Гистаминді H1 рецепторларын тағайындаушылар және аллергиялық реакцияларға қарсы күресу

Drugs that block the action of histamine
DISPLAYTITLE:H1 antagonist

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines. In common use, the term "antihistamine" refers only to H1 antihistamines. Virtually all H1 antihistamines function as inverse agonists at the histamine H1 receptor, as opposed to neutral antagonists, as was previously believed.

Adverse drug reactions are most commonly associated with the first generation H1 antihistamines. This is due to their relative lack of selectivity for the H1 receptor and their ability to cross the blood–brain barrier. The most common adverse effect is sedation; this "side effect" is utilized in many OTC sleeping aid preparations. Other common adverse effects in first generation H1 antihistamines include dizziness, tinnitus, blurred vision, euphoria, incoordination, anxiety, increased appetite leading to weight gain, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough. Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination, psychosis and erectile dysfunction. The newer, second generation H1 antihistamines are far more selective for peripheral histamine H1 receptors and have a better tolerability profile compared to the first generation agents. The most common adverse effects noted for second generation agents include drowsiness, fatigue, headache, nausea and dry mouth.

In type I hypersensitivity allergic reactions, an allergen (a type of antigen) interacts with and cross links surface IgE antibodies on mast cells and basophils. Once the allergen cross links Immunoglobulin E, tyrosine kinases rapidly signal into the cell, leading to cell degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, the histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1 receptors, produces pruritus, vasodilation, hypotension, flushing, headache, bradycardia, bronchoconstriction, increase in vascular permeability and potentiation of pain. While H1 antihistamines help against these effects, they work only if taken before contact with the allergen. In severe allergies, such as anaphylaxis or angioedema, these effects may be of life threatening severity. Additional administration of epinephrine, often in the form of an autoinjector, is required by people with such hypersensitivities. + Comparison of selected sedating antihistamines Antihistamine Dosea Time to peak Half lifeb Metabolism Anticholinergic Diphenhydramine 50 mg 2–3 hours 2–9 hours CYP2D6, others Yes Doxylamine 25 mg 2–3 hours 10–12 hours CYP2D6, others Yes Hydroxyzine 25–100 mg 2 hours 20 hours ADH, CYP3A4, others No Doxepin 3–6 mg 2–3 hours 17 hoursc CYP2D6, others No (at low doses) Mirtazapine 7.5–15 mg 2 hours 20–40 hours CYP2D6, others No Quetiapinee 25–200 mg 1.5 hours 7 hoursd CYP3A4 No (at low doses) Footnotes: a = For sleep/sedation. b = In adults. c Active metabolite nordoxepin half life is 31 hours. d Active metabolite norquetiapine half life is 9–12 hours. e Not recommended per literature reviews. Sources: See individual articles for references. See also selected reviews.

These are the oldest H1 antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly potent muscarinic acetylcholine receptor (anticholinergic) antagonists as well. These agents also commonly have action at α adrenergic receptors and/or 5 HT receptors. This lack of receptor selectivity is the basis of the poor tolerability profile of some of these agents, especially when compared with the second generation H1 antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes.

H1 receptor antagonists that are approved for over the counter sale, at least in the United States, include the following.