How to manage GI motility disorders

Gastrointestinal motility disorders are becoming a well recognized phenomenonin companion animals.

These disorders have become more challenging to manage due to the removalof cisapride, the prokinetic of choice, from the market.

Motility disorders are usually acquired and often secondary to underlyinggastrointestinal disease. They are classified as accelerated, retrogradeor delayed transit of ingesta.

Accelerated transit is the least significant clinically and is usuallyiatrogenic (drug or surgery related). Retrograde transit may be gastro-esophageal(reflux, esophagitis), or entero-gastric (bilious vomiting syndrome, vomiting).Delayed transit may be caused by a variety of conditions including megaesophagus,functional delayed gastric emptying (gastric dilatation, gastritis, ulcers,elecrolyte disturbances), ileus (drug-induced, post-operative), and megacolon.

The treatment of these disorders involves an accurate diagnosis and managementof underlying disease conditions.

Often, control of the underlying disease alone does not fully resolvethe motility disorder and dietary and medical intervention become necessary.

Diet is key

As clinicians, we are most concerned with delayed transit disorders anddiet is key to their management.

Diets should be chosen based on the knowledge that liquids tend to emptyfrom the stomach faster than solids and carbohydrates pass faster than proteinsand fat. Diets that are warmed and low in acidity and osmolality shouldbe fed frequently in small amounts to enhance transit. If motility disordersdo not respond to diet alone, prokinetic therapy becomes critical.

It is imperative to define the site of abnormal gastrointestinal motilityas proximal or distal in order to best select the prokinetic. Cisapridehad previously been the drug of choice for treating proximal disorders suchas delayed gastric emptying, followed by erythromycin, ranitidine or nizatidine.Although metoclopramide has potent central antiemetic effects, it has verylimited peripheral gastrokinetic effect and should not be considered a first-linedrug. Erythromycin, a motilin-like agonist, at low dosages (0.5-1.0 mg/kg)accelerates gastric emptying by stimulating contractions of the stomachwhich allows emptying of solids during the fed state. At anti-secretorydosages, nizatidine (2.5-5 mg/kg PO SID) and ranitidine (1-2 mg/kg PO BID)also perform as acetylcholinesterase inhibitors. They increase the amountof acetylcholine available to bind smooth muscle receptors and hence strengthenthe force of gastric contraction.

Cisapride had also been the drug of choice for treating canine and felinedistal or colonic motility disorders.

It has been documented that the canine and feline colon also respondsto ranitidine, nizatidine and possibly misoprostol.

The effects of erythromycin in the colon had never been documented untilDr. T. Melgarejo in 2001 ACVIM Forum abstract #166 demonstrated that erythromycinstimulates longitudinal and hence propulsive movements in the canine colonbut has no effect on feline colonic smooth muscle, thereby limiting itseffectiveness in feline constipation disorders.

Misoprostol, which is a prostaglandin E1 analogue, may induce a giantmigrating complex pattern and increase propulsive colonic activity in bothdogs and cats. Although not a first-choice drug, it may have a place asa secondary agent in refractory cases of constipation.

Mainstay

Cisapride had been a mainstay of motility disorder treatment due to itsvaried effects on the proximal and distal gastrointestinal tract. It waswithdrawn from the market due to effects on cardiac 5-HT4 receptors. Newdrugs within the same class but without effects on cardiac repolarizationor QT interval prolongation are being investigated.

Dr. R.J. Washabau presented information on two of these drugs at the2001 ACVIM Forum. Tegaserod (SDZ HTF 919, Novartis) is a potent 5-HT4 andweak 5-HT1D receptor agonist. Tegaserod has positive effects on canine andfeline colonic motility, however, has limited effects on gastric or smallintestinal motility.

Prucalopride (R093877, Janssen Pharmaceutical), also a potent 5-HT4 receptoragonist like tegaserod, has positive prokinetic effects on the canine andfeline colon. Unlike tegaserod, it also has apparent positive effects onthe stimulation of gastric emptying and may prove to be an excellent replacementfor cisapride.

Until these new products are released, these other drug options can managecanine and feline motility disorders with considerable success if the transitdisorder has been defined correctly.

Comments or questions can be directed to Dr. Donna Jones at VCA EmergencyAnimal Hospital and Referral Center, 2317 Hotel Circle S., San Diego, CA92108; (619) 299-2400.

BY DONNA JONES

DVM, DIPL. ACVIM

Dr. Jones is a graduate of Michigan State UniversityCollege of Veterinary Medicine. She completed her internship program atthe Animal Medical Center in New York City and her residency program atthe University of California, Davis. She recently received board certificationand is a diplomate of the American College of Veterinary Internal Medicine.She currently practices at VCA Emergency Animal Hospital & ReferralCenter in San Diego.

Additional reading

* Washabau, RJ. What's new in gastrointestinal prokinetic therapy?ACVIM Forum Presentation, 2001:538-539.

* Melgarejo, T., Simon, D., Washabau, RJ. Erythromycin stimulatescontractions of canine, but not feline longitudinal colonic smooth muscle.ACVIM Forum Abstract, 2001, #166, p. 878.

* Hall, JA, Washabau, RJ. Gastrointestinal prokinetic therapy:acetylcholinesterase inhibitors. Compend. Contin. Educ. Prac. Vet. 1997(5): 615-621.

* Hall, JA, Washabau RJ. Diagnosis and treatment of gastric motilitydisorders. Veterinary Clinics of North America: Small Animal Practice 1999(20), #2, 377-395.