Rhinosinusitis: establishing definitions for clinical research and patient care.
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Clinical Trials as Topic↗
Biomedical subjects
Eli O Meltzer
Publications and source records attributed to Eli O Meltzer.
Rhinosinusitis: Establishing definitions for clinical research and patient care.
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Clinical Trials as Topic↗
Addition of ibuprofen to pseudoephedrine and chlorpheniramine in the treatment of seasonal allergic rhinitis.
BACKGROUND: Patients with seasonal allergic rhinitis experience many nasal and concomitant nonnasal symptoms. Many patients also experience headaches and facial pain, pressure, or discomfort. Standard over-the-counter therapy with antihistamines and nasal decongestants often does not completely relieve all symptoms associated with allergic rhinitis. OBJECTIVE: To establish the contribution of ibuprofen when used with pseudoephedrine and chlorpheniramine, a standard over-the-counter regimen, to relieve the symptoms of seasonal allergic rhinitis. METHODS: In this 7-day, multicenter, randomized, placebo-controlled, double-blind, double-dummy, parallel-group trial, qualified subjects were randomly assigned to 1 of 4 treatment groups that received combined ibuprofen/pseudoephedrine/chlorpheniramine (200/30/2 mg or 400/60/4 mg), combined pseudoephedrine/chlorpheniramine (30/2 mg), or placebo. Therapy began when the subject experienced a minimum of moderate allergy-associated pain, and it continued 3 times a day for 7 consecutive days. RESULTS: Mean pain intensity reduction in both ibuprofen/pseudoephedrine/chlorpheniramine treatment groups was 40% greater than in the placebo group and 33% greater than in the pseudoephedrine/chlorpheniramine treatment group (P < .001). Mean changes from baseline in total and nonpain symptom scores for both ibuprofen/pseudoephedrine/chlorpheniramine doses were significantly greater than for placebo (P < .001) and pseudoephedrine/chlorpheniramine (P < .001-.05) but were not different from each other. Ibuprofen enhanced the chlorpheniramine and pseudoephedrine effects, resulting in incremental 33% to 34% pain relief and 17% to 22% allergy symptom relief compared with pseudoephedrine/chlorpheniramine. CONCLUSIONS: In both doses of the triple combination, ibuprofen added to the effects of chlorpheniramine and pseudoephedrine, resulting in superior relief of pain and all nonpain allergy symptoms compared with pseudoephedrine/chlorpheniramine treatment. Furthermore, the superior efficacy of the lower dose of the triple combination allowed for a decrease in the incidence of adverse effects.
Adult↗
Latino children with asthma: rates and risks for medical care utilization.
Latino families have been reported to underutilize health care services compared with families from other ethnic backgrounds. As part of a community trial in a low income Latino population designed to decrease environmental tobacco smoke (ETS) exposure in children with asthma in San Diego, we examined unscheduled medical care for asthma. Latino families (N = 193) reported information about medical care use for their children during the past 12 months. About 23% were hospitalized, 45% used the emergency department, and 60% used urgent care services. About 8.5% of families had two or more hospitalizations in 12 months. Most families were insured by Medicaid or had no insurance. Significant risk factors for a child's hospitalization were age (under age six), failure to use a controller medication, and a parental report of the child's health status as being poor. Risk factors for emergency department use were age (under age six) and male gender. These findings indicate that low-income Latino families with young children with asthma lack the medical resources necessary for good asthma control. Quality and monitored health care with optimization of asthma management could reduce costly acute care services.
Adolescent↗
Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis--a pooled analysis of three studies.
Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6-11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.
Anti-Allergic Agents↗
Histamine skin test reactivity following single and multiple doses of azelastine nasal spray in patients with seasonal allergic rhinitis.
OBJECTIVE: To determine whether azelastine nasal spray suppresses the dermal response to epicutaneous histamine in allergic patients and the duration of suppression after azelastine use is discontinued. METHODS: Seventy-eight patients with seasonal allergic rhinitis were entered into this randomized, double-blind, parallel-group, placebo-controlled study. Patients received either azelastine nasal spray (2 sprays per nostril twice daily) or placebo nasal spray for 14 days. Skin tests were performed 5 hours after the first dose of study drugs to determine the effect of a single dose of azelastine nasal spray on the wheal-and-flare response to histamine. At the end of the 14-day treatment period, skin tests were performed 5 hours after the last dose of study drugs and at 24-hour intervals thereafter, until each patient's wheal-and-flare response to histamine (1.0 and 5.0 mg/mL) returned to within 20% of baseline values. RESULTS: A single dose of azelastine nasal spray did not significantly alter the wheal-and-flare response to histamine. The wheal response was within 20% of the baseline value in 82% and 88% (1.0 and 5.0 mg/mL of histamine, respectively) of the patients 5 hours after discontinuing 14 days of treatment with azelastine nasal spray. Wheal responses were within 20% of baseline values 48 hours after treatment was discontinued, whereas flare responses returned to within 20% of baseline within 48 hours in 92% of the patients. CONCLUSIONS: Azelastine nasal spray should be discontinued for at least 48 hours before beginning allergy skin test procedures.
Administration, Intranasal↗
Efficacy and safety of clemastine-pseudoephedrine-acetaminophen versus pseudoephedrine-acetaminophen in the treatment of seasonal allergic rhinitis in a 1-day, placebo-controlled park study.
BACKGROUND: Allergic rhinitis afflicts more than 40 million people in the United States and is a leading cause of reduced productivity at work and in school. Patients with allergic rhinitis have a wide range of symptoms that are often treated with oral combination products that contain antihistamines, decongestants, and analgesics. OBJECTIVE: To evaluate the onset of action and the extent of efficacy and safety of a combination (CPA) of clemastine (0.68 mg), pseudoephedrine (60 mg), and acetaminophen (1,000 mg) versus a combination (PA) of pseudoephedrine and acetaminophen versus placebo in the treatment of seasonal allergic rhinitis (SAR). The primary goal was to evaluate the benefit of adding clemastine to the PA combination product to treat the symptoms of SAR. METHOD: A 1-day, multicenter, double-blind, double-dummy, randomized, parallel-group park study was organized, and medication was given at 9:00 AM and 3:00 PM. RESULTS: A total of 298 subjects participated at two outdoor facilities. The primary efficacy outcome was the major symptom complex score averaged over the period of 2 to 5 hours after each dose. Mean absolute and percentage reduction in major symptom complex averaged over the period of 2 to 5 hours in the CPA group was significantly superior to those of either the PA (P < 0.01) or placebo (P < 0.03) groups. Somnolence, fatigue, and nausea were the most common volunteered adverse events; only somnolence was significantly greater after CPA than after either PA or placebo. CONCLUSIONS: Treatment with CPA was safe and highly effective in reducing symptoms associated with SAR. It was more effective than either PA or placebo over most of the postdose observation period.
Acetaminophen↗
Requirements for medications commonly used in the treatment of allergic rhinitis. European Academy of Allergy and Clinical Immunology (EAACI), Allergic Rhinitis and its Impact on Asthma (ARIA).
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Administration, Intranasal↗
A questionnaire to measure quality of life in adults with nocturnal allergic rhinoconjunctivitis.
BACKGROUND: Many patients with rhinoconjunctivitis experience symptoms at night and these interfere with getting a good night's sleep. OBJECTIVE: The aim of this study was to develop the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) to measure the functional problems that are most troublesome to patients with nocturnal allergic rhinoconjunctivitis (NAR). METHODS: After generating a list of 256 potentially important items, 132 patients with NAR identified the items that were most troublesome. The top scoring 16 items are included in the NRQLQ in four domains (sleep problems, symptoms during sleep time, symptoms on waking and practical problems). The NRQLQ asks patients to recall their experiences during the previous week and score each item on a 7-point scale. RESULTS: One hundred and six patients with NAR participated in a 3 week validation study. This showed the NRQLQ to have good reliability (ICC = 0.87) and responsiveness (responsiveness index = 0.93). For both cross-sectional and longitudinal construct validity correlations between the NRQLQ and other measures of health status were close to a priori predictions. CONCLUSIONS: The NRQLQ has strong evaluative and discriminative measurement properties and can be used with confidence in both clinical practice and clinical trials to measure the functional impairments that are most troublesome to patients with nocturnal allergic rhinoconjunctivitis.
Adult↗
Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis.
BACKGROUND: This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. OBJECTIVE: This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. METHODS: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point. RESULTS: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P </=.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P <.05), including nasal congestion in the evening reflective assessment (P <.05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality. CONCLUSION: The efficacy and safety of the H(1)-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis.
Anti-Allergic Agents↗
Efficacy and patient satisfaction with cromolyn sodium nasal solution in the treatment of seasonal allergic rhinitis: a placebo-controlled study.
BACKGROUND: Because the symptoms of seasonal allergic rhinitis are readily recognizable, many individuals self-medicate with nonprescription agents. The mast-cell stabilizer cromolyn sodium is available for over-the-counter (OTC) use in the prevention and treatment of allergic rhinitis. OBJECTIVE: The goal of the study was to evaluate the efficacy of cromolyn sodium 4% nasal solution for the treatment of allergic rhinitis in self-selected patients in a nonprescription setting. A secondary objective was to determine whether the instructions and warnings in the OTC labeling provide adequate information for safe and proper OTC use. METHODS: This 2-week, multicenter study had a randomized, double-blind, placebo-controlled, parallel-group design. Advertisements were used to identify allergy sufferers who used OTC products but had not used OTC allergy medications within 48 hours of study entry and did not require prescription medications to control allergy symptoms. Enrolled patients were randomized to receive either cromolyn sodium 4% nasal solution in a metered-spray bottle containing 200 doses or an identical-appearing placebo. They were instructed to follow the directions for use on the label: that is, to administer 1 spray in each nostril every 4 to 6 hours, no more than 6 times per day, for the prevention or relief of symptoms. Daily use of study drug and concomitant medications was recorded in patient diaries. Patients also rated symptom severity, symptom relief, medication efficacy, and helpfulness of the label instructions. Relief of overall and individual rhinitis symptoms was assessed at the end of weeks 1 and 2. RESULTS: The intent-to-treat population consisted of 1150 patients (580 cromolyn sodium, 570 placebo). Cromolyn sodium provided greater relief than placebo on all efficacy measures and was statistically significantly more effective than placebo in controlling allergy symptoms (P = 0.02), providing overall symptom relief (P = 0.02), and relieving sneezing (P = 0.01) and nasal congestion (P = 0.03). The instructions for use were rated helpful to extremely helpful by >92% of patients, although only approximately 48% of patients used the drug according to the label instructions. The most common adverse events in both groups were headache and rhinitis, and there was no significant difference in the rates of such events between groups. CONCLUSION: In this study, cromolyn sodium 4% nasal solution was well tolerated and effective, suggesting that it is suitable for OTC use in the treatment of seasonal allergic rhinitis.
Adolescent↗
Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis.
BACKGROUND: Mometasone furoate nasal spray (MFNS) 400 microg, twice daily, as adjunctive treatment with oral antibiotic significantly improved symptoms of recurrent rhinosinusitis. OBJECTIVE: To evaluate the effectiveness and safety of MFNS 200 microg, twice daily, and 400 microg, twice daily, compared with placebo as adjunctive treatment with oral antibiotic for acute rhinosinusitis. METHODS: In this multicenter, double-blind, placebo-controlled study, 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin/clavulanate potassium (Augmentin, GlaxoSmithKline, Research Triangle Park, NC) 875 mg, twice daily, for 21 days with adjunctive twice daily MFNS 200 microg, MFNS 400 microg, or placebo nasal spray. Patients recorded scores of six rhinosinusitis symptoms and any adverse events twice daily. Pre- and postcosyntropin-stimulation plasma cortisol levels were measured in a subset of patients at selected study sites. RESULTS: Treatment with MFNS 200 microg or 400 microg, twice daily, produced significantly greater improvements in total symptoms score (primary efficacy variable) day 1 to day 15 average (50% and 51%, respectively) than placebo (44%, P < or = 0.017). Both doses of MFNS produced significant total symptoms score improvement over placebo by day 4, and maintained efficacy over the entire 21-day study. Relief of individual symptoms showed a similar pattern. Both doses of MFNS were well tolerated, and adverse events were similar to that of placebo. Cosyntropin stimulation showed no evidence of hypothalamic-pituitary-adrenal axis suppression. CONCLUSIONS: As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 microg or 400 microg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone.
Acute Disease↗
Clinical evidence for antileukotriene therapy in the management of allergic rhinitis.
OBJECTIVE: This article presents information summarizing the findings of several clinical trials that evaluated the efficacy and safety of leukotriene receptor antagonists in the treatment of allergic rhinitis. After reading this article, readers will have a greater understanding of these clinical findings and their implications for the management of allergic rhinitis. DATA SOURCES: Relevant and appropriately controlled clinical trials were used. Only literature in the English language was reviewed. STUDY SELECTION: Material was taken from academic/scholarly publications, published abstracts, and papers presented at a major congress. RESULTS: Similar to their contribution to the pathogenesis of asthma, cysteinyl leukotrienes have been found to exert potent inflammatory effects in the upper airways and to play a role in the pathogenesis of allergic rhinitis. The guidelines for the diagnosis and treatment of allergic rhinitis emphasize the importance of treating the pathophysiologic pathways of the disease. Thus, the use of antileukotriene therapy is a rational therapeutic option for patients with allergic rhinitis. Findings from several randomized, placebo-controlled clinical trials confirm the efficacy of leukotriene receptor antagonists in reducing the symptoms of allergic rhinitis and improving quality of life. Clinical experience with these medications has also demonstrated their tolerability and safety. CONCLUSIONS: Results from recently completed and ongoing clinical trials have expanded the body of evidence for the safety and efficacy of antileukotrienes in the treatment of allergic rhinitis.
Acetates↗
Intranasal fluticasone propionate is effective for perennial nonallergic rhinitis with or without eosinophilia.
BACKGROUND: Although response to intranasal corticosteroid therapy has been reported in patients with nonallergic rhinitis with eosinophilic syndrome (NARES), efficacy specifically in non-NARES patients has not been fully characterized. OBJECTIVE: To evaluate the efficacy of intranasal fluticasone propionate (FP) in the treatment of patients with perennial nonallergic rhinitis, with and without nasal eosinophilia. METHODS: Data from 983 patients in three randomized, double-blind, placebo-controlled PNAR trials were integrated. Patients received a total daily dose of FP 200 microg (n = 332), FP 400 microg (n = 325), or placebo (n = 326) for 28 days. Patients were > or =12 years of age with perennial rhinitis and negative skin tests to all allergens relevant to the geographic region. Nasal eosinophils were evaluated using a five-point scale. Patients were classified as non-NARES with a point score of 0 (n = 674; 69%); patients with a point score between I and 4 were classified as NARES (n = 309; 31%). Efficacy of FP was evaluated by the mean change in total nasal symptom score (TNSS), a sum of patient ratings of nasal obstruction, postnasal drip, and rhinorrhea. RESULTS: Patients with either NARES or non-NARES had similar statistically significant improvement with FP 200 microg or 400 microg compared with placebo; thus, the total group comprising both varieties of rhinitis responded to FP. In the total population, both FP treatment groups showed significantly greater improvement in TNSS compared with placebo during each week of treatment (P < or = 0.002), with mean changes in TNSS for day 22 to day 28 ranging from -84 and -85 in the FP 200 microg and FP 400 microg groups, respectively, to -64 in the placebo group. The three study treatment groups had similar proportions of non-NARES (68 to 69%) and NARES (31 to 32%) patients at baseline. In the non-NARES subgroup, mean changes in TNSS for each treatment group were similar to changes seen in the total population. In the NARES subgroup, mean changes in TNSS for the FP 200 microg and placebo groups were similar to changes seen in the total population; mean change in TNSS for the FP 400 microg group was somewhat greater than changes seen in the total population. CONCLUSIONS: Intranasal FP is an effective treatment for perennial nonallergic rhinitis with or without nasal eosinophilia (NARES or non-NARES).
Administration, Intranasal↗
Asthma management and environmental tobacco smoke exposure reduction in Latino children: a controlled trial.
OBJECTIVES: This study tested the efficacy of coaching to reduce environmental tobacco smoke (ETS) exposure among asthmatic Latino children. DESIGN: After asthma management education, families were randomly assigned to no additional service (control condition) or to coaching for ETS exposure reduction (experimental condition). SETTING: The study was conducted in San Diego, California. PARTICIPANTS: Two hundred four Latino children (ages 3-17 years) with asthma participated. INTERVENTION: Approximately 1.5 hours of asthma management education was provided; experimental families also obtained 7 coaching sessions ( approximately 45 minutes each) to reduce ETS exposure. OUTCOME MEASURES: Reported ETS exposure and children's urine cotinine were measured. RESULTS: Parents in the coached condition reported their children exposed to significantly fewer cigarettes than parents of control children by 4 months (postcoaching). Reported prevalence of exposed children decreased to 52% for the coached families, but only to 69% for controls. By month 4, mean cotinine levels decreased among coached and increased among control children. Cotinine prevalence decreased from 54% to 40% among coached families, while it increased from 43% to 49% among controls. However, cotinine levels decreased among controls to the same level achieved by coached families by the 13-month follow-up. CONCLUSIONS: Asthma management education plus coaching can reduce ETS exposure more than expected from education alone, and decreases in the coached condition may be sustained for about a year. The delayed decrease in cotinine among controls is discussed.
Adolescent↗
Use of intranasal cromolyn sodium for allergic rhinitis.
Allergic rhinitis affects 10% to 20% of Americans. It frequently coexists with other conditions, such as allergic conjunctivitis, sinusitis, and asthma, and is associated with impaired occupational function and performance in school, decreased quality of life, and increased health care costs. An efficacious agent with minimal adverse effects and a lack of drug interactions is needed to help simplify treatment of allergic rhinitis, especially in patients with comorbidities. Controlled studies of intranasal cromolyn sodium therapy for patients with seasonal and perennial allergic rhinitis are reviewed, and appropriate candidates for treatment with this agent are discussed. Cromolyn inhibits the degranulation of sensitized mast cells, thereby blocking the release of inflammatory and allergic mediators. It reduces symptoms of allergic rhinitis, and, when used prophylactically, cromolyn can prevent symptoms from occurring. Controlled studies comparing cromolyn with placebo, intranasal corticosteroids, and antihistamines have shown the efficacy of cromolyn in relieving rhinitis symptoms. In addition, because cromolyn is poorly absorbed systemically, it is well tolerated and not associated with drug interactions. Intranasal cromolyn has an excellent safety record, is available as an over-the-counter medication, and has been proved to be efficacious in patients with allergic rhinitis.
Administration, Intranasal↗
Efficacy and safety of low-dose fluticasone propionate compared with montelukast for maintenance treatment of persistent asthma.
OBJECTIVE: To compare the long-term effects of an inhaled corticosteroid with those of a leukotriene modifier on measures of clinical efficacy, subject preference, and safety in patients with persistent asthma. PATIENTS AND METHODS: Between November 17, 1998, and May 26, 2000, we conducted a multicenter, randomized, double-blind, double-dummy, parallel-group study of patients aged 15 years or older with persistent asthma. The patients were symptomatic while taking short-acting beta2-agonists alone and were treated with fluticasone propionate (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg/d) for 24 weeks. Measures of pulmonary function, asthma symptoms, albuterol use, nighttime awakenings, physician assessments of efficacy, patient satisfaction, asthma-related quality of life, and safety were evaluated. RESULTS: A total of 522 patients were randomized to receive fluticasone or montelukast, and 395 patients completed the study. At end point, treatment with fluticasone significantly improved pulmonary function, asthma symptom scores, the percentage of symptom-free days, rescue albuterol use, and the number of nighttime awakenings due to asthma when compared with montelukast (P< or = .002, each comparison). Significantly more patients were satisfied with fluticasone therapy (83%) compared with montelukast therapy (66%) (P<.001), and fluticasone therapy was rated as effective by a significantly greater portion of physicians (67%) than was montelukast therapy (54%) (P<.001). Treatment with fluticasone significantly improved asthma-related quality-of-life measures compared with montelukast (P< or =.01). The incidence of asthma exacerbations was similar in the fluticasone (19 patients, 7%) and montelukast (21 patients, 8%) treatment groups, although slightly more patients in the montelukast group were withdrawn from the study because of asthma exacerbations (6% vs 4%, respectively). CONCLUSION: Long-term treatment with a low dose of inhaled fluticasone is more effective than oral montelukast as first-line maintenance therapy for the treatment of persistent asthma.
Acetates↗
H1-antihistamines and the central nervous system.
An extensive body of research exists on CNS effects of H1-antagonists. There is great interest in this area due to the well-known adverse CNS effects associated with first-generation H1-antagonists, and the many new second-generation agents claiming to have nonsedative properties. Because the CNS effects of H1-antagonists are complex and cannot be reflected in one measurement, a variety of assessments of CNS function are required. These range from the subjective (e.g., self-rating of drowsiness) to the objective (e.g. 24 h EEG sleep latency, P300), and from the simple (e.g., critical flicker fusion) to the complex (e.g., actual driving). When these tests are applied to the evaluation of the H1-antagonists currently available, it is clear that there is a real distinction between the older first-generation H1-antagonists and the newer second-generation ones. At the recommended dosages, all the second-generation H1-antagonists are clearly less sedating in more patients than their predecessors. These newer medications do not cross the blood-brain barrier readily; are highly specific for H1-receptors; have little to no anticholinergic, antiserotoninergic, or anti-alpha-adrenergic effects; and do not enhance the adverse CNS effects of alcohol or other CNS-active substances such as the benzodiazepines. Since most second-generation H1-antagonists are found to be relatively nonsedating, their benefit/risk ratios will be determined more by their other properties such as non-CNS adverse effects (e.g., potential to cause cardiac arrhythmias), potency, onset of action, duration of action, ease of administration, and cost. The future role and usefulness of the older sedating H1-antagonists, given the availability of the safer second-generation agents, are unclear at the present time. When H1-antagonist treatment is indicated, physicians should recommend an effective H1-antagonist with a favorable clinical pharmacology profile and a wide margin of safety in patients of all ages. The common, often subclinical, adverse CNS effects produced by the old H1-antagonists remain a major concern and, therefore, these compounds are no longer medications of choice in the treatment of allergic rhinitis, allergic conjunctivitis, or urticaria.
Animals↗