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Simmonds S, Wang TH, Matthee A, Dowrick JM, Taberner AJ, Du P, Angeli‐Gordon TR. Pharmaceutical prokinetic and surgical interventions have opposing effects on gastroduodenal electromechanical coupling. Acta Physiol (Oxf) 2025; 241:e70024. [PMID: 40186361 PMCID: PMC11971589 DOI: 10.1111/apha.70024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 02/25/2025] [Accepted: 02/27/2025] [Indexed: 04/07/2025]
Abstract
Improper gastric emptying is implicated in several gastrointestinal disorders and may result from disrupted electromechanical coupling of the gastroduodenal junction (GDJ). Rhythmic "slow waves" and myogenic "spikes" are bioelectrical mechanisms that, alongside neural and hormonal co-factors, control GDJ motility. AIM To characterize the electromechanical effects of prokinetic (erythromycin) infusion and truncal vagotomy on pre-clinical in vivo porcine models. METHODS Following ethical approval, the GDJ was exposed in anesthetized crossbreed weaner pigs (N = 10), and custom high-resolution electrodes were applied to the serosal surface. An EndoFLIP catheter (Medtronic, USA) was inserted orally and positioned across the pylorus to measure luminal diameter. In all subjects, control periods preceded intravenous infusion of erythromycin. In five of those subjects, truncal vagotomy was performed approximately an hour post-infusion, before recording was resumed. RESULTS Compared to control recordings, erythromycin increased contractile amplitude ([2.9 ± 1.1] mm vs. [2.2 ± 0.9] mm; p = 0.002) and was associated with more consistent gastric slow-wave rhythms and increased amplitude of slow waves and spikes. Surgical vagotomy immediately decreased contractile amplitude ([2.90 ± 1.1] mm vs. [1.2 ± 0.6] mm; p = 0.049) and was associated with reduced slow-wave amplitude, increased gastric and duodenal slow-wave frequencies, and decreased spike patch coverage. CONCLUSIONS In conclusion, prokinetics and vagotomy produced opposing effects on GDJ electromechanical coupling and could inform diagnostic and interventional practices for patients with pathophysiological complications of this region.
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Affiliation(s)
- Sam Simmonds
- Auckland Bioengineering InstituteUniversity of AucklandAucklandNew Zealand
| | - Tim H.‐H. Wang
- Department of SurgeryUniversity of AucklandAucklandNew Zealand
| | - Ashton Matthee
- Auckland Bioengineering InstituteUniversity of AucklandAucklandNew Zealand
| | - Jarrah M. Dowrick
- Auckland Bioengineering InstituteUniversity of AucklandAucklandNew Zealand
| | - Andrew J. Taberner
- Auckland Bioengineering InstituteUniversity of AucklandAucklandNew Zealand
- Department of Engineering Science and Biomedical EngineeringUniversity of AucklandAucklandNew Zealand
| | - Peng Du
- Auckland Bioengineering InstituteUniversity of AucklandAucklandNew Zealand
- Department of Engineering Science and Biomedical EngineeringUniversity of AucklandAucklandNew Zealand
| | - Timothy R. Angeli‐Gordon
- Auckland Bioengineering InstituteUniversity of AucklandAucklandNew Zealand
- Department of SurgeryUniversity of AucklandAucklandNew Zealand
- Te Manawahoukura Rangahau CentreTe Wānanga o AotearoaTe AwamutuNew Zealand
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Mori H, Verbeure W, Tanemoto R, Sosoranga ER. Physiological functions and potential clinical applications of motilin. Peptides 2023; 160:170905. [PMID: 36436612 DOI: 10.1016/j.peptides.2022.170905] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 11/10/2022] [Accepted: 11/10/2022] [Indexed: 11/27/2022]
Abstract
Motilin is a gastrointestinal hormone secreted by the duodenum. This peptide regulates a characteristic gastrointestinal contraction pattern, called the migrating motor complex, during the fasting state. Motilin also affects the pressure of the lower esophageal sphincter, gastric motility and gastric accommodation in the gastrointestinal tract. Furthermore, motilin induces bile discharge into the duodenum by promoting gallbladder contraction, pepsin secretion in the stomach, pancreatic juice and insulin secretion from the pancreas. In recent years, it has been shown that motilin is associated with appetite, and clinical applications are expected for diseases affected by food intake, e.g. obesity, by regulating motilin levels. Gastric acid and bile are the two major physiological regulators for motilin release. Caloric foods have varying effects on motilin levels, depending on their composition. Among non-caloric foods, bitter substances reduce motilin levels and are therefore expected to have an appetite-suppressing effect. Various motilin receptor agonists and antagonists have been developed but have yet to reach clinical use.
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Affiliation(s)
- Hideki Mori
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan
| | - Wout Verbeure
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Rina Tanemoto
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
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Jaggi P, Hamdy RF, Lee B, Hersh AL, Gerber JS, Sharland M, Terrill C, Newland JG. Use of Antimicrobial Agents in Hospitalized Children for Noninfectious Indications. J Pediatric Infect Dis Soc 2020; 9:490-493. [PMID: 32677678 DOI: 10.1093/jpids/piz053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 07/03/2019] [Indexed: 12/24/2022]
Abstract
In this point-prevalence study of 32 US children's hospitals, we determined that 1.7% of hospitalized children received at least 1 antimicrobial agent for a non-infection-related reason; macrolides were used most commonly. Antimicrobial stewardship efforts to understand and affect use for these reasons is an unmet need; additional research considering the individual and societal effects of these antimicrobial-prescribing practices should be undertaken.
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Affiliation(s)
- Preeti Jaggi
- Division of Infectious Diseases, Department of Pediatrics, Emory University, Atlanta, Georgia
| | - Rana F Hamdy
- Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Division of Infectious Diseases, Children's National Medical Center, Washington, DC
| | - Brian Lee
- Department of Pediatrics, School of Medicine, Children's Mercy, Kansas City, Missouri
| | - Adam L Hersh
- Division of Infectious Diseases, Department of Pediatrics, University of Utah, Salt Lake City
| | - Jeffrey S Gerber
- Division of Infectious Diseases, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia, United Kingdom
| | - Mike Sharland
- Institute of Infection and Immunity, St George's University of London, United Kingdom
| | - Cindy Terrill
- Division of Infectious Diseases, Department of Pediatrics, Washington University St Louis, Missouri
| | - Jason G Newland
- Division of Infectious Diseases, Department of Pediatrics, Washington University St Louis, Missouri
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Deloose E, Verbeure W, Depoortere I, Tack J. Motilin: from gastric motility stimulation to hunger signalling. Nat Rev Endocrinol 2019; 15:238-250. [PMID: 30675023 DOI: 10.1038/s41574-019-0155-0] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets for treating hypomotility disorders. The genetic revolution - with the use of knockout models - sparked novel insights into the role of multiple peptides but contributed to a decline in interest in motilin, as this peptide and its receptor exist only as pseudogenes in rodents. The past 5 years have seen a major surge in interest in motilin, as a series of studies have shown its relevance in the control of hunger and regulation of food intake in humans in both health and disease. Luminal stimuli, such as bitter tastants, have been identified as modulators of motilin release, with effects on hunger and food intake. The current state of knowledge and potential implications for therapy are summarized in this Review.
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Affiliation(s)
- Eveline Deloose
- Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
| | - Wout Verbeure
- Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
| | - Inge Depoortere
- Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium.
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Somarajan S, Muszynski ND, Hawrami D, Olson JD, Cheng LK, Bradshaw LA. Noninvasive Magnetogastrography Detects Erythromycin-Induced Effects on the Gastric Slow Wave. IEEE Trans Biomed Eng 2018; 66:327-334. [PMID: 29993499 DOI: 10.1109/tbme.2018.2837647] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The prokinetic action of erythromycin is clinically useful under conditions associated with gastrointestinal hypomotility. Although erythromycin is known to affect the electrogastrogram, no studies have examined the effects that erythromycin has on gastric slow wave magnetic fields. METHODS In this study, gastric slow wave activity was assessed simultaneously using noninvasive magnetogastrogram (MGG), electrogastrogram, and mucosal electromyogram recordings. Recordings were obtained for 30 min prior to and 60 min after intravenous administration of erythromycin at dosages of 3 and 6 mg/kg. RESULTS MGG recordings showed significant changes in the percentage power distribution of gastric signal after infusion of both 3 and 6 mg/kg erythromycin at t = 1-5 min that persisted for t = 30-40 min after infusion. These changes agree with the changes observed in the electromyogram. We did not observe any statistically significant difference in MGG amplitude before or after injection of either 3 or 6 mg/kg erythromycin. Both 3 and 6 mg/kg erythromycin infusion showed retrograde propagation with a statistically significant decrease in slow wave propagation velocity 11-20 min after infusion. Propagation velocity started returning toward baseline values after approximately 21-30 min for the 3 mg/kg dosage and after 31-40 min for a dosage of 6 mg/kg. CONCLUSION Our results showed that the magnetic signatures were sensitive to disruptions in normal slow wave activity induced by pharmacological and prokinetic agents such as erythromycin. SIGNIFICANCE This study shows that repeatable noninvasive bio-electro-magnetic techniques can objectively characterize gastric dysrhythmias and may quantify treatment efficacy in patients with functional gastric disorders.
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Lau JSY, Kiss C, Roberts E, Horne K, Korman TM, Woolley I. Surveillance of life-long antibiotics: a review of antibiotic prescribing practices in an Australian Healthcare Network. Ann Clin Microbiol Antimicrob 2017; 16:3. [PMID: 28100229 PMCID: PMC5241934 DOI: 10.1186/s12941-017-0180-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Accepted: 01/11/2017] [Indexed: 12/14/2022] Open
Abstract
Background The rise of antimicrobial use in the twentieth century has significantly reduced morbidity due to infection, however it has also brought with it the rise of increasing resistance. Some patients are on prolonged, if not “life-long” course of antibiotics. The reasons for this are varied, and include non-infectious indications. We aimed to study the characteristics of this potential source of antibiotic resistance, by exploring the antibiotic dispensing practices and describing the population of patients on long-term antibiotic therapy. Methods A retrospective cross-sectional study of antibiotic dispensing records was performed at a large university hospital-based healthcare network in Melbourne, Australia. Outpatient prescriptions were extracted from the hospital pharmacy database over a 6 month period in 2014. Medical records of these patients were reviewed to determine the indication for prescription, including microbiology, the intended duration, and the prescribing unit. A descriptive analysis was performed on this data. Results 66,127 dispensing episodes were reviewed. 202 patients were found to have been prescribed 1 or more antibiotics with an intended duration of 1 year or longer. 69/202 (34%) of these patients were prescribed prolonged antibiotics for primary prophylaxis in the setting of immunosuppression. 43/202 (21%) patients were prescribed long-term suppressive antibiotics for infections of thought incurable (e.g. vascular graft infections), and 34/43 (79%) were prescribed by Infectious Diseases doctors. 66/202 (33%) patients with cystic fibrosis were prescribed prolonged courses of macrolides or fluoroquinolones, by respiratory physicians. There was great heterogeneity noted in indications for prolonged antibiotic courses, as well as antibiotic agents utilised. Conclusion Our study found that that continuous antibiotic therapy represented only a small proportion of overall antibiotic prescribing at our health network. Prolonged courses of antibiotics were used mainly to suppress infections thought incurable, but also as primary and secondary prophylaxis and as anti-inflammatory agents. More research is needed to understand the impact of long-term antibiotic consumption on both patients and microbial ecology.
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Affiliation(s)
- Jillian S Y Lau
- Monash Infectious Diseases, Monash University, Monash Health, Clayton, VIC, Australia
| | - Christopher Kiss
- Monash Infectious Diseases, Monash University, Monash Health, Clayton, VIC, Australia
| | - Erika Roberts
- Monash Health Pharmacy, Monash Health, Clayton, VIC, Australia
| | - Kylie Horne
- Monash Infectious Diseases, Monash University, Monash Health, Clayton, VIC, Australia
| | - Tony M Korman
- Monash Infectious Diseases, Monash University, Monash Health, Clayton, VIC, Australia
| | - Ian Woolley
- Monash Infectious Diseases, Monash University, Monash Health, Clayton, VIC, Australia.
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Hellström PM, Tack J, Johnson LV, Hacquoil K, Barton ME, Richards DB, Alpers DH, Sanger GJ, Dukes GE. The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying. Br J Pharmacol 2016; 173:1768-77. [PMID: 26924243 DOI: 10.1111/bph.13475] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 01/29/2016] [Accepted: 02/14/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND PURPOSE Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis. EXPERIMENTAL APPROACH In a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying ((13) C-octanoic acid breath test), pharmacokinetics and safety were primary outcomes. KEY RESULTS Nine of the 10 patients enrolled completed the study. Gastric half-emptying time decreased by -95 min (95% CI: -156.8, -34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half-emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure-response relationship was demonstrated across all doses. The effects of camicinal on gastric half-emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose-proportional pharmacokinetic characteristics and a clear exposure-response relationship with gastric emptying. CONCLUSIONS AND IMPLICATIONS Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.
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Affiliation(s)
| | | | | | | | | | | | - David H Alpers
- Washington University School of Medicine, St Louis, MO, USA
| | - Gareth J Sanger
- Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Chu H, Lin Z, Zhong L, McCallum RW, Hou X. Treatment of high-frequency gastric electrical stimulation for gastroparesis. J Gastroenterol Hepatol 2012; 27:1017-26. [PMID: 22128901 DOI: 10.1111/j.1440-1746.2011.06999.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS The aim of this study was to assess the effects of gastric electrical stimulation (GES) on symptoms and gastric emptying in patients with gastroparesis, and the effects of GES on the three subgroups of gastroparesis. METHODS A literature search of clinical trials using high-frequency GES to treat patients with gastroparesis from January 1995 to January 2011 was performed. Data on the total symptom severity score (TSS), nausea severity score, vomiting severity score, and gastric emptying were extracted and analyzed. The statistic effect index was weighted mean differences. RESULTS Ten studies (n = 601) were included in this study. In the comparison to baseline, there was significant improvement of symptoms and gastric emptying (P < 0.00001). It was noted that GES significantly improved both TSS (P < 0.00001) and gastric retention at 2 h (P = 0.003) and 4 h (P < 0.0001) in patients with diabetic gastroparesis (DG), while gastric retention at 2 h (P = 0.18) in idiopathic gastroparesis (IG) patients, and gastric retention at 4 h (P = 0.23) in postsurgical gastroparesis (PSG) patients, did not reach significance. CONCLUSIONS Based on this meta-analysis, the substantial and significant improvement of symptoms and gastric emptying, and the good safety we observed, indicate that high-frequency GES is an effective and safe method for treating refractory gastroparesis. DG patients seem the most responsive to GES, both subjectively and objectively, while the IG and PSG subgroups are less responsive and need further research.
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Affiliation(s)
- Huikuan Chu
- Division of Gastroenterology, Department of Internal Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Lee AL, Kim CB. The effect of erythromycin on gastrointestinal motility in subtotal gastrectomized patients. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2012; 82:149-55. [PMID: 22403748 PMCID: PMC3294108 DOI: 10.4174/jkss.2012.82.3.149] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2011] [Revised: 12/09/2011] [Accepted: 12/16/2011] [Indexed: 01/10/2023]
Abstract
Purpose Our objective was to determine the effect of erythromycin (EM) in improving gastrointestinal motility in subtotal gastrectomized patients. We used radio-opaque Kolomarks as an objective method. We conducted a prospective, controlled clinical trial study of 24 patients. Methods All patients underwent subtotal gastrectomy with 3 capsules containing Kolomarks (20 markers per 1 capsule) in the remnant stomach before anastomosis. From the day of the operation to the 2nd postoperative day, patients in the EM group began receiving 200 mg of EM intravenously for 30 minutes continuously. We counted the number of Kolomarks in the stomach, passed by stomach, in rectum, and in stool with serial simple abdominal X-ray films on the first postoperative day up to the 7th postoperative day. Results The study population included 14 patients in the control group and 10 patients in the EM group. The two study groups were compared in terms of their characteristics including age, gender, past medical history, cancer stage, and operation type. No significant differences were found for the demographics between the two groups. We only found a significant difference for the number of Kolomarks passed by the stomach on the 3rd postoperative day (P = 0.026). Conclusion Our results demonstrated that 200 mg of EM intravenous infusion during the postoperative period induced rapid gastric emptying, although it did not improve gastrointestinal motility for the entire gastrointestinal tract in subtotal gastrectomized patients.
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Affiliation(s)
- A-Lan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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10
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De Smet B, Mitselos A, Depoortere I. Motilin and ghrelin as prokinetic drug targets. Pharmacol Ther 2009; 123:207-23. [DOI: 10.1016/j.pharmthera.2009.04.004] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2009] [Accepted: 04/09/2009] [Indexed: 12/13/2022]
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Hawkyard CV, Koerner RJ. The use of erythromycin as a gastrointestinal prokinetic agent in adult critical care: benefits versus risks. J Antimicrob Chemother 2007; 59:347-58. [PMID: 17289772 DOI: 10.1093/jac/dkl537] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Erythromycin A, the first macrolide, was introduced in the 1950s and after years of clinical experience it still remains a commonly relied upon antibiotic. In the past, pharmacodynamic characteristics of macrolides beyond antimicrobial action such as anti-inflammatory and immune-modulating properties have been of scientific and clinical interest. The function of erythromycin as a prokinetic agent has also been investigated for a range of gastrointestinal motility disorders and more recently within the context of critically ill patients. Prokinetic agents are drugs that increase contractile force and accelerate intraluminal transit. Whilst the anti-inflammatory action may be a desirable side effect to its antibiotic action, using erythromycin A merely for its prokinetic effect alone raises the concern about promoting emergence of macrolide resistance. The objectives of this review article are: (i) to briefly summarize the modes and epidemiology of macrolide resistance, particularly in respect to that found in the Streptococcus species (a potential reservoir for the dissemination of macrolide resistance on the critical care unit); (ii) to discuss in this context the evidence for conditions promoting bacterial resistance against macrolides; and (iii) to assess the potential clinical benefit of using erythromycin A as a prokinetic versus the risks of promoting emergence of macrolide resistance in the clinical setting. We conclude, that in view of the growing weight of evidence demonstrating the potential epidemiological impact of the increased use of macrolides upon the spread of resistance, versus a lack of sufficient and convincing evidence that erythromycin A is a superior prokinetic agent to potential alternatives in the critically ill patient population, at this stage we do not advocate the use of erythromycin A as a prokinetic agent in critically ill patients unless they have failed all other treatment for impaired gastrointestinal dysmotility and are intolerant of metoclopramide. Further large and methodologically robust studies are needed to ascertain the effectiveness of erythromycin A and other alternative agents in the critically ill.
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Affiliation(s)
- Catherine V Hawkyard
- Department of Medical Microbiology, Sunderland Royal Hospital, Sunderland, SR4 7TP, UK
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Caddy GR, Moran L, Chong AKH, Miller AM, Taylor AC, Desmond PV. The effect of erythromycin on video capsule endoscopy intestinal-transit time. Gastrointest Endosc 2006; 63:262-6. [PMID: 16427932 DOI: 10.1016/j.gie.2005.07.043] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2005] [Accepted: 07/27/2005] [Indexed: 02/07/2023]
Abstract
BACKGROUND Video capsule endoscopy (VCE) will fail to reach the cecum in 20% of patients within the 8-hour battery life. The use of prokinetics to improve VCE completion rates to the cecum remains unclear. The objective of this study was to determine whether erythromycin increases the completion rate of VCE to the cecum without adversely affecting image quality. METHODS This was a prospective, randomized, single-blinded control trial at St. Vincent's Hospital, Melbourne, Australia. A total of 86 consecutive patients referred for VCE were considered for entry; 45 patients met the entry criteria. These 45 patients were prospectively randomized to no erythromycin (controls, n = 23) or 250 mg erythromycin (n = 22). Two gastroenterologists, who were unaware of which group the patients were randomized into, reported all VCEs. The number of VCEs that reached the cecum within the 8-hour study period, gastric emptying time (GET), and small-bowel transit time (SBTT) were calculated for each group. RESULTS There was no significant difference in the number of VCEs that reached the cecum (32% failed to reach the cecum in the erythromycin group compared with 22% in the control group), GET, or SBTT between the two groups. Image quality was not adversely affected by the use of erythromycin. The dose and the preparation of erythromycin used in this study may have possibly had an effect on GET and SBTT. CONCLUSIONS The use of erythromycin did not significantly increase the likelihood of the capsule reaching the cecum or affect the degree of visible peristalsis or the interpretation of capsule findings.
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Affiliation(s)
- Grant R Caddy
- Department of Gastroenterology, Ulster Hospital, Dundonald, Belfast, Northern Ireland, United Kingdom
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Abstract
Gastrointestinal promotility drugs stimulate smooth muscle contractions to enhance gastric emptying and small and large bowel transit. Currently available drug classes with prokinetic properties include antidopaminergic agents, serotonergic agents, and motilin-receptor agonists. Due to moderate prokinetic effects, poor symptomatic responses and the presence of adverse effects, there is a clear need for new classes of prokinetics. Several newer prokinetic drugs and drug classes are currently under evaluation. Selecting candidate agents and designing the appropriate therapeutic trials is hampered by the lack of insight in the pathophysiology of motility-related symptoms. As gastrointestinal motor disorders are chronic, relapsing, and remitting disorders, it seems desirable that studies with candidate prokinetic drugs establish a long-term efficacy and not only short-term effects on gastrointestinal functions.
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Affiliation(s)
- G Karamanolis
- Center for Gastroenterological Research, KU Leuven, Leuven, Belgium
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Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 2004; 127:1592-622. [PMID: 15521026 DOI: 10.1053/j.gastro.2004.09.055] [Citation(s) in RCA: 502] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This literature review and the recommendations herein were prepared for the American Gastroenterological Association Clinical Practice Committee. The paper was approved by the Committee on May 16, 2004, and by the AGA Governing Board on September 23, 2004.
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Griffith DP, McNally AT, Battey CH, Forte SS, Cacciatore AM, Szeszycki EE, Bergman GF, Furr CE, Murphy FB, Galloway JR, Ziegler TR. Intravenous erythromycin facilitates bedside placement of postpyloric feeding tubes in critically ill adults: a double-blind, randomized, placebo-controlled study. Crit Care Med 2003; 31:39-44. [PMID: 12544991 DOI: 10.1097/00003246-200301000-00006] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
UNLABELLED OBJECTIVE To evaluate the efficacy of intravenous erythromycin as a method to facilitate feeding tube placement into the small intestine in critically ill patients. DESIGN Double blind, randomized, controlled trial. SETTING Medical and surgical intensive care units in an academic medical center. PATIENTS Prospective cohort of 36 consecutive adults requiring intensive care unit care and enteral tube feeding for nutritional support. INTERVENTION Infusion of a single dose of intravenous erythromycin (500 mg) or saline before placement of 10-Fr feeding tubes using a standardized active bedside protocol. MEASUREMENTS AND MAIN RESULTS We determined the success rate of feeding tube placement into or beyond the second portion of the duodenum and the time required for this procedure by experienced nurses. The feeding tube was considered to be postpyloric when the tip was in the second portion of the duodenum or beyond. The predictive value of a serial step-up in gastrointestinal aspirate pH from < or = 5.0 to > or = 6.0 was also determined. Use of intravenous erythromycin significantly improved the rate of feeding tube placement into the duodenum or jejunum (erythromycin group, 13 of 14 patients or 93% vs. the control group, 12 of 22 patients or 55%; p < .03). Erythromycin administration also significantly decreased the procedure time from 25 +/- 3 to 15 +/- 2 mins (p < .04). Feeding tube placement into either duodenum or jejunum was confirmed in all 18 patients with a pH step-up from < or = 5.0 to > or = 6.0. CONCLUSION A single bolus dose of intravenous erythromycin facilitates active bedside placement of postpyloric feeding tubes in critically ill adult patients.
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Affiliation(s)
- Daniel P Griffith
- Nutrition and Metabolic Support Service, Emory University Hospital, Atlanta, GA 30322, USA
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Miskovitz P. Gastric prokinetic motility therapy to facilitate early enteral nutrition in the intensive care unit. Crit Care Med 2002; 30:1386-7. [PMID: 12072701 DOI: 10.1097/00003246-200206000-00046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Acalovschi M, Dumitrascu DL, Hagiu C. Oral clarithromycin enhances gallbladder emptying induced by a mixed meal in healthy subjects. Eur J Intern Med 2002; 13:104-107. [PMID: 11893467 DOI: 10.1016/s0953-6205(01)00203-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Background: In humans, erythromycin has been demonstrated to accelerate gallbladder emptying due to its motilin-like effects on the gastrointestinal tract. Recently, it was shown that clarithromycin, another macrolide, used for the eradication of Helicobacter pylori infection, also stimulated gastrointestinal motility in the fasting state. We conducted a comparative study on the effects of a single oral dose of clarithromycin and of erythromycin on gallbladder emptying in healthy subjects. Methods: Gallbladder emptying variables (residual volume, ejection fraction, area under emptying curve) were measured by ultrasound in 21 healthy subjects (11 males, 10 females, mean age 42.5+/-10.6 years). A test meal (14 g fat, 425 kcal) was ingested 30 min after a single oral dose (500 mg) of either clarithromycin or erythromycin, and the measurements were repeated the following day with the other drug (cross-over double-blind study). A control group consisting of 12 subjects (seven males, five females, mean age 50.7+/-8.2 years) was used to evaluate gallbladder emptying following the same test meal without drug administration. Differences between groups were analyzed using two-tailed Student's t-test for unpaired observations. Results: Gallbladder emptying at 60, 75, and 90 min was greater after erythromycin (P<0.05 at 90 min) and clarithromycin than it was in controls. The ejection fraction was significantly greater after clarithromycin (76.5%) and erythromycin (79.7%) than it was in controls. Gallbladder refilling occurred earlier after clarithromycin than after erythromycin. Conclusions: The prokinetic effect of clarithromycin on the gallbladder appears to be of similar amplitude but of shorter duration than that of erythromycin.
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Affiliation(s)
- Monica Acalovschi
- Department of Gastroenterology, Third Medical Clinic, University of Medicine and Pharmacy, Str. Iuliu Maniu No. 9, RO-3400, Cluj-Napoca, Romania
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Costalos C, Gounaris A, Varhalama E, Kokori F, Alexiou N, Kolovou E. Erythromycin as a prokinetic agent in preterm infants. J Pediatr Gastroenterol Nutr 2002; 34:23-5. [PMID: 11753159 DOI: 10.1097/00005176-200201000-00006] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The macrolide antibiotic erythromycin is a prokinetic agent that stimulates gastrointestinal motility. The aim of the study was to determine the effect of erythromycin on the gastrointestinal motility of preterm infants. METHODS Erythromycin 10 mg/kg, 8 hourly or a placebo, was given orally for 7 days in a double-blind randomized, crossover study of 20 preterm infants with a median gestational age of 32 weeks (range, 26-34 weeks). Antral contractility was determined by using ultrasonography to measure the decrease in the gastric antral cross-sectional area after a feed. The whole gut transit time was assessed by timing the transit of carmine red through the gut. RESULTS Antral contractility lasted for a shorter period of time during erythromycin treatment than during placebo treatment (mean [standard deviation], 31 minutes [9.9 minutes] vs. 70 minutes [13 minutes]; P < 0.01). Whole gut transit time was also shorter during erythromycin treatment (mean, 23.1 hours [12.9 hours] vs. 49.3 hours [29 hours]; P < 0.01). All infants tolerated the drug well. CONCLUSIONS Oral erythromycin in food-intolerant preterm infants enhances both antral contractility and whole gut transit time.
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Affiliation(s)
- Christos Costalos
- Department of Neonatal Medicine, Piraeus General Hospital, Nikea, Piraeus, Greece
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Abstract
Erythromycin has been used as an antibiotic for more than four decades, but only in the last 10 years have other therapeutic benefits of this agent been exploited. Animal and human studies have demonstrated a prokinetic effect on the gastrointestinal tract at sub-antimicrobial doses (typically a quarter or less of the antibiotic dose). A limited number of studies have been performed in children to investigate this action. A review of this literature is particularly pertinent given the frequency of clinical problems related to gastrointestinal dysmotility in children and the limited availability of prokinetic agents in paediatric practice, compounded by the recent withdrawal of cisapride. The prokinetic effects of erythromycin have been investigated in infants with dysmotility associated with prematurity, in low birth-weight infants recovering from abdominal surgery, and in older children with a variety of other gastrointestinal disorders. Only one randomized placebo-controlled trial has been conducted. All except one of these studies have shown a beneficial effect of erythromycin in either promoting tolerance of enteral feeds or enhancing a measured index of gastrointestinal motility. Erythromycin appears to be equally effective when given orally (as ethylsuccinate or estolate) or intravenously (as lactobionate). Significantly, no serious adverse effects have been reported in studies in which erythromycin has been used for its prokinetic effects, although fatal reactions have followed the intravenous administration of erythromycin to neonates in antibiotic doses.
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Affiliation(s)
- J I Curry
- British Association of Paediatric Surgeons, The Royal College of Surgeons of England, London, UK.
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Chapman MJ, Fraser RJ, Kluger MT, Buist MD, De Nichilo DJ. Erythromycin improves gastric emptying in critically ill patients intolerant of nasogastric feeding. Crit Care Med 2000; 28:2334-7. [PMID: 10921561 DOI: 10.1097/00003246-200007000-00026] [Citation(s) in RCA: 137] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To evaluate the effect of intravenous erythromycin on gastric emptying and the success of enteral feeding in mechanically ventilated, critically ill patients with large volume gastric aspirates. DESIGN Prospective, double-blind, randomized, and placebo-controlled trial. SETTING General intensive care unit in a university hospital. PATIENTS Twenty critically ill, mechanically ventilated patients intolerant of nasogastric feeding (indicated by a residual gastric volume of > or =250 mL during feed administration at > or =40 mL/hr). INTERVENTIONS After a gastric aspirate of > or =250 mL, which was discarded, the enteral feeding was continued at the previous rate for 3 hrs. Intravenous erythromycin (200 mg) or placebo was then administered over 20 mins. The residual gastric contents were again aspirated and the volume was recorded 1 hr after the infusion began. MEASUREMENTS AND MAIN RESULTS Gastric emptying was calculated as volume of feed infused into the stomach over 4 hrs minus the residual volume aspirated. Mean gastric emptying was 139+/-37 (+/-SEM) mL after erythromycin and -2+/-46 mL after placebo (p = .027). Nasogastric feeding was successful in nine of ten patients treated with erythromycin and five of ten who received placebo 1 hr after infusion (chi-square p = .05). CONCLUSION In critically ill patients who have large volumes of gastric aspirates indicating a failure to tolerate nasogastric feeding, a single small dose of intravenous erythromycin allows continuation of feed in the short term.
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Sato F, Marui S, Inatomi N, Itoh Z, Omura S. EM574, an erythromycin derivative, improves delayed gastric emptying of semi-solid meals in conscious dogs. Eur J Pharmacol 2000; 395:165-72. [PMID: 10794824 DOI: 10.1016/s0014-2999(00)00185-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The gastroprokinetic effects of de(N-methyl)-N-isopropyl-8, 9-anhydroerythromycin A 6,9-hemiacetal (EM574), a non-peptide motilin receptor agonist, were investigated in conscious dogs in a normal state and with experimentally-induced gastroparesis. Gastric emptying of semi-solid meals was assessed indirectly from acetaminophen absorption with simultaneous recording of gastric antral motility. In the normal state, post-prandial intraduodenal administration of EM574 (0.03 mg/kg) [corrected] stimulated antral motility and significantly enhanced gastric emptying as potently as did intravenous porcine motilin (0.003 mg/kg/h). Intraduodenal cisapride at 1 mg/kg denal cisapride at 1 mg/kg elicited antral contractions and tended to accelerate gastric emptying but at 3 mg/kg, gastric emptying was not enhanced despite a further increase in the motor index. In dogs with gastroparesis induced by intraduodenal oleic acid or intravenous dopamine, EM574 (0.03 mg/kg) increased antral motility and reversed the delayed gastric emptying completely. Cisapride (1 mg/kg) partially ameliorated the impaired emptying under these conditions. In atropinized dogs, no acceleration of gastric emptying by EM574 was observed. These results indicate that EM574 potently accelerates gastric emptying of caloric meals in dogs in a normal state and with experimentally-induced gastroparesis, and also suggest that the effect is mediated through stimulation of a cholinergic neural pathway.
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Affiliation(s)
- F Sato
- Pharmacology Laboratories II, Takeda Chemical Industries, Ltd., 2-17-85, Juso-Honmachi, Yodogawa-ku, Osaka, Japan
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Stewart JJ, Wood MJ, Parish RC, Wood CD. Prokinetic effects of erythromycin after antimotion sickness drugs. J Clin Pharmacol 2000; 40:347-53. [PMID: 10761161 DOI: 10.1177/00912700022009044] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Motion sickness and the antimotion sickness drugs scopolamine (SCP) and promethazine (PMZ) inhibit gastric emptying (GE). This study was conducted to determine if erythromycin would exert its well-known prokinetic effects in normal and motion-sick subjects given antimotion sickness drugs. Fifteen fasted volunteers (11 males, 4 females) participated in the study. In control tests, 8 subjects were given intramuscular (i.m.) saline (SAL, 0.5 ml), SCP (0.1 mg), or PMZ (25 mg). GE of liquid (300 ml) containing 1 mCi of Tc 99m diethylenetriaminepentaacetic acid (DTPA) was measured by sequential gastric scintigraphy 30 minutes after i.m. treatments. In other tests, GE was measured in 8 subjects after each i.m. treatment, followed 10 minutes later by 200 mg of erythromycin ethylsuccinate (ESS) suspension given orally. In a third group of tests, 7 subjects received an i.m. treatment, oral EES 10 minutes later, and were then brought to an advanced level of motion sickness short of vomiting. To induce motion sickness, blindfolded subjects made timed head movements while seated in a rotating chair. GE was measured immediately after rotation. GE half-life, rate constant, area under the curve (AUC), and lag time were calculated using conventional mathematical methods for analyzing exponential rate processes. GE parameters calculated for normal and motion-sick subjects given antimotion sickness drugs and EES were compared with those from subjects given i.m. treatments (control) only. In normal subjects, EES significantly (p < 0.05) increased the GE rate constant for all i.m. treatments and reduced the AUC for SAL, SCP, and PMZ by 49% (p < 0.05), 44% (p < 0.05), and 69% (p < 0.01), respectively. In motion-sick subjects, lag time was significantly (p < 0.05) increased, and the rate constant and AUC values were unchanged from control for all i.m. treatments. The authors conclude that oral EES reverses the gastrostatic actions of the antimotion sickness drugs but does not affect the inhibition of gastric emptying associated with motion sickness. The results suggest that motion sickness and antimotion sickness drugs reduce GE through different mechanisms.
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Affiliation(s)
- J J Stewart
- Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport 71130-3932, USA
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De Ponti F, Malagelada JR. Functional gut disorders: from motility to sensitivity disorders. A review of current and investigational drugs for their management. Pharmacol Ther 1998; 80:49-88. [PMID: 9804054 DOI: 10.1016/s0163-7258(98)00021-7] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Functional gut disorders include several clinical entities defined on the basis of symptom patterns (e.g., functional dyspepsia, irritable bowel syndrome, functional abdominal pain, functional abdominal bloating), for which there is no established pathophysiological mechanism. Because there is no well-defined pathophysiological target, treatment should be aimed at symptom improvement. Prokinetics and antispasmodics have been widely used in the treatment of functional gut disorders on the assumption that disordered motility is the underlying cause of symptoms, and symptom improvement is indeed achievable with these compounds in some, but not all, patients with features of hypo- or hypermotility, respectively. In the first part of this review, we cover the basic pharmacology and discuss the rationale for the clinical use of prokinetics and antispasmodics. On the other hand, in the past few years, the explosive growth in the research focusing on visceral sensitivity and visceral reflexes has suggested that at least some patients with functional gut disorders have altered visceral perception. Thus, the second part of the review covers these developments and focuses on studies addressing the issue of drugs modulating visceral sensitivity.
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Affiliation(s)
- F De Ponti
- Department of Internal Medicine and Therapeutics, University of Pavia, Italy
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26
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Delatour F, Le Guludec D, Caron F, Faurisson F, Torlotin JC, Rouveix B. Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: a scintigraphic study. Fundam Clin Pharmacol 1998; 12:292-7. [PMID: 9646062 DOI: 10.1111/j.1472-8206.1998.tb00957.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.
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Affiliation(s)
- F Delatour
- Département de Pharmacologie Clinique, INSERM U13, Paris, France
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27
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Ehrenpreis ED, Zaitman D, Nellans H. Which form of erythromycin should be used to treat gastroparesis? A pharmacokinetic analysis. Aliment Pharmacol Ther 1998; 12:373-6. [PMID: 9690728 DOI: 10.1046/j.1365-2036.1998.00302.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Erythromycin is a macrolide antibiotic that exhibits prokinetic effects. It has been shown to enhance antral contractility and accelerates gastric emptying rates, primarily by stimulating motilin receptors. AIM To determine the optimal dosage form of erythromycin for use as a prokinetic agent. METHODS Eight normal volunteers and three patients with documented gastroparesis ingested 250 mg erythromycin in tablet. suspension and intravenous forms. Serum erythromycin levels were determined at frequent intervals. These data were plotted vs. time and analysed for lag time, time to maximum concentration (tmax), maximum concentration (Cmax) and bioavailability (F). RESULTS The absorption kinetics of the erythromycin suspension was notable for short lag times and early tmax, while lag times and tmax were delayed with the tablet form. Median lag time was 15 min for the suspension vs. 90 min for the tablet (P < 0.005). Median tmax for the suspension was 45 min vs. 180 min for the tablet (P < 0.005). A non-significant decrease in F was seen with the suspension compared to the tablet (P = 0.12). CONCLUSION Based on the kinetic data from this study, erythromycin suspension is the ideal dosage form for administration of this drug as a prokinetic agent.
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Affiliation(s)
- E D Ehrenpreis
- Department of Gastroenterology, University of Chicago, Illinois 60637, USA
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28
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Mathis C, Malbert CH. Erythromycin gastrokinetic activity is partially vagally mediated. THE AMERICAN JOURNAL OF PHYSIOLOGY 1998; 274:G80-6. [PMID: 9458776 DOI: 10.1152/ajpgi.1998.274.1.g80] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Erythromycin overcomes postvagotomy gastroparesia in patients without a distal stomach and functional pylorus. We investigate the role of the vagus in gastric emptying increased by erythromycin, using a model that preserves the physiology of the distal stomach and pylorus. The effects of erythromycin lactobionate (10 mg/kg) on transpyloric flow pattern and pyloric resistance were evaluated during repetitive bilateral vagal cooling in anesthetized pigs. Vagal cooling during erythromycin infusion produced a marked decreased of pyloric outflow (23 +/- 1.1 vs 50 +/- 2.6 ml/min) related to a reduced stroke volume of the flow pulses (7.8 +/- 3.31 vs. 14.1 +/- 2.44 ml). The amplitude and frequency of gastric and duodenal pressure events were unchanged or slightly reduced during vagal cooling. The smaller stroke volume of flow pulse was the consequence of increased pyloric resistance (6.2 +/- 1.98 vs. 2.3 +/- 0.21 mmHg.ml-1.s), which is associated with changes in the temporal relationship between a pyloric pressure event and flow pulse. In conclusion, erythromycin activity on the pylorus requires the integrity of vagal pathways. Enhancement of gastric outflow by erythromycin is also modulated by the vagus, since pyloric resistance was able to overcome increased gastric motility.
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Affiliation(s)
- C Mathis
- Unité de Contrôle des Flux Digestifs et Métabolisme Protéique, Institut National de la Recherche Agronomique, Saint-Gilles, France
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Annese V, Lombardi G, Frusciante V, Germani U, Andriulli A, Bassotti G. Cisapride and erythromycin prokinetic effects in gastroparesis due to type 1 (insulin-dependent) diabetes mellitus. Aliment Pharmacol Ther 1997; 11:599-603. [PMID: 9218089 DOI: 10.1046/j.1365-2036.1997.00177.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Erythromycin, a macrolide antibiotic, has been shown to have gastric prokinetic effects and has been proposed as an alternative therapeutic option for diabetic gastroparesis. However, its efficacy has not yet been compared with that of other prokinetic drugs. AIMS The purpose of the present study was to compare the effects of erythromycin (250 mg 60 min before meals) and cisapride (10 mg 30 min before meals) on gastric emptying of healthy subjects and insulin-dependent diabetics. PATIENTS AND METHODS Six type 1 diabetic patients with a previous scintigraphic demonstration of gastroparesis and five healthy subjects were recruited for the study. Gastric emptying was scintigraphically studied by labelling the solid component of a standard test meal. Three scintigraphic studies, spaced at least 3 days apart, were carried out on each subject, basally and after erythromycin or cisapride. RESULTS Cisapride significantly accelerated gastric emptying in both the healthy subjects and the diabetic patients without any significant effect on the lag-time, whereas erythromycin in addition to a significant improvement of the overall gastric emptying also showed a pronounced effect on the lag-time in both groups (controls 25 +/- 5 vs. 37 +/- 8 min, P < or = 0.04; diabetics 65 +/- 11 vs. 112 +/- 16 min, P < 0.03). CONCLUSIONS Erythromycin may represent an effective therapeutic alternative to more established forms of treatment in patients with diabetic gastroparesis, especially when other drugs have failed.
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Affiliation(s)
- V Annese
- Divisione di Gastroenterologia, Ospedale C.S.S. -IRCCS, San Giovanni Rotondo, Italy
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Sato F, Sekiguchi M, Marui S, Inatomi N, Shino A, Itoh Z, Omura S. EM574, an erythromycin derivative, is a motilin receptor agonist in the rabbit. Eur J Pharmacol 1997; 322:63-71. [PMID: 9088872 DOI: 10.1016/s0014-2999(96)00983-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
This study was performed to examine whether an erythromycin derivative, de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) is a motilin receptor agonist in the rabbit gastrointestinal tract. EM574 and porcine motilin induced contractions in segments of isolated rabbit intestine with pEC50 values of 8.26 +/- 0.04 and 8.69 +/- 0.07, respectively, but not in rat or guinea pig preparations. The sensitivity and efficacy of the response to both compounds in rabbits decreased aborally and was insensitive to pretreatment with atropine or tetrodotoxin, but was markedly suppressed under Ca(2+)-free conditions. EM574 and porcine motilin specifically displaced [125I-Tyr23]canine motilin bound to gastric antral smooth muscle homogenates with plC50 values of 8.21 +/- 0.13 and 9.20 +/- 0.11, respectively. The pEC50 value for the contractile response and plC50 value for the receptor binding for motilin, EM574, erythromycin A and three other derivatives correlated well (r = 0.94, P < 0.01). Tissue section autoradiography in the antrum revealed that specific labeled motilin binding sites were localized in the circular muscle layer and myenteric plexus, and could be reduced in the presence of an excess of EM574. These results indicate that EM574 is a potent motilin receptor agonist in the rabbit gastrointestinal tract.
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Affiliation(s)
- F Sato
- Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd., Osaka, Japan
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Abstract
Motilin is a regulatory polypeptide of 22 amino acid residues and orginates in motilin cells scattered in the duodenal epithelium of most mammals and chickens. Motilin is released into the general circulation at about 100-min intervals during the interdigestive state and is the most important factor in controlling the interdigestive migrating contractions. Recent studies have revealed that motilin stimulates endogenous release of the endocrine pancreas. Clinical application of motilin as a prokinetic has become possible since erythromycin and its derivatives were proved to be nonpeptide motilin agonists.
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Affiliation(s)
- Z Itoh
- Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
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Kazi N, Mobarhan S. Enteral feeding associated gastroesophageal reflux and aspiration pneumonia: a review. Nutr Rev 1996; 54:324-8. [PMID: 9063023 DOI: 10.1111/j.1753-4887.1996.tb03796.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Hospital malnutrition continues to be a serious problem. Although enteral feeding of hospitalized patients is safe and less expensive than parenteral feeding, it is associated with side effects involving the gastrointestinal tract and respiratory systems.
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Affiliation(s)
- N Kazi
- Department of Gastroenterology, Loyola University Medical Center, Maywood, IL 60153, USA
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33
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Affiliation(s)
- R W McCallum
- Division of Gastroenterology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
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34
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Clinical Pharmacology Forum: Motility Agents and the Gastrointestinal Tract. Am J Med Sci 1996. [DOI: 10.1016/s0002-9629(15)41741-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Burt M, Scott A, Williard WC, Pommier R, Yeh S, Bains MS, Turnbull AD, Fortner JG, McCormack PM, Ginsberg RJ. Erythromycin stimulates gastric emptying after esophagectomy with gastric replacement: a randomized clinical trial. J Thorac Cardiovasc Surg 1996; 111:649-54. [PMID: 8601981 DOI: 10.1016/s0022-5223(96)70318-5] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
UNLABELLED Delayed gastric emptying after esophagogastrectomy can pose a significant early postoperative problem. Because erythromycin, which stimulates the gastric antral and duodenal motilin receptor, has been shown to significantly increase gastric emptying in patients with diabetic gastroparesis, we decided to evaluate its effect on gastric emptying after esophagogastrectomy. METHODS Twenty-four patients (18 men and six women, age range 41 to 79 years, median 66 years) were randomized to receive either erythromycin lactobionate (200 mg in 50 ml normal saline solution intravenously) (n = 13) or placebo (50 ml normal saline solution intravenously (n = 11) 11 days after esophagogastrectomy (with pyloric drainage procedure). After erythromycin or placebo had been infused over a 15-minute period, patients ingested a solid meal (scrambled egg with bread) labeled with technetium 99m sulfur colloid (500 microCi) over approximately 15 minutes. Dynamic images of the stomach were then acquired over 90 minutes in the supine position by gamma imaging. Results were expressed as percentage of counts retained in the stomach (percent gastric retention) over time. RESULTS There were no side effects of erythromycin. In the placebo group, the mean percent of radiolabeled meal retained in the stomach after 90 minutes was 88%, which was significantly greater than in the erythromycin group, 37% (p < 0.001). In addition, analysis of covariance demonstrated that the rate of gastric emptying (slope of the line) was significantly greater in the erythromycin-treated group than in the placebo group (p < 0.0001). CONCLUSION Early satiety after esophagogastrectomy may be due to delayed gastric emptying and not due to a decrease in the gastric reservoir. Intravenous erythromycin significantly improves gastric emptying in patients after esophagogastrectomy by stimulating gastric motility.
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Affiliation(s)
- M Burt
- Division of Thoracic Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
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36
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Shiba Y, Mizumoto A, Inatomi N, Haga N, Yamamoto O, Itoh Z. Stimulatory mechanism of EM523-induced contractions in postprandial stomach of conscious dogs. Gastroenterology 1995; 109:1513-21. [PMID: 7557133 DOI: 10.1016/0016-5085(95)90638-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
BACKGROUND & AIMS EM523, a motilin agonist, is intended to be used as a gastroprokinetic during the postprandial period, but the mechanism(s) by which EM523 stimulates postprandial contractions in the stomach has not been studied before. The aim of this study was to examine the mechanism of contraction-stimulating activity by EM523 in fed dogs. METHODS Contractile activity in the gastric antrum of 5 dogs was monitored using a long-term implanted force transducer and measured by integrating the area under the curve. Test materials were continuously infused or injected intravenously. RESULTS EM523 (1-30 micrograms/kg) induced a dose-dependent increase in fed-type contractions. EM523-induced contractile activity was partially inhibited by atropine, hexamethonium, dopamine, 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, and substance P antagonist. Atropine-resistant and EM523-induced contractions were further inhibited by 5-HT3 receptor antagonist and substance P antagonist, and the combined use of the two antagonists completely eliminated the atropine-resistant and EM523-induced contractions. CONCLUSIONS EM523-induced contractions in the fed stomach are quite different from phase III contractions in the fasted state and are mediated partially through the cholinergic pathway. The noncholinergic pathway involves 5-HT3 and neurokinin 1 receptors.
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Affiliation(s)
- Y Shiba
- Gastrointestinal Research Laboratories, Gunma University, Maebash, Japan
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37
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Sharma SS, Bhargava N, Mathur SC. Effect of oral erythromycin on colonic transit in patients with idiopathic constipation. A pilot study. Dig Dis Sci 1995; 40:2446-2449. [PMID: 7587829 DOI: 10.1007/bf02063252] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Erythromycin, a motilin receptor agonist has been shown to have prokinetic effects on the upper gastrointestinal tract and gallbladder. Colonic effects of the drug are controversial, and it is debated whether human colon contains motilin receptors. In this study we evaluated the effects of erythromycin on colonic transit and stool frequency in 11 patients with idiopathic constipation over a 1-month period in an open study. The dose used was 1 g/day for two weeks followed by 500 mg/day for another two weeks. The mean (SE) total and segmental colonic transit was measured before and seven days after therapy in seven of these patients. A daily record of stool frequency was maintained in all 11 patients. Erythromycin shortened the total colonic transit from 86.2 (14.6) to 44.8 (8.99) hr (P < 0.01); however, segmental transit studies revealed a significant effect (P < 0.01) only in the right colon and rectosigmoid region. No significant side effects were observed with short-term therapy. These preliminary results suggest that erythromycin is of therapeutic value in patients with idiopathic constipation.
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Affiliation(s)
- S S Sharma
- Department of Medicine, SMS Medical College & Hospital, Jaipur, India
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38
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Dive A, Miesse C, Galanti L, Jamart J, Evrard P, Gonzalez M, Installé E. Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients: a double-blind, randomized, placebo-controlled study. Crit Care Med 1995; 23:1356-62. [PMID: 7634805 DOI: 10.1097/00003246-199508000-00008] [Citation(s) in RCA: 99] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To document the action of erythromycin on gastric emptying and motility in mechanically ventilated patients. DESIGN Crossover, double-blind, randomized, placebo-controlled study. SETTING General intensive care unit in a university hospital. PATIENTS Ten patients, mechanically ventilated, in a stable hemodynamic condition. INTERVENTIONS Erythromycin (200 mg i.v. over 30 mins) and placebo were infused at mid-morning, on two consecutive days, in a random order. Pressure changes in the gastric antrum were recorded by means of a multi-lumen manometric tube (perfused catheter technique) over a period of 300 mins, beginning with the institution of the erythromycin or placebo infusion. Gastric emptying was simultaneously assessed by the kinetics of the absorption of acetaminophen delivered into the stomach (1 g with 20 mL of water) immediately before the infusion. MEASUREMENTS AND MAIN RESULTS Motility was quantified by determining the number of contractions, the amplitude of contractions, and the Motility Index (Motility Index = natural logarithm [sum of amplitude x number of contractions] + 1). Comparison between placebo and erythromycin was made for the first hour after the infusion and for the whole recording session. The maximal acetaminophen concentration, the time to reach the peak acetaminophen concentration, and the area under the concentration-time curve at 60 mins were obtained from serial determinations of plasma acetaminophen concentrations. Compared with placebo, the mean number of contractions (104 +/- 34 vs. 5 +/- 8; p = .003), the mean amplitude of contractions (52 +/- 16 vs. 20 +/- 17 mm Hg; p = .005), and the Motility Index (13.06 +/- 0.95 vs. 4.45 +/- 3.54; p = .004) were significantly increased during the first hour after erythromycin infusion compared with placebo. Number of contractions (p = .017) and Motility Index (p < .001) after erythromycin infusion remained significantly higher when values throughout the whole recording session were considered. The following data were noted after erythromycin was infused: a) the time to reach the peak acetaminophen concentration was shorter (32 +/- 8 vs. 171 +/- 93 mins; p = .007); b) the maximal acetaminophen concentration was higher (22.09 +/- 6.23 vs. 5.38 +/- 3.80 micrograms/mL; p = .007); and c) the area under the concentration-time curve at 60 mins increased markedly (730 +/- 269 vs. 72 +/- 42 micrograms/min/mL; p = .002) as compared with placebo. CONCLUSION In mechanically ventilated patients, intravenous erythromycin (200 mg over 30 mins) increases indices of antral motility and accelerates gastric emptying as assessed by the kinetics of acetaminophen absorption.
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Affiliation(s)
- A Dive
- Department of Intensive Care, Mont-Godinne Hospital, Louvain School of Medicine, Yvoir, Belgium
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39
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Abstract
There has been increasing interest in the potential use of erythromycin as a prokinetic agent, despite limited data on the effect of oral administration on gastrointestinal motility. We have now evaluated, in 15 conscious pigs fitted with strain gauges, the response of (i) basal gastric motility and (ii) gastric motility during inhibition with intraduodenal triglycerides infusion to increasing doses of oral erythromycin. In the basal state, erythromycin led to dose-dependent increases in both the amplitude (10-30 mg kg-1) and the frequency (10-55 mg kg-1) of gastric contractions. The corpus was more responsive than the antrum, with an increase in amplitude at lower doses. The amplitude of the duodenal contractions was also improved but not in a dose-dependent manner. Gastroduodenal coordination was unchanged regardless of the dose of erythromycin. Following inhibition of gastric motility, a dose of erythromycin below 45 mg kg-1 increased both the amplitude of gastric contractions and the gastroduodenal coordination, although individual doses produced smaller increases in amplitude than in the basal state. These results suggest that erythromycin has a different mechanism of action in the stomach compared with the duodenum. The reduced effectiveness of large doses of erythromycin has important therapeutic implications.
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Affiliation(s)
- C Mathis
- Equipe des flux digestifs, Station de Recherches porcines, INRA, Saint Gilles, France
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40
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Ramirez B, Eaker EY, Drane WE, Hocking MP, Sninsky CA. Erythromycin enhances gastric emptying in patients with gastroparesis after vagotomy and antrectomy. Dig Dis Sci 1994; 39:2295-300. [PMID: 7956594 DOI: 10.1007/bf02087641] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
We studied the effect of erythromycin on gastric emptying in nine patients with gastroparesis following truncal vagotomy and antrectomy, and assessed their clinical response to chronic oral erythromycin. Gastric emptying was evaluated using a solid-phase radio-labeled meal. Patients were studied after erythromycin 200 mg intravenously (N = 9) and after an oral suspension of erythromycin 200 mg (N = 7) each given 15 min after ingestion of the meal. Three parameters of gastric emptying were analyzed: half-emptying time (T1/2), area under the curve, and percent gastric residual at 2 hr. Nine patients were subsequently placed on oral suspension erythromycin 150 mg three times a day before meals (range 125-250 mg three times a day) and symptoms of nausea, vomiting, postprandial fullness, and abdominal pain were assessed before and after erythromycin. Intravenous erythromycin markedly accelerated the gastric emptying (all three parameters studied) of solids (P < 0.01) in seven of nine patients with postsurgical gastroparesis [baseline T1/2 154 +/- 15 min; after intravenous erythromycin, T1/2 56 +/- 17 min (mean +/- SEM)]. Oral erythromycin enhanced (P < 0.05) the gastric emptying rate (T1/2, area under the curve) in five of seven patients (baseline T1/2 146 +/- 16 min; after oral erythromycin, T1/2 87 +/- 20 min). Of the nine patients who were placed on oral maintenance erythromycin, three showed clinical improvement after two weeks. In summary, erythromycin significantly enhances gastric emptying in many patients with vagotomy and antrectomy-induced gastroparesis; however, only a small subset of patients respond clinically to chronic oral erythromycin.
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Affiliation(s)
- B Ramirez
- Department of Medicine, University of Florida, Gainesville
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41
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Abstract
Erythromycin and other macrolides with a closely related structure are widely used antibiotics. Side-effects related to administration of such drugs are mostly gastrointestinal. The direct effect of erythromycin on gastrointestinal motility was studied; it was found to have a stimulatory effect proximally, on stomach and duodenal motility, with an apparent distal inhibition. Gastric emptying was accelerated by erythromycin via an antroduodenal coordination mechanism, an effect that has proved to be beneficial in surgical and medical conditions in which gastroparesis is a problem. Erythromycin is now used experimentally and clinically; it has been found to accelerate gastric as well as gallbladder emptying and to have an effect on the oesophagus. Analogues of erythromycin have been developed that have potent gastrointestinal activity but little or no antibacterial potential. Macrolides modulate the antibacterial action of neutrophils, with some action on the oxidative burst. Finally, two new macrolide immunosuppressants have been developed that compare favourably with traditional drugs.
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Affiliation(s)
- M A Pilot
- Surgical Unit, London Hospital Medical College, UK
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42
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Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of motion sickness and antimotion sickness drugs on gastric function. J Clin Pharmacol 1994; 34:635-43. [PMID: 8083395 DOI: 10.1002/j.1552-4604.1994.tb02017.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
This study examined the effects of motion sickness and antimotion sickness drugs on gastric emptying (GE). Drugs were tested in normal and motion sick subjects. To induce motion sickness, subjects performed head movements while seated in a rotating chair. Gastric emptying of liquid (300 mL) was determined by nuclear medicine techniques, whereas gastric electrical activity, the electrogastrogram (EGG), was monitored from surface (cutaneous) electrodes positioned over the abdominal area. Gastric emptying was severely inhibited at the peak of motion sickness symptoms, but returned to normal 15 minutes later when symptoms abated. In normal (non-motion sick) subjects intramuscular (IM) scopolamine (0.1 mg) and IM promethazine (25 mg) inhibited GE, whereas erythromycin ethylsuccinate (EES) suspension (200 mg) given orally increased GE. When administered to motion sick subjects, IM scopolamine and IM promethazine added slightly, but not significantly, to the inhibition of GE already present. Oral EES did not significantly alter GE in motion sick subjects. Although EGG frequency remained within normal limits (approximately 2.5-3.5 cpm) after liquid ingestion in both normal and motion sick subjects, EGG amplitude was differentially affected in the two groups. Electrogastrogram amplitude increased twofold to fourfold after liquid ingestion in normal, but not in motion sick subjects. The results suggest that (1) maximal inhibition of GE is coincident with peak motion sickness symptoms, (2) both IM scopolamine and IM promethazine inhibit GE in normal subjects, but do not add significantly to the inhibition of GE already established during motion sickness, (3) orally administered erythromycin enhances GE in normal, but not in motion sickness subjects, and (4) the normal stimulatory effect of liquid ingestion on gastric motility does not occur in motion sick subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- J J Stewart
- Department of Pharmacology, Louisiana State University Medical Center, Shreveport 71130-3932
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43
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Pennathur A, Tran A, Cioppi M, Fayad J, Sieren GL, Little AG. Erythromycin strengthens the defective lower esophageal sphincter in patients with gastroesophageal reflux disease. Am J Surg 1994; 167:169-72; discussion 172-3. [PMID: 8311129 DOI: 10.1016/0002-9610(94)90069-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Motilin induces phase III activity of the gastrointestinal tract. Erythromycin has a motilin-like effect on the stomach and significantly increases the lower esophageal sphincter (LES) pressure in normal volunteers. This investigation was performed to evaluate the effects of erythromycin on esophageal function in patients with gastroesophageal reflux disease (GERD). Esophageal manometry was performed in 10 GERD patients before and after intravenous infusion of 500 mg of erythromycin. Values are expressed as mean +/- SEM. LES pressure increased from 13.9 +/- 2.9 mm Hg at baseline to 28.9 +/- 3.6 mm Hg after infusion of erythromycin (p < 0.01). The duration of contractions in the proximal, middle, and distal esophagus was significantly prolonged from 3.5 +/- 0.4 seconds, 3.8 +/- 0.4 seconds, and 4.1 +/- 0.5 seconds to 4.2 +/- 0.2 seconds, 4.6 +/- 0.5 seconds, and 5.6 +/- 0.6 seconds, respectively, after infusion of erythromycin (p < 0.05 for each comparison). Erythromycin did not effect esophageal body contraction amplitude or velocity, or the upper esophageal sphincter. Serum motilin decreased slightly after the administration of erythromycin. We concluded the following: (1) Erythromycin profoundly stimulates the defective LES in patients with GERD. This appears to be a direct motilin agonist-like effect rather than being mediated by release of endogenous motilin. (2) Erythromycin has less effect on the esophageal body, although it does prolong the duration of esophageal contractions.
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Affiliation(s)
- A Pennathur
- Department of Surgery, University of Nevada School of Medicine, Las Vegas
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44
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Affiliation(s)
- T L Peeters
- Department of Medical Research, University of Leuven, Belgium
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45
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Inatomi N, Satoh T, Satoh H, Itoh Z, Omura S. Comparison of the motor-stimulating action of EM523, an erythromycin derivative, and prostaglandin F2 alpha in conscious dogs. JAPANESE JOURNAL OF PHARMACOLOGY 1993; 63:209-17. [PMID: 8283832 DOI: 10.1254/jjp.63.209] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
The effect of EM523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal], an erythromycin derivative, on gastrointestinal motility was investigated using conscious dogs in the fasting state, and it was compared with those of motilin and prostaglandin F2 alpha (PGF2 alpha). EM523 and motilin given as i.v. infusions induced strong contractions in the stomach that migrated along the intestine. On the other hand, PGF2 alpha stimulated intestinal contractions, but its effect on gastric motility was weak. EM523 had 1/50 the potency of motilin and 6 times the potency of PGF2 alpha for stimulation of intestinal motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal contractions induced by EM52 EM523 or motilin and partly inhibited PGF2 alpha-induced intestinal motility. ICS-205-930, a 5HT3-receptor antagonist, at a dose of 1 mg/kg, i.v. strongly inhibited EM523 or motilin-induced gastric contractions but did not affect the action of PGF2 alpha. Infusion of EM523 at 100 micrograms/kg/hr induced strong migrating contractions even when motility was depressed by dopamine infusion or laparotomy. Infusion of PGF2 alpha at 300 micrograms/kg/hr stimulated intestinal but not gastric motility under these conditions. The results of this study indicate that the cholinergic pathway and 5HT3 receptors are involved in EM523 and motilin-induced migrating gastrointestinal contractions, whereas the cholinergic pathway seems to be only partly involved in PGF2 alpha-induced intestinal contractions.
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Affiliation(s)
- N Inatomi
- Pharmaceutical Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan
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46
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Yeo CJ, Barry MK, Sauter PK, Sostre S, Lillemoe KD, Pitt HA, Cameron JL. Erythromycin accelerates gastric emptying after pancreaticoduodenectomy. A prospective, randomized, placebo-controlled trial. Ann Surg 1993; 218:229-37; discussion 237-8. [PMID: 8103982 PMCID: PMC1242953 DOI: 10.1097/00000658-199309000-00002] [Citation(s) in RCA: 292] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
OBJECTIVE This study tested the hypothesis that erythromycin, a motilin agonist, reduces the incidence of early DGE after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA Delayed gastric emptying (DGE) is a leading cause of morbidity after pancreaticoduodenectomy, occurring in up to 40% of patients. The pathogenesis of DGE has been speculated to involve factors such as peritonitis from anastomotic leaks, ischemia to the antropyloric muscles, and gastric atony in response to resection of the duodenal pacemaker or reduction in circulating motilin levels. METHODS Between November 1990 and January 1993, 118 patients undergoing pancreaticoduodenectomy completed this prospective, randomized, placebo-controlled trial. The patients received either 200 mg of intravenous erythromycin lactobionate every 6 hours (n = 58), or an identical volume of 0.9% saline (n = 60) from the third to tenth postoperative days. On the tenth postoperative day, a dual phase radionuclide gastric emptying study was performed. RESULTS The erythromycin and control groups were comparable regarding multiple preoperative, intraoperative, and postoperative factors. The erythromycin group had a 37% reduction in the incidence of DGE (19% vs. 30%), a significantly reduced (p < 0.05) need to reinsert a nasogastric tube for DGE (6 vs. 15 patients), and a significantly reduced (p < 0.01) per cent retention of liquids at 30 minutes and solids at 30, 60, 90, and 120 minutes. No major adverse reactions to erythromycin were observed. CONCLUSIONS Erythromycin is a safe, inexpensive drug that significantly accelerates gastric emptying after pancreaticoduodenectomy and reduces the incidence of DGE by 37%. These data support the use of erythromycin to decrease early DGE after pancreaticoduodenectomy.
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Affiliation(s)
- C J Yeo
- Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
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47
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Hill AD, Walsh TN, Hamilton D, Freyne P, O'Hare N, Byrne PJ, Hennessy TP. Erythromycin improves emptying of the denervated stomach after oesophagectomy. Br J Surg 1993; 80:879-81. [PMID: 8369924 DOI: 10.1002/bjs.1800800726] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Oesophagectomy, necessitating vagotomy, is associated with delayed gastric emptying. Cisapride and erythromycin have prokinetic effects and improve emptying of the innervated stomach. Their effect on the denervated stomach following oesophagectomy is unknown. The effect of pyloroplasty, cisapride and erythromycin on the rate of gastric emptying after oesophagectomy was studied using a radiolabelled meal. Oesophagectomy was associated with a marked delay in gastric emptying (56 per cent of the test meal remaining after 4 h) compared with age- and sex-matched normal controls (16 per cent; P < 0.001). Erythromycin improved the rate of gastric emptying to preoperative control values (18 per cent). Cisapride had no significant effect on gastric emptying. After pyloroplasty, 32 per cent of the label remained at 4 h (P = 0.065). The mean(s.e.m.) half-emptying time in patients receiving erythromycin was 94(29) min, which was similar to control values, 55(3) min (P = 0.26). Erythromycin may have a role in the treatment of gastric stasis following oesophagectomy or truncal vagotomy.
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Affiliation(s)
- A D Hill
- University Department of Surgery, St James's Hospital, Dublin, Ireland
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48
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Hart LL, Hobdy-Henderson KC. Drug Information Analysis Service. Ann Pharmacother 1992. [DOI: 10.1177/106002809202600911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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49
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Fraser R, Shearer T, Fuller J, Horowitz M, Dent J. Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility. Gastroenterology 1992; 103:114-9. [PMID: 1612319 DOI: 10.1016/0016-5085(92)91103-b] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.
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Affiliation(s)
- R Fraser
- Gastroenterology Unit, Royal Adelaide Hospital, North Terrace, South Australia
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50
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Abstract
The commonly reported gastrointestinal side effects that occur with erythromycin are related to its prokinetic action on the gut, mediated, at least in part, by its motilin receptor stimulating activity. This action may be of clinical use in conditions associated with gastrointestinal hypomotility such as diabetic gastroparesis and intestinal pseudo-obstruction, although further work needs to be done to establish the long term therapeutic uses of erythromycin in these disorders. Macrolide compounds with no antibacterial properties but which have a pronounced prokinetic action on the gut have already been synthesised and are currently being developed for future use in man. These 'motilides' should provide a useful addition to our rather limited armamentarium of effective gastrointestinal prokinetic agents.
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Affiliation(s)
- S M Catnach
- Department of Gastroenterology, St Bartholomew's Hospital, London
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