摘要:

Abstract:Beta‐adrenergic blocking drugs are now commonly used in patients with ventricular arrhythmias. This review examines the possible mechanisms of their ventricular antiarrhythmic effect. Actions on the myocardial cell, as well as actions on the central and autonomic nervous system, are reviewed. Many clinical studies have attempted to show the efficacy of beta blockers in controlling ventricular arrhythmia and decreasing the incidence of sudden death after acute myocardial infarction. Although some of these clinical trials tended to show an impact on sudden death, the size of these trials or their design problems do not allow firm conclusions to be made. The Beta Blocker Heart Attack Trial (BHAT) is a placebo‐controlled, double‐blind, randomized trial of propranolol currently under way in the United States. Important additions to the previous trials include the addition of drug levels to ensure beta‐blocking dosage, long‐term electrocardiographic monitoring, and a study population of 4200 patients followed for an average of three years. These important design features will be of value in addressing some of the unanswered questions presented in th

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02684.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The ability of furosemide to induce vasodilation in the canine gastrointestinal system was studied by quantitative flowmetry. Blood flow and conductance increased maximally by 60 per cent in the stomach and duodenum and by 80 per cent in the small and large intestine. Vasodilation was evident at 2.4 mg/kg furosemide and higher. The onset of vasodilation occurred at 24 to 30 seconds and was maximal at 36 seconds in the stomach, at 66 seconds in the duodenum, at 78 to 84 seconds in the small intestine, and at 90 seconds in the large intestine. Hepatic arterial, splenic, and renal blood flows were unchanged. Simultaneous arteriovenous sampling from the small intestine indicated that the increased blood flow was not associated with increased O2consumption. However, CO2addition to the venous effluent decreased by 70 per cent. These data indicate that furosemide has a vasodilatory action on the gastrointestinal tract due either to a delayed effect on the vascular smooth muscle cell or on anaerobic bowel wall metabolism. The CO2data are compatible with, but do not prove, stimulation of secretion of HCO3– by the intestinal mucos

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02685.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:In this Phase I study, the new anthracycline aclacinomycin A was given to 22 advanced cancer patients on a schedule of daily intravenous administration for five days repeated every four weeks. The limiting toxicity was myelosuppression, which was severe at a dose of 30 mg/m2per day for five days. Platelet nadirs were more marked than those of white cells and occurred at about day 11 after the first drug dose, while maximum leukopenia occurred at day 21. Some patients had moderate nausea and vomiting. No hepatic or renal toxicity was observed, and alopecia was minimal. Cardiac function was monitored prospectively, using radionuclide left ventricular ejection fractions and serial ECGs. One patient developed transient atrial fibrillation; and one other, who had previously received 380 mg/m2doxorubicin, developed congestive heart failure. Otherwise there was no evidence of cardiac toxicity. No tumor regressions were seen. We conclude that 150 mg/m2given in five daily 30 mg/m2fractions is a maximum tolerated dose of aclacinomycin A. This is higher than the reported MTD of 120 mg/m2for single bolus injection. We recommend a Phase II starting dose of 25 mg/m2per day for good‐risk patients and 20 mg/m2per day for poor‐risk patients when the drug is given on this sched

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02686.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The efficacy and safety of loxapine were evaluated in 18 acutely ill schizophrenic criminal offenders in the Essex County Jail. The offender patients were treated for three days with intramuscular loxapine (25 mg three or four times a day), followed by seven days of oral concentrate (up to 150 mg/day in three or four divided doses). Psychiatric status was determined with the Brief Psychiatric Rating and the Clinical Global Impression scales at the time of admission, after 8, 24, 48, and 72 hours, and on days 7 and 10 of medication. Three patients did not complete treatment: one was released on bail after 24 hours of therapy, and the other two had adverse reactions (tongue swelling and muscle spasms, each in one patient) which required cessation of treatment. Statistically significant improvement in both rating scale results was evident as early as 8 hours after treatment began. By day 10, all Brief Psychiatric Rating Scale items and factors and the Clinical Global Impression results were statistically improved over baseline measurements. At the end of the study, 87 per cent (13/15) of the patients were well enough to cooperate with their attorneys and understand the procedures of the court. Adverse effects (generally extrapyramidal) appeared in four of 18 patients during parenteral administration and in two of 15 patients during oral therapy.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02687.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The clinical effects of a cardioselective beta‐adrenergic blocking drug, acebutolol, were studied in 25 patients with chronic stable angina, using a seven‐week single‐blind placebo→acebutolol (mean dose 913 mg/day) phase followed by 12‐week randomized double‐blind placebo→acebutolol (mean dose 968 mg/day) crossover protocol. Objective parameters from exercise treadmill tests showed consistent reduction in resting and maximal exercise heart rate and rate‐pressure product during both single‐ and double‐blind phases. Duration of exercise and maximal ST segment depression were not significantly altered. Subjective improvement following acebutolol was observed with reduced frequency of anginal attacks and nitroglycerin consumption during the single‐blind phase. However, no differences were seen during the double‐blind phase due to significant subjective improvment during the latter placebo period. Adverse effects observed were mild in nature and were similar to those seen with other beta blockers. These data establish acebutolol as a potent beta‐blocking agent and emphasize the importance of utilizing objective parameters over subjective variables in demonstrating the clinical antianginal e

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02688.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:To determine the efficacy and tolerance of oral quinidine sulfate in the treatment of chronic ventricular arrhythmias using contemporary definitions of drug efficacy, 20 ambulatory patients underwent a short‐term, placebo‐controlled, double‐blind trial consisting of four days of quinidine therapy at 400 mg every 6 hours. A long‐term trial was conducted in 12 additional patients where ventricular ectopic frequency during two weeks of placebo therapy was compared with that during eight weeks on quinidine sulfate at 300 mg every 6 hours. Quinidine efficacy was determined by 48 hours of Holter monitoring. Blood levels were within the therapeutic range in both trials. Side effects consisted of diarrhea, which occurred in 15 per cent of patients on the short‐term trial and 25 per cent of patients on the long‐term trial. Drug effect defined as a statistically significant (P<0.05) reduction in chronic premature ventricular complexes occurred in 70 per cent of patients on the short‐term trial and in 67 per cent of patients on the long‐term trial. In both trials, all patients with ventricular tachycardia had statistically significant suppression. Statistically significant reduction in ventricular couplets occurred in all patients on the short‐term trial but in only 73 per cent of the patients on the long‐term trial. These data can be used as reference standards for quinidine sulfate in new antiarrhythmic dru

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02689.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The antihypertensive effect and the plasma levels of guanfacine were studied for two months in 25 patients with sustained essential hypertension. In three patients, blood pressure was unchanged. In ten patients, blood pressure returned to the normal range within 15 days, at a daily dose of 2 mg. In 12 patients, increasing doses were necessary to normalize the blood pressure within two months. In these cases, the decrease in systolic pressure was negatively correlated with the daily dose of guanfacine (r= −0.40) and the steady‐state plasma level (r= −0.62;P<0.01); analysis of the curves showed that the normalization of blood pressure coincided with a plasma drug level of 8 ng/ml, i.e., a 4‐mg daily dose. This study demonstrated the efficacy of guanfacine monotherapy in hypertension and suggests that the normalization rate of blood pressure levels does not further increase with daily doses higher th

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02690.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The pharmacokinetics of lidocaine were investigated in 17 healthy young adult volunteers seven Caucasians, five Orientals, and five Blacks). With the assumption of a one‐compartment open model and linear pharmacokinetics, analysis of the data determined that there were no significant differences in the volume of distribution, clearance, elimination half‐life, and serum protein binding of lidocaine among these racial groups. Our finding that lidocaine clearance and protein binding are not significantly different in young adult Caucasians and Orientals is consistent with our previous hypothesis that drugs metabolized in the body by N‐dealkylation (lidocaine and diphenhydramine) are cleared at similar rates in young adult Caucasians and Orientals when protein binding is taken into ac

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02691.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:A pharmacokinetic profile was developed following oral administration of a single 100‐mg oral dose of isotretinoin to 12 normal male volunteers. Concentrations of isotretinoin and its isomer, tretinoin, were measured in blood samples from 12 subjects and in urine and fecal samples from three of the 12 subjects. Blood concentration‐time data during a 72‐hour sampling interval were variable and, in five of the 12 cases, showed pronounced secondary and tertiary concentration maxima which were consistent with the theory of enterohepatic circulation (EHC) of isotretinoin in man. In five of the 12 subjects, adequate fits of the data could not be obtained using classical bi‐ or triexponential equations but were successfully fitted using a recently developed recycling model. Maximum blood concentrations of isotretinoin ranged from 74 to 511 ng/ml and occurred between 1 and 4 hours after dosing. Secondary maxima generally occurred between 6 and 24 hours after dosing. The harmonic mean elimination half‐life was approximately 20 hours. These findings suggest that steady‐state blood concentrations should be observed within one week. Negligible amounts of unchanged isotretinoin were excreted in urine, whereas 53 to 74 per cent of the dose was recovered as intact isotretinoin in the feces. The amount of intact drug in the feces could reflect biliary excretion of the conjugate of isotretinoin that is deconjugated beyond the site where absorption may occur, as well as unab

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02692.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The pharmacokinetics of amikacin (5.5 mg/kg intramuscularly) and cephalothin (1000 mg/body intravenously) in bedridden elderly patients were studied in comparison with those in healthy volunteers. The eliminations of amikacin and cephalothin from the plasma followed the course of a one‐compartment open model. For amikacin, five healthy volunteers, elimination rate constantKelwas 0.396 hr−1biologic half‐lifet½was 1.80 hour, volume of distributionVdwas 0.201 l./kg; in five bedridden elderly patients,Kelwas 0.208 hr−1,t½was 3.55 hours,Vdwas 0.376 l./kg. Cumulative renal excretion of amikacin in 8 hours was 44 per cent of the total dose in bedridden elderly patients and 69 per cent in healthy volunteers. For cephalothin, in seven healthy volunteers,Kelwas 0.0353 min−1,t½was 19.7 min,Vdwas 0.176 l./kg; in four bedridden elderly patients,Kelwas 0.0127 min−1,t½was 56.4 min,Vdwas 0.283 l./kg. Cumulative renal excretion of cephalothin reached a plateau by 4 hours of 40.8 per cent of the total dose in bedridden elderly patients and of 56.7 per cent in healthy volunteers. These results suggest that in bedridden elderly patients decreased renal excretion of amikacin and cephalothin is related to decreased renal function and

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02693.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY