Biomedical subjects
I Dews
Publications and source records attributed to I Dews.
The effects of ketanserin on ventricular ectopic activity in humans.
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, crossover 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 less than 0.001) and corrected QT interval (+20 ms; p less than 0.05). The mean overall degree of ventricular ectopic activity, as represented by a score based on the Lown classification, was significantly reduced (p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
A comparison of single doses of lisinopril and enalapril in hypertension.
Sixteen patients with mild to moderate hypertension were studied in a double-blind crossover comparison of single oral doses of lisinopril 10 mg and enalapril 10 mg. Both drugs caused a marked fall in blood pressure (BP) with a clinically useful effect persisting for 24 h postdose and with no significant difference between treatments in this respect. The time to minimum systolic BP was 2 h (95% confidence limits 0-19 h) longer for lisinopril. The fall in ACE activity at 24 h was 18.5 (8.2-28.8) U/l greater for lisinopril. We conclude that, within the limits of this small study, lisinopril appears to be as effective as enalapril in lowering BP and that it may have a slower onset of action that could be clinically valuable.
Dose-ranging study of isosorbide-5-mononitrate in chronic congestive heart failure treated with diuretics and angiotensin-converting enzyme inhibitor.
The hemodynamic response of isosorbide-5-mononitrate (IS-5-MN) to the addition of the widely used therapy of diuretic drugs and the maximally tolerated dose of enalapril for heart failure was assessed in 8 patients with congestive heart failure (CHF) (New York Heart Association class II and III). The diuretic therapy was furosemide, 40 to 80 mg/day, with or without amiloride, 5 to 10 mg/day. The dose of enalapril was 5 to 20 mg/day. Four hours after the administration of the morning dose of enalapril, a Swan-Ganz catheter was positioned in the pulmonary artery. Patients received increasing doses of IS-5-MN to produce a satisfactory decrease in pulmonary capillary wedge pressure. Two of the first 3 patients studied had a large reduction in blood pressure when given 10 mg of IS-5-MN. Subsequent patients were therefore given an initial dose of 5 mg, the total dose being 5 to 20 mg over 2 hours. Results at baseline and 1 hour after the final dose of IS-5-MN are expressed as mean +/- standard deviation. Both pulmonary artery systolic and diastolic pressures decreased significantly (p less than 0.05) by 12.2 +/- 8.9/4.2 +/- 5.2 mm Hg, from 47.2 +/- 16.0/21.6 +/- 6.0 mm Hg to 35.0 +/- 15.2/17.4 +/- 9.3 mm Hg. Pulmonary capillary wedge pressure decreased by 8.6 +/- 4.4 mm Hg, from 22.1 +/- 5.4 to 13.6 +/- 7.5 mm Hg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of enalapril and bendrofluazide for treatment of systemic hypertension.
The antihypertensive and biochemical effects of the angiotensin-converting enzyme inhibitor enalapril were compared with those of the thiazide diuretic bendrofluazide. Patients with untreated mild to moderate essential hypertension were entered into a randomized, double-blind, double-dummy, parallel-group study. Blood pressure (BP) decreased significantly (p less than 0.001) with either drug therapy: from 172/103 to 147/87 mm Hg (n = 18) with enalapril and from 179/104 to 165/95 mm Hg (n = 22) with bendrofluazide; thus, enalapril produced a greater reduction (p less than 0.05) than bendrofluazide. The median dose of enalapril was 20 mg/day (range 10 to 40) and that of bendrofluazide was 5 mg/day (range 2.5 to 10). Both drugs reduced serum sodium levels by small amounts. This was significant only for enalapril (decrease of 1.3 mmol/liter, p less than 0.05). Hyponatremia was not seen in any patient. Three patients were withdrawn from each treatment group due to adverse effects, although both drugs were generally well tolerated.
Long term use of enalapril in the treatment of patients with congestive heart failure.
Fifty-five patients of both sexes, aged 39-72, suffering from congestive heart failure of varying aetiology were admitted to a double blind study in which enalapril given in a dose of 5-10 mg twice daily or placebo was added to existing medication. A significant increase in exercise performance (P less than 0.004) was seen in the group treated with enalapril, an improvement which was still evident after 24 weeks of therapy. No significant difference was seen between the mean ejection fractions but subjective assessment suggested improvement in the enalapril-treated group.