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Biomedical subjects

F Follath

Publications and source records attributed to F Follath.

At least 199 records · Page 11Linked to original sources
PubMed1982

[Digitalis therapy in the aged].

Cardiac glycosides still belong to the most frequently prescribed drugs, although the usefulness of digitalization in patients with sinus rhythm has been repeatedly challenged. In elderly patients, especially, the objective hemodynamic improvement remains minimal and treatment can often be interrupted without subsequent deterioration. On the other hand, signs of digitalis toxicity, such as nausea, vomiting, AV-block, ventricular extrasystoles or CNS-symptoms, occur in 15-30% of patients. Adverse effects are mainly due to toxic accumulation of digoxin in cases with age related reduction of kidney function. In view of its non-renal elimination digitoxin would seem to have a certain advantage in geriatric patients, however, its long t 1/2 (6-7 days) makes dose adjustments more difficult, as peak effects will only be attained after 4-5 weeks. For these reasons digitalis treatment in elderly patients should not be given without clinically manifest congestive heart failure and/or atrial fibrillation. Even in such cases a periodic reassessment of the therapeutic indication is recommended. Suspected "latent" cardiac failure or cerebrovascular insufficiency are no reasons for utilizing such potentially toxic drugs.

Aged↗
PubMed1982

[Assays of serum concentrations in drug intoxications].

Drug assays in serum and urine of patients with drug poisoning are most often performed to identify the ingested substances. Semiquantitative screening tests are usually sufficient for this purpose, while serum drug level determinations for therapeutic monitoring require rapid, specific and precise laboratory techniques. Results should be interpreted in the light of various pharmacokinetic factors and especially the presence of active metabolites, which may influence the concentration-effect relationships. Critical concentration ranges are known for several drugs but, except in cases with paracetamol overdose, drug levels alone are rarely decisive for the therapeutic procedure. Further studies are necessary to define the potential benefit of routine serum level measurements in drug poisoning.

Acetaminophen↗
PubMed1982

[Netilmicin in refractory urinary tract infections. Good therapeutic effect in spite of long dosage intervals].

Aminoglycoside antibiotics are useful--despite potential toxicity--for treating urinary tract infection when other antibacterial agents have failed to eradicate bacteriuria. That this is true of the recently introduced aminoglycoside netilmicin was shown by 16 cases of tenacious and frequently recurring urinary tract infection. In contrast to previous recommendations, but relying on well known pharmacokinetic data which show prolonged urinary excretion of aminoglycosides, netilmicin was administered according to the following dosage schedule: Intramuscular injections of 3 mg/kg in cases where renal function was unimpaired, and of 2 mg/kg where it was reduced, were administered at dosage intervals of 1 to 4 days. Peak serum levels of netilmicin measured 1 hour after intramuscular injection were within the expected range of 8-14 micrograms/ml (3 mg/kg) and 6-10 micrograms/ml (2 mg/kg). As a result of the long dosage intervals the serum trough levels were usually far below 1 microgram/ml except in patients with moderate renal failure. Urinary concentrations of netilmicin, however, remained for the most part above the limit of antibacterial activity throughout the dosage intervals of 1 to 4 days. One week after the usual three weeks treatment course, urinary concentrations were still between 1 and 5 mcg/ml, and slowly decreasing amounts of the drug could be detected at least in traces up to 3 months beyond the last dose. Considering the type of urinary tract infections selected to receive netilmicin, the response to treatment was satisfactory and seemed unaffected by the long dosage intervals. Bacteriological cure was achieved in 5 of 11 infections associated with chronic pyelonephritis or analgesic nephropathy and in 4 of 5 urinary infections in patients with renal transplants. Treatment failures could be accounted for by obstructive lesions, stones, and in one transplanted patient by infection localized to her own shrunken kidneys. No instance of ototoxicity or nephrotoxicity due to netilmicin could be detected. Netilmicin administered according to the dosage schedule described can be recommended for ambulatory treatment of tenacious, recurring urinary tract infections due to gram-negative bacteria and refractory to cure by the usual oral antibiotic therapy.

Drug Administration Schedule↗
PubMed1982

[Slower lidocaine elimination and dose adjustment in patients with heart failure].

In 21 patients with acute coronary artery disease the influence of cardiac failure on the elimination of lidocaine (L) was evaluated by repeated serum level measurements during and after a therapeutic L-infusion. Lidocaine clearance (Cl) was less than 8 ml/min/kg in 9 of 13 cases with congestive heart failure (CHF), while in 7 out of 8 patients without CHF Cl-values were 8-12 ml/min/kg. Due to wide interindividual variability in the CHF group, however, mean values were not significantly different: 7.3 +/- 2.9 vs. 9.52 +/- 1.54 ml/min/kg (p greater than 0.05). In 3 patients receiving a simultaneous nitroglycerine infusion Cl was greater than 10 ml/min/kg despite clinical signs of CHF. The t 1/2 of L was significantly prolonged in patients with CHF: 4.29 +/- 2.14 vs. 2.43 +/- 0.58 h (p less than 0.05). It was not possible to determine individual L-dose requirements by bedside clinical examination alone. Serum level monitoring is therefore recommended in order to optimize L-therapy in patients with life-threatening arrhythmias, severe congestive heart failure and hypotension.

Arrhythmias, Cardiac↗
PubMed1982

Population pharmacokinetic parameters in patients treated with oral mexiletine.

A new data analysis approach, NON-MEM, proposed by Sheiner and Beal, has been employed to estimate the population pharmacokinetic parameters of oral mexiletine in patients treated for arrhythmias. 452 serum concentration measurements in 58 patients were available for analysis. 27 patients had congestive heart failure and 8 had abnormal liver function tests at the time of the study. The population averages of the pharmacokinetic parameters and their interindividual variability were: oral total body clearance (Cl) 0.38 l/h/kg +/- 43% (C.V.), apparent volume of distribution (Vd) 5.3 l/kg +/- 40%, absorption rate constant 3.1 h-1 +/- 205%, absorption time-lag 0.3 h. Congestive heart failure and sex did not show a significant effect on Cl and Vd; the number of patients with severe liver function impairment was too small for a definite conclusion. Normalizing Cl and Vd for body weight significantly decreased their interindividual variability. Based on these results, a dosage regimen is recommended which is expected to produce a "therapeutic" serum concentration (0.8-2 mg/l) in over 60% of patients. Because of its unique features, which allow estimation of pharmacokinetic parameters and their variability from fragmentary patient data, the NONMEM system has great potential applicability to clinical pharmacokinetic studies.

Aged↗
PubMed1982

Homogeneous enzyme immunoassay for netilmicin.

A newly developed homogeneous enzyme immunoassay for the determination of netilmicin in serum was evaluated and compared with a radioenzymatic assay. A total of 102 serum samples from patients treated with netilmicin were measured by both methods. This comparison showed an excellent correlation (r = 0.993). The enzyme immunoassay has proved to be precise, accurate, and specific. Because of its rapidity and the ease of performance, this method is a useful alternative to current assays for monitoring serum netilmicin concentrations.

Gentamicins↗
PubMed1982

Theophylline serum concentration and therapeutic effect in severe acute bronchial obstruction: the optimal use of intravenously administered aminophylline.

In 20 patients with acute exacerbation of bronchial obstruction, the therapeutic effect of high (20 mg/L) and low (10 mg/L) serum concentrations of theophylline was compared in a double-blind randomized study. The theophylline dose, administered as a continuous aminophylline infusion, was individually adjusted by means of repeated measurements of serum concentrations. At 28 h after starting therapy the high concentration group showed a significantly greater improvement in pulmonary function as assessed by FEV1 (0.57 +/- 0.52 L (mean +/- SD) versus 0.1 +/- 0.18 L, p less than 0.01) and FVC (1.0 +/- 0.65 L versus 0.01 +/- 0.66 L, p less than 0.02). As a measure of the overall clinical improvement, the time during which intravenous therapy was required was also shorter in the high-dose group (61.7 +/- 25.8 h (mean +/- SD) versus 116 +/- 49.7 h, p less than 0.02). The occurrence of side effects in the two groups was not significantly different. In patients with severe acute bronchial obstruction, serum theophylline concentrations around 20 mg/L seemed to offer a definite therapeutic advantage, thus, routine serum concentration measurements and the use of accurate infusion devices for optimal dose adjustment may be justified.

Adult↗
PubMed1982

Serum concentration and antihypertensive effect of slow-release verapamil.

Serum concentrations of verapamil and its main metabolite norverapamil as measured by high-pressure liquid chromatography were compared with blood pressure responses to long-term antihypertensive therapy with a slow-release formulation of verapamil (120-240 mg b.d.) in 14 patients with essential hypertension. Trough and peak verapamil concentrations varied widely, but in individual patients relatively stable drug levels were maintained up to 8 h after a morning dose. Even at 24 h verapamil concentrations greater than 50 ng/ml were present in 11 of 14 cases. Norverapamil concentrations were higher than those of the parent drug throughout the entire dosage interval. Blood pressure reduction less than or equal to 160/95 mm Hg was achieved in 13 patients by verapamil alone, but a direct relationship between drug levels and antihypertensive effects or the patient's age was not demonstrable. Despite a marked decrease of verapamil concentrations, blood pressure reduction persisted up to 24 h after the last dose. Thus, after repetitive dosing of slow-release verapamil, adequate blood pressure control is achieved by giving the drug twice (or perhaps once) daily.

Adult↗
PubMed1981

[Relation of dose, serum concentration and side effects in intravenous aminophylline therapy].

Routine intravenous aminophylline therapy was monitored by drug level measurements in 45 hospitalized patients with chronic obstructive bronchitis. Only 44% had theophylline serum concentrations (Cp) in the optimum range (10-20 mg/l), while in 36% of patients potentially toxic Cp values were observed. The incidence of side effects was related to theophylline serum concentration: 78% in cases with Cp greater than 30 mg/l against 24% in cases with Cp less than 20 mg/l. Theophylline toxicity occurred most frequently in elderly patients with cardiac failure, who had markedly reduced theophylline clearances. To avoid excessive drug accumulation the usual aminophylline dose should be reduced by 50% when clinical signs of cardiac failure are present. In addition, measurement of theophylline serum concentration is often necessary for optimum dosage adjustment.

Adolescent↗
PubMed1981

[Diagnosis and therapy of cardiac tamponade. An analysis of 50 patients].

Cardiac tamponade (CT) is a life-threatening complication of pericardial effusion which must be diagnosed and treated as soon as possible. The diagnostic value of the various symptoms and clinical signs, and the problems of pericardial puncture and drainage are reviewed in a group of 50 patients. Dyspnea was the most frequent symptom (92%), while elevated jugular venous pressure and pulsus paradoxus were the dominant findings in all patients. Non-specific enlargement of cardiac shadow on chest x-ray (98%) and low voltage in the electrocardiogram (62%) also provided important diagnostic information. However, echocardiography was the most reliable method of confirming the presence of pericardial fluid and assessing its quantity. The underlying cause of CT was most often malignant tumor (58%), followed by uremia (16%), idiopathic pericarditis (12%) and post-cardiotomy syndrome (10%). Removal of the pericardial fluid resulted in rapid improvement in all cases. Left parasternal drainage under echocardiographic control in 23 patients with a broad (greater than 10 mm) anterior echofree space proved to be a rapid and safe alternative to subxiphoidal puncture or surgical drainage. Longterm prognosis depends on the underlying disease. As might be expected, survival time is usually short in malignant pericarditis; however, even such cases warrant active treatment to relieve subjective symptoms.

Adult↗
PubMed1981

[Use of antibiotics in hospitalized patients. Comparison of medical, surgical and gynecological units].

Antibiotic use was evaluated retrospectively in 1229 patients of a university hospital (Basle, Switzerland). The frequency with which antibiotics were prescribed, the indication, duration of treatment, side-effects and clinical results were compared in relation to various subspecialities. 38.1% of medical, 36.4% of surgical and 24.4% of gynecological patients received one or more antibiotic during hospitalization. The main indications for antibiotic treatment were respiratory infection (57.8%) and urinary tract infections (21%) in medical patients, prophylaxis (38%) and urinary tract infections (23%) in surgery, and urinary tract infections (43%) and adnexitis or endometritis (23%) in gynecology. Amoxycillin or penicillin G were the first-line drugs for respiratory infection, cotrimoxazole for urinary tract infection and cefalothin or cefacetrile for surgical prophylaxis. Patients with endometritis or adnexitis usually received clindamycin in combination with an aminopenicillin. Aminoglycosides were employed in only 9.5% of antibiotic courses. Information on adverse reactions in the records was scanty, only generalized exanthem (13 cases) and nausea/vomiting (2 cases) being specifically mentioned. The therapeutic result was classified by the responsible physician as cure in 50.8% or definite improvement in 16.4% of patients. However, in 118 cases (29.7%) the contribution of antibiotics to the clinical outcome could not be evaluated retrospectively.

Anti-Bacterial Agents↗
PubMed1981

Predicting individual phenytoin dosage.

Most previously suggested methods for predicting phenytoin dosage from steady-state drug levels (Cpss) measured in the clinical setting fail to fully exploit all relevant (population) information. A bayesian prediction method, applicable to any drug, is available. It appropriately combines all types of information. In this paper, we compare the Bayesian method as applied to phenytoin to two other prediction methods (and a baseline, nonfeedback one). Actual doses are compared to predictions in 49 patients. Each method is optimized, as far as possible, for the test data. The comparison favors the Bayesian method. Since each of the other prediction methods for phenytoin can be shown to be a theoretically suboptimal special case of the Bayesian one, the superiority of the latter may be a general phenomenon. Because the pharmacokinetic model linking steady-state phenytoin levels and dosage is so simple, a good approximation of the general Bayesian method can be implemented as a graphical device, or as a program for a programmable calculator. We present and describe both of these approximations.

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