Podophyllin
Encyclopedia
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 HPV induced genital wart
s because it contains antiwart lignan
s, although podofilox, a purified form of the main active ingredient, has become recommended due to its higher efficacy and safety.
The powder is soluble in alcohol and strong solutions of alkali
s, such as ammonia
. Its composition is somewhat complex. There are certainly at least two resin
s 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.
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 aloe
s. The best method of prescribing podophyllin is in pill form.
, with all its characteristic symptoms, and severe depression
, which may end in death. The treatment is symptom
atic, 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. 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 flavonoid
s in podophyllin.
s since its efficacy was first demonstrated in 1942, although the reliability of this early report has been questioned. 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. 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. It is unstable and therefore must be prepared shortly before use, which has possibly led to the lower efficacy shown in some clinical trials.
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
.
Corticosteroid therapy.
Application to bleeding warts, moles, birthmarks, or unusual warts with hair growing from them.
Pregnancy.
Breast-feeding.
American Mayapple
Podophyllum peltatum, commonly called mayapple , is a herbaceous perennial plant in the family Berberidaceae, native to wooded areas of eastern North America.The stems grow to 30-40 cm tall, with 2 or occasionally 3 palmately lobed...
(Podophyllum peltatum) or Podophyllum emodi by means of water acidified with hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
. It varies in color from grayish to bright yellow or greenish-brown, the first-named being the purest. It was commonly used against HPV induced genital wart
Genital wart
Genital warts is a highly contagious sexually transmitted disease caused by some sub-types of human papillomavirus . It is spread through direct skin-to-skin contact during oral, genital, or anal sex with an infected partner...
s because it contains antiwart lignan
Lignan
The lignans are a group of chemical compounds found in plants. Lignans are one of the major classes of phytoestrogens, which are estrogen-like chemicals and also act as antioxidants. The other classes of phytoestrogens are the isoflavones and coumestans...
s, although podofilox, a purified form of the main active ingredient, has become recommended due to its higher efficacy and safety.
The powder is soluble in alcohol and strong solutions of alkali
Alkali
In chemistry, an alkali is a basic, ionic salt of an alkali metal or alkaline earth metal element. Some authors also define an alkali as a base that dissolves in water. A solution of a soluble base has a pH greater than 7. The adjective alkaline is commonly used in English as a synonym for base,...
s, such as ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
. Its composition is somewhat complex. There are certainly at least two resin
Resin
Resin in the most specific use of the term is a hydrocarbon secretion of many plants, particularly coniferous trees. Resins are valued for their chemical properties and associated uses, such as the production of varnishes, adhesives, and food glazing agents; as an important source of raw materials...
s 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
Podophyllotoxin
Podophyllotoxin , otherwise known as podofilox, is a non-alkaloid toxin lignan extracted from the roots and rhizomes of Podophyllum species. Under the trade name Condylox, a topical gel, it is used on the skin to treat external genital warts, caused by some types of the human papillomavirus...
. 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 agent.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
Cholagogue
A cholagogue is a medicinal agent which promotes the discharge of bile from the system, purging it downward.In Patrick O'Brian's book "The Post Captain," which is set in the Napoleonic era, Stephen Maturin, one of the book's main characters sits in the snug of the Rose and Crown in Deal and drinks...
, but so irritating and powerful that its use in cases of jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
is generally undesirable. Its value, however, in certain cases of constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
of hepatic origin is undeniable. It is largely used in patent medicines, usually as an auxiliary to aloe
Aloe
Aloe , also Aloë, is a genus containing about 500 species of flowering succulent plants. The most common and well known of these is Aloe vera, or "true aloe"....
s. The best method of prescribing podophyllin is in pill form.
Toxicity
In toxic doses podophyllin causes intense enteritisEnteritis
In medicine, enteritis, from Greek words enteron and suffix -itis , refers to inflammation of the small intestine. It is most commonly caused by the ingestion of substances contaminated with pathogenic microorganisms. Symptoms include abdominal pain, cramping, diarrhea, dehydration and fever...
, with all its characteristic symptoms, and severe depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, which may end in death. The treatment is symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
atic, 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. 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 flavonoid
Flavonoid
Flavonoids , are a class of plant secondary metabolites....
s in podophyllin.
Medical applications
Podophyllin has been used to remove genital wartGenital wart
Genital warts is a highly contagious sexually transmitted disease caused by some sub-types of human papillomavirus . It is spread through direct skin-to-skin contact during oral, genital, or anal sex with an infected partner...
s since its efficacy was first demonstrated in 1942, although the reliability of this early report has been questioned. 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. Petroleum jelly
Petroleum jelly
Petroleum jelly, petrolatum, white petrolatum or soft paraffin, CAS number 8009-03-8, is a semi-solid mixture of hydrocarbons , originally promoted as a topical ointment for its healing properties...
, 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. It is unstable and therefore must be prepared shortly before use, which has possibly led to the lower efficacy shown in some clinical trials.
Podophyllin is also used to treat Molluscum contagiosum
Molluscum contagiosum
Molluscum contagiosum is a viral infection of the skin or occasionally of the mucous membranes. It is caused by a DNA poxvirus called the molluscum contagiosum virus . MCV has no animal reservoir, infecting only humans. There are four types of MCV, MCV-1 to -4; MCV-1 is the most prevalent and...
in the genital area. As the molluscum lesions can sometimes be quite numerous, scarring and hypopigmentation
Hypopigmentation
Hypopigmentation is the loss of skin color. It is caused by melanocyte or melanin depletion, or a decrease in the amino acid tyrosine, which is used by melanocytes to make melanin.-Treatments:...
become an issue with cryosurgery
Cryosurgery
Cryosurgery is the application of extreme cold to destroy abnormal or diseased tissue. The term comes from the Greek words cryo and surgery meaning "hand work" or "handiwork"....
.
Contraindications
Diabetes mellitus or poor circulation.Corticosteroid therapy.
Application to bleeding warts, moles, birthmarks, or unusual warts with hair growing from them.
Pregnancy.
Breast-feeding.