Aspects of the pharmacotherapy of airways disease

Asthma morbidity and mortality have been increasing in most industrialised countries over the last two decades despite anti-asthmatic medication sales at an all time high. Drug therapy remains the mainstay of treatment in asthma yet there have been concerns that modern drug therapy may be contributing to this increase in morbidity and mortality. The research presented in this thesis sought to examine several issues related to current asthma pharmacotherapy. In recent years, asthma management guidelines have emphasised the earlier introduction of inhaled corticosteroids and less reliance on ˜í‚⧂Äövává-agonists. The prescribing of anti-asthmatic drugs within Tasmania was examined from April 1991 to April 1994 using computerised dispensing records from nearly one-third of all the community pharmacies within the State. Trends in prescribing were compared with national data and regional State differences were examined. It was found that drug utilisation, both nationally and within Tasmania, appeared to be changing in line with current management guidelines with increases in inhaled corticosteroid and sodium cromoglycate usage while ˜í‚⧂Äövává-agonists usage remained fairly stable. There was a marked decrease in the ratio of ˜í‚⧂Äövává-agonists:inhaled corticosteroids dispensed over the period of the study. Nebulised ipratropium bromide (an anti-cholinergic drug) is often combined with nebulised agonists in the treatment of asthma and chronic obstructive airways disease. To reduce the time that patients spend inhaling nebulised drug ipratropium bromide is often mixed with ˜í‚⧂Äövává- agonists immediately prior to administration but is sometimes bulk mixed and stored for several days before use. A reversed-phase ion-pair assay wing UV detection was developed to study the stability of these bulk mixed nebuliser solutions. The stability of an admixture of proprietary ipratropium bromide and salbutamol nebuliser solution (1:1, v/v) was then examined for 5 days under different storage conditions. It was found that admixtures of ipratropium bromide and salbutamol nebuliser retain greater than 90% of their initial concentrations if stored at or below 22¬¨‚àû C for periods of up to 5 days. Finally, an assay using solid-phase extraction was developed to measure urinary levels of salbutamol in a relatively large group of asthmatic patients using inhaled therapy. Salbutamol levels in 'spot' urine samples were investigated as a potential indicator of over-use. Median levels of unchanged drug were 378 ng/ml (range 0-34.4 ˜í¬¿g/m1) and 2.55 tig/m1 (range 0- 49.8 ˜í¬¿g/m1) in community and hospital patients respectively. Even when conceding the limitations of 'spot' urine sampling there were large inter-patient differences in levels corrected for dosage, probably due to differences in technique of administration and pharmacokinetic variability. There were also indications of possible low level saturation of metabolism which may have clinical implications.