Thymidylate synthase inhibitor
- Thymidine depletion → DNA replication fails
- Rapidly dividing tissues suffer first: mucositis, myelosuppression, diarrhea
- Toxicity is severe where pyrimidine catabolism is impaired
Drugs with this mechanism (1)
- Fluorouracil — Thymidylate synthase inhibitor; DPD deficiency makes it lethal.
Self-check
- What makes thymidylate-synthase inhibitor toxicity especially severe?
Impaired pyrimidine catabolism. - Which rapidly dividing normal tissues are especially affected?
Mucosa and marrow.
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