[Clinical assessment of drug safety].

The environment of drug safety is changing. In addition to the current system of pharmacovigilance based on spontaneous report of adverse events, clinical data observed in a given patient with a given symptom is taken into consideration and compared with information coming from pharmacovigilance data bases, which is then analyzed for causality by the experts of both the promotor and the public network. Such information is integrated into a risk management strategy, defined together by the French drug agency (Afssaps) and the marketing authorization holder.

[Pharmacokinetics of cardiovascular drugs in the elderly].

Adverse drug effects are more frequent in elderly patients, especially with drugs that have small safety margins. This is the case of many cardiovascular drugs. Patients who are frail, owing to their age and their psychomotor, nutritional and social stratus, are particularly at risk.

[Validation of a measurement scale: example of a French Adverse Drug Reactions Preventability Scale].

Adverse drug reactions (ADRs) have been recognised as an important cause of hospital admission. Most of these drug-related admissions were expected ADRs and, thus, partly preventable. However, as far as we know, the assessment of the preventability of ADRs was addressed in only two studies performed in France.

Efficacy and tolerability of candesartan cilexetil vs. amlodipine as assessed by home blood pressure in hypertensive patients.

This randomised, double-blind study compared the anti-hypertensive efficacy and tolerability of Candesartan cilexetil (CC 8-16 mg) and Amlodipine (AML 5-10 mg) on home blood pressure (HBP) measurements in mild-to-moderate hypertensive patients. After a 2-week wash-out, patients aged 18-74 years, with a sitting diastolic blood pressure (sDBP)=95-115 mmHg, untreated or intolerant to therapy or uncontrolled were randomised to CC 8 mg or AML 5 mg O.D.

[Pharmacovigilance of hepatitis B vaccines].

Since the hepatitis B vaccine are on the market in France, until the end of 2002, 1211 observations of demyelinating disease of the central nervous system (1109 cases of which 895 multiple sclerosis) or peripheral (102 cases of which 49 Guillain Barre Syndrome), have been reported to the french network of pharmacovigilance and to the AFSSAPS. It is not possible to singularize these observations, neither from a clinical nor an epidemiological point of view. No risk factor has been detected.

Prevention of drug-induced risks.

Effective prevention of drug-induced risks depends on an accurate understanding of their triggering or predisposing factors, and the quality of information on these available to prescribing practitioners and users. All preclinical and clinical data available on the proprietary medicinal product concerned should facilitate identification of a risk, and these data should be compared with existing data on drugs sharing the same mode of action or therapeutic strategy. This information should be based on a communication plan adapted to the context of the disease under treatment, the therapeutic alternatives available and the benefits expected.

[Anti-angiogenic effects of aldosterone antagonists in the fibrin chamber in rats].

Spironolactone, a diuretic antagonist of aldosterone has an unexplained side effect of amenorrhea which could be due to an angiogenesis inhibition. In this study we compared the effects of spironolactone, canrenone an active metabolite of spironolactone and eplerenone a more selective mineralocorticoid antagonist in rats implanted with a fibrin gel chamber. Perforated plexiglass chambers filled with rat fibrin, spironolactone (50 microM), canrenone (100 microM), eplerenone (500 microM), DMSO (0.

Mild acute renal failure potentiates metformin accumulation in the diabetic rat kidney without further impairment of renal function.

Objectives: To analyze, in acute renal failure (ARF) in diabetic rats, how moderate functional ARF would modify metformin (MET) pharmacokinetics and if plasma and renal tissue MET accumulation could aggravate renal insufficiency and/or elicit plasma lactate accumulation.

Methods: Streptozotocin-induced diabetic rats were allocated to four groups: control, MET, ARF, ARF-MET (6-7 rats per group). MET (100 mg/kg/day) was given per os for two weeks before ARF was induced by drinking restriction and enalapril treatment.

Shear stress modulates vasopressin-induced renal vasoconstriction in rats.

Vasopressin is a potent renal vasoconstrictor in vitro which elicits relatively minor renal vascular effects in vivo. Efficient modulation might occur through shear stress-elicited release of vasodilator compounds from endothelial cells. The aim of this study was to evaluate in vitro, in the isolated perfused kidney, the influence of shear stress and related nitric oxide (NO) release on basal renal vascular tone and on vasopressin-induced renal vasoconstriction.

Oxytocin-induced renin secretion by denervated kidney in anaesthetized rat.

The effects of oxytocin on renin secretion by denervated kidney were investigated in vivo, by infusing the peptide directly into the renal artery of anaesthetized rats. Renin secretion was calculated by the renal veno-arterial difference in plasma renin activity multiplied by renal plasma flow. The intra-renal arterial (i.

Contribution of angiotensin II internalization to intrarenal angiotensin II levels in rats.

This study was designed to determine the involvement of AT(1) receptors in the uptake of ANG II in the kidney of rats exposed to differing salt intake. Male Wistar-Kyoto rats were treated with a normal-salt (NS; 1% NaCl, n = 7) or a low-salt (LS; 0.025% NaCl, n = 7) diet combined with (LS+Los, n = 7; NS+Los, n = 7) or without losartan (30 mg.

Effects of dietary salt changes on renal renin-angiotensin system in rats.

Renin (RA) and angiotensin-converting enzyme (ACE) activities and angiotensinogen, ANG I, and ANG II levels were measured in the kidney (cortex and medulla) and plasma of Wistar-Kyoto rats on a low-sodium (LS; 0.025% NaCl; n = 8), normal-sodium (NS; 1% NaCl; n = 7), or high-sodium (HS; 8% NaCl; n = 7) diet for 21 days. RA, ANG I, and ANG II levels increased in a manner inversely related to sodium content of the diet in both plasma and renal tissues.

[Anti-angiogenesis effects of aldosterone antagonist diuretics].

Angiogenesis requires endothelial cell proliferation and their vascular rearrangement. A report of inhibiting effect of spironolactone on smooth muscle cell proliferation led us to study in vitro the effects of this drug on the endothelial cell proliferation and migration. Spironolactone (10 to 100 microM) and one of its active metabolite, canrenone (10 to 100 microM), are added to human umbilical vein endothelial cells (HUVEC).

Influence of sodium intake on the cardiovascular and renal effects of brain mineralocorticoid receptor blockade in normotensive rats.

Objective: We have previously shown that brain mineralocorticoid receptors (MR) participate in the control of arterial pressure and renal excretory function in normotensive rats. In the present study, we evaluate the influence of sodium intake on the control of cardiovascular and renal function by brain MR in normotensive conscious rats. We hypothesize that modulation of sodium intake affects the cardiovascular and renal effects of brain MR blockade.

[Drug vigilance].

The goal of drug vigilance is to identify, analyse and anticipate adverse reactions resulting from the use of a drug. It is of utmost importance to ensure that a drug remains safely used, and to update its prescription when necessary. Vigilance is based on professional judgments by specialists who flag putative side effects to the network.

Effects of brain mineralocorticoid receptor blockade on blood pressure and renal functions in DOCA-salt hypertension.

In normotensive rats, we have previously demonstrated a role of brain mineralocorticoid receptors in blood pressure and renal function control. In the present study, the coordinate cardiovascular and renal effects of brain mineralocorticoid receptor blockade were examined by intracerebroventricular (i.c.

Renal vascular reactivity to vasopressin in rats with diabetes mellitus.

We evaluated how renal vascular reactivity to vasopressin changes when nitric oxide (NO) synthesis varies, as has been reported to occur in the course of insulin-dependent diabetes mellitus. Renal vasoconstrictor responses to vasopressin were obtained in young and older Sprague-Dawley control rats (3 and 10 months old) and in age-matched diabetic rats that had been treated with streptozotocin (60 mg/kg i.v.