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  • Orthostatic blood pressure  (3)
  • desipramine  (3)
  • Oxazepam  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Mianserin: Cardiovascular effects in elderly patients (1983)
    Springer
    Psychopharmacology 80 (1983), S. 174-177 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427964
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  • 2
    Electronic Resource
    Electronic Resource
    Cardiovascular effects of imipramine and nortriptyline in elderly patients (1981)
    Springer
    Psychopharmacology 74 (1981), S. 360-364 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432748
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  • 3
    Electronic Resource
    Electronic Resource
    Cardiovascular effects of amitriptyline in the treatment of elderly depressed patients (1985)
    Springer
    Psychopharmacology 87 (1985), S. 212-215 
    Details
    ISSN: 1432-2072
    Keywords: Elderly patients ; Antidepressive treatment ; Orthostatic blood pressure ; Systolic time intervals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirteen elderly depressed patients (age 60–82 years) were treated for 5 weeks with a fixed dose of amitriptyline 100 mg (sustained release preparation). In all patients the sum of concentrations of amitriptyline and nortriptyline exceeded 130 μg/l, which is the recommended plasma level. Cardiovascular side effects were recorded by monitoring heart rate, blood pressure, standard ECG and systolic time intervals. During treatment, a transient increase in the supine heart rate was observed without significant changes in the supine blood pressure. The orthostatic drop in blood pressure was markedly increased during treatment without a compensatory increase in heart rate, and these changes remained significant during the whole investigational period. PQ and QRS were significantly increased during treatment, and significant changes in the systolic time intervals were found indicating impairment of myocardial conduction and contractility. In three patients medication was discontinued due to cardiovascular side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431810
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  • 4
    Electronic Resource
    Electronic Resource
    Cortisol and treatment of depression: predictive value of spontaneous and suppressed cortisol levels and course of spontaneous plasma cortisol (1989)
    Springer
    Psychopharmacology 97 (1989), S. 471-475 
    Details
    ISSN: 1432-2072
    Keywords: Antidepressant medication ; Cortisol ; Dexamethasone ; Oxazepam ; Distress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 72 consecutive depressed hospitalized patients afternoon plasma cortisol was measured in three ways before treatment with antidepressants: 1) Spontaneous (n=72), 2) 2 h after oxazepam suppression (45 mg, n=28; 60 mg, n=37) and 3) 16 h after dexamethasone suppression (2 mg, n=71). In addition, spontaneous cortisol was measured after 3 weeks' treatment (n=55) and 5 weeks' treatment (n=36). Both spontaneous and suppressed cortisol levels seemed to have a predictive value in the endogenously depressed patients: complete responders had significantly lower pretreatment cortisol levels compared to poor responders. However, other covarying factors such as distress and age may as well account for the differences in treatment effect. During treatment a significant decrease of spontaneous cortisol was found from about 400 nM in poor responders and 325 nM in complete responders to about 300 nM in all groups. There was a positive correlation between pre- and post-treatment cortisol levels and between pretreatment levels and per cent fall in spontaneous cortisol levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00439550
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  • 5
    Electronic Resource
    Electronic Resource
    Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 679-684 
    Details
    ISSN: 1432-1041
    Keywords: imipramine ; sparteine ; desipramine ; drug oxidation ; monogenic polymorphism ; debrisoquine ; therapeutic outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-five imipramine treated patients were phenotyped with regard to polymorphic drug oxidation using sparteine and/or debrisoquine. During treatment with 100 mg imipramine per day the mean steady-state concentrations and ratios in 28 extensive metabolizers were: imipramine 169 nmol/l; desipramine 212 nmol/l; 2-OH-imipramine/imipramine 0.25; 2-OH-desipramine/desipramine 0.57. The corresponding values in two poor metabolizers were: imipramine 455 and 302 nmol/l; desipramine 1148 and 1721 nmol/l; 2-OH-imipramine/imipramine 0.06 and 0.05; 2-OH-desipramine/desipramine: 0.09 and 0.04 respectively. The metabolic ratios (MR) sparteine/dehydrosparteine and debrisoquine/4-OH-debrisoquine (% of dose in 12-h urine samples) correlated poorly with the imipramine steady-state concentrations during administration of 100 mg per day, but quite well with the desipramine steady-state concentrations. Significant negative correlations were found between sparteine and debrisoquine MR and the 2-OH-imipramine/imipramine and 2-OH-desipramine/desipramine ratios. In most patients the initial dose was changed to obtain concentrations in the therapeutic range, and concentrations for imipramine + desipramine of (mean ± SD) 713±132 nmol/l were achieved in 33 patients. The therapeutic dose was 50 mg per day in one poor metabolizer and ranged from 50–400 mg per day in 32 extensive metabolizers. There was a weak negative correlation between sparteine MR and daily dose. Treatment with imipramine inhibited metabolism of both sparteine and debrisoquine (MR values about doubled), but did not affect the interpatient correlations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608215
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  • 6
    Electronic Resource
    Electronic Resource
    Steady-state levels of imipramine and its metabolites: Significance of dose-dependent kinetics (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 43-49 
    Details
    ISSN: 1432-1041
    Keywords: imipramine ; desipramine ; hydroxymetabolites ; plasma concentration monitoring ; dose-dependent kinetics ; drug interaction ; levomeprazine ; perphenazine ; therapeutic response ; sparteine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seventeen hospitalized patients (age 39–66 years), received a loading dose of 100 mg imipramine HCl and then 50 mg b.i.d. The 12-h plasma concentration at steady-state varied between 40–637 nmol/l for imipramine, 49–1148 nmol/l for desipramine and 89–1603 nmol/l for imipramine + desipramine. Guided by plasma level monitoring, a final therapeutic plasma level between 548–910 nmol/l for imipramine + desipramine was achieved (therapeutic dose range: 50–400 mg/day). Mean time to reach the therapeutic level was 19 days. The mean 2-OH-imipramine/imipramine ratio was 0.24 and mean 2-OH-desipramine/desipramine ratio was 0.56. There was a significant intrapatient correlation between the two ratios, both during 100 mg imipramine/d and at the therapeutic dose level. A low ratio was associated with high imipramine and particularly with a high desipramine level. Well defined steady state levels were established at two different dose levels in 12 patients and at three dose levels in 5 patients. With increasing dose there was a marked and disproportionate rise in the desipramine level and to some extent in the imipramine level. Saturation of imipramine and desipramine hydroxylation appeared to be responsible for the dose-dependent kinetics. Concomitant treatment with levomepromazine and perphenazine in one patient resulted in a significant rise both in imipramine and desipramine concentration, apparently due to inhibition of the hydroxylation. Eleven out of twelve endogenously depressed patients responded completely to treatment, whereas the response was poor in the non-endogenously depressed patients despite optimal drug levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614194
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  • 7
    Electronic Resource
    Electronic Resource
    Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 155-160 
    Details
    ISSN: 1432-1041
    Keywords: imipramine ; desipramine ; quinidine ; sparteine oxidation ; cytochrome P450 isoforms ; genetic polymorphism ; drug interaction ; metabolic clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary On separate occasions 6 extensive metabolizers of sparteine took a single oral dose of 100 mg imipramine and desipramine before and during the intake of quinidine sulphate 200 mg/day. During quinidine the total oral clearance of imipramine on average was reduced by 35%, and that of desipramine by 85%. The clearance of imipramine via demethylation was not significantly reduced during quinidine administration, whereas its clearance by other pathways, largely 2-hydroxylation, was reduced by more than 50%. 2-OH-Imipramine and 2-OH-desipramine were detected in plasma before (maximum concentrations 30–100 nmol · l−1) but not during quinidine. It appears that quinidine is a potent inhibitor of the sparteine/debrisoquine oxygenase, P450dbl, which is responsible for the 2-hydroxylation of imipramine and desipramine, but not of the P450 isozyme responsible for the demethylation of imipramine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558224
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  • 8
    Electronic Resource
    Electronic Resource
    Benzodiazepine-induced sedation and cortisol suppression (1992)
    Springer
    Psychopharmacology 106 (1992), S. 511-516 
    Details
    ISSN: 1432-2072
    Keywords: Plasma cortisol ; Suppression ; Oxazepam ; Nitrazepam ; Sedation ; Reaction times
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The sedative and cortisol suppressing properties of oxazepam (45 and 60 mg) and nitrazepam (10 and 15 mg) were examined in eight healthy male subjects. The most clear differences between oxazepam and nitrazepam were those seen with respect to the time course and until maximal effect (Tmax) of the different measurements. Nitrazepam showed maximal sedation after 1 h, maximal benzodiazepine level (RRA), and reaction time prolongation after 2 h, and maximal cortisol suppression after 3 h. Oxazepam showed maximal sedation after 2 h, maximal benzodiazepine levels, reaction time prolongation and cortisol suppression after 3 h. After administration of oxazepam (both doses) a transient return to baseline levels of cortisol was demonstrated. Whereas the degree of sedation correlated significantly within drug groups with the concurrent benzodiazepine levels, the Tmax of sedation was recorded 1 h earlier than the peak blood concentration (RRA) for both nitrazepam and oxazepam. The time course for cortisol suppression for the two compounds differed clearly from the other measurements and was not related to the peak blood concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244823
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