Erythromycin

Erythromycin is a macrolide antibiotic which has marked stimulatory effects on gastrointestinal motility, believed to be in part due to agonism of motilin receptors.

Erythromycin causes induction of migratory motor complexes with faster gastric emptying and enhanced duodenal contractility. Although colonic motor activity is also increased, there is no stimulation of colonic peristalsis in normal subjects and so the prokinetic effects of erythromycin are in the upper gastrointestinal tract. In an awake patient these are unpleasant and cause nausea, vomiting, abdominal cramps, and diarrhea. However, following encouraging results in patients with diabetic gastroparesis, there has been interest in the use of erythromycin to stimulate motility in sedated intubated intensive care patients.

Dosage and pharmacokinetics

For its prokinetic effect erythromycin is less effective orally than intravenously. It is approximately 80 per cent bound to plasma proteins, and is mainly metabolized and excreted by the liver with only about 10 per cent appearing unchanged in the urine. Plasma half-life is approximately 75 min but is prolonged in hepatic or renal impairment.

Adverse effects and drug interactions

Peripheral intravenous administration frequently causes thrombophlebitis. Reversible cholestatic jaundice is seen rarely, but erythromycin should not be given to patients who already have hepatic dysfunction.

Erythromycin may prolong the QT interval and so should not be used with other drugs which can cause the same effect, particularly astemizole and terfenadine. Theophylline concentrations may rise in patients given erythromycin, and concentrations should be monitored carefully. Because of faster gastric emptying, erythromycin can increase the bioavailability of orally administered drugs (e.g. digoxin) which may result in toxicity. Use of erythromycin will alter gastrointestinal tract flora.

Use in critical care

Erythromycin had no significant effect on clinical markers of gut motility in patients with postoperative ileus following abdominal operations ( Bonacini §L§L 1993). In ventilated patients, erythromycin has been shown to increase acetaminophen (paracetamol) absorption compared with controls ( Dive.ei a/ 19.9.5).

The prokinetic effects of erythromycin are mainly confined to the upper gastrointestinal tract, and further studies are required to establish whether it is of benefit in establishing enteral feeding in critical care patients.

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