ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

Hits per page

hits 1 - 4 | 4 hits

Sorting

Electronic Resource

Effects and pharmacokinetics of high dose metoprolol on chest pain in patients with suspected or definite acute myocardial infarction (1997)

Everts, B. ; Karlson, B. W. ; Herlitz, J. ; [et al.]

Springer

European journal of clinical pharmacology 53 (1997), S. 23-31

add to mindlist on the mindlist

Details

ISSN: 1432-1041

Keywords: Key words Metoprolol ; Myocardial infarction ; analgesia ; α-hydroxymetoprolol ; Chest pain

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Abstract Objective: Pain intensity and the plasma concentrations of metoprolol and its major metabolite α-hydroxymetoprolol as well as noradrenaline (NA), adrenaline (A) and neuropeptide Y (NPY) were determined in patients with pain due to definite or suspected acute myocardial infarction (AMI) after graded metoprolol infusion. Pain intensity and metoprolol kinetics were assessed over 8 h. Methods: Twenty-seven patients of either sex, aged 48–84 years with ongoing chest pain upon arrival to the Coronary Care Unit (CCU) were subdivided into two groups: (1) patients with ECG signs of threatening transmural myocardial damage (n=15); and (2) patients without such ECG signs (n=12). Pain intensity was assessed by a numerical rating scale (NRS) and venous blood was obtained for determination of plasma catecholamine and NPY concentrations. A continuous infusion of metoprolol (3 mg · min−1 i.v) was started and serial blood samples for plasma catecholamines, NPY as well as metoprolol and its major metabolite α-hydroxymetoprolol were obtained from the contralateral arm. Results: Initial pain intensity was 5.9 (arbitrary units) and 5.4 in the groups with and without signs of transmural myocardial damage, respectively. One third of the patients with ST changes reported full pain relief (NRS=0) within 70 min after starting metoprolol infusion (accumulated dose, 15–180 mg). Among the patients without ST changes upon arrival, full pain relief was obtained in 70% (accumulated dose, 30–120 mg). There was a dose-dependent relation between accumulated metoprolol dose and pain relief. The diagnosis of acute myocardial infarction (AMI) was confirmed in all 15 patients with ECG signs on arrival of transmural myocardial damage. The mean metoprolol dose in this group was 91(12) mg. The mean metoprolol dose in the 12 patients without ST changes was 64(8) mg. In all, seven of these patients developed definite AMI. The terminal half-life of unchanged metoprolol ranged from 2.5 to 8.5 h in group 1 and from 2.2 to 5.2 h in group 2. In group 1, metoprolol half-life was 4.5 h and total plasma clearance (CL) 54.1 l · h−1. In group 2, the metoprolol half-life was 3.7 h and total plasma clearance 75.4 l · h−1. There was a significant difference in clearance between the groups. After the intravenous metoprolol infusion, α-hydroxymetoprolol concentrations increased gradually. In groups 1 and 2, maximal concentrations in plasma (Cmax) were 143 and 135 nmol · l−1 for α-hydroxymetoprolol and 2830 and 1653 nmol · l−1 for metoprolol, respectively. Plasma NA or NPY did not differ between the groups. In contrast, plasma A was significantly higher during the initial 90 min of observation in patients with ECG signs of transmural myocardial damage. Conclusion: High-dose intravenous metoprolol was well tolerated in patients with suspected AMI. There was a more rapid and almost complete pain relief in patients without signs of transmural ischaemia compared with the patients with ECG signs of transmural AMI at arrival. In the later group of patients, plasma clearance of metoprolol was significantly reduced.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s002280050332

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

Electronic Resource

Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics (1991)

Karlson, B. W. ; Emanuelsson, H. ; Herlitz, J. ; [et al.]

Springer

European journal of clinical pharmacology 40 (1991), S. 501-506

add to mindlist on the mindlist

Details

ISSN: 1432-1041

Keywords: angina pectoris ; exercise test ; nifedipine (extended release formulation ; rebound effect ; adverse effect

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary Nifedipine capsules t.d.s. and an extended release formulation of nifedipine, nifedipine-ER tablets, given once daily in corresponding daily doses, have been compared with placebo in a double-blind, three-way crossover study in 24 patients with stable angina pectoris. The objective was to study the influence on the antianginal effect of the different pharmacokinetics of several preparations of nifedipine. All patients received concomitant treatment with β-adrenoceptor blockers. Antianginal efficacy was assessed by a dynamic exercise test at the end of the dosage intervals, i.e. 8 and 24 h after nifedipine capsules and nifedipine-ER, respectively, as well as 6 h after dosing. Six h after dosing the time of onset of chest pain and total excercise time were longer and total work was significantly higher during both nifedipine-ER (plasma concentration 260 nmol/l) and placebo treatment than after nifedipine capsules (plasma concentration 78 nmol/l). Time to 1 mm ST depression was longer during nifedipine-ER than during nifedipine capsule treatment. No significant difference was seen between nifedipine-ER and placebo. At the end of the dosage interval (24 and 8 h after nifedipine-ER and nifedipine capsules, respectively), no significant difference was found between nifedipine-ER (plasma concentration 75 nmol/l) and the other two treatments. However, placebo was superior to nifedipine capsules (plasma concentration 58 nmol/l) both in the time to onset of chest pain and total exercise time. The lack of effect at the end of the dosage interval was probably due to the subtherapeutic plasma nifedipine level. Nifedipine capsules, but not the extended release formulation, were found to be significantly inferior to placebo both after 6 h and at the end of the dosage interval. This unexpected finding may have been induced by the rapid and extensive fluctuation in plasma levels, with a rapid decline from the peak value after the capsule formulation, since a similar deterioration was not seen with nifedipine-ER, despite similar plasma concentrations at the end of the dosage interval. This phenomenon merits further research.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00315230

Permalink