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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 285-288 
    ISSN: 1432-1041
    Keywords: hypertension ; plasma adrenaline ; plasma noradrenaline ; isoprenaline response ; noradrenaline response ; salivation ; parasympathetic nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Parameters of the autonomic nervous system were studied in normotensive subjects (NT; standing blood pressure (BP)≤125/85 mmHg) and in subjects with borderline hypertension (BHT; 140/90≤standing BP〈60/100 mmHg). No differences in plasma noradrenaline and adrenaline levels were found between NT and BHT subjects, neither at rest nor during exercise at 75% of maximum work capacity. The dose of noradrenaline required to increase systolic BP by 10 mmHg was significantly higher in NT than in BHT subjects (5.13±0.42 vs 3.50±0.57 µg · min−1). No difference between NT and BHT subjects was found in the dose of isoprenaline required to increase heart rate by 20 beats · min−1 (1.21±0.12 vs 1.09±0.11 µg · min−1). Resting salivary flow was significantly lower in BHT than in NT subjects (0.39±0.06 vs 0.98±0.06 g · min−1), suggesting decreased parasympathetic activity in the former group. The enhanced pressor effect of noradrenaline, together with the decreased parasympathetic activity, could explain the elevated blood pressure and heart rate in subjects with borderline hypertension.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 107-109 
    ISSN: 1432-1041
    Keywords: verapamil ; rifampicin ; calcium antagonist ; drug interactions ; ethambutol ; isoniazid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of antituberculosis drugs on the plasma level of verapamil was studied after its oral and intravenous administration. Six patients who had been treated for at least 6 months with a combination of rifampicin, ethambutol and isoniazid received a single oral dose of 40 mg verapamil. As compared to untreated subjects, the antituberculosis drugs greatly reduced the bioavailability of the calcium antagonist. Studies in patients in whom treatment with ethambutol and isoniazid had been discontinued revealed that the effect was due to rifampicin. The drugs for tuberculosis had no influence on the plasma level of verapamil when it was given intravenously. The findings can be explained by the induction of verapamil metabolizing liver enzymes in patients treated with rifampicin.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 43 (1992), S. 547-550 
    ISSN: 1432-1041
    Keywords: Propranolol, Atenolol, Verapamil ; pharmaco-kinetics, exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The volumes of distribution of theβ-adrenoceptor blocking agents propranolol and atenolol, and the calcium antagonist verapamil, during exercise have been investigated. Changes in the plasma concentrations of atenolol and propranolol during exhaustive exercise at 70% of maximal aerobic power were compared after 1 week of oral treatment (propranolol 80 mg b. d. and atenolol 100 mg once daily) in 12 healthy volunteers. In a second study the effect of 10 min exercise at 50 % of maximal aerobic power on steady state plasma concentrations of propranolol, atenolol and verapamil was compared in 7 healthy subjects. The drugs were administered by a continuous intravenous infusion. The plasma concentration of atenolol was not changed by exercise in either study, but the plasma concentrations of propranolol and verapamil were significantly increased in both studies. However, after correction for changes in plasma volume during exercise, the plasma propranolol concentration was not significantly elevated in the second study. From the results it is concluded that exercise led to a reduction in the volume of distribution of propranolol during prolonged exercise (25 min) at 70 % Wmax, which was not clearly demonstrable during 10 min exercise at 50 % Wmax. The volume of distribution of verapamil was reduced during 10 min exercise at 50 % Wm, No change in the volume of distribution of atenolol during exercise could be shown. The changes in the volumes of distribution of propranolol and verapamil during exercise may contribute to preventing an increase in the half-life of these drugs in patients performing prolonged physical exercise.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 101-105 
    ISSN: 1432-1041
    Keywords: Lipolysis ; Propranolol ; beta-blockade ; endurance exercise ; glycerol ; NEFA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Inhibition of adipose tissue lipolysis may be involved in the impairment of endurance capacity after administration of a β-adrenoceptor blocker. During endurance exercise, no significant decrease in plasma glycerol and free fatty acid (NEFA) concentrations after β-adrenoceptor blockade is found. However, the levels during recovery from exhaustion are lower after β-adrenoceptor blockade. This study was designed to investigate whether the lower levels after exercise are due to β-adrenoceptor blockade or to the shorter time to exhaustion after administration of a β-adrenoceptor blocker. In a single-blind study, 11 well-trained male subjects (age 23 (0.9) y) performed a cycle ergometer test at 70% Wmax until exhaustion 2 h after intake of 80 mg propranolol. One week later, the test was repeated after intake of placebo and was stopped at the time of exhaustion in the previous test. Average exercise time was 24 min. During exercise plasma glucose was lower, whereas plasma lactate and the respiratory exchange ratio were significantly higher when the subjects were on propranolol. Glycerol and NEFA concentrations during exercise were not significantly different between the two conditions. Despite an identical exercise time, glycerol and NEFA concentrations during recovery were significantly lower after propranol treatment. In conclusion, lipolysis is inhibited during exercise after propranolol, probably causing a shift from fat to carbohydrate combustion.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 405-410 
    ISSN: 1432-1041
    Keywords: verapamil ; renal failure ; norverapamil ; pharmacokinetics ; haemodialysis ; ECG ; blood pressure ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of verapamil was studied in patients with end-stage chronic renal failure and in normal subjects after i.v. injection of 3 mg and a single oral dose of 80 mg. Plasma levels of verapamil and its active metabolite norverapamil were measured by HPLC. After i.v. injection, the terminal phase half-life and total plasma clearance of verapamil in both groups were similar. Haemodialysis did not change the time course of plasma verapamil levels after i.v. administration. After a single oral dose, the plasma levels of verapamil and norverapamil in both groups of subjects were similar. Subsequently, normal volunteers and patients with renal failure were treated for 5 days with oral verapamil 80 mg t.d.s. There was no difference between the 2 groups of subjects in the trough and peak levels of verapamil or of norverapamil. Intravenous and oral administration of the calcium channel blocking agent had similar effects on blood pressure, heart rate and the PR-interval in the electrocardiogram in both groups. The study demonstrated that the disposition of verapamil was similar in normal subjects and in patients with renal failure.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: propranolol ; essential hypertension ; acute and chronic treatment ; haemodynamic effects ; plasma renin ; plasma catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of an acute intravenous and repeated oral doses of propranolol on haemodynamics, plasma and urinary catecholamines and plasma renin activity was studied in patients with essential hypertension. Intravenous injection of propranolol 5 mg produced a fall in cardiac output but had no consistent effect on blood pressure. Treatment with oral propranolol for 24 weeks lowered cardiac output and blood pressure; total peripheral resistance did not differ from the pretreatment values. Neither acute intravenous nor chronic oral administration of the beta-blocker affected the resting plasma levels of noradrenaline and adrenaline. Long-term treatment with propranolol reduced urinary excretion of vanilmandelic acid without affecting urinary catecholamine excretion. Acute intravenous injection of propranolol decreased plasma renin activity less than did chronic oral treatment with the drug. The observed time course of plasma renin activity was compatible with the view that suppression of this enzyme contributed to the antihypertensive effect of propranolol.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 541-547 
    ISSN: 1432-1041
    Keywords: ramipril (HOE 498) ; hypertension ; angiotensin converting inhibition ; dose-response relationship ; time course
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of the blood pressure lowering effect and the dose-response relationship of the new angiotensin converting enzyme inhibitor ramipril (HOE 498) were studied in 8 patients with essential hypertension. As compared with placebo, a single oral dose of 2.5 mg ramipril lowered systolic and diastolic blood pressure. The antihypertensive action of single oral doses of 5, 7.5 and 10 mg ramipril was more pronounced. No change in heart rate occurred. Angiotensin converting enzyme activity was suppressed after all doses of ramipril studied. Plasma renin activity increased after 2.5 mg and 5 mg ramipril. Plasma aldosterone was not affected by 2.5 mg, but it fell after 5 mg ramipril. Thus, ramipril produced prolonged inhibition (more than 12 hours) of angiotensin converting enzyme activity and lowered blood pressure in patients with essential hypertension.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 375-377 
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacokinetics ; exercise ; indocyanine green clearance ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol after oral and intravenous administration was studied at rest and on an exercise day in 8 healthy subjects. On the exercise day the subjects performed physical exercise for 7 h, consisting of bicycle ergometer exercise at 50% of maximal work capacity and outdoor walking. Propranolol (80 mg p.o., or 0.2 mg/kg body weight i.v.) was administered 30 min before the start of the exercise. After oral administration the terminal phase halflife, (t1/2β) and area under the curve (AUC) were both significantly reduced on the exercise day compared to the rest day. The bioavailability of propranolol was reduced by prolonged physical exercise and plasma levels of propranolol were about 30% lower at the end of the exercise day than at the end of the rest day. After intravenous administration, t1/2β was also reduced on the exercise day as compared to the rest day. AUC, clearance and volume of distribution did not differ on the two days. On the other hand, indocyanine green (ICG) clearance was significantly reduced during the bicycle ergometry periods on the exercise day. The combination of reduced ICG clearance, suggesting a reduction in hepatic blood flow, and a decreased t1/2β and unchanged clearance of propranolol on the exercise day was unexpected.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 399-406 
    ISSN: 1432-1041
    Keywords: oxprenolol ; atenolol ; beta-blockers ; blood pressure ; exercise tolerance ; perceived exertion ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of oxprenolol, a non-selective beta-blocker with moderate intrinsic sympathomimetic activity (ISA), given by the Oros delivery system, on resting and exercise heart rate and blood pressure have been compared over a 24-h period with those of atenolol, a beta1-selective blocker without ISA. The effects on maximal and submaximal exercise tolerance and perceived exertion were studied in relation to the level of beta-blockade. 9 healthy subjects were treated with placebo, atenolol, 100 mg/day and oxprenolol Oros, 16/260 mg/day in random order, each for 5 days. Progressive maximal exercise tests and submaximal endurance tests at 80% of maximum aerobic exercise capacity were performed 2, 5 and 24 h after intake of the drugs. The reduction of blood pressure 2 and 5 h after drug intake was less pronounced after oxprenolol Oros than after atenolol, but by 24 h after the last dose the effects were similar. The peak level of beta-blockade (i.e. reduction in maximal exercise heart rate) was similar after oxprenolol Oros and atenolol. The minimal level of beta-blockade 24 h after the last dose was greater after oxprenolol Oros than after atenolol. Maximal exercise capacity and submaximal exercise tolerance were impaired after both beta-blockers. The subjective feeling of exertion did not differ between placebo, atenolol and oxprenolol Oros when related to the relative work load, except after the first minute of exercise, when the rating of perceived exertion was higher after atenolol.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 143-148 
    ISSN: 1432-1041
    Keywords: metoprolol ; beta-adrenergic blockade ; maximal aerobic power ; acute and chronic administration ; exercise ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and long-term effects of the beta1-adrenoceptor blocking agent metoprolol on blood pressure and maximal aerobic power (Wmax) were studied in 10 healthy subjects. Progressive maximal bicycle ergometer tests were performed after intravenous administration of placebo and metoprolol (0.15 mg×kg−1 and 0.30 mg×kg−1), and at the end of 4-week treatment periods with placebo, conventional metoprolol (C-M) and slow-release metoprolol (SR-M). The reduction in maximal exercise heart rate (HRmax) was correlated with the log plasma metoprolol concentration. Despite a reduction in HRmax of 23 beats/min after 0.15 mg×kg−1 metoprolol, Wmax was unaffected. After 0.30 mg×kg−1 HRmax was reduced by 40 beats/min and Wmax by 5.0%. During chronic treatment, the reductions in HRmax and Wmax were 48 beats/min and 7.5% (C-M) and 45 beats/min and 6.9% (SR-M), respectively. Resting systolic blood pressure was not changed after acute administration of metoprolol but it was reduced during chronic beta-blocker treatment. Resting diastolic blood pressure was not affected after acute or chronic treatment. Exercise systolic blood pressure remained unchanged after 0.15 mg×kg−1 metoprolol i.v. The fall in exercise systolic pressure after 0.30 mg×kg−1 metoprolol i.v. (18±5 mmHg) was significantly smaller than that during chronic treatment (30±6 mmHg C-M; 30±6 mmHg, SR-M). During chronic metoprolol treatment a certain % HRmax corresponded to a higher % Wmax than during placebo treatment, but the shift appeared to be of minor practical importance. The results show that the reduction in maximal aerobic power was comparable after acute i.v. administration and after 4 weeks oral treatment with metoprolol, if the degree of beta blockade (i.e. reduction in maximal exercise heart rate) was similar.
    Type of Medium: Electronic Resource
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