Drugs online research references
Jpn Circ J. 1992 May;56(5):475-81.
Cardiac adaptation and its limitation in an experimental model of congestive heart failure.
Momomura S, Yamashita H, Sugiura S, Ohtani Y, Serizawa T, Iizuka M, Sugimoto T.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
To elucidate mechanisms of adaptation and maladaptation in heart failure, abnormalities of left ventricular function and their relationships to myocardial contractile protein were studied in the Syrian hamster Bio 14.6. Left ventricular and heart weights were both increased in 20-week-old cardiomyopathic hamsters, indicating cardiac hypertrophy as a compensatory mechanism to the disease process of cardiomyopathy. However further increase in the left ventricular weight was not observed in older (40-week-old) cardiomyopathic hamsters. On the other hand left ventricular volume and volume/mass ratio were increased progressively. Correspondingly, V3 type myosin was increased and myosin sliding velocity was decreased. Left ventricular function of cardiomyopathic hamsters evaluated using an isovolumically beating perfused heart preparation was depressed, and this functional impairment was also progressive. Chronic administration of metoprolol, a beta-blocking agent, induced further increase in left ventricular volume and mass without changing left ventricular function and myosin isozyme pattern. Thus in cardiomyopathic hamsters, left ventricular function progressively deteriorates in spite of a variety of adaptive mechanisms, and remodeling occurs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1534856&dopt=Abstract
Aviat Space Environ Med. 1981 Nov;52(11 Pt 2):S19-22.
The clinical importance of lipid solubility in beta blockers.
Neil-Dwyer G.
The comparative effects of three lipophilic beta blocking agents--propranolol (80 mg b.i.d.) metoprolol (200 mg/d) and oxprenolol (160 mg/d) and one hydrophilic agent, atenolol (100 mg/d), were studied in patients undergoing neurosurgery. The respective penetration of these compounds into brain tissue and CSF was measured and correlated with plasma levels. The brain concentration of the three lipophilic beta blockers was high--propranolol some 20 times and oxprenolol and metoprolol some 10 times greater than the concentration of the hydrophilic, atenolol. The clinical relevance of this may be important in reducing the severity of centrally-mediated side effects, such as hallucinations and sleeplessness, by using a beta blocker less likely to penetrate the blood/brain barrier.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6118118&dopt=Abstract
Zhongguo Yao Li Xue Bao. 1995 Jul;16(4):325-9.
Metoprolol alpha-hydroxylation capacity in 96 Chinese Han volunteers.
Tu ZG, Zhao LL.
Chongqing University of Medical Sciences, China.
AIM: To study the ability of oxidizing metoprolol (Met) to form alpha-hydroxymetoprolol (HM) in Chinese in vivo and in vitro. METHODS: An ion-pair reverse phase high performance liquid chromatography was used. RESULTS: In vivo study, the 8-h urinary recoveries of Met and HM after po Met tartrate 100 mg were tested in 96 unrelated healthy Chinese Han volunteers, and the capacity of Met alpha-hydroxylation expressed by lg Met/HM (metabolic ratio, MR). The frequency histogram of lg MR showed the characteristic bimodal distribution of monogenic control variation, and the phenotypical antimode of lg MR was 1.09. Only 1 man with lg MR = 2.30 was identified as poor metabolizer of Met alpha-hydroxylation. The urinary recoveries of Met and HM and the MR in 95 extensive metabolizer were 6.8 +/- 3.3%, 3.0 +/- 1.5% of dose mole and 3.1 +/- 2.5, respectively. The sex difference, smoking and tea consuming had no effects on the urinary excretions of Met, and HM, and the MR. In vitro, the adding of NADH did not affect the activities of human liver microsome Met alpha-hydroxylase. The enzyme kinetics parameters were Km = 89.60 mumol L-1 and Vmax = 39.5 ng HM mg-1 min-1. No functional absence of liver microsome Met alpha-hydroxylase was found in the tested liver samples from 8 people, and the activities of liver microsome Met alpha-hydroxylase were 31 +/- 22 ng mg-1 min-1. CONCLUSION: The incidence of poor metabolizer phenotype for Met alpha-hydroxylation in Chinese Han nationality is low, and the NADH is not involved in human liver microsome Met alpha-hydroxylation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7668102&dopt=Abstract
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