Topic overview

Start with the big picture

Histamine receptors are G-protein-coupled receptors: H1 signals through Gq, H2 through Gs, and H3 and H4 through Gi. H1 activation contributes to vasodilation, increased vascular permeability, bronchospasm, itching, pain, and wakefulness; H2 activation promotes gastric acid secretion and affects cardiac activity and vascular tone. H1 activity also underlies the triple response of red spot, flare, and wheal. H1 antihistamines act as inverse agonists. First-generation agents are generally lipophilic and may cause sedation and antimuscarinic effects, while second-generation agents are more polar and have less sedating and anticholinergic activity. Topical and intranasal options can provide local relief. The deeper lesson connects these mechanisms with clinical uses, adverse effects, interactions, contraindications, and overdose.