PMC:4110358 / 2537-11526 JSON TXT

Annnotations TAB JSON ListView MergeView

2_test

{"project":"2_test","denotations":[{"id":"25097708-19886950-132809955","span":{"begin":1756,"end":1757},"obj":"19886950"},{"id":"25097708-2773901-132809956","span":{"begin":2862,"end":2863},"obj":"2773901"},{"id":"25097708-11966504-132809957","span":{"begin":2978,"end":2979},"obj":"11966504"},{"id":"25097708-10749328-132809958","span":{"begin":4339,"end":4340},"obj":"10749328"},{"id":"25097708-11467630-132809959","span":{"begin":4651,"end":4652},"obj":"11467630"},{"id":"25097708-11467630-132809960","span":{"begin":5042,"end":5043},"obj":"11467630"},{"id":"25097708-8344110-132809961","span":{"begin":6784,"end":6785},"obj":"8344110"},{"id":"25097708-9669631-132809962","span":{"begin":6814,"end":6815},"obj":"9669631"},{"id":"25097708-1618063-132809963","span":{"begin":7042,"end":7044},"obj":"1618063"},{"id":"25097708-12483243-132809964","span":{"begin":7563,"end":7565},"obj":"12483243"},{"id":"25097708-14675269-132809965","span":{"begin":8120,"end":8122},"obj":"14675269"},{"id":"25097708-21979407-132809966","span":{"begin":8541,"end":8543},"obj":"21979407"},{"id":"25097708-12645792-132809967","span":{"begin":8762,"end":8764},"obj":"12645792"},{"id":"25097708-18795687-132809968","span":{"begin":8789,"end":8791},"obj":"18795687"}],"text":"Drugs used in gastrointestinal motility disorders and their impact on the electrogastrogram\nOne of the most common disorders of gastric motility, causing troublesome subjective symptoms, is abnormal, delayed gastric emptying – also called gastroparesis. Clinical symptoms are mainly pain in the upper abdomen, often described by patients as bloating, feeling of food retention long after meals, avoiding meals of larger volume caused by fears of many hours of postprandial discomfort. This phenomenon is particularly prevalent in patients with long-standing diabetes and is typically accompanied by gastric dysrhythmia observed in the EGG study [1].\nAnother common gastric motility disorder, causing unpleasant subjective symptoms, is impairment in gastric fundus accommodation. Physiologically, food intake causes relaxation of the gastric fundus, which acts as a reservoir. This allows for absorbance of relatively large amounts of food, its storage and pre-mixing, followed by activation of the propulsive motility moving portions of food toward the antrum. Impaired accommodation of the gastric fundus can cause discomfort in the form of early fullness after small amounts of food, with postprandial pain or discomfort in the upper abdomen.\nTreatment of gastroparesis mainly uses prokinetic drugs, which include: metoclopramide, domperidone, erythromycin, cisapride and related drugs (mosapride, prucalopride).\nMetoclopramide is used as a prokinetic drug showing also strong antiemetic action. It functions as an antagonist of dopaminergic receptor D2. Unfortunately, lack of selectivity causes metoclopramide to stimulate receptors present in the central nervous system and can trigger unpleasant side effects in the form of extrapyramidal disorders [2]. Paradoxically, despite its popularity and long-term presence in the market, metoclopramide has not yet been systematically assessed regarding its possible impact on GMA (This assertion is based on Pub Med [http://www.ncbi.nlm.nih.gov/pubmed/] search result for the product of logical term metoclopramide and the sum of logical terms: electrogastrography, gastric myoelectric* activity, gastric slow waves, gastric pacesetter) Domperidone (not available in Poland,but quite popular in other Western countries as an oral medication called Motilium) is a drug of similar action to metoclopramide. It has an affinity for the same D2 receptor, but with greater selectivity for the gastrointestinal tract, which reduces the risk of side effects. The EGG studies have shown that in patients with diabetic gastroparesis and dysrhythmia (i.e. with a relatively considerable presence of bradygastria and/or tachygastria in the electrogastrogram), the administration of domperidone normalises GMA in some patients, restoring the presence of slow waves with a frequency of approximately 3 cpm (cycles per minute) [3]. In children with type 1 diabetes and gastroparesis, domperidone seems to be even more effective than cisapride [4]. Itopride, newly introduced to the Polish market and previously registered in other countries, does not appear to have the disadvantages of metoclopramide, and it is more sophisticated than domperidone. This dopaminergic D2 receptor antagonist does not have the ability to cross the blood-brain barrier, as well as demonstrating acetylcholinesterase inhibitor activity. Due to these pharmacological properties, it is an effective prokinetic drug [5]. Two-week itopride treatment of patients with non-ulcer dyspepsia resulted in a significant increase in the relative time share of normogastria in the EGG reading and accelerated gastric emptying (Otsuba, et al. – cited by [5]). Erythromycin is a macrolide antibiotic with relatively recently discovered additional agonist properties towards motilin receptors. The result of this action is an increase in the strength of contractions of the gastric antrum and the appearance of motor activity similar to the third phase of the migrating motor complex (MMC), and hence the acceleration of gastric emptying and activation of propulsive motility. Interestingly, the positive effect of erythromycin on the GMA and the motility of the antrum is detectable even at amounts lower than the standard doses, when used as an antibiotic. This effect, in children, has been demonstrated at a dose of 3 mg/kg body weight [6]. In adults, a single dose of 50 mg of erythromycin, administered as 20-minute intravenous infusion, resulted in a slightly shorter (by approximately 17%) halftime of gastric empting of solid food in comparison with placebo treatment. Increasing the dose to 100 mg of erythromycin did not improve this effect [7]. Remarkably, following further application of erythromycin, deterioration of GMA in the postprandial period was observed – the relative normogastria time-share was reduced, and the tachygastria proportion increased. In addition, the frequency of dominant gastric slow waves decreased and the instability factor (dominant frequency instability coefficient – DFIC) significantly increased [7].\nUnquestionably, the antibacterial activity of erythromycin causes restrictions in its use as a prokinetic drug, but it is still suitable for short-term use for this purpose under hospital conditions. Erythromycin, as a drug stimulating gastric and intestinal motility, is recommended especially in emergency situations, for example: the intestinal atony, or in conditions requiring rapid gastric emptying, such as with the need of carrying out urgent endoscopy due to upper gastrointestinal tract bleeding. Many clinical trials evaluating the effects of prokinetic treatment in patients with gastroparesis have been performed using cisapride. It is agonist drug of the serotonin receptortype 4 (5-HT4). The result of this action is an increased release of acetylcholine from the nerve endings in the gastrointestinal tract and thereby increasing the tension of the lower oesophageal sphincter (antireflux action). In addition, it increases the amplitude of the propulsive waves in the stomach and duodenum (prokinetic effect). A limitation for its use is the interaction with several other medications owing to adverse effects on cardiac function – by action of lengthening the period of ventricular repolarisation, which manifests on ECG by QT segment prolongation, with an increased risk of serious ventricular arrhythmias. Nevertheless, after taking into consideration contraindications to its use and potential risks of polypragmasy, cisapride is still a valuable therapeutic drug.\nCisapride, used in patients with impaired gastric emptying, removes the clinical symptoms and improves the rate of gastric evacuation. The beneficial clinical effect of cisapride is associated with normalisation of ailments detected in the EGG record [8]. As shown by Chang et al. [9], the increased presence of tachygastria in the electrogastrogram of patients with idiopathic or diabetic gastroparesis is significantly reduced after use of cisapride. Similar observations have been made in paediatric cases [10].\nFor many years there has been on-going research into new active substances with qualities similar to cisapride, i.e. of a selective 5-HT4 receptor agonist, but deprived of its original side effects on the circulatory system. An example of such a new drug is mosapride, which, in studies on healthy volunteers, significantly accelerated gastric emptying. It has been shown that, without changing the dominant frequency of gastric slow waves, it has significantly increased their amplitude in the original EGG record [11]. Proton pump inhibitors (PPI) are among the most commonly used drugs in gastroenterology. The main indications for their use are: gastroesophageal reflux disease (GERD), functional dyspepsia, peptic ulcer disease and eradication of Helicobacter pylori. Myoelectrical gastric dysfunction has been reported in these diseases, with a positive effect of empirical PPI treatment. There are reports that correlate the clinical improvement in the upper gastrointestinal tract diseases with an improvement in the EGG record after PPI application. Chang et al. [12] reported a significant reduction in the relative time contribution of bradygastria and increased normogastria share in the postprandial period in patients with GERD after 4 weeks of treatment with 20 mg of omeprazole p.o. However, studies on healthy volunteers did not demonstrate a significant effect on the GMA, or the rate of gastric emptying of semi-solids, after a 7-day application of 20 mg of omeprazole p.o. [13].\nAnother representative of the PPI group is rabeprazole, administered to healthy volunteers for a week at a dose of 20 mg p.o., which had no effect on the EGG record performed during the maximum oral water load test [14]. However, Chen et al. [15] demonstrated that eight weeks of treatment with esomeprazole resulted in a minor, but statistically significant, increase in the relative time contribution of normogastria in patients with GERD.\n\n"}

NEUROSES

PMC:4110358 / 2537-11526 JSONTXT

Annnotations TAB JSON ListView MergeView

2_test

NEUROSES

PMC:4110358 / 2537-11526 JSON TXT