H2 receptor antagonists are agents that inhibit gastric acid production. As antihistamines, they block the binding of histamine to the H2 receptors of the parietal cells of the stomach. In addition to proton pump inhibitors, they are commonly used for gastric and duodenal ulcers and reflux disease.
What are H2 receptor antagonists?
H2 receptor antagonists are agents that inhibit stomach acid production. H2 receptor antagonists compete with histamine to occupy the H2 receptors of parietal cells. They are drugs that restrict gastric acid production. Therefore, they are used alongside proton pump inhibitors for severe gastric and duodenal ulcers. Furthermore, H2 receptor antagonists are also used in reflux disease. In reflux disease, stomach acid enters the esophagus due to a malfunction of the sphincter between the esophagus (food pipe) and the stomach. This gastric acid reflux is noticeable as heartburn. Inhibition of gastric acid production also greatly reduces gastric acid reflux. At night, stomach acid production is reduced by up to 90 percent when H2 receptor antagonists are used. However, when food is consumed, their effectiveness is only about 50 percent. H2 receptor antagonists reduce hydrochloric acid production and the secretion of the enzyme pepsin in the stomach, but they cannot eliminate the cause of increased acid production. However, with their help, the negative effects of acid on the stomach, duodenum and esophagus can be contained. Causes of increased gastric acid production include the activity of the gastric bacteria Helicobacter pylori or hormonal disorders such as Ellison-Zollinger syndrome. H2 receptor antagonists do not have a uniform chemical structure, but only a common function. They bind to H2 receptors and thus can block the binding of histamine to these receptors.
Pharmacologic action
Thus, the main effect of H2 receptor antagonists on the body is to compete with histamine in occupying H2 receptors. Histamine is a tissue hormone that plays a major role in many physiological processes in the body. It is found throughout the body and exerts its effects by binding to the histamine receptors H1, H2, H3 or H4. In addition to its function as a mediator in inflammatory reactions, it is also responsible for acid formation in the stomach. To form and secrete gastric acid and pepsin, it binds to the H2 receptors of the parietal cells of the stomach. The action of H2 receptor antagonists is to block as many receptors as possible from binding with histamine. Thus, although H2 receptor antagonists bind to H2 receptors, they do not trigger production of gastric acid or pepsin in the process. Thus, the fewer H2 receptors available for histamine, the less gastric acid can be produced.
Medical application and use
For the treatment of gastric ulcers and heartburn, H2 receptor antagonists are used to a large extent in addition to proton pump inhibitors. In this context, they have a somewhat lower efficacy against increased acid formation in the stomach than the proton pump inhibitors. The active substance class of H2 receptor antagonists is represented today by the drugs cimetidine, ranitidine, famotidine, roxatidine, nizatidine or lafutidine. Cimetidine was the first drug of these agents and was launched in the 1970s. Due to frequent side effects and interference with the metabolism of many drugs, it has been largely displaced by other agents with the same function today. Each H2 receptor antagonist exhibits individual potency. Famoditin has been shown to be most effective. While only 40 milligrams are required for the same effect, nizatidine and raniditine require as much as 300 milligrams. Cimetidine even requires 800 milligrams for the same effects. For this reason, stronger side effects develop with its use. The duration of action of the individual H2 receptor antagonists also varies. Famotidine has the longest duration of action at twelve hours. For the other H2 receptor antagonists, the duration of action is between four and six hours. The use of these agents is intended to prevent the harmful influence of acid on the stomach, duodenum or esophagus.Stomach acid can further destroy especially the mucous membranes of the stomach and duodenum damaged by bacteria, thus forming the basis for ulcers. There is no protective mucosal layer in the esophagus. When gastric acid gets there, it results in immediate cauterization, which is manifested by heartburn. H2 receptor antagonists do not directly protect the mucous membranes of the stomach, duodenum, and esophagus, but they do reduce the harmful influence of stomach acid by decreasing its concentration in the stomach.
Risks and side effects
However, side effects can also be expected when taking H2 receptor antagonists. Because cimetidine does not exert its effects until high concentrations are used, this is also where the most severe side effects occur. Hypersensitivity can lead to headaches, joint pain, dizziness, sleep disturbances, depression or even hallucinations. Furthermore, allergic skin reactions, digestive disorders or cardiac arrhythmias may occur. In particular, disruption of the metabolism of other drugs by inhibition of the cytochrome P450 system has largely driven cimetidine off the market. The other H2 receptor antagonists do not interfere with the detoxification process in the liver. However, they also exhibit side effects, but these are less frequent due to the use of smaller amounts. Ranitidine or famotidine, for example, develop similar side effects in some cases. Allergic skin reactions with itching and rashes may occur. Gastrointestinal problems with nausea, vomiting, diarrhea, or constipation are also observed. Finally, headaches and joint pain may occur in rare cases. Common to all H2 receptor antagonists is their contraindication in hypersensitivity, pregnancy, and during lactation.
