Fenfluramine-like cardiovascular side-effects of benfluorex.

Since 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects. The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2-49 kg x m(-2). No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted.

Therapeutic advances in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries inducing increased pulmonary arterial resistance. Conventional treatment is based on life style modification and nonspecific treatment (warfarine, diuretics, oxygen). Calcium channel blockers are vasodilatators that have been shown to be of great efficacy in a very specific subpopulation of patients with PAH. For the majority of patients, specific PAH therapies are still lacking. Numerous studies evaluating prostacyclin agonists, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors are now available to guide therapeutic choices. Despite those important advances there is still no cure for PAH. Fortunately, research is ongoing and many drugs show promises.

Airway hyperresponsiveness and risk of chest symptoms in an occupational model.

BACKGROUND: The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) remains unclear. A study was undertaken to evaluate the incidence of respiratory symptoms in a cohort of asymptomatic subjects with AHR at baseline. METHODS: A 3 year prospective study involving methacholine challenge tests and serially administered questionnaires was undertaken in 769 apprentices exposed to high molecular weight allergens. Analyses were performed on 428 initially asymptomatic subjects. RESULTS: Thirty eight subjects (8.9%) were airway hyperresponsive (PC(20) < or =8 mg/ml) and asymptomatic at the start of the study. Forty four apprentices (10.3%) developed two or more respiratory symptoms unrelated to work, 13 (34.2%) in the AHR group and 31 (7.9%) in the non-AHR group (risk ratio (RR) 7.88 (95% CI 2.53 to 24.55) among subjects with AHR). The RR of developing two or more respiratory symptoms increased as the degree of PC(20) decreased with a significant trend (p<0.001). In a multivariate analysis, AHR (RR 8.33, 95% CI 2.65 to 26.16) and self-reported rhinitis on exposure to pollen through an interaction with a family history of asthma (RR 6.3, 95% CI 1.29 to 31.89) were associated with the incidence of two or more respiratory symptoms; atopy was not a significant covariate. CONCLUSION: AHR in asymptomatic subjects is an important determinant for the development of respiratory symptoms outside the workplace among apprentices exposed to high molecular weight allergens in their training environment.