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Biomedical subjects

F Follath

Publications and source records attributed to F Follath.

At least 109 records · Page 6Linked to original sources
PubMed1992

Relation of the level of high-density lipoprotein subfractions to the presence and extent of coronary artery disease.

Plasma lipid profiles, including high-density lipoprotein (HDL) subfractions HDL2 and HDL3, were obtained in 115 men undergoing coronary angiography to assess the relation of lipid levels to coronary artery disease (CAD). CAD was present in 87 patients (76%) and absent in 28 (24%). The largest difference between the 2 groups were observed for HDL2 cholesterol, with a mean of 0.13 mmol/liter (5 mg/dl) in patients with CAD compared with 0.25 mmol/liter (10 mg/dl) in those without CAD (p less than 0.005). Smaller differences were found for HDL3 (1.02 mmol/liter [39 mg/dl] vs 1.19 mmol/liter [46 mg/dl]; p less than 0.005) and HDL (1.15 vs 1.42 mmol/liter [45 vs 55 mg/dl]; p less than 0.001) cholesterol, and apolipoprotein A-1 (1.37 vs 1.50 g/liter; p less than 0.01) and plasma triglycerides (1.79 vs 1.38 mmol/liter [159 vs 122 mg/dl]; p less than 0.05). No significant difference was found for plasma and low-density lipoprotein cholesterol, and apolipoprotein B levels. Simple regression analysis revealed that the most powerful independent variable associated with the extent of CAD was HDL2 cholesterol (Spearman rho = 0.311; p less than 0.001). Stepwise multiple regression analysis proved HDL2 cholesterol and age to be the strongest predictors of extent of CAD. The level of HDL2 cholesterol was reasonably well correlated with HDL cholesterol (r2 = 0.6; p less than 0.0001), but less so with plasma apolipoprotein A-1 (r2 = 0.4; p less than 0.0001). The data add to the growing body of information demonstrating an important association of HDL (and more specifically HDL2) with CAD in men.

Age Factors↗
PubMed1992

Beneficial effect of amiodarone on cardiac mortality in patients with asymptomatic complex ventricular arrhythmias after acute myocardial infarction and preserved but not impaired left ventricular function.

To determine whether the beneficial effect of low-dose amiodarone on survival in patients with complex ventricular arrhythmias after myocardial infarction was dependent on left ventricular (LV) function, results of the Basel Antiarrhythmic Study of Infarct Survival were analyzed. Two hundred twelve patients after acute myocardial infarction with asymptomatic complex arrhythmias were randomly assigned to receive amiodarone 200 mg/day or to a control group and followed up for 1 year. Results of mortality and arrhythmic events were related to baseline radionuclide LV ejection fraction. With preserved (greater than or equal to 40%) LV ejection fraction, there was a significantly lower 1-year cardiac mortality in patients treated with amiodarone (1 of 68 or 1.5%) versus control subjects (5 of 56 or 8.9%; p less than 0.03). This was not the case for patients with LV ejection fraction less than 40%. Similarly, arrhythmic events were significantly reduced only in patients with preserved LV function. These results suggest an interaction between the effects of amiodarone on survival and LV dysfunction in patients after acute myocardial infarction. Because of 2 other small studies with similar results, this finding may be of clinical relevance and should be addressed in ongoing and future research with this drug.

Aged↗
PubMed1992

[New positive inotropic drugs in acute and chronic heart failure].

Beta-adrenergic stimulants (Dobutamine and Dopamine) and recently introduced phosphodiesterase inhibitors (PDI) such as Amrinone, Milrinone, Enoximone and Piroximone are the principal inotropic agents for the treatment of acute cardiac failure. Most of the hemodynamic effects of these drugs are comparable, but peripheral vasodilatation is more marked with PDI. A potential advantage of the latter group is the lack of development tolerance, which occurs within 48 to 72 hours after beta-stimulants. On simultaneous administration, additive effects can be observed. Short term clinical results with PDI are good, especially in patients with postoperative cardiocirculatory failure, including cardiogenic shock. In contrast, long-term oral treatment with Amrinone, Milrinone and Enoximone in recent studies was disappointing. Efficacy was not superior to Digoxin, and unwanted side effects were frequent. Intermittent instead of continuous administration of positive inotropic agents should be evaluated in patients with severe congestive heart failure not responding to vasodilators and diuretics.

Adrenergic beta-Agonists↗
PubMed1992

[Drug therapy in supraventricular arrhythmia].

In view of their potentially dangerous proarrhythmic effects, antiarrhythmic drugs should only be prescribed for patients with poorly tolerated symptomatic supraventricular arrhythmias. The choice of a suitable preparation depends not only on the type of arrhythmia, but also on the underlying heart disease and left-ventricular function. Digoxin, verapamil, sotalol and quinidine remain first-line drugs, while in view of recent trials the type-1c antiarrhythmics (flecainide) should only be given in cases resistant to other agents. Amiodarone is also an important and efficacious "reserve" antiarrhythmic, which has to be utilized at low doses to avoid its well-known side effects.

Amiodarone↗
PubMed1992

[Practical problems in the long-term drug treatment of ischemic heart disease and hypertension].

In choosing drugs for treatment of ischemic heart disease or hypertension one has--next to effects on angina or blood pressure--to consider possible influences on long term course. A simple dosing-scheme with a low number of tablets as well as a thorough information of the patient about the prescribed medication are equally important for the therapeutic success.

Adrenergic beta-Antagonists↗
PubMed1992

The utility of serum drug level monitoring during therapy with class III antiarrhythmic agents.

Serum drug level monitoring facilitates dosage optimization of agents with a narrow therapeutic index. Concentration-dependent antiarrhythmic and toxic effects have been demonstrated for several class I drugs, whereas the concentration-effect relationships of class III antiarrhythmics are less well established. The efficacy and toxicity of amiodarone, in particular, may be determined more by extensive tissue deposition than by its serum concentration. Furthermore, accumulation of the active metabolite desethylamiodarone seems to play an additional role. The antiarrhythmic serum concentration range of sotalol is wide; monitoring is not required. The clinical utility of serum concentration measurements with the newly developed class III antiarrhythmic agents remains to be evaluated in properly planned therapeutic trials in patients with supraventricular and ventricular arrhythmias.

Administration, Oral↗
PubMed1991

[Is regression of atherosclerosis by drugs possible?].

The development of atheromatous wall changes and local thrombotic complications in coronary arteries may be influenced by drug treatment. Calcium antagonists appear to reduce the progression of minimal coronary lesions only, while lipid lowering agents (colestipol, niacin, fibrates and HMG-CoA-reductase inhibitors) can retard the progression of established stenotic lesions or even produce a slight regression in 20-30% of patients within two to four years. In acute stages of coronary artery disease, however, treatment with platelet inhibitors, anti-coagulants and betablockers is required to prevent life-threatening complications. Hence the optimum strategy for secondary prevention in coronary artery disease depends on the clinical presentation in individual patients.

Adrenergic beta-Antagonists↗
PubMed1991

Concentration-effect relations of 5-hydroxypropafenone in normal subjects.

To evaluate the pharmacologic activity of 5-hydroxypropafenone, electrocardiographic changes (PQ and QRS duration) and blood pressure levels were measured in 6 healthy extensive metabolizers of debrisoquine after a single oral dose of 300 mg of this metabolite as a solution in a placebo-controlled, double-blind crossover study. Well-absorbed, with a lag time of 4.4 to 9.8 minutes, 5-hydroxypropafenone reached peak concentrations of 153 to 337 ng/ml after 20 to 51 minutes. The terminal half-life was 506 to 963 minutes. To describe the temporal aspects of the concentration-effect relation, a pharmacokinetic-pharmacodynamic model with a hypothetical effect compartment was applied. The relation between electrocardiographic changes and drug concentration at the effect site could be described by a linear regression model. Significant prolongations of PQ and QRS duration were found in 5 of 6 subjects. There were no changes in QTc interval, blood pressure measurements and heart rate in the supine position. However, blood pressure measurements in the upright position revealed a greater percent decrease of systolic blood pressure than with placebo (mean +/- standard deviation -25.6 +/- 13.8% vs -3.4 +/- 13.1%, p less than 0.05). It is concluded that 5-hydroxypropafenone exerts significant pharmacologic activity in humans as well as animals. Because QRS prolongation in patients treated with class IC antiarrhythmic drugs correlates with the antiarrhythmic effect, our data suggest that 5-hydroxypropafenone may contribute to the therapeutic activity of propafenone in humans.

Administration, Oral↗
PubMed1991

Verapamil in the prophylaxis of bronchial asthma. Is the bronchoprotective effect related to the plasma level?

A single oral dose of verapamil 80 mg was shown significantly to inhibit histamine-induced broncho-constriction in 8 out of 16 asthmatic subjects (maximum increase in PD20FEVHi 416%). There was still significant protection (delta PD20FEV1Hi greater than 100%) in the responders 5 h after the oral dose. The relationship of the bronchoprotective effect to the plasma level of verapamil was also examined. Responders and non-responders did not differ significantly in the peak plasma level or the time course of the plasma verapamil concentration. The protective effect was not correlated with the peak plasma level of verapamil or with the baseline bronchial hyperreactivity.

Administration, Inhalation↗
PubMed1991

Netilmicin in the neonate: population pharmacokinetic analysis and dosing recommendations.

Netilmicin pharmacokinetics were studied in neonates of 27 to 42 weeks' gestational age and 0.8 to 5.0 kg body weight in their first 2 weeks of life by the population pharmacokinetic approach. The data were best described by a two-compartment model. Clearance depends on body weight, gestational age, and postnatal age. Volume of distribution of the central and peripheral compartments was also related to body weight. Including these patient characteristics in the population pharmacokinetic regression model resulted in a marked reduction of the unexplained interindividual variability. This enabled us to derive dosage recommendations that result in peak and average concentrations within the desired range for 95% of the neonates with gestational age above 31 weeks, thus avoiding the need for individual drug-level monitoring in a well-defined large group of patients. Only for infants with gestational age less than 31 weeks who are less than 6 days old is individual dose adjustment based on serum concentration measurements required.

Body Weight↗
PubMed1991

Population pharmacokinetics of quinidine.

1. Population pharmacokinetic parameters of quinidine were determined based on 260 serum drug concentration measurements in 60 patients treated for arrhythmias with quinidine sulphate or quinidine bisulphate (Kinidin duriles) orally. 2. Quinidine kinetics were best described by a two compartment model with zero order absorption from the gastrointestinal tract. The pharmacokinetics are influenced by severe heart or liver failure and renal function impairment. No effect was found for mild or moderate heart failure, for age, for body weight or for coadministration of nifedipine. 3. Population pharmacokinetic parameters of quinidine (assuming 100% bioavailability of oral quinidine sulphate) were: nonrenal clearance for patients without severe heart and liver failure 12.6 l h-1, reduction in patients with severe heart or liver failure to 6.8 l h-1, renal clearance (l h-1) related to creatinine clearance (ml min-1), proportionality constant 0.0566, volume of distribution of the central compartment 161 l, maximum serum drug concentration 1.4 h after administration of quinidine sulphate and 6.0 h after administration of quinidine bisulphate. 4. The results were validated by predicting the serum drug concentration in a separate group of 30 patients. The model reliably predicted both the population average and the variability of the serum concentration of quinidine. 5. Using Monte Carlo computer simulations, an a priori dosing regimen was derived that should maximize the proportion of patients having quinidine serum concentrations within the recommended range (2-5 mg l-1): initial dose of 600 mg quinidine sulphate in all patients, 3 h later first maintenance dose of quinidine bisulphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Clinical pharmacology of antiarrhythmic drugs: variability of metabolism and dose requirements.

The clinical use of the presently available antiarrhythmic agents is rendered difficult by narrow therapeutic ranges, highly variable drug elimination kinetics, and complex dose-concentration-effect relations. Because of their electrophysiological mechanisms of action, these drugs may produce proarrhythmic effects, conduction disturbances, and myocardial depression even at the assumed optimum therapeutic serum levels. Several antiarrhythmic drugs, such as procainamide, quinidine, propafenone, encainide, and amiodarone, are transformed to pharmacologically active metabolites, which may contribute to their antiarrhythmic and toxic effects. In addition to marked genetic differences in hepatic metabolism rates (polymorphic hydroxylation and acetylation), some drugs, e.g., quinidine, propafenone, and amiodarone, produce an inhibition of hepatic metabolizing enzymes and thus cause practically relevant drug interactions. A careful dosage adaptation in individual patients is therefore required to achieve maximum therapeutic benefit and to reduce the risk of unwanted side effects. Serum drug concentration measurements may contribute to an improved use of antiarrhythmic agents, but monitoring alone does not replace the electrophysiological assessment of therapeutic efficacy.

Anti-Arrhythmia Agents↗
PubMed1990

[Computer-assisted drug information].

Experience with a university hospital based drug information service (DIS) is reported. A total of 501 drug related questions were analyzed during two prospective evaluation periods of 13 and 14 months' duration respectively. Information was requested by physicians and pharmacists chiefly on practical aspects of drug treatment in individual patients (77%), such as drug choice, dosage adaptation, side effects and interactions. Inquiries on drug safety in pregnancy and lactation (8.8%), and questions on pharmaceutical properties (14.2%), including pharmacokinetics, were also frequent. Our experience indicates that a problem-oriented, comprehensive DIS necessitates close cooperation between physicians trained in clinical pharmacology and pharmacists within the same team. The use of electronic media greatly facilitates the collection of drug related information, data retrieval and storage. Drug information services can contribute to improved quality and safety of drug therapy.

Computers↗
PubMed1990

[Hemiparesis and torsade de pointes under low-dose sotalol therapy].

An 81-year-old woman with recurrent epileptic attacks, hemiparesis and rapidly changing consciousness is described in whom the most probable reason for the clinical picture was polymorphous ventricular tachycardia (torsade de pointes). Sotalol (Sotalex), which the patient received for two weeks at a dose of 80 mg twice daily because of asymptomatic ectopic ventricular beats, was identified as the causative agent. Torsade de pointes disappeared after a single intravenous injection of 2 g magnesium sulfate. The patient left the hospital a few days later completely recovered from all neurological deficits.

Aged↗
PubMed1990

[Short-term dobutamine therapy in severe cardiac insufficiency].

The feasibility of heart transplantation has stimulated new interest in the therapy of severe refractory congestive heart failure even as an interim solution. We studied the hemodynamics, clinical efficacy and practical implications of a 72-hour dobutamine infusion in 11 patients with NYHA IV refractory congestive heart failure (age 40-73, average 55 years). The dose was 250-1000 micrograms/min, with the goal of increasing cardiac output by 30-50%. Changes in the pharmacokinetics of lidocaine were studied by single dose kinetics in 7 patients. Cardiac output increased from 2.94 +/- 0.68 to 4.77 +/- 1.1 l/min and stroke volume from 35 +/- 10 to 56 +/- 12 ml (p less than 0.001). Pulmonary capillary wedge pressure decreased from 28.5 +/- 5 to 21 +/- 6 and central venous pressure from 14 +/- 6 to 7 +/- 3 mm Hg (p less than 0.007). There was marked worsening of hemodynamics 24-48 h after starting dobutamine. However, after withdrawal of dobutamine a significantly higher cardiac output and stroke volume (3.73 +/- 0.43 l/min, 42 +/- 7 mm Hg. p less than 0.05) persisted. Both clearance and distribution volume of lidocaine increased, while half life decreased significantly (6.61 +/- 1.43 to 5.33 +/- 0.77 h. p less than 0.05). 9 of 11 patients developed Lown IVb ventricular arrhythmia, while in 4 massive diuresis occurred necessitating volume substitution. 6 patients left hospital clinically improved, 2 were transplanted and 3 patients died 1 day to 3 weeks after ending dobutamine. Dobutamine had salutary hemodynamic and clinical effects outlasting the duration of dobutamine therapy. Due to its arrhythmogenic effects it should be administered under ECG monitoring. In patients treated with lidocaine, upward dose adjustments may be necessary with improving hemodynamics.

Adult↗