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

Rate
(liters/day)
Flow
9.0
H 2O
Uptake
6.0
Ion Concentrations
(mEq/liter)
Na + K + Cl _ HCO 3
_
Osmolality
60 15 60 15 variable
1329
3.0
140 6 100 30
isotonic
1.5
1.5
140 8 60 70 isotonic
1.4
0.1
40 90 15 30 isotonic
Figure 46–3. The approximate volume and composition of fluid that traverses the small and large intestines daily. Of the 9 L of fluid
typically presented to the small intestine each day, 2 L are from the diet and 7 L are from secretions (salivary, gastric, pancreatic, and
biliary). The absorptive capacity of the colon is 4-5 L per day.
feces can become inspissated and impacted, leading to
constipation. When the capacity of the colon to absorb
fluid is exceeded, diarrhea occurs.
Constipation: General Principles of Pathophysiology and
Treatment. Scientific definitions rely mostly on stool number; most
surveys have found the normal stool frequency on a Western diet to be
at least three times a week. However, patients use the term constipation
not only for decreased frequency, but also for difficulty in initiation
or passage, passage of firm or small-volume feces, or a feeling
of incomplete evacuation. By questionnaire, 25% of the population of
the U.S., more commonly women and elderly people, complain of
constipation. A survey of bowel habits of adults in the U.S. showed
that 18% of respondents used laxatives at least once a month, but
nearly one-third of users did not have constipation. Approximately
2.5 million physician visits per year are attributed to constipation.
Constipation has many reversible or secondary causes,
including lack of dietary fiber, drugs, hormonal disturbances, neurogenic
disorders, and systemic illnesses. In most cases of chronic constipation,
no specific cause is found. Up to 60% of patients
presenting with constipation have normal colonic transit. These
patients either have IBS or define constipation in terms other than
stool frequency (e.g., changes in consistency, excessive straining, or
a feeling of incomplete evacuation). In the rest, attempts usually are
made to categorize the underlying pathophysiology either as a disorder
of delayed colonic transit because of an underlying defect in
colonic motility or, less commonly, as an isolated disorder of defecation
or evacuation (outlet disorder) due to dysfunction of the neuromuscular
apparatus of the rectoanal region. Colonic motility is
responsible for mixing luminal contents to promote absorption of
water and moving them from proximal to distal segments by means
of propulsive contractions. Mixing in the colon is accomplished in
a way similar to that in the small bowel: by short- or long-duration,
stationary (nonpropulsive) contractions. Propulsive contractions in
the colon include giant migrating contractions, also known as colonic
mass actions or mass movements, which propagate caudally over
extended lengths in the colon and evoke mass transfer of feces from
the right to the left colon once or twice a day. Disturbances in motility
therefore may have complex effects on bowel movements.
“Decreased motility” of the mass action type and “increased motility”
of the nonpropulsive type may lead to constipation. In any given
patient, the predominant factor often is not obvious. Consequently,
the pharmacological approach to constipation remains empirical and
is based, in most cases, on nonspecific principles.
In many cases, constipation can be corrected by
adherence to a fiber-rich (20-35 g daily) diet, adequate
fluid intake, appropriate bowel habits and training, and
avoidance of constipating drugs. However, the association
between constipation and either fluid intake or
exercise has not withstood scientific scrutiny.
Constipation related to medications can be corrected by
use of alternative drugs where possible, or adjustment
of dosage. If non-pharmacological measures alone are
inadequate or unrealistic (e.g., because of elderly age
or infirmity), they may be supplemented with bulkforming
agents or osmotic laxatives. When stimulant
laxatives are used, they should be administered at the
lowest effective dosage and for the shortest period of
time to avoid abuse. In addition to perpetuating dependence
on drugs, the laxative habit may lead to excessive
loss of water and electrolytes; secondary aldosteronism
may occur if volume depletion is prominent. Steatorrhea,
protein-losing enteropathy with hypoalbuminemia, and
osteomalacia due to excessive loss of calcium in the
stool have been reported.
In addition to treating constipation, laxatives frequently
are employed before surgical, radiological, and
endoscopic procedures where an empty colon is desirable.
CHAPTER 46
TREATMENT OF DISORDERS OF BOWEL MOTILITY AND WATER FLUX