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Definition

Antihistamines are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the H₁ receptor sites, responsible for immediate hypersensitivity reactions such as sneezing and itching. Members of this class of drugs may also be used for their side effects, including sedation and antiemesis (prevention of nausea and vomiting).

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Purpose

Antihistamines provide their primary action by blocking histamine H₁ at the receptor site. They have no effect on rate of histamine release, nor do they inactivate histamine. By inhibiting the activity of histamine, they can reduce capillary fragility, which produces the erythema, or redness, associated with allergic reactions. They will also reduce histamine-induced secretions, including excessive tears and salivation. Additional effects vary with the individual drug used. Several of the older drugs, called first-generation antihistamines, bind non-selectively to H₁ receptors in the central nervous system as well as to peripheral receptors, and can produce sedation, inhibition of nausea and vomiting, and reduction of motion sickness. The second-generation antihistamines bind only to peripheral H₁ receptors, and reduce allergic response with little or no sedation.

ANTIHISTAMINESBrand Name (Generic Name)Possible Common Side Effects Include:*Atarax (hydroxyzine hydrochloride)Drowsiness, dry mouthBenadryl (diphenhydramine hydrochloride)Dizziness, sleepiness, upset stomach, decreased coordinationHismanal (astemiozole)Drowsiness, dry mouth, fatigue, weight gainPBZ-SR (tripelennamine hydrochloride)Dizziness, drowsiness, dry mouth and throat, chest congestion, decreased coordination, upset stomachPeriactin (cyproheptadine hydrochloride)Chest congestion, dizziness, fluttery heartbeat, loss of appetite, hives, sleepiness, vision problemsPhenergan (promethazine hydrochloride)Changes in blood pressure, dizziness, blurred vision, nausea, rashPolaramine (dexchlorpheniramine maleate)DrowinessSeldane, Seldane-D (terfenadine)Upset stomach, nausea, drowiness, headache, fatigueTavist (clemastine fumarate)Decreased coordination, dizziness, upset stomachTrinalin Repetabs (azatadine maleate, pseudoephedrine sulfate)Abdominal cramps, chest pain, dry mouth, headache*Also used in the treatment of anxiety

The first-generation antihistamines may be divided into several chemical classes. The side effect profile, which also determines the uses of the drugs, will vary by chemical class. The alkylamines include brompheniramine (Dimetapp) and chlorpheniramine (Chlor-Trimeton.) These agents cause relatively little sedation, and are used primarily for treatment of allergic reactions. Promethazine (Phenergan), in contrast, is a phenothiazine, chemically related to the major tranquilizers, and while it is used for treatment of allergies, may also be used as a sedative, the relieve anxiety prior to surgery, as an anti-nauseant, and for control of motion sickness. Diphenhydramine (Benadryl) is chemically an ethanolamine, and in addition to its role in reducing allergic reactions, may be used as a nighttime sedative, for control of drug-induced Parkinsonism, and, in liquid form, for control of coughs. Consult more detailed references for further information.

The second generation antihistamines have no central action, and are used only for treatment of allergic reactions. These are divided into two chemical classes. Cetirizine (Zyrtec) is a piperazine derivative, and has a slight sedative effect. Loratidine (Claritin) and fexofenadine (Allegra) are members of the piperadine class and are essentially non-sedating.

Recommended dosage

Dosage varies with drug, patient and intended use. Consult more detailed references for further information.

When used for control of allergic reactions, antihistamines should be taken on a regular schedule, rather than on an as-needed basis, since they have no effect on histamine itself, nor on histamine already bound to the receptor site.

Efficacy is highly variable from patient to patient. If an antihistamine fails to provide adequate relief, switch to a drug from a different chemical class. Individual drugs may be effective in no more than 40% of patients, and provide 50% relief of allergic symptoms.

Side effects

The frequency and severity of adverse effects will vary between drugs. Not all adverse reactions will apply to every member of this class.

Central nervous system reactions include drowsiness, sedation, dizziness, faintness, disturbed coordination, lassitude, confusion, restlessness, excitation, tremor, seizures, headache, insomnia, euphoria, blurred vision, hallucinations, disorientation, disturbing dreams/nightmares, schizophrenic-like reactions, weakness, vertigo, hysteria, nerve pain, and convulsions. Overdoses may cause involuntary movements. Other problems have been reported.

Gastrointestinal problems include increased appetite, decreased appetite, nausea, vomiting, diarrhea, and constipation.

Hematologic reactions are rare, but may be severe. These include anemia, or breakdown of red blood cells; reduced platelets; reduced white cells; and bone marrow failure.

A large number of additional reactions have been reported. Not all apply to every drug, and some reactions may not be drug related. Some of the other adverse effects are chest tightness; wheezing; nasal stuffiness; dry mouth, nose and throat; sore throat; respiratory depression; sneezing; and a burning sensation in the nose.

When taking antihistamines during pregnancy, Chlorpheniramine (Chlor-Trimeton), dexchlorpheniramine (Polaramine), diphenhydramine (Benadryl), brompheniramine (Dimetapp), cetirizine (Zyrtec), cyproheptadine (Periactin), clemastine (Tavist), azatadine (Optimine), loratadine (Claritin) are all listed as category B. Azelastine (Astelin), hydroxyzine (Atarax), promethazine (Phenergan) are category C.

Regardless of chemical class of the drug, it is recommended that mothers not breast feed while taking antihistamines.

Contraindications

The following are absolute or relative contraindications to use of antihistamines. The significance of the contraindication will vary with the drug and dose.

• glaucoma
• hyperthyroidism (overactive thyroid)
• high blood pressure
• enlarged prostate
• heart disease
• ulcers or other stomach problems
• stomach or intestinal blockage
• liver disease
• kidney disease
• bladder obstruction
• diabetes

Interactions

Monoamine oxidase inhibitor antidepressants (phenelzine [Nardil], tranylcypromine [Parnate]) may prolong and increase the effects of some antihistamines. When used with promethazine (Phenergan) this may cause reduced blood pressure and involuntary movements.

Key Terms

Allergen

A substance that causes an allergy.

Anaphylaxis

A sudden, life-threatening allergic reaction.

Hallucination

A false or distorted perception of objects, sounds, or events that seems real. Hallucinations usually result from drugs or mental disorders.

Histamine

A chemical released from cells in the immune system as part of an allergic reaction.

Pregnancy category

A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

For Your Information

Resources

Organizations

• Allergy and Asthma Network. 3554 Chain Bridge Road, Suite 200. (800) 878-4403.
• American Academy of Allergy, Asthma, and Immunology. 611 East Wells St, Milwaukee, WI 53202. (800) 822-2762.
• Asthma and Allergy Foundation of America. 1125 15th Street NW, Suite 502, Washington, DC 20005. (800)727-8462.

This article was updated on 08-14-2006