ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02745.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:To determine the efficacy of a cardioselective beta blocker in the treatment of atrial ectopy in patients with chronic obstructive pulmonary disease (COPD), we administered intravenous metoprolol (0.2 mg/kg) to six patients with atrial ectopic depolarizations (AEDs) and chronic partially reversible airflow limitation (FEV1= 1.24 ± 0.21 liter, mean ± S.E.). Metoprolol reduced the mean frequency of AEDs from 713 ± 237 per hour to 218 ± 127 per hour. Furthermore, three of six patients experienced an 85 per cent or greater decrease in AEDs. No changes were observed in FEV1, FVC, or FEF25–75over the course of the study. These data suggest that intravenous metoprolol is effective in reducing the frequency of AEDs and that it can be administered to patients with COPD without causing an increase in airflow limit

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02746.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Prazosin, a peripherally active alpha‐adrenoceptor antagonist, and clonidine, a centrally active alpha‐adrenoceptor agonist, both reduce blood pressure but with different alterations in sympathetic nervous system activity. We studied the effects of monotherapy with either prazosin or clonidine in 10 and 30 patients, respectively, with essential hypertension. Prazosin reduced blood pressure without affecting heart rate or circulating plasma catecholamines. Sensitivity to injected phenylephrine was markedly reduced by prazosin, and sensitivity to isoproterenol was increased, whereas baroreflex sensitivity was not significantly altered. Blood pressure response to prazosin was correlated with basal plasma norepinephrine concentration (r= 0.64,P<0.04). In contrast, clonidine reduced heart rates and plasma concentrations of both norepinephrine and epinephrine, increased the sensitivity to phenylephrine, and increased baroreflex sensitivity. Blood pressure response to clonidine was correlated with reduction in plasma norepinephrine concentration (r= 0.51,P<0.004). Thus, blood pressure reduction resulting from monotherapy with either prazosin or clonidine occurs through different antisympathetic effects, suggesting that combined therapy might be useful in those unresponsive to either drug al

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02747.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The effect of terbutaline infusion was studied in six patients with cardiogenic shock due to acute myocardial infarction. Terbutaline was initiated at 3 μg/kg/min, and the subsequent infusion rate was adjusted according to heart rate and blood pressure. At 3 hours after infusion, arterial pressure increased from 62 ± 13 mm Hg (mean ± S.D.) to 89 ± 13 mm Hg (P<0.001), cardiac index increased from 1.38 ± 0.29 liter/min/m2to 2.68 ± 0.47 liter/min/m2(P<0.001), and heart rate increased from 92 ± 32 beats/min to 112 ± 29 beats/min (P<0.005). Pulmonary artery wedge pressure fell from 24 ± 7 mm Hg to 17 ± 3 mm Hg (P<0.01), right atrial pressure fell from 12 ± 4 mm Hg to 6 ± 3 mm Hg (P<0.005), and systemic vascular resistance fell from 1880 ± 641 dyn‐sec/cm5to 1515 ± 418 dyn‐sec/cm5(P<0.05). In addition, urine flow increased from 4 ± 6 ml/hr to 314 ± 237 ml/hr (P<0.05), and subjective improvement was noted in all subjects. Undesirable effects observed were hypokalemia (all subjects), supraventricular tachycardia (one subject), and ventricular ectopic beats (three subjects), which responded to potassium replacement and other treatments. All patients required prolonged maintenance infusion to maintain adequate hemodynamic and clinical response. Four patients were weaned off from maintenance therapy after a mean duration of 4.8 days and eventually were discharged from the hospital. Two patients died, one from cardiogenic shock and one from aspiration pneumonia. This preliminary study indicates that terbutaline infusion produced beneficial hemodynamic and clinical response and may be potentially useful for the management of cardiogenic shock if careful monitoring and potassium replacem

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02748.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Intravenous terbutaline, 0.3 mg/kg/min for 30 minutes followed by 0.15 mg/min for 60 minutes, was studied in nine patients with severe heart failure due to documented coronary artery disease. Hemodynamic and myocardial metabolic effects were measured during terbutaline infusion. Cardiac index and stroke index increased, whereas mean pulmonary artery wedge pressure and pulmonary vascular resistance decreased significantly. No significant alterations in aortic oxygen content, coronary sinus oxygen content, myocardial oxygen extraction, and myocardial lactate extraction were observed during terbutaline infusion. No patient developed angina or electrocardiographic changes suggestive of ischemia. These results indicate that intravenous terbutaline infusion, at the dosage employed, produces beneficial hemodynamic effects without a deterioration of myocardial metabolism in patients with heart failure due to coronary artery disease.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02749.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Six obese (mean weight 92 kg) and five normal (60 kg) subjects received 2 mg diazepam nightly for 30 nights. Determination of diazepam and desmethyldiazepam plasma concentrations during the dosing period and for a withdrawal period indicated that accumulation half‐life for both diazepam (7.8 days in obese vs. 3.1 days in normal subjects,P<0.05) and desmethyldiazepam (30.3 vs. 7.2 days,P<0.05) was markedly prolonged in obese subjects. However, mean steady‐state plasma concentrations of diazepam (68 vs. 67 ng/ml) and desmethyldiazepam (156 vs. 91 ng/ml) did not significantly differ between groups. To determine the basis for this delay in accumulation in obese subjects, single‐dose pharmacokinetics of diazepam and desmethyldiazepam were determined. Diazepam elimination half‐life was greatly prolonged in the obese subjects (82 vs. 32 hours,P<0.005), with no change in total metabolic clearance (32 vs. 26 ml/min). Instead, a large increase in volume of distribution (228 vs. 70 liters,P<0.01) was the reason for prolongation of the elimination half‐life. Similarly for desmethyldiazepam, elimination half‐life was prolonged in obese subjects (130 vs. 56 hours,P<0.01), without a change in total metabolic clearance (13.7 vs. 19.2 ml/min), due to increased volume of distribution (151 vs. 73 liters,P<0.01). During chronic dosing with diazepam, obese patients may experience a much slower onset of maximal drug effect compared to normal‐weight patients because of the greatly delayed accumulation of diazepam and desmethyldiazepam. After stopping diazepam administration, residual drug effect may likewise persist for a prolonged period in o

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02750.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The metabolism of14C‐indapamide labeled in the indoline ring was determined after a single oral administration of a solution (4.99 mg, 90.47 μCi) to four fasted adult male volunteers.14C‐indapamide was rapidly absorbed, and peak blood concentrations of radioactivity occurred by 0.5 hour in three subjects and at 2 hours in one subject. The mean elimination half‐lives of total radioactivity were 27.0 hours in blood and 24.5 hours in plasma. The concentration of total radioactivity in blood was 5.7 times greater than in plasma, indicating extensive binding to red blood cells. Unchanged drug, as analyzed in one subject, reached a peak concentration by 0.5 hour, and had a blood half‐life of 15.8 hours. Radioactivity was primarily excreted in the urine, and more than 50 per cent of the administered radioactivity was eliminated by this route in 48 hours. By eight days, 92.8 per cent of the radioactivity was recovered, with 70.3 per cent in the urine and 22.5 per cent in the feces.14C‐indapamide was shown to be extensively metabolized, with only 7.3 per cent of the dose excreted as unchanged drug in the urine. Systemic and renal clearances of total radioactivity were 12.8 ± 1.3 and 8.6 ± 0.8 ml/min, respectively, while the renal clearance of unchanged indapamide, determined for one subject, was substantially lower (

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02751.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Six healthy females who had been nursing their infants for 6 to 11 months received a single, 200‐mg oral dose of suprofen, an analgesic which has been evaluated clinically. Blood and milk samples were collected at discrete times over an 8‐hour period and suprofen concentrations in milk and plasma were determined by HPLC. The binding of suprofen to milk and plasma proteins was determined by equilibrium dialysis. The maximum concentrations of suprofen in the milk ranged from 0.118 to 0.232 μg/ml and occurred from 1 to 2 hours after dose administration. The maximum plasma suprofen concentrations ranged from 13.8 to 28.3 μ/ml and occurred from 0.5 to 2 hours after dosing. Within any subject, the peak suprofen concentration in milk was 0.5 to 0.9 per cent of the peak concentration in plasma. Suprofen was extensively bound to plasma proteins (99.4 per cent) and minimally bound to milk proteins (10 per cent). The average milk/plasma ratio based on area‐under‐the‐curve measurements was approximately 0.014, or 1.4 per cent. This ratio agrees well with an estimated value of 1.2 per cent for the pH‐dependent, passive diffusion of suprofen from plasma into milk. From these data, it appears that there would be minimal suprofen exposure to a nursing infant after administration of recommended doses to the n

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02752.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Pharmacokinetic volumes of distribution (Vd) are commonly calculated either by the steady‐state method (Vdss) or the area method (Vdarea). Vdssis traditionally perceived as the least biased and most reliable indicator of the extent of distribution, but Vdssin fact has far greater practical and theoretical limitation than does Vdarea. After single doses or multiple discrete doses of a drug, Vdareacorrectly relates plasma concentration to amount of drug in the body at all times after distribution equilibrium is attained. Vdss, on the other hand, is a correct proportionality constant only during continuous intravenous infusion or at a single instant in time after discrete dosing. Furthermore, calculated values of Vdssare strongly dependent on the precise configuration of the initial distributional phase of the plasma concentration curve, which may be difficult or impossible to delineate because of variance arising from methodologic artefacts or unexplained causes. Such variance can lead to large nonphysiologic within‐ and between‐individual variability in VdssVdarea, on the other hand, is relatively independent of artefactual changes in the initial distribution profile. Finally, experimental observations indicate that elimination depends physiologically on distribution in the absence of changes in clearance, not the reverse. The relation of distribution and elimination holds whether the steady‐state method or the area method is used to calculate Vd. Thus, Vdareais a more reliable and generally valid descriptor of the extent of drug distribution than

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb02753.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY