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Figure showing the US images and drawing showing the position of the ultrasound probe that enabled evaluation of the GER ➀, the antral contractions (Motility index; MI) ➁, and the DGR (Reflux index; RI) ➂.
Source publication
Improvement in subjective symptoms has been reported in functional dyspepsia (FD) patients administered with acotiamide. Improvement was confirmed in meal-related symptoms, such as postprandial fullness, upper abdominal bloating, and early satiety. We examined the mechanism underlying the effects of acotiamide on gastric accommodation reflex (GAR)...
Contexts in source publication
Context 1
... before and after treatment. The key opening was carried out after all studies were finished. using US, as described previously. [13][14][15][16][17][18] The US probe was positioned vertically to permit simultaneous visualization of the antrum, superior mesenteric artery, and abdominal aorta for the evaluation of antral area (upper section of Fig. 4). The antral area was estimated by tracing the mucosal side of the antrum with the built-in calipers at 6 and 15 min after 400 mL ingestion of a liquid meal (at 1 and 10 min after the subjects changed posture). The GER was expressed as follows: (antral area at 6 min)antral area at 15 min)/antral area at 6 min after 400 ml ingestion of ...
Context 2
... 1 and 10 min after the subjects changed posture). The GER was expressed as follows: (antral area at 6 min)antral area at 15 min)/antral area at 6 min after 400 ml ingestion of a liquid meal · 100 (%). The frequency of antral contractions was defined as the number of contractions per 3-min interval using the antral vertical view (middle section of Fig. 4). The amplitude of the antral contractions was calculated from the maximal reduction in the antral area for each contraction, i.e., (antral area relaxed)antral area contracted)/antral area relaxed · 100 (%). The motility index (MI) was expressed as the product of the frequency of contractions and mean ...
Context 3
... evaluate the DGR by color Doppler US, we positioned the US probe at the level of the transpyloric plane to simultaneously visualize the antrum, pylorus, and the proximal duodenum for 5 min (lower section of Fig. 4). The color gain, high-pass filter, and angle between the US beam and the transpyloric flow were standardized for all measurements. The frequency of DGR and the distance of color signal from the pylorus during DGR were measured during a 5-min interval, beginning 9 min after 400 mL ingestion of the test meal. We defined frequency as the ...
Citations
... В результате взаимодействия акотиамида с М 1и М 2 -мускариновыми ацетилхолиновыми рецепторами и ингибирования АХЭ у пациентов с ФД нормализуется аккомодация фундального отдела желудка и ускоряется его замедленное опорожнение [7][8][9]. Характерно, что при оценке эвакуаторной функции желудка с помощью 13 С-дыхательного теста с уксусной кислотой у здоровых добровольцев акотиамид в дозе 100 и 300 мг перед едой не влиял на эвакуацию у них жидкой пищи [10,11]. ...
Aim: to evaluate the efficacy and safety of the new prokinetic drug acotiamide in the treatment of functional dyspepsia.
Key findings. Acotiamide is an antagonist of inhibitory muscarinic receptors of type 1 and 2 and a reversible inhibitor of acetylcholinesterase activity. In patients with functional dyspepsia acotiamide normalizes the accommodation of the fundal part of the stomach and accelerates delayed gastric emptying. The conducted studies have confirmed the higher efficacy of acotiamide compared to placebo in reducing the severity of such symptoms of functional dyspepsia as a feeling of epigastric postprandial fullness and bloating, early satiation. The advantage of acotiamide in comparison to other prokinetics (in particular, metoclopramide and domperidone) is the high safety of use and the absence of influence on the duration of the Q-T interval.
Conclusion. The high efficacy and safety of the application makes it advisable to use acotiamide in the treatment of patients with functional dyspepsia.
... Этому же способствует блокада пресинаптических мускариновых ауторецепторов. Влияния же на дофаминовые рецепторы не происходит [44], что способствует хорошей переносимости. Сообщалось, что акотиамид изменяет экспрессию генов, связанных со стрессом, таких как рецепторы ГАМК и нейромедин U [45], т. е. предупреждает негативное влияние на глиальные кишечные клетки, о которых шла речь в начале настоящего обзора, через гипоталамо-гипофизарно-надпочечниковую ось. ...
Functional dyspepsia, affecting up to 20% of individuals worldwide, remains both a cause of decreased activity of patients’ daily life and an obvious economic burden due to healthcare costs. Despite extensive research, the etiology of dyspepsia is unknown in most patients. Intestinal motility dysfunction has long been considered the major culprit, but recent studies suggest that immune pathophysiological and molecular effects in the duodenum are far more likely predisposing factors. Eosinophilia and an increase in mast cells in both the duodenum and gastric mucosa are identified in most patients with this disease. More and more data on the significant role of impaired paracellular permeability of the intestinal mucosa are now available. It is associated with subclinical inflammation in the submucosal layer in patients with functional dyspepsia. This explains the poor effectiveness of the treatments taken. The evidence from practice suggests that symptoms persist or return after eradication therapy in most patients. Proton pump inhibitors and antidepressants do not ease postprandial distress syndrome. Montelukast and cromolyn therapy has been proposed, but this approach is not yet widely popular. Therefore, there is an obvious need in finding other therapeutic approaches. One of them is the increased use of prokinetics, the most recent of which is acotiamide. Its mechanism of action is similar to that of prior generation prokinetics (inhibition of acetylcholinesterase activity), but is distinguished by the absence of impact on dopaminergy, due to which the drug has far fewer side effects. In addition, its effect on the production of ghrelin, which physiological role is being actively studied, is discussed.
... There were nine studies from China with 1,665 participants [3,[14][15][16][17][18][19][20][21], five studies from Belgium with 269 participants [22][23][24][25][26], one study from Germany with 548 participants [27], two studies from India with 280 participants [28] [12], six studies from Japan with 1778 participants [11,13,[29][30][31], one study from Korea with 28 participants [32], one study from Denmark, Germany, France, Sweden, and the UK, with 566 participants [33], one study from Spain with 20 participants [4], and two studies from the US with 636 participants [34,35]. ...
... Six studies compared acotiamide with placebo [11,13,[29][30][31], two studies reported in one report compared different dosages of acotiamide [13]. One study compared cinitapride with domperidone [3], and one study compared cinitapride with metoclopramide [14]. ...
... However, two studies did not report data [31,33]. Three studies reported counts of adverse events [13,30], six studies reported total adverse events [3,12,[18][19][20][21], four studies reported drug-related adverse events [3,14,30,35], and five studies reported specific adverse events [3,16,20,29,35]. Details regarding specific adverse events are described in Supplementary Table 3. ...
Background
Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.
Methods
An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.
Results
A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70–7.47), domperidone (OR: 2.29, 95%CI: 1.16–4.63), itopride(OR: 2.77, 95%CI: 1.41–5.59), acotiamide(OR: 2.63, OR: 1.33–5.36), and placebo(OR: 5.68, 95%CI: 2.98–11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75–3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.
Conclusions
Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.
... Intravenously administered felcisetrag accelerated gastric emptying and small and large bowel transit in patients with gastroparesis [121]. Acotiamide enhanced gastric accommodation and emptying and improved symptoms in patients with functional dyspepsia [122]. Tegaserod may also enhance accommodation [123], although two randomized controlled trials did not show significant benefit [124]. ...
Purpose of review:
Gastroparesis is a chronic disorder characterized by a constellation of foregut symptoms, including postprandial nausea, vomiting, distension, epigastric pain, and regurgitation in the absence of gastric outlet obstruction. Despite considerable research over the past decades, there remains to be only nominal understanding of disease classification, diagnostic criteria, pathogenesis, and preferred therapy.
Recent findings:
We critically reassess current approaches for disease identification and stratification, theories of causation, and treatment for gastroparesis. Gastric scintigraphy, long considered a diagnostic standard, has been re-evaluated in light of evidence showing low sensitivity, whereas newer testing modalities are incompletely validated. Present concepts of pathogenesis do not provide a unified model linking biological impairments with clinical manifestations, whereas available pharmacological and anatomical treatments lack explicit selection criteria or evidence for sustained effectiveness. We propose a disease model that embodies the re-programming of distributed neuro-immune interactions in the gastric wall by inflammatory perturbants. These interactions, combined with effects on the foregut hormonal milieu and brain-gut axis, are postulated to generate the syndromic attributes characteristically linked with gastroparesis. Research linking models of immunopathogenesis with diagnostic and therapeutic paradigms will lead to reclassifications of gastroparesis that guide future trials and technological developments.
Key points:
• The term gastroparesis embodies a heterogenous array of symptoms and clinical findings based on a complex assimilation of afferent and efferent mechanisms, gastrointestinal locations, and pathologies. • There currently exists no single test or group of tests with sufficient capacity to be termed a definitional standard for gastroparesis. • Present research regarding pathogenesis suggests the importance of immune regulation of intrinsic oscillatory activity involving myenteric nerves, interstitial cells of Cajal, and smooth muscle cells. • Prokinetic pharmaceuticals remain the mainstay of management, although novel treatments are being studied that are directed to alternative muscle/nerve receptors, electromodulation of the brain-gut axis, and anatomical (endoscopic, surgical) interventions.
... Thus, patients with delayed gastric emptying may benefit from a prokinetic approach, whereas patients with accelerated gastric emptying should not receive a prokinetic treatment. In addition, measurement of gastric accommodation (with a validated noninvasive test 30 ) in patients with MS may be relevant, as reduced gastric accommodation is associated with acceleration of gastric emptying and may be a target for treatment such as with the cholinesterase antagonist, acotiamide, 31 or with the 5-HT1A agonist, buspirone, 32,33 or with the NK1 antagonist, and aprepitant. 34 Our study has significant strengths given the expertise of the neurologists in characterizing the nature of the multiple sclerosis and the use of validated measurements for gastric and colonic transit and anorectal manometry. ...
Background
Most prevalent gastrointestinal symptoms in multiple sclerosis (MS) relate to lower bowel dysfunction, often in association with bladder manifestations.
Objective
To assess clinical and objective gastrointestinal motor dysfunctions in patients with MS.
Methods
This was a single‐center, retrospective study of 166 patients evaluated between 1996 and 2020. We reviewed characterization of the MS, gastrointestinal and neurological symptoms, measurements of gastrointestinal and colonic transit, and anorectal manometry.
Key Results
At the time of the gastrointestinal evaluations of the 166 patients with MS (138 women; 83%), 111 were in the relapsing‐remitting phase and 52 were in the progressive phase. In 3 patients, disease phase was not assigned due to insufficient data. Constipation was identified in 82% (136/166) of patients. Most [103/116 (88%)] patients with bladder symptoms also had constipation or fecal incontinence. Delayed gastric emptying at 4 h and colonic transit at 24 h was identified in 16% and 7% of the cohort, respectively; 22% had accelerated gastric emptying. On anorectal manometry, resting anal sphincter pressure >90 mm Hg and rectoanal pressure differential below −50mm Hg suggested evacuation disorder in patients with constipation.
Conclusions and Inferences
In addition to slow colonic transit and anorectal dysfunction leading to constipation in MS, 22% of patients had accelerated gastric emptying.
... These include impaired gastric accommodation, delayed gastric emptying [27,28], visceral hypersensitivity, gastric acid, genetics, early-life events, lifestyle, microinflammation in the duodenum, and prior infection. A close relationship between symptoms and impaired gastric accommodation in FD patients was found in a randomized, double-blind, placebo-controlled study [29]. Several reports have suggested that gastric emptying is impaired in some FD patients, and a meta-analysis indicated that it is significantly delayed in almost 35% of FD patients [26]. ...
Background
Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time.
Method
Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment.
Results and Conclusion
These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.
... Одним из перспективных направлений прокинетической терапии является воздействие на дно желудка. Исследования показали, что применение акотиамида улучшает аккомодацию и опорожнение желудка после приема жидкой пищи [32] и улучшает симптомы у пациентов с функциональной диспепсией [33]. Применение некоторых агонистов рецепторов 5-НТ 4 , таких как тегасерод (в РФ не зарегистрирован), у пациентов с функциональной диспепсией с нормальным опорожнением желудка также сопровождалось усилением аккомодации желудка [34]. ...
Prokinetic agents, or prokinetics, are medications that increase and coordinate muscle contractions in the gastrointestinal (GI) tract, including the coordination between various segments of the intestine, and thereby promote the transport of intraluminal content. This paper reviews the current approaches to the use of prokinetics for GI motor disorders. The author addresses the studies on various classes of drugs with prokinetic action that target different pathological mechanisms (including abnormalities of anthro-duodenal coordination manifesting with subjective symptoms and objective delay in stomach emptying). Meanwhile, to date, many of these medications are not approved in the Russian Federation. Domperidon, a drug that is currently used in routine practice and approved in Russia, still proves to be relevant. In functional dyspepsia, gastroparesis, and gastroesophageal reflux disease, this medication is recommended in combination with proton pump inhibitors. Domperidon provides an antiemetic effect and has a favorable safety profile when used for approved indications. KEYWORDS: functional dyspepsia, gastroesophageal reflux disease, gastroparesis, prokinetics, delay in stomach emptying, anthro-duodenal coordination, antiemetic effect. FOR CITATION: Akhmedov V.A. Gastrointestinal motor disorders: treatment with prokinetics. Russian Medical Inquiry. 2022;6(5):252–258 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-252-258.
... Bias summary of five included studies [6][7][8][9][10] ...
... Only three studies reported symptomatic improvement [7,9,10]. There were no significant differences in reported adverse effects between two groups for rise in serum prolactin (OR 1.02, 95% CI 0.64 to 1.61; n = 1709; I 2 = 44%), rise in alanine transaminase (ALT) (OR 1.27, 95% CI 0.70 to 2.33; n = 1709; I 2 = 0%), rise in serum bilirubin (OR, 0.98; 95% CI, 0.52 to 1.87; I 2 = 0%) (Figure 4). ...
... Only three studies reported adverse laboratory outcomes [7,9,10]. ...
Functional dyspepsia is a common gastrointestinal disorder characterized by postprandial fullness or early satiety and epigastric burning or pain in the absence of organic disease. Acotiamide is a novel prokinetic motility drug being used in functional dyspepsia. Databases like PubMed, PubMed Central, Embase, and Scopus were searched for studies comparing the use of acotiamide and placebo for people with functional dyspepsia. Quantitative synthesis was performed using RevMan 5.4 (Cochrane, London, United Kingdom). The improvement in symptoms of functional dyspepsia after treatment was higher in people treated with
acotiamide than placebo, although not statistically significant (OR, 1.48; 95% CI, 0.93 to 2.35; n = 1697; I2 = 59%). Among the commonly reported adverse effects, namely, raised in serum prolactin (OR 1.02, 95% CI
0.64 to 1.61; n = 1709; I2 = 44%), raised in alanine transaminase (OR 1.27, 95% CI 0.70 to 2.33; n = 1709; I 2 =
0%), and raised in serum bilirubin (OR, 0.98; 95% CI, 0.52 to 1.87; I2 = 0%) did not differ between two groups. Acotiamide seems to be a promising agent in functional dyspepsia. However, further larger studies are needed to evaluate the role of acotiamide in functional dyspepsia.
... Mechanistic studies showed that acotiamide enhanced gastric accommodation and gastric emptying of a liquid meal (Kusunoki et al., 2012) and improved symptoms in patients with functional dyspepsia (Matsueda et al., 2012). Some 5-HT 4 receptor agonists also enhance gastric accommodation, such as tegaserod in dyspeptics with normal gastric emptying (Tack et al., 2010). ...
Prokinetic agents amplify and coordinate the gastrointestinal muscular contractions to facilitate the transit of intra-luminal content. Following the institution of dietary recommendations, prokinetics are the first medications whose goal is to improve gastric emptying and relieve symptoms of gastroparesis. The recommended use of metoclopramide, the only currently approved medication for gastroparesis in the United States, is for a duration of less than 3 months, due to the risk of reversible or irreversible extrapyramidal tremors. Domperidone, a dopamine D2 receptor antagonist, is available for prescription through the FDA’s program for Expanded Access to Investigational Drugs. Macrolides are used off label and are associated with tachyphylaxis and variable duration of efficacy. Aprepitant relieves some symptoms of gastroparesis. There are newer agents in the pipeline targeting diverse gastric (fundic, antral and pyloric) motor functions, including novel serotonergic 5-HT4 agonists, dopaminergic D2/3 antagonists, neurokinin NK1 antagonists, and ghrelin agonist. Novel targets with potential to improve gastric motor functions include the pylorus, macrophage/inflammatory function, oxidative stress, and neurogenesis. In the current review, we discuss the use of pharmacological approaches with potential to enhance motor functions in the management of gastroparesis.
... [90][91][92] Multiple randomized, double-blind, placebo controlled, trials conducted in Japan have shown acotiamide was more effective than placebo for improving symptoms and quality of life related to functional dyspepsia; thus, it is currently approved for its treatment in Japan at a dose of 100 mg thrice daily. 90,91,93,94 A large phase III study in Japan One study evaluating the effect of acotiamide on gastric accommodation using ultrasound showed that acotiamide significantly enhanced gastric accommodation and gastric emptying versus placebo 95 . Additionally, a recent randomized, placebo-controlled study showed acotiamide significantly increased gastric accommodation in Japanese patients with functional dyspepsia when measured by gastric emptying scintigraphy. ...
... 92 Minimal adverse effects have been reported, including diarrhea, headache, and an increase in prolactin levels, thus rendering the drug generally safe. 92,94,95 Phase III trials are in preparation in Europe, with phase II trials completed in the United States and Europe. 97 ...
Background
Gastric accommodation is an essential gastric motor function which occurs following ingestion of a meal. Impaired gastric fundic accommodation (IFA) is associated with dyspeptic symptoms. Gastric accommodation is mediated by the vagal pathway with several important physiologic factors such as duodenal nutrient feedback playing a significant role. IFA has been described as a pathophysiologic factor in several gastrointestinal disorders including functional dyspepsia, diabetic gastropathy, post‐Nissen fundoplication, postsurgical gastrectomy, and rumination syndrome. Modalities for gastric accommodation assessment include gastric barostat, intragastric meal distribution via scintigraphy, drinking tests (eg, water load), SPECT, MRI, 2D and 3D ultrasound, and intragastric high‐resolution manometry. Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post‐meal gastric volume.
Purpose
Our aim is to provide an overview of the physiology, diagnostic modalities, and therapies for IFA. A literature search was conducted on PubMed, Google Scholar, and other sources to identify relevant studies available until December 2020. Gastric accommodation is an important gastric motor function which if impaired, is associated with several upper gastrointestinal disorders. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing.
