Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects.

BACKGROUND: The main adverse effects of inhaled long acting beta(2) agonists relate to their systemic activity. The systemic effects seen over eight hours after inhalation of three doses of salmeterol and formoterol were therefore compared in normal subjects. METHODS: A double blind, randomised, crossover study was carried out in 16 healthy subjects who inhaled formoterol 24, 48 and 96 microg (via Turbuhaler((R))), salmeterol 100, 200 and 400 microg (via Diskhaler((R))), or placebo on separate days. Heart rate, systolic and diastolic blood pressure, and plasma potassium and glucose concentrations were measured for eight hours following each drug and mean values were used to plot the time course of change after each dose. Mean maximum (or minimum) absolute values were used to construct dose-response curves to calculate the relative dose potency of the two drugs. Lunch was taken after the four hour readings and, since this caused additional changes to the main outcome measures, data from the first four hours are also presented in a post hoc analysis. RESULTS: Both salmeterol and formoterol caused an early dose dependent increase in heart rate and glucose concentrations and a fall in diastolic blood pressure and plasma potassium concentration; formoterol also caused an early increase in systolic blood pressure. The cardiovascular effects occurred more rapidly than the metabolic effects and the response to formoterol was faster than that of salmeterol, apart from the glycaemic response. The effects of salmeterol were slightly more prolonged than those of formoterol, although some dose related effects were apparent at eight hours with both drugs. The relative dose potency for formoterol compared with salmeterol at four and eight hours for the different end points excluding systolic blood pressure ranged from 1.6 to 7.0 after adjusting for baseline values. Relative dose potencies (95% CI) for maximum heart rate and plasma potassium concentrations were 4.1 (3.0 to 5.6) and 5.8 (4.1 to 8.6) over four hours and 2.4 (1.2 to 3.8) and 3.0 (1.2 to 5.7) over eight hours. CONCLUSIONS: Formoterol and salmeterol cause dose related changes in heart rate, diastolic blood pressure, and plasma glucose and potassium concentrations. Formoterol has a more rapid onset for most end points whereas salmeterol has slightly more prolonged activity. Both drugs have a relatively modest therapeutic window. The relative dose potencies of the two drugs for the main end points were similar to the fourfold difference in recommended doses. Some differences in the pharmacological profile of the two drugs emerged and are as yet unexplained.

Comparative study of visceral and parietal pleural biopsy in the etiological diagnosis of pleural diseases.

OBJECTIVE: The present study was planned to evaluate the efficacy and diagnostic reliability of conoctional parietal pleural biopsy to a technique of visceral pleural biopsy. METHOD: Study comprises of 54 diagnosed cases of pleural effusion and after establishing the clinical diagnosis for probable etiological causes. Then parietal pleural biopsy using absents punch biopsy needle and vesceral pleural biopsy using Prabhudesai et al technique was taken in all these patients. Size of the tissue yield; percentage of biopsies; diagnostic yield and sensitivity for these two techniques were compared. RESULTS: A definitive etiological diagnosis could be reached in 52 out of 54 patients on the basis of pleural biopsy (33 tuberculous, 16 malignant and 3 pyogenic), 23 (69.7%) tuberculous effusion patients were diagnosis by visceral pleural biopsy and 14 (42.4%) by parietal pleural biopsy out of 33 diagnosed tuberculous effusion cases. While for the 16 malignant effusions the visceral pleural biopsy showed suggestive histological change in 13 (81.25%) patients and the parietal pleural biopsy in seven (43.8%) with five (31.25%) of these patients being positive by both. All three pyogenic effusions showed only nonspecific inflammatory change in both pleurae. CONCLUSION: The mean size of biopsy sample obtained with modified Prabhudesai et al technique was significantly larger than that of the parietal pleural biopsy with Abrams punch (4.85 mm2 V/s 2.5 mm2 with P < 0.01). Adequate pleural tissue was identifiable in 94.4% and 90.7% of cases, respectively. The modified Prabhudesai et al technique proved to be effective safe and easily learnt. Visceral pleural sampling using this technique is a definite superior addition to the present diagnostic armamentarium of an idiopathic pleural effusion and its routine application together with parietal pleural biopsy will help to establish a definitive diagnosis in majority of patients with idiopathic pleural effusions.

Morbidity from asthma in relation to regular treatment: a community based study.

BACKGROUND: The extent to which asthma morbidity in the community occurs in patients who are having relatively little treatment or in those on step 3 or above of the British asthma management guidelines is uncertain. We have looked at this in a community population in southern Nottinghamshire. METHODS: A cross sectional review of treatment in all patients over the age of four with diagnosed asthma was carried out in five large general practices (population 38 865) in 1995/6 using computerised general practice records. The patients' usual treatment was obtained from prescription data and categorised by the appropriate step on the British guidelines on asthma management. Two measures of morbidity, the request for 10 or more short acting beta agonist inhalers a year or the need for a course of oral corticosteroids in the last year, were related to the regular treatment of the patients. RESULTS: Of the 3373 patients (8. 7%) given a diagnosis of asthma, the percentage on steps 1, 2, 3, 4, and 5 of treatment were 54%, 22%, 11%, 3.6%, and 1%, respectively, with a further 8% having had no treatment. During the past year 13. 6% had been prescribed 10 or more beta agonist inhalers and 12.5% had received at least one course of oral corticosteroids. Both measures occurred more frequently in patients taking more prophylactic treatment (step 3 or above). Nevertheless, because most patients were on steps 1 and 2 of the treatment guidelines, more than half the patients requiring high doses of inhaled beta agonists or a course of oral prednisolone came from those taking low dose or no regular inhaled corticosteroid. CONCLUSIONS: Evidence of morbidity from asthma was found in many patients taking little or no prophylactic medication and this should be amenable to improved education. A different approach may be needed for patients with continuing morbidity who are already taking higher doses of prophylactic medication.