Drugs online research references
J Cardiovasc Pharmacol. 1987;10 Suppl 3:S69-72.
Differences in vasodilating action between ketanserin, a 5-HT2-serotonergic receptor antagonist, and terazosin, an alpha 1-adrenoceptor antagonist, in anesthetized rabbits.
Ikeda K, Takata M, Tomoda F, Mikawa M, Iida H, Sasayama S.
Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
It has not yet been demonstrated clearly whether the antihypertensive action of ketanserin is due to 5-hydroxytryptamine type-2 (5-HT2)-serotonergic receptor blockade or to alpha 1-adrenergic receptor blockade. The present study was performed to evaluate in vivo the antihypertensive action of ketanserin in comparison with that of terazosin, a selective alpha 1-adrenoceptor antagonist. The changes of renal blood flow (RBF) after intrarenal injection of phenylephrine, 5-HT, or angiotensin II were measured in anesthetized rabbits. RBF responses induced by these vasoconstrictors with or without pretreatment with ketanserin (0.2, 1.0, and 5.0 mg/kg, i.v.) or terazosin (0.04, 0.2, and 1.0 mg/kg, i.v.) were examined. Following intrarenal injection, RBF decreased by 20.8%, 22.7%, and 23.0% respectively, without ketanserin and also decreased by 21.0%, 21.6%, and 24.4%, respectively, without terazosin. Following pretreatment with a small dose of ketanserin or terazosin, the vasoconstricting effects of phenylephrine were attenuated by 20% or 62% (delta% changes in RBF), respectively. The effects of 5-HT on RBF responsiveness were blocked by ketanserin in a dose-dependent manner. Ketanserin did not modify the RBF responses to angiotensin II. These findings indicate that the antihypertensive effect of ketanserin, to a certain extent, depends on the blockade of the 5-HT2-serotonergic receptor in addition to that of the alpha 1-adrenoceptor, whereas the renin-angiotensin system is not involved in the hypotensive effects of ketanserin.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2446076&dopt=Abstract
J Urol. 1988 Sep;140(3):664-7.
The alpha adrenergic binding properties of terazosin in the human prostate adenoma and canine brain.
Lepor H, Baumann M, Shapiro E.
Division of Urology, Jewish Hospital of St. Louis, MO 63110.
Clinical trials are currently underway to evaluate the efficacy of terazosin for the treatment of symptomatic benign prostatic hyperplasia (BPH). Terazosin is a potent and selective alpha 1 adrenergic blocking agent structurally similar to prazosin. The alpha adrenergic binding properties of terazosin were studied in human prostate adenomas and canine brains using radioligand receptor binding methods. Saturation analyses were performed at varying concentrations of [125I]-Heat and [3H]rauwolscine [( 3H]Ra) in human prostate adenomas and canine brains. The binding of [125I]-Heat and [3H]Ra in the human prostates and canine brains was consistently saturable and of high affinity. The equilibrium dissociation constant (Kd) for [125I]-Heat binding in the canine brains and human prostate adenomas was 84.4 +/- 4.3 pM and 65.4 +/- 19.2 pM, respectively (p greater than 0.05). The (Kd) for [3H]Ra binding in the human prostate adenomas and canine brains was 1.21 +/- 0.23 nM and 1.52 +/- 0.28 nM, respectively (p greater than 0.05). The density of alpha 1 (0.37 +/- 0.15 fmol/mg. wet wt.) and alpha 2 (0.29 +/- 0.09 fmol/mg. wet wt. adrenergic binding sites in the human adenomas were similar (p greater than 0.05). The IC50 corrected (IC50 corr) of terazosin for [125I]-Heat and [3H]Ra binding sites in the human prostate was 2.5 nM and 1.0 micron., respectively. The IC50 corr of terazosin for [125I]-Heat and [3H]Ra binding sites in the canine brain was 2.0 nM and 0.8 microM, respectively. The competitive binding assays indicate that terazosin binds selectively to alpha 1 adrenergic binding sites in the human prostate and canine brain.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2457715&dopt=Abstract
Clin Ther. 1999 Jun;21(6):1006-24.
Economic analysis of finasteride: a model-based approach using data from the Proscar Long-Term Efficacy and Safety Study.
Albertsen PC, Pellissier JM, Lowe FC, Girman CJ, Roehrborn CG.
University of Connecticut Health Center, Farmington, USA.
Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in older men in the United States. BPH is often associated with a reduction in quality of life and may progress to acute urinary retention (AUR), the inability to pass any urine. Recently, a 4-year placebo-controlled clinical trial known as the Proscar Long-Term Efficacy and Safety Study (PLESS) demonstrated that finasteride use reduces the risk of developing AUR by 57% and the need for BPH-related surgery by 55%. The economic implications of these findings were investigated using a model-based decision-analytic approach to compare finasteride with both watchful waiting and alpha-blocker therapy. The modeling used the longest-term published controlled data concerning alpha-blockers, which were for the alpha-blocker terazosin. The base case considered a 64-year-old man (the mean age of a PLESS patient) with prostatic enlargement on digital rectal examination and moderate-to-severe symptoms of BPH. The model suggested savings in surgical and AUR costs with finasteride versus watchful waiting, with an estimated 25% of total finasteride costs recouped in savings on surgical events avoided in the first year. Over 2 years, the expected cost per patient starting finasteride therapy was $2304, whereas the expected cost per patient starting terazosin was $2334. Analyses also explored the variation in economic results by baseline levels of prostate-specific antigen (PSA), a proxy for prostate volume. For patients with PSA levels > or =1.4 ng/mL, expected 2-year costs with finasteride and terazosin were $2342 and $2479, respectively. For patients with PSA levels > or =3.3 ng/mL, expected 2-year costs with finasteride were $373 less than with terazosin ($2347 vs $2720). Results were robust over a range of model assumptions and cost estimates. The analyses illustrate that all medical interventions, including watchful waiting, have associated costs. Finasteride shows cost offsets compared with watchful waiting and cost savings compared with terazosin over 2 years. Finasteride appears to be more economical in men with higher PSA levels.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10440624&dopt=Abstract
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