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Chapter: Clinical Pharmacology: Antineoplastic drugs

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Podophyllotoxins

Podophyllotoxins are semisynthetic glycosides that are cell cycle–specific and act during the G2 and late S phases of the cell cycle. They include: · etoposide · teniposide.

A subclass of antineoplastic drugs known as natural products in-cludes:

 

·                 vinca alkaloids

 

·                 podophyllotoxins.


Podophyllotoxins

 

Podophyllotoxins are semisynthetic glycosides that are cell cycle–specific and act during the G2 and late S phases of the cell cycle. They include:

·                 etoposide

 

·                 teniposide.

 

Outside activities

 

Etoposide is effective in the treatment of testicular cancer, non-Hodgkin’s lymphoma, lung cancer, and acute leukemia. Teniposide has demonstrated some activity in treating Hodgkin’s disease, lym-phomas, and brain tumors.

Pharmacokinetics

 

When taken orally, podophyllotoxins are only moderately ab-sorbed. Although the drugs are widely distributed throughout the body, they achieve poor CSF levels.

Metabolism and excretion

 

Podophyllotoxins undergo liver metabolism and are excreted pri-marily in urine.

Pharmacodynamics

 

Although their mechanism of action isn’t completely understood, podophyllotoxins produce several biochemical changes in tumor cells.

 

Arresting development

 

At low concentrations, these drugs block cells at the late S or G2 phase. At higher concentrations, they arrest the cells in the G2 phase.

 

Breaking a rung on the ladder

 

Podophyllotoxins can also break one of the strands of the DNA molecule and can inhibit nucleotide transport and incorporation into nucleic acids.

Pharmacotherapeutics

 

Etoposide is used to treat testicular cancer lymphomas, prostate cancer, and small-cell lung cancer. Teniposide is used to treat acute lymphoblastic leukemia.

Drug interactions

 

Podophyllotoxins have few significant interactions with other drugs.

 

·                 Etoposide may increase the risk of bleeding in a patient taking warfarin.

 

·                 Teniposide may increase the clearance and intracellular levels of methotrexate. (See Adverse reactions to podophyllotoxins.)

 


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