Antihistamines
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.rxlist.com/cgi/generic/terfen.htm
http://www.coreynahman.com/ura.html
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