Cardiovascular safety of prokinetic agents: A focus on drug‐induced arrhythmias

Giudicessi, John R.; Ackerman, Michael J.; Camilleri, Michael

doi:10.1111/nmo.13302

Cited by 54 publications

(50 citation statements)

References 134 publications

(171 reference statements)

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“…As stated earlier, although a number of prokinetics, such as metoclopramide, domperidone, erythromycin, azithromycin, cisapride, and tegaserod, have been developed or applied for treating gastric dysmotility, they were not available in the USA or not practically used in clinical settings due to their severe side-effects. 11,32,[64][65][66] Due to its autonomic mechanisms, the proposed SCS may also exert ameliorating effects on other pathophysiologies of gastroparesis, such as impaired gastric accommodation and visceral pain. Gastric accommodation is known to be mediated via the vagal and nitrinergic mechanisms and the SCS-induced enhancement in vagal activity may, therefore, improve gastric accommodation, which deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] On the other hand, while a number of prokinetic medications (such as cisapride) were developed to restore normal gastrointestinal motility, they have been withdrawn from the market due to their unfavorable cardiovascular safety. 11 Noteworthy is that treating overall symptoms of gastroparesis is another dilemma. Some medications can improve gastric accommodation or abdominal pain but they can reduce gastric motility, 12 or some can increase gastric motility (prokinetics) but might reduce gastric accommodation.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Approach in Spinal Cord Stimulation for Enhancing Gastric Motility: A Preliminary Study on Canines

Gharibani

Yang

et al. 2020

J Neurogastroenterol Motil

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Background/AimsGastroparesis is commonly seen in patients with diabetes and functional dyspepsia with no satisfactory therapies. Dysautonomia is one of the main reasons for the imbalanced motility. We hypothesized that spinal cord stimulation (SCS) is a viable therapy for gastroparesis via the autonomic modulation to improve gastric motility. The aim is to find an optimal method of SCS for treating gastroparesis. MethodsEight healthy-female dogs were implanted with a gastric cannula, a duodenal cannula, 2 multi-electrode spinal leads, and an implantable pulse generator. Gastric motility index (MI) was used to determine the best stimulation location/parameters of SCS. Optimized SCS was used to improve glucagon-induced gastroparesis. ResultsWith fixed parameters, SCS at Thoracic 10 (T10) was found most effective for increasing gastric MI (37.8%, P = 0.013). SCS was optimized with different parameters (pulse width: 0.05-0.6 msec, frequency: 5-500 Hz, motor threshold: 30-90%) on T10. Our findings revealed that 0.5 msec, 20 Hz with 90% motor threshold at T10 were the best parameters in increasing MI. Glucagon significantly delayed gastric emptying, and this inhibitory effect was partially blocked by SCS. Gastric emptying at 120 minutes was 25.6% in the control session and 15.7% in glucagon session (P = 0.007 vs control), while it was 22.9% with SCS session (P = 0.041 vs glucagon). SCS with the optimal parameters was found to maximally enhance vagal activity and inhibit sympathetic activity assessed by the spectral analysis of heart rate variability. ConclusionsSCS with optimized stimulation location and parameters improves gastric motility in healthy-dogs and accelerates gastric emptying impaired by glucagon via enhancing vagal activity. (J Neurogastroenterol Motil 2020;26:147-159)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Approach in Spinal Cord Stimulation for Enhancing Gastric Motility: A Preliminary Study on Canines

Gharibani

Yang

et al. 2020

J Neurogastroenterol Motil

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“…QT intervals were checked routinely prior to treatment only in case there was a history of cardiac disease, when 50 years or older of age or other in case co‐medication was used with a potential to prolong QT intervals. Despite safety concerns, a recent meta‐analysis and review stated that cardiac arrhythmias or adverse events are rare.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic strategies in gastroparesis: Results of stepwise approach with diet and prokinetics, Gastric Rest, and PEG‐J: A retrospective analysis

Strijbos

Keszthelyi

Smeets

et al. 2019

Neurogastroenterology Motil

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Background Gastroparesis is characterized by abnormal gastric motor function with delayed gastric emptying in the absence of mechanical obstruction. In our tertiary referral center, patients are treated with a stepwise approach, starting with dietary advice and prokinetics, followed by three months of nasoduodenal tube feeding with “gastric rest.” When not successful, a percutaneous endoscopic gastrostomy with jejunal extension (PEG‐J) for long‐term enteral feeding is placed. Aim To evaluate the effect of this stepwise approach on weight and symptoms. Methods Analyses of data of all referred gastroparesis patients between 2008 and 2016. Key Results A total of 86 patients (71% female, 20‐87 years [mean 55.8 years]) were analyzed of whom 50 (58%) had adequate symptom responses to diet and prokinetics. The remaining 36 (decompensated gastroparesis) were treated with three months gastric rest. Symptom response rate was 47% (17/36). Significant weight gain was seen in all patients, independent of symptom response. In the remaining 19 symptom non‐responders, the enteral feeding was continued through PEG‐J. Treatment was effective (symptoms) in 37%, with significant weight gain in all. In 84% of patients, the PEG‐J is still in use (mean duration 962 days). Conclusions and Inferences Following a stepwise treatment approach in gastroparesis, adequate symptom response was reached in 86% of all patients. Weight gain was achieved in all patients, independent of symptom response. Diet and prokinetics were effective with regard to symptoms in 58%, temporary gastric rest in 47%, and PEG‐J as third step in 37% of patients.

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“…Intravenously (no longer available), and at high oral doses, domperidone can inhibit the human Ether-a-go-go-Related Gene (hERG) gene which has been shown to cause QT prolongation in in vitro studies. 24,25 Clinical studies have been conflicting, with retrospective population data showing a correlation between domperidone use and cardiac arrhythmias, including sudden cardiac death. 26 Prospective clinical trials have not found similar effects.…”

Section: Domperidonementioning

confidence: 99%

Practical management approach to gastroparesis

Longley

2020

Internal Medicine Journal

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Gastroparesis is a syndrome characterised by delayed gastric emptying in the absence of mechanical obstruction. Symptoms can include early satiety, abdominal pain, bloating, vomiting and regurgitation which cause significant morbidity in addition to nutritional deficits. There is a higher prevalence in diabetics and females, but the incidence in the Australian population has not been well studied. Management of gastroparesis involves investigating and correcting nutritional deficits, optimising glycaemic control and improving gastrointestinal motility. Symptom control in gastroparesis can be challenging. Nutritional deficits should be addressed initially through dietary modification. Enteral feeding is a second‐line option when oral intake is insufficient. Home parenteral nutrition is rarely used, and only accessible through specialised clinics in the outpatient setting. Prokinetic medication classes that have been used include dopamine receptor antagonists, motilin receptor agonists, 5‐HT4 receptor agonists and ghrelin receptor agonists. Anti‐emetic agents are often used for symptom control. Interventional treatments include gastric electrical stimulation, gastric per‐oral endoscopic myotomy, feeding jejunostomy and gastrostomy/jejunstomy for gastric venting and enteral feeding. In this article we propose a framework to manage gastroparesis in Australia based on current evidence and available therapies.

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Cardiovascular safety of prokinetic agents: A focus on drug‐induced arrhythmias

Cited by 54 publications

References 134 publications

A Novel Approach in Spinal Cord Stimulation for Enhancing Gastric Motility: A Preliminary Study on Canines

A Novel Approach in Spinal Cord Stimulation for Enhancing Gastric Motility: A Preliminary Study on Canines

Therapeutic strategies in gastroparesis: Results of stepwise approach with diet and prokinetics, Gastric Rest, and PEG‐J: A retrospective analysis

Practical management approach to gastroparesis

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