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Biomedical subjects

M Frisk-Holmberg

Publications and source records attributed to M Frisk-Holmberg.

At least 37 records · Page 2Linked to original sources

Metabolic effects in muscle during antihypertensive therapy with beta 1- and beta 1/beta 2-adrenoceptor blockers.

The hemodynamic and metabolic consequences of long-term antihypertensive treatment with beta 1- and beta 1/beta 2-adrenoceptor blockade was investigated in five young men with mild essential arterial hypertension (World Health Organization stages I and II) at rest and during submaximal exercise in a single-blind crossover study. The drugs (atenolol and alprenolol) were given in equipotent doses as estimated from their effects on blood pressure. Leg blood flow and oxygen uptake were the same during both treatment periods. Muscle glycogen decreased by 40% during exercise, irrespective of the drug. There was a positive relationship between muscle lactate release and concentration, but for a given muscle lactate concentration the release tended to be lower during treatment with alprenolol. A negative correlation was observed between the percentage of slow-twitch fibers versus lactate release and muscle lactate concentration. The results demonstrate that during exercise muscle glycogen breaks down despite beta blockade and is neither reduced when both beta 1- and beta 2-receptors are blocked, nor when only the beta 1-receptors are blocked. It is also shown that beta blockade impairs the translocation of lactate from the muscle cell to the blood and this is greater with alprenolol than with atenolol, probably due to a membrane effect.

Adrenergic beta-Antagonists↗

Arterial blood pressure and electrodermal activity in hypertensive and normotensive subjects during inner- and outer-directed attention.

Arterial blood pressure (BP), skin conductance level (SCL) and spontaneous fluctuations in skin conductance (SFs) were monitored in 14 subjects with essential hypertension (HT), and 14 matched normotensive (NT) controls during a letter identification task (L) and mental arithmetic (MA). During both tasks, the groups displayed different response patterns such that SFs and BP tended to be negatively correlated in the HT group but were positively correlated in the NT group. No correlation between BT and SCL was obtained in any group during either task. SFs and SCL were positively correlated in the NT group during both tasks whereas no correlation was found in the HT group. The results are consistent with the hypothesis that an increased BP is associated with the rejection of the environment.

Adult↗

Clonidine kinetics in man--evidence for dose dependency and changed pharmacokinetics during chronic therapy.

1 Clonidine kinetics were studied in 21 patients with essential hypertension. All received two bolus i.v. injections in the mean dose range of (0.78--3.36 micrograms kg-1) and one single oral dose (mean dose 1.7--2.3 micrograms kg-1) on separate occasions. The kinetics were also studied in some of these patients after multiple therapeutic oral dose (mean dose 1.1 or 1.9 micrograms kg-1) twice daily during a dosage interval after 6--12 months monotherapy with clonidine. The multiple oral dosage was based on the therapeutic response. 2 With increasing i.v. doses the rate constants (alpha, beta) decreased and the plasma clearance was reduced by 74% (9.94--2.61 ml min-1 kg-1) indicating dose-dependent kinetics. The volume of distribution (Vd beta) did not change with dose in contrast to the volume of the plasma compartment (Vc) which was increased at the highest doses. 3 The single oral dose kinetics agreed with the i.v. kinetics at comparable dose. The bioavailability was 90%. 4 During multiple oral dosing the elimination rate constants decreased compared to the single dose. The plasma clearance increased (7.18 ml min-1 kg-1) compared to the corresponding single dose (4.17 ml min-1 kg-1). The latter change was probably caused by the decrease in bioavailability to about 65%. 5 The pharmacodynamic properties of the drug could explain the changes in pharmacokinetics with increased dose and during multiple doses.

Administration, Oral↗

Leg blood flow during exercise in man in relation to muscle fibre composition.

Fibre composition in the vastus lateralis muscle, leg blood flow, oxygen uptake and respiratory exchange ratio were determined in 12 healthy male volunteers during submaximal exercise (50% of V02 max). The percentage of slow-twitch fibres varied from 26 to 66. Mean leg blood flow during exercise was 4.68 +/- 0.191.min-1. The blood flow and respiratory exchange ratio correlated positively to the percentage of slow-twitch fibres in the vastus muscles. No correlation was found between the muscle fibre composition and either oxygen uptake heart rate or mechanical efficiency. The results with a dependence of muscle blood flow and carbon dioxide release to muscle fibre composition support the view that the arrangement of the vascular bed and blood supply differ between fast-twitch and slow-twitch muscle fibres in humans.

Adolescent↗

Sensitive method for the determination of chloroquine and its metabolite desethyl-chloroquine in human plasma and urine by high-performance liquid chromatography.

A method has been developed for the rapid quantitative analysis of chloroquine and its metabolite desethyl-chloroquine in plasma, blood and urine using high-performance liquid chromatography. An ethylene dichloride extract of the alkalinized biological samples was extracted with dilute acid and chromatographed on a reversed-phase column. Phosphate buffer in acetonitrile was used as the mobile phase with perchlorate as the counter-ion. Ultraviolet absorption at 254 or 340 nm or fluorescence detection was used. The fluorescence spectra and the fluorescence quantum yield of the substances were determined. Chloroquine and desethyl-chloroquine concentrations in the range of 10 nmol/l (UV-detection) and of 0.5 nmol/l (fluorescence detection) could be accurately measured with a relative standard deviation of 12%. The method should be adequate for therapeutic and pharmacokinetic studies.

Chloroquine↗

The effectiveness of clonidine as an antihypertensive in a two-dose regimen.

The therapeutic efficacy of clonidine as an antihypertensive in a b.i.d. schedule 150--300 micrograms daily was evaluated. The blood pressure reduction in patients with essential hypertension was satisfactory on this regimen and the steady-state plasma concentrations were within the BP-lowering concentration range at the end of a dosage interval.

Adult↗

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↗

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↗

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↗

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↗

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↗