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Scientific Name(S): Podophyllum peltatum L., P. hexandrum Royle syn P. emodi Wall. Family: Podophyllaceae formerly Berberidaceae)

Common Name(S): Mayapple, mandrake, American podophyllum (P. peltatum), Indian podophyllum P. hexandrum). Other common names include wild or American mandrake, devil's apple, vegetable mercury and duck's foot. The plant should not be confused with the European mandrake (Mandragora officinarum L.) which contains the anticholinergics hyoscyamine, scopolamine and mandragorine.

Botany: A perennial plant with one or two large lobed leaves that grows in moist shaded areas throughout North America, P. hexandrum is found primarily in Tibet and Afghanistan. A single white or cream-colored flower grows between the two leaves from May to August. It bears a fruity berry that turns yellow when ripe.

History: Podophyllum resin was used by the American Indians and colonists as a cathartic and anthelmintic, as an antidote for snake bites and as a poison. Podophyllum was a common ingredient in many proprietary medicines including Carter's Little Liver Pills. It has been used for almost 40 years in the treatment of topical warts, especially condylomata. The resin had long been thought to possess anticancer activity; derivatives have been used successfully in controlled clinical trials. An FDA advisory panel has established that because of its drastic effect and great potential for toxicity, podophyllum resin is not considered a safe laxative.

Uses of Podophyllum:

Podophyllum has been used to treat refractory testicular tumors, small cancer cells of the lung, a variety of lymphomas and other neoplastic diseases, warts, genital warts, and rheumatoid arthritis.

Side Effects of Podophyllum:

Podophyllm has resulted in hypokalemia, altered mental states, tachypnea, peripheral neuropathy, nausea, hypotension, vomiting, fever, and muscle paralysis with respiratory failure.

Toxicology: The ripe fruit pulp of the mayapple is edible, often being made into marmalades or jellies. Podophyllin is potentially lethal when ingested. Great care must be taken in its external use. Chronic use of podophyllum resin as a cathartic has resulted in hypokalemia sometimes associated with metabolic alkalosis. At least 3 deaths have been attributed to either oral ingestion or topical application. Podophyllum toxicity is multisystemic with characteristic neurologic manifestations. Clinical signs appear within 12 hours and include altered mental states, tachypnea, peripheral neuropathy, nausea, hypotension, vomiting, and fever. Rapidly progressive neurologic deficit varying from confusion to coma is always observed. Muscle paralysis with respiratory failure, renal failure, hallucinations, and seizures have been reported. Bone marrow suppression has been noted in acute intoxication and in chronic laxative abusers.

Seven cases of podophyllin toxicity have resulted in severe peripheral neuropathies, from topical or oral administration. The onset of the neuropathies generally occurred within hours of application or ingestion and the duration ranged from months up to four years with some neurologic deficit still present. Exact doses that were used, as well as how long they were left in contact with the treated area are often not given.

Emesis may be useful during the initial phases of toxicity. Topically administered resin should be removed with petroleum jelly. Podophyllum is lipid soluble; hemodialysis is ineffective, while charcoal hemoperfusion has reversed acute symptoms within hours.

Podophyllum is teratogenic in animals and humans. Limb deformities and septal heart defects have been associated with its ingestion by pregnant women. Preauricular skin tags and a simian crease were noted in an infant born to a woman treated with topical podophyllum resin from the 23rd to 29th week of pregnancy. Total contact with the drug was 4 hours. An intrauterine death has been reported in a woman treated with podophyllum for vulvar warts during week 32 of her pregnancy.

Summary: Podophyllum and its extracts have been used internally as drastic cathartics and externally in the treatment of venereal warts. Semisynthetic plant derivatives are used to manage a variety of neoplastic disorders. The resin is a mitotic poison, and its misuse can lead to significant toxicity. It should not be administered to children, and use in pregnant women has been associated with congenital abnormalities and fetal death.

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