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Hydroxyurea

A ribonucleotide reductase inhibitor.

Interferes with the synthesis of DNA during the S-phase of cell division and prevents conversion of ribonucleotides to deoxynucleotides.

Cytostatic agent, S-phase inhibitor, used to treat erythrocytosis and thrombocytosis in polycythemia vera and other myeloproliferative disorders.

Significantly decreases the rate of thrombosis in essential thrombocytosis.

Increases the level of hemoglobin F and improves the clinical course of patients with S/Beta thalassemia and homozygous sickle cell disease but not with Beta thalassemia.

Hydroxyurea is used to increase fetal hemoglobin levels.

Hydroxyurea is a ribonucleotide reductase inhibitor that induces fetal hemoglobin production, which is normally suppressed shortly after birth.

Hemoglobin F inhibits hemoglobin S polymerization, reducing red blood cell rigidity and hemolysis, thereby improving anemia.

Hydroxyurea also increases nitric oxide of potent vasodilator, decreasing rate, cell adhesion, and decreases leukocytes which contribute to vaso-occlusion.

Inhibits ribonucleotide reductase.

Can be oxidized by heme groups to produce nitric oxide.

Usual dose in CML 40 mg/kg/d and adjustment of the dose needed to keep white blood cell count at acceptable levels.

The most frequently prescribed first line drug for patients with essential thrombocytosis giving its ease of administration, good efficacy, modest side effects, and a low incidence of treatment resistance.

Adverse effects include pancytopenia, chronic mucocutaneous ulcers, congestive heart failure, fluid retention, and possibly mutagenicity..

Approved for sickle cell anemia in patients with clinically severe disease.

Associated with an increase in hemoglobin F levels, reducing the severity of vaso-occlusive disease, acute pain, acute chest syndrome, transfusion requirements, and hospitalizations in patients with sickle cell anemia.

Associated with bone marrow suppression, gastrointestinal upset, dermatologic reactions, alopecia, and leg ulcers.

May be associated with palmer-plantar erythrodysesthesia.

Possible exceptions for the use of Hydroxyurea include patients younger than 40 years of age, particularly women of childbearing age.
It has teratogenetic an embryotoxic effects and is not considered safe during pregnancy.
Its use in essential thrombocytosis is not associated with an increased risk of leukemia transformation unlike radioactive phosphorus, alkylating agents, particularly those receiving sequential therapy.

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