Antihistamines are drugs which treat hay fever and other allergies.
[1] Typically, people take
antihistamines as an inexpensive, not patented (generic), drug that can be bought without a prescription
and relieves from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy
with few side effects.[1] Antihistamines are usually for short-term treatment.[1] Chronic allergies
increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis,
and lower respiratory tract infection.[1] Consultation of a medical professional is recommended for
those who intend to take antihistamines for longer-term use.[1]
Although people typically use the word “antihistamine” to describe drugs for treating allergies, doctors
and scientists use the term to describe a class of drug that opposes the activity of histamine receptors in
the body.[2] In this sense of the word, antihistamines are subclassified according to the histamine
receptor that they act upon. The two largest classes of antihistamines are H1-antihistamines and H2-
antihistamines.
H1-antihistamines work by binding to histamine H1 receptors in mast cells, smooth muscle, and
endothelium in the body as well as in the tuberomammillary nucleus in the brain. Antihistamines that
target the histamine H1-receptor are used to treat allergic reactions in the nose (e.g., itching, runny
nose, and sneezing). In addition, they may be used to treat insomnia, motion sickness, or vertigo caused
by problems with the inner ear. H2-antihistamines bind to histamine H2 receptors in the upper
gastrointestinal tract, primarily in the stomach. Antihistamines that target the histamine H2-receptor are
used to treat gastric acid conditions (e.g., peptic ulcers and acid reflux).
Histamine receptors exhibit constitutive activity, so antihistamines can function as either a neutral
receptor antagonist or an inverse agonist at histamine receptors.[2][3][4][5] Only a few currently
marketed H1-antihistamines are known to function as inverse agonists.[2][5]
Contents
1 Medical uses
2 Types
2.1 H1-antihistamines
2.1.1 H1 antagonists/inverse agonists
2.2 H2-antihistamines
2.3 H3-antihistamines
2.4 H4-antihistamines
3 Atypical antihistamines
3.1 Histidine decarboxylase inhibitors
3.2 Mast cell stabilizers
4 History
5 Society and culture
6 Research
7 Special populations
8 See also
9 References
10 External links
Medical uses
Histamine makes blood vessels more permeable (vascular permeability), causing fluid to escape from
capillaries into tissues, which leads to the classic symptoms of an allergic reaction — a runny nose and
watery eyes. Histamine also promotes angiogenesis.[6]
Antihistamines suppress the histamine-induced wheal response (swelling) and flare response
(vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor
activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.
Itching, sneezing, and inflammatory responses are suppressed by antihistamines that act on H1-
receptors.[2][7] In 2014, antihistamines such as desloratadine were found to be effective to
complement standardized treatment of acne due to their anti-inflammatory properties and their ability
to suppress sebum production.[8][9]
Types
H1-antihistamines
Main article: H1-antihistamine
H1-antihistamines refer to compounds that inhibit the activity of the H1 receptor.[4][5] Since the H1
receptor exhibits constitutive activity, H1-antihistamines can be either neutral receptor antagonists or
inverse agonists.[4][5] Normally, histamine binds to the H1 receptor and heightens the receptor's
activity; the receptor antagonists work by binding to the receptor and blocking the activation of the
receptor by histamine; by comparison, the inverse agonists bind to the receptor and both block the
binding of histamine, and reduce its constitutive activity, an effect which is opposite to histamine's.[4]
Most antihistamines are inverse agonists at the H1 receptor, but it was previously thought that they
were antagonists.[10]
Clinically, H1-antihistamines are used to treat allergic reactions and mast cell-related disorders. Sedation
is a common side effect of H1-antihistamines that readily cross the blood–brain barrier; some of these
drugs, such as diphenhydramine and doxylamine, may therefore be used to treat insomnia. H1-
antihistamines can also reduce inflammation, since the expression of NF-κB, the transcription factor the
regulates inflammatory processes, is promoted by both the receptor's constitutive activity and agonist
(i.e., histamine) binding at the H1 receptor.[2]
A combination of these effects, and in some cases metabolic ones as well, lead to most first-generation
antihistamines having analgesic-sparing (potentiating) effects on opioid analgesics and to some extent
with non-opioid ones as well. The most common antihistamines utilized for this purpose include
hydroxyzine, promethazine (enzyme induction especially helps with codeine and similar prodrug
opioids), phenyltoloxamine, orphenadrine, and tripelennamine; some may also have intrinsic analgesic
properties of their own, orphenadrine being an example.
Second-generation antihistamines cross the blood–brain barrier to a much lesser extent than the first-
generation antihistamines. They minimize sedatory effects due to their focused effect on peripheral
histamine receptors. However, upon high doses second-generation antihistamines will begin to act on
the central nervous system and thus can induce drowsiness when ingested in higher quantity.
Additionally, some second-generation antihistamines, notably cetirizine, can interact with CNS
psychoactive drugs such as bupropion and benzodiazepines.[11
