erythromycin_gastroparesis

PIC Question of the Week: 11/7/05 Q: What is the rationale for using erythromycin in the treatment of diabetic gastroparesis?

A: Gastroparesis (“paralyzed stomach�) is a condition marked by delayed gastric emptying that occurs because of damage to the vagus nerve. During the digestive process, the vagus promotes peristalsis.

Without these muscular contractions, the movement of food is reduced, possibly resulting in accumulation of undigested material in the stomach. This solid mass or bezoar may produce nausea, vomiting, and obstruction. Weight and appetite fluctuations, GERD, gastrointestinal spasticity, and a premature feeling of fullness after ingesting food may also occur. It is noteworthy that up to 50% of patients with gastroparesis may be asymptomatic. Diagnosis can be made based on patient history, radioisotope imaging, and barium studies. Other diagnostic tests include endoscopy, ultrasound, and manometry. In general, type I and type II diabetics are more susceptible to vagal nerve deterioration. Sustained elevation of blood glucose results in vascular injury and reduced oxygen supply to the nervous system. While diabetics represent the largest population of patients with gastroparesis, other etiologies include: gastric surgery; metabolic, smooth muscle, or nervous system disorders; and medications such as anticholinergics, narcotics, and calcium channel blockers. There are few treatment options for this chronic problem and available therapy is primarily directed to relief of symptoms. Erythromycin has been used extensively for its prokinetic properties in the treatment of diabetic gastroparesis. This macrolide antibiotic acts as an agonist at motilin receptors to stimulate contractions of the migrating motor complex, thereby inducing peristalsis and facilitating gastric emptying. Motilin is a polypeptide hormone released by the small intestine that increases gastrointestinal motility and production of pepsin. Oral doses of erythromycin for this condition range from 150-250mg three times daily, 30 minutes before meals. Higher doses are not recommended due to the increased incidence and severity of adverse effects such as nausea, vomiting, diarrhea, and abdominal pain. The drug has also been administered intravenously for this indication. Metoclopramide is currently labeled for the treatment of gastroparesis. Other drugs evaluated in this disorder are cisapride, domperidone, and bethanechol.

Unfortunately, cisapride was withdrawn from the market because of potentially fatal cardiac arrhythmias.

Some authors have considered erythromycin the drug of choice for the management of gastroparesis. Longterm treatment of gastroparesis with erythromycin is limited due to adverse effects and the frequent development of tachyphylaxis.

References: ! National Digestive Diseases Information Clearinghouse. Gastroparesis and diabetes. http://digestive.niddk.nih.gov/ddiseases/pubs/gastroparesis/ (accessed 2005 Nov 2). ! Smith SD, Ferris CD. Current concepts in diabetic gastroparesis. Drugs 2003; 63 (13).

Barbara J. Schmitz, Pharmacy Clerkship Student Jennifer E. Huber, Pharmacy Clerkship Student