Drugs online research references
Drugs. 1988;36 Suppl 6:48-54.
Haemodynamic effects of new beta-blockers with vasodilatory properties in essential hypertension.
Tsukiyama H, Otsuka K, Horii M.
Department of Cardiovascular Diseases, Kanagawa Cancer Center, Yokohama, Japan.
Six weeks of treatment with carvedilol, N-696, celiprolol, dilevalol, acebutolol, urapidil, doxazosin and altiopril reduced blood pressure with various changes in heart rate. Cardiac index decreased and total peripheral resistance index (TPRI) stayed at the pretreatment levels in the carvedilol, N-696 and acebutolol groups, whereas TPRI tended to decrease in the celiprolol (p less than 0.05), dilevalol (p less than 0.05), urapidil, doxazosin (p less than 0.05) and altiopril groups; cardiac index was unchanged in these groups. As carvedilol and N-696 have no beta 1-selectivity and no intrinsic sympathomimetic activity (ISA), their direct vasodilating property (and the possible alpha-blocking activity of carvedilol) may precipitate in minimising an increase in TPRI induced by vascular beta 2-blockade and suppressed cardiac pump function. Celiprolol and dilevalol, with beta 2-selective ISA, reduced cardiac index slightly and insignificantly, and decreased TPRI. These results indicate that ISA on vascular beta 2-receptors may induce vasodilatation and ISA on cardiac beta 2-receptors may counteract cardiac beta 2-blockade. Differences in haemodynamic responses between these drugs with ISA and vasodilators such as alpha-blocking agents (urapidil and doxazosin) and an ACE inhibitor, altiopril, may be attributable to manifestation of cardiac beta-blockade as observed in the drugs with ISA.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2908304&dopt=Abstract
columbia.edu
OBJECTIVES: Baseline pressure/flow parameters have not correlated well with response to medical therapy for lower urinary tract symptoms (LUTS). This open-label, nonrandomized retrospective study was designed to evaluate whether the urodynamic parameter duration (in seconds) of the detrusor contraction (DCD) correlates better with alpha-blocker response than previously described urodynamic parameters. METHODS: 93 men (mean age 62.6+/-8.5) with LUTS underwent urodynamic evaluation prior to initiating therapy with doxazosin titrated to 8 mg and followed for 6 months. Parameters of evaluation included the AUA symptom score (AUASx), peak urinary flow rate (Q(max)), maximal detrusor pressure (P(max)), detrusor pressure at maximal flow (P(det)) and DCD. The correlation and predictive value of therapeutic response and baseline urodynamic parameters were assessed. RESULTS: 85 patients were evaluable at 6 months. For the entire group, AUASx decreased from 15.1+/-6.9 to 9.7+/-5.1 (-36%) and Q(max) increased from 9.3+/-3.7 to 11.9+/-5.7 ml/s (+28%). Baseline P(max) was 74.8+/-19.6 cm H(2)O, P(det) was 61.6+/-18.9 cm H(2)O and DCD was 107.6+/-28.6 s. There was weak correlation between either baseline P(max) or P(det) and therapeutic response (defined as a decrease in AUASx of 40% and an increase in Q(max) of 30%). Utilizing a baseline DCD of 90 s or more, there was a significant correlation to therapeutic response (r = 0.48, p = 0.002). CONCLUSIONS: These preliminary data suggest that DCD may be a useful urodynamic parameter to predict and optimize therapy with a-blockade. The potential utility and cost-effectiveness of DCD remains to be determined.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10720858&dopt=Abstract
Br J Clin Pharmacol. 1986;21 Suppl 1:19S-25S.
The metabolism and kinetics of doxazosin in man, mouse, rat and dog.
Kaye B, Cussans NJ, Faulkner JK, Stopher DA, Reid JL.
The metabolic fate of doxazosin was investigated in man, mouse, rat and dog using 14C-labelled compound. Bioavailability and pharmacokinetic studies were also conducted with nonlabelled drug, using a specific h.p.l.c. method. Following both oral and intravenous administration, the major route of elimination of drug-related compounds was via the faeces for all species studied. Comparison of the oral and intravenous data show that doxazosin is completely absorbed in man, mouse and rat and is moderately well absorbed in dog. The drug is extensively metabolized, e.g. only about 5% of the dose was excreted unchanged in man. Metabolism in man mainly involves 6- and 7- O-demethylation and 6' and 7'-hydroxylation. These and some minor products were common to the mouse, rat or dog and man. Plasma protein binding was high in all species studied, ranging from 95.3% in the rat to 98.3% in human patients. Oral bioavailability is 60% in dog and approximately 50% in the rat, which is similar to the value of 63% reported for man at therapeutic doses. Mean plasma clearance values were 13 ml min-1 kg-1 (dogs), 30 ml min-1 kg-1 (rats) and 1.2 ml min-1 kg-1 (human subjects). Mean plasma half-life values were 5 h in dogs and 1.2 h in rats: a value of 9 h was reported for human volunteers (cf. 2.5 h for prazosin). The long plasma half-life of doxazosin provides the basis for once-daily dosing.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2939865&dopt=Abstract
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