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Biomedical subjects

T L Svendsen

Publications and source records attributed to T L Svendsen.

At least 37 records · Page 2Linked to original sources

[Standardized prothrombin time determinations and optimal anticoagulant therapy].

WHO and other international organizations have recommended the introduction of a standardized prothrombin time determination. This would allow a universal scale for the intensity of oral anticoagulation therapy to be used. A prerequisite is the use of thromboplastin, calibrated against the international reference thromboplastin, standardized methodology etc. This permits every prothrombin time determination to be expressed as International Normalized Ratio (INR). The introduction of INR facilitates the implementation of optimal oral anticoagulation as defined by larged international studies.

Anticoagulants↗

Microvascular right-to-left pulmonary shunt demonstrated by a radionuclide method.

A 37-yr-old man with angiolymphoid hyperplasia (Kimura's syndrome), who had been treated unsuccessfully for suspected asthma, was investigated due to a decrease in arterial oxygen saturation (86%). Right heart catheterization and angiography of the pulmonary artery failed to demonstrate any right-to-left shunts. However, simultaneous scintigraphy over the lungs, kidneys, and head after injection of 150 MBq technetium-99m-labeled macroaggregated albumin i.v. and inhalation of 150 MBq krypton-81m demonstrated a right-to-left shunt in the lungs probably caused by precapillary pulmonary arteriovenous shunts.

Adult↗

[A comparative study of atenolol (Tenormin) and the combined preparation atenolol/chlorthalidone (Tenoretic Mite) in essential hypertension. A randomized double-blind study from general practice].

Two hundred and ninety-two hypertensive patients from general practice who had previously been treated with a diuretic with insufficient effect participated in a randomised trial for a period of three months. A total of 115 patients completed treatment with 50 mg atenolol (Tanormin) and 121 were treated with the combined preparation consisting of 50 mg atenolol and 12.5 mg chlothalidone (Tenoretic Mite) while 56 patients defected from the trial. In both of the groups, the average blood pressure was reduced significantly already after treatment for one month. A significantly greater number of patients receiving combined treatment achieved satisfactory diastolic blood pressures (less than 90 mmHg), the proportions being 78% and 54%, respectively. Better effects from combined treatment were found particularly in patients over 60 years of age and in females. No significant differences were observed between the side-effects of the regimes nor in the laboratory values registered during treatment.

Adolescent↗

Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease.

ICI 141,292 is a new beta 1-adrenoceptor blocking drug. The beta 1-adrenoceptor antagonistic effect of ICI 141,292 was examined in a double-blind, randomised crossover study in eight healthy young volunteers and compared with atenolol. Three doses of ICI 141,292 (1, 2 and 4 mg) and atenolol 5 mg were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous administration of four sequential doses (0.5, 0.5, 1.0 and 2.0 mg) of ICI 141,292 was examined. HR decreased 7% (P less than 0.05) following ICI 141,292 1 mg with no further decrease following the succeeding doses. Cardiac output decreased 5.2% (P less than 0.05) following a cumulative dose of 4 mg. No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent as atenolol) beta 1-adrenoceptor blocking agent possessing moderate intrinsic sympathomimetic activity.

Adrenergic beta-Antagonists↗

Haemodynamic effects of disopyramide using a new model of intravenous administration.

Intravenous treatment with disopyramide is usually performed by administration of a bolus injection of 150 mg given over 5 min. followed by a continuous infusion of 18-24 mg hour-1. A decrease in cardiac output is associated with this rapid bolus injection. Seven patients with ischaemic heart disease entered an open randomised cross-over trial to elucidate if an extension of the bolus injection time to 20 min. resulted in a smaller decrease in cardiac output. Cardiac index decreased significantly (P less than 0.001) in both situations, with maximum decrease observed at time 5 and 20 min., respectively (equivalent to the ending of the administration of 150 mg disopyramide). The decrease in Cardiac index (mean +/- S.E.M.) was identical in the two situations (2.56 +/- 0.23 to 1.78 +/- 0.21 l/min. X m2 (30%) and 2.66 +/- 0.17 to 1.94 +/- 0.19 l/min. X m2 (27%], respectively. Blood pressure was unchanged, while heart-rate (P less than 0.025) and preejection period index (P less than 0.005) increased significantly and to the same extent in the two situations. Significant correlations between the log free and log total serum concentration of disopyramide and the relative change in preejection period index of r = 0.840 (P less than 0.01) and 0.919 (P less than 0.01), respectively, were observed giving disopyramide over 5 min. A significant anticlockwise hysteresis was observed extending the time of administration to 20 min. As no haemodynamic advantages are achieved by the slower way of administration we would still recommend the bolus injection to be given over 5 min.

Disopyramide↗

Haemodynamic effects of atenolol, pindolol and propranolol during adrenaline infusion in man.

In a double blind, cross over study the haemodynamic effects of an i.v. infusion of adrenaline during concomitant administration of atenolol, pindolol, propranolol or placebo were examined in 7 healthy volunteers. During coadministration with placebo, adrenaline caused an increase in systolic blood pressure (SBP) of 26 mm Hg and a decrease in diastolic blood pressure (DBP) of 20 mm Hg. Heart rate (HR) and stroke volume (SV) were increased by about 20-30%. Total peripheral resistance (TPR) fell significantly. When the subjects were pretreated with atenolol, the adrenaline increased SBP by 16 mm Hg, the DBP did not change, HR and SV increased by 19 and 30%, and TPR fell. During concomitant administration of the non-selective betablocker pindolol, which has strong intrinsic sympathomimetic activity (ISA), adrenaline increased SBP by 11 mm Hg and DBP by 17 mm Hg. This pure pressor response led to a significant reduction in HR and SV and an increase in TPR, probably mediated through the baroreceptors. The haemodynamic response to adrenaline during coadministration of propranolol was very similar to that seen after pindolol. It is concluded that a beta1-selective blocker interferes very little with the haemodynamic response to adrenaline, whereas it is changed to a pure pressor response during coadministration of a non-selective betablockers. ISA did not significantly modify the pressor response.

Adult↗

Haemodynamic effects and kinetics of concomitant intravenous disopyramide and atenolol in patients with ischaemic heart disease.

The haemodynamic effects of concomitant intravenous administration of disopyramide (Norpace) and atenolol (Tenormin) were studied in a cross-over trial in 7 patients with ischaemic heart disease. Following 150 mg disopyramide i.v. the cardiac index (CI) and stroke volume index (SVI) decreased by 14% and 26%, respectively and the heart rate (HR) and preejection period index (PEPI) increased by 13% and 19%, respectively. A decrease in CI of 14% and HR of 21%, respectively were noted after intravenous administration of 7.5 mg atenolol; PEPI increased by 10% whereas SVI remained unchanged. The cardiac Index (CI) fell by 33% following the administration of both drugs. The effect on CI of the two drugs was additive. The effect of disopyramide and atenolol on HR, SVI and PEPI was not significantly modified by coadministration of the other drug. No change in blood pressure was observed after disopyramide or atenolol. A correlation (rho) of 0.540 and 0.387 was observed between the change in PEPI and the log free and total serum concentrations of disopyramide, respectively. Combined intravenous use of the two drugs in patients with incipient or overt heart failure is not recommended, unless it is due to the arrhythmia to be treated.

Aged↗

Kinetics of disopyramide in decreased hepatic function.

The elimination kinetics of disopyramide was studied in 9 patients with decreased hepatic function (DHF) due to histologically verified cirrhosis of the liver, and in 11 patients with ischaemic heart disease (IHD). Disopyramide 100 and 150 mg was given intravenously as a bolus to the patients with IHD and DHF, respectively, followed by a continuous infusion of disopyramide 0.3 (DHF group) and 0.4 mg X min-1 (IHD group) until steady-state was achieved. A significant (p less than 0.001) positive correlation between the percentage unbound and total serum concentration of disopyramide was demonstrated in both groups. The percentage of unbound disopyramide at a total serum concentration of 5.9 mumol X l-1 was 45.5% and 19.4% in the DHF and IHD groups, respectively. A negative correlation (r = -0,751, p less than 0.05, and r = -0.827, p less than 0.01 in the IHD and DHF patients, respectively) between the free fraction of disopyramide and alpha 1-acid glycoprotein was observed. The serum concentration of alpha 1-acid glycoprotein, the major binding protein of disopyramide, was significantly lower in the patients with DHF. The clearance of unbound disopyramide and its total volume of distribution and half-life were significantly lower in the DHF patients. No difference in total elimination clearance could be demonstrated. The clinical implication of the present findings appear to be that the dosage of disopyramide should be reduced by 25% when it is given intravenously to patients with decreased hepatic function.

Adult↗

The effects of acebutolol and metoprolol on walking distances and distal blood pressure in hypertensive patients with intermittent claudication.

The effects of acebutolol (with intrinsic sympathomimetic activity (ISA] and metoprolol (without ISA) on arm blood pressure, ankle systolic blood pressure, claudication distances (CD) and maximal walking distances (MWD) were compared in patients with essential hypertension and intermittent claudication. Fourteen patients participated in a long-term, open, randomized cross-over study. After randomization the patients received either acebutolol, 200 mg b.i.d., or metoprolol, 100 mg b.i.d. After eight weeks the drugs were shifted and after another eight weeks they were withdrawn. Arm and ankle blood pressure, CD and MWD were determined before randomization and after 4, 8, 12 and 16 weeks, and again 4-6 weeks after withdrawal of the drugs. The arm blood pressure was reduced by 20/13 mmHg after acebutolol and by 22/21 mmHg after metoprolol. In spite of a significant decrease in arm blood pressure there were no significant changes in ankle blood pressure, CD or MWD after the two drugs. After withdrawal of the drugs and after the arm blood pressure had returned to the control value no significant changes were seen in CD, MWD or ankle blood pressure. It is concluded that beta-blockers have no deleterious effect on CD, MWD or ankle blood pressure in patients with hypertension and intermittent claudication. No effect of ISA was demonstrated.

Acebutolol↗

Atenolol inhibits the elimination of disopyramide.

The effect of atenolol on the total elimination of disopyramide and its main dealkylated metabolite was studied in 6 patients and 3 volunteers. During administration of 50 mg atenolol b.i.d. the clearance of disopyramide decreased significantly (p less than 0.02) from 1.90 +/- 0.71 (mean +/- SD) to 1.59 +/- 0.68 ml/kg/min, while its half-life, concentration of the metabolite, and the volume of distribution remained unchanged. The reduction in the clearance of disopyramide by atenolol might contribute to the alleged pharmacodynamic interaction between disopyramide and beta-blocking drugs.

Adult↗

Immediate central hemodynamic effects of five different beta-adrenoceptor-blocking agents, acebutolol, atenolol, pindolol, practolol, and propranolol, in patients with ischemic heart disease.

The hemodynamic effects of acebutolol were studied in six patients with ischemic heart disease. The changes in heart rate, cardiac output, and arterial blood pressure were determined after intravenous administration of six increasing doses of acebutolol to a cumulative dose of 0.64 mg/kg. After the sixth dose of acebutolol, cardiac output and heart rate were reduced 15% and 8%, respectively. Pulmonary artery pressure was increased by 4 mm Hg. Arterial blood pressure was not changed significantly. The effects of graded doses of acebutolol on heart rate and cardiac output were compared with earlier obtained results after atenolol (0.19 mg/kg), pindolol (0.025 mg/kg), practolol (0.64 mg/kg), and propranolol (0.19 mg/kg). The effects of increasing doses of acebutolol and practolol were very similar and significantly different from the effects of the other three drugs in spite having been administered at equipotent doses. The hemodynamic effects of acebutolol support the hypothesis that the hemodynamic response to beta-adrenoceptor antagonist drugs at rest is determined primarily by the degree of intrinsic sympathomimetic activity, whereas beta-1 selectivity does not modify the central hemodynamic response.

Acebutolol↗

Influence of rifampicin and isoniazid on the kinetics of phenytoin.

Clearance of phenytoin after i.v. injection of 100 mg was studied in six patients before and after 2 weeks daily treatment with 450 mg rifampicin, and in 14 patients with tuberculosis receiving standard treatment with 450 mg rifampicin, 300 mg isoniazid, and 1200 mg ethambutol daily. Acetylator status was measured by urinary acetylated sulphadimidine. Clearance of phenytoin in patients receiving only rifampicin increased from 46.7 ml min-1 +/- 20.6 ml min-1 to 97.8 ml min-1 +/- 33.4 ml min-1 (P less than 0.01), while clearance in patients on three drugs increased from 47.1 +/- 23.4 ml min-1 to 81.3 ml min-1 +/- 41.6 ml min-1 (P less than 0.01). No significant differences were observed between the six fast acetylators and the eight slow acetylators. Phenytoin kinetics were unchanged after further 3 months of combined treatment. Rifampicin is a strong inducer of the elimination of phenytoin. Combined treatment with isoniazid has no counter-acting effect in either fast or slow acetylators.

Acetylation↗

The influence of age and smoking on the elimination of disopyramide.

The influences of smoking and age on the elimination kinetics of disopyramide were studied in 27 subjects. Total elimination clearance of disopyramide was measured after an infusion to steady state. The total elimination clearance was significantly (P less than 0.05) decreased in elderly non-smoking patients compared with young non-smoking subjects (1.54 +/- 0.33 vs 2.12 +/- 0.67 ml kg-1 min-1) (mean +/- s.d.). Smoking more than 20 cigarettes per day significantly (P less than 0.05) increased total elimination clearance in elderly (2.02 +/- 0.35 vs 1.54 +/- 0.33 ml kg-1 min-1), while no significant induction by tobacco was observed in young healthy persons. Serum concentrations of alpha 1-acid glycoprotein, the major binding protein of disopyramide, were significantly higher (P less than 0.001) in the elderly patients. However, the volume of distribution (V) was significantly (P less than 0.001) greater in the elderly patients (2.44 +/- 0.64 vs 1.16 +/- 0.15 1 kg-1). Steady-state serum concentrations of the free drug were significantly (P less than 0.01) lower in the young volunteers (0.75 +/- 0.13 micrograms ml-1) than in the elderly (0.90 +/- 0.10 micrograms ml-1). The half-life of disopyramide was significantly shorter (P less than 0.01) in the young volunteers than in the elderly patients. No difference was observed in the relationship between the serum concentration of disopyramide and its main dealkylated metabolite in the groups studied. The results indicate that it might be advisable to reduce the dosage of disopyramide by approximately 30% in elderly non-smokers compared with young subjects.

Adult↗