loratadine, Claritin
Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models.

Orzechowski RF, Currie DS, Valancius CA.

Department of Pharmaceutical Sciences, Pharmacology and Toxicology Division, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA. r.orzech usip.edu

We determined the relative rank orders of anticholinergic potencies of 10 antihistamines in two functional bioassays: (1) an in vitro assay measuring inhibition of carbachol-induced contractions of isolated guinea pig trachealis muscle, (2) an in vivo bioassay comparing systemic hypotensive responses to bolus i.v. injections of acetylcholine before and after infusions of an antihistamine in anaesthetized rats. In vitro, the rank order of anticholinergic potencies of the antihistamines was cyproheptadine>promethazine>desloratadine>diphenhydramine>loratadine>chlorpheniramine>hydroxyzine>pyrilamine. The pA2 values ranged from 8.2+/-0.4 for cyproheptadine to 4.8+/-0.4 for pyrilamine. Fexofenadine and cetirizine (up to 3 x 10(-4) M) were inactive. In vivo, five antihistamines showed anticholinergic activity: cyproheptadine>promethazine>desloratadine>loratadine>diphenhydramine. The remaining antihistamines had no significant effect at i.v. infusion doses up to 50 imol/kg. Cetirizine and fexofenadine did not antagonize cholinergic responses in either model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15627436&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis.

Bielory L, Lien KW, Bigelsen S.

Department of Medicine, Pediatrics and Ophthalmology, Division of Allergy, Immunology and Rheumatology, UMDNJ-New Jersey Medical School, Immuno-Ophthalmology Service, 90 Bergen Street, DOC Suite 4700, Newark, NJ 07103, USA. bielory umdnj.edu

Treatment for allergic conjunctivitis has markedly expanded in recent years, providing opportunities for more focused therapy, but often leaving both physicians and patients confused over the variety of options. As monotherapy, oral antihistamines are an excellent choice when attempting to control multiple early-phase, and some late-phase, allergic symptoms in the eyes, nose and pharynx. Unfortunately, despite their efficacy in relief of allergic symptoms, systemic antihistamines may result in unwanted adverse effects, such as drowsiness and dry mouth. Newer second-generation antihistamines (cetirizine, fexofenadine, loratadine and desloratadine) are preferred over older first-generation antihistamines in order to avoid the sedative and anticholinergic effects that are associated with first-generation agents. When the allergic symptom or complaint, such as ocular pruritus, is isolated, focused therapy with topical (ophthalmic) antihistamines is often efficacious and clearly superior to systemic antihistamines, either as monotherapy or in conjunction with an oral or intranasal agent.Topical antihistaminic agents not only provide faster and superior relief than systemic antihistamines, but they may also possess a longer duration of action than other classes including vasoconstrictors, pure mast cell stabilisers, NSAIDs and corticosteroids. Many antihistamines have anti-inflammatory properties as well. Some of this anti-inflammatory effect seen with 'pure' antihistamines (levocabastine and emedastine) may be directly attributed to the blocking of the histamine receptor that has been shown to downregulate intercellular adhesion molecule-1 expression and, in turn, limit chemotaxis of inflammatory cells. Some topical multiple-action histamine H(1)-receptor antagonists (olopatadine, ketotifen, azelastine and epinastine) have been shown to prevent activation of neutrophils, eosinophils and macrophages, or inhibit release of leukotrienes, platelet-activating factors and other inflammatory mediators. Topical vasoconstrictor agents provide rapid relief, especially for redness; however, the relief is often short-lived, and overuse of vasoconstrictors may lead to rebound hyperaemia and irritation. Another class of topical agents, mast cell stabilisers (sodium cromoglicate [cromolyn sodium], nedocromil and lodoxamide), may be considered; however, they generally have a much slower onset of action. The efficacy of mast cell stabilisers may be attributed to anti-inflammatory properties in addition to mast cell stabilisation. In the class of topical NSAIDs, ketorolac has been promoted for ocular itching but has been found to be inferior for relief of allergic conjunctivitis when compared with olopatadine and emedastine. Lastly, topical corticosteroids may be considered for severe seasonal ocular allergy symptoms, although long-term use should be avoided because of risks of ocular adverse effects, including glaucoma and cataract formation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15631542&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Direct-to-consumer prescription drug advertising and the public.

Bell RA, Kravitz RL, Wilkes MS.

Department of Communication, University of California, Davis 95616, USA.

OBJECTIVE: Drug manufacturers are intensely promoting their products directly to consumers, but the impact has not been widely studied. Consumers' awareness and understanding of, attitudes toward, and susceptibility to direct-to-consumer (DTC) drug advertising were examined. DESIGN: Random-digit dialing telephone survey with a random household member selection procedure (completion and response rates, 58% and 69%, respectively). SETTING: Respondents were interviewed while they were at their residences. PARTICIPANTS: Complete data were obtained from 329 adults in Sacramento County, California. MEASUREMENTS AND MAIN RESULTS: Outcome measures included awareness of advertisements for 10 selected drugs, misconceptions about DTC advertising, attitudes toward DTC ads, and behavioral responses to such promotions. The influence of demographic characteristics, health status, attitudes, beliefs, and media exposure on awareness and behaviors was examined. On average, respondents were aware of advertisements for 3.7 of the 10 drugs; awareness varied from 8% for Buspar (buspirone) to 72% for Claritin (loratadine). Awareness was associated with prescription drug use, media exposure, positive attitudes toward DTC advertising, poorer health, and insurance status. Substantial misconceptions were revealed; e.g., 43% thought that only "completely safe" drugs could be advertised. Direct-to-consumer advertisements had led one third of respondents to ask their physicians for drug information and one fifth to request a prescription. CONCLUSIONS: Direct-to-consumer advertisements are reaching the public, but selectively so, and affecting their behaviors. Implications for public policy are examined.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10571712&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Current concepts and therapeutic strategies for allergic rhinitis in school-age children.

Blaiss M.

Division of Clinical Immunology/Allergy, University of Tennessee Health Science Center, Memphis, TN, USA. mblaiss allergymemphis.com

BACKGROUND: Allergic rhinitis (AR) is a common debilitating disorder that can adversely affect the quality of life and the academic performance of school-age children. Symptoms during the day can hamper concentration and lead to learning problems. Nocturnal symptoms can cause sleep loss and secondary daytime fatigue, further undermining a child's ability to function well during the school day Oral antihistamines are the foundation of pharmacologic therapy, but there are important differences between the agents. OBJECTIVE: The purpose of this review is to provide an overview of the diagnostic and treatment challenges posed by AR in school-age children. The paper discusses and compares the available treatment modalities for this age group, with a focus on their beneficial and adverse effects. METHODS: Pertinent articles were identified in the literature through a MEDLINE search (1990-2003). Keywords used were antihistamines cetirizine fexofenadine loratadine desloratadine intranasal corticosteroids and CNS effects. Results of numerous clinical trials of first-generation early second-generation and the newer antihistamines were identified. RESULTS: This review established that the socioeconomic costs of AR are considerable. In children aged > or =12 years, direct US expenditures (eg, physician visits, medications) in 1996 amounted to $2.3 billion. Indirect costs measured by variables such as missed school days and poor performance also have an impact Major concerns include underdiagnosis and inadequate treatment, increasing the risk of serious comorbid conditions such as asthma. Advantages and drawbacks of antihistamines show that first-generation agents (eg, hydroxyzine) are effective and readily available over the counter, but are associated with sedation and the potential for suboptimal dosing. Newer agents, such as cetirizine, loratadine, desloratadine, and fexofenadine are effective and safer than the older drugs tie, no cardiotoxicity and less sedation). Of these, fexofenadine has been shown to be beneficial and nonsedating, even at higher-than-recommended doses. Other therapies reviewed include intranasal corticosteroids and leukotriene modifiers. CONCLUSIONS: AR has a considerable negative impact on children in terms of their physical, social, and psychological well-being and academic performance. An appropriate treatment must be effective and tolerable. Of particular importance for enhancing treatment adherence in the school-age population are pleasant taste and ease of use of medication. A drug that has minimal or no sedative or anticholinergic effects is optimal.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15639699&dopt=Abstract loratadine, Claritin



loratadine, Claritin
[Comparative activity of antihistamines on area under dose-response curve from histamine-induced wheal and flare responses in human skin]

[Article in Chinese]

Wang RQ, Zhang HY.

Department of Allergy, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. ruiqi_wang yahoo.com.cn

OBJECTIVE: To compare the activity of antihistamines by the index of area under dose-response curve (AUDRC) obtained from histamine-induced wheal and flare reactions. METHODS: Mizolastine 10 mg, loratadine 10 mg, and placebo were given to 90 healthy volunteers and 60 allergic patients in a double-blind and randomized manner. Histamine titration tests (histamine concentrations 54.3, 20.0, 7.3, and 2.7 mmol/L) were performed for each one before dosing and 2, 4, and 24 hours after dosing. The reactivity was evaluated by histamine-induced wheal and flare areas. The AUDRC values of the wheal and flare areas as a function of the natural logarithm transformed histamine concentration were calculated for each subject, and compared. RESULTS: There was no significant difference of the wheal and flare areas between health volunteers and allergic patients. The AUDRC(27-54.3 mmol/l.) for wheal and flare of mizolastine was 115.7, 23.4, 7.7, 49.8 and 902.1, 40.9, 2.6, 46.9 ln (mmol/L) x mm2 at each time (before dosing and 2, 4, 24 hours after dosing) respectively. Compared with loratadine [116.2, 80.2, 49.7, 71.9 and 957.6, 495.3, 153.5, 205.9 ln (mmol/L) x mm2], mizolastine decreased AUDRC(2.7 - 54.3 mmol/L significantly (P < 0.01). CONCLUSION: Histamine-induced wheal and flare inhibition test is a reliable pharmacodynamic model for antihistamines, and AUDRC may be an useful index to predict antihistamines pharmacodynamic activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15663222&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Development and bioadhesive properties of chitosan-ethylcellulose microspheres for nasal delivery.

Martinac A, Filipovic-Grcic J, Voinovich D, Perissutti B, Franceschinis E.

Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacica 1, Zagreb, Croatia.

Loratadine-loaded microspheres were prepared by spray-drying of dispersions, emulsions and suspensions differing in polymeric composition and solvents used. Conventional microspheres were obtained by spray-drying of dispersions composed of chitosan (CM) as only polymer, while composed microspheres were obtained by spray-drying of two-phase systems composed of chitosan and ethylcellulose (EC). Microspheres differed in EC/CM weight ratio (0:1, 1:2 and 1:3) and in loratadine/polymers weight ratio (1:6 and 1:8). The entrapment efficiencies were between 67.9 and 86.1%; less loratadine was entrapped as polymer/drug ratio decreased. In comparison to one-phase systems composed of CM as only polymer, spray-drying of two-phase systems composed of both, CM and EC resulted in improved loratadine entrapment (80.1-86.1%). All microspheres were positively charged, indicating the presence of chitosan at the surface, regardless of the drug content and the type of spray-dried system. The highest zeta-potential was measured for loratadine-free conventional microspheres, consisting of chitosan only (32.7+/-1.3mV). Tensile studies showed that both, EC/CM ratio and the type of spray-dried system influenced the bioadhesive properties of the microspheres in a way that the microspheres with higher chitosan content were more bioadhesive and microspheres prepared from suspensions were more bioadhesive than those prepared from emulsions, regardless of the same polymeric composition. The results suggested that the spray-drying method is useful to produce bioadhesive loratadine-loaded microspheres.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15707733&dopt=Abstract loratadine, Claritin