RESUMEN
BACKGROUND Perioperative hemodynamic instability mediated by anaphylaxis is a life-threatening complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to evaluate the effect of clemastine fumarate in this specific patient population. MATERIAL AND METHODS We enrolled 100 participants who met the inclusion criteria and randomly allocated them to the treatment group and the placebo group. Participants in the treatment group and the placebo group were treated separately with an injection of clemastine fumarate and saline, respectively. Plasma histamine concentration and blood pressure were quantified at 5 timepoints during the perioperative period, and differences between the 2 groups were assessed by repeated-measures ANOVA. The postoperative complications and in-hospital mortality also were evaluated. All participants were followed up for 7 days after cardiac surgery. RESULTS Plasma histamine concentrations increased in both groups but were statistically significantly lower in the treatment group during the perioperative period (P=0.007). Diastolic blood pressure (P=0.014) and mean arterial pressure (P=0.024) in the treatment group were significantly higher than in the placebo group during the perioperative period. The coefficients of variation for systolic (13.9±4.2% vs 17.2±4.4%, P<0.01) and diastolic (12.9±4.9% vs 15.3±5.2%, P=0.02) blood pressure were significantly lower in the treatment group compared with the placebo group. CONCLUSIONS Pretreatment with clemastine fumarate restrains the increase in histamine concentration and provides safer hemodynamics in patients undergoing cardiac surgery with CPB.
Asunto(s)
Clemastina , Hemodinámica , Enfermedades Vasculares , Anafilaxia , Puente Cardiopulmonar , Clemastina/efectos adversos , Clemastina/farmacología , Hemodinámica/efectos de los fármacos , Histamina , Humanos , Atención Perioperativa , Enfermedades Vasculares/tratamiento farmacológicoRESUMEN
We assessed the torsadogenic effects of a novel remyelinating drug clemastine for multiple sclerosis using an in vivo proarrhythmia model of acute atrioventricular block rabbit, since the drug has been demonstrated to suppress the human ether-á-go-go related gene (hERG) K+ channels. Bradycardia was induced by atrioventricular node ablation in isoflurane-anesthetized New Zealand White rabbits (n = 5), and the ventricle was electrically driven at 60 beats/min throughout the experiment, except when extrasystoles appeared. Intravenous administration of clinically relevant dose of 0.03 mg/kg of clemastine and 10-times higher dose of 0.3 mg/kg hardly affected the QT interval or duration of the monophasic action potential (MAP) of the ventricle. Additional administration of clemastine at 3 mg/kg significantly increased the QT interval, MAP duration and the short-term variability of repolarization. Meanwhile, the premature ventricular contractions with R on T phenomenon were observed in 3 out of 5 animals, and torsades de pointes arrhythmias were detected in 1 out of 5 animals. These results suggest that the torsadogenic potential of clemastine is obviously observed in the acute atrioventricular block rabbit, which will not appear within the prescribed dose for multiple sclerosis.
Asunto(s)
Clemastina/administración & dosificación , Clemastina/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Esclerosis Múltiple/tratamiento farmacológico , Torsades de Pointes/inducido químicamente , Potenciales de Acción/efectos de los fármacos , Animales , Bloqueo Atrioventricular/fisiopatología , Bradicardia/fisiopatología , Relación Dosis-Respuesta a Droga , Canal de Potasio ERG1/antagonistas & inhibidores , Ventrículos Cardíacos/efectos de los fármacos , Infusiones Intravenosas , ConejosRESUMEN
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system characterized by remyelination failure, axonal degeneration, and progressive worsening of motor functions. Animal models of demyelination are frequently used to develop and evaluate therapies for MS. We recently reported that focal internal capsule (IC) demyelination in mice with lysophosphatidylcholine injection induced acute motor deficits followed by recovery through remyelination. However, it remains unknown whether the IC demyelination mouse model can be used to evaluate changes in motor functions caused by pharmacological treatments that promote remyelination using behavioral testing and histological analysis. In this study, we examined the effect of clemastine, an anti-muscarinic drug that promotes remyelination, in the mouse IC demyelination model. Clemastine administration improved motor function and changed forepaw preference in the IC demyelinated mice. Moreover, clemastine-treated mice showed increased mature oligodendrocyte density, reduced axonal injury, an increased number of myelinated axons and thicker myelin in the IC lesions compared with control (PBS-treated) mice. These results suggest that the lysophosphatidylcholine-induced IC demyelination model is useful for evaluating changes in motor functions following pharmacological treatments that promote remyelination.
Asunto(s)
Enfermedades Desmielinizantes , Esclerosis Múltiple , Remielinización , Ratones , Animales , Enfermedades Desmielinizantes/inducido químicamente , Lisofosfatidilcolinas , Clemastina/efectos adversos , Cápsula Interna/patología , Vaina de Mielina/patología , Esclerosis Múltiple/patología , Oligodendroglía , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Cuprizona/farmacologíaRESUMEN
OBJECTIVES: Optic neuritis (ON) is the most common cause of optic neuropathy; typically presenting with a unilateral visual loss in young adults, with incidence of 1-5 in 100,000 per year. We evaluated the effect of Clemastine, a first-generation and CNS (central nervous system)-penetrant H1 receptor antagonist on visual evoked potential (VEP), retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) complex in patients with optic neuritis. PATIENTS AND METHODS: This is a prospective comparative interventional case series in 25 patients with acute optic neuritis. Patients were randomly assigned to group 1 (treated with Clemastine 1â¯mg orally twice a day for 90 days; 16 patients) or group 2 (received placebo for 90 days; 9 patients) and both groups received standard treatment of optic neuritis. We recorded VEP and peripapillary OCT (optical coherence tomography) of patients before and after three months of treatment. RESULTS: In contrast to patients treated with Clemastine, RNFL thickness loss between base line phase and after three months follow up in control group were statistically significant in temporal, supra temporal, Infrotemporal and almost global sections of RNFL map. The reduction in GCL thickness between base line phase and after three months follow up in control group were significant, while it did not reach significance in treatment group except in inferior region. CONCLUSION: In contrast to treatment group, RNFL and GCL thickness of most quadrants are decreased significantly after three months in patients with ON in control group. In contrast to control group, p100 wave's amplitude recovered in a significant manner in treatment group.
Asunto(s)
Clemastina/uso terapéutico , Potenciales Evocados Visuales/efectos de los fármacos , Fibras Nerviosas/patología , Neuritis Óptica/tratamiento farmacológico , Neuritis Óptica/patología , Células Ganglionares de la Retina/patología , Adulto , Clemastina/efectos adversos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Estudios Prospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Trastornos de la Visión/tratamiento farmacológico , Adulto JovenAsunto(s)
Clemastina/efectos adversos , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Clemastina/uso terapéutico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Hipersensibilidad Inmediata/tratamiento farmacológico , Seguridad del Paciente , Urticaria/tratamiento farmacológicoRESUMEN
An observational, historical cohort evaluation was performed to examine the hypothesis that terfenadine (Seldane) exposure increases the risk of developing life-threatening ventricular arrhythmias. The study population consisted of Medicaid recipients from 4 states that were included in the Computerized On-Line Medical Pharmaceutical Analysis and Surveillance System (COMPASS). The drug exposure period was defined prospectively as 30 days in all treatment cohorts. The primary end point was the development of life-threatening ventricular arrhythmias (ventricular tachycardia, fibrillation and flutter, and cardiac arrest and sudden death). The comparison cohorts included terfenadine (n = 181,672), over-the-counter antihistamines (n = 150,689), ibuprofen (n = 181,672) and clemastine (Tavist; n = 83,156). Over the exposure period, a total of 317 life-threatening ventricular arrhythmic events occurred, 244 of which were cardiac arrests. The incidence of total life-threatening ventricular arrhythmic events and cardiac arrests were more frequent in patients receiving over-the-counter antihistamines (relative risk 0.36) than in those receiving terfenadine, a finding that was consistent across all subgroups. There was no increased risk of life-threatening ventricular arrhythmias in the terfenadine cohort as compared with the ibuprofen cohort (relative risk 0.62), and in some analyses, the ibuprofen cohort had a significantly higher arrhythmic event rate. In all comparisons with the clemastine cohort, the terfenadine cohort had a statistically indistinguishable relative risk (1.08). Age, race, sex and cardiovascular risk were all considered in the adjusted relative-risk analyses. No baseline historical characteristic or imbalance of baseline medications explained the differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Arritmias Cardíacas/inducido químicamente , Clemastina/efectos adversos , Ibuprofeno/efectos adversos , Terfenadina/efectos adversos , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Muerte Súbita Cardíaca , Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Paro Cardíaco/inducido químicamente , Humanos , Sistemas de Información , Masculino , Persona de Mediana Edad , Medicamentos sin Prescripción/efectos adversos , Vigilancia de Productos Comercializados , Estudios Prospectivos , Factores de Riesgo , Función VentricularRESUMEN
In several clinics we carried out a comparative double-blind study of ketotifen (HC) in 260 patients with perennial rhinitis in order to reveal the clinical efficacy, safety and usefulness. We administered two different doses of HC (0.5 mg X 2 and 1 mg X 2 daily), clemastine fumarate, CF (1.34 mg X 2 daily) and their placebos. The active drugs were always given in combination with their placebos during a period of 4 weeks. The results indicated that HC, especially HC 1 mg X 2, was superior to CF in efficacy and usefulness. Side-effects were mild and the frequency in which they occurred was similar to CF. In contrast to CF, HC showed an efficacy not only in sneezing and nasal discharge but also in nasal obstruction as well.
Asunto(s)
Clemastina/uso terapéutico , Cetotifen/uso terapéutico , Pirrolidinas/uso terapéutico , Rinitis Alérgica Perenne/tratamiento farmacológico , Clemastina/efectos adversos , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Estudios de Seguimiento , Humanos , Cetotifen/administración & dosificación , Cetotifen/efectos adversos , Fases del SueñoRESUMEN
H1-antihistamines are usually associated with impairment of central nervous functions, but unacceptable decrements in performance may not be an inevitable sequel of their use. Effects are dependent on the ability of a particular drug to cross the blood brain barrier, and so compounds which cross so slowly that tolerance of the central nervous system can develop gradually without any immediate changes in performance are of interest. However, sustained release formulations and compounds which have a selective affinity for the peripheral receptor may also have their part to play in the management of allergic states in those involved in skilled activity. As far as H2-antagonists are concerned, it is likely that as they are less liposoluble they would be free of central effects. Studies on the central effects of H1 and H2 antagonists are reviewed, and tentative recommendations are made in respect of these findings concerning the possible use of these drugs in aircrew.
Asunto(s)
Medicina Aeroespacial , Sistema Nervioso Central/efectos de los fármacos , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Compuestos de Bencidrilo/efectos adversos , Clorfeniramina/efectos adversos , Cimetidina/efectos adversos , Clemastina/efectos adversos , Humanos , Fenotiazinas/efectos adversos , Prometazina/efectos adversos , Desempeño Psicomotor/efectos de los fármacos , Ranitidina/efectos adversos , Fases del Sueño/efectos de los fármacos , Relación Estructura-Actividad , Terfenadina , Agudeza Visual/efectos de los fármacos , Percepción Visual/efectos de los fármacosRESUMEN
Allergic rhinitis and mild respiratory infections have been widely accepted as temporary contraindications for fitness to dive. Nonetheless, several sport and professional divers use antihistamines to ease ear, nose, and throat (ENT) problems, especially for opening tubal ostium. Some divers know they are unfit to dive, but for a variety of reasons (e.g., money or short holiday) they try to clear their ears. Thus, the use of antihistaminic drugs (like clemastine fumarate) is common during diving. This double-blind, crossover study indicates that this special antihistamine does not increase the sedative effects of nitrogen narcosis, nor does it increase the level of cardiac arrhythmias. Liberal use of antihistamines while diving cannot be recommended because of possible complications connected with different preparations and the temporary limitations they impose on the diver.
Asunto(s)
Afecto/efectos de los fármacos , Clemastina/efectos adversos , Buceo/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Narcosis por Gas Inerte/fisiopatología , Adulto , Cámaras de Exposición Atmosférica , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Narcosis por Gas Inerte/complicaciones , Masculino , Factores SexualesRESUMEN
Selective necrosis of rat testicles is known to be produced by cadmium in subtoxic doses due to impairment of vessel structures. Classical antihistaminics in the same time in order to exclude that the lesion might have been produced by local release of histamine. Antihistaminics did not prevent necrosis. Instead, Clemastine stressed an interstitial testicular haemorrhage a bit. Methyldosulepine administered with calcium could decrease the vascular permeability because haemorrhage was almost lacking. The finding supports an idea of possible interaction between calcium and cadmium ions.
Asunto(s)
Cadmio/efectos adversos , Clemastina/efectos adversos , Dibenzotiepinas/efectos adversos , Dotiepina/efectos adversos , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Pirrolidinas/efectos adversos , Enfermedades Testiculares/patología , Animales , Dotiepina/análogos & derivados , Masculino , Necrosis , Ratas , Azúcares Ácidos/efectos adversos , Enfermedades Testiculares/inducido químicamente , Testículo/patologíaAsunto(s)
Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/prevención & control , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Hipertensión/inducido químicamente , Descongestionantes Nasales/efectos adversos , Fenilpropanolamina/efectos adversos , Adulto , Clemastina/efectos adversos , Sinergismo Farmacológico , Femenino , Humanos , Medicamentos sin Prescripción/efectos adversosAsunto(s)
Clemastina/farmacología , Ciproheptadina/análogos & derivados , Antagonistas de los Receptores Histamínicos H1/farmacología , Hidroxizina/farmacología , Pirrolidinas/farmacología , Clemastina/efectos adversos , Ensayos Clínicos como Asunto , Ciproheptadina/efectos adversos , Ciproheptadina/farmacología , Método Doble Ciego , Humanos , Hidroxizina/efectos adversos , Pruebas PsicológicasRESUMEN
OBJECTIVE: This study investigated the relevance of the cytochrome P450 (CYP) 2D6 genotype to the adverse drug reactions (ADRs) of H1-antihistamines and the level of sedation. METHODS: Japanese participants in a health screening program were asked to describe any past history of ADRs. Any subjects reporting ADRs induced by H1-antihistamines were then individually interviewed and defined as cases. Excessive daytime sleepiness, which had occurred in the cases as an H1-antihistamine-induced ADR, was assessed by the Epworth sleepiness scale (ESS), and an ESS score >or=12 was considered hypersomnia. CYP2D6*4, *5, *14, and *10 were genotyped by a panel of polymerase chain reaction techniques. RESULTS: Out of 2,074 participants, 100 cases (M:F = 37:63, mean age 51.9 +/- 9.2 years) were eligible for analysis. The most common etiological drug was chlorpheniramine, which is the most frequently used H1-antihistamine in Japan. CYP2D6*10 allele and genotypes were more frequently found in the cases than in the healthy Japanese population in a large study (P < 0.005 and P = 0.039, respectively), but no difference was observed in the null alleles and genotypes. The ESS scores in 75 cases (M:F=25:50) who had experienced excessive daytime sleepiness were 9.5 +/- 5.5 in men and 12.9 +/- 6.1 in women (P < 0.001, cases vs. 34 subjects without symptoms; P = 0.001 men vs. women). The occurrence of hypersomnia increased as the number of CYP2D6 mutant alleles increased (P = 0.045). CONCLUSION: The results suggest that the presence of the CYP2D6*10 allele is a risk factor for development of H1-antihistamine-induced ADRs in Japanese.
Asunto(s)
Citocromo P-450 CYP2D6/genética , Trastornos de Somnolencia Excesiva/inducido químicamente , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Pueblo Asiatico/genética , Clorfeniramina/efectos adversos , Clemastina/efectos adversos , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/etnología , Fatiga/inducido químicamente , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Frecuencia de los Genes , Pruebas Genéticas/métodos , Pruebas Genéticas/estadística & datos numéricos , Genotipo , Humanos , Japón , Masculino , Persona de Mediana Edad , Farmacogenética/métodos , Fenotiazinas/efectos adversos , Prometazina/efectos adversos , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Rinitis/diagnóstico , Rinitis/tratamiento farmacológico , Factores de Riesgo , Encuestas y Cuestionarios , Urticaria/diagnóstico , Urticaria/tratamiento farmacológico , Xerostomía/inducido químicamenteRESUMEN
We report the first case presenting with successive anaphylactic reaction and extra-pyramidal syndrome after treatment with thiethylperazine maleate (thiethylperazine). Both reactions were caused due to this anti-emetic drug, but an additive effect of clemastine fumarate, prescribed to treat the anaphylactic reaction, is suggested by the sequence of events. We discuss the importance of knowing the pharmacological similitudes of common prescribed drugs in order to avoid the occurrence of side effects.
Asunto(s)
Anafilaxia/inducido químicamente , Antieméticos/efectos adversos , Hipersensibilidad a las Drogas/etiología , Tietilperazina/efectos adversos , Adolescente , Antialérgicos/administración & dosificación , Antialérgicos/efectos adversos , Antieméticos/administración & dosificación , Enfermedades de los Ganglios Basales/inducido químicamente , Clemastina/administración & dosificación , Clemastina/efectos adversos , Sinergismo Farmacológico , Femenino , Humanos , Tietilperazina/administración & dosificaciónRESUMEN
Toxic pustuloderma is an acute pustular eruption of the skin occurring a few days after the initiation of treatment with the responsible drug. A case of toxic pustuloderma following treatment with the antihistamine clemastine is now reported.
Asunto(s)
Clemastina/efectos adversos , Erupciones por Medicamentos/etiología , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Adulto , Humanos , Masculino , Supuración/inducido químicamenteRESUMEN
A clinical trial was performed with a new substance (HC 20-511) derived from the cycloheptothiophene group used in the management of asthma. Twenty-four asthma patients were treated at random, with HC 20-511 or placebo or the antihistaminic substance, clemastin (Tavegyl). A statistical evaluation of the results unequivocally demonstrates good protection with a single dose of 2.0 mg or two times 1.0 mg for 3 days against a challenging antigen, compared with the placebo or the antihistaminic agent. Tolerance was excellent.
Asunto(s)
Asma/tratamiento farmacológico , Piperidinas/uso terapéutico , Tiofenos/uso terapéutico , Adolescente , Adulto , Clemastina/efectos adversos , Clemastina/uso terapéutico , Ensayos Clínicos como Asunto , Cicloheptanos/efectos adversos , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Placebos , Tiofenos/efectos adversos , Capacidad VitalRESUMEN
The efficacy and safety of loratadine, a new orally active specific H1-receptor blocking antihistamine with poor penetration into the CNS, was evaluated in a double blind comparative study. One hundred and seven hay fever patients, sensitive to birch pollen, were randomized into three parallel groups receiving loratadine 40 mg once daily, clemastine 1 mg twice daily, or placebo during the birch pollen season. Both active treatments showed reduction of symptoms in comparison with placebo, but the results were more pronounced with loratadine treatment, which significantly reduced the overall allergic condition as well as all separate allergic rhino-conjunctivitis symptoms except nasal stuffiness. Compared with placebo the sedation rate was significantly higher with clemastine treatment (P less than 0.05) but not with loratadine. Loratadine was thus concluded to be efficacious in hay fever treatment with a sedation rate not differing from placebo.