Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017168 (
gastroesophageal reflux disease
)
11,783
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To clarify the lower esophageal sphincter (LES) pressure response to alkali ingestion, normal subjects and postantrectomy patients with either a gastroduodenostomy or gastrojejunostomy were studied in a double-blind controlled fashion. LES pressure and serum gastrin concentrations were measured after ingestion of a 100 ml bolus of either 0.4 M NaHCO3 or 0.4 M NaCl. In addition, the effect of a therapeutic dose (30 ml) of a commercial antacid preparation was studied in a double-blind fashion in 14 patients with
gastroesophageal reflux disease
. Peak increases in LES pressure above basal were significantly higher (p less than 0.05) after NaHCO3 than after NaCl in normal subjects and in patients with vagotomy and Billroth I antrectomy, but not in patients with vagotomy and Billroth II antrectomy. Serum gastrin concentrations were unaffected by alkali. Thirty milliliters of liquid antacid containing
aluminum
and magnesium hydroxide resulted in a small sustained rise in LES pressure over the first 50 min after ingestion, but this was not statistically different than the placebo response. It is suggested that: 1) neither the antrum nor intact vagi nor gastrin were required for NaHCO3 ingestion to increase LES pressure; 2) the increase in LES pressure with NaHCO3 ingestion appears to rely upon an intact duodenum and may relate to volume and osmolarity of the alkali load; and 3) therapeutic doses of a liquid commercial antacid does not significantly increase LES pressure in the presence of an intact stomach.
...
PMID:Studies on the mechanism of the lower esophageal sphincter pressure response to alkali ingestion in humans. 299 Jan 96
To evaluate the efficacy of different drug combinations in treating severe
gastroesophageal reflux
(
GER
), we studied 80 children with
GER
. The patients were randomly divided into four groups: group A was treated with domperidone plus magnesium hydroxide and
aluminum
hydroxide, group B with domperidone plus alginate, group C with domperidone alone, and group D received placebo. At the time of diagnosis and 8 weeks after treatment the patients were clinically evaluated and underwent 24-h continuous esophageal pH monitoring. After treatment a complete regression of symptoms was observed in 16 of 20 patients in group A, in 8 of 20 in group B (A versus B, p < 0.018), in 9 of 20 in group C (A versus C, p < 0.034), and in 7 of 20 in group D (A versus D, p < 0.001). Moreover, there was a statistically significant improvement in several pH-metric variables studied in all treatment groups; in addition, a comparison of the pH-metric data of the four groups after treatment indicated that reflux variables were significantly lower in group A than in the other groups. We conclude that the domperidone plus magnesium hydroxide and
aluminum
hydroxide combination was more effective than the other drugs we used in treating
GER
and in modifying the objective pH-metric variables in pediatric patients.
...
PMID:Domperidone plus magnesium hydroxide and aluminum hydroxide: a valid therapy in children with gastroesophageal reflux. A double-blind randomized study versus placebo. 804 2
Gastro-oesophageal reflux disease
(GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are move variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, buy may affect absorption of H2 receptor antagonists like cimetidine and ranitidine.
Aluminium
-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of GORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H2 receptor antagonists is still the most frequently use therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decrease likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H2 receptor antagonists are recommended. The most effective medical therapy for any severity of GORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), are prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H(+)-K+ ATPase molecules, allows once daily administration in most patients. Interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may e be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in GORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in terms of longer plasma t1/2 and less toxicity. Amongst H2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control througho
...
PMID:Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease. 911 86
Antacids are commonly used self-prescribed medications. They consist of calcium carbonate and magnesium and
aluminum
salts in various compounds or combinations. The effect of antacids on the stomach is due to partial neutralisation of gastric hydrochloric acid and inhibition of the proteolytic enzyme, pepsin. Each cation salt has its own pharmacological characteristics that are important for determination of which product can be used for certain indications. Antacids have been used for duodenal and gastric ulcers, stress gastritis, gastro-
oesophageal reflux
disease, pancreatic insufficiency, non-ulcer dyspepsia, bile acid mediated diarrhoea, biliary reflux, constipation, osteoporosis, urinary alkalinisation and chronic renal failure as a dietary phosphate binder. The development of histamine H2-receptor antagonists and proton pump inhibitors has significantly reduced usage for duodenal and gastric ulcers and gastro-
oesophageal reflux
disease. However, antacids can still be useful for stress gastritis and non-ulcer dyspepsia. The recent release of proprietary H2 antagonists has likely further reduced antacid use for non-ulcer dyspepsia. Other indications are still valid but represent minor uses. Antacid drug interactions are well noted, but can be avoided by rescheduling medication administration times. This can be inconvenient and discourage compliance with other medications. All antacids can produce drug interactions by changing gastric pH, thus altering drug dissolution of dosage forms, reduction of gastric acid hydrolysis of drugs, or alter drug elimination by changing urinary pH. Most antacids, except sodium bicarbonate, may decrease drug absorption by adsorption or chelation of other drugs. Most adverse effects from antacids are minor with periodic use of small amounts. However, when large doses are taken for long periods of time, significant adverse effects may occur especially patients with underlying diseases such as chronic renal failure. These adverse effects can be reduced by monitoring of electrolyte status and avoiding
aluminum
-containing antacids to bind dietary phosphate in chronic renal failure. Antacids, although effective for discussed indications of duodenal and gastric ulcer and gastro-
oesophageal reflux
disease, have been replaced by newer, more effective agents that are more palatable to patients. Antacids are likely to continue to be used for non-ulcer dyspepsia, minor episodes of heartburn (gastro-
oesophageal reflux
disease) and other clear indications. Although their wide-spread use may decline, these drugs will still be used, and clinicians should be aware of their potential drug interactions and adverse effects.
...
PMID:Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. 1040 Apr 1
The aim of the present study was to compare the efficacy and safety of a new aluminium-free formulation of alginate with placebo in infants with recurrent gastro-
oesophageal reflux
. This was a double-blind, randomised, parallel-group study conducted at 25 centres in the UK. Of the 90 paediatric patients recruited in a general practice setting, 42 were randomised to receive alginate and 48 to receive placebo. Infants were assessed before treatment and again after seven and 14 days of treatment. Analyses were based on the last, valid, non-missing observation for each variable for the intent-to-treat (ITT) population of 42 alginate and 46 placebo patients. For the primary efficacy measure (number of vomitting/regurgitation episodes), alginate was significantly superior to placebo (p = 0.009). For the secondary efficacy measure (severity of vomiting), a trend in favour of alginate was observed (p = 0.061). Patients receiving alginate achieved superior assessments of treatment outcome by both investigators (p = 0.008) and parent/guardians (p = 0.002) alike. In addition, alginate achieved a significantly greater reduction in the mean severity of vomiting episodes recorded in a daily diary compared with placebo (p = 0.027) and resulted in more patients having at least 10% symptom-free days (p = 0.027). For none of the variables measured did placebo have a superior effect. More than one-half of all patients experienced some adverse event, although no statistically significant differences were observed between the two treatment groups (p > 0.1), and adverse events accounted for withdrawal in only 12.5% of the patients (alginate, n = 4; placebo, n = 7).
Aluminium
-free alginate demonstrated superior efficacy over placebo in treating recurrent gastro-
oesophageal reflux
in paediatric patients. The safety profile of alginate was similar to that of placebo.
...
PMID:Comparison of the efficacy and safety of a new aluminium-free paediatric alginate preparation and placebo in infants with recurrent gastro-oesophageal reflux. 1062 22
The frequency, symptoms, and complication rate of PUD seem to decrease during pregnancy. Yet clinicians often have to treat dyspepsia or pyrosis of undetermined origin during pregnancy because the frequency of pyrosis significantly increases during pregnancy, and clinicians reluctantly perform EGD during pregnancy for pyrosis to differentiate reliably between
GERD
and PUD. Dyspepsia or pyrosis during pregnancy is initially treated with dietary and lifestyle modifications. If the symptoms do not remit with these modifications, sucralfate or antacids, preferably magnesium-containing or
aluminum
-containing antacids, should be administered. Histamine2 receptor antagonists are recommended when symptoms are refractory to antacid or sucralfate therapy. Ranitidine seems to be a relatively safe H2 receptor antagonist. If symptoms continue despite H2 receptor antagonist therapy, the patient should be evaluated for possible EGD or PPI therapy. Pregnant women with hemodynamically significant upper gastrointestinal bleeding or other worrisome clinical findings should undergo EGD. Indications for surgery include ulcer perforation, ongoing active bleeding from an ulcer requiring transfusion of six or more units of packed erythrocytes, gastric outlet obstruction refractory to intense medical therapy, and a malignant gastric ulcer without evident metastases.
...
PMID:Gastric and duodenal ulcers during pregnancy. 1263 19
Duodenogastric reflux is the retrograde flow of duodenal contents into the stomach that then mix with acid and pepsin. These agents can reflux into the esophagus (ie, duodenogastroesophageal reflux ) and cause
gastroesophageal reflux disease
(
GERD
) and its complications, including stricture, Barrett's esophagus, and adenocarcinoma of the esophagus. Medical and surgical treatments of DGER can be difficult. Best medical treatment is proton-pump inhibitors, which decrease DGER by inhibiting both gastric acidity and volume, making less gastric contents available to reflux into the esophagus. The addition of the gamma-aminobutyric (GABA(B)) receptor agonist baclofen may further reduce DGER in patients not responding to proton-pump inhibitors. Bile acid-binding agents (
aluminum
-containing antacids, cholestyramine, sucralfate, urosodeoxycholic acid) have physiologic rationale, but their efficacy is unproven. Prokinetic agents can reduce DGER and its upper gastrointestinal symptoms by promoting increased gastric emptying. In patients with medically refractory symptoms, a Roux-en-Y diversion or duodenal switch operation may be helpful.
...
PMID:Duodenogastric Reflux-induced (Alkaline) Esophagitis. 1472 38
Introduction
:
Gastro-esophageal reflux disease
(
GERD
) in infants is worldwide diagnosed with increasing frequency, resulting in an increasing number of infants exposed to treatment. In this review, we focus on the safety of therapeutic options.
Areas covered
: English articles were searched from 1990 until May 2020 in PubMed and Google Scholar. Evidence suggests that non-pharmacological treatment is often effective and safe. Guidelines restrict pharmacological treatment to acid-suppressive medication, which is associated with adverse effects, often related to gastro-intestinal dysbiosis and consequences of the latter.
Aluminum
-free alginates have some efficacy and are not associated with relevant adverse effects. Especially in infants,
GERD
is often nonacid related. Prokinetics are not recommended because of lack of efficacy and numerous adverse effects.
Expert opinion
: Pediatric trials are underpowered regarding adverse effects. The number of infants exposed to anti-secretory agents is increasing worldwide, often without indication. Informing healthcare providers about adverse effects of acid-secretory medication may contribute to a more rational use. Acid inhibiting agents such as alginates are a drug class associated with limited efficacy and devoid of serious adverse effects. Regarding prokinetics, the risk of adverse effects outweighs the benefit. Reassurance of parents and nutritional management of
GERD
in infants is effective and safe.
...
PMID:Safety considerations when managing gastro-esophageal reflux disease in infants. 3311 55