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Antihistamines

Antihistamines

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 ).

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 histamineinduced 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.

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, slee-
piness, vision problems
Phenergan (promethazine
hydrochloride)
Changes in blood pressure, dizziness,
blurred vision, nausea, rash
Polaramine (dexchlorphenira-
mine 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

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.

DANIELE BOVET (19071992)

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 Bovetwith his research student Anne-Marie Staubbegan studying substances that blocked hormones similar to histamine. By 1937 he had produced the first antihistamine, 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.

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.

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. http://www.aaaai.org.

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

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.

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"Antihistamines." Gale Encyclopedia of Medicine, 3rd ed.. . Encyclopedia.com. 24 May. 2017 <http://www.encyclopedia.com>.

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"Antihistamines." Gale Encyclopedia of Medicine, 3rd ed.. . Retrieved May 24, 2017 from Encyclopedia.com: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/antihistamines-0

Antihistamines

Antihistamines

Definition

Antihistamines are drugs used to treat the symptoms of allergies and allergic rhinitis by blocking the action of histamine, a chemical released by the immune system in allergic reactions.

Description

Antihistamines are used to treat the sneezing, runny nose, and itchy eyes of allergies and allergic rhinitis, as well as allergic skin reactions and anaphylactic reactions to insect stings and certain foods. Antihistamines are available as prescription and over-the-counter tablets, topical preparations, nasal sprays, and eye drops.

Antihistamines work by blocking the effects of histamine, a chemical released by mast cells during an allergic response to an allergen. Histamine irritates and inflames the airways to produce sneezing and mucus production. Antihistamines attach to the areas on cells that histamines attach to, thereby blocking the allergic response.

Antihistamines are most effective when taken before exposure to an allergen. When used over time as an allergy treatment, antihistamines reduce the amount of histamine released by cells and decrease the likelihood that an allergic reaction will occur.

General use

Antihistamines are prescribed or recommended for infants, children, and adolescents with allergies and allergic rhinitis. Depending on the type of allergy, oral antihistamines may be taken regularly or seasonally to combat responses to allergens. Common allergens include dog and cat hair, dust mites, grass and tree pollen, and molds and mildew. For allergies that produce nasal symptoms, an antihistamine nasal spray may be used. For itchy eyes, antihistamine eye drops may be used.

Antihistamine tablets and topical creams, gels, sprays, or ointments are used to treat skin hives related to food allergies and itching and hives associated with allergic contact dermatitis and insect bites and stings .

In addition to treating allergies, some antihistamines have side effects that are used to treat other conditions. The strong sedating effect of some antihistamines is used to treat insomnia and difficulties in falling asleep. Some antihistamines also help inhibit nausea and vomiting and reduce motion sickness .

Commonly used antihistamines include the following:

  • diphenhydramine (Benadryl)
  • loratadine (Claritin)
  • cetirizine (Zyrtec)
  • fexofenadine (Allegra)
  • clemastine fumarate (Tavist)
  • chlorpheniramine (Chlor Trimeton)
  • brompheniramine (Dimetapp)

Precautions

Some antihistamines produce drowsiness, although clinical studies have shown that children are less susceptible to antihistamine-induced drowsiness than adults. Some nonsedating antihistamines can act as stimulants in children and produce hyperactivity and sleeplessness.

Children with certain medical conditions may not be able to take antihistamines. 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
  • heart disease
  • ulcers or other stomach problems
  • stomach or intestinal blockage
  • liver disease
  • kidney disease
  • bladder obstruction
  • diabetes

Side effects

The frequency and severity of adverse effects will vary depending on the antihistamine.

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, nerve pain, and convulsions.

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.

Interactions

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

Monoamine oxidase inhibitor antidepressants may prolong and increase the effects of some antihistamines.

Parental concerns

For children who resist taking pills, many antihistamines are available as flavored chewable tablets, tablets that easily dissolve on the tongue, and in flavored syrups. Because many over-the-counter allergy medicines contain multiple drugs, parents should be sure to read the prescribing and dosage information for any antihistamine their children are taking to ensure safe use.

KEY TERMS

Allergen A foreign substance that provokes an immune reaction or allergic response in some sensitive people but not in most others.

Anaphylaxis Also called anaphylactic shock; a severe allergic reaction characterized by airway constriction, tissue swelling, and lowered blood pressure.

Histamine A substance released by immune system cells in response to the presence of an allergen. It stimulates widening of blood vessels and increased porousness of blood vessel walls so that fluid and protein leak out from the blood into the surrounding tissue, causing localised inflammation of the tissue.

Mast cells A type of immune system cell that is found in the lining of the nasal passages and eyelids. It displays a type of antibody called immunoglobulin type E (IgE) on its cell surface and participates in the allergic response by releasing histamine from intracellular granules.

Resources

BOOKS

Simms, F. Estelle. Histamine and H1-Antihistamines in Allergic Disease. New York: Marcel Dekker Incorporated, 2002.

Taylor, R., J. Krohn, and E. M. Larson. Allergy Relief and Prevention, 3rd ed. Vancouver: Hartley and Marks, 2000.

ORGANIZATIONS

Allergy and Asthma Network: Mothers of Asthmatics. 2751 Prosperity Ave., Suite 150, Fairfax, VA 22031. Web site: <www.aanma.org>.

American Academy of Allergy, Asthma, and Immunology. 611 East Wells St., Milwaukee, WI 53202. Web site: <www.aaaai.org>.

WEB SITES

"All about Allergies." Nemours Foundation. Available online at <www.kidshealth.org/parent/medical/allergies/allergy.html> (accessed October 24, 2004).

Jennifer E. Sisk, MA

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"Antihistamines." Gale Encyclopedia of Children's Health: Infancy through Adolescence. . Encyclopedia.com. 24 May. 2017 <http://www.encyclopedia.com>.

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"Antihistamines." Gale Encyclopedia of Children's Health: Infancy through Adolescence. . Retrieved May 24, 2017 from Encyclopedia.com: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/antihistamines

Antihistamine

Antihistamine

Antihistamines are drugs used to relieve the symptoms of allergies caused by histamine, an organic (natural, basic) compound made from the amino acid histidine. Histamine is released from certain cells when the body is irritated by outside substances, such as pollen, or if the body thinks that a certain food is an enemy rather than a friend. The body then tries to expel the perceived invader by swelling tissues and creating the typical symptoms of an allergic reaction, such as sneezing, hives (skin rashes), or in the case of food allergies, stomach upset and diarrhea as well. Histamine was first recognized and suggested as the cause of allergic reactions by Henry Dale (1875-1968) and Patrick Playfair Laidlaw (1881-1940) in 1910. By 1932 histamines were confirmed as causative agents in allergic response.

Bovet's Research

Researchers then sought to find substances that could counteract the effects of histamines. Swiss-born Italian pharmacologist Daniel Bovet (1907-; winner of the 1957 Nobel Prize for medicine) of the Pasteur Institute in Paris, France, focused on this problem in 1936. Since histamine is extremely toxic except when introduced to the body by absorption through the intestine, Bovet reasoned that histamine must normally exist in the body in combination with a neutralizing agent (a substance that renders other matierial inactive or ineffective). Only "free" histamine would produce allergic symptoms, so an antagonist (opposite) to this free histamine had to be found. Bovet could not discover a natural antagonist to histamine, so he looked for substances that were similar in chemical structure to it, to see if they had antagonists that might be modified to work against histamine. Because the two hormones adrenaline and acetylcholine are structurally similar to histamine, Bovet investigated two groups of substances called sympatholitics and parasympatholitics, which block the effects of adrenaline and acetylcholine. This approach proved fruitful, and in 1937 Bovet and his research student Anne-Marie Staub succeeded in synthesizing the first antihistamine. This first attempt was too toxic to use in humans, however, so from 1937 to 1941 Bovet conducted thousands of experiments to produce a usable antihistamine. He succeeded with pyrilamine, which was introduced to the public in 1944.

Bovet's work laid the foundation for the safe, effective synthesis of antihistamines. In further developments, Bernard N. Halpern, a French research biologist and physician, described the use of phenbenzamine in 1942. And in 1943 a young lecturer at the University of Cincinnati named George Rieveschl developed diphenhydramine, better known as Benadryl.

Beyond Allergy Relief

Once developed, antihistamines became wildly popular. They were promoted by rival drug companies for relief of symptoms of the common cold as well as allergies. Debate still continues in the scientific community on the actual effectiveness of antihistamines against cold virus symptoms. They seem to provide only minor relief on their own, except for clemastine (in found in Tavist-1 and Tavist-D), which may provide modest relief of cold symptoms. Another function for antihistamines was discovered by accident in 1947 when an allergy patient took an antihistamine called Dramamine and unexpectedly found that for the first time in years, she did not suffer from motion sickness when she rode a streetcar.

[See also Adrenaline ; Hormone ]

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antihistamine

antihistamine (anti-hist-ă-meen) n. a drug that inhibits the action of histamine in the body by blocking the H1 or H2 receptors for histamine. When stimulated by histamine, H1 receptors may produce such allergic reactions as hay fever, pruritus (itching), and urticaria (nettle rash). Antihistamines that block H1 receptors (H1-receptor antagonists) are used to relieve these conditions. Many H1-receptor antagonists (e.g. cyclizine, promethazine) also have strong antiemetic activity and are used to prevent motion sickness. The most common side-effect of these drugs, especially the older ones (e.g. alimemazine, promethazine), is drowsiness and because of this they are sometimes used to promote sleep. Newer antihistamines (e.g. acrivastine) are less sedating. H2 receptors are found mainly in the stomach, where stimulation by histamine causes secretion of acid gastric juice. H2-receptor antagonists (e.g. cimetidine, famotidine, nizatidine, ranitidine) block these receptors and so reduce gastric acid secretion; they are used in the treatment of peptic ulcers and gastro-oesophageal reflux disease.

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antihistamine

antihistamine (ăn´tĬhĬs´təmēn), any one of a group of compounds having various chemical structures and characterized by the ability to antagonize the effects of histamine. Their principal use in medicine is in the control of allergies such as hay fever and hives. Some antihistamines are also useful as sedatives and for the prevention of motion sickness; others, such as fexofenadine (Allegra) and loratadine (Claritin) are nonsedating.

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antihistamine

antihistamine Any drug that inhibits the effects of histamine in the body and is therefore used to relieve and prevent the symptoms associated with allergic reactions, such as hay fever. Since one of the side-effects produced by antihistamines is sleepiness, some are used to prevent motion sickness and induce sleep.

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antihistamine

antihistamine Any one of certain drugs that counteracts or otherwise prevents the effects of histamine, a natural substance released by the body in response to injury, or more often as part of an allergic reaction. Histamine can produce symptoms such as sneezing, running nose, and burning eyes. See also hay fever

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antihistamine

an·ti·his·ta·mine / ˌantēˈhistəmin; -mēn/ • n. [usu. as adj.] a drug or other compound that inhibits the physiological effects of histamine, used esp. in the treatment of allergies: an antihistamine injection.

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antihistamine

antihistamine Drug that antagonizes the actions of histamine; those that block histamine H1 receptors are used to treat allergic reactions; those that block H2 receptors are used to treat peptic ulcers.

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