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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 583-587 
    ISSN: 1432-1041
    Keywords: propranolol ; pregnancy ; beta-adrenoceptor antagonist ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Propranolol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32 and 36 weeks gestation and when at least 6 weeks postparum. On both occasions, subjects were given propranolol 120 mg orally or 10 mg intravenously in randomised order with a minimum washout period of 1 week. Propranolol was assayed in plasma by gas-liquid chromatography with electron-capture detection and the pharmacokinetic parameters were investigated. There were no significant alterations in elimination half-life, clearance or apparent volume of distribution per kilogram antenatally compared with postnatally: bioavailability was also unchanged. It is concluded that the disposition of propranolol is not altered during pregnancy.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-1041
    Keywords: hypertension ; hypertensive therapy ; drug utilization ; therapeutic traditions ; international differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A questionnaire survey based on hypertension case histories was performed among a representative sample of 400 GP's and hospital doctors in Northern Ireland, Norway and Sweden, countries having markedly different utilization of antihypertensive drugs. We found a greater propensity to start antihypertensive drug treatment in Northern Ireland than in Norway and Sweden. This was true both in mild diastolic and isolated systolic hypertension. Yet the utilization of antihypertensive drugs in Sweden is about 60% higher than in Northern Ireland and 30% higher than in Norway. Swedish physicians preferred beta-blockers as their first choice to a greater extent than physicians in Northern Ireland and Norway who selected thiazides more often. In general, the choice of drugs agreed with the sales and prescribing patterns in the three countries. Besides providing more insight in therapeutic traditions the study indicates that the lower prescribing of antihypertensive drugs in Northern Ireland, and to some extent in Norway, compared to Sweden, might be due to differences in true or apparent morbidity.
    Type of Medium: Electronic Resource
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 13 (1978), S. 29-33 
    ISSN: 1432-1041
    Keywords: Microcrystalline theophylline ; chronic obstructive airways disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV1 were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUCss/AUC1, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV1 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1432-1041
    Keywords: diabetes ; therapy ; antidiabetic drugs ; therapeutic traditions ; questionnaire survey ; drug utilization ; international differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sample of 400 physicians in each country was asked to give their opinions on the choice of therapy for three model cases designed to cover the spectrum of treatment — from diet alone to insulin. Significantly more Swedish (65%) than Northern Irish (51%) and Norwegian (52%) doctors suggested diet alone for uncomplicated diabetes recently discovered in a middle aged, overweight man. For symptomatic diabetes in a 76 year old overweight woman with few retinal microaneurysms, the majority of physicians in all three countries suggested treatment with sulphonylureas. Biguanides were here a more common alternative in Northern Ireland than in Scandinavia. For suspected secondary treatment failure in a 63 year old woman with no signs of complications, insulin was suggested by 71% of the Norwegian doctors but only by 44 and 49% of those in Northern Ireland and Sweden, respectively. General practitioners tended to suggest oral treatment earlier and to maintain it longer than hospital physicians. The study has demonstrated significant differences in the approach to treatment of Type II diabetes mellitus between physicians in the three countries. However, the differences were more prominent in the choice of drugs than in the threshold of drug treatment. The results also fit with qualitative but not with quantitative differences in drug sales between the countries, suggesting that important differences may exist in the prevalence of clinically recognized Type II diabetes.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 539-543 
    ISSN: 1432-1041
    Keywords: Atenolol ; Bendrofluazide ; Psychomotor performance ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve normal male subjects received single oral doses of atenolol 100 mg (AT), bendrofluazide 5 mg (BFZ), combined atenolol 100 mg and bendrofluazide 5 mg (AT/BFZ), diazepam 5 mg (Dz), or one of two matching placebos, on each of 6 study days. Tests of psychomotor performance [digit symbol substitution (DSST), letter cancellation (LCT), continuous attention, choice reaction time (CRT), finger tapping, short-term memory, body sway], physiological measurements [critical flicker fusion (CFF), two-flash fusion (2FF)] and subjective assessments using visual analogue scales (VAS), were performed at 2 and 4 hours post-ingestion. Dz (active control) significantly worsened VAS scores at 2 h (+0.68) and reduced DSST scores at both 2 h (−15.0) and 4 h (−11.0). AT and BFZ given alone, each produced significant worsening of VAS at 2 h [AT +1.0; BFZ +1.38], but had no significant effects on performance. In combination however, AT/BFZ at 4 h produced significant impairment of DSST scores (−10.4), reduced finger tapping (−16.5) and increased involuntary rest pauses (+16.5). Despite these effects, no change in VAS scores occurred. In summary, we have demonstrated significant impairment of psychomotor performance in normal subjects with the AT/BFZ combination, which was not evident with the single agents and which occurred in the absence of a change in subjective awareness. These central effects may have important clinical implications for patients taking combined antihypertensive medication.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 46 (1994), S. 511-515 
    ISSN: 1432-1041
    Keywords: Salbutamol ; male ; female ; β2-adrenoceptor ; menstrual cycle ; systemic responses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Extrapulmonary β2-adrenoceptor mediated responses to salbutamol were evaluated in 9 healthy female subjects during the follicular (day 2–4, Visit 1) and luteal (day 21–23, Visit 2) phases of the menstrual cycle, and were compared with those of 9 age-matched male controls. At each visit, salbutamol was given by intravenous infusion for 30 minutes at a dose of 0.2 mg · kg−1 · min−1. Plasma salbutamol concentration and responses in heart rate (HR), finger tremor (Tr), Q-T interval (Q-Tc), serum potassium (K), serum insulin (Ins) and serum glucose (Glu) were measured at baseline and at 10, 20 and 30 minutes after commencing the infusion. Comparisons were made between sexes and between visits for peak responses calculated as percentage change from baseline. Mean plasma salbutamol concentration (ng · ml−1) were not significantly different between males and females on Visit 1: 6.9 (95% CI 6.01, 7.82) vs 7.3 (95% CI 6.4, 8.3), or on Visit 2: 6.9 (95% CI 6.0, 7.8) vs 7.2 (95% CI 6.3, 8.1). On Visit 1, significantly greater responses were demonstrated in females, compared with males for K (as mean difference): 6 (95% CI 1, 11)%, Tr: 17 (95% CI 1, 33)%, Q-Tc: 8 (95% CI 2, 14)% and Ins: 276 (95% CI 71, 481)%. In addition, a significantly greater response was demonstrated in females on Visit 1 compared with males on Visit 2 for HR (as mean difference): 32 (95% CI 1, 63)%, and for Ins: 262 (95% CI 57, 467)%. Thus, despite no difference in plasma salbutamol concentrations, female subjects exhibited greater responsiveness to salbutamol compared with males during the follicular phase of the menstrual cycle. This suggests that in vivo, females have enhanced sensitivity of extrapulmonary β2-adrenoceptors.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 48 (1995), S. 229-233 
    ISSN: 1432-1041
    Keywords: Atenolol ; Nifedipine ; psychomotor performance ; diazepam ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The aim of the present study was to evaluate the central effects of single doses of the β-adrenoceptor antagonist atenolol and the calcium antagonist nifedipine retard, alone and in combination, in normal subjects. Twelve normal males received single oral doses of atenolol 100 mg, nifedipine retard 20 mg, atenolol 100 mg and nifedipine retard 20 mg in combination, diazepam 5 mg (active control), and each of two matching placebos in a double-blind, randomised fashion. Psychomotor performance was assessed using digit symbol substitution, letter cancellation (LCT), continuous attention, choice reaction time, finger tapping, immediate recall and short-term memory. Two flash fusion and critical flicker fusion thresholds were measured and subjective assessments made using visual analogue scales (VAS). Diazepam 5 mg significantly worsened LCT scores at 4h, significantly impaired alertness at 2 h and 4 h, and tended to increase reaction time and impair continuous attention and physiological measurements. Atenolol 100 mg alone significantly reduced alertness at 2 h and 4 h, and also tended to impair physiological measurements. Nifedipine retard 20 mg produced no significant psychomotor effects. Combined atenolol and nifedipine retard administration produced a small but significant improvement in continuous attention and a reduction in body sway, with no adverse effects being evident on performance or subjective awareness. The results suggest that no significant adverse effects on psychomotor performance are produced by single doses of atenolol 100 mg and nifedipine retard 20 mg when given together in normal subjects. The combination may therefore be useful in the treatment of hypertensive patients requiring dual therapy, and in whom adverse central effects are of particular importance.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 35-38 
    ISSN: 1432-1041
    Keywords: atenolol ; benzodiazepines ; nadolol ; propranolol ; psychomotor tests ; β-adrenoceptor antagonists ; lipophilicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tests of psychometric function were performed in young, normal volunteers taking several β-adrenoceptor antagonists. With single doses of atenolol, a cardioselective hydrophilic β-blocker, dosedependent effects were apparent and were maximal at a dose of 200 mg. The lipophilic non-selective β-blocker, propranolol, also produced significant impairment of psychomotor tests but these were inversely related to dose, the longest effects being at a dose of 40 mg but with little effect at 320 mg. Subsequently, a multisubject comparison of propranolol and atenolol confirmed these findings and showed the effects to be of the same order of magnitude as those produced by diazepam. Chronic administration of atenolol 100 mg, nadolol 80 mg and diazepam 5 mg daily for seven days showed some effects with all drugs during the test period; however, these were sporadic rather than persistent. Overall, β-Blockers do appear to have central effects in man which can be demonstrated by psychomotor tests. However, the relevance of these central effects to maintenance therapy and skilled performance is unclear.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 229-235 
    ISSN: 1432-1041
    Keywords: digoxin ; therapeutic range ; intuitive prescribing ; prescribing aid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 37 patients on maintenance digoxin therapy were observed in hospital over an 8 day period. From day 1 to day 8 measurements of plasma digoxin and serum creatinine indicated that these patients were in the equilibrium state with regard to digoxin levels and renal function. Assuming a linear relationship between dose and plasma concentration, it was possible to calculate the doses which would have produced plasma concentrations of 1.5 ng/ml, and at the limits of the ‘usual therapeutic range’, 0.8 and 2.0 ng/ml. Doses obtained from six prescribing aids and those prescribed intuitively by the doctor were then compared. None of the methods used would have resulted in plasma digoxin concentrations within the ‘usual therapeutic range’ in more than 57% of the patients. The physicians' intuitive choice appeared to be better than the doses estimated from prescribing aids, in that they were correct as often as any assisted method, and when wrong tended to prescribe ‘too low’ rather than ‘too high’. The prescribing aids tended to overestimate dosage in many patients, as high as 65% with one. Plasma digoxin concentration measurement would appear to be the only way to ensure adequate therapeutic efficacy and avoid toxicity in patients receiving maintenance digoxin.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1432-1041
    Keywords: antihypertensive drugs ; antidiabetic drugs ; prescribing practice ; utilization ; Northern Ireland ; Norway ; Sweden
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The amount of antihypertensive and antidiabetic drugs based of defined daily doses per 1000 inhabitants per day varies two to three fold between Northern Ireland, Norway, and Sweden. We explored whether variations based on the universally applied defined daily doses might be accounted for by national differences in the actual average prescribed daily doses. Use of prescribed daily doses for antihypertensive drugs resulted in Northern Irish and Norwegian consumption figures which were respectively 40 and 21% lower than the Swedish one, compared to 38 and 25% when defined daily doses were used. The effect of population age-sex differences on the gross defined daily doses per 1000 inhabitants per day figures was determined by applying the Northern Irish or Norwegian age-sex group proportions to Swedish age-sex specific sales data. Taking population differences into account would have resulted in antihypertensive drug use being 21 rather than 38% less in Northern Ireland and 18 rather than 25% less in Norway. Also adjustment for prescribed daily doses left an unexplained difference of 23% between Sweden and Northern Ireland and 14% between Sweden and Norway. For oral antidiabetics use of prescribed daily doses resulted in a Northern Irish — Swedish difference of 62% compared to 67% when defined daily doses were used. Simultaneous adjustment for population differences and prescribed to defined daily dose variations left a 52% difference.
    Type of Medium: Electronic Resource
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