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Oral antihistamines, both prescription and over-the-counter, can provide much relief to allergy sufferers. But are they really as safe and effective as we believe?
Here, well provide some background on oral antihistamines, their pros and cons, and their role in the management of ocular allergy.
Histamine Receptor Agonists
The systemic agents used to treat allergy have historically been classified as histamine receptor antagonists. These are believed to selectively bind to and block the histamine receptor sites, preventing a response.1 Histamine receptors are present throughout many bodily tissues, including the skin, mucosal tissues, lungs, heart, gastrointestinal (GI) tract, and the central and peripheral nervous systems.2 They are also present on the surface of certain white blood cells.
Pharmacologically, histamine receptor antagonists fall into two categories: H1 receptor-blockers and H2 receptor-blockers. H1 receptor-blockers are the classic antihistamines, which are indicated for the treatment of itching, redness and edema associated with seasonal and perennial allergy. They also are indicated for other atopic conditions, including asthma, urticaria and eczema. Common antihistamines such as Benadryl (diphenhydramine, Warner-Lambert), Dimetapp (brompheniramine, Wyeth), Claritin (loratadine, Schering-Plough) and Allegra (fexofenadine, Aventis) are H1 receptor-blockers (see table).
H2 receptor-blockers diminish acid secretion from gastric parietal cells. They are used for short-term relief of occasional heartburn, gastroesophageal reflux disease, and gastric or duodenal ulcers. These medications are not indicated for use in allergy management.
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Adverse Effects
Since H1-receptors are abundant in the nasal, pharyngeal pulmonary and ocular mucosa, oral antihistamines can effectively alleviate symptoms associated with seasonal and perennial allergy, including allergic conjunctivitis. However, because H1-receptors are also located elsewhere in the body, numerous adverse effects can be associated with these agents. For example, H1-receptors in the central nervous system (CNS) help control the sleep cycle, endocrine homeostasis, cognition and memory. H1 receptor-blockers can induce undesirable CNS responses in certain individuals or when taken in excessive quantities. These include drowsiness, fatigue, dizziness, impaired mental ability and diminished psychomotor performance.2
Also, H1 receptor-blockers are widely recognized for their concurrent antagonistic effects on muscarinic receptors. This can result in significant anticholinergic effects. The most common ones include dry eye, dry mouth, urinary retention and constipation.2
Overall, second-generation antihistamines, such as Claritin and Allegra, do not penetrate the blood brain barrier as readily as first-generation antihistamines, such as Benadryl and Dimetapp. Hence, these newer agents are less likely to induce adverse CNS effects.2 Anticholinergic responses are also less common with second-generation antihistamines, though dry mouth has been noted at a higher incidence in patients taking Zyrtec (cetirizine, Pfizer) or Clarinex (desloratadine, Schering Corp.) compared with placebo.3,4
Finally, older-generation antihistamines have the capacity to blockade alpha-adrenergic receptors and cardiac ion currents in the heart, potentially resulting in tachycardia and/or arrhythmias.2 This effect was also noted in select second-generation agents, including Seldane (terfenadine, Hoechst Marion Roussel) and Hismanal (astemizole, Janssen), although these drugs are no longer available in the United States.
Oral vs. Topical Agents
In managing ocular allergies, studies have shown that topical agents may provide more rapid relief than oral antihistamines alone.5,6 Oral agents have been found to be approximately equal in efficacy to topical agents when considering long-term therapy, but these conclusions are somewhat inconsistent, and are based entirely on older topical antihistamines (i.e., levocabastine).7,8
Given the established efficacy of current topical allergy medications and the vast degree of uncertainty associated with oral antihistamines, practitioners should rely on topical agents as first-line therapy for all but the most serious ocular allergies. We tend to use oral antihistamines only when non-ocular manifestations, such as severe allergic rhinitis, urticaria or contact dermatitis, severe eczema, or atopic asthma, accompany the ocular symptoms. Even then, practitioners must warn patients of potential adverse effects when prescribing these agents.
In this regard, second-generation antihistamines are clearly preferable to first-generation. However, the cost of these newer products can be a significant consideration. Virtually all first-generation antihistamines are sold as over-the-counter preparations, so they may be far less expensive than most second-generation antihistamines. For patients who are on a fixed income or simply price conscious, we typically suggest Claritin, which is now available in a variety of formulations without a prescription. Although Claritin is still more expensive than such drugs as Benedryl or Chlor-Trimeton (chlorpheniramine, Schering-Plough), it is clearly a better choice when it comes to the safety profile.
Because oral medications represent a somewhat new and exciting addition to our therapeutic regimen, practitioners may be tempted to regularly prescribe these agents when managing ocular allergy. However, the evidence clearly suggests that oral antihistamines are not better, nor are they any safer, than our current topical allergy medications. In this arena at least, drops seem to be preferable to pills.
1. Simons FE, Simons KJ. The pharmacology and use of H1-receptor antagonist drugs. N Engl J Med 1994 Jun 9;330(23):1663-70.
2. Simons FE. Advances in H1-antihistamines. N Engl J Med 2004 Nov 18;351(21):2203-17.
3. Pfizer Laboratories. Zyrtec package insert, 2004.
4. Schering Corporation. Clarinex package insert, 2004.
5. Lanier BQ, Gross RD, Marks BB, et al. Olopatadine ophthalmic solution adjunctive to loratadine compared with loratadine alone in patients with active seasonal allergic conjunctivitis symptoms. Ann Allergy Asthma Immunol 2001 Jun;86(6):641-8.
6. Abelson MB, Welch DL. An evaluation of onset and duration of action of Patanol (olopatadine hydrochloride ophthalmic solution 0.1%) compared to Claritin (loratadine 10 mg) tablets in acute allergic conjunctivitis in the conjunctival allergen challenge model. Acta Ophthalmol Scand Suppl 2000;(230):60-3.
7. Swedish GP Allergy Team. Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis. Allergy 1994 Sep;49(8):611-5.
8. Bahmer FA, Ruprecht KW. Safety and efficacy of topical levocabastine compared with oral terfenadine. Ann Allergy 1994 May;72(5):429-34.
