Choosing the optimal antacid drug in clinical practice.
Section only for specialists in the field of medicine, pharmacy and health care!
M.I. SHCHOKINA, Ph.D., clinic “MEDSI”, gastroenterology department, Moscow, I.M. SCHERBENKOV, Ph.D., CELT, Moscow.
The problem of rational pharmacotherapy of acid-dependent diseases (ACD) of the upper gastrointestinal tract is relevant due to the high prevalence, especially among people of working age, complex etiopathogenesis, the presence of a large arsenal of drugs.
Currently, the CPZ group includes gastric ulcer and duodenal ulcer, gastroesophageal reflux disease (GERD), functional dyspepsia, symptomatic ulcers in Zollinger-Ellison syndrome, ulcers associated with the use of non-steroidal anti-inflammatory drugs, peptic ulcers (NSAIDs) hyperthyroidism, idiopathic hypersecretory state, ulcers arising from celiac enteropathy [2, 5, 8].
Today, more and more effective means of drug control of gastric acid formation appear, with a minimum of side effects. In the treatment of KZD, two main groups of drugs are widely used – antisecretory drugs and antacids, which provide effective control over acid production. The effect on the secretory function of the stomach can occur extracellularly – at the receptor level and intracellularly – at the final stage of the secretion of hydrochloric acid. Extracellular suppression of the activity of acid-peptic factor can be achieved by neutralizing hydrochloric acid already released in the lumen of the stomach and duodenum (antacids). The receptor level is realized due to the blockade of receptors of cells secreting hydrochloric acid (M-anticholinergics, blockers of H2-histamine receptors).
By acting on the intracellular enzymes of the parietal cells involved in the formation of hydrochloric acid (proton pump inhibitors – PPI), the intracellular process of blocking the secretion of hydrochloric acid is realized [1, 4, 8, 18].
The choice of a particular drug depends on a number of parameters: the required degree of inhibition of hydrochloric acid production, the duration of the effect obtained, the presence of certain adverse reactions, the possibility of long-term administration of the drug.
Antacids have been used as a treatment for CDD several centuries ago. Even with the advent of drugs of other pharmacological groups (PPIs, H2-blockers, etc.), which are currently included in the treatment standards for GERD, peptic ulcer disease, PND, antacids have not lost their importance. Against the background of the widespread use of highly effective antisecretory drugs of PPIs, data are accumulating on the possible adverse consequences of long-term treatment with PPIs.
Thus, PPIs, being agents that block the enzyme systems of the parietal cells of the stomach, can lead the latter to a more vulnerable state in relation to various damaging agents. There is more and more information about the development of hypergastrinemia, even after small courses of PPI use. Cases of PPI intolerance are also recorded, forcing doctors to cancel their intake by patients.
PPIs are of little use due to their characteristic latent period of action and for the correction of acute dyspeptic disorders where emergency anti-acid care is needed, as well as for the so-called. on-demand therapy.
Thus, a number of studies have shown an increase in the risk of community-acquired Clostridium difficile, as well as associated pseudomembranous colitis, associated with the use of PPIs. The role of long-term PPI use in infection of the respiratory system is being actively discussed. Based on a study of 135,386 patients, Yang Y. et al. (2006) reported an increased risk of hip fracture in long-term PPI patients.
In addition, against the background of prolonged alkalization of the stomach, there is a tendency to a decrease in the production of bicarbonates by the pancreas, which can lead to an increase in the viscosity of the pancreatic secretion and, as a consequence, to a violation of its outflow [2, 8, 14, 15]. This information, as well as the identification of additional properties in antacids, is the reason for their continued active use:
• firstly, antacids are able to adsorb bile acids and lysolecithin (involved in damage to the mucous membrane of the stomach and esophagus); • secondly, they have a protective effect associated with the stimulation of the synthesis of prostaglandins (and in this regard they have priority use in cases where the pathogenesis of an ulcer or damage to the mucous membrane is associated with a weakening of the protective properties of the latter); • third, the ability of antacids to bind epithelial growth factor and fix it in the area of the ulcer defect was revealed, thereby stimulating local reparative-regenerative processes, cell proliferation and angiogenesis, contributing to the full restoration of the mucous membrane in a functional respect, which significantly lengthens the remission period.
With endoscopically negative GERD, it is possible to take antacids with drugs that normalize the motility of the stomach and duodenum (prokinetics). When treating GERD, it is better to use antacids in the form of a suspension or gel containing Al and Mg hydroxide. In case of an ulcer-like variant of PD, it is recommended to use antacids, and in the absence of an effect, PPIs, blockers of H2-receptors of histamine and antacids on demand, with a nonspecific variant of PD, antacids and prokinetics.
Antacids are also included in the treatment regimens for chronic superficial and atrophic gastritis with a morphologically confirmed diagnosis. Antacids are the drugs of choice if there are contraindications to other antisecretory drugs, side effects of PPIs, histamine H2 receptors, and intolerance to these drugs [5, 7, 8, 10].
Occasional intake of antacids is also possible by healthy people when they have symptoms of gastric dyspepsia (heartburn, gastralgia, epigastric discomfort), which manifests itself in case of errors in diet, alcohol consumption, overeating, etc..
Against the background of the use of antacids, the reaction of neutralization of hydrochloric acid in the stomach cavity continues until a pH of 3.0–4.0 is reached. These values still allow the stomach to carry out physiological functions and are more favorable for the digestion process..
It is a well-known fact that the patient always gives preference to a drug that provides a quick relief of a symptom painful for him. Here antacids are out of competition. However, one should not go to the extreme, replacing the effective pathogenetic therapy of acid-dependent pathology with PPIs for albeit quick, but, unfortunately, short-term relief of the symptoms of the disease with antacids.
A modern doctor must rationally combine drugs in accordance with their pharmacological characteristics and the nature of the disease..
The heterogeneity in its properties and mechanism of action on the body, as well as the variety of antacids, creates certain difficulties in choosing the optimal option in clinical practice. All antacids act in the lumen of the stomach and / or directly at its wall and have a similar mechanism of action. It consists in direct interaction with hydrochloric acid of gastric juice. At the same time, the irritating effect of hydrochloric acid on gastric mucosa decreases, and the intragastric pH rises to 4–5.
An increase in pH in the stomach is accompanied by a decrease in the activity of a number of proteolytic enzymes and a weakening of the action of aggressive factors. The strength of the action of antacid drugs is determined by their acid-neutralizing activity (KNA), which is expressed in milliequivalents (the amount of 1N hydrochloric acid, titrated to pH 3.5 with a certain dose of the drug for a specified time). KPA of different antacids differs significantly.
It is considered low if it is less than 200 meq / day; medium – in the range of 200-400 meq / day and high – more than 400 meq / day.
The rate of onset of the antacid effect is determined by the rate of dissolution of the drug and its dosage form. The rapid development of the buffering effect is characteristic of sodium bicarbonate, calcium carbonate, and magnesium hydroxide, which dissolve quite easily in the stomach. Suspensions usually dissolve faster than solid dosage forms.
The duration of action of antacids is significantly affected by the rate of their evacuation from the stomach, which is determined, in turn, by the presence or absence of food in the stomach. An antacid drug taken 1 hour after a meal lingers longer in the stomach and provides a more lasting effect [2, 5, 9, 11].
Traditionally, all antacids are divided into absorbable (VA) and non-absorbable (NA).
• sodium bicarbonate (soda – NaHCO3); • magnesium oxide (burnt magnesia); • basic magnesium carbonate – a mixture of Mg (OH) 2, 4MgCO3, H2O; • basic calcium carbonate – CaCO3; • Bourget mixture (Na sulphate, Na phosphoric acid, Na bicarbonate); • a mixture of calcium carbonate and magnesium carbonate.
VA (sodium bicarbonate, or baking soda) – act for a short time, neutralizing hydrochloric acid. Being absorbed, they can significantly affect the exchange of electrolytes, causing the development of alkalosis (weakness, headache, loss of appetite, nausea, vomiting, abdominal pain, muscle cramps and cramps). The risk of alkalosis is especially high in patients with impaired renal function.
At the same time, sodium bicarbonate leads to alkalization of urine and promotes the formation of phosphate stones, impairs the body’s water-electrolyte metabolism. This, in turn, may cause an increase in blood pressure, increased edema and an increase in signs of heart failure in elderly patients with pathology of the cardiovascular system. VA is characterized by the phenomenon of rebound with a secondary increase in the secretion of hydrochloric acid.
An increase in acid secretion is also facilitated by the release during the neutralization reaction of carbon dioxide, which stretches the walls of the stomach and causes pain. Carbon dioxide also causes belching and flatulence, side effects that are especially undesirable for patients with GERD. In gastric peptic ulcers with a deep ulcerative defect, stretching of the stomach walls is fraught with perforation (i.e., stimulating gastric secretion), therefore, VAs are not used in the treatment of KZD. Due to the large number of side effects, they have practically lost their clinical significance and are used by the population mainly for self-medication as symptomatic means for the relief of certain symptoms of gastric dyspepsia. However, the adherence of many patients to this particular group is due to the fact that VA quickly relieves heartburn and epigastric pain.
The duration of the latent period in this group of antacids is much shorter, which means that the speed of the onset of the neutralizing effect is greater than that of AN (although the acid-neutralizing effect of the latter is longer). Therefore, some patients are not satisfied with the speed of the onset of antisecretory action and mistakenly consider NA to be ineffective [2, 8, 11, 15, 16].
HA are subdivided into 3 groups:
1st – aluminum salt of phosphoric acid; 2nd – aluminum-magnesium antacids; 3rd – aluminum-magnesium preparations with the addition of Alginate.
Since the main mechanism of action of NA is associated with the adsorption of hydrochloric acid, their effect develops somewhat more slowly (within 10–30 minutes) than that of absorbed drugs. Possessing a buffer (neutralizing) capacity greater than that of VA, the duration of their action reaches 2.5–3 hours. Most drugs from this group contain compounds of aluminum and magnesium in various proportions.
At the same time, the initial antacid effect is provided by magnesium salts, the prolonged one – by aluminum compounds.
In addition to neutralizing free hydrochloric acid in the stomach, HA adsorb pepsin and bile acids, help reduce intracavitary pressure in the stomach and duodenum, and have an indirect antispasmodic effect. HA neutralize the negative impact on the CO of duodenogastric reflux, have a cytoprotective effect.
Regardless of the composition, all HA reduce the absorption of other drugs when used together, which must be taken into account when prescribing a drug regimen (for example, cardiac glycosides, indirect anticoagulants, antihistamines, hypnotics, and many other drugs). In this regard, it is necessary to follow a single rule: the time interval between taking antacids and other drugs should be at least 2 hours.
Long-term use of antacids containing calcium can lead to hypercalcemia and the development of lactic-alkaline syndrome. In addition, hypercalcemia causes a decrease in parathyroid hormone production and, as a consequence, a delay in the excretion of phosphorus and leads to the accumulation of insoluble calcium phosphate. Against this background, tissue calcification and the development of nephrocalcinosis are possible.
Also antacids containing calcium can lead to constipation as a result of slowing down the evacuation function of the intestine [1, 4, 5, 8].
When using antacids, the daily dose of antacid is distributed and administered depending on the diet:
– it is recommended to take an antacid 1 hour after a meal – during the period of cessation of the buffering effect of food at the height of maximum gastric secretion; – Reception 3 hours after a meal – to replenish the antacid equivalent after evacuation of gastric contents; – reception before bedtime – to suppress nighttime secretion; – during the period of exacerbation of the disease, it is recommended to take antacids after 1–2 hours, followed by administration in the interdigestive period; – it is necessary to take into account the individual profile of pain, timing the intake of drugs at the time of their occurrence; – VA for relief of pain syndrome is recommended to be taken 30–40 minutes after meals, and NA – in the intervals between meals; – it is more effective to prescribe antacids in small portions, but more often.
Tactics for choosing an antacid drug.
Against the background of increased cytotoxic effects, protection factors are inevitably depleted. Excessive production of hydrochloric acid disrupts the dynamic balance between the rate of destruction and renewal of glycoproteins that make up the protective layer, which opens the way for the increasing cytotoxic effect of aggression factors. In this regard, the direct cytoprotective effect of aluminum-containing antacids is extremely important, which consists in the fact that they have an enveloping effect and create a protective film on the surface of the mucous membrane.
Aluminum promotes the binding of epithelial growth factor and its fixation in the area of the bottom of the ulcer or erosion, which stimulates the division of cells of the gastric epithelium and neoplasm of blood vessels.
Considering the above, it is necessary to remember about the cytotoxicity of bile acids and lysolecithin, which irritate the mucous membrane of the stomach and esophagus during gastroduodenal and esophagogastroduodenal reflux. Aluminum-containing antacids actively absorb bile acids and lysolecithin, which enhances the therapeutic effect [8, 11, 12, 17, 19].
Complexes containing several compounds have been increasingly used as antacids recently, which makes it possible to vary the rate of onset of the therapeutic effect, the duration of the drug’s effect, and also to minimize its side effects. From a clinical point of view, it is important that combined antacids additionally affect intestinal motor function depending on the AL / Mg ratio. Preparations containing relatively large amounts of aluminum are more likely to contribute to the development of constipation, while preparations with relatively high amounts of magnesium have a moderate laxative effect..
Gastal is a modern combined antacid containing magnesium hydroxide and aluminum hydroxide. The antacid effect of the drug manifests itself immediately after taking the pills and lasts about 2 hours. One Gastal tablet neutralizes about 21.5 mmol of hydrochloric acid. The drug inhibits the action of pepsin, lysolecithin and bile acids.
Has no systemic effect in patients with normal renal function. After interaction with hydrochloric acid of gastric juice, aluminum hydroxide reacts with phosphates and carbonates in the alkaline medium of the intestine and is excreted in the form of insoluble salts. Magnesium hydroxide reacts with hydrochloric acid in gastric juice to form magnesium chloride, which has an osmotic laxative effect in the small intestine. Magnesium is also excreted in the feces as insoluble carbonate.
A balanced ratio of aluminum and magnesium salts avoids constipation or diarrhea while taking the drug.
The high ability of the nonabsorbable antacid drug Gastal to effectively and quickly eliminate the appearance of heartburn (burning) and epigastric pain associated with an acid-peptic factor makes this drug one of the drugs of choice in the treatment of KZD in a polyclinic and hospital.
Rational pharmacotherapy of KZZ is based on the use of modern antacids, taking into account their main pharmacokinetic, pharmacodynamic properties, clinical efficacy and safety, individualization of therapy. The use of this group of drugs not only improves the prognosis of the disease, the patient’s quality of life, but also helps to increase the patient’s adherence to the therapy..
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