Antihistamine

An \antihistamine is a chemical which serves to reduce or eliminate effects mediated by histamine, an endogenous chemical of the human body released during allergic reactions, at the histamine receptor. It can be administered locally (through the skin, nose, or eyes) or systemically, based on the type of allergy, and has a wide range of effects depending on the amount and type of antihistamine used. 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.

Table of contents

1 Histamine's Action in Allergy 2 Types of Antihistamines 3 ADMET Properties 4 Adverse Effects 5 Specific Agents

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 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 (Epi-pen) 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 peptic ulcers, GERD, and other such ailments.

Types of Antihistamines

There are two groups of antihistamines:

• true antihistamines, which prevent the release of histamine. This class includes drugs such as cromolyn and nedocromil.
• histaminergic receptor antagonists, which interfere with the effects that histamine triggers at one or more of the classes of histamine receptors. These include many drugs commonly referred to as antihistamines, such as diphenhydramine and doxylamine.

The histaminergic receptor antagonists are further categorized as follows:

• first-generation H₁-receptor antagonists are the oldest antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of the symptoms of allergic rhinitis, but are typically moderately to highly potent anticholingeric agents as well. This leads to a variety of potential side-effects, the most common of which is usually drowsiness.
• second-generation H₁-receptor antagonists are newer drugs that are much more selective for peripheral H₁ receptors in preference to the central nervous system histaminergic and cholinergic receptors. This reduces most of the unpleasant side-effects of the older drugs, while still effectively relieving allergy symptoms.
• H₂-receptor antagonists work primarily against the effects of histamine in the gastrointestinal tract. These drugs reduce the secretion of gastric acid, and include ranitidine and famotidine. There is no appreciable anticholinergic effect.
• H₃-receptor antagonists do not yet have a known clinical use. The H₃ receptors are involved in the regulation and synthesis of histamine.

In addition to these drugs, which are used for their antihistaminergic effect, there are also drugs and classes of drugs which are prone to unwanted antihistaminergic side-effects. One such class of drugs is the tricyclic antidepressants.

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)
• bropheniramine (Dimetapp)
• doxylamine (Dimetapp)

Second Generation Agents:

• cetirizine hydrochloride (Zyrtec)
• azelastine hydrochloride (Astelin)
• loratadine (Claritin)
• fexofenadine (Allegra)
• astemizole (Hismanal)
• acrivastine (Semprex)