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

Table 46–3
Classification and Comparison of Representative Laxatives
LAXATIVE EFFECT AND LATENCY IN USUAL CLINICAL DOSAGE
SOFTENING OF SOFT OR SEMIFLUID WATERY EVACUATION,
FECES, 1-3 DAYS STOOL, 6-8 HOURS 1-3 HOURS
Bulk-forming laxatives Stimulant laxatives Osmotic laxatives a
Bran Diphenylmethane derivatives Sodium phosphates
Psyllium preparations Bisacodyl Magnesium sulfate
Methylcellulose
Milk of magnesia
Calcium polycarbophil
Magnesium citrate
Surfactant laxatives Anthraquinone derivatives Castor oil
Docusates
Senna
Poloxamers
Cascara sagrada
Lactulose
a
Employed in high dosage for rapid cathartic effect and in lower dosage for laxative effect.
1331
degrees, depending on its chemical nature and water
solubility. Fermentation of fiber has two important
effects:
• it produces short-chain fatty acids that are trophic
for colonic epithelium
• it increases bacterial mass
Although fermentation of fiber generally
decreases stool water, short-chain fatty acids also may
have a prokinetic effect, and increased bacterial mass
may contribute to increased stool volume. However,
fiber that is not fermented can attract water and increase
stool bulk. The net effect on bowel movement therefore
varies with different compositions of dietary fiber
(Table 46–4). In general, insoluble, poorly fermentable
fibers, such as lignin, are most effective in increasing
stool bulk and transit.
Bran, the residue left when flour is made from cereal grains,
contains >40% dietary fiber. Wheat bran, with its high lignin content,
is most effective at increasing stool weight. Fruits and vegetables
contain more pectins and hemicelluloses, which are more readily fermentable
and produce less effect on stool transit. Psyllium husk,
derived from the seed of the plantago herb (Plantago ovata; known
as ispaghula or isabgol in many parts of the world), is a component
of many commercial products for constipation (METAMUCIL, others).
Psyllium husk contains a hydrophilic mucilloid that undergoes significant
fermentation in the colon, leading to an increase in colonic
bacterial mass. The usual dose is 2.5-4 g (1-3 teaspoonfuls in 250 mL
of fruit juice), titrated upward until the desired goal is reached. A
variety of semisynthetic celluloses—e.g., methylcellulose (CITRUCEL,
others) and the hydrophilic resin calcium polycarbophil (FIBERCON,
FIBERALL, others), a polymer of acrylic acid resin—also are
available. These poorly fermentable compounds absorb water and
increase fecal bulk. Malt soup extract (MALSTSUPEX, others), an
extract of malt from barley grains that contains small amounts of
polymeric carbohydrates, proteins, electrolytes, and vitamins, is
another orally administered bulk-forming agent.
Fiber is contraindicated in patients with obstructive symptoms
and in those with megacolon or megarectum. Fecal impaction
should be treated before initiating fiber supplementation. Bloating is
the most common side effect of soluble fiber products (perhaps due
to colonic fermentation), but it usually decreases with time. Calcium
polycarbophil preparations release Ca 2+ in the GI tract and thus
should be avoided by patients who must restrict their intake of calcium
or who are taking tetracycline. Sugar-free bulk laxatives may
contain aspartame and are contraindicated in patients with phenylketonuria.
Allergic reactions to psyllium have been reported.
Osmotically Active Agents
Saline Laxatives. Laxatives containing magnesium
cations or phosphate anions commonly are called saline
laxatives: magnesium sulfate, magnesium hydroxide,
magnesium citrate, sodium phosphate. Their cathartic
action is believed to result from osmotically mediated
water retention, which then stimulates peristalsis. Other
mechanisms may contribute to their effects, including
the production of inflammatory mediators. Magnesiumcontaining
laxatives may stimulate the release of cholecystokinin,
which leads to intraluminal fluid and
electrolyte accumulation and to increased intestinal
motility. It is estimated that for every additional mEq
of Mg 2+ in the intestinal lumen, fecal weight increases
by ~7 g. The usual dose of magnesium salts contains
40-120 mEq of Mg 2+ and produces 300-600 mL of
stool within 6 hours. The intensely bitter taste of some