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<unk> -receptors, produces pruritus, vasodilation, hypotension, flushing, headache, bradycardia, bronchoconstriction, increase in vascular permeability and potentiation of pain. While<unk> -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.
H1 antagonist
GABA analogue
Muscarinic antagonist
Alpha-adrenergic agonist
Opioid antagonist
Beta-adrenergic agonist
5-HT3 antagonist
Beta2-adrenergic agonist