摘要:

We surveyed 100 women receiving short courses of estrogen post partum to suppress lactation. Thirty six had significant apprehension about estrogens, but took them. These women were significantly older and better educated and 92% of them were married. In contrast, only one third of the “nonapprehensive” women were married and they had significantly lower family incomes. More of the apprehensive women read the estrogen patient package insert (PPI) and almost 30% developed negative attitudes toward estrogens. The major concerns of these women reflected information in the PPI about cancer and thromboembolism. The reasons given for taking estrogens despite apprehension included the lower risk of short courses, assurance from physicians, nurses, or family members, and the desired therapeutic effect. These women should not be given the current estrogen PPI, which was designed to warn women of the risks of long‐term estrogen use; a PPI should be written specifically for patients receiving short courses. Similar problems will arise with the PPIs for other medications that have different risks for different therapeutic indications.Clinical Pharmacology and Therapeutics(1981)30,149–153; doi:10.1038/clpt.

ISSN:0009-9236    

DOI:10.1038/clpt.1981.140

年代:1981

数据来源: WILEY

摘要:

The effects of myocardial infarction (MI) on lidocaine disposition were investigated in eight patients during a constant infusion of 2 mg/min. Plasma lidocaine binding and total plasma and free lidocaine concentrations were measured 12, 24, 36, and 48 hr after beginning therapy and were related to α1‐acid glycoprotein (AAG) concentrations. By 48 hr total plasma lidocaine and AAG concentrations had risen, as had plasma lidocaine binding. Because of enhanced binding, free lidocaine concentrations did not change significantly over this time. There was a correlation between AAG and the binding ratio for lidocaine (r = 0.87) and between AAG and total plasma lidocaine concentrations (r = 0.81). The data suggest that the rise in AAG seen after MI is responsible for enhanced plasma lidocaine binding and may, at least in part, be related to lidocaine cumulation.Clinical Pharmacology and Therapeutics(1981)30,154–157; doi:10.1038/clpt.198

ISSN:0009-9236    

DOI:10.1038/clpt.1981.141

年代:1981

数据来源: WILEY

摘要:

We examined the hemodynamic interaction between clonidine, a centrally acting antiadrenergic drug, and minoxidil, a potent antihypertensive vasodilator in 10 inpatients with refractory or accelerated hypertension or both. Clonidine in oral doses of 150 to 900 μg/day decreased average mean blood pressure 18.6 mm Hg (p<0.01), average heart rate 16.4 bpm (p<0.01), limb blood flow 1.63 ml/100 gm · min (p<0.05), and plasma renin activity 1.13 ng/ml · hr (p<0.025). It also increased the pre‐ejection period index 12.4 msec (p<0.001), but did not alter the cardiac or total peripheral resistance indices. The addition of minoxidil in oral doses of 5 to 22.5 mg/day further decreased average mean blood pressure 24.2 mm Hg (p<0.01), preejection period index 20.6 msec (p<0.01), limb vascular resistance 13.2 mm Hg/min · 100 gm/ml (p<0.05), and total peripheral resistance 13.3 mm Hg/min · m2/l (p<0.01), pre‐ejection period index 20.6 msec (p<0.01), limb vascular resistance 13.2 mm Hg/min · 100 gm/ml (p<0.05), and total peripheral resistance 13.3 mm Hg/min · m2/l concluded that clonidine can be used as an alternative to β‐adrenergic blockers to counteract the increased sympathetic nervous activity minoxidil induces.Clinical Pharmacology and Therapeutics(1981)30,158–163; doi:10.10

ISSN:0009-9236    

DOI:10.1038/clpt.1981.142

年代:1981

数据来源: WILEY

摘要:

Supine basal plasma norepinephrine was higher in a group of newly diagnosed patients with mild essential hypertension than in age‐ and sex‐matched “laboratory‐naive” volunteers. Sympathetic activation by exercise and change of posture increased plasma norepinephrine in both groups, with a tendency toward higher values in the hypertensive patients, but norepinephrine clearance was slower and half‐life longer in these patients. Thus the estimate of neuronal norepinephrine release obtained by correction of plasma norepinephrine for individual values of clearance was in the same range in both groups. Plasma norepinephrine was lower in younger “laboratory‐adapted” subjects than in the “laboratory‐naive” normotensive subjects, but clearance was in the same range in both. Thus, variations in kinetics may contribute to differences in plasma norepinephrine between patients with essential hypertension and matched controls. In contrast, the lower plasma concentrations of norepinephrine in “laboratory‐adapted” than in “laboratory‐naive” controls appears to reflect a lower level of sympathetic activity in the former.Clinical Pharmacology and Therapeutics(1981)3

ISSN:0009-9236    

DOI:10.1038/clpt.1981.143

年代:1981

数据来源: WILEY

摘要:

Digoxin dynamics and kinetics were studied in six healthy subjects with and without amiloride. Amiloride increased mean renal digoxin clearance from 1.3 to 2.4 ml · kg−1· min−1(p<0.001) due to increased tubular secretion of digoxin, while the glomerular filtration rate was unchanged. This might be caused by an increase in intracellular potassium concentration in the tubular cells provoked by amiloride. In contrast, the extrarenal clearance of digoxin was almost blocked by amiloride; it fell from a mean of 2.1 to 0.2 ml · kg−1· min−1(p<0.025). Total body clearance tended to fall, but the decrease was not statistically significant. Evaluation of myocardial contractility by systolic time intervals revealed a concentration‐response relationship between digoxin and changes in preejection period index when digoxin was given alone (rs= 0.750, p<0.001). Pretreatment with amiloride abolished this relationship (rs= 0.307, p = NS). Blood pressure and echocardiographically determined left ventricular end‐diastolic diameter measurements indicated no changes in the left ventricular post‐ and preload. It is concluded that amiloride suppressed digoxin‐induced inotropism.Clinical Pharmacology and Therapeutics(1981)30,172–176; doi

ISSN:0009-9236    

DOI:10.1038/clpt.1981.144

年代:1981

数据来源: WILEY

摘要:

The diuretic effect of furosemide was studied in 18 patients with congestive heart failure. Subjects were divided into two groups, group I consisting of eight patients with moderate and group II of 10 patients with advanced congestive heart failure. Six hours after bolus injection of furosemide (40 mg), mean urinary sodium was 120.5 ± 36.7 mEq in group I and 68.2 ± 25.8 mEq in group II (p<0.01), mean urine volume was 1,100 ± 281 and 764 ± 257 ml (p<0.05), mean urinary furosemide excretion was 28.08 ± 2.60 and 24.00 ± 0.74 mg (p<0.05), and mean furosemide renal clearance was 73.4 ± 16.6 and 42.3 ± 11.5 ml/min (p<0.001). Diuretic effect and furosemide renal clearance, as well as urinary furosemide excretion, correlated positively. The diuretic effect of furosemide with and without hydralazine (0.2 mg/kg) was compared in eight patients in group II. Urinary sodium excretion 6 hr after furosemide rose from 77.2 ± 31.0 to 122.8 ± 42.5 mEq after furosemide with hydrlazine (p<0.01). Urine volume rose from 854 ± 278 to 1,279 ± 359 ml (p<0.001), urinary furosemide excretion rose from 23.64 ± 2.03 to 26.94 ± 2.30 mg (p<0.01), and furosemide renal clearance rose from 46.3 ± 12.2 to 62.5 ± 18.6 ml/min (p<0.01).Clinical Pharmacology and Therapeutics(1981)30,177–182; doi:10.

ISSN:0009-9236    

DOI:10.1038/clpt.1981.145

年代:1981

数据来源: WILEY

摘要:

Plasma concentrations and urinary excretion of meperidine and its metabolite normeperidine were determined after intravenous and oral administration to 11 men; five men had hepatic cirrohosis and six were normal. Systemic clearance of meperidine was smaller and bioavailability and half‐life greater in the cirrhotic patients than in the normal subjects. Plasma concentrations and 24‐hr urinary excretion of normeperidine was lower and persistence of normeperidine in plasma longer in the patients with cirrhosis. The route of administration did not alter the fraction of normeperidine generated from meperidine. The results suggest that in patients requiring repeated meperidine dosage the drug should be taken parenterally rather than orally to allow maximal analgesia and minimal formation of normeperidine. Patients with cirrhosis may be relatively protected from normeperidine toxicity because of impaired formation, but the risk of cumulative toxicity may be greater than in normal subjects because of slower elimination of the metabolite and greater sensitivity to the effects of narcotics on the central nervous system.Clinical Pharmacology and Therapeutics(1981)30,183–188; doi:10.1038/clpt.19

ISSN:0009-9236    

DOI:10.1038/clpt.1981.146

年代:1981

数据来源: WILEY

摘要:

Eight healthy subjects [who were phenotyped with a debrisoquine (D) hydroxylation test] were selected to cover a wide range in the ratio between D and 4‐hydroxydebrisoquine (4‐OH‐D) in the urine. After a single oral dose of nortriptyline (NT) the metabolic clearance by 10‐hydroxylation in the E‐position, but not in the Z‐position, correlated closely to the metabolic ratio D/4‐0H‐D (rs= ‐0.88, p<0.01). This indicates that common enzymatic mechanisms are involved in the hydroxylation of D and the E‐ but not the Z‐10‐hydroxylation of NT. Slow hydroxylators of NT and D excreted less 10‐hydroxynortriptyline in urine and had lower plasma clearance of NT than the rapid hydroxylators. The strong correlation (r = 0.96) between the total plasma clearance of NT and the metabolic clearance by E‐10‐hydroxylation shows that this metabolic reaction is important in the disposition of the drug.Clinical Pharmacology and Therapeutics(1981)30,189

ISSN:0009-9236    

DOI:10.1038/clpt.1981.147

年代:1981

数据来源: WILEY

摘要:

Quazepam, an investigational benzodiazepine, was evaluated in doses of 7.5, 15, and 30 mg in a 12‐night protocol including four nights of drug trial. All three doses were effective in inducing and maintaining sleep, with the highest degree of effectiveness after the first drug night. Carry‐over effectiveness, which was seen after withdrawal of all three doses, persisted throughout the withdrawal period after the 30‐mg dose. Quazepam's effects during both drug use and withdrawal appeared to be dose related; 15 mg induced a greater reduction in wake time after sleep onset than the 7.5‐mg dose, and 30 mg induced even greater differences in both wake time after sleep onset and total wake time. Subjective reports of improved sleep were in general agreement with the objective data at each dose level. Side effects appeared to be dose related in terms of severity. The efficacy and comparatively less severe side effects of the 7.5‐and 15‐mg doses of quazepam suggest that these doses may be optimal when the drug is considered for the adjunctive treatment of insomnia.Clinical Pharmacology and Therapeutics(1981)30,194–200; doi:10.1038

ISSN:0009-9236    

DOI:10.1038/clpt.1981.148

年代:1981

数据来源: WILEY

摘要:

Plasma nicotine and cotinine levels were measured in habitual users of smokeless tobacco. The subjects were 12 male college students who regularly used smokeless tobacco (11 dipped snuff and one chewed tobacco) and did not smoke cigarettes. Subjects abstained from tobacco use overnight and blood was drawn at 8 A.M. and again after a single day of ad libitum consumption of their own tobacco product. Subjects recorded the times at which tobacco was used and the remainder product was weighed. Plasma samples were analyzed by both gas‐liquid chromatography (GLC) and radioimmunoassay (RIA) techniques. Subjects consumed about one third of a can of moist ground snuff (10.8 gm) in eight dips spaced throughout the day. Nicotine absorption was observed and an increase in mean plasma concentration from 2.9 ng/ml after overnight abstinence to 21.6 ng/ml after 6 to 8 hr ad libitum consumption was recorded. Plasma cotinine concentrations rose from a morning mean of 137.3 ng/ml to an afternoon mean of 197.2 ng/ml, concentrations that are typical of those reached in regular cigarette smokers. Subjects fell into two subgroups by post hoc analysis: two‐thirds absorbed substantial amounts of nicotine and one‐third appeared to have almost no absorption. Subjective effects of tobacco use were not marked; there was little perception of physiologic changes, stimulation, or feelings of relaxation/satisfaction. Results are discussed in terms of pharmacologie effects, comparison of results from GLC and RIA methodologies, and implications for health behaviors.Clinical Pharmacology and Therapeutics(1981)30,201–209; doi:10.1038/clpt.

ISSN:0009-9236    

DOI:10.1038/clpt.1981.149

年代:1981

数据来源: WILEY