Receptors and Signal Transduction Pathways Involved in Autonomic Responses
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Selective inhibitors include rolipram, Ro 20–1724 (Table 13.4) and denbufylline (Table 13.3). Rolipram has undergone clinical evaluation of its antidepressant activity and has been found to be effective in the treatment of major depression. Mood elevation and neuroexcitability associated with enhanced transmitter release in the brain provide a basis for possible application in conditions associated with cerebral ischaemia. Denbufylline and other selective PDE IV inhibitors may have possible applications in senile dementia by elevating mood and improving cognitive function (Nicholson et al. 1991, Thompson 1991). Gastrointestinal side-effects occur, including an increase in gastric acid secretion. Also of major concern with selective PDE IV inhibitors is emesis arising from a central site of action (Murray & England 1992).
Magnitude of the problem
Kathleen M Berg, Dermot J Hurley, James A McSherry, Nancy E Strange, ‘Rose’ in Eating Disorders, 2018
Some patients who have induced vomiting frequently over long periods of time find that they vomit involuntarily, especially after eating larger than usual quantities of food, or vomit on such minimal provocation as hand pressure in the epigastric area. Heartburn can be a common and distressing complaint, especially in bulimia nervosa, when the lower esophageal sphincter, the valve preventing stomach contents from flowing back into the esophagus, becomes dysfunctional. Prokinetic agents (American Psychiatric Association, 2000a) such as domperidone can help by minimizing delayed gastric emptying and/or bowel transit times. H2 blockers, e.g. cimetidine and ranitidine, or proton pump inhibitors, e.g. omeprazole or pantoprazole, may also be helpful by suppressing production of gastric acid.
Perforation of the esophagus
Larry R. Kaiser, Sarah K. Thompson, Glyn G. Jamieson in Operative Thoracic Surgery, 2017
The patient often remains intubated for the first 12-24 hours. Good ventilation and full lung expansion are essential to prevent atelectasis and pneumonia. Full expansion of the lung will prevent further accumulation of pleural fluid, and hopefully the development of an empyema. We are conserva- tive with regards to extubation; if emergency reintubation is necessary, forceful mask ventilation before reintubation increases esophageal pressure and can jeopardize the integ- rity of the closure at the site of the perforation. Depending on the hemodynamic status of the patient, intensive care management may be required during the first few days or for a prolonged length of stay. The nasogastric tube must be carefully cared for and routinely flushed, as draining the stomach and esophagus is imperative. To decrease gastric acid secretion, proton pump inhibitors are administered.
Proton pump inhibitors: use and misuse in the clinical setting
Published in Expert Review of Clinical Pharmacology, 2018
Vincenzo Savarino, Elisa Marabotto, Patrizia Zentilin, Manuele Furnari, Giorgia Bodini, Costanza De Maria, Gaia Pellegatta, Claudia Coppo, Edoardo Savarino
The study of gastric acid secretion has attracted the interest of both physiologists and physicians for many years, because a great number of diseases of the upper gastrointestinal (GI) tract are related to dysfunctions in acid production. Many investigations have documented that gastric acid is produced by both resting and meal-stimulated parietal cells in the stomach, following neurocrine, paracrine, and endocrine stimulation by various substances, such as acetylcholine, histamine, or gastrin, which bind to their specific receptors placed on the basolateral membrane of the above cells [1]. Thereafter, intracellular second messenger systems are activated leading to protein kinase formation and activation of H+/K+ ATPase enzyme (proton pump), which fuse with the secretory canaliculus of the parietal cell resulting in acid production, whereby intracellular hydrogen ions are exchanged for extracellular potassium ions [2]. Once acid is produced, the lower luminal intragastric pH stimulates a feedback mechanism to maintain appropriate homeostatic control of acid secretion. This response is mediated primarily by the paracrine release of somatostatin from gastric antral D cells, which inhibit G cell production of gastrin and enterochromaffin-like (ECL) formation of histamine in order to reverse the stimulus for acid secretion [3].
Proton pump inhibitor usage associates with higher risk of first episodes of pneumonia and peritonitis in peritoneal dialysis patients
Published in Renal Failure, 2022
Yujing Zhang, Jiao Li, Zijun Chen, Lingling Liu, Xiaojiang Zhan, Fenfen Peng, Qian Zhou, Xianfeng Wu, Yingsi Zeng, Liya Zhu, Yuxin Xie, Xiaochun Lai, Zebin Wang, Yueqiang Wen, Xiaoran Feng, Jianbo Liang
The mechanism of PPIs associated with pneumonia may be explained by the following reasons. As we all know, gastric acid acted as an important barrier to prevent pathogens from invading due to its lowering of the PH value of the gastrointestinal tract. PPIs inhibited the secretion of gastric acid mainly by irreversibly binding the H-K-ATPase on the cell membrane of the gastric parietal to inactivate it, thus increasing the pH value of the stomach, which in turn led to the excessive growth and colonization of pathogens [20–22]. And PPIs also reduced the acidity of the upper gastrointestinal tract, which changed the oral flora and further led to respiratory infections [23, 24]. In addition, a basic study in mice has found that the intestinal microbiota acts as a protective mediator during pneumococcal pneumonia, and the gut microbiota enhances the function of primary alveolar macrophages [25]. In a large cohort study of healthy people, it was found that PPI use significantly increased the growth of streptococci [26], while studies on streptococcal pneumonia confirmed that PPIs was associated with an increased risk of CAP caused by streptococcus pneumonia infection [27]. There was also evidence that acid inhibitors may damage immune cell function, including T lymphocytes, neutrophils, or natural killer cells [28–32], which may increase the body’s susceptibility to infection [33].
Gastrin secretion in normal subjects and diabetes patients is inhibited by glucagon-like peptide 1: a role in the gastric side effects of GLP-1-derived drugs?
Published in Scandinavian Journal of Gastroenterology, 2019
Jens F. Rehfeld, Filip K. Knop, Meena Asmar
This study shows that GLP-1 in pharmacological doses inhibits the gastrin-response to food, both in normal subjects and in diabetes patients (Figure 1, Table 1). Gastrin is the classical hormonal regulator of the functions of the stomach. Hence, gastrin is the decisive stimulator of gastric acid and enzyme secretion during food ingestion. In addition, gastrin also has trophic effects on the gastric mucosa and maintain mucosal integrity by stimulation cell proliferation, migration and angiogenesis. Finally, gastrin may influence the motility of the stomach [22], although this has been less well studied in man. As shown in knock-out mice, lack of gastrin inhibits the acid-producing machinery; and permanent lack of acid subsequently leads to intestinal metaplasia and tumor development in the stomach [23,24]. Thus, long-term suppression of gastrin secretion may interfere with digestion and the function of the stomach, although translation of results from rodents to man requires some caution. Nevertheless, the randomized and controlled trials [10–16] have all shown that GLP-1-derived drugs have adverse gastrointestinal side effects including dyspepsia, nausea and upper abdominal pain, which are likely to originate from a malfunctioning stomach. The pronounced suppression of food-stimulated gastrin secretion in diabetes patients (Figure 1) in itself suggests that gastric functions deserve attention – including endoscopy – during long-term therapy with GLP-1-derived drugs. In this respect, especially patients with type 2 diabetes come into focus.