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  • 1
    ISSN: 1432-1041
    Keywords: Digoxin ; diuretics ; drug compliance ; drug utilization ; intoxication ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma digoxin was measured in all patients receiving digoxin (Lanacrist, Draco) in a well-defined low density population area in Sweden. The number of treated patients (n=75) corresponded to 3 % of the population. The average prescribed daily dose of digoxin was 0.25 mg, and the mean plasma concentration (n=74) was 0.85 (S.D. 0.52) ng/ml. Of the concentrations found 3 % were above and 62 % were below the apparent therapeutic range, 1 – 2 ng/ml. The findings were compared with analyses performed in a hospital laboratory (n=300), the majority being inpatients receiving a similar daily dose. In the latter, 22 % had a plasma level above and about 33 % below the apparent therapeutic range. In the former group no difference in plasma digoxin concentration could be demonstrated between patients treated with digoxin (n=34) and those treated with both digoxin and diuretics (n=40). In a group of eight patients plasma digoxin rose significantly after they were informed of the importance of taking their medicine regularly. Poor compliance with prescribed therapy was even documented in patients in cardiac failure.
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  • 2
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Systolic pressor effects after i.v. injection of tyramine (TA) were recorded in 13 patients before and during treatment with nortriptyline (NT) in doses of 1.4–5 mg/kg/day for 3–4 weeks. After NT a several fold decrease in the responsiveness to TA occurred. Patients given the same dose of NT showed markedly different decreases in the responsiveness to TA. There was no correlation between the blockade of the TA pressor effects and the dose of NT employed but there was an excellent correlation between the blockade and the plasma level of NT (p〈0.001 and p〈0.005 respectively). TA pressor effects were not changed in a small control group of depressed patients after treatment with E.C.T. The relationship between kinetics and effects of tricyclic antidepressants is discussed. The steady-state plasma level of NT seems to be an important determinant of its effects.
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  • 3
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 40 depressed patients treated with 25 or 50 mg nortriptyline (NT) t. i. d. for 3 weeks the following circulatory variables were observed prior to and during drug therapy: heart rate and blood pressure at rest (in supine and standing positions), working capacity, ECG at rest and during exercise on a bicycle ergometer. During administration of NT the heart rate increased significantly at rest in both supine and standing positions, but the orthostatic heart rate reaction remained unchanged. Diastolic blood pressure in the supine position rose slightly; in the standing position the pretreatment increase in diastolic pressure was abolished. The positive chronotropic effect did not correlate with the steady-state plasma level of NT. In one patient on NT a right bundle branch block appeared during the work test; in the remaining 39 patients the ECG records at rest and during exercise showed no adverse effects of NT.
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  • 4
    ISSN: 1432-1041
    Keywords: clinical pharmacology ; academic function ; service function ; interdisciplinary nature ; professional discipline ; drug analysis ; drug utilization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: clinical pharmacology ; tasks and aims ; service ; education ; research
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: Clonidine ; alprenolol ; amine metabolites ; cerebrospinal fluid ; hypertension ; noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Lumbar cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline (4-hydroxy-3-methoxyphenyl glycol, HMPG), serotonin (5-hydroxyindoleacetic acid) and dopamine (homovanillic acid) were measured before and during the administration of clonidine or alprenolol to hypertensive patients. The noradrenaline receptor stimulant clonidine significantly decreased the CSF level of HMPG, but there was no consistent change in the concentration of serotonin or dopamine metabolites. Patients on alprenolol showed no change in the levels of these metabolites in CSF.
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  • 7
    ISSN: 1432-1041
    Keywords: prazosin ; hypertension ; central monoaminergic neurons ; monoamine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six hypertensive patients were treated with prazosin up to a final dose of 3–4.5 mg/day. There was a significant reduction of blood pressure. The cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline, dopamine and serotonin were unchanged. This indicates that the antihypertensive effect is not mediated via central monoaminergic neurons as suggested by animal studies.
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  • 8
    ISSN: 1432-1041
    Keywords: Antidepressant ; nortriptyline ; tyramine ; noradrenaline uptake ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This report describes a phase I clinical trial of a new tricyclic imipramine analogue (Leo 640) with a hydrogen atom in one of the N-methylgroups substituted by a p-chlorobensoyl. To get an objective assessment of the effects of Leo 640 we utilized the fact that tricyclic antidepressants inhibit the uptake of tyramine (thereby blocking its indirect sympathomimetic effects) and noradrenaline into peripheral adrenergic nerves. Dose-response (systolic pressor effects) curves for tyramine (TA) were established before and during treatment with Leo 640. Adrenergic nerves from the rat iris were incubated in the patient's plasma drawn immediately before the TA tests. The inhibitory effect of the endogenous plasma level of Leo 640 (and/or its metabolites) on the uptake of3H-noradrenaline (3H-NA) in these nerves was then determined. — Leo 640 was given orally in successively increasing doses (up to 1.1–5.6 mg/kg/day) to fifteen patients with various forms of depression. The duration of treatment was usually 3–4 weeks. Leo 640 caused a blockade of TA- pressor responses. Plasma of all treated patients inhibited the uptake of3H-NA in the rat iris. The results in the two tests were reasonably well correlated (p〈0.01). — The results in the TA- and “rat-iris” tests were compared with those obtained with nortriptyline (NT) in the same dose-range in nine other patients. In comparison with NT, Leo 640 had a more pronounced inhibitory effect on TA-responsesin vivo than of3H-NA uptake in adrenergic nervesin vitro. A possible explanation might be that Leo 640 has an α-receptor blocking effect. — For both Leo 640 and NT, poor correlations were found between the doses (mg/kg) used and the objective effects, when different patients were compared, probably due to marked interindividual differences in pharmacokinetics. — It is concluded that the dose-range of Leo 640 should be similar to that of NT in terms of the effects onperipheral adrenergic neurons.
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  • 9
    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.
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  • 10
    ISSN: 1432-1041
    Keywords: prescription monitoring ; drug dosage ; Sweden ; Jämtland
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Prescribed doses of drugs for which individualisation of dosage is deemed necessary were recorded from one national and one local Swedish prescription monitoring study for the years 1976, 1982 and 1985. Dose patterns were analysed in order to determine whether the practice of individualising drug doses had become more widely adopted by physicians. Amongst drugs eliminated primarily by metabolism, (propranolol and amitriptyline were prescribed in highly variable doses (30-fold or more). The three commonest doses of these agents accounted for about 60% of the prescriptions. In general, doses decreased with increasing patient age. Prescribing practices for piroxicam differed markedly from those of propranolol and amitriptyline, with one fixed dose of piroxicam accounting for about 90% of all prescriptions. For drugs eliminated mainly by renal excretion (digoxin, cimetidine and atenolol) there was an 8–10-fold variation in the prescribed doses. The most frequent dose of these drugs accounted for 40–60% of the prescriptions. Doses of cimetidine and atenolol were lowered only in the oldest patients. The doses of digoxin decreased more evenly with increasing age, and were reduced in elderly patients on long-term maintenance therapy. The difference in digoxin dose between young and old patients increased during the study period. Prescription monitoring as a method for following-up drug usage may be instrumental in evaluating the effect of drug educational efforts.
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