podophyllin

Podophyllin is a resinous powder obtained by precipitating an alcoholic tincture of the rhizome of American Mayapple (Podophyllum peltatum) or Podophyllum emodi by means of water acidified with hydrochloric acid. It varies in color from grayish to bright yellow or greenish-brown, the first-named being the purest. It was commonly used against genital warts because it contains antiwart lignans, although podofilox, a purified form of the main active ingredient, has become recommended due to its higher efficacy and safety.^[1]

The powder is soluble in alcohol and strong solutions of alkalis, such as ammonia. Its composition is somewhat complex. There are certainly at least two resins in the powder (which is known officially as Podophylli resina), one of them being soluble and the other insoluble in ether. Each of these contains an active substance, which can be obtained in crystalline form, and is known as podophyllotoxin. It is soluble in alcohol, ether, chloroform and boiling water.

Reactivity

Alkalis decompose it into picro-podophyllic acid and picro-podophyllin, minute traces of both of which occur in a free state in the rhizome. The acid is inert, but picro-podophyllin is the active principle.

It is a crystalline body, soluble only in concentrated alcohol. Hence the inutility of the pharmacopeial tinctura podophylli, which cannot be diluted before administration. The properties of podophyllin resin vary with the reaction of the tissue with which it is in contact; where this is acid the drug is inert, the picro-podophyllin being precipitated.

The resin does not affect the unbroken skin, but may be absorbed from a raw surface, and will then cause purging. When taken internally it is both a secretory and an excretory cholagogue, but so irritating and powerful that its use in cases of jaundice is generally undesirable. Its value, however, in certain cases of constipation of hepatic origin is undeniable. It is largely used in patent medicines, usually as an auxiliary to aloes. The best method of prescribing podophyllin is in pill form.

Toxicity

In toxic doses podophyllin causes intense enteritis, with all its characteristic symptoms, and severe depression, which may end in death. The treatment is symptomatic, there being no specific antidote.

Even when podophyllin resin is used topically, it can be systemically absorbed into the body, and fatal and near-fatal reactions have been reported, particularly when it is used extensively or on mucous membranes.^[2] Neither podophyllin resin nor podofilox lotion or gel is used during pregnancy because these medications can be harmful to the fetus. The most common side effects near the application site are skin reactions, including burning, redness, pain, itching, swelling. There is some concern about the mutagenicity of some of the flavonoids in podophyllin.^[1]

Medical Applications

Podophyllin has been used to remove genital warts since its efficacy was first demonstrated in 1942, although the reliability of this early report has been questioned.^[1] This requires one application of podophyllin resin a week to the warts by a health professional, which is then washed off after 4 to 6 hours.^[1] Petroleum jelly, such as Vaseline, may be used to protect normal tissue near the warts from irritation. A health professional usually applies the resin once a week for at least 6 weeks or until warts disappear.^{[citation needed]} It is unstable and therefore must be prepared shortly before use, which has possibly led to the lower efficacy shown in some clinical trials.^[1]

Podophyllin is also used to treat Molluscum contagiosum in the genital area. As the molluscum lesions can sometimes be quite numerous, scarring and hypopigmentation become an issue with cryosurgery.

References

• This article incorporates text from the Encyclopædia Britannica, Eleventh Edition, a publication now in the public domain.

Further reading

• Kelly M, Hartwell J. L. (1954). "The biological effects and the chemical composition of podophyllin: a review.". Journal of the National Cancer Institute 14 (4): 967–1010. 
• J. L. Hartwell, A. W. Schrecker (1951). "Components of Podophyllin. V. The Constitution of Podophyllotoxin". Journal of the American Chemical Society 73 (6): 2909–2916. doi:10.1021/ja01150a143.