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Treatment and the treatment process

Antimetabolites

Antimetabolites are drugs that mimic substances the cell itself needs. They are one of the most widely used drug groups in leukemia treatment.

Last updated: ~2 min read
Among golden keys on a dark navy background are similar teal keys that do not fit the cell’s locks.
Figure 1.An antimetabolite works like a "counterfeit key".

01Short answer

To divide, a cell must build new DNA, and for this it needs "building blocks" (nucleotides) and vitamins such as folic acid. Antimetabolites closely resemble these substances: the cell uses them "by mistake", or their pathway is blocked, so DNA cannot be built. The main antimetabolites in leukemia are cytarabine (the backbone of AML treatment), methotrexate (ALL — by mouth, into a vein and intrathecally), mercaptopurine and thioguanine (ALL maintenance), fludarabine and cladribine (CLL, HCL, preparation for transplant), nelarabine (T-ALL) and clofarabine (some relapses). They mostly act in the S phase of the cell cycle. Side effects mainly involve the bone marrow, mucous membranes and liver.

02Simple explanation

A mimic. The drug looks like a substance the cell needs.

A trick. The cell uses it, and DNA building stops.

Different kinds. Some mimic DNA bricks, others folic acid.

Widely used. In ALL, AML, CLL and HCL.

03Scientific explanation

Groups: pyrimidine analogues (cytarabine), purine analogues (mercaptopurine, thioguanine, fludarabine, cladribine, clofarabine, nelarabine) and folate antagonists (methotrexate, which blocks dihydrofolate reductase) (NCI).

High-dose methotrexate: given in some ALL blocks; clearing it through the kidneys requires alkalinising the urine, plenty of fluids and measuring methotrexate levels in the blood. After a set time, folinic acid (leucovorin) "rescue" is given to protect healthy cells.

Pharmacogenetics: TPMT and NUDT15 variants increase sensitivity to mercaptopurine and thioguanine. Allopurinol can greatly raise mercaptopurine levels, so using them together requires special dose adjustment.

04What happens in the body?

How does it work?

An antimetabolite is like a "counterfeit key": it fits into the lock but does not open the door. DNA building stops, and a cell trying to divide dies.

Methotrexate

Methotrexate blocks the activation of folic acid. At low doses it is given as tablets, at high doses as a long drip, and also intrathecally. After high doses, a special "rescue" medicine is given to protect healthy cells.

A stream of light particles pools before a softly closing glowing gate.
Figure 2.Methotrexate blocks the folic acid pathway.

Side effects

Low blood counts, mouth sores, nausea, changes in liver tests and sometimes skin sensitivity. With high-dose methotrexate, the kidneys are watched closely.

Warm golden light falls on calm healthy cells while a few abnormal cells stay dim.
Figure 3.Folinic acid rescue protects healthy cells.

05How is high-dose methotrexate given?

A simplified outline.

Preparation — Fluids and alkaline urine.1PreparationFluids and alkaline urine.
Infusion — A long drip.2InfusionA long drip.
Levels — Measured in the blood.3LevelsMeasured in the blood.
Rescue — Folinic acid.4RescueFolinic acid.
EffectiveImportant in ALL.
Genetic testTPMT, NUDT15.
MonitoringKidneys and liver.

06Main antimetabolites in leukemia

DrugWhereNote
CytarabineAML, ALLPyrimidine analogue
MethotrexateALL, intrathecalFolate antagonist
MercaptopurineALL maintenanceDaily tablet
ThioguanineALLLiver monitoring
Fludarabine, cladribineCLL, HCL, pre-transplantWeaken immunity for a long time
Nelarabine, clofarabineT-ALL, relapsesNeurological monitoring (nelarabine)

* Your doctor sets the dose and schedule according to the protocol.

07Key terms

Antimetabolite
A drug that mimics a normal substance.
Purines / pyrimidines
The two groups of DNA bricks.
Folate antagonist
A drug that blocks folic acid.
Leucovorin rescue
Protecting healthy cells after methotrexate.
TPMT
An enzyme involved in breaking down mercaptopurine.
S phase
The stage of the cell cycle when DNA is copied.

08Key points

  • Antimetabolites mimic natural substances.
  • They stop DNA building.
  • They are key drugs in ALL and AML.
  • High-dose methotrexate needs special monitoring.
  • Check for interactions.
  • Mouth care matters.

09Frequently asked questions

Can I take folic acid?

During methotrexate treatment, take vitamins and supplements only with your doctor’s agreement.

Why do they check my urine?

At high doses, methotrexate clears better in alkaline urine, which protects the kidneys.

When will mouth sores heal?

Usually within one to two weeks as blood counts recover.

Can I take mercaptopurine with food?

Advice varies by protocol; follow your team’s rule.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Can I take folic acid?

  2. Why do they check my urine?

  3. When will mouth sores heal?

  4. Can I take mercaptopurine with food?

My questions

12Sources

  1. National Cancer Institute (NCI). Chemotherapy to Treat Cancer
  2. American Cancer Society. How Chemotherapy Drugs Work
  3. Cancer Research UK. Chemotherapy
  4. MedlinePlus. Cancer Chemotherapy
  5. MedlinePlus. Methotrexate
  6. MedlinePlus. Mercaptopurine
  7. Leukemia & Lymphoma Society. AML treatment
  8. MedlinePlus. Acute myeloid leukemia
  9. American Cancer Society. Treating Acute Myeloid Leukemia (AML)
  10. Cancer Research UK. Treatment for acute lymphoblastic leukaemia (ALL)
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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