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Biomedical subjects

P Lechat

Publications and source records attributed to P Lechat.

350 records · Page 20Linked to original sources
PubMedDate not supplied

[Beta-blockers and heart failure].

Several studies have suggested that beta-blockade could provide functional benefit in heart failure, suggesting a deleterious role for the compensatory sympathetic stimulation. Beta-blockade induced benefit could result from either antagonism of any myocardial beta-adrenergic stimulation or on the opposite a paradoxical cardiac beta-adrenergic responsiveness secondary to beta-adrenergic receptor up-regulation. Two recently completed large scale multicentric placebo controlled studies, the MDC trial with metoprolol and CIBIS with bisoprolol, have confirmed that beta-blockade could functionally improve patients with heart failure. The observed survival improvement in non ischemic patients was observed only in the CIBIS trial. Such a result must be confirmed with additional studies.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Atheroma and calcium antagonists].

Calcic ions play a role in the initial and chronic development of atherosclerosis lesions. Demonstration of anti atherogenic properties of calcium antagonists has open a new therapeutic approach of atherosclerosis and of its complications. Mechanism of protection remains unclear but it is essentially a preventive effect requiring very early administration before onset of lesions. Several experimental studies have shown that calcium antagonists could reduce cholesterol content of arterial wall without any modification of lipid plasma or profile. Several other mechanisms have been proposed but none of them can actually explain the observed preventive effect of these drugs. The clinical relevance in human of such a preventive effect of calcium antagonists requires further investigations.

Animals↗
PubMedDate not supplied

[Arterial hypertension: current large therapeutic trials].

In this review, the design and objectives of ongoing clinical trials in essential hypertension are discussed along with the main results obtained from previously published therapeutic trials. In a meta-analysis of 14 of the major primary prevention trials in hypertension, the difference in diastolic blood pressure between the intervention groups and the control groups was only 5-6 mmHg. This difference was associated with significant reductions in all stroke events (42 per cent), all coronary heart disease events (14 per cent) and in cardiovascular mortality (21 per cent). In elderly hypertensive patients, available studies have shown that antihypertensive treatment reduces the incidence of non-fatal cardiovascular events without significantly modifying cardiovascular mortality. Most of these results were obtained with beta-blockers or diuretics. Despite official recommendation as first line monotherapy, none of the three new antihypertensive classes has been shown to have beneficial effects on hard primary endpoints such as cardiovascular morbidity and mortality. Several ongoing large scale randomized controlled trials vs. beta-blockers or diuretics are addressing this important issue. Moreover, other effects of antihypertensive treatment such as the 'J-curve phenomenon', the rate of change in the carotid wall thickness or the exact beneficial effects in elderly patients are being investigated in some of these studies.

Aged↗
PubMedDate not supplied

[How to measure the kinetics of biological effect of a drug].

Therapeutic benefit that can be induced by a pharmaceutical compound partly relies upon the profile of its biological action. Evaluation of the drug-induced effect profile in a given pathological condition begins with the determination of the relevant biological effect related to the therapeutic benefit, which is not always obvious. Evaluation itself is based on dose-effect relationships as a function of time. During chronic treatment, such a kinetic profile oscillates between peak and trough levels. Relationships that can be established between time-dependent effect profile and pharmacokinetic data lead to PK-PD mathematical model, whose main objectives are simulation, prediction of effect and ultimately dose optimisation. The therapeutic implications of the time-dependent effect profile are well illustrated in the cases of antibiotics, diuretics such as furosemide and anti-hypertensive drugs. During drug development, PK-PD approaches can be used in the initial clinical and even pre-clinical phases and can lead to a better definition of effective dose ranges, optimisation of large scale clinical trials or identification of high risk patients. This may favour a reduction of costs and duration of development. Validation of such an approach is easier in well known therapeutic domains but can be more difficult with innovative drugs. The implications of PK-PD approaches can however, be, limited when the relevant biological or clinical parameter cannot be assessed, when the cascade of events leading to pharmacological and therapeutic effects is complex or finally when such PK-PD models require a long time to be established during the early phase of drug development.

Acquired Immunodeficiency Syndrome↗