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.

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 (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 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.

Antihistamines

Antihistamines are medicines that relieve or prevent the symptoms of hay fever and other kinds of allergy . An allergy is a condition in which the body becomes unusually sensitive to some substance, such as pollen, mold spores, dust particles, certain foods, or medicines. These substances, known as allergens, cause no unusual reactions in most people. But in people who are sensitive to them, exposure to allergens causes the immune system to overreact. The main reaction is the release of a chemical called histamine from specialized cells in the body tissues. Histamine causes such familiar and annoying allergy symptoms as sneezing, itching, runny nose, and watery eyes.

As their name suggests, antihistamines block the effects of histamine, reducing allergy symptoms. When used for this purpose, they work best when taken before symptoms are too severe. Antihistamine creams and ointments may be used to temporarily relieve itching. Some antihistamines are also used to treat motion sickness, nausea, dizziness, and vomiting. And because some cause drowsiness, they may be used as sleep aids.

Some antihistamine products are available only with a physician's prescription. Others can be bought without a prescription. These drugs come in many forms, including tablets, capsules, liquids, injections and suppositories. Some common antihistamines are astemizole (Hismanal), brompheniramine (Dimetane, Dimetapp), chlorpheniramine (Deconamine), clemastine (Tavist), diphenhydramine (Benadryl), doxylamine (an ingredient in sleep aids such as Unisom and Vicks NyQuil), loratadine (Claritin), and promethazine (Phenergan).

Recommended dosage

Recommended dosage depends on the type of antihistamine. Check with the physician who prescribed the drug or the pharmacist who filled the prescription for the correct dosage, and always take antihistamines exactly as directed. If using non-prescription (over-the-counter) types, follow the directions on the package label. Never take larger or more frequent doses, and do not take the drug longer than directed.

For best effects, take antihistamines on a schedule, not just as needed. Histamine is released more or less continuously, so countering its effects requires regular use of antihistamines.

Precautions

For best effects, people who have seasonal allergies should take antihistamines before allergy season starts or immediately after being exposed to an allergen. Even then, however, antihistamines do not cure allergies or prevent histamine from being released. They also have no effect on other chemicals that the body releases when exposed to allergens. For these reasons, antihistamines can be expected to reduce allergy symptoms by only about 50%.

In some people antihistamines become less effective when used over a long time. Switching to another type of antihistamine may help.

The antihistamines Seldane and Seldane-D were taken off the market in 1997 due to concerns that the active ingredient, terfenadine, triggered life-threatening heart rhythm problems when taken with certain drugs. Terfenadine can also be dangerous to people with liver disease . The U.S. Food and Drug Administration encouraged people who were using Seldane to talk to their physicians about switching to another antihistamine such as loratadine (Claritin) or to fexofenadine (Allegra), which is similar to Seldane but has a safer active ingredient.

The antihistamine astemizole (Hismanal) may also cause life-threatening heart rhythm problems or severe allergic reactions when taken in higher-than-recommended doses or with certain drugs. Taking astemizole with food may reduce its absorption into the bloodstream. Astemizole (Hismanal) should not be combined with any of the following:

• the antibiotics erythromycin (E-Mycin and other brands), clarithromycin (Biaxin), or troleandomycin (TAO)
• the blood pressure medicine mibefradil (Posicor)
• medicines used in treating HIV infection such as indinavir (Crixivan), ritonavir (Norvir), and nelfinavir (Viracept)
• antidepressants such as fluoxetine (Prozac), sertraline (Zoloft), or paroxetine (Paxil)
• asthma medicines such as zileuton (Zyflo)
• the antifungal drugs ketoconazole (Nizoral) or itraconazole (Sporanox)
• large doses of quinine

In addition, patients with liver disease should not take Hismanal.

People with asthma, emphysema , chronic bronchitis , or other breathing problems should not use antihistamines unless directed to do so by a physician.

Some antihistamines make people drowsy, dizzy, uncoordinated, or less alert. For this reason, anyone who takes these drugs should not drive, use machines or do anything else that might be dangerous until they have found out how the drugs affect them.

Antihistamines can interfere with the results of skin and blood tests. The antihistamine promethazine (Phenergan) can interfere with pregnancy tests and can raise blood sugar. Anyone who is taking antihistamines should notify the health care provider in charge before scheduling medical tests.

People with phenylketonuria should be aware that some antihistamine products contain aspartame (Nutrasweet), which breaks down in the body to phenylalanine.

Anyone who has sleep apnea (periods when breathing stops during sleep) should not take the antihistamine promethazine (Phenergan). This drug may also cause people with seizure disorders to have more frequent seizures.

Because children are often more sensitive to antihistamines, they may be more likely to have side effects and to suffer from accidental overdoses. Check with a physician before giving antihistamines to children under 12 years.

Older people may also be more likely to have side effects, such as nervousness, irritability, dizziness, sleepiness, and low blood pressure from antihistamines. Older men may also have problems urinating. Unless these problems are severe, they can usually be handled by taking a lower dose or switching to a different antihistamine. However, people over 80 or older people with serious physical problems or dementia may become confused, disoriented, and incoherent after taking even small amounts of the antihistamine diphenhydramine (Benadryl).

Special conditions

People with certain medical conditions or who are taking certain other medicines can have problems if they take antihistamines. Before taking these drugs, be sure to let the physician or pharmacist know about any of these conditions:

Allergies

Some antihistamine products may contain the dye tartrazine, which causes allergic reactions, including bronchial asthma, in some people. People who are allergic to aspirin may also be allergic to tartrazine.

Sodium bisulfite, a preservative, is found in some antihistamine products. People who are sensitive to this chemical may have allergic-type reactions, including anaphylaxis and severe asthma attacks. People with asthma are especially likely to be sensitive to sodium bisulfite. Ask the pharmacist which antihistamine products are sulfite-free.

Anyone who has had unusual reactions to antihistamines in the past should let his or her physician know before taking the drugs again. The physician should also be told about any allergies to foods, dyes, preservatives, or other substances.

Pregnancy

Pregnant women should not use antihistamines unless directed to do so by a physician.

Breast-feeding

Antihistamines pass into breast milk and may cause side effects in nursing babies. Women who are breast-feeding should check with their physicians before using antihistamines.

Other medical conditions

Before using antihistamines, people with any of these medical problems should make sure their physicians are aware of their conditions:

• 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

Use of certain medicines

Taking antihistamines with certain other drugs may affect the way the drugs work or may increase the chance of side effects.

Side effects

Common side effects of antihistamines include drowsiness, dizziness, poor coordination, restlessness, excitability, nervousness, and upset stomach. These problems usually go away as the body adjusts to the drug and do not require medical treatment. Less common side effects, such as dry mouth, nose, and eyes, irritability, difficulty urinating, and blurred vision , also may occur and do not need medical attention unless they do not go away or they interfere with normal activities.

If any of the following side effects occur, check with the physician who prescribed the medicine as soon as possible:

• rapid, irregular, pounding, or fluttering heartbeat
• convulsions
• sweating
• vomiting
• fever
• chills
• fainting
• breathing problems
• hallucinations
• unusual bleeding or bruising
• low blood pressure
• unusual sensitivity to light
• uncontrolled movements

Other rare side effects may occur. Anyone who has unusual symptoms after taking antihistamines should get in touch with his or her physician.

Interactions

Antihistamines may increase the effects of other drugs that slow down the central nervous system (CNS), such as alcohol , tranquilizers , barbiturates , and sleep aids. Avoid drinking alcohol while taking antihistamines, and check with a physician before combining antihistamines with other CNS depressants.

Certain antihistamines should not be used within two weeks of using monoamine oxidase inhibitors (MAO inhibitors), which are drugs used to treat Parkinson's disease, depression , and other psychiatric conditions. Examples of MAO inhibitors are Parnate and Nardil. People who have been taking MAO inhibitors or who are not sure if they have should check with their physician or pharmacist before taking antihistamines.

Although no such interactions have been reported, antihistamine loratadine (Claritin) could potentially interact with the antiulcer drugs cimetidine (Tagamet) and ranitidine (Zantac), both of which are also taken for heartburn; with antibiotics such as erythromycin and Biaxin; with the antifungal drug ketoconazole (Nizoral); and with the bronchodilator theophylline (Theo-Dur). These interactions can cause liver problems. Persons who are taking these drugs should consult with an physician or pharmacist to see whether this is an issue for them.

Check with a physician before combining the antihistamine chlorpheniramine (Deconamine) with any of the following:

• asthma medicines such as albuterol (Proventil) and bromocriptine (Parlodel)
• blood pressure drugs such as mecamylamine (Inversine), methyldopa (Aldomet), and reserpine
• narcotic painkillers such as meperidine (Demerol), oxycodone-aspirin (Percodan) and oxycodone-acetaminophen (Percocet)
• the anticonvulsant drug phenytoin (Dilantin)
• sleep aids such as triazolam (Halcion) and secobarbital (Seconal)
• tranquilizers such as diazepam (Valium) and alprazolam (Xanax)

Hismanal should not be taken with grapefruit juice or combined with any of the following drugs:

• antibiotics such as erythromycin (E-Mycin and other brands), clarithromycin (Biaxin), or troleandomycin (TAO)
• the blood pressure medicine mibefradil (Posicor)
• medicines used in treating HIV infection such as indinavir (Crixivan), ritonavir (Norvir), and nelfinavir (Viracept)
• antidepressants such as fluoxetine (Prozac), sertraline (Zoloft), or paroxetine (Paxil)
• asthma medicines such as zileuton (Zyflo)
• the antifungal drugs ketoconazole (Nizoral) or itraconazole (Sporanox)
• large doses of quinine

Check with a physician before combining any antihistamine with any of the following drugs:

• Medicines for stomach or abdominal cramps or spasms, such as dicyclomine (Bentyl).
• The antibiotics azithromycin (Zithromax), clarithromycin (Biaxin), or erythromycin (E-mycin).
• The antifungal drugs itraconazole (Sporanox) or ketoconazole (Nizoral).
• The calcium channel blocker bepridil (Vascor).
• Drugs used to treat irregular heartbeat, such as disopyramide (Norpace), procainamide (Pronestyl), or quinidine (Quinaglute Dura-Tabs, Cardioquin).
• Antidepressants such as maprotiline (Ludiomil) or tricyclic antidepressants such as desipramine (Norpramin) or imipramine (Tofranil).
• Medicines called phenothiazines, used to treat mental, emotional, and nervous disorders. Examples are chlorpromazine (Thorazine) and prochlorperazine (Compazine).
• Pimozide (Orap), used to treat symptoms of Tourette's syndrome.

Not all possible interactions of antihistamines with other drugs are listed here. Be sure to check with a physician or pharmacist before combining antihistamines with any other prescription or nonprescription (over-the-counter) medicine.

Nancy Ross-Flanigan

KEY TERMS

Allergen

—An otherwise harmless substance that can cause a hypersensitive allergic response.

Anaphylaxis

—A sudden, life-threatening allergic reaction.

Hallucination

—A sensory experience of something that does not exist outside the mind. A person can experience a hallucination in any of the five senses. Hallucinations usually result from drugs or mental disorders.

Histamine

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

Phenylketonuria

—(PKU) A genetic disorder in which the body lacks an important enzyme. If untreated, the disorder can lead to brain damage and mental retardation.

Pollen

—Dust-like grains produced by the male parts of plants and carried by wind, insects, or other methods, to the female parts of plants.

Antihistamines

Definition

Antihistamines in the group called H-1 are drugs that block the action of histamine, reducing or eliminating some of the symptoms of allergies and colds. A second group of antihistamines, termed H-2 or “H-2 receptor blockers” act on the histamine receptors responsible for the production of stomach acid. The H-2 receptor blockers are used to treat gastrointestinal upset and ulcers, but not cold or allergy symptoms.

Description

The antihistamines are a large group of drugs which all have action against immediate hypersensitivity reactions, such as the sneezing and congestion caused by histamine release. They have a large number of side effects, many of which can be useful, so that some of the drugs can be used as sedatives, or to fight nausea, cough or symptoms of parkinson's disease, to improve treatment of post-operative pain and to combat motion sickness.

The antihistamines are grouped in two ways, first by “generation,” and secondly by chemical structure. The first-generation antihistamines are traditional, and many are in common use in a variety of forms, not only for allergies, cold and sinus congestion, but also to relieve itch and as cough remedies, or for control of motion sickness. The drugs in this group, whatever their chemical structure, traditionally cause sedation, so that some are also used as nighttime sedatives. The second-generation antihistamines are more specific for the tissues they affect and have fewer side effects and significantly less sedation. They are, however, somewhat less effective for relief of the primary symptoms of allergies and colds. While some of the older antihistamines are only mildly sedating, the Merck Manual of Diagnosis and Therapy warns of their potentially serious adverse effects and discourages their use in seniors. these medications can be harmful to those with glaucoma , benign prostatic hyperplasia (enlarged Prostate gland), delirium , dementia, and orthostatic hypotension, A droop in blood pressure can occur upon standing. These drugs commonly cause dry mouth , blurred vision, urinary retention, constipation , and orthostatic hypotension.

A number of other authorities discourage the use of first generation antihistamines in the elderly. They should not be used to treat hay fever or hives in seniors, they can interact with other medications, and their adverse effects can be worsened by the presence of other illnesses. A review by the Ear, Nose and Throat Department, Mannheim University Hospital in Mannheim, Germany, goes beyond this in providing warnings: “…Use of first-generation H1 receptor antagonists in the elderly should be considered carefully because of the large number of adverse effects and potential for interactions with these agents…” A report from the Institute for Allergy and Asthma in Wheaton, Maryland, makes the point yet again by stating that the choice of which medication to use must be specific to the needs of the individual. Treatment should taken into consideration of the concomitant medications and potential drug interactions and drug-disease interactions. First-generation antihistamines should not be used for treatment of allergic rhinitis or urticaria in the elderly because age-related physiological changes can affect the medications, especially when taken with other medications and/or in the presence of another disease.

Antihistamine-containing cough preparations should also be avoided in the elderly, both for the reasons given above, and because there is no convincing evidence of efficacy to justify the risk. A meta-analysis of randomised controlled trials of over the counter cough medicines for acute cough in adults concluded that antihistamine preparations appeared to be no more effective than placebo, although the authors of the review did note that there were relatively few well designed studies, so that it was no possible to draw firm conclusions from the results.

These warnings are specific to systemic use for treatment of colds and allergies. In contrast, antihistamine lotions and creams can be extremely useful for elderly patients. This is because the elderly are subject to dry skin , which can itch, and subject to scratching, and this in turn can cause infections. Regular use of lotions, particularly those containing first-generation antihistamines, can maintain skin hydration and reduce or eliminate the itch, reducing the risk of infection.

In contrast to the warnings about the older antihistamines, the current group of second generation drugs seems to have an excellent safety record. Terfenidine, an early second-generation antihistamine was withdrawn from the market because of severe and sometimes fatal heart and liver toxicity. Loratidine, cetirizine and fexofenadine are second generation antihistamines that are not sedating and have excellent safety records, although cetirizine has been noted in a few studies to impair performance and thinking, although these effects are milder than those seen with the first generation antihistamines.

Antihistamines

• Aklylamines, generally only mildly sedating, ineffective in control of nausea and vomiting
• Brompheniramine
• Chlorpheniramine
• Dexchlorpheniramine
• Pheniramine
• Triprolidine
• Ethanolamines, generally highly sedating, likely to cause dry mouth
• Carbinoxamine
• Clemastine
• Diphenhydramine
• Ethylenediamine
• Pyrilamine
• Phenothiazines—most members of this class are used as major tranquilizers or to reduce nausea. The one example regularly used as an antihistamine is the potent sedative and anti-emetic
• Promethazine.
• Piperazine—not used for cold and allergies, but widely used for relief of itching, as a sedative before and after anesthesia, and for treatment of anxiety
• Hydroxyzine
• Piperadines—mildly to moderately sedating
• Azatadine
• Cyproheptadine—sometimes used off-label as an appetite stimulant
• Phenindamine
• Second generation antihistamines—generally have little of no central nervous system effects
• Phthalazinone
• Azalestine
• Piperazine
• Cetirizine—slightly sedating
• Piperadines
• Desloratidine
• Fexofenadine
• Lorastidine

Recommended dosage

See product specific references. Note that dosage adjustments are usually required in elderly patients because their kidneys do not clear these drugs effectively.

Precautions

The first generation antihistamines are not appropriate for self-medication by elderly patients. These drugs can be appropriate for use under medical supervision.

First generation antihistamines can impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. Cetirizine is second generation, but still has slight sedative effects which might be more pronounced in sensitive patients.

These drugs are contraindicated in patients with a history of sensitivity to the drug or any component of the formulation.

In general, antihistamines are not recommended to treat lower respiratory tract symptoms such as emphysema , chronic bronchitis , and asthma because they can thicken secretions and impair expectoration. The second generation antihistamines can show some anticholinergic effects (such as dry mouth), although they are milder than those seen with first generation drugs.

• What drug interactions are possible with antihistamines?
• Is it possible that my drug regimen is contributing to my congestion and runny nose?

KEY TERMS

Anticholinergic —Drugs which block the effects of acetylcholine. Among the effects are dry mouth, dry eyes, and possible loss of coordination.

Delirium —A mental condition marked by slurred speech, confusion, and hallucinations

Dementia —A progressive mental deterioration usually marked by memory loss and inability to plan complex activities

Glaucoma —Increased pressure inside the eye which can cause damage to the optic nerve resulting in blindness

Hypersensitivity —Excessively sensitive, used to describe development of an immune response to a harmless stimulant

Orthostatic hypotension —Low blood pressure which occurs when the patient stands up. This can be the result of drugs which dilate blood vessels so that blood drains from the head when moving from a recumbent position to a standing position. It often causes dizziness.

Rhinitis —Inflammation of the mucous membrane of the nose, resulting in congestion and sneezing

Use antihistamines with caution in patients with glaucoma, ulcers, intestinal obstruction, enlarged prostate, bladder obstruction, asthma, hyperthyroidism, cardiovascular disease and hypertension .

Side effects

These drugs have been widely used, and many adverse reactions have been reported. Consult product specific sources for detailed information.

Sedation is a well established side effect of the first generation antihistamines. In some cases, these drugs are used for their sedative properties, but when used for allergies and cold symptoms, sedation is an undesirable adverse effect.

The first generation drugs can cause other central nervous system effects including dizziness , blurred vision and double vision, headaches and agitation. See product specific literature for detailed information. In some cases, paradoxical insomnia has been reported.

Caregiver concerns

See product specific information.

Antihistamines can be expected to have an additive interaction with all drugs having similar effects and side effects. The sedative effect will increase the sedation caused by narcotic analgesics, anxiolytics, antidepressants or other drugs.

Resources

BOOKS

Reynild J (ed) Martindale the Extra Pharmacopoeia 30th ed The Pharmaceutical Press London 1993

Brody, Larner et al. Human Pharmacology Molecular to Clinical 2nd ed Mosby St. Louis

Simons FE Histamine and H1-Antihistamines in Allergic Disease Informa, Boca Raton Fl 2002

PERIODICALS

Hansen J, Klimek L, Hörmann K. Pharmacological management of allergic rhinitis in the elderly: safety issues with oral antihistamines. Drugs Aging. 2005;22(4):289-96.

Kaliner MA.1: Clin Allergy Immunol. 2002;17:465-81. Clin Allergy Immunol. 2002;17:465-81.

Laube S, Farrell AM. Bacterial skin infections in the elderly: diagnosis and treatment. Drugs Aging. 2002;19(5):331-42.

Schroeder K, Fahey T Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults. 1: BMJ. 2002 Feb 9;324(7333):329-31

Philpot EE. Safety of second generation antihistamines. Allergy Asthma Proc. 2000 Jan-Feb;21(1):15-20.

Mason J, Reynolds R, Rao N. “The systemic safety of fexofenadine HCl.” Clin Exp Allergy. 1999 Jul;29 Suppl 3: 163-70; discussion 171-3

Davies RJ; for the European Multicentre Study Group. Efficacy and Tolerability Comparison of Ebastine 10 and 20mg with Loratadine 10mg: A Double-Blind, Randomised Study in Patients with Perennial Allergic Rhinitis. Clin Drug Investig. 1998 Dec;16(6):413-420.

Sahin-Yilmaz AA, Corey JP. Rhinitis in the elderly. Clin Allergy Immunol. 2007;19:209-19.

Prenner BM, Schenkel E. Allergic rhinitis: treatment based on patient profiles. Am J Med. 2006 Mar;119(3):230-7.

Yáñez A, Rodrigo GJ. Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol. 2002 Nov;89(5):479-84.

Corey JP. Advances in the pharmacotherapy of allergic rhinitis: second-generation H1-receptor antagonists. 1: Otolaryngol Head Neck Surg. 1993 Sep;109(3 Pt 2):584-92

OTHER

http://online.factsandcomparisons.com/

http://www.medscape.com/

http://www.rxlist.com/cgi/generic/terfen.htm

http://www.coreynahman.com/ura.html

http://www.drugbank.ca/

http://www.nlm.nih.gov/medlineplus/allergy.html

ORGANIZATIONS

National Institute of Allergy and Infectious Disease, 6610 Rockledge Drive, MSC 6612, Bethesda, MD, 20892-6612, 301-496-5717, 866-284-4107, 301-402-3573, http://www3.niaid.nih.gov/links_policies/contact.htm, http://www3.niaid.nih.gov/.

Sam Uretsky PharmD

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 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 druginduced 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), and loratadine (Claritin) are all listed as category B. Azelastine (Astelin), hydroxyzine (Atarax), and 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.

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.

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.

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