Purine analogues

Purine analogues

Purine analogues are incorporated into DNA and RNA, interfering with nucleic acid synthesis and replication. They include:

• fludarabine phosphate
• cladribine
• mercaptopurine
• pentostatin
• thioguanine.

Pharmacokinetics

The pharmacokinetics of purine analogues aren’t clearly defined. They’re largely metabolized in the liver and excreted in urine.

Pharmacodynamics

As with the other antimetabolites, fludarabine, mercaptopurine, and thioguanine first must be converted via phosphorylation (introduction to a phosphate) to the nucleotide level to be active. The resulting nucleotides are then incorporated into DNA, where they may inhibit DNA and RNA synthesis as well as other metabolic reactions necessary for proper cell growth. Cladribine responds in a similar fashion.

 

Analogous to pyrimide analogues

This conversion to nucleotides is the same process that pyrimidine analogues go through but, in this case, it’s purine nucleotides that are affected. Purine analogues are cell cycle’specific as well, exerting their effect during that same S phase.

Death to T cells

Pentostatin inhibits adenosine deaminase (ADA), causing an increase in intracellular levels of deoxyadenosine triphosphate. This leads to cell damage and death. The greatest activity of ADA is in cells of the lymphoid system, especially malignant T cells.

 

Pharmacotherapeutics

Purine analogues are used to treat acute and chronic leukemias and may be useful in the treatment of lymphomas.

 

Drug interactions

No significant interactions occur with cladribine or thioguanine.

A serious flub with fludarabine

• Taking fludarabine with pentostatin may cause severe pulmonary toxicity, which can be fatal.
• Taking pentostatin with allopurinol may increase the risk of rash.
• Taking pentostatin with vidarabine may enhance the effect of vidarabine and increase the risk of toxicity.

Warning!

Adverse reactions to purine analogues

Purine analogues can cause:

• bone marrow suppression
• nausea and vomiting
• anorexia
• mild diarrhea
• stomatitis
• a rise in uric acid levels.

High-dose horrors

Fludarabine, when used at high doses, may cause severe neurologic effects, including blindness, coma, and death.

Down to the bone

• Concomitant administration of mercaptopurine and allopurinol may increase bone marrow suppression by decreasing mercaptopurine metabolism.