Antimetabolites: methotrexate, fluoropyrimidines, gemcitabine and purine analogues
How antimetabolites block nucleotide synthesis in S phase, why folinic acid rescues methotrexate but potentiates 5-FU, DPYD testing before fluoropyrimidines (MBS-funded since November 2025), TPMT and the allopurinol interaction, and the toxicities each mechanism explains.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Antimetabolites are structural analogues of folate, pyrimidines or purines. They block nucleotide synthesis or are built into DNA and RNA, so they act in S phase.
- Rapidly dividing normal cells are hit first: marrow, gut mucosa and skin. Mucositis, diarrhoea and cytopenias are class effects.
- Two drugs are made safe by pharmacogenetics: DPYD for 5-FU and capecitabine, TPMT and NUDT15 for thiopurines (see pharmacogenetics of drug metabolism).
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Sources
- eviQ cancer treatments onlineAU/NZCancer Institute NSW, 2026
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- New Medicare Benefits Schedule item for dihydropyrimidine dehydrogenase (DPYD) genotyping (item 73322)AU/NZAustralian Government Department of Health, Disability and Ageing, 2025
- MSAC application 1760: DPYD genotyping to predict fluoropyrimidine-induced toxicityAU/NZMedical Services Advisory Committee, 2024
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for DPYD genotype and fluoropyrimidine dosing: 2017 updateClinical Pharmacology & Therapeutics 2018;103:210-6, 2017
- Goodman & Gilman's The Pharmacological Basis of Therapeutics (14th ed.)McGraw Hill (Brunton and Knollmann, 2023), 2023
- Last updated
- 14 November 2026
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