ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02664.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The effects of terbutaline, a sympathomimetic amine with predominantly β2‐agonist properties, on cardiac automaticity and contractility were studied. For isolated rabbit right atria, terbutaline, 1 × 10−9to 1 × 10−5M, was significantly less potent than isoproterenol. The maximum increase in heart rate induced by terbutaline was 45 ± 17 beats/min, that by isoproterenol, 120 ± 9 beats/min. For canine Purkinje fibers, terbutaline had less effect on spontaneous rate than isoproterenol; maximum increases above control were 9.5 ± 2.5 and 18.6 ± 7.0 beats/min, respectively. For isolated feline ventricular muscle, terbutaline, 1 × 10−9to 1 × 10−6M, was significantly less potent than isoproterenol in increasing peak developed tension and the rate of tension development. Superfusion with Tyrode's solution containing terbutaline, 1 × 10−7M, plus graded concentrations of isoproterenol, 1 × 10−9to 1 × 10−6M, resulted in responses which were less than those observed when isoproterenol alone was super‐fused. Maximal effects of isoproterenol plus terbutaline were equivalent to those of isoproterenol alone. These results suggest that terbutaline is less potent then isoproterenol in its effect on cardiac contractility and automaticity and explain the clinical observation that terbutaline is less toxic than isoproterenol in its effects on cardiac rhythm and contraction when administered for the

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02665.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The effects of five different doses of a 5% inhalant solution of metaproterenol on pulmonary function were compared in a placebo‐controlled double‐blind crossover study in 40 asthmatic patients who received the drug via intermittent positive pressure breathing (IPPB). The response to metaproterenol in terms ofFVC, FEV1,RA, andFEF25–75%was significantly superior to the placebo response. The effect of metaproterenol set in within 5 minutes of administration, and clinically significant improvement in pulmonary function was sustained for 6 hours even at the lowest dose level. Global response evaluations reflected a progressive increase in effectiveness with each successive dose increment. Typical sympathomimetic side effects such as nervousness and shakiness slightly increased in frequency with higher doses. At none of the metaproterenol doses were any clinically significant changes observed in the mean blood pressure and pulse rate v

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02666.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:This study presents data on the use of penfluridol, a once‐a‐week orally administered, antipsychotic agent, in the treatment of chronic schizophrenic patients. Fifty‐nine patients participated in the initial dose titration segment during which doses of penfluridol were adjusted weekly until the patients' condition became stabilized. The starting dose did not exceed 60 mg per week, and the maximum weekly dose did not exceed 140 mg. Forty‐one of these patients continued on to participate in a double‐blind comparison of penfluridol with chlorpromazine. Maximum doses did not exceed 140 mg per dose per week for penfluridol and 7350 mg per week for chlorpromazine in the double‐blind segment. Patients were abruptly switched from their previous neuroleptic medication to penfluridol without loss of control. Side effects, mainly extrapyramidal in nature, were readily alleviated with benztropine mesylate. Penfluridol, administered orally once a week, appeared to be well tolerated; it was comparable to daily chlorpromazine in treating and maintaining schizophren

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02667.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The intravenous infusion of cetiedil to a group of ten male volunteers elicited atropine‐like side effects on salivation, bronchomotor tone and visual accommodation. With repeated infusions of cetiedil, the incidence as well as the duration of the side effects were reduced significantly, indicating the development of tolerance. Since normal subjects can tolerate repeated intravenous infusions of cetiedil, the clinical investigation of this drug in sickle cell disease can proceed, including those patients suffering from vasoocclusive crise

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02668.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Procaterol, a new beta‐adrenergic agonist, was tested in two different doses in patients with reversible airway obstruction. Single oral doses of 0.05 or 0.1 mg produce an increase in measured expiratory flow rates, and the peak and duration of action are both dose related. Side effects reported during this one‐day study were similar to those described with other compounds of this class; they were considered to be mild by the patients and the investigator. From these results, further investigation of this agent in bronchoconstrictive disease appears warran

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02669.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The clearances of inulin and gentamicin were studied before and after intravenous furosemide in seven patients. There was a significant fall in glomerular filtration rate after furosemide and a similar though less marked fall in gentamicin clearance in six of the seven subjects. Small but consistent increases in plasma gentamicin concentrations were observed after furosemide. The reduction in clearance may explain the enhanced risk of nephrotoxicity in patients receiving both aminoglycosides and diuretics.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02670.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The extent of drug binding to plasma protein does not influence the concentration ofunbounddrug in plasma at steady state but does influence the interpretation oftotaldrug concentrations. An increase in free fraction (reduction in the extent of binding) decreases the therapeutic and toxic ranges for total drug concentrations. Conversely, a reduction in free fraction (increase in the extent of binding) increases these ranges. Laboratories generally measure total rather than unbound drug concentrations, and clinicians must use caution in interpreting these total drug concentrations in clinical situations where the extent of binding of extensively bound drugs may be altered. Free drug serum or plasma concentrations are inherently more reliable indices of the intensity of drug action than are total concentrations. Methodology for routine measurement of free concentration is becoming available and should ultimately be utilized for therapeutic monitoring of drugs that are highly bound to protein.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02671.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Two different chronic dosing regimens of quinidine gluconate were administered to each of four healthy volunteers in a pilot study to evaluate quinidine for nonlinear pharmacokinetics. Analysis of plasma quinidine levels following the last dose indicates that disproportionate increases in steady‐state plasma concentrations can occur in some subjects as the daily dose increases. Measurement of 2′‐oxoquinidinone (2′‐OXO) and 3‐hydroxyquinidine (3‐OH) metabolites revealed that the formation of 2′‐OXO is proportional to the availability of quinidine base. Hydroxylation was a more variable process. Rate‐limited hydroxylation was documented in one subject, and an apparent increase in hepatic microsomal enzyme‐mediated hydroxylation was shown in a second subject who ingested large amounts of caffeine daily. By using a highly selective high‐performance liquid chromatography assay technique, the total body clearance of quinidine was found to be greater than previously published data. Our results suggest that some individuals may exhibit dose‐dependent elimination of quinidine and that the variability in quinidine's pharmacokinetics is related in part to its hydroxylation. Future studies must use highly specific quinidine assays and control for variables that may influence

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02672.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The acetylation clearance of sulfamethazine was found to be significantly dependent upon body weight in both intermediate and rapid acetylators. The correlation beween acetylation clearance and body weight was stronger in the rapid acetylator. It is recommended that weight‐corrected acetylation clearance values be used when constructing distribution histograms for phenotyping purposes. Within a phenotypic mode, body weight may be useful in providing initial estimates of dosing need

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02673.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY