is a macrolide antibiotic that was first identified as a byproduct of Streptomyces
erythraeus in 1952. The erythromycin molecule is comprised of a
14-membered lactone ring with two deoxy sugar groups.1,2 The most common
side effects of erythromycin therapy are gastrointestinal (GI) in nature and
consist of diarrhea, nausea, vomiting and abdominal cramping.3
Erythromycin has poor stability in acidic environments and is rapidly degraded
into intermediate metabolites after oral administration.3 One of these
metabolites, 8,9-anhydro-6,9-hemiketal intermediate, serves as a
motilin-receptor agonist.4 Motilin is a natural GI peptide hormone that
is responsible for amplifying migrating motor complex activity within the upper
alimentary tract. The migrating motor complex is a series of neural
impulses and smooth muscle contractions that stimulates caudal propulsion of GI
contents during periods of fasting. Motilin stimulates smooth muscle
contractions through a series of downstream effects that are depicted below.4
Activation of this pathway with erythromycin therapy leads to excessive
contractile activity that is largely responsible for GI toxicity.2,5 At
low doses (40-80 mg), side effects may also be mediated by cholinergic
facilitation, although the exact mechanism of this effect is unknown.6
Adverse effects of erythromycin are observed at normal doses of the oral base
preparation (ie, 250-500 mg every 6-12 hours). Doses exceeding 3 mg/kg
may stimulate forceful smooth muscle contractions that can lead to dumping of
gastric contents into the duodenum.6 For many years, GI side effects have
limited patient tolerability to erythromycin, prompting research for novel
agents with more favorable safety profiles.
C. Chapter 55. Protein Synthesis Inhibitors and Miscellaneous Antibacterial
Agents. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's
The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill;
DH, Winston LG, Winston LG. Chapter 44. Tetracyclines, Macrolides, Clindamycin,
Chloramphenicol, Streptogramins, & Oxazolidinones. In: Katzung BG, Masters
SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12nd ed. New York:
JM, Qamar F, Bono BR. Macrolides, ketolides, and glycylcyclines: azithromycin,
clarithromycin, telithromycin, tigecycline. Infect Dis Clin North Am. 2009
JJ, Vanner S. Basic and clinical pharmacology of new motility promoting agents.
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E, Vasina V, Poluzzi E, De Ponti F. Antibacterial macrolides: a drug class with
a complex pharmacological profile. Pharmacol Res. 2004 Sep;50(3):211-22.
KA, Wallace JL. Chapter 46. Treatment of Disorders of Bowel Motility and Water
Flux; Anti-Emetics; Agents Used in Biliary and Pancreatic Disease. In: Brunton
LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological
Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011.
http://www.accesspharmacy.com/content.aspx?aID=16675372. Accessed May 13, 2013.
JM. The evolution and role of macrolides in infectious diseases. Expert Opin
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