Frank Zerbib; Mireille SimonDisclosures
Expert Rev Clin Pharmacol. 2012;5(5):533-541.
Approximately 20–30% of patients with gastro–esophageal reflux symptoms report inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms involved are failure of the antireflux barrier (transient lower esophageal sphincter relaxations), high proximal extent of the refluxate, esophageal hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid reflux can be demonstrated in 40–50% of cases, suggesting that there is room for antireflux therapy in these patients. New antireflux compounds have been shown to decrease the occurrence of transient lower esophageal sphincter relaxations. The most promising classes of compounds are GABA type B agonists and metabotropic glutamate receptor 5 antagonists, which can reduce both reflux episodes and symptoms, but the development of these compounds has been abandoned for either safety issues or lack of efficacy. Esophageal hypersensitivity and impaired mucosal integrity may prove to be relevant therapeutic targets in the future.
Gastro–esophageal reflux disease (GERD) is a common disorder caused by the reflux of gastric contents into the esophagus. According to a recent global definition, GERD can cause esophageal and extra-esophageal syndromes, which can be associated or not in the same individual. The diagnosis of GERD can rely on typical symptoms such as heartburn and regurgitation as well as the presence of esophageal mucosal breaks at endoscopy. GERD management is primarily based on empiric therapy, with lifestyle modifications and medication, especially in general practice. Experimental and pH studies have demonstrated the major role of the acidic component of the refluxate in the pathogenesis of symptoms and mucosal damage. This is confirmed by the remarkable efficacy of proton-pump inhibitors (PPIs) for mucosal healing and symptom relief. However, although there is no consensus on the definition of failure, 30–40% of patients with reflux symptoms do not achieve adequate symptom relief after a 4-week course of a single dose of PPI. Most of these patients belong to the so-called nonerosive reflux disease (NERD) subgroup.[5,6]
Although failure of PPIs is one of the most common indications for antireflux surgery, it is generally considered by experts that antireflux surgery in these patients has a less favorable clinical outcome compared with that obtained in patients with adequate PPI symptom control.[4,7] Indeed, many patients with refractory symptoms do not have GERD, but suffer from functional heartburn or dyspepsia; however, studies with 24-h esophageal pH-impedance monitoring showed that 40–50% of patients have symptoms that are associated with persisting acid or nonacid reflux events.[8,9] These results demonstrate that, in a substantial group of patients with GERD, there is room for therapies that can restore an efficient antireflux barrier. Nevertheless, it is crucial to consider that an impaired antireflux barrier is far from being the only mechanism involved in the pathophysiology of refractory GERD. The other potential targets are an improved control of gastric acid secretion, limitation of proximal extent of the refluxate, modulation of esophageal hypersensitivity and restoration of esophageal mucosal integrity.
Expert Rev Clin Pharmacol. 2012;5(5):533-541. © 2012 Expert Reviews Ltd.
|Nitric oxide synthase||L-NAME and L-NMMA||Inhibitor||Dog and human|
|CCK1 receptor||Loxiglumide and devazepide||Antagonist||Dog and human|
|µ opioid receptor||Morphine||Agonist||Human|
|CB1 receptor||WIN55, 212-2, Δ-9-tetrahydrocannabinol||Agonist||Dog, ferret and human|
|mGluR5 receptor||MTEP and MPEP ADX10059 and AZD2066||Antagonist||Dog, ferret and human|
|GABAB receptor||Baclofen |
|Agonist||Dog, ferret, cat and human|
Acid Reflux And High Levels Of Amylase Acid Reflux (☑ Warnings) | Acid Reflux And High Levels Of Amylase To Avoidhow to Acid Reflux And High Levels Of Amylase for GABAB: GABA type B; L-NAME: L-NG-nitroarginine methyl ester; L-NMMA: L-NG-monomethylarginine; mGluR5: Metabotropic glutamate receptor 5; MPEP: 2-methyl-6-(phenylethynyl)-pyridine; MTEP: 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine.
Acid Reflux And High Levels Of Amylase Soothe The Pain (🔴 To Avoid) | Acid Reflux And High Levels Of Amylase Treatmentshow to Acid Reflux And High Levels Of Amylase for Frank Zerbib*1,2 and Mireille Simon1,2
1CHU Bordeaux, Saint André Hospital, Gastroenterology Department, Bordeaux, F-33075, France
2Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France
Financial & competing interests disclosure
F Zerbib has served as a speaker, a consultant and an advisory board member for Addex Pharma SA, Xenoport, Shire-Movetis, Norgine, Sanofi Aventis, Astrazeneca, Janssen Cilag, Renckitt Benckiser, Abbott, Pfizer and Given Imaging. M Simon has no interests to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
*Author for correspondence
Tel.: +33 5 56 79 58 06 Fax: +33 5 56 79 47 81 [email protected]
Approximately 30% of gastro–esophageal reflux disease (GERD) patients are refractory to proton-pump inhibitor therapy.
The majority of patients with persisting GERD symptoms despite proton-pump inhibitors do not have reflux-associated symptoms. Persisting reflux can be demonstrated in only 40–50% of these patients.
Transient lower esophageal sphincter relaxations represent the most prevalent mechanism of all types of reflux episodes and represent a relevant target for antireflux therapy.
The other factors associated with refractory GERD are: high proximal extent of the refluxate, esophageal hypersensitivity and impaired esophageal mucosal integrity.
Transient lower esophageal sphincter relaxation inhibitors such as GABA type B agonists and mGluR5 inhibitors have been shown to decrease GERD episodes and improve reflux-related symptoms. However, the development of these compounds has been halted for either safety issues or lack of efficacy.
Preliminary data suggest that pain modulators and agents with mucosal protective properties should be tested in patients with suspected esophageal hypersensitivity.