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Why Do Antihistamines Make You Drowsy?
Credit: Allergies photo via Shutterstock

Drowsiness is one of the major side effects of some antihistamines, such as diphenhydramine (Benadryl) and doxylamine succinate (the antihistamine found in Nyquil). And because of their powerful sedating qualities, antihistamines are also the active ingredients found in numerous over-the-counter sleep aids.

But why do antihistamines make you sleepy?

The story begins with histamines, which are chemical compounds that play a couple of roles in the body, though they're best known for their involvement in the body's local immune responses.

When you get injured or your immune system detects a potentially dangerous foreign substance, certain white blood cells and tissue cells release histamines that seek out and attach to other cells that have a histamine receptor.

Here, the histamines induce an inflammatory response — they dilate the blood vessels, increasing blood flow to the site of injury or invasion. They also make blood vessels more permeable, allowing proteins and white blood cells to seep into the damaged or infected tissue.

But there are side effects to this healing process. For example, when you're fighting a cold (the rhinovirus), histamines widen the blood vessels in your nasal cavity, causing nasal congestion.

Additionally, the increased fluid leakage from your blood vessels, combined with an increased mucous production — also caused by histamines — can result in a runny nose.

Allergies occur when your immune system erroneously thinks an innocuous foreign substance, such as pollen or pet dander, is actually dangerous. Histamines jump to action, causing the range of symptoms associated with allergies (sneezing, itchy eyes, chest congestion, wheezing, etc.).

Antihistamines are typically used to ease allergy symptoms, and work by blocking histamines' attachment to receptors, preventing the compounds from carrying out their functions.

But older, first-generation antihistamines, including diphenhydramine and doxylamine succinate, don't discriminate between which histamine receptors they block.

They can cross the blood-brain barrier and inhibit one of the other functions of histamines — that is, the pivotal role they play in regulating sleep and wakefulness. This disruption of the action of histamines in the brain results in drowsiness.

Newer antihistamines such as loratadine (Claritin) and fexofenadine (Allegra) have been shown in clinical trials to cause less drowsiness than first-generation antihistamines.

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