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Biomedical subjects

J McAinsh

Publications and source records attributed to J McAinsh.

At least 19 recordsLinked to original sources
PubMed1992

Beta blockers and quality of life.

Hypertension is an asymptomatic conditions which can be life threatening. It is thus important that hypertensive patients maintain compliance with their therapy. This can be put at risk if the patient experiences adverse affects or if the patient's lifestyle is significantly altered in some way. The ability to perform daily activities and derive satisfaction is referred to as quality of life. With this in mind the published literature is reviewed here with regard to comparative studies involving beta-blockers. The balance of the evidence reviewed indicates that there are differences in quality of life between ACE inhibitors and the non-selective, lipophilic beta blocker, propranolol, favouring the former. However, this is clearly not a class difference as atenolol, which is beta 1 selective and hydrophilic, results in a similar quality of life profile to that with either captopril or enalapril. This difference between atenolol and propranolol probably arises out of their differing pharmacology, as opposed to any fundamental difference in their blood pressure lowering ability. There are probably too few studies to compare beta blockers and either calcium antagonists or diuretics definitively with regard to quality of life. What little evidence there is suggests a difference between propranolol and verapamil, with the latter giving the better quality of life. However, no difference was observed between verapamil SR and atenolol. Although data are very limited it appears that atenolol impacts more favourably than thiazide diuretics.

Adrenergic beta-Antagonists↗
PubMed1991

Atenolol and ischaemic heart disease: an overview.

Data generated to date on the use of beta-blockers, especially atenolol, in ischaemic heart disease are reviewed and compared with the results available with the calcium antagonists. Atenolol appears to be effective as an anti-ischaemic agent in patients with obstructive coronary artery disease when reduction in myocardial oxygen supply (ischaemia not preceded by an increase in heart rate and due presumably to functional coronary stenosis) or increase in demand are the likely causes. Based on current concepts and available data, there is convincing evidence to support the use of atenolol across the spectrum of ischaemic heart disease. In contrast, results with the calcium antagonists have been disappointing and variable. Atenolol, to date, is the only beta-blocker which has been demonstrated to have a life-saving benefit in acute intervention (within 12 hours of onset) in myocardial infarction. This cardioprotective aspect of the drug is likely to be applicable to other areas of ischaemic heart disease, including silent ischaemia.

Atenolol↗
PubMed1990

Pharmacokinetic and pharmacodynamic studies in man with an antianginal agent 'Visacor'.

This randomized, double-blind, crossover study in 10 healthy male volunteers compared four single oral doses of ICI 141,292 ('Visacor'), i.e. 50, 100, 200, and 300 mg, with placebo. Venous blood samples were collected pre-dose and at various times after dosing and the concentrations of ICI 141,292 in the plasma were determined by radioimmunoassay. A standardized 4-min bicycle exercise test was also performed and before this the resting haemodynamic parameters were assessed. Peak plasma concentrations of ICI 141,292 and the area under the plasma concentration-time curve increased disproportionately with dose such that after scaling to a dose of 200 mg there remained a significant linear trend with dose. The time to peak plasma concentration displayed an increasing trend with dose and, once again, the linear component of this trend was statistically significant. The mean heart rates during exercise were all significantly reduced compared to placebo for 24 h by each of the doses (range 7.8 to 17.4 beats min-1 at 24 h, p less than 0.01). The increase in heart rate during exercise was inversely related to the logarithm of the ICI 141,292 plasma concentration with higher plasma concentrations being associated with lower heart rate increases. The mean supine resting heart rates were slightly but significantly reduced at 2 and 6 h after dosing by each treatment and by the 300 mg dose at 24 h. Each of the doses of ICI 141,292 was well tolerated.

Adrenergic beta-Antagonists↗
PubMed1990

Beta-blockers and central nervous system side effects.

Beta-adrenergic blocking drugs are a widely used, well tolerated and effective treatment for a variety of cardiovascular and noncardiovascular disorders. Over the years, beta-blockers have been associated with an incidence, albeit low, of CNS side effects. The question of interest, however, is whether the incidence is the same for all members of the class or whether other properties, such as hydrophilicity, have a bearing on the incidence of this type of side effect? This article addresses this question. In pharmacokinetic terms the lipophilic beta-blockers have been shown, both in animals and man, to readily cross the blood-brain barrier in contrast to hydrophilic beta-blockers. This is thought to have possible clinical relevance with respect to the relative incidence of CNS side-effects. To clarify the situation every published clinical paper, in which the beta-blockers propranolol (highly lipophilic, nonselective, no intrinsic sympathomimetic activity (ISA)), pindolol (moderately lipophilic, nonselective, moderate ISA), metoprolol (moderately lipophilic, beta 1-selective, no ISA) and atenolol (hydrophilic beta 1-selective, no ISA) were compared, was assessed for information pertaining to CNS side effects. This comprehensive review of the literature has shown, with few exceptions, that the incidence of CNS side effects such as sleep disturbances, dreaming, nightmares and hallucinations following clinically accepted doses of the four beta-blockers under scrutiny is generally low and that effects on short-term memory are minimal or absent. However, within this group of four drugs the incidence of these side effects is lowest with hydrophilic atenolol and generally highest with pindolol and propranolol. Metoprolol occupies an intermediate position. This order is in agreement with the pharmacokinetic observation that the more hydrophilic the molecule, the less is found in the brain tissue of both animals and man, although in the case of pindolol other factors may be important. The clinical relevance of studies involving psychometric testing is not clear.

Adrenergic beta-Antagonists↗
PubMed1990

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses.

A randomized double-blind, cross-over study using treatment periods of 12 weeks with a 2-week washout, comparing two long-acting formulations of propranolol ('Inderal' LA 160 mg daily and Half-'Inderal' LA 80 mg daily) was performed after a placebo run-in of 4 weeks on 51 patients. The study indicated that both long-acting formulations were significantly better than placebo in reducing the frequency of migraine attacks (p less than 0.01). After 12 weeks there was a significantly lower (p = 0.03) frequency of migraine attacks in patients on the higher dose formulation than in those on the lower dose formulation. There was no significant difference in the frequency of side effects produced by the two formulations.

Adolescent↗
PubMed1990

Pharmacokinetics of epanolol in elderly patients with stable angina pectoris.

The pharmacokinetic profile of a single dose of 100 mg of (+/-)-N-[2-[[3-(o-cyanophenoxy)-2-hydroxypropyl]amino]ethyl]- 2-(p-hydroxyphenyl) acetamide (epanolol, Visacor), has been determined in an open study of 15 elderly patients with stable angina pectoris. Haematological, biochemical and physiological measurements demonstrated that epanolol was well tolerated in this group of patients. A mean peak epanolol concentration of 18.4 ng/ml was observed at a mean time of 1.08 h. In about one third of patients, an analytically significant secondary peak was observed. Peak concentrations showed an interindividual variability of 16-fold. Following the peak, plasma concentrations declined biphasically. Epanolol was eliminated from plasma with a mean terminal half-life of 22 h. There was some evidence of a linear relationship between heart rate and logarithmic plasma concentration but this was not statistically significant. These data are consistent with the results of pharmacokinetic studies in healthy young volunteers.

Adrenergic beta-Antagonists↗
PubMed1986

Tissue atenolol levels following chronic beta-adrenoceptor blockade using oral atenolol in dogs.

Tissue atenolol concentrations are high following chronic continuous beta-adrenoceptor blockade in dogs. Furthermore, significant concentrations of this poorly lipid soluble drug are found within the central nervous system after chronic dosing. It is suggested that all beta-adrenoceptor blocking agents may enter the central nervous system in significant and sufficient quantities to account for a central antihypertensive action of this group of compounds. Sequestration of beta-adrenoceptor agents in the CNS or other tissues may account for other clinically observed effects including adaptive effects.

Animals↗
PubMed1984

Atenolol pharmacokinetics in patients on continuous ambulatory peritoneal dialysis.

The elimination of atenolol (20 mg i.v.) has been studied in seven patients with renal failure on continuous ambulatory peritoneal dialysis (CAPD). Although atenolol was eliminated in the peritoneal fluid, the amount recovered in 24 h was relatively low (1.2 +/- 0.15 mg). The calculated urinary (n = 4) and peritoneal (n = 7) clearance was 0.289 +/- 0.058 l/h and 0.152 +/- 0.018 l/h respectively. This was considerably less than calculated total body clearance (1.21 +/- 0.086 l/h). The kinetics of atenolol in CAPD are worthy of further study.

Adult↗
PubMed1982

The use of long-acting propranolol ('Inderal' LA) in the management of elderly hypertensive patients.

Fifteen elderly patients whose hypertension was controlled by conventional propranolol 80 mg twice a day had their medication changed to one capsule of 'Inderal' LA (160 mg) daily. The blood pressure, heart rate and propranolol concentrations were measured at various time points when the patients were receiving the conventional preparation and these assessments were repeated when the long-acting preparation was administered. Although the heart rate was lower with conventional propranolol than with 'Inderal' LA there was no significant difference in the blood pressure levels. The mean peak blood level of propranolol was, however, significantly lower with 'Inderal' LA compared with conventional propranolol and occurred later. At 12 h the plasma propranolol levels were higher after 'Inderal' LA then following the intake of conventional propranolol (p less than 0.01); there was no difference in the plasma levels at 24 h. The area under the concentration time curve was significantly higher on conventional propranolol. Compared with published data, the plasma levels were higher than those in younger patients. 'Inderal' LA was well tolerated and side effects were minimal.

Aged↗
PubMed1982

Comparative pharmacological and pharmacokinetic observations on propranolol (long acting formulation) and bendrofluazide administered separately and concurrently to volunteers.

1 The effect of long-acting (LA) propranolol, LA propranolol and bendrofluazide, and a new combined formulation of LA propranolol/bendrofluazide (Inderex) on exercise tachycardia was studied in ten normal volunteers. 2 The preparations were given in random order, double-blind, on three separate study weeks. Observations were made 0, 1, 3, 6, 8, 24, 33 and 48 h after drug administration. 3 The three preparations produced a significant reduction in exercise tachycardia up to 48 h after drug administration, and the effects of the three preparations were not significantly different from each other. 4 Following LA propranolol, LA propranolol and bendrofluazide, and the combined formulation the mean reductions in exercise heart rate 24 h after drug administration were 16.7 +/- 2.1%, 13.0 +/- 1.8% and 16.2 +/- 1.7% respectively. 5 Plasma levels of propranolol and bendrofluazide were measured at 0, 1, 2, 3, 6, 8, 10, 12, 24, 33 and 48 h after dose administration. 6 There was no significant difference in plasma propranolol levels, Cmax propranolol or AUCo-x following the three preparations. The mean apparent t1/2 beta of propranolol after LA propranolol alone was significantly shorter than following the other two preparations (P less than 0.05), but this was not associated with a different pharmacodynamic response. 7 There was no significant difference in the pharmacokinetic parameters of bendrofluazide following the two preparations containing bendrofluazide. No bendrofluazide was detected in plasma after LA propranolol alone. 8 The new combined formulation produces similar pharmacodynamic and pharmacokinetic responses to LA propranolol and bendrofluazide given separately, and to LA propranolol given alone, and so may be of value in the treatment of hypertension.

Adolescent↗
PubMed1981

Beta-adrenoceptor blockers and the blood-brian barrier.

1 This study on 21 neurosurgical patients was set up to investigate the extent to which four chronically administered beta-adrenoceptor blockers, propranolol, oxprenolol, metoprolol and atenolol, cross and blood-brain barrier and enter the cerebrospinal fluid (CSF) and brain tissue. The concentration in the CSF of the three lipophilic beta-adrenoceptor blockers, propranolol, oxprenolol and metoprolol, approximated to the free drug concentration in the plasma, and was a poor predictor of brain concentration. These three lipophilic beta-adrenoceptor blockers appeared in brain tissue at concentrations 10-20 times greater than that of hydrophilic atenolol. The approximate brain/plasma ratio for propranolol was 26, for oxprenolol 50, for metoprolol 12 and for atenolol 0.2. 2 The low concentration of atenolol in brain tissue is possibly responsible for the low incidence of central nervous system-related side effects in patients on this agent compared to lipophilic beta-adrenoceptor blockers.

Adrenergic beta-Antagonists↗
PubMed1981

Atenolol in the treatment of pregnancy-induced hypertension.

1 The pharmacological properties of atenolol suggest its possible usefulness in pregnancy-induced hypertension. The pharmacokinetics of atenolol in the pregnant woman, concentrations in cord blood, and its effects on maternal blood pressure and the foetus, are evaluated. 2 We studied 13 pregnant women with hypertension, most of them uncontrolled on methyldopa. Whole blood concentrations and urinary excretion of the drug were measured over 24 h following a 100 mg dose. Effects on maternal blood pressure, pulse rate and foetal heart rate and cardiotocograph were compared for the 4 days before treatment and the first 4 days of treatment. The birth weights and Apgar scores of the babies were recorded. 2 The pharmacokinetics of atenolol (plasma half-life of about 8 h) in pregnant women do not differ from the findings in the non-pregnant. The levels of atenolol in the cord blood were confirmed as approximately equal to those in the maternal blood. 4 In the ten women in whom blood pressure was assessed a small significant fall in blood pressure was observed. 5 A 5% mean fall in foetal heart rate resulted but in one case was a rate below 120 beats/min recorded. There was no evidence of depression of the stress response of the foetal heart. Apgar scores 5 min post partum were satisfactory. 6 Atenolol appears to be safe for use in hypertensive pregnancies. Its effectiveness as an antihypertensive agent in pregnancy requires further controlled evaluation.

Adult↗
PubMed1981

Percutaneous absorption of chlorhexidine in neonatal cord care.

The percutaneous absorption of chlorhexidine during its routine use in topical antiseptic preparations used in umbilical cord care was investigated by determining plasma chlorhexidine concentrations at ages 5 and 9 days. These showed that percutaneous absorption of chlorhexidine occurred in preterm neonates treated with a 1% solution of chlorhexidine in ethanol, but not in term infants similarly treated, or in preterm infants treated only with a dusting powder containing 1% chlorhexidine and 3% zinc oxide.

Chlorhexidine↗
PubMed1980

Pharmacokinetics of atenolol in hypertensive subjects with and without co-administration of chlorthalidone.

The pharmacokinetics of atenolol with and without the co-administration of chlorthalidone were studied in five hypertensive subjects. Concomitant administration of chlorthalidone appears to have little if any effect on the pharmacokinetics of atenolol during treatment for 7 days. The atenolol elimination half-lives were 6.7 +/- 1.1 and 6.3 +/- 0.9 h, respectively, with and without chlorthalidone. Two healthy volunteers also received a single 50 mg oral dose of chlorthalidone. Their blood profiles and pharmacokinetics were similar to those observed in hypertensive subjects, but a statistically significant difference (p < 0.01) was found between the urinary excretion half-lives of chlorthalidone. This difference may be because chronic administration of the drug caused saturation of red cell binding.

Adult↗
PubMed1980

Atenolol kinetics in renal failure.

Blood and urine levels of atenolol were measured in 12 subjects--2 anephric and 10 with creatinine clearances ranging from 0 to 122 ml/min/1.73 m2. In a single-dose study subjects were given atenolol 100 mg by mouth, and blood and urine levels were measured during the subsequent 72 hr. In a repeated-dose study 10 subjects were given atenolol 100 mg for 20 days, and blood and urine levels were measured before and for 72 hr after the final dose on day 21. In the single-dose study the peak blood level occurred later and the 24-hr plasma concentrations increased as creatinine clearance decreased. The range in peak blood level was sixfold throughout this range of creatinine clearance. The blood atenolol half-life (t1/2) increased from about 6 hr to more than 100 hr with progressive renal failure and there was a corresponding decrease in elimination rate constant and increase in area under the curve. In the repeated-dose study there was good correlation between predose blood level of atenolol and both logarithm creatinine clearance and serum creatinine, and the elimination rate constant correlated with creatinine clearance and the logarithm of serum creatinine. In the single-dose study minimum heart rates were observed just after the peak atenolol level. Blood pressure response did not correlate closely with serum atenolol levels. Dosing recommendations are suggested for patients with renal failure to take account of the effects of renal function on atenolol kinetics.

Adult↗
PubMed1980

beta-Adrenoreceptor-blocking agents and the blood-brain barrier.

1. Sixteen neurosurgical patients received (oral) beta-adrenoreceptor-blocking agents (beta-receptor blockers) for 3-22 days. 2. Lipophilic beta-receptor blockers (propranolol) and metoprolol appeared in cerebrospinal fluid at concentrations similar to the free drug plasma concentration. 3. Cerebrospinal fluid concentrations of beta-receptor blockers were poor predictors of brain concentrations. 4. Both lipophilic beta-receptor blockers appeared in high concentrations in the brain: the brain/plasma ratio was approximately 15:1. 5. Hydrophilic atenolol appeared at low concentrations in brain tissue (about 20 times lower than the lipophilic beta-receptor blockers): the brain/plasma ratio was approximately 0.1:1. 6. Central nervous system-related side effects associated mainly with lipophilic beta-receptor blockers possibly result from high brain tissue concentrations.

Atenolol↗
PubMed1979

Absorption of chlorhexidine from the intact skin of newborn infants.

34 newborn infants who had been bathed in a standard manner with Hibiscrub were studied to find out whether it was absorbed percutaneously. Low levels of chlorhexidine were found in the blood of all 10 babies sampled by heel prick, and 5 of 24 from whom venous blood was taken. The detection of chlorhexidine varied greatly with the method and timing of sampling, and no correlation was found between gestational or postnatal age and chlorhexidine levels.

Age Factors↗