Pharmacologic therapy

The pharmacologic agents most often prescribed for patients with AR include oral H1-antihistamines, intranasal or intraocular H1-antihistamines, intranasal corticosteroids, nasal decongestants, nasal or intraocular chromones, and ipratropium bromide. The ARIA guidelines specify a stepped approach to AR pharmacotherapy.


According to this treatment scheme, the best regimen is selected based on whether the patient has mild intermittent, moderate/severe intermittent, mild persistent, or moderate/severe persistent AR symptoms. Intranasal steroids are recommended as first-line treatment of patients with moderate/severe symptoms, whether they are intermittent or persistent, and for those with mild persistent AR as well. Many of these patients may also be candidates for immunotherapy.


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Oral H1-antihistamines. Many chemical mediators play a role in generating the symptoms of AR, but histamine seems to be a major contributor.3 According to the most recent update by the ARIA group, oral antihistamines can improve patients’ quality of life by alleviating histamine-mediated symptoms. Oral antihistamines are less effective against nasal stuffiness and other symptoms of nasal blockage.5

The greatest advantage of oral antihistamines is that they provide potent, selective blockage of the H1-histamine receptor, making them an effective treatment of both persistent and intermittent AR.

The first-generation oral antihistamines, including chlorpheniramine, diphenhydramine, hydroxyzine, promethazine, and triprolidine, provide symptom relief but at the cost of potentially dangerous sedation and performance impairment.3 These side effects occur because these drugs are highly lipophilic and readily cross the blood-brain barrier, significantly impairing central nervous system function. They are short-acting, which often limits their usefulness and requires that they be taken at least twice daily. They also have poor selectivity and can block adrenergic, serotonergic, and dopaminergic receptors.

Thus, these first-generation drugs are rarely the first choice for patients with AR.Second-generation antihistamines (e.g., cetirizine, desloratadine, fexofenadine, and loratadine) are longer-acting and more selective than their older counterparts, and almost always preferred. Because they are large molecules, these newer agents display little or no tendency to cross the blood-brain barrier. They exhibit preferential binding to peripheral rather than central H1 receptors and few serotonergic effects. Anticholinergic and alpha-adrenergic effects are generally minimal.3

The advantage of the second-generation antihistamines lies in their improved side-effect profile.3 These newer drugs are less likely to cause sedation, although dose escalation may increase the likelihood of sedating side effects. First- and second-generation oral agents have the extra advantage of being effective against ocular symptoms.6

Although newer antihistamines provide effective control of sneezing, nasal itching, and rhinorrhea, they have minimal decongestant effects. As a result, a decongestant is often added to the regimen.6 The agent most often used is pseudoephedrine, which leads to improvements in nasal stuffiness in most patients. The risk of sleep disturbances and anxiety may be increased by commonly used decongestants, however, especially in the elderly and in young children. Some patients are unable to tolerate the effects of the decongestant in fixed-dose combination products and may need separate products so the dosage of each can be fine-tuned.3

Intranasal corticosteroids. According to the latest publication from the ARIA workshop, intranasal corticosteroids are “the most efficacious medications available for the treatment of allergic and nonallergic rhinitis.”5 They are crucial in patients whose major AR symptom is nasal congestion. Intranasal corticosteroids are notable because they control the four major symptoms of AR: sneezing, rhinorrhea, itching, and nasal blockage. In clinical trials conducted primarily during the 1990s, intranasal corticosteroids were more effective than nasal cromolyn and oral antihistamines in patients with AR.3

In a meta-analysis that included 16 randomized trials encompassing more than 2,200 patients, intranasal corticosteroids were significantly better than oral antihistamines in relieving nasal blockage, nasal discharge, sneezing, nasal itch, postnasal drip, and total nasal symptoms. Oral antihistamines and intranasal corticosteroids did not differ in their effects on nasal discomfort, nasal resistance, or eye symptoms. The authors concluded that these results, taken in conjunction with safety and cost-effectiveness data, “support the use of intranasal corticosteroids over oral antihistamines as first-line treatment for allergic rhinitis.”7 The risk of side effects is minimal.

Intranasal corticosteroids begin to take effect in seven to eight hours after dosing, but efficacy may not be maximal until two weeks after initiation of therapy. To ensure that the airway is patent and allows full penetration of the corticosteroid, some patients may need to use a topical decongestant at the start of treatment. The currently available intranasal corticosteroids include beclomethasone, budesonide, flunisolide, fluticasone, mometasone, and triamcinolone.

The most common side effects associated with intranasal corticosteroids are localized burning, stinging, hoarseness, and sneezing. Some patients (1%-3%) experience epistaxis, but the nosebleeds are usually minor and resolve promptly.8 The incidence of septal trauma, most common when a patient is first learning how to use this type of medication, can be lessened by teaching patients how to proceed, according to these steps:

  1. Blow the nose before administering the drug.
  2. Prime and activate the delivery device as recommended.
  3. Position the head. Depending on the product used, instructions may recommend tilting the head forward or backward.
  4. Insert the tip of the applicator gently, avoiding contact with the septum.
  5. Aim the applicator tip 45° from the floor of the nose and direct it at the outer corner of the ipsilateral eye to avoid traumatizing or spraying the septum (aqueous only).
  6. Close the other nostril gently with a finger.
  7. Sniff or inhale gently while delivering the drug.9

Special concerns in the elderly. The potential adverse effects of antihistamines are magnified in the elderly, who eliminate both first- and second-generation agents more slowly than younger patients. Sedating effects and decreased reaction time of the first-generation antihistamines are more pronounced in older patients, and anticholinergic effects often include drying of the mucous membranes, blurred vision, urinary retention, and constipation.

These are all strong reasons for avoiding first-generation agents in this population, particularly in patients with symptomatic benign prostatic hypertrophy, bladder-neck obstruction, or narrow angle glaucoma in particular. Second-generation antihistamines should be started at lower doses in older patients than in younger ones.10

In contrast, intranasal corticosteroids, the mast-cell stabilizer cromolyn, and the intranasal antihistamine azelastine can be used freely in older patients. The safety profile for these drugs is excellent, and they relieve the AR symptoms that patients find so troubling.

While clinicians need to be alert to newly developed AR in their elderly patients, they should also consider the possibility of drug-induced rhinitis—a particular risk since many in this age group take multiple medications. Common offenders include ACE inhibitors, reserpine, and prazosin.11 Intranasal tumors and systemic diseases such as hyperthyroidism and Wegener’s granulomatosis should also be considered in the differential diagnosis.

Immunotherapy

Allergen immunotherapy is almost always an option for patients with AR. Factors that enter into the decision to recommend this course of treatment include the severity of the symptoms; confirmation that the symptoms are caused by an allergy; the lack of efficacy of other medications; confirmation that antigen exposure is difficult to avoid; the availability of allergen extracts; the presence of comorbid conditions; and the possibility that immunotherapy might prevent a comorbid condition, notably asthma.3 Typical candidates have seasonal symptoms that return each year, perennial symptoms, and/or worsening symptoms.

A patient with self-limiting AR triggered by a brief seasonal exposure may not be a suitable candidate for immunotherapy. Immunotherapy may be continued during pregnancy but is usually not initiated or increased at that time. The elderly and preschoolers are not generally considered good candidates for immunotherapy.

The risk of anaphylaxis exists each time a patient undergoes immunotherapy, and the procedure should always be done by trained personnel who are adept in treating anaphylaxis. If a year elapses without notable improvements, immunotherapy can be stopped. If it’s effective, it typically continues for three to five years.1

In the future, sublingual immunotherapy (SLIT) may play a central role in the immunotherapy regimen. In a three-year study of SLIT compared with standard subcutaneous immunotherapy, both appeared to be equally efficacious in patients with rhinoconjunctivitis related to birch pollen.12 A meta-analysis of 10 studies of 577 patients published between 1990 and 2004 concluded that SLIT is effective in children with AR.13

Sublingual immunotherapy’s advantages, including ease of use and pain-free administration, are likely to make it a popular alternative—offering yet another means of managing this common but potentially debilitating disease.

Dr. Slavin is a member of the Section of Allergy and Clinical Immunology at St. Louis University School of Medicine; Dr. Katial is program director, Allergy and Immunology, at National Jewish Medical Center in Denver; Dr. Marple is vice chair of the Department of Otolaryngology at the University of Texas Southwestern Medical Center in Dallas. This article was originally published as a CME activity sponsored by Boston University School of Medicine. In its current form, the article is not designated for CME credit. The original CME activity was supported by an unrestricted educational grant from AstraZeneca Pharmaceuticals.

References

1. Quraishi SA, Davies MJ, Craig TJ. Inflammatory responses in allergic rhinitis: traditional approaches and novel treatment strategies. J Am Osteopath Assoc. 2004;104(5 suppl 5):S7-S15.

2. Bousquet J, van Cauwenberge P, Khaltaev N, et al. Allergic rhinitis and its impact on asthma (ARIA). In collaboration with the World Health Organization. Allergy. 2002;57:841-855.

3. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunol.1998;81:478-518.

4. Platts-Mills TA, Vaughan JW, Carter MC, Woodfolk JA. The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease. J Allergy Clin Immunol. 2000;106:787-804.

5. Bousquet J, van Cauwenberge P, Khaled NA, et al. Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GALEN). Allergy. 2006;61:1086-1096.

6. van Cauwenberge P, Bachert C, Passalacqua G, et al. Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy. 2000;55:116-134.

7. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ. 1998;317:1624-1629.

8. Blaiss MS, Benninger MS, Fromer L, et al. Expanding choices in intranasal steroid therapy: summary of a roundtable meeting. Allergy Asthma Proc. 2006;27:254-264.

9. Benninger MS, Hadley JA, Osguthorpe JD, et al. Techniques of intranasal steroid use. Otolaryngol Head Neck Surg. 2004;130:5-24.

10. Schaub B, Lauener R, von Mutius E. The many faces of the hygiene hypothesis. J Allergy Clin Immunol. 2006;117:969-977.

11. American Academy of Allergy, Asthma, and Immunology. The Allergy Report. Available at www.aaaai.org/ar/working_vol2/001.asp. Accessed February 12, 2008.

12. Khinchi MS, Poulsen LK, Carat F, et al. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study. Allergy. 2004;59:45-53.

13. Penagos M, Compalati E, Tarantini F, et al. Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials. Ann Allergy Asthma Immunol. 2006;97:141-148.