Pyrimidine Analogues

Overview of pyrimidine analogues in medicine

Pyrimidine analogues are a class of antimetabolite medications that mimic the structure of the pyrimidine nucleotides, which are essential components of DNA and RNA. These analogues are primarily used in the treatment of various types of cancer and viral infections. By interfering with the synthesis and function of nucleic acids, pyrimidine analogues can inhibit the proliferation of rapidly dividing cells, such as cancer cells and viruses.

Mechanism of Action

Pyrimidine analogues exert their effects by incorporating into nucleic acids or by inhibiting enzymes involved in nucleotide synthesis. This disruption can lead to faulty DNA replication and RNA transcription, ultimately resulting in cell death or the inhibition of viral replication.

Incorporation into Nucleic Acids

Some pyrimidine analogues are incorporated into DNA or RNA in place of natural pyrimidines. This incorporation can cause chain termination or introduce mutations that impair the function of the nucleic acids. For example, 5-fluorouracil (5-FU) is a pyrimidine analogue that is incorporated into RNA, disrupting its processing and function.

Enzyme Inhibition

Other pyrimidine analogues inhibit key enzymes in the pyrimidine synthesis pathway. For instance, 5-FU also inhibits thymidylate synthase, an enzyme critical for the synthesis of thymidine, a nucleotide required for DNA replication. This inhibition leads to a depletion of thymidine and results in "thymineless death" of rapidly dividing cells.

Clinical Applications

Pyrimidine analogues are used in the treatment of various malignancies and viral infections. Their ability to target rapidly dividing cells makes them effective in these contexts.

Cancer Treatment

Pyrimidine analogues are used in chemotherapy regimens for several types of cancer, including:

• Colorectal cancer: 5-FU is a cornerstone of treatment for colorectal cancer, often used in combination with other agents such as leucovorin and oxaliplatin.
• Breast cancer: Capecitabine, an oral prodrug of 5-FU, is used in the treatment of metastatic breast cancer.
• Leukemias and lymphomas: Cytarabine is a pyrimidine analogue used in the treatment of acute myeloid leukemia (AML) and other hematological malignancies.

Antiviral Therapy

Some pyrimidine analogues are used as antiviral agents. For example, trifluridine is used topically to treat herpes simplex virus infections of the eye.

Side Effects

The use of pyrimidine analogues can lead to several side effects, primarily due to their effects on rapidly dividing normal cells, such as those in the gastrointestinal tract, bone marrow, and hair follicles. Common side effects include:

• Myelosuppression: Decreased production of blood cells, leading to anemia, leukopenia, and thrombocytopenia.
• Gastrointestinal toxicity: Nausea, vomiting, diarrhea, and mucositis.
• Alopecia: Hair loss due to the effect on hair follicle cells.

Also see

• Antimetabolite
• Chemotherapy
• Nucleotide analogue
• Purine analogue

Drugs for HIV Infection, in the Subclass Antiretroviral Agents

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Drugs for Influenza

• Amantadine, Oseltamivir, Peramivir, Rimantadine, Zanamivir