ATC Class:A06AB06

VA Class:GA204

AHFS Class:

• Cathartics and Laxatives 56:12

Generic Name(s):

• Casanthranol

• Cascara Sagrada

• Frangula

• Senna

• Sennosides

Chemical Name:

• 1,3,8-trihydroxy-6-methylanthraquinone

Molecular Formula:

• C₂₁H₂₀O₉

The anthraquinone group of stimulant laxatives includes the plant-derived compounds aloe (preparations containing aloe are no longer commercially available in the US), cascara sagrada (preparations containing cascara sagrada are no longer commercially available in the US), frangula, and senna.

Administration

Anthraquinone laxatives are administered orally, usually in a single dose at bedtime.

Dosage

Senna

Doses of the calcium sennosides, standardized senna concentrate, and standardized senna fruit extract are expressed in terms of sennosides.

The usual adult oral dose of senna is 0.5-2 g. The usual oral dosage of sennosides in adults and children 12 years of age and older is 12-50 mg once or twice daily. The usual laxative dosage of the senna preparations is 50% of the adult dosage for children 6-11 years of age, or 33% of the adult dosage for children 2-5 years of age.

When used to evacuate the bowel prior to colonic radiologic examinations, a dose of standardized senna fruit extract or standardized senna concentrate, to provide 105-157.5 mg of sennosides, should be administered orally 12-14 hours before the examination. To prepare for the examination, the patient should receive a residue-free diet one day before the examination; castor oil may be administered 16 hours before the examination, and a cleansing enema (e.g., tap water, soap suds, saline laxative, bisacodyl tannex enema) administered rectally on the day of the examination. Alternatively, magnesium citrate and magnesium sulfate (e.g., Citralax^®) or commercially available tablets of standardized senna concentrate in fixed-combination with docusate sodium may be administered the day before the examination, and a suppository containing bisacodyl administered rectally on the day of the examination.

Pharmacokinetics

Absorption

Following oral administration, the anthraquinone laxatives are absorbed only slightly from the small intestine. In the colon, most of the glycosides are hydrolyzed by the enzymes of colonic flora to the pharmacologically active, free anthraquinones.

Orally administered anthraquinone laxatives usually produce laxation within 6-12 hours but the effect may not occur for 24 hours. Rectally administered anthraquinone suppositories produce evacuation of the colon within 30 minutes to 2 hours.

Distribution

Distribution of anthraquinones and their metabolites into body tissues and fluids has not been fully characterized. The drugs may be distributed into bile, saliva, and the colonic mucosa. Distribution of anthraquinones into milk remains controversial; however, if the drugs are distributed into milk, it is unlikely that they appear in sufficient amounts to affect nursing infants. Although an increase in bowel activity in infants nursed by women receiving aloe (preparations containing aloe are no longer commercially available in the US), cascara sagrada (preparations containing cascara sagrada are no longer commercially available in the US), or senna preparations has been suggested, there is insufficient supporting documentation. Some studies indicate that nursing infants are not affected by maternal ingestion of usual doses of senna and that senna is not detectable in milk with usual doses.

Elimination

The absorbed anthraquinones are metabolized in the liver. Anthraquinones and their metabolites are excreted in feces via biliary elimination and/or in urine.

Chemistry and Stability

Chemistry

The anthraquinone group of stimulant laxatives includes the plant-derived compounds aloe (preparations containing aloe are no longer commercially available in the US), cascara sagrada (preparations containing cascara sagrada are no longer commercially available in the US), and senna. The active laxative principles are hydroxymethylanthraquinone derivatives that occur naturally in plants as glycosides. The amount of active drug obtained from the plants may vary widely with seasonal and other conditions.

Aloe

Aloe (no longer commercially available in the US) is the dried latex of the leaves of various species of Aloe found in the West Indies and Africa. Aloe differs in its texture and color depending on the species of Aloe; the drug has a nauseating, bitter taste and a characteristic, somewhat sour and disagreeable odor. Aloin is a microcrystalline powder consisting of a mixture of active ingredients (chiefly of barbaloin and isobarbaloin) extracted from aloe.

Cascara Sagrada

Cascara sagrada (or cascara) (preparations containing cascara sagrada are no longer commercially available in the US) is the dried bark of the buckthorn tree, Rhamnus purshiana, and occurs as flattened or transversely curved pieces or as a coarse, moderate yellowish-brown to dusky, yellowish-orange powder. Cascara sagrada has a distinct odor and a bitter and slightly acrid taste. The main active principles of cascara sagrada are 4 primary anthraquinone glycosides, cascarosides A and B (glycosides of barbaloin) and cascarosides C and D (glycosides of chrysaloin). Cascara sagrada extract, fluidextract, and aromatic fluidextract are obtained by percolating and evaporating coarse cascara sagrada powder. Cascara sagrada extract occurs as a fine powder; 1 gram of cascara sagrada extract represents 3 grams of cascara sagrada. The fluidextract and aromatic fluidextract are hydroalcoholic solutions of cascara sagrada; the fluidextract is bitter-tasting, but the aromatic fluidextract's palatability is improved by addition of magnesium oxide. Cascara sagrada fluidextract and aromatic cascara fluidextract each represent in 1 mL the active principles from 1 gram of cascara sagrada.

Casanthranol (preparations containing casanthranol are no longer commercially available in the US) is a purified, water-soluble mixture of the anthranol glycosides extracted from cascara sagrada. Casanthranol occurs as a light tan to brown, amorphous, hygroscopic powder and is freely soluble in water, with some residue. Each gram of casanthranol contains not less than 200 mg of total hydroxyanthracene derivatives, calculated on the dried basis as cascaroside A, of which not less than 80% of the derivatives consists of cascarosides (calculated as cascaroside A).

Senna

Senna, which may be unground or powdered, consists of the dried leaflet of Cassia acutifolia or of Cassia angustifolia. The primary active cathartic principles of senna are the stereoisomeric glucosides, sennosides A and B. Sennosides (formerly known as sennosides A and B) is a partially purified natural complex of anthraquinone glucosides and is prepared from Cassia angustifolia or C. acutifolia as calcium salts. The calcium salts of sennosides occur as a brownish powder. Standardized senna concentrate is a dry powder prepared from whole deseeded senna pod. Standardized senna fruit extract is a liquid extract obtained from whole senna pod. Senna fluidextract is obtained by percolating and evaporating coarse senna (leaf) powder and senna syrup is prepared from the fluidextract and syrup.

Stability

Senna

Senna fluidextract should be stored in tight, light-resistant containers and exposure to temperatures above 40°C should be avoided.

Additional Information

For further information on pharmacology, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of anthraquinone laxatives, see the Cathartics and Laxatives General Statement 56:12.