摘要:

Atrial natriuretic peptide (ANP) is a 28 amino‐acid polypeptide secreted into the blood by atrial myocytes after atrial pressure and distension. Although its role in humans is not clear, it can produce a variety of physiologic effects including vasodilatation, natriuresis, and suppression of the renin‐angiotensin‐aldosterone axis. These actions are potentially useful in a variety of pathologic states such as hypertension and congestive heart failure, and diverse methods to augment the effects of ANP in these states have been devised. The results are exciting and, despite some problems, may lead to the pharmacologic use of enhancement of ANP actions in several clinical diso

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04723.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Dietary and endogenous ligands compete with drugs for receptor occupancy and therefore should be considered during therapeutic interventions and during pharmacokinetic/pharmacodynamic modeling. When disease is the result of an overabundance of these natural ligands, antibodies and/or their Fab fragments may be useful as therapeutic agents to reverse the effects of the natural ligands.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04724.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04725.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Rapidly inflating health care costs limit patient care, and prescription drug costs constitute a major component of this expenditure. This study examines attitudes toward and knowledge of prescription drug costs of primary care physicians. Access to information about drug costs and implications for medical education are also explored. A questionnaire survey was sent to 137 internists, family, and general practitioners, randomly selected from a list provided by the Ohio State Medical Board. The questionnaire elicited information on demographic characteristics of respondents, influence of drug costs on prescribing habits, actual knowledge of prices of the 20 most commonly used drugs, attitudes toward generic drug use, sources of information on costs, and desire for emphasis on drug costs in medical education. Responding physicians indicated consideration of drug costs in therapeutic decisions, but lacked information and often made inaccurate assumptions about costs of drugs prescribed. Most felt they could provide better service and reduce costs if information about drug prices was readily available. Most agreed medical education should address drug costs. Drug cost estimates varied widely; correct responses ranged from 9% to 53%. No statistically significant pattern emerged regarding demographics of respondents or information sources used. Primary care physicians consider drug costs important and realize that cost‐effective prescribing may lower health care costs. However, because physician knowledge of drug costs is inadequate and costs are not readily accessible, implications for better physician education and improved access are substantia

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04726.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

In the treatment of hypertension in renally impaired patients, normalization of blood pressure alone may not be sufficient to prevent significant morbidity to the kidneys. Treatment must reduce pressure in the renal vasculature, otherwise glomerular filtration rate and renal plasma flow will continue to deteriorate. Isradipine, a dihydropyridine calcium‐channel blocker, has been investigated as a suitable treatment in this setting. Isradipine maintains glomerular filtration rate, preserves or enhances renal plasma flow, decreases renal vascular resistance, maintains or reduces filtration fraction, and exerts a sustained natriuretic effect, all of which may enable isradipine to slow the rate of progression of renal deterioration. In addition, isradipine may decrease proteinuria and may decrease glomerular capillary pressure by dilating both the efferent and afferent arterioles. Unlike older calcium‐channel blockers, isradipine exhibits minimal cardiodepressant activity and is not associated with any negative inotropic effects. It is metabolized in the liver and dosage adjustments may not be necessary when administered to patients with renal insufficiency. Isradipine has a favorable renal effect profile and also has several properties that meet the requirements of other patient populations where an extra measure of antihypertensive safety is required, such as diabetics, dialysis patients, and transplant recipients. Side effects with isradipine are usually mild and transient, occurring in a dose‐dependent m

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04727.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

In most cases, the antihypertensive therapy for an individual patient is selected through a process of trial and error. This study determined if, by treating each hypertensive patient sequentially, with six antihypertensive drugs, one from each of the major classes, one could decide on the best possible drug for control of hypertension. In a randomized open‐label crossover study, 19 patients (16 male and 3 female), 28–70 years of age with a sitting diastolic blood pressure of 95–110 mm Hg were given atenolol, captopril, clonidine, indapamide, prazosin, and verapamil in a sequential manner. Each drug was started at the minimum recommended or lower dose and titrated upwards every 2 weeks, if well tolerated, until blood pressure was controlled (diastolic BP<90 mm Hg). If blood pressure was controlled, the drug was continued for another 2 weeks. A washout period of at least 2 weeks was allowed between drugs. Both systolic and diastolic blood pressures were reduced significantly with all of the six drugs. In 18 of the 19 patients, blood pressure was controlled with at least one of six drugs, frequently with the lowest dose. The authors conclude that if hypertension is not controlled with the lowest recommended dose of a drug, other antihypertensive drugs should be tried sequentially rather than increasing the dose or adding a second

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04728.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The effect of intravenous (IV) libenzapril was studied in six healthy males by administering IV angiotensin I (AI) administered in stepwise increments of 20 ng/kg/5 min until the subjects' systolic blood pressure (SBP) had increased 20–30 mm Hg above baseline. The mean baseline infusion of 63 ng/kg/5 min resulted in a significant (P<0.05) increase in the ratio of AII to AI plasma levels from 0.52 ± 0.46 to 7.92 ± 4.48 and a SBP increase of 120 ± 7.1 to 147 ± 5.6. Within 15 minutes of starting the 1‐mg infusion of libenzapril over 1.5 hours, the AII/AI ratio decreased to baseline values, and the SBP had returned to baseline in 1 hour. Repeat AI challenges at 3.5 and 5 hours postdose did not increase SBP significantly. Even the 6.5‐hour challenge demonstrated only a slight increase in SBP, with an AII/AI ratio of 0.26. At 24 hours, SBP was only 40% of the baseline response, demonstrating that libenzapril is a potent long‐acting AC

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04729.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Sodium diethyldithiocarbamate (DDTC) is an investigational modulator of the toxicity produced by cisplatin. The pharmacokinetics of DDTC were evaluated after administration of 200 mg/m2/hr (n=8) and 400 mg/m2/hr (n=7) DDTC as 4‐hour intravenous infusions to normal male healthy volunteers. Diethyldithiocarbamate concentration at steady‐state (Cpss) increased disproportionally from 27.0 ± 7.6 μM for the low dose to 74.8 ± 19.3 μM for the high dose, whereas total body clearance decreased from 23.83 ± 8.23 mL/min/kg for the low dose to 15.48 ± 2.72 mL/min/kg for the high dose (P<0.05). However, the volume of distribution in the terminal phase remained unchanged. Diethyldithiocarbamate terminal elimination half‐life (t1/2β) increased from 3.74 ± 1.10 minutes for the low dose to 6.08 ± 1.07 minutes for the high dose (P<0.005). The data were then fitted using a one‐compartment open model with zero‐order infusion and Michaelis‐Menten elimination kinetics. The Km for DDTC was estimated to be 124.3 ± 19.9 μM, whereas the Vm was estimated to be 3.67 ± 1.15 μmol/min/kg. However, DDTC t1/2βwas independent of DDTC concentrations, suggesting that the nonlinearity in DDTC kinetics does not exactly follow Michaelis‐Menten elimination kinetics. Thus, DDTC pharmacokinetics are dose dependent and may not be concentration dependent. Clinically, DDTC Cpss will increase nonlinear

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04730.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A four‐way crossover pilot study was conducted to compare the pharmacodynamic response of intermittent famotidine (20 mg every 12 hr) to continuous infusions of cimetidine (1200 mg/24 hr), ranitidine (150 mg/24 hr), and famotidine (40 mg/24 hr) in six normal male volunteers. Intragastric pH was monitored continuously for 24 hours. Comparisons included percent time during the 24‐hour period that gastric pH was greater than pH 4.0, and pH 5.0, and also for the steady‐state period of each regimen (12–24 hr). Although no statistically significant difference was observed for any of these comparisons, a clinically relevant trend was observed. In crossover experiments, famotidine intermittent infusions provided gastric pH readings above 4.0 and 5.0 for a longer duration than any of the continuous infusion regimens. Famotidine intermittent infusion regimens (20 mg every 12 hr) are at least equivalent to continuous infusions of cimetidine, ranitidine, and famotidine. Based on these findings, comparative studies in an appropriate critical care population would be beneficial, but any such studies must use a crossover design because of the even higher degree of intersubject variance in pH control. For this reason, the normal volunteer crossover model used here may provide important comparative information for the various regimens used in suppression of gastric

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04731.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetic profile of penciclovir was determined after a single 500‐mg dose of its oral precursor, famciclovir, in 9 healthy volunteers and in 14 patients with chronic hepatic disease. Plasma and urine samples were analyzed for concentrations of penciclovir and 6‐deoxy‐penciclovir using a reverse‐phase high‐performance liquid chromatography (HPLC) method. Famciclovir was not quantifiable in patients with hepatic disease, and 6‐deoxy‐penciclovir was quantifiable in only a limited number of specimens. The extent of systemic availability of penciclovir, as measured by AUC0‐∞, was similar in patients with hepatic disease and in healthy subjects. In contrast, Cmaxwas significantly lower (average decrease of 43%) in subjects with hepatic disease relative to healthy normal subjects. Median Tmaxfor subjects with hepatic disease was significantly increased (by 0.75 hours) compared with subjects with normal liver function. These data suggest a decrease in the rate, but not the extent, of systemic availability of penciclovir in patients with hepatic disease. It should be unnecessary to modify the dose of famciclovir for subjects with compensated hepatic disease and norm

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb04732.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY