and skin ulcers, hyperpigmentation, and nail changes [ 1 ].
Clinical Considerations
- In clinical practice, hydroxyurea is often chosen for its effectiveness and relatively manageable side effect profile compared to other options like busulfan or interferon α [ 1 ].
- However, its use must be carefully considered, especially in younger patients due to concerns about potential long-term effects, and in women of childbearing age due to the theoretical risk of teratogenicity [ 1 ].
From the FDA Drug Label
The precise mechanism by which hydroxyurea produces its antineoplastic effects cannot, at present, be described However, the reports of various studies in tissue culture in rats and humans lend support to the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein.
The mechanism of action (MOA) of Hydroxyurea is believed to be through the inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor. This hypothesis is supported by various studies in tissue culture in rats and humans 2 2.
- Key points:
- Inhibition of DNA synthesis
- Ribonucleotide reductase inhibitor
- No interference with RNA or protein synthesis However, the precise mechanism by which hydroxyurea produces its antineoplastic effects cannot be fully described.
From the Research
Mechanism of Action of Hydroxyurea
The mechanism of action (MOA) of Hydroxyurea involves the inhibition of DNA synthesis and cell cycle arrest through the inhibition of ribonucleotide reductase, an enzyme crucial for the conversion of ribonucleotides to deoxyribonucleotides 3, 4, 5, 6, 7.
- Inhibition of Ribonucleotide Reductase: Hydroxyurea quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme and selectively inhibiting DNA synthesis 6.
- Cell Cycle Arrest: The inhibition of ribonucleotide reductase leads to cell cycle arrest in the S-phase, resulting in cell death and synchronization of the fraction of cells that survive 6.
- Inhibition of DNA Repair: Hydroxyurea also inhibits the repair of DNA damaged by chemicals or irradiation, offering potential synergy between hydroxyurea and radiation or alkylating agents 6.
- Induction of Oxidative Stress: Recent studies have shown that oxidative stress and several other mechanisms may contribute to the majority of the cytotoxic effect of hydroxyurea 7.
- Mitochondria-Targeted Effects: Mitochondria-targeted hydroxyurea has been shown to inhibit oxidative phosphorylation and induce antiproliferative and immunomodulatory effects 5.
Effects on Disease Treatment
Hydroxyurea has been used to treat various diseases, including:
- Sickle Cell Anemia: Hydroxyurea increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises 6.
- Chronic Myeloproliferative Disorders: Hydroxyurea is used as a first-line treatment for myeloproliferative disorders, such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis 4.
- Cancer: Hydroxyurea has been used in combination therapy for the management of malignant melanoma, head and neck cancers, and brain tumors 4.