Drugs online research references
Arch Otolaryngol Head Neck Surg. 1997 Aug;123(8):837-40.
Terazosin blockade of nicotine-induced skin flap necrosis in the rat.
Karien RG, Maisel RH.
Department of Otolaryngology, University of Minnesota, Minneapolis, USA.
OBJECTIVE: To examine the ability of terazosin hydrochloride to block the decrease in skin flap survival induced by nicotine. DESIGN: A randomized controlled animal trial. SUBJECTS: Ninety-two male Sprague-Dawley rats were randomized to 1 of 5 groups: double-placebo control (n = 15), nicotine opposed by oral placebo (n = 26), nicotine opposed by subcutaneous placebo (n = 16), nicotine opposed by oral terazosin (n = 21), and nicotine opposed by subcutaneous terazosin (n = 14). INTERVENTION: All rats received 1 mg of nicotine twice daily via subcutaneous injection except for those in the double-placebo control group, which received saline injections twice daily, for the 6-week study. The terazosin treatment groups received 1.5 mg of terazosin hydrochloride twice daily either orally or subcutaneously while the rest received a saline solution placebo either orally or subcutaneously for the last 4 weeks of the study. At the end of the fifth week, a 4 x 10-cm, caudally based, dorsal random-pattern flap was elevated and repositioned. The outcome was measured in percentage area of flap survival. RESULTS: The mean (+/-SEM) area of flap survival for the double-placebo control group was 79% +/- 2%. Nicotine opposed by oral placebo or subcutaneous placebo produced a significant decrease in survival areas (mean [+/-SEM] area, 73% +/- 2% and 74% +/- 2%, respectively). Nicotine opposed by oral terazosin produced a mean (+/-SEM) survival area of 81% +/- 2%, which was significantly better than the nicotine opposed by placebo group and similar to the control group (P = .02). CONCLUSION: Use of oral terazosin elevated flap survival rates to control levels in nicotine-treated rats.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9260549&dopt=Abstract
J Pharmacol Exp Ther. 1997 Aug;282(2):891-8.
Relationships between pharmacokinetics and blockade of agonist-induced prostatic intraurethral pressure and mean arterial pressure in the conscious dog after single and repeated daily oral administration of terazosin.
Witte DG, Brune ME, Katwala SP, Milicic I, Kerwin JF Jr, Hancock AA.
Pharmaceutical Products Discovery, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
The purpose of this study was to determine the potency and selectivity of the alpha-1 adrenergic receptor antagonist terazosin based on relationships between plasma concentrations and blockade of intraurethral pressure (IUP) and mean arterial pressure (MAP) responses after single dosing and to determine cumulative effects after repeated dosing. To this end, the relationships between plasma concentrations and blockade effects of terazosin on phenylephrine (PE)-induced IUP and MAP were evaluated in conscious male beagle dogs after single (0.1, 0.3 and 1 mg/kg) and repeated (0.3 and 1 mg/kg) daily oral dosing of terazosin. Blockade effects and plasma concentrations were evaluated at selected times for periods of < or = 24 hr. Terazosin produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against terazosin plasma concentration, direct relationships were observed that were well described by the sigmoidal maximal effect model and resulted in IUP and MAP IC50 values of 48.6 and 12.2 ng/ml, respectively. Repeated daily dosing resulted in little accumulation of terazosin in plasma and demonstrated consistent blockade responses over 7 days. MAP blockade was observed up to 23 hr after terazosin administration, whereas IUP blockade returned to control levels before 23 hr. Combined pharmacokinetic/pharmacodynamic analysis showed no selective antagonism of IUP by terazosin but may provide a useful way to show uroselectivity of novel agents.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9262356&dopt=Abstract
Am J Hypertens. 2000 May;13(5 Pt 1):556-9.
Role of the sympathetic nervous system during the development of obesity-induced hypertension in rabbits.
Antic V, Kiener-Belforti F, Tempini A, Van Vliet BN, Montani JP.
Institute of Physiology, University of Fribourg, Switzerland.
We have previously reported that weight gain induced by high-fat diet (HFD) leads to an increase in mean arterial pressure (MAP, +14%) and heart rate (HR, +31%) in the adult rabbit. In the present study, we tested the hypothesis that an increased activity of the sympathetic nervous system may contribute to the development of obesity-induced hypertension. A combination of alpha- and beta-adrenergic blockers (terazosin + propranolol) was chronically administered to rabbits housed in metabolic cages for continuous monitoring of arterial pressure by telemetry, 24 h a day. After 2 weeks of adrenergic blockade under control diet, animals were switched to HFD for the next 6 weeks. HFD induced a progressive increase in body weight, but no increase in mean arterial pressure (+0.2+/-2.5%) and a slight increase in heart rate (+14+/-3%). Time-control animals fed normal diet showed no changes in MAP or HR with long-term alpha- and beta-adrenergic blockade. Our results indicate that the activation of the sympathetic nervous system may play an important role in the pathogenesis of obesity-induced hypertension.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10826410&dopt=Abstract
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