The use of antacids in the complex therapy of severe gastroesophageal reflux disease
In the standard of care for gastroesophageal reflux disease (GERD), non-absorbable antacids are considered as an adjunct to course and maintenance treatment with proton pump inhibitors (PPIs). Antacids are recommended as an independent remedy only for minimally expressed symptoms of the disease [2, 7].
However, according to statistics, in 15% of patients, who often suffer from the most severe lesions of the esophagus, the use of PPIs in adequate doses does not lead to complete regression of symptoms and pronounced endoscopic dynamics. Upon closer examination of this category of patients, two reasons were identified that could explain the above phenomenon:
- resistance to the antisecretory agent used;
- the presence of severe duodenogastroesophageal reflux (DGER).
Resistance to modern PPIs is relatively low and, according to various authors, ranges from 1 to 3.5% [6]. The second component seems to us to be more significant, since bile reflux accompanies a wide range of gastroenterological diseases, in particular gastric and duodenal ulcers, dysfunction of the biliary system, cholelithiasis, chronic cholecystitis, chronic pancreatitis, and intestinal diseases accompanied by persistent flatulence.
Components of duodenal contents act as aggression factors due to bile acids and lysolecithin. It is known that lysolecithin is a product of the hydrolytic breakdown of bile lecithin by phospholipase A. Further metabolism of lysolecithin is catalyzed by phospholipase B, which is inhibited by bile acids. Thus, the simultaneous presence of bile acids and lysolecithin in the refluxate leads to the accumulation of the cytotoxic effect of both substances in relation to the mucous membranes of the esophagus and stomach. Prescribing a PPI can reduce the total volume of secretion and thereby, to some extent, reduce the severity of DGER. Antacids containing aluminum and magnesium have a high adsorbing capacity and bind bile acids and lysolecithin by 59–96%, which makes it advisable to include them in complex treatment regimens for patients with severe BGE [3, 4, 8].
In addition, the use of antacid drugs in the form of a suspension promotes clearance (cleaning) of the esophagus. Along with this and the above properties, antacids also have a cytoprotective effect on the mucous membrane of both the esophagus and the stomach, which makes it possible to quickly achieve positive clinical and endoscopic dynamics of the disease [5, 9].
A separate, extremely difficult therapeutic group consists of patients who have undergone total gastrectomy. Due to the severity and constant presence of DGER, they often develop severe erosive and ulcerative lesions of the esophagus. Standard treatment regimens for GERD are ineffective in them, since in the case of total gastrectomy, PPIs do not have a point of application due to the lack of an anatomical substrate - parietal cells. To reduce the irritating effect of duodenal reflux, it is advisable to prescribe antacid, prokinetic and cytoprotective agents.
As an example, we give our own clinical observation.
Patient R., 51 years old, was admitted to the gastroenterology department of the State Clinical Hospital of the Ministry of Internal Affairs of the Russian Federation with complaints of constant heartburn, a feeling of bitterness in the mouth, weight loss, poor sleep, frequent awakenings at night due to a feeling of sourness in the mouth, and periodic bloating. Over the past month, I have developed a feeling of discomfort when swallowing food. Follows the 1st table diet.
In 2002, he underwent a total gastrectomy for moderately differentiated adenocarcinoma of the subcardial stomach. Since 2004, there have been complaints of periodically occurring persistent heartburn and a feeling of bitterness in the mouth in the morning. Esophagogastroduodenoscopy (EGDS) revealed slight hyperemia of the lower third of the esophagus and anastomositis. A monthly course of omeprazole 40 mg per day and motilium 30 mg per day was administered with a positive clinical effect; a control endoscopy was not performed. Since 2005, heartburn became permanent, and therefore the patient sought medical help at the clinic at his place of residence. Courses of omeprazole and motilium were prescribed, which brought relief while taking the drugs, but the clinical effect was not long-lasting. After 3 weeks from the start of conservative therapy, endoscopy revealed a linear erosion measuring 0.3 cm, which corresponded to GERD grade A according to the Los Angeles classification. Prescribed omeprazole 40 mg/day, motilium 30 mg/day, stricter adherence to the diet, split meals up to 6 times a day. During the control endoscopy performed after 3 weeks, negative dynamics were noted - three non-confluent erosions were identified at the tops of the mucosal folds up to 0.4–0.6 cm, covered with fibrin; the surrounding mucosa is swollen, moderately hyperemic. The endoscopic picture made it possible to diagnose GERD grade B. The gastroenterologist decided to intensify the therapy: esomeprazole 40 mg/day was prescribed, the dose of motilium was increased to 40 mg/day. A control endoscopy performed 2 weeks later showed an increase in the size of erosions to 0.6–1.0 cm, persistence of swelling and hyperemia of the esophageal mucosa. Rabeprazole 40 mg/day was prescribed, the patient continued to take Motilium at a dose of 40 mg/day. The patient did not notice any improvement in his state of health during the therapy. 2 weeks after the control endoscopy, the appearance of confluent erosions of the esophagus was noted, which corresponds to GERD grade C. The patient was sent to hospital for examination and selection of therapy.
On examination: the patient is very anxious, exhausted by constant heartburn, expresses cancer-phobic ideas, and does not believe in the possibility of successful therapy. Asthenized. The condition is assessed as moderate. The patient has the correct physique and low nutrition. The skin is clean, pale, with a grayish tint. Above the lung area there is a percussion-pulmonary sound. Breathing is vesicular, no wheezing. Heart sounds are muffled, the rhythm is correct. Blood pressure - 105/70 mm Hg. Art., pulse 68 beats/min. The tongue is moist, thickly coated with a white-yellow coating. The abdomen is soft and painless on palpation in all parts. The liver and spleen are not palpable. Physiological functions are normal.
In blood tests (general and biochemical), general urine analysis, no changes in indicators were noted.
Chest X-ray, ultrasound examination of the abdominal organs, genitourinary system and thyroid gland, colonofibroscopy, and osteoscintigraphy revealed no diagnostically significant abnormalities.
With endoscopy dated January 30, 2006: the esophagus is freely passable, from a distance of 28 cm from the teeth and to the esophageal-small intestinal anastomosis, confluent erosions with fibrin deposits and pronounced contact bleeding of the mucous membrane can be traced along all walls. The anastomosis is freely passable, the anastomosed colon is not changed. There is massive reflux of bile into the esophagus. Conclusion: condition after gastrectomy, erosive fibrinous esophagitis.
X-ray examination: the act of swallowing is not impaired. The anastomosis is freely passable. Severe reflux of contrast material into the esophagus. The folds of the distal esophagus are dilated and swollen. No changes were detected in the small intestine. Conclusion: condition after gastrectomy; pronounced reflux of contrast into the esophagus; esophagitis.
The patient was prescribed the following therapy: domperidone (Motilium) 10 mg - 4 times 30 minutes before meals, Relzer - 10 ml 6 times according to the scheme: in the morning on an empty stomach, 4 times 20-30 minutes after meals and at night, sucralfate (Venter ) 1 tablet 4 times between meals. Particular attention was paid to sedative therapy, since it is known that the instability of the patient’s psycho-emotional status provokes aggravation of motor disorders of the gastrointestinal tract. The patient was also observed by a psychotherapist. Sulpiride (eglonil) 100 mg 2 times a day and phenazepam 0.5 mg at night were prescribed.
During endoscopy, performed 10 days after the start of therapy, certain positive dynamics were noted - the erosive fields in the esophagus decreased. Contact trauma to the mucous membrane became less pronounced. Peristalsis is slightly reduced, but no zones of akinesia are noted. Therapy was intensified by taking Relzer 8 times, 10 ml, and tofisopam (Grandaxin) 50 mg 2 times a day.
During endoscopy performed before discharge, foci of mucosal hyperemia were visualized in the patient's esophagus at the site of healed erosions. The peristaltic wave in the esophagus is active, covering all the walls of the esophagus.
Achieving and maintaining stable remission of GERD in patients with a resected stomach is an extremely difficult therapeutic problem. The prescription of PPIs, which form the basis of standard regimens, should be carried out strictly individually, taking into account the scope of surgical intervention and the preservation of the acid-producing function of the stomach. In cases of total gastrectomy, their use is unjustified.
Often patients are neurotic due to debilitating, intractable heartburn. Therefore, treatment regimens must be comprehensive, including drugs with adsorbent, prokinetic, cytoprotective activity, as well as agents that normalize the condition of both the central and peripheral nervous systems.
A special place in therapy is occupied by non-absorbable antacid drugs, characterized by a combination of several therapeutic effects, which is especially important for patients with a resected stomach. This is a pronounced adsorbing ability, which causes a decrease in the cytotoxic effect of bile components, as well as a cytoprotective effect, enhanced in the case of Relzer due to flavonoids, saponins, phenocarbolic acids and selenium compounds contained in licorice glabra. The use of antacids in suspension form promotes esophageal clearance. The therapeutic effect of antacids can be enhanced through their combined use with drugs belonging to the group of cytoprotectors (sucralfate, bismuth tripotassium dicitrate, misoprostol) and act as an additional barrier to the action of aggressive components of the duodenum [10, 11].
The choice of the antacid drug Relzer in the patient described above is determined by both the composition of the drug and the form of release. The content of aluminum and magnesium hydroxides determines the rapid onset and pronounced duration of action of the drug, as well as high adsorbing capacity.
Simethicone introduced into the retzer adsorbs intestinal gases, which further reduces intra-abdominal pressure in patients suffering from flatulence, and, as a result, serves as the prevention of pathological reflux. But the main distinctive feature of the drug is the inclusion in its composition of licorice root powder, the plant ingredients of which make a significant contribution to the total pharmacological effect of the reltser. Terpenoids and higher fatty acids reduce gas formation in the stomach, significantly complementing the effect of simethicone. Flavonoids and saponins, along with a wide range of microelements that make up licorice, have an antioxidant effect, which accelerates the regeneration processes of the mucous membrane. Various polysaccharides contained in licorice enhance the enveloping effect of Relzer and, along with flavonoids and terpenoids, neutralize the hydrochloric acid of gastric juice in patients with preserved acid-forming function.
The drug correction of the psycho-emotional status in the clinical observation we presented was due to the fact that sulpiride, being a selective antagonist of dopamine receptors, has moderate neuroleptic activity in combination with some stimulating and thymoleptic (antidepressive) effects. This drug has been widely used in gastroenterology for a long time due to its pronounced prokinetic activity, realized through a “regulating” effect on the central nervous system. Phenazepam, which is an active tranquilizer, also has vegetotropic activity. Subsequently, the treatment regimen was supplemented with tofisopam (Grandaxin), which has an anxiolytic effect and is a psychovegetative regulator.
The given clinical example illustrates the role of duodenal reflux in the formation of pathological changes in the esophageal mucosa in patients who have undergone total gastrectomy, as well as the importance of including antacids in therapeutic regimens in this category of patients.
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I. V. Mayev, Doctor of Medical Sciences, Professor D. T. Dicheva , Candidate of Medical Sciences, Associate Professor V. V. Krasnikov T. A. Buragina MGMSU, Glenmark Pharmaceuticals LTD, Moscow
