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  • 1
    Electronic Resource
    Electronic Resource
    SOTALOL AS A HYPOTENSIVE AGENT IN PREGNANCY (1980)
    Oxford, UK : Blackwell Publishing Ltd
    BJOG 87 (1980), S. 0 
    Details
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sotalol, a beta-adrenoceptor blocking drug, was administered to 12 hypertensive pregnant women. The concentration of the drug was assayed in samples of maternal plasma, amniotic fluid and mixed umbilical cord plasma at delivery and, in five mothers who elected to breast feed, in paired samples of maternal plasma and breast milk. Sotalol reduced blood pressure effectively at a mean daily dose of 433·1±54·1 mg but crossed the placental barrier. The mean maternal: fetal plasma concentration ratio was 1:1·05 and the mean amniotic fluid concentration was 7·0±2·7 μg/ml. Delivery occurred at mean gestational age of 37·7±0.7 weeks; 12 infants were liveborn with a mean weight of 2·8±0·1 kg and eight of them had no significant neonatal problems. Of the other four, two died from severe congenital anomalies, one had perinatal asphyxia and one mild transient hypoglycaemia. High sotalol concentrations were found in breast milk (mean plasma: milk ratio was 1:5·4) raising the possibility of pharmacological effect in the newborn infant. The results suggest that sotalol adequately controls blood pressure in hypertension complicating pregnancy but because, unlike results from the pregnant ewe, it crosses the human placental barrier it offers no apparent advantages over other beta-adrenoceptor antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-0528.1980.tb04618.x
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  • 2
    Electronic Resource
    Electronic Resource
    THE UTERINE AND CARDIOVASCULAR EFFECTS OF SALBUTAMOL AND PRACTOLOL DURING LABOUR (1975)
    Oxford, UK : Blackwell Publishing Ltd
    BJOG 82 (1975), S. 0 
    Details
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Intravenous salbutamol, a β-adrenoceptor stimulant, given to nine patients in normal labour, with continuous monitoring of uterine activity and of the maternal and fetal cardiovascular systems, was shown to decrease uterine activity significantly; maternal and fetal heart rates were significantly increased, and maternal systolic and diastolic arterial pressures were significantly decreased during the infusion, although no treatment had to be discontinued because of these effects. Apart from worsening of low back pain during the infusion in one patient, subjective sideeffects were trivial. With the salbutamol infusion continued at an effective maintenance rate, the cardioselective β-adrenoceptor blocking drug, practolol, given intravenously, reduced the maternal heart rate (although not significantly) but it did not alter the fetal heart rate; it also appeared to interfere transiently with the inhibiting action of salbutamol on uterine activity, but cervical dilatation was arrested until the salbutamol infusion was discontinued. At least in five patients, labour remained suppressed until oxytocin was infused intravenously.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-0528.1975.tb00667.x
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  • 3
    Electronic Resource
    Electronic Resource
    Induction of microsomal enzyme activity by flupenthixol in chronic schizophrenics (1982)
    Springer
    Psychopharmacology 78 (1982), S. 147-149 
    Details
    ISSN: 1432-2072
    Keywords: Microsomal enzymes ; Induction ; Dose ; Flupenthixol ; Schizophrenics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of long-term treatment with flupenthixol on hepatic microsomal enzyme activity was studied in 12 chronic schizophrenic outpatients who had been receiving two weekly maintenance doses for at least 6 months. Antipyrine half-life was measured in the 12 patients while they continued to receive the drug. Flupenthixol was then discontinued for 6 weeks and antipyrine half-life was repeated in 7 of the 12 patients. In the 12 patients the plasma antipyrine elimination half-life was 4–24 h (mean 9.73±1.61 h) when receiving flupenthixol and there was a significant negative correlation between antipyrine half-life and the dose of flupenthixol (r=0.582, P〈0.05). In the seven patients to whom antipyrine was given on two occasions, antipyrine half-life was 7.33±1.07 h and 12.04±1.87 h on and off flupenthixol treatment respectively. The clearance significantly decreased when flupenthixol was discontinued, but there was no change in the apparent volume of distribution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432253
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  • 4
    Electronic Resource
    Electronic Resource
    Observations on the efficacy and pharmacokinetics of sotalol after oral administration (1976)
    Springer
    European journal of clinical pharmacology 9 (1976), S. 367-372 
    Details
    ISSN: 1432-1041
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606550
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  • 5
    Electronic Resource
    Electronic Resource
    Central effects of repeated administration of atenolol and captopril in healthy volunteers (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 23-28 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; Captopril ; Central effects ; short term administration ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The central effects of atenolol (50 mg tds) and captopril (50 mg tds) ingested for a period of seven days were studied in ten healthy volunteers. A placebo and two active control drugs, methyldopa (250 mg tds) and oxazepam (10 mg), were included in the design. Oxazepam was ingested on the seventh day only, with a placebo being taken on the preceding six days. On the seventh day, central effects of the drugs were tested at 10.00–11.00 h (session 1), immediately before the subjects' last dose of each drug and at 2.5–3.5 h after the final dose of each drug (1330–1430 h, session 2). Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. Recordings of the EEG and body sway were carried out. Neither atenolol nor captopril altered performance at any of the skills tested. There were no effects on subjectively assessed alertness or mood with captopril, while atenolol significantly increased wakefulness in session 2 and when the two sessions were meaned. Similarly, captopril did not modify body sway, while with atenolol there was a significant decrease in activity in the frequency range 1.0–2.75 Hz from session 1 to session 2. Both captopril and atenolol modified the electrical activity of the brain, with captopril increasing delta and theta activity and atenolol reducing delta, alpha and beta activity. Methyldopa significantly increased the number of involuntary rest pauses in the finger tapping task, and the choice reaction time from session 1 to session 2. There was a decrease in passivity during the first session and an increase in wakefulness in session 2 with methyldopa. This drug also decreased body sway in the frequency range 1.0–2.75 Hz activity in session 2, while oxazepam decreased bodys was at 1.0 to 2.75 Hz and increased activity at 2.5–3.0 Hz in session 2. Oxazepam reduced delta, theta and alpha content of the EEG. The present study has been unable to demonstrate any development of adverse central effects with captopril over a period of 7 days of drug ingestion. With atenolol adverse effects were present following short term dosing but were not more pronounced than with acute ingestion seen in previous studies. However effects on the electrical activity of the brain with atenolol remained after 7 days suggesting that the changes reported previously with single ingestions do not disappear.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195911
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  • 6
    Electronic Resource
    Electronic Resource
    A simple aid to digoxin prescribing (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 441-445 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; nomogram ; prescribing aid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have designed a simple nomogram for predicting digoxin dosage and have tested it prospectively in two consecutive studies. These were both conducted in hospital inpatients who were not already taking digoxin but who required drug therapy for atrial tachyarrhythmias and/or cardiac failure. Study I. Sixty-seven patients received digoxin according to the nomogram and 50 completed the ten day course of the study. Fortyone of these patients were eligible for the final analysis. On the tenth day of treatment, 28 patients were within the therapeutic range for plasma digoxin (0.8 to 2.0 ng·ml−1), 12 were subtherapeutic (〈0.8 ng·ml) and one was potentially toxic (〉2.0 ng·ml−1). Study II. Thirty patients completed the second study. Digoxin was prescribed according to the nomogram with the addition of a dosage correction based on the plasma digoxin level on Day 3. On the tenth day of treatment, 24 patients were within the therapeutic range, one in the subtherapeutic and 5 in the potentially toxic. This simple digoxin nomogram, with or without the Day 3 dosage correction, should prove to be a useful aid to prescribing in patients who do not require rapid digitalisation. It is particularly relevant to elderly inpatients with atrial tachyarrhythmias and/or cardiac failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544232
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  • 7
    Electronic Resource
    Electronic Resource
    The effects of chronic dosing on the β1 and β2-adrenoceptor antagonism of betaxolol and atenolol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 467-471 
    Details
    ISSN: 1432-1041
    Keywords: Betaxolol ; atenolol ; nadolol ; cardioselectivity ; β-adrenocepter antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six normal subjects were given once daily treatment for 15 days with placebo (PL), betaxolol 10 mg (B10), 40 mg (B40); atenolol 100 mg (A100); and nadolol 40 mg (N40). Measurements of β1-adrenoceptorblockade (reduction of exercise heart rate) and of β2-adrenoceptor-blockade (attenuation of isoprenaline induced finger tremor) were made after the first, eighth and fifteenth doses of each drug. Plasma concentrations showed dose related increases between 10 mg and 40 mg doses of betaxolol, and there was significant drug accumulation at steady state compared with after single dosing. The reduction in exercise heart rate (EHR) with B10 was less in comparison with all other treatments. There were no significant differences in effects between single and chronic-dosing for any of the treatments (% reduction EHR compared with placebo, on days 1 and 15): B10 (18.2, 19.0), B40 (28.6, 26.5); A100 (22.7, 23.1); N40 (26.6, 23.8). Dose-ratios for attenuation of isoprenaline-induced finger tremor (IT100) were significantly greater with B40 compared with B10 or A100 (no dose-ratio for finger tremor could be calculated for N40). There were no differences between single and chronic-dosing (IT100 dose-ratios on days 1 and 15): B10 (3.0, 2.5), B40 (4.4, 5.3); A100 (3.0, 3.0). The attenuation of isoprenaline-induced chronotropic response (IH25) by N40 was significantly greater in comparison with all other treatments. IH25 dose-ratios (on days 1 and 15) were as follows: B10 (2.8, 3.6), B40 (5.1, 5.8); A100 (3.6, 3.6); N40 (19.0, 17.4). Thus, despite drug accumulation after chronic-dosing, there was no evidence of any increase in either β1 or β2-adrenoceptor antagonism at steady-state in comparison with after single-dosing. The apparent dissociation between plasma concentration and β-adrenoceptor antagonism after chronic-dosing my be a consequence of β-adrenoceptor up-regulation, resulting in partial attenuation of β-blockade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315224
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  • 8
    Electronic Resource
    Electronic Resource
    A dose-ranging study to evaluate the β1-adrenoceptor selectivity of bisoprolol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 135-139 
    Details
    ISSN: 1432-1041
    Keywords: Atenolol ; bisoprolol ; β-adrenoceptor ; cardioselectivity ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose-ranging study was performed to compare the β1-adrenoceptor selectivity of bisoprolol with that of atenolol and nadolol. Seven normal subjects (mean age 26 y) were given single oral doses of bisoprolol 5 mg (B5), 10 mg (B10), 20 mg (B20); atenolol 50 mg (A50), 100 mg (A100); nadolol 40 mg (N40); and placebo (PL), in a single blind randomised cross-over design. β2-adrenoceptor responses were assessed by attenuation of finger tremor and cardiovascular responses to graded isoprenaline infusions. Dose-response curves were constructed, and doses of isoprenaline required to increase finger tremor by 100% (IT100), heart rate by 25 beats/min (IH25), SBP by 25 mm Hg (IS25), cardiac output by 35% (IC35), and decrease DBP by 10 mm Hg (ID10), after each treatment were calculated. These indices were compared with placebo response and expressed as dose-ratios. Exercise heart rate (EHR) was used to assess β1-adrenoceptor blockade. There were dose-related increases in plasma concentrations of bisoprolol and atenolol. Reduction of EHR was significantly less with B5 (16.8%) in comparison with all other treatments: B10 21.9%, B20 23.1%; A50 22.5%, A100 22.6%; N40 22.9%. There were small but significant reductions in isoprenaline-induced tachycardia with bisoprolol and atenolol, although mean dose-ratios were considerably less in comparison with N40 (IH25 dose-ratios): B5 2.55, B10 3.18, B20 3.93, A50 2.91, A100 4.89, N40 17.23. There were similar patterns for the other isoprenaline responses. These results show that conventional doses of bisoprolol (10 mg) and atenolol (50 mg) produced equal antagonism of β1 and β2-adrenoceptors, and therefore possess equal degrees of β1-adrenoceptor selectivity. Increasing doses of bisoprolol and atenolol were associated with partial loss of selective β1-adrenoceptor blockade, although antagonism of β2-adrenoceptors was significantly less compared with the effects of nadolol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280067
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  • 9
    Electronic Resource
    Electronic Resource
    Plasma theophylline concentrations following the oral administration of microcrystalline theophylline and a new sustained-release theophylline preparation to normal subjects (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 351-354 
    Details
    ISSN: 1432-1041
    Keywords: Theophylline ; sustained-release ; microcrystalline ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma theophylline concentrations have been measured in 14 normal subjects following the oral administration of a microcrystalline theophylline preparation (MT) 187.5 mg every 6 h and a sustained-release theophylline preparation (SRT) 375 mg every 12 h for 5 days. During the 5 days, blood samples were drawn before and 2 h after each morning dose with MT, and before and 4.5 h after each morning dose of SRT. On days 1 and 5, more frequent samples were taken during the dose interval. With both preparations, steady-state plasma concentrations were achieved by the third day. The trough levels were significantly higher with SRT than with MT on days 3 and 4, and the levels at 4.5 h after SRT were significantly higher than those measured 2 h after MT on days 3, 4 and 5. Over the terminal 3 days of the study, mean theophylline concentrations with SRT ranged between 11.2 and 15.5 µg/ml at measured trough and peak times, whereas the mean trough levels with MT were always below 10 µg/ml. With adjustment for the dosage differences, the mean ratio of the areas under the plasma concentration/time curves for the final dosage interval for the two formulations (AUCSRT/AUCMT) was 1.29±0.56, suggesting that the SRT preparation was well absorbed. The “mean” steady-state plasma theophylline concentrations (AUC/dose interval) on day 5 were 11.5±4.7 µg/ml with MT and 13.7±5.7 µg/ml with SRT. Nine subjects experienced a total of 35 side-effects whilst taking MT, compared with 10 subjects complaining of 23 side-effects on SRT. These results indicate that, in normal subjects, SRT 375 mg every 12 h exhibited satisfactory sustained-release properties and achieved adequate mean plasma theophylline concentrations during chronic administration. It produced higher plasma levels and a lower incidence of side-effects than the same daily dose of MT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00561394
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sotalol during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 521-524 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; beta-adrenoceptor antagonist ; pregnancy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sotalol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32–36 weeks gestation and when at least 6 weeks post-partum. On both occasions, each volunteer was given sotalol 100 mg intravenously and 400 mg orally in randomised order with at least a 1 week washout period between. Plasma samples were analysed for sotalol using a fluorometric method and the pharmacokinetic profiles investigated. The systemic clearance of sotalol was significantly greater in the antenatal period (2.4±0.3 ml/min/kg) than in the post-natal phase (1.5±0.1 ml/min/kg). The apparent volume of distribution was similar in the two periods: the elimination half-life was 6.6±0.6h ante-natally and 9.3±0.7h post-natally after intravenous drug but the trend for faster elimination was not significant. The elimination half-life after oral administration (about 10h) and bioavailability (about 90%) were not altered significantly by pregnancy. It is suggested that the more rapid clearance of sotalol in pregnancy may be due to increases in renal plasma flow and glomerular filtration rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609896
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