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Biomedical subjects

G J Addis

Publications and source records attributed to G J Addis.

28 records · Page 2Linked to original sources

The influence of theophylline on maximal response to salbutamol in severe chronic obstructive pulmonary disease.

We have previously shown that inhaled salbutamol further increases the bronchodilator response after the maximum effect of theophylline has been obtained in patients with severe chronic bronchitis. We now report the results of adding maximally effective doses of theophylline to the maximum response obtainable from salbutamol in ten of these patients. We constructed dose response curves to ensure maximum possible effect from salbutamol. Response plateaus (in nine out of ten patients) were achieved with cumulative doses of between 200 micrograms and 3,000 micrograms salbutamol and there was a significant response (p less than 0.05) in every subject: the mean FVC response was 1.11 (ranging from 0.5 to 1.81) and the mean FEV1 response was 0.41 (ranging from 0.1 to 0.81). Theophylline, in their previously determined maximally effective doses, produced statistically significant (p less than 0.05) small further increases in both FVC (0.2 to 0.61) and FEV (0.1 to 0.61) in four patients only. The other six did not respond. In patients classified as chronic bronchitics there is clearly a wide variation in response to bronchodilators and a surprising degree of reversibility can be achieved. But because of this variation in response, conventional drug doses may be too small in some cases. Ideally, each bronchodilator should be prescribed after some form of individual dose response studies. Although this acute study shows little or no benefit in the height of the bronchodilator response the usefulness of this combination can only really be decided after similar studies including the duration of effect in long term administration.

Aged↗

Theophylline-salbutamol interaction: bronchodilator response to salbutamol at maximally effective plasma theophylline concentrations.

1 The effect of inhaled salbutamol following a maximally effective dose of theophylline given by intravenous infusion was determined in 12 patients with chronic bronchitis. 2 An initial single intravenous dose study was performed to estimate each patient's theophylline kinetics and to identify those patients who would respond to theophylline. 3 Pulmonary function was assessed at hourly intervals during four to five incremental steady state theophylline infusions over the concentration range 5-25 mg/l. 4 Inhaled salbutamol (400 micrograms) was administered after the maximum effect from theophylline had been achieved or when theophylline concentrations reached 25 mg/l without maximum effect: pulmonary function was again assessed. 5 Ten patients achieved a further significant improvement in pulmonary function after salbutamol: in five, predicted values for FVC were exceeded. 6 Patients with chronic bronchitis may benefit from the combination of theophylline and salbutamol if steady state theophylline concentrations of 15-20 mg/l are achieved.

Aged↗

Modelling theophylline response in individual patients with chronic bronchitis.

1 In six patients with chronic bronchitis, serial changes in both ventilatory function and plasma theophylline concentrations were measured simultaneously for 8 h following 500 mg aminophylline intravenously. 2 Using empirical mathematical models which can integrate this data, parameters were estimated which can express response as a linear function of steady state plasma theophylline levels. 3 Taking Forced Vital Capacity (FVC) as the target response, the mean (+/- s.d.) increase in FVC was 0.06 +/- 0.02 l/micrograms ml-1, starting with pretreatment values in the range 1-21. 4 This analytical approach could be used to determine whether or not a patient with chronic bronchitis could obtain a satisfactory response to theophylline at plasma levels normally encountered in clinical practice.

Adult↗

Assessment of a combination of doses of fenoterol and ipratropium suitable for a single metered-dose aerosol.

This paper reports a study of the bronchodilator effects of doses of the beta 2 agonist fenoterol and the muscarinic blocker ipratropium suitable for administering in combination as a standard dose of two discharges from a single metered-dose pressurised aerosol. In 12 middle-aged bronchitics who had already been shown to respond to both types of drug the combination was almost always a little (6% on average) more effective than either drug singly. It is possible that an equal or better effect could have been obtained if fenoterol or perhaps ipratropium had been given alone in an individually determined maximally effective dose.

Aerosols↗

Effects of oxprenolol on the airways of normal and bronchitic subjects.

In a double blind trial in 11 control subjects and 12 bronchitic patients against an inert control oxprenolol produced significant worsening in airways obstruction in 6 control and in 7 patients. There was marked individual variation in response and no way was found to predict the susceptible subjects. Objective measurement of indices of airways obstruction and the effects of oxprenolol on them is essential where there is significant respiratory impairment. Great care must continue to be exercised since a significant proportion of bronchitic patients will be adversely affected by this drug.

Adult↗

Treatment of hypertension with clonidine.

Clonidine, in a daily dosage of 0.15-4.8 mg., effectively lowered systolic and diastolic pressures in 26 out of 28 impatients with moderate to severe hypertension, including five with primary renal disease. The action of the drug did not depend on posture and was not associated with reduction in renal function. Side-effects were not severe, but mental changes occurred in four patients.Clonidine is a useful alternative to currently available antihypertensive drugs, but further evaluation of its longterm efficacy is required.

Aniline Compounds↗