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Biomedical subjects

M B Finch

Publications and source records attributed to M B Finch.

33 records · Page 2Linked to original sources
PubMed1986

Peripheral vascular effects of bufuralol in hypertensive and normal subjects: a comparison with propranolol and pindolol.

In a double-blind, single oral dose, cross-over study, the effects of bufuralol (60 mg) on heart rate, blood pressure, and peripheral vascular responses were compared with those of propranolol (160 mg), pindolol (10 mg), and placebo in a group of 12 healthy volunteers. All three beta-adrenoceptor antagonists reduced exercise tachycardia, but at the doses chosen the effects of bufuralol were less than those of propranolol. Forearm blood flow was reduced by propranolol and pindolol, but not by bufuralol. The antihypertensive and peripheral vascular effects of bufuralol (30-60 mg bd) were also compared with those of propranolol (40-80 mg bd) in a double-blind crossover study in 10 patients with mild hypertension. Propranolol and bufuralol produced comparable reductions in systemic blood pressure over a two-week period, but the decreases in forearm and finger blood flow were greater with propranolol. These studies suggest that bufuralol is a beta-adrenoceptor antagonist with antihypertensive properties, and that it produces less peripheral vasoconstriction than propranolol or pindolol.

Adult↗
PubMed1986

Effects of ICI 141,292 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man.

The beta-adrenoceptor blocking properties and cardioselectivity of ICI 141, 292 were investigated in healthy male subjects. Seven subjects received in random order oral doses of ICI 141,292 20, 50, 100, 200 and 400 mg, atenolol 50 and 100 mg and placebo. ICI 14 292 had no effect on supine heart rate which was reduced by atenolol 100 mg. ICI 141,292 50, 100 and 200 mg had no effect on standing heart rate which was reduced by 400 mg at 2 h. Both doses of atenolol caused greater reductions. The maximum percent reduction of an exercise tachycardia after ICI 141,292 200 mg (23.9 +/- 3.7%) and 400 mg (24.3 +/- 5.2%) were similar to atenolol 50 mg (27.3 +/- 4.7%) but less than atenolol 100 mg (30.8 +/- 2.9%) (P less than 0.02). Six subjects received in random order single oral doses of ICI 141,292 100, 200 and 400 mg, atenolol 50 mg, propranolol 40 mg and placebo. Following each dose each subject received graded infusions of isoprenaline sulphate until heart rate increased by 40 beats min-1. Dose-response curves were constructed for the changes in heart rate, finger tremor, blood pressure and forearm blood flow produced by each infusion. At the 4 micrograms min-1 dose of isoprenaline, ICI 141,292 200 mg caused more attenuation than atenolol 50 mg but less than propranolol 40 mg in the changes of heart rate, diastolic blood pressure and finger tremor (P less than 0.02). ICI 141,292 400 mg caused more attenuation of the changes of all parameters than atenolol 50 mg but less attenuation of the changes in diastolic blood pressure and finger tremor than propranolol 40 mg (P less than 0.02). These results indicate that ICI 141,292 is a cardioselective beta-adrenoceptor antagonist with partial agonist activity.

Adrenergic beta-Antagonists↗
PubMed1986

Comparison of the acute vascular effects of frusemide and bumetanide.

The acute peripheral vascular and diuretic effects of intravenous frusemide 10 mg and 20 mg were compared with those of bumetanide 250 micrograms and 500 micrograms in a group of 10 salt depleted volunteers. Significant reductions in forearm blood flow (FBF) were observed after frusemide 10 mg (-0.77 ml 100 ml-1 min-1 P less than 0.05) and 20 mg (-0.75 ml 100 ml-1 min-1 P less than 0.01 at 15 min). No changes were observed after bumetanide. The reductions in blood flow produced by frusemide were significantly different from those of bumetanide (P less than 0.05) at 15 min. Increases in venous capacitance (VC) and mean arterial blood pressure (MAP) were observed after frusemide but these differences were not statistically different from placebo or bumetanide. No increases were seen after bumetanide. Plasma aldosterone concentrations were unchanged after either drug but plasma renin activity (PRA) was increased after frusemide 10 mg (4.42 +/- 1.01----8.50 +/- 1.90 ng A I ml-1 h-1 P less than 0.01) and 20 mg (4.01 +/- 0.72----7.81 +/- 2.27 ng A I ml-1 h-1 P less than 0.05). No increases were observed after bumetanide and significant differences between bumetanide and frusemide were observed (P less than 0.01). This study demonstrates that the acute peripheral arterial effects of frusemide are not observed after comparable diuretic doses of bumetanide. The differences appear to be related to the ability of the drugs to stimulate acute renin release from the kidney.

Adult↗
PubMed1986

The peripheral vascular effects of nifedipine in Raynaud's syndrome associated with scleroderma: a double blind crossover study.

The effectiveness of nifedipine in the treatment of Raynaud's syndrome was assessed in 16 patients with systemic sclerosis or a variant of this condition. Changes in finger and forearm blood flow (venous occlusion plethysmography), skin temperature and digital systolic pressure were measured both during the acute period and after a 2-week treatment. Subjective assessment of efficacy was based on patient diary data. Finger blood flow increased significantly both during the acute period and after 2 weeks of nifedipine therapy compared to placebo (P less than 0.05). Digital skin temperature also increased during the study period (P less than 0.01). Forearm blood flow and digital systolic pressure did not change. Nifedipine significantly reduced the frequency (P less than 0.05), duration (P less than 0.05) and severity (P less than 0.01) of attacks. Eleven out of the sixteen patients experienced side effects while on nifedipine. These results suggest that nifedipine is of benefit in the treatment of Raynaud's syndrome in patients with systemic sclerosis over a short time course.

Adolescent↗
PubMed1985

Human pharmacokinetic and pharmacodynamic studies on Ro31-1118, a new beta-adrenoceptor antagonist.

The pharmacokinetic and pharmacodynamic effects of Ro31-1118 were examined in groups of healthy volunteers. In three subjects given 10 mg of [14C]-Ro31-1118 orally, peak levels of radioactivity (84 +/- 5 ng/ml) were 16 times those of the parent drug (approximately 5 ng/ml). Very little parent drug was recovered in the urine, although recovery of total radioactivity was nearly 80% in the urine by day 5. In five subjects studied after both oral and intravenous administration of 20 mg Ro31-1118 the average bioavailability was 57% (range 41-73%). Following intravenous infusion the apparent volume of distribution for the five subjects averaged 590 1 (range 510-700 1). The elimination half-life averaged 18 h (range 17-26 h). In eight subjects who received 40, 80, 160 and 320 mg of Ro31-1118 orally there was a linear relationship between dose and plasma concentration (r = 0.999) and between dose and AUC (r = 0.996). Ro31-1118 had no effect on resting heart rate whereas atenolol reduced resting heart rate up to 6 h after all doses. The maximum reduction of an exercise tachycardia after Ro31-1118 (320 mg) was 23.13 +/- 0.7% and compared with atenolol (100 mg) was 28.2 +/- 1.25%. At 24 h the percentage reduction after Ro31-1118 was 21.5 +/- 1.7%, while after atenolol the percentage inhibition had decreased to 11.1 +/- 1.6%. In three subjects Ro31-1118 (160 mg) orally had no effect on resting heart rate, forearm blood flow and systolic blood pressure, while atenolol (50 mg) reduced all three parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

The effects of propranolol and digoxin on the acute vascular responses to frusemide in normal man.

To examine the importance of acute frusemide-induced renin release in the production of the acute peripheral venous and arterial responses to frusemide in man, the effects of two drugs, previously described as inhibitors of acute frusemide-induced renin release, propranolol and digoxin, were examined. Propranolol abolished the acute increases in venous capacitance and blood pressure and attenuated the increases in forearm vascular resistance produced by frusemide. The acute increases in plasma renin activity and plasma aldosterone concentrations were also abolished. Pre-treatment with digoxin had no effect on the acute peripheral vascular responses to frusemide and failed to inhibit the acute increases in plasma renin activity and plasma aldosterone produced by frusemide. The study provides further evidence of a relationship between acute frusemide-induced renin release and the acute peripheral vascular effects of frusemide in man.

Adolescent↗
PubMed1985

The peripheral vascular effects of diltiazem--dose-response characteristics.

The acute effects of increasing doses of diltiazem on peripheral blood flow were observed in six subjects. Each subject received, in random order, a single oral dose of placebo or diltiazem 60, 120 or 180 mg. Supine heart rate, blood pressure, skin temperature, digital systolic pressure, forearm and digital blood flow were recorded before and at 1, 2, 3, 4 and 6 h post-dosing. Plasma diltiazem concentrations were measured at each time interval and at 12 and 24 h after the 120 mg dose. At doses of 120 and 180 mg, diltiazem significantly increased digital blood flow at 1, 2, 3, 4 and 6 h post-dosing and forearm blood flow at 2 and 3 h following 180 mg and 3 h following 120 mg. No correlation was observed between plasma diltiazem concentration and changes in peripheral blood flow.

Adult↗
PubMed1985

A comparison of the cardiovascular effects of (+)-sotalol and (+/-)-sotalol following intravenous administration in normal volunteers.

In a placebo controlled open study in six healthy male volunteers (+)-sotalol in the dose range 0.125 mg kg-1-2.0 mg kg-1 intravenously, was found to have little or no beta-adrenoceptor blocking activity in comparison to the racemic mixture (+/-)-sotalol. The repolarization effects of (+)- and (+/-)-sotalol on the QTc interval however were comparable over the same dose range. The beta-adrenoceptor blocking activity and repolarization effects of sotalol appear to be unrelated.

Adolescent↗
PubMed1984

Pharmacokinetics of digoxin alone and in the presence of indomethacin therapy.

The effects of maintenance indomethacin therapy on single dose digoxin pharmacokinetics and dynamics were studied in six healthy volunteers with normal renal function. Indomethacin did not alter the elimination half-life, systemic clearance or distribution of digoxin. No pharmacodynamic interaction as assessed by changes in the systolic time intervals QA2 and LVET was found. This study does not lend support for a significant digoxin-indomethacin interaction in man.

Adult↗
PubMed1983

The effects of captopril on the acute vascular responses to frusemide in man.

To examine the importance of angiotensin II formation in the production of frusemide's acute peripheral venous and arterial responses, the effect of pretreatment with captopril was studied. Captopril abolished the acute increases in venous capacitance and blood pressure and attenuated the increases in forearm vascular resistance produced by intravenous frusemide. The study provides evidence that angiotensin II formation performs an essential role in the production of the acute vascular effects of frusemide in man.

Adolescent↗
PubMed1983

Comparison of the effect of pindolol and propranolol on heart rate after acute and chronic administration.

1 The present study compared the effects in healthy volunteers of the acute and chronic administration of placebo, pindolol and propranolol to see if the partial agonist activity of pindolol was reduced by the beta-adrenoceptor blocking activity of pindolol on chronic administration. 2 Five subjects received in random order for 8 days placebo, propranolol 160 mg and pindolol 10 mg; on days 1 and 8 treatments were given twice at 0 and 2 h. Heart rate in supine position and at end of exercise was recorded before dosing and at 2 and 4 h post-dosing on days 1 and 8. 3 Propranolol and pindolol reduced exercise heart rate to the same extent on days 1 and 8. 4 Propranolol reduced supine heart rate more than pindolol on days 1 and 8 but the difference was only significant on day 8.

Adult↗