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Biomedical subjects

M J Kendall

Publications and source records attributed to M J Kendall.

At least 127 records · Page 7Linked to original sources
PubMed1991

Captopril and hydrochlorthiazide--a safe antihypertensive for use in general practice?

The combination of captopril and hydrochlorthiazide was assessed in 15 hypertensive patients in a general practice setting. The first aim was to determine whether the fall in blood pressure, noted after the first dose of an ACE inhibitor given alone, became unacceptable when the drug was given with a diuretic. The second aim was to assess the impact of the ACE inhibitor on the biochemical abnormalities associated with thiazide diuretic therapy. The drug combination markedly reduced blood pressure but not below 110 systolic after the first dose. In the long-term the treatment significantly lowered blood pressure but did not produce any significant or clinically relevant changes in serum chemistry.

Aged↗
PubMed1991

Controlled release metoprolol. Clinical pharmacokinetic and therapeutic implications.

Metoprolol is a relatively beta 1-selective beta-blocker used extensively to treat hypertension and angina and as a prophylaxis after myocardial infarction. Conventional formulations are usually administered twice daily and the drug has a tendency to lose its selectivity of action at higher plasma concentrations. Two controlled release formulations, metoprolol CR and metoprolol 'Oros', have made it possible to achieve sustained beta 1-blockade over an entire 24h period and to minimise the loss of selectivity associated with higher plasma concentrations. The CR formulation has been extensively investigated and is the major subject of this review. The 'Oros' formulation is pharmaceutically different from the CR, yet both produce similar plasma concentration profiles and comparable beta 1-blocking effects. The availability of these preparations occurs at a time when increasingly persuasive data are becoming available on the cardioprotective or coronary preventive action of metoprolol.

Biological Availability↗
PubMed1990

The interaction of alcohol and beta-blockers in arterial hypertension.

The acute effects of consuming alcohol after a single oral dose of 200 mg of metoprolol or placebo were examined in eight healthy men in a randomized, controlled study. Alcohol, in a dose of 0.75 g/kg body weight, did not abolish the antihypertensive effect of metoprolol upon supine systolic blood pressure. The interaction of alcohol with antihypertensive drugs requires further investigation as hypertensive patients who consume alcohol regularly are known to have less adequate blood pressure control.

Adult↗
PubMed1990

Do we need a new classification of beta-blockers?

Beta-adrenoceptor blocking drugs (beta-blockers) first came into clinical use 25 years ago. Initially, propranolol was the only beta-blocker available but a number of others, similar in chemical composition and action, became available in the following 10 years. Most blocked both beta 1- and beta 2-receptors and differed only in that some possessed membrane stabilising activity and some were partial agonists. These properties, which were the only pharmacological differences between many beta-blockers, were not found to be clinically very relevant. The main problems associated with the use of beta-blockers were caused by their unwanted effects on beta 2-receptors. The potential to prevent sympathetically-mediated bronchodilatation and thereby cause bronchospasm was, and is, the adverse effect causing most concern. The advent of relatively beta 1-selective beta-blockers, in particular metoprolol and atenolol, made it possible to achieve the therapeutic benefits of beta 1-blockade whilst reducing the unwanted effects of beta 2-blockade; which, in addition to causing less bronchospasm, also meant less impact on arterial vasodilatation and insulin, glucose and free fatty acid release. Unfortunately, beta 1-selective drugs reduce, but do not eliminate, the unwanted effects of beta 2-blockade and the larger the dose and the higher the plasma and tissue concentrations, the greater the effect on beta 2-receptor sites. Drugs which may act as beta-blockers at beta 1-receptor sites whilst having some, albeit mild, stimulatory action at beta 2-receptors are now available.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

Diuresis and natriuresis after dihydropyridines: role of prostaglandin E.

It is known that calcium antagonists may produce a natriuresis and diuresis but the mechanisms are unknown and there have been few studies of the relative potencies of different drugs. This paper reports a study designed to measure the effect of nifedipine and nitrendipine on urine volume, sodium and potassium and the renal excretion of prostaglandin E2 (PGE2) in healthy, saline-loaded volunteers. Nifedipine and nitrendipine caused a significant natriuresis. Nifedipine also caused a significant diuresis but that produced by nitrendipine failed to reach statistical significance. Neither calcium antagonist altered PGE2 excretion. There was a small and insignificant fall in urinary potassium in all treatment groups. Blood pressure was not affected by the active treatments though heart rates tended to increase. We conclude that dihydropyridines have a potentially useful acute natriuretic effect which does not seem to be mediated by PGE2.

Adult↗
PubMed1990

Investigation of the beta 2-agonist properties of dilevalol: metabolic effects of intravenous infusion.

We describe two studies which investigate the beta 2-agonist properties of dilevalol. We have previously demonstrated, by giving an infusion of terbutaline to human volunteers, that beta 2-stimulation causes a rise in plasma glucose and a fall in plasma potassium. These metabolic effects can be prevented by prior beta-blockade. We now show that infusion of dilevalol produces similar, but quantitatively smaller, metabolic effects at a dose which also produces clinically significant beta-blockade, as judged by a fall in exercise heart rate. This adds support to the claim that dilevalol is a non-selective beta-blocker with selective beta 2-agonist activity.

Adult↗
PubMed1989

A pharmacokinetic study of the active metabolite of nabumetone in young healthy subjects and older arthritis patients.

We have performed a detailed pharmacokinetic study of the plasma concentrations of the major active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid (6 MNA), attained after a single dose and during chronic administration comparing the results of a group of young healthy volunteers with those of a group of elderly arthritic patients. The latter had higher peak plasma concentrations of 6 MNA and slower rates of elimination but there is no tendency for the drug to accumulate unpredictably in the old. Disease activity also influences plasma concentration, those with more active disease, and lower serum albumin concentrations had lower AUC values.

Adolescent↗
PubMed1989

Carbidopa does not affect the renal response to atrial natriuretic factor in man.

1. The dependence of atrial natriuretic factor on renal dopamine for its renal effects in man was examined in 10 healthy volunteers using the dopa decarboxylase inhibitor carbidopa. 2. Each volunteer attended on two occasions, and received an infusion of atrial natriuretic factor (4 pmol min-1 kg-1) for 60 min after pretreatment with either placebo or carbidopa orally. These were administered in random, double-blind fashion. 3. A similar increase in plasma atrial natriuretic factor concentration was seen after atrial natriuretic factor infusion on both visits. 4. Infusion of atrial natriuretic factor produced a small unsustained rise in urinary dopamine excretion. This increase in urinary dopamine excretion was blocked by carbidopa with no effect on the natriuresis. 5. Urinary guanosine 3':5'-cyclic monophosphate excretion increased in response to the atrial natriuretic factor infusion whether placebo or carbidopa was given. Guanosine 3':5'-cyclic monophosphate, but not dopamine, may be a mediator of the renal response to atrial natriuretic factor in man.

Adult↗
PubMed1989

A comparison of the effects of flosequinan, a new vasodilator, and propranolol on sub-maximal exercise in healthy volunteers.

1. The effects of steady state flosequinan, a new vasodilator, and propranolol, on glucose mobilisation, lipolysis and plasma potassium concentration during sub-maximal exercise testing were investigated in a double-blind, randomised, three-way crossover study in 12 healthy volunteers. 2. Plasma glucose, potassium and free fatty acid concentration during and after exercise on flosequinan were similar to those on placebo. Exercise heart rates were 7% (+9.2 beats min-1) higher on flosequinan compared with placebo (P less than 0.05). During exercise on propranolol plasma glucose concentrations were comparable with those on placebo but plasma potassium concentrations were higher (mean increase 0.26 mmol l-1, P less than 0.01) whereas free fatty acid concentrations were lower (mean decrease 0.10 mmol 1-1, P less than 0.01). As expected the heart rate on exercise was 25% less (-35 beats min-1) on propranolol (P less than 0.05). 3. These data suggest that, in contrast to propranolol, flosequinan does not adversely affect the mobilisation of the two major sources of energy during sub-maximal exercise.

Adolescent↗
PubMed1989

Metoprolol-controlled release, zero order kinetics.

Metoprolol CR/ZOK (controlled release, zero order kinetics) is a new formulation of an extensively used beta 1-selective, beta-adrenoceptor blocking drug, (beta 1-blocker), designed to provide continuous, even, plasma concentrations in the therapeutic range. It should, therefore, provide an effective well-tolerated treatment for hypertension and angina pectoris and for use in secondary prevention following a myocardial infarct. The purpose of this review is to consider the need for such a formulation, to describe its pharmaceutical development, review its pharmacology and assess its efficacy and tolerability compared with other available agents.

Delayed-Action Preparations↗