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Expert Opinion on Drug Safety Jul 2016Gastroparesis is a syndrome of chronic, often debilitating symptoms related to impaired gastric motility, resulting in delayed emptying of the stomach, within the... (Review)
Review
INTRODUCTION
Gastroparesis is a syndrome of chronic, often debilitating symptoms related to impaired gastric motility, resulting in delayed emptying of the stomach, within the setting of a documented absence of any mechanical obstruction in the upper gastrointestinal tract. This disorder manifests with the presence of early satiety, postprandial fullness, nausea, vomiting, bloating and abdominal pain. The past ten years have shown significant advances in knowledge of the pathophysiology of this entity as well as in new diagnostic tests. However, in the clinical world which requires treatment of gastroparetic symptoms, the pharmacological options have been limited and sometimes less than optimal.
AREAS COVERED
This article provides an overview of the safety of the available pharmacological therapies utilized in the treatment of gastroparetic symptoms specifically addressing the safety of prokinetics, antiemetics, sensory neuromodulators and pain modifying agents. In addition, a brief overview of the evolving but yet to be officially approved agents is included.
EXPERT OPINION
None of the medications used for the treatment of gastroparesis are devoid of side effects. Therefore, when prescribing these medications, the risk/benefit ratio should be considered. Since those agents are increasingly administered in combination, awareness of possible drug interactions must be considered in a setting of the patients' medical history, age, systemic diseases and other medications.
Topics: Abdominal Pain; Drug Interactions; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Motility; Gastroparesis; Humans
PubMed: 27031006
DOI: 10.1517/14740338.2016.1173204 -
Expert Review of Gastroenterology &... Aug 2014Testing to define delayed gastric emptying is required to diagnose gastroparesis; rapid emptying is found in other patients. Commonly performed methods of gastric... (Review)
Review
Testing to define delayed gastric emptying is required to diagnose gastroparesis; rapid emptying is found in other patients. Commonly performed methods of gastric emptying testing include scintigraphy and breath testing. The SmartPill wireless motility capsule (WMC) system is US FDA-approved for evaluating suspected delayed emptying in gastroparesis and functional dyspepsia. The device measures transit in the stomach, small intestine, and colon by detecting characteristic pH transitions; and quantifies pressure waves in each gut region. WMC gastric emptying times correlate with scintigraphic measures. Incremental benefits of WMC testing in patients with suspected gastroparesis include delineation of pressure abnormalities and small intestinal and colonic transit delays. Acceptance of trial data confirming usefulness of WMC testing in suspected gastric motor disorders has been hampered by small sample sizes and design limitations. Ongoing multicenter studies will validate the utility of WMC methods in patients with suspected gastroparesis and other upper gastrointestinal motor disorders.
Topics: Animals; Dyspepsia; Equipment Design; Gastric Acidity Determination; Gastric Emptying; Gastroparesis; Humans; Hydrogen-Ion Concentration; Predictive Value of Tests; Pressure; Signal Processing, Computer-Assisted; Telemetry; Time Factors; Transducers, Pressure; Wireless Technology
PubMed: 24881810
DOI: 10.1586/17474124.2014.922869 -
Clinical Nutrition (Edinburgh, Scotland) Aug 2015Enteral nutrition is important in critically ill patients and is usually administered via a nasogastric tube. As gastric emptying is frequently delayed, and this... (Review)
Review
BACKGROUND & AIMS
Enteral nutrition is important in critically ill patients and is usually administered via a nasogastric tube. As gastric emptying is frequently delayed, and this compromises the delivery of nutrient, it is important that the emptying rate can be quantified.
METHODS
A comprehensive search of MEDLINE/PubMed, of English articles, from inception to 1 July 2014. References of included manuscripts were also examined for additional studies.
RESULTS
A number of methods are available to measure gastric emptying and these broadly can be categorised as direct- or indirect-test and surrogate assessments. Direct tests necessitate visualisation of the stomach contents during emptying and are unaffected by liver or kidney metabolism. The most frequently used direct modality is scintigraphy, which remains the 'gold standard'. Indirect tests use a marker that is absorbed in the proximal small intestine, so that measurements of the marker, or its metabolite measured in plasma or breath, correlates with gastric emptying. These tests include drug and carbohydrate absorption and isotope breath tests. Gastric residual volumes (GRVs) are used frequently to quantify gastric emptying during nasogastric feeding, but these measurements may be inaccurate and should be regarded as a surrogate measurement. While the inherent limitations of GRVs make them less suitable for research purposes they are often the only technique that is available for clinicians at the bedside.
CONCLUSIONS
Each of the available techniques has its strength and limitations. Accordingly, the choice of gastric emptying test is dictated by the particular requirement(s) and expertise of the investigator or clinician.
Topics: 3-O-Methylglucose; Acetaminophen; Breath Tests; Critical Illness; Databases, Factual; Enteral Nutrition; Gastric Emptying; Gastric Mucosa; Gastrointestinal Contents; Humans; Magnetic Resonance Imaging; Ultrasonography
PubMed: 25491245
DOI: 10.1016/j.clnu.2014.11.003 -
Reviews in Endocrine & Metabolic... Sep 2014Glucagon-like peptide 1 (GLP-1) is a cleavage product of the pre-proglucagon gene which is expressed in the α-cells of the pancreas, the L-cells of the intestine, and... (Review)
Review
Glucagon-like peptide 1 (GLP-1) is a cleavage product of the pre-proglucagon gene which is expressed in the α-cells of the pancreas, the L-cells of the intestine, and neurons located in the caudal brainstem and hypothalamus. GLP-1 is of relevance to appetite and weight maintenance because it has actions on the gastrointestinal tract as well as the direct regulation of appetite. It delays gastric emptying and gut motility in humans. In addition, interventricular injections of GLP-1 inhibit food intake, independent of the presence of food in the stomach or gastric emptying. Peripherally administered GLP-1 also affects the central regulation of feeding. It is therefore the synergistic actions of GLP-1 in the gut and brain, acting on both central and peripheral receptors that seem responsible for the effects of the hormone on satiety.
Topics: Appetite; Body Weight; Eating; Gastric Emptying; Glucagon-Like Peptide 1; Humans
PubMed: 24811133
DOI: 10.1007/s11154-014-9289-5 -
Gut May 2023Functional dyspepsia (FD) is a complex disorder, with debilitating epigastric symptoms. Evidence suggests alterations in gastrointestinal (GI) motility, visceral...
OBJECTIVE
Functional dyspepsia (FD) is a complex disorder, with debilitating epigastric symptoms. Evidence suggests alterations in gastrointestinal (GI) motility, visceral hypersensitivity, permeability and low-level immune activation in the duodenum may play a role. However, we still have a relatively poor understanding of how these factors interact to precipitate the onset of FD symptoms which are frequently meal related. The duodenal microbiota, in combination with specific dietary substrates, may be important mediators in disease pathophysiology; however, these interlinked factors have not been thoroughly investigated in FD.
DESIGN
Eighty-six individuals (56 FD, 30 controls) undergoing endoscopy were consecutively recruited and underwent detailed clinical assessment, including upper GI symptoms, gastric emptying and dietary assessment. Duodenal biopsies were obtained aseptically, and the mucosa-associated microbiota (MAM) analysed via 16S rRNA gene amplicon sequencing.
RESULTS
The relative abundances of predominant members of the Firmicutes, Bacteroidota and Fusobacteriota phyla were linked to symptom burden in FD. Inverse relationships between the relative abundances of and and the relative abundance of spp with gastric emptying time, were also observed. No significant differences in long-term nutrient intake or diet quality were found between FD and controls, and there appeared to be limited association between habitual diet and duodenal MAM profiles.
CONCLUSION
This study suggests a link between the duodenal MAM, gastric emptying and FD symptoms, and this is largely independent of long-term dietary intake.
Topics: Humans; Dyspepsia; Gastric Emptying; RNA, Ribosomal, 16S; Duodenum; Microbiota
PubMed: 36167662
DOI: 10.1136/gutjnl-2021-326158 -
Annual Review of Food Science and... Feb 2017Gastric mixing is a complex process that is governed by meal properties, such as food buffering capacity, physical properties, and the rate of breakdown as well as... (Review)
Review
Gastric mixing is a complex process that is governed by meal properties, such as food buffering capacity, physical properties, and the rate of breakdown as well as physiological factors, such as the rate of gastric secretions, gastric emptying, and gastric motility. Gastric mixing processes have been studied through the use of experimental and computational methods. Gastric mixing impacts the intragastric pH distribution and residence time in the stomach for ingested materials. Development of a fundamental understanding of the advective and diffusion processes and their roles in gastric mixing will be important in furthering our understanding of food breakdown, microbial survival, and drug dissolution during gastric digestion.
Topics: Digestion; Food; Gastric Emptying; Gastrointestinal Contents; Humans; Hydrogen-Ion Concentration
PubMed: 28125347
DOI: 10.1146/annurev-food-030216-025802 -
Sports Medicine (Auckland, N.Z.) May 2015Gastric emptying (GE) could influence exercise-induced changes in appetite and energy intake. GE also could contribute to changes in gastric symptoms and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gastric emptying (GE) could influence exercise-induced changes in appetite and energy intake. GE also could contribute to changes in gastric symptoms and the availability of nutrients during exercise, which will subsequently affect performance.
OBJECTIVE
The objective of this review was to determine the effects of acute exercise on GE using a systematic review and meta-analysis. The most common parameters to determine GE were selected, consisting of half-emptying time and volume emptied. Oral-caecal transit time (OCTT) was also examined.
DATA SOURCES
Research databases (PubMed, Scopus, Google Scholar, EBSCOhost, SPORTDiscus) were searched through November 2013 for original studies, abstracts, theses and dissertations that examined the influence of acute exercise on GE.
STUDY SELECTION
Studies were included if they evaluated GE or OCTT during and/or after exercise and involved a resting control trial.
STUDY APPRAISAL AND SYNTHESIS
Initially, 195 studies were identified. After evaluation of study characteristics and quality and validity, data from 20 studies (35 trials) involving 221 participants (157 men; 52 women; 12 unknown) were extracted for meta-analysis. Random-effects meta-analyses were utilised for the three main outcome variables, and effect sizes (ES) are reported as Hedge's g due to numerous small sample sizes.
RESULTS
Random-effects modelling revealed non-significant and small/null main effect sizes for volume emptied (ES = 0.195; 95% CI -0.25 to 0.64), half-time (ES = -0.109, 95% CI -0.66 to 0.44) and OCTT (ES = 0.089; 95% CI -0.64 to 0.82). All analyses exhibited significant heterogeneity and numerous variables moderated the results. There was a dose response of exercise intensity; at lower intensities GE was faster, and at high exercise intensities GE was slower. Walking was associated with faster GE and cycling with slower GE. Greater volume of meal/fluid ingested, higher osmolality of beverage and longer exercise duration were also associated with slower GE with exercise.
LIMITATIONS
The major limitation is that the majority of studies utilised a liquid bolus administered pre-exercise to determine GE; the relationship to post-exercise appetite and energy intake remains unknown. Study populations were also generally active or trained individuals. Furthermore, our review was limited to English language studies and studies that utilised resting control conditions.
CONCLUSIONS
These results suggest that exercise intensity, mode, duration and the nature of meal/fluid ingested all influence GE during and after acute exercise. The relationship of GE parameters with appetite regulation after exercise remains largely unexplored. Further integrative studies combining GE and alterations in gut hormones, as well as in populations such as overweight and obese individuals are needed.
Topics: Beverages; Exercise; Food; Gastric Emptying; Humans; Osmolar Concentration; Physical Exertion; Portion Size; Time Factors
PubMed: 25398225
DOI: 10.1007/s40279-014-0285-4 -
Handbook of Experimental Pharmacology 2017Symptoms referable to the upper digestive tract are associated with abnormalities of upper gastric neuromuscular function including abnormalities of motility, sensation,... (Review)
Review
Symptoms referable to the upper digestive tract are associated with abnormalities of upper gastric neuromuscular function including abnormalities of motility, sensation, and absorption. Of the upper digestive tract, the stomach is of particular importance in its role in symptom generation and is highlighted in this chapter. Gastric symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical activity and contractility. Treatment of gastric neuromuscular disorders requires an understanding of pathophysiology of the disorders, the appropriate use and interpretation of diagnostic tests, and the knowledge of effective treatment options. This chapter covers the pathophysiology and current treatment approaches to disorders of the upper gastrointestinal tract, focusing on classic disorders of the stomach, particularly gastroparesis and functional dyspepsia.
Topics: Animals; Dumping Syndrome; Enteric Nervous System; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Diseases; Gastroparesis; Humans; Stomach; Treatment Outcome
PubMed: 28105529
DOI: 10.1007/164_2016_114 -
Journal of Diabetes and Its... Nov 2019Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid... (Review)
Review
Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid gastric emptying also is a frequent and important diabetic complication. In contrast, acute hyperglycemia causes slow gastric emptying, and acute hypoglycemia causes rapid gastric emptying. Rapid gastric emptying is frequent in T2DM; however, it may also occur in T1DM, particularly in the early stages of the disease, but may persist even into late stages. Recent studies suggest that usually, the stomach restricts the emptying of nutrients to 1-4 kcals/min. This restriction is due to the action of the gastric 'braking' hormones such as GLP-1, leptin, and amylin acting via the gastric inhibitory vagal motor circuit (GIVMC). Disruption of this braking system leads to rapid gastric emptying. Acute hyperglycemia also slows gastric emptying by stimulating the GIVMC, while acute hypoglycemia causes rapid gastric emptying by stimulating the gastric excitatory vagal motor circuit (GEVMC). In contrast, chronic hyperglycemia causes rapid gastric emptying by inducing oxidative stress in the stomach wall that disrupts inhibitory neuromuscular transmission and increases the contractility of the smooth muscle, while chronic hyperglycemia may also cause slow gastric emptying via severe inflammatory stress caused by proinflammatory macrophages and reduce contractility of the smooth muscle. There is a bidirectional relationship between blood glucose and gastric emptying. Thus, rapid gastric emptying may lead to a sizeable postprandial spike, and slow gastric emptying may blunt it. Postprandial hyperglycemia is involved in the development, progression, and complications of DM. Correction of fast gastric emptying involves agents that activate GIVMC and the use of gastric 'braking' hormones or their analogs. Recognition and treatment of rapid gastric emptying may contribute to better management of postprandial hyperglycemia and prevention of some diabetic complications.
Topics: Blood Glucose; Diabetes Complications; Diabetes Mellitus; Gastric Emptying; Gastroparesis; Humans; Hyperglycemia; Postprandial Period; Prognosis; Stomach Diseases
PubMed: 31439470
DOI: 10.1016/j.jdiacomp.2019.107414 -
Comprehensive Reviews in Food Science... Jul 2020All foods harbor unique length scale-dependent structural features that can influence the release, transport, and utilization of macro- or micronutrients in the human... (Review)
Review
All foods harbor unique length scale-dependent structural features that can influence the release, transport, and utilization of macro- or micronutrients in the human gastrointestinal tract. In this regard, food destructuring and restructuring processes during gastric passage significantly influence downstream nutrient assimilation and feelings of satiety. This review begins with a synopsis of the effects of oral processing on food structure. Then, stomach-centric factors that contribute to the efficacy of gastric digestion are discussed, and exemplified by comparing the intragastric de- and restructuring of a number of common foods. The mechanisms of how intragastric structuring influences gastric emptying and its relationship to human satiety are then discussed. Finally, recently developed, non-destructive instrumental approaches used to quantitively and qualitatively characterize food behavior during gastric destructuring and restructuring are described.
Topics: Digestion; Food Analysis; Gastric Emptying; Mastication; Satiation; Stomach
PubMed: 33337100
DOI: 10.1111/1541-4337.12558