Allergies are among the more common maladies affecting average Americans. More than 10 percent of the population is believed to suffer from allergies at one time or another. Defined as a hypersensitivity disorder of the immune system, allergies result when the immune system incorrectly identifies a harmless protein (or, sometimes, a sugar-like molecule called a polysaccharide) as a threat. The immune system reacts to the presence of this “threat” by releasing a substance called histamine, which triggers the inflammatory response. 

This in turn prompts the release of a cascade of inflammatory proteins, which causes symptoms ranging from itching, watery eyes to a stuffy (or runny) nose, swollen nasal passages, and more. Since histamine plays a crucial role in promoting this cascade of immune system chemicals, blocking histamine’s action is one way to nip the allergic response in the bud. Antihistamines are drugs that do just that.

Histamines are released by specialized immune system cells called mast cells. When prompted by the presence of an allergen, mast cells release their supply of histamine and other chemicals. Histamine floods local tissues and quickly binds with specialized receptors on other cells. Working much like a key in a lock, histamine engages with histamine receptors to trigger the release of still more immune system chemicals. Excessive and inappropriate inflammation is the response and miserable allergy symptoms are the result.

Antihistamines are chemicals that mimic histamine closely enough to bind with the histamine receptors, thus blocking the ability of natural histamine to engage with these receptors. Although they block receptors, antihistamines do not trigger the same responses in cells that histamine does. Although antihistamines first came on the scene in the late 1940s as prescription drugs, they are now widely available as over-the-counter drugs. Examples include loratadine (Claritin), cetirizine (Zyrtec), and fexofenadine (Allegra). In fact, second-generation antihistamine drugs with 24-hour activity are often available relatively inexpensively in pharmacies, grocery stores, and even discount club-style warehouse retailers.

The First Generation

The first antihistamine, diphenhydramine HCl (e.g. Benadryl), was originally available by prescription only. Eventually it went generic, which lowered the cost of the drug. The drug was very popular.

Other examples of first-generation antihistamines include brompheniramine (Dimetapp), chlorpheniramine (Chlor-Trimeton), and dimenhydrinate (Dramamine). Ultimately, manufacturers developed second-generation antihistamines to compete with diphenhydramine and other first-generation antihistamines.

In time, the FDA agreed to allow diphenhydramine to be sold without a prescription. Eventually, a number of second-generation antihistamines followed this pattern, which greatly increased the availability and affordability of these safe and effective allergy medications. Although the arrival of diphenhydramine on the market represented an important breakthrough for allergy sufferers, it had one notable side effect: the drug makes some people sleepy. 

In fact, this side effect has been exploited by manufacturers, who repackage the drug as a sleep aid. Diphenhydramine appears in a wide range of over-the-counter sleep aid formulations, due to its ability to induce drowsiness. This effect occurs because diphenhydramine crosses the blood-brain barrier. The blood-brain barrier is a sort of physiological filter that blocks many substances from entering the brain. This offers some degree of protection to the sensitive central nervous system. 

Diphenhydramine, and other first-generation medications, are able to cross this barrier and bind with histamine receptors in brain cells, which accounts for their sedating effects. For better or worse, this side effect of diphenhydramine has led many people to associate antihistamine use in general with drowsiness. But second-generation drugs, such as cetirizine, or loratadine, are not sedating. In fact, second-generation antihistamines have very few side effects in healthy adults.

Use With Caution

Because they can induce sleepiness, first-generation antihistamines should be used with extreme caution, especially when driving or operating heavy machinery. These drugs should not be taken along with sedatives, sleeping pills, or muscle relaxants, except under a doctor’s supervision.

When taken to induce or enhance sleep, some first-generation antihistamines may be associated with a next-day sedative effect, which might be described as a sort of “hangover.” Not all people experience this effect, however.