Second-generation H1-receptor Antagonists Research Articles

Comparative study on the efficacy and safety of bepotastine besilate versus levocetirizine in chronic spontaneous urticaria: A randomised, open-label, parallel study.

Background Urticaria is a common skin disease which often causes impairment in the quality of life. The ideal drug for chronic urticaria would have antihistaminic and anti-inflammatory actions. Bepotastine besilate is a recently approved novel anti-allergic agent with multiple mechanisms of action; levocetirizine is a potent and selective second-generation H1 receptor antagonist used in the treatment of urticaria. Aim To compare the efficacy and safety of bepotastine besilate versus levocetirizine in patients with chronic spontaneous urticaria. Methods The study design is a randomised, open-label, parallel-group, prospective interventional study. The study subjects were randomly assigned to either of the two groups a and b, each group had 50 patients with chronic urticaria. Statistical analyses were performed using (SPSS, version 18) for all the variables. Chi-square test was used for comparison between categorical variables. An unpaired student's t-test was done for quantitative variables. Results There was a significant decrease in mean urticaria activity score (P < 0.001), chronic urticaria quality of life (P < 0.001) and clinical global improvement (P < 0.001) in both the treatment groups but this improvement was higher in the bepotastine than in the levocetirizine group. There was no significant difference in the mean of absolute eosinophil count, C-reactive protein, aspartate transaminase, alanine transaminase from baseline to 4th week between the two study groups. Visual analogue scale showed statistically significant improvement from baseline to 4th week (P < 0.001) of follow-up but this increase was higher in levocetirizine group (0.64-4.24) than in bepotastine group (0.56-2.56) Limitations Blinding was not done. To assess the efficacy and safety of bepotastine, a larger study can be planned. Conclusion This study found that bepotastine is superior to levocetirizine and showed a statistically significant reduction in mean urticaria activity score 7, improved quality of life and clinical global improvement in patients with urticaria.

Isolation, structure elucidation, and high-performance liquid chromatography quantification of photolytic degradation impurities in acrivastine.

Acrivastine is a second-generation H1-receptor antagonist, and its structure is sensitive to ultraviolet. Four unknown and one reported degradation products can be detected in the ultraviolet radiation solutions of acrivastine. To improve the quality control of acrivastine, the photodegradation impurities were isolated and structurally elucidated. There are four new impurities (1-3 and 5), and one reported compound (4). The isolation strategy was designed as preparative high-performance liquid chromatography using a reversed phase column with volatile acid addition in the mobile phase, combined with preparative thin-layer chromatography using silica gel with alkaline addition in the mobile phase. Using the developed methods, five impurities (1-5) were efficiently purified after two or three chromatography runs with purities > 95%. The structures of compounds 1-5 are elucidated based on spectroscopy analysis of MS, and nuclear magnetic resonance spectroscopy. Using the impurity standard, the high-performance liquid chromatography method was developed and validated. The method was proved to be sensitive, accurate (Recovery% 96.1-107.7%), linear (0.15-0.75 μg/mL, R2 >0.996), robust, and specific, and it was successfully used to determine the degradation impurities of acrivastine and its formulation.

Crystal structure analysis of ebastine [4-(4-benzhydryloxy-1-piperidyl)-1-(4-tert-butylphenyl) butan-1-one]: an oral histamine antagonist

Ebastine belongs to the category of second-generation non-sedating H1 receptor antagonists and is chiefly used for the treatment of allergic rhinitis and chronic urticaria. The present paper reports findings on the crystal and molecular structure of ebastine, employing the technique of single-crystal X-ray diffraction. Ebastine crystallizes in the monoclinic P21/c space group with unit-cell dimensions a = 16.5890 (12), b = 10.9575 (8), c = 16.6795 (11) Å, β = 113.623 (2)°, V = 2777.8 (3) Å3, Z = 4 and calculated density amounting to 1.123 Mg m−3. The structure factor value was observed 1016 and final R = 0.0496 for 4360 unique reflections. The piperidine ring in the ebastine molecule was found to exist in a chair conformation, and the C—N bond length was 1.459 (3) Å, thereby showing good agreement with the standard C—N bond length of 1.472 Å.

Investigation of Patient-Specific Characteristics Associated with Treatment Outcomes for Chronic Urticaria

Identifying clinical characteristics of patients with chronic urticaria (CU) responsive to medication may help guide clinicians select treatment. The objective of this study was to investigate patient characteristics and medication use associated with urticaria control. A retrospective longitudinal chart review of adult patients with CU was conducted at a multisite allergy practice. Inclusion criteria required at least 4 CU office visits to allow for pre- and posttreatment assessment. Control corresponding to medication(s) used was assessed each visit. Univariate analysis followed by multiple logistic regression was performed. A total of 221 patients with CU were included; 140 (63%) achieved complete control. The average time to control was 1.4 ± 2.7 years, which required 1-3 classes of medications. Dermatographia odds ratio (OR) = 1.85 (95% CI 1.3-2.7) or other physical urticarias, OR = 1.51 (1-2.4) and neutrophilic infiltrates on skin biopsy were markers of poor control. Thyroid autoantibodies were associated with better control using an H1-antihistamine. Whereas 22% were controlled on a second-generation H1-receptor antagonist plus a leukotriene receptor antagonist (LTRA), an additional 33% were controlled when cyclosporine was added. Use of a first or second H1-antagonist or LTRA was associated with a 3.5-16.9 times higher odds of complete CU control in those with dermatographia. The odds of achieving control for other forms of physical urticaria was greatest when colchicine was added (aOR = 32.6 [12.7-83.2]). Patient-specific CU characteristics associated with medication-disease control may be useful for selecting treatment regimens. A subset of CU patients remains poorly controlled that indicates an unmet need for novel therapeutic agents.

Comparison of clinical effectiveness of acupuncture and a Western drug on allergic rhinitis: study protocol for a randomized controlled trial

ObjectiveTo compare the efficacy of an acupuncture regimen for persistent allergic rhinitis (PER), aimed at improving a patient's mind or Shen in Traditional Chinese Medicine, to that of a second-generation H1-receptor antagonist, cetirizine hydrochloride. MethodsThis multicenter, randomized, controlled clinical trial on PER will be conducted at three institutions in China. The total study period will be 9 weeks. After a 1-week preparatory screening period, 240 eligible participants with PER will be randomized to receive acupuncture or pharmacotherapy (1: 1) for 4 weeks with a 4-week follow-up. The primary outcome will be changes in 7-day average total nasal symptom score. Secondary outcome measures include rhinoconjunctivitis quality of life questionnaire score and total non-nasal symptom score. ResultsThe presence and seriousness of psychological and emotional impairments should be considered in therapeutic programs for allergic rhinitis. No clinical trial for treating allergic rhinitis via acupuncture regulation of psychological and emotional activities has been reported. ConclusionThe findings of the trial will allow us to determine the effects of the mind (Shen)-regulation treatment approach. We will also be able to confirm if the effects of acupuncture are equivalent to those of the conventional drug cetirizine hydrochloride.

Chronic Idiopathic Urticaria in Taiwan: A Clinical Study of Demographics, Aggravating Factors, Laboratory Findings, Serum Autoreactivity and Treatment Response

Chronic idiopathic urticaria (CIU) is not uncommon, yet there is little information about the clinical features of CIU patients in Taiwan. The purpose of this study was to investigate the clinical features of CIU in Taiwan. Patients with CIU were collected consecutively from the Urticaria Special Clinic in a medical center in northern Taiwan from December 2005 to May 2006. Clinical features and laboratory findings were studied. We also evaluated the therapeutic response of CIU patients with second-generation H1 receptor antagonist monotherapy for 6 weeks. A total of 62 CIU patients were investigated. The female to male ratio was 2.1:1 with a mean age of 31.8 years. The mean duration of the disease was 25.7 months (1.5-180 months). The most common aggravating factor was weather (79.7%), especially hot weather (50.8%). Fifty percent of the patients had atopy, and 37.3% of patients had positive autologous serum skin test. Besides, 61.3% of patients had at least one serum specific IgE antibody to the 18 common allergens examined. Finally, 60.7% of patients responded well to second-generation H1 receptor antagonist. Non-responders tended to have atopy (p = 0.0471), especially allergic rhinitis (p = 0.0107). This study provided an overview of CIU patients in a medical center in northern Taiwan. We found that atopy did not influence the severity or durtation of CIU. Nevertheless, atopy was associated with a poor therapeutic response of second-generation antihistamine. A survey of personal atopy history, especially allergic rhinitis, is important for management of CIU patients in Taiwan.

In vitro studies of the interaction between cetirizine and H2 receptor antagonists using spectrophotometry and reversed-phase high-performance liquid chromatography

Cetirizine, a second-generation H1 receptor antagonist, is used for the treatment of allergic disorders. For some of these diseases, combined H1 and H2 therapy generally is more effective than treatment exclusively with H1 or H2, although this synergistic effect has not been found in all studies. Moreover, extensive in vivo studies have investigated the effects that the coadministration of the H2 receptor antagonists have on the pharmacokinetics and pharmacodynamics of the H1 receptor antagonists. The current study therefore adopted an in vitro approach to investigate the interaction of cetirizine with commonly administered H2 receptor antagonists (i.e., cimetidine, ranitidine, and famotidine) in simulating body fluids at different pH levels and at 37°C using reversed-phase high-performance liquid chromatography (RP-HPLC) and ultraviolet (UV) spectrophotometry. An RP-HPLC method also was developed and validated for the simultaneous determination of these drugs. The mobile phase consisted of methanol:water (80:20) pumped at a flow rate of 1 mL/min. The chromatogram was monitored at 230 nm. The results from the UV spectrophotometry and RP-HPLC clearly indicated that the availability of cetirizine was unaffected by simultaneous administration of H1 and H2 receptor antagonists. Hence the two drugs can be safely administered with one another.

Effects of sedative and non-sedative H1 antagonists on cognitive tasks: behavioral and near-infrared spectroscopy (NIRS) examinations

It is well known that the newer H1-receptor antagonists elicit better performance of working memory and selective attention relative to the first generation drugs in this class. However, the neural correlates of the poorer performance associated with first-generation H1-receptor antagonists remain unknown. This study examined the effects of first- and second-generation H1-receptor antagonists on neural correlates of cognitive tasks using near-infrared spectroscopy (NIRS), a novel method of brain imaging suitable for psychological experiments. We measured the NIRS responses of 12 healthy volunteer subjects during the performance of working memory, selective attention, and visual perception tasks, 3 h after taking a first-generation antagonist (ketotifen), second-generation antagonist (epinastine), or placebo. We also measured subjective sleepiness by visual analogue scale (VAS) test. Cortical activation at the lateral prefrontal region increased during the performance of working memory and selective attention tasks in subjects receiving epinastine and placebo but not in those who took ketotifen. No significant difference was observed at the occipital region in the visual perception task among the three drug groups. VAS score and the behavioral performance during working memory and visual perception tasks indicated sedative effects of ketotifen consistent with the findings of previous studies. Our results suggest that the neural response for working memory and selective attention task was impaired by the administration of ketotifen in comparison with that of epinastine and placebo. The sedative effect in the neural response was not observed after epinastine administration.

Pharmacological Management of Allergic Rhinitis in the Elderly

An increasing number of elderly persons in our society experience allergic rhinoconjunctivitis. Different agents are used in the pharmacological treatment of allergic rhinitis, with histamine H1 receptor antagonists (antihistamines) being the most frequently prescribed class. However, drug therapy of aged persons differs to a degree from that in other age groups primarily because of quantitative pharmacotherapeutic problems. The main problems are co-morbidities and polymedication, which may lead to drug-drug interactions. H1 receptor antagonists block the action of histamine at specific receptors and are available for both topical and systemic administration. First-generation H1 receptor antagonists are lipophilic and therefore may cross the blood-brain barrier; they also lack specificity for the H1 receptor. Second-generation H1 receptor antagonists have reduced capacity to cross the blood-brain barrier and greater specificity for the H1 receptor. 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. Second-generation H1 receptor antagonists such as desloratadine, levocetirizine and ebastine provide good selective H1 receptor blockade without anticholinergic or alpha-adrenoceptor antagonist activity. Furthermore, they inhibit proinflammatory cytokines and are safe. Second-generation H1 receptor antagonists also offer therapeutic possibilities in patients with severe liver and/or renal dysfunction.

Effects of fexofenadine, diphenhydramine, and placebo on performance of the Test of Variables of Attention (TOVA)

To determine the effects of diphenhydramine 50 mg and fexofenadine 180 mg on cognitive performance using the Test of Variables of Attention (TOVA), and to ascertain whether the TOVA was sufficiently sensitive to differentiate between the effects of these first- and second-generation H1-receptor antagonists on performance. The study used a double-blind, placebo-controlled, randomized, crossover design. Forty-two subjects completed four separate TOVA tests: at baseline and after administration of placebo, diphenhydramine 50 mg, and fexofenadine 180 mg. On each occasion, subjects rated subjective feelings of drowsiness on a visual analog scale (VAS) before taking the TOVA. Compared with placebo, diphenhydramine caused an increased response time (P = 0.0230) and more omission errors (P = 0.0398). Diphenhydramine was also associated with increased drowsiness VAS ratings (P = 0.0065) compared with placebo. Diphenhydramine caused significantly more commission errors than fexofenadine (P = 0.0354). Neither placebonor fexofenadine 180 mg caused significant changes in any TOVA or VAS measurements compared with baseline. Fexofenadine was not statistically different from placebo for any evaluation. The TOVA was sufficiently sensitive to differentiate between the central nervous system effects of fexofenadine and diphenhydramine. Fexofenadine 180 mg had no significant effect on the TOVA measures of performance or on self-reported drowsiness compared with placebo. In contrast, diphenhydramine 50 mg caused significant increases in omission errors and response time on the TOVA and increases in self-reported drowsiness compared with placebo [corrected].

An investigation into the effects of cetirizine on cognitive function and psychomotor performance in healthy volunteers

The cognitive and psychomotor effects of 2.5, 5 and 10 mg cetirizine, a second-generation H1 receptor antagonist, were compared with loratadine 10, 20 and 40 mg, promethazine 25 mg and placebo in 24 healthy volunteers in a double-blind, randomised cross-over study. Following each dose, subjects were required to perform a series of tests of cognitive function and psychomotor performance at 1.5, 3 and 6 h post-dose. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task (CTT) and assessment of subjective sedation (LARS). Cetirizine and loratadine at all doses tested were not significantly different from placebo in any of the tests used. However, as expected for a verum, all measures with the exception of CTT were significantly disrupted by promethazine (P < 0.05). Promethazine caused a reduction in CFF threshold at all test points; these differences were significant at 3 h and 6 h post-dose (P < 0.05). There was also a significant increase in total reaction time at 3 h post-promethazine administration. Subjective reports of sedation were significantly greater following the administration of promethazine at all time points (P < 0.05). These results allow the conclusion that cetirizine at its recommended therapeutic dose of 10 mg is demonstrably free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the positive control, promethazine 25 mg.

H1‐receptor antagonists: effects on leukocytes, myth or reality?

H1-receptor antagonists of the first and second generation have been used for many years to relieve symptoms arising from the action of histamine on the H1 receptor. However, allergic inflammation is more than histamine release and action. Leukocyte infiltration during late allergic manifestations was demonstrated as being a hallmark of allergic inflammation. Second-generation H1-receptor antagonists were studied in models of mast cell degranulation in vitro and of leukocyte infiltration in vivo. Analysis of the literature showed that a drug which is no more metabolized than cetirizine and fexofenadine allows a better relevance of in vitro models. Up to now, cetirizine was the only product in vivo able to reduce eosinphil infiltration in skin, nose, eyes and lungs during experimental allergenic challenges and late allergic inflammatory manifestations. Today, relevance of these properties can be seen in the recently published clinical results showing that cetirizine prevents the development of asthma in specifically sensitized infants with atopic dermatitis.

Cardiovascular safety of fexofenadine HCl

Certain first- and second-generation H1-receptor antagonists are associated with prolongation of the corrected QT interval (QTc) and, in rare instances, with ventricular dysrhythmias, including torsades de pointes ventricular tachycardia. To assess the effect of fexofenadine HCl, a new non-sedating antihistamine, on QTc. Dose-tolerance, safety, and drug-interaction studies with healthy volunteers; and clinical efficacy studies with seasonal allergic rhinitis patients were conducted. Twelve-lead ECG data were collected pre- and postdosing or serially throughout these studies. Outliers were defined as QTc >440 msec with a >/=10 msec increase from baseline. Fexofenadine HCl at single doses up to 800 mg q.d. (once daily) and multiple doses up to 690 mg b.d. for 28 days in healthy volunteers resulted in no increases in QTc (recommended dose range is 120-180 mg daily); QTc changes were similar to placebo. Compared with placebo, there were no statistically significant QTc increases in patients receiving fexofenadine HCl 80 mg b.d. for 3 months, 60 mg b. d. for 6 months, or 240 mg q.d. for 12 months. No statistically significant increases in QTc were detected when fexofenadine HCl 120 mg b.d. was administered in combination with erythromycin (500 mg t. d.) or ketoconazole (400 mg q.d.) after dosing to steady-state (6.5 days). In seasonal allergic rhinitis patients (n = 1160) treated with 40, 60, 120, or 240 mg b.d. fexofenadine HCl for 2 weeks, there were no dose-related increases in QTc and no significant increases in mean QTc compared with placebo. Frequency and magnitude of QTc outliers with fexofenadine HCl and placebo were similar in all studies. No case of fexofenadine-associated torsades de pointes has been observed in controlled trial experience with more than 6000 patients. Fexofenadine HCl has been investigated more extensively for possible electrophysiological effects than any other antihistamine. Fexofenadine HCl has no significant effect on QTc, even at doses much higher than those used in clinical practice.

Loratadine: a non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation.

Although equally potent at blocking the H1 receptor, first- and second-generation antihistamines can be distinguished with respect to their different effects on the central nervous system (CNS). First-generation antihistamines readily cross the blood-brain barrier leading to significant drowsiness, altered mood, reduced wakefulness, and impaired cognitive and psychomotor performance. This paper reviews of studies CNS functioning conducted with loratadine, a second-generation H1-receptor antagonist, at its therapeutic dose of 10 mg per day. Studies employing self-report measures, such as diary cards, visual analogue scales, rating scales, and mood inventories have shown that the effect of loratadine on somnolence, fatigue, and mood was comparable to those found with placebo. In studies exploring physiological indices of CNS functioning, such as EEG-evoked potentials, and sleep latency tests, loratadine has been shown to be free of CNS effects. In addition, studies have investigated the effects of loratadine on actual driving performance, and on tests of cognitive and psychomotor functioning. On all of these performance measures, loratadine has been shown to have effects comparable to placebo. In contrast, diphenhydramine, a common first-generation antihistamine, usually available without a doctor's prescription, has significant adverse effects on vigilance, divided attention, working memory and psychomotor performance. Impairment has been shown to occur even in the absence of self-reported sleepiness.

Direct effects of second-generation H1-receptor antagonists on the activation of human basophils.

The present study was performed to investigate the putative suppressive effects of H1-receptor antagonists (HRA) of the second generation (astemizole (AS), cetirizine (CT), loratadine (LO), oxatomide (OX) and terfenadine (TF)) on the mediator release from human basophils activated by two classical stimuli. Anti-IgE-mediated histamine release was inhibited in a dose-dependent fashion by TF (maximum inhibitory value: 33.8 +/- 7.6%, 100 microM, n = 7), whereas the other HRA exhibited weaker activity. The anti-IgE-induced LTC4 production was strongly suppressed by TF, LO and OX (92.4 +/- 6.3%, 90.8 +/- 6.0% and 88.5 +/- 5.6%, 100 microM, n = 4-5), while AS was less active (56.4 +/- 4.1%, 100 microM, n = 5). Histamine release induced by incubation with grass pollen antigen (0.01%) was inhibited by TF (40.7 +/- 4.1%, 50 microM, n = 4), but the other HRA showed only low activity. The present findings suggest that some HRA might exhibit direct inhibitory effects on activation of IgE-receptor bearing cells.

In vitro effects of H1-antihistamines on histamine and PGD2 release from mast cells of human lung, tonsil, and skin.

Mast cells from different anatomic sites differ in cytochemistry and response to various secretory stimuli. We have investigated whether responsiveness to the second-generation H1-receptor antagonists, which are important first-line drugs for the relief of symptoms in patients with chronic urticaria and allergic rhinoconjunctivitis, also differs according to the site of origin of mast cells. The effects of terfenadine, ketotifen, and cetirizine were therefore examined in relation to the IgE-dependent release of histamine and prostaglandin D2 (PGD2) from dispersed human lung, tonsil, and skin mast cells. Terfenadine had a biphasic effect on lung and skin mast cells: at low concentrations, a concentration-dependent inhibition of histamine release from lung and skin mast cells was observed, whereas at higher concentrations the drug stimulated mediator release. Even at a high concentration, terfenadine inhibited mediator release from tonsil mast cells. Ketotifen had low potency as an inhibitor of mediator release from lung and tonsil mast cells. In skin mast cells, no inhibition of mediator release was observed below 1.0 microM, and above that concentration it induced mediator release. Cetirizine, a much less lipophilic drug than the others tested, did not induce mediator release from mast cells even at concentrations up to 100 microM. This drug showed concentration-dependent inhibition of IgE-dependent mediator release from lung and tonsil mast cells only. Our results show that human mast cells are heterogeneous with respect to modulation of mediator release by these H1-antihistamines. In particular, differences were observed between skin mast cells and those dispersed from lung and tonsils.

A pharmacokinetic evaluation of the second-generation H1-receptor antagonist cetirizine in very young children

The pharmacokinetics of the second-generation H1-receptor antagonist cetirizine was studied in eight children younger than 4 years of age who were treated with a single dose of cetirizine solution (5 mg). These children were hospitalized with suspected allergic respiratory problems or recurrent respiratory tract infections. Blood samples were collected at 1/2, 1, 1 1/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine collection was performed in five of the samples. The findings obtained in children were compared with those obtained in 16 healthy young adults (mean +/- SD, 24.6 +/- 4.1 years) who received a single 20 mg dose. Cetirizine was absorbed more slowly in children (p = 0.006; mean +/- SD, 1.44 +/- 1.12 hours) than in adults (0.62 +/- 0.22 hours). The plasma elimination half-life of cetirizine was significantly shorter in children (p < 0.001; 4.91 +/- 0.6 hours) than in adults (8.6 +/- 2.1 hours), and the clearance rate was significantly higher in children (p < 0.001; 1.48 +/- 0.41 ml/min/kg) than in adults (0.80 +/- 0.17 ml/min/kg). Urinary excretion of unchanged cetirizine was significantly lower in children (p < 0.001; 37.8% +/- 5.2%; n = 5) than in adults (57.7% +/- 11.8%). Therefore the metabolism of cetirizine is faster in young children than in adults. This effect must be taken into account in future pharmacodynamic studies in this age group.

Pharmacokinetics and pharmacodynamics of ebastine in children

Ebastine is a new piperidine-containing, relatively nonsedating second-generation H1-receptor antagonist. In a double-blind, parallel-group study of a single 5 mg or 10 mg dose of ebastine syrup used to treat allergic rhinitis in 20 children aged 6 to 12 years, we tested the hypothesis that the medication would have a duration of action of at least 24 hours. We measured plasma concentrations of carebastine, the pharmacologically active metabolite of ebastine, and the wheals and flares produced by epicutaneous tests with histamine phosphate, 1.0 mg/ml. Ebastine was absorbed well; peak carebastine concentrations occurred approximately 3 hours after dosing. Mean plasma elimination half-life values of carebastine ranged from 10 to 14 hours. The pharmacokinetics of carebastine were linear and dose independent in the dosage range studied. After the 5 or 10 mg dose, there were no significant differences between mean plasma elimination half-life values, mean oral clearance values, or mean apparent volumes of distribution. Mean peak plasma carebastine concentrations and mean areas under the plasma carebastine concentration-time curve after the 10 mg dose were 1.93 and 1.76 times, respectively, the values obtained after the 5 mg dose. Both doses significantly reduced the histamine-induced wheal-and-flare areas for up to 28 hours compared with predose values. The differences in effect between the doses generally were not statistically or clinically significant. No adverse effects were noted. We conclude that ebastine, an effective H1-receptor antagonist with a prompt onset of action and a long duration of action, is suitable for once-daily administration to children.

Loratadine. A review of recent findings in pharmacology, pharmacokinetics, efficacy, and safety, with a look at its use in combination with pseudoephedrine.

Antihistamines are considered first-line therapy for the relief of symptoms from allergic rhinitis and chronic urticaria. The newer, second-generation, nonsedating antihistamines reduce the central nervous system and anticholinergic side effects commonly found with previous drugs. The availability of H1-receptor antagonists that produce therapeutic effects without causing unwanted CNS effects fulfills an important practical need, since these drugs are clearly preferable in patients who drive or operate heavy machinery, or who are involved in activities requiring full alertness. Physicians and patients alike are pleased with the efficacy and safety the second-generation antihistamines bring to the treatment of allergy symptoms. Loratadine is an especially effective second-generation H1-receptor antagonist and is comparable to many of the other second-generation antihistamines. Loratadine may be particularly advantageous because of its low dose and the convenience of once-daily dosing. A more subtle advantage, loratadine's antiallergic properties, may warrant its use for specific treatment situations as future research clarifies the nature of the inflammatory response and the mechanisms of action antiallergic antagonists have in this regard.

H 1-receptor antagonist treatment of seasonal allergic rhinitis

H1-receptor antagonists are usually first-line treatment given for seasonal allergic rhinitis. However, many patients suffer with symptoms of allergic rhinitis rather than tolerate the sedative and anticholinergic side effects of the first-generation H1-receptor antagonists. Researchers have sought to replace these older H1-receptor antagonists with a new generation of H1-receptor antagonists that approach the optimal therapy: clinically effective, safe, free of side effects, and convenient for the patient. Among the new second-generation H1-receptor antagonists are terfenadine and astemizole (already marketed) and loratadine and cetirizine, which are expected to be approved soon. All four demonstrate efficacy, convenience, and minimal side effects on the central nervous system. In this review of the current treatment of seasonal allergic rhinitis, the clinical studies that compare these four new second-generation H1-receptor antagonists are discussed.