Antihistamines – Over a Century of Pharmacological Wonder!
Most allergy sufferers are familiar with antihistamines such as Benadryl (diphenhydramine), Chlor-Trimeton (chlorpheniramine), Allegra (fexofenadine), Claritin (loratadine), Clarinex (desloratadine), Zyrtec (cetirizine), and Xyzal (levocetirizine). The newer antihistamines, released since the 1980s, have much better characteristics with respect to efficacy and safety. Older ones like Benadryl and Chlor-Trimeton are much more sedating, drying, and should have limited roles in daily use. Furthermore, long-term use of older antihistamines such as Benadryl and Chlor-Trimeton are associated with dementia in the elderly and impaired learning in the young and emphasize need for limited use.
The evolution of improving the pharmacologic actions of antihistamines started with the de novo synthesis of histamine in 1907, which lead to the research to understand histamine’s actions in the human body around 1910/1911. Histamine is an important chemical messenger exerting its effects through 4 different known receptors throughout the body. As a comparison, serotonin, an important chemical messenger/neurotransmitter, has 15 known receptors. Histamine has several functions such as neurologic transmission, cell proliferation, and wound healing to name a few. Wounds sometimes itch due to excessive histamine. Excessive histamine release perpetuates inflammation through this cellular proliferation (cell growth). Histamine is “kindling” for an inflammatory fire – antihistamines help put out the fire.
The first antihistamine was synthesized in 1937 and used clinically in 1942 but was “too drying” and toxic for continued use. Benadryl was introduced in the USA in 1946. Today, there are over 45 antihistamines available world-wide. Interestingly, selective serotonin reuptake inhibitors (SSRIs) like Prozac (fluoxetine), were discovered by tweaking the Benadryl (diphenhydramine) in the early 1970s. Of note, SSRIs have recently been shown to be antiviral as well.
Antihistamines have very good evidence for helping allergies including rhinitis, conjunctivitis, and itching. They are also used for several other conditions such as nausea, migraines, insomnia, viral infections. Of note, recently and most exciting is the potential for antihistamines to help the immune system fight cancers and virus by changing the chemicals surrounding the cancers and virally infected cells. It has been shown that excessive histamines distract the “killer T cells” which have been shown to “kill” cancers and “kill” “virally infected cells”. Antihistamines are not a primary treatment for viral infections or cancer but may support the immune system’s healing ability by “mopping up” excessive histamines that may be counter-productive to healing.
Since antihistamines have been around a long time with a good safety record, I believe allergy sufferers benefit from their usage. They are associated with improved outcomes of food and inhalant allergy immunotherapy. I recommend usage of the newer non-sedating antihistamines (Zyrtec, Allegra, etc.) while taking allergy shots. I also recommend taking them when fighting a virus or cancer. However, always check with your prescriber before taking therapy even though they are over the counter medications.
Obviously, any medication can have unwanted side effects. Allegra (fexofenandine) and Clarinex (desloratadine) have no sedation properties and commercial airline pilots are permitted to take them while flying. With other antihistamines such as Zyrtec and Xyzal, some patients feel sedated, foggy, experience dry mouth, weight gain, urinary retention, or constipation. Again, the newer ones are less likely to cause these untoward effects.
In summary, in my opinion, there are several immunologic benefits of antihistamines when considering the allergy relief, anti-viral, and anti-cancer effects. Allergy immunotherapy has been shown to markedly reduce the need for antihistamine usage in the long-term. However, while building up in your allergy shots, one should strongly consider taking newer, safer antihistamines for better long-term outcomes.