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Biomedical subjects

M Frisk-Holmberg

Publications and source records attributed to M Frisk-Holmberg.

16 recordsLinked to original sources
PubMed1979

Chloroquine serum concentration and side effects: evidence for dose-dependent kinetics.

Serum concentrations of chloroquine were determined fluorometrically in 100 rheumatoid patients who had been treated with 0.25 gm daily for at least 2 mo. The total dose varied between 3.7 and 400 gm. No patient received more than 75 gm annually. In 15% of the patients side effects were noted. There was a relationship between serum concentrations and side effects but not with the total dose administered. Chloroquine displayed dose-dependent kinetics, which may indicate that close monitoring of serum concentrations is an aid to the safe and rational use of the drug.

Adult↗
PubMed1979

Metabolic changes in muscle on long-term alprenolol therapy.

Muscle biopsies from the vastus muscle were taken at rest and immediately after upright bicycle exercise at 50% of the individual VO2max, before and during 6 wk of alprenolol treatment (200 to 400 mg twice daily) in 6 untrained patients with essential hypertension. Resting muscle concentrations (mmole - kg-1 - wet weight) of glycogen, glucose, lactate, and high-energy phosphates [adenosine triphosphate (ATP) and creatine phosphate (CP)] were not affected by alprenolol treatment, but after 10 min after exercise the glycogenolysis increased and depletion of ATP and CP was enhanced. The relationship between blood and muscle lactate was altered by alprenolol, indicating that alprenolol prevents lactate translocation from the muscle to the blood. The results show that during moderate exercise, leg muscle metabolism is influenced by long-term antihypertensive therapy.

Adenosine Triphosphate↗
PubMed1979

Central and peripheral circulation in relation to muscle-fibre composition in normo- and hyper-tensive man.

1. Fibre composition in the vastus lateralis muscle, and blood pressure, were determined in age-matched normotensive (n = 22) subjects and previously untreated patients (n = 19) with essential hypertension. 2. In all subjects the muscle fibres were classified, as fast-twitch (FT) and slow-twitch (ST), and blood pressure was recorded. Eleven patients and seven of the normotensive subjects participated in an extended haemodynamic study with intra-arterial pressure measurements and determinations of leg blood flow. 3. In both normo- and hyper-tensive subjects, ambulant and intra-arterial blood pressure and leg vascular resistance were negatively correlated to the percentage of ST fibres; no significant correlation was found to total leg blood flow. 4. The findings show that muscles with a high proportion of FT fibres have a higher resistance than muscles rich in ST fibres and suggest that the type of fibre in skeletal muscle might be of importance for the development of the hypertensive disease.

Adult↗
PubMed1978

Pharmacokinetics of clonidine and its relation to the hypotensive effect in patients.

1 The kinetics of clonidine and its relation to the blood pressure response after single intravenous doses of 75 micrograms--275 micrograms in hypertensive patients were determined. 2 Clonidine disposition could be described by a two compartment open model and pharmacokinetic parameters show a rapid distribution phase of 20--30 min and a mean plasma clearance of 4.6 ml min-1 kg-1 (75--200 microgram). The half-life of the beta-phase was found to be in the range of 7.4--11.4 h. Indications of dose dependent kinetics were obtained. 3 A dose-dependent decrease in blood pressure was obtained. 4 The maximal reduction in MAP (mean arterial blood pressure) was significantly (P less than 0.01) related to plasma concentrations of clonidine. 5 The reduction in MAP was always related to plasma concentrations of clonidine (r = 0.88, P less than 0.01) when pseudoequilibrium of distribution of the drug was achieved.

Adult↗
PubMed1977

Influence of alprenolol on hemodynamic and metabolic responses to prolonged exercise in subjects with hypertension.

In 7 young men with essential hypertension, central and regional hemodynamics and leg metabolism were studied at rest, during and after a prolonged exercise, and with and without long-term alprenolol treatment. Alprenolol (200 mg twice daily) lowered arterial blood pressure. Heart rate decreased in relation to plasma levels during and after exercise. Cardiac output was not significantly influenced, but leg blood flow was reduced at rest. Lipolysis was also attenuated by treatment both at rest and during exercise, and the increment in plasma insulin after exercise was decreased. A reduction in the release of leg muscle lactate was noted during exercise.

Alprenolol↗
PubMed1977

Differential inhibition of lipolysis in human adipose tissue by adrenergic beta receptor blocking drugs.

The effects of various adrenergic beta receptor agonists and antagonists on lipolysis (measured as glycerol release) in human adipose tissue in vitro were studied. Of the agonists investigated, the potency rank order was isoproteronol greater than norepinephrine greater than salbutamol. Adrenergic beta receptor blocking drugs inhibited catecholamineinduced lipolysis competitively. Propranolol was the overall most effective compound, followed by metoprolol, alprenolol and practolol, whereas butoxamine and H35/25 were weak inhibitors. The results indicate that the adrenergic reciptor mediating lipolysis in human adipose tissue is of type beta-1. Basal and theophylline-induced lipolysis was reduced when higher concentrations of these drug were used.

Adipose Tissue↗
PubMed1976

Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. I. Relationship between plasma concentration and adrenergic beta-receptor blockade.

Mean steady-state plasma concentrations of alprenolol were studied in relationship to the degree of beta-blockade, in sixteen patients receiving 600 mg daily in divided doses. Steady-state alprenolol concentrations were determined from the area under the plasma concentration-time curve during one eight-hour dosage interval after treatment for six weeks. Beta-blockade during alprenolol treatment was assessed from the chronotropic response to intravenous isoprenaline compared to the response after six weeks of placebo therapy. Although there was interindividual variability in the mean steady-state alprenolol concentration (range 11 - 141 ng/ml), and in the degree of beta-blockade (7-fold), the correlation between the two variables was highly significant (r = 0.80, p less than 0.001). The prescribed dose of alprenolol (mg/kg) was not significantly correlated with the plasma level of alprenolol or the beta-blockade. The chronotropic effects of isoprenaline during placebo and alprenolol were significantly interrelated (r = 0.79, p less than 0.001).

Adrenergic beta-Antagonists↗
PubMed1976

Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. II. Relationship to its effect on blood pressure and plasma renin activity.

The kinetics of alprenolol, in relation to its effect on blood pressure and plasma renin activity, have been studied in sixteen patients. A within-patient comparison was made between therapy for six weeks with placebo or alpronolol 200 mg thrice daily. Thirteen patients responded to alprenolol by a signoficant fall in blood pressure. In three other patients treatment did not lower blood pressure. In the group as a whole there was no significant correlation between the fall in systolic, diastolic or mean blood pressure, and the steady-state plasma alprenolol concentration, renin status, or degree of beta blockade. However, the thirteen responsive patients showed a significant relationship (p less than 0.05 - 0.001) between the log mean steady-state plasma alprenolol concentration and the hypotensive response.

Adult↗
PubMed1976

Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension.

The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagoinst of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metroprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 +/- 3.8 (SEM)/10 +/- 2.1 mm Hg in the lying position and 23 +/- 4.4/9 +/- 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p less than 0.05) and decrease in exercise tachycardia (r = 0.65, p less than 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mg/kg. Metoprolol decreased PRA by 67 +/- 1.9 and 71 +/- 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p less than 0.05) but not to the plasma steady-state levels of metoprolol, the degree of beta receptor blockade, and the decrease in PRA.

Adrenergic beta-Antagonists↗
PubMed1976

Plasma binding and the affinity of propranolol for a beta receptor in man.

The effects of plasma drug binding on the relationship between propranolol concentration and the antagonism of isoproterenol tachycardia have been investigated in 8 normal subjects and 8 hypertensive patients. During chronic intravenous infusion of propranolol giving a narrow range of total plasma concentrations (22.5 to 50 ng/ml), there was, at best, a poor correlation with effects. On the other hand, there was excellent correlation between efficacy and free drug concentration, which fitted the predictions of the receptor theory of competitive antagonism. The true affinity constant for the binding of propranolol to its receptor can be calculated in terms of free drug concentration (KAfree) and was found to vary 2-fold compared to the affinity constant in terms of total plasma concentration (KAtotal) which varied 4-fold, the greater variation being due to plasma binding differences. Compared to normal subjects, KAfree and KAtotal were smaller in hypertensive subjects, implying lesser sensitivity to the drug, and plasma propranolol binding was greater. There was no difference in KAfree between high- and low-renin essential hypertensives, but KAtotal was smaller in the high-renin group due to increased plasma binding which did not reach statistical significance. It is concluded that the effect of propranolol on heart rate is a predictable function of free drug concentration in man and that the contribution of individual variation in receptor sensitivity to differences in oral dosage requirement is minor compared to that of variations in bioavailability.

Adult↗
PubMed1976

Effect of long-term anti-hypertensive beta-receptor-blocking treatment on haemodynamic and metabolic responses to prolonged exercise in man.

1. Central and regional haemodynamics and leg metabolism at rest, during and after a prolonged exercise were studied in seven untreated hypertensive males before and after a long-term treatment (6 weeks) with an unselective beta-receptor-blocking drug (alprenolol). 2. Alprenolol treatment (200-400 mg, twice daily) decreased arterial blood pressure at rest and during exercise; it reduced heart rate in relation to drug plasma concentrations during and after exercise; it left cardiac output unchanged; it reduced leg blood flow at rest, but had no effect on leg blood flow during exercise. 3. Alprenolol treatment also decreased lipolysis and lactate release in relation to drug plasma concentrations during exercise.

Adult↗