Pyrimidine analogues

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Pyrimidine analogues
Pyrimidine analogues are a diverse group of drugs that inhibit production of pyrimidine nucleotides necessary for DNA synthesis. They include:
  • capecitabine
  • cytarabine
  • floxuridine
  • fluorouracil
  • gemcitabine.

Now I get it!
How pyrimidine analogues work
To understand how pyrimidine analogues work, it helps to consider the basic structure of deoxyribonucleic acid (DNA).
Climbing the ladder to understanding
DNA resembles a ladder that has been twisted. The rungs of the ladder consist of pairs of nitrogenous bases: adenine always pairs with thymine, and guanine always pairs with cytosine. Cytosine and thymine are pyrimidines; adenine and guanine are purines.
 
One part sugar…
The basic unit of DNA is the nucleotide. A nucleotide is the building block of nucleic acids. It consists of a sugar, a nitrogen-containing base, and a phosphate group. It’s on these components that pyrimidine analogues do their work.
 
In the guise of a nucleotide
After pyrimidine analogues are converted into nucleotides, they’re incorporated into DNA, where they may inhibit DNA and ribonucleic acid synthesis as well as other metabolic reactions necessary for proper cell growth.
Like most antineoplastic drugs, pyrimidine analogues can cause:
Pharmacokinetics
Because pyrimidine analogues are poorly absorbed when they’re given orally, they’re usually administered by other routes.
 
Distribution, metabolism, and excretion
With the exception of cytarabine, pyrimidine analogues are well distributed throughout the body, including in cerebrospinal fluid (CSF). They’re metabolized extensively in the liver and are excreted in urine. Intrathecal cytarabine may be given with or without cranial radiation to treat CNS leukemia.
Pharmacodynamics
Pyrimidine analogues kill cancer cells by interfering with the natural function of pyrimidine nucleotides. 
 
Pharmacotherapeutics
Pyrimidine analogues may be used to treat many tumors. However, they’re primarily indicated in the treatment of:
  • acute leukemias
  • GI tract adenocarcinomas, such as colorectal, pancreatic, esophageal, and stomach adenocarcinomas
  • cancers of the breast and ovaries
  • malignant lymphomas.
Warning!
Adverse reactions to pyrimidine analogues
Like most antineoplastic drugs, pyrimidine analogues can cause:
  • fatigue and lack of energy
  • inflammation of the mouth, esophagus, and throat
  • bone marrow suppression
  • nausea and anorexia.
Cytarabine
  • Severe cerebellar neurotoxicity
  • Chemical conjunctivitis
  • Diarrhea
  • Fever
  • Hand-foot syndrome
  • Crab erythema (when high-dose cytarabine is combined with continuous infusions of fluorouracil)
Fluorouracil
  • Diarrhea
  • Hair loss
  • Mucositis (when combined with folinic acid)
Drug interactions
No significant drug interactions occur with most of the pyrimidine analogues; however, several drug interactions are possible with capecitabine.
  • Antacids, when given with capecitabine, may increase absorption of capecitabine.
  • Capecitabine can increase the pharmacodynamic effects of warfarin, thereby increasing the risk of bleeding.
  • Capecitabine may increase serum phenytoin levels.

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