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How can H1 antihistamines reduce itching and swelling from insect bites?

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antihistamines, including Benadryl — antihistamine Antihistamines such as Benadryl (diphenhydramine) and Claritin (loratadine) can be purchased without prescriptions. Both of those agents act by blocking H₁ receptors. However, whereas Benadryl binds to those receptors in the central nervous system (CNS), causing drowsiness, Claritin does not readily enter the CNS and thus does not normally cause drowsiness.

H1 antihistamines reduce the itching and swelling caused by insect bites by competing with histamine for occupation of H1 receptor sites.1

When an insect bite occurs, the body releases histamine from [mast cells]. This histamine binds to H1 receptors, triggering a localized immune response that includes the dilation of blood vessels and increased capillary permeability. This process allows plasma proteins and fluid to escape into tissue spaces, resulting in the characteristic redness, swelling, and itching associated with the bite.21

By acting as H1 receptor antagonists, these drugs effectively block histamine from binding to its receptors. By preventing this interaction, H1 antihistamines inhibit the subsequent physiological effects—such as fluid leakage and nerve stimulation—thereby alleviating the discomfort of the bite.21