Ribonucleotide reductase inhibitors

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Ribonucleotide reductase inhibitors

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A 72-year-old woman comes to the dermatology clinic because of an enlarging lesion on the nose, which she first noticed 6-months ago. The patient has also experienced increased confusion and forgetfulness. Vitals are within normal limits. Physical examination reveals the findings below. An excisional biopsy is obtained and confirms the diagnosis of nodular melanoma. On additional evaluation, the patient is found to have multiple metastatic lesions in the brain. The patient is prescribed a medication that acts by blocking the action of ribonucleotide reductase. Which of the following adverse effects is most likely associated with this medication?
Image reproduced from DermNetNZ


Ribonucleotide reductase inhibitors, as their name implies, are a class of medications that act by blocking an enzyme called ribonucleotide reductase. They are mainly used as anticancer agents that target a specific phase of the cell cycle.

At a quick glance, the life of a cell - its cell cycle - has an interphase, made up of subphases G1, S, and G2, during which the cell is preparing for division; and mitosis, during which the cell actively divides.

During the S phase, the cell performs DNA replication - which is when its 46 chromosomes are duplicated so that each daughter cell can get its own copy of the genetic material.

Now, a single chromosome is made up of a single DNA molecule that has two strands, which wrap around one another to form a double helix.

Each single strand of DNA is composed of a sequence of DNA nucleotides.

Now, nucleotides are the building blocks of nucleic acids such as deoxyribonucleic acid, or DNA; and ribonucleic acid, or RNA.

The most basic structure of the nucleotide can be broken down into three subunits; a five carbon sugar, a phosphate group, and a nitrogenous base, also known as a nucleobase.

The five carbon sugar is either deoxyribose in DNA or ribose in RNA.

Now, the nucleobases can be either pyrimidines or purines.

The 3 pyrimidine bases are cytosine, or C; thymine, or T, which is DNA specific; and uracil, or U, which is RNA specific.

There are also two purine bases, adenine, or A; and guanine, or G.

Now, if we link up just the sugar and the nucleobase, we’ve got ourselves a nucleoside.

To make a nucleotide, all we’ve got to do is add a phosphate group to the 5th carbon of the sugar on a nucleoside.

Okay, so in order to make DNA nucleotides we use RNA nucleotides.

RNA nucleotides are usually in the monophosphate form and we need to change them into the diphosphate form for DNA.

So a cytoplasmic enzyme called ribonucleotide reductase, also known as ribonucleoside diphosphate reductase, will reduce the ribose within them into deoxyribose, creating deoxyribonucleotides, which then travel to the nucleus where DNA synthesis takes place.

Alright, now the cancer cells are going through the phases of the cell cycle like normal cells, but they divide much more frequently.


Ribonucleotide reductase inhibitors are a class of drugs that act by blocking an enzyme called ribonucleotide reductase. They are mainly used as anticancer agents that target DNA synthesis and cell growth. Ribonucleotide reductase inhibitors include drugs like hydroxyurea, fludarabine phosphate, and gemcitabine. Hydroxyurea is used for the treatment of myeloproliferative disorders and sickle cell disease; Fludarabine phosphate is used for leukemias and lymphomas; whereas gemcitabine is used for a variety of carcinomas and non-Hodgkin's lymphoma. Common side effects include myelosuppression, gastrointestinal disturbances, pulmonary toxicity, and liver toxicity.


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