Principle of antihistamine
Antihistamine (histamine antagonist, anti-histamine) generally refers to a drug that inhibits the action of histamine, which is involved in allergic reactions such as hives, redness, and itching. In other words, it is a drug that inhibits the action of histamine by inhibiting histamine from binding to histamine receptors, or inhibits the activity of histidine decarboxylase (HDC), a catalytic enzyme that converts histidine to histamine, thereby inhibiting the synthesis of histamine.
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| When the carboxyl group of histidine is removed by HDC, it becomes histamine. (Front. Immunol. 2018) |
Histamine, as mentioned here, is a basic component of the human body and is a protein involved in cell proliferation, differentiation, blood cell production, inflammatory response, tissue regeneration, and neurotransmission (Middleton's allergy 2009). Histamine is naturally produced to repair damaged tissue from external stimuli (wounds or allergens) and causes allergic inflammatory responses such as swelling, fever, rash, and runny nose, which are normal immune responses. However, when histamine is secreted excessively due to genetic and environmental factors, it often develops into a chronic disease with various uncomfortable symptoms, which has a significant impact on the patient's quality of life.
Since the causes of allergies are diverse, antihistamines cannot improve all allergic diseases. However, since histamine is related to the inflammatory response of most allergic diseases, and especially in diseases where histamine is a major factor, such as allergic rhinitis, allergic conjunctivitis, urticaria, and pruritus, symptoms can be alleviated by inhibiting histamine, antihistamines are widely used for allergic diseases.
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| Zyrtec, a representative 2nd generation antihistamine |
Types of antihistamines
Histamine acts through four histamine receptors in the body: H1, H2, H3, and H4. In addition to H1, histamine receptors for H2, H3, and H4 were discovered only after the 1990s. Traditionally, H1-antihistamines were used in clinical practice, and they began to be used as treatments for allergic diseases in the 1950s when their anti-allergic properties were discovered.
His function varies depending on the type of histamine receptor. Vasodilation and increased vascular permeability occur through H1 and H2 receptors, itching due to skin nerve stimulation and contraction of bronchial smooth muscles are H1 receptors, increased gastric acid is H2 receptors, secretion of neurotransmitters is H3 receptors, and inflammatory responses and differentiation of bone marrow cells are H4 receptors.
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| Histamine receptor-specific characteristics (J Allergy Clin Immunol 2011) |
Currently, only H1 and H2 receptor inhibitors are approved for use, and since common allergic symptoms occur through the H1 receptor, antihistamines usually mean H1-receptor antagonists.
There are several types of H1 antihistamines, and more than 40 types of antihistamines are used worldwide, with the first generation introduced after the 1940s, the second generation newly developed in the 1980s, and the third generation developed in the 2000s and used together.
Side effects of antihistamines
H1 antihistamines can be classified according to their chemical structure and function. They are divided into six groups according to their chemical structure (chemical class), and are classified into first and second generation according to their function and whether they can penetrate the blood-brain barrier (J Allergy Clin Immunol 2011).
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| Classification of H1 antihistamines and antihistamines used in Korea (yellow mark)(J Allergy Clin Immunol 2011) |
The first generation has the advantage of being fast-acting, inexpensive, and available as an injectable, but it easily enters the central nervous system due to its lipophilicity, small molecular weight, and positive charge.
Under normal conditions, histamine stimulates the central nervous system during the day and decreases relatively at night, reducing arousal. However, if the histamine level (even in the brain) decreases after taking the first generation antihistamine, it can cause central nervous system side effects such as drowsiness, fatigue, headache, and memory loss.
Since allergy symptoms usually worsen at night, it is sometimes taken before bed, but first generation antihistamines increase the latency period until REM sleep begins, lowering the quality of sleep, and have a very long half-life, so the central nervous system reaction continues the next day, so caution is required when administering them. Central nervous system side effects of antihistamines are more common in women, the elderly, small body types, people with impaired liver and kidney function, and those with central nervous system abnormalities.
Antihistamines do not have a specific antidote in case of overdose.
In the case of the first generation, cardiotoxic effects (ventricular arrhythmia) or central nervous system abnormalities due to anticholinergic effects may occur (Allergy 2010), and in children or sensitive individuals, coma may occur.
Second-generation antihistamines become dipolar ions at physiological pH (approximately pH 7.4), so their polarity is strong and they cannot pass through the blood-brain barrier, so they have fewer central nervous system side effects. Therefore, if the initial reaction is minimal, the recommended dose can be increased up to four times, but if more than five times the recommended dose is administered, various side effects such as dizziness, diarrhea, fatigue, headache, and itching may occur, so care must be taken not to overuse them.
Since they have fewer central nervous system side effects, second-generation antihistamines are usually recommended primarily for allergic diseases such as allergic rhinitis and urticaria. A representative example is Cetirizine, which is familiar under the brand name Zyrtec. It is convenient because it can be purchased at a pharmacy without a prescription as an over-the-counter drug. Zyrtec is released as a generic drug, so there are cheaper copy drugs, so go to the pharmacy and ask for a cheaper copy of Zyrtec. It is less than half the price, but the effect is the same when you take it.
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| Zyrtec and generic drugs |
Recently, third-generation antihistamines such as levocetirizine have been used, and since they are metabolites of second-generation drugs, they are also called 2.5-generation antihistamines. They have been improved to have less of an effect on the brain than the second-generation drugs, and they have the advantage of being able to be taken at any time, but there is not much research on whether they are more effective. And like most first-generation drugs, they are prescription drugs, so you need a doctor's prescription to purchase them.
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| levocetirizine |
Antihistamines are inverse agonists for histamine receptors, and the appropriate dosage varies depending on the amount of histamine in each individual, and the effectiveness and side effects of antihistamines often vary from person to person. If you need to take an antihistamine for mild allergy symptoms in daily life, I recommend Zyrtec, which can be purchased at a pharmacy without a prescription, but whether it is 1st, 2nd, or 3rd generation, it is right to try it and choose the drug that suits your body well.
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| Second-generation antihistamines available without a prescription |
It has been reported that second-generation antihistamines do not develop tolerance or acute tolerance (tachyphylaxis) even with regular long-term use (J Allergy Clin Immunol 2011; N Engl J Med 2004; Middleton's allergy 2009). However, little research has been done on other side effects of long-term use. Therefore, in any case, care must always be taken not to misuse drugs.
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