Laxatives

General adverse effects and adverse reactions

If laxatives of any type are heavily used, not necessarily to the point of abuse, diarrhea will be common, as well as a tendency to nausea and fluid and electrolyte imbalance. The possibility of laxative-induced colonic injury, with damage to the autonomic nervous innervation of the large intestine, has been much discussed and was probably a problem with the violent cathartics formerly used (podophyllin, aloes, and cascara), but is not on record with the laxatives normally used today. Chronic abuse of laxatives, such as senna, can cause changes in colonic structure and function.

Habitual, usually secretive, abuse of laxatives is much more common in women than in men and there is overlap with the anorectic/bulimic syndrome. Abuse of irritant agents such as senna and cascara have been the commonest varieties [ ], but many proprietary laxatives have been abused. Abuse can lead to a condition characterized by chronic diarrhea, hypokalemia, and fluid depletion. The features also include hypomagnesemia, hypocalcemia, and hypoalbuminemia, with thirst, lassitude, weight loss, edema, and occasionally osteomalacic bone pain and clubbing. In one small series of cases of laxative abusers, pseudo-Bartter’s syndrome was induced; the complications included confusion, convulsions, muscle weakness (with or without paralysis or rhabdomyolysis), and bone changes; hypokalemia and hypophosphatemia were common, and when the laxatives were withdrawn some patients suffered prolonged edema [ ].

Bulk-forming laxatives

The bulking agents include vegetable fiber products (such as bran), paraffin and methylcellulose (which absorbs water into the intestinal tract), agar (which expands to form a gel), and psyllium seeds or other mucilaginous plant products. Bulking agents are largely free of adverse reactions, but any non-absorbable agent can aggravate symptoms associated with pre-existent intestinal stricture. Abdominal bloating due to bacterial fermentation of unabsorbed carbohydrate is a common sequel to excessive intake. The sugar content of some bulk laxatives can be sufficient to impair diabetic control; the vegetable matter in other preparations can cause bezoars and is potentially allergenic.

Stimulant laxatives

All of the anthraquinones can cause cramping and abdominal discomfort. Chronic use can be associated with melanosis coli. The urine can be colored red. The possibility of colonic injury has been discussed (see General adverse effects of laxatives in this monograph). Hepatitis, confirmed by rechallenge, has been reported, possibly because of re-absorption of rhein anthron produced in the intestine [ ].

The Food and Drug Administration (FDA) has ruled that the stimulant laxatives aloe (including aloe extract and aloe flower extract) and Cascara sagrada (including casanthranol, cascara fluidextract aromatic, cascara sagrada bark, cascara sagrada extract, and cascara sagrada fluid extract) in over-the-counter formulations are not safe and effective or are misbranded [ ].

Anthranoid derivatives occur in various laxative herbs (such as aloe, Cascara sagrada , medicinal rhubarb, and senna) in the form of free anthraquinones, anthrones, dianthrones, and/or O- and C-glycosides derived from these substances. They produce harmless discoloration of the urine. Depending on intrinsic activity and dose, they can also produce abdominal discomfort and cramps, nausea, violent purgation, and dehydration. However, they are all mutagenic and carcinogenic and should not be used in the long term.

In an epidemiological study, chronic abusers of anthranoid laxatives (identified by the detection of pseudo-melanosis coli) had an increased relative risk of 3.04 (95% CI = 1.18, 4.90) for colorectal cancer [ ].

Anatomical changes in the colon have been reported in patients taking chronic stimulant laxatives, defined as laxative ingestion more than three times a week for a year or more [ ]. Loss of haustra, which suggests neuronal injury, or damage to colonic longitudinal musculature, was seen in eight of 29 patients who used a variety of diphenylmethane and anthranoid laxatives but in none of the 26 patients who were not using these drugs. In 18 consecutive patients who were chronic users of stimulant laxatives, there was loss of haustra in 15 who took bisacodyl, phenolphthalein, senna, or casanthranol.