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D Piovan

Publications and source records attributed to D Piovan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Ajmaline test in a patient with chronic renal failure. A pharmacokinetic and pharmacodynamic study.

Pharmacokinetic and pharmacodynamic properties were studied after intravenous administration of ajmaline 1 mg/kg in an anuric patient, who underwent the electrophysiological ajmaline test. The magnitude and rate of onset of the typical electrophysiological effects of ajmaline (prolongation in atrio-Hisian and His-ventriculum conduction times) were within the range of normal values. The plasma concentration curve showed a triexponential decay with half-lives as follows: initial phase (t1/2 alpha) 1.34 min, fast elimination phase (t1/2 beta) 10.13 min and terminal (slow) phase (t1/2 gamma) 258.6 min. Other relevant pharmacokinetic parameters calculated were: total plasma clearance 45.91 L/h; volume of distribution 285.6L; protein binding 47%. Five hours after administration the patient underwent a 3.5h haemodialysis without any substantial increase in the slope of the final elimination phase of the curve. A major problem in interpreting the pharmacokinetic results is the lack of reliable reference data in healthy subjects. It is likely that the ajmaline t1/2 reported in the literature (13.4 min) does not reflect the true terminal t1/2 of the drug, because it was determined during an unduly short sampling period (30 min). Nevertheless, if we compare just the first 30 min of the concentration-time curves, our results are nearly superimposable on those found in healthy subjects.

Aged↗
PubMed1991

[The relevance of the receptor system in the determination of hypertension].

A pathogenetic role of the receptor mechanisms has been proved or suspected in various diseases. According to a widely accepted hypothesis also essential hypertension may be due to an unbalance between vasoconstricting and vasodilating receptor systems. Although several studies have demonstrated alterations in the number or in the response of specific receptors, it is often difficult to distinguish the primary, causal changes from the secondary, adaptive ones.

Animals↗
PubMed1989

The influence of acidosis on the myocardial uptake and electrocardiographic effects of disopyramide.

The time course for the ECG effects and myocardial uptake of disopyramide was studied in isolated perfused guinea pig hearts under different pH conditions. At pH 7.46 the drug depressed the overall AV conduction time (PR) by 16.64%, the His-ventriculum conduction time (HV interval) by 30.46% and delayed the ventricular repolarization (QT interval) by 8.08%, on average. The maximum intraventricular pressure (Pmax) was also depressed by 35.6%. The maximum effect on the QT interval (constant rate: 0.609 min-1) was reached faster than the maximum effect on the PR and HV intervals (constant rates: 0.399 and 0.400 min-1, respectively), while the myocardium uptake process was complete before any ECG parameter reached a steady state (uptake constant: 1.58 min-1). Under conditions of extracellular acidosis (pH 6.92), the disopyramide disposition parameters (uptake rate constant and myocardial concentration) were not modified. However, the drug exerted significantly smaller effects on the HV and QT intervals and on myocardial contractility. These results are in contrast with those obtained previously with lidocaine and quinidine, and indicate that the influence of acidosis on class 1 antiarrhythmic agents may also depend on the characteristics of the individual drug.

Acidosis↗
PubMed1989

Present and future trends in research and clinical applications of inodilators.

The rationale of combining vasodilatation with positive inotropic intervention in the treatment of chronic heart failure has found a new implementation in the "inodilator" drugs. Inodilators are characterized by the properties of exerting positive inotropic effect and inducing systemic vasodilatation. The cellular mechanisms involved in the regulation of contractility of cardiac and vascular muscle and the pathophysiological events occurring in heart failure are briefly discussed, and the pharmacological profile as well as the therapeutic use of these drugs are reviewed. On the basis of the mechanism of action, two groups of inodilators are distinguished, the phosphodiesterase inhibitors and the dopaminergic agents. The increase of [cAMP]i induced by the phosphodiesterase inhibitors is responsible for their vasodilating effect and for the positive inotropic action, but many of them have in addition the ability to enhance the Ca2+ sensitivity of cardiac contractile proteins. The complex organization and the cardinal role of the catecholaminergic receptor system in the control of cardiovascular function and its contribution to the pathophysiological events occurring in heart failure are the rational basis of the therapeutic use of dopaminergic agents. These drugs, acting on DA, beta-, and alpha-receptors, exert not only positive inotropic and vasodilating effects, but also a diuretic action, and can reduce aldosterone and renin secretion, blunt an excessive sympathetic activity, and possibly promote the release of atrial natriuretic peptide. The multireceptor mechanism of dopamine-like drugs, which accounts for their favorable hemodynamic, neurohumoral, and diuretic effects, represents the most promising approach to inodilator therapy.

Adrenergic beta-Agonists↗
PubMed1989

[Pharmacodynamics and pharmacokinetics of flecainide in cardiac pre-excitation of the bundle of Kent].

In order to identify the flecainide plasma concentrations capable to inhibit the abnormal Kent's pathways, 9 patients affected by a Wolff-Parkinson-White syndrome were studied. One of them (a female 21 years old) previously received 200 mg oral flecainide "una tantum", 8 received 100 mg bid for at least 2 weeks. They had a short PR interval and an evident delta wave on the surface ECG, diagnostic for pre-excitation syndrome. The flecainide plasma half-life calculated in 6 patients chronically treated correlated directly and strictly with age. In all patients the flecainide treatment blocked the conduction through the bundle of Kent (normal PR, no delta wave), then the treatment was stopped and the elimination kinetics of flecainide were studied while a Holter 24h ECG monitoring was performed; thus we could extrapolate the flecainide plasma concentrations at which, during the elimination phase, the PR interval became short and the delta wave reappeared. Since short PR and delta wave are the expression of pre-excitation, we were able to determine the minimum concentrations capable to inhibit conduction through the abnormal bundles (290.0 ng ml-1 in the acutely treated patient and average 275.0 ng ml-1 in the chronically treated patients). These plasma levels are near to the lower therapeutic range accepted for ventricular ectopic arrhythmias (200 divided by 800 ng ml-1). Only larger studies will indicate if a relationship exists between the blockade of abnormal pathways and the preventive effect of flecainide on arrhythmias of Wolff-Parkinson-White syndrome. Another open question is whether a simple, non-invasive pharmacodynamic and pharmacokinetic procedure like that one described in the present paper can be used to predict the efficacy of treatment in patients with cardiac pre-excitation.

Adult↗
PubMed1988

Verapamil pharmacokinetics and liver function in patients with cirrhosis.

In seven patients with liver cirrhosis, verapamil plasma levels were measured in blood drawn simultaneously from the hepatic vein and from an artery during the post-distributive phase after an intravenous bolus infusion of 5 mg of verapamil. In addition the hepatic plasma flow was measured using the indocyanine-green constant infusion technique. From these data the verapamil hepatic clearance and verapamil intrinsic clearance were calculated. The verapamil hepatic clearance was 423 +/- 92 ml/m, the hepatic plasma flow was 819 +/- 318 ml/m, and the verapamil intrinsic clearance was 1431 +/- 961 ml/m. As compared to values reported in the literature, a decrease of the verapamil hepatic clearance by 50% approximately was found, while the hepatic plasma flow was in the normal range and the verapamil intrinsic clearance was reduced by 75%. These data show that in patients with cirrhosis the decrease in verapamil clearance is due to an impairment in the capacity of the liver to remove the drug, and not to a decrease in liver perfusion.

Adult↗
PubMed1987

Effects of SAS 1310, a new calcium antagonist, on isolated myocardial and smooth muscle preparations.

Some features of the effects of the diltiazem derivative SAS 1310 on in vitro myocardial and smooth muscle preparations were compared to those of the effects of diltiazem. Left atria, aortic strips and taenia coli of guinea-pigs were used. SAS 1310 induced a negative inotropic response of the left atria driven at 1 Hz similar to the response to diltiazem (IC50 values: SAS 1310 1.34 microM, diltiazem 0.8 microM). The inotropic effect of diltiazem (5 microM) was clearly rate-dependent whereas the reduction of left atria contractility induced by SAS 1310 (5 microM) was not modified by changes of the stimulation rate (the range of frequencies used was 0.5-2 Hz, with stepwise changes of 0.5 Hz). Diltiazem (0.1-0.5 microM) was more effective than SAS 1310 (0.1-5 microM) in inhibiting the contractile response to calcium of taenia coli depolarized by high K+ as well as in relaxing the aortic strips contracted by high K+ (IC50 SAS 1310 12.3 microM, diltiazem 0.41 microM). The response of aortic strips to norepinephrine (50 microM) in Ca2+-free medium was inhibited by SAS 1310 (50 microM) and was not affected by diltiazem (2 microM). The drug concentrations used were equiactive in inhibiting the high K+-induced contraction of the aortic strips. The different effects of diltiazem and its derivative on left atria contraction at different force-frequency ratios and on aortic strip contraction induced by norepinephrine in a Ca2+-free medium suggest that the actions of the two drugs differ qualitatively.

Animals↗
PubMed1986

Plasma and tissue levels of flecainide in rats.

The time-courses of flecainide plasma and tissue levels were studied in Wistar male rats after i.v. administration (4 mg/Kg). Drug assay in plasma and tissue was performed with a specific and accurate HPLC technique. The final half lives in plasma and tissues were about 4 hours, except in the brain where the half life value was 9.8 hours. The mean tissue/plasma (T/P) ratios in myocardial, kidney, liver, skeletal and muscle tissues were 9.11, 13.8, 14.37, 6.31 respectively, while in the brain the T/P ratio rose progressively over the sampling time to 10.0. These data suggest that flecainide may accumulate in the central nervous system during prolonged treatment. Flecainide levels in adipose tissue were very low. Finally, there was an early "bulge" in the concentration curve, possibly reflecting enterohepatic circulation or non-linear elimination kinetics.

Animals↗
PubMed1986

Variability of positive inotropic response to acute amrinone administration in chronic cardiac failure.

To determine the factors conditioning the variability of positive inotropic response after intravenous acute amrinone administration, 14 patients with chronic cardiac failure were studied by quantitative M-mode and cross-sectional echocardiography. Six patients had idiopathic dilated cardiomyopathy and 8 patients had severe chronic aortic insufficiency. Myocardial contractility (evaluated as peak arterial systolic pressure/end-systolic volume ratio: PAP/ESV) did not change in patients with idiopathic cardiomyopathy, a significant increase of myocardial contractility occurred in patients with aortic regurgitation only if the control value of PAP/ESV was greater than 1. Mean systolic wall stress decreased significantly in all patients, independent of aetiology of cardiac failure and was the factor determining the improvement of left ventricular performance (evaluated as fractional shortening) in patients without changes in myocardial contractility. Maximum improvement in left ventricular performance occurred 10 minutes after amrinone administration. It is concluded that the possibility of detecting the positive inotropic properties of amrinone in man depends on the aetiology of the cardiac failure and on the basal level of myocardial contractility.

Adult↗
PubMed1986

The myocardial levels of the antiarrhythmic drugs: clinical relevance.

Valuable knowledge has been recently achieved in the field of pharmacokinetics of antiarrhythmics, but few data are still available about myocardial concentrations attainable by such drugs, especially as far as the clinical implications of the binding mechanisms and the relationships with plasma levels are concerned. According to the "modulated receptor theory", not only beta-blockers or verapamil but also class I agents should act by a receptor mechanism. In general, antiarrhythmics attain myocardial levels largely higher than the plasmatic concentrations and the non-specific binding greatly exceeds the specific one. Moreover, some relevant causes of lack of correlation between plasma levels and drug response (such as active metabolites, acid-base or ionic disorders, ischemia, receptor changes etc.) are not removed by the determination of myocardial level, which is quite unpractical and does not offer clear advantages in comparison to the conventional plasma monitoring.

Animals↗
PubMed1985

Plasma levels and myocardial content of verapamil, norverapamil and two N-dealkyl-metabolites in man.

The plasma levels and myocardial content of verapamil and its metabolites norverapamil, N-dealkylverapamil and N-dealkylnorverapamil were determined in 15 patients with valvular [3] or ischaemic [12] heart disease. The mean myocardial plasma concentration ratio (M/P) was 7.05 for verapamil, 11.45 for norverapamil, 8.93 for N-dealkylverapamil, and 11.33 for N-dealkylnorverapamil, with great interpatient variability. The highest M/P ratios of verapamil were generally found in patients with the lowest plasma levels, suggesting that saturable tissue uptake may occur.

Adult↗
PubMed1985

Once per week oral administration of amiodarone in the prophylaxis of supraventricular paroxysmal tachycardia.

In eight patients who had previously responded to treatment with oral amiodarone for prevention of recurrent supraventricular paroxysmal tachycardia, a new regimen of oral amiodarone dosing was evaluated. Each patient received the entire dose, previously taken throughout one week (600 to 1,200 mg), on a single day, once each week. After six weeks on this regimen, all patients were still free of arrhythmias and there were no adverse reactions to the drug. In the first week of the new treatment, amiodarone plasma levels gradually fell from 1.83 mg/l, to 0.48 mg/l, on average. The trough level was similar to that obtained when the drug was given on a daily basis. It is concluded that this new regimen can be used for patients receiving oral amiodarone, and it may be advantageous in improving the compliance of some patients.

Amiodarone↗