Opiates, the Pylorus, and Gastroparesis

Camilleri, Michael; Sanders, Kenton M.

doi:10.1053/j.gastro.2020.04.072

Cited by 15 publications

(10 citation statements)

References 60 publications

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“…The role of endogenous opiates in the regulation of pyloric function has also been shown. 40 The presence of enkephalinergic nerves has been confirmed in the muscularis of the pylorus in dogs and humans. 41 , 42 The neural response to opiates has been characterized in dogs as inhibition of cholinergic excitatory and nitrergic inhibitory junction potential in pyloric muscle.…”

Section: Pyloric Physiology and Dysfunction In Gastroparesismentioning

confidence: 96%

Targeting the pylorus in gastroparesis: From physiology to endoscopic pyloromyotomy

Soliman

Gourcerol

2023

Neurogastroenterology Motil

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Gastroparesis is defined as delayed gastric emptying (GE) of solid food in the absence of mechanical obstruction. 1 Cardinal symptoms include nausea, vomiting, gastric fullness, early satiety, bloating, and abdominal pain/discomfort. 2 These symptoms can overlap with those of functional dyspepsia, but gastroparesis has to be confirmed by an objective measurement of GE, either by scintigraphy, or by 13 Coctanoic acid breath test. The prevalence of diagnosed gastroparesis has been evaluated in the United States at 0.24% of the population. 3 Recent epidemiological data from the United Kingdom confirm a similar prevalence of 0.13% in Europe based on the diagnostic code, although the disease appears to be underdiagnosed. 4 Gastroparesis leads to an economic burden, evaluated between US$4000 and US$9000 per patient per year in a recent study. 5 Moreover, delayed GE has been associated with increased mortality, independently of age, sex, or the etiology of the disease. 6 The first-line treatment relies on dietary modification and medical treatment, with prokinetic drugs such as metoclopramide. 7,8 However, the efficacy of medical treatment is limited, and up to 40% of patients are considered to be refractory after appropriate treatment. 9 Severe refractory gastroparesis can lead to dehydration, weight loss, and impaired quality of life and could become a challenging condition. 10 Thus, invasive techniques have been developed to improve the symptoms of such patients.Considering the role of pyloric dysfunction in gastroparesis, 11 gastric peroral endoscopic pyloromyotomy (G-POEM) has emerged as an alternative therapeutic technique in patients with refractory gastroparesis. The first human case was described in 2013 by Khashab et al. 12 The technique is based on the principles of peroral endoscopic myotomy of the lower esophageal sphincter, used to treat achalasia. Since then, cohort studies have assessed the clinical efficacy and the safety of G-POEM in refractory gastroparesis.This review aims to detail the role of the pylorus in the pathophysiology of gastroparesis, and then to report the efficacy, modalities, and the place of G-POEM, based on the results of published studies.

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Section: Pyloric Physiology and Dysfunction In Gastroparesismentioning

confidence: 96%

Targeting the pylorus in gastroparesis: From physiology to endoscopic pyloromyotomy

Soliman

Gourcerol

2023

Neurogastroenterology Motil

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“…ICC generate and propagate slow waves in both the stomach and small intestine, 30 and there is reduction in the density of ICC networks within a narrow zone between the pylorus and duodenum that appears not to support propagation of slow waves, thereby facilitating independent electrical and motor activities in the 2 organs. 48 Enteric inhibitory neurotransmission, measured by inhibitory junction potentials in canine pyloric muscles, is mediated primarily by NO and by a purine neurotransmitter 50,51 acting through activation of small conductance Ca 2þ -activated K þ channels. Inhibition of inhibitory junction potentials unmasked excitatory junction potentials in the myenteric region and increased the excitability of SMCs and contractions in the submucosal region of the pylorus.…”

Section: Specializations Of the Pyloric Sphinctermentioning

confidence: 99%

Gastroparesis

Camilleri

Sanders

2022

Gastroenterology

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“…It is increasingly recognized that patients on long-term opioid medications may present with gastroparesis ( Hasler et al, 2019 ). The mechanisms associated with the effects of opiates or opioid medications are reviewed elsewhere ( Camilleri and Sanders, 2020 ). Opioids can induce pyloric dysfunction in addition to inhibition of antral motor function, both of which contribute to delayed gastric emptying.…”

Section: Introduction: Definitions and Currently Available Prokinetic Treatmentsmentioning

confidence: 99%

New Developments in Prokinetic Therapy for Gastric Motility Disorders

Camilleri

Atieh

2021

Front. Pharmacol.

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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.

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Opiates, the Pylorus, and Gastroparesis

Abstract: Conflicts of interestMichael Camilleri receives funding for research in gastroparesis from Takeda, and serves as a consultant to AlfaSigma and Takeda with compensation to his employer, Mayo Clinic. Kenton Sanders has nothing to disclose.

Cited by 15 publications

References 60 publications

Targeting the pylorus in gastroparesis: From physiology to endoscopic pyloromyotomy

Targeting the pylorus in gastroparesis: From physiology to endoscopic pyloromyotomy

Gastroparesis

New Developments in Prokinetic Therapy for Gastric Motility Disorders

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