Graphic by MarVistaVet

One of the stomach's most important functions is to grind the food we eat into fine slurry that will pass through the intestines freely. To accomplish this, the stomach's muscle layers contract in a coordinated rhythm that is initiated by a pacemaker area, similar to the way the heart's contraction rhythm is initiated by its own pacemaker area. The rhythm of contraction is called the stomach's motility. If the stomach's motility becomes abnormal, the stomach cannot grind or move food properly.

When it comes to correcting motilty, two medications in particular come to mind: metoclopramide and cisapride. Both will help reduce the nausea created by food pooling in the stomach. Metoclopramide acts on the stomach's pacemaker to normalize stomach contractions. This not only helps digested food continue its journey forward but also reduces reflux of food backward from the intestine into the stomach. Metoclopramide also can cross into the brain to help control the sensation of nausea. This sounds great but crossing into the brain also can lead to hyperexcitability in some patients, which can be a big problem.

Cisapride represents an improvement over metoclopramide in that the entire GI tract from stomach to colon can gain improved motility. Not only are stomach contractions improved but so is motility in the entire tract, opening the door to treating constipation disorders. Furthermore, cisapride does not cross into the brain, thus providing an alternative for patients who experienced hyperexcitability on metoclopramide.

Metoclopramide also had the disadvantage of causing neurologic side effects in the occasional patient by virtue of its ability to act on the brain. Cisapride is not able to cross the blood-brain barrier and thus cannot cause such side effects.

Cisapride was withdrawn from the human market because when it was combined with any of several commonly prescribed drugs, heart rhythm disturbances ensued. Often people see different medical specialists for different body problems, and it is not unusual for one doctor to be unaware of the medications that another doctor has prescribed. Human risk and legal liability were felt to outweigh the human benefits and the drug was removed from the market; veterinary patients must employ a compounding pharmacy to obtain cisapride. The heart rhythm side effect appears to be limited to the human population and pets have not been affected.

How this Medication is Used

Cisapride is given up to three times daily. It is used to treat nausea due to motility problems in the stomach, though it does not treat the nausea sensation directly in the brain as does its cousin, metoclopramide. It is particularly helpful in patients who have adverse neurologic reactions to metoclopramide but still require stomach motility treatment.

Cisapride has been found helpful in some cases of megaesophagus and is a common treatment for feline megacolon.

Cisapride may be given with or without food. If a dose is accidentally skipped, do not double up on the next dose.

Because of its effect on smooth muscle contraction, cisapride can also be used in urinary retention situations to strengthen bladder contraction. This use is currently uncommon.

Side Effects

If too great a motility effect is created, diarrhea and cramping may result. Vomiting may also result.

Signs of actual overdose include: drooling, incoordination, muscle twitches (and even seizures), agitation and high body temperature.

Interactions with other Drugs

• Cisapride and some antiacids affect each other when given together.
• The antiacid Cimetidine increases the amount of cisapride absorbed into the
  bloodstream. Ranitidine does not.
• Cisapride enhances the sedating properties of the benzodiazepine drugs (such as diazepam or alprazolam).
• Cisapride enhances the sedating properties of alcohol (generally not a concern in veterinary patients).
• Cisapride works less well with the concurrent use of medications with anticholinergic side effects (antihistamines, some heart medications, some psychoactive drugs).

The drug interaction that led to removing cisapride from the human market was the induction of ventricular (heart) arrhythmias when cisapride was used with the antifungal agents ketoconazole or itraconazole, or with silymarin, the active ingredient in milk thistle supplements (commonly used to support liver function). Additional medications that could lead to arrhythmias with cisapride include: chloramphenicol (an antibiotic); amiodarone (a heart medication); clarithromycin (an antibiotic); cimetidine (the antacid mentioned above); procainamide (a heart medicine); sotalol (a heart medicine); and the macrolide class of antibiotics (with the exception of azithromycin); and tricyclic antidepressants such as amitriptyline.

Concerns and Cautions

• Cisapride products should be stored according to the recommendations of the compounding pharmacy that made them.

• If there is question about an intestinal obstruction or perforation, it is best not to use a motility modifier such as cisapride.

• Cisapride is not felt to be safe during pregnancy and may also reduce fertility in females taking it.