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  • 1
    ISSN: 1432-1041
    Keywords: d-propoxyphene ; norpropoxyphene ; pharmacokinetic changes ; deep peripheral compartment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
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  • 3
    ISSN: 1432-1041
    Keywords: dextropropoxyphene ; norpropoxyphene ; pharmacokinetics ; single dose ; multiple dose ; prediction ; saturation ; auto-induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of dextropropoxyphene (DP) and its main metabolite norpropoxyphene (NP) were studied in 6 healthy male subjects after a single oral dose of 195 mg DP HCl, and during and after 12 daily single oral doses of 195 mg DP HCl. The kinetics varied up to five-fold between individuals after the single dose, the apparent mean elimination half-life (t1/2) was 16 h for DP and 29 h for NP. The mean apparent overall plasma clearance (CL) for DP was 2.61/min. There was no systematic difference in DP clearance between the single and multiple doses, but the accuracy of individual predictions from single to multiple doses was poor, probably because of imprecise determinations of the AUC and t1/2 in the single dose experiments. The individual correlation between single and multiple dose kinetics was good for NP, although the predicted plasma levels during steady state were significantly higher than the observed levels (mean AUCss/AUCsd: 0.81). There was no sign of saturation kinetics on repeated administration. In fact, autoinduction, resulting in significantly lower plasma concentrations after treatment for 1 week was found for NP and was indicated for DP. On discontinuing DP after 12 days of treatment, the apparent mean t1/2 of DP was 23 h and of NP 25 h.
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  • 4
    ISSN: 1432-1041
    Keywords: clinical pharmacology ; European Medical Schools ; teaching ; organization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A World Health Organisation (European Regional Office) working party has been established to review the progress of clinical pharmacology in European countries. As part of this review a questionnaire on the teaching of chlinical pharmacology was sent to the Deans of all 350 medical schools in the region. Very few replies were received from U.S.S.R., Greece and Portugal and these countries' returns were not analysed further. The overall compliance rate (excluding these countries) was 82% with a figure of 84% from Western Europe and 74% from Eastern Europe. An average time of 96 h (range 0–320) was devoted to pharmacology teaching in the medical curriculum in Western Europe with 124 (0–240) h in Eastern Europe. In contrast 28 h (0–210) was devoted to clinical pharmacology teaching in Western Europe and 27 h (0–90) in Eastern Europe. On average in Western Europe each medical school had 2 individuals trained in clinical pharmacology with 1.3 posts in the subject and the figures for Eastern Europe were 2.3 and 1.1 respectively. However these figures hide a wide variance in the teaching of clinical pharmacology. Particularly in Western Europe there are a number of medical schools in Italy, Spain and the Federal Republic of Germany (FRG) where clinical pharmacology is not taught and there is a dearth of individuals trained in the subject. Every effort to encourage clinical pharmacology and its teaching should be made, particularly in these countries.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Elderly patients ; Mianserin therapy ; Plasma level monitoring ; Orthostatic blood pressure ; 24-h Electrocardiographic recording ; Systolic time intervals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cardiovascular effects of the tetracyclic antidepressant drug mianserin were examined in a prospective study including ten elderly depressed patients (age 60–77 years). During 1 week on placebo and 5 weeks on mianserin, 60 mg per day, orthostatic blood pressure testing, recording of standard electrocardiogram, 24-h electrocardiographic recording and systolic time intervals were carried out along with frequent monitoring of plasma levels of mianserin (13–57 μg/l) and the primary metabolite desmethylmianserin (7–27 μg/l). Mianserin caused a significant increase in orthostatic systolic blood pressure drop, and this correlated well with the plasma mianserin levels (r s=0.70). There were no significant changes in supine blood pressure or in orthostatic changes in heart rate. No cardiac conduction disturbances or arrhythmias were provoked, but mianserin caused changes in systolic time intervals indicating impairment of left ventricular contractility and performance. Like tricyclic antidepressants mianserin should thus be used with caution in patients with latent or overt cardiovascular disease.
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  • 6
    ISSN: 1432-2072
    Keywords: Serotonin (5-HT) uptake inhibition ; Anti-depressants ; Citalopram ; Plasma levels ; Long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a phase II study the antidepressive effect of citalopram, a selective and potent serotonin reuptake inhibitor, was examined in 20 endogenously and three nonendogenously depressed hospitalized patients. Four endogenously depressed patients dropped out due to deterioration early in the treatment period. The remaining 19 patients completed a 4–6 week treatment schedule. Of 16 endogenously depressed patients 11 responded, one was a partial responder and four did not respond. Of three patients with non-endogenous depressions, two responded and one did not respond. No correlation between plasma citalopram concentration and therapeutic outcome was found. Fourteen patients were given maintenance treatment for 8–113 weeks. One patient developed depression when the dose was reduced from 60 to 40 mg and one patient became manic. After discontinuation of treatment seven patients had a depressive relapse and six of these who again were treated with citalopram responded completely. Side effect rating scores of symptoms usually associated with depression or treatment with tricyclic antidepressants declined during treatment. Three patients complained of increased need of sleep for a period after several weeks of treatment. Apart from an unspecific, transient rise in liver enzymes in two patients, detailed biochemical laboratory tests were all normal. There were no effects on blood pressure, pulse rate, orthostatic reaction, or electrocardiogram. One patient took an overdose of citalopram resulting in plasma levels about six times higher than the average therapeutic level, but there were no signs of severe toxicity. In particular no change in consciousness, electrocardiogram or blood pressure occurred. Pharmacokinetic variables such as dose schedule, steady state kinetics, and metabolism are discussed.
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  • 7
    ISSN: 1432-2072
    Keywords: Serum levels ; Depot neuroleptic ; Zuclopenthixol decanoate ; Schizophrenia ; Clinical state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum concentrations of zuclopenthixol were determined in a group of 20 patients treated with a depot preparation, zuclopenthixol decanoate in Viscoleo. Clinical assessments according to a Clinical Global Impression (CGI) scale, Comprehensive Psychological Rating Scale (CPRS), 16-item subscale for schizophrenia, and the UKU side effect scale were performed on 3 consecutive days of injection. The serum concentrations showed a limited individual variation and a high and significant correlation between dose and serum concentration. One patient had a particularly high serum concentration of zuclopenthixol. This patient also had an elevated concentration of the N-dealkyl metabolite, but a low concentration of the sulphoxide. For serum concentrations versus clinical state and side effects some significant correlations were found. All correlations were positive, which means that the higher the serum concentration the poorer the clinical state of the patient. We think that this probably reflects a common clinical pattern of increasing the dose, when the antipsychotic response is unsatisfactory. The study also showed that for moderately ill patients, who were given the optimum dose of drug, the subgroup of patients not experiencing side effects had significantly lower serum concentrations than the subgroup with side effects.
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  • 8
    ISSN: 1432-2072
    Keywords: Elderly patients ; Antidepressive treatment ; Orthostatic blood pressure ; Systolic time intervals ; 24-hour ambulatory ECG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cardiovascular effects in elderly depressed patients (age 62–78 years) treated with imipramine (N=11) or nortriptyline (N=10) were recorded by monitoring of heart rate, blood pressure, systolic time intervals, standard ECG and 24-h ECG. The two drugs exhibited distinctly different cardiovascular reactions. The use of imipramine was severely limited by orthostatic hypotension occurring at subtherapeutic plasma levels, which resulted in falls with fracture in two patients. In contrast, nortriptyline at therapeutic drug levels did not significantly influence orthostatic blood pressure regulation. Nortriptyline caused moderate changes in systolic time intervals, indicating impairment in myocardial contractility. This effect was not seen with imipramine, but a majority of the patients did not reach therapeutic plasma levels because of the blood pressure reactions. Neither imipramine nor nortriptyline induced changes in cardiac conduction time measurements or arrhythmias. In addition to the blood pressure reactions, the use of imipramine was complicated by dose dependent kinetics.
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  • 9
    ISSN: 1432-2072
    Keywords: Imipramine ; Nortriptyline ; Elderly ; Dose dependent kinetics ; Depression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a group of elderly depressed patients treated with imipramine (50–200 mg/day), six patients had the dose changed after 1–3 weeks of treatment. In all cases an increased dose resulted in a considerably disproportional rise in the plasma level of the active metabolite desipramine. In a group of elderly depressed patients treated with nortriptyline (40–100 mg/day) the dose/plasma level ratio could be examined in 6 patients, and there was no tendency towards a disproportional rise in plasma level, when the dose was raised. Dose changes, thus, may result in unpredictable changes in plasma levels during imipramine treatment and therapy control by plasma level monitoring may be difficult in these patients. Additional treatment with perphenazine (8–16 mg/day) to patients on imipramine (N=3) or nortriptyline (N=2) caused a marked rise in drug levels for imipramine in particular affecting the desipramine levels.
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  • 10
    ISSN: 1432-2072
    Keywords: Depression rating ; Improvement scores ; Hamilton Depression Scale ; Antidepressant treatment ; Effect monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A total of 97 patients, who participated in two studies on the relationship between the clinical effect and plasma levels of imipramine and clomipramine, were examined for improvement curves by use of weekly ratings on the Hamilton Depression Scale (HDS). Although we confirmed that our six-item HDS subscale, in contrast to the total 17-item HDS, was a one-dimensional measure of depression, the Rasch analysis showed that the weekly improvement in subscale scores only applied to the individual patient, i.e. an average improvement curve for a group of depressed patients is an abstraction to which the individual curves cannot be transferred. Our results indicate, however, that when the subscale scores are transformed into three clinical categories of depression: no, mild (minor), moderate/-severe (major) they could be described by a common improvement curve for all patients. This is illustrated by the percentage of patients who, week to week, changed from major to minor or no depression, or from minor to no depression. We found no specific improvement pattern for imipramine or clomipramine which could be used diagnostically. There is reason to assume that patients completing a controlled trial necessarily will follow a monotonic improvement curve, and the improvement pattern of all patients fulfilling the entry criteria should, therefore, always be reported. The present study thus indicates that calculation of average improvement curves is neither clinically nor statistically meaningful, and should be replaced by measures of changes in number of patients in different main severity categories, or by the final rating score. No difference in outcome between imipramine and clomipramine was shown neither on the subscale nor on the 17-item HDS.
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