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

1336 sodium bicarbonate and potassium bitartrate. When administered
rectally, the suppository produces CO 2
, which initiates a bowel
movement in 5-30 minutes.
SECTION VI
DRUGS AFFECTING GASTROINTESTINAL FUNCTION
ANTI-DIARRHEAL AGENTS
Diarrhea: General Principles and Approach to
Treatment. Diarrhea (Greek and Latin: dia, through,
and rheein, to flow or run) does not require any definition
to people who suffer from “the too rapid evacuation
of too fluid stools.” Scientists usually define diarrhea
as excessive fluid weight, with 200 g per day representing
the upper limit of normal stool water weight for
healthy adults in the Western world. Because stool
weight is largely determined by stool water, most cases
of diarrhea result from disorders of intestinal water and
electrolyte transport.
An appreciation and knowledge of the underlying causative
processes in diarrhea facilitates effective treatment. From a mechanistic
perspective, diarrhea can be caused by an increased osmotic
load within the intestine (resulting in retention of water within the
lumen); excessive secretion of electrolytes and water into the intestinal
lumen; exudation of protein and fluid from the mucosa; and
altered intestinal motility resulting in rapid transit (and decreased
fluid absorption). In most instances, multiple processes are affected
simultaneously, leading to a net increase in stool volume and weight
accompanied by increases in fractional water content.
Many patients with sudden onset of diarrhea have
a benign, self-limited illness requiring no treatment or
evaluation. In severe cases, dehydration and electrolyte
imbalances are the principal risk, particularly in infants,
children, and frail elderly patients. Oral rehydration
therapy therefore is a cornerstone for patients with
acute illnesses resulting in significant diarrhea. This is
of particular importance in developing countries, where
the use of such therapy saves many thousands of lives
every year. This therapy exploits the fact that nutrientlinked
cotransport of water and electrolytes remains
intact in the small bowel in most cases of acute diarrhea.
Sodium and chloride absorption is linked to glucose
uptake by the enterocyte; this is followed by
movement of water in the same direction. A balanced
mixture of glucose and electrolytes in volumes matched
to losses therefore can prevent dehydration. This can be
provided by many commercial premixed formulas
using glucose-electrolyte or rice-based physiological
solutions.
Pharmacotherapy of diarrhea in adults should be
reserved for patients with significant or persistent symptoms.
Nonspecific anti-diarrheal agents typically do not
address the underlying pathophysiology responsible for
the diarrhea; their principal utility is to provide symptomatic
relief in mild cases of acute diarrhea. Many of
these agents act by decreasing intestinal motility and
should be avoided as much as possible in acute diarrheal
illnesses caused by invasive organisms. In such cases,
these agents may mask the clinical picture, delay clearance
of organisms, and increase the risk of systemic
invasion by the infectious organisms; they also may
induce local complications such as toxic megacolon.
Bulk-Forming and Hydroscopic Agents. Hydrophilic
and poorly fermentable colloids or polymers such as
carboxymethylcellulose and calcium polycarbophil
absorb water and increase stool bulk (calcium polycarbophil
absorbs 60 times its weight in water). They usually
are used for constipation but are sometimes useful
in acute episodic diarrhea and in mild chronic diarrheas
in patients suffering with IBS. The mechanism of this
effect is not clear, but they may work as gels to modify
stool texture and viscosity and to produce a perception
of decreased stool fluidity. Some of these agents also
may bind bacterial toxins and bile salts. Clays such as
kaolin (a hydrated aluminum silicate) and other silicates
such as attapulgite (magnesium aluminum disilicate;
DIASORB, others) bind water avidly (attapulgite absorbs
eight times its weight in water) and also may bind
enterotoxins. However, binding is not selective and may
involve other drugs and nutrients; hence these agents
are best avoided within 2-3 hours of taking other medications.
A mixture of kaolin and pectin (a plant polysaccharide)
is a popular over-the-counter remedy
(KAOPECTOLIN, others) and may provide useful symptomatic
relief of mild diarrhea.
Bile Acid Sequestrants. Cholestyramine, colestipol, and
colesevalam effectively bind bile acids and some bacterial
toxins. Cholestyramine is useful in the treatment
of bile salt–induced diarrhea, as in patients with resection
of the distal ileum. In these patients, there is partial
interruption of the normal enterohepatic circulation of
bile salts, resulting in excessive concentrations reaching
the colon and stimulating water and electrolyte secretion.
Patients with extensive ileal resection (usually
>100 cm) eventually develop net bile salt depletion,
which can produce steatorrhea because of inadequate
micellar formation required for fat absorption. In such
patients, the use of cholestyramine aggravates the diarrhea.
The drug also has had an historic role in treating
mild antibiotic-associated diarrhea and mild colitis due
to Clostridium difficile. However, its use in infectious
diarrheas generally is discouraged because it may
decrease clearance of the pathogen from the bowel.