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Cisapride is a third generation benzamide that is used in human and veterinary medicine as a motility enhancement drug. Motility disorders of the gastrointestinal (GI) tract are a common clinical problem in companion animals. Post-operative ileus is a common and particularly difficult complication seen after abdominal surgery in horses. Cisapride was once used as a motility enhancement drug in human medicine but it is no longer manufactured or used for this purpose.
Cisapride activates acetylcholine release from the mesenteric plexus which in turn stimulates GI smooth muscle. Cisapride is a serotonergic agonist. Cisapride can show activity on the smooth muscle through out the GI tract. Anatomic differences between species can effect clinical efficacy. For example, cisapride is not generally used for the management of megaesophagus in dogs because they lack smooth muscle in the esophagus. Like Cisapride, Metoclopramide and domperidone are also drugs in the benzamide class. Cisapride does not increase gastric acid secretion.
Cisapride has been widely used in the treatment of gastric
emptying disorders, intestinal transit and other motility disorders in
both dogs and cats. It accelerates the emptying of the stomach and propulsion
of food through the intestines by increasing peristalsis. Cisapride is used in
cats in the management of chronic constipation and megacolon.
Work in humans has shown that cisapride is better absorbed when given
with food. In small animal practice it is usually recommended that cisapride
be given orally 15 minutes before feeding.
Post-operative ileus (POI) is a common and serious complication in horses that have had abdominal surgery, particularly surgery of the small intestine. Several clinical trials in the early 1990's supported the use of cisapride in the treatment of POI in the horse but more recent work done in vitro demonstrated some receptor differences in the horse jejunum. Possible species differences and the variable results of different research models indicate a need for more research. Because POI may be caused by multiple factors (endotoxemia, distension, inflammation) it is possible that the response to prokinetic agents such as cisapride may be influenced by these different underlying causes. At this time the effect of cisapride on gastrointestinal motility in the horse remains unclear and there does not appear to be a consensus of opinion regarding the use of prokinetic agents in the prevention of POI. Cisapride absorption in the horse has been investigated when given orally, intravenously, intra-muscularly, and rectally. Absorption after rectal administration is negligible.
• Common: GI symptoms including abdominal pain and diarrhea.
• Prokinetic drugs such as cisapride should not
be used when increased GI motility may be harmful (mechanical obstruction,
impaction, potential perforation or GI hemorrhage).
• The dose of cisapride should be reduced in animals with decreased
liver function. Elimination of cisapride is not significantly influenced
by decreased renal function.
• Animals with cardiac arrhythmia or conduction disorders may require
additional monitoring.
• High doses of cisapride were found to decrease fertility, and increase
embryonic losses in laboratory animals. Cisapride is excreted in milk.
It should only be used during pregnancy or lactation when the benefits
clearly outweigh the risks.
• Prokinetic drugs such as cisapride increase gastric
motility and speed GI transit. This may affect the absorption of other
oral medications.
• Cisapride should not be used with ketoconazole, itraconazole, IV
miconazole, or troleandomycin, erythromycin, fluconazole, clarithromycin.
These combinations may result in potentially fatal ventricular arrhythmias.
• Cisapride may increase the rate of absorption of the histamine
H2 antagonists, cimetidine, and ranitidine. Cimetidine may increase the
absorption of cisapride.
• Cisapride may increase the effect of anticoagulants. Additional
monitoring of clotting times, and dose adjustments may be necessary.
• Cisapride may increase sedation when used with benzodiazepine tranquilizers
or alcohol.
There is a wide margin of safety with cisapride. Extremely high doses can potentially cause GI distress, difficulty breathing, and CNS signs. Oral overdose of Cisapride should be handled using standard GI emptying procedures, activated charcoal, and supportive care. Cardiac monitoring for arrhythmia is suggested.
Dr.
Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania.
She has a master's degree in animal science from the University of Delaware
and graduated from the University of Pennsylvania School of Veterinary Medicine
in 1982.
She began to develop her interest in client education and medical writing 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.
You can purchase books by Dr. Forney at www.exclusivelyequine.com
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