Ribonucleotide reductase inhibitors Flashcards
What are the most basic structures of nucleotide ?
- A 5 carbon sugar ( ribose in RNA) and Deoxyribose in DNA).
- Phosphate group
- A nitrogenous base.
What are the pyramidine bases of DNA / RNA ?
Cytosine , DNA specific Thymine, and RNA specific uracil.
What are the purine bases of DNA/ RNA ?
Adenine and guanine.
What is the difference b/w nucleotide and nucleoside ?
Nucleotide composed of nitrogenous base+ ribose + phosphate group. Where as Nucleoside composed of only nitrogenous base and ribose.
What is the action of the enzyme ribonucleotide diphosphate reducatase ?
It is responsible for converting the RNA nucelotide which is in the monophosphate form to DNA nucleotide which is in the diphosphate form.
What phase of the cell cycle ribonucleotide reductase inhibitors act ?
S phase.
What are the commonly used riboneucleotide reductase inhibitors ?
Hydroxyurea, Fludarabine phosphate, and Gemcitabine.
What is the MOA and indication of hydroxyurea?
It is an oral drug which binds to the iron molecules of the ribo-neucleotide reductase and prevent them from functioning.
It is indicated to treat myeloproliferative disorders such as CML and polycythemia vera. It is also used to treat sickle cell disease as it stimulates the production of foetal haemoglobin.
What are the main side effects of hydroxyurea ?
Severe myelosuppression, thrombocytopaenia, Leukopaenia, and macrocytic anaemia. In addition they may cause GI disturbance, and pneumonitis.
What is the MOA of Fludarabine phosphate ?
It is the flurinated and phosphorylated analogue of the anti-viral agent vidarabine. It can be given PO or IV. In the body it gets converted to fludarabine triphosphate which directly inhibits riboneucleotide reductase. It also intercalates into the DNA and prevents the action of DNA polymarase. These two actions together leads to impaired DNA synthesis and cell death.
What are the indications and side effects of Fludarabine phosphate ?
To treat CLL and low grade lymphomas. The main side effects are myelosuppression, fever, and GI disturbances.
What is the MOA of Gemcitabine ?
It is an IV drug which gets converted to gemcitabine diphosphate and directly inhibit ribonucelotide reductase enzyme. It’s tri-phosphate form blocks the DNA polymarase together leading to impaired DNA synthesis and cell death.
What are the indications and side effects of gemcitabine ?
It is indicated for the Tx of several carcinomas and non-hodgkin’s lymphoma. The side effects are pulmonary toxicity and myelosuppression.
