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

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SECTION VI
DRUGS AFFECTING GASTROINTESTINAL FUNCTION
Table 46–4
Properties of Different Dietary Fibers
WATER %
TYPE OF FIBER SOLUBILITY FERMENTED
Nonpolysaccharides
Lignin Poor 0
Cellulose Poor 15
Noncellulose
polysaccharides
Hemicellulose Good 56-87
Mucilages and gums Good 85-95
Pectins Good 90-95
preparations may induce nausea and can be masked
with citrus juices.
Phosphate salts are better absorbed than magnesium-based
agents and therefore need to be given in larger doses to induce
catharsis. The most frequently employed preparations of sodium
phosphate are an oral solution (FLEET PHOSPHO-SODA) and tablets
(VISICOL, OSMOPREP). Over-the-counter oral sodium phosphate products
for bowel cleansing were withdrawn from the market in 2008
following the determination by the FDA that only prescription medications
should be available for this purpose. To reduce the likelihood
of acute phosphate nephropathy, oral phosphates should be
avoided in patients at risk (the elderly, patients with known bowel
pathology or renal dysfunction, and patients on angiotensin-converting
enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs],
and nonsteroidal anti-inflammatory drugs [NSAIDs]) and the twodose
regimens should be split evenly with the first dose taken the
evening before the exam and the second starting 3-5 hours before
the exam. Adequate fluid intake (1-3 L) is essential for any oral
sodium phosphate regimen used for colonic preparation.
Magnesium- and phosphate-containing preparations must be
used with caution or avoided in patients with renal insufficiency, cardiac
disease, or preexisting electrolyte abnormalities, and in patients
on diuretic therapy. Patients taking >45 mL of oral sodium phosphate
as a prescribed bowel preparation may experience electrolyte
shifts that pose a risk for the development of symptomatic dehydration,
renal failure, metabolic acidosis, tetany from hypocalcemia,
and even death in vulnerable populations.
Nondigestible Sugars and Alcohols. Lactulose (CEPHU-
LAC, CHRONULAC, others) is a synthetic disaccharide of
galactose and fructose that resists intestinal disaccharidase
activity. This and other non-absorbable sugars
such as sorbitol and mannitol are hydrolyzed in the
colon to short-chain fatty acids, which stimulate colonic
propulsive motility by osmotically drawing water into
the lumen. Sorbitol and lactulose are equally efficacious
in the treatment of constipation caused by opioids and
vincristine, of constipation in the elderly, and of idiopathic
chronic constipation.
They are available as 70% solutions, which are given in doses
of 15-30 mL at night, with increases as needed up to 60 mL per day
in divided doses. Effects may not be seen for 24-48 hours after dosing
is begun. Abdominal discomfort or distention and flatulence are
relatively common in the first few days of treatment but usually subside
with continued administration. A few patients dislike the sweet
taste of the preparations; dilution with water or administering the
preparation with fruit juice can mask the taste.
HO
H
CH 2 OH
O
H
OH
H
HOCH 2
HOCH 2
H
OH
OH H
C C C C
H
H
H
OH H
OH OH
SORBITOL
CH 2 OH
Lactulose also is used to treat hepatic encephalopathy.
Patients with severe liver disease have an impaired capacity to detoxify
ammonia coming from the colon, where it is produced by bacterial
metabolism of fecal urea. The drop in luminal pH that
accompanies hydrolysis to short-chain fatty acids in the colon results
in “trapping” of the ammonia by its conversion to the polar ammonium
ion. Combined with the increases in colonic transit, this therapy
significantly lowers circulating ammonia levels. The therapeutic
goal in this condition is to give sufficient amounts of lactulose (usually
20-30 g, three to four times per day) to produce two to three soft
stools a day with a pH of 5-5.5.
Polyethylene Glycol–Electrolyte Solutions. Long-chain
polyethylene glycols (PEGs; molecular weight ~3350 Da)
are poorly absorbed, and PEG solutions are retained in
the lumen by virtue of their high osmotic nature. When
used in high volume, aqueous solutions of PEGs with
electrolytes (COLYTE, GOLYTELY, others) produce an
effective catharsis and have replaced oral sodium phosphates
as the most widely used preparations for colonic
cleansing prior to radiological, surgical, and endoscopic
procedures. Usually 240 mL of this solution is taken
every 10 minutes until 4 L is consumed or the rectal
O
LACTULOSE
H
H
C C C C
OH OH H
MANNITOL
CH 2 OH
H
H O
OH HO
H
OH OH
H
CH 2 OH
CH 2 OH