RESUMO
Disturbances in haemodynamic, biochemical and enzymatic factors have been observed in chronic venous diseases (CVD). These changes lead to the development of varices, telangiectasies and skin disorders. They affect vessels, blood, skin tissues and cells. It is now possible to describe their time course and interdependance of these changes. Orthostatism pressure on vein wall may lead to fluid leakage and oedema, these resulting in vein enlargement. These processes may be further influenced by genetic or acquired risk factors. Skin microvessels suffer more from hypoxia than from hypertension. Indeed, hypoxia affects not only endothelial cells, but also red and white blood cells and modifies particularly, but not exclusively, TGF-beta1 production. This substance is, an important modulator of zinc dependent-metallo-proteinases and their tissue inhibitor of metallo-proteinases (TIMP) in the skin. Imbalance in this enzymatic system seems to lead either to sclerosis or ulcer. Of course, other biochemical events (also in this review) play a role in vessel wall and skin deterioration in CVD. The aim of the present review is to assess the role of pathophysiological factors in CVD and the influence of different therapies, including the venotropic agent calcium dobesilate, on some of these haemodynamic or biochemical aspects.
Assuntos
Doenças Vasculares/fisiopatologia , Veias/fisiopatologia , Capilares/fisiopatologia , Doença Crônica , Humanos , Hipóxia , Microcirculação/fisiologia , Músculo Liso Vascular/fisiopatologia , Pele/irrigação sanguíneaRESUMO
The effects of zolpidem 10 mg, flunitrazepam 1 mg, and placebo, administrated at bedtime, were studied in 12 healthy male insomniac patients. The assessments included polygraphic sleep recordings during the night and a battery of cognitive tests (sign crossing test, dichotic listening test, digit span test, visual recognition test and free recall test during four times during the following day. Compared with placebo, both active drugs improved sleep parameters. However, with zolpidem, the results were not statistically different from placebo. Zolpidem dit not alter sleep architecture in contrast to flunitrazepam, which significantly increased stage 2 and decreased slow wave sleep and REM sleep. No significant interaction was found between time of day for the evaluation of cognitive function. Flunitrazepam significantly impaired attention and memory compared with zolpidem and placebo, while zolpidem did not differ from placebo. These results indicate that zolpidem 10 mg preserved sleep structure and daytime cognitive functions in contrast to flunitrazepam.
Assuntos
Cognição/efeitos dos fármacos , Flunitrazepam/uso terapêutico , Moduladores GABAérgicos/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Piridinas/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/psicologia , Sono/efeitos dos fármacos , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , ZolpidemRESUMO
STUDY OBJECTIVE: To assess the effects of repeated 10-mg oral doses of zolpidem on diurnal and nocturnal respiratory function, as well as on diurnal vigilance and physical performance in COPD patients with disordered sleep. DESIGN: Prospective single-blind placebo-controlled clinical study. SETTING: Outpatients of a respiratory medicine department. PATIENTS AND METHODS: Patients with stable COPD were enrolled for 10 days (D0 to D10), ie, 9 consecutive nights (N1 to N9). They received placebo on N1 and N9 and zolpidem, 10 mg, from N2 to N8. MEASUREMENTS: The following parameters were measured: nocturnal polysomnographic recordings with respiratory signals and arterial blood gas values on retiring and awakening on N0, N1, N2, N8, and N9; subjective evaluation of the quality of sleep and of diurnal vigilance by visual analog scales every day from D0 to D10; pulmonary function test, central control of breathing, and walking test on D0 and D9; biological laboratory tests and theophylline level on D0 and D8. RESULTS: Ten COPD patients (PaO2 = 72.7 +/- 7.6 mm Hg; PaCO2 = 47.7 +/- 5.4 mm Hg; FEV1 = 0.84 +/- 0.3 L; FEV1/vital capacity = 42.5 +/- 12.3%), 56.8 +/- 8.3 years old, were studied. Compared with placebo, no significant change was found for the various sleep architecture parameters, except an increase in the duration of stage 2 during the D8/N8 night (p < 0.05). In contrast, the autoevaluation score for the quality of sleep was significantly improved during the D6/N6 night relative to that with placebo (p < 0.05), with no change in the other subjective criteria. No variable of the nocturnal respiratory parameters, pulmonary function test, central control of breathing, and physical performance was altered by zolpidem. Arterial blood gas values on awakening were not altered. Clinical and biological tolerance of zolpidem was correct with no significant variation of the theophylline level. CONCLUSION: This study shows that repeated 10-mg oral doses of zolpidem during 8 days does not impair nocturnal respiratory and sleep architecture parameters or diurnal pulmonary function tests, central control of breathing, and physical performances in patients with stable COPD.
Assuntos
Nível de Alerta/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Hipnóticos e Sedativos/uso terapêutico , Pneumopatias Obstrutivas/tratamento farmacológico , Desempenho Psicomotor/efeitos dos fármacos , Piridinas/uso terapêutico , Respiração/efeitos dos fármacos , Sono/efeitos dos fármacos , Administração Oral , Idoso , Assistência Ambulatorial , Broncodilatadores/sangue , Broncodilatadores/uso terapêutico , Dióxido de Carbono/sangue , Teste de Esforço , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Placebos , Polissonografia/efeitos dos fármacos , Estudos Prospectivos , Piridinas/administração & dosagem , Método Simples-Cego , Teofilina/sangue , Teofilina/uso terapêutico , Capacidade Vital/efeitos dos fármacos , ZolpidemRESUMO
In a parallel-group, placebo-controlled, polysomnographic study with randomization, the possible occurrence of rebound insomnia was evaluated in 24 patients suffering from moderate to severe chronic insomnia and receiving either triazolam 0.5 mg, zolpidem 10 mg, or placebo. Treatment duration was 27 nights, followed by three placebo-controlled withdrawal nights. Both drugs showed significant efficacy compared to placebo during the active treatment period. A trend toward tolerance was noted in the triazolam group but not in the zolpidem one. The increase in total sleep time in the zolpidem group was accompanied by an increase in the number of sleep cycles. When active treatment was discontinued, clear rebound insomnia was present in the triazolam group while it was not possible to observe any rebound in the placebo and zolpidem groups. Subjective feelings of the patients, which were assessed by means of visual analog scales, correlated well with polysomnographic data. Our findings tend to indicate that, even after long-term treatment, zolpidem does not induce rebound insomnia or daytime anxiety.