Stimulant laxatives

A number of herbal medicines producing a laxative effect contain mix- tures of anthranoid compounds including glycosides of anthraquinones, anthranols, dianthrones, and anthrones. These herbs are classified as stimulant laxatives because they stimulate peristalsis via mucosal irri- tation or intraneural nerve plexus activity, which results in increased motility. However, what is even more important is their action on colonic mucosal cells resulting in the opening of Cl – channels; this stimulates active Cl – secretion with a net reduction of liquid and electrolyte absorp-

tion in the colon. The subsequent increase in water and electrolytes in the colonic lumen results in greater pressure in the intestine that leads to a laxative action. 40

The anthranoid glycosides are essentially prodrugs. Upon oral administration, they pass to the colon unmodified, where they are hydrolyzed by the enzymes of the microbial flora of the gut to the free anthranoids plus glucose, rhamnose, or apiose. In addition, the free anthraquinones are inactive and are reduced by the microbial flora to the more active anthrones. Because the administered compounds must reach the colon to be activated, their effects are delayed and occur between six and twelve hours after ingestion. Therefore, a single bed- time dose promotes a morning bowel movement. These agents are indi- cated for constipation in patients who do not respond to milder drugs or have disorders such as anal fissures or hemorrhoids and after anal– rectal surgery in which an easy evacuation of the bowel with a soft stool is desired. They are also used for bowel evacuation before investigative procedures or surgery. 41

Adverse effects of these medications include abdominal cramps (also known as griping), nausea, electrolyte disturbances (e.g., hypokalemia, hypocalcemia, metabolic acidosis, or alkalosis), and increased mucus secretion. Because of the loss of potassium (hypokalemia), the effect of digitalis cardiac glycosides may be potentiated. Another drawback to their use includes their tendency to promote overemptying and reduction of spontaneous bowel function, thus leading to development of the so-called laxative habit. For this reason, chronic use of stimulant laxatives should be discouraged and use beyond one week should be avoided.

Chapter three: Digestive system problems

33 Being absorbed into the general circulation, anthranoids find their

way not only into the bile, urine, and saliva, but also into the milk of lac- tating women. Renal excretion of the compounds may cause abnormal coloration of the urine (yellowish brown that turns red with increasing pH). Large doses may produce nephritis, and when they are taken over extended periods, melanotic pigmentation of the colonic mucosa (melano- sis coli) has been observed. This is reversible and thought to be benign, but its presence may help confirm a suspicion of laxative abuse.

In recent years, evidence has been reported that several anthraquinones are mutagenic in the Ames test. Some have been found to induce genotoxic effects in cultured mammalian cells and to behave as possi- ble tumor promoters. As a consequence, in 1996 the FDA reclassified the OTC laxatives aloe, cascara sagrada, and senna from category I (safe and effective) to category III (more data needed); however, these drugs were allowed to stay on the market. Human clinical and epidemiological stud- ies do not clearly suggest that use of anthraquinone herbal laxative drugs represents a risk for colorectal cancer or mutagenic effects under normal use conditions. 42,43 With this in mind, however, it would be prudent not to use these agents continuously over long periods of time.

Stimulant laxatives