摘要:

We evaluated the effect of additional chlorthalidone therapy on blood pressure and body fluid volumes in 10 patients with essential hypertension who did not respond to chronic converting enzyme inhibition with enalapril. Values assessed after 3 days and 6 weeks of combined enalapril and chlorthalidone therapy were compared with initial values during enalapril monotherapy. After 3 days the mean arterial pressure (MAP), plasma volume (PV), blood volume (BV), and extracellular fluid volume (ECFV) decreased. There was a positive correlation between the percentage decreases in MAP and BV. After 6 weeks the MAP decreased further, but the decreases in PV, BV, and ECFV were less pronounced. At this time there was a positive correlation between the percentage decreases in MAP and ECFV. Our results support the hypothesis that contraction of the ECFV is an antihypertensive mechanism of diuretics. The antihypertensive effect of diuretics is enhanced during converting enzyme inhibition, while the body remains protected against volume deficits, possibly by the lower blood pressure itself.Clinical Pharmacology and Therapeutics(1986)39,60–64; doi:10.1038/clpt.1986.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.11

年代:1986

数据来源: WILEY

摘要:

The influence of bepridil on steady‐state serum digoxin concentrations (SDCs) and the pharmacodynamic actions of both drugs were tested in 48 healthy subjects in a randomized, double‐blind study. Subjects were assigned to one of two groups of 24 subjects each: One group received placebo 1, while the other received digoxin, 0.375 mg/day, loaded with doubled doses on days 1 and 2, for 14 days. After 7 days the groups were subdivided into four groups of 12 subjects each and received concurrent dosing of digoxin with either placebo 2 or bepridil, 300 mg/day, loaded with 900 mg on day 8. Mean (± SD) SDCs rose during concurrent bepridil dosing from 0.93 ± 0.22 to 1.25 ± 0.25 ng/ml (P<0.001). Noninvasive cardiovascular parameters from ECG, systolic time intervals, and electrical impedance cardiography were not influenced by the placebos. Digoxin and bepridil reduced heart rate and prolonged the PQ interval because of negative chronotropic and dromotropic properties. Positive inotropism from digoxin shortened the corrected electromechanical systole (QS2c) and the preejection period and increased impedance cardiography [(dZ/dt)/RZ index]; the opposite effects occurred after bepridil, indicating negative inotropism. The QT interval corrected for heart rate (QTc) showed a similar pattern of changes, as did QS2cfor each drug. Concurrent dosing of both drugs resulted in an addition of their chronotropic effects, whereas the dromotropic effects of each drug alone was not intensified. The strengthened digoxin effect from the increased SDC diminished the negative inotropic effect of bepridil. Overall, drug coadministration resulted in a nearly unchanged digoxin‐induced positive inotropism. In relation to the pretreatment value, QTcwas only moderately prolonged after concurrent dosing; however, there was a strong effect evident on the basis of the previous digoxin‐shortened interval. Patients receiving digoxin and bepridil should be monitored carefully, but a general reduction in digoxin dosages does not seem necessary.Clinical Pharmacology and Therapeutics(1986)39,65–71; doi:10.1038

ISSN:0009-9236    

DOI:10.1038/clpt.1986.12

年代:1986

数据来源: WILEY

摘要:

Twenty‐nine boys with attention deficit disorder/hyperactivity were randomly assigned to receive desipramine (DMI; n = 17) or placebo (n = 12) for 14 days in a noncrossover, double‐blind study. There was immediate behavioral improvement with DMI at day 3 that was sustained for 2 weeks; behavioral improvement did not correlate with plasma concentrations of DMI, hydroxy‐DMI, or their sum at either days 3 or 14. There were no untoward side effects; there was a drug‐induced increase in pulse and diastolic blood pressure. During drug therapy, the urinary excretion of norepinephrine, vanillymandelic acid, and 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) was decreased at both days 3 and 14. The plasma MHPG level was decreased at days 3 and 14 and (standing) plasma NE levels increased at day 14. The decreases in both urinary and plasma MHPG levels showed significant correlations with behavioral improvement during the second week. These data corroborate previous findings on sympathomimetic effects of tricyclic antidepressants in children and support a noradrenergic mechanism in the mediation of drug effects on attention deficit disorder/hyperactivity.Clinical Pharmacology and Therapeutics(1986)39,72–81; doi:10.1

ISSN:0009-9236    

DOI:10.1038/clpt.1986.13

年代:1986

数据来源: WILEY

摘要:

Forearm venous tone and brachial artery hemodynamics, including determinations of the arterial diameter and compliance by the use of pulsed Doppler systems, were measured in 16 patients with sustained essential hypertension before and after acute oral cadralazine dosing. Systolic and diastolic blood pressures significantly decreased, whereas heart rate increased. Brachial artery diameter and vascular resistance decreased, respectively, from 0.501 ± 0.015 to 0.485 ± 0.015 cm (P<0.001) and from 124.8 ± 13.8 to 99.3 ± 11.9 mm Hg/ml · sec (P<0.01). Blood flow velocity increased (P<0.05) but volumic flow, pulse wave velocity, and brachial artery compliance did not change. Forearm venous tone increased but the increase was inversely related to the degree of arteriolar vasodilatation. Our results indicate that, with cadralazine, (1) forearm vascular resistance decreased while forearm blood flow was unchanged, (2) the dilatation of small arteries contrasted with a significant reduction in the diameter of the large brachial artery, and (3) the decrease in blood pressure was associated with a lack of increase in arterial compliance and changes in venous tone. This suggests an overriding influence of the activation of the autonomic nervous system on the action of cadralazine on large arteries and veins.Clinical Pharmacology and Therapeutics(1986)39,82–88; doi:10.1038/clpt.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.14

年代:1986

数据来源: WILEY

摘要:

In a double‐blind, single‐dose, parallel‐group study, ketorolac (5, 10, or 20 mg) was compared with acetaminophen (500 or 1000 mg) when taken by mouth for postoperative orthopedic pain. Analgesic measurements were made by trained nurse observers who used standard verbal rating and visual analog scales. Acetaminophen, 1000 mg, was statistically superior to 500 mg acetaminophen, demonstrating assay sensitivity. Ketorolac, 20 mg, was distinguished from 500 mg acetaminophen, 5 mg ketorolac, and 10 mg ketorolac, but not from 1000 mg acetaminophen. The higher doses of ketorolac induced a longer lasting peak analgesic effect than did acetaminophen, but the magnitude of the peak pain relief was changed little by an increased ketorolac dose. Overall, 10 mg ketorolac appeared equivalent to 1000 mg acetaminophen. Acetaminophen, 500 mg, induced less sedation than the higher doses of ketorolac, but neither drug caused untoward side effects.Clinical Pharmacology and Therapeutics(1986)39,89–93; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1986.15

年代:1986

数据来源: WILEY

摘要:

To investigate whether chronic hydrochlorothiazide (HCTZ) therapy increases synthesis of tissue vasodilator prostaglandins (PG), we used intravenous furosemide as a standardized stimulus of renal PG synthesis before and after HCTZ dosing. Sixteen subjects with mild hypertension received placebo for 4 weeks, followed by HCTZ, 50 mg/day, and potassium chloride, 60 mmol/day, for 4 weeks. Nine subjects had decreased mean arterial pressure (−12.2 ± 0.9 mm Hg) after HCTZ (responders), while seven others had no antihypertensive effect (nonresponders). Responders increased their excretion of the prostacyclin (PGI2) hydrolysis product 6‐keto‐PGF1αin the first 10 minutes after furosemide, from 17.8 ± 2.7 ng after placebo to 34.9 ± 7.5 ng (P<0.05) after HCTZ, whereas nonresponders showed no such increase. These groups could not be distinguished on the basis of sex, age, or pretreatment plasma renin activity. After HCTZ dosing, responders showed evidence of increased action of PGI2by increased plasma renin activity 10 minutes after furosemide (6.10 ± 1.06 vs. 3.39 ± 0.4 ng/ml/hr; P<0.05). Furthermore, creatinine clearance was maintained in responders (while decreasing slightly in nonresponders) despite lower blood pressure, a finding consistent with increased vasodilator effect. We conclude that an antihypertensive response to HCTZ is accompanied by an increase in renal PGI2synthesis and action.Clinical Pharmacology and Therapeutics(1986)39,94–101; doi:10.103

ISSN:0009-9236    

DOI:10.1038/clpt.1986.16

年代:1986

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1986)39,102–103; doi:10.1038/clpt.1986.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.18

年代:1986

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1986)39,104–105; doi:10.1038/clpt.1986.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.19

年代:1986

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1986)39,106; doi:10.1038/clpt.1986.20

ISSN:0009-9236    

DOI:10.1038/clpt.1986.20

年代:1986

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1986)39,107–122; doi:10.1038/clpt.1986.

ISSN:0009-9236    

DOI:10.1038/clpt.1986.21

年代:1986

数据来源: WILEY