Cetirizine mechanism of action
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Cetirizine Mechanism of Action: H1 Receptor Antagonism
Cetirizine is a second-generation antihistamine that works primarily by blocking histamine H1 receptors. By acting as a potent and selective H1 receptor antagonist, cetirizine prevents histamine—a key mediator in allergic reactions—from binding to its receptors, thereby reducing symptoms such as itching, swelling, and redness in conditions like allergic rhinitis, urticaria, and other allergic disorders 149.
Selectivity and Central Nervous System Effects
Cetirizine is a carboxylated metabolite of hydroxyzine and is classified as a piperazine derivative. Unlike first-generation antihistamines, cetirizine has minimal ability to cross the blood-brain barrier due to its larger size and lipophobic nature. This results in fewer central nervous system side effects, such as sedation, making it a nonsedating antihistamine. Its high selectivity for peripheral H1 receptors over central receptors further contributes to its low sedative profile 1489. At standard doses, cetirizine does not cause significant sedation, although higher doses may show mild EEG changes without behavioral signs of drowsiness .
Anti-Inflammatory and Antieosinophilic Properties
Beyond H1 antagonism, cetirizine exhibits additional anti-inflammatory effects. It inhibits the infiltration of eosinophils into tissues, which is important in controlling the late-phase allergic response and tissue damage seen in chronic urticaria and other allergic conditions . Cetirizine also enhances the release of prostaglandin E2 (PGE2) from monocytes and macrophages, which may contribute to its anti-inflammatory action . These effects are thought to involve interactions with both H1 and H2 histamine receptors and modulation of immune cell activity 26.
Mast Cell Stabilization
Cetirizine has been shown to stabilize mast cells, preventing their degranulation and the subsequent release of histamine and other inflammatory mediators. This mast cell-stabilizing effect is more potent than that of some first-generation antihistamines, such as diphenhydramine, and may further enhance its effectiveness in preventing allergic reactions .
Additional Mechanisms and Clinical Implications
Recent research suggests that cetirizine may also modulate pain pathways and enhance the analgesic effects of other drugs, such as morphine, through interactions with GABA-A receptors in the brain, although these effects are still being explored . In experimental models, cetirizine has also been linked to inhibition of tumor metastasis by blocking the histamine H1 receptor axis and suppressing key signaling pathways involved in inflammation and angiogenesis .
Conclusion
Cetirizine’s primary mechanism of action is potent, selective antagonism of peripheral histamine H1 receptors, leading to effective relief of allergic symptoms with minimal sedation. Its additional anti-inflammatory, antieosinophilic, and mast cell-stabilizing properties further contribute to its clinical benefits in allergy management. These combined actions make cetirizine a widely used and effective option for treating a range of allergic conditions 146910.
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