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Biomedical subjects

M J Kendall

Publications and source records attributed to M J Kendall.

At least 109 records · Page 6Linked to original sources
PubMed1993

The lipolytic effect of beta 1- and beta 2-adrenoceptor activation in healthy human volunteers.

1. We investigated the effect of activation beta 1- and beta 2-adrenoceptors on the process of lipolysis in human volunteers. Ten male subjects underwent a single-blind randomized cross-over trial using infusions of terbutaline (a specific beta 2-adrenoceptor agonist), xamoterol (a partial beta 1-agonist with beta 2-adrenoceptor blocking activity) and saline (placebo control). The effect of these infusions on plasma potassium, glucose, free fatty acids (FFA) (total and individual) and insulin levels was studied. 2. Terbutaline infusion induced a significant rise in plasma glucose and a fall in plasma potassium in keeping with its beta 2-adrenoceptor stimulant properties. Xamoterol infusion had no significant effect on these values. Terbutaline infusion caused a greater rise in total and individual FFA than xamoterol, but both effects were significantly different from placebo. 3. The possible reasons for these results and their implications on the beta-adrenergic control of lipolysis are discussed.

Adult↗
PubMed1993

The treatment of elderly hypertensive patients.

Treatment of hypertension in the elderly has hitherto been considered to be potentially dangerous. Three recent studies have clearly shown that in selected elderly hypertensives, blood pressure reduction very effectively reduces cardiovascular complications without causing unacceptable adverse effects. The impact on non-fatal stroke was most striking although a reduction in coronary events was also achieved. Thiazide diuretics were used in all three trials, and beta-blockers were used in two. Thiazide diuretics had a major beneficial effect. In this review the applicability of these results to the whole unselected population of elderly hypertensives is considered, and the choice of therapy in different subgroups of patients discussed.

Adrenergic beta-Antagonists↗
PubMed1993

A comparison of the beta 1-selectivity of conventional metoprolol and metoprolol CR during exercise in healthy volunteers.

This paper reports on a randomized double-blind crossover study to compare the effects of daily treatment with 100 mg conventional metoprolol (M100), 50 or 100 mg slow-release metoprolol CR (CR50, CR100) and placebo on the response to treadmill walking exercise in 12 healthy volunteers. Twenty minutes of exercise was undertaken at 1.5 h post-dose (Ex1) and again at 4 h (Ex2). During Ex1 all metoprolol preparations caused a reduction in the exercise-induced increase in heart rate when compared to placebo (P < 0.001). The exercise-induced increase in plasma glycerol, an indicator of lipolysis, was diminished by all metoprolol preparations but to a greater extent by M100 (P < 0.05). Rises in plasma ammonia were used to assess the net degradation of energy-rich adenine nucleotides by skeletal muscle during exercise. When compared to placebo, a significant elevation in plasma ammonia was seen only during exercise with M100 (P < 0.05). The perceived exertion at the end of exercise was also greatest on conventional metoprolol. The differences between the effects of conventional and CR formulations of metoprolol were less when exercise was repeated 4 h post dosing. We conclude that metoprolol CR may offer advantages over the conventional preparation, in subjects regularly engaging in exercise, by reducing the metabolic stress imposed upon skeletal muscle.

Adult↗
PubMed1993

The impact of a short course of three lipid lowering drugs on fat oxidation during exercise in healthy volunteers.

We examined the impact of three lipid lowering drugs on fat oxidation during a 120 minute treadmill walk, at an exercise intensity of 50% maximal oxygen uptake (VO2 max). Subjects (N = 24) were healthy male volunteers with normal serum chemistry, assigned to three groups (n = 8). Group A received simvastatin 20 mg twice daily, Group B received gemfibrozil 600 mg twice daily, Group C received acipimox 600 mg twice daily. Each subject performed two 120 minute walks, once with drug, and once with placebo (4 days treatment plus a final dose on the morning of the exercise trial). Treatment order was reversed for half of each group. Compared to placebo, simvastatin treatment, had no impact on fat oxidation (40.9 +/- 8.6% vs 40.9 +/- 9.7%), or on plasma concentration of free fatty acids (FFA), glycerol or glucose. Treatment with gemfibrozil, showed lower fat oxidation (32.3 +/- 13.9% vs 39.7 +/- 7.9%), and lower plasma concentrations of FFA and glycerol, but differences did not reach significance at the 0.05 level. Acipimox treatment, produced significantly lower fat oxidation (36.9 +/- 12.8% vs 50.2 +/- 16.1%, P = 0.011), and lower plasma concentrations of FFA and glycerol (P = < 0.0001 and P = < 0.0001, respectively). Plasma glucose showed a trend toward lower values with acipimox (P = 0.088). These data demonstrate that selective lipid lowering drugs can reduce fat availability for exercise metabolism, placing increased demands on carbohydrates which may reduce exercise tolerance.

Adult↗
PubMed1993

Sudden cardiac death and the potential role of beta-adrenoceptor-blocking drugs.

Sudden cardiac death is a major health problem in the industrially developed countries. The risk of sudden cardiac death may be reduced by early detection of coronary heart disease, elimination of the risk factors, treatment of the ischaemia in patients known to have coronary heart disease and suppression of ventricular arrhythmias. Of all the therapeutic measures currently available to reduce the risk of sudden cardiac death, beta-adrenoceptor-blocking drugs (beta blockers) appear to be the most effective. In this paper their actions are reviewed and evidence for their efficacy is presented.

Adrenergic beta-Antagonists↗
PubMed1992

Co-administration of misoprostol or ranitidine with indomethacin: effects on pharmacokinetics, abdominal symptoms and bowel habit.

This three-way randomized crossover study in 18 healthy male volunteers compared the pharmacokinetics of 50 mg indomethacin b.d. during concomitant twice daily dosing with 400 micrograms misoprostol, 150 mg ranitidine or placebo. Plasma indomethacin concentrations were determined by HPLC assay of samples collected over 12 h after the first dose, and over 14 h after the last dose on Day 8 of each dosing period. A daily diary of bowel habits, and the occurrence and severity of abdominal symptoms, was kept by each subject throughout the study. Statistical comparisons were made by analysis of variance. In the presence of misoprostol there was a 13% decrease in the area under the plasma concentration-time curve of indomethacin over one dosing interval on Day 1 (P less than 0.01), and at steady state there was a 24% decrease in the maximum plasma concentration (P less than 0.02). The pharmacokinetics of indomethacin were not affected by co-administration of ranitidine. Accumulation of indomethacin after repeated oral dosing was not significantly altered by the co-administration of either misoprostol or ranitidine. The frequency and severity of abdominal symptoms was significantly increased (P less than 0.01) during misoprostol dosing, compared with either ranitidine or placebo plus indomethacin. When the dosing phase (Days 1-8) was compared with the washout phase (Days 9-15) in each period, misoprostol, but not ranitidine or placebo, plus indomethacin resulted in an increase (P less than 0.001) in abdominal symptom severity, frequency of bowel motions and a decrease in faecal consistency.

Abdominal Pain↗
PubMed1992

Hypertension, coronary artery disease and insulin resistance--linked disorders with an impact on treatment.

Coronary artery disease is a very common disorder for which hypertension is a well-recognized risk factor. However many trials of antihypertensive therapy have failed to demonstrate a reduction in the incidence of coronary events. One explanation is that hypertension is a disorder associated with hyperinsulinaemia, obesity and non-insulin dependent diabetes. Furthermore certain antihypertensive drugs, notably thiazide diuretics, increase the hyperinsulinaemia and thereby increase one of the other coronary risk factors. In this review the links between hypertension and hyperinsulinaemia are explored and the mechanisms whereby an increased plasma insulin can lead to the more rapid development of coronary artery disease are explained. These observations may influence the choice of drugs used to treat hypertension.

Arteriosclerosis↗
PubMed1992

Metabolic effects of beta 2-agonists.

Catecholamines produce a number of biochemical changes most of which result from stimulation of beta 2-receptors. Interest in these metabolic effects has increased recently as a consequence of the concern over the relatively high mortality from acute asthma attacks. In this review the data on the impact of beta 2-agonists on glucose production, insulin release and lipolysis are presented. Thereafter the subject of hypokalaemia, the mechanism for its production by beta 2-agonists and its relevance to cardiac arrhythmias are considered in detail. Finally the fall in plasma magnesium and the possible role of beta 2-agonists in the production of lactic acidosis are discussed.

Acidosis, Lactic↗
PubMed1992

Pilot study to compare the bronchodilator and metabolic responses to terbutaline infusion in seven asthmatic subjects--are they correlated?

We compared the changes in peak expiratory flow rate (PEFR), plasma potassium and plasma glucose during and after an infusion of the beta 2-agonist, terbutaline, in seven asthmatic subjects. Our aim was to establish whether these metabolic parameters could be correlated with PEFR. The percentage changes in PEFR were significantly correlated with the percentage changes in glucose (r = 0.60, P less than 0.001) and potassium (r = -0.64, P less than 0.001). Values for glucose and potassium changes were also correlated significantly with each other (r = 0.86, P less than 0.001). This suggests that in asthmatic subjects on beta 2-agonist treatment, plasma potassium could be used as a surrogate marker for beta 2 activity at bronchi. It also implies that the most effective beta 2-agonist bronchodilators will produce the greatest fall in plasma potassium. Further studies with a larger number of patients are needed to confirm this.

Adult↗
PubMed1992

A metabolic assessment of the beta 1 selectivity of bisoprolol.

Twelve healthy volunteers were given single oral doses of bisoprolol 5 mg, 10 mg and 20 mg and atenolol 50 mg and 100 mg in a randomised, placebo-controlled study. The effects of these drugs on beta 2-stimulated hypokalaemia and hyperglycaemia (produced by intravenous terbutaline infusion) were studied. Comparable beta-blockade was achieved with bisoprolol 20 mg, and atenolol 50 mg and 100 mg as measured by attenuation of exercise heart rate. Measurements of areas under or over the curve (AUC and AOC) of hypokalaemic or hyperglycaemic response to terbutaline infusion showed that bisoprolol (10 mg and 20 mg) and atenolol (50 mg and 100 mg) were significantly less beta 1 selective than 5 mg bisoprolol. Furthermore, there was a trend towards decreasing beta 1 selectivity with increasing doses of bisoprolol. Bisoprolol, an effective once daily antihypertensive and antianginal treatment, has comparable beta 1 selectivity to atenolol as measured by metabolic response. At a dose of 5 mg, bisoprolol has a measurable impact on beta 1 receptors but minimal effect on beta 2 receptors.

Adrenergic beta-Antagonists↗
PubMed1991

Assessment of beta-1 selectivity of bisoprolol and atenolol by means of their influence on the lipolytic response to an infusion of terbutaline.

We have investigated the beta-1 selectivity of a new beta-blocker, Bisoprolol, by comparing its effect on lipolysis induced by intravenous terbutaline infusion with that of Atenolol. At a dose of 5 mg, Bisoprolol had virtually no beta-2 blocking activity as measured by free fatty acid (FFA) release during terbutaline infusion. At a dose of 10 mg, Bisoprolol had a small but statistically insignificant effect on FFA release similar to 50 mg Atenolol. At a dose of 20 mg, Bisoprolol had significant beta-2 blocking activity. At lower doses, therefore, Bisoprolol is a very selective beta-blocker.

Adrenergic beta-Antagonists↗
PubMed1991

Investigation of the effects of beta-2 stimulation on free fatty acids in man.

In this study we present evidence that lipolysis in man is under beta-2 adrenergic control and that beta-2 stimulation produces a characteristic profile of individual free fatty acid (FFA) release. Twelve healthy volunteers received infusions of placebo (N Saline), terbutaline (a selective beta-2 agonist) and dilevalol (a new non-selective beta-blocker with beta-2 agonist activity). Plasma FFA concentrations during and after the infusions were measured using gas chromatography. A significant rise in total and individual FFAs was seen after 30 min of terbutaline infusion. This was most marked for oleic acid. Total and individual FFA concentrations also rose after 30 min of dilevalol infusion; this was only significant for oleic acid and was approximately 15% of the rise induced by terbutaline infusion. Placebo infusion did not cause any significant changes in FFA levels.

Adult↗
PubMed1991

Pathophysiology of hypertension in diabetes mellitus--implications for management.

A variety of mechanisms may lead to the initiation and progression of hypertension in patients with diabetes mellitus; an understanding of their nature may provide a rational basis for the choice of management. Nevertheless, a decision on the management of an individual patient remains a matter of clinical skill and judgement.

Antihypertensive Agents↗
PubMed1991

A comparison of the metabolic effects of flosequinan and propranolol in patients with non-insulin-dependent diabetes mellitus.

The effects of steady-state flosequinan, a new peripheral vasodilator, and propranolol on glucose tolerance and plasma lipids in 22 non-insulin-dependent diabetics were investigated in a randomized double-blind placebo-controlled, three-way crossover trial. Flosequinan produced no impairment of glucose tolerance compared with placebo. Propranolol produced significant increases in fasting plasma glucose (P less than 0.01) and increases in the area under the glucose tolerance curve (P less than 0.05) compared to placebo. No significant effects on cholesterol levels were seen on either treatment but triglyceride levels were significantly elevated on propranolol compared with placebo (P less than 0.01). These data suggest that flosequinan, used in therapeutic dosage, has no adverse metabolic effects on the non-insulin-dependent diabetic and this may be an advantage for a drug used in the treatment of hypertension or congestive heart failure.

Adult↗