H1 receptor antagonists

H1 receptor antagonists competitively inhibit histamine binding at H1 receptors, which are Gq-coupled receptors found on vascular smooth muscle, bronchial smooth muscle, and CNS neurons. By blocking these receptors, they reduce vasodilation, capillary permeability, bronchoconstriction, and pruritus associated with allergic responses.

First-generation agents (e.g., diphenhydramine, chlorpheniramine, hydroxyzine, doxylamine) are lipophilic and cross the blood-brain barrier, causing sedation, anticholinergic effects (dry mouth, urinary retention, constipation, blurred vision), and antiemetic/antivertigo properties (useful in motion sickness via vestibular H1 blockade). They also have alpha-adrenergic and muscarinic blocking activity, contributing to side effects like hypotension and tachycardia. Diphenhydramine is also used for extrapyramidal symptoms and as a sleep aid.

Second-generation agents (e.g., loratadine, fexofenadine, cetirizine, desloratadine) are more selective for peripheral H1 receptors and less lipophilic, resulting in minimal CNS penetration and reduced sedation and anticholinergic effects. They are preferred for chronic allergic conditions like allergic rhinitis and chronic urticaria due to better side effect profiles and once-daily dosing.

Clinical uses include allergic rhinitis, urticaria, atopic dermatitis (adjunct), anaphylaxis (adjunct to epinephrine), motion sickness, and insomnia (first-gen only). Contraindications/cautions include narrow-angle glaucoma, BPH (due to anticholinergic effects with first-gen), and caution in elderly patients due to increased fall risk and cognitive impairment (Beers criteria flags first-generation antihistamines in elderly).

Key boards points: distinguish first vs second generation based on sedation/anticholinergic effects; understand mechanism as competitive antagonism at H1 receptor; know clinical uses and adverse effect profiles for USMLE pharmacology questions.