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Biomedical subjects

D G McDevitt

Publications and source records attributed to D G McDevitt.

At least 55 records · Page 3Linked to original sources
PubMed1992

General practitioners' use of non-steroidal anti-inflammatory drugs in Tayside and Fife regions.

The objectives of this study were to assess the prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) by general practitioners and to determine their attitudes to problems caused by this class of drugs. The study consisted of two parts. The first was a questionnaire survey among general practitioners in Fife and Tayside, and the second was an analysis of NSAID prescribing over 12 months among the doctors in the Carnoustie Health Centre, using duplicate prescriptions. In the questionnaire survey 61% of the general practitioners responded. The three most preferred drugs were buprofen (56%), naproxen (20%) and mefenamic acid (7%); choice of drug was determined by efficacy and personal experience. Gastrointestinal side effects were most frequently encountered, although there was little consensus amongst respondents as to their management. The duplicate prescription study showed that 14% of patients (1607 individuals) received at least one NSAID prescription in the year of study. Ibuprofen (31%), naproxen (20%) and piroxicam (15%) were most frequently prescribed and up to 16% of the patients were co-prescribed a gastroprotective agent; ranitidine (75%) was the most commonly prescribed. Despite the introduction of newer NSAIDs, ibuprofen and naproxen are still the most commonly prescribed drugs. Furthermore, although gastrointestinal side effects are commonly encountered, there is some uncertainty about their management.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

The effects of enalapril and spironolactone on terbutaline-induced hypokalemia.

OBJECTIVE: To investigate whether enalapril (E) 10 mg and spironolactone (S) 100 mg attenuate the hypokalemic effect of inhaled terbutaline (T). DESIGN: Randomized single-blind crossover. Subjects received the following treatment combinations: (a) placebo (P), (b) T alone, (c) T + E, or (d) T + S. SETTING: University Department of Clinical Pharmacology. PARTICIPANTS: Twenty healthy volunteers (ten male, ten female) of mean age 22.8 +/- 3.1 years. MAIN OUTCOME MEASURES: Serum potassium, magnesium, ECG changes (R-R interval, T wave, and QTc interval) for 4 h after terbutaline inhalation. MAIN RESULTS: Baseline serum potassium levels were higher following prior treatment with E and S; P, 3.78 mmol/L (3.67 to 3.88); T + E, 3.93 mmol-1 (3.82 to 4.03); and T + S, 4.03 mmol/L (3.93 to 4.14) (p less than 0.05). Mean potassium concentrations over 4 h were also higher following prior treatment with E and S; T, 3.58 mmol/L (3.54 to 3.63); T + E, 3.68 mmol/L (3.64 to 3.72) (p less than 0.05); and T + S, 3.73 mmol/L (3.68 to 3.78) (p less than 0.01). CONCLUSIONS: Enalapril and spironolactone protect against the fall in serum potassium over 4 h by elevating baseline potassium concentration. These potassium-sparing drugs, however, should not be used to prevent the hypokalemic and electrocardiographic sequelae of inhaled beta 2-agonists.

Adult↗
PubMed1991

A dose-ranging study to evaluate the beta 1-adrenoceptor selectivity of bisoprolol.

A dose-ranging study was performed to compare the beta 1-adrenoceptor selectivity of bisoprolol with that of atenolol and nadolol. Seven normal subjects (mean age 26 y) were given single oral doses of bisoprolol 5 mg (B5), 10 mg (B10), 20 mg (B20); atenolol 50 mg (A50), 100 mg (A100); nadolol 40 mg (N40); and placebo (PL), in a single blind randomised cross-over design. Beta 2-adrenoceptor responses were assessed by attenuation of finger tremor and cardiovascular responses to graded isoprenaline infusions. Dose-response curves were constructed, and doses of isoprenaline required to increase finger tremor by 100% (IT100), heart rate by 25 beats/min (IH25), SBP by 25 mmHg (IS25), cardiac output by 35% (IC35), and decrease DBP by 10 mmHg (ID10), after each treatment were calculated. These indices were compared with placebo response and expressed as dose-ratios. Exercise heart rate (EHR) was used to assess beta 1-adrenoceptor blockade. There were dose-related increases in plasma concentrations of bisoprolol and atenolol. Reduction of EHR was significantly less with B5 (16.8%) in comparison with all other treatments: B10 21.9%, B20 23.1%; A50 22.5%, A100 22.6%; N40 22.9%. There were small but significant reductions in isoprenaline-induced tachycardia with bisoprolol and atenolol, although mean dose-ratios were considerably less in comparison with N40 (IH25 dose-ratios): B5 2.55, B10 3.18, B20 3.93, A50 2.91, A100 4.89, N40 17.23. There were similar patterns for the other isoprenaline responses. These results show that conventional doses of bisoprolol (10 mg) and atenolol (50 mg) produced equal antagonism of beta 1 and beta 2-adrenoceptors, and therefore possess equal degrees of beta 1-adrenoceptor selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Comparison of hypokalaemic, electrocardiographic and haemodynamic responses to inhaled isoprenaline and salbutamol in young and elderly subjects.

The purpose of the study was to compare beta-adrenoceptor responsiveness to salbutamol (beta-2 selective agonist) and isoprenaline (non-selective) in young (n = 10, age 23 y) and elderly (n = 7, age 71 y) subjects. Subjects were given cumulative doubling doses of inhaled isoprenaline or salbutamol (500-4000 micrograms), and placebo, in a single-blind randomised cross-over design. Plasma potassium, electrocardiographic (R-R, T-wave, Q-Tc) and blood pressure responses were measured at baseline and at each dose step. There were no difference between baseline values for each of the three study days within each group of subjects. Hypokalaemia was significantly greater in response to salbutamol compared with isoprenaline in both the young (as change from baseline): -0.61 versus -0.10 mmol.l-1: and in the elderly: -0.68 versus -0.20 mmol.l-1. There were no differences between young and elderly responses. T-wave amplitude fell significantly in response to isoprenaline and salbutamol, although this effect was progressively attenuated with increasing doses of isoprenaline. Maximum T-wave response (change from baseline) was greater with salbutamol than isoprenaline in the young: -0.22 versus -0.11 mV: and in the elderly: -0.17 versus -0.08 mV, and there were no differences between the two groups. There were no differences between the effects of isoprenaline and salbutamol on Q-Tc prolongation or heart rate. Chronotropic responses to salbutamol were greater in the elderly: 39 versus 24 beats.min-1. There were larger increases in SBP with isoprenaline in both groups. Falls in DBP in response to isoprenaline and salbutamol were significantly greater in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

The effects of chronic dosing on the beta 1 and beta 2-adrenoceptor antagonism of betaxolol and atenolol.

Six normal subjects were given once daily treatment for 15 days with placebo (PL), betaxolol 10 mg (B10), 40 mg (B40); atenolol 100 mg (A 100); and nadolol 40 mg (N40). Measurements of beta 1-adrenoceptorblockade (reduction of exercise heart rate) and of beta 2-adrenoceptor-blockade (attenuation of isoprenaline induced finger tremor) were made after the first, eighth and fifteenth doses of each drug. Plasma concentrations showed dose related increases between 10 mg and 40 mg doses of betaxolol, and there was significant drug accumulation at steady state compared with after single dosing. The reduction in exercise heart rate (EHR) with B10 was less in comparison with all other treatments. There were no significant differences in effects between single and chronic-dosing for any of the treatments (% reduction EHR compared with placebo, on days 1 and 15): B10 (18.2, 19.0), B40 (28.6, 26.5); A100 (22.7, 23.1); N40 (26.6, 23.8). Dose-ratios for attenuation of isoprenaline-induced finger tremor (IT100) were significantly greater with B40 compared with B10 or A100 (no dose-ratio for finger tremor could be calculated for N40). There were no differences between single and chronic-dosing (IT100 dose-ratios on days 1 and 15): B10 (3.0, 2.5), B40 (4.4, 5.3); A100 (3.0, 3.0). The attenuation of isoprenaline-induced chronotropic response (IH25) by N40 was significantly greater in comparison with all other treatments. IH25 dose-ratios (on days 1 and 15) were as follows: B10 (2.8, 3.6), B40 (5.1, 5.8); A100 (3.6, 3.6); N40 (19.0, 17.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effects of xamoterol in acute myocardial infarction: blood pressure, heart rate, arrhythmias and early clinical course.

Xamoterol is a novel partial agonist of beta 1 adrenoceptors that reduces myocardial ischaemia and improves ventricular function in patients with mild to moderate heart failure. In a double blind, randomised, placebo controlled study, the effects of xamoterol given in a dose of 200 mg twice daily were studied in 51 consecutive patients with acute myocardial infarction, including 17 receiving diuretics for left ventricular failure. Treatment was started on the third day of admission and continued for 7 days. Blood pressure was recorded at 0900 daily, and 24 hour ambulatory electrocardiogram monitoring was commenced at this time on days 1 (pre-treatment), 4, 6 and 9 of admission. Additional drug therapy was recorded daily throughout the study. One patient died prior to randomisation and three were withdrawn (1 placebo, 2 xamoterol) with ventricular arrhythmias and/or disturbances of conduction. Compared to placebo, xamoterol had no effect on the rate of ventricular premature beats or ventricular tachycardia. Xamoterol increased nocturnal heart rate (0000-0600 hrs 79 +/- 2; placebo 72 +/- beats/min; P less than 0.03) but did not change blood pressure. Three patients receiving xamoterol, and 7 on placebo, required new (after randomisation) antianginal therapy. One patient treated with placebo developed new heart failure. These results show that xamoterol can be administered safely to selected patients following myocardial infarction, including those treated for mild heart failure.

Adrenergic beta-Agonists↗
PubMed1991

Central effects of the calcium antagonist, nifedipine.

1. Central effects of the calcium antagonist, nifedipine retard (10, 20 and 40 mg) and nifedipine capsules (10 mg) were studied in 14 healthy male subjects. Two placebos and an active control drug, oxazepam (15 mg), were included. Medication was administered double-blind at 10.00 h. The effects of drugs on performance and subjective feelings were assessed before and from 1.5-2.5 h and 3.5-4.5 h after ingestion, and recordings of the electrical activity of the brain (EEG) and body sway carried out. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. The EEG was recorded with eyes open while the subjects carried out a mental arithmetic task, and with eyes closed, when they were required to relax. Body sway was recorded with eyes open and with eyes closed. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. 3. Nifedipine did not alter performance levels on any of the skills tested, while oxazepam (15 mg) increased the number of errors (P less than 0.01) and reduced accuracy at continuous attention (P less than 0.01). 4. Nifedipine (10 mg) reduced total power of the EEG in the frequency range (0.5-30 Hz), and nifedipine (20 mg) increased total alpha power (7.5-13 Hz) (P less than 0.05). Oxazepam reduced alpha and increased beta 1 power (13.5-21 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The effects of frusemide and triamterene on the hypokalaemic and electrocardiographic responses to inhaled terbutaline.

Fifteen normal volunteers were given 5000 micrograms inhaled terbutaline following three separate 4 day oral treatment periods with placebo, frusemide 40 mg, and frusemide 40 mg plus triamterene 50 mg. Serum potassium (K), and electrocardiographic (ECG) responses were measured after 30 min rest and 30 min after inhalation of terbutaline. Frusemide produced significant hypokalaemia compared with placebo (means and 95% CI): 3.58 mmol l-1 (3.5-3.66) vs 3.88 mmol l-1 (3.8-3.96) (P less than 0.001), and this effect was significantly attenuated by the addition of triamterene: 3.80 mmol l-1 (3.72-3.88) (P less than 0.05). Terbutaline alone also caused significant hypokalaemia: from 3.88 mmol l-1 (3.8-3.96) to 3.35 mmol l-1 (3.24-3.46) (P less than 0.001), and a lower absolute level of K was seen when combined with frusemide: 3.13 mmol l-1 (3.02-3.24) (P less than 0.05). The addition of triamterene conferred no significant protection against the combined hypokalaemia: 3.29 mmol l-1 (3.18-3.4). Changes in T wave amplitude during the study periods showed a similar pattern of response to the hypokalaemic effects. These results show that the hypokalaemic response to terbutaline was additive to that of frusemide, and that triamterene attenuated the hypokalaemic response to frusemide, but not terbutaline.

Administration, Inhalation↗
PubMed1991

The effects of time and dose on the relative beta 1- and beta 2-adrenoceptor antagonism of betaxolol and atenolol.

1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 40 mg (B40), 80 mg (B80); atenolol 50 mg (A50), 200 mg (A200); or placebo (PL). Measurements of beta 1-adrenoceptor blockade (reduction of exercise heart rate) and of beta 2-adrenoceptor blockade (attenuation of isoprenaline responses) were made at baseline, and at 2, 4, 6, 8 and 24 h after drug ingestion. 2. Mean values for Cmax and tmax were as follows: B10 (33 ng ml-1, 3.7 h), B40 (84 ng ml-1, 4.0 h), B80 (179 ng ml-1, 3.7 h); A50 (261 ng ml-1, 2.7 h), A200 (1369 ng ml-1, 2.0 h). 3. Reduction of exercise heart rate (EHR) occurred in dose-dependent fashion up to a ceiling at B40 (as % reduction c.f. placebo, at peak and 24 h): B10 16.2 to 10.2%, B40 27.1 to 16.2%, B80 27.0 to 18.7%; A50 20.9 to 9.1%, A200 28.8 to 15.8%. There were also dose-related increases in beta 2-adrenoceptor antagonism (IT100 dose ratios, at peak and 24 h): B10 2.1 to 1.2, B40 4.7 to 2.6, B80 6.0 to 4.7; A50 2.0 to 1.2, A200 4.7 to 1.8. There were similar trends for attenuation of heart rate and DBP responses to isoprenaline. 4. Ratios of beta 1:beta 2-adrenoceptor antagonism were calculated (as % reduction EHR divided by IT100 dose ratio); to provide an index of beta 1-adrenoceptor selectivity at peak and 24 h: B10 7.7 to 8.5, B40 5.8 to 6.2, B80 4.5 to 4.0; A50 10.5 to 7.6, A200 6.1 to 8.8.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Magnesium deficiency may be an important determinant of ventricular ectopy in digitalised patients with chronic atrial fibrillation.

Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.

Aged↗
PubMed1991

Measurement of normal human airways response to beta-adrenoceptor stimulation using a forced oscillation technique.

The purpose of the present study was to evaluate the responsiveness of normal human airways to beta-adrenoceptor stimulation using a forced oscillation technique. Seven normal volunteers (aged 25 +/- 2 year) were studied on three occasions, separated by weekly intervals, using a single-blind randomized design. On day 1, subjects were given cumulative doses of inhaled salbutamol (100, 200, 500, 1000 micrograms); and identical placebo was given on the other two visits. Respiratory oscillation impedance (Ros) was measured at baseline and 15 min after each dose increment. The coefficients of variation (CV) for short-term intra-individual variability on each placebo day were 7.5 and 9.5, and 9.6% for long-term variability (measured over all three visits). The 95% confidence values (2SD) for the change in Ros required to exclude natural variability were 0.39, 0.50 and 0.53 cmH2O l-1 s, respectively. There was a small fall in Ros in response to salbutamol although the mean maximum change (0.46 cmH2O l-1 s) was not significant (by ANOVA). Thus, the change in Ros (sensitivity) was no greater than the 95% confidence value for natural variability (reproducibility). Regression analysis also showed no evidence of a dose-response relationship for Ros.

Adrenergic beta-Agonists↗
PubMed1991

A double-blind placebo-controlled trial of theophylline in general practice.

Patients with moderate to severe asthma, from two urban general practices, entered a double-blind randomised placebo-controlled crossover trial of sustained-release theophylline versus placebo. Theophylline was given in therapeutic dosage (to ensure serum levels of between 10 and 20 micrograms/ml) for two months, followed by two months of placebo or vice versa. The results from the 24 patients who entered both theophylline and placebo treatment arms were compared, using outcome measures relevant to general practice care. Theophylline is shown to be of value in the management of asthma in general practice.

Adult↗
PubMed1991

Clinical audit of theophylline use in general practice.

The use of therapeutic drug monitoring for theophylline therapy was evaluated in two urban general practices. Of 55 patients studied, 44 (80%) had a sub-therapeutic serum theophylline concentration, 11 (20%) had a therapeutic concentration (10-20 micrograms/ml), and none had an above therapeutic concentration. Patients were reviewed at weekly intervals and had their theophylline dosages adjusted according to serum levels. A therapeutic concentration was achieved in 37 patients (67%). This task proved to be 'laborious but not difficult'. Side-effects were less common than previous reports suggest. The general practice workload involved in adjusting theophylline dosage was approximately four consultations, one dose change and two serum assays per 'average' patient.

Adolescent↗
PubMed1990

Oral magnesium reduces ventricular ectopy in digitalised patients with chronic atrial fibrillation.

We have examined the effects of magnesium replacement therapy upon post-exercise heart rate and incidence of ventricular premature beats (VPB) in digitalised patients with AF. In 11 such patients, all of whom had serum magnesium concentrations of less than 0.85 mmol/l, treatment with magnesium glycerophosphate was associated with a significant reduction in number of VPBs (982 v. 416 VPB/24 h). Five patients had a high prevalence of ventricular ectopy (greater than 300 VPB/24 h) and these subjects showed particularly marked decreases in VPBs during magnesium treatment (1998 v. 690 VPB/24 h). Three patients had slightly increased QTc intervals but these did not change during magnesium replacement. No significant changes were seen in the mean post-exercise heart rate although 2 subjects did show falls of 25% or more during magnesium replacement. We conclude that treatment with magnesium glycerophosphate may be associated with a decreased prevalence of ventricular ectopy in some digitalised patients with chronic AF and mild-moderate hypomagnesaemia.

Aged↗
PubMed1990

Subsensitivity of beta-adrenoceptor responses in asthmatic patients taking regular low dose inhaled salbutamol.

Tremor (Tr), chronotropic (HR) and metabolic (K, Glu) responses to cumulative doses of inhaled salbutamol (100 micrograms to 4000 micrograms) were compared in an age and sex matched group of 7 normal (N) and asthmatic (A) subjects. Comparison of regression lines between groups showed differences in HR and K. This was also reflected in attenuation of maximum responses in group A, for HR and K. These results show subsensitivity of chronotropic and hypokalaemic responses in patients with asthma, which may reflect tachyphylaxis from the effects of long term inhaled salbutamol therapy.

Administration, Inhalation↗
PubMed1990

Comparison of the efficacy and systemic effects of 4 mg and 8 mg formulations of salbutamol controlled release in patients with asthma.

The purpose of the present study was to compare the efficacy and systemic effects of 4 mg and 8 mg doses of salbutamol controlled release (SCR) after single dosing and at steady state in patients with asthma. Fifteen asthmatic patients (Age 36 y, FEV1 85% predicted) were given SCR 4 mg and 8 mg twice daily for 7 days in a randomised double-blind cross-over design, with at least 7 days washout between treatments. There were no differences between the bronchodilator effects of 4 mg and 8 mg doses. There was no evidence of tolerance to the bronchodilator effects after chronic dosing. Morning and evening PEFR measurements also showed improvements during treatment with SCR 4 mg and SCR 8 mg, although there were no differences between the two formulations. Both doses of SCR caused significant objective tremor responses which were maintained after chronic dosing. The 8 mg dose produced a larger tremor response after single dosing, but not at steady-state. Subjective tremor occurred in 7 patients with SCR 8 mg, and in 2 patients with SCR 4 mg. There were no cardiac arrhythmias on Holter ECG monitoring. These results suggest that the 8 mg dose of SCR was no more effective than the 4 mg formulation, and was associated with more systemic adverse effects.

Adult↗
PubMed1990

Neuroendocrine changes post myocardial infarction: effects of xamoterol.

This study reports the effects of the new beta 1 adrenoceptor partial agonist, xamoterol, on neuroendocrine activity after acute myocardial infarction (AMI). Fifty-one consecutive patients with AMI were randomized to treatment with xamoterol, 200 mg twice a day, or placebo; patients were also stratified as to whether or not diuretic therapy was given for left ventricular dysfunction. Noradrenaline, plasma renin activity (PRA), and atrial natriuretic factor (ANF) were measured over a 10-day period. Noradrenaline concentrations are higher (p less than 0.05) in patients treated with diuretics at the time of admission and fell over the subsequent 10 days (p less than 0.01). Treatment with xamoterol did not affect this noradrenaline response to myocardial infarction. PRA was also significantly higher in the patients treated with diuretics, and there was a nonsignificant trend for xamoterol to blunt the PRA response in these patients. There was no difference in ANF levels between those patients who were treated with diuretics and those who were not; xamoterol did not affect ANF. Thus xamoterol does not further elevate noradrenaline levels as do conventional beta blockers, and it does not activate the renin-angiotensin system as do potent nonselective beta agonists. Furthermore, xamoterol does not increase ANF levels, probably because it is not negatively inotropic. We conclude that xamoterol does not cause deleterious neuroendocrine changes in patients with AMI even in those treated for heart failure.

Adrenergic beta-Agonists↗