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Antihistamines

Definition, Purpose, Recommended dosage, Side effects, Interactions

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).

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.

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.

Antihistamines

Antihistamines
Brand Name (Generic Name) Possible Common Side Effects Include:
*Also used in the treatment of anxiety
*Atarax (hydroxyzine hydrochloride) Drowsiness, dry mouth
Benadryl (diphenhydramine hydrochloride) Dizziness, sleepiness, upset stomach, decreased coordination
Hismanal (astemiozole) Drowsiness, dry mouth, fatigue, weight gain
PBZ-SR (tripelennamine hydrochloride) Dizziness, drowsiness, dry mouth and throat, chest congestion, decreased coordination, upset stomach
Periactin (cyproheptadine hydrochloride) Chest congestion, dizziness, fluttery heartbeat, loss of appetite, hives, sleepiness, vision problems
Phenergan (promethazine hydrochloride) Changes in blood pressure, dizziness, blurred vision, nausea, rash
Polaramine (dexchlorpheniramine maleate) Drowiness
Seldane, Seldane-D (terfenadine) Upset stomach, nausea, drowiness, headache, fatigue
Tavist (clemastine fumarate) Decreased coordination, dizziness, upset stomach
Trinalin Repetabs (azatadine maleate, pseudoephedrine sulfate) Abdominal cramps, chest pain, dry mouth, headache

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

Drug interactions will vary with the chemical class of antihistamine. In general, antihistamines will increase the effects of other sedatives, including alcohol.

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.

Resources

ORGANIZATIONS

Allergy and Asthma Network. 3554 Chain Bridge Road, Suite 200. (800) 878-4403.

American Academy of Allergy and Immunology. 611 East Wells Street, Milwaukee, WI 53202. (800)822-2762.

Asthma and Allergy Foundation of America. 1125 15th Street NW, Suite 502, Washington, DC 20005. (800)727-8462.

Samuel Uretsky, PharmD

DANIELE BOVET (1907–1992)


A gifted researcher in therapeutic chemistry, Daniele Bovet was born in Neuchatel, Switzerland, one of four children of a professor of experimental education. Bovet studied zoology and comparative anatomy at the University of Geneva, receiving his doctor of science degree in 1929. He then joined the Pasteur Institute in Paris, becoming director of the Laboratory of Therapeutic Chemistry in 1936.

Bovet investigated histamine, thought to cause allergy symptoms. No antagonist of histamine was known, so Bovet—with his research student Anne-Marie Staub— began studying substances that blocked hormones similar to histamine. By 1937 he had produced the first anti-histamine, thymoxydiethylamine. Since this substance was too toxic for human use, Bovet and Staub performed thousands more experiments seeking less toxic antihistamines. This work formed the basis for the development of subsequent clinically useful antihistamines.

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.

Additional topics

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