Drugs online research references
Eur J Clin Pharmacol. 1992;42(1):47-53.
Differential cardiovascular effects of propranolol, atenolol, and pindolol measured by impedance cardiography.
Thomas SH, Cooper RC, Ekwuru M, Fletcher S, Gilbody J, Husseyin TS, Ishaque M, Jagathesan R, Reddy G, Smith SE.
Division of Pharmacological Sciences and Toxicology, United Medical School, London, UK.
We have evaluated Sramek's method of impedance cardiography as a non-invasive way of detecting the cardiovascular effects of drugs. We made cardiovascular measurements using the method during passive tilting and exercise 2 h after the oral administration of atenolol (50 and 100 mg), propranolol (40 and 80 mg), pindolol (5 and 10 mg), and placebo in seven separate studies involving eight healthy male volunteers. Equivalent doses of the pure antagonists atenolol (beta 1) and propranolol (beta 1, beta 2) produced similar reductions in heart rate, systolic blood pressure, and cardiac index, and increases in stroke volume and total peripheral resistance, particularly during exercise. In contrast the partial agonist pindolol produced increases in heart rate and cardiac index, and reductions in peripheral resistance at rest. During passive tilting and exercise pindolol reduced heart rate, but cardiac output and total peripheral resistance were unchanged except at the highest levels of exercise. The similar cardiovascular effects of atenolol and propranolol, but differing effects of pindolol, are consistent with reports using other methods of measurement. This suggests that impedance cardiography may have a place in the non-invasive assessment of the cardiovascular effects of drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1541316&dopt=Abstract
Tohoku J Exp Med. 1984 Mar;142(3):275-82.
Distribution of alpha-adrenergic receptors in the rabbit nephron.
Kusano E, Nakamura R, Asano Y, Imai M.
In order to determine the distribution of alpha-adrenergic receptors within a nephron, a method was used to determine the specific binding of [3H]-prazosin to isolated fragments of rabbit renal tubules. When 10(-8) moles/liter [3H]-prazosin was incubated with proximal convoluted tubules, 61.4% of total binding was accounted for specific binding. The [3H]-prazosin binding to the proximal convoluted tubule was a linear function of the tubular length and reversible. It was inhibited with 10(-4) moles/liter phenoxybenzamine by about 60%, and with 10(-4) moles/liter norepinephrine by about 25%, but not with either atenolol or isoproterenol. No specific binding of [3H]-prazosin was observed in the proximal straight tubule and in the cortical collecting tubule. These data are in good agreement with the view that alpha-1 adrenergic receptors are mainly distributed in the proximal convoluted tubules.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6328696&dopt=Abstract
Clin Pharmacol Ther. 1989 Apr;45(4):403-10.
The pharmacokinetics of the enantiomers of atenolol.
Boyd RA, Chin SK, Don-Pedro O, Williams RL, Giacomini KM.
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
A number of studies have demonstrated that lipophilic beta-adrenoceptor blocking agents, eliminated almost exclusively by hepatic metabolism, are stereoselectively metabolized in human beings. Previous studies in our laboratory have demonstrated that pindolol, a beta-adrenoceptor blocking agent of intermediate lipophilicity that is eliminated by both hepatic metabolism and renal excretion, is eliminated stereoselectively in the kidney. In the present study we examined the pharmacokinetics of the enantiomers of atenolol, a hydrophilic cardioselective beta-adrenoceptor blocking agent that is eliminated almost exclusively by the kidney. A single 100 mg oral dose of racemic atenolol was administered to six healthy adult men. Concentrations of d- and l-atenolol in plasma and urine were measured by a stereospecific HPLC analytic procedure. In each subject the peak concentration of d-atenolol was greater than the peak concentration of l-atenolol (mean +/- SD of 420 +/- 81 ng/ml vs 366 +/- 61 ng/ml; p less than 0.05). The peak concentration of both enantiomers was reached at the same time in each subject (between 2 and 3 hours). The renal clearances of d- and l-atenolol were not significantly different (109.7 +/- 33.5 ml/min vs 112.5 +/- 36.7 ml/min), probably because the major route of renal elimination is glomerular filtration. The half-lives of d- and l-atenolol were not significantly different (mean +/- SD of 4.6 +/- 1.1 hours vs 5.2 +/- 0.9 hours). However, both the AUC and the amount excreted unchanged in the urine in 24 hours Ae [0-24]) were significantly greater for d-atenolol than for l-atenolol (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2702798&dopt=Abstract
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