Can colchicine potentiate the anticoagulant effect of fluindione?
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Aged↗
Biomedical subjects
Jean-Louis Imbs
Publications and source records attributed to Jean-Louis Imbs.
[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. Only the chronology could suggest a causal relationship, the vaccine preceding the pathology in all the cases notified.
Adolescent↗
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.r.a.) infusion of oxytocin (1.5 or 15 ng/kg/min, 10 min) induced a sixfold increase in renin secretion as compared to vehicle-treated controls, without effects on renal blood flow, mean arterial blood pressure, glomerular filtration rate or natriuresis. The effect of oxytocin (1.5 ng/kg/min) was prevented by pretreatment with an oxytocin receptor antagonist, desGly-NH(2),d(CH(2))(5)[D-Tyr(2),Thr(4),Orn(8)]vasotocin] (5.6 microg/kg bolus i.v. 20 min before oxytocin infusion, followed by 2.8 microg/kg/min i.r.a.). Nadolol (2.5 mg/kg i.v.), a beta-adrenoceptor antagonist, also blocked the oxytocin-induced increase in renin secretion. These results show that oxytocin is able to stimulate renin release by activating oxytocin receptors but that beta-adrenoceptors also seem to be involved.
Anesthetics↗
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. Rat kidneys were perfused at a constant flow rate of 8 ml/min with Tyrode's solution (relative viscosity eta=1) or, in order to increase shear stress, with Tyrode's solution supplemented with 4.7% Ficoll 400 (Ficoll 400; eta=2.3), which is representative of the relative viscosity found in small vessels. Renal shear stress was further elevated during vasoconstriction elicited by vasopressin. Basal renal true vascular conductance, which reflects mean blood vessel radius, was 2.5-fold higher and overall wall shear stress doubled in Ficoll 400 - as compared to Tyrode-perfused kidneys. The decrease in vascular conductance elicited by NO synthase inhibition with N(omega)-nitro-L-arginine (L-NNA) increased with the viscosity of the perfusate. Shear stress was elevated during vasopressin-induced renal vasoconstriction, all the more kidneys were Ficoll 400-perfused. In these kidneys, the concentration-response curve to vasopressin was shifted to the right, giving evidence of hyporeactivity to the peptide. L-NNA potentiated vasoconstriction to vasopressin particularly in Ficoll 400-perfused kidneys, although additional inhibition of cyclooxygenase and/or cytochrome P(450) was without effect. These results provide in vitro evidence that shear stress enhanced by perfusate viscosity increases basal renal vascular conductance by an NO-dependent mechanism. Together with shear stress enhanced during vasoconstriction, it blunts vasopressin-induced renal vasoconstriction.
Animals↗
[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. To ascertain causality between drug use and possible side-effects, the available evidence is discussed within the vigilance network, closely involving the health professional who originally identified a possible effect, and with reference to the French drug vigilance database, as well as the existing relevant literature. The possibility of a side-effect triggers an alarm, and generates an investigation, which must often he completed by an epidemiological analysis when the risk associated with the drug is low. Drug vigilance is crucial to public health. It currently collects data both from the relevant units in pharmaceutical companies and the public drug vigilance networks.
Adverse Drug Reaction Reporting Systems↗
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. DESIGN AND METHODS: We examined the effect of intracerebroventricular (ICV) administration of MR antagonist (RU28318) on systolic blood pressure (SBP), heart rate, and urinary excretion of water and electrolytes in normotensive Wistar rats subjected to different dietary sodium content. Rats were fed high (8%), normal (0.4%), or depleted (0%) sodium for 3 weeks. SBP and heart rate measurements were performed using an indirect tail cuff method. Metabolic cages were used to assess renal function. RESULTS: ICV injection of 100 ng RU28318 induced a long-lasting decrease ( 0.01) in SBP in rats submitted to different sodium intake. At 8 h, the decrease in SBP did not differ between rats on high (30 +/- 5 mmHg), normal (28 +/- 6 mmHg), and low (21 +/- 3 mmHg) sodium diets. At 24 h, the decrease in SBP was also comparable between rats on different sodium diets. Increased diuresis was observed during the period 0-8 h after ICV injection of RU28318; this was less pronounced in rats on the low sodium diet. Urinary excretions of potassium and chloride were also increased during this period, particularly in rats on the high and normal sodium diets compared with rats with low sodium intake. Urinary excretion of sodium was increased only in the rats fed high and normal sodium diets. Measurement of plasma renin activity, which was suppressed and stimulated, respectively, by high and low sodium intake, indicated that the effects on SBP and renal function induced by ICV RU28318 were independent from the level of activation of the renin-angiotensin system. CONCLUSION: In contrast to our hypothesis, in normotensive Wistar rats, sodium intake does not affect the hypotension induced by brain MR blockade. However, sodium depletion attenuated the renal effects of brain MR blockade.
Animals↗
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. The LS diet resulted in a 16-, 2.8-, and 1.8-fold increase in plasma RA, ANG I, and ANG II levels, respectively, compared with those in HS rats. In the renal cortex and medulla, RA, ANG I, and ANG II levels were also increased by diminution of dietary salt content but, in contrast to plasma, ANG II levels increased much more than RA or ANG I levels [5.4 (cortex)- and 4.7 (medulla)-fold compared with HS rats]. In summary, we demonstrated variations of ANG II levels in the kidney during dietary salt modifications. Our results confirm that RA and ACE activity are not the steps limiting intrarenal ANG II levels. Nevertheless, despite RA and ACE activity differences between renal cortex and medulla, ANG I and ANG II levels are equivalent in these two tissues; these results argue against a compartmentalization of RAS in these two intrarenal areas.
Angiotensin 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. kg(-1). day(-1)), an AT(1) receptor antagonist. Renin (RA) and angiotensin-converting enzyme (ACE) activities and angiotensinogen, ANG I, and ANG II levels were measured in plasma, renal cortex, and medulla. In LS rats, in both plasma and renal cortex, the increase in RA was associated with an increase in ANG I and ANG II levels compared with NS rats, but intrarenal ANG II levels increased more than ANG I levels. In NS+Los rats, the increase in RA in plasma was followed by a marked increase in plasma ANG I and ANG II levels compared with NS rats whereas in the kidney the increase of renal RA was followed by a decrease of the levels of these peptides. The same pattern was observed in LS+Los rats, but the decrease in renal ANG II levels was much more pronounced in LS+Los rats than in NS+Los rats. Our results suggest that the increase in renal ANG II levels after salt restriction results mainly from an uptake of ANG II, via AT(1) receptors. Such elevated intrarenal ANG II levels could contribute to maintain sodium and fluid balance and arterial blood pressure during salt-deficiency states.
Angiotensin I↗
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.
Drug-Related Side Effects and Adverse Reactions↗
[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. In contrast, several other studies have been performed, mainly in the USA, and using different methods of assessing preventability. None of these methods were clearly evaluated with regard to reproducibility, validity or relevance. The purpose of this study was to initiate the validation of a French preventability scale. Here, we propose the first two phases of validation: the content validity and reliability of the scale. A working group of pharmacovigilance experts has been specifically established for this purpose. The content validity was assessed by collecting items representative of preventability. The choice and the formulation of items and a proposal of a score (global and for each item) were adopted after the consensus of the experts. A definitive version of the ADR preventability scale was used for the assessment of reliability. During the second phase, experts independently tested the new scale from observations of ADRs (49 central nervous system haemorrhages with antivitamine K). The concordance of the experts' judgements was calculated using two statistical methods (Kappa statistic and correlation coefficient). The content validity phase was performed during several workshops where experts discussed the choice and formulation of the best items. We decided to construct a scale with a small number of items, allowing a rapid evaluation of the preventability of ADRs. On the basis of a global score, four categories of preventability of ADRs ("preventable", "potentially preventable", "unclassable", "not preventable" ADRs) were proposed. The agreement of experts regarding the global score was low, with a poor correlation coefficient value (coefficient interclass = 0.491). Classification of ADRs in the four categories by the experts showed discrepancies (Kappa = 0.1136). The preventability assessment using this scale was feasible, although poor concordance between the judges has raised some questions. Several experts found use of this scale difficult in terms of a clear understanding of the items, and found that two of them were redundant. We have oversimplified some items and revision of their formulation will be necessary. Moreover, most of ADR notifications were poorly documented, resulting in a frequent choice of an "unevaluable" item. This represented an important bias in the calculation of the global score. This experience suggests the need for further studies to improve this French ADR preventability scale and validate it in differing circumstances, in order to provide a useful tool to enhance the rational use of drugs.
Adverse Drug Reaction Reporting Systems↗
[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. Two pharmacokinetic factors appear to be of major concern, namely the age-related decrease renal function and changes in drug metabolism and distribution. Renal function is probably the single factor most responsible for altered drug levels in the elderly. The normal age-related decrease in creatinine clearance can lead to the accumulation of drugs that are normally excreted by the kidneys without being inactivated Dose adjustment of such drugs is usually based on the Cockcroft-Gault formula of creatinine clearance. Changes in hepatic metabolism and drug distribution are less commonly taken into account. The avoidance of drug toxicity requires familiarity with the medications prescribed and particular vigilance for signs of adverse effects.
Age Factors↗