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Atenolol

Distribution by Scientific Domains

Medical Sciences	73%
Chemistry	11%
Life Sciences	9%

Distribution within Medical Sciences

Pharmacology & Pharmaceutical Medicine	30%
Cardiovascular Disease	20%
10 Other Subdomains	50%

Kinds of Atenolol

blocker atenolol

Selected Abstracts

The Effects of Antihypertensive Treatment on the Doppler-Derived Myocardial Performance Index in Patients with Hypertensive Left Ventricular Hypertrophy: Results from the Swedish Irbesartan in Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA)

ECHOCARDIOGRAPHY, Issue 7 2009
Stefan Liljedahl M.D.
Objectives: To investigate the effects of antihypertensive treatment on the Doppler-derived myocardial performance index (MPI) in patients with hypertensive left ventricular hypertrophy. Methods: The MPI was measured at baseline and after 48 weeks of antihypertensive treatment in 93 participants of the SILVHIA trial, where individuals with primary hypertension and left ventricular hypertrophy were randomized to double blind treatment with either irbesartan or atenolol. Results: Antihypertensive treatment lowered MPI (mean difference ,0.03 ± 0.01, P = 0.04). Changes in MPI by treatment were associated with changes in left ventricular ejection fraction (,-coefficient ,0.35 P = 0.005), stroke volume/pulse pressure (reflecting arterial compliance, ,-coefficient ,0.39 P < 0.001) and peripheral vascular resistance (,-coefficient 0.28 P < 0.04). Furthermore, there was a borderline significant association between changes in MPI and changes in E-wave deceleration time (reflecting diastolic function, ,-coefficient 0.23, P = 0.06). No associations were found between changes in MPI and changes in blood pressure, E/A-ratio, left ventricular mass index, relative wall thickness or heart rate. A stepwise multivariable regression model confirmed the association between changes in MPI and changes in ejection fraction and stroke volume/pulse pressure (all P < 0.05), as well as the trend for E-wave deceleration time (P = 0.08), but not in the case of peripheral vascular resistance. Conclusion: The MPI exhibited a modest decrease after 48 weeks of antihypertensive treatment in patients with hypertensive left ventricular hypertrophy. Changes in MPI were associated with changes in left ventricular function and vascular compliance, rather than with changes in left ventricular remodeling or blood pressure. [source]

An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and Flunarizine

PAIN MEDICINE, Issue 1 2010
Abouch V. Krymchantowski MD, FAHS
ABSTRACT Background., Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine. Methods., Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as <50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed. Results., Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients. Conclusions., Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations. [source]

Heart rate reduction by inhibition of If or by ,-blockade has different effects on postsystolic wall thickening

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2007
L Lucats
Background and purpose: Postsystolic wall thickening (PSWT) is part of thickening that occurs after end-systole and represents wasted effort as it does not contribute to ejection. The effects of antianginal drugs on PSWT remain to be established. We compared the effects on PSWT of two agents that reduce heart rate, the ,-blocker atenolol and the selective inhibitor of If current, ivabradine. Experimental approach: Six dogs were prepared to measure wall thickening by sonomicrometry in the conscious state, at rest and during exercise, after administration of saline, atenolol (1mg.kg -1) or ivabradine (1mg.kg -1). Key results: Atenolol and ivabradine similarly reduced heart rate vs saline at rest (about 10-20%) and during exercise (about 30%). Atenolol but not ivabradine decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest (0.35±0.07 vs 0.21±0.03mm, respectively) and during exercise (0.30±0.04 vs 0.15±0.04mm, respectively). In contrast, ivabradine did not alter PSWT. Importantly, atenolol but not ivabradine increased the ratio of postsystolic to systolic wall thickening by 80±23%. This enhanced thickening during diastole with atenolol was accompanied by impeded isovolumic relaxation of the left ventricle, as illustrated by the significant correlation between the isovolumic relaxation time constant , and the postsystolic to systolic wall thickening ratio. None of these effects of atenolol were abolished when heart rate was controlled with atrial pacing. Conclusion and implications: For a similar heart rate reduction at rest and during exercise, ivabradine, but not atenolol, did not alter PSWT and preserved the part of thickening contributing to ejection. British Journal of Pharmacology (2007) 150, 335,341. doi:10.1038/sj.bjp.0706996 [source]

The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study

DIABETIC MEDICINE, Issue 5 2004
R. Rachmani
Abstract Objective The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension. Patients and methods Sixty female diabetic patients aged 45,70 years with blood pressure (BP) 140,180/90,110 mmHg, serum creatinine (sCr) , 160 µmol/l, HbA1c , 10%, and albuminuria were treated by atenolol 12.5,75 mg/d and hydrochlorothiazide 6.25,25 mg/d. Titration-to-target helped to reach BP values , 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K+. sCr and HbA1c were assessed at baseline and at weeks 12, 16, 36 and 60. Results The average BP at week 12 was 128 ± 4/81 ± 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124,1571) to 216 (64,875) mg/g (P = 0.001), and on cilazapril to 302 (90,975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 µmol/l, P = 0.02) on cilazapril. Conclusion At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect. [source]

An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54)

DIABETIC MEDICINE, Issue 6 2001
A. Gray
Abstract Aims To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or , blocker (atenolol) in patients with Type 2 diabetes. Design A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. Setting Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. Subjects Hypertensive patients (n= 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the , blocker atenolol. Main outcome measures Life expectancy and mean cost per patient. Results There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was £6485 in the captopril group, compared with £5550 in the atenolol group, an average cost difference of £935 (95% confidence interval £188, £1682). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. Conclusions Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438,444 (2001) [source]

Ventricular PKC-, and humoral signaling in DOCA-Salt rats treated with labedipinedilol-A

DRUG DEVELOPMENT RESEARCH, Issue 3 2003
Jwu-Lai Yeh
Abstract Effects of oral antihypertensive monotherapy with labedipinedilol-A, labetalol, atenolol, amlodipine, prazosin (20 mg kg,1 day,1), and short-acting nifedipine (3 mg kg,1 day,1) on DOCA-salt-induced translocation of ventricular protein kinase C-,(PKC-,), humoral signaling, and the cardiovascular system were investigated in rats for 4 weeks. The triple blocking activities of labedipinedilol-A (,/,-adrenoceptor blockade and calcium entry blockade) were compared with single blocking activities of selective drugs. Cytosolic PKC-, immunoreactivity was decreased by labedipinedilol-A, short-acting nifedipine, amlodipine, prazosin, labetalol, atenolol, and losartan. Membranous PKC-, immunoreactivity was significantly decreased by labedipinedilol-A, amlodipine, prazosin, labetalol, and atenolol. Labedipinedilol-A and prazosin more potently decreased membranous than cytosolic PKC-, expression. Labedipinedilol-A, labetalol, and atenolol effectively inhibited DOCA-salt-induced increases in angiotensin II (Ang II). All antihypertensive agents reduced endothelin-1 (ET-1) levels in urine and cardiac weight growth. Treatments with labedipinedilol-A, labetalol, atenolol, and amlodipine normalized DOCA-salt-induced ANP increases. Prazosin did not decrease ANP. Short-acting nifedipine elevated ANP. During long-term antihypertensive therapy in DOCA-salt hypertensive rats, single blockade drugs did not fully inhibit ventricular PKC-, translocation or Ang II, ET-1, and ANP humoral signaling. However, triple blockade labedipinedilol-A therapy had a wide range of ,/,-adrenergic receptor and calcium channel inhibitory activities, including diminished reflux tachycardia, inhibition of PKC-, translocation, and reduction of Ang II, ET-1, and ANP formation. Drug Dev. Res. 59:307,315, 2003. 2003 Wiley-Liss, Inc. [source]

The Effects of Antihypertensive Treatment on the Doppler-Derived Myocardial Performance Index in Patients with Hypertensive Left Ventricular Hypertrophy: Results from the Swedish Irbesartan in Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA)

Sensitive analysis of donepezil in plasma by capillary electrophoresis combining on-column field-amplified sample stacking and its application in Alzheimer's disease,

ELECTROPHORESIS, Issue 17 2008
Hsin-Hua Yeh
Abstract Field-amplified sample stacking (FASS) in capillary electrophoresis (CE) was used to determine the concentration of donepezil, an acetylcholinesterase inhibitor, in human plasma. A sample pretreatment by liquid,liquid extraction with isopropanol/n -hexane (v/v 3:97) and subsequent quantification by FASS-CE was used. Before sample loading, a water plug (0.5,psi, 6,s) was injected to permit FASS. Electrokinetic injection (7,kV, 90,s) was used to introduce sample cations. The separation condition for donepezil was performed in electrolyte solutions containing Tris buffer (60,mM, pH 4.0) with sodium octanesulfonate 40,mM and 0.01% polyvinyl alcohol as a dynamic coating to reduce analytes' interaction with capillary wall. The separation was performed at 28,kV and detected at 200,nm. Using atenolol as an internal standard, the linear ranges of the method for the determination of donepezil in human plasma were over a range of 1,50,ng/mL. The limit of detection was 0.1,ng/mL (S/N=3, sampling 90,s at 7,kV). One female volunteer (54 years old) was orally administered a single dose of 10,mg donepezil (Aricept®, Eisai), and blood samples were drawn over a 60,h period for pharmacokinetic study. The method was also applied successfully to monitor donepezil in sixteen Alzheimer's disease patients' plasmas. [source]

Influence of microemulsion chirality on chromatographic figures of merit in EKC: Results with novel three-chiral-component microemulsions and comparison with one- and two-chiral-component microemulsions

ELECTROPHORESIS, Issue 17 2007
Kimberly A. Kahle
Abstract Novel microemulsion formulations containing all chiral components are described for the enantioseparation of six pairs of pharmaceutical enantiomers (atenolol, ephedrine, metoprolol, N -methyl ephedrine, pseudoephedrine, and synephrine). The chiral surfactant dodecoxycarbonylvaline (DDCV, R - and S -), the chiral cosurfactant S -2-hexanol, and the chiral oil diethyl tartrate (R - and S -) were combined to create four different chiral microemulsions, three of which were stable. Results obtained for enantioselectivity, efficiency, and resolution were compared for the triple-chirality systems and the single-chirality system that contained chiral surfactant only. Improvements in enantioselectivity and resolution were achieved by simultaneously incorporating three chiral components into the aggregate. The one-chiral-component microemulsion provided better efficiencies. Enantioselective synergies were identified for the three-chiral-component nanodroplets using a thermodynamic model. Additionally, two types of dual-chirality systems, chiral surfactant/chiral cosurfactant and chiral surfactant/chiral oil, were examined in terms of chromatographic figures of merit, with the former providing much better resolution. The two varieties of two-chiral-component microemulsions gave similar values for enantioselectivity and efficiency. Lastly, the microemulsion formulations were divided into categories based on the number of chiral microemulsion reagents and the average results for each pair of enantiomers were analyzed for trends. In general, enantioselectivity and resolution were enhanced while efficiency was decreased as more chiral components were used to create the pseudostationary phase (PSP). [source]

Effect of alkali metal hydroxides on the enantioseparation of amines using di- O -isopropylidene-keto- L -gulonic acid as the selector in NACE

ELECTROPHORESIS, Issue 22 2006
Ylva Hedeland Dr.
Abstract The present work demonstrates the importance of the ionic composition in the BGE for enantioseparation. (,)-2,3:4,6-di- O -Isopropylidene-2-keto- L -gulonic acid ((,)-DIKGA) has been used as the chiral selector in methanolic and ethanolic BGEs. The influence of added alkali metal hydroxides on the EOF and the chiral separation of amines (atenolol, isoprenaline, pindolol and propranolol) have been studied. The ion-pair formation constants in ethanol were determined by precision conductometry for the enantiomers of pindolol with (,)-DIKGA, for Li+, Na+ and Cs+ with (,)-DIKGA, and also for the corresponding alkali metal hydroxides. The effective mobilities and the enantiomeric mobility differences were affected by the type of alkali metal hydroxide (LiOH, NaOH, KOH, RbOH or CsOH) added to the BGE. The effective mobility and mobility difference were increased with decrease in solvated radius of the alkali metal cation. These differences could partly be correlated to the ion-pair formation constants of the alkali metal cations with the chiral selector, affecting the equilibrium concentration of the free selector. The electroosmosis was also affected by the alkali metal hydroxide added to the BGE. The cathodic electroosmosis decreased with decreasing solvated radius of the alkali metal cation added to the BGE. Interestingly, the cathodic EOF was even reversed, i.e. became anodic in the ethanolic BGEs containing KOH, RbOH or CsOH and the methanolic ones with RbOH and CsOH. [source]

Quantitation of talinolol and other ,-blockers by capillary electrophoresis for in vitro drug absorption studies

ELECTROPHORESIS, Issue 15 2003
Bilal Awadallah
Abstract A capillary zone electrophoresis method is described for the enantioseparation of talinolol using heptakis(2,3-diacetyl-6-sulfo)-,-cyclodextrin (HDAS-,-CD) as a chiral selector. After liquid-liquid extraction of talinolol from physiological solution, electrokinetic injection was employed to improve the sensitivity. The use of a coated capillary was necessary to achieve stable and reproducible enantioseparations. A baseline separation of the talinolol enantiomers was achieved in less than 10 min using 100 mM phosphate solution as background electrolyte and pH 3.5, at the presence of 3.0 mM HDAS-,-CD and at 20°C. In addition, this analytical condition proved to be useful for the enantioseparation of a number of other ,-blocking agents such as alprenolol, atenolol, bisoprolol, celiprolol, metipranolol, oxprenolol, and sotalol. For determing talinolol, the method could be validated in terms of precision, accuracy and linearity, and was found to be suitable in determination of talinolol enantiomers in highly diluted samples obtained from in vitro experiments. [source]

Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the Ebro river basin (Northeast Spain)

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007
Meritxell Gros
Abstract The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflam-matories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and ,-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60,90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the ,-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low ,g/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption. [source]

Instant centre frequency at anaesthetic induction , a new way to analyse sympathovagal balance,

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2003
Edmundo Pereira De Souza Neto
Abstract The instant centre frequency (ICF) of RR interval has been proposed as a global index to analyse the sympathovagal interaction in the heart. The aim of this study was to assess the ICF during anaesthesia to test if it can reliably capture the neural control of the cardiovascular system. Twenty-four ASA II or III patients scheduled for cardiac surgery were included in the study. They were allocated in two groups: control, no treatment (group 1, n = 12), and beta-adrenergic blockade by atenolol (group 2, n = 12). Spectra of pulse interval series were computed with a time,frequency method and they were divided into: very low frequency (VLF, 0.000,0.040 Hz), low frequency (LF, 0.050,0.150 Hz) and high frequency (HF, 0.160,0.500 Hz). Normalized power was obtained by dividing the cumulative power within each frequency band (LF or HF) by the sum of LF and HF; the ratio of LF/HF was also calculated. Instant centre frequency is a time-varying parameter that the evolution along time of the gravity centrum of a local spectrum. All spectral indexes were recorded at the following time points: before induction, after induction and before intubation, during intubation, and after intubation. The atenolol group had lower normalized LF and the LF/HF ratio (P < 0.05) higher HF before induction; and lower LF/HF ratio after induction and before intubation (P < 0.05). The ICF was higher in atenolol group at all times. The ICF shifted towards HF frequency after induction and before intubation and shifted towards LF during intubation in both groups. The autonomic nervous system control on the heart through the interaction of sympathetic and parasympathetic reflex mechanisms could be studied by the ICF. The ICF may assess the autonomic cardiac modulation and may provide useful information for anaesthetic management. [source]

Effects of six antihypertensive drugs on blood pressure and hypothalamic GABA content in spontaneously hypertensive rats

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2001
Ying Guan
In order to investigate the effects of antihypertensive drugs on blood pressure and ,-amino butyric acid (GABA) content in the hypothalamus and the possible relationship between blood pressure decrease and GABA content changes, blood pressure and GABA contents after chronic (20 weeks) treatments of nitrendipine, atenolol, captopril, hydrochlorothiazide, dihydralazine and prazosin were studied in spontaneously-hypertensive rats (SHR). The acute and subacute (1 week) effects of nitrendipine on GABA contents was also observed in SHR. It was found that 20 week treatments with six different antihypertensive agents produced a decrease in systolic blood pressure and an increase in GABA content. The blood pressure level was significantly correlated with GABA content in the hypothalamus, but not with that in the cortex. Acute treatment with a single dose of nitrendipine, did not alter GABA content. Bicuculline, a GABA receptor antagonist, did not attenuate the hypotensive effect of nitrendipine. In conclusion, chronic treatments by different antihypertensive agents produced an increase of hypothalamic GABA content and a decrease of blood pressure. The increase of GABA content induced by nitrendipine seems likely to be secondary to blood pressure decrease. [source]

Adrenaline inhibits macrophage nitric oxide production through ,1 and ,2 adrenergic receptors

IMMUNOLOGY, Issue 3 2000
L. B. Sigola
Summary This study was conducted to investigate the role of the acute stress hormone adrenaline on macrophage nitric oxide (NO) production. Murine peritoneal macrophages were stimulated in vitro with lipopolysaccharide (LPS) in the absence or presence of adrenaline. Adrenaline inhibited the LPS-induced nitrite response in a dose-dependent manner. The suppressive effect of adrenaline on NO production was mediated via ,1 and ,2 adrenergic receptors since isoprenaline (a non-selective ,1 and ,2 agonist), dobutamine and salbutamol (selective ,1 and ,2 agonists, respectively) had similar effects on the NO response. In addition, the inhibitory effect of adrenaline on NO was abrogated by both propranolol (a non-specific , blocker) and atenolol (a specific ,1 inhibitor). In contrast to , receptor activation, the , adrenergic agonist phenylephrine had no effect on the LPS NO response, and furthermore, phentolamine (an , receptor antagonist) did not ameliorate adrenaline's inhibitory action. [source]

Environmental risk assessment of human pharmaceuticals in the European Union: A case study with the ,-blocker atenolol

INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue S1 2010
Anette Küster
Abstract ,-Adrenergic receptor blockers (,-blockers) are applied to treat high blood pressure, ischemic heart disease, and heart rhythm disturbances. Due to their widespread use and limited human metabolism, ,-blockers are widely detected in sewage effluents and surface waters. ,-Adrenergic receptors have been characterized in fish and other aquatic animals, so it can be expected that physiological processes regulated by these receptors in wild animals may be affected by the presence of ,-blockers. Because ecotoxicological data on ,-blockers are scarce, it was decided to choose the ,-blocker atenolol as a case study pharmaceutical within the project ERAPharm. A starting point for the assessment of potential environmental risks was the European guideline on the environmental risk assessment of medicinal products for human use. In Phase I of the risk assessment, the initial predicted environmental concentration (PEC) of atenolol in surface water (500,ng L,1) exceeded the action limit of 10,ng L,1. Thus, a Phase II risk assessment was conducted showing acceptable risks for surface water, for groundwater, and for aquatic microorganisms. Furthermore, atenolol showed a low potential for bioaccumulation as indicated by its low lipophilicity (log KOW,=,0.16), a low potential for exposure of the terrestrial compartment via sludge (log KOC,=,2.17), and a low affinity for sorption to the sediment. Thus, the risk assessment according to Phase II-Tier A did not reveal any unacceptable risk for atenolol. Beyond the requirements of the guideline, additional data on effects and fate were generated within ERAPharm. A 2-generation reproduction test with the waterflea Daphnia magna resulted in the most sensitive no-observed-effect concentration (NOEC) of 1.8,mg L,1. However, even with this NOEC, a risk quotient of 0.003 was calculated, which is still well below the risk threshold limit of 1. Additional studies confirm the outcome of the environmental risk assessment according to EMEA/CHMP (2006). However, atenolol should not be considered as representative for other ,-blockers, such as metoprolol, oxprenolol, and propranolol, some of which show significantly different physicochemical characteristics and varying toxicological profiles in mammalian studies. Integr Environ Assess Manag 2010;6:514,523. © 2009 SETAC [source]

Role of Endothelium/Nitric Oxide and Cyclic AMP in Isoproterenol Potentiation of 17ß-Estradiol-Mediated Vasorelaxation

JOURNAL OF CARDIAC SURGERY, Issue 6 2002
HY Chan
Estrogen exerts vasorelaxation and cardiac protection via multiple cellular mechanisms. Estrogen modifies vasodilatation induced by certain relaxants such as ß-adrenoceptor agonists. However, little is known whether low concentrations of ß-adrenoceptor agonists would also influence the acute relaxant response to estrogen. The present study was designed to investigate the synergistic interaction between isoproterenol and 17ß-estradiol, and to study the role of endothelium and cyclic AMP-dependent pathway in this interaction. Changes in vessel tone of the isolated rat mesenteric artery rings were measured by force-displacement Grass transducer. In 9,11-dideoxy-11,, 9,-epoxy-methanoprostaglandin F2, - preconstricted endothelium-intact rings, 17ß-estradiol induced concentration-dependent relaxation with pD2 of 5.074 ± 0.043. Pretreatment of endothelium-intact rings with isoproterenol (1-3 × 10 -9 M, 1-h incubation time) significantly enhanced 17,-estradiol-induced relaxation. Longer incubation (2.5 h) did not produce further amplifying effect. This effect was inhibited by Rp-cGMPS triethylamine (3 × 10 -6 M), and disappeared in the presence of 3 × 10 -5 M NG -nitro-L-arginine methyl ester or in the endothelium-denuded rings. The effect of isoproterenol was partially antagonized by propranolol (3 × 10 -6 M), ICI 118,551 (3 × 10 -6 M) but not by atenolol (10 -5 M). None of three ,-adrenoceptor antagonists affected 17ß-estradiol-induced relaxation in the absence of isoproterenol. Rp-cAMPS triethylamine (3 × 10 -6 M) abolished the effect of isoproterenol. Besides, exposure to 3 × 10 -9 M forskolin for 1 h also potentiated the relaxant response to 17,-estradiol. In summary, this isoproterenol enhancement was dependent on the presence of endothelium and abolished by L-NAME via a ,2 -adrenoceptor-mediated cyclic AMP-dependent mechanism. These data also indicate the possible existence of cyclic AMP-dependent nitric oxide-producing pathway in the regulation of the vascular response to vasodilators. (supported by UPGC Direct Grant) [source]

The combination of atenolol and amlodipine is better than their monotherapy for preventing end-organ damage in different types of hypertension in rats

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2009
Ping Han
Abstract Combinations therapy is often used in hypertensive patients whether combination therapy is necessary for preventing end-organ damage is not known. The objective of this study was to determine in four different hypertensive animal models the necessity of adding the calcium channel blocker amlodipine to therapy with the ß-blocker atenolol to modulate end-organ damage. Spontaneously hypertensive rats, DOCA-salt hypertensive rats, two-kidney, one-clip renovascular hypertensive rats and Lyon genetically hypertensive rats were used to study this objective. These animal models have different sensitivities to atenolol and amlodipine. The dosages of therapy employed were 10 mg/kg atenolol alone, 1 mg/kg amlodipine, 10 mg atenolol + 1 mg/kg amlodipine and 5 mg/kg atenolol+0.5 mg/kg amlodipine. BP was continuously recorded in all animals. After determination of baroreflex sensitivity, rats were sacrificed for end-organ damage evaluation. The combination of amlodipine and atenolol had a synergistic inhibitory effect on blood pressure and blood pressure variability, and end-organ damage as compared with monotherapy with atenolol or amlodipine in all animal models. Baroreflex sensitivity also improved with the combination therapy more than with monotherapy. In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end-organ damage. The superior effect of the combination was observed in all four models of hypertension. [source]

Physicochemical interactions between drugs and superdisintegrants

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2008
Nelly Fransén
We have evaluated the interactions between superdisintegrants and drugs with different physicochemical characteristics, which may affect the in-vivo absorption e.g. after mucosal administration. The binding of sodium salicylate, naproxen, methyl hydroxybenzoate (methylparaben), ethyl hydroxybenzoate (ethylparaben), propyl hydroxybenzoate (propylparaben), atenolol, alprenolol, diphenhydramine, verapamil, amitriptyline and cetylpyridinium chloride monohydrate (CPC) to different superdisintegrants (sodium starch glycolate (SSG), croscarmellose sodium (CCS) and crospovidone) and one unsubstituted comparator (starch) was studied spectrophotometrically. An indication of the in-vivo effect was obtained by measuring the interactions at physiological salt concentrations. SSG was investigated more thoroughly to obtain release profiles and correlation between binding and ionic strength. The results showed that the main interactions with the anionic hydrogels formed by SSG and CCS were caused by ion exchange, whereas the neutral crospovidone exhibited lipophilic interactions with the non-ionic substances. The effect of increased ionic strength was most pronounced at low salt concentrations and the ion exchange interactions were almost completely eradicated at physiological conditions. The release profile of diphenhydramine was significantly affected by the addition of salt. It was thus concluded that the choice of buffer was of great importance for in-vitro experiments with ionic drugs. At physiological salt concentrations the interactions did not appear to be strong enough to influence the in-vivo bioavailability of any of the drug molecules. [source]

Prediction of human pharmacokinetics , renal metabolic and excretion clearance

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2007
Urban Fagerholm
The kidneys have the capability to both excrete and metabolise drugs. An understanding of mechanisms that determine these processes is required for the prediction of pharmacokinetics, exposures, doses and interactions of candidate drugs. This is particularly important for compounds predicted to have low or negligible non-renal clearance (CL). Clinically significant interactions in drug transport occur mostly in the kidneys. The main objective was to evaluate methods for prediction of excretion and metabolic renal CL (CLR) in humans. CLR is difficult to predict because of the involvement of bi-directional passive and active tubular transport, differences in uptake capacity, pH and residence time on luminal and blood sides of tubular cells, and limited knowledge about regional tubular residence time, permeability (Pe) and metabolic capacity. Allometry provides poor predictions of excretion CLR because of species differences in unbound fraction, urine pH and active transport. The correlation between fraction excreted unchanged in urine (fe) in humans and animals is also poor, except for compounds with high passive Pe (extensive/complete tubular reabsorption; zero/negligible fe) and/or high non-renal CL. Physiologically based in-vitro/in-vivo methods could potentially be useful for predicting CLR. Filtration could easily be predicted. Prediction of tubular secretion CL requires an in-vitro transport model and establishment of an in-vitro/in-vivo relationship, and does not appear to have been attempted. The relationship between passive Pe and tubular fraction reabsorbed (freabs) for compounds with and without apparent secretion has recently been established and useful equations and limits for prediction were developed. The suggestion that reabsorption has a lipophilicity cut-off does not seem to hold. Instead, compounds with passive Pe that is less than or equal to that of atenolol are expected to have negligible passive freabs. Compounds with passive Pe that is equal to or higher than that of carbamazepine are expected to have complete freabs. For compounds with intermediate Pe the relationship is irregular and freabs is difficult to predict. Tubular cells are comparably impermeable (for passive diffusion), and show regional differences in enzymatic and transporter activities. This limits the usefulness of microsome data and makes microsome-based predictions of metabolic CLR questionable. Renal concentrations and activities of CYP450s are comparably low, suggesting that CYP450 substrates have negligible metabolic CLR. The metabolic CLR of high-Pe UDP-glucuronyltransferase substrates could contribute to the total CL. [source]

Determination of atenolol by the micelle-stabilized room-temperature phosphorescence methodology

LUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 6 2007
Marcela A. Castillo
Abstract A micellar-stabilized room-temperature phosphorescence (MS,RTP) method for the determination of atenolol has been developed in micellar solutions of sodium dodecylsulphate (SDS) in the presence of thallium(I) as a heavy atom and sodium sulphite as an oxygen scavenger. The effects of thallium(I) nitrate, SDS and sodium sulphite concentrations on atenolol MS,RTP intensity were studied. Optimized conditions to obtain maximum sensitivity were 0.015 mol/L thallium(I) nitrate, 0.1 mol/L SDS and 0.0075 mol/L sodium sulphite. The maximum phosphorescence signal was completely developed in 10 min and the intensity was measured at ,ex = 272 nm and ,em = 412 nm. The linear range of application obtained was 2.01,16.00 µg/mL. The detection limit estimated from the least-squares regression analysis was 0.86 µg/mL and the relative standard deviation of 10 replicates was 1.7%. The proposed method was applied to the determination of atenolol in a pharmaceutical formulation. The quantitation was carried out by means of standard calibration, standard-additions calibration and Youden calibration. These three experiments were necessary to evaluate the presence of constant and proportional errors due to the matrix. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Successful treatment with enoximone for severe poisoning with atenolol and verapamil: a case report

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2004
C. Sandroni
Combined poisoning with calcium channel blockers (CCBs) and beta-blockers is usually associated with severe hypotension and heart failure. Due to the block of the beta receptors, treatment with adrenergic agonists, even at high doses, can be insufficient, and beta-independent inotropes, such as glucagon, may be required. Phosphodiesterase III (PDEIII) inhibitors represent a possible alternative to glucagon in these cases as they have an inotropic effect which is not mediated by a beta receptor. [source]

An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and Flunarizine

Syncope and sinus bradycardia from combined use of thalidomide and , -blocker,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2008
Takashi Yamaguchi MD
Abstract We present a case of a 76-year-old Japanese man with hypertension and multiple myeloma (MM) presented with syncope and sinus bradycardia. Thalidomide therapy for MM was added to longstanding atenolol therapy one month prior to presentation. His heart rate (HR) was around 70 beats per minute (bpm) before addition of Thalidomide. His HR on presentation was less than 30,bpm. He was treated with intravenous atropine followed by temporary pacemaker and taken off atenolol. His HR returned to around 70,bpm few days after discontinuation of atenolol, even though he was still taking thalidomide, permitting outpatient management without a pacemaker. Both thalidomide and atenolol have been reported to cause bradycardia. Neither agent caused bradycardia when used alone in this patient, but simultaneous use caused symptomatic bradycardia. As thalidomide is prescribed more frequently, clinicians should be aware of the possibility of drug-induced sinus bradycardia due to the interaction of thalidomide and , -blockers. Copyright © 2008 John Wiley & Sons, Ltd. [source]

A pharmacodynamic assessment of the impact of antihypertensive non-adherence on blood pressure control

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2000
DrPh, Peter W. Choo MD
Abstract Objectives To evaluate if antihypertensive regimens that conform to present FDA guidelines by maintaining ,,50% of their peak effect at the end of the dosing interval protect patients during sporadic lapses in adherence. Methods 169 patients on monotherapy for high blood pressure underwent electronic adherence monitoring for 3 months. Blood pressures were measured during non-study office visits and were retrieved from automated medical records. Questionnaires were used to obtain other covariate information. The ratio of the dosing interval to the half-life of drug activity (I,) was used to capture conformity with FDA guidelines. Data analysis focused on the interaction between I, and the impact on blood pressure of delayed dosing. Results The average (,±,standard deviation) blood pressure during the study was 139.0 (,±,12.0)/85.0 (,±,6.9) mm Hg. Lisinopril followed by sustained-release verapamil, atenolol, and hydrochlorothiazide were the most frequently prescribed agents. The majority of regimens (99%) conformed to FDA dosing guidelines. Of the patients 23% missed a dose before their blood pressure check. Non-adherence, however, did not have a direct impact on blood pressure, and no interaction with I, of was detected. Conclusions Among patients with relatively mild hypertension on single-drug therapy, regimens that conform to current FDA dosing guidelines may prevent losses of blood pressure control during episodic lapses of adherence. These findings should be replicated in other patient populations with standardized blood pressure measurement to confirm their validity. Copyright © 2000 John Wiley & Sons, Ltd. [source]

Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction in Diabetic Rats through Enhancement of Nitric Oxide Signaling

THE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010
Javier Angulo PhD
ABSTRACT Introduction., Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective ,1 -adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism. Aim., We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues. Methods., Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined. Main Outcome Measures., The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses. Results., Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals. Conclusions., Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes. Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling. J Sex Med 2010;7:2681,2697. [source]

ORIGINAL RESEARCH,BASIC SCIENCE: Effects of ACE Inhibition and Beta-Blockade on Female Genital Structures in Spontaneously Hypertensive Rats

THE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007
Jorge E. Toblli MD
ABSTRACT Introduction and Aim., This study evaluated the possible differences between an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker concerning their potential protective role on female external genitalia in spontaneously hypertensive rats (SHR). Main Outcome Measures., Morphological changes in the clitoris after antihypertensive treatments. Methods., For 6 months, SHR received no treatment; SHR + ramipril (RAM), SHR + atenolol (AT), and control Wistar Kyoto (WKY) rats received no treatment. Clitorises were processed for immunohistochemistry using anti-,-smooth muscle actin (,-SMA), anti-collagen I and III, anti-transforming growth factor ,1 (TGF,1), and anti-endothelial nitric oxide synthase (eNOS) antibodies. Results., SHR + RAM and SHR + AT presented significantly lower blood pressure in both groups vs. untreated SHR. Compared with WKY, ,-SMA was increased in the arteries and in the cavernous spaces of the clitoris together with a marked increase in wall/lumen ratio in clitoral vessels in untreated SHR. All these alterations were diminished in SHR + AT (P < 0.01). SHR + RAM presented differences with respect to SHR + AT in the reduction of these variables. TGF,1 expression in the vessel wall from the clitoris and collagen I and III deposition in the interstitium from the clitoris in untreated SHR were significantly more (P < 0.01) than in WKY. While SHR + AT showed a mild decrease in these variables, SHR + RAM presented a significant reduction (P < 0.01) in TGF,1 expression interstitial fibrosis and in both types of collagens. Positive immunostaining of eNOS in the sinusoidal endothelium from the clitoris was less (P < 0.01) in untreated SHR (3.4 ± 1.3%) and SHR + AT (5.1 ± 1.2%) than in SHR + RAM (17.2 ± 1.6%) and WKY (15.9 ± 1.7%). Untreated SHR and SHR + AT presented more surrounding connective tissue at the perineurium in the clitoris (P < 0.01) than SHR + RAM. Conclusion., ACE inhibition provided a considerable protective role on the female external genitalia structures in SHR by a mechanism that may be, at least in part, independent of the degree of blood pressure lowering. Toblli JE, Cao G, Casabé AR, and Bechara AJ. Effects of ACE inhibition and beta-blockade on female genital structures in spontaneously hypertensive rats. J Sex Med 2007;4:1593,1603. [source]

,2 -adrenoceptors are critical for antidepressant treatment of neuropathic pain,

ANNALS OF NEUROLOGY, Issue 2 2009
Ipek Yalcin PharmD
Objective Tricyclic antidepressants (TCAs) are one of the first-line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs. Methods We used pharmacological and genetic approaches in mice to study the role of ARs in the antiallodynic action of the TCA nortriptyline. Peripheral neuropathy was induced by the insertion of a polyethylene cuff around the main branch of the sciatic nerve. The specific role of ,2 -AR was evaluated by studying ,2 -AR,/, mice. We used von Frey filaments to assess mechanical allodynia. Results The antiallodynic action of nortriptyline was not affected by cotreatment with the ,2 -AR antagonist yohimbine, the ,1 -AR antagonists atenolol or metoprolol, or the ,3 -AR antagonist SR 59230A. On the contrary, the ,-AR antagonists propranolol or sotalol, the ,1/,2 -AR antagonists alprenolol or pindolol, or the specific ,2 -AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in ,2 -AR,deficient mice. Interpretation Stimulation of ,2 -AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between ,-blockers that affect ,2 -AR and antidepressant drugs in patients treated for neuropathic pain. Ann Neurol 2009;65:218,225 [source]

Evidence showing that ,-adrenoceptor subtype responsible for the relaxation induced by isoprenaline is principally ,2 but not ,1 in guinea-pig tracheal smooth muscle

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2004
Y. Tanaka
Summary 1 The present study was carried out to pharmacologically identify the ,-adrenoceptor subtype that mediates isoprenaline-elicited relaxation in the isolated guinea-pig tracheal smooth muscle, to answer the question whether it is ,1 - or ,2 -subtype? 2 Isoprenaline as well as salbutamol, a well-known ,2 -selective adrenoceptor agonist, produced a concentration-dependent relaxation with a pD2 value of 8.12 vs. 7.54 for salbutamol. 3 Isoprenaline-elicited relaxation was not affected by ,1 -selective antagonists, atenolol and CGP-20,712A, within the concentration ranges supposed to antagonize ,1 -subtype: atenolol, ,10,6 m; CGP-20,712A, ,10,8 m. 4 By contrast, the concentration,response curves for isoprenaline as well as salbutamol were shifted rightwards in a competitive fashion by atenolol at the concentrations ,3 × 10,6 m. However, pA2 values of atenolol against isoprenaline (5.86) and salbutamol (5.71) were consistent with the value corresponding to ,2 - but not to ,1 -subtype (around 7.00), and these values were not significantly different from each other. 5 Competitive antagonism of the relaxations to isoprenaline and salbutamol were also obtained with ,2 -selective antagonists, butoxamine and ICI-118,551. Against isoprenaline and salbutamol, the pA2 values of butoxamine (6.51 vs. 6.81) and ICI-118,551 (8.83 vs. 8.90) were substantially identical. Thus the primary mediation of ,2 -receptor in the relaxations was strongly supported. 6 The present findings provide evidence that the ,-adrenoceptor which mediates isoprenaline-elicited relaxation of guinea-pig tracheal smooth muscle is essentially ,2 - but not ,1 -subtype. The present study also indicates the importance of using multiple receptor antagonists with different pA2 values to pharmacologically identify the responsible receptor subtype in smooth muscle mechanical responses. [source]

The relative importance of the time-course of receptor occupancy and response decay on apparent antagonist potency in dynamic assays

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2000
M. Corsi
1 The potency of the ,1 -adrenoceptor antagonist atenolol was measured as an inhibitor of responses to isoprenaline in guinea-pig left atria. Measurements were made in two ways, firstly, by pre-incubating the atria with a given concentration of atenolol followed by an isoprenaline dose,response curve and, secondly, by measuring the response to isoprenaline followed by addition of atenolol. 2 It was found that the estimation of atenolol potency as an antagonist of ,1 -adrenoceptors by these two methods gave divergent results. Specifically, it was found that the isoprenaline-induced increased rate of myocardial relaxation was resistant to receptor blockade. Thus, the rate-limiting step in the relaxation response was dissociated from receptor activation and therefore, could not be used for the measurement of receptor occupancy. 3 In contrast, the positive inotropic response was very responsive to receptor occupancy. However, when atenolol was used to block a steady-state isoprenaline response, there was a complicating depression of basal inotropy after receptor blockade that obfuscated measurement of receptor blockade. 4 In general, these data indicated that the blockade of a steady-state agonist response to measure the potency of an antagonist might in some cases yield erroneous results. These studies indicate some caution in the interpretation of blockade responses in pre-contracted or pre-stimulated pharmacological preparations. [source]