Diphenylmethane laxatives

B. Large-bowel irritant laxatives diphenylmethane derivatives... 

Stimulant laxatives increase intestinal motility thereby decreasing absorption of water and electrolytes. Included in this group are diphenylmethane derivatives and anthraquinones. 

The two most important diphenylmethanes are phenolphthalein and bisacodyl. Senna and cascara are the sources of anthraquinone laxatives. However, although still available in some countries phenolphthalein is now removed from most markets because of concerns over carcinogenicity. As recent as 2006 the United States Food and Drug Administration (FDA) has categorized castor oil as generally recognized as safe and effective (GRASE) for over-the-counter use as a laxative. On the other hand, in 2002 cascara was banned by the FDA. 

Laxatives in this group exert an irritant action on the enteric mucosa (A). Consequently, less fluid is absorbed than is secreted. The increased filling of the bowel promotes peristalsis excitation of sensory nerve endings elicits enteral hypermotility. According to the site of irritation, one distinguishes the small-bowel irritant castor oil from the large-bowel irritants anthraqui-none and diphenylmethane derivatives (for details see p.178). 

Stimulant laxatives fall into two main groups diphenylmethane derivatives and anthraquinones. 

For most persons with acnte constipation, infrequent use (less than every few weeks) of laxative products is acceptable. Acute constipation may be relieved by the nse of a tap-water enema or a glycerin suppository if neither is effective, the use of oral sorbitol, low doses of diphenylmethane or anthraquinone laxatives, or saline laxatives (e.g., milk of magnesia) may provide relief. If laxative treatment is required for longer than 1 week, the person should be advised to consult a physician to determine if there is an underlying cause of constipation that reqnires treatment with other modalities. 

For some bedridden or geriatric patients, or others with chronic constipation, bnlk-forming laxatives remain the first line of treatment, but the use of more potent laxatives may be required relatively frequently. Fiber shonld be avoided in bedridden patients who are cognitively impaired. When other than bulk-forming laxatives are used, they should be administered in the lowest effective dose and as infreqnently as possible to maintain regular bowel function (more than three stools per week). Agents that may be used in these situations inclnde diphenylmethane and anthraquinone derivatives, milk of magnesia, and sorbitol or lacmlose. Mineral oil should be avoided. 

Phenolphthalein, once among the most popular components of laxatives, has been withdrawn from the market in the United States because of potential carcinogenicity. Oxyphenisatin, another older drug, was withdrawn due to hepatotoxicity. Sodium picosulfate (Lubrilax, SUR-LAX) is a diphenylmethane derivative widely available outside of the United States. It is hydrolyzed by colonic bacteria to its active form, and hence acts locally only in the colon. Effective doses of the diphenylmethane derivatives vary as much as four- to eightfold in individual patients. Consequently, recommended doses may be ineffective in some patients but may produce cramps and excessive fluid secretion in others. 

Stimulant laxatives have direct effects on enterocytes, enteric neurons, and G1 smooth muscle and probably induce a limited low-grade inflammation in the small and large bowel to promote accumulation of water and electrolytes and stimulate intestinal motility. Included in this group are diphenylmethane derivatives, anthraquinones, and ricinoleic acid. 

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