In allergy sufferers, for unknown reasons, the immune system "blots" harmless flower pollen, food particles and other substances that are normally health-neutral with dangerous germs or parasites. It mobilizes immune cells to strenuous and chronic struggle with the apparent but mass influxing "aggressor" - an allergen. The result of this fight are symptoms that cause serious damage to health.
Allergy treatment is dominated by antihistamines.
Modern antihistamines effectively fight the symptoms of allergic rhinitis, conjunctivitis, and idiopathic urticaria. Modern antihistaminics remove watery cold, persistent sneezing attacks, and so the symptoms that prevail in allergic rhinitis; it counteracts pruritus, watery eyes, etc. In asthma, antihistamines are sometimes used as adjunctive therapy.
How does antihistamines work on the body?
- do they ask themselves this question about allergies and asthma? Do not they have unwanted side effects? Below we will answer these questions.
What is the role of histamine in allergic diseases?
Histamine initiates the development of allergic inflammation. This mediator works pro-inflammatory, as well as influences on secretion of mediators of allergic reaction - cytokines. Cytokines are proteins and peptides secreted mainly by cells of the immune system. They control the course of inflammatory processes (and the action and maturation of immune cells). These include interleukins, interferons and growth factors of bone marrow cells. Histamine through excessive release of cytokines - co-determines the development of a highly deleterious allergic reaction to health.
How do antihistamines work?
Antihistamines act by blocking special cellular receptors for histamine - mainly so-called H1 receptors. These cellular receptors (abundantly present in some immune cells - e.g. mast cells) - are special proteins associated either with the membrane or with the interior of the cell. They are highly sensitive chemically to the selected active physiologically-protein mediator transferring specific orders, whether the hormone controlling physiological processes, etc. Histamine receptors are the chemical "lock" of many immune cells that unnecessarily opens histamine. Histamine, by binding to its receptor, opens, for example, access to calcium ions, which results in the escalation of acute allergy symptoms.
Certain substances block the histamine receptors and act therapeutically
However, it turned out that the chemical structure of cellular receptors, including histamine receptors, is very sensitive to the influence of some external substances. If the receptor substance changes earlier under the influence of a chemical blocker, it will lose its ability to bind to the physiologically appropriate substance, which is histamine. This feature of the receptors has been used by the manufacturers of antihistamines.
What determines the effectiveness of antihistamines?
The therapeutic effectiveness of antihistamines depends on how strongly the active substance is bound to the cellular receptor - thereby blocking its other potential reactions to histamine.
It is easy to see the efficacy of an antihistaminic drug depends on "winning" competition with histamine for the receptor. The ability to bind early and adequately to the H-1 receptor allows this battle to be won. At the same time, it closes access to histamine which is abundantly secreted in response to an allergen. Thus, blockade of the drug effectively protects against the entry of calcium into the interior of cells of many organs and associated symptoms of allergic diseases.
A few years ago, antihistamines were used not very readily - although they were already effective.
The cause was the side effects - drowsiness, fatigue, weight gain and alcohol intolerance. Even then, they were much safer than corticosteroids - because even with prolonged use they did not cause serious consequences. However, pharmaceutical laboratories constantly work on improving the safety of this group of medicines and achieving better therapeutic effects. The result of these works are so-called II generation.
Why is modern medicine attaches great importance to the improvement of antihistamines?
The answer stems from the physiology of the allergic reaction. Histamine is the most abundant substance secreted by mast cells. Admittedly, other inflammatory mediators are released along with it: prostaglandins D2, leukotrienes C4 and D4 and platelet activating factor - however, histamine is secreted in hundreds of times more than the other substances.
Health damage caused by excessive secretion of histamine
In the case of histamine, both its large amount and its physicochemical properties cause strong and severe physiological reactions. The abundant "burst" of histamine from mast cells arouses the so-called early allergic reaction. It consists of the release of nitric oxide by endothelial cells, which causes the expansion of small blood vessels and increases their permeability. As a result, blood cells penetrate into the extravascular space and cause edema and inflammation of the nasal mucous membranes, nasivadas, bronchi, sometimes intestinal mucosa, or - in the case of skin allergy - redness, swelling and inflammation of the skin of the smooth body. Long-term histamine secretion by mast cells induces a number of subsequent disease-related symptoms.
Histamine and allergy
What conditions should an effective and safe antihistamine meet?
An ideal antihistamine should be characterized by a rapid onset of curative activity and 24-hour duration of action. This means that he should reach the maximum concentration in the blood as soon as possible. Secondly, it should not cause adverse side effects and not accumulate in the tissues, not be broken down in the liver and expelled in possibly unchanged form. Meeting the above conditions should effectively block annoying allergy symptoms.
What properties are currently available in this field?
Most antihistamines, called histamine receptor antagonists (so-called H1 receptors), are rapidly absorbed and often reach peak plasma concentrations within 2 hours. The active substances of drugs are largely bound by blood proteins and do not accumulate in the tissues. It has also been documented that the effectiveness of antihistamines is high.
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For example, one of the newest generation drugs - fexofenadine
This substance is absorbed quickly because it reaches its maximum concentration in 2.6 hours. It binds only to blood proteins and in unchanged form it is excreted in the faeces (80%) and urine (12%). Only 5% of the drug undergoes metabolism, with the hepatic metabolism being minimal (around 5-5.5%) and the result is the inactive metabolite.The half-life of the drug is - 11-15 hours, which brings its action time to an ideal pattern, because the action blocking histamine receptors is maintained even when the drug concentration in plasma is minimal.
Are there any side effects of antihistamines?
Until recently, first generation antihistamines caused a number of symptoms, such as dry mouth, headaches, urinary retention and impaired perception and drowsiness. These last symptoms, especially the distraction of attention, made it impossible to drive motor vehicles, aircraft, etc., which prevented or impeded work, learning or traveling. Most of the side effects of the first generation drugs were not shown by the second generation drugs.
The first drug that did not cause such symptoms was astemizole. It turned out, however, that in combination with other drugs it can cause heart problems, so it is now withdrawn in most countries. Another drug was cetirizine; shortly after, loratadine was synthesized. Both of these drugs are now called "second generation antihistamines", although it is still not recommended to drive a car when using cetirizine (the same applies to high doses of loratadine). These drugs, thanks to convenient dosage - once a day - have become very popular.They are a convenient alternative to hormones in allergic rhinitis, eye conjunctiva and in cases of urticaria; in asthma they are sometimes used as supportive care.
Statements of doctors treating patients with antihistamines
Here is what one of the well-known physicians is saying about the safety of using antihistamines for such side effects as impaired perception and drowsiness:
"- We evaluated 15 healthy elderly volunteers to evaluate the effect of several antihistamines: those who received a second generation drug (loratidine or cetirizine) felt significantly less of these drugs than those receiving first-generation drugs." Antihistamines have undergone a significant change from first-generation drugs to second-generation drugs such as fexofenadine or loratadine, which are better tolerated and equally effective in the treatment of allergic rhinitis or idiopathic urticaria. It is worth noting that the latest generation drugs - eg the mentioned fexofenadine, as well as ebastine do not show any effects on the nervous system.
Safe for the heart and circulatory system
Reservations regarding the safety of antihistamines against the heart and circulatory system appeared in the late 1980s. Initially, they concerned cardiac ventricular fibrillation after astemizole overdose. A thorough study of the causes of these disorders, which also appeared under the influence of another terhistamine - an antihistaminic drug - revealed that their cause is inhibition of the so-called channels that carry potassium ions to the heart - which hindered the supply of this bioelement, necessary for correct contractility of muscle fibers of the heart. The resulting tachyarrhythmia - it was life-threatening for the patient. These drugs have been withdrawn, and in some countries there is no other drug registered - ebastine, which also inhibited the transport of potassium to the heart muscle. Under the influence of the above negative experiences - the study of new drugs, in terms of their impact on the patency of potassium channels - has become the standard. For example, the latest generation of antihistamines - fexofenadine has been thoroughly tested in this respect in many preclinical and clinical studies. It was only after careful verification of the absence of side effects and was admitted to the general medical practice.
Antihistamines are not toxic
Before going on sale, the drug undergoes multilateral and precise preclinical and clinical tests testing its effect on the body. In the case of antihistamines, such tests are first performed on animals, using very high doses (in order to determine the minimum effective dose for humans), and then only the therapeutic effect on humans is first examined (first only the effect on volunteers). In the latter studies, the effects of the drug on the liver, kidneys and other important organs and functions of the body are assessed. For example, during the comprehensive studies of one of the drugs (fexofenadine) no significant side effects of the drug were observed. In animal studies, for example, no negative effects on fertility, litter size or fetal death were found. In spite of this, due to the high level of caution of drugs from this group, as well as many other safe for animals are not recommended for pregnant women, as well as for nursing mothers. However, the safety of this group of drugs for patients can be demonstrated by the use of one of the drugs (cetirizine) in the prevention of asthma in high-risk infants, i.e. allergic to dust mites and grass pollen. Despite the high doses of the drug, the percentage of small patients who discontinued the treatment was low and the side effects were rare.
No interactions and side effects
The advantage of new generation antihistamines is - unlike the old one - lack of clear antagonism with foods, alcohol (in moderate doses) and medicines used to treat allergic diseases. Interactions with other drugs are very rare and irrelevant to health. On the contrary, in the case of combined treatment with glucocorticosteroids, a synergy is found to reduce the dose of the latter. (And as we know, glucocorticoids are not always indifferent to health.)
Thanks to the progress in the pharmaceutical industry
Currently, thanks to the latest medications, the treatment of symptoms of allergic diseases - because we can not cure diseases themselves except through desensitization - has become effective and safe today!
This does not diminish the cardinal role of anti-legal prophylaxis
The drugs themselves, however, are not enough.People with allergies should follow a healthy lifestyle: do not smoke, avoid alcohol (wine and beer can be a strong allergen), fight overweight (especially important for patients with asthma), take a lot of movement, avoid excessive sun exposure. They should also, if they know their allergen, eliminate as far as possible from their surroundings; there are special vacuum cleaners for patients with asthma, there are calendars available with dusting periods for individual plant species, etc.
Final warning
But beware - safe drugs do not mean that the disease itself does not put us at risk of an unexpected allergic reaction to a strong allergen. Therefore, if sometimes we are tempted to experiment with an extremely effective medicine, which the doctor prescribed the familiar
