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Metoclopramide, the only drug approved by the FDA for treatment of diabetic gastroparesis, but used off-label for a variety of other gastrointestinal indications, has many potentially troublesome adverse neurologic effects, particularly movement disorders. In this article, we comprehensively review the indications and side effects of metoclopramide, and describe some common pitfalls and strategies to minimize the medicolegal risks to the prescribing physician. Metoclopramide accounts for nearly a third of all drug-induced movement disorders, a common reason for a malpractice suit. The entire spectrum of drug-induced movement disorders, ranging from subtle to life-threatening, can ensue from its use; akathisia and dystonia are generally seen early in the course of metoclopramide-induced movement disorders, whereas tardive dyskinesia and parkinsonism seem to be more prevalent in chronic users. Female sex, age and diabetes are the major risk factors for metoclopramide-induced movement disorders. It is therefore incumbent on gastroenterologists and other prescribing physicians to become familiar with the adverse neurologic effects associated with the use of metoclopramide, and to take appropriate preventive and defensive measures.

BackgroundThe pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S) in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-β-synthetase (CBS) in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH). CVH was induced by colonic injection of 0.5% acetic acid (AA) in 10-day-old rats and experiments were performed at 8–10 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall.ResultsIn rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation.ConclusionOur results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

This clinical review on the treatment of patients with gastroparesis is a consensus document developed by the American Motility Society Task Force on Gastroparesis. It is a multidisciplinary effort with input from gastroenterologists and other specialists who are involved in the care of patients with gastroparesis. To provide practical guidelines for treatment, this document covers results of published research studies in the literature and areas developed by consensus agreement where clinical research trials remain lacking in the field of gastroparesis.

Summary Background Eosinophilic oesophagitis (EoE) is a growing cause of dysphagia. Current therapies include dietary manipulation, steroids and biological drugs. Aim To perform a systematic review and summarise the effect of different medical interventions on EoE. Methods Two reviewers searched Pubmed and Embase for studies on treatment for EoE. We included randomised controlled trials (RCT) limited to pharmacological interventions. Two reviewers selected studies. Meta‐analysis was done using random effects model to estimate odds ratio (OR). Heterogeneity was determined by Cochran's Q statistic and I2. Results Seventeen references met our inclusion criteria. Eleven RCTs involving 455 participants were included in the meta‐analysis. 325 participants were evaluated for symptomatic improvement and 330 were evaluated for histological remission. Symptomatic improvement with topical steroids (7 studies, 250 participants) compared to the control group (placebo or PPI) was noted (OR: 3.03, 95% confidence interval, CI: 1.57–5.87). Histological remission was also noted in nine studies involving 330 participants (OR: 13.66, 95% CI: 2.65–70.34) comparing topical steroids to a control (placebo or PPI). There was no difference between anti‐IL‐5 drugs and placebo in terms of symptomatic improvement (OR: 0.69, 95% CI: 0.34–1.42). Conclusions Topical steroids induce significant symptomatic and histological remission, and should be considered as a first line treatment. Anti‐IL‐5 therapy has a minor effect on eosinophilic oesophagitis. Future research in eosinophilic oesophagitis should standardise methodology according to published guidelines to improve quality and allow direct comparison between therapies.

Gastrotomy closure with a perorally delivered flexible stapling device created a leak-resistant transmural line of staples followed by full-thickness healing of the gastric wall incision. Increasing the length of the instrument and adding device articulation will further facilitate its use for NOTES procedures.

Post-surgical gastroparesis (PSG) is recognized as a consequence of vagal nerve injury following upper abdominal surgery. It has been well documented following vagotomy for peptic ulcer surgery. With the increasing role of surgical treatment in the management of GERD and morbid obesity, PSG is now being diagnosed after fundoplication and bariatric surgery. PSG has also been reported after heart and lung transplantation, possibly due to opportunistic viral infection or motor-inhibitory effects of the immunosuppressive drugs, in addition to vagal nerve injury. Initial postoperative management of PSG should be conservative as many symptoms following abdominal surgery resolve with time. This occurs possibly because the enteric nervous system is able to adapt to the loss of vagal input or vagal reinnervation occurs. Persistent symptoms are difficult to manage and require a multidisciplinary team approach. Gastric electrical stimulation has shown promise in small series.

Background We have demonstrated previously that in vivo supplementation of tetrahydrobiopterin (BH4); a co-factor for neuronal nitric oxide synthase (nNOS) significantly restored delayed gastric emptying and attenuated nitrergic relaxation in diabetic rat. In this study, we have investigated whether supplementation of sepiapterin (SEP), a precursor for BH4 biosynthesis via salvage pathway restores gastric emptying and nitrergic system in female diabetic rats. Methods Diabetic rats (streptozotocin-induced) were supplemented with BH4 or SEP (20 mg kg−1 body weight). Gastric nitrergic relaxation in the presence or absence of high glucose and SEP were measured by electric field stimulation. Gastric muscular strips from healthy or diabetic female rats were incubated in the presence or absence of high glucose, SEP and/or methotrexate (MTX). Nitric oxide release was measured colorimetrically by NO assay kit. The expression of nNOSα and dimerization was detected by Western blot. Key Results In vitro studies on gastric muscular tissues showed that MTX, an inhibitor of BH4 synthesis via salvage pathway, significantly decreased NO release. In vivo treatment with MTX reduced both gastric nitrergic relaxation and nNOSα dimerization. Supplementation of SEP significantly attenuated delayed gastric emptying in diabetic rats. In addition, SEP supplementation restored impaired nitrergic relaxation, gastric nNOSα protein expression and dimerization in diabetic rats. Conclusions & Inferences The above data suggests that supplementation of SEP accelerated gastric emptying and attenuated reduced gastric nNOSα expression, and dimerization. Therefore, SEP supplementation is a potential therapeutic option for female patients of diabetic gastroparesis.