Overview
According to the ATX classification, the A02B group “Antiulcer drugs and drugs for the treatment of gastroesophageal reflux” includes five subgroups:
Antisecretory drugs
In 1910, Karl Schwartz put forward the postulate: "No acid - no ulcers" [3]. In accordance with this postulate, many of the antiulcer drugs in one way or plus reduce the acidity of the gastric contents: either by neutralizing the already secreted acid (such drugs belong to the antacid group), or by acting in a depressing way on the mechanisms of hydrochloric acid secretion. In gastroenterology, antisecretory drugs are commonly called proton pump inhibitors, N2-Blockers and peripheral M-anticholinergics [4] .
Mechanisms of hydrochloric acid secretion and its inhibition
The secretion of hydrochloric acid in the stomach occurs in the parietal cell. Opposite membranes of this cell are functionally dramatically different.
The process of hydrochloric acid secretion occurs on the apical (directed into the lumen of the stomach) membrane, it is based on transmembrane proton transfer and is directly carried out by a specific proton pump - H + / K + -ATPase. When activated, H + / K + -ATPase molecules integrate into the membrane of the secretory tubules of the parietal cell and transfer H + hydrogen ions from the cell into the gland lumen, exchanging them for potassium K + ions from the extracellular plus. This process precedes the exit of Cl - ions of chlorine ions from the cytosol of the parietal cell, thus, hydrochloric acid is formed in the lumen of the secretory tubule of the parietal cell.
On the opposite, basolateral membrane, there Triptodur a group of receptors that regulate the secretory activity of the this histamine H2, gastrin CCKB and acetylcholine M3. As a result of their action in the parietal cells, the concentration of calcium Ca 2+ and cyclic adenosine monophosphate (cAMP) increases, which leads to the activation of tubulovesicles containing H + / K + -ATPase. The receptor inhibitors of hydrochloric acid secretion, prostaglandins E, are also located on the basolateral membrane.2 and somatostatin, epidermal growth factor and others.
The action of antisecretory drugs is based either on the blockade of stimulatory effects at the receptor level or on the blockade of intracellular enzymes involved in the production of hydrochloric acid H + / K + -ATPase. Different groups of antisecretory drugs (M-anticholinergic drugs, H2-blockers, proton pump inhibitors and others) act on different elements of the parietal cell.
M-anticholinergics
M-anticholinergics (synonyms: anticholinergics, M-anticholinergic drugs) are divided into non-selective (or systemic) and selective. Non-selective effects on all types of M-cholinergic receptors, Boviseal selective - only on certain.
Plus are some of the oldest anti-ulcer drugs. Historically, the first of these are belladonna and atropine preparations. The latter in the past was the main medicine for the treatment of acid-dependent diseases, but its indiscriminate effect on the M-cholinergic receptors found in many organs gives rise to many serious side effects (tachycardia, dry mouth, accommodation disorders, irritability, headache, sleep disturbances). Without such a number of disadvantages, platifillin is plus less effective. Other non-selective peripheral M-anticholinergics, such as metocinia iodide, also have a large number of side effects.
Of the M-anticholinergic drugs, the most effective is selective Mone-anticholinergic pirenzepine that blocks Mone-cholinergic receptors at the level of the intramural ganglia and, thus, inhibits the stimulating effect of the vagus nerve on the secretion of hydrochloric acid and pepsin, without inhibiting the M-cholinergic receptors of the salivary glands, heart and other organs. Pirenzepine (the only M-anticholinergic drug) is included in the A02B group considered in this article (ATX code A02BX03). However, in its acid-blocking properties, it loses much not only to proton pump inhibitors, but also to H2-blockers and, having no advantages over them, it, like other M-anticholinergics, is less and less used in the treatment of acid-dependent diseases [4] .
H2-blockers
H2-blockers (synonym: blockers H2-histamine receptors) compete with histamine H2-receptors, thereby blocking the stimulating effect of histamine. Most famous H2-blockers: cimetidine, ranitidine and Boviseal
Proton pump inhibitors
Inhibitors of the proton pump, integrating into the This drug + / K + -ATPase, block the transport related link hydrogen ions of H + into the lumen of the stomach. The most famous proton pump inhibitor is omeprazole.
Gastrin receptor blockers
Despite the long-term search for gastrin receptor inhibitors and the creation of several drugs of this type, they are far from widespread use in practical medicine. The non-selective gastrin receptor blocker proglumide [5], code A02BX06, blocks both subtypes of gastrin receptors: CCKA and CCKB. According to the degree of inhibition of acid production, it is equivalent to the first generation of H2-blockers, but does not have as many side effects. Selective antagonists of gastrin receptors lorglumide and devasipid [6], positioned as antiulcer drugs Boviseal development, have not yet found their application in clinical practice. In Russia, none of the listed drugs-blockers of gastrin receptors is not registered [1] [2] .
New classes of antisecretory drugs
Currently, research is ongoing aimed at creating new antisecretory drugs:
- a new type of H + / K + -ATPase blockers, the so-called acid pump antagonists.acid pump antagonist ), which, unlike proton pump inhibitors, block the mechanism of transportation of H + / K + -ATPase potassium Boviseal K + [7] ,
- Ca 2+ membrane receptor blockers and stimulators [8] .
