PubMed Health⌕ Search

Biomedical subjects

D G McDevitt

Publications and source records attributed to D G McDevitt.

At least 145 records · Page 8Linked to original sources
PubMed1983

Investigation of diurnal changes in the disposition of theophylline.

The mechanism of observed temporal variations in plasma theophylline concentrations has been investigated. Eight healthy volunteers were given both oral and intravenous doses of theophylline (5 mg/kg) at 09.00 h and 21.00 h under controlled conditions. Regular plasma concentration measurements were made following each dose in order to determine the diurnal and nocturnal disposition of the drug. Plasma theophylline concentrations at 0.5 h following each oral dose were 6.9 +/- 0.8 micrograms/ml, a.m., and 3.9 +/- 0.6 microgram/ml, p.m. (P less than 0.05). Time to peak concentration was 1.69 +/- 0.28 h, a.m.; 2.13 +/- 0.23 h, p.m. (P less than 0.05). Values for ka were not significantly different, however. Overall bioavailability, volume of distribution and systemic clearances, calculated for the 12 h period after each dose, did not differ significantly between day and night. Diurnal variations in theophylline disposition do not appear to be the result of changes in metabolism or excretion, but may reflect minor differences in absorption.

Administration, Oral↗
PubMed1983

Prediction of maintenance oral theophylline dosage using single oral doses in patients with obstructive airways disease.

This study was designed to test whether single oral doses of theophylline, rather than the specified single intravenous infusions, could be used with a nomogram designed to predict the maintenance oral dose necessary to establish plasma theophylline concentrations of 10 micrograms ml (Koup et al., 1979) in patients with obstructive airways disease. A test dose of theophylline (5 mg kg) was administered on two separate occasions as an oral elixir and as an intravenous infusion. Exactly 6 h after each test dose, plasma theophylline concentration was measured, and the result used to predict daily maintenance dose requirements. During subsequent oral administration, a sustained-release preparation was given in equally divided 12-hourly doses, and 'steady-state' concentrations were measured at trough. Nineteen patients completed the study, and on doses ranging from 4.2 to 21.1 mg kg-1 day-1, trough concentrations of 5.4 to 15.8 micrograms ml (mean 10.0 +/- 0.7 micrograms ml) were achieved. No significant differences were noted between the dose predictions made following either the oral or the intravenous test doses, and the predictive accuracy using the oral route was not compromised. This would suggest that the test dose of theophylline may be administered orally, instead of intravenously, with this nomogram without reducing its efficiency.

Administration, Oral↗
PubMed1983

An assessment of physiological finger tremor as an indicator of beta-adrenoceptor function.

Physiological finger tremor has been assessed as an indicator of beta-adrenoceptor function. Tremor was not correlated with the sex, age, weight or height of the subjects and was stable over 5 min when the hand and fingers were held horizontally. It was not increased by mental arithmetic, the Valsalva manoeuvre or 3 min exercise. Satisfactory dose-response curves could be constructed for the isoprenaline enhanced increases in finger tremor. In six subjects, practolol 120 mg produced a small shift to the right of the isoprenaline dose-response curve for finger tremor (dose ratio 2.1) but propranolol 40 mg was seven times more effective (dose ratio 17.1). Physiological finger tremor appears to be a stable parameter which may be useful in the investigation of the selectivity of beta-adrenoceptor blocking drugs.

Adult↗
PubMed1983

Heart rate and blood pressure responses to intravenous boluses of isoprenaline in the presence of propranolol, practolol and atropine.

Six healthy subjects were studied on two occasions. Graded bolus injections of isoprenaline sulphate were given intravenously and control dose-response curves were drawn for the changes in heart rate and blood pressure. In a random order each subject received an intravenous infusion of either propranolol or practolol and further dose-response curves were constructed PRE- and POST-atropine (0.04 mg/kg). Exercise tachycardia was reduced 26.1 +/- 2.7% by propranolol and this was not significantly different from the reduction by practolol (21.2 +/- 1.9%). Propranolol attenuated the isoprenaline tachycardia (dose ratio 43.7) and after atropinisation the dose ratio was not significantly altered (41.1). Practolol also attenuated the isoprenaline tachycardia (dose ratio 4.4) but after atropinisation the dose ratio was significantly increased to 8.8, though this remained significantly less than the dose ratio for propranolol. At a heart rate increase of 25 beats/min, the isoprenaline-induced control fall in mean blood pressure was 9-11 mm Hg. After propranolol administration this fall was converted to a small increase of + 2.3 +/- 1.3 mm Hg. Following practolol, however, the mean blood pressure reduction was 19.7 +/- 2.9 mm Hg. Practolol did not significantly block the isoprenaline-induced fall in diastolic pressure. The difference in potency of propranolol and practolol, demonstrated by their effect on isoprenaline induced tachycardia at doses shown to have equal effects on exercise tachycardia, is contributed to but not fully explained by the reflex withdrawal of cardiac vagal tone which occurs with cardioselective but not non-selective antagonists.

Adrenergic beta-Antagonists↗
PubMed1983

Diuretic withdrawal--a need for caution.

Diuretic therapy was withdrawn from 42 patients receiving modest drug doses for reasons other than hypertension, active heart failure and renal or hepatic oedema, with frequent assessment by clinical, biochemical and radiological methods for 12 weeks. Of 38 patients who could have completed the study, 27 (71%) did so without ill-effect. Eleven (29%) patients deteriorated clinically or radiologically, 7 within 2 weeks of discontinuing diuretics, and 1 of them died after acute pulmonary oedema and a haematemesis, despite intensive resuscitation. The outcome of drug withdrawal could be predicted in 35 of the patients using a multifactorial discriminant analysis but individual parameters had poor predictive value. The lack of demonstrable benefit in many patients and the incidence of adverse effects associated with long-term diuretic therapy suggest that withdrawal should be considered more often in this type of patient. However, there is a need for caution in this situation and withdrawal should only be attempted if close medical supervision and radiological examination of the chest are possible.

Adult↗
PubMed1982

Induction of microsomal enzyme activity by flupenthixol in chronic schizophrenics.

The effect of long-term treatment with flupenthixol on hepatic microsomal enzyme activity was studied in 12 chronic schizophrenic outpatients who had been receiving two weekly maintenance doses for at least 6 months. Antipyrine half-life was measured in the 12 patients while they continued to receive the drug. Flupenthixol was then discontinued for 6 weeks and antipyrine half-life was repeated in 7 of the 12 patients. In the 12 patients the plasma antipyrine elimination half-life was 4-24 h (mean 9.73 +/- 1.61 h) when receiving flupenthixol and there was a significant negative correlation between antipyrine half-life and the dose of flupenthixol (r = 0.582, P less than 0.05). In the seven patients to whom antipyrine was given on two occasions, antipyrine half-life was 7.33 +/- 1.07 h and 12.04 +/- 1.87 h on and off flupenthixol treatment respectively. The clearance significantly decreased when flupenthixol was discontinued, but there was no change in the apparent volume of distribution.

Adult↗
PubMed1981

Does the frequency of daily dosage influence compliance with digoxin therapy?

1 The influence of daily dosage frequency on drug compliance has been studied in 80 outpatients for whom maintenance digoxin 0.25 mg daily had been prescribed. 2 Each patient took one tablet (0.25 mg) daily, two tablets (0.125 mg) daily and four tablets (0.0625 mg) daily in randomised order for 2 month periods. 3 Compliance was assessed by tablet counting and by serial measurement of the plasma digoxin concentration. 4 Of the 67 patients (100%) who could have completed the study, 19 (28.4%) were withdrawal for a variety of reasons; in the majority these were consistent with gross non-compliance. 5 The remaining 48 patients (71.6%) took significantly more tablets when prescribed once daily (98.5 +/- 1.0% of the total) or twice daily (96.4 +/- 1.6%) than when given four times daily (92.2 +/- 1.9%). However, there were no significant differences between the plasma digoxin levels obtained at the three dosage frequencies. 6 We conclude that the small improvement in compliance with once or twice daily dosage was clinically unimportant. Dosage frequency did not appear to have a major influence on the grossly non-compliant patients.

Digoxin↗
PubMed1980

Effects of thyroid dysfunction on propranolol kinetics.

Propranolol kinetics was studied in six hyperthyroid and six hypothyroid patients who received single oral and intravenous doses of propranolol when they had thyroid dysfunction and again when they had become euthyroid. Change in thyroid status from hyperthyroid to euthyroid produced no change in the elimination half-life (t 1/2) of oral propranolol (3.2 +/- 0.5 to 4.1 +/- 0.7 hr), the oral clearance (38.4 +/- 7.3 to 27.4 +/- 2.4 ml/min/kg), the elimination t 1/2 of intravenous propranolol (2.5 +/- 0.3 to 3.5 +/- 0.7 hr), and the apparent volume of distribution (4.8 +/- 0.4 to 3.8 +/- 0.5 l/kg). The systemic clearance of propranolol, however, was greater when the patients were hyperthyroid (20.8 +/- 2.5 ml/min/kg) than when they had become euthyroid (11.7 +/- 1.7 ml/min/kg). The elimination t 1/2 after oral propranolol was longer in the hypothyroid (3.7 +/- 0.5 hr) than in the euthyroid state (2.0 +/- 0.1 hr). No other changes were observed in the kinetic parameters measured when these hypothyroid patients had become euthyroid. Adequate beta-adrenoceptor blockade in hyperthyroid patients may require higher propranolol dosage than expected.

Adult↗
PubMed1980

Sotalol as a hypotensive agent in pregnancy.

Sotalol, a beta-adrenoceptor blocking drug, was administered to 12 hypertensive pregnant women. The concentration of the drug was assayed in samples of maternal plasma, amniotic fluid and mixed umbilical cord plasma at delivery and, in five mothers who elected to breast feed, in paired samples of maternal plasma and breast milk. Sotalol reduced blood pressure effectively at a mean daily dose of 433.1 +/- 54.1 mg but crossed the placental barrier. The mean maternal: fetal plasma concentration ratio was 1:1.05 and the mean amniotic fluid concentration was 7.0 +/- 2.7 microgram/ml. Delivery occurred at mean gestational age of 37.7 +/- 0.7 weeks; 12 infants were liveborn with a mean weight of 2.8 +/- 0.1 kg and eight of them had no significant neonatal problems. Of the other four, two died from severe congenital anomalies, one had perinatal asphyxia and one mild transient hypoglycaemia. High sotalol concentrations were found in breast milk (mean plasma: milk ratio was 1:5.4) raising the possibility of pharmacological effect in the newborn infant. The results suggest that sotalol adequately controls blood pressure in hypertension complicating pregnancy but because, unlike results from the pregnant ewe, it crosses the human placental barrier it offers no apparent advantages over other beta-adrenoceptor antagonists.

Adolescent↗