Correlation of Gastric Scintigraphy and Clinical Symptoms in the Diagnosis of Gastroparesis and its Impact on Quality of Life: A Pan India Real World Study

Background: Gastroparesis with its varied etiology is one of the major health issues in India. Poor correlation between delayed gastric emptying and its symptoms is well-known. This study was planned to evaluate the proportion of confirmed gastroparesis by scintigraphy among patients with suggestive clinical features, their underlying aetiologies and clinical profiling in a real-world setting in India. Settings and Design: Patients clinically diagnosed with gastroparesis, presenting varyingdegreesofsymptoms for at least 12-weeks, were enrolled in this multic-entric,cross-sectional, clinico-epidemiological study. Results: Overall, 196/201 enrolled patients underwent gastric scintigraphy; 88 (45%) were found to be scintigraphically positive and 108 (55%) patients were only clinically positive. Underlying etiologies of gastroparesis were idiopathic (51.2%), type-2 diabetes (44.8%), type-1 diabetes (2.5%) and psychological conditions (1.5%). Most patients presented symptoms like postprandial fullness (75.6%), bloating (50.7%), abdominal pain (45.3%), nausea (41.3%), abdominal discomfort (40.3%), early satiety (37.8%) and vomiting (17.9%) of moderate severity. Common dietary risk factors were fatty diet (66.7%), fiber-rich food (57.7%) and carbonated drinks (18.9%). Weight loss (6.5%), esophagitis (5.5%) and electrolyte disturbances (0.5%) were the associated complications. About 89.8% were on proton-pump inhibitors, followed by prokinetics (51.8%) and antiemetics (8.4%). The mean PAGI-QoL score was 3.6 ± 0.94, suggesting a moderate effect of gastroparesis on QoL. Conclusion: Poor correlation exists between gastric scintigraphy and gastrointestinal symptoms, thus reiterating the significance of the clinical diagnosis of gastroparesis, especially in diabetes. Only about half of the patients were prescribed prokinetics, emphasizing the need for appropriate pharmacotherapy using prokinetics for holistic management of gastroparesis.

Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.

Drug-induced Gastrointestinal Hypomotility and Current Issues on Safety of Prokinetics in Critically Ill Patients

Impaired gastrointestinal (GI) motility is extremely common in the intensive care unit (ICU), affecting up to 50% of mechanically ventilated patients and up to 80% of patients with traumatic brain injury. This includes disturbances in esophageal, gastric, small intestinal, and colonic function; alone or in combination. Impaired upper GI motility can lead to reflux, aspiration, vomiting, high gastric residuals, and interruptions in enteral nutrition. In critically ill patients, prolonged constipation may cause delayed weaning from mechanical ventilation, lengthened ICU stay, and inability to take in enteral nutrition; at least one study has suggested an association between delayed defecation and both increased bacterial infections and mortality. Drugs used for analgesia and sedation are commonly associated with impaired gastric and small intestinal motility in critically ill patients. Drugs frequently impair gastric motility via one or more mechanisms, and the precise mechanisms of drug-induced hypomotility are often unknown. Therefore, measures to prevent drug-induced motility disturbances include correction of fluid and electrolyte imbalances, early enteral feeding, and judicious use of drugs known to alter motility. Prokinetic agents are currently the mainstay of therapy for impaired GI motility in the critically ill. Of the available prokinetic agents, current information, while limited, suggests that erythromycin or metoclopramide (alone or in combination) are effective in management of feeding intolerance for the critically ill in terms of evidence-based practice. Based on the current evidence evaluating the adverse effects of prokinetic agents in critical illnesses and the lack of prokinetic agents with a safer adverse effect profile, the ongoing need for prokinetic drugs in these patients should be reviewed daily in order to minimize avoidable adverse effects.

Prokinetics——now and in the future / 中华实用儿科临床杂志

Gastrointestinal motility disorders are in high incidence in children.Due to moderate prokinetic effects,poor symptomatic responses and the presence of adverse effects,there is a clear need for new classes of prokinetics.Currently available drug classes in adult include antidopami-nergic agents,serotonergic agents,and motilin-receptor while there are less available drug classes in children.The aim of the present article is to review and address the present use of promotility drugs in the treatment of different gastrointestinal motor disorders,as well as the potential for future developments.

Uso racional de antieméticos na gastroenterite aguda / Rational use of antiemetics in acute gastroenteritis

A concomitância de episódios de vômito com a diarreia aguda é alta em crianças com gastroenterite aguda (GECA), possivelmente devido à estimulação do centro do vômito por sinais periféricos resultantes da irritação da mucosa intestinal. Apesar do vômito ser um sintoma autolimitado que representa uma resposta fisiológica para livrar o organismo de compostos tóxicos, inúmeros estudos já demonstraram que, na prática clínica, os antieméticos são comumente prescritos para crianças com GECA, por ser o vômito um sintoma desconfortável, que pode aumentar a probabilidade de desidratação, desequilíbrio eletrolítico, aspiração pulmonar e necessidade de hidratação endovenosa. O dimenidrinato, um anti-histamínico que bloqueia os receptores H1 no núcleo do trato solitário e os receptores muscarínicos-colinérgicos do centro do vômito, é considerado um antiemético seguro para a população pediátrica. Embora o comprimido de dimenidrinato já tenha um início de ação relativamente rápido dentre os antieméticos mais utilizados, uma nova formulação líquida em cápsula gelatinosa mole (Capsgel) foi desenvolvida com o objetivo de acelerar sua dissolução, uma vez que a forma menos complexa de oferecer um composto ao trato gastrointestinal é administrá-lo como uma solução, o que remove qualquer etapa limitante para a dissolução no processo de absorção, que pode tornar-se mais rápida e uniforme. A apresentação do dimenidrinato em cápsulas gelatinosas moles pode ser uma alternativa terapêutica em crianças com GECA para as quais se julgar que os potenciais benefícios de um medicamento antiemético sobrepujam os riscos...

DA-9701: A New Multi-Acting Drug for the Treatment of Functional Dyspepsia

Motilitone(R) (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profile of DA-9701 is also preferable to that of other treatments.

Gastroparesia y dispepsia funcional: diagnóstico y tratamiento / Gastroparesis and functional dyspepsia: diagnosis and treatment

Gastroparesis corresponds to the clinical picture of a non-obstructive alteration in gastric emptying. The most common causes are idiopathic, postsurgical and diabetes mellitus. Endoscopy and gastric emptying scintigraphy are necessary for diagnosis. Fractionating the diet and avoiding fat are recommended actions. Prokinetics are fundamental in gastroparesis therapy. Domperidone is the first choice because it has a better safety profile. It is advisable to rotate prokinetics. In refractory cases it is suggested to try other prokinetics (such as erythromycin or prucalopride), effective management of nausea and nutrition optimization. In selected cases, therapies such as electrical stimulation could be evaluated. Functional dyspepsia is defined as symptoms that probably originate in the gastroduodenal region, having ruled out other possibilities. Therefore, endoscopy should show no alterations that could explain the symptoms. The most frequently encountered pathophysiological alterations are slow gastric emptying, impaired accommodation and hypersensitivity. None has been linked unequivocally to a pattern of symptoms. It is suggested to start with proton-pump inhibitors therapy. In refractory cases, prokinetics should be added. If there is no adequate response, 24-hour pH monitoring and gastric emptying should be ordered. In case of altered gastric emptying, adjust prokinetics. If gastric emptying is normal, bupirone or mianserin could be used.

La gastroparesia corresponde a un cuadro clínico debido a mal vaciamiento gástrico no obstructivo del estómago. Sus causas más frecuentes son idiopática, diabetes mellitus y postquirúrgica. La endoscopia y el cintigrama de vaciamiento gástrico son necesarios para el diagnóstico. Se recomienda fraccionar la dieta y evitar las grasas. Los procinéticos son fundamentales en el tratamiento de la gastroparesia. La domperidona es la primera opción por su mejor perfil de seguridad. Es aconsejable rotar los procinéticos. En casos refractarios se puede intentar otros procinéticos (como eritromicina o prucalopride), manejar específicamente las náuseas y optimizar la nutrición. En casos seleccionados se puede intentar terapias como estimulación eléctrica. La dispepsia funcional está definida por síntomas que probablemente se originan en la región gastroduodenal, habiendo descartado otras posibilidades. Por esto, requiere un estudio endoscópico sin alteraciones que expliquen los síntomas. Los hallazgos fisiopatológicos más frecuentemente encontrados son alteraciones del vaciamiento gástrico, trastornos de la acomodación e hipersensibilidad. Ninguno de ellos ha sido asociado inequívocamente a algún patrón de síntomas. Se sugiere iniciar tratamiento con inhibidores de la bomba de protones. En casos refractarios, es aconsejable agregar procinéticos. Si no hay adecuada respuesta, se sugiere estudiar con una ph-metría de 24 horas y vaciamiento gástrico. En caso de vaciamiento alterado, ajustar los procinéticos. En caso de vaciamiento normal, se sugiere uso de buspirona o mianserina.

Effects of the Oral Administration of Mosapride Citrate on Capsule Endoscopy Completion Rate

BACKGROUND/AIMS: In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion. METHODS: In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitalization, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time. RESULTS: The univariate analysis showed that oral mosapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mosapride citrate (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT). CONCLUSIONS: Oral mosapride citrate reduced the GTT and SBTT during CE and improved the CE completion rate.

Acatisia associada à bromoprida em um paciente deprimido usando fluvoxamina / Akathisia associated with bromopride in a depressed patient using fluvoxamine

CONTEXTO: A acatisia é definida clinicamente como uma sensação de agitação associada à necessidade de produção de movimentos, comumente deflagrada por bloqueadores dopaminérgicos, como os neurolépticos, podendo ocorrer também durante o tratamento com inibidores seletivos de recaptação de serotonina. É possível que drogas não psiquiátricas que bloqueiem receptores dopaminérgicos, como a bromoprida, possam causar sintomas extrapiramidais. OBJETIVOS: Descrever um desfecho desfavorável caracterizado por acatisia em um paciente depressivo previamente estabilizado com fluvoxamina, após usar bromoprida. MÉTODOS: Descrição de um caso. RESULTADOS: Sr. J., paciente deprimido de 47 anos, estava estabilizado com fluvoxamina 200 mg por dia. Iniciou abruptamente com quadro de inquietação e necessidade de produzir movimentos voluntariamente a fim de aliviar esse desconforto. Há quatro dias havia iniciado o uso de bromoprida 30 mg por dia para tratamento de dispepsia. A suspensão da bromoprida promoveu alívio imediato dos sintomas. CONCLUSÃO: A bromoprida, um bloqueador dopaminérgico, pode ter deflagrado acatisia em um paciente em uso de fluvoxamina. Os mecanismos farmacológicos relacionados a esse desfecho são discutidos.

BACKGROUND: Akathisia is clinically defined as a sensation of restlessness associated to a necessity to produce movements, commonly triggered by dopaminergic blockers, like neuroleptics, and it might occur during treatment with selective serotonine reuptake inhibitors. It is possible that non psychiatric drugs that block dopaminergic receptors, like bromopride, might cause patients to develop extrapyramidal symptoms. OBJECTIVES: To describe an unfavorable outcome clinically characterized by akathisia in a depressed patient previously stabilized with fluvoxamine, after using bromopride. METHODS: Case report. RESULTS: Mr J, 47 year-old depressed patient, had been stabilized with fluvoxamine 200 mg a day. He began abruptly with restlessness and an urgency to produce voluntary movements in order to alleviate such discomfort. Four days earlier he began using bromopride 30 mg a day to treat dyspepsia. Withdrawn of bromopride promoted an immediate relieve of the symptoms. CONCLUSION: Bromopride, a dopaminergic blocker, might have triggered akathisia in a patient using fluvoxamine. The pharmacologic mechanisms regarding this outcome are discussed.

Refluxo gastroesofágico em cães anestesiados: fisiopatologia, clínica, diagnóstico e terapêutica / Gastroesophageal reflux in anesthetized dogs: physiopathology, clinic, diagnosis and therapeutics

O refluxo gastroesofágico pode afetar várias espécies e apresenta diversas etiologias, sendo as anestesias gerais uma das principais causas de esofagite em cães, devido à redução do tônus do esfíncter esofagogástrico, ocasionada por fármacos anestésicos. São fatores responsáveis pela lesão esofágica em consequência do refluxo, o tipo do material refluído, o volume, a frequência, a duração do refluxo e a integridade da mucosa esofágica. É importante prevenir o refluxo durante a anestesia, devido ao risco de ocasionar além da esofagite pós-operatória, outras graves complicações como a formação de estenoses esofágicas ou ainda resultar em pneumonia por aspiração. Para isso, é importante estabelecer protocolos anestésicos que não modifiquem a função do esfíncter esofagogástrico, bem como determinar estratégias terapêuticas que reduzam a incidência do refluxo. Neste artigo, são revisados os aspectos anatômicos e fisiológicos da junção esofagogástrica, assim como os relacionados com o refluxo gastroesofágico em cães anestesiados.

Gastroesophageal reflux can affect various species and presents several etiologies, and general anesthesia can be considered one of the main causes of esophagitis in dogs, due to the reduction of the gastroesophageal sphincter tonus caused by anesthetic drugs. There are many factors responsible for the esophageal lesion due to reflux, including type of refluid material, reflux volume, frequency and duration, and esophageal mucosa integrity. It is important to prevent reflux during anesthesia because of the risk of causing not only post operatory esophagitis but also other serious complications such as formation of esophageal stenosis, or aspiration pneumonia . Thus, it is important to establish anesthetic protocols that do not modify the function of the gastroesophageal sphincter, as well as determine therapeutic strategies that could reduce reflux incidence. This research reviews the anatomic and physiological aspects of gastroesophageal junction as well as those aspects related with gastroesophageal reflux in anesthetized dogs.

Gastrointestinal Motility Modulating Drugs

Gastrointestinal motility modulating drugs include all compounds which have pharmacological activity of modulating (stimulating or inhibiting) gastrointestinal motility. They are mainly used for the treatment of functional gastrointestinal diseases. Gastrointestinal motility modulating drugs include 5HT receptor agonists, antagonists, and antidopaminergic agents. Many new gastrointestinal motility modulating drugs are currently under investigation. The aims of this article are to review the mechanism of action, efficacy and side effects of the gastrointestinal motility modulating drugs.