Letters to the EditorPRACTOLOL TREATMENT IN ASTHMATICS
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Cited by (46)
Exacerbations of asthma-Precipitating factors: Drugs
2011, Revue des Maladies RespiratoiresLes exacerbations asthmatiques sont parfois déclenchées par les médicaments, essentiellement les anti-inflammatoires non stéroidiens (AINS) et les bêtabloquants. Les crises d’asthme induites par les AINS sont de survenue rapide et peuvent être sévères. Le syndrome de Widal est une entité particulière dont la physiopathologie reste encore incomplètement expliquée. L’asthme y est volontiers sévère et corticodépendant ; certains auteurs proposent une accoutumance à l’aspirine, mais cela reste controversé. Les bêtabloquants restent globalement contre-indiqués chez l’asthmatique ; la « cardiosélectivité » β1 n’est pas absolue, disparaissant aux fortes doses, et les « agonistes partiels » ne sont pas mieux tolérés. Cependant, certains auteurs remettent en cause l’effet néfaste des bêtabloquants au long cours chez l’asthmatique. Des études plus larges sont nécessaires, mais ces données suggèrent que, dans certains cas, la prescription d’un bêtabloquant est possible sous surveillance pneumologique rapprochée. D’autres molécules peuvent poser problème chez l’asthmatique (dipyridamole, hormones sexuelles de synthèse, certains excipients). Au total, peu de nouveautés apparaissent concernant les médicaments à risque chez l’asthmatique. L’enjeu pour l’avenir sera de préciser la physiopathologie de certaines intolérances, et la catégorie de patients pouvant tolérer des bêtabloquants. L’enjeu de santé publique que représentent les pathologies cardiovasculaires doit rendre les pneumologues attentifs à ce débat.
Asthmatic exacerbations are sometimes triggered by medications, primarily the non-steroidal anti-inflammatory agents (NSAIDS) and beta-blockers. Asthma attacks induced by NSAIDS occur rapidly and can be severe. Widal syndrome is a specific disease entity whose physiopathology remains incompletely explained. Asthma is characteristically severe and steroid dependent; desensitisation with aspirin has been proposed, but this remains controversial. Beta-blockers are contra-indicated in asthma; the β1 “cardioselectivity” of some agents is not absolute, disappearing at high doses and the “partial agonists” are not better tolerated. However, certain authors have called into question the harmful effect of beta-blockade in moderate and stable asthma. More studies are needed, but the current data suggest that in some cases beta-blockers may be safe but their use requires close supervision. Other molecules can pose problems in asthmatics (dipyridamole, synthetic sex hormones and certain excipients). On the whole, there has been little innovation concerning the hazard that drugs can pose for some asthmatics. The task for the future will be to specify the physiopathology of Widal syndrome, and to clarify the categories of patients in whom beta-blockers can be safely employed as the public health consequences of cardiovascular pathologies make this an important issue for lung specialists.
Drug-induced airway diseases
2004, Clinics in Chest MedicineThe cardioselectivity of beta adrenoceptor antagonists
1990, Pharmacology and TherapeuticsPharmacologic aspects of cardioselectivity in a beta-blocking drug
1987, The American Journal of Cardiologyβ2 adrenoceptors have been subdivided into β1 and β2 receptors, both by the varying response of different tissues to sympathomimetic amines and, more recently, by radioligand-binding techniques. It would appear that β1 receptors occur predominantly in the heart, whereas β2 receptors are found in lungs, peripheral blood vessels and uterus, and are also involved with glycogenolysis and glucagon and insulin secretion. In addition, the distribution of β1 receptors appears to relate to the density of sympathetic innervation of an organ or tissue, but tissues without sympathetic innervation are found to contain β2 receptors. Thus, β1 adrenoceptors may be considered as physiologically innervated receptors mediating responses to neuronally released norepinephrine, and β2 receptors as mediating responses to circulating catecholamines, particularly epinephrine. Radioligand-binding studies have also shown that the heart contains β2 receptors and the lung β1 receptors, but these are in the minority, and their role has not been identified. For many years, cardioselective β1-adrenoceptor antagonists have been available. This was considered to be a dose-dependent phenomenon but recent evidence has cast doubt on the concept that cardioselectivity is lost during dose increases within the therapeutic range. Nevertheless, even small doses of cardioselective drugs may show some β2-receptor antagonism, and may have adverse effects on patients with obstructive airways disease. Finally, nonselective drugs may result in a diastolic pressor effect in the presence of circulating catecholamines in contrast to the “vascular sparing” seen with cardioselective drugs.
Pharmacologic aspects of intrinsic sympathomimetic activity in beta-blocking drugs
1987, The American Journal of CardiologyThe possession of intrinsic sympathomimetic activity (ISA) by a β-adrenoceptor blocking drug results in a number of different pharmacologic properties. Most profound are the central hemodynamic effects. A drug with a significant degree of ISA results in less of a decrease in heart rate at rest and cardiac output, and, at least partly because of this, less of a decrease in peripheral blood flow. If prevailing sympathetic tone is low enough (e.g., during sleep) and the degree of ISA is sufficient, an increase in heart rate may be seen from an ISA-possessing drug. If the drug possesses β2 ISA, then a peripheral vasodilation action from stimulation of β2 vasodilator receptors may also be relevant. If high levels of exercise and full dosages of the drugs are used, a β-blocking drug with ISA produces less of a decrease in heart rate. In asthmatic subjects, the modest β-stimulant action on bronchial smooth muscle is not important, as these patients are potentially sensitive to any receptor blockade. Isoprenaline responses are inhibited to a similar degree compared with inhibition of exercise tachycardia, by nonselective drugs with and without ISA, whereas β1 selective agents produce much less inhibition of isoprenaline-induced tachycardia. A drug with ISA “down regulates” β receptors; thus, when the drug is withdrawn there is no post-β-blocking drug hypersensitivity in contrast to agents without ISA. There is evidence that ISA results in less of a disturbance in certain metabolic processess, particularly lipid metabolism and the metabolism of liver-metabolized drugs.
The clinical significance of intrinsic sympathomimetic activity
1987, International Journal of Cardiology