RESUMO
The immunoglobulin E (IgE) antibody plays a central role in the allergic immune responses. The ability to reduce circulating IgE with a humanized monoclonal antibody (omalizumab) represents a new therapeutic approach for the treatment of IgE-mediated allergic diseases. The use of an anti-IgE antibody in the treatment of asthma was first suggested in preliminary studies in which omalizumab demonstrated efficacy in attenuating both the early- and late-phase bronchial responses to inhaled aeroallergens. Therapy with omalizumab has demonstrated both a significant beneficial effect on a number of measures and a favorable safety profile. It reduces the frequency of asthma exacerbations and the need for inhaled corticosteroids (ICSs), and improves asthma symptoms, lung function, and quality of life. The anti-IgE approach to asthma treatment has several potential advantages, such as the treatment of other concomitant atopic diseases (allergic conjunctivitis and rhinitis, atopic dermatitis, and food allergy) regardless of atopiC of allergic sensitization.
Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Imunoglobulina E/imunologia , Doenças Respiratórias/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Humanos , Omalizumab , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Because of the central role that immunoglobulin (Ig)E has in allergic responses, a mechanism by which allergic diseases might be treated, especially asthma, is to effectively deplete the body of IgE. This paper discusses the basic concepts and the issues behind the biotechnical and clinical development of omalizumab, a recombinant humanized monoclonal antibody to IgE for potential use in the treatment of human allergic disease.
Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/etiologia , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Humanos , Hipersensibilidade/imunologia , OmalizumabRESUMO
Long-acting beta(2)-adrenoceptor agonists attenuate the allergen-induced late asthmatic reaction. We evaluated whether other mechanisms in addition to airway smooth muscle relaxation may be implicated in this protective effect. The effects of formoterol (Foradil Aerolizer(TM), 24 microg dry powder) on the late asthmatic reaction were assessed by a randomised crossover factorial study in 24 patients with asthma. Four challenge/treatment combinations were tested: (A) saline/placebo, (B) saline/formoterol, (C) allergen/placebo, (D) allergen/formoterol. Formoterol and placebo were administered double blind after the last inhalation of the allergen or saline. FEV(1) was measured up to 32 h. The bronchodilator effect of formoterol was estimated as (B-A) and the overall protective effect as (D-C). The effect not due to bronchodilation was estimated as [(D-C)-(B-A)]/2. The bronchodilator effect of formoterol was statistically significant up to 5h (all P< or =0.015). Formoterol significantly attenuated the late asthmatic reaction between 3 and 32 h after allergen inhalation (all P< or =0.0012). The difference between this protective effect and the bronchodilator effect was statistically significant at 5 h and between 7 and 28 h after allergen inhalation (all P< or =0.035). Our results suggest that functional antagonism may not be the sole mechanism by which formoterol attenuates the allergen-induced late asthmatic reaction.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Alérgenos/efeitos adversos , Asma/tratamento farmacológico , Asma/fisiopatologia , Broncodilatadores/farmacologia , Etanolaminas/farmacologia , Adolescente , Adulto , Asma/etiologia , Brônquios/efeitos dos fármacos , Broncoconstritores/administração & dosagem , Broncoconstritores/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Fumarato de Formoterol , Humanos , Masculino , Cloreto de Metacolina/administração & dosagem , Cloreto de Metacolina/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Fatores de TempoRESUMO
BACKGROUND: Although formoterol, a new long-acting beta(2)-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). AIM: The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. METHODS: The protective effect of a formoterol (12 microg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. RESULTS: Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV(1) after exercise being 29.3 +/- 14.3% and 22.9 +/- 13. 7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV(1) after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV(1) after formoterol was 5.9+/-7.2% at 15 min (p < 0.0001), and 5.8 +/- 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. CONCLUSIONS: This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Asma Induzida por Exercício/tratamento farmacológico , Etanolaminas/uso terapêutico , Administração por Inalação , Adolescente , Agonistas Adrenérgicos beta/administração & dosagem , Adulto , Criança , Estudos Cross-Over , Método Duplo-Cego , Etanolaminas/administração & dosagem , Feminino , Volume Expiratório Forçado , Fumarato de Formoterol , Humanos , Masculino , Esportes , Fatores de TempoRESUMO
Pentisomide, a new class I anti-arrhythmic drug, was compared to placebo in 50 hospitalized patients with frequent (greater than 30 h-1) and stable ventricular premature beats (VPB) (variation less than 50% between two preliminary and one placebo 24-h Holter recordings). All patients underwent a single-dose acute oral testing followed by a short-term testing with 300 mg t.i.d. for 4 days and then by a 4-day placebo period. For the studied population, a 56.4% reduction of simple VPB and a 98.8% decrease of couplets and runs were the minimum required to define the drug efficacy and to exclude spontaneous variability, using the linear regression analysis. Pentisomide was found effective in 27 (54%) of the 50 patients after the acute test and in 23 (46%) after the short-term test. The drug induced a mild increase of PR and QRS intervals, while QTc, heart rate, blood pressure and ejection fraction showed no significant variations. Subjective tolerability was excellent.
Assuntos
Antiarrítmicos , Complexos Cardíacos Prematuros/tratamento farmacológico , Eletrocardiografia Ambulatorial/efeitos dos fármacos , Propilaminas/uso terapêutico , Piridinas , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Sistema de Condução Cardíaco/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Pentisomide (CM 7857) is a new class I antiarrhythmic drug whose effect on sustained ventricular tachycardia has only been slightly investigated to date. The aim of this paper is to examine the pentisomide action on selected patients with ventricular tachycardia inducible during intracavitary electrophysiological study. Thus, 12 patients (9 M, 3 F, mean age: 45.2 years, range: 24-78), all but two with detectable heart disease, underwent electropharmacological tests with pentisomide after they had resulted "non responders" (8 patients) or had had a proarrhythmic worsening effect (3 patients) to electropharmacological tests with amiodarone or flecainide or propafenone or mexiletine. After the inducibility and the reproducibility of ventricular tachycardia has been assessed in the basal state, all patients underwent several attempts to reinduce ventricular tachycardia, during the i.v. infusion of pentisomide 1.5 mg/kg/5 min followed by continuous infusion of 1 mg/kg/h, at the same time drug plasma level was assessed. Ventricular tachycardia inducibility was still inducible after pentisomide, but with a longer cycle length (446 +/- 88 versus 337 +/- 82 msec) than in the basal state (p less than 0.0025). No patients had proarrhythmic worsening effects. The pentisomide plasma level (available in 5 patients) ranged from 3.4 to 22.3 (mean 8.9 micrograms/ml). Four patients underwent chronic oral treatment (in 1 pt in association with amiodarone) with a good clinical outcome (mean follow-up 6.25 months, range 1-12). We stress the absence of proarrhythmic worsening effects and the powerful effect of the drug on ventricular tachycardia cycle length.(ABSTRACT TRUNCATED AT 250 WORDS)