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Varghese C, Van Hove S, Schamberg G, Wu B, Poonawala N, Law M, Dachs N, Johnston G, Fitt I, Foong D, Parkman HP, Abell T, Ho V, Calder S, Gharibans AA, Andrews CN, O'Grady G. Predicting symptomatic response to prokinetic treatment using Gastric Alimetry. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.01.30.25321436. [PMID: 39973985 PMCID: PMC11838638 DOI: 10.1101/2025.01.30.25321436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Background Chronic neurogastroduodenal disorders are challenging to manage, with therapy often initiated on a trial and error basis. Prokinetics play a significant role in management, but responses are variable and have been associated with adverse events, impacting widespread use. We investigated whether body surface gastric mapping (BSGM) biomarkers (using Gastric Alimetry ® ) could inform patient selection for prokinetic therapy. Methods Patients with chronic gastroduodenal symptoms taking oral prokinetic, regardless of gastric emptying status, were prospectively recruited and underwent BSGM (30 m baseline, 482 kcal standardised meal, 4 h postprandial recording) whilst off prokinetic. Patients were followed up with daily symptom diaries. A subset was compared to matched patients not taking prokinetics. Prokinetic responders were defined based on symptom improvement greater than a minimum clinically important difference methodology. Key Results 42 patients (88% female; median age 36; median BMI 26) taking prokinetics were analysed. Prokinetic prescribing, compared to matched patients, was independent of BSGM metrics (p>0.15). In patients on existing prokinetics (withheld for BSGM), lower amplitudes predicted reduced symptom burden, whereas low rhythm stability predicted a worse symptom burden (p<0.05). In prokinetic-naive patients (i.e. started on a prokinetic during the study), a lower postprandial amplitude predicted responders (mean 37.5±10.6 uV in responders [n=5] vs mean 54.8±6.6 uV among non-responders [n=3], p=0.047). Conclusions Gastric Alimetry biomarkers may help in the prediction of prokinetic response in patients with chronic gastroduodenal symptoms. Lower post-prandial amplitudes, indicating a reduced meal response, appear to predict benefit, whilst impaired rhythm stability predicted poorer therapeutic response.
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Bell DSH. Detecting and treating the protean manifestations of diabetic autonomic neuropathy. Diabetes Obes Metab 2023; 25:1162-1173. [PMID: 36748121 DOI: 10.1111/dom.15004] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/17/2023] [Accepted: 02/02/2023] [Indexed: 02/08/2023]
Abstract
The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic.
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Gastroparesis in pregnancy. Am J Obstet Gynecol 2022; 228:382-394. [PMID: 36088986 DOI: 10.1016/j.ajog.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 08/21/2022] [Accepted: 09/05/2022] [Indexed: 01/30/2023]
Abstract
Gastroparesis is a functional gastrointestinal disorder that more commonly affects women, with most cases being diagnosed during childbearing age. However, there is a paucity of data and guidelines to specifically highlight the epidemiology, disease course, maternal and fetal impact, and the management of existing gastroparesis during pregnancy. Apart from metoclopramide, there is no approved therapy specifically indicated for gastroparesis. More importantly, pregnant and breastfeeding women are excluded from clinical trials evaluating pharmacologic agents in the management of gastroparesis. This poses a real challenge to healthcare providers in counseling and managing patients with gastroparesis. In this systematic review, we summarize the current available literature and the knowledge gaps in the impact of pregnancy on gastroparesis and vice versa. We also highlight the efficacy and safety profiles of available pharmacologic and nonpharmacologic therapies in the management of patients with gastroparesis, with emphasis on judicious use of dietary approaches that are deemed relatively safe during pregnancy.
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Tendulkar P, Kant R, Rana S, Yadav P, Mirza AA, Agarwal D. Efficacy of Pro-Kinetic Agents in Type 2 Diabetes Mellitus Patients With Gastroparesis Using Lactulose Hydrogen Breath Testing: A Randomized Trial. Cureus 2022; 14:e20990. [PMID: 35154966 PMCID: PMC8817741 DOI: 10.7759/cureus.20990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/06/2022] [Indexed: 11/08/2022] Open
Abstract
Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.
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Asha MZ, Khalil SFH. Pharmacological Approaches to Diabetic Gastroparesis: A systematic review of randomised clinical trials. Sultan Qaboos Univ Med J 2019; 19:e291-e304. [PMID: 31897312 PMCID: PMC6930032 DOI: 10.18295/squmj.2019.19.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 07/10/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023] Open
Abstract
Pharmacological interventions of diabetic gastroparesis (DG) constitute an essential element of a patient’s management. This article aimed to systematically review the available pharmacological approaches of DG, including their efficacy and safety. A total of 24 randomised clinical trials (RCTs) that investigated the efficacy and/or safety of medications targeting DG symptoms were identified using several online databases. Their results revealed that metoclopramide was the only approved drug for accelerating gastric emptying and improving disease symptoms. However, this medication may have several adverse effects on the cardiovascular and nervous systems, which might be resolved with a new intranasal preparation. Acceptable alternatives are oral domperidone for patients without cardiovascular risk factors or intravenous erythromycin for hospitalised patients. Preliminary data indicated that relamorelin and prucalopride are novel candidates that have proven to be effective and safe. Future RCTs should be conducted based on unified guidelines using universal diagnostic modalities to reveal reliable and comprehensive outcomes.
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Affiliation(s)
- Mohammad Z Asha
- Department of Internal Medicine, Dr Mohamad Amine Zbeib Polyclinic, Doha, Qatar
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Abstract
PURPOSE OF REVIEW Gastroparesis remains a difficult-to-treat disease with limited therapeutic options. Though patients often have a common syndrome of stereotypic symptoms, the underlying pathophysiology is heterogeneous, often leading to variable treatment responses. Due to limitations in medical and surgical therapies, endoscopic options have been increasingly explored. These options can be broadly categorized into pyloric-directed therapy, non-pyloric-directed therapy, and nutritional support. In this review, we will highlight current and emerging endoscopic options, such as gastric per-oral endoscopic myotomy (G-POEM). RECENT FINDINGS Early retrospective studies on G-POEM offer encouraging results up to one year out, with an acceptable safety profile. Other pyloric-directed therapies, such as pyloric dilation and stenting, have also been explored. While emerging endoscopic therapeutic options are encouraging, efficacy will likely depend on a better characterization of underlying pathophysiology and improved patient selection. Future prospective, controlled studies are needed.
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Affiliation(s)
- Andrew Su
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 10945 Le Conte Avenue, Suite 2114, Los Angeles, CA, 90095, USA.
| | - Jeffrey L Conklin
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 10945 Le Conte Avenue, Suite 2114, Los Angeles, CA, 90095, USA.,Gastrointestinal Motor Function Laboratory, UCLA, Los Angeles, CA, USA
| | - Alireza Sedarat
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 10945 Le Conte Avenue, Suite 2114, Los Angeles, CA, 90095, USA
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7
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Abstract
PURPOSE OF REVIEW The goal of this review is to review the current status of prokinetics and to place it in historical context. Impaired motility and thus propulsion have long been thought to play important roles in the pathogenesis of a number of gastrointestinal disorders including gastroesophageal reflux disease (GERD), gastroparesis, chronic idiopathic pseudo-obstruction, and constipation. Historically, disordered motility was also thought to contribute to a number of functional gastrointestinal disorders such as functional dyspepsia (FD) and irritable bowel syndrome (IBS). RECENT FINDINGS As we learn more of the pathophysiology of FD, IBS, GERD, constipation, and gastroparesis, the limitations of a therapeutic strategy based on the stimulation of motility (i.e., the use of a prokinetic) have become apparent and the disappointments of the past explained. The development of prokinetic drugs has also been hampered by the non-selective nature of many of the agents studied to date which resulted in some unexpected side effects. There is still an unmet need for an effective and safe prokinetic, but drug development in this area must be mindful of the challenges of the area and the need for selectivity for a given target receptor.
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Affiliation(s)
- Eamonn M M Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Houston, TX, USA.
- Division of Gastroenterology and Hepatology, The Methodist Hospital, 6550 Fannin St, SM 1201, Houston, TX, 77030, USA.
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Yin J, Xu X, Song G, Han HS, Kim HW, Chen JDZ. Prokinetic effects of a new 5-HT 4 agonist, YKP10811, on gastric motility in dogs. J Gastroenterol Hepatol 2017; 32:625-630. [PMID: 27418395 DOI: 10.1111/jgh.13490] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/10/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIM Prokinetics have been considered the first-line medicine for treating delayed gastric emptying. The aim of this study was to explore the effects and mechanisms of a new 5-HT4 receptor agonist, YKP10811, on gastric motility in dogs. METHODS Four experiments were performed in dogs: (i) dose-response effects of YKP10811 on liquid gastric emptying; (ii) effects and mechanisms of YKP10811 on solid gastric emptying delayed by glucagon; (iii) effects of low-dose YKP10811 on antral contractions; and (iv) effects of low-dose YKP10811 on gastric accommodation. RESULTS No adverse events or cardiac dysrhythmia was noted. (i) High-dose YKP10811 (30 mg/kg) accelerated liquid gastric emptying from 15 to 90 min without inducing adverse events or cardiac dysrhythmia. YKP10811 at low doses (0.3, 1, and 3 mg/kg) accelerated gastric emptying in a dose-dependent manner. (ii) YKP10811 (0.1 mg/kg), but not tegaserod (0.3 mg/kg), significantly accelerated glucagon-induced delayed gastric emptying of solid, and the effect was completely blocked by GR113808. (iii) YKP10811 (0.3 mg/kg) enhanced antral contractions. (iv) YKP10811 did not alter gastric accommodation. CONCLUSIONS YKP10811 seems to improve antral contractions and accelerate gastric emptying without altering gastric accommodation in dogs via the 5-HT4 mechanism and is substantially more potent than tegaserod. No adverse events were noted at a dose 300 times the lowest effective dose. YKP10811 may have a therapeutic potential for gastroparesis.
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Affiliation(s)
- Jieyun Yin
- Division of Gastroenterology, University of Texas Medical Branch, Galveston, Texas, USA.,VA Medical Center, Veterans Research and Education Foundation, Oklahoma, Oklahoma, USA
| | - Xiaohong Xu
- VA Medical Center, Veterans Research and Education Foundation, Oklahoma, Oklahoma, USA
| | - Gengqing Song
- VA Medical Center, Veterans Research and Education Foundation, Oklahoma, Oklahoma, USA
| | - Hyun Sil Han
- Non-Clinical Development Group, Division of Pharm Development, SK Life Science, Inc., Fair Lawn, New Jersey, USA
| | - Hong Wook Kim
- Non-Clinical Development Group, Division of Pharm Development, SK Life Science, Inc., Fair Lawn, New Jersey, USA
| | - Jiande D Z Chen
- Division of Gastroenterology, University of Texas Medical Branch, Galveston, Texas, USA
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9
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Lee MC, Ha W, Park J, Kim J, Jung Y, Kim BJ. Effects of Lizhong Tang on gastrointestinal motility in mice. World J Gastroenterol 2016; 22:7778-7786. [PMID: 27678361 PMCID: PMC5016378 DOI: 10.3748/wjg.v22.i34.7778] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 06/07/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of Lizhong Tang, a traditional Chinese medicine formula, on gastrointestinal motility in mice.
METHODS The in vivo effects of Lizhong Tang on GI motility were investigated by measuring the intestinal transit rates (ITRs) and gastric emptying (GE) values in normal mice and in mice with experimentally induced GI motility dysfunction (GMD).
RESULTS In normal ICR mice, the ITR and GE values were significantly and dose-dependently increased by Lizhong Tang (ITR values: 54.4% ± 1.9% vs 65.2% ± 1.8%, P < 0.01 with 0.1 g/kg Lizhong Tang and 54.4% ± 1.9% vs 83.8% ± 1.9%, P < 0.01 with 1 g/kg Lizhong Tang; GE values: 60.7% ± 1.9% vs 66.8% ± 2.1%, P < 0.05 with 0.1 g/kg Lizhong Tang and 60.7% ± 1.9% vs 72.5% ± 1.7%, P < 0.01 with 1 g/kg Lizhong Tang). The ITRs of the GMD mice were significantly reduced compared with those of the normal mice, which were significantly and dose-dependently reversed by Lizhong Tang. Additionally, in loperamide- and cisplatin-induced models of GE delay, Lizhong Tang administration reversed the GE deficits.
CONCLUSION These results suggest that Lizhong Tang may be a novel candidate for development as a prokinetic treatment for the GI tract.
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Abstract
Constipation is common in the general population and for those on opioids and/or who are suffering from advanced cancer. Self-management consists of dietary changes, exercise, and laxatives. However, responses to self-management efforts are often inadequate to relieve the subjective and objective experience of constipation. Multiple new anti-constipating medications have recently been tested in randomized trials and the following are available commercially: probiotics, prucalopride, lubiprostone, linaclotide, elobixibat, antidepressants, methylnaltrexone, alvimopan, and naloxegol. This review will discuss the evidence-based benefits of these medications and outline an approach to managing constipation.
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Affiliation(s)
- Mellar Davis
- Cleveland Clinic Lerner School of Medicine Case, Western Reserve University, 9500 Euclid Avenue, T34, Cleveland, OH, 44195, USA.
- Clinical Fellowship Program, Cleveland, OH, USA.
- Palliative Medicine and Supportive Oncology Services, Taussig Cancer Institute, Cleveland, OH, USA.
| | - Pamela Gamier
- Cleveland Clinic Lerner School of Medicine Case, Western Reserve University, 9500 Euclid Avenue, T34, Cleveland, OH, 44195, USA
- Clinical Fellowship Program, Cleveland, OH, USA
- Palliative Medicine and Supportive Oncology Services, Taussig Cancer Institute, Cleveland, OH, USA
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11
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Quigley EMM. Prokinetics in the Management of Functional Gastrointestinal Disorders. J Neurogastroenterol Motil 2015; 21:330-6. [PMID: 26130629 PMCID: PMC4496896 DOI: 10.5056/jnm15094] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 06/23/2015] [Indexed: 12/12/2022] Open
Abstract
A variety of common and some not common gastrointestinal syndromes are thought to be based on impaired gut motility. For some, the role of motility is well defined, for others and the functional gastrointestinal disorders, in particular, the role of hypo- or dysmotility remains unclear. Over the years pharmacological and physiological laboratories have developed drugs which stimulate gut motility; many have been evaluated in motility and functional disorders with what can best be described as mixed results. Lack of receptor specificity and resultant expected and unexpected adverse events have led to the demise of some of these agents. Newer, more selective agents offer promise but the heterogeneity of the clinical disorders they target continues to pose a formidable challenge to drug development in this area.
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Affiliation(s)
- Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Department of Medicine, Houston Methodist Hospital, Houston, Texas, USA
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12
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Abstract
PURPOSE OF REVIEW The gastrointestinal tract is the most common extra-cutaneous organ system involved with systemic sclerosis (SSc) affecting approximately 90% of patients. This review summarizes the recent advances in the evaluation and management of gastrointestinal manifestations of SSc. RECENT FINDINGS There is a growing body of evidence that uncontrolled GERD can play a significant role in the pathogenesis of SSc-associated interstitial lung disease. Newer forms of management of Barrett esophagus are showing significant promise as potentially curative therapy. Gastric antral vascular ectasias have strongly been associated with the presence of RNA polymerase III antibody. Newer technologies have advanced the assessment of gastrointestinal dysmotility in SSc. Evidence of probiotic use for the treatment of gastrointestinal complications is emerging. The UCLA SCTC GIT 2.0 questionnaire is being increasingly accepted by the SSc experts as a validated instrument for evaluation of patient-reported outcomes involving the gastrointestinal tract. SUMMARY Our knowledge of the complex pathogenesis of gastrointestinal manifestations of SSc has expanded substantially in the last few decades. There has also been considerable technological progress in the evaluation of these manifestations. Patient care is being optimized by close collaboration of rheumatologists and gastroenterologists, leading to a more coordinated approach in the management of these complications.
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Abstract
Gastroparesis is a complication of long-standing type 1 and type 2 diabetes mellitus. Symptoms associated with gastroparesis include early satiety, prolonged postprandial fullness, bloating, nausea and vomiting, and abdominal pain. Mortality is increased in patients with diabetic gastroparesis. A subset of patients with diabetic gastroparesis have pylorospasm that results in obstructive gastroparesis. Current treatment approaches include improving glucose control with insulin and prescribing antinauseant drugs, prokinetic agents, and gastric electric stimulation. Future directions include improved diet counseling based on gastric emptying rate, continuous insulin delivery systems with glucose sensor-augmented monitoring, and drugs for correcting gastric neural and electric abnormalities.
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Affiliation(s)
- Kenneth L Koch
- Section on Gastroenterology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
| | - Jorge Calles-Escandón
- Section on Endocrinology, MetroHealth Regional, Case Western Reserve University School of Medicine, 2500 Metrohealth Drive, Cleveland, OH 44109, USA
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14
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Lee A. Gastroparesis: what is the current state-of-the-art for evaluation and medical management? What are the results? J Gastrointest Surg 2013; 17:1553-6. [PMID: 23801519 DOI: 10.1007/s11605-013-2254-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 06/10/2013] [Indexed: 01/31/2023]
Abstract
Gastroparesis is a chronic motility disorder that leads to delayed gastric emptying and negatively impacts morbidity, mortality, and quality of life. This paper provides an overview of the pathophysiology leading to symptoms in gastroparesis, discusses tests for diagnosis, and examines the evidence behind different treatment options for gastroparesis. Although delayed gastric emptying is the cardinal finding in gastroparesis, other physiologic abnormalities may contribute to the pathogenesis of symptoms. Gastric emptying scintigraphy is considered the gold standard for the diagnosis of gastroparesis but novel tests are currently available. Although metoclopramide is the only FDA approved medication to treat gastroparesis, alternative therapeutic options are available and should be tailored according to symptoms as well as physiologic abnormalities.
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Affiliation(s)
- Allen Lee
- University of Vermont, 111 Colchester Ave, MS 320FL4, Burlington, VT 05401, USA.
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Stevens JE, Jones KL, Rayner CK, Horowitz M. Pathophysiology and pharmacotherapy of gastroparesis: current and future perspectives. Expert Opin Pharmacother 2013; 14:1171-86. [PMID: 23663133 DOI: 10.1517/14656566.2013.795948] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Gastroparesis is an important clinical disorder characterised by delayed gastric emptying in the absence of mechanical outlet obstruction. Idiopathic, diabetes and postsurgical causes represent the most common aetiologies. The condition commonly manifests as upper gastrointestinal symptoms, including nausea, vomiting, postprandial fullness, early satiety, abdominal pain and bloating. AREAS COVERED This paper provides a review of the prevalence, pathophysiology and clinical features associated with gastroparesis, with a particular focus on current pharmacological management options and novel and emerging therapies. A literature search was undertaken using the search terms: gastroparesis, diabetic gastroparesis, idiopathic gastroparesis, gastric emptying, prokinetic, metoclopramide, domperidone, erythromycin, motilin, alemcinal, KC11458, mitemcinal, ghrelin, TZP-101, TZP-102, RM-131, tegaserod, prucalopride, naronapride, velusetrag, levosulpiride, itopride, botulinum toxin, gastric electrical stimulation, Enterra. EXPERT OPINION Strategies for the management of gastroparesis include correction of malnutrition, dehydration and electrolyte imbalance, relief of symptoms by appropriate use of prokinetic and antiemetic agents and, in patients with gastroparesis associated with diabetes or critical illness-induced hyperglycaemia, optimisation of glycaemic control. Conventional prokinetic agents form the mainstay of treatment. While novel pharmacotherapies are in development, compelling evidence for their efficacy, particularly in symptom relief, remains to be established.
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Affiliation(s)
- Julie E Stevens
- University of South Australia, School of Pharmacy and Medical Sciences, Adelaide, Australia.
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Timratana P, El-Hayek K, Shimizu H, Kroh M, Chand B. Laparoscopic gastric electrical stimulation for medically refractory diabetic and idiopathic gastroparesis. J Gastrointest Surg 2013; 17:461-70. [PMID: 23288718 DOI: 10.1007/s11605-012-2128-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Accepted: 07/19/2012] [Indexed: 01/31/2023]
Abstract
BACKGROUND Gastric electrical stimulator (GES) implantation is effective in certain patients with gastroparesis; however, laparotomy is often employed for placement. The aim of this study is to review outcomes of patients who underwent laparoscopic GES therapy for diabetic and idiopathic gastroparesis at a large referral center. METHODS Patients who underwent GES (Enterra Therapy System; Medtronic, Minneapolis, MN) implantation with subsequent interrogation and programming between March 2001 and November 2011 were analyzed. RESULTS A total of 113 patients underwent GES placement or revision during the study period. One hundred eleven patients underwent primary GES at our institution, while two patients underwent GES generator revision at our institution. Primary operations were completed laparoscopically in 110 of 111 cases, with one conversion to laparotomy due to severe adhesions. At a mean follow-up of 27 months (1-113), symptom improvement was achieved in 91 patients (80 %) and was similar for both the diabetic and idiopathic subgroups. Need for supplemental nutrition (enteral and/or parental) decreased in both groups. CONCLUSIONS GES placement is feasible using a laparoscopic approach. Medical refractory gastroparesis in the diabetic and idiopathic groups had significant symptom improvement with no difference between the two groups. Need for supplemental nutrition is decreased following GES.
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Affiliation(s)
- P Timratana
- Cleveland Clinic, Bariatric and Metabolic Institute, Cleveland, OH 44195, USA.
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17
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Idiopathic gastroparesis: case report and literature review of diagnostic and treatment modalities. Am J Ther 2013; 20:111-7. [PMID: 21799394 DOI: 10.1097/mjt.0b013e31820543e7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Gastroparesis is a disorder characterized by a delay in gastric emptying of a meal in the absence of a mechanical gastric outlet obstruction. The most common etiologies include diabetes, postsurgical and idiopathic. Idiopathic Gastroparesis is at least as common as diabetic Gastroparesis in most case series. Diagnosis of Gastroparesis is based on the presence of symptoms such as nausea, vomiting, postprandial abdominal fullness, and on an objectively determined delay in gastric emptying. The true prevalence of Gastroparesis is unknown. Gastric emptying can be assessed by scintigraphy and stable isotope breath tests. Management of Gastroparesis consists of dietary and lifestyle measures, possible pharmacological interventions (prokinetics, antiemetics, intrapyloric botulinum toxin injection) and/or interventions that focus on adequate nutrient intake either through a nasoduodenal tube, percutaneous gastrostomy, or jejunostomy. New advances in drug therapy and gastric electrical stimulation techniques have been introduced and might provide new hope to patients. Presented here is an interesting case of idiopathic Gastroparesis along with its management and review of the literature.
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18
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Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. Clinical guideline: management of gastroparesis. Am J Gastroenterol 2013; 108:18-37; quiz 38. [PMID: 23147521 PMCID: PMC3722580 DOI: 10.1038/ajg.2012.373] [Citation(s) in RCA: 720] [Impact Index Per Article: 60.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This guideline presents recommendations for the evaluation and management of patients with gastroparesis. Gastroparesis is identified in clinical practice through the recognition of the clinical symptoms and documentation of delayed gastric emptying. Symptoms from gastroparesis include nausea, vomiting, early satiety, postprandial fullness, bloating, and upper abdominal pain. Management of gastroparesis should include assessment and correction of nutritional state, relief of symptoms, improvement of gastric emptying and, in diabetics, glycemic control. Patient nutritional state should be managed by oral dietary modifications. If oral intake is not adequate, then enteral nutrition via jejunostomy tube needs to be considered. Parenteral nutrition is rarely required when hydration and nutritional state cannot be maintained. Medical treatment entails use of prokinetic and antiemetic therapies. Current approved treatment options, including metoclopramide and gastric electrical stimulation (GES, approved on a humanitarian device exemption), do not adequately address clinical need. Antiemetics have not been specifically tested in gastroparesis, but they may relieve nausea and vomiting. Other medications aimed at symptom relief include unapproved medications or off-label indications, and include domperidone, erythromycin (primarily over a short term), and centrally acting antidepressants used as symptom modulators. GES may relieve symptoms, including weekly vomiting frequency, and the need for nutritional supplementation, based on open-label studies. Second-line approaches include venting gastrostomy or feeding jejunostomy; intrapyloric botulinum toxin injection was not effective in randomized controlled trials. Most of these treatments are based on open-label treatment trials and small numbers. Partial gastrectomy and pyloroplasty should be used rarely, only in carefully selected patients. Attention should be given to the development of new effective therapies for symptomatic control.
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Affiliation(s)
- Michael Camilleri
- Department of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA.
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19
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Abstract
Within the last 50 years, diabetic gastroparesis has become a well recognized complication of type 1 and type 2 diabetes. It is a syndrome characterized by abnormal gastric function, resulting in delayed emptying of the stomach in the absence of any evident mechanical obstruction, predominantly manifested by early satiety, postprandial fullness, nausea, vomiting, and weight loss. The past five years have shown significant advances in its pathophysiology and in new diagnostic tests. Prokinetic medications remain the therapeutic focus for improving clinical symptoms of gastroparesis through enhanced gastric emptying. This article summarizes the present knowledge of prokinetics, with emphasis on medications currently available, as well as drugs under clinical investigation, including some agents in advanced clinical trials that are likely to be used in the treatment of diabetic gastroparesis in the future. These include the ghrelin agonists and newer 5-HT4 agonists devoid of cardiac side effects.
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Affiliation(s)
- Reza A Hejazi
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, 79905, USA.
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20
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Abstract
AIM The aim of the present study was to evaluate the effect of amoxicillin/clavulanate (A/C) on gastrointestinal motility. METHODS Twenty consecutive pediatric patients referred for antroduodenal manometry received 20 mg/kg of A/C into the small bowel lumen. In 10 patients (group A), A/C was given 1 hour after and in 10 (group B), 1 hour before ingestion of a meal. Characteristics of the migrating motor complex, including presence, frequency, amplitude, and propagation of duodenal phase III and phase I duration and phase II motility index (MI), were evaluated 30 minutes before and after A/C administration. RESULTS There were no statistically significant differences in age and sex between the 2 groups. Manometry studies were considered normal in 8 patients in each group. In group A, 2 patients developed duodenal phase III after receiving A/C, and no significant difference was found in the MI before and after the drug administration. In group B, 9 patients developed duodenal phase III (P <0.05 vs group A). All phase III occurred within a few minutes from the medication administration. Most duodenal phase III contractions were preceded by an antral component during fasting but never after the medication was administered in either of the 2 groups (P<0.001 vs fasting). In group B, the duration of duodenal phase I was shorter after drug administration (P<0.05). There was no significant difference in duodenal phase II MI before and after A/C administration for the 2 study groups. CONCLUSIONS In children, administration of A/C directly into the small bowel before a meal induces phase III-type contractions in the duodenum, with characteristics similar to those present in the fasting state. These data suggest the possible use of A/C as a prokinetic agent. Further studies are needed to clarify its specific mechanism of action and the group of patients most likely to benefit from its use.
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21
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Bernardo-Escudero R, Alonso-Campero R, de Jesús Francisco-Doce MT, Cortés-Fuentes M, Villa-Vargas M, Angeles-Uribe J. Comparison of the pharmacokinetics of a new 15-mg modified-release tablet formulation of metoclopramide versus a 10-mg immediate-release tablet: a single- and multiple-dose, randomized, open-label, parallel-group study in healthy Mexican male volunteers. Clin Ther 2011; 33:630-43. [PMID: 21665047 DOI: 10.1016/j.clinthera.2011.04.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2011] [Indexed: 10/18/2022]
Abstract
BACKGROUND Metoclopramide is a prokinetic and antiemetic agent. OBJECTIVE The goal of this study was to assess the pharmacokinetics of a new, modified-release metoclopramide tablet and compare it with an immediate-release tablet to obtain marketing approval from the Mexican regulatory agency. METHODS This was a single-center, randomized, open-label, parallel-group, single- and multiple-dose, pharmacokinetic study. Investigational products were administered to healthy Mexican male volunteers for 3 consecutive days: one 15-mg modified-release tablet every 12 hours or one 10-mg immediate-release tablet every 8 hours. Multiple blood samples were collected after the first and last doses of metoclopramide over a 24-hour period. Plasma metoclopramide concentrations were determined by using a validated HPLC method. Safety and tolerability were assessed by measurement of vital signs, clinical evaluations, and spontaneous reports from study subjects. RESULTS All 26 subjects were included in the analyses (mean [SD] age: 25 [6] years [range, 18-40 years]; body mass index, 23.44 [2.31] kg/m(2) [range, 18.26-27.49 kg/m2]). Peak plasma concentrations were lower (C(max), 33.13 [7.25] vs 46.04 [17.27] ng/mL after the first dose [P < 0.05]; C(max,ss), 48.60 [8.52] vs 75.23 [21.27] ng/mL after the last dose [P < 0.05]) and occurred later (P < 0.05) with the modified-release formulation. In terms of average plasma concentrations (C(avgτ), 20.98 [3.94] vs 23.38 [7.35] ng/mL after the first dose; C(avg,ss), 22.20 [5.64] vs 23.02 [7.77] ng/mL after the last dose), differences did not reach the level of statistical significance (P > 0.05). Four adverse events were reported in the test group (abdominal distention [n = 2], epigastric pain [n = 1], and somnolence [n = 1]), and 3 were reported in the reference group (epigastric pain [n = 1], diarrhea [n = 1], and hiccups [n = 1]). CONCLUSIONS This study in a sample of selected healthy Mexican male volunteers suggests that the metoclopramide15-mg modified-release tablets have features compatible with the slow-release formulation (lower C(max) and longer T(max)) compared with immediate-release tablets.
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Affiliation(s)
- Roberto Bernardo-Escudero
- Asociación Mexicana para la Investigación Clínica, A.C. (Mexican Association for Clinical Research), Pachuca, Hidalgo, Mexico.
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22
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Abstract
Symptoms suggestive of gastroparesis occur in 5% to 12% of patients with diabetes. Such a complication can affect both prognosis and management of the diabetes; therefore, practicing clinicians are challenged by the complex management of such cases. Gastroparesis is a disorder characterized by a delay in gastric emptying after a meal in the absence of a mechanical gastric outlet obstruction. This article is an evidence-based overview of current management strategies for diabetic gastroparesis. The cardinal symptoms of diabetic gastroparesis are nausea and vomiting. Gastroesophageal scintiscanning at 15-minute intervals for 4 hours after food intake is considered the gold standard for measuring gastric emptying. Retention of more than 10% of the meal after 4 hours is considered an abnormal result, for which a multidisciplinary management approach is required. Treatment should be tailored according to the severity of gastroparesis, and 25% to 68% of symptoms are controlled by prokinetic agents. Commonly prescribed prokinetics include metoclopramide, domperidone, and erythromycin. In addition, gastric electrical stimulation has been shown to improve symptoms, reduce hospitalizations, reduce the need for nutritional support, and improve quality of life in several open-label studies.
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Affiliation(s)
- Badr M. Aljarallah
- Department of Medicine, Gastroenterology Division, King Fahad Specialist Hospital, Faculty of Medicine, Qassim University, Maledia, Saudi Arabia,Address for correspondence: Dr. Badr M. Aljarallah, Department of Medicine, Gastroenterology Division, King Fahad Specialist Hospital, Faculty of Medicine, Qassim University, Maledia - 51452, Saudi Arabia. E-mail:
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23
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Abstract
Gastroparesis is a chronic disorder that affects a significant subset of the population. Diabetes mellitus is a risk factor for the development of gastroparesis. Currently, metoclopramide is the only US FDA-approved medication for the treatment of gastroparesis. However, the FDA recently placed a black-box warning on metoclopramide because of the risk of related side effects, including tardive dyskinesia, the incidence of which has been cited to be as high as 15% in the literature. This review will investigate the mechanisms by which metoclopramide improves the symptoms of gastroparesis and will focus on the evidence of clinical efficacy supporting metoclopramide use in gastroparesis. Finally, we seek to document the true complication risk from metoclopramide, especially tardive dyskinesia, by reviewing the available evidence in the literature. Potential strategies to mitigate the risk of complications from metoclopramide will also be discussed.
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Affiliation(s)
- Allen Lee
- Tufts Medical Center, Boston, MA, USA
| | - Braden Kuo
- Massachusetts General Hospital, Blake 4, 55 Fruit St, Boston, MA 02114, USA
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24
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Waseem S, Moshiree B, Draganov PV. Gastroparesis: Current diagnostic challenges and management considerations. World J Gastroenterol 2009; 15:25-37. [PMID: 19115465 PMCID: PMC2653292 DOI: 10.3748/wjg.15.25] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.
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Stapleton J, Wo JM. Current treatment of nausea and vomiting associated with gastroparesis: antiemetics, prokinetics, tricyclics. Gastrointest Endosc Clin N Am 2009; 19:57-72, vi. [PMID: 19232281 DOI: 10.1016/j.giec.2008.12.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Gastroparesis is a symptomatic chronic disorder characterized by delayed gastric emptying without a mechanical obstruction. Gastroparesis is most often associated with diabetes, gastric surgery, and systemic disorders affecting the neuromuscular control of the stomach. However, no underlying etiology can be found in up to 40% of patients, a condition referred to as idiopathic gastroparesis. Due to the numerous potential etiologies and the highly variable clinical manifestations, the management of gastroparesis is particularly challenging. The purpose of this review is to provide an update on the use of antiemetics, prokinetics, and tricyclics for the treatment for nausea and vomiting associated with gastroparesis.
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Affiliation(s)
- Jeremy Stapleton
- Division of Gastroenterology/Hepatology, Department of Medicine, University of Louisville School of Medicine, 550 S Jackson Street, ACB 3rd floor, Louisville, KY 40202, USA
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26
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Camilleri M, Andresen V, Keller J, Layer P, Montori VM. Pharmacological and non-pharmacological interventions for symptomatic gastroparesis. Hippokratia 2008. [DOI: 10.1002/14651858.cd007116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Michael Camilleri
- Mayo Clinic; Clinical Enteric Neuroscience Translational & Epidemiological Research; Charlton 8110 Rochester Minnesota USA MN 55905
| | - Viola Andresen
- Israelitic Hospital, University of Hamburg; Internal Medicine; Orchideenstieg 14 Hamburg Germany D-22297
| | - Jutta Keller
- Israelitic Hospital, University of Hamburg; Internal Medicine; Orchideenstieg 14 Hamburg Germany D-22297
| | - Peter Layer
- Israelitic Hospital, University of Hamburg; Internal Medicine; Orchideenstieg 14 Hamburg Germany D-22297
| | - Victor M Montori
- Mayo Clinic; Division of Endocrinology, Department of Internal Medicine; 200 1st Street Southwest Rochester MN USA 55905
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27
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Sellin JH, Chang EB. Therapy Insight: gastrointestinal complications of diabetes--pathophysiology and management. ACTA ACUST UNITED AC 2008; 5:162-71. [PMID: 18268523 DOI: 10.1038/ncpgasthep1054] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2007] [Accepted: 12/10/2007] [Indexed: 12/26/2022]
Abstract
Patients with diabetes often have gastrointestinal symptoms, but the extent and severity of this problem and the specificity of the symptoms are not nearly as well defined as frequently assumed. Any part of the gastrointestinal tract can be affected, and the presenting symptoms depend on the composite of dysfunctional elements. Gastroesophageal reflux, Candida esophagitis, gastroparesis, diarrhea and constipation are among the many common gastrointestinal complications of diabetes. No specific risk factor for the development of these complications has been identified and their etiology is most likely to be multifactorial, involving both reversible and irreversible processes. Treatment should be directed at tighter glycemic and symptom control, which can bring about clinical improvement for many patients. For other patients, however, effective clinical management is problematic because no therapies are available to prevent or correct the underlying disease mechanisms. Studies now suggest that reduced levels of key trophic factors cause transdifferentiation of pacemaker interstitial cells of Cajal into a smooth-muscle-like phenotype. If this really is the case, therapies directed at restoring the normal milieu of trophic signals could correct the dysfunction of the interstitial cells of Cajal and resolve many gastrointestinal complications. Advances in stem cell technology also hold promise to provide a cure for diabetes and to correct abnormalities in gastrointestinal pathology.
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Affiliation(s)
- Joseph H Sellin
- Inflammatory Bowel Disease Center at the University of Texas Medical Branch, Galveston, TX, USA
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28
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Friedenberg FK, Parkman HP. Delayed gastric emptying: Whom to test, how to test, and what to do. ACTA ACUST UNITED AC 2006; 9:295-304. [PMID: 16836948 DOI: 10.1007/s11938-006-0011-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Gastroparesis, or delayed gastric emptying, is a common cause of chronic nausea and vomiting as seen in a gastroenterology practice. Diabetic, postsurgical, and idiopathic causes remain the three most common forms of gastroparesis. In addition to nausea and vomiting, symptoms of gastroparesis may include early satiety, postprandial fullness, and abdominal pain. Physiologic changes that may explain symptoms in patients with gastroparesis, in addition to delayed gastric emptying, include impaired fundic accommodation, antral hypomotility, gastric dysrhythmias, pylorospasm, and perhaps visceral hypersensitivity. Diagnosis of gastroparesis is best determined using a radioisotope-labeled solid meal with scintigraphic imaging for at least 2 hours, and preferably 4 hours, postprandially. Most commonly, a 99mTc sulfur colloid-labeled egg sandwich with imaging at 0, 1, 2, and 4 hours is used. Extension of the gastric emptying test to 4 hours improves the accuracy of the test, but unfortunately, this is not commonly performed at many centers. Emptying of liquids remains normal until the late stages of gastroparesis and is less useful. The aims of treatment should be to control symptoms and maintain adequate nutrition and hydration. Patients should be advised to eat small meals and to limit their intake of fat and fiber. Additional dietary recommendations may include increasing caloric intake in the form of liquids. For diabetic patients, control of blood glucose levels is important, as symptom exacerbation is frequently associated with poor glycemic control. Specific treatment often begins with metoclopramide, 10 mg, up to four times daily, after a discussion of possible side effects with the patient. An antiemetic agent, such as prochlorperazine, 5 to 10 mg orally or 25 mg by suppository, can be added on an as-needed basis every 4 to 6 hours to control nausea. If these antiemetic medications are not effective, or if side effects develop, orally dissolving ondansetron, 8 mg every 8 to 12 hours, can be tried on an as-needed basis. If this regimen is unsuccessful, then alternative prokinetic agents--erythromycin, 125 mg, or tegaserod, 6 mg, prior to meals--can be tried. For cases refractory to these treatments, referral to a center with US Food and Drug Administration permission to use domperidone should be considered. Alternatively, symptom modulators such as low-dose tricyclic antidepressants can be tried to reduce symptoms, but these do not improve gastric emptying. In patients for whom all medical therapy fails, other options that are tried at experienced centers include the injection of botulinum toxin into the pylorus, placement of a feeding jejunostomy, and/or placement of a gastric electrical stimulator.
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Affiliation(s)
- Frank K Friedenberg
- Temple University School of Medicine, Gastroenterology Section, Parkinson Pavilion, 8th Floor, 3401 North Broad Street, Philadelphia, PA 19140, USA. henry.parkman@ temple.edu
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Abstract
Gastroparesis refers to chronically abnormal gastric motility characterized by symptoms suggestive of mechanical obstruction and delayed gastric emptying in the absence of mechanical obstruction. It may be idiopathic or attributable to neuropathic or myopathic abnormalities, such as diabetes mellitus, postvagotomy, postviral infection, and scleroderma. Dietary and behavioral modification, prokinetic drugs, and surgical interventions have been used in managing patients with gastroparesis. Although mild gastroparesis is usually well managed with these treatment options, severe gastroparesis may be very difficult to control and may require referral to a specialist center if symptoms are intractable despite pharmacological therapy and dietetic support. New advances in drug therapy, botulinum toxin injection, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. This article critically reviews the advances in the field from the perspective of the clinician.
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Affiliation(s)
- Moo-In Park
- Department of Internal Medicine, College of Medicine, Kosin University, Busan, Korea
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30
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Abstract
Gastrointestinal promotility drugs stimulate smooth muscle contractions to enhance gastric emptying and small and large bowel transit. Currently available drug classes with prokinetic properties include antidopaminergic agents, serotonergic agents, and motilin-receptor agonists. Due to moderate prokinetic effects, poor symptomatic responses and the presence of adverse effects, there is a clear need for new classes of prokinetics. Several newer prokinetic drugs and drug classes are currently under evaluation. Selecting candidate agents and designing the appropriate therapeutic trials is hampered by the lack of insight in the pathophysiology of motility-related symptoms. As gastrointestinal motor disorders are chronic, relapsing, and remitting disorders, it seems desirable that studies with candidate prokinetic drugs establish a long-term efficacy and not only short-term effects on gastrointestinal functions.
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Affiliation(s)
- G Karamanolis
- Center for Gastroenterological Research, KU Leuven, Leuven, Belgium
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31
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Vandenplas Y, Hauser B, Salvatore S. Current pharmacological treatment of gastroparesis. Expert Opin Pharmacother 2005; 5:2251-4. [PMID: 15500371 DOI: 10.1517/14656566.5.11.2251] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The aetiology of gastroparesis differs between children and adults. During childhood, gastroparesis is quite rare, and is mostly seen in preterm infants, with either immaturity of the gastrointestinal tract, or when allergic to cow's milk protein. Acute, delayed gastric emptying may be observed following viral infections. In adults, most patients with gastroparesis are either idiopathic or of diabetic origin. As a consequence, approaches in the treatment of children and adults differ. Metoclopramide, domperidone, cisapride and erythromycin have all been studied. Evidence for benefit is strongest for the latter two drugs, although most studies have methodological shortcomings. From a paediatric perspective, it seems astonishing that more trials with erythromycin analogues have not been performed, as the few data available suggests that these analogues are more powerful, without the side effects of long-term, low-dose administration of antibiotics. Gastric electrical stimulation seems the most promising therapeutic option available at present.
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Affiliation(s)
- Y Vandenplas
- Academic Hospital, Department of pediatrics, VUB, Laarbeeklaan 101, 1090 Brussels, Belgium.
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32
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Dar S, Dalton H. Gastrointestinal drugs. SIDE EFFECTS OF DRUGS ANNUAL 2005:401-414. [DOI: 10.1016/s0378-6080(05)80458-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 2004; 127:1592-622. [PMID: 15521026 DOI: 10.1053/j.gastro.2004.09.055] [Citation(s) in RCA: 489] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
This literature review and the recommendations herein were prepared for the American Gastroenterological Association Clinical Practice Committee. The paper was approved by the Committee on May 16, 2004, and by the AGA Governing Board on September 23, 2004.
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Smith DS, Williams CS, Ferris CD. Diagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction. Gastroenterol Clin North Am 2003; 32:619-58. [PMID: 12858609 DOI: 10.1016/s0889-8553(03)00028-1] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Chronic gastroparesis and CIP are debilitating disorders that are difficult to treat with currently available therapies. Failure of proper migration and differentiation of enteric neurons or ICC can result from specific genetic mutations and lead to phenotypes of CIP with or without concomitant gastroparesis. Intestinal dysfunction in diabetes may reflect a depletion of NO production (and perhaps other neurotransmitters or modulators), which is manifest as a syndrome of gastroparesis, diarrhea, or constipation in individual patients. As the key molecular changes underlying these disorders are defined, clinicians will begin to understand their precise etiology and rational medical therapy may become possible. In the future, testable hypotheses regarding the etiology of other functional bowel disorders (e.g., functional dyspepsia, irritable bowel syndrome, and so forth) may be developed.
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Affiliation(s)
- D Scott Smith
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville Veterans Affairs Medical Center, Nashville, TN 37232, USA
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