Comparision of efficacy of levocetirizine with montelukast and levocetirizine alone in persistent allergic rhinitis

To compare the efficacy of levocetirizine with montelukast and levocetirizine alone in patients with persistent allergic rhinitis in our setup. Patients with symptoms of AR attending ENT clinic were registered and divided into two groups based on drug given. Patients with odd numbers were included in group A receiving levocetirizine 5mg with montelukast 10mg once daily while patients with even numbers were included in group B receiving only levocetirizine 5mg once daily. Data was collected at visit 1 prior to medication, visit 2 one week after medication and visit 3 two weeks after medication. Medication history review, nasal symptom assessment and anterior rhinoscopy were done at each visit. Patients were evaluated for rhinorrhea, sneezing, nasal itching and nasal obstruction on a scale. Total symptom complex score [TSCS] was calculated by adding scores of all four variables under study using proforma. Lower the score more effective will be the drug. One hundred twenty four patients were included in study; 63 were male and 61 were female. TSCS was 9 -10 in 73.3% patients at visit 1 in levocetirizine + montelukast group that improved to 4-5 in 28.3% and 3- 4 in 65% patients at visit 2 and 3 respectively. Patients receiving levocetirizine alone had TSCS of 9 to 10 in 52.9% at visit 1 with an improvement to 3-4 in 9.4% and 49.1% at visit 2 and visit 3 respectively. Levocetirizine with montelukast is superior to levocetirizine alone in controlling overall symptoms of AR.

Comparative efficacy of levocetirizine, desloratidine and fexofenadine by histamine wheal suppression test.

BACKGROUND: Histamine is the major mediator of allergic reactions. Newer H1 antihistaminics like levocetirizine, fexofenadine, and desloratadine are used in the treatment of seasonal and perennial allergic rhinitis and urticaria. The ability to block the cutaneous response to intradermal histamine is used to evaluate the potential of antihistamines. AIMS: To compare the potency, onset, and duration of action of the commonly used antihistamines-levocetirizine, fexofenadine, and desloratadine. METHODS: Thirty volunteers were given three single doses of levocetirizine, fexofenadine and desloratadine at weekly intervals. A pretest was performed by using the intradermal histamine prick test. After administration of the drugs, the intradermal test was repeated at (1/2), 1, 2, 3, 6 and 24 h, and the sizes of the wheal were measured. The mean values were taken and were compared by using Levene's t-test. RESULTS: At 30 min, fexofenadine showed a statistically significant suppression of wheal size compared to levocetirizine and desloratadine. Two and three hours after administration, levocetirizine and fexofenadine showed statistically significant inhibition of wheal size while only levocetirizine had this effect after six hours when compared to desloratadine. Desloratadine showed greater inhibition of wheal size at the end of 24 h when compared to levocetirizine and fexofenadine but this was not statistically significant. CONCLUSIONS: Fexofenadine had the earliest onset of action while levocetirizine showed maximum inhibition of wheal response after three and six hours.

New antihistamines: a critical view

OBJETIVO: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas. FONTES DOS DADOS: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos. SíNTESE DOS DADOS: Os anti-histamínicos de segunda geração diferenciam-se dos de primeira geração por sua elevada especificidade e afinidade pelos receptores H1 periféricos e pela menor penetração no sistema nervoso central (SNC), com conseqüente redução dos efeitos sedativos. Embora os anti-histamínicos de segunda geração sejam, geralmente, melhor tolerados do que seus predecessores, alguns efeitos adversos, principalmente cardiotoxicidade, surgiram com alguns deles. Nos últimos 20 anos, novos compostos, com diferentes farmacocinéticas, foram sintetizados. A maioria deles manifesta propriedades antiinflamatórias que independem de sua atividade no receptor H1. Aprimoramentos mais recentes, geralmente na forma de metabólitos ativos, levaram ao uso do termo anti-histamínico de terceira geração. Esse termo surgiu espontaneamente, sem uma descrição clara de seu significado e implicações clínicas, criando grande confusão entre os profissionais da saúde. CONCLUSÕES: Com base nas evidências sobre anti-histamínicos anti-H1, nenhum deles pode ser considerado como "anti-histamínico de terceira geração". Para tanto, seria preciso comprovar que a nova classe de anti-histamínicos possui vantagens clínicas distintas sobre os compostos existentes e preenche pelo menos três pré-requisitos: ausência de cardiotoxicidade, de interações medicamentosas e de efeitos sobre o SNC.

OBJECTIVE: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders. SOURCES: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines. SUMMARY OF THE FINDINGS: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. CONCLUSIONS: On the basis of the evidence on H1 antihistamines, none of them deserve the title"third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.

evaluate and compare the effects of first generation anti-histamine [chlorpheniramine maleate] and second generation anti-histamine [Cetirizine dihydrochloride] on isolated trachea of rabbit

Histamine is generally considered as the principal mediator of the acute inflammatory process and the allergic and anaphylactic reaction in both the upper and lower respiratory airways. Chlorpheniramine maleate is a stable, most potent, .first generation antihistamine. It is clinical efficacy in the treatment of IgE mediated histamine disorders is well established. Cetirizine dihydrochloride is a potent, non-sedative HI receptor antagonist, belongs to second generation antihistamines. It is highly effective and safe drug for treating seasonal and perennial allergic rhinitis amid urticaria. Also used in chronic idiopathic urticaria and atopic dermatitis. The purpose of study was to evaluate the antagonostic effects of chlorpheniramine maleate and cetirizine dihydrochloride on histamine induced contractions in isolated trachea of rabbit and to compare the effects of first generation anti-histamine [chlorpheniramine maleate] and second generation anti-histamin [cetirizine dihydrochloride] on isolated trachea of rabbit. In this study twenty-four experiments were performed on isolated trachea of rabbit, in the presence of selected standard concentration of histamine dihydrochloride antagonistic effects of various concentrations of chlorpheniramine male-ate [10e-18 to 10e-3 gm/ml] and cetirizine dihydrochloride from concentrations to 10-3 gml ml were recorded by Polygraph Model 7B in terms of rate and amplitude. Chlorphenimmine maleate showed non-significant antagonistic effect from concentrations 10e-18 to 10e-9 gm/ml in case of rate and 10e-18 to 10e-8 gm/ml in case of amplitude. Significant response showed from concentrations 10e-8 to 10e-3 gm/ml in care of rate [P<0.001] and 10e-7 to 10e-3, gm/ml in case of amplitude [P<0.001] while, cetirizine showed non-significant response front concentrations to, gm/ml in case of rate and 10e-18 to 10e-12 gm/ml in case of amplitude. Significant response observed from concentrations 10e-12 to 10e-3 gm/ml in case of rate [P<0.001] and 10e-11 to 10e-3 gm/ml in case of amplitude [P<0.001]. It was concluded that chlorpheniramine maleate antagonized thetukl tisatnmd mine induced contractions 80.65% at concentration la, gm/ml in case of amplitude 11.35% at concentration 10e-3 gm/ml in case of rate and cetirizine dihydrochloride 82.69% in case of amplitude and 12.33% in case of rate

Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in various experimental models.

The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated on various allergic and asthmatic test models. This newly developed peptide was found to be more potent than clinically used drug disodium cromoglycate (DSCG). Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced bronchoconstriction in actively sensitized guinea pigs in dose dependent manner like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly inhibited by this newly developed hexapeptide in the same fashion as ketotifen and DSCG did but at comparatively lower dose. Egg albumin-induced histamine release was also blocked by this hexapeptide from chopped lung tissues of sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent inhibitory effect on immediate hypersensitivity reactions thereby inhibiting mediator release from mast cell. Moreover, this newly synthesized peptide is orally active and effective at lower doses as compared to standard drugs.

Modification of antihistaminic activity of cetirizine by nimesulide.

OBJECTIVE: To study the effect of nimesulide (4-nitro-2-phenoxymethane sulfonanilide) a non-steroidal anti-inflammatory drug, on antihistaminic activity of cetirizine. METHOD: A randomized, double blind, cross over study was conducted in ten healthy male volunteers. Wheal and flare responses to histamine were measured by performing intradermal injection of histamine (2 micrograms base) diluted in 100 microliters volume of saline on the volar surface of forearm, on four occasions (0, 2, 4, and 6 hrs. post-dosing). Each volunteer was randomized to receive either treatment A (cetirizine 10 mg + placebo) or treatment B (cetirizine 100 mg + nimesulide 100 mg), with one week wash out period in between each administration. Wheal and flare responses were measured ten minutes after each histamine injection. RESULTS: Both cetirizine 10 mg alone and cetirizine 10 mg + nimesulide 100 mg, decreased wheal and flare responses significantly at 2 hrs. and this continued till 6 hrs. post-dosing. This decrease was highly significant when cetirizine was given along with nimesulide. CONCLUSION: The results suggest a synergistic effect exhibited by the combined use of cetirizine with nimesulide.

Estudo clínico comparativo entre cetirizina e placebo no tratamento de pacientes com rinite alérgica perene / Comparative clinical study between cetirizine and placebo in the treatment of patients with perennial allergic rhinitis

O estudo teve como objetivo avaliar a tolerabilidade, a eficácia clínica e a segurança do uso da cetirizina (CTZ) no tratamento da rinite alérgica perene. O estudo foi comparativo contra placebo (PLB), duplo-cego, randomizado, cruzado. Os pacientes receberam um período de 15 dias com CTZ (10 mg em dose única di ria), seguido de outro período de 15 dias com PLB, ou vice-versa de acordo com lista de aleatorizaçäo. Setenta e dois pacientes foram admitidos e 52 deles completaram os dois períodos de tratamento previstos. A CTZ mostrou superioridade nos seguintes sintomas de rinite alérgica: coriza, obstruçäo nasal, crises de espirro, prurido nasal e conjuntivite. O sintoma tosse näo foi modificado por qualquer dos tratamentos. Os sinais físicos de rinite alérgica, como coloraçäo da mucosa, hipertrofia de cornetos, secreçäo nasal e inflamaçäo faríngea, mantiveram-se inalterados com os dois tratamentos. O mesmo ocorreu com os sinais vitais: pressäo arterial, frequência cardíaca, frequência respiratória e peso. Durante o período de tratamento com a CTZ foram observados eventos adversos em sete pacientes (12,3 por cento) e no período PLB foram observados eventos adversos em oito pacientes (14 por cento). Os eventos adversos mais frequentes no período de tratamento com CTZ foram sonolência e aumento subjetivo de peso (nÝo confirmado ao exame físico); no período PLB foram tontura, aumento de apetite e cefaléia. Durante o período de tratamento com a CTZ nove pacientes interromperam o tratamento, sendo oito pacientes por abandono ou falta de colaboraçäo do paciente e um por evento adverso (urticária ao frio näo controlada). Durante o período PLB 11 pacientes interromperam o tratamento, sendo dez pacientes por abandono ou falta de colaboraçäo do paciente e um por evento adverso (tontura e calafrios). Concluímos que a CTZ se mostrou clinicamente superior ao PLB em efic cia, proporcionando alívio dos sintomas da rinite alérgica perene e sintomas conjuntivais. A incidência de eventos adversos com CTZ nÝo diferiu da observada com PLB. A cetirizina é um anti-histamínico eficaz e bem tolerado, com posologia cômoda em relaçäo aos anti-histamínicos clássicos, podendo ser utilizada para tratamento da rinite alérgica.

Acciones de diversos fármacos sobre la hiperreactividad bronquial y el asma: consideraciones fisiopatogénicas y terapéuticas / Actions of different drugs on the bronchial hyperreactivity and the asthma: considerations physiopathogenic and therapy

En 48 pacientes asmáticos atópicos leves o moderados se investigó la respuesta a diversos fármacos. Luego de una semana de tratamiento con dipropionato de beclometasona (BECLO) o terfenadina (TER) o cetirizina (CET) o cromoglicato disódico (CGDS) o nedocromil sódico (NED), se evaluó: a)la evolución espirográfica tomando como parámetros VEF y FM antes y después de cada uno de los tratamientos. En el cotejo de los resultados obtenidos con cada fármaco se encontró que, tomando los promedios de ambos parámetros, el CGDDS, con el 50 por ciento, es el fármaco que mejor actua; luego siguen en orden decreciente, TER 38 por ciento, BECLO 35 por ciento, CET 29 por ciento y NED 7 por ciento. Las diferencias son estadísticamente significativas entre CGDS vs. NED, p<0,05. b) La capacidad de protección de cada uno de esos fármacos sobre la hiperreactividad bronquial con aire frío (HRB). Aquí el orden de protección para la broncoobstrucción, si se toman ambos parámetros(VEF y FM) es para la CET, del 65 por ciento, BECLO 50 por ciento, CGDS 46 por ciento y TER 8 por ciento. Si en lugar de considerar los promedios para ambos parámetros, se toma el número de evaluaciones espirográficas que son protegidas más del 10 por ciento ante la estimulación con aire frío, se observa que a la CET le corresponde el 90 por ciento de protección, al CGDS al 61,5 por ciento, a la BECLO el 60 por ciento a la TER el 28,6 por ciento y al NED el 12.5 por ciento. Estadísdicamente la CET es superior a TER y NED (P<0,02) y CGDS también vs. TER y NED p<0,02. Se concluye que si bien la HRB es una expresión del asma, en ésta se suma a la inflamación basal y broncoobstrucción, donde la histamina tiene un papel más importante que en las respuestas de HRB. Y que en la HRB por aire frío la acción antiinflamatoria de los fármacos u otras acciones, como anti PAF, puedan ofrecer mejores resultados, por lo que habría que elaborar criterios terapéuticos individuales de acuerdo con la mejor acción preventiva para cada una de las situaciones