Pharmacology of Podophyllotoxin and Related Compounds

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Podophyllotoxin (podofilox) and its derivatives, etoposide and teniposide, are all cytostatic (antimitotic) glucosides.

Podofilox is an extract of the mayapple which generally acts as a cell poison which cells undergoing mitosis (division) are particularly vulnerable to. It isn't itself used as a chemotherapy agent; instead, it is used in creams such as Oclassen's Condylox as a treatment for genital warts. Genital warts, which are caused by the human papillomavirus (HPV), have been associated with cancers of the genitals (squamous cell carcinomas).

Adverse reactions to topical applications of podofilox include burning, inflammation, etc. When the drug was being investigated as a chemotherapy agent, it caused reactions such as nausea, vomiting, fever, mouth ulcers, diarrhea, nervous system problems, seizures, kidney damage, etc. Thus far, research hasn't shown whether using podofilox to treat warts can harm the children of pregnant or nursing mothers or not, but to be on the safe side they probably shouldn't use the drug.

[image of etoposide molecule]

Etoposide and teniposide both block the cell cycle in two specific places: they block the phase between the last division and the start of DNA replication (the G1 phase) and they block the replication of DNA (the S phase). However, researchers don't have a very good understanding of how the compounds do this.

Etoposide (which is sold by Bristol-Myers Squibb as VePesid, aka VP-16) is administered intravenously or orally as liquid capsules. It is used mainly to treat testicular cancer which hasn't responded to other treatment and as first-line treatment for small-cell lung cancers. It is also used to treat chorionic carcinomas, Kaposi's sarcoma, lymphomas and malignant melanomas. Major side effects include hair loss, nausea, anorexia, diarrhea, and low leukocyte and platelet counts. Very rarely, some people have severe allergic reactions to the drug. It can also cause genetic damage and may increase a patient's risk of developing leukemia. Etoposide is known to cause fetal damage and birth defects, and so it should not be used by pregnant or nursing women.

Teniposide is used less often than etoposide; mainly, it is used to treat lymphomas. It has similar side effects.

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References:

Budavari, Susan, ed. 1989. The Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ, Merck & Co.

Goodman, Louis Sanford, Alfred Gilman, and Alfred Goodman Gilman, eds. 1990.The Pharmacological Basis of Therapeutics, 8th Edition. Elmsford, NY, Pergamon Press.

Mutschler, Ernst, and Hartmut Derendorf. 1995. Drug Actions: Basic Principles and Therapeutic Aspects. Stuttgart, Germany, medpharm Scientific Publishers.

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