All About Antihistamines

During an allergic reaction, histamine binds to receptors throughout the body, causing fluid to escape from capillaries into tissues and leading to the classic allergy symptoms. Histamine also regulates some gut functions, acts as a neurotransmitter, plays a role in the inflammatory response, and can mediate itching.

While some individuals use the term antihistamine to refer to any anti-allergy drug, medical experts use it exclusively for medications that interact with histamine. Most of the drugs block the effects of histamine binding to its receptors. Because histamine's functions are so widespread, this has a range of effects beyond reducing allergy symptoms, though this is the most common. Some antihistamines help decrease stiffness and tremors in people with Parkinson's disease, and some doctors prescribe them to manage anxiety.

Histamine receptors have constitutive activity, meaning they do not necessarily need to bind to anything to produce a biological response. Because of this, most antihistamines are receptor antagonists or inverse agonists. Receptor antagonists prevent a biological response by binding to and blocking a receptor. Inverse agonists bind to the receptor, causing it to create a response opposite to that of the histamine.

By far, the most popular antihistamines inhibit the activity of the H1 receptor. These medications can either be receptor antagonists or inverse agonists, though antagonists are more common. Depending on the allergic condition, many H1 antihistamines are available for topical use through the eyes, nose, or skin. These medications are ideal for treating allergic reactions in the nose, though they have seen use as insomnia, motion sickness, and vertigo treatments, as well.

Similarly to H1-antihistamines, H2-antihistamines can be either inverse agonists or receptor antagonists. They act on the H2 receptors in the stomach, decreasing the body's production of stomach acid. This has several effects but is most useful for treating peptic ulcers, indigestion, and gastroesophageal reflux disease. Additionally, H2-antihistamines can prevent stress ulcers and aspiration pneumonitis. Some over-the-counter medications for heartburn and other gastric issues are H2-antihistamines, which are significantly more effective than general antacids in reducing the symptoms of excess gastric acid.

H3 receptors exist primarily in the brain and play a role in the signal processing of the nerves responsible for the release of histamine. Researchers have studied H3-antihistamines as treatments for a wide range of neurological issues. Several antihistamine clinical trials are underway for treating narcolepsy — the medications help release histamine into the cerebrospinal fluid, promoting wakefulness. Other conditions that experts hope to treat include Alzheimer's disease, ADHD, and schizophrenia.

Not much is known about H4 receptors because they were discovered only recently. These receptors reside mostly in bone marrow and white blood cells and seem to play a role in eosinophil shape change and mast cell chemotaxis, meaning they may have important immune response functions. Using H4-antihistamines, doctors may be able to treat asthma and many allergies. Research suggests that some H4-antihistamines may also have anti-inflammatory and antihyperalgesic effects, making them potential treatments for symptoms of long-term opioid use or other inflammatory conditions.

Most people use antihistamines exclusively to manage allergy symptoms. Because there are so many antihistamines, it can be difficult to choose the correct one. Some medication packages identify a drug as first, second, or third generation. First-generation antihistamines are the oldest, don't last as long, and cause drowsiness. Newer generation antihistamines target more specific receptors, so their effects are more targeted and last longer. Individuals with any questions regarding taking antihistamines should speak with their doctor or pharmacist.

Antihistamine side effects vary from brand to brand and type to type. Medications for allergy relief are generally safe but may cause drowsiness, dry mouth, dizziness, changes in vision, and decreased appetite. H2-antihistamine side effects include headache, dizziness, confusion, diarrhea, constipation, and rash. Side effects of H3-antihistamines are largely neuropsychiatric, with insomnia, headache, and anxiety being most common. Because they are the rarest and newest, H4-antihistamines have the least amount of research behind them. Their side effects may include constipation, drooling, muscle stiffness, tremors, bed-wetting, and hyperglycemia.

Ultimately, it is best for a medical professional to determine which medications are necessary. Despite their general safety, antihistamines for allergies do have some potential issues and may negatively interact with other medications. Anyone using antihistamines for other reasons should speak with their doctor if they have any concerns.