Content study of N-nitroso impurities in 5 types of β-blockers / 中国药房

OBJECTIVE To determine the contents of N-nitroso impurities in raw materials/formulations of propranolol， metoprolol， atenolol， esmolol and bisoprolol， and clarify the attention threshold. METHODS Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q/Orbitrap HRMS）was adopted. An ACE Excel 3 C18-AR column was used for the separation and a mixture of 0.2% formic acid solution with 0.01 mol/L ammonium acetate and methanol was employed as the mobile phase by gradient elution， at a flow rate of 0.60 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The heated electrospray ionization source was employed in the positive full mass spectra-selected ion monitoring mode. The contents of N-nitroso impurities in raw materials/formulations of 15 batches of β-blockers from 10 manufacturers were determined by this method. Discovery Studio software was applied to predict the toxicity of the impurities and estimate the attention threshold. RESULTS Among 5 kinds of β-blockers， the linear ranges of N-nitroso propranolol， N-nitroso metoprolol， N-nitroso atenolol， N-nitroso esmolol and N-nitroso bisoprolol were 1.01-503.38， 1.02-508.38， 0.97-483.63， 1.11-554.27 and 1.05-523.92 ng/mL， respectively （r＞0.999）. The limits of quantitation were 1.04， 0.25， 0.05， 0.55 and 1.05 ng/mL， and the limits of detection were 0.52， 0.08， 0.02， 0.17 and 0.52 ng/mL， respectively. RSDs of precision， reproducibility， recovery， stability and durability tests were all lower than 7.5% （n＝6 or n＝5）. Among the 15 batches of samples， except for 1 batch， N-nitroso propranolol （1.07-8.91 ng/mg）， N-nitroso metoprolol （1.43-3.37 ng/mg）， N-nitroso atenolol （1.33 ng/mg）， N-nitroso esmolol （0.19 ng/mg） and N-nitroso bisoprolol （1.27 ng/mg） were detected in all other batches. According to predictions， the above 5 impurities had varying degrees of reproductive toxicity， mutagenicity and carcinogenicity， with attention thresholds of 1.0， 0.4， 4.3， 0.2 and 46.7 ng/mg， respectively. CONCLUSIONS The established method is simple， rapid， sensitive and specific， the estimated attention thresholds are clear， which can be used for the control of N-nitroso impurities in various β-blockers.

Advances in the application of nonselective β-receptor blockers in treatment of liver cirrhosis / 临床肝胆病杂志

Nonselective β-receptor blockers (NSBBs) are first-line drugs for the prevention and treatment of complications in cirrhotic patients with portal hypertension and are widely used in the primary and secondary prevention of esophagogastric variceal bleeding. In recent years, studies have shown that in patients with clinically significant portal hypertension (CSPH), NSBBs can used to prevent liver decompensation events besides variceal bleeding, such as ascites and hepatic encephalopathy. However, in patients without CSPH, current research evidence does not support the use of NSBBs. Although reliable data currently support the use of NSBBs in end-stage liver cirrhosis, there are still drug safety issues in patients with refractory ascites and spontaneous bacterial peritonitis, and further studies are needed to explore the dose and timing of administration. This article reviews the clinical research advances in the use of NSBBs (especially carvedilol) in patients with liver cirrhosis and summarizes the therapeutic window used reasonably in the whole-course management of liver cirrhosis, so as to provide a basis for clinical decision-making.

Analysis of β-blockers associated with acute renal failure signal based on data mining method / 中国药房

OBJECTIVE To excavate and evaluate β-blockers associated with acute renal failure（ARF）signal. METHODS Using the report odds ratio （ROR）method and Bayesian confidence interval progressive neural network （BCPNN）method，signal detection and analysis were performed for 4 kinds of β-blockers（metoprolol，bisoprolol，atenolol，nebivolol）associated with ARF Δ 基金项目：重庆市临床药学重点专科建设项目 （No.渝卫办发 in FDA adverse event reporting system （FAERS）from the two 〔2020〕68号）；重庆医科大学未来医学青年创新团队发展支持计划项 dimensions of Standard International Dictionary of Medical 目（No.W0081） Terms （MedDRA） analysis query （SMQ） term set and ＊药师，硕士研究生。研究方向：药物警戒。电话：023-68485161。 preferred term （PT） level terms. When the two methods E-mail：2020121624@stu.cqmu.edu.cn detected positive signals at the same time ，it indicated that # 通信作者：主任药师，硕士生导师。研究方向：临床药学、药物警 suspicious signals were detected. RESULTS Totally 14 328 戒。电话：023-63625666。E-mail：jiayuntaomail@hospital.cqmu.edu.cn ARF reports of 4 kinds of β-blockers were retrieved within the ·1380· China Pharmacy 2022Vol. 33 No. 11 中国药房 2022年第33卷第11期 narrow sense of “acute renal failure ”in SMQ term set ，of which men （6 964）were more than women （6 206）. The age of patients was mainly concentrated in the middle-aged and elderly （≥45 years old ），and serious adverse events accounted for 77.23％. The results of signal retrieval based on SMQ term set showed that ROR values and 95％ confidence intervals of metoprolol ，bisoprolol， atenolol and nebivolol detected by ROR method were 2.58（2.51，2.65），5.30（5.14，5.47），2.80（2.69，2.91）and 3.28（3.04， 3.53）respectively. The signal components （IC）detected by BCPNN method and the lower limit of IC were 1.29（1.25），2.26 （2.22），1.42（1.36）and 1.64（1.53）respectively，suggesting suspicious signals were detected in these four kinds of β-blockers associated ARF. The results of signal detection based on PT level terms showed that 37 positive signals were detected by ROR method，38 positive signals were detected by BCPNN method ，and 36 suspicious signals were detected by the two methods at the same time. For each drug ，12 suspicious signals of metoprolol were detected at the same time ，9 suspicious signals of bisoprolol and atenolol were detected at the same time ，and 6 suspicious signals of nebivolol were detected at the same time ；the number and type of signals were different among the 4 kinds of drug. CONCLUSIONS Four kinds of β-blockers may cause ARF. Compared with metoprolol and atenolol ，bisoprolol and nebivolol have strong statistical correlation with ARF ，suggesting that medical personnel should pay attention to the possible renal related adverse reactions of these drugs in the process of clinical use.

Effects of antihypertensive drugs on renal function after percutaneous transluminal coronary angioplasty / 药学实践杂志

Objective To evaluate the effects of antihypertensive drugs on renal function after percutaneous transluminal coronary angioplasty. Methods A retrospective analysis was performed on 193 patients who underwent percutaneous transluminal coronary angioplasty and took antihypertensive drugs regularly. Those patients were admitted to Nanjing Drum Tower Hospital during January 2020 to December 2020. The patients were divided into ACEI/ARB group, β-blockers, calcium channel blockers and hydration control group. All patients received routine hydration during the perioperative period. The changes of serum creatinine (Scr), blood urea nitrogen (BUN), estimated glomerular filtration rate(eGFR) and endogenous creatinine clearance rate (Ccr) before and after operation were compared. Results The incidence of CIN was 0% in four groups. Compared with the preoperative, there was no significant change in Scr and Ccr in every group. Except for the hydration control group, the BUN levels in three treated groups were reduced after postoperative. Specifically, the BUN reduction in β-blockers group has statistically significant difference compared to the hydration control group and CCB group. In addition, eGFR levels were significantly reduced in the β-blockers group. Preoperative Scr and Ccr levels in patients with high blood pressure (SBP≥140 or DBP≥90) were significantly different from the patients with normal blood pressure (SBP<140 and DBP<90). Conclusion The use of ACEI/ARB and CCB before percutaneous transluminal coronary angioplasty had no effect on renal function in the short term. β-blockers can slightly reduce renal function, especially in patients with high blood pressure, who should receive special attention.

Rapid and sensitive analysis of trace β-blockers by magnetic solid-phase extraction coupled with Fourier transform ion cyclotron resonance mass spectrometry / 药物分析学报

A rapid and sensitive method for analyzing trace β-blockers in complex biological samples,which involved magnetic solid-phase extraction(MSPE)coupled with Fourier transform ion cyclotron reso-nance mass spectrometry(FTICR-MS),was developed.Novel nanosilver-functionalized magnetic nano-particles with an interlayer of poly(3,4-dihydroxyphenylalanine)(polyDOPA@Ag-MNPs)were synthesized and used as MSPE adsorbents to extract trace β-blockers from biological samples.After extraction,the analytes loaded on the polyDOPA@Ag-MNPs were desorbed using an organic solvent and analyzed by FTICR-MS.The method was rapid and sensitive,with a total detection procedure of less than 10 min as well as limits of detection and quantification in the ranges of 3.5-6.8 pg/mL and 11.7-22.8 pg/mL,respectively.The accuracy of the method was also desirable,with recoveries ranging from 80.9％to 91.0％following the detection of analytes in human blood samples.All the experimental results demonstrated that the developed MSPE-FTICR-MS method was suitable for the rapid and sensitive analysis of trace β-blockers in complex biological samples.

Simultaneous enantioseparation and simulation studies of atenolol,metoprolol and propranolol on Chiralpak(R) IG column using supercritical fluid chromatography / 药物分析学报

Enantioseparation of three β-blockers,i.e.,atenolol,metoprolol and propranolol,was studied on amylose tris(3-chloro-5-methylphenylcarbamate) immobilized chiral stationary phase using supercritical fluid chromatography (SFC).The effect of organic modifiers (methanol,isopropanol and their mixture),col-umn temperature and back pressure on chiral separation of β-blockers was evaluated.Optimum chro-matographic separation with respect to resolution,retention,and analysis time was achieved using a mixture of CO2 and 0.1％ isopropyl amine in isopropanol:methanol (50:50,V/V),in 75:25 (V/V) ratio.Under the optimized conditions,the resolution factors (Rs) and separation factors (α) were greater than 3.0 and 1.5,respectively.Further,with increase in temperature (25-45 ℃) and pressure (100-150 bars)there was corresponding decrease in retention factors (k),α and Rs.However,a reverse trend (α and Rs)was observed for atenolol with increase in temperature.The thermodynamic data from van't Hoff plots revealed that the enantioseparation was enthalpy driven for metoprolol and propranolol while entropy driven for atenolol.To understand the mechanism of chiral recognition and the elution behavior of the enantiomers,molecular docking studies were performed.The binding energies obtained from simulation studies were in good agreement with the elution order found experimentally and also with the free energy values.The method was validated in the concentration range of 0.5-10 μg/mL for all the enan-tiomers.The limit of detection and limit of quantitation ranged from 0.126 to 0.137 μg/mL and 0.376-0.414 μg/mL,respectively.The method was used successfully to analyze these drugs in pharmaceutical preparations.

Effects of Non-selective β-blockers on Mortality of Patients with Cirrhosis and Ascites：A Meta-analysis / 中国药房

OBJECTIVE：To syste matically evaluate the effects of non-selective β-blockers（NSBB）on mortality of patients with cirrhosis and ascites ，and to provide evidence-based reference for clinical drug use. METHODS ：Retrieved from PubMed ，the Cochrane Library ，Embase，Web of Science ，CNKI and Wanfang database ，randomized controlled trials （RCTs）and cohort studies about the effects of NSBB on mortality of patients with cirrhosis and ascites were collected from the date of database establishment to Sept. 30th，2019. The patients in the trial group were treated with NSBB ，the patients in the control group were treated with blank control or isosorbidemononitrate ，variceal ligation or other measures to prevent variceal bleeding. After literature screening and data extraction ，the quality of RCTs and cohort studies were evaluated by using bias risk evaluation tool recommended by Cochrane system evaluator manual 5.1.0 and Newcastle-Ottawa scale . Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS ：Totally 18 studies were included ，involving 8 649 patients，4 RCTs and 14 cohort studies. Results of Meta-analysis showed that ，there was no significant difference in all-cause mortality between the patients using NSBB of trial group [RR ＝0.85，95％ CI（0.65，1.11），P＝0.22]，severe ascites [RR ＝0.58，95％ CI（0.15，2.22），P＝0.42] or refractory ascites [RR ＝0.85，95％CI（0.61，1.20），P＝0.36] and the control group. Subgroup analysis showed that ，there was no significant difference in all-cause mortality between the patients using NSBB of trial group and control group according to the research method （RCT vs. cohort study ）and the type of drug use （P＞0.05）. CONCLUSIONS ：The use of NSBB does not increase the incidence of all-cause mortality in cirrhosis patients with ascites ，or even in those with severe ascites or refractory ascites.

β-Adrenergic Receptor and Insulin Resistance in the Heart

Insulin resistance is characterized by the reduced ability of insulin to stimulate tissue uptake and disposal of glucose including cardiac muscle. These conditions accelerate the progression of heart failure and increase cardiovascular morbidity and mortality in patients with cardiovascular diseases. It is noteworthy that some conditions of insulin resistance are characterized by up-regulation of the sympathetic nervous system, resulting in enhanced stimulation of β-adrenergic receptor (βAR). Over-stimulation of βARs leads to the development of heart failure and is associated with the pathogenesis of insulin resistance in the heart. However, pathological consequences of the cross-talk between the βAR and the insulin sensitivity and the mechanism by which βAR over-stimulation promotes insulin resistance remain unclear. This review article examines the hypothesis that βARs over-stimulation leads to induction of insulin resistance in the heart.

Benefit and Application of β-blocker Therapy for Patients with AMI in the Era of PCI / 沈阳医学院学报

[ Abstrct] Back in the 1980s, β?blockers was widely used because of decreased myocardial infarction mortality and protected heart function. In recent years, with the rapid development of percutaneous coronary intervention ( PCI) technology, the mortality of pa?tients with acute myocardial infarction ( AMI) significantly decreased. The issue of whether patients with AMI continue to benefit fromβ?blockers treatment is disputed. This review is aim to retrospect the researches about the effects ofβ?blockers on patients with AMI in aspects of myocardial infarct size, heart failure and mortality after AMI, meanwhile summarizing the rational use ofβ?blocker therapy in the PCI era.

Meta-analysis of effect of β-blockers on treatment of postural orthostatic tachycardia syndrome in children / 中华实用儿科临床杂志

Objective To evaluate the efficacy of β-blockers in treatment of postural orthostatic tachycardia syndrome( POTS) in children. Methods Clinical controlled trials were collected from a variety of medical electronic databases including PubMed(1990-2014),Excerpta Medica database(EMBASE 1990-2014),ELSEVIER(1990-2014),China National Knowledge Internet(CNKI 1990—2014) and WANFANG(1990—2014) by 2 researchers simultaneously and respectively based on same inclusion and exclusion criteria. Studies were assessed based on the Juni scale evaluation,and the Meta-analysis was conducted using the Rev-Man 5. 0 software. Results In total 8 clinical trials were included out of over 200 papers. Possible publication bias were assessed by Funnel plot analysis. Meta analy-sis of the 8 studies demonstrated that compared with the placebo group, metoprolol group showed significantly better ef-ficacy in treating children with POTS(RR=0. 37,95%CI:0. 21-0. 64,P=0. 000 5). Furthermore,these included trials were divided into different subgroups based on trial design ( randomized controlled trial/non-randomized con-trolled trial and Scored/N-scored) . Although no statistical heterogeneities were detected within each subgroups by the subgroup analysis,marked heterogeneities were found among subgroups; there was no significant difference of efficacy between metoprolol and placebos in treating POTS in non-randomized controlled trial group(RR=0. 68,95%CI:0. 45-1. 02,P=0. 06). Conclusions Low-dose metoprolol is effective in treating POTS,but the conclusion still needs to be tested by more large-scaled,multi-centered and standardized clinical randomized controlled trials.

Regulation of Cardiac β3-Adrenergic Receptors in Hyperglycemia.

Beta-adrenoceptors (β-AR), members of the G protein-coupled receptors play important roles in the regulation of heart function. A positive inotropic action of catecholamines is mediated through their interaction with β-AR, located on the sarcolemma, while they can also mediate some deleterious effects, such as cardiac arrhythmias or myocardial apoptosis. The well-known β-AR-associated signaling in heart is composed of a coupled mechanism among both β1- and β2-AR and stimulatory G protein (Gs). This coupled mechanism further leads to the activation of adenylyl cyclase and thereby increases in intracellular cAMP level. However, recent studies have emphasized the contribution of constitutive β3-AR coupling to Gi proteins, thereby initiating additional signal transduction pathways, particularly under physiopathological conditions. Diabetic cardiomyopathy, as a distinct entity is recognized due to its diminished responsiveness to β1-AR agonist stimulation in the heart from diabetic rats with no important changes in the responses mediated with β2-AR. Furthermore, an upregulation of β3-AR has been shown in diabetic rat heart with a strong negative inotropic effect on left ventricular function. Experimental data provide evidences that the mechanisms for the negative inotropic effect with β3-AR activation appear to involve a pertussis toxin (PTX)-sensitive G protein and the activation of a nitric oxide synthase pathway. On the other hand, β-blockers demonstrate marked beneficial effects in heart dysfunction with scavenging free radicals and/or acting as an antioxidant with both sex- and dose-dependent manner. However, further investigations are needed to clarify the roles of both altered expression and/or responsiveness of β-AR and the benefits with β-blocker treatment in diabetes. This review discusses the role of β-AR activation, particularly β3-AR in cardiac pathological remodeling under hyperglycemia.

Efficacy of βblockers for hypertension:a systematic review and Meta-analysis / 中国基层医药

Objective To evaluate the efficacy and safety of βblockers and other antihypertensive drugs on morbidity and mortality endpoints in adults with essential hypertension .Methods We searched the Cochrane Librar-y,MEDLINE( 1966 to July 2013 ) , EMbase ( 1980 to July 2013 ) , CNKI ( 1980 to July 2013 ) , CBM ( 1980 to July 2013),WanFang Data(1978 to July 2013).Randomized controlled trials or controlled clinical trials selection and as-sessment were undertaken by two reviewers .The quality of the included studies was evaluated by GRADE system and principle of Cochrane Reviewer Handbook 5.1.6 RCT.Meta-analyses were performed with RevMan 5.1.6 software. Results Twelve randomized studies were selected .The results showed that βblockers had a significantly higher risk of developing a stroke than those on other antihypertensive drugs [RR=1.21,95%CI(1.04,1.41),P=0.01] and total mortality was significantly higher for βblockers compared to CCBs [RR=1.07,95%CI(1.00,1.14),P=0.05].The effect of βblockers therapy on coronary heart disease [RR=1.02,95%CI(0.91,1.15),P=0.74],car-diovascular mortality[RR=1.10,95%CI(0.97,1.25),P=0.13]ect.were no significantly different from other anti-hypertensive drugs[RR=1.02,95%CI(0.91,1.15),P=0.74].Conclusion βblocker had a significantly higher risk of developing a stroke than other antihypertensive drugs and total mortality was significantly higher for βblocker compared to CCBs ,so the available evidence does not support the use of beta-blockers as first line drugs in the treat-ment of hypertension .Because of the studies limited ,further randomized controlled trials is required in this field to the quality of life after surgery and clarify the effect of surgery on ovarian function .

Effects of the β-blockers on cardiac protection and hemodynamics in patients with septic shock:a prospective study / 中华危重病急救医学

Objective To investigate the effects of β-blockers on cardiac protection and hemodynamic in patients with septic shock. Methods A prospective randomized controlled trial was conducted. Forty-one patients with septic shock in accordance with early goal directed treatment and met the target within 6 hours,and admitted to intensive care unit (ICU)of Affiliated Huxi Hospital of Jining Medical College from January 2012 to January 2014 were enrolled. The patients were divided into treatment group (n=21)and control group (n=20)by random number table. The patients in both groups were given the standard treatment,esmolol was giving to patients in treatment group in order to control the heart rate (HR)below 100 bpm within 2 hours,and the patients in control group only received standard treatment. The changes in hemodynamic parameters〔mean arterial pressure(MAP),central venous pressure(CVP), HR,cardiac index(CI),stroke volume index(SVI),systemic vascular resistance(SVRI),global end diastolic volume index(GEDVI)〕,biochemistry metabolic of tissue〔central venous oxygen saturation(ScvO2),lactic acid(Lac)〕,and cardiac markers 〔troponin I (cTnI)〕before and 12,24,48,72 hours after the treatment were recorded. Results①Before treatment,the hemodynamic parameters,tissue metabolism index and cTnI had no significant differences in both groups (all P>0.05).②The hemodynamic parameters after treatment in the control group showed no significant difference compared with that before treatment. HR and CI in the treatment group were gradually declined after treatment,SVRI and GEDVI were gradually increased. There were significant differences in HR,CI,SVRI,and GEDVI between treatment group and control group from 12 hours on〔HR(bpm):93±4 vs. 118±13,CI (L·min-1·m-2):3.3 ±0.8 vs. 4.5 ±0.6,SVRI (kPa·s·L-1·m-2):159.2 ±27.4 vs. 130.5 ±24.2,GEDVI(mL/m2):668 ±148 vs. 588 ±103,P0.05). The ScvO2 was not decreased in both groups.④Compared with before treatment,cTnI in the control group was gradually increased,peaked at 72 hours,and that in the treatment group was gradually increased,peaked at 24 hours and then gradually declined. Compared with control group,the cTnI (μg/L)in the treatment group was decreased significantly at 24,48,72 hours (1.15 ±0.57 vs. 1.74 ±0.77,0.93 ±0.52 vs. 2.15 ±1.23,0.52 ±0.36 vs. 2.39 ±1.17,all P<0.01). Conclusionsβ-blockers (esmolol) can improve cardiac function and myocardial compliance,reduce the myocardial injury in patients with sepsis shock. Although β-blockers can decrease cardiac output,it has no influence on the circulation function and tissue perfusion.

Enantioseparation and Determination of Propranolol in Human Plasma on a New Derivatized β-Cyclodextrin Bonded Phase by HPLC / 分析化学

A 6-azido-β-cyclodextrin was synthesized and derivatized with p-nitrophenyl isocyanate as chiral ligand. Following that the ligand was chemically bonded to mesoporous SBA-15 via a ‘Click Chemistry ’ reaction of the azido group with alkynyl group. A new p-nitrophenylcarbamoylatedβ-cyclodextrin bonded SBA-15 chiral stationary phase ( NPCSP ) for HPLC was obtained. The new stationary phase was first used to enantioseparate propranolol in human plasma under the polar organic solvent mode. The effects of methanol content , additive concentration of glacial acetic acid/triethylamine in mobile phase and the temperature on the enantioseparation were studied. The optimal chromatographic conditions were as follows: mobile phase was acetonitrile/methanol/glacial acetic acid/triethylamine (90:10:1. 25:2. 25, V/V), temperature 288 K, flow rate of 0. 5 mL/min, injection volume of 20 μL, detection wavelength at 290 nm. The resolution was 2. 04 with a short run time (< 15 min) under the above conditions. The composition of propranolol in plasma was quantitatively measured by HPLC-MS selected ion monitoring mode ( [ M +H ]+ m/z 260 . 10 ) with hydrochlorothiazide as internal standard. And linear range was 2. 5-250 μg/L and with a good linear relationship. The detection limit was 1 μg/L according to S/N=3. The experimental results showed that the chiral stationary phase exhibited excellent chiral separation ability to propranolol and the analysis method for propranolol in plasma was sensitive, accurate, simple and fast, which could be used for the determination of propranolol in plasma and pharmacokinetic studies.

Adherence to treatment guidelines in the pharmacological management of chronic heart failure in an Australian population / 老年心脏病学杂志（英文版）

Background To document the pharmacotherapy of chronic heart failure (CHF) and to evaluate the adherence to treatment guidelines in Australian population.Methods The pharmacological management of 677 patients (female 46.7%,75.5±11.6 years) with CHF was retrospectively analyzed.Results The use of angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) and fl-blockers were 58.2%and 34.7%,respectively.Major reasons for non-use of ACE inhibitors/ARBs were hyperkalemia and elevated serum creatimne level.For patients who did not receive β-blockers,asthma and chronic obstructive pulmonary disease were the main contraindications.Treatment at or above target dosages for ACE inhibitors/ARBs and β-blockers was low for each medication (40.3% and 28.9%,respectively).Conclusions Evidenced-based medical therapies for heart failure were under used in a rural patient population.Further studies are required to develop processes to improve the optimal use of heart failure medications.

Medications Prescribed at Discharge for Patients with Acute Myocardial Infarction : Evidence-to-Practice Gap in Janan / General Medicine

BACKGROUND: The existence of a gap between research evidence and clinical practice has been described recently. Several drugs are effective in preventing secondary events after acute myocardial infarction (AMI), but it is not certain whether this evidence is employed in daily practice. We investigated the drugs currently employed for patients with a history of AMI in Japan.<BR>METHODS: Medical records of patients who developed AMI during the calendar year of 1999 were retrospectively identified at three teaching hospitals in Japan. We collected data on drugs prescribed at three time points (upon admission for AMI, at the time of discharge, and one year after discharge) for each patient.<BR>RESULTS: Data were available for 149 patients with AM!. Drugs prescribed at the time of discharge were aspirin (77.5%), nitrates (68.3%), and angiotensin converting enzyme inhibitors (52.8%) . β-blockers were prescribed for only 12.0% of patients. The drugs used one year after discharge were to a large extent similar to those at the time of discharge. There were no significant correlations between the use of these drugs and comorbidity.<BR>CONCLUSION: Despite established evidence that β-blockers offer benefits to patients with a history of AMI, they have not been prescribed frequently, for reasons that remain unclear. To improve the quality of clinical care, further systematic effort is needed to bridge this evidence to practice gap.

Pharmacophores of the dual acting α, β-blockers as deduced, from molecular dynamics simulations.

The dual acting α, β-blockers have an important place in the management of hypertension. Molecular dynamics simulations have been carried out on all stereoisomers of seven dual acting α,β-blockers namely adimolol, amosulalol, bucindolol, carvedilol, labetalol, medroxalol and primidolol. Three families of conformations have been identified for the group of compounds. The pharmacophores for α and β-activity have been constructed for two of these families.