摘要:

In this study 116 subjects were asked to quantify the descriptive pain terms commonly used in analgesimetry by using the visual analog scale as a tool. The results showed highly variable responses. Several words that have been assigned the same value on an ordinal scale do not convey the same meanings as on the visual analog scale. The words some and terrible are probably the least useful terms to quantify pain. The word complete for describing pain relief showed the least variation. The data on global ratings varied greatly; 10% of the participants gave the same values to the terms very good and excellent. The unequal differences between descriptive terms that are commonly considered equidistant on an ordinal scale are clearly demonstrated. We propose an approach to quantifying pain that takes into account the interindividual variations in interpretation of descriptive pain terms.Clinical Pharmacology and Therapeutics(1982)32,143–148; doi:10.1038/clpt.1982.1

ISSN:0009-9236    

DOI:10.1038/clpt.1982.139

年代:1982

数据来源: WILEY

摘要:

After a 7‐day placebo lead‐in period, one of three β‐adrenergic antagonists was taken for 2 wk by 10 healthy male subjects. The drugs were metoprolol (cardioselective) and propranolol and nadolol (both nonselective). Dosage was according to currently recommended regimens and was increased after the first week (50 to 100 mg b.i.d., 20 to 40 mg q.i.d., and 80 to 160 mg q.d.). Pulmonary mechanics and density dependence (DD) of maximal expiratory flow were measured before and at the end of the placebo lead‐in period and the low‐ and high‐dose treatment weeks. Total lung capacity (TLC), residual volume (RV), and RV/TLC all rose (P<0.05) after high‐dose nadolol. Forced vital capacity (FVC) and expiratory reserve volume fell (P<0.05) after high‐dose metoprolol. There was no change in forced expiratory volume in 1.0 sec (FEV1), FEV1/FVC, maximal midexpiratory flow rate, or airway resistance with any of the β‐antagonists. Decreases (P<0.05) in maximal expiratory flow determined at 50% of the vital capacity occurred after propranolol and metoprolol, but not after nadolol. A dose‐related decrease in DD at 50% of the vital capacity accompanied nadolol dosing, but was significant only after the high‐dose regimen. The decreases in DD with nadolol, as well as its effect on RV/TLC, are consistent with small airway narrowing. The findings with metoprolol and propranolol suggest that they affect central as well as peripheral airways.Clinical Pharmacology and Therapeutics(1982)32,149–155;

ISSN:0009-9236    

DOI:10.1038/clpt.1982.140

年代:1982

数据来源: WILEY

摘要:

Combined use of prazosin and propranolol was effective in preoperative management of three patients with norepinephrine(NE)‐secreting pheochromocytoma (PHEO). On admission, all were symptomatic and had moderate to severe hypertension despite treatment with diuretics, propranolol, and sympatholytics. Optimal symptomatic and blood pressure (BP) control was achieved with 6 to 10 mg/day prazosin and 120 to 480 mg/day propranolol every 6 hr in equally divided doses. With this therapy, BP and hematocrit were reduced to levels similar to those found in the postoperative period. The daily urinary excretion of catecholamines and their metabolites was not modified during therapy with prazosin and propranolol. There was a drop in supine systolic (40 to 64 mm Hg) and diastolic (32 to 52 mm Hg) BP in all patients 1 to 2 hr after the first dose of prazosin (1‐mg tablet); in two subjects this was accompanied by a larger orthostatic fall (74 and 92 mm Hg systolic; 65 and 78 mm Hg diastolic BP). The high incidence of first‐dose effect suggests that a single oral dose of 1 mg of prazosin could aid in the diagnosis of PHEO. The effectiveness of prazosin in controlling the hypertension induced by NE‐secreting PHEO suggests that, in man, pressure responses to augmented levels of NE are mediated solely through α1‐receptors.Clinical Pharmacology and Therapeutics(1982)32,156–160; doi:10.1038/

ISSN:0009-9236    

DOI:10.1038/clpt.1982.141

年代:1982

数据来源: WILEY

摘要:

Binding of (‐)[3H]‐dihydroalprenolol (3H‐DHA) to lymphocytes from five thyrotoxic patients and five age‐ and sex‐matched controls were examined to ascertain whether β‐adrenergic receptor number or binding affinity were altered in thyrotoxicosis. Whereas an increase in β‐adrenoceptor density has been reported in triiodothyronine‐induced hyperthyroidism, we did not find changes in β‐adrenergic receptor density or binding affinity. In one patient studied sequentially, we did not find alteration in3H‐DHA binding before or after the subject was rendered euthyroid. We conclude that lymphocyte β‐adrenergic receptor density and affinity are not altered in spontaneous hyperthyroidism.Clinical Pharmacology and Therapeutics(1982)32,161–16

ISSN:0009-9236    

DOI:10.1038/clpt.1982.142

年代:1982

数据来源: WILEY

摘要:

Effects of varying doses of troleandomycin (TAO) on methylprednisolone disposition were examined in five steroid‐dependent asthmatic patients. The characteristic reduction in methylprednisolone elimination in the presence of TAO after a 40 mg IV methylprednisolone was also present after methylprednisolone doses as low as 4 mg. In patients receiving continuous TAO on an every‐other‐day basis, inhibition of methylprednisolone elimination was impaired to a greater extent on the “day on” TAO than on the “day off” TAO. Methylprednisolone elimination on the day off TAO was still slower than that before TAO, however. TAO on a multiple‐dose schedule resulted in greater reduction of methylprednisolone elimination than after a single TAO dose. These results suggest that TAO induces immediate and continued inhibition of methylprednisolone disposition.Clinical Pharmacology and Therapeutics(1982)32,166–171; doi:10.

ISSN:0009-9236    

DOI:10.1038/clpt.1982.143

年代:1982

数据来源: WILEY

摘要:

With data on adults from two previous articles it was found that the average steady‐state plasma concentration of verapamil in subjects on long‐term oral therapy of 80 mg every 6 hr (Y) correlated strongly with the area under the curve from zero to infinity (AUC0‐∞/6(X) where the area refers to that for a single oral dose of 80 mg (Ŷ = 2.41X, n = 15, r = 0.923, P<0.001). Steady‐state concentrations are predictable from the single‐dose data, with an average absolute deviation of 11.1%. We gave seven children (7 to 19 yr old) an initial intravenous bolus dose of 0.1 mg/kg, followed by a 20‐min constant rate infusion of 0.007 mg/kg/min. Twenty‐four hours after the bolus dose they were put on oral therapy (40 or 80 mg every 6 hr) and 1 mo later the minimum steady‐state verapamil plasma concentration (Cminss) was measured. Plasma concentration‐time data obtained after the infusion were fitted to biexponential (two sets) or triexponential equations (five sets). The coefficients of the postinfusion poly exponential equations were converted to those for the 0.1‐mg/kg bolus dose alone. Mean parameters estimated were: plasma clearance 0.500 l/min, steady‐state volume of distribution 279 l, Vβ394 l, half‐life 9.17 hr, and mean residence time 10.0 hr. Many correlations were made between the oral Cminssvalues and functions obtained from the intravenous data. The best correlation was that between Cminssand the predicted steady‐state concentration at 3 hr after dosing when bolus doses would be given at 6‐hr intervals based on the single‐dose intravenous data (r = 0.985, P<0.001); this correlation allowed Cminssto be predicted with an average absolute deviation of 10%. Norverapamil was measured in plasma after oral dosing, but was not detectable after intravenous dosing.Clinical Pharmacology and Therapeutics(1982)32,

ISSN:0009-9236    

DOI:10.1038/clpt.1982.144

年代:1982

数据来源: WILEY

摘要:

14C‐Captopril was given intravenously to four normal subjects in a 4‐mg priming dose followed by constant intravenous infusion of 1.7 mg/hr for 3.5 hr with and without concomitant probenecid. Steady‐state levels of unchanged captopril were obtained between 1.5 and 3.5 hr. In the presence of probenecid, the average steady‐state blood levels of total radioactivity were higher (36%) than on captopril alone. Unchanged captopril levels were slightly higher (14%) in the presence of probenecid. Kinetic evaluations were carried out exclusively on data for unchanged captopril. The average total body clearance (ClT) and renal clearance (ClR) of captopril in the absence of probenecid were 775 and 388 ml/kg/hr. The corresponding values for captopril with probenecid (631 and 217 ml/kg/hr) were lower. The average ratio of ClRto ClTfor captopril alone was 0.50 and fell to 0.35 in the presence of probenecid. When captopril alone was given, a minimum of 78% of the renal excretion of captopril during steady‐state could be attributed to net tubular secretion, but when captopril was given with probenecid, net tubular secretion was only 57%. The volume of distribution of captopril during steady state was not altered by probenecid. For the first 3.5 hr, cumulative renal excretion of total radioactivity with and without probenecid was 55% and 60%, but cumulative excretion of unchanged captopril was higher after captopril alone (36% of dose) than after the combination (21% of dose).Clinical Pharmacology and Therapeutics(1982)32,182–189; doi:10.1038/c

ISSN:0009-9236    

DOI:10.1038/clpt.1982.145

年代:1982

数据来源: WILEY

摘要:

To establish therapeutic guidelines, benoxaprofen kinetics were examined in 26 adult subjects with normal and decreased renal function. Mean peak plasma concentrations after a single 600‐mg dose ranged from 58 to 72 mg/l, independent of renal function. Elimination half‐life and benoxaprofen plasma clearance correlated with creatinine clearance. Hemodialysis did not remove benoxaprofen from plasma. A dosage nomogram was derived from which a dose one half of the normal maintenance dose was suggested for patients with severe renal failure.Clinical Pharmacology and Therapeutics(1982)32,190–194; doi:10.1038/clpt.19

ISSN:0009-9236    

DOI:10.1038/clpt.1982.146

年代:1982

数据来源: WILEY

摘要:

A mechanism postulated for drug‐ or chemical‐induced systemic lupus erythematosus (SLE) is that the chemical is covalently bound to nuclear macromolecules increasing the immunogenicity of the macromolecule. This may require metabolic activation by oxidation. There are many similarities between drug‐induced and idiopathic SLE. Twelve patients with idiopathic SLE and 12 normal subjects were given 100 mg pentobarbital orally to evaluate their microsomal hydroxylating activity. Plasma pentobarbital concentration was measured by gas‐liquid chromatography. Mean plasma pentobarbital half‐life was 24 ± 10 (mean ± SD) hr in the SLE patients, which is only slightly shorter than the 26 ± 12 hr in the control subjects. The mean apparent volume of distribution in the patients was 1.28 ± 0.30 l/kg, which is slightly above the 1.00 ± 0.37 l/kg in the normal subjects (P<0.05). Mean metabolic clearance rate in the SLE patients was 0.045 ± 0.022 l/hr/kg, which is more than the 0.028 ± 0.008 l/hr/kg in the normal control subjects (P<0.02). Since the metabolic clearance rate of a drug is the proper value for evaluating metabolism rate, we conclude that patients with SLE have an increased elimination rate for drugs or other foreign compounds that are biotransformed by microsomal oxidation and may more rapidly bioactivate chemicals to reactive compounds.Clinical Pharmacology and Therapeutics(1982)32,195–200; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1982.147

年代:1982

数据来源: WILEY

摘要:

Psychomotor and psychologic effects of single doses of buspirone (10 and 20 mg) and lorazepam (2.5 mg) alone or combined with alcohol (1 gm/kg) were investigated in 12 healthy young men. crossover study in 12 healthy young men. Lorazepam alone impaired psychomotor skills (tracking, body balance, extraocular muscle balance, and flicker recognition), the effects being maximal at 180 min. This impairment was not subjectively perceived by the subjects. Neither dose of buspirone alone impaired objective measurements, although buspirone, especially in the 20‐mg dose, was felt to cause drowsiness, weakness, and faintness. Lorazepam, but not buspirone, interacted with alcohol.Clinical Pharmacology and Therapeutics(1982)32,201–207; doi:10.1038/clpt.1982

ISSN:0009-9236    

DOI:10.1038/clpt.1982.148

年代:1982

数据来源: WILEY