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, lymphomas, and brain tumors.
Pharmacokinetics
When taken orally, podophyllotoxins are only moderately absorbed. Although the drugs are widely distributed throughout the body, they achieve poor CSF levels.
Metabolism and excretion
Podophyllotoxins undergo liver metabolism and are excreted primarily 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.)
Warning!
Adverse reactions to podophyllotoxins
The majority of patients receiving podophyllotoxins experience hair loss. Other adverse reactions include:
- nausea and vomiting
- anorexia
- stomatitis
- bone marrow suppression, causing leukopenia and, less commonly, thrombocytopenia
- acute hypotension (if a podophyllotoxin is infused too rapidly I.V.).
Thanks for your visit..!