DRUGS THAT
DECREASE GI MOTILITY
Diarrhea is the frequent
passage of watery, unformed stools. Its many causes include IBS, infectious
disorders, thyrotoxicosis, malabsorption, medication side effect, and laxative
abuse. Attempts to treat diarrhea should first fo-cus on the patient’s list of
medications followed by a search for an underlying systemic disorder. Opioids
and 5-HT3 receptor antagonists, such as alosetron, slow motil-ity
and can therefore decrease or eliminate diarrhea.
Most of the opioids have a constipating action; mor-phine was used in the
treatment of diarrhea before it was used as an analgesic. Unfortunately, many
of the opium preparations, while relieving diarrhea and dysentery, also produce
such objectionable side effects as respiratory depression and habituation . The opioids are capable of altering the
motility pat-tern in all parts of the GI tract. These compounds usu-ally
produce an increase in segmentation and a de-crease in the rate of propulsive
movement. The feces become dehydrated as a result of their longer stay in the
GI tract. The tone of the internal anal sphincter is increased, and the
subjective response to the stimulus of a full rectum is reduced by the central
action of the opioids. All of these actions produce constipation. Opioids
should not be used indiscriminately in bloody diarrhea, since their use in
inflammatory bowel disease involving the colon may increase the risk of
megacolon and their use in infectious enterocolitis may promote intestinal
perforation.
The dangers of dependency and
addiction clearly preclude the use of such compounds as morphine, meperidine,
and methadone as treatment for diarrhea. Antidiarrheal specificity therefore is
of paramount im-portance in choosing among the synthetic opioids and their
analogues (e.g., diphenoxylate and loperamide).
Diphenoxylate (marketed in
combination with at-ropine as Lomotil
in the United States) is chemically re-lated to both analgesic and
anticholinergic compounds. It is as effective in the treatment of diarrhea as
the opium derivatives, and at the doses usually employed, it has a low
incidence of central opioid actions. Diphen-oxylate is rapidly metabolized by
ester hydrolysis to the biologically active metabolite difenoxylic acid.
Lomotil is recommended as adjunctive therapy in the manage-ment of diarrhea. It
is contraindicated in children under 2 years old and in patients with
obstructive jaundice. Adverse reactions often caused by the atropine in the
preparation include anorexia, nausea, pruritus, dizzi-ness, and numbness of the
extremities.
Loperamide hydrochloride (Imodium) structurally resembles both
haloperidol and meperidine. In equal doses, loperamide protects against
diarrhea longer than does diphenoxylate. It reduces the daily fecal volume and
decreases intestinal fluid and electrolyte loss. Loperamide produces rapid and
sustained inhibition of the peristaltic reflex through depression of
longitudinal and circular muscle activity. The drug also possesses
an-tisecretory activity, presumably through an effect on in-testinal opioid
receptors. Loperamide is effective against a wide range of secretory stimuli
and can be used in the control and symptomatic relief of acute di-arrhea that
is not secondary to bacterial infection. Adverse effects associated with its
use include abdomi-nal pain and distention, constipation, dry mouth,
hyper-sensitivity, and nausea and vomiting.
Tincture of opium (10% opium)
is a rapidly acting preparation for the symptomatic treatment of diarrhea.
The more widely used
paregoric (camphorated opium tincture) is equally effective and is frequently
used in combination with other antidiarrheal agents. Codeine also has been used
for short-term symptomatic treat-ment.
Alosetron (Lotronex) is a 5-HT3 receptor
antagonist. Blocking this receptor results in decreased GI motility. Alosetron
received FDA approval in February 2000 for the treatment of women with
diarrhea-predominant IBS. In November 2000, at the request of the FDA, the drug
was voluntarily withdrawn due to reported cases of ischemic colitis, including
some fatalities.
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