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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 127-131 
    ISSN: 1573-7241
    Keywords: beta blockers ; ketanserin ; bendrofluazide ; elderly hypertensives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Beta-adrenoceptor antagonists (beta blockers) are a well-established first-line treatment for hypertension, but they have been associated with unwanted symptoms including cold extremities, lethargy, and nightmares. Ketanserin is a serotonin S2-receptor antagonist that has previously been shown to reduce blood pressure in hypertensive patients by reducing systemic vascular resistance. Hypertensive patients whose sitting diastolic blood pressure was ≥95 mmHg, despite at least 4 weeks therapy with an optimal dose of beta blocker, were selected for the study. The beta-blocker dose remained constant throughout the study, but patients were randomly allocated to receive ketanserin 20 mg twice daily, ketanserin 40 mg twice daily, or bendrofluazide 5 mg each morning plus placebo at night in addition to the beta-blocker therapy. One hundred and forty two patients completed the symptom questionnaire at randomization and after 12 weeks treatment. The treatment groups were well matched for age, sex, weight, and blood pressure. Blood pressure was reduced significantly by all treatments, and there were no between-group differences. Bendrofluazide adversely affected alertness (p〈0.05) and concentration (p〈0.01) whereas ketanserin had no significant effect and the ketanserin 20 mg twice daily group had better concentration than the bendrofluazide group (p〈0.05). Ketanserin treatment reduced the incidence of nightmares (p〈0.05 for 20 mg twice daily and 40 mg twice daily) and was an improvement over bendrofluazide treatment in this respect (p〈0.05). Leg pain on walking (p〈0.01) and at rest (p〈0.05) was worse on bendrofluazide, whereas ketanserin treatment 20 mg twice daily improved incidence of leg pain on walking (p〈0.05) and was an improvement over bendrofluazide treatment in this respect (p〈0.05). Incidence of flushing was reduced by ketanserin 40 mg twice daily (p〈0.01) more effectively than by bendrofluazide treatment (p〈0.05). The present study indicated that serotonin antagonism by ketanserin can reduce the nightmares and sleep disturbance and reverse the deterioration in peripheral circulation that may accompany treatment with beta blockers.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 93-95 
    ISSN: 1573-7241
    Keywords: QT interval ; potassium-losing diuretics ; ketanserin ; hypokalaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ketanserin is a serotonin S2-receptor antagonist that lowers blood pressure and inhibits platelet aggregation. Ketanserin treatment is also associated with prolongation of the corrected QT interval. The recently reported Prevention of Atherosclerotic Complications with Ketanserin (PACK) trial confirmed this prolongation of QT and also revealed a significant excess of deaths in patients receiving ketanserin together with potassium-losing diuretics. The investigators suggested that this excess of deaths may have been attributable to exacerbation of hypokalemia-induced ventricular arrhythmias by the repolarization-prolonging effect of ketanserin. However, drugs that prolong the QT interval may affect ventricular ectopic activity beneficially, and our study was designed to evaluate the effects of ketanserin on ventricular ectopic activity. Twenty patients (18 male, 2 female) aged 42–73 years were studied, each having at least 15 ventricular ectopic beats/hour. The study design was a double-blind, cross-over comparison of ketanserin, 40 mg twice daily, and placebo, both given for 1 week. Ventricular ectopic activity was assessed by 48-hour Holter electrocardiogram (ECG) tapes at the end of each treatment period. Ketanserin treatment was associated with prolongation of repolarization, as reflected by the significant mean increases in both QT interval (+30 ms; p〈0.001) and corrected QT interval (+20 ms; p〈0.05). The mean overall degree of ventricular ectopic activity, as represented by a score based on the Lown classification, was significantly reduced (p〈0.05). This was associated with a concordant improvement in the individual indices of ectopic activity. Our results show that ketanserin significantly suppressed ventricular ectopic activity in our normokalemic patients. It would seem that the implications of ketanserin treatment for cardiac rhythm depend on the electrolyte environment. The drug appears to be potentially beneficial at normal potassium concentrations, but may carry the possibility of precipitating ventricular arrhythmias in the face of hypokalemia.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 89-92 
    ISSN: 1573-7241
    Keywords: ketanserin ; pharmacokinetics ; hospital ; general practice ; elderly hypertensive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ketanserin is a serotonin S2-receptor antagonist that is an effective antihypertensive agent with a greater blood pressure reduction in older patients. We have reviewed the data from two studies of ketanserin pharmacokinetics in elderly patients, one in general practice (GP) and one in hospital patients. We compared these data with the results from two of our previous studies in young volunteers. The purpose was to determine whether the enhanced efficacy of ketanserin in elderly hypertensive patients could be due to altered pharmacokinetics. After a single dose of ketanserin, elderly hypertensives showed about a 60% increase in bioavailability compared with young volunteers. This increase is likely to be explained by a reduced metabolism of ketanserin on first pass through the liver. The elimination half-life of ketanserin was found to be longer in elderly hospital outpatients, but not in our elderly subjects in general practice. This prolongation of the elimination half-life of ketanserin appears to be unrelated to age, since the hospital outpatient elderly and elderly subjects in general practice were of similar ages. The elimination half-life of ketanserinol was longer in the hospital elderly subjects. This probably reflects a slight diminution of renal function in the elderly hospital outpatients, resulting in reduced clearance of ketaserinol. The peak and trough ketanserin concentrations were similar in young and elderly subjects during chronic treatment, and it is therefore unlikely that the increased efficacy of ketanserin in elderly patients is due to altered pharmacokinetcs.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 115-117 
    ISSN: 1573-7241
    Keywords: elderly hypertensives ; ketanserin ; efficacy tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly, and it is in this group of patients that the maximum benefit of treatment might be expected. The present study was designed to study in detail the efficacy and tolerability of ketanserin in an elderly population. Seventeen elderly (〉 70 years) patients with a lying systolic blood pressure of 160 mmHg and/or a diastolic blood pressure of ≥ 90 mmHg were included in the study. For the 12 patients who completed the study, the mean blood pressure was significantly reduced on ketanserin compared with placebo (p〈0.001) in the supine and erect positions. The mean net changes in blood pressure after 8 weeks were 21/17 mmHg and 23/16 mmHg erect. Heart rate was also significantly reduced (p〈0.001) by a mean of 8 beats/min lying and 9 beats/min erect. Analysis of ambulatory 24-hour ECG tapes showed no significant effect of ketanserin on heart rhythms. Ketanserin therapy had no significant effect on routine hematology, plasma electrolytes, biochemistry, or urinalysis. Total exchangeable sodium and potassium and body weight were also unchanged. On ketanserin treatment, the overall quality of life score was significantly improved (p=0.002; analysis of variance on log transformed data) compared with the placebo phase.
    Type of Medium: Electronic Resource
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