AntiallergicsAntihistamines are therapeutically used substances that weaken the effect of the body’s own messenger substance histamine. Histamine plays a central role in allergic reactions, inflammations, sensations such as nausea and in the regulation of the sleep-wake rhythm. Especially in the treatment of allergies, such as hay fever, antihistamines are indispensable.

Antihistamines are also very effective drugs for the symptomatic treatment of travel sickness (for example with Vomex®). Many preparations are available without prescription in pharmacies. Histamine is found in many tissues of the body.

It is formed from the amino acid histidine and stored in so-called mast cells. It can be released by endogenous and exogenous factors. Histamine unfolds its effect after its release by binding to histamine receptors.

Histamine is particularly highly concentrated in the mucous membranes of the stomach and bronchi and in the skin. Lower histamine concentrations are found in blood cells, the so-called basophilic leukocytes and thrombocytes. Histamine also plays a role as a signal transmitter in the central nervous system.

You can find more information on this topic at: HistamineHistamine is a messenger substance. It is released from the affected cells when tissue damage occurs, such as sunburn, burns, cuts, bruises, etc. As a result, surrounding blood vessels dilate to ensure better blood circulation in the damaged tissue and increase the permeability of the blood vessel walls.

As a result, components of the defence system can enter the damaged tissue, inflammatory cells can migrate, destroyed cell fragments can be transported away and the tissue can renew itself. In the stomach, histamine increases the production of gastric acid; in certain regions of the brain, it serves as a messenger substance for the transmission of information between nerve cells. It influences the sleep-wake rhythm, nausea and vomiting.

Histamine can be released by mechanical stimuli, e.g. pressure on tissue, but solar radiation and heat can also have this effect. In addition, certain substances can cause histamine to be released into surrounding tissue. These substances can be endogenous hormones such as gastrin on the one hand, or exogenous substances such as insect venoms, drugs or so-called antigens on the other.

Antigens are substances that provoke a defensive reaction of the body. Nowadays, many people suffer from a hypersensitive defence system. They react very sensitively to contact with certain substances, such as pollen, house dust, food, cosmetics, etc.

If antigens bind to cell surfaces, e.g. an inhaled pollen on cells of the nasal mucosa, the antigen “pollen” is recognized as foreign by the immune system. The cell is destroyed and the histamine it contains is suddenly released. For the allergy sufferer, this histamine release can be felt in different ways, for example through reddening of the skin with wheals, swelling of the mucous membranes of the upper and lower respiratory tract or through itching.

Histamine mediates its effect by binding to a histamine receptor after its release from the mast cells on adjacent cell surfaces. This signal usually causes the cell to activate or deactivate certain processes by sending out further messenger substances. There are 4 different types of histamine receptors: H1, H2, H3 and H4.

When histamine binds to an H1 receptor, it produces the following effects in varying degrees: Blood vessels contract, the walls of the vessels become more permeable, mucous membranes swell, the bronchial tubes in the lungs constrict, the skin shows redness as a result of the increased blood flow and may form small wheals. Excessive histamine release, as is the case with allergic reactions or hives (urticaria), is usually accompanied by annoying itching. Itching is caused by histamine-stimulated nerve endings in the skin.

H1-receptors are also found in the brain. There, histamine acts as a transmitter between nerve cells and influences the sleep-wake rhythm. On the one hand, it is involved in the wake-up reaction and increases the waking state.

On the other hand it controls the feeling of nausea and the nausea stimulus. H2-receptors are mainly found in the gastrointestinal tract. Histamine is stored in the so-called ECL cells (enterochromaffin-like cells).

The cells can be stimulated to release histamine by the hormone gastrin. The histamine then binds to H2 surface receptors of neighbouring document cells, whereupon these cells produce gastric acid and thus promote digestion. In addition, the activation of H2 receptors results in accelerated heart activity and the contraction of blood vessels.

When histamine binds to H3 receptors, this has self-regulating effects on histamine release. Activated H3 receptors inhibit the release of histamine in the brain and regulate the release of other messenger substances. As a result, hunger, thirst, day-night rhythm and body temperature are controlled.

H4 receptors have not yet been sufficiently researched. However, there are indications that they play a role in allergic asthma. Of the types of histamine receptors described above, only drugs that bind to H1 and H2 receptors are currently on the market; these are known as H1 or H2 antihistamines.

The term “antihistamines” means “drugs that counteract histamine”. This works as follows: the respective active ingredients compete with the body’s own histamine for the binding site at the receptor on cell surfaces. The active ingredient usually has a better binding capacity and can displace the body’s own histamine from the receptor.

Unlike histamine, however, the bound active ingredient does not trigger a reaction. It merely blocks the binding site so that the histamine-typical effect does not occur. H1 antihistamines cancel the effect of histamine on H1 receptors.

This is particularly desirable in allergic diseases such as hay fever, non-infectious itchy skin symptoms such as hives (urticaria) or insect bites. These complaints can thus be effectively alleviated. However, this is only a temporary, symptomatic treatment.

The cause cannot be eliminated in this way. The class of H1 antihistamines has been continuously developed. For this reason, the associated active ingredients are divided into first, second and third generation H1 antihistamines.

The disadvantage of first-generation H1 antihistamines is that they act not only on H1 receptors but also on other types of receptors. This may result in side effects such as dry mouth, headache, dizziness, nausea or fatigue. The latter, in turn, has been made therapeutically useful.

Some in first-generation H1 antihistamines are also used as sedatives to promote sleep. Some active ingredients, which also belong to first-generation H1 antihistamines, show pronounced effects against the symptoms of motion sickness, such as nausea and vomiting. H1 antihistamines of the second generation have hardly any sedative side effects and have a primarily anti-allergic effect.

For antiallergic therapy, the first generation antihistamines were further modified. A major disadvantage of the old antihistamines (e.g. clemastine, dimetinden) was the sleep-promoting side effect. For this reason, the substances of the second generation were modified so that they could no longer cause increased fatigue in the central nervous system.

As a result, the second generation antihistamines are characterised above all by a strong anti-allergic effect. In the context of an allergic reaction, there is a strong inhibition of swelling and reduced itching and pain. In addition, the antihistamines cause a slight dilatation of the bronchi.

The best-known second-generation active ingredients include cetirizine and loratadine. Terfenadine, which was frequently used for a long time, has led to considerable cardiac rhythm disturbances and is therefore no longer approved for the market in Germany. H1 antihistamines are a very important group of drugs for the treatment of allergies.

They effectively relieve symptoms such as itchy, watery eyes, swollen nasal mucous membranes with the feeling of a blocked nose, itchy nose with the associated sneezing stimulus. H1 antihistamines are also used to treat skin symptoms such as itching, wheals and redness of the skin, which can be found in allergies, chronic urticaria, sunburn, minor burns and insect bites. The second generation lacks the sedative, sleep-inducing effect.

That is why active ingredients of this generation are preferred nowadays, if this effect is not desired. Another field of application is histamine intolerance. Some active ingredients of the first generation of H1 antihistamines have an anti-nausea and vomiting effect, often also calming.

Therefore, they can be taken as a preventive measure against motion sickness or nausea and vomiting. With some H1 antihistamines, the anti-allergic effect recedes into the background compared to the sedative effect, so that they are primarily used as sedatives and sleep-inducing agents. H2 antihistamines have a different field of application from H1 antihistamines.

They reduce the production of stomach acid and can be used to treat stomach acid-related complaints such as reflux disease and stomach or small intestinal ulcers. Individual preparations (terfenadine, astimezole) cause considerable cardiac rhythm disturbances and have therefore already been withdrawn from the market in some countries. These substances cause an extension of the QT time of the heart in the ECG (excitation propagation and regression of the heart), which can lead to severe disturbances of the heart rhythm with an increased risk of sudden cardiac death. With many other preparations, a significantly increased heartbeat often occurs during therapy. Individual patients report a tachycardia and inner restlessness.