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Biomedical subjects

D W Duhme

Publications and source records attributed to D W Duhme.

16 recordsLinked to original sources

Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program.

Of 17,068 hospitalized medical patients monitored in a drug surveillance program, 2,367 (13.9 per cent) received furosemide. Of these patients, 53 per cent were hospitalized with a primary (first) diagnosis of cardiovascular disease; many other patients had cardiovascular disorders coincident with other diseases. In 78 per cent of cases the indication for furosemide therapy was congestive heart failure. Adverse reactions were attributed to furosemide in 239 patients (10.1 per cent), but in only 14 instances were the unwanted effects considered life-threatening. The most common adverse reactions were: intravascular volume depletion (4.6 per cent of furosemide recipients), hypokalemia (3.6 per cent), and other eletrolyte disturbances (1.5 per cent). Many patients experienced more than one manifestation of toxicity. The over-all frequency of adverse reactions increased progressively with higher daily doses of furosemide, but was not correlated with total furosemide dose. Among furosemide recipients who also recieved potassium-supplements or potassium-sparing diuretics, hypokalemia was less frequent, less severe, and of slower onset. Coadministration of other diuretics with furosemide was associated with a higher frequency of volume depletion. The findings indicate that furosemide is a relatively safe diuretic in a wide range of clinical situations. Serious adverse reactions are uncommon, and occur primarily in the seriously ill.

Adult

Variability of 24-hour urinary creatinine excretion by normal subjects.

Creatinine excretion was studied in eight healthy males who collected 54 to 97 24-hour urine specimens. Significant differences among subjects in mean creatinine excretion were only partly explained by differences in body weight and surface area. Considerable daily within-subject variation in creatinine excretion during normal activity was found. Standard deviations were from 10.5 to 14.4 per cent of the mean, and ranges varied from 50 to 79 per cent of the mean. Day-to-day variation appeared to be time dependent rather than entirely random, and could not be explained by unreliability of the assay technique or by incomplete collections. Creatinine excretion values were normally distributed in seven of eight subjects. Individual variation from day to day limits the value of urinary creatinine excretion as an index of the completeness of 24-hour urine collections.

Adult

Assessment of methodology in single-dose studies of digoxin bioavailability.

Eight healthy males received 0.75 mg of digoxin by ten modes of administration in a single-dose multicrossover bioavilability study. Digoxin concentration in multiple blood samples drawn after each dose and in six consecutive 24-hour urine collections were used to calculate the areas under the 4-, 8-, and 24-hour serum concentration curve (A-4, A-8, A-24), and the excretion of digoxin during 1 day (U-1) and 6 days (U-6) following each dose. All five methods of assessment gave very similar information on bioavailability. Individual values of A-4 and A-8 were highly correlated (r=0.973) and had similar variability. A-24 was more variable than A-4 and A-8, and was not as well correlated with either. U1- and U-6 were highly correlated (r=0.944), and had nearly identical variability which was less than that of any of the area measures. Thus, urinary excreation data provides more reliable and reproducible information about completeness of absorption of digoxin than data based upon serum concentrations. Extending the period of urine collection beyond 1 day or the blood sampling period beyond 4 or 8 h does not enhance the reliability or usefulness of digoxin bioavailability studies.

Administration, Oral

Pharmacotherapy of essential hypertension.

Practical clinical aspects of the evaluation and treatment of essential hypertension are reviewed. Drug therapy discussed includes diuretics, and as adjunctive therapy, sympathoplegic agents, peripheral vasodilators and beta blockers. Also covered are treatment of less common forms of essential hypertension, other forms of antihypertensive therapy, and the use of fixed combinations of antihypertensive drugs.

Adrenergic beta-Antagonists