Hydroxyurea

It is not very common that a drug like hydroxyurea is so exceptionally incredible, yet it has not gained as much traction and attention as it should have. It may be due to several factors, the fear of the perceived side effects being one of them. In a series of articles, we shall get well acquainted with this wonder drug, to provide both the clinician and their patient, with the knowledge, that is enough to enable them to make informed decisions when it comes to hydroxyurea use in sickle cell disease. This first part will provide a glimmer of light into what the drug is and how it works. Let’s get this started.

Scientists originally developed hydroxyurea as a drug that treats cancer, especially blood cancers like leukaemia, skin cancers like melanoma, and ovarian cancer. It was, however, not until 1984, that doctors tested hydroxyurea in sickle cell disease.

From 1984 to date, several clinical trials have shown that hydroxyurea is safe to use among toddlers, infants, children, adolescents, and adults.

Hydroxyurea is an important therapeutic option for children and adolescents with recurrent vaso-occlusive events. It has shown the ability to prevent or reverse chronic organ damage as a long term benefit.

Related article: COMPLETE BLOOD COUNT: What You Need to Know.

As we’ve noted earlier, the effect of hydroxyurea, as an effective therapy in sickle cell anaemia, hasn’t been felt yet. It may be due to the lack of knowledge among health care providers. Patients and their families often decline or don’t get treatment due to unrealistic fears for the drug. Another reason may be that the drug is costly: there are still no deliberate efforts to make it available widely. It implies that not every patient will afford it.

It is worth noting that the risks associated with the use of hydroxyurea can be acceptable when compared to the risks associated with untreated sickle cell disease.

When administered to people with sickle cell disease, hydroxyurea induces the bone marrow to produce fetal haemoglobin, in ways that aren’t yet understood. Fetal haemoglobin (HbF) doesn’t sickle. It means that its presence in substantial concentrations will almost reverse the deleterious effects of sickle haemoglobin (HbS).

Hydroxyurea inhibits the enzymes that are involved in the synthesis of DNA leading to cytotoxicity. Because the inhibition of these enzymes is reversible once the drug is no longer in circulation, it implies that the cytotoxic effect is intermittent. When this occurs in the cells that produce red blood cells, it induces them to increase the production of fetal haemoglobin.

The cytotoxic effects of hydroxyurea lead to reduced marrow production of neutrophils, reticulocytes, and platelets. All these cells are, in one way of the other, potent mediators of inflammation. We have observed that neutrophils and reticulocytes have the ability to promote vaso-occlusion by enhancing adhesion in the vessels. Lowering the white cell count will eventually lead to a reduced mortality and morbidity risk.

The effects of hydroxyurea on the red blood cells are enormous. It leads to increased cell volume, mean corpuscular haemoglobin.

The cells become well hydrated. There’s less hemolysis as well as reduced concentrations of sickled red cells. Because of this, there’s an improvement in the flow of blood, an increase in the levels of haemoglobin. Importantly, lactate dehydrogenase and bilirubin levels are also significantly reduced.
Hydroxyurea has a moiety of nitrous oxide, which is directly released. Nitrous oxide leads to widespread vasodilatation. It also fends off hemolysis related to nitrous oxide consumption.

It is worth noting that the body readily absorbs hydroxyurea after taking it orally, with the peak levels of the drug seen in plasma around 1 to 4 hours after the oral dose. There are no known effects of food on the drug to date. It distributes throughout the body. It has a tremendous affinity for white blood cells as well as red blood cells in which it concentrates most.
Metabolism of half of the administered drug is through unknown mechanisms. We believe that gut bacteria degrade the drug. Then, the liver and kidney do the excretion.

This pretty sums up the quick facts about hydroxyurea. In the next article, we shall explore the features that make hydroxyurea a perfect drug for a disease like sickle cell disease as well as the indications for its use in sickle cell disease.

By IAmDrSsekandi

I am a medical officer interested in maternal and child health. I am a content creator, author and founder of https://ssekandima.com. I do private practice with a public touch. I am a certified digital marketer. I earned certificates in Understanding Clinical Research and Writing in Sciences from the University of Cape Town and Stanford University respectively.

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