Abstract:
:Methods of expressing the effects of beta-adrenoceptor blocking drugs on exercise heart rate have been evaluated using a standardised exercise test. In six normal subjects given atropine (0.04 mg/kg) on two separate occasions, the mean +/- s.e. mean exercise heart rate rose by 10.3 +/- 1.8 beats/min and by 11.0 +/- 1.6 beats/min respectively. This increase was designated the 'vagal effect and was not significantly different in the two studies. After atropinsation, propranolol (0.2 mg/kg) reduced mean +/- s.e. mean exercise heart rate by 45.3 +/- 2.6 beats/min and 0.4 mg/kg by 50.8 +/- 4.5 beats/min. This mean sympathetic blockade was not altered significantly by increasing the dose of propranolol but, in four of the six subjects, the larger dose produced an increased effect of 4, 6, 12 and 16 beats/min, suggesting that maximum sympathetic blockade may not have been produced by 0.2 mg/kg. Knowledge of the vagal effect in each subject with standardised exercise enabled prediction to be made of the exercise heart rate after propranolol (0.4 mg/kg) without previous atropinisation. Propranolol (0.4 mg/kg) was then given intravenously to each subject and the actual exercise heart rate measured. There was no significant difference between the predicted and observed exercise heart rates. Propranolol (0.6 mg/kg) without atropine was then given to the four subjects who had shown increased effect with (0.4 mg/kg) and the sympathetic blockade was measured. In one subject, a further increase in sympathetic blockade of 10 beats/min was found. The intrinsic heart rate at rest and on exercise was measured for propranolol (0.2 and 0.4 mg/kg) and, for propranolol (0.6 mg/kg), the intrinsic heart rate on exercise was calculated. At rest, although no significant difference was found between the two dose levels, three subjects did not appear to have maximum autonomic blockade at 0.2 mg/kg. Similarly, several subjects had lower intrinsic heart rates on exercise after 0.4 or 0.6 mg/kg than after 0.2 mg/kg. The intrinsic heart rate on exercise was significantly greater than that obtained at rest. Using the maximum sympathetic blockade obtained in each subject as the sympathetic component of exercise, the effects of increasing oral doses of practolol on exercise heart were measured as percentage blockade of sympathetic effect and this was compared with other conventional methods of measuring beta-adrenoceptor blockade. It was found that percentage blockade of sympathetic effect correlated most closely with both percentage and absolute reduction of exercise heart rate. Correlations with exercise heart rate after drug and percentage inhibition of tachycardia, whilst also significant, did not appear as good. When the effects of practolol were expressed in terms of the potential blockade, a plateau occurred between 70 and 80% of 'maximum' sympathetic blockade. The failure to achieve higher levels with practolol may be the result of its partial agonist or intrinsic sympathomimetic activity.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Carruthers SG,Shanks RG,McDevitt DGdoi
10.1111/j.1365-2125.1976.tb00348.xsubject
Has Abstractpub_date
1976-12-01 00:00:00pages
991-9issue
6eissn
0306-5251issn
1365-2125journal_volume
3pub_type
杂志文章abstract::The classical taxanes (paclitaxel, docetaxel), the newer taxane cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely used anticancer drugs. Still, the optimal use and the value of pharmacological personalization of the taxanes is still controversial. We give an overview on the pharmacologica...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14678
更新日期:2020-11-28 00:00:00
abstract:AIMS:The aim was to assess the impact of a campaign for general practitioners (GPs) to reduce clinically-important drug-drug interactions (DDIs) in poly-treated elderly patients. METHODS:We compiled a list of 53 DDIs and analyzed reimbursed prescriptions dispensed to poly-treated (≥four drugs) elderly (>65 years) pati...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12754
更新日期:2015-12-01 00:00:00
abstract::1. We studied the effects of pre-treatment with oral indomethacin (25 mg four times daily for 3 days) on the pharmacokinetics, haemodynamics and diuretic properties of oral felodipine (10 mg single dose) in 12 healthy male volunteers using a placebo controlled double-blind four-way crossover protocol. 2. Felodipine wi...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1988.tb05295.x
更新日期:1988-11-01 00:00:00
abstract:AIM:We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here 'BZD') use. METHODS:A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) w...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12294
更新日期:2014-06-01 00:00:00
abstract:AIMS:To test the existence of an association between reports of hypoglycaemia and angiotensin converting enzyme inhibitors, in a spontaneous reports database. METHODS:The French Pharmacovigilance database was examined for an association between adverse drug reaction reports mentioning hypoglycaemia, and angiotensin co...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1997.00615.x
更新日期:1997-11-01 00:00:00
abstract::Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups: omeprazole (n = 32), pantopraz...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14267
更新日期:2020-08-01 00:00:00
abstract::1 As part of a prospective study on the use of digoxin in a general practice, plasma digoxin concentrations were measured in all patients receiving the drug. 2 A low mean plasma digoxin concentration was observed, suggesting a cautious approach to digitalization. 3 The correlation between plasma digoxin concentration ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1977.tb00720.x
更新日期:1977-06-01 00:00:00
abstract::Activation of mu opioid receptors on sensory nerves in the lung represents an attractive mechanism for reducing cough and reflex bronchoconstriction. We have examined the effect of the peptide 443C81, a peripherally acting mu opioid agonist, on the cough and reflex increase in respiratory resistance (Rrs) produced by ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1991.tb03966.x
更新日期:1991-11-01 00:00:00
abstract:AIMS:Increased exposure to fondaparinux, as observed in patients with renal impairment, may increase bleeding risk. This study aims to determine the time course of major bleeding after major orthopaedic surgery, identify predictors of bleeding and simulate the effect of a reduced dose of fondaparinux on bleeding for pa...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/bcp.13663
更新日期:2018-10-01 00:00:00
abstract::1 Cardiovascular responses to intravenous prizidilol hydrochloride (SK&F 92657) 0.86 mg/kg were studied in eight supine resting healthy volunteers. Five subjects were slow and the remaining three were fast acetylators of sulphamethazine. Compared with pre-infusion values, mean resting systolic and diastolic blood pres...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01266.x
更新日期:1981-10-01 00:00:00
abstract::1 Soluble aspirin, 600 mg and 1200 mg, and placebo were compared in a double-blind, cross-over study in 12 patients with post-operative pain following removal of impacted lower third molars. 2 Significant analgesia after 600 mg aspirin occurred only at 45 min after administration, whereas significant analgesia after 1...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1982.tb01870.x
更新日期:1982-06-01 00:00:00
abstract::1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case-control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03841.x
更新日期:1990-11-01 00:00:00
abstract::The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken to date with these o...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12557
更新日期:2015-05-01 00:00:00
abstract::1. Medication errors are common in general practice and in hospitals. Both errors in the act of writing (prescription errors) and prescribing faults due to erroneous medical decisions can result in harm to patients. 2. Any step in the prescribing process can generate errors. Slips, lapses, or mistakes are sources of e...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03425.x
更新日期:2009-06-01 00:00:00
abstract:AIMS:To test the feasibility of a novel rivastigmine nasal spray as prospective treatment for dementia. METHODS:A single dose, crossover absolute bioavailability and safety study was conducted with rivastigmine intravenous solution (1 mg) and nasal spray (3.126 mg) in eight healthy elderly individuals, aged 58-75 year...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.13133
更新日期:2017-03-01 00:00:00
abstract::1. Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. The purpose of this study was to investigate the effects of basal nitric oxide synthesis on cardiac function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1995.tb04550.x
更新日期:1995-10-01 00:00:00
abstract::Six human volunteers were each given single oral doses of aspirin (ASA) ranging from 300-1,500 mg. The unchanged ASA excreted in the urine was proportional to dose and urinary pH. The mean percent (+/- s.d.) of dose excreted was 1.9 +/- 0.67. The clearance for ASA was 1.42 +/- 0.28 1/h. The rate of in vitro hydrolysis...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb02030.x
更新日期:1982-10-01 00:00:00
abstract::WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Reflux oesophagitis is a common clinical disorder associated with significant morbidity. Proton pump inhibitors are the current pharmacotherapy of choice, but not all treated patients achieve symptom relief. Little is known about the efficacy of mosapride, a prokinetic agent wh...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2010.03696.x
更新日期:2010-08-01 00:00:00
abstract:AIMS:Paracetamol-containing combination analgesics are widely prescribed but the use of paracetamol/dextropropoxyphene (co-proxamol) is particularly controversial. We aim to examine the prescribing patterns of the paracetamol-containing analgesics in Ireland. METHODS:A national primary care prescribing database was us...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2005.02500.x
更新日期:2005-12-01 00:00:00
abstract::1 Theories linking 5-hydroxytryptamine (5-HT) with depression are briefly reviewed. The various experimental strategies adopted to investigate this relationship, examination of autopsy data, CSF metabolite data, 5-HT re-uptake patterns in human blood platelets and imipramine binding studies in human platelets, are dis...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02130.x
更新日期:1983-01-01 00:00:00
abstract::Paracetamol disposition was studied in groups of pregnant and non-pregnant women of comparable age. Paracetamol apparent oral clearance was 58% higher and elimination half-life was 28% lower in the pregnant women compared to the control group. The higher clearance in the pregnant women was due to increased activity of...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb02901.x
更新日期:1986-09-01 00:00:00
abstract:AIMS:Intravenous formulations of busulfan have recently become available. Although busulfan is used frequently in children as part of a myeloablative regimen prior to bone marrow transplantation, pharmacokinetic data on intravenous busulfan in children are scarce. The aim was to investigate intravenous busulfan pharmac...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2002.01555.x
更新日期:2002-04-01 00:00:00
abstract::The efficacy of calcitonin gene-related peptide (receptor) (CGRP-(R)) blocking therapeutics in the treatment of acute migraine headache provided proof-of-concept for the involvement of CGRP in the pathophysiology of this disorder. One of the major hurdles for the development of any class of drugs, including CGRP block...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12704
更新日期:2015-11-01 00:00:00
abstract:AIMS:To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. METHODS:This was an anonymous questionnaire survey carried out in a single...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.0306-5251.2001.01505.x
更新日期:2002-01-01 00:00:00
abstract::1. The effect of nomifensine on the uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) into human platelet-rich plasma has been studied. 2. A significant inhibition of DA uptake was observed at nomifensine 10(-6) M. 3. 5-HT uptake was significantly inhibited only at nomifensine 10(-4) M or more. 4. These results a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1977.tb05745.x
更新日期:1977-01-01 00:00:00
abstract::1. A double-blind placebo-controlled study was conducted on the effects of oral terbutaline (beta 2-adrenoceptor agonist) and propranolol (beta 1 beta 2-adrenoceptor antagonist) on basal heat production of skeletal muscle, measured ex vivo by direct microcalorimetry. Terbutaline slow-release 7.5 mg, propranolol 80 mg,...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1993.tb04193.x
更新日期:1993-06-01 00:00:00
abstract::1. The pharmacokinetics of proguanil were evaluated in patients with acute P. falciparum malaria receiving concomitantly proguanil hydrochloride and atovaquone. The population consisted of 203 Blacks, 112 Orientals and 55 Malays; 274 males and 96 females. Of the 370 patients, 114 and 256 patients were classified as 'p...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1996.tb00114.x
更新日期:1996-11-01 00:00:00
abstract:AIMS:To estimate the rates of common adverse events in patients treated with the proton pump inhibitors omeprazole, lansoprazole and pantoprazole in general practice in England. METHODS:In prescription-event monitoring cohort studies, data on dispensed prescriptions prescribed by general practitioners in England soon ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2000.00262.x
更新日期:2000-10-01 00:00:00
abstract:AIMS:To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy. METHODS:We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Gro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,评审
doi:10.1111/bcp.12083
更新日期:2013-11-01 00:00:00
abstract:AIMS:SNF472 is a calcification inhibitor being developed for the treatment of cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients. This study investigated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients. METHODS:This ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13752
更新日期:2018-12-01 00:00:00