Effects of erythromycin on human colonic circular muscle in idiopathic chronic constipation

Chieppa, D. Mitolo; Mansi, G.; Rinaldi, Rosanna; Serio, M; Nacci, Carmela; Montagnani, Monica; Potenza, Maria Assunta; Salvia, Maria Antonietta De; Mitolo, C. I.; Rinaldi, Marcella; Altomare, D. F.

doi:10.1046/j.1365-2362.2000.00589.x

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…is is consistent with prior literature in which erythromycin has been shown to reduce colonic transit time; however, the mechanism of action is not well understood [50,51]. One antigout medication, colchicine, has been researched for possible use in all-cause chronic constipation [48].…”

Section: Discussionsupporting

confidence: 88%

“…In the context of this study, patients with covariates for all-cause chronic constipation may be more susceptible to OIC by interactions between mechanisms. Diabetes, quinolones, erythromycin, and antigout medications have been associated with all-cause chronic constipation [47][48][49][50][51][52][53][54]. However, it is important to note that this work extends the literature by reporting these covariates among a cohort experiencing constipation due to incident opioid exposure.…”

Section: Discussionmentioning

confidence: 82%

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Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort

FitzHenry

Eden

Denton

et al. 2020

Pain Research and Management

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Objectives. This research describes the prevalence and covariates associated with opioid-induced constipation (OIC) in an observational cohort study utilizing a national veteran cohort and integrated data from the Center for Medicare and Medicaid Services (CMS). Methods. A cohort of 152,904 veterans with encounters between 1 January 2008 and 30 November 2010, an exposure to opioids of 30 days or more, and no exposure in the prior year was developed to establish existing conditions and medications at the start of the opioid exposure and determining outcomes through the end of exposure. OIC was identified through additions/changes in laxative prescriptions, all-cause constipation identification through diagnosis, or constipation related procedures in the presence of opioid exposure. The association of time to constipation with opioid use was analyzed using Cox proportional hazard regression adjusted for patient characteristics, concomitant medications, laboratory tests, and comorbidities. Results. The prevalence of OIC was 12.6%. Twelve positively associated covariates were identified with the largest associations for prior constipation and prevalent laxative (any laxative that continued into the first day of opioid exposure). Among the 17 negatively associated covariates, the largest associations were for erythromycins, androgens/anabolics, and unknown race. Conclusions. There were several novel covariates found that are seen in the all-cause chronic constipation literature but have not been reported for opioid-induced constipation. Some are modifiable covariates, particularly medication coadministration, which may assist clinicians and researchers in risk stratification efforts when initiating opioid medications. The integration of CMS data supports the robustness of the analysis and may be of interest in the elderly population warranting future examination.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 82%

Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort

FitzHenry

Eden

Denton

et al. 2020

Pain Research and Management

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“…Studies with erythromycin or other motilin receptor agonists on human colonic motility in vivo are equivocal, suggesting no activity (Jameson et al ., 1992; Venkatasubramani et al ., 2008), increased colonic motility (Bassotti et al ., 1998) or shortening of colonic transit time (Sharma et al ., 1995). Nevertheless, motilin receptor agonists have been reported to facilitate neuronally mediated contractions in colon from patients with idiopathic chronic constipation (Chieppa et al ., 2000). Perhaps, therefore, motilin will have some direct effect on the colon in certain patients, so further studies are warranted.…”

Section: Discussionmentioning

confidence: 99%

Regional‐ and agonist‐dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists

Broad

Mukherjee

Samadi

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSEDelayed gastric emptying is poorly managed. Motilin agonists are potential treatments but inadequate understanding into how enteric nerve functions are stimulated compromises drug/dose selection. Resolution is hampered by extreme species dependency so methods were developed to study human gastrointestinal neuromuscular activities and the neurobiology of motilin. EXPERIMENTAL APPROACHProtocols to study neuromuscular activities were developed for different regions of human stomach and intestine (71 patients) using circular muscle preparations and electrical field stimulation (EFS) of intrinsic nerves. Other tissues were fixed for immunohistochemistry. KEY RESULTSEFS evoked contractions and/or relaxations via cholinergic and nitrergic neurons, with additional tachykinergic activity in colon; these were consistent after 154 min (longer if stored overnight). Motilin 1-300 nM and the selective motilin agonist GSK962040 0.1-30 mM acted pre-junctionally to strongly facilitate cholinergic contractions of the antrum (Emax ª 1000% for motilin), with smaller increases in fundus, duodenum and ileum; high concentrations increased baseline muscle tension in fundus and small intestine. There were minimal effects in the colon. In the antrum, cholinergic facilitation by motilin faded irregularly, even with peptidase inhibitors, whereas facilitation by GSK962040 was long lasting. Motilin receptor immunoreactivity was identified in muscle and myenteric plexus predominantly in the upper gut, co-expressed with choline acetyltransferase in neurons. CONCLUSIONS AND IMPLICATIONSMotilin and GSK962040 strongly facilitated cholinergic activity in the antrum, with lower activity in fundus and small intestine only. Facilitation by motilin was short lived, consistent with participation in migrating motor complexes. Long-lasting facilitation by GSK962040 suggests different receptor interactions and potential for clinical evaluation. LINKED ARTICLE AbbreviationsChAT, choline acetyltransferase; EFS, electrical field stimulation; Emax, maximum response to agonist; L-NAME, Nw-nitro-L-arginine methyl ester; MMC, migrating motor complex; NK, neurokinin; TTX, tetrodotoxin BJP British Journal of Pharmacology

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“…Erythromycin has been administered for its prokinetic effects with success; however, its efficacy in treatment of nausea is limited due to its adverse gastrointestinal side effects. [33][34][35][36] Metoclopramide may have several mechanisms of action in this setting. 5,8,20,35,37,38 It produces increased gut transit times through enhancement of acetylcholine response in the gastrointestinal tract.…”

Section: Treatmentmentioning

confidence: 99%

Management of Opioid‐Induced Gastrointestinal Effects in Patients Receiving Palliative Care

2002

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Opioid-induced gastrointestinal side effects, namely, nausea and constipation, are bothersome yet often easy to manage. Due to their widespread frequency, it is imperative that prophylactic and treatment modalities be understood. Although many pharmacotherapeutic agents are available with which to prevent or treat these side effects, few randomized, placebo-controlled studies have been conducted in terminally ill patients, thus limiting most treatment decisions to empiric therapies based on extrapolated data. A strong understanding of the pathophysiology of the sequelae is therefore paramount. Common agents administered for nausea are butyrophenones, phenothiazines, metoclopramide, and serotonin-receptor antagonists. Those given to manage constipation are stimulant laxatives and stool softeners, individually or in combination.

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Effects of erythromycin on human colonic circular muscle in idiopathic chronic constipation

Cited by 8 publications

References 26 publications

Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort

Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort

Regional‐ and agonist‐dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists

Management of Opioid‐Induced Gastrointestinal Effects in Patients Receiving Palliative Care

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