Gastrointestinal motor effects of erythromycin in humans

Sarna, Sushil K.; Soergel, Konrad H.; Koch, Timothy R.; Stone, John; Wood, Carol M.; Ryan, Robert P.; Arndorfer, Ronald C.; Cavanaugh, John H.; Nellans, Hugh N.; Lee, Martha B.

doi:10.1016/0016-5085(91)90383-v

Cited by 133 publications

(90 citation statements)

References 18 publications

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“…However, in the later period of treatment, azithromycin can be tapered to 3 times a week and thus the cost can then be greatly decreased. Erythromycin is effective with a low price, but it could result in much more gastrointestinal discomfort (31,32) and vein-stimulation adverse effects (33), and it may result in poor patient compliance because of the need for frequent administration. Therefore, we suggest that azithromycin has more advantages than erythromycin and that azithromycin represents a better choice for DPB therapy.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Azithromycin on Patients with Diffuse Panbronchiolitis: Retrospective Study of 51 Cases

Zhou

Feng

et al. 2011

Intern. Med.

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Background Patients with diffuse panbronchiolitis (DPB) are routinely treated with erythromycin, clarithromycin, and roxithromycin. The clinical effect of azithromycin on DPB has not been confirmed in a large cohort. Objective The present study was undertaken to investigate the clinical effects of azithromycin on patients with DPB. Methods Fifty-one patients with DPB treated with azithromycin in Shanghai Pulmonary Hospital, China, from July 2001 to April 2007 were analyzed retrospectively. Azithromycin (500 mg a day) was administrated intravenously in the first 1-2 weeks, taken orally (500 mg, once a day) for 3 months, and tapered to 3 times a week for 6-12 months. The patients were followed up until September 1, 2009. The therapeutic effect, according to their clinical and radiological findings, arterial gas analysis, lung function, and sputum bacterium before and after the therapy, was categorized into the following five grades: 1) cured; 2) improved; 3) no response; 4) aggravation, and 5) relapse. Results With azithromycin therapy, 14 (27.5%) patients with DPB were completely cured. The symptoms were eliminated to certain degrees for the other 36 cases (70.6%) of DPB. Five-year survival in this cohort was 94.1%. Conclusion Azithromycin is effective and well tolerated for patients with diffuse panbronchiolitis.

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Section: Discussionmentioning

confidence: 99%

“…Several studies verified the efficiency of 14-membered and 15-membered ring macrolides for DPB (21-23, 29, 30). However, the adverse effects of erythromycin, such as gastrointestinal (31,32) or hepatic dysfunction (33), and its administration frequency (usually 3 times a day) (26), have limited its clinical application.…”

Section: Introductionmentioning

confidence: 99%

Effect of Azithromycin on Patients with Diffuse Panbronchiolitis: Retrospective Study of 51 Cases

Zhou

Feng

et al. 2011

Intern. Med.

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“…It depends on coordination among several mechanisms, including pyloric contractions and tone, antro-pyloro-duodenal coordination, fundic adaptive relaxation followed by gradual increase in tone, and propagating RPCs in the body of the stomach (25,46). It is, therefore, critical that the stimulation of gastric RPCs by promotility drugs does not adversely affect the other regulatory mechanisms so as to negate their beneficial effects (65). For example, concurrent stimulation of RPCs in the duodenum or increase of pyloric tone and RPCs may deteriorate antropyloro-duodenal coordination and adversely affect the rate of gastric emptying (25,65).…”

Section: Strategies For the Design And Development Of Gut Promotilitymentioning

confidence: 99%

“…It is, therefore, critical that the stimulation of gastric RPCs by promotility drugs does not adversely affect the other regulatory mechanisms so as to negate their beneficial effects (65). For example, concurrent stimulation of RPCs in the duodenum or increase of pyloric tone and RPCs may deteriorate antropyloro-duodenal coordination and adversely affect the rate of gastric emptying (25,65). In this regard, erythromycin that accelerates the rate of gastric emptying stimulates the postprandial RPCs in the stomach but it suppresses them in the duodenum (65).…”

Section: Strategies For the Design And Development Of Gut Promotilitymentioning

confidence: 99%

Molecular, functional, and pharmacological targets for the development of gut promotility drugs

Sarna

2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Molecular, functional, and pharmacological targets for the development of gut promotility drugs. Am J Physiol Gastrointest Liver Physiol 291: G545-G555, 2006. First published March 24, 2006 doi:10.1152/ajpgi.00122.2006.-The science of gastrointestinal motility has made phenomenal advances during the last fifty years. Yet, there is a paucity of effective promotility drugs to treat functional bowel disorders that affect 10 -29% of the U.S. population. A part of the reason for the lack of effective drugs is our limited understanding of the etiology of these diseases. In the absence of this information, mostly an ad hoc approach has been used to develop the currently available drugs, which are modestly effective or effective in only a subset of the patients with functional bowel disorders. This review discusses a grounds-up approach for development of the next generation of promotility drugs. The approach is based on our current understanding of 1) the different types of contractions that produce overall motility function of mixing and orderly net distal propulsion in major gut organs, 2) the regulatory mechanisms of these contractions, 3) which receptors and intracellular signaling molecules could be targeted to stimulate specific types of contractions to accelerate or retard transit, and 4) the strengths and limitations of animal models and experimental approaches that could screen potential promotility drugs for their efficacy in human gut propulsion in functional bowel disorders. smooth muscle; slow waves; enteric neurons; excitation-contraction coupling; peristaltic reflex; irritable bowel syndrome; prokinetic agents; gastroparesis; functional bowel disorders THE SCIENCE OF GASTROINTESTINAL MOTILITY has made phenomenal advances during the last fifty years. Our understanding of the individual regulatory mechanisms of motility function [excitation-contraction coupling in smooth muscle cells; enteric motor, sensory, and interneurons; enteric neurotransmitters, neuromodulators, and hormones; extrinsic neurons including spinal cord and central nervous system (CNS)] has matured (7, 18 -20, 26, 28, 39, 42, 53, 54, 57, 59, 60, 76, 78). However, significant gaps remain in our understanding of how and when the inputs from these mechanisms integrate to produce the normal mixing and propulsive motor functions of the gut; defects in these regulatory mechanisms result in motility dysfunction in diseases such as irritable bowel syndrome, inflammatory bowel disease, gastroparesis, and gastroesophageal reflux. Finally, our understanding of which receptors and intracellular signaling molecules in circular smooth muscle cells and enteric neurons could be targeted to normalize function in motility disorders is still rudimentary.Most currently available promotility drugs or those under development seem to have their origins in a known physiological or pharmacological effect or in their established role in a different system. For example, CCK receptor antagonists (loxiglumide and deloxyglumide) are thought to be potential promotil...

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“…This property is explained by the fact that CLA is a macrolide with a chemical structure similar to that of erythromycin, the motor effect of which mimics that of motilin [3, 4, 5, 6, 7, 8], the duodenal hormone which is considered responsible for the occurrence of phase III of the migrating motor complex (MMC) in the gastroduodenal tract. Phase III is a burst of peristaltic contractions that cyclically involves the stomach and intestine clearing the gut lumen during the interdigestive period [9].…”

Section: Introductionmentioning

confidence: 99%

Dose-Related Stimulatory Effect of Clarithromycin on Interdigestive Gastroduodenal Motility

Bortolotti

Annese²,

Mari³

et al. 2000

Digestion

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Background/Aims: The effect on interdigestive gastroduodenal motility of different doses of clarithromycin, an antibiotic commonly used for Helicobacter pylori eradication, has been investigated. Methods: Gastroduodenal motility was recorded by means of a low-compliance manometric system in 15 healthy subjects. Thirty minutes after the first phase III of the migrating motor complex, clarithromycin (CLA) was infused intravenously at a dose of 100 mg in 5, 250 mg in 5 and 400 mg in 5 subjects, randomly and in a double-blind manner, continuing the recording for at least 1 h. A further study was carried out on 10 subjects, 5 of whom received 50 mg CLA and 5 normal saline with the same modalities. Results: After 100 mg CLA a premature gastroduodenal phase III ensued in all cases, which showed a duration, propagation velocity and wave frequency not significantly different from the spontaneous one and was followed by a clear phase I. A premature gastroduodenal phase-III-like activity occurred in 3 cases of 250 mg CLA and 2 cases after 400 mg CLA, followed by a very short or absent phase I and characterized by a long duration of the antral phase III, while in the remaining cases a long-lasting sequence of about 1/min of antral waves propagated to the duodenum appeared, sometimes preceded by an antral phase-III-like activity not propagated to the duodenum. After 50 mg CLA a premature phase III appeared in 2 cases, while a not premature phase III appeared in 2 cases after saline. Conclusion: CLA shows a dose-related stimulatory effect on interdigestive gastroduodenal motility varying from the initiation of a typical phase III to a prolonged sequence of gastroduodenal coordinated waves. These motor effects of CLA suggest potential therapeutic applications.

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Gastrointestinal motor effects of erythromycin in humans

Cited by 133 publications

References 18 publications

Effect of Azithromycin on Patients with Diffuse Panbronchiolitis: Retrospective Study of 51 Cases

Effect of Azithromycin on Patients with Diffuse Panbronchiolitis: Retrospective Study of 51 Cases

Molecular, functional, and pharmacological targets for the development of gut promotility drugs

Dose-Related Stimulatory Effect of Clarithromycin on Interdigestive Gastroduodenal Motility

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