ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03742.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are capable of inducing a variety of renal function abnormalities, particularly in high‐risk patients with decreased renal blood perfusion who depend on prostaglandin synthesis to maintain normal renal function. Fluid retention is the most common NSAID‐related renal complication, occurring to some degree in virtually all exposed individuals; however, clinically detectable edema occurs in less than 5% of patients and is readily reversible on discontinuation of the NSAID. Other electrolyte complications, notably hyperkalemia, are seen infrequently and occur in specific at‐risk patients. The next most worrisome complication is acute deterioration of renal function, which occurs in high‐risk patients and is also reversible. Nephrotic syndrome with interstitial nephritis is a rare problem of NSAID use and is reversible. Papillary necrosis is the only permanent complication of NSAIDs and is very rare. Altogether, these renal function abnormalities, with the exception of mild fluid retention, are clinically detectable in approximately 1% of exposed patients. Given the number of patients who take NSAIDs on a prescription or over‐the‐counter basis, the absolute number of at‐risk patients is relatively large. Consequently, an appreciation for the risk factors and pathophysiology of NSAID‐induced renal function abnormalities is required for optimal u

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03743.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03744.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The effect of administration of pirmenol, an extensively metabolized and plasma protein‐bound antiarrhythmic agent, was evaluated in ten patients on chronic warfarin therapy. After a 3‐week baseline period and 7 days of placebo administration, patients received 150 mg of oral pirmenol every 12 hours for 14 days. Prothrombin time was determined during the baseline and placebo periods, during pirmenol administration, and 14 days after the last pirmenol dose (washout). There was no significant difference between mean baseline, placebo, pirmenol, and washout prothrombin times. Coadministration of pirmenol does not appear to affect the anticoagulant activity of warfa

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03745.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The influence of chlorthalidone (100 mgpo) on the pharmacokinetics and pharmacodynamics of Org 10172 (IV bolus injection of 3250 anti‐Xa units), a low molecular weight heparinoid, was studied in six healthy male volunteers using an open randomized two‐way crossover design. Chlorthalidone produced a slight decrease in clearance of anti‐Xa activity from 7.1 ± 1.0 to 6.6 ± 0.8 mL/min and a decrease of the volume of distribution from 0.20 ± 0.05 to 0.16 ± 0.04 L/kg, whereas the volume of distribution of antithrombin activity increased from 0.14 ± 0.05 to 0.26 ± 0.10 L/kg (all differencesP<.05). During the entire study period no adverse events occurred. In summary, chlorthalidone showed separate effects on different fractions of Org 10172. The clinical implication of the slight change observed in plasma anti‐Xa activity is likely to be limited, whereas the 80% increase in distribution volume of plasma antithromhin activity can not be defined as yet in terms of clini

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03746.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment. In volunteers, systemic vancomycin clearance at steady‐state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para‐aminohippurate. Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours. Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min). Groups did not differ demographically. Audiograms were obtained before and after vancomycin. Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies. Serum concentration versus time data were fit to a two‐compartment model for vancomycin and a one‐compartment model for tobramycin. For all volunteers, creatinine, inulin and para‐aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups. No significant effect of tobramycin on vancomycin pharmacokinetics was observed. Conversely, vancomycin had no significant effect on tobramycin pharmacokinetics. The nephrotoxic synergism of vancomycin and tobramycin is not explained by short‐term differences in ren

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03747.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Phenylpropanolamine, a widely consumed over‐the‐counter drug, is known to elevate blood pressure, but the mechanism is unknown; it may be both a direct and indirect sympathomimetic. This study investigated the effects of 75‐mg sustained‐release phenylpropanolamine, 75‐mg phenylpropanolamine plus 400‐mg caffeine, and 150‐mg phenylpropanolamine on blood pressure, plasma norepinephrine, and epinephrine levels in 16 normotensive subjects in a double‐blind, placebo‐controlled crossover design. Mean peak phenylpropanolamine levels of 317 ± 26, 152 ± 17, and 157 ± 17 ng/mL for 150‐mg phenylpropanolamine, 75‐mg phenylpropanolamine, and 75‐mg phenylpropanolamine plus 400‐mg caffeine, respectively, were reached at about 3.6 hours after dosing. The maximal increases in supine diastolic blood pressures after all three phenylpropanolamine‐containing drugs were almost three times that after placebo (P<.05), but peak blood pressures occurred at about 2.3 hours earlier than peak phenylpropanolamine levels. Blood pressure increases correlated with phenylpropanolamine plasma levels (r =.49 for systolic blood pressure andr =.34 for diastolic blood pressure; P<.0001 for both). Norepinephrine levels increased after the administration of 150‐mg phenylpropanolamine and 75‐mg phenylpropanolamine plus 400‐mg caffeine; norepinephrine increases correlated with phenylpropanolamine levels (r =.34, P<.0001). The expected increment in norepinephrine induced by standing was significantly decreased by phenylpropanolamine in a dose‐dependent mode. The study supports the idea that phenylpropanolamine is both a direct (at alpha‐1 and alpha‐2 recept

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03748.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

A randomized, double blind, placebo‐controlled crossover study on 20 patients with exercise‐induced angina pectoris and reproducible ST‐segment depression during exercise‐stress test was performed to compare the effect of a single dose of 120 mg of isosorbide dinitrate in a slow‐release form with that of a twice‐daily application of 20 mg of isosorbide‐5‐mononitrate. Symptom‐limited exercise tests were done, and nitrate plasma levels were measured in the subjects 6, 10, and 24 hours after the first administration of the drug. Both drugs produced a highly significant reduction in the size of exercise‐induced ST‐depressions (P<.001) 6 and 10 hours after the first administration of isosorbide dinitrate as well as 6 hours after the first and 4 hours after the second dose of isosorbide‐5‐mononitrate. The effect was still significant (P<.05) 24 hours after the administration of isosorbide dinitrate in a slow‐release form and 18 hours after the second dose of isosorbide‐5‐mononitrate. In the case of the drug isosorbide dinitrate, nitrate plasma levels for its metabolite, isosorbide‐5‐mononitrate, were highest 10 hours after first application. In the case of the drug isosorbide‐5‐mononitrate, nitrate plasma levels were highest 4 hours after the second dose. Two 20 mg doses of isosorbide‐5‐mononitrate and a single dose of 120 mg isosorbide dinitrate in a slow release form have a comparable effect on the reduction

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03749.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Nicotinic acid is a water‐soluble B‐complex vitamin that has been shown, in high doses, to lower total plasma cholesterol (C), LDL‐C, and VLDL‐triglycerides (Tg), while raising HDL‐C in patients with type II, III, IV, and V hyperlipoproteinemia. Its exact mechanism of action is not known, but it appears to lower the production of VLDL in the liver while activating lipoprotein lipase. The drug may also influence the metabolism of HDL‐C. The drug is a second or third choice for isolated hypercholesterolemia because of a high incidence of side effects. However, it has a therapeutic advantage as a monotherapy when reduction of both LDL‐C and triglycerides are needed in patients with severe combined hyperlipidemia. The drug can be used in combination with other cholesterol‐lowering agents to maximize lipid‐lowering activity. Nicotinic acid has been associated with a reduced risk of cardiovascular morbidity i

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03750.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Serum concentration‐time course profiles, serum protein binding, and disposition parameters of lorazepam (LRZ), a benzodiazepine with sedative‐hypnotic, anxiolytic, and antiseizure properties, were studied as part of a systematic effort to define population‐specific pharmacokinetic behavior in humans with chronic spinal cord injury (SCI). Twenty‐four healthy subjects (nine tetraplegic, six paraplegic, nine able‐bodied) were given an IV bolus of 2.0 mg of LRZ. Noncompartmental estimation of pharmacokinetic parameters disclosed a 37% decrease in the total systemic clearance (CL) of LRZ in tetraplegic patients. Altered LRZ clearance was observed independently of significant changes in volume of distribution or serum protein binding. The early elimination of LRZ (0–10 hr) was characterized by wide fluctuations in serum concentration suggestive of impaired enterohepatic circulation and could be distinguished from LRZ elimination observed in able‐bodied subjects. We conclude that decreased systemic CL and the altered terminal elimination profile of LRZ are attributable to the pathophys

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb03751.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY