ANTIHISTAMINES are drugs which treat allergic rhinitis and other
Although typical people 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. 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
* 1 Medical uses
* 2 Types
* 2.1 H1-antihistamines
* 2.1.1 H1 antagonists * 2.1.2 H1 inverse agonists
* 2.2 H2-antihistamines
* 3 Research
* 3.1 H3-antihistamines * 3.2 H4-antihistamines
* 4 Related agents
* 5 History
* 6 Society and culture
* 7 Research
Itching , sneezing , and inflammatory responses are suppressed by antihistamines that act on H1-receptors . In 2014 antihistamines such as desloratadine were found to be effective as adjuvants to standardized treatment of acne due to their anti-inflammatory properties and their ability to suppress sebum production.
Main article: H1-antihistamine
H1-antihistamines refer to compounds that inhibit the activity of the H1 receptor . Since the H1 receptor exhibits constitutive activity , H1-antihistamines can be either neutral receptor antagonists or inverse agonists . 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 reduce its activity, an effect which is opposite to histamine's.
The vast majority of marketed H1-antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor. 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 , are therefore 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.
Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first-generation antihistamines. Their main benefit is they primarily affect peripheral histamine receptors and therefore are less sedating. However, high doses can still induce drowsiness through acting on the central nervous system . Some second-generation antihistamines, notably cetirizine , can interact with CNS psychoactive drugs such as bupropion and benzodiazepines .
Examples of H1 antagonists include:
* Acrivastine (see _Benadryl_ entry in this section) * Azelastine * Benadryl is a brand name for different H1 antagonist anitihistamine preparations in different regions: acrivastine is the active component of Benadryl Allergy Relief and cetirizine of Benadryl One a Day Relief in the UK; Benadryl is diphenhydramine in the US and Canada.(see http://www.benadryl.ca/adult-allergy-medicine/benadryl-caplets) * Bilastine * Bromodiphenhydramine * Brompheniramine * Buclizine * Carbinoxamine * Cetirizine (see _Benadryl_ entry in this section) * Chlorodiphenhydramine * Chlorphenamine * Chlorpromazine (antipsychotic) * Clemastine * Cyclizine * Cyproheptadine * Dexbrompheniramine * Dexchlorpheniramine * Dimenhydrinate (most commonly used as an antiemetic ) * Dimetindene * Diphenhydramine (see _Benadryl_ entry in this section) * Doxylamine (most commonly used as an over-the-counter drug sedative ) * Ebastine * Embramine * Fexofenadine (Allegra) * Hydroxyzine (Vistaril) * Loratadine (Claritin) * Meclizine (most commonly used as an antiemetic) * Mirtazapine (primarily used to treat depression, also has antiemetic and appetite-stimulating effects) * Olopatadine (used locally) * Orphenadrine (a close relative of diphenhydramine used mainly as a skeletal muscle relaxant and anti-Parkinsons agent) * Phenindamine * Pheniramine * Phenyltoloxamine * Promethazine * Quetiapine (antipsychotic; trade name Seroquel) * Rupatadine * Tripelennamine * Triprolidine
H1 Inverse Agonists
The H1 receptor inverse agonists include:
* Cetirizine (does not cross the blood–brain barrier )
Main article: H2-antihistamine
H2-antihistamines, like H1-antihistamines, occur as inverse agonists and neutral antagonists . They act on H2 histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H2 to stimulate acid secretion; drugs that inhibit H2 signaling thus reduce the secretion of gastric acid.
H2-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease . Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses..
These are experimental agents and do not yet have a defined clinical use, although a number of drugs are currently in human trials. H3-antihistamines have a stimulant and nootropic effect, whereas H4-antihistamines appear to have an immunomodulatory role.
Main article: H3-antihistamine
An H3-ANTIHISTAMINE is a classification of drugs used to inhibit the
action of histamine at the H3 receptor . H3 receptors are primarily
found in the brain and are inhibitory autoreceptors located on
histaminergic nerve terminals, which modulate the release of histamine
Examples of selective H3-antihistamines include:
HISTIDINE DECARBOXYLASE INHIBITORS
Inhibit the action of histidine decarboxylase :
MAST CELL STABILIZERS
Main article: Mast cell stabilizer
Mast cell stabilizers are drugs which prevent mast cell degranulation .
* cromolyn sodium * Nedocromil * β-agonists
Currently most people who use an antihistamine to treat allergies use a second generation drug.
The first generation of antihistamine drugs became available in the
1930s. This marked the beginning of medical treatment of nasal
allergies. Research into these drugs let to the discovery that they
H1 antagonists and also to the development of
H2 antagonists ,
where H1 antihistamines affected the nose and the H2 antihistamines
affected the stomach. This history has led to contemporary research
into drugs which are
H3 receptor antagonist and which affect the
SOCIETY AND CULTURE
The United States government removed two second generation antihistamines, terfenadine and astemizole , from the market based on evidence that they could cause heart problems.
Not much published research exists which compares the efficacy and safety of the various antihistamines available. The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions. Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time. Newer antihistamines have been demonstrated to be effective in treating hives. However, there is not research comparing the relative efficacy of these drugs.
Most studies of antihistamines reported on people who are younger, so the effects on people over age 65 are not as well understood. Older people are more likely to experience drowsiness from antihistamine use than younger people. Also, most of the research has been on white people and other ethnicities are not as represented in the research. The evidence does not report how antihistamines affect women differently than men. Different studies have reported on antihistamine use in children, with various studies finding evidence that certain antihistamines could be used by children 2 years of age, and other drugs being safer for younger or older children.
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_Q_ _R_ _S_ _T_ _U_ _V_ _W_ _X_ _Y_
Consumer Reports (2013), _Using
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"Antihistaminic, anti-inflammatory, and antiallergic properties of the
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the evidence" . _World Allergy Organ J_. 4 (2): 47–53. PMC 3500039
. PMID 23268457 . doi :10.1097/WOX.0b013e3182093e19 . The
H1-receptor is a transmembrane protein belonging to the G-protein
coupled receptor family. Signal transduction from the extracellular to
the intracellular environment occurs as the GCPR becomes activated
after binding of a specific ligand or agonist. A subunit of the
G-protein subsequently dissociates and affects intracellular messaging
including downstream signaling accomplished through various
intermediaries such as cyclic AMP, cyclic GMP, calcium, and nuclear
factor kappa B (NF-κB), a ubiquitous transcription factor thought to
play an important role in immune-cell chemotaxis, proinflammatory
cytokine production, expression of cell adhesion molecules, and other
allergic and inflammatory conditions.1,8,12,30–32 ... For example,
NF-κB in both a constitutive and
agonist-dependent manner and all clinically available
H1-antihistamines inhibit constitutive H1-receptor-mediated NF-κB
Importantly, because antihistamines can theoretically behave as
inverse agonists or neutral antagonists, they are more properly
described as H1-antihistamines rather than
* ^ Panula P, Chazot PL, Cowart M, et al. (2015). "International
Union of Basic and Clinical Pharmacology. XCVIII.