From Wikipedia, the free encyclopedia.
Histamine (beta-aminoethylimidazole)is an endogenous chemical of the human body. It has a wide range of effects depending on the amount and the histamine receptor that it binds to. Antihistamines serve clinically to block the action of histamine (specifically at H1 receptors) in allergic reactions. These agents can be used locally (topical, nasal, ophthalmologic) or systemically, depending on the type of allergy.
Histamine's Action in Allergy
In allergic reactions an antigen (antibody-generating substance) interacts with an IgE antibody molecule and subsequently binds to mast cells and basophils. Once the mast cell-antibody-antigen complex is formed a complex series of events occurs that eventually leads to the release of histamine from the mast cell. Once released, histamine can react with local or widespread tissues. Some of the effects of histamine include the constriction of the bronchioles, dilation of local blood vessels, increases the force of the heart's contraction, increases the the heart rate (speeds up AV depolarization), and more. It is a combination of these effects that is so dangerous in people with severe anaphylaxis, or allergy. Epinephrine, often in the form of an autoinjector (EpiPen) is a must-have for people with severe allergies. As an aside, it is useful to know that histamine has other effects besides those in allergic responses. Most notably histamine also plays a role in excessive gastric secretion, causing ulcers, GERD, and other such ailments.
Use of Antihistamines
Antihistamines are used clinically in the prophylaxis and treatment of chronic and/or seasonal allergies. Antihistamines block the binding site for histamine on the H1 receptor (there are also H2 and H3 receptors that mediate other responses). The general structure of antihistamines, or H1 antagonists, is a substituted, tertiary ethylamine moiety connected to two aromatic rings. Most of the antihistamines have similar pharmacological activities. Antihistamines as a group are able to block most of the responses of smooth muscle to histamine. This means that bronchial constriction and vasodilation are prevented. Antihistamines can also block histamine's increase in capillary permeability. This action helps reduce redness and itching.
ADMET Properties
For those drugs taken orally they are well absorbed from the GI tract and reach maximum levels in 2-6 hours depending on the specific agent. The half-life is 4-8 hours and are metabolized by liver enzymes. A problem with antihistamines, that is common with many drugs, is that they induce (increase the production of) liver enzymes responsible for their own metabolism and the metabolism of other drugs. There seems to be no cancer risk associated with antihistamines.
Adverse Effects
Most of the adverse effects are associated with the first generation agents. The most common side effect is that of drowsiness (this is the basis of OTC sleep aids). The intake of alcohol can add to this effect. Other first generation agent adverse effects include dizziness, tinnitus, fatigue, blurred vision, urinary retention, cough, dry mouth, and others.
Specific Agents
First Generation Agents: carbinoxamine maleate (Rondec) chlorpheniramine maleate (Chlor-Trimeton) clemastine fumarate (Tavist) diphenhydramine hydrochloride (Benadryl) hydroxyzine hydrochloride (Atarax) hydroxyzine pamoate (Vistaril) meclizine hydrochloride (Antivert) promethazine hydrochloride (Phenergan)
Second Generation Agents: cetirizine hydrochloride (Zyrtec) azelastine hydrochloride (Astelin) loratidine (Claritin) fexofenadine (Allegra)
