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J Tweney

Publications and source records attributed to J Tweney.

5 recordsLinked to original sources
PubMed1991

Oral almitrine in treatment of acute respiratory failure and cor pulmonale in patients with an exacerbation of chronic obstructive airways disease.

The effects of oral almitrine bismesylate, a respiratory stimulant that acts on peripheral arterial chemoreceptors, was studied in patients with chronic obstructive airways disease and hypoxaemic cor pulmonale. Twenty three patients admitted to hospital with an acute exacerbation of ventilatory failure were randomised to receive either almitrine 100 mg twice a day reducing to 50 mg twice a day over 48 hours or placebo in addition to conventional treatment. On admission the mean (SE) values for blood gas tensions were PaO2 4.8 (0.3) and PaCO2 7.7 (0.3) kPa in the 12 patients who received almitrine and PaO2 4.9 (0.1) and PaCO2 7.6 (0.3) kPa in the 11 who received placebo. After three hours of oxygen therapy at 1 1/min there was a similar rise in PaO2 in both groups, 6.4 (0.2) kPa in those receiving almitrine and 6.6 (0.4) kPa in those receiving placebo. After 24 hours of oxygen therapy values of PaO2 were again similar at 6.3 (0.8) kPa and 6.7 (2.2) kPa respectively. Arterial blood gas tensions improved during the study in those who survived but no significant differences were apparent between the two groups. There were six deaths, five in the almitrine group and one in the placebo group. There were no differences between the groups in respiratory rate, results of spirometry, oxygen requirement, or degree of dyspnoea (on visual analogue scale). The results did not show any benefit from oral almitrine in patients with acute respiratory failure secondary to chronic obstructive airways disease. Plasma almitrine concentrations, however, were often below the optimum therapeutic range, suggesting impaired drug absorption.

Administration, Oral↗
PubMed1990

Almitrine bismesylate and oxygen therapy in hypoxic cor pulmonale.

The effect of oral treatment with the thiazine derivative almitrine bismesylate was studied in 28 patients with chronic obstructive pulmonary disease and arterial hypoxaemia receiving long term domiciliary oxygen therapy in a placebo controlled, double blind crossover trial. The initial treatment was given for three months and the second for two months. Because almitrine had an unexpectedly prolonged washout effect crossover analysis could not be performed; data from the placebo treatment administered in the second arm of the trial were used to calculate the half life of almitrine. Nine patients were withdrawn from the study (5 almitrine, 4 placebo). Patients' tolerance of the drug was good. The estimated plasma half life of almitrine was 20.5 days, considerably longer than previously reported. Almitrine caused a significant improvement in arterial oxygen tension (PaO2) with a mean maximum increase of 0.7 kPa at a plasma concentration of 500 ng/ml. Higher plasma concentrations were not associated with any further increase in PaO2. There was no significant effect on arterial carbon dioxide tension (PaCO2). In a second, acute study at the end of each arm of the chronic trial nine patients were subjected to increasing oxygen delivery rates (2, 4, and 6 l/min) for 90 minutes or until blood gas concentrations plateaued. Almitrine increased PaO2 in a dose dependent fashion at all delivery rates, but the effect diminished as PaO2 approached normoxic levels. There was no significant effect on PaCO2. Almitrine treatment results in a significant improvement in PaO2 over that achieved by oxygen alone, an effect that diminishes at high flow rates. Whether this is of clinical benefit is not known. In view of the prolonged half life revised dosage schedules are required.

Almitrine↗
PubMed1987

Almitrine bismesylate.

There is a place in therapy for an orally active respiratory stimulant. Almitrine bismesylate is a respiratory agonist which: 1. Effectively increases PaO2 in a unique way, principally by stimulation of the peripheral chemoreceptors. 2. Appears to have an effect on blood gases through mechanisms other than stimulation of ventilation which could be on ventilation-perfusion relationships, or even metabolic, for which there is as yet no firm evidence. 3. After chronic administration has a plasma elimination half-life of 20-30 days. This could result in plasma accumulation of the drug, and means that drug intolerance problems are not readily resolved by stopping the tablets. Special dosing schedules may be required. 4. Has an action on the pulmonary vasculature which is mainly vasoconstrictor (and vasodilator in acute hypoxia in animal studies). Present evidence regarding the effect of long-term administration on pulmonary haemodynamics is conflicting. 5. May have an adverse, possibly dose-related effect on dyspnoea in some patients - more work is needed on patient characteristics associated with good drug tolerance. 6. Has an adverse effect on peripheral nerve function in some patients. Whether this is de novo, or aggravation of a preexisting lesion has yet to be established. Thus, although almitrine is effective in increasing PaO2 and as an experimental drug is fascinating, its clinical use remains to be clearly defined. The most powerful argument for the therapeutic use of almitrine would be the demonstration of a beneficial effect on mortality; either in acute exacerbations of respiratory failure, or in the same way as LTO2 exerts an effect in chronically hypoxaemic patients.

Almitrine↗