• A subgroup of antimetabolite drugs.
  • All purine analogs may cause immunosuppression on long-term use.
  • Should be given cotrimoxazole for Pneumocystis prophylaxis.
  • Drugs included:
    • 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), fludarabine phosphate & cladribine.

Important drug details:

1. 6-mercaptopurine (6-MP) & 6-thioguanine (6-TG):

  • MOA:
    • Purine antimetabolites activated by hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) –> Resulting nucleotides –> Inhibiting several enzymes in purine biosynthesis & metabolism.
  • 6-MP:
    • Metabolized by xanthine oxidase.
    • When administered along with allopurinol (xanthine oxidase inhibitor), 6-MP dose (also azathioprine) should be reduced to 1/4th of original dose.
  • Uses:
    • Mainly for leukemias treatment (both acute leukemias & CML).
  • Adverse effects:
    • Bone marrow suppression (dose-limiting toxicity).
    • Hepatotoxicity.

2. Fludarabine phosphate:

  • DOC for chronic lymphocytic leukemia (CLL).
  • Severe pulmonary toxicity – Combination of pentostatin with Fludarabine.

3. Cladribine (adenine analogs):

  • Resistant to degradation by adenosine deaminase.
  • DOC for hairy cell leukemia treatment.


  • Drugs included: 
    • Cytarabine (cytosine arabinoside), 5-fluorouracil (5-FU), capecitabine, gemcitabine, 5-azacytidine & decitabine.

Important drug details:

1. Cytarabine:

  • Single most effective agent for induction of remission in AML.
  • MOA: 
    • Activated by kinases to form arabinoside CTP
    • Arabinoside CTP – DNA polymerase inhibitor.
  • Adverse effect: 
    • Neurotoxicity (ataxia & peripheral neuropathy) – High dose.

2. 5-FU:

  • MOA: 
    • Converted to 5’-dUMP inhibiting TS.
    • Causes single strand breaks thus affecting both DNA & RNA.
    • 5-FU is catabolized by dihydropyrimidine dehydrogenase (DPD).
  • Metabolism:
    • Conversion to CO (major route of metabolism) & elimination by respiratory pathway.
    • Leucovorin augments of 5-FU action.

3. Capecitabine:

  • Oral pro-drug of 5-FU.
  • Can cause hyperbilirubinemia.
  • Adverse effects:
    • Capecitabine & 5-FU: Causes hand and foot syndrome (a form of erythromelalgia manifested as tingling, numbness, pain, erythema, swelling and increased pigmentation).

4. Thiopurines (6MP & 6-TG): Metabolized by thiopurine methyltransferase 2 (TPMT).

5. Gemcitabine:

  • Very potent radiosensitizer.
  • DOC for pancreatic cancer.

6. 5-Azacytidine:

  • MOA: Acts by DNA hypomethylation.
  • Approved for myelodysplasia treatment.

Exam Important

  • Purine & pyrimidine analogs are the subgroups of antimetabolite drugs.
  • Drugs included in purine analogs are 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), fludarabine phosphate & cladribine.
  • 6-MP when administered along with allopurinol (xanthine oxidase inhibitor), 6-MP dose (also azathioprine) should be reduced to 1/4th of original dose.
  • Fludarabine phosphate is DOC for chronic lymphocytic leukemia (CLL).
  • Combination of pentostatin with Fludarabine causes severe pulmonary toxicity.
  • Cladribine (adenine analogs) is DOC for hairy cell leukemia treatment.
  • Drugs included in pyrimidine analogs are cytarabine (cytosine arabinoside), 5-fluorouracil (5-FU), capecitabine, gemcitabine, 5-azacytidine & decitabine.
  • Cytarabine is a single most effective agent for induction of remission in AML.
  • High dose of cytarabine causes neurotoxicity (ataxia & peripheral neuropathy).
  • 5-FU is catabolized by dihydropyrimidine dehydrogenase (DPD).
  • Capecitabine is an oral pro-drug of 5-FU.
  • Capecitabine & 5-FU causes hand and foot syndrome.
  • Thiopurines (6MP & 6-TG) are metabolized by thiopurine methyltransferase 2 (TPMT).
  • Gemcitabine is DOC for pancreatic cancer.
  • 5-Azacytidine acts by DNA hypomethylation which is approved for myelodysplasia treatment.
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