Antidiarrheals

Antidiarrheal Agents

Causes of diarrhea : Many bacteria
(e.g., Vibrio cholerae) secrete toxins
that inhibit the ability of mucosal enterocytes
to absorb NaCl and water and, at
the same time, stimulate mucosal secretory
activity. Bacteria or viruses that invade
the gut wall cause inflammation
characterized by increased fluid secretion
into the lumen. The enteric musculature
reacts with increased peristalsis.
The aims of antidiarrheal therapy
are to prevent: (1) dehydration and
electrolyte depletion; and (2) excessively
high stool frequency. Different therapeutic
approaches (in green) listed
are variously suited for these purposes.
Adsorbent powders are nonabsorbable
materials with a large surface
area. These bind diverse substances, including
toxins, permitting them to be
inactivated and eliminated. Medicinal
charcoal possesses a particularly large
surface because of the preserved cell
structures. The recommended effective
antidiarrheal dose is in the range of
4–8 g. Other adsorbents are kaolin (hydrated
aluminum silicate) and chalk.
Oral rehydration solution (g/L of
boiled water: NaCl 3.5, glucose 20,
NaHCO3 2.5, KCl 1.5). Oral administration
of glucose-containing salt solutions
enables fluids to be absorbed because
toxins do not impair the cotransport of
Na+ and glucose (as well as of H2O)
through the mucosal epithelium. In this
manner, although frequent discharge of
stool is not prevented, dehydration is
successfully corrected.
Opioids. Activation of opioid receptors
in the enteric nerve plexus results
in inhibition of propulsive motor activity
and enhancement of segmentation
activity. This antidiarrheal effect was
formerly induced by application of opium
tincture (paregoric) containing morphine.
Because of the CNS effects (sedation,
respiratory depression, physical
dependence), derivatives with peripheral
actions have been developed.
Whereas diphenoxylate can still produce
clear CNS effects, loperamide does not
affect brain functions at normal dosage.
Loperamide is, therefore, the opioid
antidiarrheal of first choice. The prolonged
contact time of intestinal contents
and mucosa may also improve absorption
of fluid. With overdosage,
there is a hazard of ileus. It is contraindicated
in infants below age 2 y.
Antibacterial drugs. Use of these
agents (e.g., cotrimoxazole,) is
only rational when bacteria are the
cause of diarrhea. This is rarely the case.
It should be kept in mind that antibiotics
also damage the intestinal flora
which, in turn, can give rise to diarrhea.
Astringents such as tannic acid
(home remedy: black tea) or metal salts
precipitate surface proteins and are
thought to help seal the mucosal epithelium.
Protein denaturation must not include
cellular proteins, for this would
mean cell death. Although astringents
induce constipation (cf. Al3+ salts,),
a therapeutic effect in diarrhea
is doubtful.
Demulcents, e.g., pectin (home
remedy: grated apples) are carbohydrates
that expand on absorbing water.
They improve the consistency of bowel
contents; beyond that they are devoid
of any favorable effect.