DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

The terms laxatives, cathartics, purgatives, aperients,
and evacuants often are used interchangeably.
There is a distinction, however, between laxation (the
evacuation of formed fecal material from the rectum)
and catharsis (the evacuation of unformed, usually
watery fecal material from the entire colon). Most of
the commonly used agents promote laxation, but some
are actually cathartics that act as laxatives at low doses.
Laxatives generally act in one of the following
ways: (1) enhancing retention of intraluminal fluid by
hydrophilic or osmotic mechanisms; (2) decreasing net
absorption of fluid by effects on small- and large-bowel
fluid and electrolyte transport; or (3) altering motility
by either inhibiting segmenting (nonpropulsive) contractions
or stimulating propulsive contractions. Based on
their actions, laxatives can be classified as shown in
Table 46–1; their known effects on motility and secretion
are listed in Table 46–2. However, studies indicate
considerable overlap among these traditional categories.
A variety of laxatives, both osmotic agents and stimulants,
increase the activity of NO synthase and the
biosynthesis of platelet-activating factor in the gut.
Platelet-activating factor is a phospholipid proinflammatory
mediator that stimulates colonic secretion and
GI motility (Izzo et al., 1998). NO also may stimulate
intestinal secretion and inhibit segmenting contractions
in the colon, thereby promoting laxation. Agents that
reduce the expression of NO synthase or its activity can
prevent the laxative effects of castor oil, cascara, and
bisacodyl (but not senna), as well as magnesium sulfate.
Table 46–1
Classification of Laxatives
1. Luminally active agents
Hydrophilic colloids; bulk-forming agents (bran, psyllium,
etc.)
Osmotic agents (non-absorbable inorganic salts or
sugars)
Stool-wetting agents (surfactants) and emollients
(docusate, mineral oil)
2. Nonspecific stimulants or irritants (with effects on
fluid secretion and motility)
Diphenylmethanes (bisacodyl)
Anthraquinones (senna and cascara)
Castor oil
3. Prokinetic agents (acting primarily on motility)
5-HT 4
receptor agonists
Dopamine receptor antagonists
Motilides (erythromycin)
An alternate way to classify laxatives is by the
pattern of effects produced by the usual clinical dosage
(Table 46–3).
Dietary Fiber and Supplements
Under normal circumstances, the bulk, softness, and
hydration of feces depend on the fiber content of the
diet. Fiber is defined as that part of food that resists
enzymatic digestion and reaches the colon largely
unchanged. Colonic bacteria ferment fiber to varying
Table 46–2
Summary of Effects of Some Laxatives on Bowel Function
SMALL BOWEL
COLON
TRANSIT MIXING PROPULSIVE MASS STOOL
AGENT TIME CONTRACTIONS CONTRACTIONS ACTIONS WATER
Dietary fiber å ? ä ? ä
Magnesium å — ä ä ää
Lactulose å ? ? ? ää
Metoclopramide å ? ä ? —
Cisapride å ? ä ? ä
Erythromycin å ? ? ? ?
Naloxone å å — — ä
Anthraquinones å å ä ä ää
Diphenylmethanes å å ä ä ää
Docusates — ? ? ? —
ä, increased; å, decreased; ?, no data available; —, no effect on this parameter. Modified from Kreek, 1994, with permission. http://lww.com.