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Biomedical subjects

G Cheymol

Publications and source records attributed to G Cheymol.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Acute effects of intravenous prifuroline and amiodarone on canine cardiac automaticity, conduction, and refractoriness.

We compared the acute electrophysiologic properties of prifuroline (P), a new aminopyrroline derivative, to those of amiodarone (A) in pentobarbital-anesthetized dogs using His bundle recordings and programmed stimulation. Ten dogs received in randomized order four cumulative doses of P (2.5-20 mg/kg) and of A (1.25-10 mg/kg) with a 14-day interval between drug administrations. In a control group of four dogs receiving the diluent of the drugs, no significant changes occurred in cardiac automaticity, conduction, and refractoriness except for the atrioventricular (AV) nodal functional refractory period (RP), which increased with time (p less than 0.05). P and A produced a significant dose-related decrease in heart rate and in sinus node recovery time, with A being 3.7-3.1 times more potent than P. While atrionodal conduction time increased with both drugs, only P resulted in a significant dose-related increase in the His-Purkinje system conduction time. Prifuroline was 2.9 times more potent than A in increasing the atrial effective refractory period, while A was 2.5 times more potent than P in increasing the ventricular effective refractory period. Both drugs increased the AV nodal refractoriness in a dose-dependent way. These results suggest that the new compound prifuroline possesses some properties similar to intravenous amiodarone on sinus automaticity, atrionodal conduction, and atrial and ventricular refractoriness. However, its effects on the His-Purkinje System are typical of those of a class I quinidine-like agent.

Amiodarone↗
PubMedDate not supplied

Comparative cardiac electrophysiologic study of PK 10139, a new antiarrhythmic agent, and quinidine in anesthetized dogs: plasma concentration-response relationships.

Cardiac electrophysiologic effects of PK 10139 (PK), a new quinoleic antiarrhythmic agent, were compared with those of quinidine sulphate (Q) after three cumulative intravenous doses of 0.75, 1.5, and 3 mg/kg of PK and 5, 10, and 20 mg/kg of Q in anesthetized dogs. A control group of animals received saline solution only. Both PK and Q provoked an increase, correlated with plasma concentrations, in atrionodal (St-H), His-Purkinje system (HV), and auriculoventricular (QS) conduction times, and auricular effective and functional refractory periods (AERP, AFRP). The effects of PK on conduction times were more marked than those of Q. Slopes of the plasma concentration-effect curves were similar for the two drugs for HV and QS but different for St-H. PK was 42.5 times more potent than Q in increasing HV and 46 times more potent than Q in increasing QS. Effects of PK on AFRP and nodal FRP did not differ from those observed in control animals. These findings demonstrate more marked effects of PK, when compared with Q, at doses 6.7 times lower and at plasma concentrations 15 to 42 times less, without chronotropic effects or significant alterations in blood pressure, and without adverse reactions on the central nervous system.

Anesthesia↗
PubMedDate not supplied

[Modalities of therapeutic follow-up of cyclosporine].

The therapeutic use of cyclosporine (CsA) requires total blood levels to be monitored with a specific assay, since this drug is nephrotoxic, has a narrow therapeutic index, shows wide intra- and inter-individual differences in its pharmacokinetic behaviour and can interact with other drugs. The parameter generally measured is the residual blood concentration at equilibrium; levels are occasionally again measured four or six hours after CsA administration. Patients are monitored every two days during the first two weeks following organ transplantation, a frequency which gradually declines to monthly determinations at four to six months in the absence of complications. The therapeutic range of blood CsA concentrations is still poorly defined. In renal, liver, heart and bone marrow transplantation most authors recommend concentrations of 100-250 ng/ml for the first three months when renal function is satisfactory. Ways of administration (i.e. continuous infusion or dividing up of the daily dose) must be taken into consideration to assess values of blood concentration of CsA.

Cyclosporine↗
PubMedDate not supplied

[Therapeutic follow-up of cyclosporine. Main factors involved in the interpretation of results].

The therapeutic drug monitoring of cyclosporine (CsA) requires not only correct methodological conditions but also taking into consideration of numerous other factors involved in the value of blood drug concentrations. Main factors concern: the clinical state of patients. Liver function and bile flow act predominantly on drug clearance; the choice of monitoring parameters and of sampling time. Comparison was done of information given respectively by area under the curve and different sampling times. Usually blood concentration is monitored with trough level plus eventually another concentration measured 4-6 h after drug administration; the time-table. Blood concentrations are measured at steady-state period. Bioavailability of CsA increases in the immediate postoperative period after transplantation; ways of CsA administration. Trough level is influenced by dividing up of the daily dose. In case of continuous i.v. infusion mean blood concentration, but not trough concentration, is measured; drug interactions. Several drugs modify blood concentrations of CsA. Others induce an additive nephrotoxicity or immunosuppressive effect. Recommended blood trough concentrations vary with clinical indications, experience and therapeutic habits of each transplant center. Currently recommended values (CsA whole blood concentration determined by specific method) are 150-250 ng/ml in renal, heart, liver and bone marrow grafts, during the 3 months after transplantation, with good renal function. Concentrations are often higher for lung transplantation.

Cyclosporine↗
PubMedDate not supplied

[Treatment with iloprost of critical ischemia of the lower limbs associated with cardiac insufficiency. Study of interaction with the pharmacokinetics of digoxin].

We have treated with intravenous iloprost twelve patients suffering from cardiac insufficiency compensated under oral digoxin (NYHA class II) associated with severe limb ischaemia due to arterial insufficiency. Our aim was to study its possible interaction on digoxin levels and to evaluate the long-term efficacy of iloprost. Although iloprost slowed the digoxin absorption by approximately one hour, we found no clinically significant difference between the digoxin pharmacokinetic data before and during treatment by iloprost. Moreover, 11 out of the 12 patients had a good clinical fate after the treatment, which persisted at 6 months. The pain disappeared in 4 and diminished in 7; and all skin ulcers healed. This improvement has lasted up to two and a half years in two patients. The clinical tolerance of iloprost was acceptable despite frequent headache and flushing associated with hypotension and nausea. We conclude that iloprost seems to be a very promising treatment of severe limb ischaemia when no intervention on the proximal arteries is possible. The patients on digoxin can continue their treatment without dose alteration while starting on iloprost.

Adult↗
PubMedDate not supplied

[Drug interactions with calcium inhibitors in man].

The most common interactions concern cardiovascular drugs. The combination of calcium antagonists (CA) and beta-blockers is more effective than single-agent therapy in stable effort angina and hypertension. But there is an increased risk of hemodynamic or electrophysiological side effects in patients with left ventricular or sinus dysfunction, or disturbances of conduction. Pharmacokinetic interactions have been observed in particular with verapamil (VE) which increases propranolol bioavailability. VE increases the T1/2 of elimination and plasma digoxin concentration following single or prolonged administration. The primary mechanism appears to be renal. These modifications increase the risk of digitalis intoxication. Diltiazem (DTZ) inconsistently increases steady state plasma digoxin levels. In healthy subjects, nifedipine (NF) increases plasma digoxin concentrations and decreases digoxin renal clearance. These findings have not been observed in patients with heart failure. NF therefore leads to less marked modifications in digitalis pharmacokinetics than do VE and DTZ. Nitrendipine and nicardipine interact only slightly with digoxin, and consequently there are no pharmacodynamic effects. In healthy subjects, VE increases quinidine t1/2 and markedly decreases its metabolic clearance. Conversely, quinidine increases plasma NF levels. The primary CA are extensively metabolized by liver microsome oxidases. These result in interactions with the drugs that are also metabolized by these enzymes, or able to modify their activity. VE and DTZ decrease antipyrine and carbamazepine clearance. VE, DTZ and nicardipine lead to a marked increase in plasma ciclosporin levels. Cimetidine, but not ranitidine, increases plasma NF levels. The effects on VE are controversial. Prolonged rifampicin treatment decreases plasma VE levels.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Recording of the his bundle potential at the surface of the thorax in healthy volunteers. Application to the study of propranolol].

New analogic-digital technology contributions to standard electrocardiography may allow to record the his bundle potential from the body surface. The aim of this work has been to study the validity of this method by its application to estimate the dromotropic effect of propranolol in healthy volunteers. His bundle potential from body surface was recorded in 19 out of 26 enrolled subjects. The negative dromotropic effect of propranolol (40 mg orally) was observed in only 10 volunteers. The direction of the PR and PH interval changes was used to estimate sensibility (0.9) and specificity (0.89) of this method. There was also a significant correlation (0.89 less than p 0.05) between PR and PH interval changes. This new non-invasive method could be used in clinical pharmacology but the subjects must be preselected.

Adult↗
PubMedDate not supplied

[Pharmacokinetics of oral propafenone in patients with supraventricular arrhythmia].

The efficacy of propafenone (P), a class IC antiarrhythmic drug with weak beta-blocking properties was studied over a four day period in 10 patients with supraventricular arrhythmias (atrial fibrillation 7, flutter 1 and tachycardia 2). Group 1 included five patients (3M, 2F) who received 300 mg of P on days 1 and 4. Group 2 included five patients (4M, 1F) who received 600 mg on days 1 and 4. All the patients received 1200 mg/day on days 2 and 3. Pharmacokinetics parameters were calculated for the first and the final dosing. Half of the patients were converted to sinus rythm after a delay ranging from 12 to 55 h after the first dosing. The duration of arrhythmia was shorter and the left atrial diameter was significantly lower in the responder group than in the non-responders. No relationship was observed between clinical efficacy and dose or plasma concentration of P. After the first administration of P, major interindividual variability in pharmacokinetic parameters was observed. Seven patients correspond to the extensive metabolizer phenotype with t1/2 el less than 10 h (mean: 5.4 +/- 2.2 SD). In this group t1/2 el increased from day 1 to day 4 and the AUC final/AUC initial ratio ranged between 4 to 17.5. Three patients showed the non-extensive metabolizer phenotype with t1/2 el ranging from 12.4 to 13.7 h and a moderate increase in AUC over chronic dosing. Adverse effects (cardiac conduction abnormalities, visual and digestive disturbances) were observed in the 3 oldest patients (70-73 yrs).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗