Patient Care - Allergy & Immunology - October 2007 - (Page 20)

I Allergic rhinitis One therapeutic area in which montelukast may play a unique role is the combination of mild asthma and seasonal allergic rhinitis. The sneeze: AR pathophysiology Classically, the pathophysiology of seasonal AR is characterized by a type I immediate hypersensitivity reaction that is mediated by specific IgE antibodies to a seasonal allergen, such as wind-pollinated plants, which leads to mediator release and acute allergic responses followed by mucosal inflammation.1 The allergic reaction is characterized by an early-phase and a late-phase inflammatory response. Early-phase response Mast cell degranulation is the key component of the early-phase response, and histamine is the predominant mediator. In addition to histamine, mast cells generate leukotrienes, prostaglandins, and chemotactic factors that maintain the inflammatory response by attracting basophils, neutrophils, eosinophils, and T lymphocytes to the site of allergen exposure. These T lymphocytes become activated and release cytokines that are primarily responsible for maintaining the late-phase response, which occurs several hours after allergen challenge.7 Late-phase response Nasal congestion is part of both the acute- and late-phase allergic response, and several lines of evidence suggest that the cysteinyl leukotrienes, LTC4, LTD4, and LTE4, might contribute to the symptom.8 Nasal challenge studies with highdose leukotrienes have shown that the cysteinyl leukotrienes can induce nasal congestion, while causing few other symptoms.9,10 The potential actions of histamine and the cysteinyl leukotrienes in the allergic cascade support the possibility that LTRAs may play a role in the treatment of AR. Based on the possible effect of leukotrienes on nasal congestion, LTRAs might be expected to improve this symptom. How effective are the newer-generation antihistamines? A wealth of clinical evidence supports the use of the newer-generation antihistamines in the treatment of seasonal AR (see Table 1, page 21). Antihistamines effectively relieve the symptoms of itching, nasal drainage, sneezing, and vasodilation by blocking histamine H1 receptors located on the sensory nerve endings, mucous glands, and nasal vasculature. In addition, antihistamines are associated with relieving nasal congestion, an effect that is attributed to their additional anti-inflammatory properties.11,12 Indications The newer-generation prescription antihistamines—cetirizine, 10 mg; levocitirizine, 5 mg; desloratadine, 5 mg; and fexofenadine, 180 mg, all given once daily—are indicated for seasonal AR. Several placebo-controlled clinical studies have evaluated their efficacy and safety and have consistently demonstrated that all agents were superior to placebo in reducing the severity of seasonal AR symptoms in adults.11-15 In addition, all agents have proven to be well tolerated; reported adverse events were similar across active agents and placebo. Pediatric use In large clinical studies, cetirizine and fexofenadine have been shown to be significantly superior to placebo in alleviating the symptoms of seasonal AR in the pediatric population.16-20 Comparative clinical efficacy studies in adults have also demonstrated that the 2 agents significantly reduce the symptoms of seasonal AR to a similar degree.21-23 In these comparative studies, while cetirizine and fexofenadine were equally effective at relieving seasonal AR symptoms, cetirizine was associated with more drowsiness and impairment. Nasal congestion relief In contrast to the oldergeneration antihistamines, these newer agents also are effective in relieving nasal congestion as expected, given that histamine plays a predominant role in the early phase of an allergic response.11,22 For example, in a pan-European comparative study of fexofenadine and loratadine in more than 600 patients with seasonal AR, both agents were significantly superior to placebo at reducing total symptoms.11 When compared with placebo and loratadine, fexofenadine also produced a significant reduction in nasal congestion. The relief reported with some of the newer-generation antihistamines in seasonal AR is thought to be due to their high potency and selectivity for the H1 receptor and to their anti-inflammatory properties.24 20 PATIENT CARE ALLERGY & IMMUNOLOGY www.patientcareonline.com http://www.patientcareonline.com

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Patient Care - Allergy & Immunology - October 2007 Research Digest Contents Medicine in the News When to Suspect Celiac Disease and How to Proceed From There Averting Angioedema’s Potentially Dire Consequences Is There a Role for Leukotriene Receptor Antagonists in Treating Allergic rhinitis? Clinical Clips Dermatology Case Challenge Classified Advertising

Patient Care - Allergy & Immunology - October 2007

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