[The effect of second generation histamine antagonists on the heart]. / Wplyw leków przeciwhistaminowych drugiej generacji na serce.

The review summarizes recent progress in the study of the cardiac actions of second--generation antihistamines. Terfenadine and astemizole, two antihistamines of the second generation, are in vitro potent blockers of potassium channels (K+). It has been considered to be responsible for QT prolongation of the electrocardiogram and life--treating ventricular tachycardias called torsades de pointes. Loratadine and descarboethoxyloratadine, the major metabolite of loratadine were studied on a human cardiac K+ channel (hKv 1.5) cloned from human ventricle. Parent compound and its metabolite in high concentration blocked hKv1.5 channels. However, loratadine (10 mumol/L) failed to inhibit HERG potassium channel and HERG K+. Ebastine also inhibit potassium channels, cloned human Kv 1.5. Cetirizine was completely devoid of any inhibitory action on HERG K+ channels in concentration up to 30 mumd/L. On the other hand terfenadine and astemizole effectively blocked HERG K+ channels with nanomolar affinities (330 and 480 nmol/L, respectively), whereas loratadine was about 300-fold less potent. Fexofenadine--the major metabolite of terfenadine, does not block either HERG or Kv1.5. The quinea pig model (in vitro) revealed that only terfenadine, astemizole and ebastine produced significant QT interval prolongation and arrhythmogenic effects. The other nonsedating antihistamines including cetirizine, loratadine and the major metabolite of ebastine (carabastine), terfenadine (feksofenadine) and astemizole (norastemizole) were devoid of QT interval prolongation and other adverse ECG effects.

[Evaluation of the relationship between the clinical course of severe asthma and ventilatory parameters]. / Ocena zwiazków miedzy klinicznym przebiegiem ciezkiej astmy oskrzelowej a wskaznikiem wentylacji.

The aim of the study was the assessement of relations between the clinical symptoms of asthma, ventilatory parameters and nonspecific bronchial hyperresponsiveness. 22 patients with severe asthma, 12 females and 10 men, aged 43-68 years (mean 56) were observed for two years. The duration of asthma ranged from 6 to 38 years (mean 18). All the patients were treated with inhalatory steroids in dose 800-1200 mg. Three months before entering the study the patients had no exacerbation or respiratory tract infection. Throughout the study diary cards were filled and the symptoms were recorded on 0-4 scale. PEF was measured two times a day, the highest value noted. Spirometry and reversibility tests were performed. On the last day patients underwent histamine challenge test. Data from four weeks were analyzed statistically. The significant correlation was established between PEF variability and clinical symptoms scores, both mean and measured in the last day of the study. The relationship between mean PEF variability and bronchial hyperresponsiveness was also observed.

[Histamine as a mediator of allergic inflammation]. / Histamina jako mediator zapalenia alergicznego.

The allergic process is believed to consist of two phases: early and late. The early phase reaction is mainly induced by histamine released from mast cells. Histamine binding specific cell receptors produces clinical allergic symptoms. This mediator also activates neutrophils and eosinophils as well as being a chemoattractant for these cells. Histamine increases IL-8 level and evokes leukocyte rolling on endothelial cells. Thus histamine participates in both early and late-phase allergic responses.

[Second generation topical antihistaminics]. / Leki przeciwhistaminowe drugiej generacji o dzialaniu miejscowym.

The article presents two topical antihistaminics: levocabastine and azelastine. Most attention is paid to discussing the pharmacokinetics and antihistamine, antiallergic and antiinflammatory activities of these drugs. Their clinical usefulness in allergic rhinitis and conjunctivitis is also presented. Finally the authors describe the adverse reaction observed after administrating of topical antihistaminics.

[The effect of new H1-receptor antagonists on cardiovascular system]. / Wplyw leków przeciwhistaminowych drugiej generacji na serce.

The authors present effects of new H1-receptor antagonists--terfenadine and astemizol on cardiovascular system in humans. The role of interactions between terfenadine and astemizol and other drugs is underlined. Effects of hepatic and heart diseases as well as astemizol and terfenadine overdose on their pharmacokinetics are also showed.